P-319 Pre-Transfer Progesterone Evaluation in Women with Endometriosis or Adenomyosis Undergoing Assisted Reproductive Technology

Abstract Study question Are progesterone levels lower in women with endometriosis or adenomyosis undergoing an embryo transfer compared to unaffected? Summary answer Progesterone levels before embryo transfer in women with adenomyosis and endometriosis are not significantly lower compared to controls. What is known already Endometriosis and adenomyosis are gynecological conditions associated with infertility. The hormonal environment plays a critical role in the success of embryo transfer, and progesterone levels are particularly crucial during the luteal phase. Recent clinical studies demonstrate the mechanistic pathways through which progesterone influences endometrial morphology and function, particularly in the inflammatory uterine environment characteristic of endometriosis and adenomyosis. Moreover it has been recently suggested that women affected by these conditions may have suboptimal absorption of progesterone, which could result in a lower implantation rate. Study design, size, duration We conducted a single-center prospective study on women with adenomyosis, endometriosis, or both, who underwent their first frozen embryo transfer (FET) of a blastocyst at Reproductive Medicine Center of San Raffaele Hospital in Milan from 2020 to 2024. We excluded patients receiving injective progestin supplementation to focus on vaginal absorption. Progesterone levels were analyzed on the day of embryo transfer. Participants/materials, setting, methods Patients were divided based on different ultrasound diagnosis (adenomyosis, endometriosis or both) and different endometrial preparation protocols (medicated cycle or spontaneous modified cycle). FET at the blastocyst stage was planned when an endometrial thickness > 7mm was reached, and performed on day 6 of vaginal progesterone. Our primary outcome was to compare the levels of circulating progesterone (P) sampled 10 to 5 minutes prior to FET between women affected versus not affected. Main results and the role of chance 2374 patients were examined (396 had only endometriosis, 469 only adenomyosis, 128 both conditions and 1381 controls). There was no statistically significant difference in progesterone levels in any subgroup regardless of the endometrial preparation. We had the same results analyzing exclusively the group of patients who conceived; while in those who not conceive, a lower level of progesterone at FET was observed in patients with either isolated adenomyosis or adenomyosis with endometriosis compared to controls (P = 13.98 ± 5.66 vs ng/ml versus P = 15.09 ± 6.08 ng/ml and P = 13.07 ± 4.94 ng/ml vs 15.09 ± 6.08 ng/ml, p values 0.037 and 0.027, respectively). Performing multiple linear regression in the group of women with adenomyosis, we observed that circulating P level is influenced by BMI (P-value 0.007) and the dose of vaginal progesterone administered (P-value 0.047). The overall implantation rate (positive betaHCG test/FET) in the control group was 48.4% and it was comparable among women with endometriosis and/or adenomyosis (48.4%). The ongoing pregnancy rates (viable pregnancy beyond week 8 of gestation/FET) were respectively 35.3% and 34.9% , with a 15.5 % and 13.3% biochemical miscarriage rate in the two groups respectively and a 13.7% and 16.7% clinical miscarriage rate in the two groups respectively. Limitations, reasons for caution This is a preliminary and retrospective study and the diagnosis of endometriosis and/or adenomyosis was performed using different ultrasound devices operated by various practitioners. Wider implications of the findings Further large-scale, controlled studies are warranted to elucidate the underlying mechanisms by which progesterone influences implantation and pregnancy maintenance in these challenging clinical scenarios. Trial registration number No