Gonadotrophin-releasing hormone antagonists for assisted conception

Al-Inany HG, Abou-Setta AM, Aboulghar M

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Summary

Gonadotrophin-releasing hormone antagonists in subfertile couples undergoing ovulation induction as part of an assisted conception program

Gonadotrophin-releasing hormone (GnRH) antagonist was introduced in assisted conception programs as an alternative to GnRH agonist in order to prevent cycle cancellation secondary to premature LH surge. This updated review evaluated the efficacy of GnRH antagonist compared to the most widely used protocol of GnRH agonist (long protocol). Twenty one randomized controlled open-label trials with 3865 women were included, and the pooled data showed that pregnancy rates were significantly lowered in the GnRH antagonist treated group. This should be balanced against the significant reduction in incidence of severe ovarian hyperstimulation syndrome observed in the antagonist treated group. The duration of ovarian stimulation, whole cycle treatment and amount of gonadotrophin used were also significantly lower in the antagonist treated group

This is a Cochrane review abstract and plain language summary, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2010 Issue 1, Copyright © 2010 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).
This record should be cited as: Al-Inany HG, Abou-Setta AM, Aboulghar M. Gonadotrophin-releasing hormone antagonists for assisted conception. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD001750. DOI: 10.1002/14651858.CD001750.pub2.

This version first published online: October 23. 2001
Last assessed as up-to-date: May 19. 2006

Abstract

Background

Gonadotrophin-releasing hormone antagonists produce immediate suppression of gonadotrophin secretion, hence, they can be given after starting gonadotrophin administration. This has resulted in dramatic reduction in the duration of treatment cycle. Two different regimes have been described. The multiple-dose protocol involves the administration of 0.25 mg cetrorelix (or ganirelix) daily from day six to seven of stimulation, or when the leading follicle is 14 to15 mm, until human chorionic gonadotrophin (HCG) administration and the single-dose protocol involves the single administration of 3 mg cetrorelix on day seven to eight of stimulation. Assuming comparable clinical outcome, these benefits would justify a change from the standard long protocol of GnRH agonists to the new GnRH antagonist regimens.

Objectives

To evaluate the evidence regarding the efficacy of gonadotrophin-releasing hormone (GnRH) antagonists with the standard long protocol of GnRH agonists for controlled ovarian hyperstimulation in assisted conception.

Search strategy

We searched Cochrane Menstrual Disorders and Subfertility Group's Specialised Register, MEDLINE and EMBASE databases from 1987 to February 2006, and handsearched bibliographies of relevant publications and reviews, and abstracts of scientific meetings. We also contacted manufacturers in the field.

Selection criteria

Randomized controlled studies comparing different protocols of GnRH antagonists with GnRH agonists in assisted conception cycles were included in this review.

Data collection and analysis

Two authors independently assessed trial quality and extracted data. If relevant data were missing or unclear, the authors have been consulted

Main results

Twenty seven RCTs comparing the GnRH antagonist to the long protocol of GnRH agonist fulfilled the inclusion criteria. Clinical pregnancy rate was significantly lower in the antagonist group. (OR = 0.84, 95% CI = 0.72 to 0.97). The ongoing pregnancy/ live-birth rate showed the same significant lower pregnancy in the antagonist group (P = 0.03; OR 0.82, 95% CI 0.69 to 0.98).
However, there was statistically significant reduction in incidence of severe OHSS with antagonist protocol. The relative risk ratio was (P = 0.01; RR 0.61, 95% CI 0.42 to 0.89). In addition, interventions to prevent OHSS (e.g. coasting, cycle cancellation) were administered more frequently in the agonist group (P = 0.03; OR 0.44, 95% CI 0.21 to 0.93).

Authors' conclusions

GnRH antagonist protocol is a short and simple protocol with good clinical outcome with significant reduction in incidence of severe ovarian hyperstimulation syndrome and amount of gonadotrophins but the lower pregnancy rate compared to the GnRH agonist long protocol necessitates counseling subfertile couples before recommending change from GnRH agonist to antagonist.

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