Tiroid Hastaligi / Antikorlari IUI/YUT gebelik hizini etkiler mi?

1. TiroidHastaligi/ Antikorlari IUI/YUT gebelikhizinietkiler mi? • Prof DrOnurKarabacak • GaziUniv Tip Fak AP/IVF unitesi 1

2. 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

3. 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

4. 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

5. 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

6. Hypothyroidism: from the desire for pregnancy to deliveryOuzounian S, Bringer-Deutsch S, Jablonski C, Théron-Gérard L, et alGynecol 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

7. Retrospective Gazi IVF Data Design 7

8. Ozellikler: Levatiron + / Cont

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

10. Infert nedeni dagilimi Calisma/ Cont

11. Gebelik hizi vaka genisligi 500 vakadan sonra anlamli farkli olabilir

12. 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

13. 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.

14. 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

15. 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.

16. 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?

17. Tesekkurler