NEWS FROM REPRODUCTIVE PARTNERS

On May 16, 2000 Organon, Inc. announced the availability of the Follistim (follitropin beta for injection)/Antagon (ganirelix acetate) kit. Reproductive Partners Medical Group, Inc. was a participant in North America Antagon study and therefore we are very familiar with the use of this medication. We felt that the release of this important medication justified reprinting this article from a previous edition of Reproductive Times. 

Antagon - A New and Simpler Alternative to Lupron
by David R. Meldrum, M. D.

GnRH agonists have been routinely used for IVF cycles since they prevent ovulation before egg retrieval, improve the ovarian response, and increase the success rate approximately two-fold over IVF cycles without use of a GnRH agonist. These benefits are produced by suppression of luteinizing hormone (LH). Leuprolide acetate (Lupron) has been the most common GnRH agonist used for IVF, although Synarel (a form given by nasal spray) has been tried with similar success. Lupron is given by injections under the skin, sometimes overlapping with an oral contraceptive, but often given starting about one week after ovulation.

For a GnRH agonist to suppress luteinizing hormone, it must first stimulate the release of gonadotropins (FSH and LH). This can complicate the IVF cycle by causing a cyst to form and by requiring extra time for LH and the estrogen level to be suppressed. Generally about 3 weeks of treatment is required but individual patients may require longer treatment. 

A new medication, Antagon (a GnRH antagonist) which suppresses LH within hours is now available. Therefore, it can be used only during the latter period of egg maturation when it is important to avoid excessive LH levels and when LH could rise enough to cause release of the eggs. It is usually used for only 3 to 5 days. Injection discomfort is similar or less than Lupron. Its most important advantage is in avoiding menopausal symptoms that occur with use of GnRH agonist after suppression and before estrogen rises with ovarian stimulation. In some women these can be severe with headache, moodiness or problems with recent memory. Such side effects could be more important with certain occupations (for example lapses in memory could be very disturbing for a trial lawyer or for someone giving lectures).

Large trials in Europe and North America have compared Antagon to GnRH agonist. A slightly lower egg yield and success rate (about 5%) was noted. However, Antagon was compared to GnRH agonist protocols that have been refined for over 10 years and with which the investigators were very familiar. It actually seems remarkable that the results with Antagon came so close with a first pass at defining an optimal protocol.

I have been involved in research on GnRH analogs for almost 20 years and Reproductive Partners was involved in the North America Antagon study. Based on the results I have advised using an oral contraceptive in the preceding cycle to improve egg yield and to allow flexibility in scheduling the egg retrieval. Since the LH levels were quite low on Antagon, and low LH levels could reduce egg quality, we are recommending that women on Antagon should take 1 or 2 ampules of hMG (Pergonal, Humegon or Repronex), that contains LH. These modifications should bring the Antagon results to levels very close or equal to Lupron. At Reproductive Partners we will be involved in additional studies to examine both of these variables over the next year or two, but I would feel confident that patients who wish to use Antagon would not significantly influence their results.

The large trials described above excluded poor responders. Since poor responders can have improved results by avoiding suppression with a GnRH agonist, they may do particularly well on Antagon. We will be doing a controlled study comparing Antagon with the mini-Lupron flare, which is currently the protocol of choice for poor responders.

In summary, Antagon should provide the same benefits as the GnRH agonist with fewer injections and no menopausal side effects, thus further simplifying ovarian stimulation for IVF. 

Viagra and Fertility

A poster presented at the recent conjoint meeting of the American Society for Reproductive Medicine and the Canadian Fertility and Andrology Society concluded that men taking Viagra do not need to worry about its effects on their fertility.

This study, which was performed in vitro (outside the body), involved incubating sperm with various concentrations of Viagra and a control solution. The test had to be performed in the laboratory rather than on test subjects because the length of time required to see an effect on sperm in vivo would require the test subjects to be on the drug constantly for almost three months. In this test, the authors concluded that Viagra had no effect on a normal sperm's motility, viability or membrane integrity.

Since this study was done in the laboratory and measured limited parameters, many further studies will be needed before couples can be reassured that Viagra has no significant effects on the chromosomes of the sperm in vivo or if it may have the potential to produce birth defects.