Effect of Continuous Versus Flexible Recombinant Luteinizing Hormone Supplementation in the Luteal Phase Long Protocol on Pregnancy Outcomes in Advanced-Age Women: A Retrospective Cohort Study

Abstract

Objective: 

To evaluate the impact of different timings of recombinant luteinizing hormone (rLH) supplementation during controlled ovarian stimulation (COS) with the luteal phase long protocol on pregnancy outcomes in women of advanced reproductive age.

Methods: 

This retrospective study analyzed 727 infertile women aged 35–39 years who underwent COS with the luteal phase long protocol at the Reproductive Medicine Center of Xiamen Women and Children’s Hospital between January 2017 and July 2023. Patients were categorized into two groups according to the timing of rLH supplementation: continuous and flexible. Baseline characteristics, stimulation parameters, and pregnancy outcomes were compared between groups. Multivariate logistic regression was used to assess the independent effect of rLH supplementation timing on pregnancy outcomes.

Results: 

Of the 727 patients, 300 were in the continuous supplementation group, whereas 427 were in the flexible supplementation group. Baseline characteristics were generally balanced; however, the continuous supplementation group had significantly higher basal follicle-stimulating hormone (FSH) and lower LH and progesterone levels on the human chorionic gonadotropin (hCG) trigger day (P < 0.05). Across fresh embryo transfer cycles, the live birth rate was significantly higher in the continuous supplementation group than in the flexible supplementation group (50.5% vs. 40.4%, P = 0.039). After adjusting for key confounders, including age, infertility duration, anti-Müllerian hormone, antral follicle count, basal FSH, number of oocytes retrieved, and number of embryos transferred, multivariate logistic regression confirmed that continuous supplementation was an independent predictor of a higher live birth rate (adjusted odds ratio [aOR] = 1.59, 95% confidence interval [CI]: 1.10–2.36, P = 0.015), as well as improved implantation (aOR = 1.65, 95% CI: 1.10–2.48, P = 0.016) and clinical pregnancy rates (aOR = 1.51, 95% CI: 1.03–2.23, P = 0.036). No significant differences between groups were observed concerning gonadotropin starting dose, duration of stimulation, endometrial thickness on the hCG day, number of retrieved oocytes, or number of high-quality embryos (all P > 0.05).

Conclusion: 

For women of advanced reproductive age undergoing the luteal phase long protocol, the strategy of continuous rLH supplementation from the start of stimulation is superior to a flexible, delayed approach, significantly improving live birth rates in fresh transfer cycles. These findings suggest that early and sustained LH support may optimize outcomes in this patient population, including those with signs of diminished ovarian reserve.