Skip to main content
Top
Published in: Reproductive Biology and Endocrinology 1/2016

Open Access 01-12-2016 | Research

What affects functional ovarian reserve, thyroid function or thyroid autoimmunity?

Authors: Andrea Weghofer, David H. Barad, Sarah Darmon, Vitaly A. Kushnir, Norbert Gleicher

Published in: Reproductive Biology and Endocrinology | Issue 1/2016

Login to get access

Abstract

Background

Thyroid dysfunction is the most common autoimmune endocrine disorder in women of reproductive age, and is associated with menstrual irregularities, anovulation and infertility. Whether it is thyroid function or thyroid autoimmunity that affects functional ovarian reserve (FOR, i.e., the small growing ovarian follicle pool) reflected in anti-Müllerian hormone (AMH) has, however, remained under dispute.

Methods

We investigated in 225 infertile women whether thyroid function, after adjustment for thyroid autoimmunity, affects FOR within what is considered normal thyroid function (TSH, 0.4–4.5μIU/mL) by assessing AMH levels in reference to TSH levels, stratified for TSH < or ≥3.0μIU/mL. Thyroid autoimmunity was defined by presence of anti-thyroid peroxidase, −thyroglobulin and/or -thyroid receptor antibodies.

Results

Mean age of studied women was 38.4 ± 5.0 years; their mean AMH was 1.3 ± 2.0 ng/mL and mean TSH 1.8 ± 0.9 μIU/mL. Thyroid autoimmunity was present in 11.1 % of patients. Women with TSH <3.0μIU/mL presented with significantly higher AMH compared to those with TSH ≥3.0μIU/Ml (P = 0.03). This difference remained significant after adjustment for thyroid autoimmunity as well as age (P = 0.02).

Conclusions

Even after adjustment for thyroid autoimmunity and age, TSH <3.0μIU/mL in euthyroid infertility patients is associated with significantly better FOR (higher AMH) than TSH ≥3.0μIU/mL. This observation suggests a direct beneficial effect of lower TSH levels on follicular recruitment, and warrants investigations of thyroxin supplementation in infertile women with TSH levels ≥3.0μIU/mL in attempts to improve FOR.
Literature
1.
go back to reference Krassas GE, Pontikides N, Kaltsas T, Papadopoulou P, Paunkovic J, Paunkovic N, Duntas LH. Disturbances of menstruation in hypothyroidism. Clin Endocrinol (Oxf). 1999;50:655–9.CrossRef Krassas GE, Pontikides N, Kaltsas T, Papadopoulou P, Paunkovic J, Paunkovic N, Duntas LH. Disturbances of menstruation in hypothyroidism. Clin Endocrinol (Oxf). 1999;50:655–9.CrossRef
2.
go back to reference Poppe K, Velkeniers B. Female infertility and the thyroid. Best Pract Res Clin Endocrinol Metab. 2004;18:153–65.CrossRefPubMed Poppe K, Velkeniers B. Female infertility and the thyroid. Best Pract Res Clin Endocrinol Metab. 2004;18:153–65.CrossRefPubMed
3.
go back to reference Mintziori G, Anagnostis P, Toulis KA, Goulis DG. Thyroid diseases and female reproduction. Minerva Med. 2012;103:47–62.PubMed Mintziori G, Anagnostis P, Toulis KA, Goulis DG. Thyroid diseases and female reproduction. Minerva Med. 2012;103:47–62.PubMed
4.
go back to reference Reid SM, Middleton P, Cossich MC, Crowther CA, Bain E. Interventions for clinical and subclinical hypothyroidism pre-pregnancy and during pregnancy. Cochrane Database Syst Rev. 2013;5:CD007752.PubMed Reid SM, Middleton P, Cossich MC, Crowther CA, Bain E. Interventions for clinical and subclinical hypothyroidism pre-pregnancy and during pregnancy. Cochrane Database Syst Rev. 2013;5:CD007752.PubMed
5.
go back to reference Negro R, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Stagnaro-Green A. Thyroid antibody positivity in the first trimester of pregnancy is associated with negative pregnancy outcomes. J Clin Endocrinol Metab. 2011;96:E920–924.CrossRefPubMed Negro R, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Stagnaro-Green A. Thyroid antibody positivity in the first trimester of pregnancy is associated with negative pregnancy outcomes. J Clin Endocrinol Metab. 2011;96:E920–924.CrossRefPubMed
6.
go back to reference Fumarola A, Grani G, Romanzi D, Del Sordo M, Bianchini M, Aragona A, Tranquilli D, Aragona C. Thyroid function in infertile patients undergoing assisted reproduction. Am J Reprod Immunol. 2013;70:336–41.CrossRefPubMed Fumarola A, Grani G, Romanzi D, Del Sordo M, Bianchini M, Aragona A, Tranquilli D, Aragona C. Thyroid function in infertile patients undergoing assisted reproduction. Am J Reprod Immunol. 2013;70:336–41.CrossRefPubMed
7.
go back to reference Reh A, Grifo J, Danoff A. What is a normal thyroid-stimulating hormone (TSH) level? Effects of stricter TSH thresholds on pregnancy outcomes after in vitro fertilization. Fertil Steril. 2010;94:2920–2.CrossRefPubMed Reh A, Grifo J, Danoff A. What is a normal thyroid-stimulating hormone (TSH) level? Effects of stricter TSH thresholds on pregnancy outcomes after in vitro fertilization. Fertil Steril. 2010;94:2920–2.CrossRefPubMed
8.
go back to reference Murto T, Bjuresten K, Landgren BM, Stavreus-Evers A. Predictive value of hormonal parameters for live birth in women with unexplained infertility and male infertility. Reprod Biol Endocrinol. 2013;11:61.CrossRefPubMedPubMedCentral Murto T, Bjuresten K, Landgren BM, Stavreus-Evers A. Predictive value of hormonal parameters for live birth in women with unexplained infertility and male infertility. Reprod Biol Endocrinol. 2013;11:61.CrossRefPubMedPubMedCentral
9.
go back to reference Benaglia L, Busnelli A, Somigliana E, Leonardi M, Vannucchi G, De Leo S, Fugazzola L, Ragni G, Fedele L. Incidence of elevation of serum thyroid-stimulating hormone during controlled ovarian hyperstimulation for in vitro fertilization. Eur J Obstet Gynecol Reprod Biol. 2014;173:53–7.CrossRefPubMed Benaglia L, Busnelli A, Somigliana E, Leonardi M, Vannucchi G, De Leo S, Fugazzola L, Ragni G, Fedele L. Incidence of elevation of serum thyroid-stimulating hormone during controlled ovarian hyperstimulation for in vitro fertilization. Eur J Obstet Gynecol Reprod Biol. 2014;173:53–7.CrossRefPubMed
10.
go back to reference Stuckey BG, Yeap D, Turner SR. Thyroxine replacement during super-ovulation for in vitro fertilization: a potential gap in management? Fertil Steril. 2010;93:2414 e2411-2413.CrossRef Stuckey BG, Yeap D, Turner SR. Thyroxine replacement during super-ovulation for in vitro fertilization: a potential gap in management? Fertil Steril. 2010;93:2414 e2411-2413.CrossRef
11.
go back to reference Scoccia B, Demir H, Kang Y, Fierro MA, Winston NJ. In vitro fertilization pregnancy rates in levothyroxine-treated women with hypothyroidism compared to women without thyroid dysfunction disorders. Thyroid. 2012;22:631–6.CrossRefPubMedPubMedCentral Scoccia B, Demir H, Kang Y, Fierro MA, Winston NJ. In vitro fertilization pregnancy rates in levothyroxine-treated women with hypothyroidism compared to women without thyroid dysfunction disorders. Thyroid. 2012;22:631–6.CrossRefPubMedPubMedCentral
12.
go back to reference Busnelli A, Somigliana E, Benaglia L, Sarais V, Ragni G, Fedele L. Thyroid axis dysregulation during in vitro fertilization in hypothyroid-treated patients. Thyroid. 2014;24:1650–5.CrossRefPubMed Busnelli A, Somigliana E, Benaglia L, Sarais V, Ragni G, Fedele L. Thyroid axis dysregulation during in vitro fertilization in hypothyroid-treated patients. Thyroid. 2014;24:1650–5.CrossRefPubMed
13.
go back to reference Krassas GE, Doumas A, Kaltsas T, Halkias A, Pontikides N. Somatostatin receptor scintigraphy before and after treatment with somatostatin analogues in patients with thyroid eye disease. Thyroid. 1999;9:47–52.CrossRefPubMed Krassas GE, Doumas A, Kaltsas T, Halkias A, Pontikides N. Somatostatin receptor scintigraphy before and after treatment with somatostatin analogues in patients with thyroid eye disease. Thyroid. 1999;9:47–52.CrossRefPubMed
14.
go back to reference Broer SL, Broekmans FJ, Laven JS, Fauser BC. Anti-Mullerian hormone: ovarian reserve testing and its potential clinical implications. Hum Reprod Update. 2014;20:688–701.CrossRefPubMed Broer SL, Broekmans FJ, Laven JS, Fauser BC. Anti-Mullerian hormone: ovarian reserve testing and its potential clinical implications. Hum Reprod Update. 2014;20:688–701.CrossRefPubMed
15.
go back to reference Weghofer A, Dietrich W, Ortner I, Bieglmayer C, Barad D, Gleicher N. Anti-Mullerian hormone levels decline under hormonal suppression: a prospective analysis in fertile women after delivery. Reprod Biol Endocrinol. 2011;9:98.CrossRefPubMedPubMedCentral Weghofer A, Dietrich W, Ortner I, Bieglmayer C, Barad D, Gleicher N. Anti-Mullerian hormone levels decline under hormonal suppression: a prospective analysis in fertile women after delivery. Reprod Biol Endocrinol. 2011;9:98.CrossRefPubMedPubMedCentral
16.
go back to reference van den Berg MH, van Dulmen-den Broeder E, Overbeek A, Twisk JW, Schats R, van Leeuwen FE, Kaspers GJ, Lambalk CB. Comparison of ovarian function markers in users of hormonal contraceptives during the hormone-free interval and subsequent natural early follicular phases. Hum Reprod. 2010;25:1520–7.CrossRefPubMed van den Berg MH, van Dulmen-den Broeder E, Overbeek A, Twisk JW, Schats R, van Leeuwen FE, Kaspers GJ, Lambalk CB. Comparison of ovarian function markers in users of hormonal contraceptives during the hormone-free interval and subsequent natural early follicular phases. Hum Reprod. 2010;25:1520–7.CrossRefPubMed
17.
go back to reference Kuroda K, Uchida T, Nagai S, Ozaki R, Yamaguchi T, Sato Y, Brosens JJ, Takeda S. Elevated serum thyroid-stimulating hormone is associated with decreased anti-Mullerian hormone in infertile women of reproductive age. J Assist Reprod Genet. 2015;32:243–7.CrossRefPubMedPubMedCentral Kuroda K, Uchida T, Nagai S, Ozaki R, Yamaguchi T, Sato Y, Brosens JJ, Takeda S. Elevated serum thyroid-stimulating hormone is associated with decreased anti-Mullerian hormone in infertile women of reproductive age. J Assist Reprod Genet. 2015;32:243–7.CrossRefPubMedPubMedCentral
18.
go back to reference Dosiou C, Barnes J, Schwartz A, Negro R, Crapo L, Stagnaro-Green A. Cost-effectiveness of universal and risk-based screening for autoimmune thyroid disease in pregnant women. J Clin Endocrinol Metab. 2012;97:1536–46.CrossRefPubMed Dosiou C, Barnes J, Schwartz A, Negro R, Crapo L, Stagnaro-Green A. Cost-effectiveness of universal and risk-based screening for autoimmune thyroid disease in pregnant women. J Clin Endocrinol Metab. 2012;97:1536–46.CrossRefPubMed
19.
go back to reference Xue H, Yang Y, Zhang Y, Song S, Zhang L, Ma L, Brosens JJ, Takeda S. Macrophage migration inhibitory factor interacting with Th17 cells may be involved in the pathogenesis of autoimmune damage in Hashimoto’s thyroiditis. Mediators Inflamm. 2015;2015:621072. Xue H, Yang Y, Zhang Y, Song S, Zhang L, Ma L, Brosens JJ, Takeda S. Macrophage migration inhibitory factor interacting with Th17 cells may be involved in the pathogenesis of autoimmune damage in Hashimoto’s thyroiditis. Mediators Inflamm. 2015;2015:621072.
20.
go back to reference Karmisholt J, Laurberg P. Serum TSH and serum thyroid peroxidase antibody fluctuate in parallel and high urinary iodine excretion predicts subsequent thyroid failure in a 1-year study of patients with untreated subclinical hypothyroidism. Eur J Endocrinol. 2008;158:209–15.CrossRefPubMed Karmisholt J, Laurberg P. Serum TSH and serum thyroid peroxidase antibody fluctuate in parallel and high urinary iodine excretion predicts subsequent thyroid failure in a 1-year study of patients with untreated subclinical hypothyroidism. Eur J Endocrinol. 2008;158:209–15.CrossRefPubMed
21.
go back to reference Gleicher N, Kim A, Weghofer A, Kushnir VA, Shohat-Tal A, Lazzaroni E, Lee HJ, Barad DH. Hypoandrogenism in association with diminished functional ovarian reserve. Hum Reprod. 2013;28:1084–91.CrossRefPubMed Gleicher N, Kim A, Weghofer A, Kushnir VA, Shohat-Tal A, Lazzaroni E, Lee HJ, Barad DH. Hypoandrogenism in association with diminished functional ovarian reserve. Hum Reprod. 2013;28:1084–91.CrossRefPubMed
22.
go back to reference La Marca A, Nelson SM, Sighinolfi G, Manno M, Baraldi E, Roli L, Xella S, Marsella T, Tagliasacchi D, D'Amico R, Volpe A. Anti-Mullerian hormone-based prediction model for a live birth in assisted reproduction. Reprod Biomed Online. 2011;22:341–9. La Marca A, Nelson SM, Sighinolfi G, Manno M, Baraldi E, Roli L, Xella S, Marsella T, Tagliasacchi D, D'Amico R, Volpe A. Anti-Mullerian hormone-based prediction model for a live birth in assisted reproduction. Reprod Biomed Online. 2011;22:341–9.
23.
go back to reference Dittrich R, Beckmann MW, Oppelt PG, Hoffmann I, Lotz L, Kuwert T, Mueller A. Thyroid hormone receptors and reproduction. J Reprod Immunol. 2011;90:58–66.CrossRefPubMed Dittrich R, Beckmann MW, Oppelt PG, Hoffmann I, Lotz L, Kuwert T, Mueller A. Thyroid hormone receptors and reproduction. J Reprod Immunol. 2011;90:58–66.CrossRefPubMed
24.
go back to reference Krassas GE, Poppe K, Glinoer D. Thyroid function and human reproductive health. Endocr Rev. 2010;31:702–55.CrossRefPubMed Krassas GE, Poppe K, Glinoer D. Thyroid function and human reproductive health. Endocr Rev. 2010;31:702–55.CrossRefPubMed
25.
go back to reference Revelli A, Casano S, Piane LD, Grassi G, Gennarelli G, Guidetti D, Massobrio M. A retrospective study on IVF outcome in euthyroid patients with anti-thyroid antibodies: effects of levothyroxine, acetyl-salicylic acid and prednisolone adjuvant treatments. Reprod Biol Endocrinol. 2009;7:137.CrossRefPubMedPubMedCentral Revelli A, Casano S, Piane LD, Grassi G, Gennarelli G, Guidetti D, Massobrio M. A retrospective study on IVF outcome in euthyroid patients with anti-thyroid antibodies: effects of levothyroxine, acetyl-salicylic acid and prednisolone adjuvant treatments. Reprod Biol Endocrinol. 2009;7:137.CrossRefPubMedPubMedCentral
26.
go back to reference Toulis KA, Goulis DG, Venetis CA, Kolibianakis EM, Negro R, Tarlatzis BC, Papadimas I. Risk of spontaneous miscarriage in euthyroid women with thyroid autoimmunity undergoing IVF: a meta-analysis. Eur J Endocrinol. 2010;162:643–52.CrossRefPubMed Toulis KA, Goulis DG, Venetis CA, Kolibianakis EM, Negro R, Tarlatzis BC, Papadimas I. Risk of spontaneous miscarriage in euthyroid women with thyroid autoimmunity undergoing IVF: a meta-analysis. Eur J Endocrinol. 2010;162:643–52.CrossRefPubMed
27.
go back to reference Polyzos NP, Sakkas E, Vaiarelli A, Poppe K, Camus M, Tournaye H. Thyroid autoimmunity, hypothyroidism and ovarian reserve: a cross-sectional study of 5000 women based on age-specific AMH values. Hum Reprod. 2015;30:1690–6.CrossRefPubMed Polyzos NP, Sakkas E, Vaiarelli A, Poppe K, Camus M, Tournaye H. Thyroid autoimmunity, hypothyroidism and ovarian reserve: a cross-sectional study of 5000 women based on age-specific AMH values. Hum Reprod. 2015;30:1690–6.CrossRefPubMed
28.
go back to reference Velkeniers B, Van Meerhaeghe A, Poppe K, Unuane D, Tournaye H, Haentjens P. Levothyroxine treatment and pregnancy outcome in women with subclinical hypothyroidism undergoing assisted reproduction technologies: systematic review and meta-analysis of RCTs. Hum Reprod Update. 2013;19:251–8.CrossRefPubMed Velkeniers B, Van Meerhaeghe A, Poppe K, Unuane D, Tournaye H, Haentjens P. Levothyroxine treatment and pregnancy outcome in women with subclinical hypothyroidism undergoing assisted reproduction technologies: systematic review and meta-analysis of RCTs. Hum Reprod Update. 2013;19:251–8.CrossRefPubMed
29.
go back to reference Magri F, Capelli V, Gaiti M, Brambilla E, Montesion L, Rotondi M, Spinillo A, Nappi RE, Chiovato L. Impaired outcome of controlled ovarian hyperstimulation in women with thyroid autoimmune disease. Thyroid. 2013;23:1312–8.CrossRefPubMed Magri F, Capelli V, Gaiti M, Brambilla E, Montesion L, Rotondi M, Spinillo A, Nappi RE, Chiovato L. Impaired outcome of controlled ovarian hyperstimulation in women with thyroid autoimmune disease. Thyroid. 2013;23:1312–8.CrossRefPubMed
30.
go back to reference Tuten A, Hatipoglu E, Oncul M, Imamoglu M, Acikgoz AS, Yilmaz N, Ozcil MD, Kaya B, Misirlioglu AM, Sahmay S. Evaluation of ovarian reserve in Hashimoto’s thyroiditis. Gynecol Endocrinol. 2014;30:708–11.CrossRefPubMed Tuten A, Hatipoglu E, Oncul M, Imamoglu M, Acikgoz AS, Yilmaz N, Ozcil MD, Kaya B, Misirlioglu AM, Sahmay S. Evaluation of ovarian reserve in Hashimoto’s thyroiditis. Gynecol Endocrinol. 2014;30:708–11.CrossRefPubMed
31.
go back to reference Saglam F, Onal ED, Ersoy R, Koca C, Ergin M, Erel O, Cakir B. Anti-Mullerian hormone as a marker of premature ovarian aging in autoimmune thyroid disease. Gynecol Endocrinol. 2015;31:165–8.CrossRefPubMed Saglam F, Onal ED, Ersoy R, Koca C, Ergin M, Erel O, Cakir B. Anti-Mullerian hormone as a marker of premature ovarian aging in autoimmune thyroid disease. Gynecol Endocrinol. 2015;31:165–8.CrossRefPubMed
32.
go back to reference Magri F, Schena L, Capelli V, Gaiti M, Zerbini F, Brambilla E, Rotondi M, De Amici M, Spinillo A, Nappi RE, Chiovato L. Anti-Mullerian hormone as a predictor of ovarian reserve in ART protocols: the hidden role of thyroid autoimmunity. Reprod Biol Endocrinol. 2015;13:106.CrossRefPubMedPubMedCentral Magri F, Schena L, Capelli V, Gaiti M, Zerbini F, Brambilla E, Rotondi M, De Amici M, Spinillo A, Nappi RE, Chiovato L. Anti-Mullerian hormone as a predictor of ovarian reserve in ART protocols: the hidden role of thyroid autoimmunity. Reprod Biol Endocrinol. 2015;13:106.CrossRefPubMedPubMedCentral
Metadata
Title
What affects functional ovarian reserve, thyroid function or thyroid autoimmunity?
Authors
Andrea Weghofer
David H. Barad
Sarah Darmon
Vitaly A. Kushnir
Norbert Gleicher
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2016
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-016-0162-0

Other articles of this Issue 1/2016

Reproductive Biology and Endocrinology 1/2016 Go to the issue