The Impact of Suppressing Estradiol During Ovarian Stimulation on the Unsupported Luteal Phase: A Randomized Controlled Trial

Author:

Dreyer Holt Marianne1ORCID,Skouby Sven Olaf2,Bülow Nathalie Søderhamn3,Englund Anne Lis Mikkelsen1,Birch Petersen Kathrine4,Macklon Nicholas Stephen15

Affiliation:

1. Department of Gynecology and Obstetrics, The Fertility Clinic and ReproHealth Consortium, Zealand University Hospital , Lykkebækvej 14, 4600 Køge , Denmark

2. Department of Gynecology and Obstetrics, The Fertility Clinic, Herlev University Hospital , Borgmester Ib Juuls Vej 1, 2730 Herlev , Denmark

3. Department of Gynecology and Obstetrics, The Fertility Clinic, Rigshospitalet , Blegdamsvej 9, 2100 Copenhagen , Denmark

4. TFP Stork Fertility, The Fertility Partnership , Store Kongensgade 40G 1., 1264 Copenhagen , Denmark

5. London Women’s Clinic , 113-115 Harley Street, London W1G 6AP , UK

Abstract

Abstract Context Supraphysiological sex steroid levels at the follicular-luteal phase transition are implicated as the primary cause of luteal insufficiency after ovarian stimulation (OS) for in vitro fertilization. Objective We aimed to determine the impact of suppressing estradiol levels during OS of multiple dominant follicles on the unsupported luteal phase and markers of endometrial maturation. Methods At 2 university hospitals, 25 eligible egg donors were randomized to undergo OS using exogenous gonadotropins with or without adjuvant letrozole 5 mg/day. Final oocyte maturation was triggered with a GnRH agonist. No luteal support was provided. The primary outcome was the duration of the luteal phase. Secondary outcomes were luteal phase hormone profiles and the endometrial transcriptomic signature 5 days after oocyte pick up (OPU + 5). Results The median (interquartile range [IQR]) luteal phase duration was 8.0 (6.8-11.5) days compared with 5.0 (5.0-6.8) days in the intervention and control group, respectively (P < 0.001). Estradiol levels were effectively suppressed in the letrozole group with a median of 0.86 (0.23-1.24) nmol/L at OPU compared to 2.82 (1.34-3.44) nmol/L in the control group. Median (IQR) progesterone levels at OPU + 5 were 67.05 (15.67-101.75) nmol/L in the letrozole group vs 2.27 (1.05-10.70) nmol/L in the control group (P < 0.001). In the letrozole group, 75% of participants revealed endometrial transcriptomic signatures interpreted as post-receptive. In the control group, 40% were post-receptive and 50% noninformative. Conclusion Suppressing estradiol levels in the follicular phase with adjuvant letrozole significantly reduces the disruption of the unsupported luteal phase after OS.

Funder

Gedeon Richter and the Zealand Health Region

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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