Tao Zhang1,2, Chunyu Huang1,2, Yan Du3, Ruochun Lian1,2, Meilan Mo1,2, Yong Zeng1,2, Gil Mor4. 1. Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China. 2. Shenzhen Zhongshan Institute for Reproductive Medicine and Genetics, Shenzhen, China. 3. Office of Clinical Epidemiology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. 4. Division of Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
Abstract
PROBLEM: Effective therapy for endometrial receptivity of patients with repeated embryo implantation failure (RIF) is far undeveloped. Whether intrauterine perfusion of dexamethasone (DXM), local administration of drugs with less systematic side-effects, benefit for embryo implantation by suppressing uterine NK (uNK) cells to improve endometrial receptivity remains unknown. METHOD OF STUDY: Women with RIF were analyzed for the correlation between the percentage of uNK cells during implantation window and following clinical pregnancy rate to determine the appropriate range of uNK for embryo implantation. Women with RIF and extremely increased uNK cells were treated with transvaginal intrauterine perfusion of DXM. Quantification of uNK cells before and after this treatment was analyzed by immunohistochemistry staining for understanding potential underlying mechanism. Pregnancy outcome was evaluated for the efficiency and safety of this novel therapy. RESULTS: The clinical pregnancy rate was decreased if the percentage of uNK cells was higher than the 75th percentile (18.06%), which was considered as the cutoff value for increased uNK cells. All eight patients with increased uNK cells responded to DXM-induced decrease on uNK cells number, and seven got clinical pregnancy. Three delivered with a healthy baby at term without any pregnancy complication and three achieved an ongoing pregnancy, but one suffered from early miscarriage. CONCLUSION: We report for the first time the beneficial effect of intrauterine perfusion of DXM for patients with RIF characterized by high number of uNK cells. The potential mechanism is downregulation of the proportion of uNK cells, which may improve endometrial receptivity and enhance embryo implantation.
PROBLEM: Effective therapy for endometrial receptivity of patients with repeated embryo implantation failure (RIF) is far undeveloped. Whether intrauterine perfusion of dexamethasone (DXM), local administration of drugs with less systematic side-effects, benefit for embryo implantation by suppressing uterine NK (uNK) cells to improve endometrial receptivity remains unknown. METHOD OF STUDY: Women with RIF were analyzed for the correlation between the percentage of uNK cells during implantation window and following clinical pregnancy rate to determine the appropriate range of uNK for embryo implantation. Women with RIF and extremely increased uNK cells were treated with transvaginal intrauterine perfusion of DXM. Quantification of uNK cells before and after this treatment was analyzed by immunohistochemistry staining for understanding potential underlying mechanism. Pregnancy outcome was evaluated for the efficiency and safety of this novel therapy. RESULTS: The clinical pregnancy rate was decreased if the percentage of uNK cells was higher than the 75th percentile (18.06%), which was considered as the cutoff value for increased uNK cells. All eight patients with increased uNK cells responded to DXM-induced decrease on uNK cells number, and seven got clinical pregnancy. Three delivered with a healthy baby at term without any pregnancy complication and three achieved an ongoing pregnancy, but one suffered from early miscarriage. CONCLUSION: We report for the first time the beneficial effect of intrauterine perfusion of DXM for patients with RIF characterized by high number of uNK cells. The potential mechanism is downregulation of the proportion of uNK cells, which may improve endometrial receptivity and enhance embryo implantation.
Authors: Beverly G Reed; Samir N Babayev; Lucy X Chen; Bruce R Carr; R Ann Word; Patricia T Jimenez Journal: Reproduction Date: 2018-12 Impact factor: 3.906