GnRH DURING CHEMOTHERAPY DOES NOT IMPROVE PREGNANCY RATES

NEW YORK (Reuters Health) Dec 21 - Menses and ovulation are more likely to resume spontaneously after chemotherapy if ovarian function is suppressed during the treatment - but the odds of spontaneous pregnancy don't improve, a meta-analysis shows.

The authors of the study note that roughly one in 49 women will develop cancer in her reproductive years. Almost 70% now survive for at least 5 years, so preservation of fertility after gonadotoxic therapy is more important than ever.

Cryopreservation -- of embryos, unfertilized eggs or whole tissue - is expensive, may dangerously delay treatment, and isn't available everywhere. An alternative is ovarian suppression with a gonadotropin-releasing hormone (GnRH) analog, but studies of this technique have yielded mixed results.

Senior author Dr. Tommaso Falcone, from the Cleveland Clinic Foundation in Ohio, and his associates searched the literature for randomized controlled trials comparing GnRH cotreatment with chemotherapy alone in premenopausal women. Their findings appeared online December 10th in Fertility and Sterility.

The six trials included in their meta-analysis included 173 women randomly assigned to a GnRH analog plus chemotherapy and 167 randomized to chemotherapy alone. The indications for chemotherapy were Hodgkin's disease, ovarian cancer, and breast cancer. GnRH analogs included buserelin, diphereline, triptorelin, and goserelin.

None of the trials had information on premature ovarian failure, the primary outcome.

All six trials reported the incidence of spontaneous menstruation, which significantly favored GnRH: 99/173 (57%) in the GnRH group vs 59 of 167 (35%) in the control group, odds ratio 3.46.

The authors saw a similar pattern in the two trials that reported incidence of spontaneous ovulation: 29/48 (60%) vs 11/50 (22%), respectively; OR 5.70.

However, three trials showed low spontaneous pregnancy rates that did not differ significantly between groups: 1/52 (2%) with GnRH vs 4/55 (7%) with chemotherapy alone.

Still, Dr. Falcone's team maintains that GnRH agonist cotreatment with chemotherapy "may be beneficial in preserving future fertility." It has the additional advantage of suppressing menstruation, thereby helping to prevent menorrhagia-associated anemia.

"In the future," they conclude, "more well-designed, powered, and reported trials are needed to address all possible outcomes and strengthen the body of evidence."

Fertil Steril. Posted online Decembe 10, 2010. Abstract