Comparing Clinical Outcomes Between Flexible and Fixed Progestin-Primed Ovarian Stimulation

Abstract

Controlled ovarian stimulation (COS) is essential in assisted reproductive technology (ART) to obtain multiple oocytes. Gonadotropin-releasing hormone (GnRH) analogues have been used to prevent the premature luteinizing hormone (LH) surges. However, daily injections and high cost cause inconvenience and limit patients’ adherence. Recently, progestin-primed ovarian stimulation (PPOS) has emerged as an alternative. However, the optimal timing of progesterone administration remains unclear. This systematic review aimed to compare clinical outcomes between a fixed regimen that initiates progestin at the beginning of the cycle and a flexible regimen that initiates progestin later in the cycle. A comprehensive literature search was conducted in PubMed, Cochrane, Medline, and Embase Library to identify relevant studies published between January 2018 and April 2024. It was supplemented by manual searches, which identified 3 eligible retrospective cohort studies directly comparing fixed and flexible PPOS protocols. Selected studies were systematically appraised. Two studies in women with diminished ovarian reserve (DOR) found no significant differences between the two regimens, whereas one study in poor ovarian responders (POR) found a higher cumulative live birth rate (CLBR) and lower progesterone use in the flexible group, especially in older, low-prognosis women. Flexible and fixed PPOS regimens show comparable outcomes in DOR patients. Still, preliminary evidence shows potential advantages of the flexible timing in women with advanced age or POR. Therefore, future large-scale prospective studies are needed to validate these findings.