More Live Births in Primary Subfertile Intracytoplasmic Sperm Injection-Treated Women with High Normal TSH Levels

Constance Repelaer Van Driel-Delprat, Eveline Van Dam, Peter Van De Ven, Khadija Aissa, Melanie Ter Haar, Yikke Feenstra, Aletta De Roos, Gaby Beelen, Roel Schats, Cornelis Lambalk

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Objectives: The aim of this study was to analyze the fertility outcome in intracytoplasmic sperm injection (ICSI)-treated women across normal range thyroid-stimulating hormone (TSH) levels. Published results are inconclusive about optimal TSH levels and fertility. Design: This is a retrospective cohort study in 752 ICSI-treated women with predominantly severe male factor subfertility, starting treatment between the first of January 2008 and the first of March 2012 with a follow-up until 2014. Participants/Materials, Setting, Methods: Women aged 22-45 years with TSH 0.3-4.5 mIU/L without thyroid hormone substitution were included in Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands, an iodine-sufficient area. Demographic and baseline characteristics were compared between groups of patients based on TSH, using one-way ANOVA, Kruskal-Wallis ANOVA, and test. The patient was the unit of analysis: all cumulative cycles per patient were analyzed up to and including the first ongoing pregnancy. The primary outcome was a cumulative live birth rate. Clinical pregnancy rate, pregnancy loss, and ongoing pregnancy rate were secondary outcomes. The test and logistic regression were used to compare interquartile groups while adjusting for confounders. Logistic regression was used with the natural logarithm of TSH as a continuous predictor. Primary and secondary subfertile women were analyzed separately. Results: Analysis of the total cohort (n = 752) showed no difference in fertility outcomes across the normal TSH range. The cumulative live birth rate for the 4 groups of primary subfertile women (n = 455) was 76% in the upper TSH quartile compared to 56%, 60%, and 59% in the lower TSH quartiles. Limitations: Levels of thyroxine and presence of thyroid autoimmunity were not measured in this retrospective cohort study. Conclusions: The observation that a higher live birth rate was found in primary subfertile ICSI-treated women with high but allegedly normal TSH levels contributes to the hypothesis that in certain subfertile women in addition to a male factor, female factors such as subtle hypothyroidism and/or thyroid autoimmunity may play a role in keeping them from conception, which can be overcome by the process of ICSI.

Original languageEnglish
Pages (from-to)398-407
Number of pages10
JournalGynecologic and Obstetric Investigation
Issue number4
Publication statusPublished - 1 Sept 2021


  • Intracytoplasmic sperm injection
  • Primary subfertility
  • Reproductive outcome
  • Thyroid-stimulating hormone

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