Pregnancy

Q. What is infertility?

A. Infertility is a disease or condition of the reproductive system that interferes with the ability to conceive. It’s typically defined as not being able to get pregnant after having regular unprotected sex for one year. “Regular” is considered every few days when a woman is ovulating–the time of the month when one or more eggs are released from the ovaries. Couples may want to seek medical treatment sooner than the one-year mark if the woman is over 35 or if there is a history of irregular menstrual cycles or diseases of the reproductive system.Infertility also includes the inability to carry a pregnancy to term, as in the case of someone who’s had multiple miscarriages, says Diane Clapp, director of medical information at RESOLVE, a nonprofit advocacy organization for men and women facing infertility. “Some people think that infertility is all in the head and can be fixed with relaxation or a vacation,” says Clapp, who is a registered nurse. “But infertility is a medical disease that most people can be treated for.” About two-thirds of people who are treated for infertility will become pregnant, according to RESOLVE.

Q. What kinds of doctors evaluate and treat infertility?

A. Obstetrician-gynecologists (OB-GYNs) can evaluate and treat infertility in women. OB-GYNs specialize in general medical care of women, including care related to pregnancy and the reproductive tract. Urologists, who specialize in the urinary tract and the male reproductive organs, can evaluate and treat infertility in men.More resistant and complex problems are typically handled by “fertility specialists,” board-certified reproductive endocrinologists who have completed training in obstetrics and gynecology, followed by specialized training in hormonal problems and infertility. One example of a complex problem is a history of failure to conceive despite regular unprotected intercourse in a woman who has regular menstrual periods and whose male partner has normal sperm. Other examples of complex problems include a woman who has experienced multiple miscarriages or who has severely damaged fallopian tubes requiring the need for treatment with assisted reproductive technologies (ART)–the joining of eggs and sperm in a lab so that fertilization can occur.The decision about when to ask for a referral to a fertility specialist is a personal one. Experts say that couples should consider the age of the woman, the complexity of their problems, and how they are feeling about the progress of their treatment. Consumers should be proactive about asking their doctors for a referral to a specialist and about investigating the qualifications of the specialist. A certificate of special qualification in reproductive endocrinology and infertility from the American Board of Obstetrics and Gynecology ensures that the specialist has completed a rigorous course of training.

Q. What goes into a fertility evaluation?

A. A standard fertility evaluation includes physical exams and medical and sexual histories of both partners. Men undergo a semen analysis that evaluates sperm count and sperm movement. “We look at the percent that are moving and how they are moving–are the sperm sluggish? Are they wandering?” says Robert G. Brzyski, M.D., Ph.D., associate professor of obstetrics and gynecology at the University of Texas Health Science Center at San Antonio. “Often, it’s not possible to identify a specific reason for a sperm disorder,” he says. “But there is new recognition that very low sperm or no sperm may be related to genetics–an abnormality of the Y chromosome.”For women, doctors first check to see whether ovulation is occurring. This can be determined and monitored through blood tests that detect hormones, ultrasound examinations of the ovaries, or an ovulation home test kit. “An irregular menstrual pattern would make us suspicious of an ovulation problem, but it’s also possible for a woman with regular periods to have an ovulation disorder,” Brzyski says.If a woman is ovulating, doctors then move to a standard test called the hysterosalpingogram, a type of X-ray of the fallopian tubes and uterus. This test involves placing a radiographic dye solution into the uterine cavity. Multiple X-rays are taken. If the fallopian tubes are open, the dye will flow through the tubes and be visible in the abdominal cavity. If the fallopian tubes are blocked, the dye will be retained in the uterus or fallopian tubes, depending on the location of the blockage.

Doctors have begun to assess the ovarian reserve by measuring hormone levels and seeing how the ovaries respond to various fertility treatments. This helps evaluate the availability of eggs and the likelihood that a healthy pregnancy will result. “Some women who are 35 are fertile while others are not because their supply of eggs is depleted,” Brzyski says. “In the last decade, we’ve learned this can be investigated through a blood test on the third day of the menstrual cycle. If the numbers are normal, it doesn’t guarantee fertility. But if the numbers are abnormal, it points to a serious problem. Up to 20 percent of women who seek infertility care have an abnormal ovarian reserve test.”There are also tests that evaluate how sperm and eggs interact, as well as whether either party is developing antibodies to the sperm. This occurs when the man’s or the woman’s immune system recognizes the sperm as something foreign and attacks it.

Q. What are the conventional treatments for infertility?

A. Conventional therapies, such as drugs or surgery, are used to treat 85 percent to 90 percent of infertility cases. Examples of reproductive surgery for men are vasectomy reversal and varicocele repair, a procedure that may restore fertility by treating varicose veins in the scrotum. Examples of fertility-related surgery for women include removal of noncancerous tumors in the uterus called fibroids, and the removal of endometriosis implants, which can cause infertility. There are two types of ovulation drug treatments approved by the FDA. Clomid and Serophene (clomiphene citrate) are taken by mouth. Repronex and Pergonal (human gonadotropins) are injected. Both types stimulate the ovaries to produce eggs.

Clomiphene is usually the first line of treatment in women with ovulation problems. “In women who are not ovulating, 60 percent to 85 percent of women will ovulate with clomiphene, and 30 percent to 40 percent will become pregnant,” says Audrey Gassman, M.D., a medical reviewer in the FDA’s Division of Reproductive and Urologic Drug Products. One of the risks of ovulation-inducing drugs is that more than one fetus may result.  

Drugs that stimulate ovulation are often used with intrauterine insemination, a procedure in which millions of sperm are inserted into a woman’s uterus around the time of ovulation to increase the chance of pregnancy. A partner’s sperm or donor sperm may be used.  

Q. What are the side effects of fertility drugs?

A. Among the most common bothersome side effects of clomiphene are hot flashes, which occur in 10 percent of women. Abdominal discomfort and bloating is seen in less than 5 percent. Less common are nausea, vomiting, and breast discomfort, which occur in 2 percent of women. Gonadotropins can cause side effects similar to clomiphene. The most common serious adverse event with gonadotropins is ovarian hyperstimulation syndrome. This causes ovarian enlargement and pain and an accumulation of fluid in the abdomen that is potentially dangerous. This results in pain in the pelvic area.  

The occurrence of ovarian hyperstimulation syndrome varies with the gonadotropin used, but with most gonadotropins, hyperstimulation occurs in 5 percent to 7 percent of women, with severe cases affecting less than 2 percent of patients, according to Gassman. Mild cases may result in the development of ovarian cysts. “In severe cases of this, patients may need to be hospitalized for lung, kidney, and liver problems, and deaths have been reported, but this is rare,” Gassman says. People who experience bothersome side effects while taking fertility drugs should see their doctors.

The incidence of multiple pregnancies with clomiphene is about 8 percent, and the incidence of multiple pregnancies with gonadotropins is up to 20 percent. In contrast, the rate of multiple infant births is 3 percent in the general U.S. population, according to a 2001 report on ART success rates published by the Centers for Disease Control and Prevention (CDC) and the ASRM. Most of the cases of multiple pregnancies due to ovulation-stimulating drugs result in twins, according to the ASRM, but up to 5 percent result in triplets or a higher number of babies. A multiple pregnancy significantly raises the risk of preterm labor, pregnancy complications for the mother, and low birth weight and long-term disability in babies. 

 Q. Do fertility drugs cause ovarian cancer?

A. Concern over a link between fertility drugs and ovarian cancer came from studies published in the early 1990s that suggested the risk of ovarian cancer might be significantly increased in women exposed to ovulation drugs. “But more recent studies have failed to corroborate a strong association between fertility drugs and ovarian cancer in the general population,” Gassman says.  

One study, supported by the National Cancer Institute, evaluated more than 12,000 women and did not find a strong link between ovulation-stimulating drugs (clomiphene and gonadotropins) and ovarian cancer. The researchers also concluded that slight but non-significant elevations in risk with drug use among certain subgroups support the need to continue monitoring long-term risks. The study was published in the June 2004 issue of Obstetrics and Gynecology, the journal of the American College of Obstetricians and Gynecologists. Gassman says, “The FDA continues to monitor adverse events possibly associated with these drugs and takes appropriate action when necessary based on our current understanding of the risks and benefits.”