| 【Background】 Over the past 40 years,more than 9 million babies have been conceived by assisted reproductive technology.ART-related adverse effects on offspring health have attracted widespread attention.Nowadays many studies have found that the perinatal outcome of ART conception is poor.Adverse delivery outcomes may originate from fetal intrauterine growth abnormalities.Fetal intrauterine growth is regulated by many factors.The characteristics of infertility population and the procedures of drug use,embryo operation and in vitro culture in ART treatment are likely to affect the embryo growth trajectory as an environmental factor.However,there are still many challenges to clarify the relationship between ART treatment and fetal intrauterine growth.First of all,previous studies on intrauterine growth of fetuses in the middle and late pregnancy are retrospective cohort studies based on hospital monitoring,and it is difficult to obtain detailed information of assisted reproductive treatment cycle and sufficient confounding factors,and the sample size is relatively small.Secondly,it is not clear whether the difference between ART pregnancy and natural pregnancy is caused by ART technology itself or by infertility factors that encourage people to use ART pregnancy.Finally,studies on ART and fetal intrauterine growth in mid-late pregnancy mainly come from abroad,and there is no research report on Chinese population.Therefore,based on a large-scale prospective cohort study,this study compared the intrauterine growth and birth weight of ART pregnant infants and natural pregnant infants,and further explored the effects of specific ART treatments and specific infertility diagnosis on fetal growth trajectory.【Method】This article was a prospective cohort study based on the Jiangsu birth cohort,including all singleton live birth whose mother had pregnancies up to 20weeks’ s gestation between August 2016 and May 2019 and had ultrasound data during 20-36 gestational weeks(1157 ART-and 2969 spontaneous-pregnancies).By retrieving and integrating the information from different sources such as clinical reproductive medicine management system,hospital information system,and ultrasound data system,the exposure variables related to the diagnosis and treatment of infertility in assisted reproductive couples,the information of maternal diseases during pregnancy,and the information of intrauterine growth parameters were obtained.The baseline information,pregnancy and delivery information of the population were obtained through standardized questionnaire face-to-face follow-up survey,electronic case extraction and export,and telephone follow-up.Linear mixed model was used to estimate the specific association between assisted reproduction and fetal growth measured by ultrasound during 20-36 gestational weeks.Linear regression was used to evaluate the correlation between ART treatment and fetal birth weight.The association of ART treatment and infertility factors with fetal intrauterine growth was analyzed in ART pregnant population.Then,the difference of intrauterine growth between ART pregnancy subgroup and natural pregnancy was studied by selecting significant variables during 20-36 gestational weeks.We use the growth parameters predicted by the mixed effect model to fill in the ultrasound data of each gestational week and calculate the difference between the different ART treatment plans and infertility factors in each gestational week relative to the intrauterine growth of the fetus in the natural pregnancy population【Results】 Our final analysis included 1093 ART pregnant families and 2676 natural pregnant families.In this study,pregnant women with ART pregnancy were older than those with natural pregnancy,their educational level and socioeconomic level were lower than those with natural pregnancy,and the ratio of obesity or overweight was greater than that of natural pregnancy.The proportion of primiparous was greater in ART pregnant women and their proportion of pregnant women with diabetes or high blood pressure during pregnancy is greater than that of pregnant women with natural pregnancy,and the proportion of alcohol consumption during pregnancy is less than that of pregnant women with natural pregnancy.The EFW,AC,and FL of ART-conceived fetus are 18.74g(95%CI: 11.25-26.24),0.31cm(95%CI:0.24,0.39)and 0.05cm(95%CI: 0.04,0.07)larger than those of natural-conceived fetuses during 20-36 weeks,respectively,there was no significant difference in HC between ART-conceived and natural-conceived fetus(0.06 [-0.002,0.13]),and the birth weight was 166.18 g heavier than natural-conceived fetus(95% CI: 158.4,173.96).There was no significant difference in HC between ART-conceived fetuses and natural-conceived fetuses(β [95%CI]: 0.06 [-0.002,0.13]).We analyzed the effects of specific ART treatment and infertility diagnosis on the growth parameters of fetuses in the middle and late pregnancy in ART-conceived fetuses,and it was found that FET have greater EFW(β [95% CI]: 28.07 [13.98,42.17]),HC(adjusted β[95% CI]: 0.47 [0.34,0.61]),AC(β [95% CI]: 0.30 [0.14,0.45])and FL(β [95% CI]:0.05 [0.02,0.09])during the second and third trimester of pregnancy compared than fresh embryo transplantation.Compared with the group of agonist protocol,the group of antagonist protocol have greater HC during the second and third trimester of pregnancy(β [95%CI]: 0.13 [0.03,0.23]).ART-conceived fetuses who have diagnosis of endometriosis(β [95%CI]:-0.24 [-0.42,-0.06]),thyroid factors(β [95%CI]:-0.29[-0.5,-0.09])or sperm abnormalities(β [95%CI]:-0.12 [-0.21,-0.02])have smaller HC than the ART pregnancy group without these factor separately.Stratified analysis has been done according to the above influencing factors to compared the differences in fetal growth parameters between ART pregnancy and natural pregnancy,and it was found that FET had greater EFW,AC and FL during the second and third trimester of pregnancy(β [95%CI]: EFW: 22.9 [15.07,30.74],HC: 0.15 [0.08,0.22],AC: 0.36[0.28,0.44],FL: 0.06 [0.05,0.08]).The EFW difference between fetuses conceived by FET and natural-conceived fetuses increased after 23 gestational weeks.HC of fetus concieved by fresh-FT(-0.32 [-0.45,-0.20])was smaller than that of natural-conceived fetuses while other parameters were greater than natural-conceived fetuses during the second trimester of pregnancy and tend to be no difference between two groups from 28 gestational weeks on ward.The HC of ART-conceived fetuses in the antagonist protocol ovulation induction group,non-endometriosis group,non-thyroid factor group and non-sperm abnormality group was greater than that of natural-conceived fetuses during the second and third trimester of pregnancy(antagonist protocol ovulation induction group: 0.19 [0.10,0.27],non-endometriosis group: 0.10 [0.03,0.17],non-thyroid factor group: 0.10 [0.03,0.17],non-sperm abnormality group: 0.16 [0.08,0.25]).HC of ART-conceived fetuses with diagnosis of endometriosis(β [95% CI]:-0.32 [-0.50,-0.14])and thyroid factors(β [95% CI]:-0.26 [-0.48,-0.04])was significantly smaller than that of natural-conceived fetuses during the second and third trimester of pregnancy.【Conclusion】In this prospective cohort study,we found that ART-conceived fetuses growth greater than natural-conceived fetuses,and the effect tend increased as the gestational week increased.The difference in intrauterine growth between the two groups could be partly attributed to specific ART treatment and infertility diagnosis.Compared with fresh-ET,FET have greater EFW,HC,AC and FL during the second and third trimester of pregnancy.The HC of ART conceived with sperm abnormality,endometriosis and thyroid abnormality were smaller than ART conceived without these factors.In addition,and the HC of antagonist protocol group was smaller than microstimulation protocol group.The intrauterine growth of ART-conceived fetuses during the second and third trimester of pregnancy was greater than that of natural-conceived fetuses,which could be partly attributed to FET and antagonist protocol.Endometriosis and thyroid factors can affect fetal growth,resulting in a smaller HC during the second and third trimester of pregnancy than that in natural pregnancy.There was no difference in HC between ART conceived pregnancy with sperm abnormality and natural pregnancy.This study evaluated the growth status of ART progeny with intrauterine growth parameters,which enriched the understanding of the effect of ART conception on fetal growth;Provides clues to the mechanism research to explore the reasons for the difference in growth and development between ART pregnancy and natural pregnancy... |
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