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.