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Elevated early follicular progesterone levels and in vitro fertilization outcomes: a prospective intervention study and meta-analysis.
Fertil Steril. 2014 Aug; 102(2):448-454.e1.FS

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.

Authors+Show Affiliations

Department of Reproductive Medicine and Gynecology, University Medical Centre Utrecht, Utrecht, the Netherlands. Electronic address: O.Hamdine@umcutrecht.nl.Department of Reproductive Medicine and Gynecology, University Medical Centre Utrecht, Utrecht, the Netherlands; Academic Unit of Human Development and Health, Princess Anne Hospital, University of Southampton, Southampton, United Kingdom.Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, the Netherlands.Division of Reproductive Medicine, Erasmus University Medical Centre, Rotterdam, the Netherlands.Department of Gynecology and Fertility, Isala Clinics, Zwolle, the Netherlands.Department of Gynecology and Fertility, Maasstad Hospital, Rotterdam, the Netherlands.Department of Gynecology and Fertility, Catharina Hospital, Eindhoven, the Netherlands.Department of Gynecology and Fertility, Tergooi Hospital, Blaricum, the Netherlands.Division of Reproductive Medicine, VU University Medical Centre, Amsterdam, the Netherlands; Department of Gynaecology-Obstetrics, Centre for Reproductive Medicine of the University Hospital of Ghent, Ghent, Belgium.Department of Gynecology and Fertility, Medisch Spectrum Twente Hospital Group, Enschede, the Netherlands.Department of Gynecology and Fertility, Bronovo Hospital, the Hague, the Netherlands.Department of Gynecology and Fertility, Albert Schweitzer Hospital, Zwijndrecht, the Netherlands.Department of Gynecology and Fertility, Leiden University Medical Centre, Leiden, the Netherlands.Department of Gynecology and Fertility, ZGT Almelo, Almelo, the Netherlands.Department of Gynecology and Fertility, St. Antonius Hospital, Nieuwegein, the Netherlands.Department of Reproductive Medicine and Gynecology, University Medical Centre Utrecht, Utrecht, the Netherlands.Department of Reproductive Medicine and Gynecology, University Medical Centre Utrecht, Utrecht, the Netherlands.No affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Systematic Review

Language

eng

PubMed ID

24929258

Citation

Hamdine, Ouijdane, et al. "Elevated Early Follicular Progesterone Levels and in Vitro Fertilization Outcomes: a Prospective Intervention Study and Meta-analysis." Fertility and Sterility, vol. 102, no. 2, 2014, pp. 448-454.e1.
Hamdine O, Macklon NS, Eijkemans MJ, et al. Elevated early follicular progesterone levels and in vitro fertilization outcomes: a prospective intervention study and meta-analysis. Fertil Steril. 2014;102(2):448-454.e1.
Hamdine, O., Macklon, N. S., Eijkemans, M. J., Laven, J. S., Cohlen, B. J., Verhoeff, A., van Dop, P. A., Bernardus, R. E., Lambalk, C. B., Oosterhuis, G. J., Holleboom, C. A., van den Dool-Maasland, G. C., Verburg, H. J., van der Heijden, P. F., Blankhart, A., Fauser, B. C., & Broekmans, F. J. (2014). Elevated early follicular progesterone levels and in vitro fertilization outcomes: a prospective intervention study and meta-analysis. Fertility and Sterility, 102(2), 448-e1. https://doi.org/10.1016/j.fertnstert.2014.05.002
Hamdine O, et al. Elevated Early Follicular Progesterone Levels and in Vitro Fertilization Outcomes: a Prospective Intervention Study and Meta-analysis. Fertil Steril. 2014;102(2):448-454.e1. PubMed PMID: 24929258.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Elevated early follicular progesterone levels and in vitro fertilization outcomes: a prospective intervention study and meta-analysis. AU - Hamdine,Ouijdane, AU - Macklon,Nick S, AU - Eijkemans,Marinus J C, AU - Laven,Joop S E, AU - Cohlen,Bernard J, AU - Verhoeff,Arie, AU - van Dop,Peter A, AU - Bernardus,Rob E, AU - Lambalk,Cornelis B, AU - Oosterhuis,Gerrit J E, AU - Holleboom,Caspar A G, AU - van den Dool-Maasland,Grada C, AU - Verburg,Harjo J, AU - van der Heijden,Petrus F M, AU - Blankhart,Adrienne, AU - Fauser,Bart C J M, AU - Broekmans,Frank J, AU - ,, Y1 - 2014/06/11/ PY - 2014/02/05/received PY - 2014/05/01/revised PY - 2014/05/02/accepted PY - 2014/6/16/entrez PY - 2014/6/16/pubmed PY - 2014/9/30/medline KW - Clinical outcome KW - GnRH antagonist KW - IVF KW - progesterone levels SP - 448 EP - 454.e1 JF - Fertility and sterility JO - Fertil. Steril. VL - 102 IS - 2 N2 - 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. SN - 1556-5653 UR - https://www.unboundmedicine.com/medline/citation/24929258/Elevated_early_follicular_progesterone_levels_and_in_vitro_fertilization_outcomes:_a_prospective_intervention_study_and_meta_analysis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0015-0282(14)00414-2 DB - PRIME DP - Unbound Medicine ER -