FDA Consumer ReprintOvercoming Infertility

This article originally appeared in the January-February 1997 FDA Consumer.
The version below is from a reprint of the original article and contains revisions made in February 1997.

Overcoming Infertility

by Tamar Nordenberg

Myth or fact: If a couple is having trouble conceiving a child, the man should try wearing loose underwear? That's a fact, according to a study on "Tight-fitting Underwear and Sperm Quality" published June 29, 1996, in the scientific journal The Lancet. Tight-fitting underwear--as well as hot tubs and saunas--is not recommended for men trying to father a child because it may raise testes temperature to a point where it interferes with sperm production.

But couples having difficulty getting pregnant can tell you the solution is almost never as simple as wearing boxers instead of briefs. Lisa (who asked that her last name not be used) tried for more than two years to get pregnant without success. "Everyone gave me advice," she says. "My mother said I should just go to church and pray more. My friends said, 'Try to relax and not think about it' or 'You're just overstressed. You work too much.'"

Actually, psychological stress is more likely a result of infertility than the cause, according to Resolve, a nonprofit consumer organization specializing in infertility.

"Fertility problems are a huge psychological stressor, a huge relationship stressor," says Lisa Rarick, M.D., director of the Food and Drug Administration's division of reproductive and urologic drug products.

So, while going on a relaxing vacation may temporarily relieve the stress that comes with fertility problems, a solution may require treatment by a health-care professional. Treatment with drugs such as Clomid or Serophene (both clomiphene citrate) or Pergonal, Humegon, Metrodin, or Fertinex (all menotropins) are used in some cases to correct a woman's hormone imbalance. (See "Drug Supply Restored.") Surgery is sometimes used to repair damaged reproductive organs. And in about 10 percent of cases, less conventional, high-tech options like in vitro fertilization are used.

Will the therapies work? "Talking about the success rate for fertility treatments is like saying, 'What's the chance of curing a headache?'" according to Benjamin Younger, M.D., executive director of the American Society for Reproductive Medicine. "It depends on many things, including the cause of the problem and the severity." Overall, Younger says, about half of couples that seek fertility treatment will be able to have babies.

A Year Without Pregnancy

Infertility is defined as the inability to conceive a child despite trying for one year. The condition affects about 5.3 million Americans, or 9 percent of the reproductive age population, according to the American Society for Reproductive Medicine.

Ironically, the best protection against infertility is to use a condom while you are not trying to get pregnant. Condoms prevent sexually transmitted diseases, a primary cause of infertility.

Even a completely healthy couple can't expect to get pregnant at the drop of a hat. Only 20 percent of women who want to conceive become pregnant in the first ovulation cycle they try, according to Younger.

To become pregnant, a couple must have intercourse during the woman's fertile time of the month, which is right before and during ovulation. Because it's tough to pinpoint the exact day of ovulation, having intercourse often during the approximate time maximizes the chances of conception.

After a year of frequent intercourse without contraception that doesn't result in pregnancy, a couple should go to a health-care professional for an evaluation. In some cases, it makes sense to seek help for fertility problems even before a year is up.

A woman over 30 may wish to get an earlier evaluation. "At age 30, a woman begins a slow decline in her ability to get pregnant," says Younger. "The older she gets, the greater her chance of miscarriage, too." But a woman's fertility doesn't take a big drop until around age 40.

"A man's age affects fertility to a much smaller degree and 20 or 30 years later than in a woman," Younger says. Despite a decrease in sperm production that begins after age 25, some men remain fertile into their 60s and 70s.

A couple may also seek earlier evaluation if:

• The woman isn't menstruating regularly, which may indicate an absence of ovulation that would make it impossible for her to conceive without medical help.
• The woman has had three or more miscarriages (or the man had a previous partner who had had three or more miscarriages).
• The woman or man has had certain infections that sometimes affect fertility (for example, pelvic infection in a woman, or mumps or prostate infection in a man).
• The woman or man suspects there may be a fertility problem (if, for example, attempts at pregnancy failed in a previous relationship).

The Man or the Woman?

Impairment in any step of the intricate process of conception can cause infertility. For a woman to become pregnant, her partner's sperm must be healthy so that at least one can swim into her fallopian tubes. An egg, released by the woman's ovaries, must be in the fallopian tube ready to be fertilized. Next, the fertilized egg, called an embryo, must make its way through an open-ended fallopian tube into the uterus, implant in the uterine lining, and be sustained there while it grows. (See diagram.)

It is a myth that infertility is always a "woman's problem." Of the 80 percent of cases with a diagnosed cause, about half are based at least partially on male problems (referred to as male factors)--usually that the man produces no sperm, a condition called azoospermia, or that he produces too few sperm, called oligospermia.

Lifestyle can influence the number and quality of a man's sperm. Alcohol and drugs--including marijuana, nicotine, and certain medications--can temporarily reduce sperm quality. Also, environmental toxins, including pesticides and lead, may be to blame for some cases of infertility.

The causes of sperm production problems can exist from birth or develop later as a result of severe medical illnesses, including mumps and some sexually transmitted diseases, or from a severe testicle injury, tumor, or other problem. Inability to ejaculate normally can prevent conception, too, and can be caused by many factors, including diabetes, surgery of the prostate gland or urethra, blood pressure medication, or impotence.

The other half of explained infertility cases are linked to female problems (called female factors), most commonly ovulation disorders. Without ovulation, eggs are not available for fertilization. Problems with ovulation are signaled by irregular menstrual periods or a lack of periods altogether (called amenorrhea). Simple lifestyle factors--including stress, diet, or athletic training--can affect a woman's hormonal balance. Much less often, a hormonal imbalance can result from a serious medical problem such as a pituitary gland tumor.

Other problems can also lead to female infertility. If the fallopian tubes are blocked at one or both ends, the egg can't travel through the tubes into the uterus. Such blockage may result from pelvic inflammatory disease, surgery for an ectopic pregnancy (when the embryo implants in the fallopian tube rather than in the uterus), or other problems, including endometriosis (the abnormal presence of uterine lining cells in other pelvic organs).

A medical evaluation may determine whether a couple's infertility is due to these or other causes. If a medical and sexual history doesn't reveal an obvious problem, like improperly timed intercourse or absence of ovulation, specific tests may be needed.

Tests for Both

The man's evaluation focuses on the number and health of his sperm. The laboratory first examines a sperm sample under a microscope to check sperm number, shape and movement. Further tests may be needed to look for infection, hormonal imbalance, or other problems.

Male tests include:

• X-ray: If damage to one or both of the vas deferens (the ducts in the male that transport the sperm to the penis) is known or suspected, an x-ray is taken to examine the organs.
• Mucus penetrance test: Test of whether the man's sperm are able to swim through a drop of the woman's fertile vaginal mucus on a slide (also used to test the quality of the woman's mucus).
• Hamster-egg penetrance assay: Test of whether the man's sperm will penetrate hamster egg cells with their outer cells removed, indicating somewhat their ability to fertilize human eggs.

For the woman, the first step in testing is to determine if she is ovulating each month. This can be done by charting changes in morning body temperature, by using an FDA-approved home ovulation test kit (which is available over the counter), or by examining cervical mucus, which undergoes a series of hormone-induced changes throughout the menstrual cycle.

Checks of ovulation can also be done in the physician's office with simple blood tests for hormone levels or ultrasound tests of the ovaries. If the woman is ovulating, further testing will need to be done.

Common female tests include:

• Hysterosalpingogram: An x-ray of the fallopian tubes and uterus after they are injected with dye, to show if the tubes are open and to show the shape of the uterus.
• Laparoscopy: An examination of the tubes and other female organs for disease, using a miniature light-transmitting tube called a laparoscope. The tube is inserted into the abdomen through a one-inch incision below the navel, usually while the woman is under general anesthesia.
• Endometrial biopsy: An examination of a small shred of uterine lining to see if the monthly changes in the lining are normal.

Some tests require participation of both partners. Samples of cervical mucus taken after intercourse can show whether sperm and mucus have properly interacted. Also, a variety of tests can show if the man or woman is forming antibodies that are attacking the sperm.

Drugs and Surgery

Depending on what the tests turn up, different treatments are recommended. Eighty to 90 percent of infertility cases are treated with drugs or surgery.

Therapy with the fertility drug Clomid or with a more potent hormone stimulator--Pergonal, Metrodin, Humegon, or Fertinex--is often recommended for women with ovulation problems. The benefits of each drug and the side effects, which can be minor or serious but rare, should be discussed with the doctor. Multiple births occur in 10 to 20 percent of births resulting from fertility drug use.

Other drugs, used under very limited circumstances, include Parlodel (bromocriptine mesylate), for women with elevated levels of a hormone called prolactin, and a hormone pump that releases gonadotropins necessary for ovulation.

If drugs aren't the answer, surgery may be. Because major surgery is involved, operations to repair damage to the woman's ovaries, fallopian tubes, or uterus are recommended only if there is a good chance of restoring fertility.

In the man, one infertility problem often treated surgically is damage to the vas deferens, commonly caused by a sexually transmitted disease, other infection, or vasectomy (male sterilization).

Other important tools in the battle against infertility include artificial insemination and the so-called assisted reproductive technologies. (See "Science and Art.")

Fulfillment Regardless

Lisa became pregnant without assisted reproductive technologies, after taking ovulation-promoting medication and undergoing surgery to repair her damaged fallopian tubes. Her daughter is now 4 years old.

"It was definitely worth it. I really appreciate having my daughter because of what I went through," she says. But Lisa and her husband won't try to have a second child just yet. "At some point you have to stop trying to have a baby, stop obsessing over what might be an unreachable goal," she says.

When having a genetically related baby seems unachievable, a couple may decide to stop treatment and proceed with the rest of their lives. Some may choose to lead an enriched life without children. Others may choose to adopt.

And no, according to Resolve, you're not more likely to get pregnant if you adopt a baby.

To get more information about infertility, send a self-addressed stamped envelope to: Resolve, 1310 Broadway, Somerville MA 02144-1731, or call their National Helpline at (617) 623-0744.

Tamar Nordenberg is a staff writer for FDA Consumer.

Science and ART

Sometimes it may be necessary or preferable to get pregnant without intercourse. A woman may choose to get pregnant with the sperm of someone who is not her partner.

In some cases, a woman may not be able to become pregnant with her partner because his sexual problems make it impossible for him to ejaculate normally during sex, or because the sperm have to bypass the vagina if the vaginal mucus cannot support them, or for other reasons. In these cases, through artificial insemination, the semen is placed into the woman's uterus or vaginal canal using a hollow, flexible tube called a catheter.

New, more complex assisted reproductive technologies, or ART, procedures, including in vitro fertilization (IVF), have been available since the birth 18 years ago of Louise Brown, the world's first "test tube baby." IVF makes it possible to combine sperm and eggs in a laboratory for a baby that is genetically related to one or both partners.

IVF (illustrated in the diagram at right) is often used when a woman's fallopian tubes are blocked. First, medication is given to stimulate the ovaries to produce multiple eggs. Once mature, the eggs are suctioned from the ovaries (1) and placed in a laboratory culture dish with the man's sperm for fertilization (2). The dish is then placed in an incubator (3). About two days later, three to five embryos are transferred to the woman's uterus (4). If the woman does not become pregnant, she may try again in the next cycle.

Other ART procedures, based on many of the same principles, include:

• Gamete intrafallopian transfer, or GIFT: Similar to IVF, but used when the woman has at least one normal fallopian tube. Three to five eggs are placed in the fallopian tube, along with the man's sperm, for fertilization inside the woman's body.
• Zygote intrafallopian transfer, or ZIFT (also called tubal embryo transfer): A hybrid of IVF and GIFT. The eggs retrieved from the woman's ovaries are fertilized in the lab and replaced in the fallopian tubes rather than the uterus.
• Donor egg IVF: For women who, for example, have impaired ovaries or carry a genetic disease that can be transferred to the offspring. Eggs are donated by another healthy woman and fertilized in the lab with the male partner's sperm before being transferred to the female partner's uterus.
• Frozen embryos: Excess embryos are frozen, to be thawed in the future if the woman doesn't get pregnant on the first cycle or wants another baby in the future.

New treatments for male factors are fast-evolving. Intracytoplasmic sperm injection is one of the most exciting new procedures, according to Benjamin Younger, M.D., executive director of the American Society for Reproductive Medicine. A single egg is injected with a single sperm to produce an embryo that can implant and grow in the uterus.

About two-thirds of births from ART procedures are single births. Of the rest, almost all are twins, with about 6 percent resulting in the birth of triplets or more.

--T.N.

Drug Supply Restored

The availability of sufficient supplies of the FDA-approved fertility drugs Pergonal, Metrodin, and Humegon, and the recent FDA approval of the fertility drug Fertinex have ended a sh0rtage of these types of drugs in the United States. Since the drugs are not in short supply anymore, FDA will no longer allow the importation of unapproved versions of fertility drugs, even for personal use.

In February 1995, FDA became aware of a shortage of the approved fertility drugs Pergonal and Metrodin, both manufactured by Serono Laboratories Inc of Switzerland.

Because of the shortage, FDA has allowed people to temporarily import unapproved foreign versions of fertility drugs for their own use. "FDA used its enforcement discretion to allow the importation of unapproved versions of fertility drugs on a personal use basis," says Thomas Gardine, director of the agency's division of import operations and policy.

FDA asked doctors to wait until the supply of approved drugs increased unless a patient was in the midst of therapy. "There's always a danger in taking unapproved drugs because they are of unknown quality and haven't been shown to FDA to be safe, effective, and adequately labeled," Gardine says.

The Serono manufacturing plant in Switzerland is again supplying adequate amounts of Pergonal and Metrodin for U.S. patients. Also, other products are now available for the same use.

"The drug shortage no longer exists to merit our allowing importation of the unapproved products," Gardine says. After a reasonalbe time to make the public aware of the change in FDA's position, the agency will no longer allow the unapproved versions of these drugs to enter the country.

The following fertility drugs are approved by FDA and can be obtained with a doctor's prescription:

• Some of these drug products may be sold under other brand names by distributors who buy the products from the listed manufacturers.
• Chorionic gonadotropin is not normally used alone as a fertility drug--it is normally administered after administration of menotropins or urofollitropin.

(Illustrations in this article drawn by Renée Gordon.)

Publication No. (FDA) 97-1269

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