Levothyroxine for a High-normal TSH in Unexplained Infertility

Overview

Journal Clin Endocrinol (Oxf)

Specialty Endocrinology

Date 2023 Dec 5

PMID 38050786

Authors

Francesca Galbiati

Tahereh Orouji Jokar

Lars M Howell

Runjia Li

Lindsay T Fourman

Hang Lee

Jong-Hyeon Jeong

Pouneh K Fazeli

Affiliations

Soon will be listed here.

Abstract

Objective: Unexplained infertility affects nearly one-third of infertile couples. Women with unexplained infertility are more likely to have a high-normal thyroid-stimulating hormone level (TSH: 2.5-5 mIU/L) compared to women with severe male factor infertility. Practice guidelines vary on whether treatment should be initiated for TSH levels >2.5 mIU/L in women attempting conception because the effects of treating a high-normal TSH level with levothyroxine are not known. We evaluated conception and live birth rates in women with unexplained infertility and high-normal TSH levels.

Design, Patients And Measurements: Retrospective study including 96 women evaluated for unexplained infertility at a large academic medical centre between 1 January 2000 and 30 June 2017 with high-normal TSH (TSH: 2.5-5 mIU/L and within the normal range of the assay) who were prescribed (n = 31) or not prescribed (n = 65) levothyroxine. Conception and live birth rates were assessed.

Results: The conception rate in the levothyroxine group was 100% compared to 90% in the untreated group (p = .086 unadjusted; p < .05 adjusted for age; p = .370 adjusted for TSH; p = .287 adjusted for age and TSH). The live birth rate was lower in the levothyroxine group (63%) compared to the untreated group (84%) (p = .05 unadjusted; p = .094 adjusted for age; p = .035 adjusted for TSH; p = .057 adjusted for age and TSH).

Conclusions: Women with unexplained infertility and high-normal TSH levels treated with levothyroxine had a higher rate of conception but lower live birth rate compared to untreated women, with the limitation of a small sample size. These findings assert the need for prospective, randomized studies to determine whether treatment with levothyroxine in women with unexplained infertility and high-normal TSH is beneficial.

Citing Articles

The association of higher thyroid stimulating hormone levels in the normal range with unexplained infertility: A cross-sectional study.

Jalili M, Azizi R, Aflatoonian A, Ghadiri-Anari A Int J Reprod Biomed. 2024; 22(5):357-362.

PMID: 39091424 PMC: 11290196. DOI: 10.18502/ijrm.v22i5.16434.

References

Baloch Z, Carayon P, Conte-Devolx B, Demers L, Feldt-Rasmussen U, Henry J . Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid. 2003; 13(1):3-126. DOI: 10.1089/105072503321086962. View

. Subclinical hypothyroidism in the infertile female population: a guideline. Fertil Steril. 2015; 104(3):545-53. DOI: 10.1016/j.fertnstert.2015.05.028. View

Smith S, Pfeifer S, Collins J . Diagnosis and management of female infertility. JAMA. 2003; 290(13):1767-70. DOI: 10.1001/jama.290.13.1767. View

Cramer D, Sluss P, Powers R, McShane P, Ginsburgs E, Hornstein M . Serum prolactin and TSH in an in vitro fertilization population: is there a link between fertilization and thyroid function?. J Assist Reprod Genet. 2003; 20(6):210-5. PMC: 3455321. DOI: 10.1023/a:1024151210536. View

De Groot L, Abalovich M, Alexander E, Amino N, Barbour L, Cobin R . Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012; 97(8):2543-65. DOI: 10.1210/jc.2011-2803. View

Dhillon-Smith R, Middleton L, Sunner K, Cheed V, Baker K, Farrell-Carver S . Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception. N Engl J Med. 2019; 380(14):1316-1325. DOI: 10.1056/NEJMoa1812537. View

Agarwal A, Mulgund A, Hamada A, Chyatte M . A unique view on male infertility around the globe. Reprod Biol Endocrinol. 2015; 13:37. PMC: 4424520. DOI: 10.1186/s12958-015-0032-1. View

Wakim A, Paljug W, Jasnosz K, Alhakim N, Brown A, Burholt D . Thyroid hormone receptor messenger ribonucleic acid in human granulosa and ovarian stromal cells. Fertil Steril. 1994; 62(3):531-4. DOI: 10.1016/s0015-0282(16)56941-6. View

van Dijk M, Vissenberg R, Fliers E, van der Post J, van der Hoorn M, de Weerd S . Levothyroxine in euthyroid thyroid peroxidase antibody positive women with recurrent pregnancy loss (T4LIFE trial): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2022; 10(5):322-329. DOI: 10.1016/S2213-8587(22)00045-6. View

10.

. Fertility evaluation of infertile women: a committee opinion. Fertil Steril. 2021; 116(5):1255-1265. DOI: 10.1016/j.fertnstert.2021.08.038. View

11.

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):281-295. PMC: 7923920. DOI: 10.1159/000512790. View

12.

Poppe K . MANAGEMENT OF ENDOCRINE DISEASE: Thyroid and female infertility: more questions than answers?!. Eur J Endocrinol. 2021; 184(4):R123-R135. DOI: 10.1530/EJE-20-1284. View

13.

Reindollar R, Regan M, Neumann P, Levine B, Thornton K, Alper M . A randomized clinical trial to evaluate optimal treatment for unexplained infertility: the fast track and standard treatment (FASTT) trial. Fertil Steril. 2009; 94(3):888-99. DOI: 10.1016/j.fertnstert.2009.04.022. View

14.

Dhillon-Smith R, Tobias A, Smith P, Middleton L, Sunner K, Baker K . The Prevalence of Thyroid Dysfunction and Autoimmunity in Women With History of Miscarriage or Subfertility. J Clin Endocrinol Metab. 2020; 105(8). DOI: 10.1210/clinem/dgaa302. View

15.

Cooper T, Noonan E, von Eckardstein S, Auger J, Baker H, Behre H . World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2009; 16(3):231-45. DOI: 10.1093/humupd/dmp048. View

16.

Zhang S, Carrillo A, Darling D . Expression of multiple thyroid hormone receptor mRNAs in human oocytes, cumulus cells, and granulosa cells. Mol Hum Reprod. 1997; 3(7):555-62. DOI: 10.1093/molehr/3.7.555. View

17.

Maraka S, Mwangi R, McCoy R, Yao X, Sangaralingham L, Singh Ospina N . Thyroid hormone treatment among pregnant women with subclinical hypothyroidism: US national assessment. BMJ. 2017; 356:i6865. PMC: 5266622. DOI: 10.1136/bmj.i6865. View

18.

. Testing and interpreting measures of ovarian reserve: a committee opinion. Fertil Steril. 2020; 114(6):1151-1157. DOI: 10.1016/j.fertnstert.2020.09.134. View

19.

Thoma M, McLain A, Louis J, King R, Trumble A, Sundaram R . Prevalence of infertility in the United States as estimated by the current duration approach and a traditional constructed approach. Fertil Steril. 2013; 99(5):1324-1331.e1. PMC: 3615032. DOI: 10.1016/j.fertnstert.2012.11.037. View

20.

Thangaratinam S, Tan A, Knox E, Kilby M, Franklyn J, Coomarasamy A . Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. BMJ. 2011; 342:d2616. PMC: 3089879. DOI: 10.1136/bmj.d2616. View