Technology Meets Biology: Infertility is Usually Treatable

About 12% of women aged 15 to 44 in the US had difficulty getting pregnant or carrying a baby to term in 2002, according to the most recent statistics from the Centers for Disease Control and Prevention (CDC). However, infertility is not a woman's problem alone. In only about one-third of cases is infertility due to the woman (female factors). In another one-third of cases, infertility is due to the man (male factors). The remaining cases are caused by a mixture of male, female, and unknown factors.

Causes of Infertility
Paul A. Robb, MD, Medical College of Wisconsin Assistant Professor of Obstetrics and Gynecology, practices at the Froedtert & The Medical College of Wisconsin Reproductive Medicine Clinic. He says there are several possible causes of infertility, involving both partners. "In female infertility," he explains, "about 40% are caused by ovulatory problems, another 40% are tubal-related problems, about 10% are due to other unusual problems, and another 10% is unexplained ."

In males, causes are broadly related to abnormalities of sperm production, sperm function, or obstruction of the ductal system. Lifestyle issues come into play too, says Dr. Robb: "Marijuana and other recreational drugs are not good for sperm, nor is sitting in a hot tub." Alcohol, environmental and workplace toxins, medications, and age can all contribute to a man's sperm production as well. But the boxers vs. briefs controversy has been laid to rest: "There's no difference in sperm production in men who wear boxers and men who wear briefs," Dr. Robb notes.

When to Seek Help
"It's usually recommended that a couple seek treatment after a year of unprotected intercourse without a pregnancy," Dr. Robb advises. However, if there is a known problem, couples should see a physician whenever they decide they want to have a child. "If the woman has very irregular cycles, or she knows her tubes are blocked, or if the man has had a vasectomy, we wouldn't want these patients to wait a full year." In addition, Dr. Robb says, "Fertility declines with age. If a woman is older than 35 and wants to become pregnant, she should be seen sooner rather than later."

In diagnosing an infertility problem, Dr. Robb says, "History is very important, especially the history of menstrual periods, because that often will tell us whether a woman is ovulating or not." Ovulation is obviously a key to achieving pregnancy. "One of the first steps is that the woman needs to make an egg and release that egg, so when a woman has a very regular cycle and has symptoms such as breast tenderness or bloating just before her menstrual period, it's very likely that she is ovulating, and we do not need to do a lot of tests around that," Dr. Robb explains.

Ovulation Issues
If Dr. Robb does suspect an ovulation problem, "We will do blood testing to check for such things as thyroid disease or an elevation in the hormone prolactin, both of which can affect ovulation," he says.

An estimated 5% to 10% of women of childbearing age have Polycystic Ovarian Syndrome (PCOS). "Those women usually have irregular cycles and also some signs of elevated male hormones, which may manifest in things like facial hair or acne," says Dr. Robb. "If that's the case, then we need to do further testing to check on these male hormone levels, as those hormones can prevent ovulation or may be a sign of a more serious disease process.

"One of the first treatments we often begin with is the medication called Clomiphene Citrate, which blocks estrogen receptors in the brain. That tricks the brain into thinking the ovaries are not working, and it then gives the ovaries more stimulation," Dr. Robb says. "Normally a woman only ovulates one egg a month, but with Clomiphene you might get two or three eggs growing, so about 7% of women receiving this treatment have multiple births, the vast majority of these will be twins. Over 90%, however, are single births.

Sometimes a few cycles of Clomiphene treatment are enough, if the problem is just ovulation. "But if there are male factors involved, or if the infertility is unexplained, we use Clomiphene and intrauterine inseminations together to get the best results," says Dr. Robb. In an insemination, sperm is put directly into the uterus. "That maximizes things on the male side, to get the most number of sperm in the right place at the right time."

Another treatment option is in-vitro fertilization, or IVF. Dr. Robb explains, "The woman is given injectable medications that stimulate the ovaries to make more eggs, and we then collect the eggs. Fertilization takes place outside the body, and we put the resulting embryos back into the uterus."

In cases where the woman is older or has compromised ovarian function, she can use a donor's eggs. "In this case," says Dr. Robb, "a donor, usually anonymous, goes through an IVF cycle and we collect her eggs. We mix them with the patient's partner's sperm to create embryos and the embryos then are placed into the patient's uterus and she carries the pregnancy."

We also can offer the technology of Pre-implantation Genetic Diagnosis (PGD) which helps doctors identify potential problems related to chromosomal abnormalities or to check for certain defects when parents are carriers of genetic diseases. That way we can avoid putting back embryos that could lead to a miscarriage or a genetic disease.

Tubal Problems
If a woman is ovulating properly, Dr. Robb next looks at her fallopian tubes. "As far as tubal factors, we'd probably want to do a hysterosalpingogram (HSG). That puts dye into the uterine cavity itself, and under fluoroscopy we can see the dye flowing through the uterus." Polyps and fibroids, which can affect implantation, can also be seen as the dye flows around them. "Then the dye goes into the tubes, and we can see that it goes through the tubes," explains Dr. Robb. "When we see that happening, we know that the tubes are open."

If tubal problems are found, surgery can be performed to correct the defect. But Dr. Robb says that the more common treatment is IVF, because the tubes are simply bypassed with this technology. "In tubal issues, we decide between surgery and IVF based mainly on age. If the woman is older it is often best to go straight to IVF, which is the quickest way to achieve a pregnancy.

Male Factors
The male partner must also be checked for possible problems involving his sperm. Sperm disorders can be caused by factors such as genetics (e.g., cystic fibrosis), individual structure (e.g., scarring or blockages), environment (e.g., chemical exposure), hormonal problems, or, most commonly, varicoceles.

"We first do a semen analysis to screen for male factor issues," says Dr. Robb. If the man is impotent or has problems with premature ejaculation, behavioral therapy and/or medication can often help. If significant varicoceles are found these can be surgically corrected and for more significant problems IVF can be used.

"A varicocele, which is a dilation of the veins going to the testicle, is very common," says Dr. Robb. When varicoceles are thought to be a part of the problem, repair will often lead to an increase in sperm count and result in a pregnancy. Based on the data from our clinic, approximately 70% of couples will see a significant improvement in sperm count, movement, or appearance following varicocele repair, with about 40% to 45% of the couples achieving natural conception. This assumes that there are no significant female factors present. This also underscores the necessity of both partners being evaluated, as it does not help to treat one partner without knowing the status of the other.

Another common infertility issue occurs in men who have had vasectomies, then decide to reverse them, usually due to the fact that they have a new partner. "If you're looking at doing a vasectomy reversal," says Dr. Robb, "you need to make sure there are no problems on the female side too. One needs to realize that it takes at least 3 months for new sperm to mature and make their way into the ejaculate, so that it will be at least that long before we see a significant number of sperm in the ejaculate. Then it will usually take several months of trying to achieve a pregnancy.

"If the women is already in her later reproductive years this waiting may be a detriment to fertility and so we may suggest going directly to IVF by retrieving sperm from the testicles. " He estimates that at Froedtert, more than 90% of vasectomy reversals are technically successful; "success" being defined as getting sperm back, with approximately 50% of couples conceiving on their own.

"For severe problems with male factors," says Dr. Robb, "we have something called ICSI - Intracytoplasmic Sperm Injection. In this technology an individual sperm is placed directly into an egg to achieve fertilization. In some patients, usually due to a blockage, the sperm does not go through the vas deferens (the spermatic duct from the testicle) and out the ejaculatory ducts, so sperm needs to be retrieved directly from the testicle. Sperm collected in this way will require IVF and ICSI as the sperm is very immature, and could not fertilize an egg without the ICSI procedure.

"We have a urologist on staff, Dr. Sandlow, who is fellowship-trained in male infertility. This means we can offer all available options for retrieving sperm from the testes in cases where there is no sperm in the ejaculate but sperm in the testes," says Dr. Robb. "Not all urologists are able to offer the microsurgical techniques which may be required in some cases."

Most Couples Will Become Pregnant
While not all the causes of infertility are known, most are diagnosed and successfully treated. "Overall," says Dr. Robb, "we have very good success with fertility treatments, and most of our patients will become pregnant. Some of them might require donor eggs or other intervention, but the overall success rate is very good if patients are open to all treatment modalities."

P. J. Early
HealthLink Contributing Writer

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.