Follitropin alfa versus follitropin alfa/lutropin alfa (rFSH/rLH) in progestin-primed ovarian stimulation: a prospective two-center observational cohort study

Background The contribution of recombinant LH during progestin-primed ovarian stimulation (PPOS) remains uncertain. We compared recombinant FSH alone (GON) with recombinant FSH plus recombinant LH (PER) in a prospective two-center observational cohort. Methods The full enrolled cohort included 213 women (121 GON; 92 PER), including 11 with day-3 transfer. MII oocyte count was the primary outcome. The primary negative binomial model adjusted for female age, AMH, baseline AFC, previous failed cycles and center. Propensity scores used the same covariates; matching was 1:1, exact within center, using Mahalanobis distance within a logit propensity-score caliper. The per-protocol (PP) population comprised the 202 women whose embryos were cultured to day 5; in the full-cohort (ITT) analysis, the 11 women with day-3 transfer contributed zero day-5 blastocysts. Results The primary adjusted MII incidence rate ratio (IRR) for PER versus GON was 1.01 (95% CI 0.91–1.11; p = 0.910); the PP IRR was 1.00 (95% CI 0.91–1.11; p = 0.939). The number of MII oocytes was similar in both groups (median 11 in both), and this finding did not change after adjustment for baseline characteristics or after propensity-score matching. PER was associated with more day-5 blastocysts (median 4 vs. 3) and more top-quality blastocysts (median 2 vs. 1), and these differences persisted after adjustment and matching. Positive β-hCG rates after the first frozen embryo transfer were similar (47.6% vs. 43.2%). OHSS was rare (1 PER and 2 GON cases, all mild), and no cycle was canceled. Conclusions No statistically significant difference in MII count was detected, and equivalence was not established. The higher day-5 blastocyst counts associated with PER may reflect an effect of LH on embryo developmental competence rather than on oocyte yield; this exploratory finding does not establish a causal or clinical benefit and requires confirmation in randomized trials. https://clinicaltrials.gov/study/NCT07348757 , NCT07348757.