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Optimal Endometrial Preparation Protocols for Frozen-thawed Embryo Transfer Cycles by Maternal Age

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Abstract

This retrospective cohort study aimed to explore the optimal endometrial preparation protocols among different maternal age groups. A total of 16,867 frozen-thawed embryo transfer (FET) cycles were categorized into three groups based on endometrial preparation protocols: Natural cycle (NC n = 3893), artificial cycles (AC, n = 11456) and AC with GnRH-a pretreatment (AC+GnRH-a, n = 1518). To account for repeat cycles, a generalized estimating equation (GEE) method was applied to examine the associations between cycle regimens and pregnancy outcomes. Subgroup analyses were conducted to evaluate the best preparation methods for different maternal age groups. Primary outcomes were live birth and early miscarriage rates. After completing GEE, in overall population, the live birth rate [(NC as reference; AC: adjusted odds ratio (aOR) = 0.837, 95% confidential interval (CI) 0.771–0.908; AC+GnRHa: aOR = 0.906, 95%CI 0.795–1.031)] in NC was significantly higher than that in AC, while comparable that in AC+GnRH-a. The early miscarriage rate (AC: aOR = 1.420, 95%CI 1.225–1.646; AC+GnRHa: aOR = 1.545, 95%CI 1.236–1.931) was significantly lower in NC compared to either AC group. Subgroup analysis showed that in younger women, the incidences of live birth (AC: aOR = 0.900, 95%CI 0.804–1.007; AC+GnRHa: aOR = 1.091, 95%CI 0.904–1.317) were equivalent between groups, with a slightly higher in AC+GnRH-a. Early miscarriage rate (AC: aOR = 1.462, 95%CI 1.165–1.835; AC+GnRHa: aOR = 1.137, 95%CI 0.948–1886) was only significantly lower in NC compared to that in AC. In older women, the live birth rate (AC: aOR = 0.815, 95%CI 0.722–0.920; AC+GnRHa: aOR = 0.759, 95%CI 0.627–0.919) was significantly higher, and early miscarriage rate (AC: aOR = 1.353, 95%CI 1.118–1.638; AC+GnRHa: aOR = 1.704, 95%CI 1.273–2.280) was significantly lower in NC compared to either AC group. Our study demonstrated that NC is associated with lower early miscarriage late in overall IVF population. There is a mild favor of AC+GnRH-a in younger women, while the priority of NC is remarkable in older women. Maternal age should be a considerable factor when determining endometrial preparation method for FET.

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Acknowledgements

We gratefully acknowledge all the staff of the fertility center in the Shenzhen Zhongshan Urologic Hospital for their support and cooperation. We also thank Mr. Zhiqiang Liu for the help with the statistical analysis.

Funding

This work was supported by the National Key Research & Developmental Program of China (2018YFC1003900/2018YFC1003904) and Sanming Project of Medicine in Shenzhen (SZSM201502035). The funding body has not participated in the design of the study and collection, analysis, interpretation of data or in writing the manuscript.

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Authors and Affiliations

  1. Shenzhen Key Laboratory of Reproductive Immunology for Peri-Implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, No. 1001, Fuqiang Road, Futian District, Shenzhen, 518045, Guangdong Province, People’s Republic of China

    Qizhen Zheng, Hongzhan Zhang, Shiru Xu, Shan **ao, Xue** Wang, Meilan Mo & Yong Zeng

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  1. Qizhen Zheng
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  2. Hongzhan Zhang
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  3. Shiru Xu
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  4. Shan **ao
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  5. Xue** Wang
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  6. Meilan Mo
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  7. Yong Zeng
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Contributions

YZ and MLM supervised the entire study, including the design, procedures, and revisions to the article. ZQZ designed the study, analyzed the data and drafted the manuscript. SX and XJS took part in acquisition and analysis of data. HZZ and SRX took part in critical discussion and revision of the article. All the authors read and approved the final manuscript.

Corresponding authors

Correspondence to Meilan Mo or Yong Zeng.

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This study was approved by the Institutional Review Board of the Shenzhen Zhongshan Urology Hospital (approval SZZSECHU-F-2020043).

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The authors declare no competing interests.

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Zheng, Q., Zhang, H., Xu, S. et al. Optimal Endometrial Preparation Protocols for Frozen-thawed Embryo Transfer Cycles by Maternal Age. Reprod. Sci. 28, 2847–2854 (2021). https://doi.org/10.1007/s43032-021-00538-x

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  • DOI: https://doi.org/10.1007/s43032-021-00538-x

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