Over six million American couples face problems related to fertility. Infertility is often defined as the inability to conceive a child after one year of unprotected intercourse, or the inability to carry a pregnancy to term. Depending on the source however, the definition varies, and the time to conceive a child before infertility is diagnosed ranges anywhere from six months to two years.

Cases of infertility are seen equally among both men and women. That is, neither gender is more responsible for present rates of infertility than the other. For women, the most common cause of infertility is anovulation, or hormonal problems related to the normal production of healthy eggs. Similarly, male factor infertility is often the result of hormonal imbalances that cause problems in the production of healthy sperm. Not surprisingly then, many of the recent developments in treating infertility are concerned with changes in how hormones are used and administered.

Gonal-F^(R)

After extensive testing, the US Food and Drug Administration (FDA) announced approval of a 37.5 IU dose of Gonal-F (follitropin alfa for injection), complementing the 75 IU and 150 IU strength formulations. Gonal-F, produced by Serono S.A., is a pure follicle-stimulating hormone (FSH) and is the first FSH to be produced by recombinant DNA technology. Recent studies have linked the 37.5 IU adjustment to low occurrences of multiple pregnancy and higher pregnancy rates compared to those patients receiving the typical 75 IU adjustments.

Unlike other fertility drugs that only encourage hormone production, FSH is the actual hormone responsible for producing and releasing healthy eggs in women, as well as for the production of sperm in men. In the ovaries, follicles are tiny sacs containing eggs and fluid. Stimulating the development of follicles is most important in treating certain types of infertility such as anovulation, polycystic ovary syndrome (PCOS), and conditions where ovaries have become overstimulated.

In treating male factor infertility, Gonal-F is the first and only product of its kind, offering males an effective way to induce healthy sperm production through subcutaneous injection. Clinical studies found that 63% of men with infertility caused by factors other than testicular failure, and who received two to three dosages (150 IU each) of Gonal-F per week, achieved a sperm count adequate for conception.

The new dosing flexibility will allow physicians to individually tailor treatments to the needs of each patient, as well as offer cost-effective and convenient alternatives to adjusting dose increments. Side effects of Gonal-F remain the same with observed occurrences of headaches, nausea, and ovarian cysts in women, and breast pain, acne, and tiredness among men.

Crinone^(R)

In related news, changes in the administering of the hormones progesterone and estrogen are improving clomiphene citrate therapies. Clomiphene citrate, also known as Serophene^(R), is often the first line of treatment to induce ovulation. Women are usually prescribed Serophene tablets before any other form of treatment in order to stimulate the body's natural production and release of FSH and luteinizing hormone (LH). And, while the treatment is generally effective in women who experience abnormal ovulation cycles, it seems to have an adverse effect on endometrial thickness, thereby increasing the likelihood of implantation failure. The endometrium, or uterus lining, supports the embryo from the very first stage of pregnancy; its receptivity to an embryo is crucial for success.

Studies have shown that adding progesterone and estrogen when taking Serophene significantly increases endometrial thickness, thus improving rates of pregnancy while reducing the likelihood of miscarriage. That is, the hormones appear to counterbalance the negative effects of a Serophene regimen.

These findings were similarly confirmed by Italian researchers in the January 2000 issue of Fertility and Sterility. Dr. Vittorio Unfer and colleagues at the Center for Reproductive Medicine and Infertility Therapy in Rome found that those women who received estrogen in conjunction with clomiphene citrate therapy had far greater endometrial thickness than those women who took the clomiphene citrate therapy alone. The former group also experienced higher rates of pregnancies and lower rates of miscarriage.

Normally, progesterone is administered as a daily intramuscular injection using a 1.5-inch needle. The sometimes-painful injections pass through the liver, often leading to a sedative effect. Then, once the injections are discontinued, the patient may experience withdrawal and anxiety. Now, however, progesterone may be administered in gel form. Crinone, a vaginal progesterone gel marketed by Serono, offers patients an equally effective alternative to daily injections. Women prefer using the gel over other forms of progesterone therapies and find it not only cleaner and more convenient, but less painful as well.

Studies comparing the various methods of administering the hormone found similar rates of clinical pregnancies, yet women overwhelmingly preferred the use of Crinone over injections and vaginal suppositories (91% and 90%, respectively). The gel is also ideal since there are no negative withdrawal effects associated with it, and it improves pregnancy rates without increasing costs or monitoring requirements.

Side effects of Crinone may include constipation, breast enlargement, and nausea. When taking Crinone in conjunction with such assisted reproductive technologies (ART) as intrauterine insemination (IUI), side effects may include breast pain, headaches, and cramping.

Nontraditional Approaches

Lately there has been a great deal of excitement and interest in the claim that Viagra^(R) (sildenafil citrate), the popular breakthrough treatment for impotence in males, can now be used in treating some fertility problems in women. The theory is that since Viagra increases blood flow, it may also improve endometrial thickness. As discussed above, a thin uterine lining prevents embryos from successful implantation.

Dr. Geoffrey Sher of the Sher Institute for Reproductive Medicine in New Orleans, LA, prescribed Viagra to four different women based on this theory, and found that three of the four became pregnant as a result. Now hailed by some as a revolutionary miracle drug, others stress caution and advocate strict clinical studies before unrealistic claims are made.

Sher's results are criticized as anecdotal; clearly, a sample size of four individuals acting outside of a controlled research environment does not indicate a valid form of treatment. Women treated for infertility often take a variety of fertility drugs, and usually in addition to ART such as in vitro fertilization (IVF). It is unknown at this point whether the results of the successful pregnancies were due to the Viagra, the other treatments, or the combination of both. And while the results are certainly promising enough to warrant further study, many fear that false claims made now will lead women to use the drug on their own, without their physician's advice, and before more concrete research is conducted.

Interestingly, in a completely unrelated study, researchers found that high doses of sildenafil significantly reduce sperm motility (referring to the swimming ability of the sperm). Fertilization is much more difficult to accomplish when sperm motility is reduced. So while sildenafil may reduce cases of infertility in women, it may just have the opposite effect on men.

According to a study in the May issue of the American Journal of Obstetrics and Gynecology, sildenafil at 200 mg/mL had no effect on sperm motility; yet at 2,000 mg/mL, sperm motility was reduced by 50%. High dosages of sildenafil added to semen also results in a mean decrease of pH from 8.6 to 7.84. Although high doses of sildenafil negatively affect sperm motility, this effect may be due to the drop in pH.

Like the Viagra claim, however, the effects of sildenafil on sperm motility need further study and review. And although the literature in this area is still fairly limited, it is important to reach a conclusion on how the drug will ultimately affect the quality and quantity of sperm. Answers to these questions will provide us with greater insight into treating male factor infertility.

This article was written by science correspondent Heather Monroe.

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