LH supplementation in ovarian stimulation: propensity score and generalized estimating equations analysis over 2000 embryos.

RESEARCH QUESTION: Does luteinizing hormone (LH)-activity supplementation during ovarian stimulation (OS) influence embryo-ploidy rate compared with follicle-stimulating hormone (FSH)-only stimulation in in vitro fertilization (IVF) cycles with preimplantation genetic testing for aneuploidy (PGT-A)?

METHODS

Retrospective single-center cohort study (January 2018-January 2024) including 4,417 IVF/PGT-A cycles using gonadotropin-releasing hormone antagonist or progesterone-primed protocols. After exclusions, 952 cycles were selected via 1:1 propensity score-matching for female age and oocyte yield: 476 OS with recombinant FSH alone and 476 with added LH activity (recombinant LH or human menopausal gonadotropin). As the primary outcome, euploidy was assessed by trophectoderm biopsy and next-generation sequencing. Generalized estimating equations accounted for within-patient clustering. Secondary endpoints were clinical pregnancy, live birth, and miscarriage after frozen euploid embryo transfer (FEET).

RESULTS

There were no significant differences between FSH-only and FSH + LH activity groups with regard to oocyte yield, maturation, fertilization rates, or embryo euploidy rates (45.8% vs. 45.2%; p=0.749). Female age was identified as an independent negative predictor of euploidy (OR = 0.899; p< 0.001), while good-quality embryos had significantly higher odds of being euploid compared with poor-quality embryos (OR = 2.053; p< 0.001). Secondary outcomes showed no significant differences in clinical pregnancy rate, live birth rate, or miscarriage rate following FEET between groups. The addition of LH activity during ovarian stimulation was not independently associated with embryo ploidy status or live birth outcomes.

CONCLUSIONS

In a large matched IVF/PGT-A cohort, LH activity supplementation during OS did not improve blastocyst euploidy or reproductive outcomes. Gonadotropin regimens should be individualized rather than routinely including LH in unselected patients.