Contents lists available at ScienceDirect Reproductive Biology journal homepage: www.elsevier.com/locate/repbio Original article The association between treatment parameters on the day of gonadotropin- releasing hormone antagonist initiation during a flexible protocol and oocyte maturation rate Avital Wertheimer*, Shir Danieli-Gruber, Alyssa Hochberg, Galia Oron, Onit Sapir, Yoel Shufaro, Avi Ben-Haroush IVF and Infertility Unit, Helen Schneider Hospital for Women, Rabin Medical Center-Beilinson Hospital, Petach Tikva, 4941492, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 6901128, Israel ARTICLE INFO Keywords: GnRH antagonist Oocyte maturation Estradiol IVF ABSTRACT This study aimed to evaluate the effects of different treatment parameters on the day of GnRH antagonist in- itiation on oocyte maturation rate. We performed a retrospective cohort study of women aged ≤ 38 who un- derwent their first IVF-ICSI treatment using a flexible GnRH antagonist protocol in a single university-affiliated medical center during 2005-2015. Treatment parameters of three groups of oocyte maturation rates (< 60%, 60- 90%, > 90%) were compared. Multivariate analysis was conducted to detect an association between treatment parameters on the day of GnRH antagonist initiation and oocyte maturation rate. The cohort included 458 patients, of whom 180 (39%) had a high oocyte maturation rate (≥90%), 211 (46%) had an oocyte maturation rate between 60-90% and 67 (15%) had a low maturation rate (≤60%). Women with a high maturation rate had longer duration of treatment (10.3 ± 2.9 days vs. 9.6 ± 2.5 vs. 9.5 ± 3.2, P = 0.019), lower levels of estradiol (1985 ± 1357 vs. 2406 ± 1666 vs. 2325 ± 1811, P = 0.027) and lower estradiol/maximal follicular diameter ratio on the day of GnRH antagonist initiation (137 ± 89 vs. 165 ± 103 vs. 163 ± 125, P = 0.019) as compared to women with medium and low maturation rates, respectively. Using linear regression multivariate analysis, lower estradiol and lower estradiol/maximal follicular diameter ratio on GnRH antagonist initiation day were associated with higher oocyte maturation rate. Further prospective studies to determine the best timing for GnRH antagonist initiation are needed. 1. Introduction The use of Gonadotropin-releasing hormone (GnRH) antagonist protocol for controlled ovarian stimulation during in vitro fertilization (IVF) has significantly increased over recent decades. This is due to its several advantages, including shorter duration of treatment, reduced gonadotropin dosage, lower incidence of ovarian hyperstimulation syndrome, and avoidance of hypo-estrogenic symptoms and ovarian cyst formation [1]. Conversely, one of the GnRH antagonist protocol’s disadvantages is a lower oocyte maturation rate that may result from decreased follicular synchronization [2,3]. One proposed mechanism for decreased follicular synchronization is the lack of inhibition of en- dogenous FSH during the luteal-follicular transition phase [4–6]. Pre- vious studies [7,8] have demonstrated that early initiation of a GnRH antagonist from the beginning of the menstrual cycle may increase follicular synchronization. On the other hand, prolonged exposure to a GnRH antagonist may have a negative effect on the follicles by in- hibiting the cell cycle and decreasing the synthesis of locally produced growth factors [9–11]. The GnRH antagonist is initiated either on day 6 of stimulation (fixed regimen) or when the leading follicle reaches a diameter of 12 – 14 mm (flexible regimen) [2,11,12]. Treatment outcomes and LH sup- pression in both regimens are comparable, but the flexible protocol affords a significant reduction in both GnRH antagonist and gonado- tropin dosages [2,3,13–15]. In the flexible regimen, GnRH antagonist may be initiated on different stimulation days, with different follicular sizes and estradiol levels. Initiation of a GnRH antagonist when the leading follicle reaches 14 - 15.9 mm in diameter on cycle day 6, or when the estradiol level ranges between 1530 and 1880 pmol/L, was found to be associated with a better clinical pregnancy rate [16]. Data regarding the effects of these parameters on oocyte maturation is scarce. Thus, we aimed to investigate the effects of different treatment https://doi.org/10.1016/j.repbio.2020.04.004 Received 28 January 2020; Received in revised form 12 April 2020; Accepted 17 April 2020 ⁎ Corresponding author. E-mail address: avital.wer@gmail.com (A. Wertheimer). Reproductive Biology xxx (xxxx) xxx–xxx 1642-431X/ © 2020 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved. Please cite this article as: Avital Wertheimer, et al., Reproductive Biology, https://doi.org/10.1016/j.repbio.2020.04.004