P-425 Premature follicular-phase progesterone increase in ART cycles and endometrial receptivity: evaluation of new, more reliable predictors
Authors: Cappellini C , Garzia E , Galiano V , Guarnaccia L , Riparini J , Sulpizio P , Marconi A.M 
Published: June 2022

Abstract

Study question
Is plasma Progesterone (P) at HCG administration more sensitive in predicting endometrial receptivity in fresh IVF cycles than PFI (progesterone-follicles index) and POI (progesterone-oocytes index)?

Summary answer
Our data suggest that POI predicts endometrial receptivity defect better than the P assay alone, thus allowing better decision making.

What is known already
The premature increase in plasma P in the follicular phase of stimulated IVF cycles has been associated with a lower embryo implantation rate because of reduced endometrial receptivity. There is still no consensus on how this impediment to implantation should occur and what threshold should be used. Moreover,since the efficacy of P increase in conditioning reproductive outcomes is more intense in patients with normo- and poor-response and generally inversely proportional to the ovarian response to stimulation, PFI and POI, which better reflect the average amount of P secreted from the follicles, have been suggested as potential additional markers of receptivity.

Study design, size, duration
Retrospective analysis of fresh IVF-ET cycles. PFI was obtained dividing the plasma P level on the day of hCG administration by the number of follicles ≥14 mm; POI by the number of oocytes retrieved. Pearson correlations, ROC curves, multivariate logistic regression analysis and Cox regression were performed to evaluate the predictive value of PFI and POI for the main outcomes we considered: ongoing pregnancy rate (OPR) and live birth rate (LBR).

Participants/materials, setting, methods
Women undergoing IVF cycles at San Paolo University Hospital in Milan between 2016 and 2021 were enrolled. As exclusion criteria, we considered previous ovarian surgery, endometriosis, severe male factor and cycle interruption before the embryo transfer. We collected the following data: age of the woman; stimulation protocol; total amount of FSH administered; P and Estradiol (E2) levels and number of follicles &gt;14 mm on induction day; number of oocytes collected; OPR and LBR.

Main results and the role of chance
A total of 662 fresh embryo transfers (ETs) were performed and 214 pregnancies were achieved. We observed a statistically significant difference in age, number of total embryos and POI between women who became pregnant and those who did not. Specifically, Pearson’s correlation revealed a significant positive correlation between pregnancy and number of total embryos (r = 0.165, p &lt; 0.001), and a significant negative correlation between pregnancy and age (r = 0.201, p &lt; 0.001) and POI (r=-0.096, p = 0.013). Multivariate logistic regression revealed POI to be the most significant predictive parameter of pregnancy, with a odds ratio of 4.374 (p = 0.007, CI: 1.496-12.797). The ROC curve confirmed the highest predictive value of POI for OPR. Finally, Cox regression showed that POI &lt;0.18 was correlated with better OPR (odds ratio=1.419, p = 0.012), suggesting the potential clinical impact of identifying an optimal cut-off of POI to reconsider patient management.

Limitations, reasons for caution
The results of this study are limited by the small population size.

Wider implications of the findings
Since the effect on endometrial receptivity of increased plasma P is inversely proportional to ovarian response,we suggest using a marker that accounts for response characteristics. POI has been found to be a reliable index for predicting IVF-ET cycle outcomes,supporting a limit beyond which the fresh embryo transfer should be reconsidered.

Trial registration number
N/A