Elevated early follicular progesterone levels and in vitro fertilization outcomes: a prospective intervention study and meta-analysis
Ouijdane Hamdine, Nick S Macklon, Marinus J C Eijkemans, Joop S E Laven, Bernard J Cohlen, Arie Verhoeff, Peter A van Dop, Rob E Bernardus, Cornelis B Lambalk, Gerrit J E Oosterhuis, Caspar A G Holleboom, Grada C van den Dool-Maasland, Harjo J Verburg, Petrus F M van der Heijden, Adrienne Blankhart, Bart C J M Fauser, Frank J Broekmans, CETRO trial study group, Ouijdane Hamdine, Nick S Macklon, Marinus J C Eijkemans, Joop S E Laven, Bernard J Cohlen, Arie Verhoeff, Peter A van Dop, Rob E Bernardus, Cornelis B Lambalk, Gerrit J E Oosterhuis, Caspar A G Holleboom, Grada C van den Dool-Maasland, Harjo J Verburg, Petrus F M van der Heijden, Adrienne Blankhart, Bart C J M Fauser, Frank J Broekmans, CETRO trial study group
Abstract
Objective: To assess the impact of elevated early follicular progesterone (P) levels in gonadotropin-releasing hormone (GnRH) antagonist cycles on clinical outcome using prospective data in combination with a systematic review and meta-analysis.
Design: Nested study within a multicenter randomized controlled trial and a systematic review and meta-analysis.
Setting: Reproductive medicine center in an university hospital.
Patient(s): 158 in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) patients.
Intervention(s): Recombinant follicle-stimulating hormone (FSH) (150-225 IU) administered daily from cycle day 2 onward; GnRH antagonist treatment randomly started on cycle day 2 or 6; assignment into two groups according to P level on cycle day 2: normal or elevated (>4.77 nmol/L or >1.5 ng/mL, respectively).
Main outcome measure(s): Ongoing pregnancy rate (OPR) per started cycle.
Result(s): The incidence of elevated P was 13.3%. A non-statistically-significant difference in OPR was present between the normal and elevated P groups (27.0% vs. 19.0%). No differential impact of early or late GnRH antagonist initiation on the effect of elevated or normal P on OPR was observed. A systematic search of Medline and EMBASE from 1972-2013 was performed to identify studies analyzing elevated early P levels in GnRH antagonists. The meta-analysis (n=1,052) demonstrated that elevated P levels statistically significantly decreased the OPR with 15% (95% CI -23, -7 %). Heterogeneity across the studies, presumably based on varying protocols, may have modulated the effect of elevated P.
Conclusion(s): From the present meta-analysis it appears that early elevated P levels are associated with a lower OPR in GnRH antagonists. The incidence of such a condition, however, is low.
Clinical trial registration number: NCT00866034.
Keywords: Clinical outcome; GnRH antagonist; IVF; progesterone levels.
Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Source: PubMed