Comparison of Ovarian Hyperstimulation Risk and Stimulation Duration Between Natural and OCP-Pretreated IVF Cycles: A Randomized Clinical Trial
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Abstract
Background: Controlled ovarian stimulation (COS) is integral to in-vitro fertilization (IVF) but carries a risk of ovarian hyperstimulation syndrome (OHSS). Oral contraceptive pill (OCP) pretreatment is commonly used for cycle programming; however, its influence on OHSS risk and stimulation duration remains controversial, particularly in low- and middle-income settings.
Objective: To compare the incidence of severe to critical OHSS and the duration of ovarian stimulation between natural cycle initiation and OCP-pretreated IVF cycles.
Methods: This single-centre, open-label randomized clinical trial included 86 women undergoing IVF at a Nigerian tertiary centre. Participants were randomized in a 1:1 ratio to either natural cycle initiation (n = 43) or OCP pretreatment prior to COS (n = 43). Both groups underwent COS using a short GnRH agonist protocol. The primary outcome was the incidence of severe to critical OHSS, while the secondary outcome was the duration of ovarian stimulation. Data were analyzed using an intention-to-treat approach, with a significance level set at p < 0.05.
Results: The mean age was comparable between the OCP and natural cycle groups (33.05 ± 3.65 vs. 33.05 ± 3.96 years). Severe to critical OHSS occurred in one participant (2.3%) in the OCP group and none in the natural cycle group, with no statistically significant difference (p = 0.314). The duration of ovarian stimulation was significantly shorter in the OCP-pretreated group compared with the natural cycle group (11.09 ± 2.86 vs. 11.51 ± 1.62 days; p = 0.016).
Conclusion: OCP pretreatment did not increase the risk of severe OHSS and was associated with a shorter duration of ovarian stimulation compared with natural cycle initiation. These findings support the safe and efficient use of OCPs for IVF cycle scheduling, although larger multicentre trials are required to confirm these results.
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