Xuefeng Lu1, Zheng Yan1, Renfei Cai1, Shuzin Khor1, Ling Wu1, Lihua Sun2, Yun Wang1, Yao Xu3, Hui Tian2, Qiuju Chen1, Jie Qiao4, Bing Li1, Biaobang Chen3, Yu Cao5, Qifeng Lyu1, Lei Wang3, Yanping Kuang1. 1. Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. 2. Department of Assisted Reproduction, Shanghai East Hospital, Shanghai Tongji University School of Medicine, Shanghai, China. 3. State Key Laboratory of Genetic Engineering, MOE Key Laboratory of Contemporary Anthropology and Collaborative Innovation Center of Genetics and Development, School of Life Science, Fudan University, Shanghai, China. 4. Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. 5. Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Abstract
CONTEXT: The LH/chorionic gonadotropin receptor (LHCGR) is mainly expressed in gonads and plays important roles in estradiol production, ovulation, and luteal formation. Women with pathogenic LHCGR variants suffer from infertility, and successful fertility treatments for such women have never been reported. OBJECTIVE: The purpose of this study was to determine whether women with pathogenic LHCGR variants can achieve successful pregnancies through in vitro fertilization. DESIGN: Three women with LH resistance and infertility and their parents underwent exome sequencing. The biochemical characteristics and functional effects of LHCGR mutation were assessed in transfected human embryonic kidney -293T cells and primary granulosa cells. RESULTS: All affected women harbored pathogenic LHCGR variants. The LHCGR variants lacked cell surface localization and signal transduction abilities in vitro and in vivo. After dual triggering and prolonging the interval between triggering and oocyte pick-up, all three patients achieved oocytes and high-quality embryos. After frozen embryo transfer, one woman successfully birthed twins, and one woman successfully birthed a live boy. Apart from difficulties in oocyte retrieval, no obvious abnormalities in fertilization or during embryo development and pregnancy were identified in these patients. CONCLUSIONS: This study is, to our knowledge, the first to report successful assisted reproductive treatment of women with pathogenic LHCGR variants using their own oocytes. Our results supported that defects in LHCGR disrupted ovulation but had no effect on fertilization and embryo development.
CONTEXT: The LH/chorionic gonadotropin receptor (LHCGR) is mainly expressed in gonads and plays important roles in estradiol production, ovulation, and luteal formation. Women with pathogenic LHCGR variants suffer from infertility, and successful fertility treatments for such women have never been reported. OBJECTIVE: The purpose of this study was to determine whether women with pathogenic LHCGR variants can achieve successful pregnancies through in vitro fertilization. DESIGN: Three women with LH resistance and infertility and their parents underwent exome sequencing. The biochemical characteristics and functional effects of LHCGR mutation were assessed in transfected human embryonic kidney -293T cells and primary granulosa cells. RESULTS: All affected women harbored pathogenic LHCGR variants. The LHCGR variants lacked cell surface localization and signal transduction abilities in vitro and in vivo. After dual triggering and prolonging the interval between triggering and oocyte pick-up, all three patients achieved oocytes and high-quality embryos. After frozen embryo transfer, one woman successfully birthed twins, and one woman successfully birthed a live boy. Apart from difficulties in oocyte retrieval, no obvious abnormalities in fertilization or during embryo development and pregnancy were identified in these patients. CONCLUSIONS: This study is, to our knowledge, the first to report successful assisted reproductive treatment of women with pathogenic LHCGR variants using their own oocytes. Our results supported that defects in LHCGR disrupted ovulation but had no effect on fertilization and embryo development.
Authors: Yongzhe Chen; Zesong Wang; Yueren Wu; Wenbin He; Juan Du; Sufen Cai; Fei Gong; Guangxiu Lu; Ge Lin; Can Dai Journal: Front Genet Date: 2021-05-19 Impact factor: 4.599