Comparative Efficacy of r-hFSH Alfa + r-LH Versus r-hFSH Delta + hMG in Poor Ovarian Responders

Giorgio Maria Baldini¹Domenico Baldini^2*Dario Lot²ANTONIO MALVASI¹Antonio Simone Laganà³Mario Palumbo⁴Gianluca Raffaello Damiani¹Giuseppe Trojano⁵

• ¹Universita degli Studi di Bari Aldo Moro, Bari, Italy
• ²MOMO' FERTILIFE, Bisceglie, Italy
• ³Universita degli Studi di Palermo, Palermo, Italy
• ⁴Universita degli Studi di Napoli Federico II, Naples, Italy
• ⁵Presidio Ospedaliero Madonna delle Grazie, Matera, Italy

Poor ovarian response represents one of the most complex challenges in reproductive medicine, with therapeutic interventions rarely resulting in relevant clinical improvements. Although different gonadotropin combinations have been used, direct comparisons between r-hFSH alpha + r-LH and r-hFSH delta + hMG in poor responders are still lacking. The objective of this study is to compare the clinical and pharmacoeconomic outcomes of two controlled ovarian stimulation (COS) protocols, r-hFSH alpha + r-LH versus (Pergoveris) r-hFSH delta + hMG (Rekovelle + Meropur) in women diagnosed as poor responders. This retrospective study analyzed 437 women diagnosed as poor ovarian responders, who underwent treatment between January 2018 and October 2022. The primary outcomes were the number of oocytes retrieved, metaphase II (MII) oocytes, and embryos obtained. Secondary outcomes included biochemical pregnancy (β-hCG positivity) and clinical pregnancy rates. A multivariate logistic regression model was used to assess the association between the stimulation protocol and clinical pregnancy, adjusting for age, anti-Müllerian hormone (AMH) levels, body mass index (BMI), and duration of stimulation. Additionally, a pharmacoeconomic analysis was conducted to estimate the cost per MII oocyte retrieved for each protocol. The group treated with r-hFSH alpha + r-LH obtained a significantly higher number of total oocytes (p = 0.01), MII (p = 0.02) and embryos (p = 0.03). However, multivariate logistic regression did not show a statistically significant association between the type of protocol and clinical pregnancy rate (OR: 1.12; 95% CI: 0.79–1.59; p = 0.54). Pergoveris protocol required a lower total dose of gonadotropins and generated a mean saving of €690 per additional MII oocyte retrieved. The r-hFSH alpha + r-LH protocol showed greater efficiency in terms of ovarian response and cost per MII oocyte but did not translate into a significant improvement in pregnancy rates. The results confirm the management complexity of patients who are poor responders and underscore the need for further prospective, randomized studies. Given its retrospective, single-center design, the study's results require cautious interpretation due to possible selection bias and confounding, despite a generally homogeneous population. Further prospective, randomized trials are warranted to confirm these observations and guide optimal treatment strategies.