Use of regenerative medicine in the treatment of endometritis in mares: A systematic review and meta-analysis

Defining the optimal therapy for endometritis remains a significant challenge for clinicians. Given the public health threat posed by antibiotic resistance and the inconclusiveness of traditional therapies, regenerative medicine has been proposed as an alternative. The objective of this study was to conduct a comprehensive systematic review and meta-analysis, to investigate the efficacy of regenerative medicine products in the treatment of both post-breeding persistent and chronic degenerative endometritis (PBIE/CDE) in mares, following the PRISMA guidelines. This research could be a comprehensive scientific reference for determining appropriate treatments and clinical strategies. All studies exploring the use of regenerative medicine therapies (i.e., plasma products, autologous conditioned serum, mesenchymal stem cells MSCs, and MSC derivatives) in the treatment of PBIE/CDE were included, regardless of the specific protocol used, the evaluated outcomes, or the diagnostic method employed. Two au- thors independently gathered data and evaluated the risk of bias for each study. Treatment effects were assessed using risk ratios for dichotomous data, accompanied by 95 % confidence intervals. Data were aggregated uti- lizing the fixed-effects model. The quality of evidence for each outcome was evaluated using GRADE criteria. Eighteen studies were included in the systematic review, while fifteen trials were included in the meta- analysis. A sub-meta-analysis was conducted separately on platelet-derived products, as well as on MSCs and their derivatives. The results demonstrated an overall positive effect of regenerative therapies in treating PBIE/ CDE, particularly those involving MSCs and their derivatives. The positive outcomes include an anti- inflammatory effect, characterized by reduced intrauterine fluid accumulation, neutrophils, and cytokine con- centrations. Additionally, improvements in pregnancy, foaling, and embryo recovery rates have been observed in some cases. Despite the limited number of randomized controlled studies and the high variability among pro- tocols, including the timing of treatment, type, and volume of products used, the use of regenerative products, especially MSCs and their derivatives, has promising results in terms of both efficacy and safety for treating PBIE/ CDE in mares.