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Relationship Protocol: Couples Counseling

DearSugar — Mon, 16 Jun 2008 10:00:00 -0700

I’m always quick to mention therapy as an option for people in relationships who are working through what can seem like insurmountable issues. The effects of communication in a safe environment with a third party professional vary from person to person but have the potential to be quite powerful. That said, I’m not convinced that therapy is the answer for every relationship, especially those that have yet to commit to a lifetime partnership, marriage or otherwise. If you’re two years in and having problems, maybe that means you’re just not meant to be.

I’m being tough, I know, but do you agree that couples counseling is best left to the long-term and lifelong committed relationships? Or do you think therapy is viable for any couple that wants to make it work?

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Ask a Buddhist: Can I "Find Myself" While With Someone?

TresSugar — Mon, 13 Jul 2009 09:00:00 -0700

Conventional Wisdom is a different kind of advice column. Your questions will be answered by people from all walks of life rather than by advice experts. Today, a person who believes in Buddhist teachings will offer her common sense advice to a 24-year-old looking to find herself. You can submit questions here.

Today's Question:

Is it possible to figure out what you want out of your life while in a committed relationship? My boyfriend and I started dating when we were 16, when we were still young and impressionable. Now, we're both 24 years old, and while we are very much in love with one another, we're both feeling as though we do not know ourselves as individuals. And while we want to figure ourselves out while being together, we have tried - though not very successfully - and it hasn't quite worked so far. So, is it possible to figure yourself out while in a relationship? Or is it best to just cut ties despite the love you feel for another and take time out for yourself, alone?

- In Love but Confused

To find out what the Buddhist has to say, read more.

Dear In Love and Confused,

Wow. Your question really hits home, and I'll try to answer it with the wisdom of my experiences and those of my friends.

I, too, asked this question when I was 24 after having been with my boyfriend, my first love, since I was 18. (Not quite as long you.) I had the 20-something equivalent of the seven-year-itch. I'd never been with another person, I'd moved in with the boyfriend at a young age, and although we had different things going on (he was older and had a career that he loved and I was in college), I felt that there was a big world out there I wasn't exploring so we could be together.

In my case, ultimately, the decision was easier because my restlessness had to do with wanting to having other sexual experiences with people. I loved him, but knew that if I stayed with him, my curiosity would get the better of me. Although it was one of the toughest decisions I had to make, and there were many doubts and tears, I didn't regret my decision to break up with him and move on.

Having said that, I also know people who have remained with the people they fell in love with as teens who are leading happy and fulfilled lives in which the experiences they have separately add to the relationship they have together. The relationship, for each of them, is a place where they not only share experiences that expand their sense of self (they travel together, volunteer together, have similar hobbies), but where, after they do their own thing separately (with their own set of friends, their own travel adventures, etc.) they can come back to the relationship without the other person feeling left out or intimidated by their partner's separateness.

This is where it can get tricky. What experiences contribute to that feeling of "individuality" as you refer to it? There are things you might not be able to discover while in a committed relationship - in my case, it was experiences with other people. Or let's say you want to travel abroad. Unless your boyfriend can do that with you, you might have to spend some time apart. Will you both be OK with being apart and being monogamous? Would you be able to take a break from your relationship, and the monogamy, with an agreement to be back together and see how it goes? Maybe counseling could help you figure out what it is exactly that feels missing, so you could experiment before you "cut ties" with this person you sound like you're really in love with. (I'm curious about what it was you tried and wasn't successful.)

Whether you met when you were 16 or 25 (or 35, 45 or 55!), the challenge of maintaining your individuality in a couple will remain. I know some people who met at ripe old ages who are in stifling relationships that end up being excuses for not exploring who they really are. You definitely have a challenge, but one that's not insurmountable. The question is, how creative can you be, how honest can you be, how flexible can you be? Try out everything you can, and if at the end of the day, you decide that the only way you can find yourselves is to be apart, maybe you can make a pact to meet up again at a certain age and see if it works?

Not losing yourself in a relationship is something everyone - of all ages - experiences. I have a feeling you two can be honest with each other to try everything out to see what works best for you. If you were meant to be together, it will all work out in the end. Good luck, stay present with what you're feeling, and be honest with yourself and your boyfriend.

- A Buddhist

Infertility in women

FitSugar — Wed, 08 Oct 2008 17:35:02 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New At-Home Fertility Test for Couples

Fertell is a new at-home fertility test kit for couples. It screens for sperm motility concentrations and follicle-stimulating hormone (FSH) levels. Fertell may be helpful as an initial test for infertility, but for a definitive diagnosis it is important to consult a doctor. Infertility can be due to many different factors.

Intracytoplasmic Sperm Injection Overused for Female Infertility

The assisted reproductive technology intracytoplasmic sperm injection (ICSI) is being increasingly used in combination with in vitro fertilization (IVF), even for couples who do not have problems with male infertility, suggests a 2007 study in the New England Journal of Medicine. Researchers found that use of ICSI has increased 5-fold in the past decade. Some doctors are now recommending ICSI for women who have failed prior IVF cycles or who have few or poor-quality eggs. Doctors caution that ICSI should be used only to improve pregnancy chances for couples with male-factor infertility.

Clomiphene Best for PCOS-Associated Infertility

The infertility drug clomiphene (Clomid) works better than the diabetes drug metformin (Glucophage) for treating infertility resulting from polycystic ovarian syndrome (PCOS), indicates a 2007 study in the New England Journal of Medicine.

Fertility Drugs and Breast Cancer

Fertility drugs such as clomiphene and gonadotropins do not increase the risk for breast cancer, indicate several studies. In fact, according to a 2006 study in the Archives of Internal Medicine, clomiphene may decrease breast cancer risk.

Iron Deficiency and Female Infertility

Iron deficiency may increase the risk for ovulatory infertility, suggests a 2006 study in Obstetrics and Gynecology. Researchers found that women who took daily iron supplements were 40% less likely to be infertile than women who did not take supplements. Some experts recommend screening for iron deficiency as part of the clinical evaluation for infertility.

Introduction

Infertility is the failure of a couple to become pregnant after one year of regular, unprotected intercourse. In both men and women the fertility process is complex.

About 10% of couples who wish to have a baby are still unable to after a year of unprotected sex. About half of these couples can achieve pregnancy within 2 years after appropriate treatment of the woman, the man, or both. Even under ideal circumstances, the probability that a woman will get pregnant during a single menstrual cycle is only about 30%. And, when conception does occur, only 50 - 60% of pregnancies advance beyond the 20th week. (The inability of a woman to produce a live birth because of abnormalities that cause miscarriages is called infecundity and is not discussed in detail in this report.)

Males and females each account for 40% of infertility. In the remaining 20%, either both partners are responsible or the cause is unclear. Although this report specifically addresses infertility in women, it is equally important for the male partner to be tested at the same time. [See In-Depth Report #67: Infertility in men.]

The Reproductive System

The Primary Organs and Structures in the Reproductive System. The primary structures in the reproductive system are:

The uterus is a pear-shaped organ located between the bladder and lower intestine. It consists of two parts, the body and the cervix.
When a woman is not pregnant the body of the uterus is about the size of a fist, with its walls collapsed and flattened against each other. During pregnancy the walls of the uterus are pushed apart as the fetus grows.
The cervix is the lower portion of the uterus. It has a canal opening into the vagina with an opening called the os, which allows menstrual blood to flow out of the uterus into the vagina.
Leading off each side of the body of the uterus are two tubes known as the fallopian tubes. Near the end of each tube is an ovary.
Ovaries are egg-producing organs that hold 200,000 - 400,000 follicles (from folliculus, meaning "sack" in Latin). These cellular sacks contain the materials needed to produce ripened eggs, or ova.
The inner lining of the uterus is called the endometrium. During pregnancy, it thickens and becomes enriched with blood vessels to house and support the growing fetus. If pregnancy does not occur, the endometrium is shed as part of the menstrual flow. Menstrual flow also consists of blood and mucus from the cervix and vagina.

The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.

Reproductive Hormones. The hypothalamus (an area in the brain) and the pituitary gland regulate the reproductive hormones.

Click the icon to see an image of the hypothalamus and pituitary gland.

The pituitary gland is often referred to as the master gland because of its important role in many vital functions, many of which require hormones. In women, six key hormones serve as chemical messengers that regulate the reproductive system:

The hypothalamus first releases the gonadotropin-releasing hormone (GnRH).
This chemical, in turn, stimulates the pituitary gland to produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

Click the icon to see an image of the pituitary gland.

Estrogen, progesterone, and the male hormone testosterone are secreted by the ovaries at the command of FSH and LH and complete the hormonal group necessary for reproductive health.

Ovulation. The process leading to fertility is very intricate. It depends on the healthy interaction of two sets of organs and hormone systems in both the male and female. In addition, reproduction is limited by the phases of female fertility. Nevertheless, this astonishing process results in conception within a year for about 80% of couples. Only 15% conceive within a month of their first attempts, however, and about 60% succeed after 6 months.

A woman's ability to produce children occurs after she enters puberty and begins to menstruate. The process of conception is complex:

With the start of each menstrual cycle, follicle-stimulating hormone (FSH) stimulates several follicles to mature over a 2-week period until their eggs nearly triple in size. Only one follicle becomes dominant, however, during a cycle.
FSH signals this dominant follicle to produce estrogen, which enters the bloodstream and reaches the uterus. There, estrogen stimulates the cells in the uterine lining to reproduce, therefore thickening the walls.
Estrogen levels reach their peak around the 14th day of the cycle (counting days beginning with the first day of a period). At that time, they trigger a surge of luteinizing hormone (LH).

LH serves two important roles:

First, the LH surge around the 14th cycle day stimulates ovulation. It does this by causing the dominant follicle to burst and release its egg into one of the two fallopian tubes. Once in the fallopian tube, the egg is in place for fertilization.
Next, LH causes the ruptured follicle to develop into the corpus luteum. The corpus luteum provides a source of estrogen and progesterone during pregnancy.

Click the icon to see an image of the corpus luteum.

Fertilization. The so-called "fertile window" is 6 days long and starts 5 days before ovulation and ends the day of ovulation. Fertilization occurs as follows:

The sperm can survive for up to 3 days once it enters the fallopian tube. The egg survives 12 - 24 hours unless it is fertilized by a sperm.
If the egg is fertilized, about 2 - 4 days later it moves from the fallopian tube into the uterus where it is implanted in the uterine lining and begins its 9-month incubation.
The placenta forms at the site of the implantation. The placenta is a thick blanket of blood vessels that nourishes the fertilized egg as it develops.

Click the icon to see an image of the placenta.

The corpus luteum (the yellow tissue formed from the ruptured follicle) continues to produce estrogen and progesterone during pregnancy.

If the egg is not fertilized, the corpus luteum degenerates into a form called the corpus albicans, and estrogen and progesterone levels drop. Finally, the endometrial lining sloughs off and is shed during menstruation.


Menstrual Phases	Typical No. of Days	Hormonal Actions
Follicular (Proliferative) Phase	Cycle Days 1 - 6: Beginning of menstruation to end of blood flow.	Estrogen and progesterone start out at their lowest levels. FSH levels rise to stimulate maturity of follicles. Ovaries start producing estrogen and levels rise, while progesterone remains low.
	Cycle Days 7 - 13: The endometrium (the inner lining of the uterus) thickens to prepare for the egg implantation.
Ovulation	Cycle Day 14:	Surge in LH. Largest follicle bursts and releases egg into fallopian tube.
Luteal (Secretory) Phase, also known as the Premenstrual Phase	Cycle Days 15 - 28:	Ruptured follicle develops into corpus luteum, which produces progesterone. Progesterone and estrogen stimulate blanket of blood vessels to prepare for egg implantation.
	If fertilization occurs:	Fertilized egg attaches to blanket of blood vessels that supplies nutrients for the developing placenta. Corpus luteum continues to produce estrogen and progesterone.
	If fertilization does not occur:	Corpus luteum deteriorates. Estrogen and progesterone levels drop. The blood vessel lining sloughs off and menstruation begins.

Onset of Menstruation (Menarche). Previous evidence had set the onset of menstruation, called the menarche, at an average age of 12 or 13. Recent studies, however, set the time of onset earlier by about 1 year in Caucasian girls and 2 years in African-American girls. Currently, the youngest possible age for normal puberty is 7 years old for Caucasians and 6 years old for African-Americans, down from a previous low of 8 years for both.

Evidence is pointing to the increasing incidence of childhood obesity as a major cause of the trend in earlier menarche onset. (Obesity is also highly associated with hormonal disorders in girls entering puberty at young ages.) Environmental estrogens found in chemicals and pesticides are also suspects.

Length of Monthly Cycle. The menstrual cycle can be very irregular for the first 1 - 2 years, usually being longer than the average of 28 days. The length then generally stabilizes to an average of 28 days, although the cycle length may range from 20 - 45 days and still be considered normal. A variation of 10 days or more -- either more or fewer days -- may have an impact on fertility, however. When a woman reaches her 40s the cycle lengthens, reaching an average of 31 days by age 49. Several factors can affect cycle length at any age.


Risk Factors for Shorter Cycles	Risk Factors for Longer Cycles
Regular alcohol use	Being under 21 and over 44
Stressful jobs	Being very thin (also at risk for short bleeding periods)
	Competitive athletics (also at risk for short bleeding periods)

Length of Periods. Periods average 6.6 days in young girls. By the age of 21, menstrual bleeding averages 6 days until women approach menopause. However, about 5% of healthy women menstruate less than 4 days, and 5% menstruate more than 8 days.

Normal Absence of Menstruation. Normal absence of periods can occur in any woman under the following circumstances:

Menstruation stops during the duration of pregnancy. Some women continue to have irregular bleeding during the first trimester. This bleeding may indicate a threatened miscarriage and requires immediate attention by the doctor.
When women breastfeed they are unlikely to ovulate. After that time, menstruation usually resumes, and they are fertile again.
Perimenopause starts when the intervals between periods begin to lengthen, and it ends with menopause itself (the complete cessation of menstruation). Menopause usually occurs at about age 51, although smokers often go through menopause earlier.

Risk Factors

In the U.S., an estimated 10.2% of women ages 15 - 44, or about 6.1 million women, have impaired fertility, and the incidence is increasing. About 25% of women experience some period of infertility during their reproductive years.

As a woman ages, her chances for fertility decline. Infertility in older women appears to be mostly due to a higher risk for chromosomal abnormalities that occur in her eggs as they age. Older women are also more likely to have health problems that may interfere with fertility. If fertilization occurs, older, healthy women can usually successfully bear a fetus to term, although they have a higher risk for miscarriage. Using population studies, experts have come up with estimated odds for pregnancy at different ages, given no fertility intervention. One analysis of pregnancy rates based on conception on the day of ovulation suggested that women ages 19 - 26 have twice the pregnancy rates as those ages 35 - 39.


Age	Fertility %
Up until age 34	90%
By age 40	Declining to 67%
By age 45	Declining to 15%

Although most of a woman's estrogen is manufactured in her ovaries, 30% is produced in fat cells by a process that transforms circulating adrenal male hormones into estrogen. Because a normal hormonal balance is essential for the process of conception, it is not surprising that extreme weight levels, either high or low, can contribute to infertility.

Being Overweight. Being overweight or obese (fat levels that are 10 - 15% above normal) can contribute to infertility in various ways. Obesity is highly associated with polycystic ovarian syndrome (PCOS), which is the cause of infertility in some cases. In one study, overweight women without PCOS were classified in one of five grades, depending on the severity of the obesity. The risk for irregular or absent periods increased two-fold by each increase in grade. In this group, amenorrhea (absent periods) was also highly associated with type 2 diabetes and blood sugar abnormalities.

Being Underweight. Body fat levels 10 - 15% below normal can completely shut down the reproductive process. Women at risk include:

Women with eating disorders, such as anorexia or bulimia.
Women on very low-calorie or restrictive diets are at risk, especially if their periods are irregular.
Strict vegetarians might have difficulties if they lack important nutrients, such as vitamin B12, zinc, iron, and folic acid.
Marathon runners, dancers, and others who exercise very intensely. (Lower body fat contributes to menstrual irregularities in competitive athletes, but other mechanisms are also involved.)

Exposure to environmental hazards (herbicides, pesticides, industrial solvents) may affect fertility. Estrogen-like hormone-disrupting chemicals are of particular concern for infertility in men and for effects on offspring of women.

Phthalates, chemicals used to soften plastics, are under particular scrutiny for their ability to disrupt hormones. Specific phthalates of special concern include dibutyl phthalate (DBP) and others found in many products, including cosmetics and clay products sold to children (Fimo, Sculpey). Animals exposed to phthalates have significantly impaired sperm count and abnormalities in reproductive structures, such as the testes. In addition, there is some concern that exposure in pregnant women may affect the offspring.

Neurotransmitters (chemical messengers) act in the hypothalamus gland, which controls both reproductive and stress hormones. Severely elevated levels of stress hormone can, in fact, shut down menstruation. Whether stress has any significant effect on fertility or fertility treatments is unclear. One 2005 study found that psychological stress does not affect the success or failure of in vitro fertilization.

Click the icon to see an image of the hypothalamus.

Causes

Causes of infertility can be found in about 90% of infertility cases but, despite extensive tests, about 10% of couples will never know why they cannot conceive. Between 10 - 30% of cases of infertility have more than one cause. Male or female infertility each account for about 30 - 40% of cases. In men, sperm defects (their quality and quantity) are usually responsible. Female infertility is more complex.

Pelvic inflammatory disease (PID) is the major cause of female infertility worldwide. PID comprises a variety of infections caused by different bacteria that affect the reproductive organs, appendix, and parts of the intestine that lie in the pelvic area. The sites of infection most often implicated in infertility are in the fallopian tubes, a specific condition referred to as salpingitis.

Causes of PID. PID may result from many different conditions that cause infections. Among them are:

Sexually transmitted diseases (cause of most PIDs). Chlamydia trachomatis is an infectious organism that causes 75% of infertility in the fallopian tubes. Gonorrhea is responsible for most of the remaining cases.
Pelvic tuberculosis (a growing global problem as tuberculosis cases increase)
Nonsterile abortions
Ruptured appendix
Herpes virus (suggested for some cases, but not confirmed as a cause).

Symptoms of PID. The infection may be subclinical (occurring without any symptoms), or there may be fever, chills, or pelvic pain indicating inflammation of the entire pelvic area.

Effects of PID. Severe or frequent attacks of PID can eventually cause scarring, abscess formation, and tubal damage that result in infertility. About 20% of women who develop symptomatic PID become infertile. PID also significantly increases the risk of ectopic pregnancy (fertilization in the fallopian tubes). The severity of the infection, not the number of the infections, appears to pose the greater risk for infertility.

Endometriosis may account for as many as 30% of infertility cases. Some evidence suggests that between 30 - 50% of women with endometriosis are infertile. Often, however, it is difficult to determine if endometriosis is the primary cause of infertility, particularly in women who have mild endometriosis. Endometriosis rarely causes an absolute inability to conceive, but, nevertheless, it can contribute to it both directly and indirectly.

Endometriosis is the condition in which the tissue that normally lines the uterus (endometrium) grows on other areas of the body causing pain and irregular bleeding.

Direct Effect of Endometrial Cysts. Endometrial cysts may directly cause infertility in several ways:

If implants occur in the fallopian tubes, they may block the egg's passage.
Implants that occur in the ovaries prevent the release of the egg.
Severe endometriosis can eventually form rigid webs of scar tissue (adhesions) between the uterus, ovaries, and fallopian tubes, thereby preventing the transfer of the egg to the tube.

Immune Factors and the Inflammatory Response. Researchers are focusing on defects in the immune system that not only may be responsible for endometriosis in the first place but may also cause the infertility associated with endometriosis. Even in early stage endometriosis, investigators have observed increased immune system activity.

Other Conditions Linking Endometriosis and Infertility. Researchers have sometimes noted unusually low levels of specific substances that enable a fertilized egg to adhere to the uterine lining. (Such abnormalities are more often a factor in infertility in women with mild-to-moderate endometriosis than in those with severe cases.)

One study found that the eggs in women with endometriosis appeared to have more genetic abnormalities than those in women without the disorder.

Polycystic ovarian syndrome (PCOS) is a condition in which the ovaries produce high amounts of androgens (male hormones), particularly testosterone. PCOS occurs in about 6% of women, and amenorrhea or oligomenorrhea (infrequent menses) is quite common. According to one study, nearly 30% of obese women with PCOS had amenorrhea. (The rate was lower -- 4.7% -- in women with normal weight.)

Click the icon to see an image of polycystic ovarian syndrome.

In PCOS, increased androgen production produces high luteinizing hormone (LH) levels and low follicle-stimulating hormone (FSH) levels, so that follicles are prevented from producing a mature egg. Without egg production, the follicles swell with fluid and form into cysts. Every time an egg is trapped within the follicle, another cyst forms, so the ovary swells, sometimes reaching the size of a grapefruit. Without ovulation, progesterone is no longer produced, whereas estrogen levels remain normal.

The elevated levels of androgens (hyperandrogenism) can cause obesity, facial hair, and acne, although not all women with PCOS have such symptoms. Other male characteristics, such as deepening voice and clitoral enlargement, are rare.

PCOS also poses a high risk for insulin resistance, particularly in women who are also obese. Insulin resistance is associated with diabetes type 2, in which insulin levels are normal or high but the body cannot use this hormone efficiently. About half of PCOS patients, in fact, also have diabetes.

Premature ovarian failure is the early depletion of follicles before age 40, which, in most cases, leads to premature menopause. It affects about 1% of women and is typically preceded by irregular periods, which might continue for years. In this condition, follicle-stimulating hormone (FSH) levels are elevated, as they are during perimenopause. Premature ovarian failure is a significant cause of infertility, and women who have this condition have only a 5 - 10% chance to conceive without fertility treatments.

Causes of Premature Ovarian Failure. There are numerous causes of premature ovarian failure. Often the cause of this disorder or other causes of premature ovarian failure is unknown. In some cases, premature ovarian failure may represent an acceleration of the aging process.

The following conditions may produce premature ovarian failure:

Adrenal, pituitary, or thyroid gland deficiencies.
Genetic factors related to the X chromosome. A woman needs two functioning X chromosomes for normal reproduction. When one is abnormal, ovarian function fails. The most severe example is Turner syndrome, a genetic condition, in which one of the two X-chromosomes is missing or malfunctioning. Milder cases of ovarian failure can occur in fragile X syndrome and other rare inherited conditions that cause partial X-chromosome abnormalities.
Cancer treatments (radiation, chemotherapy, or both). Women who are undergoing cancer treatments and who want to become pregnant should see a reproductive specialist to discuss their options. According to the American Society of Clinical Oncology's 2006 guidelines, the fertility preservation method with the best chance of success is embryo cryopreservation. This procedure involves harvesting a woman's eggs (oocytes), followed by in vitro fertilization and freezing of embryos for later use. Other treatments under investigation include egg preservation, collecting and freezing unfertilized eggs, removing and freezing a part of the ovary for later reimplantation, and using hormone therapy to protect the ovaries during chemotherapy. Women may be able to access these investigational approaches through enrolling in clinical trials.
Autoimmunity. Autoimmune diseases -- including type 1 diabetes, systemic lupus erythematosus, autoimmune hypothyroidism, and autoimmune Addison's disease -- are associated with a higher risk for early menopause. Autoimmunity, however, may also play a role in some cases of premature ovarian failure without the presence of specific autoimmune diseases. In such cases, antibodies specifically attack the cells that secrete reproductive hormones thus causing ovarian failure.
Other causes of premature ovarian failure include sarcoidosis, mumps, some sexually transmitted diseases, and tuberculosis. Women with epilepsy are at higher risk for premature ovarian failure.

Idiopathic hypogonadotropic hypogonadism is a rare condition in which follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are underproduced, preventing the development of functional ovaries. There are no other abnormalities in the hypothalamus-pituitary axis (such as tumors or abnormal stress hormones or prolactin). In most cases, the causes of hypergonadotropic hypogonadism are unknown. Genetic factors, including Kallman syndrome, have been identified in about 20% of these cases.

Functional hypothalamic amenorrhea (FHA) is the absence of menstruation due to disturbances in the thyroid gland and hypothalamus-pituitary-adrenal (HPA) system, which regulates reproduction and other important functions. The eating disorders anorexia and bulimia are most often associated with FHA. FHA may be due to other different factors, most unknown.

Luteal phase defect is a general term referring to problems in the corpus luteum that result in inadequate production of progesterone. Because progesterone is necessary for thickening and preparing the uterine lining, the ovum fails to successfully implant in the endometrium. Between 25 - 60% of women who have recurrent miscarriages may have a luteal phase defect. A luteal phase defect, however, can also occur in fertile women, so other factors may be responsible for implantation failure.

Benign fibroid tumors in the uterus are extremely common in women in their 30s. The effect of fibroids on fertility is controversial. One analysis suggested that they may account for infertility in only 1 - 2.4% of women who are having trouble conceiving.

Large fibroids may cause infertility impairing the uterine lining, by blocking the fallopian tube, or by distorting the shape of the uterine cavity or altering the position of the cervix.

Some evidence suggests that even small fibroids may reduce the chances of pregnancy in women who are undergoing assisted reproductive techniques. Treatments to reduce fibroids may be helpful in such women, although there has been little research on this subject.

Click the icon to see an image of uterine fibroids.

Prolactin is a hormone produced in the pituitary gland that stimulates breast development and milk production in association with pregnancy. High levels of prolactin (hyperprolactinemia) reduce gonadotropin hormones and inhibit ovulation. Hyperprolactinemia in women who are not pregnant or nursing can be caused by hypothyroidism or pituitary adenomas. (These are benign tumors that secrete prolactin. They can cause headache and visual problems as well as breast secretions.) Some drugs, including oral contraceptives and some antipsychotic drugs, can also elevate levels of prolactin.

Secretions from the breast not related to pregnancy or nursing (called galactorrhea) are a telltale symptom of high prolactin levels and should be investigated.

Inborn Abnormalities. Inborn genital tract abnormalities may cause infertility. Mullerian agenesis is a specific malformation in which no vagina or uterus develops. Even in these cases, some women can become mothers by undergoing in vitro fertilization and having the fertilized egg implanted in another woman who is willing and able to carry the pregnancy (a surrogate mother).

Uterine or Abdominal Scarring. Bands of scar tissue that bind together after abdominal or pelvic surgery or infection (called adhesions) can restrict the movement of ovaries and fallopian tubes and may cause infertility. Asherman syndrome, for example, is scarring in the uterus that can cause obstructions and secondary amenorrhea. It may be caused by surgery, repeated injury, or unknown factors. Laparoscopic surgery is less likely to cause adhesions than standard open surgery.

In some of these cases, surgery may be helpful. One technique, called pressure lavage under ultrasound guidance (PLUG), may prove to be useful for treating some cases of mild scarring in the uterus (intrauterine adhesions). This technique is based on transvaginal sonohysterography, which uses ultrasound along with saline infused into the uterus to enhance visualization. Continuous accumulation of saline in the procedure is used to break up the scars.

Ectopic Pregnancies. Ectopic pregnancies increase the risk for infertility, although subsequent pregnancy rates are quite variable. Ectopic pregnancies that terminate without treatment appear to pose a lower risk for future infertility. Even a ruptured tube does not appear to reduce the chance for a future pregnancy in most women. Such an event however can be dangerous and even life threatening for the woman. Laparoscopic surgery to remove a fallopian tube affected by an ectopic pregnancy may preserve fertility better than traditional abdominal surgery.

Click the icon to see an image of an ectopic pregnancy.

Medications. Among the medications that can cause temporary infertility are those used to treat chronic disorders, as well as antidepressants, hormones, painkillers, and antipsychotic drugs.

Inflammatory Bowel Disease. Inflammatory bowel disease (particularly Crohn's disease or surgery for ulcerative colitis) can affect fertility.

Click the icon to see an image of Crohn's disease.

Celiac Sprue. Celiac sprue is a disease in which the patient cannot tolerate gluten, a common food chemical. The disorder is also highly associated with infertility in men and women, possibly through multiple effects on nutrition, immune factors, and hormones. The mechanisms are not altogether clear, but infertility is usually reversible with strict dietary control.

Click the icon to see an image of celiac sprue.

Iron Intake. Nutritional iron deficiency may contribute to female infertility. According to a 2006 study, women who take iron supplements are 40% less likely to experience ovulatory infertility than women who do not take iron supplements. Some researchers suggest that screening for iron deficiency should be part of the standard work-up of infertility tests.

Epilepsy. In one study of women with epilepsy, fertility rates were 33% lower than among women in the general population, perhaps due to certain antiepileptic drugs that increase the risk for birth defects. The social effects of epilepsy may also lead to marriage at an older age, which can be associated with delayed attempts to get pregnant and thereby affect fertility.

Thyroid Problems. Thyroid problems, either too much thyroid hormone (hyperthyroidism) or too little (hypothyroidism), can interrupt cycles.

Click the icon to see an image of hyperthyroidism.

Click the icon to see an image of hypothyroidism.

Metabolic Syndrome (also Called Syndrome X). Doctors diagnose this condition when at least three of the following abnormalities are present:

Abdominal obesity
Low HDL (good) cholesterol levels
High triglyceride levels
High blood pressure
Insulin resistance

Metabolic syndrome is a pre-diabetic condition that is significantly associated with heart disease. One study reported that, as with polycystic ovarian syndrome, women with metabolic syndrome have higher levels of male hormones and are therefore at risk for infertility. Another study estimated that 24% of the population now has this condition.

Other Medical Conditions. Medical conditions associated with delayed puberty and amenorrhea (absence of periods) include Cushing's disease, sickle cell disease, HIV, kidney disease, and diabetes. Genetic mutations that affect luteinizing hormone may also be responsible for some cases of light or absent menstruation. Other rare genetic disorders, such as Kallman syndrome, cause abnormalities in the hypothalamus of the brain.

Diagnosis

In any fertility work-up, both male and female partners are tested if pregnancy fails to occur after a year of regular unprotected sexual intercourse. Fertility testing should be done earlier if a woman is over 35 years old or if either partner has known risk factors for infertility. An analysis of the man's semen should be performed before the female partner undergoes any invasive testing.

The first step in any infertility work up is a complete medical history and physical examination. Sexual technique and timing, menstrual history, lifestyle issues (such as smoking and drug, alcohol, and caffeine consumption), any medications being taken, and a profile of the patient's general medical and emotional health can help the doctor decide on appropriate tests.

Before embarking on an expensive fertility work-up, the following steps are free or low-cost and can be helpful:

Monitor basal body temperature. This is accurate in determining if ovulation is actually taking place.
Test the consistency of your cervical mucus. Collect some mucus between your two fingers and stretch it apart. If you are near the time of ovulation, the mucus will stretch more than 1 inch before it breaks. As an alternative, at-home kits can test saliva as substitute for checking cervical mucus.
Take an over-the-counter urine test for detecting luteinizing hormone (LH) surges. This helps determine the day of ovulation.
Fertell is the first at-home test kit for couples that is approved by the Food and Drug Administration. Women can test their urine for levels of follicle-stimulating hormone (FSH), while men can test their semen for sperm motility (ability of sperm to move). Fertell became available online and in some pharmacies in June 2007.

Several laboratory tests may be used to detect the cause of infertility and monitor treatments:

Hormonal Levels. Blood and urine tests are taken to evaluate hormone levels. Hormonal tests for ovarian reserve (the number of follicles and quality of the eggs) are especially important for older women.

Examples of possible results include:

High follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and low estrogen levels suggest premature ovarian failure or hypogonadotropic hypogonadism.
High LH and low FSH may suggest polycystic ovary syndrome or luteal phase defect.
High FSH and high estrogen levels on the third day of the cycle predicts poor success rates in older women trying fertility treatments.
LH surges indicate ovulation.
Blood tests for prolactin levels and thyroid function are also measured. These are hormones that may indirectly affect fertility.

Clomiphene Challenge Test. Clomiphene citrate (Clomid, Serophene), a standard fertility drug, may be used to test for ovarian reserve. With this test, the doctor measures FSH on day 3 of the cycle. The woman takes clomiphene orally on days 5 and 9 of the cycle. The doctor measures FSH on the tenth day. High levels of FSH either on day 3 or day 10 indicate a poor chance for a successful outcome.

Tissue Samples. To rule out luteal phase defect, premature ovarian failure, and absence of ovulation, the doctor may take tissue samples of the uterus 1 - 2 days before a period to determine if the corpus luteum is adequately producing progesterone. Tissue samples taken from the cervix may be cultured to rule out infection.

Tests for Autoimmune Disease. Tests for autoimmune disease, such as hypothyroidism and diabetes, should be considered in women with recent ovarian failure that is not caused by genetic abnormalities.

If an initial fertility work-up does not reveal abnormalities, as happens in about 40% of cases, more extensive tests will reveal abnormal tubal or uterine findings. The three major approaches for examining the uterus are ultrasound (particularly a variation called saline-infusion sonohysterography), hysterosalpingography, and hysteroscopy. Although combinations of these diagnostic approaches are often used to confirm diagnoses, one study indicated that with the introduction of saline-infusion sonohysterography, all are equally accurate and combinations do not increase accuracy. Furthermore, the ultrasound procedure is significantly less painful than the other two, suggesting that this should be the procedure of choice, if available.

Ultrasound and Sonohysterography. Ultrasound is the standard imaging technique for evaluating the uterus and ovaries, detecting fibroids, ovarian cysts and tumors, and also obstructions in the urinary tract. It uses sound waves to produce an image of the organs and entails no risk and very little discomfort.

Transvaginal sonohysterography uses ultrasound along with saline infused into the uterus, which enhances the visualization of the uterus. This technique is proving to be more accurate than standard ultrasound in identifying potential problems. It is currently the gold standard for diagnosing polycystic ovaries.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) gives a better image of any fibroids that might be causing bleeding, but it is expensive and not usually necessary.

Hysteroscopy. Hysteroscopy is a procedure that may be used to detect the presence of endometriosis, fibroids, polyps, pelvic scar tissue, and blockage at the ends of the fallopian tubes. Some of these conditions can be corrected during the procedure by cutting away any scar tissue that may be binding organs together or by destroying endometrial implants. (It may miss cases of uterine cancer, however, and is not a substitute for more invasive procedures, such as dilation and curettage ( D&C) or endometrial biopsy, if cancer is suspected.)

It is done in the office setting and requires no incisions. The procedure uses a long flexible or rigid tube called a hysteroscope, which is inserted into the vagina and through the cervix to reach the uterus. A fiber optic light source and a tiny camera in the tube allow the doctor to view the cavity. The uterus is filled with saline or carbon dioxide to inflate the cavity and provide better viewing. This frequently causes cramping.

There are small risks of bleeding, infection, and reactions to anesthesia. Many patients experience temporary discomfort in the shoulders after the operation due to residual carbon dioxide that puts pressure on the diaphragm. The wound itself is minimally painful.

Hysterosalpingography. Hysterosalpingography is performed to discover possible blockage in the fallopian tubes and abnormalities in the uterus:

The doctor inserts a tube into the cervix through which a special dye is injected. (The patient may experience some cramping and discomfort.)
The dye passes into the uterus and up through the fallopian tubes.
An x-ray is taken of the dye-filled uterus and tubes.
If the dye is seen emerging from the end of the tube, no blockage is present. (In some cases, hysterosalpingography may even restore fertility by clearing away tiny tubal blockages.)
If results show blockage or abnormalities, the test may need to be repeated. In case of blockage, hysterosalpingography may reveal a number of conditions, including endometrial polyps, fibroid tumors, or structural abnormalities of the uterus and tubes.

The test has significant rates of false diagnoses, both positive and negative. There is a small risk of pelvic infection, and antibiotics may be prescribed prior to the procedure. One study suggested that flushing the tubes with an oil-based fluid (lipiodol) during this procedure may improve fertility rates in women with infertility of unknown causes.

As women age, the number of follicles (and therefore their egg supply) declines. Researchers are developing tests that may help determine how many are left. Such tests include the following:

Calculating the volume of the ovaries. In general, the smaller the ovaries, the fewer the remaining eggs.
Counting antral follicles. Antral follicles are those that develop but do not become dominant follicles. Instead, they form a fluid-filled space called an antrum. Women who have fewer than three to five antral follicles appear to have a poor chance of fertility.
Measuring inhibin B. Inhibin B is a growth factor produced in the ovaries. Low levels suggest fewer eggs.

Eventually these markers may be useful for determining which women need more aggressive treatments.

Genetic testing may be warranted in cases of male infertility or when genetic factors may be causing pregnancy failure in the woman. If genetic abnormalities are suspected in either partner, counseling is recommended.

A technique called preimplantation genetic diagnosis (PGD) is now available in some centers that can examine all the chromosomes in a human embryo. It helps identify abnormalities that increase the risk for infertility, treatment failures, or genetic defects in the offspring.

Treatment

Some doctors recommend that if a couple fails to conceive after 1 - 2 years of frequent unprotected sex, they should consult a fertility expert. Women who are 35 or older, however, may want to begin exploring their options if they do not become pregnant within 6 months to a year.

Several approaches can treat infertility, depending on the cause:

Lifestyle measures (healthy lifestyle, planning sexual activity with ovulation cycle, managing stress and emotions)
Treatments for endometriosis, fibroids, or menstrual disorders
Use of anti-estrogen drugs, such as clomiphene, to induce ovulation in women with ovarian dysfunction
Surgery (standard or laparoscopic) to unblock fallopian tubes
Use of hormone treatments (clomiphene or progestins) for luteal phase defect
Assisted reproductive technologies (ART) such as in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI)

Choosing a good fertility clinic is important. Those offering assisted reproductive techniques are not always regulated by the government, and abuses have been reported, including lack of informed consent, unauthorized use of embryos, and failure to routinely screen donors for disease.

The clinic should always provide the following information:

The live-birth rate (not just pregnancy success rate) for other couples with similar infertility problems. (Multiple births, such as twins or triplets, are counted as one live birth.)
Such statistics should include high-risk women, such as those who are older or fail to produce eggs. (Some disreputable clinics give success percentages that exclude high-risk women from their total, thereby making the percentage of success much higher.)

Advanced fertility procedures and medications are extremely expensive and often not covered by insurance. Couples should be cautious about offers of rebates in the event of failure; the clinics offering them are often significantly more expensive than those that don't offer such gimmicks.


Causes of Infertility	Treatments
Endometriosis	Conservative surgery (typically laparoscopy) is the appropriate approach for restoring fertility. GnRH agonists or progestins, used to treat endometriosis itself, have no effect on fertility. Possible exceptions are GnRH agonists used after surgery. In one study, this treatment helped improve conception rates in women who subsequently underwent assisted reproductive techniques. Assisted reproductive technologies (ART). (Fertility drugs alone have no effect.) It is not clear, in any case, whether either laparoscopy for removing endometrial implants or ART has additional advantages in many of these women compared to simply trying to become pregnant through non-aggressive means.
Hyperprolactinemia	Dopamine agonists, including bromocriptine (Parlodel) or cabergoline (Dostinex). Surgery in some cases.
Luteal phase defect	Clomiphene or superovulation drugs (FSH drugs or hMG).
Hyperprolactinemia (elevated prolactin)	Bromocriptine, cabergoline to shrink tumors that result in over secretion of prolactin. Cabergoline is more effective, but bromocriptine has been used longer. Once ovulation starts, women who want to become pregnant should stop cabergoline one month before attempting conception. Surgery may be needed for women who do not respond to medications or who have large tumors.
Hypogonadotropic Hypogonadism	Fertility drugs (hMG preferable to FSH alone) with or without assisted reproductive technologies.
Pelvic Inflammatory Disease	Screening high-risk women for the presence of Chlamydia trachomatis and treating the organism before it causes symptoms could reduce the risk of PID by almost 60%. If any sexually transmitted infection is detected, both partners should receive antibiotics, even if there are no symptoms. If PID symptoms develop, particularly lower abdominal pain, fertility can be preserved if women receive antibiotics within 2 days. A delay significantly increases the risk for scarring.
Polycystic Ovarian Syndrome	Lifestyle changes (weight loss and exercise in women who are overweight.) Clomiphene is the standard first-line treatment for polycystic ovarian syndrome (PCOS)-related infertility. Although some research has indicated that the diabetes drug metformin (Glucophage) might help treat infertility in women with PCOS, a 2007 study in the New England Journal of Medicine indicated that clomiphene is much more effective.
Premature Ovarian Failure	Assisted reproductive technologies with donor eggs.
Preserving fertility after cancer treatments	Removal and freezing (called cryopreservation) of ovarian tissue containing embryos or freezing immature and unfertilized eggs to use for later reimplantation. (Freezing before cancer treatment appears to offer the best chance.) Under investigation: Ovarian transplantation procedures and gonadotropin-releasing hormone analogues, which put women in a temporary pre-pubescent state during chemotherapy and may preserve fertility.
Fallopian tubal blockage	Surgical procedures (laparoscopy or salpingostomy) to clear the tubes. (Average pregnancy rate after salpingostomy is about 30%, but they can vary widely.) Flushing the tubes with an oil-based fluid (lipiodol) during hysterosalpingography (investigative). In a 2002 study, this procedure improved pregnancy rates in women with infertility of unknown causes. Assisted reproductive technologies.
Unexplained infertility	Lifestyle measures. Fertility drugs. Assisted reproductive technologies.

Lifestyle Changes

Although there are no dietary or nutritional cures for infertility, a healthy lifestyle is important. Ovulatory problems are reversible by changing behavioral patterns. Such conditions include:

Maintain a healthy weight. Women who are either over- or underweight are at risk for fertility failure, including a lower chance for achieving success with fertility procedures. Everyone should have a diet rich in fresh fruits and vegetables and whole grains and low in saturated fats.
Stop smoking. Smoking increases the risk for infertility in both men and women, and poses a future health risk for the mother and infant. Everyone should quit.
Avoid caffeine and alcohol.
Avoid excessive exercise if it causes menstrual irregularity. However, moderate and regular exercise is essential for good health. Few women exercise to the extent that their periods are affected. For those who do, one study found that simply adding calories can restore menstruation in many cases.
Don't use electric blankets. In one study, a 74% higher incidence of spontaneous abortion was associated with using an electric blanket during the month of conception. There was no association with heated waterbeds or electromagnetic waves.
Avoid any unnecessary medications.

There is no evidence of harm to a developing fetus from low exposure to microwaves or electromagnetic waves. Women who remain anxious may derive comfort by avoiding some of these devices (such as cellular phones or electric blankets) and remaining a foot or so away from others (such as computers or microwave ovens).

Both male and female hormone levels fluctuate according to the time of day, and they vary from day to day and month to month. Some timing tips might be helpful.

Male Hormone Levels and Sexual Activity. Male hormone levels are highest in the morning. (Sexual interest also tends to be higher in the morning.) In one study of men, their sexual activity was highest in October, when conception rates were also high.

Fertility and Seasonal Changes. Different studies have reported higher sperm counts in the winter than in the summer. For women, fertility rates as measured by treatment success are highest in months when days are longest.

Monitoring Basal Body Temperature. To determine the most likely time of ovulation and therefore the time of fertility, a woman is instructed to take her body temperature, called her basal body temperature. This is the body's temperature as it rises and falls in accord with hormonal fluctuations.

Each morning before rising, the woman takes her temperature with a specialized basal body thermometer and marks the result on a graph-paper chart.
The woman also notes the days of menstruation and sexual activity.
The so-called "fertile window" is 6 days long, starts 5 days before ovulation, and ends the day of ovulation.
The chances for fertility are considered to be highest between days 10 and 17 in the menstrual cycle (with day 1 being the first day of the period, and ovulation occurring about 2 weeks later). However, cycles vary from woman to woman. Researchers suggest that women track the length of their cycles, which can run anywhere from between 19 and 60 days. A long cycle, for example, suggests a delayed ovulation date.
Immediately after ovulation the body temperature increases sharply in about 80% of cases. (Some women can be ovulating normally yet not show this temperature pattern.)

By studying the temperature patterns after a few months, couples can begin to anticipate ovulation and plan their sexual activity accordingly. Couples must try to avoid becoming fixated on the chart, however, in scheduling their sexual activity. Spontaneity can be lost, and the stress on the relationship can be quite severe.

Hormone Monitoring Systems. A device called a saliva fertility monitor (Fertility Tracker) uses a microscope to view slides containing saliva and monitors estrogen levels. Home test kits that monitor reproductive hormone levels in the urine (ClearBlue) are also available. They are less costly than the saliva test but are messier. Monitoring hormones levels helps to determine when a woman is ovulating.

Frequency of Intercourse. The question of how often a couple should have intercourse is in debate. Some doctors say that having sex more than 2 days a week adds no benefits. Moreover, frequent sexual activity lowers sperm count per ejaculation. Other studies have indicated, however, that having intercourse every day, or even several times a day, before and during ovulation, improves pregnancy rates. Although sperm count per ejaculation is low, a constantly replenished semen supply is more likely to result in a fertilized egg.

The fertility process is a roller coaster of emotions that are present throughout and in both failure and success. There are almost no sure ways to predict which couples will eventually conceive. Some couples with multiple problems will overcome great odds, while other, seemingly fertile, couples fail to conceive. Many of the new treatments are remarkable, but a live birth is never guaranteed. The emotional burden on the couple is considerable, and some planning is helpful.

Planning for Emotional Turmoil.

Decide in advance how many and what kind of procedures will be emotionally and financially acceptable and attempt to determine a final limit. Fertility treatments are expensive. A successful pregnancy often depends on repeated attempts.
Determine alternatives (adoption, donor sperm or egg, or having no children) as early as possible in the fertility process. This can reduce anxiety during treatments and feelings of hopelessness in case conception does not occur.

Managing Emotional Stress During the Process. Managing negative emotions can be viewed as important as medical treatment. The following are some ways women reduce stress while trying to conceive:

Talking to one's spouse, family, and friends is very beneficial. The best support comes from the spouse. Studies suggest that a positive attitude on the husband's part is essential for enabling his wife to deal effectively with either the success or failure of fertility treatments. Men and women may cope differently with the stress, and each should understand the other's special needs. Women tend to want greater personal space and also to want to share the burden with their husbands. Men tend to cope by seeking to improve themselves (for example being strong, or being the "best").
Almost half of women seeking fertility treatments practice good-luck rituals, including praying and wearing charms or special jewelry. No evidence exists that these practices increase fertility, but they may help reduce anxiety and enhance a sense of control.
Cognitive-behavioral therapy, which uses methods that include relaxation training and stress-management, have been associated with higher pregnancy rates. (In one study, 42% became pregnant without medical intervention.)
Attending support groups or counseling services before and after treatment helps many women endure the process and ease the grief should treatment fail. One study indicated that pregnancy rates were twice as high in women who coped with their depression by reaching out to others rather than repressing guilt or rage. (These results held only in cases in which women, not their mates, were infertile.)
Acupuncture may help some women. Some evidence suggests that this alternative treatment has beneficial effects on chemicals in the brain involved with stress and reproduction. Acupuncture is safe, but studies have been mixed on whether it can help improve pregnancy rates. One study indicated that women who received acupuncture achieved significantly higher success rates during fertility treatments (42.5%) than those who did not receive it (26.3%). Several 2006 studies suggested that acupuncture may improve pregnancy success for women who undergo in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) procedures. One of these studies found that acupuncture had a positive effect if it was given during the luteal phase (post-ovulatory period of menstrual cycle.) Another study suggested that acupuncture should be given on the day of embryo transfer.

Managing the Emotional Effects of the Outcome. After enduring the process, the couple must face the outcome, and even a positive outcome has emotional repercussions.

Effects of Failure. The emotional stress of failure can be devastating even on the most loving and affectionate relationships and even in those who have prepared for the possibility of failure. Neither the male nor female partner should hesitate to seek professional help if the emotional burdens are too heavy.
Effects of Genetic Testing. As advanced technologies allow testing and greater genetic information at the earliest stage, potential parents will have to learn to deal with the uncertainties of possible chromosomal abnormalities, which may or may not be significant.
Effects of Successful Treatments. Some studies have indicated that even if successful, some women experience higher stress and fear of failure during pregnancy. According to one study, however, women who achieved pregnancy using fertility treatments felt increasingly better and had higher self esteem and less anxiety as the pregnancy progressed than women whose pregnancies were not due to medical intervention.
Effects of Multiple Births. A successful pregnancy that results in a multiple birth introduces new complexities and emotional problems. One study reported a very high rate of depression in women with triplets, particularly if they had little help from others, and especially if their husbands weren't involved.
Effects on Parenting. Once the fertility treatment-assisted child arrives, parents (both men and women) are more likely to be anxious and to have less confidence than those who conceive naturally.

Medications

Fertility drugs are often used alone as initial treatment to induce ovulation. If they fail as sole therapy, they may be used with assisted reproductive procedures or artificial insemination to produce multiple eggs, a process called superovulation.

Clomiphene citrate (Clomid, Serophene) is usually the first fertility drug of choice for women with infrequent periods and long cycles. Unlike more potent drugs used in superovulation, clomiphene is gentler and works by blocking estrogen, which tricks the pituitary into producing

follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This boosts follicle growth and the release of the egg. Clomiphene can be taken orally, is relatively inexpensive, and the risk for multiple births (about 5%, mostly twins) is lower than with other drugs.

Women with the best chances for success with this drug are those who have the following conditions:

Polycystic ovarian syndrome (PCOS)
Ability to menstruate but irregular menstrual cycle

Women with poorer chances of success with this drug have the following conditions:

Infertility but with normal ovulation
Low estrogen levels
Premature ovarian failure (early menopause)

One or two tablets are taken each day for 5 days, usually starting 2 - 5 days after the period starts. If successful, ovulation occurs about a week after the last pill has been taken. If ovulation does not occur, then a higher dose may be given for the next cycle. If this resgimen is not successful, treatment may be prolonged or additional drugs may be added. Doctors usually do not recommend more than 6 cycles.

Clomiphene often reduces the amount and quality of cervical mucus and may cause thinning of the uterine lining. In such cases, other hormonal drugs may be given to restore thickness. Other side effects of clomiphene include ovarian cysts, hot flashes, nausea, headaches, weight gain, and fatigue. There is a 5% chance of having twins with this drug, and a slightly increased risk for miscarriage.

If clomiphene does not work or is not an appropriate choice, gonadotropin drugs are a second option. Gonadotropins include several different types of drugs that contain either a combination of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), or only FSH. Clomiphene works indirectly by stimulating the pituitary gland to secrete FSH, which prompts follicle production. In contrast, the gonadtropin hormones directly stimulate the ovaries to produce multiple follicles.

Gonadotropins are given in a shot. (Your doctor may show you how to self-administer the injection.) Gonadotropins include:

Human Menopausal Gonadtropins (hMG), also called menotropins
Human Chorionic Gonadotropins (hCG)
Urofollitropin and Follitropin, natural and synthetic forms of FSH
Gonadotropin-releasing hormone (GnRH) analogs, which include GnRH agonists and GnRH antagonists

Gonadotropin drugs are either natural compounds extracted from urine or synthetic compounds that are genetically engineered in a laboratory using recombinant DNA.

Human Menopausal Gonadotropin (hMG). HMG drugs, also called menotropins, contain a mixture of both FSH and LH. These drugs (Pergonal, Repronex, Metrodin, Humegon) are all derived from the urine of postmenopausal women. HMG is administered as a series of injections 2 - 3 days after the period starts. Injections are usually given for 7 - 12 days, but the time may be extended if ovulation does not occur. In such cases, a shot of human chorionic gonadotropin (hCG) may trigger ovulation.

Human Chorionic Gonadotropin (hCG). Human chorionic gonadotropin (hCG) is similar to LH. It mimics the LH surge, which stimulates the follicle to release the egg. Natural hCG drugs, derived from the urine of pregnant women, include Pregnyl, Profasi, Novarel, APL, Chorex, and Follutein. Ovidrel is the only available genetically modified hCG drug. Ovidrel has fewer side effects at the injection site, and its quality can be better controlled than the natural drugs. It is generally used after hMG or FSH to stimulate the final maturation stages of the follicles. Ovulation, if it occurs, does so about 36 - 72 hours after administration.

Urofollitropin and Follitropin. Urofollitropin (Bravelle, Fertinex) is a purified form of FSH, derived from the urine of postmenopausal women. Follitropin drugs (Gonal-F, Follistim) are synthetic versions of FSH. These FSH drugs are sometimes given in combination with an hCG drug.

GnRH Analogs (Agonists or Antagonists). Gonadotropin-releasing hormone (GnRH) is a hormone produced in the hypothalamus part of the brain. GnRH stimulates the pituitary gland to produce LH and FSH. GnRH analogs are synthetic drugs that are classified as either agonists or antagonists. They are similar to natural GnRH but have very different actions. While natural GnRH stimulates LH and FSH, these drugs actually prevent the LH and FSH surge that occurs right before ovulation. This action helps prevent the premature release of the eggs before they can be harvested for assisted reproductive technologies.

GnRH agonists include leuprolide (Lupron), nafarelin (Synarel), and goserelin (Zoladex).
GnRH antagonists include ganirelix (Antagon) and cetrorelix (Cetrotide). GnRH antagonists suppress FSH and LH more than GnRH agonists, and they may require fewer injections.

Women with endometriosis often have an especially hard time getting pregnant. A 2006 review suggested that GnRH agonists may help women with endometriosis quadruple their chances of becoming pregnant when the drug is used 3 - 6 months prior to in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). [See In-Depth Report #74: Endometriosis.]

Multiple Births. Overproduction of follicles can lead to ovarian enlargement. This event increases the risk for multiple births. There is a 25% chance of multiple births (about 17% for twins and 8% for triplets and or more).

Ovarian Hyperstimulation Syndrome. The most serious complication with superovulation is ovarian hyperstimulation syndrome (OHS), which is associated with the enlarged ovary (although the precise cause is unknown). This can result in dangerous fluid and electrolyte imbalances and endanger the liver and kidney. OHS is also associated with a higher risk for blood clots. In rare cases, it can be fatal. Symptoms include abdominal bloating, nausea, vomiting, and shortness of breath.

Bleeding and Rupture of Ovarian Cysts. Overproduction of follicles, if unchecked, may result in bleeding and rupture of ovarian cysts.

Cancer Concerns. There has been concern that clomiphene and gonadotropins may increase the risks for ovarian and breast cancer. Most evidence to date does not indicate that ovulation-stimulating drugs increase the risks for these types of cancers. However, more research needs to be done. Some studies suggest that clomiphene, which is chemically related to the breast cancer drug tamoxifen, may actually decrease the risk for breast cancer.

Progesterone. Progesterone is a hormone that is produced by the body during the menstrual cycle. Progesterone drugs are sometimes given to women who have experienced frequent miscarriages (a possible sign of progesterone deficiency). A progesterone drug may also be given after egg retrieval during an in vitro fertilization (IVF) cycle to help thicken the uterine lining (endometrium) so it can better hold the egg following implantation.

Aromatase Inhibitors. Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many major body tissues. These drugs include anastrozole (Arimidex) and letrozole (Femara). These drugs are used for treating breast cancer and are being investigated for stimulating ovulation in infertile women. Although letrozole is not approved for treatment of infertility, it has become widely used for this purpose in recent years. Some doctors were concerned that letrozole could increase the risk of birth defects. However, a major 2006 study indicated that letrozole does not increase risk to the fetus. The study compared the rate of birth defects among babies whose mothers conceived with letrozole and those who used clomiphene (the standard first-line fertility drug). Researchers found no differences in birth outcomes between the two groups.

Tamoxifen. Tamoxifen (Nolvadex) is a drug known as a selective estrogen-receptor modulator (SERM). It is used to prevent breast cancer in high-risk women. Studies suggest that it may equal clomiphene in its ability to induce ovulation. It may be especially useful when used along with IVF for preserving fertility in breast cancer patients. This drug is less expensive than clomiphene, but it poses some health hazards, including a risk for blood clots and uterine cancer.

Glucocorticoids. Glucocorticoids are steroid hormones that are sometimes used in combination with IVF and intracytoplasmic sperm injection (ICSI). It is thought that anti-inflammatory effect of these drugs can help make the lining of the uterus more responsive to egg implantation. However, a 2007 review indicated that glucocorticoids do not help improve pregnancy success rates and should not be used routinely with assisted reproductive technologies.

Regimens to induce ovulation vary widely according to individual need. A typical procedure, involving superovulation and in vitro fertilization (IVF) may be as follows:

Doctors make sure that the patient is not pregnant or in the luteal phase of her menstrual cycle (the premenstrual period).
Injections of either human menopausal gonadtropins, which contains luteinizing hormone (LH) and follicle-stimulating hormone (FSH) or pure FSH are administered daily 2 - 4 days after day 1 of the next cycle. Either drug may be used.
After 4 - 8 days of treatment, estrogen levels are monitored. Increasing levels on the fourth day of treatment may be strong indicators of success. If estrogen levels indicate that ovaries are responding, ultrasound is then performed to detect possible overproduction of follicles. Such evaluation should then be conducted every 1 - 2 days and dosages adjusted accordingly.
Gonadotropin-releasing hormone analogs are used to prevent a premature release of LH hormone (and therefore ovulation). GnRH agonists are typically administered either early on or a few days after ovulation in the cycle previous to the one planned for IVF. This approach is referred to as the long protocol, and it serves to suppress the pituitary gland and allows time for the eggs to mature before harvesting. Other protocols using GnRH antagonists are under investigation, but to date the long protocol has the best pregnancy rates.
When at least three follicles have reached a diameter of 18 mm, human chorionic gonadotropins (hCG) is typically administered to release the egg. It is not given if there are signs of overproduction of follicles, which suggests a risk for ovarian hyperstimulation syndrome (OHS), a dangerous complication. (One study reported that giving high doses of progesterone to high-risk women the day of hCG administration may prevent OHS.)
Egg retrieval may be performed about 36 hours following hCG administration, with the transfer of the embryo (the fertilized egg) back into the woman 2 - 3 days after retrieval.
Embryos are transferred to the uterus through a small tube. This process does not require an anesthetic, although the procedure can cause cramping.

Natural (Unstimulated) In Vitro Fertilization Cycles. An alternative to superovulation for some couples is natural in vitro fertilization (IVF) cycles. It allows multiple, consecutive cycles of treatment. Natural IVF is far less expensive than standard hyperstimulation methods and avoids their risks, including multiple births and ovarian hyperstimulation syndrome (OHS).

The process involves ultrasound and hormonal monitoring starting 5 days before the estimated ovulation day.
No superovulation drugs are used, such as follicle-stimulating hormone (FSH) and human menopausal gonadtropins (hMG). The doctor, however, may administer an injection of human chorionic gonadotropins (hCG) to stimulate the luteinizing hormone (LH) surge.
The egg retrieval timing is based on detecting LH surge.
A single egg is retrieved. The procedure that follows is similar to other IVF cycles.

The basic disadvantage to this approach is that the eggs may be released before there is a chance for them to be harvested. Women report far lower stress levels with this approach, however, even though it requires more treatment cycles. In one study, the live-birth rate was 32%. Not all women are appropriate candidates, however. Women should have regular menstrual cycles and infertility of unknown cause or associated with problems in the fallopian tubes. Pregnancy rates are still very low in older women.

Clomiphene. Another gentler alternative to superovulation is the use of clomiphene before IVF, which works slightly better than unstimulated IVF.

Assisted Reproductive Technologies

Assisted reproductive technologies (ART) are medical techniques that help couples conceive. These procedures involve either:

A couple’s own eggs or sperm
Donor eggs, sperm, or embryos

Fertilization may occur either in the laboratory or in the uterus. In the U.S., the number of live birth deliveries from ART increased by 128% between 1996 and 2002. More than 45,000 babies are now born in the U.S. each year using assisted reproductive technologies.

ART includes fertility drug treatments, artificial insemination (AI), in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and other procedures.

Artificial insemination (AI) is the least complex of the assisted reproductive technologies and is often tried first in uncomplicated cases of infertility. AI either involves placing the sperm directly in the cervix (called intracervical insemination) or into the uterus (called intrauterine insemination, or IUI). IUI is the standard AI procedure.

It is useful under the following circumstances:

When the woman's cervical mucus is unreceptive
When donor sperm are required
If the man's sperm count is very low
When unexplained infertility exists in both partners

Those in whom AI fails, couples with specific fertility defects, or older women may be candidates for more advanced reproductive technologies.

Pregnancy Rates. A review of 45 studies reported that in unexplained infertility cases, the per-cycle pregnancy rates were 4% for intrauterine insemination (IUI) alone and 8 - 17% per cycle for IUI combined with superovulation, a procedure that uses fertility drugs to bolster egg recovery.

Researchers in one study suggested IUI as a reasonable first option for many women under age 43. It is less expensive and poses less risk for multiple births than the more advanced assisted reproductive technologies (ART), such as in vitro fertilization. Although IVF procedures are more effective per cycle, couples tend to be able to afford more IUI cycles, so the pregnancy rates over time are very similar.

The Artificial Insemination Procedure. The AI procedure is as follows:

A woman usually (but not always) takes fertility drugs in advance.
The man must produce sperm at the time the woman is ovulating.
The sperm are subjected to certain so-called "washing" procedures. They are then inserted into the uterine cavity through a long, thin catheter.

The administration of fertility drugs and sperm retrieval is timed so that the process can coincide with ovulation.

About 71% of assisted reproductive technologies (ART) procedures now use in vitro fertilization (IVF) with the woman's own eggs. An in vitro procedure is one that is performed in the laboratory. Advances in these procedures have dramatically increased the rate of live births.

The best candidates for IVF are women with damaged fallopian tubes, and some experts believe it is a better option than attempting surgical repair. IVF is also used when infertility is unexplained or when the male partner has the infertility problem. A typical IVF procedure is as follows:

The doctor first induces superovulation using fertility drugs so that several eggs can be harvested from the ovary before they have been released from the follicles. Higher doses of fertility drugs for subsequent cycles do not appear to add any advantage in women who have a poor response the first time.
To harvest eggs, the doctor generally inserts a probe into the vagina and is guided by ultrasound. A needle is then used to drain the liquid from the follicles, and several eggs are retrieved.
The eggs and sperm are combined in a Petri dish. Between 48 - 72 hours later the eggs are usually fertilized.
The resulting embryos (the first stage toward the development of the fetus) are reimplanted into the woman's uterus.
It takes about 2 weeks to determine if the process is successful.

IVF success rates for the first three cycles of treatment are about equal. They then decline modestly for the fourth cycle and drop significantly after the fifth cycle.

Gamete/Zygote Intrafallopian Transfer. Gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT) are adaptations of IVF. GIFT and ZIFT are used in unexplained female infertility and in mild male infertility. The success rates are similar to those of IVF, but a woman must have at least one functioning fallopian tube.

GIFT: The procedure is as follows:

The eggs are harvested as in IVF.
They are mixed with the sperm but not actively fertilized.
They are immediately injected back into the woman. Laparoscopy, a technique that employs a miniature viewing device, is used with this procedure to guide the placement of the embryos or egg through a long, thin catheter into the fallopian tubes.
The sperm and egg are placed exactly where they would be in natural fertilization.

ZIFT: The procedure is as follows.

The eggs are harvested as in IVF.
They are then mixed with the sperm and, in this case, are fertilized in the laboratory.
They are then implanted in the fallopian tubes as in GIFT. (The advantage of this procedure over GIFT is that the doctor and couple are assured that fertilization has taken place, and the eggs can be examined for defects before implantation.)

In 2002, more than 45,000 American babies were born using in vitro fertilization (IVF). Success rates have increased in all age groups (although they are still considerably lower in older than in younger women). Chances for assisted reproductive technologies (ART) success are also greater among women who do not have uterine abnormalities and have had previous successful pregnancies.

Success rates are also higher or lower depending on whether the woman uses her own eggs or whether they are donated and also whether the eggs are fresh or frozen. The highest live birth rates are with donated fresh eggs (an average of 50% per transfer). The lowest rates are when a woman uses her own frozen eggs (an average of 29% per transfer). However, using frozen eggs is less expensive than fresh eggs, so a couple may be able to afford more cycles with frozen eggs.

Use of Donor Eggs. Older women are more likely to use donor eggs. In a 2002 study, success rates were the same for women who used donors with an age range of 20 - 40. There were also no differences in delivery rates for recipients up to age 45. Women over 45, however, increasingly had problems with implantation, pregnancy, and delivery.

Use of Frozen Eggs. Frozen eggs tend to have lower success rates because of toxins released by cells damaged in the freezing and thawing tissues.

Intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology used for couples when male infertility is the main problem. It involves injecting a single sperm into an egg obtained from in vitro fertilization (IVF). The procedure is very simple:

A tiny glass tube (called a holding pipet) stabilizes the egg.
A second glass tube (called the injection pipet) is used to penetrate the egg's membrane and deposit a single sperm into the egg.
The egg is released into a drop of cultured medium.
If fertilized, the egg is allowed to develop for 1 - 2 days, then it is either frozen or implanted.

The greatest concern with this procedure has been whether it increases the risk for birth defects. However, several studies have reported no higher risks of birth defects in children born using ICSI procedures. While some studies have shown a higher number of birth defects in children conceived with ICSI, experts think that this may have more to do with the genetic background of the parents than ICSI itself. Recent research suggests that ICSI children develop normally. A 2006 study of 8-year-old children conceived with ICSI found no important differences between these children and children who were conceived naturally.

A 2007 study in the New England Journal of Medicine indicated that ICSI use has increased 5-fold over the past decade, even though the proportion of men receiving treatment for male infertility has remained the same. In 1995, 11% of IVF cycles used ICSI. By 2004, 57.5% of IVF cycles used ICSI. Doctors caution that while ICSI is an important assisted reproductive technology for male infertility, it may be overused. Some doctors recommend ICSI for women who have failed prior IVF attempts or who have few or poor-quality eggs, even if their male partners have normal semen measurements. There is little evidence that ICSI helps improve pregnancy success for couples who do not have a problem with male factor infertility, according to the Society for Assisted Reproductive Technology.

In Vitro Maturation. A technique called in vitro maturation allows fertilization without the use of fertility drugs. In this process, follicles are harvested a few days before ovulation. In such cases, up to 50 have already begun to mature. At this time, about 15 of these maturing follicles can be removed, out of which 2 or 3 can produce healthy embryos.

Blastocyst Transfer. Blastocyst transfer is very promising. Instead of implanting the standard 2- or 3-day-old embryos in the uterus, the procedure implants blastocysts, which are more complex, 5-day-old embryos. Fewer blastocysts than embryos need to be implanted, reducing the risk for multiple births. (There is, however, a higher risk for identical twins compared to other procedures.) Offspring may be more likely to be males than females. Pregnancy rates are about 36% with a first attempt but then drop significantly. The procedure is more likely to be successful in younger than older women.

Ooplasmic Transfer. Ooplasmic transfer is a controversial experimental procedure that uses the woman's own egg and a female donor's egg and the male sperm for fertilization. Genetic material from the donor's egg plus the sperm are added to the woman's own egg. This has been successful in a few cases, but studies are very early and long-term effects are unknown. Research on this and similar procedures is currently conducted outside the U.S.

Complications of Assisted Reproductive Technologies

Since assisted reproductive technology (ART) procedures have become more widespread since 1980, multiple births have significantly increased. About 35% of all ART births are multiple ones, with 4.3% being triplets or more. Multiple births increase the risk of complications, for both the mother and the child.

Assisted reproductive technology (ART), and multiple births, increase the risks for pregnancy complications. According to a 2005 study, the type of complications may depend on the infertility treatment:

Fertility drugs. Increase risks of the placenta becoming detached from the uterus (“placental abruption”), third trimester miscarriage, and gestational diabetes.
In vitro fertilization. Increase risks of placental abruption, the placenta developing in the lower section of the uterus (“placenta previa”), dangerously high blood pressure during pregnancy (“pre-eclampsia”), and Caesarean sections.

Multiple births can also increase the risk of pregnancy death. A 2006 study indicated that women who carry multiple fetuses have a 3.6 times greater risk of dying from pregnancy complications than women with singleton pregnancies. The leading causes of death were blood clot (embolism), high blood pressure complications, excessive bleeding (hemorrhage), and infections.

The main risks for children conceived with assisted reproductive technology (ART) are complications associated with pregnancy problems and multiple births. Children conceived with ART are more likely to be born premature and to have extremely low birth weight. These conditions increase the risk for heart and lung problems, as well as learning and developmental disabilities. Premature delivery is also associated with cerebral palsy, a brain injury condition that affects muscle coordination. A 2006 study indicated that children born after in vitro fertilization have an increased risk for cerebral palsy.

However, studies suggest that ART does not increase the risk for chromosomal damage or other major birth defects. Couples undergoing ART may have other factors, such as older age or genetic predispositions, which make complications more likely. Infertility itself, even without ART, can pose a risk factor for birth defects. Children conceived naturally by couples with infertility problems tended to have more disorders of the nervous system, digestive system, and musculoskeletal system than children born to fertile couples, according to a 2006 study in the British Medical Journal. Children born to couples treated for infertility with ART may also have a slightly increased risk for these problems, as well as genital organ malformations, but the overall risk for birth defects appears to be very small.

ART remains a good option for many infertile couples. The likelihood of having a healthy single child of normal birth weight using ART is about 94%. The likelihood of having a child free of major birth defects is about 91%. Frozen eggs do not appear to pose any higher risk for developmental problems.

Preimplantation genetic diagnosis (PGD) is now available in some fertility centers. It can help identify genetic defects in the offspring and may help parents determine future problems. Such testing, however, also raises significant emotional issues that should be addressed beforehand.

Given the hazards of multiple births, parents must make some hard decisions if the treatment produces multiple embryos. The choices are limited:

Carry all of them to term, which increases health risks for both the mother and the developing fetuses
Complete abortion
Embryo reduction, in which the doctor removes one or more embryos (possibly endangering the remaining embryos)

At this time, the best approach is to limit the number of implanted embryos in the first place. Researchers are attempting to develop methods to reduce the risk for multiple births:

Most centers now implant two to three embryos at a time, and the remainder can be frozen for future use. (Frozen eggs do not appear to pose a risk for developmental problems in children conceived using them.) This limits the chance for success, but implanting more than three embryos only increases success rates very slightly, whereas the risk for multiple births increases significantly.
Reducing the dosage of fertility drugs also reduces the risk for multiple births, but not significantly, and it also reduces the chance for successful outcome.
Blastocyst transfer may help reduce the chances for multiple births.

Resources

www.resolve.org -- National Infertility Association
www.asrm.org -- American Society for Reproductive Medicine
www.theafa.org -- American Fertility Association
www.endometriosisassn.org -- The Endometriosis Association
www.acog.org -- American College of Obstetricians and Gynecologists
www.endo-society.org -- The Endocrine Society
www.aace.com -- American Association of Clinical Endocrinologists
www.cdc.gov/reproductivehealth/index.htm -- Centers for Disease Control: Assisted Reproductive Technology Reports

References

Boomsma CM, Keay SD, Macklon NS. Peri-implantation glucocorticoid administration for assisted reproductive technology cycles. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD005996.

Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Iron intake and risk of ovulatory infertility. Obstet Gynecol. 2006 Nov;108(5):1145-52.

Dieterle S, Ying G, Hatzmann W, Neuer A. Effect of acupuncture on the outcome of in vitro fertilization and intracytoplasmic sperm injection: a randomized, prospective, controlled clinical study. Fertil Steril. 2006 May;85(5):1347-51.

Hvidtjorn D, Grove J, Schendel DE, Vaeth M, Ernst E, Nielsen LF, et al. Cerebral palsy among children born after in vitro fertilization: the role of preterm delivery--a population-based, cohort study. Pediatrics. 2006 Aug;118(2):475-82.

Jain T, Gupta RS. Trends in the use of intracytoplasmic sperm injection in the United States. N Engl J Med. 2007 Jul 19;357(3):251-7.

Jensen A, Sharif H, Svare EI, Frederiksen K, Kjaer SK. Risk of breast cancer after exposure to fertility drugs: results from a large Danish cohort study. Cancer Epidemiol Biomarkers Prev. 2007 Jul;16(7):1400-7. Epub 2007 Jun 21.

Lee SJ, Schover LR, Partridge AH, Patrizio P, Wallace WH, Hagerty K, et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J Clin Oncol. 2006 Jun 20;24(18):2917-31.

Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA, et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007 Feb 8;356(6):551-66.

Mackay AP, Berg CJ, King JC, Duran C, Chang J. Pregnancy-Related Mortality Among Women With Multifetal Pregnancies. Obstet Gynecol. 2006 Mar;107(3):563-568.

Ombelet W, Martens G, De Sutter P, Gerris J, Bosmans E, Ruyssinck G, et al. Perinatal outcome of 12,021 singleton and 3108 twin births after non-IVF-assisted reproduction: a cohort study. Hum Reprod. 2006 Apr;21(4):1025-32.

Sallam HN, Garcia-Velasco JA, Dias S, Arici A. Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD004635.

Shevell T, Malone FD, Vidaver J, Porter TF, Luthy DA, Comstock CH, et al. Assisted reproductive technology and pregnancy outcome. Obstet Gynecol. 2005 Nov;106(5 Pt 1):1039-45.

Smith C, Coyle M, Norman RJ. Influence of acupuncture stimulation on pregnancy rates for women undergoing embryo transfer. Fertil Steril. 2006 May;85(5):1352-8.

Terry KL, Willett WC, Rich-Edwards JW, Michels KB. A prospective study of infertility due to ovulatory disorders, ovulation induction, and incidence of breast cancer. Arch Intern Med. 2006 Dec 11-25;166(22):2484-9.

Tulandi T, Martin J, Al-Fadhli R, Kabli N, Forman R, Hitkari J, et al. Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil Steril. 2006 Jun;85(6):1761-5.

Westergaard LG, Mao Q, Krogslund M, Sandrini S, Lenz S, Grinsted J. Acupuncture on the day of embryo transfer significantly improves the reproductive outcome in infertile women: a prospective, randomized trial. Fertil Steril. 2006 May;85(5):1341-6.

Zhu JL, Basso O, Obel C, Bille C, Olsen J. Infertility, infertility treatment, and congenital malformations: Danish national birth cohort. BMJ. 2006 Sep 30;333(7570):679. Epub 2006 Aug 7.

Review Date:
10/29/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

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'Til TiVo Do You Part: Tech Decisions Newlyweds Must Make

GeekSugar — Wed, 17 Jun 2009 10:30:16 -0700

The honeymoon phase should be sweet and lovely - but beware that it may not take much to disrupt your blissful state, be it a spate of heartbreaking movies or even your iPhone, cell phone bill, etc. Don't let technology be the thing that lands you on the couch at couples' counseling - figure out these issues for after you say "I do."
Bauer-Griffin Online

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Genetic Counseling

FitSugar — Wed, 08 Oct 2008 17:34:50 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Genetic Counseling

Modern genetics allows us to understand how genetic diseases are inherited based on DNA, genes, and chromosomes. We can now test couples and fetuses for certain inherited disorders, as well as other chromosomal and genetic abnormalities such as neural tube defects, Down syndrome, and cystic fibrosis.

Couples who are thinking about having a child may consider genetic counseling and prenatal diagnosis before conception to predict any possible abnormalities in their child. Others may use the tests after they conceive to evaluate the condition of the fetus.

People who are at increased risk of passing genetic abnormalities on to their children include:

Jews of Eastern European descent, who may have a high risk of having children with Tay-Sachs or Canavan’s, metabolic disorders that lead to death in early childhood.
African-Americans, who may risk passing on sickle-cell anemia to their children.
Couples of Southeast Asian or Mediterranean origin, who are at increased risk of having children with thalassemia, a severe form of anemia.
People with family histories of inherited disorders, or those who have previously had children with genetic disorders.
Women who were exposed to toxins that could cause birth defects.
Women with prior medical conditions or diseases that may affect their fetus, such as diabetes.
Couples who share a common ancestor.
Women with a history of multiple miscarriages.
Couples who have family members with birth defects or severe developmental problems.

Prenatal testing for genetic problems may be done before or after conception. Testing for spina bifida or Down syndrome is done after a pregnancy is established. Besides the couples listed above, counseling and diagnosis are also recommended for mothers over the age of 35, and those who have received abnormal alpha-fetoprotein test results. For more information about the alpha-fetoprotein test, and when and why you might have it, see alpha-fetoprotein.

For those who may be at risk, genetic counseling and prenatal diagnosis are used to help answer some important questions, such as:

Should we have a baby? Are the chances of having a baby with a genetic defect so high that choosing adoption or artificial insemination may be a better way to start a family?
How can we treat the fetus' potential defects? Are there surgical techniques available or other medical interventions that may help alleviate problems?
How do we prepare, physically and psychologically, for the possible outcome of a pregnancy? Are there special educational classes, training, or information that we need in order to raise a child with defects?
Should we continue the pregnancy? Are the fetus' abnormalities so severe that we might choose to have an abortion?

It is important to remember that preconception testing can only give you the odds of having a child with a certain birth defect; a genetic counselor maps out the specific numbers. You may learn, for example, that you have a one in four chance of having a child with a certain disorder. If you decide to conceive, the fetus may be able to undergo prenatal testing to show whether or not the baby has inherited the disorder.

How Can I Prepare?

You may wish to discuss genetic counseling with your family, as well as your health care provider, who may refer you to a genetic counselor specially trained to understand the complex issues surrounding heredity and pregnancy. Find out if any medical problems run in your family, especially any problems with child development, miscarriages, stillbirths, or severe childhood illnesses. If you decide to get the blood-screening test, make sure your health care provider talks to you beforehand and answers any of your questions.

What Will Happen?

You will be required to fill out an in-depth family history, and discuss your family's medical past with the counselor. You and your partner may also take simple blood tests, or undergo an analysis of your chromosomes known as karyotyping. All this information will be considered together to help determine what genetic patterns you may pass on to your children. If you choose to be tested after conception, one of the following tests will be used to obtain fetal cells whose genetic and chemical makeup can be analyzed in a laboratory:

Amniocentesis, in which fluid is withdrawn from the amniotic sac and analyzed. See amniocentesis for more information.
Chorionic villus sampling (CVS), which takes a sampling of the cells of the placenta. See CVS for more information.
Percutaneous umbilical blood sampling (PUBS), which draws fetal blood from the umbilical cord. See PUBS for more information.

What Are The Risks?

The tests used for genetic counseling have virtually no risks. The tests used after conception, however, may cause infection, damage to the fetus, or miscarriage. For further information, see the articles on amniocentesis, CVS, and PUBS.

Frequently Asked Questions

Q: If I am in a risk group, do I have to get tested?

A: No. It is up to you whether or not to undergo genetic counseling and prenatal testing. Your religious or philosophical beliefs, family circumstances, and personal desires all are a part of the decision-making process.

Q: If I discover I am a carrier of a certain disease, will I still be allowed to have a baby?

A: Absolutely. The point of genetic counseling and prenatal diagnosis is simply to provide parents with information that they need to make important decisions. A good genetic counselor will help you figure out how to use the information you discover, but will not make any decisions for you. If you are at risk of having a baby with a disorder, you may be able to use assisted reproductive technologies to reduce the chance that your baby will be affected.

Review Date:
2/19/2007
Reviewed By:
Douglas A. Levine, MD, Gynecology Service, Memorial Sloan-Kettering Cancer Center, New York, NY. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

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Pregnancy Center Links

Katie Keeps It Local While Peter Celebrates Bollywood in China

PopSugarUK — Fri, 12 Jun 2009 03:00:00 -0700

Katie Price and Peter Andre were on opposite sides of the world yesterday, as it was revealed that they tried marriage counselling in a bid to save their relationship. Kate, who has bought a new horse, was in London, wearing a cheeky t shirt for a meeting and then changing into an animal print dress for a night out at Nobu, never missing an opportunity for self-promotion. Meanwhile, Peter was in China for the International Indian Film Academy Awards. Known as the Bollywood Oscars, Peter will present an award at the ceremony and joked about moving in to Indian cinema. He spoke about how he's coping with the split, saying:

"The past four weeks have been the worst of my life. It was hell. No matter what happens, you never stop loving someone. Initially I couldn’t even have thought about work – my head was everywhere. It still is everywhere. But it’s been a month now and I know I’ve got to start pulling myself together. The response I’ve had since being in China has been absolutely amazing. This, and the work I am doing now, is beginning to give me confidence again. Singing has given me something to focus on. I never expected the attention I’ve been getting and I am so glad this is happening. I’ve only been here a couple of days but it’s already turned out better than I ever hoped. Finally, I am beginning to smile again. It’s not like I’m a bundle of joy now, but it’s getting better. I’m even cracking terrible jokes!"

It's good to see Kate and Peter focusing on their passions to help deal with their separation.

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Vasectomy and vasovasostomy

FitSugar — Wed, 08 Oct 2008 17:35:49 -0700

In This Report

Highlights
Introduction
Considerations
Male Contraception
Surgery
Complications
Unexpected Pregnancy
Long-Term Complications
Reversal Surgery
Assisted Reproductive Techn...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Search Continues for the "Male Pill"

Research is progressing on a male contraceptive, but there have also been setbacks. The drug miglustat (Zavesca), which is used to treat a rare condition called Gaucher's disease, had shown success in animal studies but failed to work in a clinical trial, according to results published in 2007 in Human Reproduction. Researchers are now investigating an experimental drug, Adjudin (AF-2364), which disrupts sperm production.

Reversible Inhibition of Sperm Under Guidance

Reversible inhibition of sperm under guidance (RISUG) is one of the investigational male contraceptives furthest along in clinical trials. It is currently in phase III trials in India, but it is not yet known when or if clinical trials will be conducted in the United States. RISUG is a non-hormonal contraceptive method that uses an injectable polymer gel to stop sperm flow within the vas deferens.

No-Scalpel Vasectomy

The no-scalpel vasectomy is gaining in popularity as an alternative to standard vasectomy, but it requires a well-trained doctor to perform it. Performed correctly by an experienced doctor, no-scalpel vasectomy can result in shorter surgical time and less bleeding, infection, pain, and postoperative complications, according to a 2007 review published in the Cochrane Database. If you are considering a no-scalpel vasectomy, make sure that your doctor has performed at least 15 - 20 of these procedures.

Vasectomy Reversal

Vasectomy reversal may work better than assisted reproductive technologies (such as sperm retrieval) for men who have had a vasectomy but later decide to have children, according to research presented at the 2007 annual meeting of the American Urological Association.

Introduction

In the United States, vasectomy emerged as a popular method of permanent contraception during the 1960s. Within a decade, 750,000 men were undergoing vasectomies each year. Vasectomy rates markedly declined in the 1990s and have now plateaued at about 500,000 a year. Worldwide, an estimated 42 million couples use vasectomy as a method of birth control.

The procedure works by surgically interrupting the route that the sperm take from the testicles (where they are produced) to the penis. After vasectomy, the testicles still continue to generate sperm, but their movement is blocked at the site of the vasectomy. Eventually the sperm die, and the patient's body absorbs them. During sex, semen is produced in the same amount as before vasectomy, but this fluid does not contain sperm.

The testes are where sperm are manufactured in the scrotum. The epididymis is a tortuously coiled structure topping the testis, and it receives immature sperm from the testis and stores it several days. When ejaculation occurs, sperm is forcefully expelled from the tail of the epididymis into the deferent duct. Sperm then travels through the deferent duct through up the spermatic cord into the pelvic cavity, over the ureter to the prostate behind the bladder. Here, the vas deferens joins with the seminal vesicle to form the ejaculatory duct, which passes through the prostate and empties into the urethra. When ejaculation occurs, rhythmic muscle movements propel the sperm forward.

Click the icon to see an animation about vasectomy.

Vasectomy should not be confused with castration. It has no noticeable impact on a man's ability to perform sexually, or on his sensation of orgasm and pleasure. It does not affect the balance of male hormones, male sex characteristics, or sex drive. Testosterone continues to be produced in the testes and delivered into the bloodstream. Sperm form a very small portion of semen, so patients notice no difference in the amount of semen produced during orgasm.

The male reproductive tract performs three functions:

It enables a man to produce offspring.
It provides him with a supply of male hormones.
It enables him to experience sexual pleasure.

The Traveling Sperm. The sperm's journey through the male body -- from the testes (the testicles) to the final stage (the orgasm) -- is long and complex:

Sperm are produced in the testes at a rate of 50,000 an hour within tiny ducts called seminiferous tubules.
Sperm do not mature in the testes. They must first pass into the epididymis, a C-shaped storage chamber adjoining the testes composed of a 20-foot coiled tube. The sperms' journey through the epididymis takes about 2 - 3 weeks. They are held here until sexual activity forces them to move on.
When a man experiences sexual excitement, nerves stimulate the muscles in the epididymis to contract. This forces the sperm to pass into one of two rigid and wire-like muscular channels, called the vasa deferentia. (A single channel is called a vas deferens. It is the vas deferens that is cut during vasectomy.)
Muscle contractions in the vas deferens from sexual activity propel the sperm along past the seminal vesicles, which are clusters of tissue that contribute fluid, called seminal fluid, to the sperm. The vas deferens also collects fluid from the nearby prostate gland. This mixture of various fluids and sperm is the semen.
Each vas deferens then joins together to form the ejaculatory duct. This duct, which now contains the sperm-containing semen, passes down through the urethra. (The urethra is the same channel in the penis through which a man urinates. During orgasm, however, the prostate closes off the bladder so urine cannot enter the urethra.)
The semen is forced through the urethra during ejaculation, the final stage of orgasm when the sperm is literally thrown out of the penis.

Click the icon to see an image of sperm.

Considerations

Having a vasectomy is a serious decision. The surgery is intended to be permanent. The great majority of men who seek a vasectomy have been married for 10 years or more. Not all are good candidates, however. It is important that both the woman and the man completely agree that they no longer want to have children. They should also agree that permanent birth control is the right decision for them. Ideally, the couple should view the operation as a mutual commitment to an already successful marriage or relationship. Vasectomy generally is not a good idea if the couple's relationship is under great stress. It is not a cure for emotional or sexual problems between a man and woman.

After deciding that permanent birth control is the best solution, a couple still has the option of either vasectomy for the male or tubal ligation for the female.

Studies indicate that 5 -11% of men who have vasectomies regret the decision. In one study, 56% of men seeking treatment for fertility were hoping to reverse their vasectomies. Thirty years ago, this percentage was only 5%.

A reversal procedure called vasovasostomy is available, but it is a major operation that provides no guarantee of restored fertility. In a study of procedures performed between 1980 - 1996, vasectomy rates had leveled off but vasovasostomy rates had increased in men by nearly 70% in the most recent 5-year period compared to the earliest 5-year period.

Vasectomies may be right for:

Men in relationships in which both partners agree they have all the children they want and both do not want to use or are unable to use other methods of contraception
Men in relationships whose partners have health problems that make pregnancy unsafe
Men in relationships in which one or both have genetic disorders that they do not want to transmit

Vasectomies may not be right for:

Men in relationships in which one partner is unsure about his or her desire to have children in the future. (Couples in which the woman is working when they make the decision are at particular risk for regretting the decision later on.)
Men whose current relationships are unstable, going through a stressful phase, or are marked by substantial conflict
Men who are considering the operation just to please their partners
Men who are counting on having children later by storing sperm or by surgical reversal of the vasectomy
Young men, who still have many life changes ahead
Men who are single (including those divorced or separated) at the time of vasectomy
Men who are having the operation primarily for the sake of their partners and not wholly for their own reasons
Men or couples whose only motive is freedom from distraction imposed by other contraceptive methods during sexual activity

Vasectomy should not be undertaken in response to temporary stressful situations that might block the desire for children. Such conditions may include illness, temporary financial crisis, death in the family, or birth of a child. Couples should wait through such short-term stresses or seek counseling or psychotherapy to be sure that they are not making a decision they will later regret.

All Future Scenarios. Before deciding on a vasectomy, the couple should consider all future scenarios for their life together, such as the following examples:

If a couple already has children, how would they feel about a vasectomy if one of their children died?
If financial stress is triggering the decision for a vasectomy, would improved affluence increase their desire for children?
How would the man consider the vasectomy if his current relationship ended, either by divorce or the woman's death?

The word "sterilization" has a deep emotional connotation for many people. Even though a couple may rationally accept the idea of a vasectomy, it is extremely important for each partner to be as open as possible about any negative feelings they might associate with the procedure. Such feelings on the part of either partner can have devastating consequences on a relationship if they surface only after the procedure has been performed. Openness with each other is essential in order to make a decision that is clear of any hidden apprehensions. Neither partner should be too embarrassed to request counseling if the emotional aspects involved in making the decision are too difficult to solve between themselves.

What the man may be feeling:

A man may have a poor self image, including concerns for his own physical health or sexual ability. Such men are likely to have a difficult time adjusting psychologically to vasectomy.
A man may not actually really want the procedure but may not want to confront a partner he loves who wants him to have it.

What the woman may be feeling:

A woman might believe, incorrectly, that a vasectomy is emasculating, but she might not want to express this idea to her partner.
On the other hand, some women fear that vasectomy may make their partner more attractive and encourage outside affairs. (Research from the 1970s indicates that married men who have a vasectomy are no more likely to indulge in extramarital sex than fertile men.)

Storing frozen sperm in a sperm bank before vasectomy might enable men to have children later. Before the vasectomy, the man collects sperm, which are frozen and stored until he wants to have a child. In one study, 1.5% of men who had stored sperm later used it for conception and most were successful. Other studies have shown a lower success rate, however, and it is a very expensive process. Experts believe that a man who wants to bank sperm should probably reconsider his decision to have a vasectomy because such a concern may indicate doubts about giving up his ability to father a child.

Male Contraception

As many as 40% of couples seeking vasectomy have experienced a failure with their previous method of nonpermanent birth control. Such failures can occur from misplacement of a diaphragm, an incorrectly implanted intrauterine device (IUD), or noncompliance with an oral contraception regimen. Couples who are unsure about permanent sterility should still consider carefully all birth control options.

Withdrawal before ejaculation is a form of natural contraception, but it is extremely risky and most people find it unsatisfactory. If used on a regular basis, the average risk for pregnancy is 24%.

The only other form of male contraception currently available is the condom. However, the average rate of pregnancy for couples that rely only on condoms for protection is still 12%. In adolescents, the risk with condoms is even higher, 18%. Even for those who use a good-quality condom correctly, the annual risk for pregnancy is 3%.

The condom should be put on before intercourse when the penis is erect, long before ejaculation, since the male can discharge sufficient semen to cause pregnancy before ejaculation occurs. (Even after a vasectomy, men who are not in a monogamous relationship with an HIV-negative partner should always wear a condom during sex for protection against sexually transmitted diseases. Vasectomy is not protective.)

Click the icon to see an illustrated series detailing how to apply a condom.

Condom Materials.

Latex. Condoms made of latex rubber are the most common types. When they are contoured for better fit and contain a spermicide, they can provide fairly effective protection. Some people are allergic to latex, however, and in some cases the reaction can be very dangerous. The latex smell may also be unpleasant for some people.
Polyurethane. Polyurethane condoms (Avanti, eZ-on) are also available. At this point, they have good acceptance by couples but have a higher breakage rate (6 - 7.2%) compared to the latex condom (1.1 - 2%). Other synthetic materials are under investigation.
Animal Membranes. Condoms made from animal membrane can prevent pregnancy, but sexually transmitted infections can permeate them.
Lubricants. Lubricants can be used to prevent tearing. Petroleum-based products (such as Vaseline and baby oil) and vegetable oils should not be used because they can corrode the condom.

Spermicides. Some condoms come prelubricated with sperm-killing substances called spermicides. The standard active ingredient in spermicides in the U.S. is nonoxynol-9, which attacks the surface of the sperm cell. These spermicidal-coated condoms, however, are no longer recommended for a number of reasons. Side effects include irritation of the vagina or penis, particularly if used often or in large amounts. It can also promote yeast and urinary tract infections in women. Evidence now strongly suggests that nonoxynol-9 does not provide any additional protection against sexually-transmitted diseases. In fact, research indicates that it actually increases the risk for HIV in women, possibly by causing injury in the vaginal area. Spermicides are no longer recommended for use with male condoms.

Researchers are developing male hormonal contraceptives that reduce levels of sperm. Animal studies and clinical trials are progressing, and a "male pill" may become a reality in the not-so-distant future. Current trials are focusing on male hormonal contraceptives that combine testosterone (the primary male sex hormone) with progestin, a synthetic form of progesterone (one of the primary female sex hormones).

Testosterone suppresses levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH). LH and FSH are hormones that stimulate ovulation in women and production of testosterone in men. Low levels of these hormones interfere with sperm production, but they do not completely stop it. For this reason, researchers are investigating combining testosterone with progestin. The addition of progestin further decreases LH and FSH levels, along with sperm counts. Researchers are also investigating combining testosterone with gonadotropin-releasing hormone (GnRH), another type of hormone that interferes with LH and FSH secretion.

Most of the male contraceptives currently in late-stage clinical trials deliver hormones through implant, injection, or both. The implant is surgically placed under the skin where it releases a steady stream of the hormone. The injection is given once every several months. Some of the investigational male hormonal contraceptives use a testosterone implant with progestin injections, while others use a progestin implant with testosterone injections. Forms taken by mouth are also being investigated. It generally takes around 3 - 4 months for the treatment to take effect, and for sperm production to be reduced. Research indicates that the male hormonal contraceptives are easily reversible. A 2006 study in the Lancet reported men regained their full fertility within 3 - 4 months after stopping hormonal treatment.

Side effects of male hormonal contraceptives include weight gain, acne, and changes in mood. These side effects are typical of hormone-based therapies.

Because of hormonal side effects, researchers are also investigating non-hormonal male contraceptives. Several initially promising drugs (such as miglustat) have performed well in animal studies, but have failed in human studies. Some non-hormonal research is now focusing on an experimental drug called Adjudin, which appears to work by disrupting sperm maturation in the testes. A 2006 animal study showed positive results, but it is still unknown if this drug will work in humans.

Researchers are investigating procedures that block sperm flow in the vas deferens using various drugs or materials that are reversible. One promising method is called Reversible Inhibition of Sperm Under Guidance (RISUG). RISUG is a non-hormonal contraceptive that uses a polymer gel. The gel is injected into the vas deferens, where it coats the vas deferens' inner walls and kills sperm. The gel can be injected through the skin through a needle or by using the no-scalpel vasectomy technique of making a tiny hole in the skin. The procedure takes around 10 - 15 minutes to perform, and men can resume sexual activity within a week.

The effects of RISUG are long-lasting. Studies indicate that a single injection can provide contraceptive effect for 10 years or more. It is also easily reversible. When a man wishes to discontinue the contraceptive, the gel is removed by flushing the vas deferens with a solvent. The major side effect so far has been a temporary swelling of the scrotum following the injection.

RISUG is mostly being investigated in human trials in India. American researchers are also interested in investigating RISUG, but animal studies need to be conducted first. It will be several years before any human trials are started in the U.S.

The intra vas device (IVD) is an investigational non-hormonal contraceptive that uses tiny silicone plugs to block sperm from traveling through the vas deferens. The plugs are surgically inserted into the vas using the no-scalpel vasectomy procedure. In 2006, the Food and Drug Administration granted approval to expand human trials of the IVD in several U.S. cities.

Unlike hormonal contraceptives, the IVD does not cause side effects like weight gain and acne. But researchers are still figuring out how to make this contraceptive method reversible.

Gossypol, a yellow pigment extracted from the roots, seeds, and stems of the cotton plant, has been used in China, Africa, and Brazil as a male contraceptive. Cotton root was also used as folk medicine in the American South to treat menstrual pain and to induce abortions. The chemical destroys the lining of tubules in the testicles where sperm are produced, thereby inhibiting their formation.

Gossypol does not appear to reduce sexual desire or frequency of intercourse. In about 20% of men, sperm production does not come back, so it should be considered as potentially permanent birth control. It also may not be effective in some men, since small numbers of sperm may survive. Researchers are investigating gossypol-derived compounds that may have less toxicity. No one should take any so-called natural gossypol product without consulting their doctors.

Surgery

Vasectomy is a minor operation that takes about 30 minutes and is usually performed in a doctor's office or a family planning clinic. If the operation is performed under local anesthesia, the cost ranges from about $500 - $1,000. Most insurance policies will cover vasectomies performed as a minor outpatient procedure, but will not cover vasectomies performed as major surgery in an operating room. If a Vasclip procedure is performed, there may be an additional cost of $400 - $500 for this device.

The Procedure.

To prevent increased risk of bleeding, patients should avoid taking aspirin or NSAIDs (Advil, Motrin) for 10 days prior to the procedure.
Before the operation, the patient's scrotum is shaved and cleaned.
A local anesthetic is injected into the scrotum. Patients should ask their doctor about applying an anesthetic cream (EMLA) before the injection to reduce its pain.
The surgeon makes a tiny incision on one side of the scrotum and locates one vas deferens. The vas deferens is isolated, drawn through the incision, and clamped at two sites close to each other.
The segment between the clamps (which should be more than 15 mm, or a little over 1/2 inch) is then removed.
The surgeon then seals off (ligates) the tube with surgical clips, sutures, or cauterization with an electric needle. Fascial interposition is an additional technique that may be used in combination with these methods to improve closure. With fascial interposition, the surgeon pulls the fibrous layer covering the vas (the fascia) over the cut end of the vas and sews it closed. This increases the barrier and further reduces residual sperm. Recent research suggests that fascial interposition combined with cauterization or ligation/excision is the best method for sealing off the vas.
The surgeon may choose to close off either one end of the vas (called an open-ended procedure) or both ends (closed-ended technique). In the open-ended procedure, the vas section connected to the testis is left open, and the one leading to the prostate is sealed. In the closed-ended approach, both are sealed. Many surgeons now prefer the open-ended version because it has lower complication and failure rates than the closed-ended method, and it results in fewer cases of chronic pain.
After closing off the tube, the vas deferens is gently placed back into the scrotum.
The procedure is then repeated on the other side.
After a short rest, usually about half an hour, the patient can leave the doctor's office or clinic. Arrangements should be made ahead of time for someone else to drive the patient home.

Click the icon to see an illustrated series detailing a vasectomy.

A method of vasectomy called no-scalpel vasectomy (NSV) that does not require the use of a scalpel was developed in China in 1974. NSV is now used in at least one-third of vasectomies.

The technique takes about 10 minutes and is performed in a doctor's office or a family planning clinic. The no-scalpel vasectomy differs from a conventional vasectomy in the method of accessing the vasa deferentia:

In NSV, the doctor feels for the vas deferens under the skin and holds them in place with a small ring clamp.
Instead of making two incisions, the doctor employs a sharp hemostat, a special instrument that makes one tiny puncture and then is used to gently stretch the opening until the vas deferens can be pulled through it. (The surgeon must rotate his wrist to pull the vas out -- called a supination maneuver -- which may be difficult to perform.)
The vas is then sealed off using the same methods (clips, sutures, cauterization using an electric needle, or some combination) as conventional vasectomy. As with standard vasectomy, the closures can be open- or closed-ended.
There is very little bleeding with the no-scalpel vasectomy. No stitches are needed to close the tiny opening, which heals quickly and leaves no scar.

When performed correctly, NSV works just as well as conventional vasectomy, takes less time, and (according to a 2007 review) causes less bleeding, infection, and pain. Current research indicates that NSV is the safest type of vasectomy procedure. NSV is difficult to perform, however, and most surgeons must do about 15 - 20 procedures in order to be proficient. NSV is becoming a popular alternative to standard vasectomy, but it is important to select a doctor who is experienced with this procedure.

A simpler method of NSV, called percutaneous vasectomy, is now being used. Recent research suggests that it works as well as standard NSV and is easier to perform. Percutaneous vasectomy uses the same instruments as no-scalpel vasectomy, but with a different surgical technique. The hemostat is used to first puncture the skin (instead of spearing the vas and lifting it out). The ringed clamp is then passed through the incision and used to enclose the section of the vas that is then pulled out for closure. This avoids the need for the difficult wrist maneuver in NSV.

Vasclip. The Vasclip is a recent alternative to standard vasectomy. This very small rice-sized plastic clip locks around the vas deferens and stops the flow of sperm. Some studies have reported fewer post-surgical complications than with standard vasectomy, including infection and swelling. It may be more easily reversible than a standard vasectomy.

Complications

Vasectomy is a low-risk procedure, and the complications, which occur in about 10% of patients, are usually easy to control. One study of no-scalpel vasectomy, for example, reported only 7 complications out of 4,255 procedures and they were mostly minor. Pain or soreness typically lingers for a few days after the procedure, but this is normal and usually does not require a return visit to the doctor. No deaths resulting from vasectomy have been reported in the United States.

Nearly all men recover completely in a few days. The following are some guidelines after the operation to help recovery:

The local anesthetic wears off about 1 - 2 hours after the procedure, and most patients then experience a dull ache in the testicles and groin. The doctor may prescribe a painkiller for the first few days, continuing with mild over-the-counter pain relievers if discomfort persists. Acetaminophen (Tylenol) with or without codeine is the primary choice for postoperative pain. Aspirin, ibuprofen (Advil, Medipren, Motrin, Nuprin), naproxen (Aleve), or other non-steroidal anti-inflammatory drugs (NSAIDs) can cause bleeding and should be avoided.
The patient should stay in bed on his back for at least one day and apply ice packs for 8 hours. The doctor may suggest that the patient wear an athletic supporter.
Some oozing of blood onto the gauze pads is normal during the first 2 days after the operation.
The patient should not perform any heavy physical labor for at least 2 days. Sports and heavy lifting may be resumed 2 - 3 weeks after surgery.
A semen analysis is done about 6 - 12 weeks after surgery to ensure that no live sperm remain in the semen. Many urologists recommend delaying a semen analysis until 2 months after a vasectomy or 12 ejaculations (whichever comes first). The semen is usually collected at home in a small jar and delivered to the doctor's office, where it is examined under a microscope. A second semen analysis is sometimes performed again about 4 months after the vasectomy, although many experts now believe that a second sample is unnecessary unless sperm found the first time were motile (still able to move). According to a 2006 study, 25% of men never bother to return for follow-up sperm testing. Without a follow-up test, men do not know whether the vasectomy was successful. Until test results verify that there are no sperm in the semen, men are at risk of fathering unwanted pregnancies.

All men experience some pain in the scrotum (the sac that contains the testes) after the operation. This pain generally disappears within two days, although the patient may feel sore for a few more days. In rare cases, pain can be persistent, which is known as post-vasectomy pain syndrome. The cause of this is unclear.

A few men may have an allergic reaction to the local anesthesia and develop itching and hives.

Frequently, blood may seep under the skin, so that the scrotum and penis appear to be bruised. If there is no dangerous swelling, this painless problem usually disappears without treatment within 1 - 2 weeks. If the patient bleeds excessively in the days after the operation and requires more than two or three gauze changes per day, he should call his doctor.

In 2 - 5% of cases, bleeding inside the scrotum can cause a painful swelling known as a hematoma. In these cases, the scrotum swells up shortly after vasectomy. The doctor should be called immediately.

Infections occur in 4 - 9% of men after vasectomy. The incision site may become infected, causing redness and swelling around the incision. Antibiotics, antimicrobial creams or ointments, or both, along with hot baths several times a day will usually clear the infection in a few days. There have been a few cases of infections in the lining of the heart (endocarditis) and severe gangrene of the scrotum, but they are extremely rare.

Unexpected Pregnancy

Pregnancy rates after a vasectomy are estimated to be very low, about 1 in 1,000. There are two main reasons for an unexpected pregnancy:

Residual sperm were still alive when the partners had unprotected sex. This is the most common reason for an unexpected pregnancy after a vasectomy. Men should make sure they have follow-up sperm analysis testing. They should also continue to use birth control until their doctor notifies them that the test results confirm sterility.
Failure of the procedure and recanalization. Failure in some cases is due to a technical error, but most often it is due to recanalization -- when the cut ends of the vas spontaneously reconnect. Success rates are best when an experienced surgeon performs the vasectomy.

Once the patient feels comfortable, he can resume sexual activity, usually in about a week. During ejaculation, the patient may experience some discomfort in the groin and testicles at first due to the contraction of the vas deferens. This almost always diminishes as the tissues heal.

However, after the operation there are always some active sperm left in the semen for several months so the risk for pregnancy persists. It is essential that the patient and his partner continue to use other methods of birth control until his sperm count is zero. The patient is considered sterile only when there are no live or moving (motile) sperm in his semen. It takes, on average, around 3 months or 20 ejaculations to clear the viable sperm from the reproductive system, but it may take some men as long as 6 months to become sterile.

About a third of men experience a recurrence or persistence of sperm that have no ability to move (immotile) 12 weeks after surgery and, in one study, about 7% had persistently immotile sperm. Immotile sperm, however, cannot swim up the vaginal canal and pose no danger for fertility. In rare cases, vasectomies have to be repeated because live sperm persisted in the semen. The risk for sperm surviving indefinitely is, however, very low.

The primary reason for vasectomy failure itself is recanalization-- when the cut ends of the vas deferens spontaneously reconnect. Recanalization in some cases may be due to sperm granulomas. These are tiny balls of debris that form from sperm, scar tissue, and white blood cells at the incision site. Cells lining the inside of the vas deferens grow through the scar tissue and form a new channel through which the sperm can now move. In general, surgeons can reduce the risk for recanalization by leaving a gap between the two cut ends.

This natural vasectomy reversal can occur after any vasectomy surgical procedure, but it is uncommon, with most studies reporting it occurring in less than 1% of cases. When recanalization does occur, sperm counts are almost always very low and pregnancies are still rare. Most cases of recanalization develop within several months after the operation. In very rare cases (about 0.6%), sperm have reappeared a year or even longer after vasectomy.

Long-Term Complications

Sperm Granulomas. After vasectomy, sperm often leak from the vasectomy site or from a rupture in the epididymis, the tightly coiled, thin tube that connects the testicle to the vas deferens. Sperm elicit a very strong response from the immune system, which views them as foreign substances and attacks them. Sperm leakage therefore provokes an inflammatory reaction. The body forms pockets to trap the sperm in scar tissue and inflammatory cells. Firm balls of tissue about 1/2 inch in diameter then form; these are known as sperm granulomas. They occur in about 60% of vasectomy patients.

Although they rarely cause serious problems, one study reported that sperm granulomas were troublesome in 15% of patients. In about 3 - 5% of cases, sperm granulomas obstruct the already blocked ends of the vas deferens and generate pressure build-up in the epididymis. This can cause a rupture from the pressure of the fluid. In such cases, the testicles may become enlarged and painful. A damaged epididymis can be repaired, but if the patient later wishes a reversal of the vasectomy, disruption of this tiny tube makes success much less likely.

Epididymitis. Epididymitis occurs when an inflammation at the site of the vasectomy causes swelling of the epididymis. This condition may occur within the first year and can be treated with heat and anti-inflammatory medications. It usually clears up within a week.

The male reproductive structures include the penis, the scrotum, the seminal vesicles and the prostate.

Positive Effects. Surveys indicate that about 90% of men are satisfied with vasectomy and that the feeling persists. One study reported even higher satisfaction in the partners, with more than 95% of wives reporting satisfaction with the procedure. Younger and older couples, with or without children, were all equally likely to have favorable reactions to vasectomies. Most men who have vasectomies feel relieved that the worry about pregnancy is over, and most couples respond well to their new-found contraceptive freedom.

Negative Effects. Some men go through a brief period of self-consciousness, wondering whether others notice some difference in their masculinity. About half of vasectomy patients keep their operations a secret. They may believe that vasectomy is tainted by the stigma of emasculation and that knowledge of it would degrade them in the eyes of their friends and family. For most men, this tentativeness passes quickly.

In a few men, however, problems of poor self-image persist and require counseling. Some may experience depressed and angry emotions. They may actually require a mourning period over the loss of their reproductive ability (similar to what some women go through during menopause). These negative feelings usually resolve over time as the patient moves on to the next stage of his life.

A small percentage of couples experience serious difficulties with the adjustment. Their emotional distress most often manifests itself in sexual dysfunction, such as impotence, premature ejaculation, or painful intercourse. In such cases, however, the vasectomy is probably the catalyst but not the cause of such extreme reactions. Studies have indicated that men who experience erectile dysfunction after vasectomy are more likely to have female partners who are unable to accept the operation.

Research indicates that up to a third of men have some pain in or around the testes that lasts longer than 3 months. In a study of 700,000 patients with vasectomies, up to 10% reported long-term chronic pain around the testicles. In one survey, 19% of subjects reported chronic pain that was simply a nuisance, and 12% reported more severe pain. Another study that followed men for an average of 19 months reported that 27% had some pain in the testicles, although, in the great majority, the pain was brief.

Causes of Chronic Pain. In many cases the source of the pain after vasectomy is not known, although some of the following conditions may be a source of pain:

Scarring from the surgery
Obstruction of part of the epididymis that causes swelling in another section
Pinched nerves
In about 1% of all vasectomies, the epididymis becomes so congested with dead sperm and fluid that the patient feels a dull ache in his testicles. This condition, called chronic orchialgia, usually disappears within 6 months.
Some doctors believe that granulomas may cause more chronic pain than generally believed. Others point out, however, that open-ended procedures, which increase the risk for granuloma production, result in less pain than closed-ended techniques that produce fewer granulomas.

Treatments for Chronic Pain. Surgery may be required if time or more conservative measures fail to relieve pain. Procedures may include:

Removal of the epididymis and surrounding tissue tends to be effective if the pain is in the scrotum (the sac that contains the testes) and if abnormalities in the epididymis can be observed using ultrasound.
A surgical procedure that blocks nerves in the sperm cord can bring relief in severe cases.
Surgery to reverse vasectomy (vasovasostomy) may relieve chronic pain. In one study, nearly 70% of men became pain free, although researchers were unable to discover any biologic differences after the procedure that might explain such relief.

Prostate Cancer. Prostate cancer is the second most common cause of cancer death among American men. About 30% of all American men will develop at least localized prostate cancer at some time in their lives. Long-term high-normal levels of testosterone may be associated with an increased risk for prostate cancer. Because testosterone levels remain higher for a longer period in men who had vasectomy, experts have been concerned that such men have a greater chance for developing the cancer.

Click the icon to see an image of prostate cancer.

A 2002 review indicated a 10% increase in risk for every 10 years after the procedure. The authors of the study reported, however, that such increased risk may not be caused by vasectomy since the association was small and could be due to bias. Most recent studies report no higher danger. A rigorous 2002 study from New Zealand, which has the highest vasectomy rates in the world, found no increased risk of prostate cancer from the procedure, even 25 years after the operation. Another 2002 study, in fact, reported a lower risk for prostate cancer in men who had had vasectomies.

It is possible that the higher rates reported in the early studies may simply be due to earlier prostate screening in men who have had vasectomies. One study reported that about 25% of doctors screened men with vasectomies earlier for prostate cancer than those without the operation.

An expert panel has recommended that vasectomy reversal is not warranted to prevent prostate cancer and that screening criteria for prostate cancer should be the same for men with and without vasectomies. Men with a family history of prostate cancer can discuss the risks and benefits of vasectomy with their doctors, although the weight of evidence to date indicates there is no link between vasectomy and prostate cancer.

Testicular Cancer. There have also been some concerns that vasectomy could increase the risk of testicular cancer. However, studies show there is no association between the two.

Vasectomy is known to provoke immune system changes.

Anti-sperm Antibodies. Sperm continue to be produced after vasectomy but are disposed of in the body. In some men the immune system mistakes these sperm as foreign proteins (antigens) and produces anti-sperm antibodies that are designed to target and interfere with sperm's motility (ability to move). Up to two thirds of vasectomized men develop such anti-sperm antibodies. Infections in the genital tract, such as orchitis or sexually transmitted diseases, increase the risk for anti-sperm antibodies. The anti-sperm response itself appears to be a problem only if a man wishes to reverse the vasectomy.

Heart Disease and Other Changes. Some researchers are concerned that changes in the immune system might cause damage in other parts of the body, including contributing to heart disease. However, a large 2002 follow-up study of men who had vasectomies found no increase in risk for heart disease, stroke, or peripheral artery disease, even after more than 20 years. Nor did researchers find any evidence of greater risk for hardening of the arteries (atherosclerosis) or inflammation, which play a role in cardiovascular disease.

Click the icon to see an image of atherosclerosis.

Some experts have voiced concern that vasectomy may increase the risk for the bone-thinning condition known as osteoporosis. However, evidence to date does not support an association.

Studies suggest that men younger than their mid-40s who have vasectomies have twice the risk for kidney stones as their peers who have not had vasectomies. The increased risk persists for up to 14 years after the operation. Kidney stones are not life threatening, but they can be extremely painful. Drinking plenty of fluids is the best way to prevent kidney stones.

Click the icon to see an image of kidney stones.

Reversal Surgery

Although men should consider vasectomy a permanent decision, vasovasostomy is a reversal procedure that may restore fertility in men who change their minds. Vasovasostomies are also effective in relieving chronic pain from vasectomies in the rare case that this occurs.

One Australian study suggested that although the rate of vasectomies has not changed over the past few decades, the desire for reversal surgery increased by over 70% in the late 1990s compared to the early 1980s. Men who had vasectomies in their 20s are more likely to seek reversal later on than older men. The main reasons for requesting a reversal are remarriage, the death of a child, or an improvement in finances. Reversal may also be performed to relieve post-vasectomy pain, which occurs in a small percentage of men. However, fewer than 10% of patients who request reversals do so because of physical or psychological problems following vasectomy.

Standard Procedure. Vasovasostomy reconnects the severed ends of the vas deferens to reestablish the flow of sperm. The procedure is difficult:

It involves sewing together the two tiny ends of both tubes, each with pinhead-sized openings.
If the vas deferens is blocked, the surgeon may try to connect the epididymis to an area in the vas deferens that bypasses the blockage.

Vasovasostomy can usually be done on an outpatient basis, and patients can usually return to work within 1 - 2 weeks. It is far more difficult and expensive than vasectomy itself, however, and is even costlier if the procedure involves connecting the vas to the epididymis, which takes about 3 hours. It should be noted that reversal surgery is usually not reimbursed by insurance companies, and that the results may not be known for some time.

Microscopic versus Magnification Techniques. The surgeon may view the surgical site using either magnification instruments (called macroscopic vasovasostomy) or microscopic techniques. Advanced microscopic techniques are proving to increase the chances of a reversal's success. Although macroscopic vasovasostomy has a slightly lower success rate, pregnancy rates can still be over 50%, and it is less expensive and has a shorter operating time than microscopic procedures. Still, a 2003 study suggested the microscopic approach is preferable for repeat vasovasostomies when the initial procedure failed.

Laser Techniques. Laser surgery is being investigated and may prove to require less surgical expertise, reduce operating time, and result in fewer complications. At this time, however, results vary widely.

An Australian study reported that the pregnancy rates in the late 1990s after reversal surgery were nearly four times higher than they were in the early 1980s. Pregnancy rates of over 50% are now being reported after vasovasostomy. One study indicated that when successful conception occurs, it does so at an average of 1 year after the surgery.

A successful reversal is more likely if the following conditions are present:

The section removed during vasectomy was not long.
The original procedure was performed on straight sections of the vas deferens.
The pieces joined during the vasovasostomy are of equal size.

The closer in time the vasovasostomy is to the original vasectomy, the better. In one large study, the pregnancy rates were 76% for those who had vasectomy less than 3 years before reversal surgery, but decreased to 30% for those men who had a vasectomy more than 15 years earlier. The decrease in rates as time goes by is probably due to an increase in the chance for obstruction of the epididymis and the development of anti-sperm antibodies. Success rates, according to some studies, are slightly better if the male partner does not change female partners after the procedure. Other studies suggest that it makes no difference if the man has a new female partner. The age of the woman is an important factor, and the chances of achieving pregnancy are best for women younger than age 35. Some research suggests that men who have a vasectomy reversal may have a greater rate of sperm chromosomal abnormalities than normal fertile men.

Even though tubes are re-opened and sperm is restored in as many as 85% of men who undergo vasovasostomy, pregnancy is not guaranteed. Several factors may play a role in the failure of reversal surgery.

Epididymis Obstruction. If the sperm count does not recover within a reasonable period after vasovasostomy, it is often due to blockage from scarring that has occurred in the epididymis. This sometimes can be corrected with a second procedure. The doctor may be able to detect obstruction before the vasovasostomy by pressing and manipulating (palpating) the epididymis. If any part seems swollen or larger than other parts, an obstruction is very likely to be present and the patient is likely to need a vasoepididymostomy, which creates a bypass around the obstruction.

Antisperm Antibodies. In many cases in which vasovasostomy fails, the reversal procedure reopens the tubes but fertility is impaired because of a process called autoimmunity. With this condition, important immune factors called antibodies attack the body's own cells, mistaking them for antigens (any foreign microinvader that the immune system perceives as a threat).

In the case of vasectomy, the autoantibodies attack the sperm, and so are called antisperm antibodies. Such antibodies develop when sperm continue to be produced after vasectomy, but, instead of being confined to the reproductive passages, they leak out into the body. Once out of their natural habitat, the immune system perceives them as foreign invaders and develops antibodies to attack them.

Antigens are large molecules (usually proteins) on the surface of cells, viruses, fungi, bacteria, and some non-living substances such as toxins, chemicals, drugs, and foreign particles. The immune system recognizes antigens and produces antibodies that destroy substances containing antigens.

The antisperm antibodies bind to specific parts of the sperm (the head or tail) and cause problems depending on the site of attachment. Sperm may stick together (agglutinate), fail to interact with the woman's cervix, or fail to penetrate the egg. Even after vasovasostomy, such antibodies often persist.

Oxidation. The immune factors that trigger the autoimmune process may have other harmful effects as well. In a process called oxidation, they can trigger the release of particles called free radicals, highly reactive oxygen molecules that, in excess, can do considerable damage to cells and genetic material. When high levels of free radicals persist after a vasectomy, they may, in theory at least, injure sperm DNA, contributing to infertility.

Repeat Vasovasostomy. If pregnancy fails, in some cases a repeat vasovasostomy may be effective. Success rates depend on several factors:

The doctor's skill
Complications from the original operation
Effects of anti-sperm antibodies
Time elapsed since vasectomy (the shorter the better)
History of previous children. In one study, conception rates after reoperations were highest (80%) in couples who had had previous children. The pregnancy rate was only 17% when men had remarried.

A 2003 study indicated that the microscopic approach may be preferable for many repeat vasovasostomies.

Vasoepididymostomy. Vasoepididymostomy is a microsurgical technique that is useful when a vasovasostomy has failed because of damage to the epididymis. This procedure creates a bypass around the obstruction. It may be done on one or both sides of the testes.

To appreciate the difficulty of this operation, one should realize that the epididymis is 1/300th of an inch wide with a wall thickness of 1/1000th of an inch. Microscopic techniques are critical for the success of this procedure and require a surgeon who specializes in them. Refinements in vasoepididymostomy techniques are showing promising results, opening tubes in 77 - 85% of cases.

Success rates are higher for repairing obstructions closer to the testicles, because the epididymis is wider in this area. In general, pregnancy rates are around 25%, but higher rates have been reported. In one study of men who had vasectomy reversal more than 15 years after the original procedure, 62% required vasoepididymostomy, and the overall pregnancy rate was 43%. Pregnancy rates ranged from 49% in those who had had their vasectomy 15 - 19 years earlier to 25% in those who had the surgery 25 or more years before, with the highest rates occurring, not surprisingly, in those with the youngest wives.

Damage in other ducts and small tubes are a major reason for vasoepididymostomy failure. Ultrasound before the operation may be valuable to determine if these abnormalities exist, which would make it unlikely that the procedure would be successful.

If an initial vasoepididymostomy fails but conditions are favorable, a repeat procedure may still succeed.

If the patient did not contribute sperm for freezing and banking before vasectomy, some doctors suggest freezing sperm obtained during vasovasostomy as insurance against failure. Such sperm can be used in assisted reproductive methods later on if natural intercourse fails to achieve pregnancy.

There is some controversy, however, surrounding routine use of frozen sperm before a vasovasostomy. One study reported that so many sperm were non-motile at the time of the reversal surgery that freezing sperm obtained during the procedure provided little benefit. Nevertheless, new fertilization techniques are using even non-motile sperm with some success. Studies report successful pregnancies with frozen sperm. Some experts recommend routine sperm retrieval only for men undergoing bilateral vasovasostomy (those performed on both sides) and possibly for men who are having vasovasostomy with vasoepididymostomy. Men should discuss these options with their doctor.

Even though newer techniques such as intracytoplasmic sperm injection (ICSI) are improving pregnancy rates after vasectomy, vasovasostomy is still a better choice than assisted reproductive technologies (ART) for most men who want children.

Success rates with reversal surgeries are improving, and the costs are lower than with ART. In addition, a vasovasostomy does not pose a risk for multiple births. In one study, the pregnancy rate for vasovasostomy was 52%, whereas success after intracytoplasmic sperm injection (ICSI) was between 25 - 30%. (ICSI is the ART treatment of choice for men who have had vasectomy.) Even for men who have failed vasovasostomy, a repeat procedure appears to be less expensive than embarking on fertility treatments at that time.

ART may, however, be a better approach than reversal for men with evidence of anti-sperm autoantibodies due to vasectomy. ICSI may also be more effective than reversal surgeries in men whose vasectomy was conducted at least 15 years earlier.

Assisted Reproductive Technologies

Assisted reproductive technologies (ART) are available for men who want to conceive children after a vasectomy. The shorter the period since the vasectomy the better the chances of success. In one study, success rates after ART were highest (34%) when it was performed within 10 years of the vasectomy and lowest (8%) when ART occurred more than 20 years after vasectomy. Of course, the couples would be older as the duration between procedures increased, so pregnancy rates would be lower in any case. However, time elapsed after vasectomy appears to have an effect independent of a couple's age. Debate is ongoing about its advantages versus reversal surgeries for men who have had vasectomies and want children. Research presented at the 2007 American Urological Association annual meeting suggested that vasectomy reversal may work better than sperm retrieval or other ART.

The best assisted reproductive technology procedure for men who have had vasectomies or failed reversal surgery is intracytoplasmic sperm injection (ICSI). In this procedure, sperm are taken from the epididymis or testes using needles or microsurgical techniques.

The procedure itself injects a single sperm into an egg with the aid of powerful microscopic and robotic instruments. The fertilized egg is then implanted in the woman. [See In-Depth Report #67: Infertility in men.]

If a reversal surgery is not successful, a doctor may be able to retrieve sperm from the testes or the epididymis for use in assisted reproductive technologies (ART). Various techniques are now available for retrieval. The procedure may be done under local or general anesthesia, using a spring-loaded biopsy device, a thin needle, incisions, or microsurgical techniques. Rigorous trials on the best technique are lacking, although all can be successful. The choice will depend on the experience of the clinic and any underlying problems.

Testicular Fine Needle Aspiration. Testicular fine needle aspiration (TFNA) employs a fine needle to remove sperm. This can be performed with local anesthetic and by surgeons who do not have to be experienced in microsurgeries.

Microsurgical Epididymal Sperm Aspiration. Microsurgical epididymal sperm aspiration (MESA) uses microsurgical techniques to collect sperm that are close to blocked portions of the epididymis. It involves an open incision and may be done under general or spinal anesthesia in a hospital setting, although the patient can often go home the same day. The doctor accesses the epididymis and retrieves sperm with an extremely fine needle-like device. It has the advantage that it can retrieve the largest number of sperm compared to other procedures. However, as with any invasive procedure, it carries some risk of complications, such as bleeding or infection.

Percutaneous Epididymal Sperm Aspiration. Percutaneous epididymal sperm aspiration (PESA( uses a needle to obtain mature sperm from areas in the upper parts of the epididymis (the coiled tube where sperm are stored before ejaculation). It is done under local anesthesia, sometimes in the doctor's office, is less expensive than other techniques, and recovery is fairly painless. However, it has less of a chance of achieving sufficient sperm than MESA, and there is also a chance of hitting a blood vessel, causing bleeding.

Testicular Sperm Extraction. Testicular sperm extraction (TESE) is a microsurgery that removes a small amount of tissue from one or more areas of the testes using incisions and microsurgery techniques. The tissue is placed in a culture and chopped into tiny pieces. Sperm are liberated from the tiny tubes and extracted. It is a complex process, however. This is the second best method for men with vasectomies, according to some experts. It is more painful than PESA, however. In addition, if the procedure is repeated too often it can cause permanent alterations in testicular function that may reduce male hormone levels.

Testicular Sperm Aspiration. Testicular sperm aspiration (TESA) uses a needle-like biopsy device to draw a small sample of testicular tissue. Multiple attempts are sometimes required to retrieve sperm, and it is not as effective or as safe as TESE, although imaging techniques using ultrasound may improve results.

Resources

www.engenderhealth.org -- EngenderHealth
www.nichd.nih.gov -- National Institute of Child Health and Human Development
www.plannedparenthood.org -- Planned Parenthood
www.fhi.org -- Family Health International
www.auanet.org -- American Urological Association
www.urologyhealth.org -- Urology Health
www.newmalecontraception.org -- Male Contraception Information Center
www.imccoalition.org -- International Male Contraception Information Coalition
www.vasectomy.com -- Information on vasectomy

References

Amory JK, Muller CH, Page ST, Leifke E, Pagel ER, Bhandari A, et al. Miglustat has no apparent effect on spermatogenesis in normal men. Hum Reprod. 2007 Mar;22(3):702-7. Epub 2006 Oct 25.

Cook LA, Pun A, van Vliet H, Gallo MF, Lopez LM. Scalpel versus no-scalpel incision for vasectomy. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD004112.

Mruk DD, Wong CH, Silvestrini B, Cheng CY. A male contraceptive targeting germ cell adhesion. Nat Med. 2006 Nov;12(11):1323-8. Epub 2006 Oct 29.

Review Date:
10/17/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Do You Text at the Dinner Table?

YumSugar — Fri, 29 May 2009 11:45:08 -0700

Modern society has widely embraced technology in every aspect of life, from music and shopping to reading and cooking. But have we gone too far? A recent New York Times article weighs in on the issue of texting, emailing, and tweeting while eating - something that etiquette expert Cindy Post Senning calls "texting anarchy." Marriage and family therapists also concur, citing texting while eating as an increasing complaint among couples in counseling. I'm no stranger to sending a text or two at the table, especially if my companion is in the restroom or on the phone as well. Still, I have to agree that this form of communication should probably stay away from the dinner table, unless it is necessary and relevant. What are your thoughts? Are you guilty of texting at the table?

Source

Infertility in men

FitSugar — Wed, 08 Oct 2008 17:35:50 -0700

In This Report

Highlights
Introduction
Male Reproductive System...
Sperm Abnormalities
Causes
Diagnosis
Treatment
Assisted Reproductive Techn...
Complications of Assisted R...
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New At-Home Fertility Test Kit

Fertell, the first at-home fertility test kit, became commercially available in June 2007. The Fertell kit contains tests to screen for both male and female infertility. Men can test their semen for concentrations of motile sperm, while women can test their urine for levels of follicle-stimulating hormone (a marker for egg quality). Results are available in fewer than 90 minutes and, according to the test kit's manufacturer, are 95% accurate. However, Fertell does not screen for all types of infertility problems and should not be used as a replacement for a complete evaluation by a doctor.

Intracytoplasmic Sperm Injection May Be Overused

Use of intracytoplasmic sperm injection (ICSI), in combination with in vitro fertilization (IVF), has increased 5-fold over the past decade, even though the proportion of men treated for male infertility has remained the same. This increase suggests that doctors are now using ICSI to treat problems other than male infertility, according to a 2007 study in the New England Journal of Medicine. Some doctors recommend ICSI for women who have failed IVF cycles or who have few or poor-quality eggs. According to the Society for Assisted Reproductive Technology, there is little evidence that ICSI can help couples conceive when male infertility is not a factor.

Infertility and Birth Defects

Although there has been concern that assisted reproductive technologies (ART) may increase the risk for birth defects, infertility itself may be a risk factor, regardless of whether ART is used. Even children born to infertile couples who do not use ART have a slightly increased risk for birth defects, indicates a 2006 study in the British Medical Journal.

Varicocele Embolization

Varicocele embolization, a minimally invasive surgical approach to varicocele repair, can help improve sperm count and motility, according to research presented at the 2006 annual meeting of the Radiological Society of North America. Varicoceles (varicose veins in the testicles) are often linked to male infertility.

Introduction

Infertility is the failure of a couple to become pregnant after one year of regular, unprotected intercourse. In both men and women the fertility process is complex. Even under ideal circumstances, the probability that a woman will get pregnant during a single menstrual cycle is only about 30%. And, when conception does occur, only 50 - 60% of pregnancies advance beyond week 20. In many cases, infertility is caused by a combination of problems in both partners that conspire to prevent conception from occurring.

About 8 - 10% of couples of reproductive age experience infertility, and in around 40% of these cases male infertility is the major factor. Another 40% of infertility problems are caused by abnormalities of the woman's reproductive system, and the remaining 20% involve couples who both suffer reproductive difficulties.

Infertility affects one in 25 American men. More than 90% of male infertility cases are due to low sperm counts, poor sperm quality, or both. Whether sperm counts are declining overall in industrialized countries is a controversial issue. However, over the last few years the number of assisted reproductive procedures that target male infertility have increased, while female procedures have declined.

The male reproductive system creates sperm that is manufactured in the seminiferous tubules within each testicle. The head of the sperm contains the DNA, which when combined with the egg's DNA, will create a new individual. The tip of the sperm head is the portion called the acrosome, which enables the sperm to penetrate the egg. The midpiece contains the mitochondria which supplies the energy the tail needs to move. The tail moves with whip-like movements back and forth to propel the sperm towards the egg. The sperm have to reach the uterus and the fallopian tube in order to fertilize a woman's egg.

Male Reproductive System

Male fertility depends on the proper function of a complex system of organs and hormones:

The process begins in the area of the brain called the hypothalamus-pituitary axis, a system of glands, hormones, and chemical messengers called neurotransmitters, all of which are critical for reproduction.
The first step in fertility is the production of gonadotropin-releasing hormone (GnRH) in the hypothalamus, which prompts the pituitary gland to manufacture follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
FSH maintains sperm production, and LH stimulates the production of the male hormone testosterone.
Both sperm and testosterone production occurs in the two testicles, or testes, which are contained in the scrotal sac (the scrotum). (This sac develops on the outside of the body because normal body temperature is too high to allow sperm production.)

The male reproductive structures include the penis, the scrotum, the seminal vesicles, and the prostate.

Sperm are manufactured in several hundred microscopic tubes, known as seminiferous tubules, which make-up most of the testicles.

Surrounding these tubules are clumps of tissue containing so-called Leydig cells. Here, testosterone is manufactured.

Sperm Development. The life cycle of sperm consists of a remarkable journey that depends on hormonal signals combined with a mechanical process. It takes about 74 days:

Sperm begin partially embedded in nurturing amoebae-like cells known as Sertoli cells, which are located in the lower parts of the seminiferous tubules.
As they mature and move along, they are stored in the upper part of the tubules. Young sperm cells are known as spermatids.
When the sperm has completed the development of its head and tail, it is released from the cell into the epididymis. This remarkable C-shaped tube is 1/300 of an inch in diameter and about 20 feet long. It loops back and forth on itself within a space that is only about one and a half inches long. The sperm's journey through the epididymis takes about 3 weeks.
The fluid in which the sperm is transported contains sugar in the form of fructose, which provides energy as the sperm matures. In the early stages of its passage, the sperm cannot swim in a forward direction and can only vibrate its tail weakly. By the time the sperm reaches the end of the epididymis, however, it is mature and looks like a microscopic squirming tadpole.
At maturity, each healthy sperm consists of a head that contains the man's genetic material, his DNA, and a tail that lashes back and forth at great speed to propel the head forward at about four times its own length every second. The ability of a sperm to move forward rapidly and straight is probably the most significant determinant of male fertility.

Ejaculation. When a man experiences sexual excitement, nerves stimulate the muscles in the epididymis to contract, which forces the sperm out through the penis:

In the penis, the sperm first pass into one of two rigid and wire-like muscular channels, called the vasa deferentia. (A single channel is called a vas deferens.)
Muscle contractions in the vas deferens from sexual activity propel the sperm along past the seminal vesicles. These are clusters of tissue that contribute fluid, called seminal fluid, to the sperm. The vas deferens also collects fluid from the nearby prostate gland. This mixture of various fluids and sperm is the semen.
Each vas deferens then joins together to form the ejaculatory duct. This duct, which now contains the sperm-containing semen, passes down through the urethra. (The urethra is the same channel in the penis through which a man urinates, but during orgasm, the prostate closes off the bladder so urine cannot enter the urethra.)
The semen is forced through the urethra during ejaculation, the final stage of orgasm when the sperm is literally shot out of the penis.

Click the icon to see an image of the vas deferens.

Semen. In addition to providing the fluid that transports the sperm, semen also has other benefits:

It provides a very short-lived alkaline environment to protect sperm from the harsh acidity of the female vagina. (If the sperm do not reach the woman's cervix within several hours, the semen itself becomes toxic to sperm and they die.)
It contains a gelatin-like substance that prevents it from draining from the vagina too quickly.
It contains sugar in the form of fructose to provide instant energy for sperm locomotion.

The Path to the Egg. The sperm's passage to the egg is a perilous journey.

Usually about 100 - 300 million sperm are delivered into the ejaculate at any given time. Even under normal conditions, however only about 15% of these millions of sperm are sound enough to fertilize an egg.
To compound the problem, after the stress of ejaculation, only about 400 sperm survive the orgasm to complete the journey.
Out of this number, a mere 40 or so sperm survive the toxicity of the semen and the hostile environment of the vagina to reach the vicinity of the egg. Normally, the cervical mucus forms an impenetrable barrier to sperm. However, when a woman ovulates (releases her egg, the oocyte), the mucous lining thins to allow sperm penetration.
Sperm that manage to reach the mucous lining in the woman's cervix (the lower part of her uterus) must survive about four more days to reach the woman's fallopian tubes. (Here, the egg is positioned for fertilization for only 12 hours each month.)
The few remaining sperm that penetrate the cervical mucus and are able to reach the fallopian tubes become capacitated.
Capacitation is a one-time explosion of energy that completes the sperm's journey. It boosts the motion of the sperm and triggers the actions of the acrosome, a membrane that covers the head of the sperm and resembles a warhead. The acrosome is dissolved, and enzymes contained within it are released to allow the sperm to drill a hole through the tough outer coating of the egg.
In the end, only one sperm gets through to fertilize the egg.

Click the icon to see an image of the uterus.

Sperm Abnormalities

More than 90% of male infertility cases are due to low sperm counts, poor sperm quality, or both. In 30 - 40% of cases of sperm abnormalities, the cause is unknown. It may be the end result of one or more factors that include chronic illness, malnutrition, genetic defects, structural abnormalities, and environmental factors. Partial obstruction anywhere in the long passages through which sperm pass can reduce sperm counts. In one study, obstruction was believed to be a contributing factor in over 60% of low sperm count cases. Obstruction itself can be caused by many factors.

Sperm abnormalities are categorized by whether they affect sperm count, sperm quality, or sperm shape.

In the past, a sperm count of less than 40 million/mL in the ejaculate was believed to cause infertility. Now, however, if the woman is fertile and young, a count as low as 10 million can often accomplish conception over time, even without treatment. In fertilization clinics, men with low sperm counts report fertilization rates of about 30%, while those with average sperm counts have rates between 60 - 80%. Sperm count varies widely over time, and temporary low counts are common. Therefore, a single test that reports a low count may not be a representative result.

Sperm motility is the sperm's ability to move. If movement is slow, not in a straight line, or both, the sperm have difficulty invading the cervical mucous or penetrating the hard outer shell of the egg. If 60% or more of sperm have normal motility, the sperm is at least average in quality. If less than 40% of sperm are able to move in a straight line, the condition is considered abnormal. Sperm that move sluggishly may also have genetic or other defects that render them incapable of fertilizing the egg. An important 2001 study identified a protein in the tail of the sperm called CatSper, which might play a central role in the ability of the sperm to swim and penetrate the egg.

Morphology refers to the shape and structure of an object. Morphology may be even more important than count or motility in determining potential fertility. Abnormally shaped sperm cannot fertilize an egg. About 60% of the sperm should be normal in size and shape for adequate fertility.

The perfect structure is an oval head and long tail. Abnormally shaped sperm may include a number of variations:

A very large round head. (In one study, if 14% or more of sperm had round enlarged heads, the chances for pregnancy fell to about 20%. Such an abnormality indicates early unraveling of genetic material.)
An extremely small pinpoint head
A tapered head
A crooked head
Two heads
A tail with kinks and curls

Sperm carry half the genetic material necessary to make a complete human being. (The egg holds the other half.) Genes are contained in the rod-like structures called chromosomes. The genes themselves are made up of chains of molecules called DNA, which carry the information that defines a human. Genetically fragile sperm are important factors in male infertility. Such sperm have fragmented DNA chains, which make them less capable of fertilization and may also contribute to low quality.

Causes

In one study, the causes of infertility in men seeking to conceive included:

Vasectomy. In the study, 56% of men were seeking a reversal of this procedure. Thirty years ago, this was a factor in only 5% of men seeking help for fertility.
Varicocele (14%). A network of veins carries blood away from the testicles and back up into the body. If these veins become enlarged, twisted, and swollen (similar to varicose veins in the leg), this condition is termed a varicocele. Varicoceles can impair testicular function and fertility.
Unknown infertility (8%).
Absence of sperm (6%). There are many biologic and environmental factors that can lead to low sperm count. For instance, abnormalities in production or obstruction of the tubes that carry sperm can reduce sperm levels. A condition called Sertoli cell-only syndrome is one in which the cells that produce sperm (the Sertoli cells) are absent. This can be a congenital problem that a man is born with or caused by infection, injury, medication, radiation, or genetics. In addition, other conditions may cause infertility in men.

The effect of aging on male fertility is not totally clear. However, growing evidence suggests that it may be a factor (although not to the extent that it is in women). This evidence indicates that age-related sperm changes in men are not abrupt, but are a gradual process. Aging can adversely affect sperm counts and sperm motility (the sperm's ability to swim quickly and move in a straight line). A 2006 study also suggested that the genetic quality of sperm declines as a man ages. The researchers found that poor sperm motility was associated with DNA fragmentation. This led to some older men having an increased risk of passing on gene mutations that cause dwarfism and possibly other genetic diseases.

Nearly any major physical or mental stress can temporarily reduce sperm count. Some common conditions that lower sperm count, temporarily in nearly all cases, include:

Emotional Stress. Stress may interfere with the hormone GnRH and reduce sperm counts.

Sexual Issues. In fewer than 1% of cases, impotence, premature ejaculation, or psychological or relationship problems contribute to male infertility, although these conditions are usually very treatable. Lubricants used with condoms, including spermicides, oils, and Vaseline, can affect fertility. Astroglide, Replens, or mineral oil may not be as harmful to sperm. However, oil-based lubricants can damage latex condoms and should be avoided.

Testicular Overheating. Overheating, such as from high fevers, saunas, and hot tubs, may temporarily lower sperm count. Persistent exposure to high temperatures during work may impair fertility. Several studies have found no negative effects on fertility from wearing tight trousers, briefs, or athletic supports, even every day.

Substance Abuse. Cocaine or heavy marijuana use appears to temporarily reduce the number and quality of sperm by as much as 50%. Sperm actually have receptors for certain compounds in marijuana that may impair the sperm's ability to swim and also inhibit their ability to penetrate the egg. Alcohol does not appear to affect fertility, unless it is so abused that it causes liver damage.

Smoking. Smoking impairs sperm motility, reduces sperm lifespan, and may cause genetic changes that affect the offspring. One study found that men or women who smoke have lower success rates with assisted reproductive technologies. Another study reported that men who smoke also have lower sex drives and less frequent sex.

Malnutrition and Nutrient Deficiencies. Deficiencies in certain nutrients, such as vitamin E, vitamin C, selenium, zinc, and folate, may be particular risk factors for infertility

Obesity. Obesity may be a risk factor for male infertility. A 2006 epidemiological study found that a 20-pound increase in a man's weight increased the chance for infertility by about 10%.

Bicycling. Bicycling has been linked to impotence in men and also may affect fertility. Pressure from the bike seat may damage blood vessels and nerves that are responsible for erections. Mountain biking, which involves riding on off-road terrain, exposes the perineum (the region between the scrotum and the anus) to more extreme shocks and vibrations and increases the risk for injuries to the scrotum. One study found that men who mountain bike are far more likely to have scrotal abnormalities, including calcium deposits, cysts, and twisted veins. Men who cycle can reduce such risks by:

Taking frequent rests while biking
Wearing padded bike shorts
Using a padded or specially contoured bike seat that is raised high enough and sits at the proper angle

Problems in the genes that regulate male fertility and in the genetic material of sperm itself are important contributors to infertility problems in men. In fact, even in men with no known fertility problems, 19% of the sperm are genetically defective. Certain inherited medical conditions also contribute to male infertility. Defective genes themselves can be inherited, produced by environmental assaults (such radiation exposure), or both. Of some concern is the possibility that these mutations will be passed to offspring in men who undergo fertilization techniques that retrieve sperm and directly fertilize the egg. (Under natural conditions, genetically abnormal sperm would be very unlikely to reach and fertilize the egg.)

Defective Genetic Material. Sperm carry half the genetic material necessary to make a human being. Infertile men have been reported to have a relatively high percentage of sperm with broken or damaged DNA (the molecular chain that makes up a gene).

Genetic Factors Specifically Affecting Sperm Production or Quality. Abnormalities in genes that specifically regulate sperm production and quality are major factors in male infertility. Some research suggests that about 10% of cases of male infertility may be due to problems, most likely genetic, in the acrosome. The acrosome is the enzyme-filled membrane cap on the sperm -- its warhead -- that is critical for piercing the egg. In one study, pregnancy was impaired if 7% or more of sperm had abnormalities in the acrosome.

Inherited Disorders that Affect Fertility. Certain inherited disorders can impair fertility. Examples include:

Cystic fibrosis patients often have missing or obstructed vas deferens (the tubes that carry sperm). In fact, men whose infertility is caused by an inborn missing vas deferens have a 60% chance that they carry the gene for cystic fibrosis (even if they don't have the disease itself).
Klinefelter syndrome patients carry two X and one Y chromosomes (the norm is one X and one Y), which leads to the destruction of the lining of the seminiferous tubules in the testicles during puberty, although most other male physical attributes are unimpaired.
Kartagener syndrome, a rare disorder that is associated with a reversed position of the major organs, also includes immotile cilia (hair-like cells in lungs and sinuses that have a structure similar to the tails of sperm). Sperm motility may also be impaired by this condition.
Polycystic kidney disease, a relatively common genetic disorder that causes large cysts to form on the kidneys and other organs during adulthood, may cause infertility as the first symptom if cysts develop in the reproductive tract.

Exposure to toxins, chemicals, or infections may reduce sperm count by either affecting testicular function or altering hormone systems. The extent of the impact and specific environmental assaults involved, however, are often controversial. Some researchers believe environmental toxins are contributing to a general worldwide decline in male fertility. Data indicate that testosterone levels in American men may have declined over the last several decades. The reasons for this decline have not yet been determined. However, even if testosterone levels are declining, the proportion of men treated for fertility problems has not changed much over the past decade.

Free Radicals (Oxidants). The primary suspects in the link between environmental assaults and infertility are free radicals, also called oxidants. These are unstable molecules, usually containing oxygen, that are released as a by-product of many natural chemical processes in the body. Infections, chemicals, and other environmental assaults can produce high levels of these particles. High levels may even affect the genetic material in cells. Sperm are particularly vulnerable to the damaging effects of this oxidation process. There have been reports that significant levels of oxidants occur in the semen of about 25% of infertile men.

Exposure to Estrogen-Like and Hormone-Disrupting Chemicals. European studies have increasingly reported a worsening in male reproductive health and an increase in testicular and prostate cancers. Many investigators strongly suspect environmental causes, particularly excessive chemicals that disrupt hormones, as a major cause for both these events. Estrogen-like chemicals found in pesticides and other chemicals are of particular concern. Overexposure to estrogen in male animals reduces the number of Sertoli cells (the cells necessary for the initial development of sperm). Some hormone-disrupting chemicals under investigation include:

Treatment of prostate cancer varies depending on the stage of the cancer and may include surgical removal, radiation, chemotherapy, hormonal manipulation or a combination of these treatments.

Bisphenol A is a widely used chemical found in plastic food containers and bottles that has provoked concern. It has potent estrogen-like effects in low dose. Use of the chemical in female rats has produced prostate abnormalities in their male offspring.
Phthalates, chemicals used to soften plastics, are under particular scrutiny for their ability to disrupt hormones. Specific phylates of special concern include dibutyl phthalate (DBP), which is found in many products, including cosmetics and clay products sold to children (Fimo, Sculpey). Animals exposed to phylates have significantly impaired sperm count and abnormalities in their reproductive structures, such as the testes. In addition, there is some concern that exposure in pregnant women may affect the offspring,
Organochlorines are compounds that combine chlorine and organic substances -- usually petrochemicals. Many have estrogen-like effects, including those previously used to make plastics (PCBs) and pesticides (DDT and p,p-DDE). Some, such as dioxins and furans, are byproducts of many chemical processes. Fortunately, most of these chemicals have been banned, but they were heavily used in manufacturing before 1970 and are still widespread in the environment. Studies report that when men had a history of moderate or high on-the-job exposure to pesticides containing organochlorines, their fertility rates were lower than men without such exposures. Studies have found a strong correlation between high levels of polychlorinated biphenyls (PCBs) or p,p-DDE with reduced sperm quality and quantity. In one of the studies, even men with healthy sperm with high organochlorine levels had a lower sperm count than those with lower levels of these compounds.

Most evidence on the hormone of chemical estrogens has occurred in animals and birds. Tests of single chemicals containing estrogen have reported little danger for people. Some studies suggest, however, that exposure to more than one of these chemicals may be very harmful. At this time, there is no strong evidence supporting a serious harmful effect in people who have normal exposure to these chemicals. Major efforts are underway to determine the extent of any possible harm from these chemicals.

Exposure to Heavy Metals. Chronic exposure to heavy metals such as lead, cadmium, or arsenic may affect sperm quality. Trace amounts of these metals in semen seem to inhibit the function of enzymes contained in the acrosome, the membrane that covers the head of the sperm.

Radiation Treatments. X-rays and other forms of radiation affect any rapidly dividing cell, so cells that produce sperm are quite sensitive to radiation damage. Cells exposed to significant levels of radiation may take up to 2 years to resume normal sperm production and, in severe circumstances, may never recover.

Men with fertility problems because of low semen levels when they ejaculate may have a structural abnormality in the tubes transporting the sperm. (A normal amount of semen is 2.5 - 5 mL, or about 1/2 - 1 teaspoon.)

A varicocele is an abnormally enlarged and twisted (varicose) vein in the spermatic cord that connects to the testicle. Varicoceles are found in 15 - 20% of all men and in 25 - 40% of infertile men, although it is not clear how or even if they affect fertility. They tend to occur more commonly (85%) on the left side. Some theories supporting their possible effect on infertility include:

Click the icon to see an image of a varicocele.

Varicoceles may partially obstruct the passages through which sperm pass.
Varicoceles may elevate temperature in the testes.
Varicoceles may produce higher levels of nitric oxide, a substance that has beneficial effects on blood flow and other functions but which might, in excess, injure sperm.
Varicoceles may block oxygen supply to the sperm.
Varicoceles have been associated with abnormalities in cellular material in the sperm. One study suggested that some men with fertility problems may have genetic defects that cause both varicoceles and impaired sperm.

Some reports indicate that only varicoceles that are large enough to be felt (or palpable) may impact fertility. On the other hand, however, an 8-year study of men with and without varicoceles found no differences in sperm quality or in the ability to conceive. Furthermore, the few well-conducted studies on repair of varicoceles suggest that the procedure does not improve pregnancy rates. Their effect on fertility remains unclear.

Hypogonadism is the general name for a severe deficiency in gonadotropin-releasing hormone (GnRH), the primary hormone that signals the process leading to the release of testosterone and other important reproductive hormones. Low levels of testosterone from any cause may result in defective sperm production.

Hypogonadism is uncommon and is most often present at the time of birth, usually the result of rare genetic diseases affecting the pituitary gland that may include selective deficiencies of the hormones FSH and LH, Kallman syndrome, or panhypopituitarism, in which the pituitary gland fails to make almost all hormones. It can also develop later in life from brain or pituitary gland tumors or as a result of radiation treatments. Defects in the gene on the X chromosome that regulates receptors that bind to androgens (male hormone) may also prove to be very important causes of male infertility.

Click the icon to see an image of the pituitary gland.

Autoimmunity is a condition in which antibodies of the immune system attack specific cells in the body, mistaking them for foreign microinvaders. In the case of male infertility, these so-called autoantibodies ("self" antibodies) target the sperm. Antibodies bind to specific parts of the sperm, such as the head or tail and, depending on the site of attachment, cause various problems:

Sperm may stick together (agglutinate)
They may fail to interact with cervical mucous
They may be unable to penetrate the egg

Some experts believe that in most cases the presence of these antibodies will not prevent conception unless a large percentage of sperm are affected.

Vasectomy and Anti-Sperm Antibodies. Vasectomy, the primary sterility procedure in men, is the most common cause of sperm autoantibodies (also called anti-sperm antibodies). Their typical development may be as follows:

Vasectomy works by severing the vas deferens, the tube that carries sperm from the testicles to the urethra (which leads out of the penis).
After vasectomy, sperm continue to be produced but, instead of being confined to the reproductive passages, they leak out into the body.
Here, the immune system may perceive them as foreign invaders and develop antibodies to attack them.

Such antibodies often persist, even if a man restores sperm flow by a successful reversal procedure (vasovasostomy). The persistence of anti-sperm antibodies may result in infertility.

Click the icon to see an illustrated series detailing vasectomy.

Other Causes of Autoantibodies. Antibodies to sperm can also appear in men without previous vasectomies and have been reported to be present in 10% of all men with fertility problems. They may be linked to genital infections or injury, although the cause is usually not known.

Retrograde ejaculation occurs when the muscles of the urethra do not pump properly during orgasm and sperm are forced backward into the bladder instead of forward out of the urethra. Sperm quality is often impaired.

Retrograde ejaculation can be the consequence of several conditions:

Surgery to the lower part of the bladder or prostate (the most common cause of retrograde ejaculation)
Diabetes
Multiple sclerosis
Back surgery
Spinal cord injury

Medications such as tranquilizers, certain antipsychotics, or hypertension medications also may cause temporary retrograde ejaculation.

Any structural abnormalities that affect the testes, tubes, or other reproductive structures can have a profound effect on fertility.

Testicular Dysgenesis Syndrome. Testicular dysgenesis syndrome is a recently observed occurrence of three conditions -- impaired sperm production and quality, testicular cancer, and genital tract abnormalities. Environmental factors that increase damage from oxidants are believed to be responsible.

The genital abnormalities identified with this syndrome are undescended testes and hypospadias, each of which is associated with infertility:

Undescended Testes (Cryptorchidism). In some cases, there is a failure of the testes to descend from the abdomen into the scrotum during fetal life. Cryptorchidism is associated with mild to severe impairment of sperm production. In one survey, 38% of men who as youngsters had two undescended testicles and 10% of men with one undescended testicle were infertile, compared with 5% of men who had normal testes. Even one undescended testicle may impair fertility. In cryptorchidism, the testes are exposed to the higher internal body heat, but this may not totally explain the damage in sperm production that can occur. (Men who suffer from this condition should be aware that even if the testicle is surgically moved to the scrotum, their risk of testicular cancer is significantly increased, warranting careful self-exams and regular follow-up with a doctor.)
Hypospadias. This is a birth defect in which the urinary opening is on the underside of the penis, can prevent sperm from reaching the cervix if not surgically corrected.

Click the icon to see an image of an undescended testicle.

Click the icon to see an image of hypospadias.

Blockage in the Tubes that Transport Sperm. Some men are born with a blockage in the epididymis or ejaculatory ducts or other problems that later affect fertility. One center reported that 2% of men seeking treatment had no vas deferens.

Anorchia. In the very rare condition known as anorchia, a man is born without any testes.

Syringomyelia. This is a disease of the spinal cord that results in no ejaculate at all (aspermia).

Birth rates among cancer survivors are only 40 - 85% of normal rates. Certain cancers, particularly testicular cancer, impair sperm production, often severely. Cancer treatments such as chemotherapy and radiation can damage sperm quality and quantity, causing infertility. The closer radiation treatments are to reproductive organs, the higher the risk for infertility. Fortunately, while men may fail to produce sperm for as long as 5 years after radiation therapy, many men eventually recover their sperm production ability. Chemotherapy with drugs that harm reproductive function tends to affect fertility more severely in men than in women. New drug regimens are helping to improve fertility rates.

Adolescents and adult men undergoing cancer treatments who may want to father children should consider banking and freezing their sperm for later use in assisted reproductive therapies. This technique is called sperm cryopreservation. Sperm cryopreservation is recommended by the American Society of Clinical Oncology as the method with the highest likelihood of success for male cancer survivors. However, these banking methods are not appropriate for pre-adolescent boys being treated for childhood cancers such as leukemia. Researchers are investigating ways that stem cell transplantation may someday help these children regain their fertility while avoiding leukemia relapse.

There is some controversy over the effect of infections on infertility. Simply detecting the presence of an infection in infertile men does not necessarily mean that it has any relationship to the infertility itself. The immune response to some infections may release inflammatory factors and oxidants, chemically unstable particles that can damage sperm. The exact impact of this process on sperm is unclear, however. Infections may alter the liquidity of semen and sperm motility, although these are likely to be temporary effects. Among the infections most implicated in infertility are:

Sexually Transmitted Diseases. Repeated Chlamydia trachomatis or gonorrhea infections are most often associated with male infertility. Such infections can cause scarring and block sperm passage. Human papilloma viruses, the cause of genital warts, may also impair sperm function.

Mycoplasma. Mycoplasma is an infectious organism that appears to fasten itself to sperm cells and render them less motile.

Mumps. When mumps develops after puberty, it damages the testicles in 25% of men afflicted with the disease. (Interferon, an anti-viral drug, may help prevent infertility in adult males with active mumps, but the drug is highly toxic and caution is essential.)

Glandular Infections in the Urinary Tract or Genitals. Glandular infections that may affect fertility include prostatitis (in the prostate gland), orchitis (in the testicle), semino-vesculitis (in the glands that produce semen), or urethritis (in the urethra), perhaps by altering sperm motility. Even after successful antibiotic treatment, infections in the testes may leave scar tissue that blocks the epididymis.

Medical Conditions. Other medical conditions that can affect male fertility include any severe injury or major surgery, diabetes, HIV, thyroid disease, Cushing syndrome, heart attack, liver or kidney failure, and chronic anemia.

The effects of medications on sperm quality and count have not been rigorously studied, and many medicines are commonly prescribed without knowing whether they impair fertility. Anabolic steroids (which are often abused by weight lifters and other athletes) deserve special notice because they are known to severely impair sperm production. Among the other drugs that can affect male fertility are cimetidine (Tagamet), sulfasalazine (Azulfidine), salazopyrine, colchicine, methadone, methotrexate (Folex), phenytoin (Dilantin), corticosteroids, spironolactone (Aldactone), thioridazine (Mellaril), and calcium channel blockers.

Diagnosis

In any fertility work-up, both male and female partners are tested if pregnancy fails to occur after a year of regular unprotected sexual intercourse. It should be done earlier if a woman is over age 35 or if either partner has known risk factors for infertility. A work-up can not only uncover the causes of infertility but also detect other potentially serious medical problems as well, including genetic mutations, cancer, or diabetes.

The patients will provide the doctor with a detailed history of any medical or sexual factors that might affect fertility:

Frequency and timing of sexual intercourse
Duration of infertility and any previous fertility events
Childhood illnesses and any problems in development
Any serious illness (diabetes, respiratory infections, cancer, previous surgeries)
Sexual history, including any sexually transmitted diseases
Any exposure to toxins, such as chemicals or radiation
History of any medications and allergies
Any family history of reproductive problems

A fertility specialist, usually a urologist, will perform a physical examination. A physical examination of the scrotum, including the testes, is essential for any male fertility work-up. It is useful for detecting large varicoceles, undescended testes, absence of vas deferens, cysts, or other physical abnormalities.

Varicoceles large enough to possibly interfere with fertility can be felt during examination of the scrotum. In such cases, they are described as feeling like "a bag of worms." They disappear or are greatly reduced when the patient lies down, so the patient should be examined for varicocele while standing.
Checking the size of the testicles is helpful. Smaller-sized and softer testicles along with tests that show low sperm count are strongly associated with problems in sperm formation. Normal testicles accompanied by a low sperm count, however, suggest possible obstruction. The doctor may also take the temperature of the scrotum with a test called scrotal thermography.
The doctor will also check the prostate gland for abnormalities.
The penis is checked for warts, discharge from the urinary tract, and hypospadias (incorrect location of the urethra opening).

A urine sample to detect sperm after ejaculation may rule out or indicate retrograde ejaculation. It also may be used to test for infections.

The basic test to evaluate a man's fertility is a semen analysis. The sperm collection test for men who can produce semen involves the following steps:

A man should abstain from ejaculation for several days before the test because each ejaculation can reduce the number of sperm by as much as a third. To ensure an accurate sample, most doctors recommend abstaining from ejaculation for at least 2 days, but not more than 5 days, prior to semen collection.
A man collects a sample of his semen in a collection jar during masturbation either at home or at the doctor's office. Proper collection procedure is important, since the highest concentration of sperm is contained in the initial portion of the ejaculate. Specially designed condoms are also available that enable collection of a sample during sexual intercourse. (Regular condoms are not useful, since they often contain substances that kill sperm.)
The sample should be kept at body temperature and delivered promptly. If the sperm are not analyzed within 2 hours or kept reasonably warm, a large proportion may die or lose motility.
A semen analysis should be repeated at least three times over several months.

The sperm count test is performed if a man's fertility is in question. It is helpful in determining if there is a problem in sperm production or quality of the sperm as a cause of infertility. The test may also be used after a vasectomy to make sure there are no sperm in the semen.

The man and woman should both be present when the doctor discusses the results of this analysis so that both partners understand the implications. The analysis report should contain results of any abnormalities in sperm count, motility, and morphology as well as any problem in the semen. However, semen analysis alone is not necessarily a definitive indicator of either infertility or fertility.

In June 2007, the first at-home fertility test kit became commercially available. Fertell includes both male and female tests that allow couples to test sperm motility (for men) and follicle-stimulating hormone (for women). Results are available in less than 90 minutes, and are 95% accurate. The test is available on-line and at some pharmacies. It does not require a prescription. However, Fertell does not screen for all types of fertility problems and should not be used as a substitute for a professional evaluation by a doctor.

Sperm Count. A low sperm count should not be viewed as a definitive diagnosis of infertility but rather as one indicator of a fertility problem. Although in a large analysis sperm counts below 13.5 million were considered a strong indication of infertility, pregnancy was possible so long as any motile sperm were present. If there are no sperm cells at all in the semen, the doctor checks for obstruction in the tubes or for Sertoli cell-only syndrome, in which there are no sperm-producing cells in the testes. An at-home test (FertilMARQ) is now available to help gauge sperm quantity.

Sperm Motility. Motility (the speed and quality of movement) is graded on a 1 - 4 ranking system. For fertility, motility should be greater than 2.

Grade 1 sperm wriggle sluggishly and make little forward progress. (Sperm that, in fact, clump together may indicate that antibodies to the sperm are present.)
Grade 2 sperm move forward, but they are either very slow or do not move in a straight line.
Grade 3 sperm move in a straight line at a reasonable speed and can home in on an egg accurately.
Grade 4 sperm are as accurate as Grade 3 sperm, but move at terrific speed.

More than 63% of sperm should be motile for normal fertility, but even men whose motile sperm constitutes only about a third of the total sperm count should not rule out conception. Testing for sperm motility is particularly valuable for predicting the success of artificial insemination and which men might be candidates for the intracytoplasmic sperm injection (ICSI) fertilization technique, in which the sperm is inserted directly into the egg and motility plays almost no role.

Sperm Morphology. Morphology is the shape and structure of the sperm and, of the three main sperm values, may be the best predictor of fertility. Older reports indicated that about 60% of the sperm should be normal in size and shape for adequate fertility. However, one major analysis used a much broader range of criteria for sperm morphology and concluded that values over 12% were good predictors of fertility. Determining the morphology of the sperm is particularly important for the success of the fertility treatments in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).

Seminal Fluid. The seminal fluid (semen) itself is analyzed for abnormalities. The color is checked and should be whitish-gray.

The amount of semen is important. Most men ejaculate 2.5 - 5 milliliters (mL) or cubic centimeters (cc) (1/2 - 1 teaspoon) of semen. Either significantly higher or lower amounts can be a sign of trouble:

Amounts greater than 1 cc but lower than 2.5 cc may indicate prostate problems or frequent intercourse.
A semen sample that is less than 1 cc could indicate a blockage of the ejaculatory ducts or other tubular abnormalities.
No ejaculate at all may signal retrograde ejaculation.
High amounts of ejaculate may, in some cases, also contribute to infertility.

The semen will be tested for how liquid it is. (Normal semen is liquefied within 20 minutes after adding certain enzymes.) Abnormal results suggest the following:

Overly sticky fluid suggests problems in the prostate gland (which adds fluid to sperm)
Overly watery fluid suggests lack of sperm

The amount of sugar (fructose) in sperm will be measured:

Since fructose is added to the semen in the epididymis, an absence of fructose indicates that an obstruction has occurred either in the vas deferens or the epididymis.
Conversely, if there is fructose in the semen but no sperm, then the channel from the epididymis is open but there is a defect in sperm production.

Other factors may also be measured:

White blood cell counts are taken to detect infection.
Low levels of a substance called inhibin B, which appears to be produced only in the testes, may indicate blockage or other defects in the seminiferous tubules.
Low levels of another compound, alpha-glucosidase, may also indicate blockage in the epididymis.

Blood tests are used for measuring several factors that might affect fertility:

Hormonal Levels. Tests for certain hormone levels are indicated if semen analysis is abnormal (especially if sperm concentration is less than 10 million per milliliter) or there are other indications of hormonal disorders.

Blood tests for testosterone and follicle-stimulating hormone (FSH) levels are usually taken first.
If testosterone levels are low, then luteinizing hormone (LH) are measured.

Low levels of FSH, LH, and testosterone indicate a diagnosis of hypogonadotropic hypogonadism. Very high FSH levels with normal levels of other hormones indicate abnormalities in initial sperm production. Usually this occurs only if the testicles are severely defective, causing Sertoli cell-only syndrome, in which sperm-manufacturing cells are absent. Other hormones, such as prolactin, estrogen, or stress hormones may be measured if there are symptoms of other problems, such as low sexual drive or the presence of breasts.

Infections. Blood tests can also determine the presence of any infections that might affect fertility, including HIV, hepatitis, and Chlamydia.

The postcoital test, also known as the cervical mucus penetration test, is designed to evaluate the effect of a woman's cervical mucus on a man's sperm. Typically, a woman is asked to come into the doctor's office within 2 - 24 hours after intercourse at mid-cycle (when ovulation should occur). A small sample of her cervical mucus is examined under a microscope. If the doctor observes no surviving sperm or no sperm at all, the cervical mucus should then be cultured for the presence of infection. The test cannot evaluate sperm movement from the cervix into the fallopian tubes or the sperm's ability to fertilize an egg.

If a man has had a vasectomy reversed and still cannot conceive or if semen analysis shows sperm clumping together, blood tests for anti-sperm antibodies will be conducted. Anti-sperm antibodies may also develop after genital infection or injury to the testes. The primary negative effect of these antibodies is to bind the sperm to the woman's cervical mucus, preventing the sperm from swimming further up.

Occasionally, a testicle biopsy may be performed, particularly for the following:

If Sertoli cell-only syndrome is suspected, in which sperm-producing cells in the testes are absent. It should be noted that specific cellular patterns can determine whether this condition is congenital (inborn) or caused by some later injury. This distinction is important in predicting the potential success of later sperm retrieval procedures.
For detecting obstruction in the transport system when sperm production looks normal but the count is low.

The standard biopsy procedure requires incisions (called an open approach) under anesthesia. It can be painful afterward. More than one biopsy may be needed in the case of suspected Sertoli cell-only syndrome, since one area may not have cell-producing cells, but other regions may contain normal sperm. Biopsies of both testes are more accurate than one. (Doctors must be careful to avoid the epididymis during a biopsy, since it is a continuous tiny tube and would be destroyed.) Patients may consider freezing any sperm retrieved during biopsy for later use.

Ultrasound imaging may be used to accurately determine the size of the testes or to detect cysts, tumors, abnormal blood flow, or varicoceles that are too small for physical detection (although such small veins may have little or no effect on fertility). It also can detect testicular cancer, which some experts believe make it worthwhile as a routine procedure for any male infertility work-up.

Click the icon to see an image of testicular ultrasound.

Genetic testing may be warranted in men who are severely deficient in sperm and who show no evidence of obstruction, particularly in men undergoing the intracytoplasmic sperm injection (ICSI) procedure. One study of men attending a fertility clinic showed that a third had genetic defects. If genetic abnormalities are suspected in either partner, counseling is recommended. Researchers are testing techniques such as preimplantation genetic diagnosis (PGD) that can examine all the chromosomes in a human embryo and detect defective genes, such as those for cystic fibrosis, at the very earliest stages. If it proves useful, it may help identify numerous abnormalities that increase the risk for infertility, treatment failures, or genetic defects in the offspring. In fact, a 2003 study suggested that performing an initial genetic analysis to determine DNA fragmentation in sperm may be a better way of predicting whether conception will succeed than analyzing semen.

In men who wish to undergo fertility treatments, certain tests will help determine the right strategies.

The Hamster Test. The hamster test, or micro-penetration assay test, uses the sperm sample to fertilize hamster eggs that have had their covering removed to allow penetration. If fewer than 5 - 20% of the eggs are fertilized, infertility is diagnosed. It may be useful for determining the best assisted reproductive treatment options for men with infertility.

The Human Zona Penetration Test. The human zona penetration test uses sperm to fertilize dead human eggs, which are usually obtained from an ovary that was removed for medical purposes. (Like the hamster test, the procedure cannot result in a living embryo.) Results may provide the same information as the hamster test and also indicate whether the sperm can penetrate the outer coating of an egg.

Acrosome Reaction Test. Tests that induce the ability of the sperm's enzyme-rich covering (acrosome) to dissolve can be very useful.

Other Tests. Additional advanced laboratory tests to measure sperm function, such as computer-aided sperm motility analysis, may also be performed. Some of these tests assess such factors as level of cell-damaging oxidants.

Treatment

Many men diagnosed with infertility in the past would be considered treatable now, even some men with spinal cord injuries. Unless a man produces no sperm at all, recent developments in treatment have made fertility possible for many men willing to undergo treatment and bear the expense. Before undergoing more advanced procedures, most couples trying to conceive should attempt some simple lifestyle changes.

Both male and female hormone levels fluctuate according to the time of day, and they also vary from day to day and month to month. Some timing tips might be helpful.

Male Hormone Levels and Sexual Activity. Male hormone levels are highest in the morning. In one study of men, their sexual activity was highest in October, when conception rates were also high.

Hormone Monitoring Systems for Women. A device called a saliva fertility monitor (Fertility Tracker) uses a microscope to view slides containing saliva and monitors estrogen levels. Home test kits that monitor reproductive hormone levels in the urine are also available. They are less costly than the saliva test but are messier. Monitoring hormone levels helps to determine when a woman is ovulating.

Frequency of Intercourse. The question of how often a couple should have intercourse is in debate. Some experts say that having sex more than 2 days a week adds no benefits. And, in fact, frequent sexual activity lowers sperm count per ejaculation. Some studies have indicated, however, that having intercourse every day, or even several times a day, before and during ovulation, improves pregnancy rates. Although sperm count per ejaculation is low, a constantly replenished semen supply is more likely to result in a fertilized egg.

Everyone should eat a healthy diet rich in fresh fruits, vegetables, and whole grains. Replace animal fats with monounsaturated oils, such as olive oil. Fish is also a good choice, and fish oils may have benefits for men with infertility. Certain specific nutrients, vitamins and minerals may also improve fertility.

Higher antioxidant intakes of vitamin C, vitamin E, and beta-carotene may help improve sperm numbers and motility, according to a 2005 study. The study included both food and supplement sources.
Vitamins C and E may also help repair DNA damage to sperm. According to a 2005 study, men who took 1 gram per day of these vitamins significantly reduced their percentage of DNA sperm fragmentation within 2 months.
The dietary supplements L-carnitine and L-acetylcarnitine may help improve sperm motility, according to several recent clinical trials.

A man who wants to increase his sperm count should also pursue a healthy lifestyle.

Avoid cigarettes and any drugs that may affect sperm count or reduce sexual function.
Overweight men should try to reduce their weight.
Get sufficient rest, and exercise moderately but regularly. (Those who exercise excessively might cut back, but not stop altogether.)
Stress may contribute to reduced sperm quality. It is not known if stress reduction techniques can improve fertility, but they may help couples endure the difficult processes involved in fertility treatments.
Although studies now indicate that tight underwear and pants pose no threat to male fertility, there is no harm in wearing looser clothing.
To prevent overheating of the testes, men should avoid hot baths, showers, and steam rooms.

The fertility process is a roller coaster of emotions that are present throughout both failure and success. There are almost no sure ways to predict which couples will eventually conceive. Some couples with multiple problems will overcome great odds, while other seemingly fertile couples fail to conceive. Many of the new treatments are remarkable, but a live birth is never guaranteed. The emotional burden on the couple is considerable, and some planning is helpful.

Planning for Emotional Turmoil.

Decide in advance how many and what kind of procedures will be emotionally and financially acceptable and attempt to determine a final limit. Fertility treatments are expensive.
Determine alternatives (adoption, donor sperm or egg, or having no children) as early as possible in the fertility process. This can reduce anxiety during treatments and feelings of hopelessness in case conception does not occur.

Managing Emotional Stress During the Process. Managing negative emotions in both men and women can be viewed as important as medical treatment. The process of fertility evaluation can be very difficult for many men. In a 2003 study, over 10% of men who required a second semen sample were unable to collect a semen sample using masturbation. Such men had had no problems with a first collection, but after being asked for additional samples they suffered severe anxiety during both masturbation in the fertility clinic and during regular sexual activity at home. Numerous studies reported a significant association between psychologic factors, particularly anxiety, and fertility treatment failure in women.

Managing the Emotional Effects of the Outcome. After enduring the process of fertility evaluation, the couple must face the outcome, and even a positive outcome has emotional repercussions.

Effects of Failure. Needless to say, the emotional stress of failure can be devastating even on the most loving and affectionate relationships and even in those who have prepared for the possibility of failure. Neither the male nor female partner should hesitate to seek professional help if the emotional burdens are too heavy.
Effects of Genetic Testing. As advanced technologies allow testing and greater genetic information at the earliest stage, potential parents will have to learn to deal with the uncertainties of possible chromosomal abnormalities, which may or may not be significant.
Effects of Multiple Births. A successful pregnancy that results in a multiple birth introduces new complexities and emotional problems. One study reported a very high rate of depression in women with triplets, particularly if they had little help from others, and especially if their husbands weren't involved.
Effects on Parenting. Once the fertility treatment-assisted child arrives, parents (both men and women) are more likely to be anxious and to have less confidence than those who conceive naturally.

Assisted Reproductive Technologies

Assisted reproductive technologies (ART) are medical techniques that help couples conceive. These procedures involve either:

A couple's own eggs or sperm
Donor eggs, sperm, or embryos

Fertilization may occur either in the laboratory or in the uterus. In the U.S., the number of live birth deliveries from ART increased by 128% from 1996 - 2002. More than 45,000 babies are now born in the U.S. each year using assisted reproductive technologies.

ART includes fertility drug treatments, artificial insemination (AI), in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and other procedures.

Choosing a good fertility clinic is important. The government does not always regulate centers offering assisted reproductive techniques, and abuses have been reported, including lack of informed consent, unauthorized use of embryos, and failure to routinely screen donors for disease.

The clinic should always provide the following information:

The live-birth rate (not just pregnancy success rate) for other couples with similar infertility problems. (Multiple births, such as twins or triplets, are counted as one live birth.)
Such statistics should include high-risk women, such as those who are older or fail to produce eggs. (Some disreputable clinics give success percentages that exclude high-risk women from their total, thereby making the percentage of success much higher.)

Advanced fertility procedures and medications are extremely expensive and often not covered by insurance. Couples should be cautious about offers of rebates in the event of failure. The clinics offering them are often significantly more expensive than those that don't.

Artificial insemination it is the least complex of the assisted reproductive technologies and is often tried first in uncomplicated cases of infertility. Artificial insemination either involves placing the sperm directly in the cervix (called intracervical insemination) or into the uterus (called intrauterine insemination, or IUI). IUI is the standard artificial insemination procedure.

It is useful under the following circumstances:

When the woman's cervical mucus is unreceptive.
When donor sperm are required.
If the man's sperm count is very low (although it is preferable if at least 5 million per milliliter are motile).
When unexplained infertility exists in both partners.

Those in whom artificial insemination fails, couples with specific fertility defects, or older women may be candidates for more advanced reproductive technologies.

Researchers in one study suggested IUI as a reasonable first option for many women under age 43. It is less expensive and poses less risk for multiple births than the more advanced assisted reproductive technologies (ART), such as in vitro fertilization. Although in vitro fertilization procedures are more effective per cycle, couples tend to be able to afford more IUI cycles, so the pregnancy rates over time are very similar.

The Artificial Insemination Procedure. The artificial insemination procedure is as follows:

A woman usually (but not always) takes fertility drugs in advance.
The man must produce sperm at the time the woman is ovulating.
The sperm are subjected to certain so-called "washing" procedures. They are then inserted into the uterine cavity through a long, thin catheter.

The administration of fertility drugs and sperm retrieval is timed so that the process can coincide with time of ovulation. One study suggested that women who lay quietly for 10 minutes after sperm were implanted had a significantly higher rate of pregnancy than those who got up immediately.

Intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology used for couples when male infertility is the main factor. It involves injecting a single sperm into an egg obtained from in vitro fertilization (IVF). The procedure is very simple:

A tiny glass tube (called a holding pipet) stabilizes the egg.
A second glass tube (called the injection pipet) is used to penetrate the egg's membrane and deposit a single sperm into the egg.
The egg is released into a drop of cultured medium.
If fertilized, the egg is allowed to develop for 1 - 2 days and then is either frozen or implanted.

The greatest concern with this procedure has been whether it increases the risk for birth defects. However, several studies have reported no higher risks of birth defects in children born using ICSI procedures. While other studies have shown a higher number of birth defects in children conceived with ICSI, the results may have more to do with the genetic background of the parents than ICSI itself. A 2006 study of 8-year-old children conceived with ICSI, meanwhile, found no important differences between these children and children who were conceived naturally.

While ICSI is an important assisted reproductive technology for male infertility, it may be overused. Some doctors recommend ICSI for women who have failed prior IVF attempts or who have few or poor-quality eggs, even if their male partners have normal semen measurements. There is little evidence that ICSI helps improve pregnancy success for couples who do not have a problem with male factor infertility, according to the Society for Assisted Reproductive Technology.

About 71% of ART procedures now use in vitro fertilization (IVF) with the woman's own eggs. An in vitro procedure is one that is performed in the laboratory. Advances in these procedures have dramatically increased the rate of live births.

The doctor first induces superovulation using fertility drugs so that several eggs can be harvested from the ovary before they have been released from the follicles. Higher doses of fertility drugs for subsequent cycles do not appear to add any advantage in women who have a poor response the first time.
To harvest eggs, the doctor generally inserts a probe into the vagina and is guided by ultrasound. A needle is then used to drain the liquid from the follicles, and several eggs are retrieved.
The eggs and sperm are combined in a Petri dish. Between 48 - 72 hours later the eggs are fertilized.
The resulting embryos (the first stage toward the development of the fetus) are reimplanted into the woman's uterus.
It takes about 2 weeks to determine if the process is successful.

IVF success rates for the first three cycles of treatment are about equal. They then decline modestly for the fourth cycle and drop significantly after the fifth cycle.

GIFT: The procedure is as follows:

The eggs are harvested as in IVF.
They are mixed with the sperm but not actively fertilized.
They are immediately injected back into the woman. Laparoscopy, a technique that employs a miniature viewing device, is used with this procedure to guide the placement of the embryos or egg through a long, thin catheter into the fallopian tubes.
The sperm and egg are placed exactly where they would be in natural fertilization.

ZIFT: The procedure is as follows.

The eggs are harvested as in IVF.
They are then mixed with the sperm and, in this case, are fertilized in the laboratory.
They are then implanted in the fallopian tubes as in GIFT. (The advantage of this procedure over GIFT is that the doctor and couple are assured that fertilization has taken place and the eggs can be examined for defects before implantation.)

Success rates have increased in all age groups (although they are still considerably lower in older than in younger women). Chances for assisted reproductive technology success are also greater among women who do not have uterine abnormalities and have had previous successful pregnancies.

Success rates are also higher or lower depending on whether the woman uses her own eggs or whether they are donated and also whether the eggs are fresh or frozen. The highest live birth rates are with donated fresh eggs (an average of 50% per transfer) and the lowest rates are when a woman uses her own frozen eggs (an average of 29% per transfer). However, using frozen eggs is less expensive than fresh eggs, so a couple may be able to afford more cycles with frozen eggs.

Use of Donor Eggs. Older women are more likely to use donor eggs. In one study, success rates were the same for women who used donors with an age range of 20 - 40. There were also no differences in delivery rates for recipients up to age 45. Women over age 45, however, increasingly had problems with implantation, pregnancy, and delivery.

Use of Frozen Eggs. Frozen eggs tend to have lower success rates because of toxins released by cells damaged in the freezing and thawing tissues.

In Vitro Maturation. A new technique called in vitro maturation allows fertilization without the use of fertility drugs. In this process, follicles are harvested a few days before ovulation. In such cases, up to 50 have already begun to mature. About 15 of these maturing follicles can be removed, out of which 2 or 3 can produce healthy embryos.

Before fertilization using intrauterine insemination (IUI) or advanced assisted reproductive technologies (ART) can take place, the sperm must be collected and prepared for optimal chances for success.

Retrieval Procedures

When a man has no available sperm in the ejaculate (usually from blockage, vasectomy, or lack of vas deferens), the sperm must be retrieved from the testes or the epididymis. Various microsurgical techniques are now available for retrieval. The procedure may be done under local or general anesthesia, using a spring-loaded biopsy device, a thin needle, incisions, or microsurgical techniques.

Surgical Biopsy. In men without obstruction, sperm can be retrieved using a surgical testicular biopsy.

Testicular Fine Needle Aspiration. With testicular fine needle aspiration (TFNA), the surgeon uses a fine needle to remove sperm. This can be performed with local anesthetic and by surgeons who do not have to be experienced in microsurgeries.

Percutaneous Epididymal Sperm Aspiration. Percutaneious epididymal sperm aspiration (PESA) uses a needle to obtain mature sperm from areas in the upper parts of the epididymis (the coiled tube where sperm are stored before ejaculation). It is done under local anesthesia, sometimes in the doctor's office, is less expensive than other techniques, and recovery is fairly painless. However, it has less of a chance of achieving sufficient sperm than MESA, and there is also a chance of hitting a blood vessel, causing bleeding.

Testicular Sperm Extraction. Testicular sperm extraction (TESE) is a microsurgery that removes a small amount of tissue from one or more areas of the testes using incisions and microsurgery techniques. The tissue is placed in a culture and chopped into tiny pieces. Sperm are liberated from the tiny tubes and extracted. It is a complex process, however. This is the second best method for men with vasectomies, according to some experts. It is more painful than PESA, however. In addition, if the procedure is repeated too often, it can cause permanent alterations in testicular function that may even reduce male hormone levels.

Sperm Washing

A sperm's energy output is 20 times greater once it is removed from the seminal fluid. Methods for washing sperm can have a dramatic effect on the ability of sperm to move towards the egg. The simplest method involves:

The sperm is mixed with a nutrient-rich fluid (or culture media) in a test tube.
They are then centrifuged (spun very rapidly) for about 5 minutes.
The sperm, which are heavy, settle on the bottom, forming a dense button of millions of pure sperm. The fluid left on top is siphoned off.
This procedure may be repeated.

This simple method of sperm washing, however, does not eliminate heavy debris, such as dead sperm, white blood cells, or bacteria, which may impair fertility. Scientists are developing new techniques, such as adding a substance called platelet-activating factor during the sperm washing process, which may enhance pregnancy rates.

Swim-Up Technique

The swim-up technique is not only a useful diagnostic procedure for testing the ability of sperm to escape from the semen into the cervical mucus, but it also achieves the goal of removing sperm from semen.

A specially prepared semen sample is placed in a tube.
A culture media (a nutrient-rich substance in which cells thrive) is placed on top of the sample.
The medium is a hospitable environment for sperm, and those that are healthy will swim up to it.
After an hour or more, the culture is examined, and the number of sperm that have reached the medium is compared to the number still remaining in the semen.

The result gives a fair estimation of the number of sperm potentially capable of fertilization. It is superior to sperm washing because the live sperm will swim up to the culture media, leaving behind most of the debris, although some may float up into the medium. There is also some evidence that such sperm may have fewer genetic abnormalities than those retrieved through sperm washing. The strongest sperm, which are those at the top of the medium, can be collected for in vitro fertilization or artificial insemination. A good swim test yields about half a million very active sperm.

Freezing Sperm

Sperm can be fresh or frozen in advance. Studies are reporting that frozen sperm provide excellent results and can be used confidently for fertilization procedures. Fresh sperm, however, are preferred by some centers for cases when low sperm count is not caused by obstruction.

Complications of Assisted Reproductive Technology

Fertility drugs. Increase risks of the placenta becoming detached from the uterus (placental abruption), third trimester miscarriage, and gestational diabetes.
IVF. Increase risks of placental abruption, the placenta developing in the lower section of the uterus (placenta previa), dangerously high blood pressure during pregnancy (pre-eclampsia), and Caesarean sections.

However, unlike earlier research, recent studies suggest that ART does not increase the risk for chromosomal damage or other major birth defects. Couples undergoing ART may have other factors, such as older age or genetic predispositions, which make complications more likely. Infertility itself, even without ART, can pose a risk factor for birth defects. Children conceived naturally by couples with fertility problems tended to have more disorders of the nervous system, digestive system, and musculoskeletal system than children born to fertile couples, according to a 2006 study in the British Medical Journal. Children born to couples treated for infertility with ART may also have a slightly increased risk for these problems, as well as genital organ malformations, but the overall risk for birth defects appears to be very small.

Preimplantation genetic diagnosis (PGD) is now available in a few fertility centers. It can help identify genetic defects in the offspring and may help parents determine future problems. Such testing, however, also raises significant emotional issues that should be addressed beforehand.

Given the hazards of multiple births, parents must make some hard decisions if the treatment produces multiple embryos. The choices are limited:

Carry all of them to term, which increases health risks for both the mother and the developing fetuses
Complete abortion
Embryo reduction, in which the doctor removes one or more embryos (possibly endangering the remaining embryos)

At this time, the best approach is to limit the number of implanted embryos in the first place. Experts are attempting to develop methods to reduce the risk for multiple births:

Most centers now implant two to three embryos at a time, and the remainder can be frozen for future use. (Frozen eggs do not appear to pose a risk for developmental problems in children conceived using them.) This limits the chance for success, but implanting more than three embryos only increases success rates very slightly, whereas the risk for multiple births increases significantly.
Reducing the dosage of fertility drugs also reduces the risk for multiple births, but not significantly and it too reduces the chance for successful outcome.
Blastocyst transfer may help reduce the chances for multiple births.

Other Treatments

Hormone therapy has been effective for women with infertility problems, but has been disappointing in men except in a few specific cases:

Gonadotropin-releasing hormone (GnRH) is often very helpful in restoring fertility in men with gonadotropin deficiency and hypogonadism.
GnRH may be useful for restoring sperm production after chemotherapy treatments.
Sperm production occasionally responds to low doses of estrogen and testosterone or testosterone alone, menotropins (Pergonal, Repronal), clomiphene citrate (Clomid), human chorionic gonadotropin (hCG), or human follicle-stimulating hormone (r-hFSH, Gonal-F).
Prolonged treatment with follicle-stimulating hormone (FSH) prior to intracytoplasmic sperm injection (ICSI) may improve implantation rates.
Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many major body tissues. These drugs include anastrozole (Arimidex) and letrozole. (Femara). They may be helpful for specific men whose infertility is associated with abnormal testosterone-to-estrogen ratios.

Bromocriptine. Bromocriptine (Parlodel) is used in men whose infertility is related to excess prolactin manufactured by the pituitary.

Antibiotics. Infections interfering with fertility may be successfully treated with antibiotics.

Mast Cell Blocking Antihistamines. Studies report that certain antihistamines that block mast cells may be beneficial for some men with low sperm counts. Mast cells are inflammatory immune factors that may play a role in lower sperm quality. Studies have reported that two such drugs used overseas, ebastine and tranilast, improved pregnancy rates. Similar antihistamines in the U.S. are fexofenadine (Allegra), loratadine (Claritin), and cetirizine (Zyrtec).

Repair of a varicocele (varicocelectomy) in men with infertility problems is a common surgical practice. Nevertheless, although many urologists favor varicocele repair, the few well-conducted studies on this procedure suggest that it does not improve the chances for a successful pregnancy. Some experts argue that such studies were not using the most advanced techniques, which may be more effective. Some studies report that repair may improve the success rate of assisted reproductive technologies, such as intrauterine insemination (IUI). Still, the overall benefits remain uncertain, and additional rigorous trials are needed. In any case, the procedure does not appear to be beneficial for improving fertility in men whose varicoceles are very small.

Varicocele repair for fertility is sometimes considered when the following conditions are met:

When the varicocele can be felt during a physical examination.
Surgical treatment of varicoceles may be important in boys and adolescents to prevent later testicular damage.
When the male partner with varicoceles has abnormal semen quality or abnormal sperm function test results.
When the couple has known infertility, and the man has varicoceles but the woman is either fertile or can be treated for her infertility.

Varicocelectomy. Varicocelectomy, the standard repair procedure, involves tying off the swollen and twisted veins. Recovery takes 6 days, and most men cannot resume full activity for about 3 weeks. This technique eliminates 90% of varicoceles.

Recent surgical techniques use laparoscopy, which only requires tiny incisions (less than an inch). This approach allows for quicker recovery, although the procedure itself takes longer. It also has a higher rate of complications than the standard approach.

Varicocele Embolization. A nonsurgical technique called varicocele embolization may eventually prove to be an effective and less painful treatment for varicoceles, including those in young boys. It involves inserting a narrow tube (catheter) through a small incision in the neck or leg. Tiny steel plugs are passed through the catheter to block off the affected veins. The procedure takes 15 - 45 minutes to perform and uses local anesthetic. Some studies suggest that recurrence occurs in more than 10% of men, often requiring conventional surgery. This procedure is not yet widely available, and it may not be appropriate for some men.

Men with retrograde ejaculation and failure of emission caused by surgery, severe disease, or spinal cord injury are treated with various methods.

Drugs known as alpha-adrenergic agonists, including pseudoephedrine (Sudafed, Actifed), stimulate muscle contraction and help ejaculation. The tricyclic antidepressant imipramine (Tofranil) has similar effects, and in one analysis of 35 studies was more effective than pseudoephedrine. Promising investigational drugs include amezinium, which increases blood pressure.
If drugs are not effective, a technique called electrovibration (or electrical stimulation) is often beneficial. (Drugs in any case are not helpful for men with complete failure of emission.)

With any of these methods, the sperm can be collected for intrauterine insemination or assisted reproductive techniques. Spontaneous conception is possible, but not common, even with these treatments.

To prepare sperm for in vitro fertilization (IVF), men with retrograde ejaculation typically use sodium bicarbonate four times a day to reduce the acidity of the urine. After ejaculation, the man urinates or has a catheter (a tube) inserted to withdraw urine, which is then submitted for washing techniques to separate out the sperm.

Procedures that assist ejaculation are helping men with spinal cord injury conceive children. Vibratory or electronic stimulation is proving to be very beneficial for many of these men. The sperm retrieved using these methods are inserted into the women using self-insemination, intrauterine insemination, in vitro fertilizaiton, or intracytoplasmic sperm injection. Nearly a third of couples achieve pregnancy, a success rate that approaches natural conception.

Vasovasostomy. For men who wish to conceive after vasectomy, reversal surgery (vasovasostomy) may restore fertility. In vasovasostomy the severed ends of the vas deferens (which were cut during vasectomy) are reconnected to reestablish the flow of sperm. The reversal procedure is difficult. It involves sewing together the two ends of both tubes, each with pinhead sized openings. [See In-Depth Report #37: Vasectomy and vasovasostomy.]

Pregnancy Rates After Vasovasostomy. An Australian study reported that pregnancy rates in the late 1990s after reversal surgery were nearly four times higher than they were in the early 1980s. Pregnancy rates of over 50% are now being reported after a vasovasostomy. One study indicated that when successful conception occurs, it does at an average of 1 year after the surgery.

A successful reversal is more likely if the following conditions are present:

The section removed during vasectomy was not long
The original procedure was performed on straight sections of the vas deferens
The pieces joined during the vasovasostomy are of equal size

Reversal Versus Assisted Reproductive Technologies. Even though newer techniques such as ICSI are improving pregnancy rates after vasectomy, vasovasostomy is still a better choice than assisted reproductive technologies (ART) for most men who want children.

Success rates with reversal surgeries are improving, and the costs are lower than with ART. In addition, a vasovasostomy does not pose a risk for multiple births. In one study, the pregnancy rate for vasovasostomy was 52%, whereas success after intracytoplasmic sperm injection (ICSI) was 25 - 30% (ICSI is the ART treatment of choice for men who have had vasectomy). Even for men who have failed vasovasostomy, a repeat procedure appears to be less expensive than embarking on fertility treatments at that time.

Surgical Treatment of Obstructions. Obstructions in the area of the ejaculatory ducts have been successfully treated by excising or scraping the area where the prostate gland surrounds the urethra and by reconstructing the ducts.

Correcting Undescended Testicles. Undescended testicles of young boys may be repositioned surgically to prevent later infertility. It is important to perform the operation before 15 - 18 months of age to prevent the destruction of most of the sperm-producing cells, which occurs if the testicles remain in the abdomen.

Stem Cells. Researchers are investigating using sperm stem cells to treat male infertility. The research is still in its earliest stages. In 2004, researchers announced that they had successfully grown sperm progenitor cells in the laboratory. These types of cells could potentially develop into sperm cells capable of fertilizing an egg. This discovery was an important first step for developing stem cell infertility treatments.

Resources

www.resolve.org -- National Infertility Association
www.asrm.org -- American Society for Reproductive Medicine
www.urologyhealth.org -- American Urological Association
www.afafamilymatters.com -- American Fertility Association
www.ssmr.org -- Society for the Study of Male Reproduction
www.sart.org -- Society for Assisted Reproductive Technology
www.cdc.gov/ART/index.htm -- Centers for Disease Control: Assisted Reproductive Technology Report

References

Jain T, Gupta RS. Trends in the use of intracytoplasmic sperm injection in the United States. N Engl J Med. 2007 Jul 19;357(3):251-7.

Travison TG, Araujo AB, O'Donnell AB, Kupelian V, McKinlay JB. A population-level decline in serum testosterone levels in American men. J Clin Endocrinol Metab. 2007 Jan;92(1):196-202. Epub 2006 Oct 24.

Zhu JL, Basso O, Obel C, Bille C, Olsen J. Infertility, infertility treatment, and congenital malformations: Danish national birth cohort. BMJ. 2006 Sep 30;333(7570):679. Epub 2006 Aug 7.

Review Date:
10/17/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Smoking

FitSugar — Wed, 08 Oct 2008 17:34:57 -0700

In This Report

Highlights
Introduction
Nicotine Addiction
Health Risks
Secondhand Smoke
Smoking Bans
Quitting Smoking
Symptoms of Withdrawal
Failure to Quit
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Smoking and Your Health

Smoking may worsen knee osteoarthritis in men. A study published in the Annals of Rheumatic Disease found that male smokers have more pain and cartilage loss than men who do not smoke. Previous studies have not found such a link.
Smoking greatly increases the risk of age-related macular degeneration. An Australian study reports that smokers are four times more likely to develop the eye condition than those who have never smoked. Smokers also developed the condition at an earlier age.
Analysis of several studies suggests that smoking cigarettes and, in some cases, cigars or pipes, may reduce the risk of Parkinson's disease. However, smoking causes many other serious health conditions and should not be considered a means for preventing Parkinson's.
A small study suggests that infants who are breastfed just after their mother smokes sleep less than those whose mothers did not smoke.

Smoking Cessation

Certain genes may make it easier for you to quit smoking. Researchers at Duke University have identified more than 200 genes that distinguish those who have successfully kicked the habit. It is the first time such genes have been identified. The findings could lead to new smoking cessation therapies that target a person's specific genetic makeup.

Smoke Free Zones

More and more households in the United States are banning smoking. The U.S. Centers for Disease Control and Prevention (CDC) reports that 75% of households now forbid smoking at any time or place in the home.

Smoking in the Movies

Teens who see actors smoke on screen are more likely to become established smokers, according to an updated study in the Archives of Pediatric Adolescent Medicine. Study authors say the likelihood of smoking increases with exposure to movies that depict such behavior.

Introduction

More than 20% of adults in the United States smoke, according to a 2006 report by the U.S. Centers for Disease Control and Prevention (CDC). More than 80% of them smoke every day. Although smoking had steadily declined among adults in recent years, the trend now appears to have stalled. Between 2004 and 2005, the CDC says there was no observable change in smoking rates among U.S. adults.

The addictive effects of tobacco have been well documented. Tobacco is considered to be a mood and behavior altering substance that is psychoactive and abusable. Tobacco is believed to be as potentially addictive as alcohol, cocaine, and morphine. Tobacco and its various components increase the risk of cancer (especially in the lung, mouth, larynx, esophagus, bladder, kidney, pancreas, and cervix), heart attacks, strokes, and chronic lung disease.

The younger children start smoking, the more likely they will smoke as an adult. Smoking is often immediately addictive. According to the American Cancer Society, the earlier you start smoking, the more likely you are to develop long-term nicotine addiction.

In the past, advertising was responsible for encouraging some teens to smoke. New regulations have made it much more difficult for advertisers to promote smoking to young people. However, scenes that show people smoking are still common in movies and television shows, often in a positive light. This may be a major influence on the attitude toward smoking in children and adolescents. An updated study in the Archives of Pediatric Adolescent Medicine found that adolescents that watch movies that portray smoking are more likely to become established smokers.

To prevent children from smoking, parents should not smoke, and they should tell their child that they disapprove of smoking. Schoolchildren who believed that both their parents strongly disapproved of smoking were less than half as likely to smoke as those kids whose parents did not show as much disapproval towards smoking. Other research has supported these findings.

Children whose parents closely monitor their television and music-listening habits are less likely to drink, use drugs, and smoke cigarettes.

Neglected children, or children with absentee parents, were four times as likely to abuse drugs, drink, and smoke as children living with parents who were regularly present and who offered a structured lifestyle.

In a 2002 study, children who regularly attended religious services were also less likely to smoke.

Doctors can have a major effect on young people. However, in one survey, less than half of teenagers had ever been asked by their doctors if they smoked or were counseled not to smoke, even though most teen smokers said they would admit to it if asked.

More American men smoke than women. The following chart details the rate of current smoking in the United States among adults aged 18 years and over, grouped by age and sex:

Age	Total	Men	Women
18 - 44 years	24.1%	27.1%	21.2%
45 - 64 years	21.9%	25.2%	18.8%
65 years and older	8.6%	8.9%	8.3%

Source: CDC/National Health Interview Survey 2005

While the number of adults over 65 who smoke is lower than those in other age groups, older adults usually have smoked for a long time (about 40 years) and tend to be heavier smokers, according to the American Lung Association. Because of this, older smokers are more likely to have smoking-related illnesses.

Caucasian students (under age 18) are more likely to smoke than Hispanics and African-Americans. In 2005, the rate of smoking was highest among American Indians and Alaskan natives. Hispanics and Asians had the lowest rates.

In general, the rate of smoking is highest in the Midwest and South and lowest in the Northeast and West. Utah has the lowest rate of smoking in the United States.

A major U.S. government study reported that people who have not graduated from high school or received their General Education Development (GED) certificate tend to have higher smoking rates than those who attended college.

Higher rates of cigarette smoking have been reported among adults who have earned a GED and those with a 9 – 11 grade education. The lowest rates are seen among those with advanced college degrees.

People with low self-esteem and adolescents with behavioral problems have a higher risk for smoking. Men and women with mental disorders are 50% more likely to smoke than those without such illness.

For example, depression and schizophrenia are known risk factors for smoking. Both may actually have biologic effects that are responsible for this higher risk.

Smoking is much more common among persons with disabilities than those without emotional, mental, or physical limitations. A 2007 Centers for Disease Control study found that the rate of smoking is nearly 50% higher among persons with disabilities. The CDC survey included those with mental illness and drug and alcohol addictions in the disabled group.

Evidence now strongly supports the idea that genes play a role in a person's dependence on nicotine. Researchers are now targeting specific genes that may be responsible for nicotine dependence. So far, research has been shown that there is a common genetic vulnerability to both nicotine and alcohol dependence.

Some studies suggest that the cheaper it is to buy cigarettes and smoke, the more widespread smoking will be. For example, states that have low taxes on cigarettes have a high proportion of smokers. Making it more expensive to smoke may reduce the number of smokers.

Nicotine Addiction

Nicotine is the chemical in cigarettes that makes them addictive. Higher levels of nicotine in a cigarette can make it harder to quit smoking. A report by the Massachusetts Department of Health found that the amount of nicotine in cigarettes has steadily increased over the last 6 years. Higher nicotine levels were found in all cigarette categories, including “light" brands. Massachusetts is one of several states that require tobacco manufacturers to submit yearly reports regarding cigarettes.

Some researchers feel nicotine is as addictive as heroin. In fact, nicotine has actions similar to heroin and cocaine, and the chemical affects the same area of the brain.

Depending on the amount taken in, nicotine can act as either a stimulant or a sedative. Cigarette smoking has definite immediate positive effects. For example, it can:

Boost mood and relieve minor depression
Suppress little fits of anger
Enhance concentration and short-term memory
Produce a modest sense of well-being

Most smokers have a special fondness for the first cigarette of the day because of the way brain cells respond to the day's first nicotine rush. Nicotine, particularly taken in the first few cigarettes of the day, increases the activity of dopamine, a chemical in the brain that elicits pleasurable sensations, a feeling similar to achieving a reward.

Over the course of a day, however, the nerve cells become desensitized to nicotine. Smoking becomes less pleasurable, and smokers may be likely to increase their intake to get their "reward." A smoker develops tolerance to these effects very quickly and requires increasingly higher levels of nicotine.

A smoker may "forget" their craving for nicotine if a part of the brain called the insula becomes damaged. A 2007 study published in the journal Science found that smokers with brain damage to this area were 136 times more likely to forget their addiction to nicotine. The findings may one day lead to new drugs that better help a person quit.

Smokeless tobacco, also called spit tobacco, includes chewing tobacco (dip and chew), tobacco powder (snuff), as well as flavored tobacco lozenges. These products also contain nicotine. There are two forms of spit tobacco.

These products allow tobacco to be absorbed by the digestive system or through mucous membranes. Smokeless tobacco contains at least 28 cancer-causing substances. Smokeless tobacco is not a safe substitute for smoking cigarettes or cigars. According to the National Institutes of Health, chewing on an average-size piece of chewing tobacco for 30 minutes can deliver as much nicotine as smoking three cigarettes.

Although research is inconsistent, some evidence suggests that smokeless tobacco produces a 50-fold increase in the risk of oral cancer, gingivitis, and tooth loss.

Health Risks

Smoking -- even just a few cigarettes a day -- has been linked to many serious health risks. Some are listed below.

According to the American Lung Association, smoking is directly responsible for about 90% of the deaths due to lung cancer. Smoking is also responsible for the majority of deaths due to chronic obstructive pulmonary disease (COPD), which includes emphysema and chronic bronchitis.

A study in the July 2006 American Journal of Respiratory and Critical Care Medicine showed that smokers with asthma who give up smoking can improve their lung function in as little as 1 week. The small study involved 21 smokers with asthma. Ten of them quit smoking for 10 weeks, while the others continued to smoke. After just a week, lung function test scores in those who stopped smoking improved considerably. In less than 2 months, lung function scores among those who stopped smoking improved by more than 15%.

Study authors say their findings show that there is a “reversible component to the harmful effects of smoking on the airways in asthma.”

All forms of tobacco raise heart attack risk. Smoking, chewing tobacco, and being exposed to secondhand smoke greatly increase the risk of a heart attack. In some cases, the risk of heart problems in people who smoke or are exposed to smoke may be three times greater, according to a study published in the journal Lancet. However, the study also found that the risk of a heart attack among those who stopped smoking slowly decreased over time.

Smoking has a negative affect on a man's sexuality and fertility. Heavy smoking is frequently cited as a contributory factor in impotence because it decreases the amount of blood flowing into the penis. One study noted that among men with high blood pressure, smoking caused a 26-fold increase in impotence.

Smoking impairs sperm motility, reduces sperm lifespan, and may cause genetic changes that can affect a man's offspring. One 2002 trial found that men or women who smoke have lower success rates with fertility treatments. An earlier study reported that men who smoke also have lower sex drives and less frequent sex.

Studies have linked cigarette smoking to many reproductive problems. Continuing to smoke during pregnancy may also cause health problems in the baby.

Negative effects of smoking on female fertility include:

Greater risk for infertility. Women at greatest risk for fertility problems are those who smoke one or more packs a day and who started smoking before age 18.
Earlier menopause. Women who smoke tend to start menopause at an earlier age than nonsmokers, perhaps because toxins in cigarette smoke damage eggs.
Pregnancy complications. Women who smoke have a greater risk for ectopic pregnancy and miscarriage.

Click the icon to see an image of an ectopic pregnancy.

Effects on Unborn Child. Smoking during pregnancy increases the risk for stillbirth, prematurity, and low birth weight in their babies. Women who smoke during pregnancy have lower levels of folate, a B vitamin that is important for preventing birth defects.

Children of mothers who smoke during pregnancy may also be at increased risk for obesity and diabetes.

Some women have particular genes that may make them especially likely to deliver low birth weight infants if they smoke, although newborns of all female smokers have a greater risk for low weight. The good news is that women who quit before becoming pregnant or even during the first trimester reduce the risk for a low birth weight baby to that of women who never smoked.

Women who want to become pregnant should make every attempt to quit and should use smoking cessation aids before they try to conceive. After birth, if new mothers cannot quit, they should at least be sure not to smoke in the same room as their infant.

Smoking and Breastfeeding. Smoking right before breastfeeding may interrupt the child's sleep patterns. A small study found that such infants sleep less than other infants, and that their sleep time dropped significantly as levels of nicotine in breast milk increased.

Smoking has many harmful effects on bones and joints:

Smoking can keep new bone from forming. Women who smoke are at high risk for loss of bone density and osteoporosis.

Click the icon to see an image of osteoporosis.

Postmenopausal women who smoke have a significantly greater risk for hip fracture than those who do not.
Men who smoke may have more severe symptoms of knee arthritis, according to a study published in the Annals of Rheumatic Disease.
Smokers are more apt to develop degenerative disorders and injuries in the spine.
Smokers have more trouble recovering from surgeries, including knee or hip replacements. A 2006 study published in the Journal of Bone & Joint Surgery suggests that smoking delays tendon-bone healing, which may lead to a slower recovery after rotator cuff repair surgery.
Smokers whose jobs involve lifting heavy objects are more likely to develop low back pain than nonsmokers.
Smoking may increase the risk of rheumatoid arthritis in some older women. A 2006 study in Annals of the Rheumatic Diseases showed that smoking nearly doubled the risk of rheumatoid arthritis in postmenopausal women who did not have the most established genetic risk factor for the disease, a genotype called HLA-DRB1 SE.

Click the icon to see an image of rheumatoid arthritis.

Smoking may increase the risk of developing diabetes. Researchers involved in the Insulin Resistance Atherosclerosis Study (IRAS) looked at the relationship between smoking and diabetes and found that 25% of smokers who started the trial with normal blood sugar had diabetes 5 years later compared to 14% of nonsmokers. The results were published in Diabetes Care.

A study released in 2006 supports earlier beliefs that smokers have a higher risk of developing glucose intolerance, a condition that precedes diabetes. The study, published in the British Medical Journal, involved 4,572 people. The findings suggest that chemicals in smoke could affect the pancreas. The pancreas is the organ that produces insulin, which helps control blood sugar (glucose) levels.

Smoking increases acid production in the stomach. It also reduces blood flow and production of compounds that protect the stomach lining.

Diverticulitis. One study suggested that smoking was a major risk factor in diverticulitis, a condition in which small bumps develop in the wall of the colon. In addition, smokers were at risk for complications from diverticulitis, including bleeding and abscess. Diverticulitis mostly affects people over age 50.

Inflammatory Bowel Disease. Smoking has mixed effects on inflammatory bowel disease. Inflammatory bowel disease is the collective term for ulcerative colitis and Crohn's disease. Smokers have been shown to have lower than average rates of ulcerative colitis, but higher than average rates of Crohn's disease. Smokers with Crohn's disease who quit are said to have less severe symptoms.

Click the icon to see an image of inflammatory bowel disease.

Peptic Ulcers. Results of studies on the effect of smoking on ulcers are mixed. Some evidence suggests that smoking delays the healing of gastric and duodenal ulcers. One study reported that after ulcers healed, about half of smokers relapsed after a year, and that all heavy smokers relapsed after 3 months. Other studies, however, have found no increased risk for ulcers in smokers. Smoking does not appear to increase susceptibility to Helicobacter pylori (H. pylori), the bacteria that causes many peptic ulcers.

Click the icon to see an image of peptic ulcers.

Hepatitis and Cirrhosis. Smoking is linked to increased liver scarring (cirrhosis) caused by either excessive drinking or chronic hepatitis B or C viruses.

Cyanide, a chemical found in tobacco smoke, interferes with thyroid hormone production. Smoking triples the risk for developing thyroid disease, particularly hyperthyroidism and hypothyroidism. Women smokers with subclinical hypothyroidism (a symptom-free condition in which the thyroid gland is mildly underactive) have a higher risk for developing full-blown hypothyroidism than their nonsmoking peers. Smoking has also been linked to goiter, a swelling of the thyroid that occurs in people who do not get enough iodine.

Click the icon to see an image of the thyroid.

Smokers are at increased risk for heart and circulatory problems and delayed wound healing after surgery. In one study, patients who were able to cut down or quit smoking 6 - 8 weeks prior to knee or hip replacement surgery were much less likely to suffer complications.

The following age-related conditions occur at higher rates in smokers than nonsmokers:

Cataracts. Quitting smoking reduces your chances of needing cataract surgery in the future, although not to the level seen with nonsmokers.

Click the icon to see an image of a cataract.

Age-related macular degeneration (AMD). AMD is a leading cause of blindness in older people. An Australian study, published in 2007 found that the condition is four times more likely in persons who smoke than those who have never done so. Symptoms of macular degeneration include a loss of central vision, which makes it difficult to read.
Gum disease and tooth loss. A government study found that more than half of the cases of severe gum disease in adults in the United States may be due to cigarette smoking.
Wrinkles. Studies confirm that smokers are nearly five times more likely to develop more and deeper wrinkles as they age compared to nonsmokers.
Baldness and premature gray hair. Certain chemicals in smoke break down in hair cells, which leads to hair damage.
Hearing loss, particularly high-frequency hearing loss. Some experts believe that losing the ability to hear high pitched sound in smokers may be due to a decrease in blood flow to the cochlea, the part of the ear that carries sound to the brain.
Incontinence. One study of 600 women indicated that smokers and former smokers are twice as likely to develop incontinence as women who never smoked.

Secondhand Smoke

Secondhand smoke is produced by a burning cigarette or other tobacco product. An estimated 4 million children a year get sick from being around secondhand smoke. Parental smoking has been shown to affect the lungs of infants as early as the first 2 - 10 weeks of life, and such abnormal lung function could persist throughout life.

Exposure to secondhand smoke in the home increases the risk for asthma and asthma-related emergency room visits in children who have existing asthma.

Parental smoking is believed to increase the risk for lower respiratory tract infections (such as bronchitis or pneumonia) by 50%. Environmental exposure to smoke is thought to be responsible for 150,000 - 300,000 such cases every year.

Smoking Bans

Smoking bans have spread across the country. By October 2007, at least 22 states and the District of Columbia have passed some type of law banning smoking in almost all public places and workplaces, including restaurants and bars. The date an individual state's ban takes effect varies greatly; some do not take effect until 2008 or 2009.

As of January 1, 2006, nine states were considered "smoke-free" -- California, Connecticut, Delaware, Massachusetts, Maine, New York, Rhode Island, Vermont, and Washington.

Quitting Smoking

It's never too late to quit smoking. According to the American Cancer Society, about half of all smokers who keep smoking will die from a smoking-related disease. Quitting has immediate health benefits.


Time after last cigarette	Physical Response
20 minutes	Blood pressure and pulse rates return to normal.
8 hours	Levels of carbon monoxide and oxygen in the blood return to normal.
24 hours	Chance of heart attack begins to decreases.
48 hours	Nerve endings start to regrow. Your ability to taste and smell increases.
72 hours	Bronchial tubes relax and the lungs can fill with more air.
2 weeks to 3 months	Improved circulation; lung function increases up to 30%.
1 to 9 months	Decreased rates of coughing, sinus infection, fatigue, and shortness of breath; regrowth of cilia in the airways, increasing the ability to clear mucus and clean the lungs and reducing the chance of infection; overall energy level increases.
Long-Term Effects	After a year, the risk of dying from heart attack and stroke is reduced by up to 50%.

According to the National Institutes of Health, about 40% of smokers who want to quit make a serious attempt to do so each year, but fewer than 5% actually succeed. A June 2006 report published by the NIH says that the available smoking cessation products and therapies are greatly underused. If more smokers asked for or were offered such help, the agency says quit rates could double or triple.

Some people have certain genes that make quitting easier. Researchers at Duke University have identified more than 200 genes that distinguish those who have successfully kicked the habit. It is the first time such genes have been identified. The findings could lead to new smoking cessation therapies that target a person's specific genetic makeup.

Methods of quitting smoking include counseling and support groups, nicotine patches, gums, lozenges, and sprays, smoking cessation pills, and slowly cutting back on the number of cigarettes smoked (incremental reduction).

About 4% of smokers who quit without any outside help succeed. Nevertheless, most people try to quit alone, and many have reported activities that can help the process of withdrawal. The primary obstacle in trying to quit alone is making the behavioral changes necessary to eliminate the habits associated with smoking. Excellent books, tapes, and manuals are available and are strongly recommended to help people who want to quit without other assistance.

Nicotine replacement therapy involves the use of products that provide low doses of nicotine that do not contain the contaminant found in smoke. The goal of therapy is to relieve cravings for nicotine and ease the symptoms of withdrawal.

In general, nicotine replacement therapy benefits moderate-to-heavy smokers the most. However, it does appear somewhat helpful for light smokers (people who smoke fewer than 15 cigarettes a day).

Nicotine Patches. Nicotine patches deliver nicotine through the skin. This is called transdermal nicotine delivery. It is effective in reducing symptoms during withdrawal. Nicotine patches are available over the counter.

Patches may work in different ways:

Step-Down Approach. Patches that use this method include NicoDerm CQ. The patches come in three strengths (21, 14, and 7 mg). You use the strongest dose first and reduce it gradually over a period of 8 - 10 weeks. A 21 mg patch is about equal to 15 cigarettes. A heavy smoker may need to wear two patches at first.
Single-Step Approach. The single-step patch (Nicotrol) can be taken off after 16 hours and replaced 8 hours later. It can be used for only 6 weeks.

Patches are applied and used in similar ways:

A single patch is worn each day and replaced after 24 hours.
To avoid skin irritation it is applied to different hairless locations above the waist and below the neck each day.
People can wear the patches for 24 hours, but some have reported odd dreams and have disliked the sensation of the patch during the night. People who wear the patch all the time, however, have fewer withdrawal symptoms and slightly better abstinence rates than those who take it off at night.
Patches should be stored and discarded safely, particularly in homes with small children. Small children have been poisoned and gotten sick from wearing, chewing, or sucking on nicotine patches. There have been no reports of death from children who have been poisoned.
The FDA recommends using the patches for 3 - 5 months, although some studies suggest that using them for 8 weeks achieves the maximum benefits.

Children should not come in contact with the patches, even while the smoker is wearing them. If the child has worn the patch, the affected skin should be washed right away. Urgent medical care may be required if the child has eaten nicotine or worn a patch for a prolonged time.

Nicotine Gum. Nicotine gum (Nicorette) is available over the counter and has helped many people quit. Some prefer it to the patch because they can control the nicotine dosage, and chewing satisfies the oral urge associated with smoking.

Tips for using the gum:

If you are just starting to quit, chew 1 - 2 pieces each hour. A smoker should not chew more than 20 pieces a day.
The goal is to stop using the gum by 6 months, but about 3% of people continue to use it long after they have quit smoking.
The gum must be chewed slowly until it develops a peppery taste. It is then tucked between the gum and cheek where it is stored so that the nicotine can be absorbed.
Coffee, tea, soft drinks, and acidic beverages may interfere with nicotine absorption, so people should wait at least 15 minutes after drinking before chewing a piece of gum.

Some people prefer other methods or cannot use the gum for the following reasons:

They find the gum unpleasant tasting.
Side effects specific to the gum may include upset stomach, mouth ulcers, hiccups, and throat irritation.
They are embarrassed by chewing gum.
They wear dentures.

Long-term dependence may be a problem with the gum. Although such dependence is probably safer than smoking, research is needed to confirm this, and experts recommend people chew gum for no more than 6 months.

The Nicotine Inhaler. The nicotine inhaler resembles a plastic cigarette holder. It comes with a number of nicotine cartridges, which are inserted into the inhaler and "puffed" for about 20 minutes, up to 16 times a day. The dose is gradually decreased. It requires a prescription in the United States. Several studies have reported that the inhaler triples abstinence rates (between 17 - 28%) compared with placebo (6 - 9%) after 6 months. It has some specific advantages over other nicotine replacement products:

The inhaler provides varying doses of nicotine on demand (as opposed to continuously with the patch or the gum) and is relatively fast-acting. Blood nicotine levels peak about 20 minutes after using the inhaler, comparable to the gum and faster than the 2 - 4 hours seen with the patch.
It satisfies oral urges.
Most of the nicotine vapor is delivered in the mouth, not into the lung airways (although some people experience mouth or throat irritation and cough).

Using a combination of the inhaler and the patch may be particularly effective. In one study, the combination led to an abstinence rate of over 60% after 6 weeks. While this percentage dropped off over time, it was still a large improvement over the use of the inhaler and a placebo patch.

The Nicotine Nasal Spray. The nasal spray satisfies immediate cravings by providing doses of nicotine rapidly and thus may play a useful role in conjunction with slower-acting nicotine replacement therapies. (Nicotine levels peak within 5 - 10 minutes after administering the spray). The spray can irritate the nose, eyes, and throat, so it may not be suitable for those with allergies or sinus infections. Most people, however, can tolerate the side effects, which usually go away within the first few days.

Nicotine Lozenge. A nicotine lozenge (Commit) is available over the counter. It is made from pressed tobacco and comes in two strengths for heavier or lighter smokers. In a large 2002 study, 15 - 18% of smokers who used it remained smoke free, compared to 6 - 10% who were given a dummy lozenge. Side effects included heartburn, hiccups, nausea, headaches, and cough. The Commit lozenge also contains phenylalanine, a chemical that certain people may need to avoid.

Facts about Nicotine Replacement Therapy:

Not cheating on the very first day of nicotine-replacement use increases the chance of quitting permanently by tenfold.
The more cigarettes a patient smokes, the higher the dose of nicotine replacement may be required at the start.
Adding a counseling program may boost the effect of any nicotine replacement program.
Do not smoke while using nicotine replacement. It can cause nicotine to build up to toxic levels.
Nicotine replacement helps prevent weight gain while it is being used, but people are still at higher risk for gaining weight when they stop all nicotine.

Side Effects. Side effects of any nicotine replacement product may include headaches, nausea, and other gastrointestinal problems. People often experience sleeplessness in the first few days, particularly with the patch, but the insomnia usually passes. Patients using very high doses are more likely to have symptoms. Reducing the dose can prevent them.

Special Concerns for Specific Individuals. There has been some concern that the patch might be harmful for people with heart or circulatory disease, but studies are finding that it poses no danger for these individuals. In fact, it may help reduce angina attacks brought on by exercise. However, unhealthy cholesterol levels (lower HDL levels) caused by smoking remain abnormal with use of the nicotine patch. HDL levels improve when all nicotine is stopped.

Nicotine replacement may not be completely safe in pregnant women, although it has been used successfully in this group without ill effect. There is an increase in heart rates in unborn children of women who use the patch as compared with those who smoke.

Keep all nicotine products away from children. Nicotine is a poison. All nicotine products should be kept safely away from small children. A parent should call a physician or a poison control center immediately if a child has been exposed to a nicotine replacement product, even for a short duration. Parents should also call the doctor if a small child has been exposed to a nicotine product and has any symptoms, including stomach upset, irritability, headaches, a rash, or fatigue.

Warnings Against Long-Term Use. No one should use nicotine replacement therapies as a long-term substitute for smoking. Any nicotine replacement therapy should be temporary. In one study, use of nicotine gum for more than a year was associated with insulin resistance, an abnormality that occurs in diabetes. Some studies have now suggested that nicotine itself may have properties that increase the risk for cancer, independent of carcinogenic chemicals in smoke. More studies are needed.

Bupropion (Zyban, Wellbutrin) is a type of antidepressant that is also an FDA-approved product for smoking cessation. It differs from most other antidepressants because it increases the effects of dopamine, the brain chemical that appears to play a strong role in nicotine addiction. Using Zyban along with nicotine replacement therapy may help you better control cigarette smoking cravings. Zyban does not contain nicotine. In most cases, Zyban is taken a week or two before quitting, and must be taken for 7 - 12 weeks. The usual maintenance dose is 150 mg tablet twice a day. No single dose should be higher than 150 mg.

Side effects of bupropion include gastrointestinal problems, headaches, insomnia, dry mouth, and irritation. In very rare cases, seizures have occurred, although usually in people who exceeded the recommended dose or who already had risk factors for seizures.

A newer drug called varenicline (Chantrix) may significantly reduce cigarette cravings and work better than Zyban. A study in the Archives of Internal Medicine found that almost 50% of those who took varenicline successfully quit. Varenicline mimics some effects of nicotine on the brain, but blocks others. Previous studies published in the Journal of the American Medical Association showed that Chantrix works twice as well as Zyban and quadruples one’s chances of successfully quitting. The FDA approved Chantrix as a smoking cessation aid in May 2006. It is for use in cigarette smokers age 18 and older. It should not be combined with nicotine replacement therapy.

The tricyclic antidepressant nortriptyline (Pamelor, Aventyl) may help reduce nicotine action. Quit rates with either of these medicines are as high as 30%. Long-term abstinent rates are more than twice those of placebo. Most other antidepressants, including fluoxetine (Prozac), have no additional benefits for smokers.

Nortriptyline has been specifically studied for helping smokers. It is best to start taking the medication 10 - 28 days before your intended quit date. Studies have reported quit rates of 14 - 24%. Side effects of nortriptyline include dry mouth and changes in taste. It should be noted that in rare cases, tricyclics can have serious side effects, and overdose can be deadly. Tricyclics may pose a danger for some patients with certain types of heart disease.

Smokers who use outside help have the best record for quitting, with success rates of 25 - 35%. Those who are counseled in addition to using nicotine replacement and Zyban have the best chance. Brochures, audio tapes, and other self-help materials are often ineffective when used alone, but may be helpful in conjunction with a counseling program.

Types of behavioral approaches:

Problem Solving or Coping Strategies. Smokers more likely to quit smoking when they learn thinking (cognitive) and behavioral techniques for breaking the link between certain cues and smoking, stress management techniques, and ways to handle the symptoms of withdrawal and the urge to relapse. The more intense the counseling program, the better. Smokers should look for programs that offer the following:

Session lengths of 20 - 30 minutes
Four to seven sessions
A 2-week program
Additional 2 weeks or more of follow-up contact

Scheduled Reduction. Scheduled reduction is a gradual way to stop smoking.

Divide the number of minutes per day that you are awake by the number of daily cigarettes you smoke. The number you get is how long you wait between smokes.
Week 1: Set up a schedule with time intervals based on this result and using a timer, smoke only at those intervals. If the "cigarette appointment" is missed by more than 5 minutes, you must skip that cigarette.
Week 2: Reduce the number of cigarettes you smoke by one-third and recalculate your time between smokes based on the lower number.
Week 3: Reduce the count again.
Week 4: Quit smoking

Those who are unable to smoke during working hours could try calculating the intervals based on the usual smoking times of the day.

The Staged Approach. The intent of the staged approach is to plan quitting interventions customized for each individual rather than imposing some general method for quitting. The approach takes the smoker through six stages with behavioral interventions at each point:

Pre-contemplation
Contemplation
Preparation
Action
Maintenance
Termination

Although some studies report this approach is significantly more effective than non-staged methods, an analysis of 23 trials did not find the staged approach to be any more effective than other methods. Most studies, however, were weak, and better research is needed on this approach.

People who follow this approach do not proceed from one stage to another in a simple, step-by-step fashion. They actually cycle or spiral back and forth, so that they may move from stage 1 to 2 to 3, and then back to 2 again. They may stay in maintenance mode for years and then fall back to stage 2. Remember that this is normal -- if you tried quitting in the past and didn't stick with it, don't consider yourself a failure. Just try again.

Stage 1: Pre-Contemplation.

People at this stage have no plans or desire to stop smoking. They aren't even considering quitting. People at this stage are generally unaware of the specific benefits that quitting can bring. Or, they may simply have "failed" in the past and have given up. There's no point in talking about how to start a cessation program at this stage. Instead, it is important to think about how quitting will help you feel better, have more confidence, or live longer. The benefits must be identified before a person will consider quitting. If you are at this stage, a good activity is to ask several friends or family members why they quit.

Stage 2: Contemplation.

A person at this stage is thinking, "I think I should probably quit, but I need help getting started." People at this stage know that quitting is good for them, but it seems like a daunting task or they don't think they can pull it off. Some may have tried and failed in the past. It's important for people at this stage to consider some of the truths and falsehoods of quitting. If you are at this stage, write down (brainstorm) all your potential roadblocks -- the things that you believe make quitting difficult -- and learn strategies for overcoming or side-stepping those hurdles. People at this stage might benefit from making a pledge, contract, or other commitment that they are going to get more active in the near future. The goal is to identify the roadblocks and ways to overcome these hurdles, and make a commitment to quitting.

Stage 3: Preparation.

Smokers at this stage are ready to quit. The goal of this stage is to create a specific action plan that takes all factors into account, so that quitting is successful. People at this stage need to know what methods work and what support exists to help them. If you are at this stage, you should consider some backup plans -- what to do when the urge to smoke hits you.

Stage 4: Action!

People at this stage have just quit. This stage is where the most behavioral change occurs. It requires significant commitment and energy. If you are at this stage, keep talking to friends and family for inspiration. Review your backup plans. Reward yourself for small achievements. Having a fellow smoker quit with you can be a huge support as you both get through this stage.

Stage 5: Maintenance.

People at this stage have been smoke-free at least 6 months. The goal now is to prevent relapse. If you are at this stage, continue to be wary of roadblocks and keep reminding yourself of the benefits you have gained. Think about what you have found most enjoyable about being smoke-free.

Hypnosis. Although rigorous studies are lacking, some people report successful cessation from smoking when hypnosis is given in individual sessions. The process is effective only if you trust the therapist and can feel completely at ease in the vulnerable and passive state necessary for hypnotic suggestion.

During a typical session, the hypnotherapist will use various techniques (such as imagery, silent counting) to put you in a relaxed state.

When you are very relaxed, but not asleep, the hypnotherapist quietly suggests motivations for not smoking. The hypnotherapist should also reinforce a positive self-image while you are in deep relaxation. This helps many people avoid the depression that accompanies withdrawal.

The sessions usually takes about 1 hour.

You should be taught methods of self-hypnosis to use at home, and follow-up once to reinforce what you've learned.

Acupuncture and Acupressure. The acupuncture technique for quitting smoking usually uses very tiny curved staples inserted into three different points around the edge of the ear. The procedure is painless. You will be told to press each staple in a certain order for a few seconds whenever the craving for a cigarette occurs. The acupuncturist may also use acupuncture points elsewhere on the body. There are no side effects except for some soreness if the acupuncture staple is pressed too hard.

A related technique called acupressure involves simply pressing select points on the body when a craving hits. Some studies have reported good quit rates with acupuncture, but few rigorous studies have been conducted using this approach.

Aim to Quit Completely

Everyone who quits should aim to quit completely. Most people who return to smoking "cheat" in the first few weeks. Quitting completely is essential to regain good health and reverse bad effects caused by smoking. Reducing smoking, even by half, does not eliminate the risk for cancer and other health problems. Although smokers take in less smoke and nicotine, the body is still unable to heal itself from the ongoing intake of toxins. It should also be noted that changing to low-tar cigarettes is not a solution. In fact, smokers of these cigarettes tend to inhale deeper, perhaps even increasing health risks.

Create a List

Write down 10 reasons to quit. In addition to health reasons, the list might include having better smelling hair, clothes, and breath; having fewer wrinkles; enjoying the taste of food; and saving money. Read the list often during the quitting process to help stay motivated.

Decide on a Specific Quit Date

Some people find it helpful to choose a particular date to quit when little or no stress is anticipated for at least the first 3 days. Women affected by PMS should avoid quitting right before their menstrual cycle. It may help to write out a quit contract, putting the date on paper, and getting a friend to sign it. Discard all smoking paraphernalia on the eve before the quit date, and make plans to stay busy on the day itself, and especially at night, when the urge to smoke will be high.

Make an Oath

Take an extreme oath. For example, "If I smoke one more cigarette my dog will die." Although this seems absurd, some people, even well-educated individuals, who have failed all other methods have reported that they quit completely and successfully after taking such an oath.

Let the Body and Mind Heal During Withdrawal

Retreat from the world when cravings become overwhelming. Take naps, warm baths or showers, meditate, or read novels.
Help your body get rid of nicotine. Drink plenty of water, eat fresh fruits, vegetables, whole grains, and fiber-rich foods. Carrots, apples, and celery are good munching foods.
When cravings occur, hold your breath as long as possible or take a few deep rhythmic breaths.
Use meditation or relaxation and deep breathing exercises. In fact, taking deep breaths when the urge to smoke occurs is a good stopgap measure.

Get Family and Friends Involved

Tell all your friends and family that you've already quit, so you'll be embarrassed if they catch you smoking.
Pay a family member or friend if they catch you smoking. The amount should be large enough ($5 - 20) to be a deterrent, but not so large as to be ridiculous.
If your partner or friend smokes, try persuading them to quit or, at the very least, not to smoke around you and others.

Exercise

Studies continue to show that smokers who exercise can greatly increase their ability to quit smoking while reducing their risk for weight gain. Move the muscles when cravings occur. Dance, run, walk, jump up and down, stretch, do push-ups. Yoga is an excellent exercise program for quitting. Older people and anyone with health problems should consult their health care provider before starting such a program.

Maintain a Healthy Diet

Eat plenty of fresh, crunchy fruits and vegetables. This is also a useful way of satisfying oral cravings without adding many calories.
Drink plenty of water and healthy beverages.
Moderate intake of coffee or tea may be helpful. A small study suggested that drinking caffeinated beverages (such as coffee or tea) while on nicotine replacement may enhance energy expenditure and may help prevent weight gain. Moderate coffee intake may also have antidepressant properties. Avoid caffeine in the evening, however, since sleep disturbances can be a problem during withdrawal.

Change Daily Habits

Change your daily schedule, particularly eating times, as much as possible. Eat at different times or eat many small meals instead of three large ones. Sit in a different chair or even a different room.
If you smoke after eating, find other ways to end a meal. Play a tape or CD, eat a piece of fruit, get up and make a phone call, or take a walk (a good distraction that burns calories as well). For example, if you normally have a cigarette with coffee, drink tea instead or use a different cup.
Substitute oral habits by eating celery, chewing sugarless gum, sucking on a cinnamon stick, or carrying worry beads.
Go to public places and restaurants where smoking is prohibited or restricted.
Set short-term quitting goals and reward yourself when they are met.
Every day put the money normally spent on cigarettes in a jar and buy something pleasurable at the end of a predetermined period of time.
Find activities that focus the hands and mind but are not taxing or fattening: Computer games, solitaire, knitting, sewing, whittling, and crossword puzzles.

Denormalization is the idea that smoking is no longer normal. This concept of denormalization is best instituted by laws and local regulations making smoking inaccessible in public places, raising prices, and putting stricter limitations on cigarette advertising.

Increasing taxes on cigarettes may be one of the most important methods for reducing smoking in the population, particularly in younger people.

Evidence is suggesting that banning smoking in work and public places may be leading to a higher quit rate than in places where smoking is permitted.

Denormalization can also work on a personal level. A British study showed that when one spouse makes healthy changes, including quitting smoking, the other one follows. In couples where smoking continues, it usually continues in both.

Symptoms of Withdrawal

After you quit smoking, you with have some withdrawal symptoms. Such symptoms generally peak in intensity 3 -5 days after you quit, and usually disappear after 2 weeks, although some may persist for several months.

The symptoms of withdrawal include both physical and mental difficulties.

Physical Symptoms.

Tingling in the hands and feet
Sweating
Intestinal disorders (cramps, nausea)
Headaches
Sore throat, coughing, and signs of a cold

Withdrawal symptoms should be treated accordingly, just as you would with physical symptoms due to an illness or disease.

Mental and Emotional Symptoms. Tension and craving build up during periods of withdrawal, sometimes to a nearly intolerable point. Nearly every moderate-to-heavy smoker experiences more than one of the following strong emotional and mental responses to withdrawal:

Temper tantrums, intense needs, feelings of dependency, and a state of near paralysis
Insomnia
Mental confusion, vagueness, or difficulty concentrating
Irritability, restlessness, impatience, or anger
Anxiety
Depression

The first signs of nicotine withdrawal seem to appear within 30 minutes of a smoker’s last cigarette. The findings, published in Psychopharmacology, are believed to be the first to show just how early nicotine withdrawal occurs. The study involved 50 people who smoked a pack of cigarettes daily. Half refrained from smoking for 4 hours, while the others smoked as usual. After 30 minutes, those who did not have a cigarette craved one and did more poorly on tasks requiring attention than those in the smoking group. Within 3 hours, the non-smoking group showed increases in anxiety, sadness, and difficulty concentrating.

Depression is common during withdrawal and over the long term. In the short term, it may mimic the feelings of grief felt when a loved one is lost. A smoker should plan on a period of actual mourning in order to get through the early withdrawal depression.

There is a significant association between cigarette smoking and a susceptibility to depression. People who are prone to depression face a 25% chance of becoming depressed when they quit smoking, and this increased risk persists for at least 6 months. What's more, depressed smokers have a very low level of success. Only about 6% remain smoke-free after a year. There are strong reasons for this:

Smoking may be masking depression, which can become severe even after the early stages of withdrawal have passed.
For some smokers, the future physical damage incurred by smoking is an abstraction, which fails to motivate quitting when measured up against the very real emotional pain triggered by nicotine withdrawal.
Not only does the smoker suffer, but the negative emotions often harm relationships with friends and family, who might even urge the ex-smoker to take up cigarettes again.

People who suffer from depression while quitting might do better using a combination of emotionally supportive therapy (as opposed to behavioral therapy), nicotine replacements, and antidepressants, such as bupropion (Zyban). If severe depression lasts beyond the withdrawal period, professional help should be sought as soon as possible.

Quitting smoking does increase the risk for weight gain. But, kicking the habit of smoking may cause more weight gain than previously thought. A study in Health Services Research found that the average weight gain among former smokers was about 21 pounds, rather than the 5 - 15 pounds commonly cited. But, fear of weight gain shouldn’t stop a person from quitting smoking. Instead, the study authors encourage weight-control measures after quitting. To come up with a new average, the scientists re-analyzed data from the 1998 Lung Health Study of 5,887 American smokers. That study found that those who quit smoking gained about 12 pounds.

Smoking uses up calories -- about 200 a day according to one study. Burning calories helps you lose weight. After quitting, the body's metabolism slows down, and food is digested better. Insulin levels increase, enabling the body to process more sugar for energy. When you quit smoking, you may snack more frequently.

How to Keep the Weight Off After Smoking. Exercise is very helpful in controlling weight. To burn the same amount of calories as you did while smoking, you need only take an extra 15-minute daily walk and eliminate 100 calories a day from meals. Just a moderate increase in physical activity can help keep weight gain to a minimum.

Nicotine replacement therapy can help protect against weight gain. See the section on "Quitting Smoking" in this report.

Failure to Quit

Biologic, psychological, behavioral, and cultural factors all play a role in nicotine addiction, making smoking one of the hardest addictions to beat. About half of people who quit return to smoking. Even after years of not smoking, some ex-smokers still have occasional cravings for cigarettes.

Some experts suggest that, in addition to depression, there are three major areas responsible for the inability to quit:

Mental performance. Nicotine improves concentration and thinking. Quitting smoking temporarily impairs one's mental performance.
Stress. Although smoking many not reduce stress, stopping certainly increases it.
Weight gain. Quitting smoking can cause you to gain weight. Studies are mixed on whether weight gain is permanent in most smokers or not. Certainly, it is a major factor in relapse. [See "Weight Gain" section in this report.]

How well a person does in the first 2 weeks is critical to their success. Smokers should not be shy about seeking all the help they can during this period. Although withdrawal symptoms can be intense, treatments are available to reduce them.

Attempts to quit are never a waste of time, since the amount of smoking is reduced during these periods. People who keep trying still have a 50 - 50 chance of finally quitting.

Researchers have been trying to discover individual risk factors or sets of behaviors that can help predict why specific people fail to quit. Some factors include:

Being female
Being a heavy smoker
Inhaling deeply
Being a long-term smoker
Having severe withdrawal symptoms

Among many studies, however, only one found a single consistent factor for failure to quit:

Cheating during the first 2 weeks of withdrawal, even with the patch, nearly guarantees that a person will smoke again in 6 months.

Studies show that women have a harder time trying to quit smoking and have less success with abstinence programs than men. There are many proposed reasons for this:

Nicotine has different effects on mood in women compared to men. Women who quit may have greater anxiety and stress than men who quit.
Women are not as physically dependent on nicotine as men, but they are more addicted to the actual behavior of smoking, which is the more powerful deterrent to quitting. This may be the reason why nicotine replacement, which only reduces cravings, tends not to be as effective in women.
Women may fear weight gain after quitting more than men.
Certain phases in the menstrual cycle may reduce the response to drugs that are used to help women quit smoking.
Men may be less supportive than women in helping their partners to quit.
Women trying to quit may miss the feeling of control associated with smoking more than men.

On the positive side, evidence suggests that when women quit, their lung function seems to improve more rapidly than in men who quit.

Lifestyle Changes

Smokers and former smokers should immediately begin to implement a healthier lifestyle and change any other behaviors that might be damaging their health.

Everyone should also maintain a healthy diet, with foods rich in whole grains and fruits and vegetables (particularly dark colored ones). Avoid saturated fats and instead choose monounsaturated fats, which are found in olive oil or fats from oily fish. Two studies have indicated that eating fish more than twice a week might help limit the tobacco damage in people who do not smoke more than a pack and a half a day.

Even with a healthful diet, however, smoking reduces the levels of a number of vitamins, importantly vitamin C. Some research suggests that supplementation of folic acid, a B vitamin, and the antioxidants vitamins E and C and selenium may improve lung function or reduce the damage done by cigarette smoke. Studies have shown that daily vitamin E supplements are associated with reduced risk for prostate cancer among smokers and that higher levels of vitamin E are linked to a lower risk for lung cancer. The best way of achieving healthy levels of important nutrients is from healthy foods.

Click the icon to see an image of the benefits of vitamin E.

Click the icon to see an image of the sources of vitamin E.

Women who are pregnant and continue to smoke must be sure to take appropriate vitamins, particularly folic acid. In this way, they might reduce the increased risk of fetal injury and death, although they do not eliminate that risk.

Regular exercise reduces a smoker's risk of heart disease (although still not to the level of a nonsmoker). Exercise does not lower a smoker's risk for lung cancer or emphysema.

If you smoke, you should be screened for any smoking-related disorders. Have your cholesterol and blood pressure checked regularly. Women should have annual Pap smears to detect cervical cancer. All older adults should be screened for colon cancer. Computed tomography (CT) screening programs, which are becoming increasingly available, may detect lung cancer at an early stage. Ask your health care provider if you should have this test, and if your insurance will cover it.

Resources

www.cancer.org -- American Cancer Society
www.lungusa.org -- The American Lung Association

References

Alati R, Al Mamun A, O'Callaghan M, Najman JM, Williams GM. In utero and postnatal maternal smoking and asthma in adolescence. Epidemiology. 2006 Mar;17(2):138-44.

Amin S, Niu J, Guermazi A, et al. Cigarette smoking and the risk for cartilage loss and knee pain in men with knee osteoarthritis. Ann Rheum Dis. 2007 Jan;66(1):18-22. Epub 2006 Dec 7.

Breslau N., Novak SP, Kessler RC. Psychiatric disorders and stages of smoking. Biological Psychiatry. 55(1):69-76, 2004.

Centers for Disease Control and Prevention (CDC). Tobacco use among adults -- United States, 2005. MMWR. 2006 Oct 27;55(42):1145-8.

Centers for Disease Control and Prevention (CDC). Annual smoking-attributable mortality, years of potential life lost, and productivity losses -- United States, 1997-2001. MMWR. 2005;54:625-628.

Centers for Disease Control and Prevention (CDC). State-specific prevalence of smoke-free home rules -- United States, 1992-2003. MMWR. 2007 May 25;56(20):501-4.

Chaudhuri R, Livingston E, McMahon AD, et al. Effects of smoking cessation on lung function and airway inflammation in smokers with asthma. Am J Respir Crit Care Med. 2006 Jul 15;174(2):127-33.

Dobson R. Smoking may increase abdominal obesity. BMJ. 2005 Sep 17;331(7517):596.

Eisenberg D, Quinn BC. Estimating the effect of smoking cessation on weight gain: an instrumental variable approach. Health Services Research. 2006 July 6; (early online version).

Galatz LM, Silva MJ, Rothermich SY, Zaegel MA, Havlioglu N, Thomopoulos S. Nicotine delays tendon-to-bone healing in a rat shoulder model. J Bone Joint Surg Am. 2006 Sep;88(9):2027-34.

Health, United States, 2005, with Chartbook on Trends in the Health of Americans. Hyattsville, Md. National Center for Health Statistics; 2005.

Hendricks P, Ditre J, Drobes D, Brandon T. The early time course of smoking withdrawal effects. Psychopharmacology. 2006;187(3): 385-396.

Houston TK, Person SD, Pletcher MJ, Liu K, Iribarren C, Kiefe CI. Active and passive smoking and development of glucose intolerance among young adults in a prospective cohort: CARDIA study. BMJ. 2006 May 6;332(7549):1064-9.

Linn-Rasker SP, van der Helm-van Mil AHM, van Gaalen FA, et al. Smoking is a risk factor for anti-CCP antibodies only in rheumatoid arthritis patients who carry HLA-DRB1 shared epitope alleles. Ann Rheum Dis. 2006;65:366-371.

Li YF, Langholz B, Salam MT, Gilliland FD. Maternal and grandmaternal smoking patterns are associated with early childhood asthma. Chest. 2005 Apr;127(4):1232-41.

Mennella JA, Yourshaw LM, Morgan LK. Breastfeeding and smoking: short-term effects on infant feeding and sleep. Pediatrics. 2007 Sep;120(3):497-502.

Naqvi NH, Rudrauf D, Damasio H, Bechara A. Damage to the insula disrupts addiction to cigarette smoking. Science. 2007 Jan 26;315(5811):531-4.

Nides M, Oncken C, Gonzales D, et al. Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up. Arch Intern Med. 2006 Aug 14-28;166(15):1561-8.

Oncken C, Gonzales D, Nides M, Rennard S, Watsky E, Billing CB, Anziano R, Reeves K. Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation. Arch Intern Med. 2006 Aug 14-28;166(15):1571-7.

Ritz B, Ascherio A, Checkoway H, et al. Pooled analysis of tobacco use and risk of Parkinson disease. Arch Neurol. 2007 Jul;64(7):990-7.

Sargent JD, Stoolmiller M, Worth KA, et al. Exposure to smoking depictions in movies: its association with established adolescent smoking. Arch Pediatr Adolesc Med. 2007 Sep;161(9):849-56.

Teo KK, Ounpuu S, Hawken S, et al. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study. Lancet. 2006 Aug 19;368(9536):647-58.

The Health Consequences Of Smoking: A Report Of The Surgeon General. Atlanta, GA: US Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, US Dept of Health and Human Services; 2004.

Tonnesen P, Mikkelsen K, Bremann L. Nurse-conducted smoking cessation in patients with COPD using nicotine sublingual tablets and behavioral support. Chest. 2006 Aug;130(2):334-42.

Uhl GR, Liu QR, Drgon T, Johnson C, Walther D, Rose JE. Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs. BMC Genet. 2007 Apr 3;8:10.

Wagena EJ, Knipschild P, Zeegers MP. Should nortriptyline be used as a first-line aid to help smokers quit? Results from a systematic review and meta-analysis. Addiction. 2005;100:317-326.

Review Date:
10/8/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

A.D.A.M. Copyright

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