Normalization of endometrial histopathology and endometrial NK cells concentration predict successful pregnancy in repeated implantation failure.

OBJECTIVE: The primary objective was to establish the endometrial predictors of clinical pregnancy in a population of repeated implantation failure with oocyte donation after specific endometrial treatment. The secondary one was to evaluate reproduction outcomes in terms of Implantation rate (IR), Clinical pregnancy (CP), Live birth delivery rate (LBDR) and Prematurity, in relation to normalization or no-normalization of the predictors. METHODS: 66 patients were assigned to the study. We ran a Pipelle endometrial biopsy to investigate the endometrium lymphocyte population by Flow Cytometry and abnormal/normal patterns by histopathology in pre/post-treatment. We employed the binary logistic regression model to identify the predictors for CP. For the secondary objective, we assessed the clinical outcomes in function to the normalization or no normalization in post-treatment. RESULTS: Endometrial histopathology and endometrial NK cell counts resulted in CP predictors (Wald chi2 test (p=0.044 and 0.001)), respectively. We had a higher IR, CP and LBDR when both predictors were normalized in comparison with no normalization (p<0.001). There was a high percentage of prematurity in both normalized vs. non-normalized groups (34.4% (11/32) and 71.43% (5/7), respectively) without significant differences. CONCLUSION: Endometrial histopathology and endometrial NK cell counts showed that they are valid predictors of pregnancy outcome in repeated implantation failure after treatment. In post-treatment, the pregnancy outcomes were significantly higher in the presence of both normalized predictors. Pregnancy rates were zero in the no-normalization of both predictors. There was a high percentage of prematurity in both groups.

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

OBJECTIVE: Our primary objective was to evaluate the endometrial changes before and after the transfer of endometrial mesenchymal stem cells (enMSCs) in a population of thinned endometrium women, with absence or hypo-responsiveness 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 histopathology (enHP) and endometrial immunohistochemistry (enIHQ). The variables were analyzed after the intervention (Post-treatment) regarding previous values (Pretreatment). 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 pretreatment, 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.

Repeated implantation failure in oocyte donation. What to do to improve the endometrial receptivity?

OBJECTIVE: To determine the role of polyvalent endometrial treatment in patients undergoing IVF-ET who had recurrent implantation failure (RIF) in a program of oocyte donation (OD). The results were expressed in terms of live birth rate (LBR). Secondly analyze changes of endometrial leukocyte population evaluated by flow cytometer (FC) and histopathology. METHODS: Prospective study of a model-based control with analog abductive methodology. Over initial population of 75 patients with RIF in ovodonation, thirty cycles / patient of IVF/ET were selected in this study. A control group of 12 patients was established to variables FC. All patients were transferred to day 5-6 with a maximum of 2 expanded blastocysts with at least one of optimum quality. A versatile treatment was applied in all cases with both assessments in pre and postreatment. RESULTS: Chronic endometritis was diagnosed in 14/30 (46.7%) with endometrial identifying germs in 12/30 (40%) and 6/30 (20%) was associated with endometrial thinning. A significant increase in endometrial thickness associated with a decrease in abnormal histopathology and Li/PC was observed at postreatment in relation with a pretreatment (P=0.047 and P=0.002) respectively. An increase of uterine killer cells (Nku) was observed in postreatment in absence of pregnancy. CD4/CD3 was established with prognostic value when their values are close to those of the control group. CONCLUSION: Our findings demonstrate the reversibility of endometrial histological changes, both sonographics as immunological in RIF group under a polyvalent therapeutic; which is capable of modifying the immunology and endometrial histopathology and to obtain live birth.