Elevated early follicular progesterone levels and in vitro fertilization outcomes A prospective intervention study and meta analysis

Elevated progesterone levels on cycle day 2 affect ongoing pregnancy rates in gonadotropin-releasing hormone antagonist cycles.


Ouijdane Hamdine, M.D., Nick S. Macklon, M.D., Ph.D., Marinus J. Eijkemans, Ph.D., Joop S Laven, M.D., Ph.D., Bernard J. Cohlen, M.D., Ph.D., Arie Verhoeff, M.D., Ph.D., Peter A. van Dop, M.D., Ph.D., Rob E. Bernardus, M.D., Ph.D., Cornelis B. Lambalk, M.D., Ph.D., Gerrit J. Oosterhuis, M.D., Ph.D., Caspar A. Holleboom, M.D., Ph.D., Grada C. van den Dool-Maasland, M.D., Harjo J. Verburg, M.D., Petrus F. van der Heijden, M.D., Ph.D., Adrienne Blankhart, M.D., Bart C. Fauser, M.D., Ph.D., Frank J. Broekmans, M.D., Ph.D.

Volume 102, Issue 2, Pages 448–454.e1



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.


Nested study within a multicenter randomized controlled trial and a systematic review and meta-analysis.


Reproductive medicine center in an university hospital.


158 in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) patients.


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.


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.


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:


Read the full text at: http://www.fertstert.org/article/S0015-0282(14)00414-2/fulltext