Comparison of IVF Outcomes in Natural and Programmed Menstrual Cycles Prior to Ovarian Stimulation in a Nigerian Tertiary Centre: A Randomized Clinical Trial

Abstract

Background: Controlled ovarian stimulation (COS) is essential in assisted reproductive technology to achieve synchronized follicular development and optimize oocyte yield for in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Combined oral contraceptive pills (OCPs) are widely used for cycle scheduling to facilitate patient batching and laboratory planning. Contemporary evidence from high-income settings suggests that short-term OCP pretreatment does not adversely affect ovarian response; however, concerns persist regarding excessive hormonal suppression, altered endocrine milieu, and potential impairment of follicular recruitment. Data from low- and middle-income countries, where patient characteristics and stimulation protocols may differ, remain limited. Objective: The present study compared oocyte yield and reproductive outcomes following controlled ovarian stimulation initiated in natural menstrual cycles versus cycles scheduled with combined oral contraceptive pills among women undergoing IVF in a Nigerian tertiary centre. Methods: This was a prospective, open-label randomized controlled trial conducted at the Federal Medical Centre, Abuja, Nigeria, between July and October 2022. Using consecutive sampling, 86 eligible and consenting women undergoing IVF were recruited and randomized in a 1:1 ratio (43 per group) using sealed opaque envelopes to either natural cycle initiation or OCP-programmed cycle initiation. Controlled ovarian stimulation was commenced on cycle day 2 or 3 in both groups using individualized follicle-stimulating hormone dosing based on age, body mass index, and baseline ovarian reserve. The primary outcome was mean oocyte yield. Secondary outcomes included duration of gonadotropin stimulation, embryo cleavage and blastocyst formation rates, biochemical and clinical pregnancy rates, ovarian hyperstimulation syndrome, and patient satisfaction. Analyses were conducted on an intention-to-treat basis using IBM SPSS version 23 with a 95% confidence level (p ≤ 0.05). Adjusted analyses were not performed; therefore, residual confounding was considered. Results: Eighty-six women were analyzed (43 per group). Mean age was comparable between the OCP-programmed and natural cycle groups. Mean oocyte yield did not differ significantly between groups (natural cycle: 11.09 ± 2.86 vs OCP-programmed: 11.51 ± 1.62; p = 0.379). Clinical pregnancy rates were similar between groups (p = 0.659), indicating no statistically significant difference. The OCP-programmed group required a shorter duration of gonadotropin stimulation (p = 0.016). Embryo cleavage rates, blastocyst formation rates, and patient satisfaction scores were comparable. No significant difference was observed in the incidence of severe or critical ovarian hyperstimulation syndrome. Conclusion: Combined oral contraceptive pretreatment for cycle scheduling before controlled ovarian stimulation does not adversely affect oocyte yield or pregnancy outcomes compared with natural cycle initiation. While transient hormonal suppression may occur, ovarian responsiveness and reproductive outcomes remain preserved. OCP-based scheduling offers logistical advantages without compromising IVF success in this Nigerian tertiary centre.