Thyroid function modifications in women undergoing controlled ovarian hyperstimulation for in vitro fertilization: a systematic review and meta-analysis

Serum thyroid-stimulating hormone level significantly increases in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. This alteration was particularly pronounced in women treated for hypothyroidism.

VOLUME 116, ISSUE 1, P218-231


Andrea Busnelli, M.D., Federico Cirillo, M.D., Paolo Emanuele Levi-Setti, M.D.



To investigate the impact of controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF) on thyroid function.


Systematic review and meta-analysis.


Not applicable.


Infertile women undergoing conventional IVF or intracytoplasmic sperm injection.


Systematic search of PubMed, MEDLINE, Embase, Scopus, and Web of Science from inception until November 2020. Studies could be included only if they met the following criteria: subjects were classified as euthyroid or hypothyroid; serum thyroid-stimulating hormone (TSH) and/or free thyroxine (FT4) levels were evaluated before COH; and the same thyroid function test was reassessed after COH (i.e., at the time of trigger for final follicle maturation and/or at pregnancy test).

Main Outcome Measure(s)

Mean difference (MD) between the serum TSH or FT4 levels assessed after COH and before COH.


In euthyroid women, the serum TSH levels assessed at the time of trigger and at the time of pregnancy test were significantly higher than those at baseline (MD: 0.69 mIU/L, 95% confidence interval [CI]: 0.30–1.08, I2 = 93% and MD: 0.67, 95% CI: 0.49–0.85, I2 = 72%, respectively). The serum FT4 levels did not undergo significant changes. Subanalysis confirmed an increase in the TSH level after restricting the analysis to women treated with gonadotropin-releasing hormone agonist protocols and to those who achieved pregnancy. A pronounced increase in the TSH level was observed in women treated for hypothyroidism (MD: 1.50 mIU/L, 95% CI: 1.10–1.89, I2 = 0%).


Pooling of the results showed a significant increase in serum TSH level in women undergoing COH for IVF. This change was particularly pronounced in women treated for hypothyroidism. New thyroid function screening strategies for women undergoing COH are warranted.

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