Tiroid Hastaligi/ Antikorlari IUI/YUT gebelik hizini etkiler mi? Prof Dr Onur Karabacak Gazi Univ Tip Fak AP/IVF unitesi 1

Hipotez: IVF gebelik hizi tiroid antikoru arttikca azalir. Antikor arttikca once tiroid doku yikimi olur Once tsh artar subklinik hipotiroidi denir Sonra tsh artmis iken tf4 azalir klinik hipotiroidi olur Antikor arttikca hipotiroidi riski artar, Hipotiroidide antikorlar artik cok yuksektir 2

increased risk of complications, pre-eclampsia, perinatal mortality, Indian J Endocrinol Metab. 2012 Dec;16(Suppl 2):S350-1. Recurrent pregnancy loss in patients with thyroid dysfunction. Sarkar D. increased risk of complications, pre-eclampsia, perinatal mortality, and miscarriage. thyroid function must be examined in female with preganacy loss or menstrual disturbances. 3

Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review. van den Boogaard E, Vissenberg R, Land JA, van Wely M, et al. Hum Reprod Update. 2011 Sep-Oct;17(5):605-19. Netherlands. 38 were appropriate for meta-analyses. No articles about hyperthyroidism were selected. Subclin hypothyroid in early pregnancy, vs normal thyroid, pre-eclampsia [ OR 1.7, 95% CI 1.1-2.6] increased risk of perinatal mortality (OR 2.7, 95% CI 1.6-4.7) thyroid antibodies increased risk of unexplained subfertility (OR 1.5, 95% CI 1.1-2.0), miscarriage (OR 3.73, 95% CI 1.8-7.6), recurrent miscarriage (OR 2.3, 95% CI 1.5-3.5), preterm birth (OR 1.9, 95% CI 1.1-3.5) and maternal post-partum thyroiditis (OR 11.5, 95% CI 5.6-24) when compared with the absence of thyroid antibodies. 4

Interventions for clinical and subclinical hypothyroidism in pregnancy Interventions for clinical and subclinical hypothyroidism in pregnancy. Reid SM, Middleton P, Cossich MC, Crowther CA. Cochrane Database Syst Rev. 2010 Jul 7;(7). Levothyroxine treatment of clinical hypothyroidism in pregnancy is standard practice benefits earlier non-randomised studies. Whether levothyroxine should be utilised in autoimmune and subclinical hypothyroidism for reduction in preterm birth and miscarriage. Selenomethionine as an intervention in women with thyroid autoantibodies is promising, particularly in reducing postpartum thyroiditis. There is a probable low incidence of adverse outcomes from levothyroxine and selenomethionine. High-quality evidence is lacking and large-scale randomised trials are needed. No evidence for universal screening, targeted thyroid function testing in pregnancy at risk and suppl 5

Hypothyroidism: from the desire for pregnancy to delivery Ouzounian S, Bringer-Deutsch S, Jablonski C, Théron-Gérard L, et al Gynecol Obstet Fertil. 2007 Mar;35(3):240-8. Epub 2007 Feb 23. Thyroid autoimmunity (detection of anti peroxydase antibodies) may account repetitive miscarriages. In infertility clinical hypothyroidism, personal, familial history of thyroid or other auto immune diseases (such as type I diabetes), unexplained anovulation. Detection of thyroid antibody seems @ recurrent miscarriages, benefit of thyroid supplementation. In pregnant women, adequate foetal development. Untreated maternal hypothyroidism & disturbances of brain development and low intellectual quotient. foetal (growth deficiency, premature birth, low birth weight) as well as maternal (gestational hypertension, pre-eclampsia...) problems thyroid screening should be extended to the overall pregnant population. The objective is to adjust L- thyroxin supplementation to maintain serum TSH concentrations below the threshold of 2.5 mUI/l. Finally, iodine deficiency, supplemention 6

Retrospective Gazi IVF Data Design 7

Ozellikler: Levatiron + / Cont

Levatiron alan grupta TPO belirgin daha yuksek / Grup 2 Cunki bu grup artik levatiron alacak seviyede tiroid hastasi

Infert nedeni dagilimi Calisma/ Cont

Gebelik hizi vaka genisligi 500 vakadan sonra anlamli farkli olabilir

D3 ve ET gunu Antikor seviye degisimi Ovulasyon induksiyonu levatiron alan grubun Anti T antikor seviyesini %4 p=0.3 dusurur, almiyan grubun %14 p<0.02 arttirir OI lev alan grup Anti TPO % 8 P=0.08 dusurur. Almiyan %136 p<0.0001 artar. Gruplar Anti TPO seviyesi olarak biribirine benzer hale gelirler

Anti T antikor ilaca bagimsiz, gebelige bagimlidir. Gebelik olmasi durumunda Anti T antikor levatiron almak veya almamak ile anlamsiz azalmasina ragmen gebe yok ise ilac a bagimsiz anlamsiz ARTMAKTADIR. mm,n.n Anti T antikor ilaca bagimsiz, gebelige bagimlidir.

Gebe kalimiyan grupta Anti TPO % 68 anlamlı ARTTIĞI izlenmistir ( p=0,03*) Levatiron kullanarak gebelik %16 Anti TPO yu azaltirken, ilacsiz gebe kalmama anlamli artirmaktadir

Sonuclar 1- Eve gidecek bilgi Ivf yapilan tiroid hast/ antikor yuksek hastalarin en az %50 si aciklanamiyan infertilitedir. Tiroid hastaligi nedeni ile levatiron almak PRCT anlamli cikacak gebelik hiz artisi sagliyacak gozukmektedir. IVF Ovulasyon induksiyonu Anti T/TPO yu belirgin ARTTIR. Levatiron vermek bunu durdurur, hatta dusurur. Anti T ilaca bagimsiz, gebelige bagimli azalir konumda. Anti TPO ilaca ve gebelige bagimli %16 azalirken, ikisi olamadigi konumda %68 belirgin artmaktadir.

Sonuclar 2 RCT de levatiron vermek Anti TPO yu dusurucu etkisi ile gebelik hizini arttiriyor cikacaktir. – Hipotez Aciklanamiyan infertilite, RecGb kayibi, basarisiz IVF te ozellikle TSH yaninda Anti TPO bakisi onemlidir. Bu calisma/literatur pre eklamsi vakalarinda da TSH yaninda Anti TPO bakma fayda getirebilirmi? -Hipotez Acaba Tsh 2.40, preklamtik Tansiyon Aldomet 1tb/4h, dusmuyor ise, Anti TPO da yuksek ise levatiron 25 mg eklemek tedavi edici midir?

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