COMMENTARY

How Does Thyroid Autoimmunity Affect IVF Outcomes?

Peter Kovacs, MD, PhD

Disclosures

August 31, 2016

The Impact of Thyroid Autoimmunity on IVF/ICSI Outcomes: A Systematic Review and Meta-analysis

Busnelli A, Paffoni A, Fedele L, Somigliana E
Hum Reprod Update. 2016 Jun 20. [Epub ahead of print]

Background

Hypothyroidism is known to be associated with adverse reproductive outcomes, including increased risk for miscarriage, adverse obstetric outcome, fetal anomalies, and infertility.[1] Hypothyroidism is diagnosed when the level of thyroid-stimulating hormone (TSH) is elevated and levels of thyroid hormones are reduced. In subclinical hypothyroidism (SCH), the TSH level is elevated but levels of thyroid hormones are in the normal range.

SCH is seen in 4% to 9% of the population, and the incidence increases with age.[2] One of the most common reasons for hypothyroidism is antibody production against thyroid peroxidase and thyroglobulin. Antibodies are often detected in people with overt or subclinical thyroid dysfunction, but they can also be found in otherwise euthyroid women.[2]

Thyroid autoimmunity is more prevalent in infertile women.[3] There is some evidence that the presence of thyroid antibodies is associated with an increased risk for miscarriage.

In this meta-analysis, the impact of isolated thyroid autoimmunity on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes was evaluated.

The Study

The analysis involved 12 cohort studies of women undergoing IVF/ICSI treatment (4176 without antibodies, 700 with antibodies). Studies in which patients received treatment for thyroid dysfunction were excluded. The pooled analysis revealed the following:

  • The live birth rate was lower in women with positive antibodies than in those with negative antibodies (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.49-0.87).

  • The number of eggs retrieved and rates of fertilization and implantation did not differ between antibody-positive and antibody-negative women.

  • Clinical pregnancy rates were similar in antibody-positive and antibody-negative women.

  • Miscarriage rates were higher in women with positive antibodies than in those with negative antibodies (OR, 1.44; 95% CI, 1.06-1.95).

  • When age and TSH levels were included in a meta-regression analysis, neither parameter had an effect on clinical pregnancy or miscarriage rates.

The authors concluded that the presence of thyroid antibodies has a negative impact on IVF/ICSI outcomes; higher miscarriage rates and lower live birth rates can be expected.

Viewpoint

During pregnancy, thyroid activity is usually increased by about 30%. Therefore, a normal TSH value in pregnant women or in women who plan to become pregnant ranges from 0.4 to 2.5 mIU/L.[1,2]

The management of patients with TSH levels between 2.5 and 4 mIU/L is somewhat controversial. Although treatment with L-thyroxine seems to benefit those with TSH levels above 4 mIU/L and normal thyroxine levels, those with TSH levels between 2.5 and 4 mIU/L do not always benefit from treatment.[1,2]

The presence of thyroid antibodies seems to modify this picture. Higher miscarriage and lower live birth rates, as well as an increased risk for adverse obstetric outcomes, can be seen in women with thyroid autoimmunity. It is possible that thyroid autoimmunity is part of a more general immune dysregulation or might affect implantation. Various treatments have been proposed (glucocorticoids, L-thyroxine), but the data on their benefit are limited.[4,5]

General screening for thyroid dysfunction is not recommended during pregnancy. Infertile women who expect to undergo expensive treatment might be an exception. When elevated TSH levels are identified, it would be advisable to check for antibodies, too. L-thyroxine could be used for those with TSH levels between 2.5 and 4 mIU/L who have positive antibodies, but for women with positive antibodies and TSH levels below 2.5 mIU/L, treatment is not recommended.[1,3]

Future studies should explore the exact pathomechanism of thyroid autoimmunity in infertile women, and the results could be used to propose better treatments to improve reproductive outcome.

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