Background Thyroid autoimmunity (TAI) has been demonstrated to be associated with adverse pregnancy including recurrent miscarriage, unexplained infertility, and implantation failure. To settle with the fertility problem, prescribing aspirin combined with prednisone (P + A) to women positive for anti-thyroid antibodies is frequent in clinical practice, but the underlying effect remains controversial. Methods A multicenter, retrospective study was conducted in three reproductive centers from 2017 to 2020. A total of 494 euthyroid infertile women were recruited who were positive for anti-thyroperoxidase and/or thyroglobulin antibodies (TPOAb and TgAb, respectively) with thyroid-stimulating hormone (TSH) levels ranging 0.35-4.0mIU/L and underwent their first in vitro fertilization and embryo transfer (IVF-ET) cycle. Ultimately, 346 women were included of which 150 women were treated with prednisone (10 mg/d) and aspirin (100 mg/d). The remaining 196 women were untreated (control group). Treatment started on the day of embryo transfer and continued until clinical pregnancy was determined. Results The clinical pregnancy rate was 57.5% vs. 63.5% in the control and treated groups (P = 0.414) for first fresh embryo transfer cycles and 57.8% vs. 61.8% for frozen-thawed embryo transfer cycles (P = 0.606). In addition, the live birth rate for the fresh embryo transfer was 49.6% vs. 47.3% in the control and treated groups (P = 0.762). Logistic regression revealed that aspirin plus prednisone did not improve the clinical pregnancy rate or miscarriage rate. Furthermore, it was observed that low free triiodothyronine (FT3) was associated with high miscarriage rates. Conclusions Utilizing an adjuvant treatment of P + A after the embryo transfer may not be necessary in euthyroid women with thyroid autoimmunity undergoing their first IVF-ET, regardless of the embryo type (fresh or frozen).

ObjectiveAutoimmune thyroid disease (AITD) is known to be associated with unexplained infertility in women. Although the presence of antithyroid antibodies have been speculated to be a marker of an immune imbalance that might lead to implantation failure, its underlying mechanism influencing the endometrial receptivity remains to be elucidated. In this study, we used single-cell RNA sequencing (scRNA-seq) to dissect immune microenvironment in endometrium of AITD patients during window of implantation (WOI).MethodsWe collected CD45+ immune cell populations of endometrium samples of unexplained infertile women with AITD (n=3), as well as samples of AITD- controls (n=3). The cells were then processed with 10X Genomics Chromium for further analysis.ResultsWe characterized 28 distinct immune cell subtypes totally, and uncovered differences in the composition and gene expression patterns between AITD patients and controls. The proportions of T CD4+, cNK, ILC3, T CD8+GZMK+, T CD8+ Cytotoxic and ILC3 CD3E- cells were increased, and CD366+ uNK1 was decreased in AITD+ patients. And the abnormal expression of GNLY and chemokines was observed in AITD patients. In addition, uNK and T CD8+ Cytotoxic cells showed lower cytotoxicity but activation of immune response. Genes enriched in cell adhesion of ILC3 and Tregs were downregulated, while the number of ILC3 and Tregs were increased.ConclusionImmune imbalance exists in endometrium during WOI, which may impact embryo implantation.

Objective Thyroid autoimmunity (TAI) per se has been demonstrated to be related to adverse pregnancy outcomes, including recurrent miscarriage and unexplained infertility. Although therapy of glucocorticoid to infertile remains controversial, aspirin combined with prednisone(P + A) are used frequently in antithyroid antibodies (ATA) positive infertile women in clinical practice. Methods A multicenter retrospective study was performed in the Second Affiliated Hospital of Zhejiang University School of Medicine, Ningbo Women and Children's Hospital and People's Hospital of Jinhua. We recruited 494 euthyroid infertile women positive for anti-thyroperoxidase antibody (TPOAb) and/or thyroglobulin antibody (TgAb) with thyroid stimulating hormone 0.35-4.0mIU/L, who undergoing first in vitro fertilization and embryo transfer (IVF-ET) cycle during the period of 2017 to 2020. 346 women were ultimately recruited, including 187 patients receiving fresh embryo transfer and 159 patients receiving frozen-thawed embryo transfer. Among them, infertile 150 women were treated with prednisone(10mg/d) and aspirin(100mg/d), while the other 196 infertile women were untreated as control group. The treatment commenced on the day of embryo transfer and continued until the clinical pregnancy was determined by ultrasonography around 30 days after embryo transfer. Results Clinical pregnancy rate (CPR) of the first fresh embryo transfer cycle was 57.5% vs. 63.5% in control vs. in treated group (P = 0.414) and CPR was 57.8% versus 61.8% in the two groups in the frozen-thawed embryo transfer cycle(P = 0.606). Additionally, the prevalence of delivering a live birth at the fresh embryo transfer was 49.6% in the non-treatment group and 47.3% in the P + A treated group(P = 0.762). Cumulative CPR was similar in the groups at the fresh embryo transfer (control vs treated group: 56.9% vs 61.0%, P = 0.534). By conducting logistic regression, combined treatment of P + A appeared to have no influence on CPR or miscarriage rates (MR) at the first embryo transfer. Furthermore, the low but within the reference level of free triiodothyronine (FT3) was seen as a poor predictor of spontaneous abortion at the fresh embryo transfer. Conclusions To conclude, with regard to euthyroid women with TAI undergoing the first IVF-ET cycle, adjuvant treatment of P + A after the embryo transfer may be unnecessary irrespective of the fresh or frozen-thawed embryo transfer.

Background: Some women at reproductive age have positive antithyroid antibodies (ATAs). ATA includes thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). Women with ATAs, no matter with or without thyroid dysfunction, they have a higher risk of adverse reproductive outcomes, such as infertility, miscarriage and preterm birth.Methods: This study aimed to evaluate the impact of ATAs on maturation of women reproductive system and pregnancy outcomes. And it’s a prospective study, performed in three independent centers from January 2019 to June 2020. Women were tested for TSH, free T3, free T4, total T3, total T4, TPOAb and/or TgAb. They were divided into four groups: TPOAb+TgAb+, TPOAb+TgAb-, TPOAb-TgAb+ and TPOAb-TgAb-. Descriptive statistics were obtained for all the parameters. Mean and standard deviation were used for all quantitative parameters. The continuous variables that were nonnormally distributed were compared using the Kruskal-Wallis test. The χ2 test or Fisher exact test was used to compare categorical variables.Results: A total of 3457 women undergoing TPOAb and/or TgAb testing were enrolled in this study. 13.77% and 16.85% women were positive for TPOAb and TgAb, respectively. TgAb positivity had a strong correlation with TPOAb (F=1160.568, P＜0.001). ATAs had no effect on age of menarche and menstrual cycle. Some obstetric complications occurred in both positive subjects, but TPOAb, TgAb and TSH alone or in combination cannot predict the presence of complications during pregnancy. Administration of L-T4 to pregnant women with TSH 2.5-4.94mIU/ml may reduce the risk of PROM in ATA- women. Of the women with one or two ATAs, there were no significant differences between LT4 therapy group and untreated group in other pregnancy outcomes.Conclusion: TPOAb or TgAb is probably not the main reason for poor pregnancy outcomes.

Background Thyroid autoimmunity (TAI) has been associated with adverse pregnancy outcomes. To settle with fertility problem, prescribing aspirin combined with prednisone (P+A) to women positive for antithyroid antibodies (ATA) is frequent in clinical practice, but the real effect remains controversial. Methods A multicenter, retrospective study was conducted in three reproductive centers from 2017 to 2020. We recruited 494 euthyroid infertile women positive for anti-thyroperoxidase and/or thyroglobulin antibodies (TPOAb and TgAb, respectively) with thyroid stimulating hormone (TSH) levels ranging 0.35-4.0mIU/L who were undergoing their first in vitro fertilization and embryo transfer (IVF-ET) cycle. Ultimately, 346 women were included of which 150 women were treated with prednisone (10mg/d) and aspirin (100mg/d), while the remaining 196 women were untreated (control group). Treatment started on the day of embryo transfer and continued until clinical pregnancy was determined. Results Clinical pregnancy rate (CPR) was 57.5% vs. 63.5% in the control and treated groups (P=0.414) for first fresh embryo transfer cycles and 57.8% vs. 61.8% for frozen-thawed embryo transfer cycles (P=0.606). Additionally, the live birth rate (LBR) at the fresh embryo transfer was 49.6% vs. 47.3% in the control and treated groups (P=0.762). Logistic regression revealed that P+A did not improve CPR or miscarriage rates (MR). Furthermore, we observed that low free triiodothyronine (FT3) was associated with high MR. Conclusions Utilizing an adjuvant treatment of P+A after the embryo transfer may be unnecessary in euthyroid women with TAI undergoing their first IVF-ET, regardless of embryo type (fresh or frozen).