Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, California 94158, USA.
Department of Epidemiology and Biostatistics, University of California, San Francisco, California 94158, USA.
J Clin Endocrinol Metab. 2023 Jan 17;108(2):315-322. doi: 10.1210/clinem/dgac589.
Assisted reproductive technologies (ART) and non-in vitro fertilization 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.
This work aimed to describe metabolic differences in children conceived by ART and NIFT compared to children conceived spontaneously by infertile couples.
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 intracytoplasmic sperm injection [ICSI]) and children conceived spontaneously by subfertile couples. Principal component analysis and multivariable regression were used to compare the distribution of metabolites between groups.
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 < .001). Propionylglycine levels were elevated in the ICSI (both fresh and frozen) vs the spontaneous group (P < .001). Finally, 5-oxoproline levels were decreased in frozen ART compared to the spontaneous group (P < .001).
NIFT-conceived children did not show any metabolic differences compared 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.
辅助生殖技术（ART）和非体外受精生育治疗（NIFT）是治疗不孕不育的方法。这些技术可能会对儿童的长期健康产生影响，例如高血压、葡萄糖不耐受和高三酰甘油血症的发病率增加。很少有研究比较过接受 ART 和 NIFT 治疗后出生的儿童与因生育能力低下而自然受孕的儿童。
本研究旨在描述通过 ART 和 NIFT 受孕的儿童与因生育能力低下而自然受孕的儿童之间的代谢差异。
在加利福尼亚大学旧金山分校接受不孕不育治疗的父母所生育的儿童，于 2000 年至 2017 年期间被邀请参加通过生殖技术生育的儿童发展流行病学研究（DESCRT）。使用来自 143 名已入组儿童（年龄 4-12 岁，43%为女性）的血清代谢组学分析样本，这些儿童是通过 NIFT 或 ART（使用新鲜或冷冻胚胎，有无胞浆内单精子注射[ICSI]）受孕的，以及因生育能力低下而自然受孕的儿童。采用主成分分析和多变量回归比较组间代谢物的分布。
基于治疗或性别，代谢物没有分离。NIFT 受孕的儿童与自然受孕的对照组相比没有差异。只有自然受孕的儿童的代谢组学特征与新鲜 ART、冷冻 ART 和所有 ICSI 受孕的儿童不同。与自然受孕组相比，新鲜 ART 受孕的儿童中 pantothenate 和丙酰基甘氨酸的水平升高（P <.001）。ICSI（新鲜和冷冻）受孕的儿童中丙酰基甘氨酸的水平高于自然受孕组（P <.001）。最后，冷冻 ART 受孕的儿童中 5-氧脯氨酸的水平低于自然受孕组（P <.001）。
与自然受孕的儿童相比，NIFT 受孕的儿童没有表现出任何代谢差异。ART 受孕的儿童与自然受孕的儿童之间的代谢差异很小，但不太可能具有临床意义，但应在未来的研究中进行检验。
