***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 Long-term follow-up studies on the health of children born after assisted reproduction technologies  are m and atory . Vision and hearing are the most important senses that continue to develop during childhood . There are few reports on vision and hearing in preschool children born after assisted conception . This prospect i ve controlled blinded follow-up study examined 276 term-born singleton intracytoplasmic injection ( ICSI ) children and 273 spontaneously conceived controls at a mean age of 5.5 years and performed detailed  vision and hearing test and clinical ly examined eyes and ears . There was no significant difference between ICSI and control children regarding the occurrence of vision or hearing impairments . Unsurprisingly , children with abnormalities in otoscopy were more likely to have an abnormal hearing test compared with children without abnormalities . Only 8.5 % of ICSI parents and 25.4 % of control parents whose children showed an abnormal hearing test knew about the hearing problems of their child . In conclusion , there was no difference in the development of hearing and vision in ICSI children and spontaneously conceived controls . But only few parents knew about hearing problems of their child after undergoing routine screening examinations . Parental interviews would therefore not be sufficient in order to assess vision and hearing in follow-up studies Recent studies have given conflicting results regarding growth in children born following assisted reproductive treatments up to the age of 18years . It has been suggested that children conceived via IVF may be taller than naturally conceived children and that this may due to subtle epigenetic alteration of imprinted genes as a result of the IVF process . A prospect i ve match-controlled study was performed to investigate the growth of children born in the UK following st and ard IVF and intracytoplasmic sperm injection ( ICSI ) up to the age of 12years . The study assessed 143 IVF and 166 ICSI children with 173 matched naturally conceived controls . Primary end-points were height and weight at various time points : birth , 5years , 7 - 9years and 10 - 12years . In addition , head circumference was assessed at birth . No significant differences were observed regarding head circumference , height and weight between the three groups at any of the time points . In conclusion , this preliminary study provides reassuring information regarding the growth of  IVF and ICSI children up to 12years . Further studies must continue to investigate the growth and other outcomes in assisted-conception children as they develop through puberty into early adulthood 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 Background : There is accumulating evidence that in vitro conception in humans may be associated with adverse health outcomes later in life . It has been proposed that suboptimal early life conditions may ‘ program ' key endocrine systems . A disturbance of the hypothalamic-pituitary-adrenal ( HPA ) axis leading to alterations in cortisol secretion in the offspring may be such a mechanism . To date , no data on cortisol levels in children conceived by intracytoplasmic sperm injection ( ICSI )  are available in the literature . Methods : In this cross-sectional study , salivary cortisol known as a key regulator of metabolism was measured and results were compared between 201 pubertal ICSI children and 196 spontaneously conceived ( SC ) counterparts . Results : ICSI females had lower mean salivary cortisol levels ( 9.0 µg/l ; 95 % CI 8.1 - 9.9 ) than SC females ( 10.6 µg/l ; 95 % CI 9.7 - 11.5 ; p = 0.01 ) . This difference remained after adjusting for current characteristics , early life factors and maternal characteristics . In ICSI males , no difference in cortisol levels was found in comparison with the SC group . Conclusion : In our study , 14-year-old female but not male ICSI teenagers were found to have lower salivary cortisol concentrations in comparison with SC peers . However , before definite conclusions can be drawn , our results should be completed by longitudinal sampling The aim of this prospect i ve follow-up study of children born after intracytoplasmic sperm injection ( ICSI )  was to compile data on karyotypes , congenital malformations , growth parameters and developmental milestones in order to evaluate the safety of this new technique . The study design included karyotyping of the parents and their agreement to genetic counselling and prenatal diagnosis and it was based on a physical examination of the child at the Centre for Medical Genetics at the ages of 2 months , 1 year and at 2 years , where major and minor malformations and psychomotor evolution are recorded . Here we describe the first 57 children born from 40 ICSI pregnancies with epididymal spermatozoa ( group 1 ) , the first 50 children born from 34 ICSI pregnancies with testicular spermatozoa ( group 2 ) and the first 58 children born from 48 pregnancies after replacement of cryopreserved ICSI embryos ( group 3 ) . Parental karyotypes were obtained from only 72/246 ( 29 % ) parents and were all normal .  Prenatal karyotypes were determined for a total of 70 sample s ( 40 % ) : 21 in group 1 , 15 in group 2 and 34 in group 3 . In this last group 2 abnormal 47,XXY karyotypes ( 5.8 % ) and no structural aberrations were found . This increase in de-novo sex-chromosomal aberrations has already been described with regard to the first 877 children born after ICSI carried out at our Centre and is probably linked directly to the characteristics of the infertile men treated rather than to the ICSI procedure itself . Major malformations , defined as those causing functional impairment or requiring surgical correction , were observed in four children : two born after ICSI with epididymal spermatozoa , one after ICSI with testicular spermatozoa and one after ICSI and cryopreservation . No particular malformation was disproportionally frequent . In the follow-up examinations at 2 months ( 107/161 or 66.5 % ) and at 1 year ( 37/161 or 22.9 % ) , no additional anomalies were observed . Lost for follow-up rate at 2 months was 33.5 % . These observations on a limited number of children do not suggest a higher incidence of diseases linked to imprinting , nor do they suggest a higher incidence of congenital malformations . These observations are still limited in number and should be further completed by others and by collaborative efforts . In the meanwhile patients should be told about the available data before any treatment : there appears to be some risk of transmitted chromosomal aberrations , of de-novo , mainly sex-chromosomal aberrations and of transmitting fertility problems to the offspring . Patients should also be reassured that until now there seems to be no higher incidence of congenital malformations in children born after ICSI with epididymal or testicular spermatozoa or after replacement of ICSI embryos STUDY QUESTION Does ovarian hyperstimulation , the in vitro procedures required for in vitro fertilization (IVF)/ intracytoplasmic sperm injection or the combination of both , affect the  neurological outcome  of 4-year-old singletons ? SUMMARY ANSWER Ovarian hyperstimulation , the in vitro procedure and the combination of both , were not associated with the worse neurological outcome in 4-year-old singletons . WHAT IS KNOWN ALREADY Assisted reproduction techniques ( ARTs ) are not associated with neurological dysfunction during the first post-natal years ; however , effects on the long-term neurological outcome are still inconclusive . An increased time to pregnancy ( TTP , a proxy for the severity of subfertility ) has been associated with a less optimal neurological condition at age 2 . The present study focuses on the neurodevelopmental outcome of 4-year-old ART-offspring . STUDY DESIGN , SIZE , DURATION Longitudinal , prospect i ve follow-up study . PARTICIPANTS , SETTING , METHODS Four-year-old singletons born to subfertile parents ( subfertile group , n = 195 ) , including singletons born after controlled ovarian hyperstimulation IVF ( COH-IVF , n = 63 ) , modified natural cycle IVF ( MNC-IVF , n = 53 ) and natural conception ( Sub-NC , n = 79 ) . Data on underlying cause of subfertility and TTP were present . In addition , we assessed newly recruited 4-year-old singletons born to fertile parents after natural conception ( reference group , n = 98 ) . Neurological development was evaluated with the neurological examination according to Hempel , result ing in a neurological optimality score ( NOS ) , a fluency score and the occurrence of the clinical ly relevant form of minor neurological dysfunction ( complex MND ) . The primary outcome was the fluency score , as fluency of movements is easily reduced by subtle brain dysfunction . Data were analysed with univariable and multivariable regression analyses , in which special attention was paid to sex differences in the neurological outcome . MAIN RESULTS AND THE ROLE OF CHANCE The fluency score , NOS and the prevalence of complex MND were similar in COH-IVF , MNC-IVF and Sub-NC children . The neurological condition of children born to subfertile parents was similar to that of children of fertile parents and was independent of the underlying cause of subfertility . No statistically significant associations were found between TTP and the fluency score and NOS . However , a positive correlation was found between TTP and the prevalence of complex MND ( TTP in years , adjusted odds ratio [ OR ] [ 95 % confidence interval , CI ] : 1.207 [ 1.038 to 1.404 ] , P = 0.014 ) ; a correlation which could be attributed to girls , in whom an evident positive correlation was present ( adjusted OR [ 95 % CI ] : 1.542 [ 1.161 to 2.047 ] , P = 0.003 ) . A similar association was absent in boys . LIMITATIONS , REASONS FOR CAUTION The prospect i ve design of our study and small post-natal attrition rate ( 9.3 % ) reduced potential selection bias based on the child 's development or health . The assessors were blind to the mode of conception , except for the group of children born to fertile parents , which was newly recruited . The study lacks sufficient power to conclude firmly that increased TTP is associated with a higher prevalence of complex MND . WIDER IMPLICATION S OF THE FINDINGS Our study suggests that the severity of subfertility , rather than its simple presence or components of IVF treatment , affects the neurological outcome . Moreover , girls may be neurologically more vulnerable for the effect of severity of subfertility . The finding that the severity of subfertility may be the decisive factor rather than the presence of a history of subfertility per se corro 
    Output:
    
Growth , vision , and hearing of ICSI and SC offspring also appear comparable , although important differences in general physical health , and particularly metabolic and reproductive health have been described , including recently poorer semen quality among ICSI-conceived young adult men compared to SC peers .
Whilst neurodevelopment , growth , vision , and hearing appear similar between ICSI and SC children , evidence suggests differences in general physical health , and metabolic and reproductive endpoints .