Impact of thyroid autoimmunity on assisted reproductive technology outcomes and ovarian reserve markers: an updated systematic review and meta-analysis
Abstract
Background: Thyroid autoimmunity (TAI) has a high prevalence among women of reproductive age. Investigating its possible impact on ovarian function and fertility is, thus, of utmost relevance. The aim of this systematic review and meta-analysis was to elucidate the effect of TAI on both assisted reproductive technology (ART) outcomes and ovarian reserve. Methods: This systematic review and meta-analysis was restricted to two groups of research articles investigating the association between TAI and: (1) autologous ART outcomes (i.e., fertilization rate [FR], implantation rate, clinical pregnancy rate [CPR], miscarriage rate, and live birth rate), (2) markers of ovarian reserve (i.e., anti-Müllerian hormone, basal follicle stimulating hormone, antral follicle count, and number of oocytes retrieved). Studies including women affected by overt hypo/hyperthyroidism were excluded. Relevant studies were identified by a systematic search in PubMed, MEDLINE, ClinicalTrials.gov, Embase, and Scopus, from database inception to May 1, 2022. Results: From a total of 432 identified publications, 22 studies were included in Group 1 and 26 studies in Group 2. The presence of TAI was associated with a higher risk of miscarriage (7606 participants, odds ratio [OR] 1.52, confidence interval [CI 1.14–2.01], p = 0.004, I 2 = 53%), lower chance of embryo implantation (7118 participants, OR 0.72, [CI 0.59–0.88], p = 0.001, I 2 = 36%), and live birth (11417 participants, OR 0.73, [CI 0.56–0.94], p = 0.02, I 2 = 71%). These associations were no longer observed in a subgroup analysis of patients who exclusively underwent intracytoplasmic sperm injection (ICSI). The FR and CPR as well as the mean values of surrogate markers of oocyte quantity appeared not to be affected by TAI. Conclusions: This data synthesis suggest a higher risk of adverse ART outcomes in women with positive TAI. However, the reliability of these findings is hampered by the relatively low quality of the evidence and significant heterogeneity in many of the meta-analyses. The possible protective effect of ICSI is promising but should be confirmed in controlled prospective clinical trials. PROSPERO Registration ID : CRD42021236529.
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A recent systematic review and meta-analysis documents that assisted reproduction treatment results in a decrease in free T4 and rise in TSH in women with normal thyroid function before stimulation.
“A recent systematic review and meta-analysis documents what has long been suspected, that this treatment results in a decrease in free T4 and rise in TSH in women with normal thyroid function before stimulation.”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [89]
The decrease in free T4 and rise in TSH after ovarian stimulation is due to a rapid increase of thyroid hormone-binding protein production that far exceeds the rate of increase in a normal pregnancy, with extent determined by the duration and intensity of ovarian stimulation.
“This is due to a rapid increase of thyroid hormone-binding protein production that far exceeds the rate of increase in a normal pregnancy, the extent of which is also determined by the duration and intensity of ovarian stimulation (OS) (89).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [89]
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- Authors
- Busnelli, A., Beltratti, C., Cirillo, F., Bulfoni, A., Lania, A., & Levi-Setti, P. E.
- Affiliations
- Humanitas University (IT)
- IRCCS Humanitas Research Hospital (IT)
- Division of Obstetrics and Gynecology, Humanitas S. Pio X Hospital, Rozzano, Italy.
- Corresponding author
- Busnelli, Andrea
- Venue
- Thyroid
- Publisher
- SAGE Publications
- Published
- 2022-09
- Volume
- 32
- Issue
- 9
- Pages
- 1010-1028
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- OpenAlex
- W4285077205
- Cited by
- 36
- References
- 81
- Citations by year
- 2026: 15 · 2025: 5 · 2024: 11 · 2023: 5
- FWCI
- 0.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Thyroid (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Health and Technologies
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- thyroid autoimmunity, assisted reproduction outcomes, ovarian reserve, miscarriage, embryo implantation, live birth rate, anti-Müllerian hormone, antral follicle count, follicle-stimulating hormone, intracytoplasmic sperm injection, female fertility, oocyte quantity, oocyte retrieval number, fertilization rate, clinical pregnancy rate
- MeSH terms
- Abortion, Spontaneous, Female, Follicle Stimulating Hormone, Humans, Pregnancy, Prospective Studies, Thyroid Gland, Reproducibility of Results, Biomarkers, Autoimmunity, Pregnancy Rate, Reproductive Techniques, Assisted, Live Birth, Anti-Mullerian Hormone, Ovarian Reserve
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