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MEAN DIFFERENCES IN ENDOMETRIAL THICKNESS BETWEEN HORMONE REPLACEMENT THERAPY AND NATURAL CYCLE FROZEN EMBRYO TRANSFER: A SYSTEMATIC REVIEW AND META-ANALYSIS OF OBSERVATIONAL STUDIES
Abstract   Open access   Peer reviewed

MEAN DIFFERENCES IN ENDOMETRIAL THICKNESS BETWEEN HORMONE REPLACEMENT THERAPY AND NATURAL CYCLE FROZEN EMBRYO TRANSFER: A SYSTEMATIC REVIEW AND META-ANALYSIS OF OBSERVATIONAL STUDIES

Maria Than, Emma Phelps, Karen M. Summers, Chris Childs, Patrick Ten Eyck, Eyup Duran and Abey Eapen
Fertility and sterility, Vol.124(6 Supplement), pp.e376-e376
12/2025
DOI: 10.1016/j.fertnstert.2025.07.1171
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https://doi.org/10.1016/j.fertnstert.2025.07.1171View
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Abstract

OBJECTIVE Several recent studies suggest that reproductive outcomes are better following a natural cycle (NC) frozen embryo transfer (FET) compared to a hormone replacement therapy (HRT) FET. The superior outcomes established in those studies are mostly attributed to changes in the endocrine milieu rather than an endometrial factor. Therefore, we decided to synthesize evidence to compare the mean endometrial thickness between these two treatment protocols. MATERIALS AND METHODS The study was registered with Prospero (CRD42024576032). A systematic literature search was conducted using the terms to represent the broad concept of ‘endometrial thickness’ and ‘frozen embryo transfer’ in PubMed, Embase, Scopus, Web of Science, CINAHL, and the Cochrane Library. A total of 6,893 citations published until Oct 31, 2024, were screened. The primary outcome of interest was mean differences in endometrial thickness. The results of the meta-analysis were reported as the mean difference with a 95% confidence interval. RESULTS We included a total of 156,033 women from 63 studies from 14 countries in the final qualitative analysis. From this sample, 100,347 had HRT treatment and 55,686 women had a NC-FET treatment. The endometrial thickness (mm) in women with HRT-FET was significantly thinner than women who had a NC-FET, mean difference (MD) of -0.4 mm (95% CI (-0.5; -0.2). Women in the HRT-FET group were younger [MD = -0.3, 95% CI (-0.5; -0.1)] and had a higher BMI [MD = 0.3, 95% CI (0.2; 0.5)]. Compared to women who had NC-FET, women with HRT-FET had a significantly higher miscarriage rate [odds ratio (OR) = 1.3, 95% CI (1.2; 1.4)] and a subsequent significantly lower live birth rate [OR = 0.8, 95% CI (0.8; 0.9)]. CONCLUSIONS In this systematic review and meta-analysis, we report evidence that the endometrial thickness in women with HRT-FET was significantly thinner than those who had a NC-FET. Therefore, our analysis suggests that an endometrial factor may contribute to observed improvements in reproductive outcomes following a natural cycle FET beyond improvements due to changes in endocrine milieu. IMPACT STATEMENT It is well known that endometrial thickness plays an important role predicting ART outcomes. This study suggests that endometrial thickness and livebirth rate in natural cycle FET is superior to HRT-FET, which should be communicated to women as part of informed decision making.

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