Impact of gonadotropin type on progesterone elevation during ovarian stimulation in GnRH antagonist cycles

STUDY QUESTION: Does hormonal stimulation with corifollitropin alpha (CFA) only, mimicking a step down protocol, result in lower incidence of progesterone elevation on the day of hCG-trigger as compared to sustained stimulation with recombinant FSH (rFSH)? SUMMARY ANSWER: The current findings support the concept that sustained FSH stimulus contributes to premature progesterone elevation in stimulated IVF cycles. WHAT IS KNOWN ALREADY: Serum progesterone rise during the follicular phase of ovarian stimulation for IVF treatment seems to be related to a poorer reproductive outcome. However, the mechanism by which the rise in progesterone is caused is not yet fully understood. STUDY DESIGN: This study was a post hoc analysis of data from two multi-centre, randomised, double-blind, double-dummy, active-controlled, non-inferiority trials, ENGAGE and PURSUE, conducted from June 2006 to January 2008 and from July 2010 to October 2012 respectively. PARTICIPANTS/MATERIALS, SETTING, METHODS: In the ENGAGE-study, 1506 women, aged 18-36 years, were allocated to either a single injection of 150 mg CFA or daily injections of 200 IU rFSH in the first week of stimulation, using a standard GnRH antagonist protocol. In the PURSUE-study, a total of 1390 women, aged 35-42 years, were allocated to either a single injection of 150 mg of CFA or daily 300 IU of rFSH for the first week, again using a standard GnRH antagonist protocol. In both trials, daily rFSH was continued until three follicles reached >17 mm in size. All women had a body weight of between 50 and 90 kg, regular menstrual cycles and an indication for ovarian stimulation before IVF. The incidence of progesterone elevation on day of hCG-trigger in patients with CFA only or rFSH stimulation, and triggered on Day 8 of stimulation, was analysed. MAIN RESULTS AND THE ROLE OF CHANCE: Of patients with CFA only stimulation, 5.4% (13/239 patients) showed a progesterone elevation above 1.5 ng/ml on day of hCG-trigger, whereas patients with rFSH stimulation had a significant higher incidence of progesterone elevation (18.3%; 62/339 patients) (P < 0.001). LIMITATIONS, REASONS FOR CAUTION: Post hoc analysis of data from previously published trials could be considered as a reason for caution. WIDER IMPLICATIONS OF THE FINDINGS: Future studies should evaluate whether it would be possible to prevent a premature progesterone rise in cycles stimulated with daily FSH by using a step down protocol towards the end of the follicular phase. STUDY FUNDING/COMPETING INTERESTS: Financial/Material Support was provided by Merck & Co., Inc., Kenilworth, NJ, USA. Davis Gates is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and may own stock and/or hold stock options in the company. Fabiola Beligotti is an employee of MSD, Italy, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and may own stock and/or hold stock options in the company. Barbara Lawrenz, Nils Engelmann. Authors: Lawrenz B, Beligotti F, Engelmann N, Gates D, Fatemi HM. ;Full Source: Human Reproduction. 2016 Sep 12. [Epub ahead of print] and Human M. Fatemi have no conflict of interest. ;