title: GnRH agonist for triggering final oocyte maturation in the GnRH antagonist ovarian hyperstimulation protocol: a systematic review and meta-analysis.
abstract: Triggering final oocyte maturation with GnRH agonist during ovarian stimulation is feasible when inhibition of premature LH surge is performed with GnRH antagonists, and we aimed to systematically collate evidence on the clinical efficacy of GnRH agonist triggering in patients undergoing assisted reproduction in GnRH antagonist protocols. Twenty-three publications were identified by a comprehensive literature search that included PubMed, Embase and the Cochrane Library. Three publications out of 23 fulfilled the inclusion criteria for meta-analysis, which were (i) prospective, randomized controlled study design; (ii) stimulation with gonadotropins for induction of multifollicular development; (iii) suppression of endogenous LH by a GnRH antagonist; (iv) triggering of final oocyte maturation with GnRH agonist; (v) control group randomized to receive HCG for final oocyte maturation and (vi) any means of luteal phase support other than HCG. The participants were normoovulatory women undergoing IVF. The outcomes assessed were clinical pregnancy per randomized patient; number of oocytes retrieved; proportion of metaphase II oocytes; fertilization rate; embryo quality score; first trimester abortion rate; ovarian hyperstimulation syndrome (OHSS) incidence. Results are presented as combined standardized differences of the mean and combined odds ratios, as appropriate, with 95% confidence intervals. No significant difference was found for the number of oocytes retrieved (-0.94, -0.33-0.14), proportion of metaphase II oocytes (-0.03, -0.58-0.52), fertilization rate (0.15, -0.09-0.38) or embryo quality score (0.05, -0.18-0.29). No OHSS occurred in two of the studies, whereas in one study OHSS incidence was not reported. Thus from the available data, no conclusion can be drawn as regards OHSS incidence after GnRH agonist triggering. In comparison to HCG, GnRH agonist administration is associated with a significantly reduced likelihood of achieving a clinical pregnancy (0.21, 0.05-0.84; P = 0.03). The odds of first trimester pregnancy loss is increased after GnRH agonist triggering; however, the confidence interval crosses unity (11.51, 0.95-138.98; P = 0.05). In conclusion, the use of GnRH agonist to trigger final oocyte maturation in IVF, where inhibition of premature LH surge is achieved with GnRH antagonists, yields a number of oocytes capable to undergo fertilization and subsequent embryonic cleavage, which is comparable to that achieved with HCG. However, the likelihood of an ongoing clinical pregnancy after GnRH agonist triggering is significantly lower as compared to standard HCG treatment.
authors.affiliation: Department of Obstetrics and Gynecology, University Clinic of Schleswig-Holstein, Campus Luebeck, Luebeck, Germany. georg.griesinger@frauenklinik.uni-luebeck.de
authors.forename: G
authors.initials: G
authors.lastname: Griesinger
authors.forename: K
authors.initials: K
authors.lastname: Diedrich
authors.forename: P
authors.initials: P
authors.lastname: Devroey
authors.forename: E M
authors.initials: EM
authors.lastname: Kolibianakis
mesh_terms: D000022:Abortion, Spontaneous / Q000453:epidemiology; D004622:Embryo, Mammalian / Q000502:physiology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists* / Q000037:antagonists & inhibitors*; D006801:Humans; D015994:Incidence; D008677:Metaphase; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D016471:Ovarian Hyperstimulation Syndrome / Q000139:chemically induced* / Q000453:epidemiology; D010062:Ovulation Induction / Q000009:adverse effects / Q000379:methods*; D011247:Pregnancy; D018873:Pregnancy Rate; D000078202:Systematic Reviews as Topic
chemical_list: D007987:Gonadotropin-Releasing Hormone