Urinary Pregnanediol-3-Glucuronide and Pregnancy Outcomes in Frozen Embryo Transfer Cycles: A Pilot Study

Background Frozen embryo transfers (FETs) have become more common than fresh transfers over the past decade. Progesterone levels around embryo transfer day are known to impact reproductive outcomes, albeit no clear guidelines exist regarding the optimal route, dosage, or duration of luteal phase support (LPS). A circulating progesterone threshold of about 10 ng/mL is generally accepted, but varying endometrial absorption across administration routes challenges its reliability, suggesting a need for validation through alternative progesterone measurement methods. Pregnanediol-3-glucuronide (PDG), the main urinary metabolite of progesterone, may serve as a non-invasive marker for monitoring support. This study aims to explore the association between PDG levels and pregnancy outcomes in FET cycles. Materials and methods This prospective pilot study was conducted at a private in vitro fertilization (IVF) center in Greece from October 2022 to May 2023. Nineteen patients undergoing FET with autologous or donor oocytes were included. Eligible participants were ≤50 years old, had a triple-layer endometrial thickness ≥6.5 mm, and received vaginal progesterone for LPS. Exclusion criteria included intrauterine anomalies, kidney disease, fresh cycles, or use of alternative endometrial preparation protocols. All patients received oral estradiol (2 mg every eight hours) for 14 days, followed by vaginal progesterone (200 mg every six hours). Spot urine samples were collected approximately 10 minutes post-transfer to assess PDG levels through ELISA (Enzyme-Linked Immunosorbent Assay). The primary outcome was the ongoing pregnancy rate (OPR); secondary outcomes included clinical pregnancy rate (CPR), biochemical pregnancy (BP), miscarriage rate (MR), and live birth rate (LBR). Results The median urinary PDG level was 3.5 pg/mL (interquartile range (IQR): 2.0-5.0); 21% of patients had values above 10 pg/mL, exceeding the assay's upper detection limit. No significant associations were found between urinary PDG levels and any pregnancy outcomes (p > 0.05). A significant correlation was observed only between endometrial thickness and CPR (p < 0.05). Conclusion In this pilot cohort, urinary PDG levels on embryo transfer day showed no significant association with pregnancy outcomes, though the small sample size may limit conclusions. Larger studies, with standardized 24-hour urine collection, are needed to assess PDG's role in optimizing LPS in FET cycles.