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Elevated early follicular progesterone levels and in vitro fertilization outcomes: a prospective intervention study
Ouijdane Hamdine1, Nick S Macklon2, Marinus J C Eijkemans3
1Department of Reproductive Medicine and Gynecology, University Medical Centre Utrecht, Utrecht, the Netherlands.
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.
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