The optimal timing of immunotherapy may improve pregnancy outcome in women with unexplained recurrent pregnancy loss: A perspective follow-up study in northeastern China.

Problem: To determine whether patients with unexplained recurrent pregnancy loss (URPL) can benefit from pre-conception immunotherapy or on the early phase of the first trimester.

Method Of Study: The prospective follow-up study which involved pre-conception patients diagnosed with URPL following rigorous etiology screening in the medical center of recurrent pregnancy loss. In this study, pre-conception immunotherapy included lymphocyte immunotherapy (pre-LIT). Post-conception immunotherapy (post-IM) included LIT or intravenous immunoglobulin (IVIG). Patients were recommended to undergo post-IM immediately from human chorionic gonadotrophin (hCG) elevation. Autoimmune antibodies (AIA) and anti-paternal lymphocytotoxic antibodies (APLA) were tested before and after pre-LIT. Favorable outcome was defined as pregnancy over 14 weeks. Unfavorable outcomes included biochemical pregnancy loss (BPL) and pregnancy loss with clear implantation location (PLCIL).

Results: In this study, URPL accounted for 12.9% of recurrent pregnancy loss (217/1682). Frequency of BPL was significantly lower in patients with post-IM than that without post-IM [2.8% vs 28.2%; adjusted relative risk (aRR), 0.06; 95% confidence interval (CI), 0.01-0.24]. There was a significant positive conversion in the AIA induced by pre-LIT (0.0% vs 31.0%). Frequency of PLCIL in patients with positive iatrogenic AIA conversion induced by pre-LIT was higher than that in patients without AIA conversion [30.4% vs 5.8%; aRR, 7.53; 95% CI, 1.31-43.34].

Conclusion: Pre-LIT of patients with URPL contributed to a positive iatrogenic AIA conversion, which was associated with an increased risk of PLCIL. Post-IM immediately initiated from the time of hCG elevation can reduce the incidence of BPL.