Embryo Transfer Strategies for Women with Recurrent Implantation Failure During the Frozen-thawed Embryo Transfer Cycles: Sequential Embryo Transfer or Double-blastocyst Transfer?

OBJECTIVE: Both sequential embryo transfer (SeET) and double-blastocyst transfer (DBT) can serve as embryo transfer strategies for women with recurrent implantation failure (RIF). This study aims to compare the effects of SeET and DBT on pregnancy outcomes. METHODS: Totally, 261 frozen-thawed embryo transfer cycles of 243 RIF women were included in this multicenter retrospective analysis. According to different embryo quality and transfer strategies, they were divided into four groups: group A, good-quality SeET (GQ-SeET, n=38 cycles); group B, poor-quality or mixed-quality SeET (PQ/MQ-SeET, n=31 cycles); group C, good-quality DBT (GQ-DBT, n=121 cycles); and group D, poor-quality or mixed-quality DBT (PQ/MQ-DBT, n=71 cycles). The main outcome, clinical pregnancy rate, was compared, and the generalized estimating equation (GEE) model was used to correct potential confounders that might impact pregnancy outcomes. RESULTS: GQ-DBT achieved a significantly higher clinical pregnancy rate (aOR 2.588, 95% CI 1.267-5.284, P=0.009) and live birth rate (aOR 3.082, 95% CI 1.482-6.412, P=0.003) than PQ/MQ-DBT. Similarly, the clinical pregnancy rate was significantly higher in GQ-SeET than in PQ/MQ-SeET (aOR 4.047, 95% CI 1.218-13.450, P=0.023). The pregnancy outcomes of GQ-SeET were not significantly different from those of GQ-DBT, and the same results were found between PQ/MQ-SeET and PQ/MQ-DBT. CONCLUSION: SeET relative to DBT did not seem to improve pregnancy outcomes for RIF patients if the embryo quality was comparable between the two groups. Better clinical pregnancy outcomes could be obtained by transferring good-quality embryos, no matter whether in SeET or DBT. Embryo quality plays a more important role in pregnancy outcomes for RIF patients.

Autoimmune thyroid disease disrupts immune homeostasis in the endometrium of unexplained infertility women-a single-cell RNA transcriptome study during the implantation window.

Objective: Autoimmune 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). Methods: We 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. Results: We 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. Conclusion: Immune imbalance exists in endometrium during WOI, which may impact embryo implantation.

IVF/ICSI outcomes of euthyroid infertile women with thyroid autoimmunity: does treatment with aspirin plus prednisone matter?

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).