Regenerative therapy by endometrial mesenchymal stem cells in thin endometrium with repeated implantation failure. A novel strategy

Abstract

Objective: Our primary objective was to evaluate the endometrial changes before and after the transfer of endo-metrial mesenchymal stem cells (enMSCs) in a population of thinned endometrium women, with absence or hypo-re-sponsiveness to estrogen and repeated implantation failure (RIF). The secondary objective was to evaluate the clinical outcomes of the intervention in terms of clinical pregnancy (CP), early abortions, ongoing pregnancy and live birth delivery rate (LBDR) per in vitro fertilization (IVF) cycle. Methods: A longitudinal and experimental study. The intervention was defined as "subendometrial inoculation of enMSCs," and the post-intervention changes were evaluated by the following variables: endometrial thickness (Eth), endometrial flow cytometry (enFC), endometrial histopa-thology (enHP) and endometrial immunohistochemistry (enIHQ). The variables were analyzed after the intervention (Post-treatment) regarding previous values (Pretreat-ment). Results: Eth values before and after treatment with enMSCs were 5.24±1.24 mm vs. 9.93±0.77 (p=0.000), respectively. Endometrial Flow Cytometry showed significant differences in favor of Normalized variables in the post-treatment assessment, associated with the pre-treatment, LT/Li, LB/Li, NK/Li, CD8/CD3+ and CD4/CD8 (p≤0.015), respectively. Only two variables Li/PC and CD4/ CD3 had NS (p=0.167 and 0.118). A similar analysis was performed on enHP with an HP increase post-treatment (p=0.007). The CP rate was 79.31% (23/29), a live birth delivery rate per embryo transfer was 45.45% (10/22) and ongoing pregnancy 7/29 (24.14%). Conclusion: Subendometrial enMSCs inoculation produces a significant increase in endometrial thickness; normalize the enHP, enIHQ and enFC. As a result, IVF after treatment with enMSCs yields a higher rate of CP and LBDR.