Female Infertility And Thyroid Dysfunction

Author: Dr. Om J Lakhani

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Questions and Answers

• Q. Is there a link between thyroid dysfunction and infertility?

  • Yes
  • Current evidence suggests a definite link between over thyroid dysfunction (hyperthyroidism and hypothyroidism) and infertility and substantial improvement in fertility with treatment.

• Q. Summarize the approach to a woman with thyroid dysfunction and having a history of recurrent first-trimester abortion?

  • 

• Q. Summarize the approach to Hypothyroidism and Female infertility?

  • 

• Q. Summarize the guidelines for Euthyroid women with Anti-TPO positivity and infertility?

  • 

• Q. Summarize the evidence available for Anti-TPO positivity and fertility outcomes?

  • 

• Q. Is it true that women with PCOS are more likely to have anti-TPO antibody-positive?

  • Yes

• Q. Is it true that women with Anti-TPO positive with or without TSH elevation are more likely to be infertile?

  • Limited evidence does suggest that women with female factor infertility are more likely to have TPO antibody positive compared to age-matched women who are not infertile.

• Q. What are the potential mechanisms linking Anti-TPO positivity and infertility?

  • T cell abnormality
  • Hyperactivity and elevated mass of natural killer cells
  • Polyclonal B cell activation and non-organ-specific autoantibodies
  • Cross-reactivity
  • Vitamin D deficiency
  • Concurrent autoimmunity (i.e., endometriosis)
  • 

• Q. Should all women with infertility undergo thyroid function testing?

  • Yes.

• Q. Is LT4 treatment recommended in women with subclinical hypothyroidism with anti-TPO negative who have infertility but not planned for ART?

  • There is insufficient evidence for or against using LT4 in this group of patients.

• Q. A woman is to undergo ART and have subclinical hypothyroidism with a TSH of 6.0 mU/l. Would you treat this woman?

  • Yes
  • The guidelines suggest that subclinical hypothyroidism in women who are to undergo ART should be treated.
  • The target for TSH is < 2.5.

Clinical Pearl

• Subclinical hypothyroidism (with an anti-TPO negative), with infertility:

  • Those not undergoing ART - insufficient evidence for or against to treat.
  • Those undergoing ART - treat and keep TSH < 2.5 mU/l (Strong recommendation)

• Q. What about anti-TPO-positive women with euthyroidism undergoing ART?

  • The guidelines recommend that there is insufficient evidence to suggest for or against treatment in such a scenario; however, the benefits compared to harm are less, so giving a small dose of LT4 in a dose of 25-50 mcg/day may not be harmful.

Clinical Pearl

• Subclinical hypothyroidism and ART:

  • Subclinical hypothyroidism and ART with or without anti-TPO positive – treat (strong recommendation)
  • Euthyroidism with Anti-TPO positive undergoing ART – consider treatment with LT4 25-50 mcg to improve ART outcomes (Weak recommendation)

• Q. Does ovulation induction (ovarian stimulation impact thyroid function test)?

  • Physiologically, it is prudent to understand that ovarian hyperstimulation or ovulation induction may impact thyroid function
  • HCG, which is used here, may act on TSH receptors and increase thyroid hormones, while estrogen, which is produced in excess, may increase TBG and reduce free thyroid hormone.
  • Hence the impact of this is opposing and challenging to judge, but it does affect thyroid function.

• Q. What are the recommendations as far ovulation induction is concerned?

  • If a thyroid function test is done, then it must be done either before or 2 weeks after ovulation induction, since drugs used here may interfere with thyroid function test
  • If a woman becomes pregnant with ovulation induction – then do a thyroid function and treat as per the guidelines.
  • If the woman does not become pregnant, repeat the test after 2-4 weeks when levels may normalize.

Recent Updates

Recent updates in 2024 on the topic of "Female Infertility and Thyroid Dysfunction" have provided new insights and evidence. Here's a mini-review of the latest findings:

Thyroid Hormone Receptor and Female Fertility

A study on zebrafish has revealed the crucial role of thyroid hormone receptor alpha (thrab) in female fertility. Disruption of the thrab gene led to female infertility due to oviductal blockage at the genital papilla. This research suggests that thyroid hormones may directly influence both the reproductive tract and ovary development and function[1].

Thyroid Autoimmunity and Infertility

Recent studies have shown a higher prevalence of thyroid autoantibodies in women with infertility compared to healthy controls[7]. However, a Mendelian randomization study suggested that overall thyroid function levels may not be a significant predictor of infertility risk[6].

Impact on Assisted Reproduction

A retrospective cohort study found an association between thyroid autoimmunity (TAI) and reduced reproductive outcomes in women undergoing intrauterine insemination (IUI) for unexplained infertility. However, a meta-analysis incorporating multiple studies did not show statistically significant differences in clinical pregnancy rates or live birth rates between TAI-positive and TAI-negative groups[9].

Prevalence of Hypothyroidism in Infertile Women

A meta-analysis of Indian studies revealed a pooled prevalence of hypothyroidism in women with infertility at 28% (95% CI: 20% to 36%). This high prevalence suggests the need for thyroid screening during infertility workups[10].

Ovarian Reserve and Thyroid Function

Some evidence indicates that subclinical or overt hypothyroidism may be associated with diminished ovarian reserve in infertile women, independent of thyroid autoimmunity[5].

In conclusion, while the relationship between thyroid dysfunction and female infertility continues to be complex, recent studies emphasize the importance of considering thyroid function in fertility evaluations. However, more research is needed to fully understand the mechanisms and to establish definitive guidelines for management.

References:

1. Disruption of Thyroid Hormone Receptor Thrab Leads to Female Infertility in Zebrafish. Endocrinology. 2024.
2. Thyroid Disease in Pregnancy: ACOG Practice Bulletin, Number 223. Obstet Gynecol. 2020.
3. Clinical Strategies in the Testing of Thyroid Function. MDText.com, Inc. 2024.
4. Risk Factors for Thyroid Dysfunction in Pregnancy. Thyroid. 2024.
5. Subclinical/overt hypothyroidism may be associated with diminished ovarian reserve in infertile women independent of thyroid autoimmunity. Hum Reprod. 2024.
6. Causal association between thyroid function and the risk of infertility. Fertil Steril. 2024.
7. Prevalence of thyroid autoantibody positivity in women with infertility. Hum Reprod Update. 2024.
8. A Review of Autoimmune Thyroid Diseases and Their Complex Relationship with Fertility and Pregnancy. Front Endocrinol. 2024.
9. The impact of thyroid autoimmunity on pregnancy outcomes in women with unexplained infertility undergoing intrauterine insemination. Front Endocrinol. 2024.
10. Pooled prevalence of hypothyroidism among Indian females with infertility: A systematic review and meta-analysis. Indian J Med Res. 2024.

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