POSEIDON classification and the proposed treatment options for groups 1 and 2: time to revisit? A retrospective analysis of 1425 ART cycles

STUDY QUESTION: Do live birth outcomes differ when Patient-Oriented Strategy Encompassing IndividualizeD Oocyte Number (POSEIDON) stratified groups are compared with women with good prognosis (non-POSEIDON group) undergoing ART? SUMMARY ANSWER: The current study showed no significant difference in the live birth rates (LBRs) per embryo transfer between POSEIDON groups 1 and 2 when compared with women in the non-POSEIDON group undergoing ART. WHAT IS KNOWN ALREADY: Recently, there has been a lot of focus on the POSEIDON classification for low prognosis women undergoing ART and various management options have been advocated. For POSEIDON groups 1 and 2, low starting dose and gonadotrophin receptor polymorphism have been suggested as possible reasons for a hyporesponse, and increasing the starting gonadotrophin dose, the addition of recombinant LH and dual stimulation have been suggested as treatment options. Most of these treatment options are hypothetical in nature and need validation. STUDY DESIGN, SIZE, DURATION: In the current cohort study, a total of 1425 cycles were analyzed retrospectively following a single cycle fresh embryo transfer. The study period was from January 2013 to June 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women undergoing ART at a tertiary level infertility clinic were included. Clinical and treatment-related details were obtained from the hospital's electronic medical records. The ART outcomes in a non-POSEIDON group (women with an adequate ovarian reserve and/or optimal ovarian response i.e. >9 oocytes retrieved in the previous ART cycle) and a low prognosis group stratified by POSEIDON criteria were compared. We also examined the effectiveness of the modifications made in the current ART treatment protocols among women with an adequate ovarian reserve who had a history of poor/suboptimal response (POSEIDON 1 and 2). MAIN RESULTS AND THE ROLE OF CHANCE: There was no statistically significant difference in the LBR per embryo transfer in POSEIDON group 1 (32/109, 29%) and group 2 (17/58, 29%) when compared with the non-POSEIDON group (340/1041, 33%) (adjusted odds ratio (aOR) 0.69; 95% CI 0.37-1.27 and aOR 0.93, 95% CI 0.43-1.97, respectively), while significantly lower LBR were observed in POSEIDON groups 3 (17/97, 17.5%) and 4 (12/120, 10%) (aOR 0.49; 95% CI 0.28-0.89 and aOR 0.38, 95% CI 0.19-0.74, respectively). The gonadotrophin dose alone was increased in one-quarter of the cycles and in another 27% the dose was increased along with the protocol change among POSEIDON group 1. In POSEIDON group 2, a change in the dose alone and in combination with protocol change was performed in 5 and 41% of cycles, respectively. LIMITATIONS, REASONS FOR CAUTION: A limitation of our study is the retrospective nature of the study with an inherent risk of unknown confounders influencing the outcomes. Other limitations are the lack of cumulative live birth data and the relatively small sample within POSEIDON group 2, which could lead to a type II error. WIDER IMPLICATIONS OF THE FINDINGS: The current study showed no significant difference in the LBR between the POSEIDON groups 1 and 2 when compared with the non-POSEIDON group of women, while groups 3 and 4 had significantly lower LBR. The simple gonadotrophin/protocol changes in groups 1 and 2 resulted in LBRs comparable to women with good prognosis. These findings call for revisiting the proposed treatment strategies for POSEIDON groups 1 and 2.