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Open Access 01-12-2018 | Study protocol

Gonadotropin-releasing hormone antagonist versus progestin for the prevention of premature luteinising hormone surges in poor responders undergoing in vitro fertilisation treatment: study protocol for a randomised controlled trial

Authors: Yun Wang, Yanping Kuang, Qiuju Chen, Renfei Cai

Published in: Trials | Issue 1/2018

Abstract

Background

Progress in vitrification techniques has allowed reproductive physicians to consider new strategies for using progestin as an alternative to a GnRH analogue to improve in vitro fertilisation (IVF). However, the role of progestin in blocking luteinising hormone (LH) surges and its potential in clinical practice are unclear, especially for poor responders. We designed a prospective randomised controlled trial (RCT) to compare the efficacy of a gonadotropin-releasing hormone (GnRH) antagonist and progestin in blocking LH surges and premature ovulation in poor responders.

Methods/design

Poor responders who meet the Bologna criteria will be randomised to one of two stimulation regimens—gonadotropin-releasing hormone (GnRH) antagonist or progestin-primed ovarian stimulation (PPOS)—using a computer-generated random number. Fresh embryos were transferred in the GnRH antagonist group and frozen embryos were transferred in the PPOS group. The primary outcome is the incidence of premature LH surges. Secondary outcomes include the number of oocytes retrieved, the number of embryos available for transfer, implantation rates and clinical pregnancy. The sample size for this trial is estimated as 340 participants, with 170 participants in each group. The data analysis will be by intention to treat.

Discussion

To our knowledge, this is the first RCT to examine the efficacy of administering progestin orally to block LH surges and premature ovulation compared with the GnRH antagonist protocols in poor responders undergoing IVF treatment.

Trial registration

www.chictr.org.cn. ChiCTR-IPR-17010906. Registered on 18 March 2017.

Available only for authorised users

Hall JE, et al. Evidence of differential control of FSH and LH secretion by gonadotropin-releasing hormone (GnRH) from the use of a GnRH antagonist. J Clin Endocrinol Metab. 1988;67(3):524–31.CrossRefPubMed

Al-Inany HG, et al. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2016;4:CD001750.PubMed

Lambalk CB, et al. GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type. Hum Reprod Update. 2017;23(5):560–79.CrossRefPubMed

Blockeel C, et al. A fresh look at the freeze-all protocol: a SWOT analysis. Hum Reprod. 2016;31(3):491–7.CrossRefPubMed

Kuang Y, et al. Luteal-phase ovarian stimulation is feasible for producing competent oocytes in women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, with optimal pregnancy outcomes in frozen-thawed embryo transfer cycles. Fertil Steril. 2014;101(1):105–11.CrossRefPubMed

Kuang Y, et al. Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Fertil Steril. 2015;104(1):62–70.CrossRefPubMed

Massin N. New stimulation regimens: endogenous and exogenous progesterone use to block the LH surge during ovarian stimulation for IVF. Hum Reprod Update. 2017;23(1):211–20.PubMed

Chen Q, et al. Controlled ovulation of the dominant follicle using progestin in minimal stimulation in poor responders. Reprod Biol Endocrinol. 2017;15:71.CrossRefPubMedPubMedCentral

Dierschke DJ, et al. Blockade by progesterone of estrogen-induced LH and FSH release in the rhesus monkey. Endocrinology. 1973;92(5):1496–501.CrossRefPubMed

10.

Kasa-Vubu JZ, et al. Progesterone blocks the estradiol-induced gonadotropin discharge in the ewe by inhibiting the surge of gonadotropin-releasing hormone. Endocrinology. 1992;131(1):208–12.CrossRefPubMed

11.

Richter TA, et al. Progesterone can block the preovulatory gonadotropin-releasing hormone/luteinising hormone surge in the ewe by a direct inhibitory action on oestradiol-responsive cells within the hypothalamus. J Neuroendocrinol. 2005;17(3):161–9.CrossRefPubMed

12.

Attardi B, et al. Facilitation or inhibition of the oestradiol-induced gonadotrophin surge in the immature female rat by progesterone: effects on pituitary responsiveness to gonadotrophin-releasing hormone (GnRH), GnRH self-priming and pituitary mRNAs for the progesteronereceptor A and B isoforms. J Neuroendocrinol. 2007;19(12):988–1000.CrossRefPubMed

13.

Soules MR, et al. Progesterone modulation of pulsatile luteinizing hormone secretion in normal women. J Clin Endocrinol Metab. 1984;58(2):378–83.CrossRefPubMed

14.

Sitruk-Ware R. New progestagens for contraceptive use. Hum Reprod Update. 2006;12(1):169–78.CrossRefPubMed

15.

Reichman DE, et al. Diminished ovarian reserve is the predominant risk factor for gonadotropin-releasing hormone antagonist failure resulting in breakthrough luteinizing hormone surges in in vitro fertilization cycles. Fertil Steril. 2014;102(1):99–102.CrossRefPubMed

16.

Chow SC, et al. Sample size calculation in clinical research. 2nd ed. New York: Taylor and Francis; 2007.

17.

Wu YG, et al. Aging-related premature luteinization of granulosa cells is avoided by early oocyte retrieval. J Endocrinol. 2015;226(3):167–80.CrossRefPubMed

18.

Albano C, et al. Ovarian stimulation with hMG: results of a prospective randomized phase III European study comparing the luteinizing hormone-releasing hormone (LHRH)-antagonist cetrorelix and the LHRH-agonist buserelin. European Cetrorelix Study Group. Hum Reprod. 2000;15(3):526–31.CrossRefPubMed

19.

Mansour RT, et al. The use of gonadotropin-releasing hormone antagonist in a flexible protocol: a pilot study. Am J Obstet Gynecol. 2003;189(2):444–6.CrossRefPubMed

20.

Messinis IE, et al. Alternate day and daily administration of GnRH antagonist may prevent premature luteinization to a similar extent during FSH treatment. Hum Reprod. 2005;20(11):3192–7.CrossRefPubMed

Title: Gonadotropin-releasing hormone antagonist versus progestin for the prevention of premature luteinising hormone surges in poor responders undergoing in vitro fertilisation treatment: study protocol for a randomised controlled trial
Authors: Yun Wang
Yanping Kuang
Qiuju Chen
Renfei Cai
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Trials / Issue 1/2018
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-018-2850-x

At a glance: The STEP trials

Springer Medicine

Gonadotropin-releasing hormone antagonist versus progestin for the prevention of premature luteinising hormone surges in poor responders undergoing in vitro fertilisation treatment: study protocol for a randomised controlled trial

Abstract

Background

Methods/design

Discussion

Trial registration

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods/design

Discussion

Trial registration

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