Abstract

Abstract Study question Do progestin primed ovarian stimulation (PPOS) cycles have lower euploidy yield compared to pituitary suppression with gonadotropin releasing hormone (GnRH) antagonists? Summary answer The choice of pituitary suppression method has no bearing on euploid retrieval per blastocyst tested. What is known already Progestin primed ovarian stimulation cycles are an alternative to GnRH antagonists when fresh embryo transfer is not a priority. While the two approaches have been shown to be similar in terms of conventional stimulation outcomes such as mature oocyte retrieval, and blastulation rates, there is still some lingering controversy regarding cumulative pregnancy rates and the effects of progestins on embryo genetic constitution. Study design, size, duration This was a multicenter retrospective cohort study including data from two tertiary-level treatment centers. Participants/materials, setting, methods Infertile women undergoing ovarian stimulation with either progestin primed or GnRH antagonist pituitary suppression with the intention of transfer after PGT-A embryo testing with next-generation sequencing. The main outcome parameter was euploid embryo count per blastocyst tested and was modeled with mixed-effects log-binomial regression models. Results were adjusted for patient age and laboratory performing the PGT-A tests while they were not adjusted for embryo quality to avoid collider bias. Main results and the role of chance A total of 1425 PGT-A tested blastocysts from 383 cycles of 365 patients were included in the analysis. 243 cycles (63.4%) received GnRH antagonists for pituitary suppression while 140 (36.5%) received progestins. The overall euploidy rates per blastocyst tested in the GnRH antagonist and PPOS groups were 38.8% vs. 31.1%, 30.2% vs. 29.4%, 27.0% vs. 25.2%, and 13.8% vs. 14.5% for the age categories <35, 35-37, 38-40, and >40, respectively. After adjusting for the effect of female age at testing and the laboratory performing the PGT-A test, the type of pituitary suppression was not significantly associated with euploid retrieval per blastocyst tested (adjusted risk ratio: 0.94, 95% CI: 0.70 - 1.28, P = 0.701). After testing, 191 women received 233 embryo transfers. Human chorionic gonadotropin (hCG) positivity per transferred embryo was not significantly different between progestin primed and GnRH antagonist cycles (RR: 0.89, 95% CI: 0.71 – 1.08, P = 0.268). Limitations, reasons for caution This is a retrospective study with data from multiple centers with a non-standardized selection of blastocysts to be tested. In addition, the sample size and retrospective nature of the data may have biased the estimates. Wider implications of the findings The choice of pituitary suppression method does not appear to have a significant effect on euploid embryo retrieval rates or hCG positivity per transfer. The choice of medication can be based on the needs of the individual case without concern for suboptimal PGT-A outcomes. Trial registration number Not Applicable

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