The relationship between thyroid autoimmunity and poor response to ovarian stimulation in in vitro fertilization women with infertility

Introduction: Thyroid autoimmunity (TAI) is the most common autoimmune disorder. Patients with TAI are usually euthyroid, and the presence of anti-thyroid peroxidase (anti-TPO) in patients with or without thyroid dysfunction is associated with infertility, recurrent embryo implantation failure, and early pregnancy loss. We aimed to investigate the relationship between low ovarian reserve, pregnancy outcomes, and TAI. Material and methods: This retrospective cohort study was conducted in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) patients between 2010 and 2018. All patients (n = 1400) for whom thyroid autoantibody testing was requested were detected. A study group was formed from patients with anti-TPO positivity (n = 363). The control group (n = 555) comprised euthyroid anti-TPO negative patients matched to the study group regarding age and body mass index (BMI). Results: Mean serum TSH value was 2.35 ± 1.70 mIU/mL in anti-TPO-positive patients and 1.81 ± 1.2 mIU/mL in controls, and the difference was significant (p < 0.05). Total dose of gonadotropins used in ovulation induction in anti-TPO-positive and control patients were 3000 IU and 2700 IU, respectively, and the difference was statistically significant (p < 0.05). The number of metaphase 2 oocytes was significantly lower in the anti-TPO-positive group (p < 0.05). Embryo transfer number and embryo grade were significantly lower in the anti-TPO-positive group (p < 0.01). Poor ovarian response was significantly higher in anti-TPO-positive patients (40%) as compared to anti-TPO-negative controls (30%) (p < 0.01). Clinical pregnancy rate was significantly lower in the anti-TPO-positive group (29.2%), as compared to the antibody-negative group (38.4%) (p < 0.01). Conclusions: There are controversial data regarding the impact of antithyroid antibodies on ovarian reserve and pregnancy outcome after IVF treatment. The results of this study indicate that there was a relationship between TAI and poor ovarian response, and that TAI adversely affects IVF outcomes. Further investigations are required to explore the mechanism behind these effects

Investigation of patterns of t helper-1, t helper-2 and t helper-17 associated cytokines in pregnant patients with hashimoto thyroiditis

Giriş ve Amaç: Otoimmün Tiroid Hastalıkları doğurganlık çağındaki kadınlarda sık görülmektedir. Tiroid antikor pozitifliğinin ve hipotiroidinin; tekrarlayan gebelik kayıpları ve infertilite ile ilişkisi gösterilmiştir. Tiroid otoimmünitesi olan olgularda T helper -1 (Th1) ve T helper-2 (Th2) arasındaki dengenin Th1 lehine bozulduğu ve aktive T lenfositlerin uterusta başarılı gebeliği engellediği düşünülmektedir. Bu çalışmadaki amaçlarımız da Hashimoto Tiroiditi (HT) olan gebelerde Th1/Th2 ve Th17 ile ilişkili sitokin düzeylerinin sağlıklı gebelerden farklı olup olmadığını incelemek, gebelik seyrinin bu sitokin düzeylerine etkisini değerlendirmek ve L-Tiroksin (LT4) tedavisinin bu seyire katkısı olup olmadığını araştırmaktır. Ayrıca bu sitokin düzeylerini infertil HT olan olgularda da inceleyerek infertilite patogenezinde tiroid otoimmünitesinin rolü olup olmadığını araştırmaktır. Gereç ve Yöntem: Çalışmaya gebeliğin başında HT tanısı alan ve LT4 tedavisi almayan 20 gebe, gebelikten önce bilinen HT olan 15 gebe ve kontrol grubu olarak , bilinen otoimmün tiroid hastalığı olmayan 19 gebe dahil edildi. Gebe olguların ilk ve ikinci trimestirde tiroid fonksiyon testleri, tiroid otoantikor düzeyleri, Th1/Th2 ve Th17 ile ilişkili sitokin düzeyleri ölçüldü tiroid ultrasonografileri yapıldı. Çalışmaya ayrıca HT olan infertilite nedeni açıklanamayan 21 kadın ve HT olan fertil 18 olgu alınmıştır. Bu olguların tiroid fonksiyon testleri, tiroid otoantikor düzeyleri, Th1/Th2 ve Th17 ile ilişkili sitokin düzeyleri ölçüldü ve tiroid ultrasonografileri yapıldı. Bulgular: HT tanısını ilk trimestirde alan gebelerde Th1 ilişkili sitokin olan IL-2 düzeyi kontrol grubundan anlamlı yüksek bulundu [7,29 (0,88-24,05) e karşılık 2,07 (0-9,19), p<0,05]. Bu grupta benzer şekilde Th17 ile ilişkili sitokin olan IL-17 düzeyi kontrol grubundan anlamlı yüksek bulundu [ 4,53 (0,94-8,19) e karşılık 1,79 (0,84-5,75), p<0,05]. Gruplar arasında ilk trimestirde Th2 ile ilişkili sitokin olan IL-4 ve IL-10 düzeyleri açısından anlamlı farklılık saptanmadı. İkinci tirmestirde ölçülen Th1, Th2 ve Th17 ile ilişkili sitokin düzeyleri açısından anlamlı fark bulunmadı. HT i olan infertil ve fertil olgular arasında Th1, Th2 ve Th17 ile ilişkili sitokin düzeyleri açısından anlamlı fark bulunmadı. Sonuç: HT I olan gebelerde Th1 ve Th17 ile ilişkili sitokin düzeyleri ilk trimestirde kontrol grubuna göre yüksekken ikinci trimestirde kontrol grubu ile fark göstermemiştir. Bu patolojik artışın ikinci trimestirde düzelmesi LT4 tedavisinin olumlu katkısı sonucu olmuş olabilir. HT i olan infertil ve fertil olgular arasında Th1, Th2 ve Th17 ile ilişkili sitokin düzeyleri açısından anlamlı fark bulunmamış olması açıklanamayan infertilitenin patogenezinde immün sistem dengesizliği dışında başka nedenlerin rol oynayabileceğini düşündürmektedir.Introduction: Thyroid autoimmunity is common in women during the reproductive years of their lives. There is a relationship between thyroid autommunity and recurrent pregnancy loss and infertility. In pregnant patients with thyroid autoimmunity T helper-1 (Th1)/T helper-2 (Th2) ratio may shift to Th1 type response and these activated T lymphocytes may lead to implantation failure. Aims of this study are to investigate Th1, Th2 and T helper-17 (Th17) associated cytokines such as IL-2, IL-4, IL-6, IL-10, IL-12 and IL-17 in pregnant patients with Hashimoto Thyroiditis (HT), to evaluate the changes of this cytokines with L-thyroxin (LT4) treatment in pregnant state. We also examine these cytokines in patients with infertility and HT to investigate the possible role of thyroid autoimmunity in infertility. Material and method: Twenty pregnant women whom HT was diagnosed in first timester of pregnancy and were not on LT4 treatment, fifteen pregnant women whom HT was known before pregancy and were on LT4 treatmet already and nineteen pregnant patients without thyroid autoimmunity were included in this study. Thyroid funciton tests, thyroid autoantibodies and cytokine levels of pregnant patients were measured at first and second trimester. Twenty one women with HT and infertility of unknown etiology and eighteen fertile women with HT were also included in this study. Thyroid funciton tests, thyroid autoantibodies and cytokine levels of this patients were measured. Serum-free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), autoantibodies against thyroid peroxidase (anti-TPO), autoantibodies against thyroglobulin (anti-Tg) levels were measured using a chemiluminecent, immunometric method, and cytokine levels were measured using ELISA. Results: In pregnant patients, whom was diagnosed HT in first trimester of pregnacy,serum IL-2 level was significantly higher than control group. [7,29 (0,88-24,05) vs 2,07 (0-9,19), p<0,05]. In this group, serum IL-17 was significantly higher than control group [4,53 (0,94-8,19) vs 1,79 (0,84-5,75), p<0,05]. There was no significant difference between groups for serum IL-4 and IL-10 levels. In second trimester no significant difference was found between groups for all cytokines measured. There was no significant difference between infertile and fertile patients with HT for all cytokines measured. Conclusion: In first trimester we found a significant difference for Th1 and Th17 associated cytokines between HT and control group. There was no difference between groups for these cytokines in second trimester. This action, which correlates with a reduction in thyroid peroxidase antibody titers, may be associated with clinical benefits of LT4 treatment

Subacute THYROiditis Related to SARS-CoV-2 VAccine and Covid-19 (THYROVAC Study): A Multicenter Nationwide Study.

Context The aims of the study are to compare characteristics of subacute thyroiditis (SAT) related to different etiologies, and to identify predictors of recurrence of SAT and incident hypothyroidism. Methods This nationwide, multicenter, retrospective cohort study included 53 endocrinology centers in Turkey. The study participants were divided into either COVID-19-related SAT (Cov-SAT), SARS-CoV-2 vaccine-related SAT (Vac-SAT), or control SAT (Cont-SAT) groups. Results Of the 811 patients, 258 (31.8%) were included in the Vac-SAT group, 98 (12.1%) in the Cov-SAT group, and 455 (56.1%) in the Cont-SAT group. No difference was found between the groups with regard to laboratory and imaging findings. SAT etiology was not an independent predictor of recurrence or hypothyroidism. In the entire cohort, steroid therapy requirement and younger age were statistically significant predictors for SAT recurrence. C-reactive protein measured during SAT onset, female sex, absence of antithyroid peroxidase (TPO) positivity, and absence of steroid therapy were statistically significant predictors of incident (early) hypothyroidism, irrespective of SAT etiology. On the other hand, probable predictors of established hypothyroidism differed from that of incident hypothyroidism. Conclusion Since there is no difference in terms of follow-up parameters and outcomes, COVID-19- and SARS-CoV-2 vaccine-related SAT can be treated and followed up like classic SATs. Recurrence was determined by younger age and steroid therapy requirement. Steroid therapy independently predicts incident hypothyroidism that may sometimes be transient in overall SAT and is also associated with a lower risk of established hypothyroidism