POSEIDONE 1 and 2: Probable Causes and Proposed Treatment Strategies? An Evidence-based Update

Aim and objective: To elucidate the cause of poor ovarian response to controlled ovarian hyperstimulation during in vitro fertilization in women with good ovarian reserve and the potential treatment options for them. Background: There has been a steady increase in number of in vitro fertilization (IVF) cycles being performed across the world. An important step of IVF is controlled ovarian hyperstimulation (COH), with an aim to achieve multifollicular response. Conventionally the protocol and gonadotropin dose is tailored to ensure adequate oocyte yield and minimize complications. Studies suggest that maximizing oocyte yield increases the cumulative LBR. However, in spite of high dose of gonadotropin usage during COH, many women have poor response (<4 oocytes retrieved) and/or low oocyte yield (4–9 oocytes retrieved). Patient-Oriented Strategies Encompassing Individualize D Oocyte Number (POSEIDON) criteria to classify poor responders were introduced in 2016 to achieve better stratification of poor responders and achieve an individualized treatment approach for the patients. Review results: Some of the proposed reasons include suboptimal gonadotropin dose, gonadotropin receptor resistance due to gonadotropin receptor polymorphism and issues with ovulation trigger. Two most studied single nucleotide polymorphism are those at position 307 and 680 of exon 10 of Follicle stimulating hormone receptor. Some studies have demonstrated that homozygous Asparagine at position 680 required lesser gonadotropin dose and had more oocyte yield in normoovulatory women compared with other variants at position 680. However, other studies have reported contradictory findings. Similarly contradictory results have been reported from various studies regarding ovarian response with respect to variants at locus 307. Some of the proposed treatments for patients with unexpected responders include increasing the dose of Inj. FSH, adding Inj. Luteinizing hormone receptor (LH) to ovarian stimulation, use of dual trigger, synchronizing the follicular cohort, use of adjuvants during IVF, and dual stimulation. Conclusion: The exact reason for such a response is still unclear although role of FSH/LH polymorphism has been studied extensively. However, no specific FSH/LH polymorphism has been consistently been associated with such unexpected hyporesponse. There is no high quality evidence for other proposed treatment options.