Diana Alecsandru1, Ana Barrio2, Nicolás Garrido3, Pilar Aparicio4, Antonio Pellicer5, Ashley Moffett6, Juan A García-Velasco7. 1. Department of Immunology, IVI RMA Madrid, Madrid, Spain; IVI Foundation, Health Research Institute La Fe, Valencia, Spain. Electronic address: diana.alecsandru@ivirma.com. 2. Department of Reproductive Endocrinology and Infertility, IVI RMA Madrid, Madrid, Spain. 3. IVI Foundation, Health Research Institute La Fe, Valencia, Spain. 4. Department of Immunology, IVI RMA Madrid, Madrid, Spain. 5. IVI Foundation, Health Research Institute La Fe, Valencia, Spain; Department of Reproductive Endocrinology and Infertility, IVI RMA Roma, Rome, Italy. 6. Centre for Trophoblast Research, University of Cambridge, Cambridge, United Kingdom. 7. IVI Foundation, Health Research Institute La Fe, Valencia, Spain; Department of Reproductive Endocrinology and Infertility, IVI RMA Madrid, Madrid, Spain; Rey Juan Carlos University, Madrid, Spain.
Abstract
OBJECTIVE: To study the pregnancy, miscarriages, and live birth rates (LBRs) according to maternal killer cell immunoglobulin-like receptor (KIR) genes expressed by uterine natural killer cells and paternal or oocyte donor human leukocyte antigen-C (HLA-C) genes expressed by trophoblast cells in patients with recurrent reproductive failure. DESIGN: Prospective observational cohort study. SETTING: Private infertility center. PATIENT(S): Participants included 204 women with recurrent miscarriage or recurrent implantation failure. INTERVENTION(S): The KIR and HLA-C genotypes of all women and HLA-C of their partners, gamete donors, miscarriage tissue, and babies were analyzed. MAIN OUTCOME MEASURE(S): All clinical variables (pregnancy, miscarriage, and LBRs) were analyzed and categorized based on KIR, oocyte origin, and single embryo transfer (SET)/double embryo transfer (DET). RESULT(S): A higher miscarriage rate was observed after DETs in KIR AA mothers (47.8% egg donation and 37.5% in vitro fertilization [IVF]) compared with KIR AB (10.5% egg donation and 12.5% IVF) or KIR BB (6.7% egg donation and 0% IVF). A significantly decreased LBR was observed after DETs with oocyte donation in KIR AA patients (4.3%) compared with KIR AB (26.3%) or BB (46.7%). The LBR decreased significantly as the fetal HLA-C2 load increased in KIR AA women. CONCLUSION(S): Elective SET improves the reproductive outcomes compared with DET. An increased embryo HLA-C2 load has a negative impact on the LBR in KIR AA patients. The selection of HLA-C1 over HLA-C2 donors could have a positive impact on the LBR in KIR AA patients. CLINICAL TRIAL REGISTRATION NUMBER: NCT04052438.
OBJECTIVE: To study the pregnancy, miscarriages, and live birth rates (LBRs) according to maternal killer cell immunoglobulin-like receptor (KIR) genes expressed by uterine natural killer cells and paternal or oocyte donor human leukocyte antigen-C (HLA-C) genes expressed by trophoblast cells in patients with recurrent reproductive failure. DESIGN: Prospective observational cohort study. SETTING: Private infertility center. PATIENT(S): Participants included 204 women with recurrent miscarriage or recurrent implantation failure. INTERVENTION(S): The KIR and HLA-C genotypes of all women and HLA-C of their partners, gamete donors, miscarriage tissue, and babies were analyzed. MAIN OUTCOME MEASURE(S): All clinical variables (pregnancy, miscarriage, and LBRs) were analyzed and categorized based on KIR, oocyte origin, and single embryo transfer (SET)/double embryo transfer (DET). RESULT(S): A higher miscarriage rate was observed after DETs in KIR AA mothers (47.8% egg donation and 37.5% in vitro fertilization [IVF]) compared with KIR AB (10.5% egg donation and 12.5% IVF) or KIR BB (6.7% egg donation and 0% IVF). A significantly decreased LBR was observed after DETs with oocyte donation in KIR AA patients (4.3%) compared with KIR AB (26.3%) or BB (46.7%). The LBR decreased significantly as the fetal HLA-C2 load increased in KIR AA women. CONCLUSION(S): Elective SET improves the reproductive outcomes compared with DET. An increased embryo HLA-C2 load has a negative impact on the LBR in KIR AA patients. The selection of HLA-C1 over HLA-C2 donors could have a positive impact on the LBR in KIR AA patients. CLINICAL TRIAL REGISTRATION NUMBER: NCT04052438.
Authors: Ee Von Woon; Orene Greer; Nishel Shah; Dimitrios Nikolaou; Mark Johnson; Victoria Male Journal: Hum Reprod Update Date: 2022-06-30 Impact factor: 17.179
Authors: Karolina Piekarska; Paweł Radwan; Agnieszka Tarnowska; Andrzej Wiśniewski; Michał Radwan; Jacek R Wilczyński; Andrzej Malinowski; Izabela Nowak Journal: Front Immunol Date: 2021-10-22 Impact factor: 7.561