Metabolomic Profile of Children Conceived With Medically Assisted Technologies

Abstract

Background Assisted reproductive technologies (ART) and non-IVF fertility treatments (NIFT) are treatments for infertility. These technologies may have long-term health effects in children such as increased hypertension, glucose intolerance, and hypertriglyceridemia. Few studies have compared children born following ART and NIFT to those conceived spontaneously by subfertile couples. Objective Describe metabolic differences in children conceived by ART and NIFT compared to children conceived spontaneously by infertile couples. Methods Children conceived by parent(s) receiving infertility care at the University of California, San Francisco between 2000 and 2017 were invited to participate in the Developmental Epidemiological Study of Children born through Reproductive Technology (DESCRT). Serum metabolomic analyses were conducted using samples from 143 enrolled children (age range 4-12 years, 43% female) conceived using NIFT or ART (with fresh or frozen embryos with and without ICSI) and children conceived spontaneously by subfertile couples. Principal component analysis and multivariable regression were used to compare the distribution of metabolites between groups. Results There was no separation in metabolites based on treatment or sex. NIFT conceived children showed no differences compared to spontaneously conceived controls. Only spontaneously conceived children had different metabolomics profiles from children conceived from fresh ART, frozen ART, and all ICSI. Pantoate and propionylglycine levels were elevated in fresh ART compared to the spontaneous group (p < 0.001). Propionylglycine levels were elevated in the ICSI (both fresh and frozen) versus spontaneous group (p < 0.001). Finally, 5-oxoproline levels were decreased in frozen ART compared to the spontaneous group p < 0.001) Conclusion NIFT conceived children did not show any metabolic differences with spontaneously conceived children. The metabolic differences between ART-conceived children and children conceived spontaneously were small but unlikely to be clinically significant but should be examined in future studies.

Lactate as a myokine and exerkine: drivers and signals of physiology and metabolism

“…Lactate fuels the spiral mitochondrial reticulum at the base of the sperm head. The event of conception is followed by the influence of lactate on embryonic development ( 17 , 242 ), and subsequently over the lifespan ( 238 ).…”

“…However, as investigators turn the page and delve into new areas of lactate biology we will better understand how perturbations in lactate turnover and accumulation, sensing and signaling could have beneficial or other, sometimes detrimental, consequences. For instance, Rinaudo and coworkers ( 237 ) showed that the hyperoxic environment of in vitro fertilization can result in perturbations in the L/P and ROS generation that are associated with insulin resistance and loss of metabolic flexibility in offspring ( 238 ). In concert, it has been shown that pyruvate is indispensable for preimplantation development and zygotic gene activation (ZGA) beyond 2-cell (2C) stage of development, following which either pyruvate or lactate can facilitate continued cell development and ZGA ( 239 – 241 ).…”