Metaphase-II oocyte competence is unlinked to the gonadotrophins used for ovarian stimulation: a matched case-control study in women of advanced maternal age

Abstract

Purpose: An impact of different gonadotrophins selection for ovarian stimulation (OS) on oocyte competence has yet to be defined. In this study, we asked whether an association exists between OS protocol and euploid blastocyst rate (EBR) per metaphase-II (MII) oocytes.

Methods: Cycles of first preimplantation genetic testing for aneuploidies conducted by women ≥ 35 years old with their own metaphase-II oocytes inseminated in the absence of severe male factor (years 2014-2018) were clustered based on whether recombinant FSH (rec-FSH) or human menopausal gonadotrophin (HMG) was used for OS, then matched for the number of fresh inseminated eggs. Four groups were outlined: rec-FSH (N = 57), rec-FSH plus rec-LH (N = 55), rec-FSH plus HMG (N = 112), and HMG-only (N = 127). Intracytoplasmic sperm injection, continuous blastocyst culture, comprehensive chromosome testing to assess full-chromosome non-mosaic aneuploidies and vitrified-warmed euploid single embryo transfers (SETs) were performed. The primary outcome was the EBR per cohort of MII oocytes. The secondary outcome was the live birth rate (LBR) per first SETs.

Results: Rec-FSH protocol was shorter and characterized by lower total gonadotrophin (Gn) dose. The linear regression model adjusted for maternal age showed no association between the Gn adopted for OS and EBR per cohort of MII oocytes. Similarly, no association was reported with the LBR per first SETs, even when adjusting for blastocyst quality and day of full blastulation.

Conclusion: In view of enhanced personalization in OS, clinicians shall focus on different endpoints or quantitative effects related to Gn action towards follicle recruitment, development, and atresia. Here, LH and/or hCG was administered exclusively to women with expected sub/poor response; therefore, we cannot exclude that specific Gn formulations may impact patient prognosis in other populations.

Keywords: Euploid blastocyst; Gonadotrophin; Live birth; Oocyte competence; Ovarian stimulation.

Fig. 1

Boxplots reporting the euploid blastocyst rate per cohort of metaphase-II (MII) oocytes according to the gonadotrophins (Gn) adopted for ovarian stimulation (OS) within different ranges of maternal age at oocyte retrieval. The dotted black lines outline the average (avg.) value per cluster of maternal age. The one-way ANOVA highlighted no significant difference in the 4 groups. The generalized linear model adjusted for maternal age confirmed the absence of a significant association between the Gn adopted for OS and the primary outcome under investigation (partial eta-squared = 0.014, power = 0.425 and p value = 0.18)