Should the Treatment of Patients with Repeated Embryo Implantation Failure Be Adapted as a Function of the Endometrial Cytokine Profile? A Single-Center Experience

Abstract

Repeated embryo implantation failures (RIF) is a source of distress and frustration for patients and clinicians alike. Today’s approaches for treating RIF are largely empirical and have limited effectiveness. The main causes of RIF are poor endometrial receptivity and poor-quality embryos. Recent studies have suggested the involvement of immune dysregulation due to an imbalance between T-helper (Th) 1 and Th2 cytokines; this opens up perspectives for treating women with RIF and increasing the implantation rate. We conducted an interventional, longitudinal, prospective cohort study of the impact of correcting the cytokine imbalance on the clinical pregnancy rate in women with RIF. Seventy-seven women with RIF underwent an endometrial biopsy during the implantation window. The cytokine profile was evaluated by studying the activation and maturation of uterine natural killer (uNK) cells, the IL-15/Fn-14 mRNA ratio (a biomarker of uNK activation/maturation), and the IL-18/TWEAK mRNA ratio (a marker of angiogenesis and the Th1/Th2 balance). Personalized treatment was initiated for women with an abnormal endometrial cytokine profile (hyper-activation or hypo-activation). We documented the clinical pregnancy rate after subsequent embryo transfers. In total, 72.7% (56/77) of patients had an abnormal endometrial cytokine profile (hyper-activation in 68.8% (n = 53) and hypo-activation in 3.9% (n = 3). After treatment (or not) as a function of the endometrial profile, the overall clinical pregnancy rate was 30.2%. Our results indicated a potential positive effect of appropriate treatment on the ongoing pregnancy rate in women with RIF, despite the small number of cases analyzed. The results must now be validated in randomized studies with larger numbers of well-characterized patients. By applying a previously published decision tree, this treatment approach could be implemented in clinics worldwide.