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Changes in thyroid function during controlled ovarian hyperstimulation (COH) and its impact on assisted reproduction technology (ART) outcomes: a systematic review and meta-analysis

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Abstract

Background

To investigate the thyroid function changes during controlled ovarian hyperstimulation (COH) and ascertain its impact on reproductive outcomes.

Methods

We conducted meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was performed to identify studies reported changes in thyroid parameters during COH. We analyzed thyroid-stimulating hormone (TSH) levels, free thyroxin (fT4) levels, changes in estrogens (E2), thyroxine-binding globulin (TBG), relative risks (RRs) of clinical pregnancy rate (CPR), live birth rate (LBR), and mean difference (MD) of TSH increment between the miscarriage group and ongoing pregnancy group.

Results

This meta-analysis included fifteen individual studies (n = 1665 subjects). At the end of COH, the mean TSH (2.53 mIU/L; 95% CI, 2.19 to 2.88; I2 = 92.9%) exceeded the upper limit (2.5 mIU/L) and remained above the threshold until one month following embryo transfer (ET). Thyroxin decreased from baseline to the end of COH (−0.18 ng/l; 95% CI, −0.35 to 0.00; I2 = 92.2%). The CPR and LBR of patients with TSH exceeding the cutoff after COH were significantly lower than those of patients with TSH below the threshold (CPR: RR, 0.62; 95% CI, 0.47 to 0.82; I2 = 0.0% and LBR: RR, 0.64; 95% CI, 0.44 to 0.92; I2 = 0.0%). The MD of the increment in TSH levels between the miscarriage and ongoing pregnancy groups was 0.40 mIU/L (95% CI, 0.15 to 0.65; I2 = 0.0%).

Conclusions

This meta-analysis shows that TSH increases and fT4 decreases during COH. COH-induced thyroid disorder impairs reproductive outcomes.

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Data availability

The data that supports the findings of this study are available in the supplementary material of this article.

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Acknowledgements

We would like to thank all investigators and participants in this study, especially the guidance of professor Yu. We acknowledge that Danpei Li provided data sources and technical support during the analysis of this study. We also acknowledge the support from Endocrinology Division of Tongji Hospital.

Funding

This study was supported by grants from the National Key R&D Program of China (2016YFC0901203) and the National Natural Science Foundation of China (81974109, 81570740).

Author information

Author notes

  1. Danpei Li and Sitao Hu contributed equally to this work.

Authors and Affiliations

  1. Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Danpei Li & Xiaoyu Meng

  2. Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

    Sitao Hu

  3. Branch of National Clinical Research Center for Metabolic Diseases, Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China

    Xuefeng Yu

Authors
  1. Danpei Li
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Contributions

Dr. Yu and D. Li had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Li.

Acquisition, analysis, or interpretation of data: Li and Hu.

Drafting of the manuscript: Li.

Critical revision of the manuscript for important intellectual content: All authors. Obtained funding: the National Key R&D Program of China (2016YFC0901203) and the National Natural Science Foundation of China (81974109, 81570740).

Statistical analysis: Li and Hu.

Administrative, technical, or material support: Yu.

Study supervision: Yu.

Corresponding author

Correspondence to Danpei Li.

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Li, D., Hu, S., Meng, X. et al. Changes in thyroid function during controlled ovarian hyperstimulation (COH) and its impact on assisted reproduction technology (ART) outcomes: a systematic review and meta-analysis. J Assist Reprod Genet 38, 2227–2235 (2021). https://doi.org/10.1007/s10815-021-02206-0

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