Recombinant LH priming improves follicular efficiency and pregnancy outcomes in women with diminished ovarian reserve undergoing antagonist IVF stimulation

Diletta Guglielmi, Claudio Maurizio Maria Brigante, Silvana Gippone, Roberta Iemmello, Mariabeatrice Dal Canto, Mario Romano Mignini Renzini

Women with diminished ovarian reserve represent a low-prognosis population in assisted reproduction, in whom improving the efficiency of converting the available antral follicle pool into retrievable oocytes may be clinically relevant. We conducted a retrospective single-center cohort study including 232 IVF/ICSI cycles (232 women) performed between January 2022 and April 2025 in POSEIDON groups 3–4 (anti-Müllerian hormone <1.2 ng/mL), comparing a high-dose antagonist regimen preceded by combined oral contraceptive pretreatment plus recombinant luteinizing hormone priming (150 IU/day for 7 days; LHP, n = 93) with a comparable high-dose antagonist regimen without priming (no-LHP, n = 139). Both groups received fixed high-dose stimulation with recombinant follicle-stimulating hormone (300 IU/day) plus recombinant luteinizing hormone (150 IU/day). The primary outcome was ongoing pregnancy at ≥12 weeks. Cycle suspension before oocyte retrieval was less frequent with LHP than with no-LHP (1.1% vs. 10.1%). Follicular efficiency also favored LHP, with higher follicular output rate (59.4% vs. 52.8%) and follicle-to-oocyte index (82.6% vs. 70.9%). In fresh transfers, ongoing pregnancy was higher with LHP per started cycle (18.3% vs. 9.4%) and per embryo transfer (30.4% vs. 15.5%), with a similar trend per oocyte retrieval (18.5% vs. 10.4%). In multivariable logistic regression analyses, LH priming remained independently associated with ongoing pregnancy after adjustment for age, body mass index, and anti-Müllerian hormone, with consistent effect estimates across models (odds ratio range 2.20–2.41). Combined first-transfer ongoing pregnancy, defined as the fresh transfer or, when no fresh transfer occurred, the first subsequent frozen embryo transfer derived from the same stimulation cycle, also showed a favorable trend (29.7% vs. 17.0%). On updated follow-up, all pregnancies that had reached the ongoing stage in both groups resulted in live birth. In low-prognosis women, a COC-based recombinant luteinizing hormone priming protocol within a high-dose antagonist framework was associated with improved follicular efficiency, fewer pre-retrieval suspensions, and higher ongoing pregnancy rates in fresh cycles. Prospective studies are warranted to confirm these findings and better define patient selection.