Human Reproduction Update Advance Access originally published online on March 27, 2006
Human Reproduction Update 2006 12(4):333-340; doi:10.1093/humupd/dml001
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GnRH antagonists in ovarian stimulation for IVF
1 Unit for Human Reproduction, 1st Department of Obstetrics and Gynaecology, Aristotle University of Thessaloniki, Thessaloniki, Greece, 2 Department of Reproductive Medicine and Gynaecology, University Medical Centre, Utrecht, Netherlands, 3 Department of Gynecology and Obstetrics, Division of Gynaecological Endocrinology and Reproductive Medicine, University Clinic of Schleswig-Holstein, Campus Luebeck, Luebeck, Germany and 4 Centre for Reproductive Medicine, Dutch-Speaking Brussels Free University, Brussels, Belgium
5 To whom correspondence should be addressed at: 1st Department of Obstetrics and Gynaecology, Aristotle University of Thessaloniki, Unit for Human Reproduction, Papageorgiou General Hospital, Nea Efkarpia Peripheral Road, Thessaloniki 54603, Greece. E-mail: tarlatzis{at}hol.gr
Submitted on December 21, 2005; accepted on January 13, 2006
The present review describes, on the basis of the currently available evidence, the consensus reached by a group of experts on the use of gonadotropin-releasing hormone (GnRH) antagonists in ovarian stimulation for IVF. The single or multiple low-dose administration of GnRH antagonist during the late-follicular phase effectively prevents a premature rise in serum luteinizing hormone (LH) levels in most women. Although controversy remains, most comparative studies suggest a slight, not significant reduction in the probability of pregnancy after IVF using GnRH antagonist versus GnRH agonist co-treatment. Published meta-analyses suggest that this slight difference in pregnancy rates is not attributed to chance. Further studies applying varying treatment regimens and outcome measures are required. Data are not in favour of a need to modify the starting dose of gonadotropins. Data are not in favour of increasing gonadotropin dose at GnRH antagonist initiation. The addition of LH from the initiation of ovarian stimulation or from GnRH antagonist administration does not appear to be necessary. Replacement of human chorionic gonadotropin (HCG) by GnRH agonist for triggering final oocyte maturation is associated with a lower probability of pregnancy. The optimal timing for HCG administration needs to be explored further. GnRH antagonist initiation on day 6 of stimulation appears to be superior to flexible initiation by a follicle of 14–16 mm, although earlier GnRH antagonist administration is worth further evaluation. Luteal phase supplementation in GnRH antagonist protocols remains mandatory in IVF. Effects of GnRH antagonist co-treatment on the incidence of ovarian hyperstimulation syndrome remains uncertain, although a trend is present in favour of the GnRH antagonists. The role of GnRH antagonists in ovarian stimulation for IVF appears to be promising, although many questions regarding preferred dose regimens and effects on clinical outcomes remain.
Key words: GnRH antagonists / IVF / ovarian stimulation / pregnancy rates
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