NEW YORK (Reuters Health) – Compared with the standard long protocol using gonadotrophin-releasing hormone (GnRH) agonists during ovarian stimulation, the use of GnRH antagonists results in comparable live-birth rates with a markedly reduced risk of ovarian hyperstimulation syndrome.

That’s according to the findings of new Cochrane Systematic Review of the topic, published in The Cochrane Library on May 11.

The authors, led by Dr. Hesham G. Al-Inany, at Cairo University in Egypt, explain that GnRH analogues are used during stimulation of ovulation to prevent a premature luteinizing hormone (LH) surge leading to cycle cancellation. The two main categories of analogues are agonists and antagonists, they continue, and these agents act in completely different ways.

“While the agonists act by down-regulation of the pituitary GnRH receptors and desensitization of the gonadotrophic cells, the antagonists bind competitively to the receptors thereby preventing the endogenous GnRH from exerting its stimulatory effects on the pituitary cells,” the researchers elaborate.

GnRH antagonists act rapidly and the approach is simpler and less expensive, but an earlier Cochrane review in 2001 concluded that women given GnRH antagonists had lower live-birth rates than those given agonists. However, now there are more data from recent randomized controlled trials to evaluate the two strategies.

The current review is based on 45 RCTs comparing the rapid antagonist protocol to the long agonist protocol in 7511 women. The pooled data showed no statistically significant differences in rates of live-births (odds ratio 0.86) or ongoing pregnancy rates (OR 0.87), the investigators found.

However, there was a significantly lower risk of ovarian hyperstimulation syndrome with the GnRH antagonist approach (OR 0.43), according to the report.

Earlier GnRH antagonists were hampered by allergic side effects caused by induced histamine release, but third-generation agents have overcome this problem, Dr. Al-Inany and colleagues note.

“The GnRH antagonist protocol is a short and simple protocol with a comparable live-birth rate to longer protocols with GnRH agonists,” they conclude. “It is associated with a highly significant reduction in incidence of severe ovarian hyperstimulation syndrome compared to the GnRH agonist long protocol and therefore justifies a move away from the standard GnRH agonist long protocol to a GnRH antagonist protocol.”

Gonadotrophin-releasing hormone antagonists for assisted reproductive technology
Cochrane Database Syst Rev 2011;5.