Mental, psychomotor, neurologic, and behavioral outcomes of 2-year-old children born after preimplantation genetic screening: follow-up of a randomized controlled trial. Assessment of vision and hearing in children conceived spontaneously and by ICSI: a prospective controlled, single-blinded follow-up study. Neurological sequelae in twins born after assisted conception: controlled national cohort study Fertility treatment and risk of childhood and adolescent mental disorders: register based cohort study The Groningen ART cohort study: ovarian hyperstimulation and the in vitro procedure do not affect neurological outcome in infancy. Effect of pregnancy planning and fertility treatment on cognitive outcomes in children at ages 3 and 5: longitudinal cohort study Growth of children conceived by IVF and ICSI up to 12years of age. Neuromotor development and mental health at 5.5 years of age of singletons born at term after intracytoplasmatic sperm injection ICSI: results of a prospective controlled single-blinded study in Germany. Pregnancy course and outcome after intracytoplasmic sperm injection: a controlled, prospective cohort study. Neurological Condition of Infants Born After In Vitro Fertilization With Preimplantation Genetic Screening Increased time to pregnancy is associated with less optimal neurological condition in 4-year-old singletons, in vitro fertilization itself is not. Cognitive and psychomotor development of 5- to 6-year-old singletons born after PGD: a prospective case-controlled matched study. Psychological follow-up of children born after in-vitro fertilization. Birth defects among children born to a population occupationally exposed to pesticides in Colombia. Commentary on the Cochrane Review of acupuncture and assisted conception. The Groningen assisted reproductive technologies cohort study: developmental status and behavior at 2 years. Four-year follow-up of children born to women in a randomized trial of prenatal DHA supplementation. Cognitive and motor development of 8-year-old children born after ICSI compared to spontaneously conceived children. Mental health and developmental outcomes for children born after ART: a comparative prospective study on child gender and treatment type. Children born after assisted fertilization have an increased rate of major congenital anomalies. The effect of preimplantation genetic screening on neurological, cognitive and behavioural development in 4-year-old children: follow-up of a RCT. Advanced reproductive age and fertility. Language assessment of non-handicapped twins at 5 years of age.
OBJECTIVE To evaluate the effect of preimplantation genetic screening ( PGS ) on neurodevelopmental outcomes in children . DESIGN Prospect i ve , assessor-blinded , follow-up study of children born to women r and omly assigned to in vitro fertilization or intracytoplasmic sperm injection ( IVF/ICSI ) with or without PGS .  SETTING University Medical Center , Groningen , and Academic Medical Center , Amsterdam , the Netherl and s. PATIENT(S ) Fifty-four PGS children and 77 controls .  INTERVENTION(S ) PGS . MAIN OUTCOME MEASURE(S ) Mental , psychomotor , neurologic , and behavioral outcomes in 2-year-old children  as measured with the Bayley Scales of Infant Development , the Hempel neurologic examination , and the Child Behavior Check List . RESULT ( S ) The mental , psychomotor , and behavioral outcomes at 2 years in children born after IVF with and without PGS were similar overall . The PGS children showed lower neurologic optimality scores than the control children . Scores on all tests were within the normal range . CONCLUSION ( S ) Conception with PGS does not seem to be associated with impaired mental , psychomotor , or behavioral outcomes by age 2 . However , the lower neurologic optimality scores found in the PGS children may signal less favorable long-term neurologic outcomes in PGS children . Our findings stress the need for safety evaluations with new assisted reproductive techniques before large-scale implementation 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 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 Objective To assess the mental health of children born after fertility treatment  by comparing their risk of mental disorders with that of spontaneously conceived children . Design Prospect i ve register based cohort study . Setting Nationwide register based information from Danish National Health Registers cross linked by a unique personal identification number assigned to all citizens in Denmark . Participants All children born in Denmark in 1995 - 2003 with follow-up in 2012 when the children were aged 8 - 17 ; 33 139 children were conceived after fertility treatment and 555 828 children were born after spontaneous conception .  Main outcome measures Absolute risks and hazard ratios for overall and specific mental disorders estimated with adjustment for potential confounding variables . Estimated association between the risk of mental disorders and subtypes of procedures , hormone treatments , gamete types , and cause of infertility . Results The risk of mental disorders in children born after in vitro fertilisation or intracytoplasmic sperm injection was low , and was no higher than in spontaneously conceived children , except for a borderline significant increased risk of tic disorders ( hazard ratio 1.40 , 95 % confidence interval 1.01 to 1.95 ; absolute risk 0.3 % ) . In contrast , children born after ovulation induction with or without insemination had low but significantly increased risks of any mental disorder ( 1.20 , 1.11 to 1.31 ; absolute risk 4.1 % ) , autism spectrum disorders ( 1.20 , 1.05 to 1.37 ; 1.5 % ) , hyperkinetic disorders ( 1.23 , 1.08 to 1.40 ; 1.7 % ) , conduct , emotional , or social disorder ( 1.21 , 1.02 to 1.45 ; 0.8 % ) , and tic disorders ( 1.51 , 1.16 to 1.96 ; 0.4 % ) . There was no risk systematic ally related to any specific type of hormone drug treatment . Conclusions There was a small increase in the incidence of mental disorders in children born after ovulation induction/intrauterine insemination . Children born after in vitro fertilisation/intracytoplasmic sperm injection were found to have overall risk comparable with children conceived spontaneously 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 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 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 assess the neurodevelopmental health of children born after intracytoplasmatic sperm injection ( ICSI ) .  DESIGN Prospect i ve controlled blinded study . SETTING Tertiary care center . PATIENT(S ) A total of 276 term-born singletons conceived by ICSI and 273 matched spontaneously conceived ( SC ) singletons at the age of 5.5 years . MAIN OUTCOME MEASURE(S ) Neuromotor development assessed by a detailed neurologic examination , including the st and ardized motor test MOT 4 - 6 , and emotional/behavioral development and intelligence assessed with the Kaufman- Assessment Battery for Children . RESULT ( S ) There were no significant differences between ICSI children and control children regarding the neurologic examination , motor skills , emotional/behavioral development , and intelligence . CONCLUSION ( S ) The ICSI children born at term develop normally , similar to SC children OBJECTIVE To determine pregnancy course and major malformation rate  after intracytoplasmic sperm injection ( ICSI ) .  DESIGN Prospect i ve , controlled , multicenter , nationwide German cohort study . SETTING Tertiary infertility centers in Germany . PATIENT(S ) Three thous and three hundred seventy-two children and fetuses and 8,016 children and fetuses after the 16th week of gestation in pregnancies after ICSI and natural conception , respectively . INTERVENTION(S ) St and ardized prospect i ve follow-up . MAIN OUTCOME MEASURE(S ) Major malformation rate . RESULT ( S ) The major malformation rate was 8.7 % ( 295/3,372 ) for the ICSI cohort and 6.1 % ( 488/8,016 ) for the population -based control cohort ( relative risk , 1.44 [ 1.25 - 1.65 ] ) . After adjustment for risk factors , the risk declined ( adjusted odds ratio , 1.24 [ 95 % CI , 1.02 - 1.50 ] ) . Regarding singletons , there was a significant difference for birth weight and gestational age , with a higher number of preterm and low birth weight children in pregnancies achieved after ICSI . CONCLUSION ( S ) Children who are born after intracytoplasmic sperm injection have an increased risk of a major congenital malformation compared with those born after spontaneous conception . This risk is mainly due to paternal and maternal risk factors , which are more prevalent in couples who use ICSI for reproduction . An infertility-linked risk is highly probable for the observed findings . A technique-related risk , however , can not be ruled out Aim of this study was to evaluate the effect of preimplantation genetic screening ( PGS ) on  neurodevelopmental outcome in children . We conducted a prospect i ve follow-up study of children born to women r and omly assigned to in vitro fertilization with or without PGS .  Primary outcome was adverse neurologic outcome at 18 mo ; secondary outcomes were types of minor neurologic dysfunction ( MND ) , neurologic outcome before 18 mo , neonatal intensive care admission , and congenital malformations .  Twenty women in the PGS group participated with 25 children and 26 women in the control group participated with 31 children . Five PGS pregnancies ( 25 % ) and four control pregnancies ( 15 % ) result ed in birth of at least one child with an adverse neurologic outcome ( adjusted odds ratio : 2.3 [ 0.4–12.0 ] ) . Dysfunction in fine motor abilities and posture and muscle tone dysregulation tended to be present more frequently after PGS .  Neurologic outcome before 18 mo , neonatal intensive care admission , and prevalence of congenital malformations were similar in study and control pregnancies . Nevertheless , at child level , rates of adverse outcome were higher after PGS . In conclusion , outcome in pregnancies after in vitro fertilization ( IVF ) with and without PGS was similar . The small sample size precludes the conclusion that PGS is not associated with less favorable neurologic outcome . Safety of new assisted reproductive techniques should be evaluated before large-scale implementation 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 corroborates previous reports . Our results can not be generalized to multiples , as we studied singletons only . STUDY FUNDING /COMPETING INTERESTS The study was financially supported by the University Medical Center Groningen , grant number : 754510 , the Junior Scientific Masterclass , the Postgraduate School Behavioural and Cognitive Neurosciences and the Cornelia Foundation , Groningen , The Netherl and s. The authors have no conflicts of interest to declare STUDY QUESTION Do preschool preimplantation genetic diagnosis ( PGD ) children differ in their cognitive and psychomotor development from children born after ICSI and spontaneous conception ( SC ) ? SUMMARY ANSWER The cognitive development of PGD pre-schoolers was comparable to children born after ICSI and SC but motor development differed between ICSI and SC groups . STUDY DESIGN , SIZE DURATION The cognitive abilities and motor skills of 5- to 6-year-old singletons born after PGD ( n = 47 ) were assessed in comparison with 49 ICSI and 48 SC children in a prospect i ve , case-controlled , matched follow-up study between April 2011 and May 2013 . PARTICIPANTS / MATERIAL S , SETTING , METHODS PGD singletons , ICSI and SC children of preschool age were examined with the Wechsler Preschool and Primary Scale of Intelligence ( WPSSI-III-NL ) and the Movement ABC ( M ABC ) . The WPSSI-III-NL revealed scores for Full IQ , Verbal IQ and Performance IQ . The M ABC yields a total score and comprising scores for measurements of balance , dexterity and ball skills . Since embryo biopsy is the only technical difference between the PGD and ICSI procedures , ICSI children were included as controls . These children were part of a Dutch-speaking cohort of children conceived after assisted reproduction technology ( ART ) at the Universitair Ziekenhuis Brussel ( UZ Brussel ) who received longitudinal follow-up . The SC children acted as a second control group similar to the fertile PGD sample and in contrast to the ICSI group . The SC group was recruited through announcements in a variety of media . The children were matched for age , gender , birth order and educational level of the mother . The assessment s carried out for the ART groups were blinded whenever possible . The data were analysed using analysis of covariance ( ANCOVA ) and partial eta squared ( η(2 ) ) , which was used as a measurement of effect size . MAIN RESULTS AND THE ROLE OF CHANCE The overall cognitive development of PGD singletons did not differ from controls [ P = 0.647 , η(2 ) = 0.006 ; 95 % confidence interval ( CI ) ( 0 , 0.043 ) ] . The partial IQ scores for Verbal and Performance intelligence revealed similar results . Analysis of motor development based on the total score as well as subscales did indicate a significant difference between the three conception groups [ P = 0.033 , η(2 ) = 0.050 , 95 % CI ( 0 , 0.124 ) ] . Post hoc analysis indicated that the significant difference was situated between performances of ICSI and SC children . Balance capacities [ P = 0.004 , η(2 ) = 0.079 , 95 % CI ( 0.025 , 0.163 ) ] and its post hoc analysis yielded equivalent results . Motor capacities of PGD singletons , however , did not differ from any of the two other conception groups . LIMITATIONS , REASONS FOR CAUTION Given that we only assessed Caucasian singletons born after PGD , caution is required when drawing more general inferences from our results . The small sample size may be a limitation . A priori power analysis , however , revealed that at least 52 children per group were needed to detect a medium effect and 80 % power using ANCOVA . Originally our sample met this threshold but we had to exclude six cases in order to remove outliers and due to missing data . WIDER IMPLICATION S OF THE FINDINGS Long-term follow-up of children born after embryo biopsy , in this case for PGD , is needed to confirm that the development of these children remains comparable to ICSI and SC children . Our findings do support the safety of the PGD technique and will reassure patients with hereditary genetic diseases regarding the health of their future offspring conceived with PGD . STUDY FUNDING /COMPETING INTERESTS Funding for this study was obtained from the OZR ( Research group of the Vrije Universiteit Brussel ) , the FWO ( Fonds Wetenschappelijk Onderzoek ) and the Wetenschappelijk Fonds Willy Gepts . The UZ Brussel and the Centre of Medical Genetics received funding from pharmaceutical firms for data collection . UZ Brussel and the Centre for Medical Genetics have received many educational grants for organizing the data collection , from IBSA , Ferring , Organon , Shering-Plough , Merck and Merck Belgium . M.B. has received consultancy and speaker 's fees from Organon , Serono Symposia and Merck 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 A case-referent study of birth defects was nested in a prevalence survey of adverse reproductive outcomes carried out among 8867 floriculture workers in Bogotá , Colombia . A total of 535 children born to these workers and reported by their parents as malformed and 1070 children selected at r and om as referents were invited to a medical examination including consultation with a geneticist and a clinical teratologist and a review of the medical records . Seventy-six percent of both groups attended the examination . Of 403 children reported as malformed , a birth defect was confirmed for only 154 ( 38 % ) . On the other h and , of the 817 children reported as normal , 735 ( 90 % ) were normal , but 68 had a birth defect and 14 had other conditions . A case-referent analysis was then carried out including 222 children with birth defects and 443 referents . An increased risk was found only for birthmarks , and specifically for hemangiomas , for children with parents exposed to pesticides in the floriculture industry Background —Acupuncture has recently been studied in assisted reproductive treatment ( ART ) although its role in reproductive medicine is still debated . Objectives —To determine the effectiveness of acupuncture  in the outcomes of ART . Search strategy —All reports which describe r and omised controlled trials of acupuncture in assisted conception were obtained through search es of the Menstrual Disorders and Subfertility Group Specialised Register , CENTRAL , Ovid MEDLINE ( 1996 to August 2007 ) , EMBASE ( 1980 to August 2007 ) , CINAHL ( Cumulative Index to Nursing & Allied Health Literature ) ( 1982 to August 2007 ) , AMED , National Research Register , Clinical Trials register ( www . clinical trials.gov ) , and the Chinese data base of clinical trials . Selection Criteria —R and omised controlled trials of acupuncture for couples who were undergoing ART comparing acupuncture treatment alone or acupuncture with concurrent ART versus no treatment , placebo or sham acupuncture plus ART for the treatment of primary and secondary infertility . Women with medical illness deemed contraindications for ART or acupuncture were excluded . Data Collection and Analysis —Sixteen r and omised controlled trials were identified that involved acupuncture and assisted conception . Thirteen trials were included in the review and three were excluded . Quality assessment and data extraction were performed independently by two review authors . © 2010 Elsevier Inc. All rights reserved . Corresponding author : Eric Manheimer , MS , Research associate , University of Maryl and School of Medicine , Center for Integrative Medicine East Hall , 520 W. Lombard Street Baltimore , MD 21201 , emanheimer@compmed.umm.edu , Telephone : 410 - 706 - 6169 , Fax : 410 - 706 - 6214 . * Both authors contributed equally to this work . The Cochrane Complementary Medicine Field is the group within the Cochrane Collaboration focused on facilitating the conduct of Cochrane systematic review s of CAM therapies . The CAM Field represents an international collaborative effort among research ers , clinicians , consumers , and CAM practitioners from nearly every continent . The Field ’s central office is located at the Center for Integrative Medicine , University of Maryl and School of Medicine , 520 W. Lombard St , Baltimore , MD 21201 . For more information , contact Eric Manheimer at : emanheimer@compmed.umm.edu . Publisher 's Discl aim er : This is a PDF file of an unedited manuscript that has been accepted for publication . As a service to our customers we are providing this early version of the manuscript . The manuscript will undergo copyediting , type setting , and review of the result ing proof before it is published in its final citable form . Please note that during the production process errors may be discovered which could affect the content , and all legal discl aim ers that apply to the journal pertain . NIH Public 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 Four-Year Follow-up of Children Born to Women in a R and omized Trial of Prenatal DHA Supplementation Despite the paucity of evidence , recommendations exist internationally for pregnant women to increase their docosahexaenoic acid ( DHA ) intake to optimize fetal brain development . Our r and omized controlled trial ( RCT ) , in which pregnant women were allocated to 800 mg/d of DHA or matched placebo , showed that children ’s mean cognitive , language , and motor scores did not differ between groups at 18 months , although fewer children in the DHA group had delayed development compared with controls.1 Surprisingly , girls in the DHA group had poorer language scores than girls in the control group.1 Herein we report neurodevelopmental outcomes at 4 years , which is when any subtle to moderate effects on development should have emerged and can be more reliably assessed 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 STUDY QUESTION Do children born after assisted reproductive techniques ( ART ; IVF/ICSI )  display more mental health issues or social and cognitive developmental problems at 7 - 8 years than naturally conceived ( NC ) controls , and does child gender play a role ? SUMMARY ANSWER ART children do not differ with regard to mental health or social and cognitive developmental problems when compared with controls , but some gender-specific differences do exist . WHAT IS KNOWN ALREADY Systematic review s have not found any evidence of delays in neurocognitive or sensorimotor development in ART children . However findings on the effect of the type of ART treatment ( IVF versus ICSI ) on the offspring 's physical and mental development have not been uniform . Knowledge of the role of child gender in ART research is scarce . STUDY DESIGN , SIZE , DURATION This prospect i ve follow-up study compares mental health and social and cognitive developmental problems between 7 - 8-year-old ART and NC children , controlling for the father 's age , length of the parents ' partnership , mother 's parity , child 's gestational age , and the need of neonatal intensive care unit ( NICU ) . Further , within the ART group , we analysed whether the treatment type ( IVF versus ICSI ) and the child 's gender are associated with the mental health and developmental outcomes . PARTICIPANTS / MATERIAL S , SETTING , METHODS In this study , 255 singleton ART children ( IVF and ICSI ) were compared with 278 NC children on parent-reported internalizing and externalizing symptoms , and social ( social skills and peer relations ) and cognitive development ( executive functioning , perception , memory , and language ) . Within the ART group , 164 IVF and 76 ICSI children were compared on the same outcomes . Statistics included analyses of covariates ( ANCOVA ) with group main effects , group and gender interaction effects , and Bonferroni post hoc tests . MAIN RESULTS AND THE ROLE OF CHANCE ART and NC children did not differ generally in terms of their internalizing and externalizing symptoms or in the number of social and cognitive developmental problems ( Group main effects , P > 0.05 ) , but gender-specific group differences existed . The ART boys showed lower levels of cognitive problems than the NC boys , whereas ART girls showed higher levels of cognitive problems than the NC girls ( Group × Gender-interaction effects with Bonferroni post hoc tests on mother-reports , P < 0.01 ) . Further , unlike in the NC group , where boys showed more externalizing symptoms and social and cognitive developmental problems than girls ( Group × Gender-interaction effects with Bonferroni post hoc tests for both parents ' reports , P < 0.05 ) , gender differences were not found in the ART group . Within the ART group , IVF and ICSI children did not differ in terms of mental health or developmental outcomes , and no significant gender differences emerged . LIMITATIONS , REASONS FOR CAUTION The information on children 's mental health and development was based on parental reports only . The dropout rate between the child 's first year and the school age assessment s was very high for fathers ( 57.4 % ) and substantial for mothers ( 30.1 % ) , and the participating group was biased for older age of both parents and for better education of the fathers . WIDER IMPLICATION S OF THE FINDINGS The findings indicate the importance of considering child gender in learning about multiple developmental outcomes among children born after ART . STUDY FUNDING /COMPETING INTERESTS This study was supported by the Academy of Finl and ( # 11232276 ) , the Emil Aaltonen Foundation , The Family Federation of Finl and , Helsinki University Central Hospital Research Funds , and the National Graduate School of Psychology . None of authors has any competing interests to declare OBJECTIVE To study the occurrence of major congenital anomalies ( CAs ) among children born after IVF ( IVF , microinjections , and frozen embryo transfers ) and after ovulation inductions with or without insemination ( other assisted reproductive technologies [ ART ] ) .  DESIGN Register-based study . SETTING Data regarding CAs were obtained from the Register of Congenital Malformations . PATIENT(S ) Children from IVF ( n = 4,559 ) , children from other ART ( n = 4,467 ) , and controls ( n = 27,078 , a r and om sample of naturally conceived children ) from the Medical Birth Register . INTERVENTION(S ) In vitro fertilization and other ART treatment in ordinary practice . MAIN OUTCOME MEASURE(S ) Rate of major CAs . Children from IVF and other ART were compared with control children , both overall and by plurality , controlling for confounding factors by logistic regression . RESULT ( S ) For IVF children , the adjusted odds ratio ( OR ) was 1.3 ( 95 % confidence interval [ CI ] , 1.1 - 1.6 ) . Stratifying by gender and plurality showed that the risk was only increased for boys , and the risk was decreased for multiple IVF girls ( OR = 0.5 , 95 % CI 0.2 - 0.9 ) . The crude OR of major CA for other ART children was 1.3 ( 95 % CI 1.1 - 1.5 ) , but adjusted differences by gender and plurality were statistically insignificant . CONCLUSION ( S ) In vitro fertilization was associated with an increased risk for major CAs among singleton boys and a decreased risk among multiple girls . The risk after other ART was only slightly increased STUDY QUESTION Does embryo biopsy inherent to preimplantation genetic screening ( PGS ) affect neurological , cognitive and behavioural development  of 4-year-old children ? SUMMARY ANSWER PGS does not seem to affect neurological , cognitive and behavioural development of 4-year-old singletons ; however , our data suggest that it may be associated with altered neurodevelopment in twins . WHAT IS KNOWN ALREADY Evidence concerning the safety of PGS on neurodevelopmental outcome in offspring is scarce . The present study provides information on neurodevelopmental , cognitive and behavioural outcome of 4-year-old PGS offspring . STUDY DESIGN , SIZE , DURATION A prospect i ve , assessor-blinded follow-up study of children born to women who participated in a multi-centre RCT on the effect of IVF with or without PGS .  PARTICIPANTS / MATERIAL S , SETTING , METHODS At 4 years , 49 children ( 31 singletons , 9 sets of twins ) born following IVF with PGS and 64 children ( 42 singletons , 11 sets of twins ) born following IVF without PGS ( controls ) were assessed ( post-natal attrition 18 % ) . Neurological development was evaluated with the st and ardized , age-specific and sensitive neurological examination according to Hempel , result ing in a neurological optimality score ( NOS ) , a fluency score and the rate of adverse neurological outcome . Primary outcome was the fluency score , as fluency of movements is easily reduced by subtle dysfunction of the brain . Cognitive development was evaluated with the Kaufman Assessment Battery for Children ; behavioural development was evaluated with the Child Behavior Checklist . The effect of PGS was analysed with a mixed effects model . MAIN RESULTS AND THE ROLE OF CHANCE Based on the intention to treat analysis , neurodevelopmental outcome of PGS children was similar to that of controls . However , additional analyses indicated that PGS affected neurodevelopmental outcome of twins in a different way than that of singletons . The fluency score of singletons born following PGS was similar to that of control singletons [ mean values , 95 % confidence intervals ( CIs ) : 12.2 ( 11.5;12.8 ) and 12.2 ( 11.6;12.8 ) ] , respectively , P = 0.977 ) that was also true for the other neurodevelopmental parameters . The fluency score of PGS twins was significantly lower than that of control twins [ mean values , 95 % CIs : 10.6 ( 9.8;11.3 ) and 12.3 ( 11.5;13.1 ) ] , respectively , P = 0.001 ) ; the same was true for the NOS . In addition , PGS in twins was associated with a higher sequential intelligence quotient score . On the other h and , other neurodevelopmental parameters were similar for PGS twins and control twins . Post hoc sample size calculation for the primary outcome parameter , the fluency score , indicated that the study groups , including the subgroups of singletons and twins , were adequately powered . LIMITATIONS , REASONS FOR CAUTION We assessed singletons and twins who contributed to the generalizability of the study . A limitation of our study is the relative small size of our study groups and the selective dropout in both groups ( dropouts PGS group : higher gestational age ; control group : less well-educated parents ) . These preclude the conclusion that PGS per se is not associated with neurodevelopmental , cognitive and behavioural problems in singletons and the conclusion that PGS is associated with altered neurodevelopmental outcome in twins . WIDER IMPLICATION S OF THE FINDINGS The need for careful long-term monitoring of children born following  embryo biopsy  remains , as it is still applied in the form of PGD and it is still unknown whether embryo biopsy affects long-term neurodevelopmental outcome OBJECTIVE To improve awareness of the natural age-related decline in female and male fertility with respect to natural fertility and assisted reproductive technologies ( ART ) and provide recommendations for their management , and to review investigations in the assessment of ovarian aging . OPTIONS This guideline review s options for the assessment of ovarian reserve and fertility treatments using ART with women of advanced reproductive age presenting with infertility . OUTCOMES The outcomes measured are the predictive value of ovarian reserve testing and pregnancy rates with natural and assisted fertility . EVIDENCE Published literature was retrieved through search es of PubMed or Medline , CINAHL , and The Cochrane Library in June 2010 , using appropriate key words ( ovarian aging , ovarian reserve , advanced maternal age , advanced paternal age , ART ) . Results were restricted to systematic review s , r and omized controlled trials/controlled clinical trials , and observational studies . There were no date or language restrictions . Search es were up date d on a regular basis and incorporated into the guideline to December 2010 . VALUES The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care . Recommendations for practice were ranked according to the method described in that report ( Table ) . BENEFITS , HARMS , AND COSTS Primary and specialist health care providers and women will be better informed about ovarian aging and the age-related decline in natural fertility and about options for assisted reproductive technology . RECOMMENDATIONS 1 . Women in their 20s and 30s should be counselled about the age-related risk of infertility when other reproductive health issues , such as sexual health or contraception , are addressed as part of their primary well-woman care . Reproductive-age women should be aware that natural fertility and assisted reproductive technology success ( except with egg donation ) is significantly lower for women in their late 30s and 40s . ( II-2A ) 2 . Because of the decline in fertility and the increased time to conception that occurs after the age of 35 , women > 35 years of age should be referred for infertility work-up after 6 months of trying to conceive . ( III-B ) 3 . Ovarian reserve testing may be considered for women ≥ 35 years of age or for women < 35 years of age with risk factors for decreased ovarian reserve , such as a single ovary , previous ovarian surgery , poor response to follicle-stimulating hormone , previous exposure to chemotherapy or radiation , or unexplained infertility . ( III-B ) 4 . Ovarian reserve testing prior to assisted reproductive technology treatment may be used for counselling but has a poor predictive value for non-pregnancy and should be used to exclude women from treatment only if levels are significantly abnormal . ( II-2A ) 5 . Pregnancy rates for controlled ovarian hyperstimulation are low for women > 40 years of age . Women > 40 years should consider IVF if they do not conceive within 1 to 2 cycles of controlled ovarian hyperstimulation . ( II-2B ) 6 . The only effective treatment for ovarian aging is oocyte donation . A woman with decreased ovarian reserve should be offered oocyte donation as an option , as pregnancy rates associated with this treatment are significantly higher than those associated with controlled ovarian hyperstimulation or in vitro fertilization with a woman 's own eggs . ( II-2B ) 7 . Women should be informed that the risk of spontaneous pregnancy loss and chromosomal abnormalities increases with age . Women should be counselled about and offered appropriate prenatal screening once pregnancy is established . ( II-2A ) 8 . Pre-conception counselling regarding the risks of pregnancy with advanced maternal age , promotion of optimal health and weight , and screening for concurrent medical conditions such as hypertension and diabetes should be considered for women > age 40 . ( III-B ) 9 . Advanced paternal age appears to be associated with an increased risk of spontaneous abortion and increased frequency of some autosomal dominant conditions , autism spectrum disorders , and schizophrenia .  Men > age 40 and their partners should be counselled about these potential risks when they are seeking pregnancy , although the risks remain small . ( II-2C ) BACKGROUND The aim of the present study was to determine language levels in twins and singletons born after at least 34 weeks gestation and without identifiable neurological abnormality and to evaluate whether in vitro fertilization ( IVF ) affects language development in twin pregnancies . METHODS A prospect i ve study of a large cohort of all children born between 1 January 2001 and 31 December 2003 was carried out at Gazi University Hospital . All live-born twin pairs in which both twins survived were identified , and a comparable sample of families with pairs of singletons were chosen . The  Stanford-Binet Intelligence Scale Form and the translated Turkish form of the Peabody Picture Vocabulary Test  were completed at 60 months . RESULTS Even after excluding the most premature twins and those with diagnosable neurological damage , twins performed worse than singletons on language development tests . Twin girls had better scores than twin boys . A statistically significant difference was found between the scores of term and preterm twins . No significant difference was noted when compared according to birth order . Appropriate for gestational age ( AGA ) twins did better than small for gestational age ( SGA ) twins in the test scores . All twin girls did not differ from singleton girls , but all twin boys performed worse than singleton boys . Term twins had similar results with term singletons , but preterm twins had lower scores than preterm singletons . SGA singletons had better scores than SGA twins , while AGA twins and singletons did not differ . When the children were compared with regard to method of conception , IVF children had significantly lower scores on the tests than those in the spontaneous conception group . CONCLUSION It is hoped that the present findings could lead to a more precise assessment of children for speech impairment and , above all , to more efficient preventive intervention . Whatever mechanisms are involved , the present results indicate that twins born as a result of IVF , are at a disadvantage in terms of language development in comparison with spontaneously conceived twins
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
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 .