Jingjie Li1, Yue Gao2, Lihuan Guan2, Huizhen Zhang2, Pan Chen3, Xiao Gong4, Dongshun Li2, Xiaoyan Liang1, Min Huang2, Huichang Bi2. 1. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China. 2. Center of Reproductive Medicine, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. 3. Department of Pharmacy, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. 4. School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China.
Abstract
CONTEXT: Late follicular phase elevation in serum progesterone (P) during controlled ovarian hyperstimulation negatively affects the outcome of assisted reproductive technology by contributing to endometrial-embryo asynchrony. There are still no data on lipid metabolite alterations during this process. OBJECTIVES: To investigate alterations in the lipid profile during the window of implantation in patients with premature P rise. DESIGN: Lipidomic variations in the endometrium were evaluated by ultrahigh-performance liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry. SETTING: University assisted reproductive medicine unit. PATIENTS OR OTHER PARTICIPANTS: Forty-three patients undergoing in vitro fertilization/intracytoplasmic sperm injection because of a tubal factor or male factor infertility were included in this study. The patients were divided into a high P group (P ≥ 1.5 ng/mL, 15 patients) and a normal P group (P < 1.5 ng/mL, 28 patients) on the day of human chorionic gonadotropin administration. INTERVENTIONS: The endometrial tissues were obtained by Pipelle biopsy 7 days after human chorionic gonadotropin administration. MAIN OUTCOME MEASURES: Alterations in lipid metabolites. RESULTS: A total of 1026 ions were identified, and 25 lipids were significantly upregulated. The endometrial lipid profile was characterized by substantial increases in the concentrations of phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine, diacylglycerol, ceramide, phosphatidylinositol, and phosphatidylserine in patients with a premature P rise at the end of the follicular phase. The correlation analysis between P levels and lipids showed a stronger negative correlation between phosphatidylethanolamine or phosphatidylserine and P levels. CONCLUSIONS: Premature P elevation disrupts the lipid homeostasis of the endometrium during the peri-implantation period. The altered lipid levels may impair endometrial receptivity and early embryo implantation.
CONTEXT: Late follicular phase elevation in serum progesterone (P) during controlled ovarian hyperstimulation negatively affects the outcome of assisted reproductive technology by contributing to endometrial-embryo asynchrony. There are still no data on lipid metabolite alterations during this process. OBJECTIVES: To investigate alterations in the lipid profile during the window of implantation in patients with premature P rise. DESIGN:Lipidomic variations in the endometrium were evaluated by ultrahigh-performance liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry. SETTING: University assisted reproductive medicine unit. PATIENTS OR OTHER PARTICIPANTS: Forty-three patients undergoing in vitro fertilization/intracytoplasmic sperm injection because of a tubal factor or male factor infertility were included in this study. The patients were divided into a high P group (P ≥ 1.5 ng/mL, 15 patients) and a normal P group (P < 1.5 ng/mL, 28 patients) on the day of human chorionic gonadotropin administration. INTERVENTIONS: The endometrial tissues were obtained by Pipelle biopsy 7 days after human chorionic gonadotropin administration. MAIN OUTCOME MEASURES: Alterations in lipid metabolites. RESULTS: A total of 1026 ions were identified, and 25 lipids were significantly upregulated. The endometrial lipid profile was characterized by substantial increases in the concentrations of phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine, diacylglycerol, ceramide, phosphatidylinositol, and phosphatidylserine in patients with a premature P rise at the end of the follicular phase. The correlation analysis between P levels and lipids showed a stronger negative correlation between phosphatidylethanolamine or phosphatidylserine and P levels. CONCLUSIONS:Premature P elevation disrupts the lipid homeostasis of the endometrium during the peri-implantation period. The altered lipid levels may impair endometrial receptivity and early embryo implantation.