title: Ovarian hyperstimulation and the in vitro fertilization procedure do not influence early neuromotor development; a history of subfertility does. Development of children born after ovarian superovulation induced by long-acting gonadotropin-releasing hormone agonist and menotropins, and by in vitro fertilization. Cognitive and motor development of 8-year-old children born after ICSI compared to spontaneously conceived children. Physical health at 5.5 years of age of term-born singletons after intracytoplasmic sperm injection: results of a prospective, controlled, single-blinded study. Outcome in children from cryopreserved embryos. Effect of pregnancy planning and fertility treatment on cognitive outcomes in children at ages 3 and 5: longitudinal cohort study Neurological sequelae in twins born after assisted conception: controlled national cohort study Growth, psychomotor development and morbidity up to 3 years of age in children born after IVF. Health of children born after ovulation induction. Fertility therapies, infertility and autism spectrum disorders in the Nurses' Health Study II. Health of Children Born as a Result of In Vitro Fertilization Psychological follow-up of children born after in-vitro fertilization. Infant outcome of 957 singletons born after frozen embryo replacement: the Danish National Cohort Study 1995-2006. Growth and development of children conceived by in vitro fertilization. A special path to parenthood: parent-child relationships in families giving birth to singleton infants through IVF. The Groningen assisted reproductive technologies cohort study: developmental status and behavior at 2 years. A prospective longitudinal study of the physical, psychomotor, and intellectual development of singleton children up to 5 years who were conceived by intracytoplasmic sperm injection compared with children conceived spontaneously and by in vitro fertilization. Medical and developmental outcome at 1 year for children conceived by intracytoplasmic sperm injection The Groningen ART cohort study: ovarian hyperstimulation and the in vitro procedure do not affect neurological outcome in infancy.
abstract: OBJECTIVE To evaluate specific effects of ovarian hyperstimulation , the in vitro procedure , and a history of subfertility on neuromotor development at 3 months of age . DESIGN Prospect i ve , cohort study . SETTING University Medical Center Groningen , The Netherl and s. PATIENT(S ) Singletons conceived after controlled ovarian hyperstimulation-IVF/intracytoplasmic sperm injection ( COH-IVF ; n = 68 ) or modified natural cycle-IVF/intracytoplasmic sperm injection ( MNC-IVF ; n = 57 ) , and naturally conceived singletons of subfertile couples ( NC ; n = 90 ) . Data from a reference population were available ( n = 450 ) . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) Quality of general movements ( GMs ) , classified as normal-optimal , normal-suboptimal , mildly abnormal , or definitely abnormal . Definitely abnormal GMs indicate brain dysfunction , mildly abnormal GMs normal but non-optimal brain function . RESULT ( S ) Mildly abnormal and definitely abnormal GMs were observed equally frequently in COH-IVF , MNC-IVF , and NC singletons . The three subfertile groups showed a reduction in GM quality , in particular more mildly abnormal GMs , in comparison with the reference population . CONCLUSION ( S ) Singletons born after IVF ( with or without ovarian hyperstimulation ) are not at increased risk for abnormal GMs compared with naturally conceived peers of subfertile parents . Mildly abnormal GMs occur more often in infants of subfertile parents than in the general population , suggesting that factors associated with subfertility rather than those related to IVF procedures may be associated with less-optimal early neurodevelopmental outcome . These results need confirmation through replication and follow-up at older ages The use of a gonodotropin-releasing hormone ( Gn-RH ) agonist in an in vitro fertilization ( IVF ) program raises the question of any influence on the physical , neurologic , and mental development of the children . We compared the development of children born after long-acting Gn-RH agonist treatment with that of children born after spontaneous pregnancies . Children from singleton pregnancies and > or = 28 months of age were examined by a pediatric neurologist and a psychologist who did not know to which group the children belonged . The General Cognitive Index test was used . Each group included 30 children . Five children cooperated only partly . Physical and neurologic findings were normal in all children , except that one in the group born after in vitro fertilization had diffuse hypotonia , attention-deficit hyperactivity disorder , and hyperactivity . The General Cognitive Index for the 26 children in the study group and the 29 children in the control group who fully cooperated were 102 + /- 13.3 and 106 + /- 13.5 , respectively ( p = 0.37 ) . The verbal perception , motor , and memory indexes were not significantly different . We conclude that the long-acting Gn-RH agonist had no clinical ly identifiable influence on the development of these children BACKGROUND As a continuation of two large-scale , multicentre studies on the development of 5-year-old ICSI children , we present results of the follow-up study undertaken on the cognitive and motor development of 8-year-old ICSI children . METHODS Developmental outcomes of 151 8-year-old singletons born through ICSI after 32 weeks of gestation were compared with those of 153 singletons of the same age born after spontaneous conception ( SC ) . Part of this population was seen in a cohort at the age 5 years . Outcome measures include Wechsler Intelligence Scale for Children-Revised ( WISC-R ) and Movement Assessment Battery for Children ( ABC ) . RESULTS Regarding intellectual functioning , ICSI children tend to obtain significantly higher total ( P < 0.01 ) , verbal ( P < 0.01 ) and performance ( P < 0.05 ) intelligence scores than SC children , nevertheless remaining in similar ranges . These effects are small ( Cohen 's d < 0.50 ) . High maternal educational level stayed in the regression as a factor accounting for some of the variance in total IQ between the groups . In terms of motor development , no significant differences were found between ICSI and SC children regarding overall motor skills , manual , balance and ball skills . CONCLUSION In this follow-up study , ICSI and SC children show a comparable cognitive and motor development until the age of 8 years OBJECTIVE To study the health of children born after ICSI and of spontaneously conceived control children at the age of 4 - 6 years . DESIGN Prospect i ve , controlled , blinded study . SETTING Tertiary-care center . PATIENT(S ) Two hundred seventy-six term-born singletons conceived by ICSI and 273 matched spontaneously conceived singletons at the age of 5.5 years . INTERVENTION(S ) Detailed physical examination , interview of the parents , and collection of data from each child 's examination booklet . MAIN OUTCOME MEASURE(S ) Biometrical data ; current health status ; acute , chronic and childhood illnesses ; hospitalizations ; and surgeries . RESULT ( S ) Detailed physical examination did not reveal any relevant differences between ICSI and spontaneously conceived children . There were no relevant differences regarding the incidence of childhood illnesses , acute or chronic illnesses , accidents , and surgeries up to the age of 5.5 years . However , a history of undescended testicles was found significantly more often in boys born after ICSI  ( 5.4 % vs. 0.7 % ) , with the consequence that they had significantly more urogenital surgery ( 19.2 % vs. 8.9 % ) . Significantly more ICSI children had been hospitalized ( 37.6 % vs. 27.2 % ) , although we did not find any specific reason for the increased hospitalization rate . CONCLUSION ( S ) Other than an increased risk of undescended testicles and therefore an increase in urogenital surgeries in ICSI boys , the physical health of ICSI children was comparable to that of spontaneously conceived children at the age of 5.5 years A cohort of 91 children from cryopreserved embryos and 83 control children who were conceived normally had their development assessed using the Griffiths 's scales of mental development . The controls ( 81 singletons and two twins ) of a similar age , sex , and social class were selected from siblings , cousins , and peers of the  cryopreserved embryo group ( 68 singleton , 20 twins , and three triplets ) . Children from cryopreserved embryos had a lower mean birth weight and mean gestational age and a higher proportion were born by caesarean section .  One child from the cryopreserved embryo group had Down 's syndrome , three had squints , and four had conductive hearing loss while in the control children , six had squints , and nine had conductive hearing loss . In both groups , including the child with Down 's syndrome , the mean Griffiths 's quotient was greater than the st and ard 100 . In the children from cryopreserved embryos , the singleton and multiple birth subgroups had statistically similar assessment results . The mean ( SD ) Griffiths 's quotient was 105.69 ( 13.55 ) in children from cryopreserved embryos and 108.18 ( 9.80 ) in controls at a chronological age of 25.08 ( 12.86 ) and 29.19 ( 14.65 ) months respectively . Overall , the development in children from cryopreserved embryos did not cause concern though formal testing had highlighted small differences compared with other children conceived normally and of a similar social class Objective To investigate how pregnancy planning , time to conception , and infertility treatment influence cognitive development at ages 3 and 5 . Design Prospect i ve population based cohort study . Setting Millennium Cohort Study in the United Kingdom . Participants 18 818 children recruited at 9 months and followed up at 3 and 5 years . 11 790 singletons with available data on pregnancy , cognitive outcomes , and confounders were included in analyses at age 3 and 12 136 at age 5 . Exposure measures Mothers reported whether the pregnancy was planned , and their feelings when first pregnant ; those in whom the pregnancy was planned provided time to conception , and details of any assisted reproductive technologies . The population was divided into “ unplanned ” ( unplanned and unhappy ) , “ mistimed ” ( unplanned but happy ) , “ planned ” ( planned , time to conception < 12 months ) , “ subfertile ” ( planned , time to conception ≥12 months ) , “ induced ovulation ” ( received clomiphene citrate ) , and “ assisted reproduction ” ( in vitro fertilisation or intracytoplasmic sperm injection ) . The “ planned ” group was the comparison group in all analyses . Outcome measures Three components of the British Ability Scales ( BAS II ) . Naming vocabulary assessed verbal ability at age 3 ; this test was repeated at age 5 with the picture similarities and pattern construction subscales , which measure non-verbal and spatial abilities . Results In unadjusted analyses , the scores on all scales in children from unplanned pregnancies were significantly lower than in those from planned pregnancies — for example , the difference in mean verbal ability score at age 3 was −4.8 ( 95 % confidence interval −6.0 to −3.7 ; P<0.05 ) , equivalent to an average delay of four months . After adjustment for sociodemographic factors these differences were attenuated : −0.3 ( −1.3 to 0.7 ) , equivalent to no delay . Children born after assisted reproduction performed consistently better in verbal ability tests ( 3.8 ( −0.2 to 7.9 ) at age 3 and 3.5 ( 0.2 to 6.8 ) at age 5 ) , which suggests that on average these children are three to four months ahead ; this difference did not completely disappear with adjustment for confounders . Children born after infertility treatment had lower mean scores in non-verbal tests ( −1.2 ( −4.1 to 1.6 ) after assisted reproduction and −1.5 ( −3.5 to 0.4 ) after induced ovulation ) and in spatial ability tests ( −2.7 ( −6.9 to 1.6 ) after assisted reproduction ) , though the differences were not significant . Conclusions Pregnancy planning , subfertility , or assisted reproduction do not adversely affect children ’s cognitive development at age 3 or 5 . The differences observed in the unadjusted analyses are almost entirely explained by marked inequalities in socioeconomic circumstances between the groups Abstract Objective To compare neurological sequelae in twins born after assisted conception with singletons after assisted conception and naturally conceived twins and to assess neurological sequelae in children conceived after in vitro fertilisation ( IVF ) compared with intracytoplasmic sperm injection ( ICSI ) .  Design Controlled , national register based , cohort study . Participants Twins ( n = 3393 ) and singletons ( n = 5130 ) conceived by using assisted reproductive technologies and naturally conceived twins ( n = 10 239 ) born in Denmark between 1995 and 2000 . The children 's age at time of follow up was 2 - 7 years . Data sources Children were identified by cross linkage of the national medical birth registry and the national registry for in vitro fertilisation . Neurological and psychiatric diagnoses were retrieved from the national patients ' registry and the Danish psychiatric central registry . Main outcome measures Neurological sequelae , defined as cerebral palsy , mental retardation , severe mental developmental disturbances , and retarded psychomotor development . Further we made separate analyses on the specific cerebral palsy diagnosis . Results The crude prevalence rates per 1000 of neurological sequelae in twins and singletons after assisted conception and in naturally conceived twins were 8.8 , 8.2 , and 9.6 , and of cerebral palsy 3.2 , 2.5 , and 4.0 , respectively . In twins after assisted conception compared with control twins , the odds ratios of neurological sequelae and specifically of cerebral palsy , adjusted for child sex and year of birth , were 0.9 ( 95 % confidence interval 0.6 to 1.4 ) and 0.8 ( 0.4 to 1.6 ) , respectively . The corresponding odds ratios for twins after assisted conception compared with singletons after assisted conception were 1.1 ( 0.7 to 1.7 ) for neurological sequelae and 1.3 ( 0.6 to 2.9 ) for cerebral palsy . The odds ratio of neurological sequelae in children conceived by ICSI was 0.9 ( 0.5 to 1.7 ) ν children conceived by IVF . Conclusions Twins from assisted conception have a similar risk of neurological sequelae as their naturally conceived peers and singletons from assisted conception . Children born after ICSI have the same risk of neurological sequelae as children born after IVF BACKGROUND To examine the long-term child outcome  after IVF until the age of 3 years in Northern Finl and , we conducted a population -based cohort study . METHODS First , a cohort of 299 IVF children born in 1990 - 1995 was compared with a cohort of 558 controls representing the general population in terms of a multiple birth rate of 1.2 % , r and omly chosen from the Finnish Medical Birth Register ( FMBR ) and matched for sex , year of birth , area of residence , parity , maternal age and social class ( full sample analyses ) . Second , IVF singletons ( n = 150 ) were compared with singleton controls ( n = 280 ) . Third , a plurality matched control cohort ( n = 100 ) for IVF twins ( n = 100 ) was r and omly chosen , matched as above , from the FMBR and analysed separately . Infant mortality rate was compared with the national rate from the FMBR . RESULTS Infant mortality in the IVF group was > 2-fold higher compared to the national rate in the general population . The risk ( OR , 95 % CI ) of low weight and height , below the lowest quartile , at 1 year of age ( 1.6 , 1.1 - 2.2 ; 1.6 , 1.1 - 2.4 ) and 2 years of age ( 1.5 , 1.1 - 2.4 ; 1.7 , 1.2 - 2.5 ) was significantly higher in the IVF group when compared with the general population control group . No statistically significant differences were found in the psychomotor development between the cohorts . Cumulative incidence of different diseases up to 3 years of age was significantly higher among IVF children in the full sample and singleton analyses ( OR , 95 % CI : 2.3 , 1.7 - 3.2 ; 2.1 , 1.3 - 3.3 respectively ) especially regarding respiratory diseases ( 3.5 , 1.9 - 6.5 ; 3.1 , 1.0 - 9.4 ) and diarrhoea ( 3.7 , 2.2 - 6.2 ; 5.7 , 2.6 - 12.7 ) , but not in twin comparisons . CONCLUSIONS The growth of IVF children was behind that of control children during the first 3 years of life , but their psychomotor development was similar . Their postnatal health was worse , probably reflecting the problems in the neonatal period OBJECTIVE To study the health of children born after ovulation induction ( OI ) . DESIGN Nationwide register-based study . SETTING The OI children were followed up to the age of 4 years and compared with other children . PATIENT(S ) The OI children ( N = 4,467 ) . Two control groups : all other children ( excluding children born after IVF , N = 190,398 ) and a r and om sample of those children ( n = 26,877 ) . INTERVENTION(S ) Ovulation induction treatment in ordinary practice . MAIN OUTCOME MEASURE(S ) Mortality rates and adjusted odds ratios for perinatal outcomes , hospitalizations , health-related benefits , and long-term medication use . RESULT ( S ) A total of 12 % of OI and 2 % of control children were multiples . Even after stratifying for multiplicity and adjusting for the available confounding factors ( region , smoking , maternal age , socioeconomic position , and parity for perinatal health and mother 's socioeconomic position for other indicators ) , most indicators showed worse health among OI children compared with control children . The OI children had poorer perinatal health and more episodes of long hospitalization than the control children . Singleton OI children had more long-term illnesses in childhood , as measured by child disability allowance , long-term medication use , and hospital care episodes . CONCLUSION ( S ) Either OI treatment or the reasons for the treatment increase the risk of health problems in early childhood BACKGROUND An increasing number of women are utilizing fertility treatments , but little is known about their relation to autism spectrum disorders ( ASD ) . METHODS To determine the association between  maternal fertility therapy use and risk of having a child with ASD  , we conducted a nested case-control study within the Nurses ' Health Study II ( n = 116,430 ) . Maternally reported diagnoses of ASD were confirmed through a supplementary question naire and , in a subgroup , the Autism Diagnostic Interview-Revised . Controls were r and omly selected by frequency matching to case children 's year of birth . Associations were examined by self-reported infertility and type of therapy using conditional logistic regression . RESULTS In all , 9 % of the 507 cases and 7 % of 2,529 controls indicated  fertility therapy  use for the index pregnancy . No significant associations with self-reported fertility therapies or history of infertility were seen in primary analyses . In subgroup analyses of women with maternal age ≥ 35 years ( n = 1,020 )  , artificial insemination  was significantly associated with ASD ; ovulation inducing drug ( OID ) use was significantly associated in crude but not adjusted analyses ( odds ratio 1.81 , 95 % CI 0.96 - 3.42 ) . Results were similar by diagnostic subgroup , though within the advanced maternal age group , OID and artificial insemination  were significantly associated with Asperger syndrome and pervasive developmental disorder not-otherwise specified , but not autistic disorder . CONCLUSION [ corrected ] Assisted reproductive therapy and history of infertility did not increase risk of having a child with ASD in this study . However , the associations observed  with OID and artificial insemination  among older mothers , for whom these exposures are more common , warrant further investigation OBJECTIVE . The purpose of this study was to use nationwide registries to examine the health of children up to 4 years of age who were born as a result of in vitro fertilization . METHODS . Children born after in vitro fertilization ( N = 4559 ) from 1996 to 1999 were monitored until 2003 . Two control groups were selected from the Finnish Medical Birth Register as follows : all other children ( excluding children born after ovulation induction ) from the same period ( N = 190398 , for study of perinatal health and hospitalizations ) and a r and om sample of those children ( n = 26877 , for study of health-related benefits ) . Mortality rates and odds ratios for perinatal outcomes , hospitalizations , health-related benefits , and long-term medication use were calculated . RESULTS . Although the health of most in vitro fertilization children was good , such children had more health problems than other children . A total of 35.7 % of in vitro fertilization children and 2.2 % of control children were multiple births , and the health of multiple births was worse than that of singletons . Perinatal outcomes of in vitro fertilization children were worse and hospital episodes were more common than among control children . Risks for cerebral palsy and psychological and developmental disorders were increased . Among in vitro fertilization singletons , worse results for perinatal outcomes and hospitalizations , but no increased risk for specific diseases , were found . The health of in vitro fertilization multiple births was comparable to the health of control multiple births . CONCLUSIONS . Reducing the number of transferred embryos would improve the health of in vitro fertilization children . Additional studies are needed to explain the poorer health of in vitro fertilization singletons , as well as follow-up studies to examine the health of in vitro fertilization children from 4 years onward We have studied from birth up to the 3rd year the psychological attitude of 33 in-vitro fertilization ( IVF ) children compared to two other groups : children born after ovarian stimulation without IVF ( n = 33 ) and children conceived naturally ( n = 33 ) during the same period . Fourteen children , born by oocyte donation , were also studied by the same methodology . In the IVF group , we found some feeding difficulties and sleep disorders in the infants at 9 months and some signs of depression in mothers . All these symptoms disappeared afterwards . The development of all the children is satisfactory and the relationship with their mother is excellent . In this preliminary study , we conclude that the method of assisted reproduction has no bad influence on the psychomotor development of these children OBJECTIVE To examine infant outcome of singletons born after cryopreservation of embryos ( Cryo ) .  DESIGN National population -based controlled follow-up study . SETTING Denmark , 1995 - 2007 . PATIENT(S ) The study population was 957 Cryo singletons ( Cryo-IVF , n=660 ; Cryo-ICSI , n=244 ; Cryo-IVF/-ICSI , n=53 ) . The first control group was all singletons born after fresh IVF or intracytoplasmic sperm injection ( ICSI ) during the same period ( IVF  , n=6904 ; ICSI , n=3425 ) . The second control group comprised a r and om sample of non-assisted reproductive technology ( ART ) singletons ( n=4800 ) . INTERVENTION(S ) All observations were obtained from national registers . MAIN OUTCOME MEASURE(S ) Low birth weight ( LBW ; < 2500 g ) , preterm birth ( PTB ; < 37 weeks ) , congenital malformations , mortality , and morbidity . RESULT ( S ) Birth weight was higher in Cryo ( mean=3578 g , SD=625 ) versus fresh ( mean=3373 g , SD=648 ) and in Cryo versus non-ART ( mean=3537 g , SD=572 ) , and this was also the case for first birth only . Lower adjusted risk of LBW ( odds ratio [OR]=0.63 ; 95 % confidence interval [ CI ] , 0.45 - 0.87 ) and PTB ( OR=0.70 ; 95 % CI , 0.53 - 0.92 ) was observed in Cryo versus fresh . Similar LBW and PTB rates were observed when comparing Cryo with non-ART , but the perinatal mortality rate was doubled in Cryo ( 1.6 % ) compared with non-ART ( 0.8 % ) singletons , and the adjusted risks of very preterm birth ( < 34 weeks ) and neonatal admittance were also significantly increased . No significant differences in the prevalence rates of birth defects , neurological sequelae , malignancies , and imprinting-related diseases were observed between the Cryo and the two control groups . However higher malformation and cerebral palsy rates were observed in the total Fresh vs. non-ART group . CONCLUSION ( S ) Cryo singletons have better neonatal outcome than offspring after fresh ET but poorer compared with non-ART singletons To assess the physical and mental development of infants born after in vitro fertilization ( IVF )  , we performed a general physical and developmental examination ( Bayley and Stanford-Binet scales ) on a cohort of 116 IVF children , conceived and born at our institution between February 1985 and March 1989 , and on 116 non-IVF matched controls . Study and control groups were each composed of 66 singletons , 19 pairs of twins and 4 sets of triplets , whose age at examination ranged from 12 to 45 months . The developmental indices of IVF infants were within the normal range and did not differ from those of their matched controls . The indices were positively correlated to gestational age , birth weight , head circumference at birth and at examination , and mother 's education . Mean birth weight , gestational age , and birth weight percentile of IVF infants were lower than the mean of the healthy population . Mean percentiles of weight and length at examination ( mean age 22.4 months ) were equally low but did not differ from those of the matched controls . However , mean percentiles of head circumference at birth and at examination compare well with the normal mean , both in IVF and control groups . Twins and triplets ( IVF and controls ) had significantly lower physical and mental indices as compared to singletons Infertility and its treatment are increasingly viewed as public issues as well as a private concern . Treatments such as IVF draw on public re sources and pose psychological and ethical dilemmas for the community . The current paper integrates findings from a prospect i ve longitudinal study that assessed the quality of parenting in families conceiving through IVF  from an attachment theory perspective . Seventy families who conceived singleton infants through IVF and a naturally conceiving control group of 63 couples were seen during pregnancy and at 4 and 12 months postpartum . Two observational procedures were used to assess maternal sensitivity to the baby , infant responsiveness and security of attachment at 4 and 12 months respectively . There were no IVF control group differences in maternal sensitivity at 4 months or in security of attachment at 12 months . Implication s of the findings for clinicians and contemporary controversies requiring further research are discussed OBJECTIVE To evaluate whether children 's  cognitive and psychomotor development and behavior at 2 years are affected by ovarian hyperstimulation and the IVF laboratory procedures or subfertility . DESIGN Prospect i ve longitudinal cohort study . SETTING University Medical Center Groningen , the Netherl and s. PATIENT(S ) Singletons born after controlled ovarian hyperstimulation (COH)-IVF ( n=66 ) and modified natural cycle-IVF ( n=56 ) , singletons born to subfertile couples who conceived naturally ( subfertile-naturally conceived , n=87 ) , and a reference group of 101 2-year-old singletons born to fertile couples . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) Bayley Scales of Infant Development and Achenbach Child Behavior Checklist . RESULT ( S ) Mental and psychomotor development and behavioral outcome in COH-IVF , modified natural cycle-IVF , and subfertile-natural cycle groups was not different . Developmental outcome and behavior of the subfertile groups were largely similar to those of the fertile reference group . Nevertheless , the subfertile groups scored higher on the scale of anxious-depressed behavior than the reference group . CONCLUSION ( S ) This present relatively small study found no differences in cognitive and psychomotor development and behavior at 2 years in children born after COH-IVF or modified natural cycle-IVF or naturally conceived children of subfertile parents . Replication of the study is needed before firm conclusions can be drawn . Furthermore , long-term follow-up is needed to confirm these findings in older children OBJECTIVE To assess the somatic , psychomotor , and intellectual development of children conceived through intracytoplasmic single sperm injection ( ICSI )  over the whole preschool period . DESIGN Prospect i ve , controlled , cohort study . SETTING Fertility clinic in Brussels , Belgium . PATIENT(S ) Sixty-six ICSI-conceived children prospect ively compared with 52 IVF-conceived and 59 spontaneously conceived children . All children were full-term singletons . INTERVENTION(S ) Home visits by a trained psychologist . St and ardized interviews . Assessment s using the revised Brunet-Lézine scale and the revised Wechsler preschool and primary scale of intelligence . MAIN OUTCOME MEASURE(S ) Physical growth and general health . Formal developmental and intellectual assessment s. RESULT ( S ) Children conceived by ICSI were healthy : no significant differences appeared in the incidence of combined congenital malformations ( 11.3 % ) , health problems ( 44.1 % ) , surgical interventions ( 18.6 % ) , and hospitalizations ( 6.8 % ) , nor for the developmental assessment s ( mean developmental quotient at 9 months : 93.9 ; at 18 months : 102.0 ) . For the intellectual assessment s , the between-group differences disappeared when adjusted for levels of parental education ( mean intelligence quotient at 3 years : 97.0 ; at 5 years : 103.3 ) . CONCLUSION ( S ) This pilot study shows that throughout the preschool period , ICSI-conceived children have psychomotor and intellectual development similar to that of IVF-conceived and spontaneously conceived children . These conclusions need to be confirmed by multicenter studies BACKGROUND Intracytoplasmic sperm injection ( ICSI ) was introduced as a new form of in-vitro fertilisation ( IVF ) in 1993 and is now accepted as the treatment of choice for severe male infertility in many centres around the world . However , there is little information about the long-term outcome of children conceived by ICSI .  We aim ed to find out the medical and developmental outcome of children conceived by ICSI  at age 1 year . METHODS In this prospect i ve study , we compared the medical and developmental outcome at 1 year of 89 children conceived by ICSI with 84 children conceived by routine IVF , and with 80 children conceived naturally .  Formal developmental assessment was done with Bayley Scales of Infant Development ( 2nd edition ) from which a mental development index ( MDI ) was derived . FINDINGS There was no significant difference in the incidence of major congenital malformations or major health problems in the first year of life . However , the mean Bayley MDI was significantly lower for the children conceived by ICSI than for the children conceived by routine IVF or naturally ( 95.9 [ SD 10.7 ] , 101.8 [ 8.5 ] , and 102.5 [ 7.6 ] , respectively , p < 0.0001 ) . 15 ( 17 % ) of 89 children conceived by ICSI experienced mildly or significantly delayed development ( MDI < 85 ) at 1 year compared with two ( 2 % ) of the 84 children conceived by IVF and one ( 1 % ) of the 80 children conceived by natural conception ( p < 0.0001 ) . INTERPRETATION Although most children conceived by ICSI are healthy and develop normally , there is an increased risk of mild delays in development at 1 year when compared with children conceived by routine IVF or conceived naturally . These findings support the need for ongoing developmental follow-up of children conceived by ICSI to see whether they are at increased risk of intellectual impairment or learning difficulties at school age BACKGROUND Due to the growing number of children born following assisted reproduction technology  , even subtle changes in the children 's health and development are of importance to society at large . The aim of the present study was to evaluate the specific effects of ovarian hyperstimulation and the in vitro procedure on neurological outcome in 4 - 18-month-old children . METHODS In this prospect i ve assessor-blinded cohort study , we included singletons born following controlled ovarian hyperstimulation in vitro fertilization ( IVF ) or intracytoplasmic sperm injection ( ICSI ) ( COH-IVF ; n = 68 ) or modified natural cycle-IVF/ICSI ( MNC-IVF ; n = 57 ) or naturally conceived singletons of subfertile couples ( NC ; n = 90 ) . Children were assessed with st and ardized , age-specific and sensitive neurological assessment s ( TINE and Hempel assessment ) at 4 , 10 and 18 months . Neurological examination result ed in a neurological optimality score ( NOS ) , a fluency score and a clinical neurological classification . Fluency of movements is easily affected by neurological dysfunction and is therefore a sensitive measure for minimal changes in neuromotor development . RESULTS The NOS and the fluency score were similar in COH-IVF , MNC-IVF and NC children . None of the children showed major neurological dysfunction and rates of minor neurological dysfunction at the three ages were not different between the three conception groups . CONCLUSIONS We found no effects of ovarian hyperstimulation or the in vitro procedure itself on neurological outcome in children aged 4 - 18 months . The findings of our study are reassuring , nevertheless it should be kept in mind that subtle neurodevelopmental disorders may emerge when children grow older . Continuation of follow-up in older and larger groups of children is therefore still needed
target: RESULT ( S ) For infants , studies on psychomotor development showed no deficits , but few investigated cognitive or behavioral development .
  Studies on toddlers generally reported normal cognitive , behavioral , socio-emotional , and psychomotor development .
  For children in middle childhood , development seems comparable in children born after assisted reproduction and controls , although fewer studies have been conducted with follow-up to this age .
  ( S ) It may tentatively be concluded that the neurodevelopment of children born after  fertility treatment  is overall comparable to that in children born after spontaneous conception
background: OBJECTIVE To systematic ally review the existing literature on neurodevelopmental outcomes in children born after medically assisted reproduction  compared with those of children born after spontaneous conception .