Thyroid Autoimmunity and Implantation Failure
Keywords:
Thyroid autoimmunity; Subclinical hypothyroidism; Recurrent implantation failure; Recurrent pregnancy loss.Abstract
Thyroid hormones directly affect reproductive hormones. Hypothyroidism and hyperthyroidism are common, important and often reversible or preventable causes of infertility. Subclinical hypothyroidism is a milder form of hypothyroidism defined as an elevated TSH concentration in conjunction with normal free thyroxine (FT4) levels. Hypothyroidism
is associated with decreased plasma concentrations of estrogens and androgens with deficient LH secretion. There may be reduced libido and anovulation. So, tight control of thyroid function is a must for better reproductive outcomes. Thyroid autoimmunity is associated with miscarriage and there is fair evidence that it is associated with infertility.
Levothyroxine is the recommended treatment to improve pregnancy outcomes in women with hypothyroidism and positive thyroid antibodies, especially if the TSH level is over 2.5 mIU/L. In hyperthyroidism, there may be inadequate mid-cycle LH surges leading to anovulation. With IVF stimulation, the condition might exacerbate. In hyperthyroidism, FT4
should upper-end reference range & low TSH level (0.1-0.4 mU/L) and propyl thiouracil (PTU) is recommended before pregnancy and in the 1st trimester and 2nd trimesters it is preferable to shift to methimazole (MMI)/ carbimazole (CMZ). In recurrent IVF failure, thyroid antibodies screening should be done in euthyroid women and intravenous immunoglobulins can be given in positive cases. Data were obtained from PubMed, Google scholar and individual searches.
How to cite this article:
Agarwal K, Banerjee K. Thyroid Autoimmunity and Implantation Failure. Int J Adv Res Gynaecol Obstet. 2022; 3(1): 1-4.
References
Boivin J, Bunting L, Collins JA, Nygren KG. International estimates of infertility prevalence and treatment-seeking: Potential need and demand for infertility medical care. Hum. Reprod. 2007; 22: 1506-1512.
Margalioth, E.J. Ben-Chetrit, A.Gal, M. Eldar-Geva, T. Investigation and treatment of repeated implantation
failure following IVF-ET. Hum. Reprod. 2006; 21: 3036-3043.
D. Unuane, B. Velkeniers. Impact of thyroid disease on fertility and assisted conception. Best Practice &
Research Clinical Endocrinology & Metabolism 2020;34: 101378.
Zhong YP, Ying Y, Wu HT, et al. Relationship between antithyroid antibody and pregnancy outcome following
in vitro fertilization and embryo transfer. Int J Med Sci 2012;9:121e5.
Busnelli A, Paffoni A, Fedele L, et al. The impact of thyroid autoimmunity on IVF/ICSI outcome: a systematic review and meta-analysis. Hum Reprod Update 2016;22:793e4.
Lukazuk K, Kunicki M, Kulwikowska P, et al. The impact of the presence of antithyroid antibodies on
pregnancy outcome following intracytoplasmatic sperm injection-ICSI and embryo transfer in women with normal thyrotropine levels. J Endocrinol Invest 2015;38:1335e43.
Sakar MN, Unal A, Atay AE, et al. Is there an effect of thyroid autoimmunity on the outcomes of assisted reproduction? J ObstetGynaecol2016;36:213e7.
Tan S, Dieterle S, Pechlavanis S, et al. Thyroid autoantibodies per se do not impair intracytoplasmic
sperm injection outcome in euthyroid healthy women. Eur J Endocrinol 2014;170:495e500.
Li W, Fan G, Chen L, Zhang R, Zhang K, Sun Y, et al. A new type of natural bispecific antibody with
potential protective effect in Hashimoto thyroiditis. J Clin Endocrinol Metabol. 2014;99:1602-9.
Huang C, Liang P, Diao L, Liu C, Chen X, Li G, et al. Thyroid autoimmunity is associated with decreased cytotoxicity
T cells in women with repeated implantation failure. Int J Environ Res Public Health. 2015;12:10352-61.
Toulis KA, Goulis DG, Venetis CA, et al. Risk of spontaneous miscarriage in euthyroid women with
thyroid autoimmunity undergoing IVF: a meta-analysis. Eur J Endocrinol 2010;162:643e52.
Negro R, Formoso G, Mangieri T, Pezzarossa A, et al. Levothyroxine treatment in euthyroid pregnant
women with autoimmune thyroid disease: Effects on obstetrical complications. J. Clin. Endocrinol. Metab.
; 91: 2587-2591.
Lee Y. L, Ng H.P, Lau et al. Increased fetal abortion rate in autoimmune thyroid disease is related to circulating
TPO autoantibodies in an autoimmune thyroiditis animal model. Fertil. Steril. 2009; 91: 2104-2109.
Kim N.Y, Cho H.J, Kim H.Y, Yang K.M, Ahn H.K, et al. Thyroid autoimmunity and its association with cellular
and humoral immunity in women with reproductive failures. Am. J. Reprod. Immunol. 2011; 65: 78-87.
Du YJ, Xin X, Cui N, Jiang L, Yang AM, Hao GM, Gao BL. Effects of controlled ovarian stimulation on
thyroid stimulating hormone in infertile women. Eur J ObstetGynecolReprod Biol. 2019 Mar;234:207-212.
Twig G, Shina A, Amital H, Shoenfeld Y, Pathogenesis of infertility and recurrent pregnancy loss in thyroid autoimmunity. J. Autoimmune. 2012; 38: J275-J281. Monteleone P, Parrini D, Faviana P, et al. Female infertility related to thyroid autoimmunity: the ovarian follicle hypothesis. Am J Reprod Immunol 2012;66:108e14.
Wu et al. Hashimoto’s thyroiditis impairs embryo implantation by compromising endometrial
morphology and receptivity markers in euthyroid mice. Reproductive Biology and Endocrinology. 2019; 17:94.
Muller A, Verhoeff A, Mantel M, et al. Decrease of free thyroxine levels after controlled ovarian hyperstimulation.J Clin Endocrinol Metab2000;85:545e8.
Poppe K, Glinoer D, Tournaye H, et al. Impact of ovarian hyperstimulation on thyroid function in women with e
and without thyroid autoimmunity. J Clin Endocrinol Metab2004;89:3808e12.
Poppe K, Glinoer D, Tournaye H, et al. Impact of the ovarian hyperstimulation syndrome on thyroid function. Thyroid 2008;18:801e2.
Practice Committee of the American Society for Reproductive Medicine. Subclinical hypothyroidism in the infertile female population: a guideline. Fertil Steril2015;104:545–553.
Alexander EK, Elizabeth N, Pearce EN, et al. Guidelines of the American thyroid association for the diagnosis
and management of thyroid disease during pregnancy and the postpartum. Thyroid 2017;27:315e89.
Negro R, Mangieri T, Coppola L, et al. Levothyroxine treatment in thyroid peroxidase antibody-positive
women undergoing assisted reproduction technologies: a prospective study. Hum Reprod2005;20:1529e33.
Wang H, Gao H, Chi H, et al. Effect of levothyroxine on miscarriage among women with normal thyroid
function and thyroid autoimmunity undergoing in vitro fertilization and embryo transfer: a randomized clinical
trial. J Am Med Assoc 2017;318:2190e8.
Dhillon-Smith RK, Middleton LJ, Sunner KK, et al. Levothyroxine in women with thyroid peroxidase
antibodies before conception. N Engl J Med 2019;380:1316e25.
Bliddal S, Feldt-Rasmussen U, Rasmussen AK, Kolte AM et al. Thyroid Peroxidase Antibodies and Prospective
Live Birth Rate: A Cohort Study of Women with Recurrent Pregnancy Loss. Thyroid. 2019;29,10:1465.
Fan Y, Xu S, Zhang H, Cao W, Wang K, Chen G, Di H, Cao M, Liu C. Selenium supplementation for autoimmune
thyroiditis: a systematic review and metaanalysis. Int J Endocrinol 2014:904573.
Karanikas G, Schuetz M, Kontur S, Duan H, Kommata S, Schoen R, Antoni A, Kletter K, Dudczak R, Willheim M.
No immunological benefit of selenium in consecutive patients with autoimmune thyroiditis. Thyroid 2008;18:7–12.
Korevaar T, Muetzel R, Medici M, et al. Association of maternal thyroid function during early pregnancy
with offspring IQ and brain morphology in childhood: a population-based prospective cohort study. Lancet diabetes Endocrinol 2016;4:35e43.
Maraka S, Mwangi R, McCoy RG, et al. Thyroid hormone treatment among pregnant women with subclinical
hypothyroidism, US national assessment. BMJ 2017,25
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