Ishodi trudnoće i karakteristike novorođenčadi kod žena sa tiroidnim autoantitlima u folikularnoj tečnosti u postupku asistirane reprodukcije

Ishodi trudnoće i novorođenčadi u asistiranoj reprodukciji

  • Sanja Medenica Odjeljenje endokrinologije, Interna klinika, Klinicki centar Crne Gore
  • Eliana Garalejic In Vitro Fertilisation Department, Clinic for Gynecology and Obstetrics "Narodni front", Belgrade, Serbia
  • Dzihan Abazovic Emergency Medicine Center of Montenegro, Podgorica, Montenegro
  • Zoran Bukumiric Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Serbia
  • Stavroula A. Paschou Endocrine Unit and Diabetes Centre, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
  • Biljana Arsic In Vitro Fertilisation Department, Clinic for Gynecology and Obstetrics "Narodni front", Belgrade, Serbia
  • Snezana Vujosevic Department of Endocrinology, Internal Medicine Clinic, Clinical Center of Montenegro, School of Medicine, University of Montenegro, Podgorica, Montenegro
  • Bijana Medjo Pediatric Intensive Care Unit, University Children’s Hospital, Belgrade, Serbia
  • Milos Zarkovic Department of Thyroid Gland Disease, Clinic of Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, Belgrade, Serbia
DOI: https://doi.org/10.5937/jomb0-35243
Ključne reči: asistirana reproduktivna tehnologija, folikularna tečnost, trudnoća, tiroidna autoimunost

Sažetak


Uvod: Povišeni nivoi tiroidnih autoantitela u folikularnoj tečnosti (FF) kod žena sa tiroidnom autoimunošću (TAI) nalaze se u snažnoj korelaciji sa nivoima istih u serumu i mogu uticati na postimplantacioni razvoj embriona. Podaci iz literature govore o značaju primene  levotiroksina (LT4) u smislu smanjenja rizika od neželjenih ishoda trudnoće. Cilj studije je bio da se proceni ishod trudnoće i karakteristike novorođenčeta žena sa tiroidnim autoantitelima u FF u postupku asistirane reprodukcije (ART).

Metode: Ispitivana populacija je uključila 24 žene sa potvrđenom kliničkom trudnoćom, 8 TAI pozitivnih i 16 TAI negativnih žena. LT4 suplementacija je primenjena kod 20,8% pacijentkinja, pozitivnih na TAI.

Rezultati: Ishodi u trudnoći bili su: stopa blizanačke trudnoće 41,7%, stopa ranih sponatnih pobačaja 8,3%, stopa kasnih sponatnih pobačaja 4,2%, stopa prevremenog porođaja 16,7%, stopa terminskog porođaja 70,8%, stopa živorođenosti 96,0%. Postojala je značajna razlika vrednostima antitela na Tg u serumu i u FF (p<0,001) između grupa shodno TAI, dok je serumski fT3 bio niži u grupi sa TAI (p=0,047). Serumski fT4 je bio viši u grupi koja je primala terapiju sa LT4 (p=0,005), sa TAI, a novorođenčad u ovoj grupi imala su veću porođajnu težinu (p=0,001) i visinu (p=0,008). Komplikacije kod majke bile su prisutne kod 23,8% pacijenata. Nisu zabeležene urođene malformacije kod novorođenčadi.

Zaključak: Tiroidna autoantitela u FF mogu da utiču na postimplantacioni razvoj embriona, ali nemaju uticaja na dalji tok trudnoće. Posebna korist terapije LT4 na uspešan ishod ART-a je pokazana za antropometrijske parametre novorođenčeta.

Reference

1.            Rao M, Zeng Z, Zhao S, Tang L. Effect of levothyroxine supplementation on pregnancy outcomes in women with subclinical hypothyroidism and thyroid autoimmuneity undergoing in vitro fertilization/intracytoplasmic sperm injection: an updated meta-analysis of randomized controlled trials. Reprod Biol Endocrinol 2018; 16: 92.


2.            Cho MK. Thyroid dysfunction and subfertility. Clin Exp Reprod Med 2015; 42: 131-5.


3.            Gracia CR, Morse CB, Chan G, Schilling S, Prewitt M, Sammel MD, et al. Thyroid function during controlled ovarian hyperstimulation as part of in vitro fertilization. Fertil Steril 2012; 97: 585–591.


4.            Poppe K, Unuane D, D'Haeseleer M, Tournaye H, Schiettecatte J, Haentjens P, et al. Thyroid function after controlled ovarian hyperstimulation in women with and without the hyperstimulation syndrome. Fertil Steril 2011; 96: 241–5.


5.            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.


6.            Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum.  Thyroid 2017; 27: 315-389.


7.            Wang H, Gao H, Chi H, Zeng L, Xiao W, Wang Y, et al. Effect oflevothyroxine on miscarriage among women with Normal thyroid functionand thyroid autoimmunity undergoing in vitro fertilization and embryotransfer: a randomized clinical trial. JAMA 2017; 318: 2190–2198.


8.            Medenica S, Garalejic E, Arsic B, Medjo B, Bojovic Jovic D, Abazovic D, et al. Follicular fluid thyroid autoantibodeis, thyrotropin, free thyroxine levels and assisted reproductive technology outcome. PLoS One 2018; 13(10): e0206652.



  1. Zhong YP, Ying Y, Wu HT, Zhou CQ, Xu YW, Wang Q, et al. Relationship between antithyroid antibody and pregnancy outcome following in vitro fertilization and embryo transfer. Int J Med Sci 2012; 9: 121-125.

  2. Pravilnik o sadrzaju i obimu prava na zdravstvenu zastitu iz obaveznog zdravstvenog osiguranja i o participaciji za 2011. godinu. Article 10, vol. 7/2011: Sluzbeni glasnik RS, 2011. [Serbian].

  3. Zarkovic M, Ciric J, Beleslin B,Ciric S,Bulat P,Topalov D,et al. Further studies on delineating thyroid-stimulating hormone (TSH) reference range. Horm Metab Res 2011; 43: 970–6.

  4. Tarín JJ, Pascual E, García-Pérez MÁ, Gómez R, Cano A. Women's morbid conditions are associated with decreased odds of live birth in the first IVF/ICSI treatment: a retrospective single-center study. J Assist Reprod Genet 2019; 36: 697-708.


13.         Busnelli A, Paffoni A, Fedele L, Somigliana E. The impact of thyroid autoimmunity on IVF/ICSI outcome: a systematic review and meta-analysis.  Hum Reprod Update 2016; 22: 775-790.


14.         Matalon ST, Blank M, Levy Y, Carp JAH, Arad A,  Burek L, et al. The pathogenic role of anti-thyroglobulin antibody on pregnancy: evidence from an active immunization model in mice. Hum Reprod. 2003; 18: 1094-9.


15.         Unuane D, Velkeniers B, Bravenboer B, Drakopoulos P, Tournaye H, Parra J, et al. Impact of thyroid autoimmunity in euthyroid women on live birth rate after IUI.  Hum Reprod 2017; 32: 915-922.


16.         Safarian GK, Gzgzyan AM, Dzhemlikhanova Lyailya K, Niauri Dariko A. Does subclinical hypothyroidism and/or thyroid autoimmunity influence the IVF/ICSI outcome? Review of the literature. Gynecol Endocrinol 2019; 35(sup1): 56-9.


17.         Aghajanova L, Lindeberg M, Carlsson IB, Stavreus-Evers A, Zhang P, Scott JE, et al Receptors for thyroid-stimulating hormone and thyroid hormones in human ovarian tissue. Reprod Biomed Online 2009; 18: 337-347.



  1. Vissenberg R, Manders VD, Mastenbroek S, Fliers E, Afink GB, Ris-Stalpers C, et al. Pathophysiological aspects of thyroid hormone disorders/thyroid peroxidase autoantibodies and reproduction. Hum Reprod Update 2015; 21: 378–387.


19.         Benhadi N, Wiersinga WM, Reitsma JB, Vrijkotte TGM, Bonsel GJ. Higher maternal TSH levels in pregnancy are associated with increased risk for miscarriage, fetal or neonatal death. Eur J Endocrinol 2009; 160: 985–991.


20.         Li J, Shen J, Qin L. Effects of Levothyroxine on Pregnancy Outcomes in Women With Thyroid Dysfunction: A Meta-analysis of Randomized Controlled Trials.  Altern Ther Health Med 2017; 23: 49-58.


21.         Thangaratinam S, Tan A, Knox E, Kilby MD, Franklyn J, Coomarasamy A. Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. BMJ 2011; 9: 342:d2616.


22.         Männistö T, Vääräsmäki M, Pouta A, Hartikainen AL, Ruokonen A,  Surcel HM,  et al. Perinatal outcome of children born to mothers with thyroid dysfunction or antibodies: a prospective population-based cohort study. J Clin Endocrinol Metab 2009; 94: 772-9.


23.         Carty DM, Doogan F, Welsh P, Dominiczak AF, Delles C. Thyroid stimulating hormone (TSH) >/=2.5mU/l in early pregnancy: Prevalence and subsequent outcomes. Eur J Obstet Gynecol Reprod Biol 2017; 210: 366–9.


24.         Medici M, Timmermans S, Visser W, de Muinck Keizer-Schrama SM, Jaddoe VW, Hofman A, et al. Maternal Thyroid Hormone Parameters During Early Pregnancy and Birth Weight: The Generation R Study. J Clin Endocrinol Metab 2013; 98: 59-66.


25.         Dong AC, Stephenson MD, Stagnaro-Green AS. The Need for Dynamic Clinical Guidelines: A Systematic Review of New Research Published After Release of the 2017 ATA Guidelines on Thyroid Disease During Pregnancy and the Postpartum. Front Endocrinol (Lausanne) 2020; 11: 193.


26.         Zhao L, Jiang G, Tian X, Zhang X, Zhu T, Chen B, et al. Initiation timing effect of levothyroxine treatment on subclinical hypothyroidismin pregnancy.Gynecol Endocrinol 2018; 34: 845–8.


27.         Poppe K, Autin C, Veltri F, Kleynen P, Grabczan L, Rozenberg S, et al. Thyroid autoimmunity and intracytoplasmic sperm injection outcome: a systematic review and meta-analysis. J Clin Endocrinol Metab 2018. doi: 10.1210/jc.2017-02633. Online ahead of print.


 


 

Objavljeno
2022/06/29
Broj časopisa
Vol. 42 Br. 1 (2023): Journal of Medical Biochemistry
Rubrika
Original paper

Sva prava zadržana (c) 2022 Sanja Medenica, Eliana Garalejic, Dzihan Abazovic, Zoran Bukumiric, Stavroula A. Paschou, Biljana Arsic, Snezana Vujosevic, Bijana Medjo, Milos Zarkovic

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