Talk given in Indian Thyroid Update in 2021

1. TSH and fertility
Karthik ◦ June 27, 2021
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2. Infertility
Definition Inability to conceive after 1 year of regular unprotected sexual intercourse
Prevalence Approximately 10 to 15 %
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3. Male vs Female
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4. Basic physiology
T4
TSH

5. Relationship
TSH Fertility
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6. Thyroid hormones and female fertility 1
Direct mechanism
■ FSH + T3 ⇒ granulosa
cells
■ Thyroid hormone
regulation of aromatase
activity, follicle
development
■ T3 /TSH receptors
present on mature &
developing oocyte
Indirect mechanism
■ Altered clearance
■ Decreased SHBG
■ Increased peripheral
aromatase activity
■ Increased prolactin
1
Poppe K. Thyroid and female infertility: more questions than answers?! Eur J Endocrinol
2021;184(4):R123–35.

7. Evidence - Epidemiological
Do infertile couples have higher prevalence of hypothyroidism or hyperthyroidism?
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8. TSH and fertility within the normal range2
2
Orouji Jokar T et al. J Clin Endocrinol Metab 2018;103(2):632–9.

9. Prevalence of hypothyroidism in infertility3
After treatment for hypothyroidism, 76.6% of infertile women conceived within 6 weeks
to 1 year
3
Verma et al Int J Appl Basic Med Res 2012;2(1):17–9.
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10. Thyroid and male fertility
Mechanisms
■ Increased prolactin
■ Hypogonadotropic hypogonadism
■ Low libido
■ Low sperm motility
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11. What happens after treatment?4
4
Ambigapathy JS et al Indian J Endocrinol Metab 2020;24(3):265–9.
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12. What about low TSH?
■ Subclinical hyperthyroidism is rarer than subclinical hypothyroidism
■ Suppressed TSH was found isn 2.1% of infertile women in a prospective study by
Poppe et al, compared to 3 % in the control population 5
Prevalence of suppressed TSH is same in infertile women and controls
↓ TSH
5
Poppe K et al Thyroid dysfunction and autoimmunity in infertile women. Thyroid 2002 12 997–1001
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13. Thyroid Issues
↓ Hormone Autoimmunity ↓ Micronutrient
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14. Antibody and increased risk
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Poppe et al. J Clin Endocrinol Metab 2003;88:4149-52

15. Autoimmunity and fertility
■ Prevalence of Thyroid autoimmunity is significantly higher in infertile couples (19 %
vs 13 %) 6
Which antibodies to test?
anti TPO 4 %
anti TG 5 %
Both 8 %
6
Unuane D, Velkeniers B, Anckaert E, et al. Thyroglobulin autoantibodies: is there any added value in the
detection of thyroid autoimmunity in women consulting for fertility treatment? Thyroid 2013;23(8):1022–8.
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16. Autoimmunity and fertility
■ Prevalence of Thyroid autoimmunity is significantly higher in infertile couples (19 %
vs 13 %) 6
Which antibodies to test?
anti TPO 4 %
anti TG 5 %
Both 8 %
It doesn’t matter which antibody we choose to test
6
Unuane D, Velkeniers B, Anckaert E, et al. Thyroglobulin autoantibodies: is there any added value in the
detection of thyroid autoimmunity in women consulting for fertility treatment? Thyroid 2013;23(8):1022–8.
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17. Can I treat the autoimmunity?
No role for any drug in reducing thyroid autoimmunity
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18. Iodine and fertility
■ Iodine is taken up avidly by the ovary and endometrium.
■ Iodine deficiency is associated with reduced fertility 7
■ The use of high iodine concentration contrast media has recently been shown to
improve conception rates in couples with unexplained infertility (UI)
7
Mathews DM, Johnson NP, Sim RG et al Iodine and fertility: do we know enough? Hum Reprod
2021;36(2):265–74
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19. Selenium , TSH and pregnancy
■ Selenium deficiency associated with adverse pregnany outcomes8
■ Supplementation at 83 mcg/d reduces anti TPO antibody levels, improves outcome
■ No reliable serum markers + low therapeutic index
■ NOT recommended by ATA
8
Duntas LH. Selenium and at-risk pregnancy: challenges and controversies. Thyroid Res 2020;13:16.
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20. Selenium sources

21. Treatment

22. Principle of treatment
Treatment trifecta
■ Does thyroid ”problem” cause infertility?
■ Does treatment of thyroid ”problem” improve live birth rates?
■ Does the treatment have favourable risk/benefit ratio, after caferul
consideration of alternatives and natural course?
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23. ↓ Hormone Autoimmunity ↓ Micronutrient

24. ↓ Hormone Autoimmunity ↓ Micronutrient
✓ × ×
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25. TSH is abnormal -What to do ?
TSH < 2.5 TSH 2.5 to 4 TSH 4 to 10 TSH > 10
Normal Abnormal
Next
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26. Guidelines - ATA 2017
TSH Antibody + Antibody -
< 2.5 No Rx No Rx
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27. Guidelines - ATA 2017
TSH Antibody + Antibody -
< 2.5 No Rx No Rx
2.5 - 4 Consider No Rx
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28. Guidelines - ATA 2017
TSH Antibody + Antibody -
< 2.5 No Rx No Rx
2.5 - 4 Consider No Rx
4 -10 Treat Consider
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29. Guidelines - ATA 2017
TSH Antibody + Antibody -
< 2.5 No Rx No Rx
2.5 - 4 Consider No Rx
4 -10 Treat Consider
> 10 Treat Treat
Guidelines ”err” on the side of treatment in antibody positive women
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30. What about ART? 9
NOR ( number of oocytes retrieved) is NOT influenced by thyroid function or thyroid au-
toimmunity. LT4 does NOT improve ooctyle retrieval rate
WomenwithhypothyroidismtreatedwithLT4priortoARTshouldhaveaserumTSHlevel
<2.5 mIU/L
ART
9
Poppe K, Bisschop P, Fugazzola L, Minziori G, Unuane D, Weghofer A. 2021 European Thyroid Association
Guideline on Thyroid Disorders prior to and during Assisted Reproduction. Eur Thyroid J 2021;9(6):281–95.
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31. Screening
■ Symptomatic women
■ Women above 35 years
■ Family history of thyroid illness
■ Irregular menstruation
■ Recurrent pregnancy loss
■ Infertility
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32. Summary
■ Thyroid dysfunction affects fertility
■ Patients with infertility should be screened for thyroid dysfunction
■ For TSH > 2.5 , antibody testing may tilt the decision in favor of treatment
Take Home messages
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33. Thank you !
This presentation can be downloaded from
www.medicalruminations.wordpress.com
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