Do cumulative live birth rates (CLBRs) after one complete ART cycle differ between the three commonly used controlled ovarian stimulation (COS) protocols (GnRH antagonist, depot GnRHa (GnRH agonist) and long GnRHa) in normal responders undergoing IVF/ICSI?

SUMMARY ANSWER

There were similar CLBRs between the GnRH antagonist, depot GnRHa and long GnRHa protocols.

WHAT IS KNOWN ALREADY

There is no consensus on which COS protocol is the most optimal in women with normal ovarian response. The CLBR provides the final success rate after one complete ART cycle, including the fresh and all subsequent frozen–thawed embryo transfer (ET) cycles. We suggest that the CLBR measure would allow for better comparisons between the different treatment protocols.

STUDY DESIGN, SIZE, DURATION

A prospective controlled, randomized, open label trial was performed between May 2016 and May 2017. A total of 819 patients were allocated to the GnRH antagonist, depot GnRHa or long GnRHa protocol in a 1:1:1 ratio. The minimum follow-up time from the first IVF cycle was 2 years. To further investigate the potential effect of COS with the GnRH antagonist, depot GnRHa or long GnRHa protocol on endometrial receptivity, the expression of homeobox A10 (HOXA10), myeloid ecotropic viral integration site 1 (MEIS1) and leukemia inhibitory factor (LIF) endometrial receptivity markers was evaluated in endometrial tissue from patients treated with the different COS protocols.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Infertile women with normal ovarian response (n = 819) undergoing IVF/ICSI treatment were randomized to the GnRH antagonist, depot GnRHa or long GnRHa protocol. Both IVF and ICSI cycles were included, and the sperm samples used were either fresh or frozen partner ejaculates or frozen donor ejaculates. The primary outcome was the live birth rate (LBR) per fresh ET cycle, and the CLBR after one complete ART cycle, until the birth of a first child (after 28 weeks) or until all frozen embryos were used, whichever occurred first. Pipelle endometrial biopsies from 34 female patients were obtained on Days 7–8 after oocyte retrieval or spontaneous ovulation in natural cycles, respectively, and HOXA10, MEIS1 and LIF mRNA and protein expression levels in the human endometrium was determined by quantitative real-time PCR and western blot, respectively.

MAIN RESULTS AND THE ROLE OF CHANCE

There were no significant differences in CLBRs between the GnRH antagonist, depot GnRHa or long GnRHa protocol (71.4 versus 75.5 versus 72.2%, respectively). However, there was a significantly higher LBR per fresh ET cycle in the depot GnRHa protocol than in the long GnRHa and GnRH antagonist protocols (62.6 versus 52.1% versus 45.6%, P < 0.05). Furthermore, HOXA10, MEIS1 and LIF mRNA and protein expression in endometrium all showed significantly higher in the depot GnRHa protocol than in the long GnRHa and GnRH antagonist protocols (P < 0.05).