Letrozole Co-Administration in Progestin-Primed Ovarian Stimulation (PPOS) Protocols for Patients Undergoing In Vitro Fertilization: A Systematic Review

Objective: To systematically analyze and synthesize the evidence from the literature, we compared outcomes of the PPOS + LE protocol versus standard PPOS in patients undergoing IVF. Materials and Methods: We systematically searched the MEDLINE, Scopus, EMBASE, and Science Citation Index databases to identify relevant studies. The clinical questions were developed according to the PICO framework. Quality assessment of the included studies was performed using the Newcastle–Ottawa Scale. Primary outcomes were ovarian stimulation outcomes (oocyte retrieved and mature oocytes). Secondary outcomes were hormonal levels during COS and pregnancy outcome. Results: Five retrospective studies compared oocyte yields between the PPOS and PPOS + LE protocols across diverse populations. While some authors reported significantly higher numbers of retrieved and mature oocytes with letrozole co-administration in a normal infertile population and in POSEIDON group 4, others found no benefit in the PCOS or POSEIDON 3 groups, indicating variable efficacy depending on patient characteristics. Conclusions: Incorporating letrozole counteracts the intense pituitary suppression typically associated with standard PPOS, increasing LH levels and the number of retrieved and mature oocytes in normal and poor responders, but not in PCOS women. Retrospective data do not allow for definitive conclusions to be drawn. Further studies are needed to confirm these results.