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The impact of the presence of antithyroid antibodies on pregnancy outcome following intracytoplasmatic sperm injection-ICSI and embryo transfer in women with normal thyreotropine levels

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Abstract

Purpose

The aim of our study was to investigate the impact of anti-thyroid peroxidase antibodies (Anti-TPO) on pregnancy outcome following the in vitro fertilization and embryo transfer (IVF-ET) in general groups and in subgroups divided according to AMH level and age.

Methods

A total of 114 patients positive for anti-thyroid peroxidase antibodies (Anti-TPO+ group) and 495 infertile women negative for anti-thyroid peroxidase antibodies (Anti-TPO− group) undergoing IVF with ICSI from April 2010 to April 2012 were analyzed retrospectively.

Results

There were no significant differences in age, BMI, basal FSH, LH, AMH levels and duration of infertility between the two main groups. No significant differences in terms of the days of ovarian stimulation, estradiol level in day 8, total gonadotropin dose, number of oocytes retrieved, available embryos and blastocysts, number of embryos transferred nor in rates of fertilization, implantation, clinical pregnancy, live birth and abortion rate between two main groups were found. The only statistically significant difference among the groups with different anti-TPO antibodies levels was found in basal FSH concentration and BMI. Among the clinical outcomes of IVF with respect to the different anti-TPO levels, the only significant difference was found for the number of oocytes retrieved. Analysis of the baseline parameters in relationship to age categories and AMH levels found significant differences between women positive and negative for thyroid antibodies with respect to basal FSH and LH levels for women >37 years and for basal FSH in AMH <0.6 subgroup.

Conclusions

The present study reveals that patients with anti-TPO antibodies showed no significant differences in fertilization, implantation, pregnancy rates, live birth rates and no higher risk for miscarriage following IVF-ET when compared with those negative for anti-thyroid antibodies.

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References

  1. Thomas R, Reid RL (1987) Thyroid-disease and reproductive dysfunction—a review. Obstet Gynecol 70(5):789–798

    CAS  PubMed  Google Scholar 

  2. Speroff L (1999) Clinical Gynecologic Endocrinology and Infertility. 6 edn. Lippincott Williams & Wilkins,

  3. Trokoudes KM, Skordis N, Picolos MK (2006) Infertility and thyroid disorders. Curr Opin Obstet Gynecol 18(4):446–451. doi:10.1097/01.gco.0000233941.89919.31

    Article  PubMed  Google Scholar 

  4. Poppe K, Velkeniers B, Glinoer D (2007) Thyroid disease and female reproduction. Clin Endocrinol 66(3):309–321. doi:10.1111/j.1365-2265.2007.02752.x

    Article  CAS  Google Scholar 

  5. Swain M, Swain T, Mohanty BK (2005) Autoimmune thyroid disorders-An update. Indian J Clin Biochem IJCB 20(1):9–17. doi:10.1007/bf02893034

    Article  CAS  PubMed  Google Scholar 

  6. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC (2000) The Colorado thyroid disease prevalence study. Arch Intern Med 160(4):526–534. doi:10.1001/archinte.160.4.526

    Article  CAS  PubMed  Google Scholar 

  7. Ghazeeri GS, Kutteh WH (2001) Autoimmune factors in reproductive failure. Curr Opin Obstet Gynecol 13(3):287–291. doi:10.1097/00001703-200106000-00007

    Article  CAS  PubMed  Google Scholar 

  8. Kotani T (1998) Anti-TPO autoantibodies. Rinsho byori The Japanese journal of clinical pathology 46(4):324–330

    CAS  PubMed  Google Scholar 

  9. Abalovich M, Mitelberg L, Allami C, Gutierrez S, Alcaraz G, Otero P, Levalle O (2007) Subclinical hypothyroidism and thyroid autoimmunity in women with infertility. Gynecol Endocrinol 23(5):279–283. doi:10.1080/09513590701259542

    Article  CAS  PubMed  Google Scholar 

  10. Marcocci C, Chiovato L (2000) The Thyroid: Afundamental and clinical text. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  11. Ghoraishian SM, Hekmati Moghaddam SH, Afkhami-Ardekani M (2006) Relationship between Anti-Thyroid Peroxidase Antibody and Thyroid Function Test. Iranian J Immunol 3(3):146–149. doi:IJIv3i3A8

  12. Gleicher N, Elroeiy A, Confino E, Friberg J (1989) Reproductive failure because of autoantibodies—unexplained infertility and pregnancy wastage. Am J Obstet Gynecol 160(6):1376–1385

    Article  CAS  PubMed  Google Scholar 

  13. Unuane D, Poppe K (2015) Female infertility: do we forget the thyroid? J Endocrinol Invest 38(5):571–574. doi:10.1007/s40618-015-0280-0

    Article  CAS  PubMed  Google Scholar 

  14. Revelli A, Casano S, Delle Piane L, Grassi G, Gennarelli G, Guidetti D, Massobrio M (2009) 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. doi:10.1186/1477-7827-7-137

    Google Scholar 

  15. Abbassi-Ghanavati M, Casey BM, Spong CY, McIntire DD, Halvorson LM, Cunningham FG (2010) Pregnancy Outcomes in Women With Thyroid Peroxidase Antibodies. Obstet Gynecol 116(2):381–386. doi:10.1097/AOG.0b013e3181e904e5

    Article  PubMed  Google Scholar 

  16. Bussen S, Steck T, Dietl J (2000) Increased prevalence of thyroid antibodies in euthyroid women with a history of recurrent in vitro fertilization failure. Hum Reprod 15(3):545–548. doi:10.1093/humrep/15.3.545

    Article  CAS  PubMed  Google Scholar 

  17. Muller AF, Verhoeff A, Mantel MJ, Berghout A (1999) Thyroid autoimmunity and abortion: a prospective study in women undergoing in vitro fertilization. Fertil Steril 71(1):30–34. doi:10.1016/s0015-0282(98)00394-x

    Article  CAS  PubMed  Google Scholar 

  18. Kutteh WH, Yetman DL, Carr AC, Beck LA, Scott RT (1999) Increased prevalence of antithyroid antibodies identified in women with recurrent pregnancy loss but not in women undergoing assisted reproduction. Fertil Steril 71(5):843–848. doi:10.1016/s0015-0282(99)00091-6

    Article  CAS  PubMed  Google Scholar 

  19. Monteleone P, Parrini D, Faviana P, Carletti E, Casarosa E, Uccelli A, Cela V, Genazzani AR, Artini PG (2011) Female infertility related to thyroid autoimmunity: the ovarian follicle hypothesis. Am J Reprod Immunol 66(2):108–114. doi:10.1111/j.1600-0897.2010.00961.x

    Article  CAS  PubMed  Google Scholar 

  20. De Groot L, Abalovich M, Alexander EK, Amino N, Barbour L, Cobin RH, Eastman CJ, Lazarus JH, Luton D, Mandel SJ, Mestman J, Rovet J, Sullivan S (2012) Management of thyroid dysfunction during pregnancy and postpartum: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 97(8):2543–2565. doi:10.1210/jc.2011-2803

    Article  PubMed  Google Scholar 

  21. Benaglia L, Busnelli A, Somigliana E, Leonardi M, Vannucchi G, De Leo S, Fugazzola L, Ragni G, Fedele L (2014) Incidence of elevation of serum thyroid-stimulating hormone during controlled ovarian hyperstimulation for in vitro fertilization. Eur J Obstet Gynecol Reprod Biol 173:53–57. doi:10.1016/j.ejogrb.2013.11.003

    Article  CAS  PubMed  Google Scholar 

  22. Busnelli A, Somigliana E, Benaglia L, Sarais V, Ragni G, Fedele L (2014) Thyroid axis dysregulation during in vitro fertilization in hypothyroid-treated patients. Thyroid 24(11):1650–1655. doi:10.1089/thy.2014.0088

    Article  CAS  PubMed  Google Scholar 

  23. La Marca A, Nelson SM, Sighinolfi G, Manno M, Baraldi E, Roli L, Xella S, Marsella T, Tagliasacchi D, D’Amico R, Volpe A (2011) Anti-Mullerian hormone-based prediction model for a live birth in assisted reproduction. Reproductive Biomed Online 22(4):341–349. doi:10.1016/j.rbmo.2010.11.005

    Article  Google Scholar 

  24. Lukaszuk K, Liss J, Lukaszuk M, Maj B (2005) Optimization of estradiol supplementation during the luteal phase improves the pregnancy rate in women undergoing in vitro fertilization-embryo transfer cycles. Fertil Steril 83(5):1372–1376. doi:10.1016/j.fertnstert.2004.11.055

    Article  CAS  PubMed  Google Scholar 

  25. Practice Committee SfARTatASfRM (2004) Guidelines on the number of embryos transferred. Fertil Steril 82(3):773–774

    Article  Google Scholar 

  26. Cappelli C, Rotondi M, Pirola I, Agosti B, Formenti A, Zarra E, Valentini U, Leporati P, Chiovato L, Castellano M (2012) Thyreotropin levels in diabetic patients on metformin treatment. Eur J Endocrinol 167(2):261–265. doi:10.1530/eje-12-0225

    CAS  PubMed  Google Scholar 

  27. Busnelli A, Somigliana E, Benaglia L, Leonardi M, Ragni G, Fedele L (2013) In vitro fertilization outcomes in treated hypothyroidism. Thyroid 23(10):1319–1325. doi:10.1089/thy.2013.0044

    Article  CAS  PubMed  Google Scholar 

  28. Weghofer A, Himaya E, Kushnir VA, Barad DH, Gleicher N (2015) The impact of thyroid function and thyroid autoimmunity on embryo quality in women with low functional ovarian reserve: a case-control study. Reprod Biol Endocrinol. doi:10.1186/s12958-015-0041-0

    Google Scholar 

  29. Reh A, Chaudhry S, Mendelsohn F, Im S, Rolnitzky L, Amarosa A, Levitz M, Srinivasa S, Krey L, Berkeley AS, Grifo JA, Danoff A (2011) Effect of autoimmune thyroid disease in older euthyroid infertile woman during the first 35 days of an IVF cycle. Fertil Steril 95(3):1178–1181. doi:10.1016/j.fertnstert.2010.09.053

    Article  PubMed Central  PubMed  Google Scholar 

  30. Velkeniers B, Van Meerhaeghe A, Poppe K, Unuane D, Tournaye H, Haentjens P (2013) Levothyroxine treatment and pregnancy outcome in women with subclinical hypothyroidism undergoing assisted reproduction technologies: systematic review and meta-analysis of RCTs. Human Reprod Update 19(3):251–258. doi:10.1093/humupd/dms052

    Article  CAS  Google Scholar 

  31. Hasegawa I, Yamanoto Y, Suzuki M, Murakawa H, Kurabayashi T, Takakuwa K, Tanaka K (1998) Prednisolone plus low-dose aspirin improves the implantation rate in women with autoimmune conditions who are undergoing in vitro fertilization. Fertil Steril 70(6):1044–1048. doi:10.1016/s0015-0282(98)00343-4

    Article  CAS  PubMed  Google Scholar 

  32. Negro R, Mestman JH (2011) Thyroid disease in pregnancy. Best Pract Res Clin Endocrinol Metab 25(6):927–943. doi:10.1016/j.beem.2011.07.010

    Article  CAS  PubMed  Google Scholar 

  33. Y-p Zhong, Ying Y, H-t Wu, Zhou C-q Xu, Y-w Wang Q, Li J, X-t Shen, Li J (2012) Relationship between antithyroid antibody and pregnancy outcome following in vitro fertilization and embryo transfer. Int J Med Sci 9(2):121–125. doi:10.7150/ijms.3467

    Article  Google Scholar 

  34. Kim CH, Chae HD, Kang BM, Chang YS (1998) Influence of antithyroid antibodies in euthyroid women on in vitro fertilization-embryo transfer outcome. Am J Reprod Immunol 40(1):2–8

    Article  CAS  PubMed  Google Scholar 

  35. Toulis KA, Goulis DG, Venetis CA, Kolibianakis EM, Negro R, Tarlatzis BC, Papadimas I (2010) Risk of spontaneous miscarriage in euthyroid women with thyroid autoimmunity undergoing IVF: a meta-analysis. Eur J Endocrinol 162(4):643–652. doi:10.1530/eje-09-0850

    Article  CAS  PubMed  Google Scholar 

  36. Stagnarogreen A, Roman SH, Cobin RH, Elharazy E, Alvarezmarfany M, Davies TF (1990) Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies. JAMA 264(11):1422–1425. doi:10.1001/jama.264.11.1422

    Article  CAS  Google Scholar 

  37. Glinoer D, Soto MF, Bourdoux P, Lejeune B, Delange F, Lemone M, Kinthaert J, Robijn C, Grun JP, Denayer P (1991) Pregnancy in patients with mild thyroid abnormalities—maternal and neonatal repercussions. J Clin Endocrinol Metab 73(2):421–427

    Article  CAS  PubMed  Google Scholar 

  38. Tan S, Dieterle S, Pechlavanis S, Janssen OE, Fuhrer D (2014) Thyroid autoantibodies per se do not impair intracytoplasmic sperm injection outcome in euthyroid healthy women. Eur J Endocrinol 170(4):495–500. doi:10.1530/eje-13-0790

    Article  CAS  PubMed  Google Scholar 

  39. van den Boogaard E, Vissenberg R, Land JA, van Wely M, van der Post JAM, Goddijn M, Bisschop PH (2011) Significance of (sub) clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review. Human Reprod Update 17(5):605–619. doi:10.1093/humupd/dmr024

    Article  Google Scholar 

  40. Karacan M, Alwaeely F, Cebi Z, Berberoglugil M, Batukan M, Ulug M, Arvas A, Camlibel T (2013) Effect of antithyroid antibodies on ICSI outcome in antiphospholipid antibody-negative euthyroid women. Reprod Biomed Online 27(4):376–380. doi:10.1016/j.rbmo.2013.07.002

    Article  CAS  PubMed  Google Scholar 

  41. Mintziori G, Goulis DG, Gialamas E, Dosopoulos K, Zouzoulas D, Gitas G, Venetis CA, Toulis KA, Kolibianakis EM, Tarlatzis BC (2014) Association of TSH concentrations and thyroid autoimmunity with ivf outcome in women with tsh concentrations within normal adult range. Gynecol Obstet Invest 77(2):84–88. doi:10.1159/000357193

    Article  CAS  PubMed  Google Scholar 

  42. Polyzos NP, Sakkas E, Vaiarelli A, Poppe K, Camus M, Tournaye H (2015) Thyroid autoimmunity, hypothyroidism and ovarian reserve: a cross-sectional study of 5000 women based on age-specific AMH values. Human reproduction (Oxford, England) 30(7):1690–1696. doi:10.1093/humrep/dev089

    Article  Google Scholar 

  43. Unuane D, Velkeniers B, Anckaert E, Schiettecatte J, Tournaye H, Haentjens P, Poppe K (2013) Thyroglobulin autoantibodies: is there any added value in the detection of thyroid autoimmunity in women consulting for fertility treatment? Thyroid 23(8):1022–1028. doi:10.1089/thy.2012.0562

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Fumarola A, Grani G, Romanzi D, Del Sordo M, Bianchini M, Aragona A, Tranquilli D, Aragona C (2013) Thyroid function in infertile patients undergoing assisted reproduction. Am J Reprod Immunol 70(4):336–341. doi:10.1111/aji.12113

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors wish to thank the laboratory staff of Invicta Fertility Centre for the technical support in blood collecting and hormonal analyses. We wish to thank Mrs. A. Knight for native-speaker language editing.

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    Authors and Affiliations

    1. Department of Obstetrics and Gynecological Nursing, Faculty of Health Sciences, Medical University of Gdańsk, Gdańsk, Poland

      K. Łukaszuk, P. Kulwikowska & E. Pastuszek

    2. INVICTA Fertility and Reproductive Center, Gdańsk, Poland

      K. Łukaszuk, J. Liss & E. Pastuszek

    3. INVICTA Fertility and Reproductive Center, Invicta Złota 6 Str, 00019, Warsaw, Poland

      K. Łukaszuk & M. Kunicki

    4. Department of Chemical and Process Engineering Chemical Faculty, Gdansk University of Technology, Gdańsk, Poland

      M. Jaszczołt

    5. Department of Gynecological Endocrinology, Poznan Univeristy of Medcial Sciences, Poznan, Poland

      B. Męczekalski

    6. Institute of Computer Science, Faculty of Mathematics, Physics and Informatics, University of Gdansk, Gdańsk, Poland

      K. Skowroński

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    1. K. Łukaszuk
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    Correspondence to M. Kunicki.

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    All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards

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    K. Łukaszuk and M. Kunicki contributed equally to this work.

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    Łukaszuk, 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 thyreotropine levels. J Endocrinol Invest 38, 1335–1343 (2015). https://doi.org/10.1007/s40618-015-0377-5

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