| Objective: the incidence rate of infertility has been increasing year by year,and it has become the third major disease that seriously affects human health after cardiovascular diseases and tumors.Assisted reproductive technology(Art)was born to solve the fertility problem of refractory infertility patients to a certain extent.Since the birth of the world’s first vitro fertilization-embryo transfer baby in 1978,assisted reproductive technology has developed rapidly and its derivative technology has been constantly updated,now 8 million newborns have been born by assisted reproductive technology.With the continued increasing proportion of ART births in the social population,the safety of ART technology,especially the health condition of offspring,has attracted widespread attention from the whole society and the medical circle.This study retrospectively analyzed the impact of assisted reproductive technology on the pregnancy outcome of assisted pregnant female,prospective cohort study of preschool physical and neurobehavioral development of offspring and its influencing factors,and discussed the safety of the assisted reproductive technology.Method:1.A total of 13,200 clinical pregnant female who received assisted reproductive technology(including fresh embryo cycle and frozen embryo cycle)in Shenyang Jinghua Hospital Reproductive Medicine Center from January 2016 to December 2019 were collected,and their general information before pregnancy and follow-up data during and after assisted pregnancy were collected for retrospective study.Analyze its early abortion rate,late abortion rate,pregnancy complications,and partial outcomes of offspring(including premature birth,low birth weight,deformity,stillbirth,and neonatal death).2.Children who received ART assisted pregnancy from January 1,2013 to December 31,2018 at Shenyang Jinghua Hospital Reproductive Medicine Center and Shengjing Hospital were recruited as ART progeny group,and children who lived in Shenyang and its surrounding cities at the age of 1 to 5 years were included as ART offspring group,and children born during the same period of natural conception were used as control group(NC group).The Gaiser Development Scale(GDS)was used to evaluate the neurobehavioral development of two groups of children,and their height and weight were measured to evaluate their physical growth and development.Results:A.Analysis of pregnancy outcome and influencing factors of IVF / ICSI couples1.basic informationA total of 13,200 clinical pregnant female who received in vitro fertilization-embryo transfer assisted pregnancy(including fresh embryo cycle and frozen embryo cycle)from January 2016 to December 2019 were collected.49 of them were lost to follow-up,and the rate of loss-to-follow-up rate was 0.37%.A total of 13151 infertile couples ART-assisted infertile couples were enrolled finally.The average age of the female was32.42±4.34 years old.The mean age of males was 34.41±5.30 years.The fresh embryo cycle was 5733 cases,accounting for 43.6%;the frozen embryo cycle was 7418 cases,accounting for 56.4%.,The IVF group had 9345 cases,accounting for 71.1%;the ICSI group had 3300 cases,accounting for 25.1%;the IVF + ICSI group had 506 cases,accounting for 3.8%.2.Analysis of the influencing factors of ART fertility outcomeThe total abortion rate was 15.71%(2066/13151),the early abortion rate was 11.55%(1519/13151),the late abortion rate was 4.16%(547/13151),the ectopic pregnancy rate was 1.13%(148/13151),and the delivery rate was 83.16%(10937/13151).(1)The woman’s age,years of infertility,body mass index,fresh embryo/frozen embryo transfer,fertility method,woman’s smoking history,PCOS,male infertility factors and embryo transfer stage are all related to the ART fertility outcome(P<0.05).Early abortion: the male with low level of education,female age,male factors,the probability of early abortion of frozen embryo and blastocyst was increased(P < 0.05).Logistic regression analysis showed that age of female,BMI,transfer of fresh embryo/frozen embryo,and assisted pregnancy were independent risk factors for early abortion.After adjusting for basic information of both sexes,causes of infertility,stage of embryo transfer,etc.,the risk of early abortion was relatively increased with the increase of age and BMI,frozen embryo transfer,ICSI assisted pregnancy,etc.(3)Late abortion: the female with low level of education,female smoking,female with polycystic ovary syndrome,and female with polycystic ovary syndrome,frozen embryos and blastocyst stage embryos of late abortion female are more likely to occur.Logistic regression analysis showed that age,BMI,female education level,female smoking status,and whether the polycystic ovary syndrome late abortion are independent risk factors.(4)Ectopic pregnancy: the female with high level of education,male factors,IVF assisted pregnancy,fresh cycle transplantation and cleavage embryo transfer are more likely to have ectopic pregnancy.Logistics regression analysis found that female’s education level and assisted pregnancy method were independent risk factors for ectopic pregnancy.After adjusting for basic information of both male and female,infertility causes and embryo transfer stage,the risk of ectopic pregnancy was relatively increased for female with high education level and IVF assisted pregnancy.3.Correlation analysis of ART pregnancy complications(1)Univariate analysis of hypertension during pregnancy showed that female with older male age,longer infertility years,increased BMI,female household registration in Heilongjiang Province,polycystic ovary syndrome and single birth were more likely to suffer from hypertension during pregnancy.Logistics regression analysis found that BMI,polycystic ovary syndrome and pregnancy-assisted method were independent risk factors for hypertension during pregnancy.After adjusting for basic information of both male and female,causes of infertility and stage of embryo transfer,the risk of increased BMI,polycystic ovary syndrome and IVF-assisted pregnancy-assisted hypertension during pregnancy was relatively increased.(2)Univariate analysis of gestational diabetes mellitus: female with increased age,increased BMI,lower male education,fallopian tube factors,polycystic ovary syndrome and fresh cycle transplantation were more likely to develop gestational diabetes mellitus.Logistics regression analysis found that age,infertility,age,BMI,fresh cycle or refrigeration cycle transplantation,transplanted embryonic stages are independent risk factors for gestational diabetes,correction of male and female both parties after the basic information,cause of infertility,the transplanted embryonic stage,increasing age,BMI increased,fresh cycle transplantation,cleavage stage embryos for female.There is a relative increased risk of developing gestational diabetes.4.Analysis of ART offspring outcomeA total of 10,445 cycles were delivered,12,024 newborns were born,of which 1,729 cycles were premature,with a premature birth rate of 16.57%.1553 low birth weight infants(12.92%);45 cases of neonatal death,the incidence of 0.37%;16 cases of stillbirth,the incidence of 0.01%;6268 boys and 5756 girls were born,with a male-to-female ratio of ≈ 1:1.089.(1)Analysis of the influencing factors of premature birth.Univariate analysis showed that female with low educational level,polycystic ovary syndrome,IVF assisted pregnancy,fresh cycle transplantation,cleavage embryo transfer and twins were more likely to give birth prematurely.Logistics regression analysis found that BMI,polycystic ovary syndrome,fresh cycle transfer/freezing cycle and embryo transfer stage were independent risk factors for preterm birth.After adjusting for basic information of both male and female,causes of infertility,embryo transfer stage,etc.,people with increased BMI,polycystic ovary syndrome,fresh cycle transfer,and transfer of cleavage embryos are at increased risk of preterm birth.(2)Analysis of influencing factors of low birth weight.Univariate analysis showed that female with younger age,higher education,polycystic ovary syndrome,fresh embryo transfer and twin birth were more likely to have low birth weight.Logistic regression analysis showed that the number of years of infertility and polycystic ovary syndrome were independent risk factors for low birth weight infants.After adjusting the basic information of both male and female,the reasons for infertility and the stage of embryo transfer,the increase of the number of years of infertility and the risk of low birth weight infants in female with polycystic ovary syndrome were relatively increased.(3)Analysis of sex ratio at birthUnivariate analysis showed that IVF assisted pregnancy,frozen cycle transplantation and blastocyst transplantation were more likely to have boys.Logistic regression analysis showed that female BMI and the way of assisted pregnancy had a significant impact on the gender of newborns.After adjusting the basic information of both men and women,the causes of infertility and the situation of embryo transfer,the female BMI increased and the probability of IVF assisted pregnancy women having boys increased.(4)Types of fetal malformations.In 13151 cases,130 cases of fetal malformations,the incidence rate was 0.99%,of which9 fetuses combined with 2 kinds of malformations,the total number of malformations was 139.There were 69 cases of induced labor due to malformation and 61 cases of neonatal malformation.6 cases of fetal malformations were found in the central nervous system.8 cases of eyes,ears,face and neck;24 cases of cardiovascular circulatory system;12 cases of cleft lip and palate;3 cases of respiratory system;10 cases of gastrointestinal tract and digestive system;there were 8 cases of genitourinary system,24 cases of skeletal musculature system,25 cases of chromosomal abnormalities,and 19 cases of other abnormalities that were not followed up.5.Correlation analysis of the outcome of fresh embryo cycle assisted pregnancy(1)In the group of female transplanted with fresh embryos,perform logistics regression analysis on whether they suffer from gestational hypertension and gestational diabetes,and adjust the treatment plan,the woman’s age,the length of infertility,the woman’s body mass index,the method of fertility,and the woman’s culture It was found that with the increase of BMI,the risk of hypertension and gestational diabetes during pregnancy increased significantly.In addition,female with IVF assisted pregnancy and high education level had gestational diabetes.The risk is relatively increased.(2)Logistics regression analysis was performed on whether there were low birth weight infants,stillbirths,neonatal deaths and neonatal sex ratio.The risk of low birth weight of female with IVF assisted pregnancy was increased by adjusting treatment plan,female’s age,years of infertility,female’s body mass index,methods of assisted pregnancy,education level of both sexes,ethnic groups of both sexes.An increase in BMI in female is associated with a relative increase in the risk of neonatal death;the information had no effect on whether the baby was stillborn or the sex of the newborn.B.Evaluation of neurobehavior and growth of IVF / ICSI assisted offspring and analysis of its influencing factors1.236 cases were practically enrolled in ART,including 105 offspring after fresh cycle transplantation;131 offspring after frozen embryo cycle transplantation and 210 offspring of natural pregnancy(NC group)were included.2.SPSS independent sample t test was used to compare the basic information of the two groups.Between the two groups,parents’ age,parent’s BMI,twins,parent’s education,father’s household registration,parent’s smoking status,mother’s folic acid or vitamin supplementation before pregnancy,pregnancy complications There were differences in symptoms,delivery methods,weeks of premature delivery,feeding methods,whether there was other medical history,and whether the newborn was a low birth weight infant(P<0.05),no obvious difference was found between the rest.In addition,two groups of children’s developmental quotient have obvious difference,the large motor development,adaptive development quotient and language development quotient natural pregnancy group were higher than ART,fine motor development quotient and personal-social development quotient did not see obvious difference,the ART and NC groups has the influence factors of the development of suppliers in the multifactor linear regression analysis,after propensity matching score,There were no statistically significant differences in developmental quotients between the two groups(P> 0.05).3.Effects of different single factors on each development quotient(1)The total development quotient,gross motor development quotient,fine motor development quotient,language development quotient and person-social development quotient of girls were higher than those of boys(93.9±10.5 vs 91.3±14.0,97.2±11.2 vs94.1±12.1,96.7±11.1 vs 93.0±13.8,96.1±15.0 vs 88.9±15.8,99.8±9.7 vs 93.7±13),the difference was statistically significant(P < 0.05).(2)The language development quotient of children whose parents had college education or above was higher than that of children whose parents had college education or below(93.3±14.9 vs 90.1±16.9,93.3±15.0 vs 90.0±16.8),with statistical difference(P < 0.05).(3)The language development quotient of children with urban household registration was higher than that of children with rural household registration(93.2±15.1 vs 87.3±17.6,93.2±16.5 vs 88.1±13.3),and there was a statistical difference(P < 0.05).(4)There was statistical difference in the effect of maternal nutrition supplement on the fine motor development quotient of offspring(96.7±12.2 vs 93.7±11.9)(P < 0.05).(5)The influence of maternal pregnancy complications on language development quotient of offspring was statistically significant(93.1±14.5 vs 89.4±18.1)(P < 0.05).(6)The total development quotient score of full-term infants was significantly higher than that of premature infants(93.4%)± 12.8 vs 87.7 ± 6),and the indexes of development quotient(GMDQ 96.1 ± 11.5 vs 87.7 ± 11.6;The fine motor development quotient was 95.4 ± 13.0 vs91.0 ± 11.7;The adaptive development quotient was 93.2 ±13.6 vs 88.0 ± 11.8;Language development quotient 92.6 ± 15.9 vs 88.5 ± 15.7;Personal social development quotient 97.1 ± 12.3 vs 92.3 ± 9),there were significant differences(P < 0.05).(7)The total development quotient,fine motor development quotient,adaptive development quotient,language development quotient and personal-social development quotient of breast-fed children were higher than those of artificially fed children(93.1±12.4 vs 88.9±13.6,95.4±12.6 vs 91.6±12.3,92.9±13.7 vs 88.8±13.5,93.4±16.2 vs87.3±17.0,97.0±11.8 vs 92.4±14.7)were significantly different(P < 0.05),but there was no significant difference in gross motor development quotient between the two groups.(8)The fine motor development quotient and personal-social development quotient of the children who received neonatal rescue were lower than those who did not receive neonatal rescue(90.6±13.0 vs 95.0±12.8,91.4±12.1 vs 96.8±12.3),and the difference was statistically significant(P < 0.05).(9)The development quotient of emaciated children was higher than that of non-emaciated children(103.1±17.4 vs 92.2±12.6),and the adaptive development quotient(103.1±17.4 vs 92.0±13.2)was statistically significant(P < 0.05).(10)The total development quotient and adaptive development quotient(adaptive development quotient)of children whose mothers’ reproductive age was greater than 31.5years old were lower than those of children whose mothers’ reproductive age was less than 31.5 years old(91.0±13.1 vs 93.7±12.3,91.0±13.1 vs 93.5±13.6),with significant difference(P < 0.05).(11)The personal-social development quotient of children with developmental delay was lower than that of children without developmental delay(88.1±14.1 vs 96.5±12.2),with statistical difference(P < 0.05).(12)The developmental quotient of children with low body weight was higher than that of children without low body weight(15.2±2.6 vs 12.5±0.6).There were significant differences between adaptive development quotient(15.2±2.6 vs 13.2±0.6)and language development quotient(17.7±3.1 vs 15.6±0.8)(P < 0.05).(13)The developmental quotients of children born to obese,overweight,normal or lean mothers were 89.5±11.0,90.2±14.3,94.1±12.3,91.6±12.2,respectively.There were statistical differences between the groups(P<0.05).Developmental quotient,fine motor development quotient,adaptive development quotient and language development quotient were significantly different(P<0.05).(14)The number of pregnancies,nationality of both husband and wife,smoking history of both husband and wife,mother’s previous pregnancy history,mother’s supplementation of folic acid or vitamins before pregnancy,mother’s postpartum hemorrhage,mother’s mode of delivery,offspring ’s food and drug allergy,mother’s menarche age greater than or equal to 14 years old,father’s childbearing age greater than or equal to 33 years old,father’s weight and other factors,It had no effect on the development quotient of children.4.The influence of different intervention factors on development quotient in the art group.In the ART group,there was no significant difference in the development quotient of offspring by the induction scheme,the method of assisted pregnancy and the fresh cycle or frozen cycle transplantation.However,the total development quotient and person-social development quotient of children transplanted with blastocyst embryos were higher than those of children transplanted with blastocyst embryos(92.2±12.2 vs88.9±11.2,97.0±12.8 vs 94.0±10.2)with statistical significance(P < 0.05).Through multiple linear regression analysis Refrigeration cycle transplant the offspring of total development business and personal-social development quotient offspring than fresh cycle transplant,children always cleavage stage embryos development business and personal-social development quotient above offspring blastocyst stage embryos(P <0.05),the row of ART style,promoting has no effect on children development business.5.Multivariate analysis of total development quotient.Premature birth,underweight children,physical retardation of children,gender,maternal age of menarche and maternal BMI had statistically significant effects on development quotient(P < 0.05).The developmental quotient of premature and stunted children was lower than that of full-term and non-stunted children.The developmental quotient of female children and underweight children was higher than that of male children and non-underweight children.As the mother’s menarche age and BMI increase,the children’s development quotient decline.(1)Multivariate analysis of large motor development quotient.maternal BMI,children gender,preterm birth,father’s ethnicity and age of menarche had statistical significance on large motor development quotient(P < 0.05).With the increase of maternal age and BMI,the children’s gross motor quotient decreased;female children’s gross motor development quotient is higher than that of male children.The gross motor development quotient of premature infants and children whose fathers were Han nationality was lower than that of children whose fathers were ethnic minority.(2)Multivariate analysis of fine motor development quotient.Children’s gender,premature birth,and twins have statistically significant effects on the fine motor development quotient(P<0.05).The fine motor quotient of female children and twin children was higher than that of male children and single children,and that of premature children was lower than that of full-term children.(3)Multivariate analysis of adaptive development quotient.premature birth,low weight and growth retardation had significant effects on adaptive development quotient(P <0.05).The adaptive development quotient of preterm and stunted children is lower than that of full-term and non stunted children.The adaptive development quotient of underweight children is higher than that of non underweight children.(4)Multivariate analysis of language development quotient.The children’s gender,mother’s BMI,mother’s household registration,birth weight,children’s weight loss and children developmental retardation had a statistically significant effect on language quotient(P < 0.05).The language development quotient of female,children and underweight children is higher than that of males,children and children who are not underweight.The language development quotient of children whose mothers are rural residents and children with developmental delays is lower than that of children whose mothers are urban residents and non-developmental children.The mother’s BMI increased and the children’s language development quotient decreased,and the language development quotient increased with birth weight.(5)Multivariate analysis of individual social development quotient.Gender,premature birth,growth retardation and emaciation had statistically significant effects on personal social development quotient(P < 0.05).The personal social development quotient of female and emaciated children was higher than that of male and non-emaciated children,the personal social development quotient of premature and stunted children is lower than that of full-term and non stunted children.Conclusion:1.With the increase of the female age and BMI,the risk of early abortion and late abortion increased;frozen embryo transfer and ICSI assisted pregnancy,increased the risk of early abortion,and PCOS late abortion.2.Increased BMI,PCOS and IVF assisted pregnancy,increased risk of hypertension during pregnancy;increased age,increased BMI,fresh cycle transplantation,cleavage embryo transfer,fresh cycle IVF assisted pregnancy and female with high education level,pregnancy occurs.The risk of diabetes is increased.3.BMI and PCOS increased the risk of premature birth;the risk of low birth weight infants increased with the increase of infertility years,PCOS,IVF assisted pregnancy in fresh cycle and elderly female;increase of infertility years,BMI,age,double birth increased risk of neonatal death;BMI increases,and IVF helps to increase the probability of having a boy.4.There was no significant difference in the total development quotient,grand motor development quotient,fine motor development quotient,adaptive development quotient,language development quotient and personal-social development quotient between ART born offspring and those natural born(NC)offspring.ART had no significant negative effect on the neurobehavioral development of offspring.5.In terms of physical development,the offspring birth of the ART group was not lower than that of the natural pregnancy group(NC).ART itself had no negative effect on the physical development of offspring.6.Among the offspring born with ART,the total development quotient and person-social development quotient scores of cryo-cycle transplantation and cleavage embryo transplantation were relatively high.7.Preterm birth,physical retardation of children and increased BMI of mothers have negative effects on neurobehavioral development of offspring. |
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