Clomiphene Citrate Priming Increases Sensitivity During Ovarian Stimulation in Poor Ovarian Responders Undergoing In Vitro Fertilization Treatment: A Retrospective Cohort Study

Abstract Background: Since ovarian stimulation was introduced as an assisted reproductive technology, poor ovarian response (POR) management has challenged clinicians. Guidance on optimally managing patients with poor response and/or low sensitivity to ovarian stimulation is still lacking. We aimed to investigate whether a clomiphene citrate (CC) priming protocol could increase ovarian sensitivity in poor ovarian responders. Methods: This single-center retrospective cohort study included 294 patients (374 ovarian stimulation cycles). Of these, 193 cycles were treated by a CC priming antagonist protocol (study group) and 181 by the classical flexible gonadotropin-releasing hormone antagonist protocol (control group). Stimulation data and laboratory and clinical outcomes were compared between the groups. Results: Total gonadotropin dosage and dosage per follicle were considerably lower, the follicle-to-oocyte index was significantly higher, and the gonadotropin duration was shorter in the study group. After adjusting for potential confounders, multivariate regression analysis showed that cumulative ongoing pregnancy remained comparable between the groups (adjusted odds ratio: 0.761, 95% confidence interval: 0.300-1.933, P = 0.566). Age, body mass index, gonadotropin dosage per follicle, and the follicle-to-oocyte index were directly associated with the reproductive outcomes. The result of the sensitivity analysis showed that patients stimulated by the CC priming antagonist protocol were administered less gonadotropin (1,739.09 ± 719.39 vs. 3,114.77 ± 1,171.23, P < 0.001) at a lower gonadotropin dosage per follicle (637.36 ± 373.05 vs. 1286.26 ± 976.66, P < 0.001) and for a shorter duration (6.58 ± 2.23 vs. 9.80 ± 1.90, P < 0.001). Conclusions: The CC priming antagonist protocol offered a convenient and patient-friendly way to increase ovarian sensitivity during ovarian stimulation in poor ovarian responders.