Temporary Increased LDL-C in Offspring with Extreme Elevation of Maternal Preconception Estradiol: A Retrospective Cohort Study

Abstract

Objective

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

Acknowledgments

We would like to thank Editage (www.editage.cn) for English language editing.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was supported by the National Key Research and Development Program of China (2018YFC1004301), Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (2020RU001), Shandong Provincial Key Research and Development Program (2018YFJH0504), Natural Science Foundation of Shandong Province of China (ZR2020MH065), and Taishan Scholars Program for Young Experts of Shandong Province (tsqn201909195).