ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Reproduction
This article is part of the Research TopicNew Advances in Embryo Development and Embryo-endometrial InterfaceView all 8 articles
Impact of estradiol-to-progesterone ratio before progesterone initiation on pregnancy outcomes in frozen embryo transfer cycles with hormone replacement therapy: an analysis of over 25,000 cycles
Provisionally accepted
- 1Women and Children’s Hospital of Chongqing Medical University, Chongqing, China
- 2Chongqing Health Center for Women and Children, Chongqing, China
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ABSTRACT Background: Endometrial receptivity in hormone replacement therapy–frozen embryo transfer (HRT-FET) cycles depends on a precisely coordinated estradiol–progesterone environment. An imbalance between estradiol (E2) and progesterone (P) before progesterone exposure may impair the endometrial transition from proliferation to secretory transformation. This study investigated whether the estradiol-to-progesterone (E2/P) ratio prior to the initiation of progesterone is associated with pregnancy outcomes. Methods: This retrospective cohort study analyzed HRT-FET cycles performed between 2017 and 2022 at a single reproductive medicine center. Serum E2 and P levels were measured prior to the initiation of progesterone, and the E2/P ratio was calculated to reflect their relative concentrations. Patients were categorized into quartiles according to their E2/P ratios. Multivariable and multi-model logistic regression analyses were conducted to evaluate the association between E2/P ratios and clinical pregnancy rate (CPR) as well as live birth rate (LBR). Results: Both CPR and LBR declined progressively with increasing E2/P ratios across quartiles (CPR: 60.6%, 57.7%, 52.7%, and 47.7%; LBR: 50.6%, 47.1%, 42.6%, and 36.7% from the lowest to highest quartile, respectively; P < 0.001). After adjusting for confounders including female age, body mass index, infertility diagnosis, infertility indication, embryo transfer stage, number of embryos transferred, and endometrial thickness, higher E2/P ratios remained independently associated with reduced CPR and LBR. The trend remained significant in all regression models (P for trend < 0.001). Conclusions: In HRT-FET cycles, higher pre-progesterone E2/P ratios were associated with lower clinical pregnancy and live birth rates. The E2/P ratio may reflect the hormonal status of the endometrium, but its clinical utility requires confirmation through prospective studies.
Keywords: Clinical pregnancy rate, estradiol-to-progesterone ratio, Frozen-thawed embryo transfer, Hormone Replacement Therapy, live birth rate
Received: 26 Nov 2025; Accepted: 16 Feb 2026.
Copyright: © 2026 Shuai, Liu, LUO, Zhang, Ye and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Weiwei Liu
Guoning Huang
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