Immunoregulatory Therapy Improves Reproductive Outcomes in Elevated Th1/Th2 Women with Embryo Transfer Failure

Abstract

Objective. Immunological disturbance is one of the crucial factors of implantation failure. Limited data exists evaluating immunoregulatory therapy in patients with implantation failures. Methods. This is a retrospective cohort study on patients who had failed embryo transfer cycle and had elevated Th1/Th2 cytokine ratios between 1/2019 and 3/2020. Patients were assigned into two groups based on whether they received immunoregulatory treatment during a frozen transfer cycle. The primary outcome was live birth rate. Secondary outcomes included clinical pregnancy, implantation rate, and neonatal outcomes. Results. Of 71 patients enrolled, 41 patients received immunoregulatory therapy and 30 patients did not. Compared to untreated patients, rate of live birth was significantly elevated in the treated group (41.5% vs. 16.7%, $P=0.026$ ). Rate of biochemical pregnancy, implantation, clinical pregnancy, and ongoing pregnancy between two groups were 56.1% vs. 40% ( $P=0.18$ ), 36.5% vs. 23.9% ( $P=0.15$ ), 51.2% vs. 30% ( $P=0.074$ ), and 41.5% vs. 16.7% ( $P=0.03$ ), respectively. Although there was no statistical significance, women receiving treatment also had a tendency of lower frequency of pregnancy loss (19.0% vs. 44.4%, $P=0.20$ ). No adverse events were found between newborns of the two groups. Immunoregulatory therapy, age, infertility type, ovulation induction protocol, number of oocytes retrieved, artificial cycle embryo transfer, and cleavage transfer were associated with live birth in univariate analysis (all $P<0.05$ ). Only immunoregulatory therapy was associated with live birth after adjustment of confounders ( $\text{OR}=5.02$ , 95% CI: 1.02-24.8, $P=0.048$ ). Conclusions. Immunoregulatory therapy improves reproductive outcomes in elevated Th1/Th2 cytokine ratio women with embryo transfer failure.