Stavridis Konstantinos, Balafoutas Dimitrios, Kastora Stavroula-Lila, Kalampokas Theodoros, Simopoulou Mara, Joukhadar Ralf, Vlahos Nikos
Department of Obstetrics and Gynaecology, Aretaieion University Hospital, Athens, GRC.
Faculty of Population Health Sciences, EGA (Elizabeth Garrett Anderson) Institute for Women's Health, University College London, London, GBR.
Cureus. 2025 May 8;17(5):e83709. doi: 10.7759/cureus.83709. eCollection 2025 May.
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.
在过去十年中，冷冻胚胎移植（FET）已变得比新鲜胚胎移植更为常见。已知胚胎移植日前后的孕酮水平会影响生殖结局，尽管关于黄体期支持（LPS）的最佳途径、剂量或持续时间尚无明确指南。一般认为循环孕酮阈值约为10 ng/mL，但不同给药途径下子宫内膜吸收情况各异，这对其可靠性提出了挑战，这表明需要通过其他孕酮测量方法进行验证。孕二醇-3-葡萄糖醛酸苷（PDG）是孕酮的主要尿液代谢产物，可作为监测支持情况的非侵入性标志物。本研究旨在探讨FET周期中PDG水平与妊娠结局之间的关联。
本前瞻性试点研究于2022年10月至2023年5月在希腊一家私立体外受精（IVF）中心进行。纳入了19例接受自体或供体卵母细胞FET的患者。符合条件的参与者年龄≤50岁，子宫内膜三层厚度≥6.5 mm，并接受阴道孕酮进行LPS。排除标准包括子宫内异常、肾脏疾病、新鲜周期或使用替代子宫内膜准备方案。所有患者接受口服雌二醇（每8小时2 mg）14天，随后接受阴道孕酮（每6小时200 mg）。在移植后约10分钟收集即时尿样，通过酶联免疫吸附测定（ELISA）评估PDG水平。主要结局是持续妊娠率（OPR）；次要结局包括临床妊娠率（CPR）、生化妊娠（BP）、流产率（MR）和活产率（LBR）。
尿PDG水平中位数为3.5 pg/mL（四分位间距（IQR）：2.0 - 5.0）；21%的患者值高于10 pg/mL，超过了该检测的上限。未发现尿PDG水平与任何妊娠结局之间存在显著关联（p > 0.05）。仅观察到子宫内膜厚度与CPR之间存在显著相关性（p < 0.05）。
在这个试点队列中，胚胎移植日的尿PDG水平与妊娠结局无显著关联，不过样本量较小可能会限制结论。需要开展更大规模的研究，并采用标准化的24小时尿液收集方法，以评估PDG在优化FET周期LPS中的作用。
