Clinical Epidemiology (Apr 2022)
Temporary Increased LDL-C in Offspring with Extreme Elevation of Maternal Preconception Estradiol: A Retrospective Cohort Study
Abstract
Wanbing Feng,1– 6 Di Zhang,1– 6 Linlin Fu,1– 6 Jingmei Hu,1– 6 Shanshan Gao,1– 6 Xiaocui Song,1 Linlin Cui1– 6 1Center for Reproductive Medicine, Department of Reproductive Medicine, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 3Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, People’s Republic of China; 4Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, People’s Republic of China; 5Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, People’s Republic of China; 6National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Linlin Cui; Xiaocui Song, Center for Reproductive Medicine, Department of Reproductive Medicine, The Second Hospital, Cheeloo College of Medicine, Shandong University, No. 157, Jingliu Road, Shizhong District, Jinan, Shandong, People’s Republic of China, 250001, Tel +86 531 85651598, Fax +86 531 87068226, Email [email protected]; [email protected]: To investigate the effect of maternal estradiol (E2) elevation on long-term metabolic manifestations in the offspring.Study Design and Setting: This was a retrospective cohort study. Overall, 3690 children conceived by in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) between July 2014 and December 2017 were recruited and divided into four groups categorized by maternal E2 quartiles (Q1, < 2420; Q2, 2420– 3839; Q3, 3839– 5599; and Q4, ≥ 5599 pg/mL). The metabolic profiles were measured during childhood. Linear mixed models were used to evaluate the association between maternal E2 elevation and metabolic phenotypes of the offspring.Results: Lipoprotein cholesterol (LDL-C) was significantly higher in the highest quartile group than in the lowest quartile group during infancy (adjusted mean difference [95% confidence interval, CI]): 0.11 [0.02, 0.20], P = 0.005), but the difference disappeared in the later childhood phase. In children born after fresh embryo transfer, LDL-C showed an increasing trend with the increase in maternal E2 level (adjusted mean difference [95% CI]: Q2 vs Q1, − 0.01 [− 0.11, 0.08], Q3 vs Q1, 0.06 [− 0.04, 0.15], Q4 vs Q1, 0.10 [0, 0.20]). Other metabolic variables were comparable across increasing quartiles of maternal E2 levels.Conclusion: This study demonstrates a temporary increase in LDL-C levels in infants with higher levels of maternal preconception E2 levels. However, the long-term safety of hyperestrogens after ovarian stimulation in the next generation is favorable. The mechanism underlying the transiently increased metabolic dysfunction risk in infants conceived by IVF/ICSI requires investigation in future studies.Keywords: offspring, supraphysiologic estradiol, controlled ovarian hyperstimulation, assisted reproductive technology
