Intracytoplasmic Sperm Injection Children Research Articles

Association between intracytoplasmic sperm injection and neurodevelopmental outcomes among offspring

PurposeTo compare the risk of neurodevelopmental disorders in children conceived via intracytoplasmic sperm injection (ICSI) and those conceived naturally.Materials and methodsA population-based cohort study using data retrieved from the Taipei Medical University Research Database (TMURD) from January, 2004 to August, 2016. The data included maternal pregnancy history, perinatal history and developmental follow up of their babies up to 5 years of age. The study included 23885 children, of whom 23148 were naturally conceived and 737 were conceived via ICSI. Neurodevelopmental disorders defined by 21 ICD-9-CM codes.ResultsOf the 23885 children enrolled for analysis, 2778 children were included for further subgrouping analysis after propensity matching to reduce bias from maternal factors. The single-birth group included 1752 naturally conceived (NC) children and 438 ICSI children. The multiple-birth group included 294 NC and 294 ICSI children. The risk of neurodevelopmental disorders was not increased for ICSI children in both groups (single birth: adjusted hazard ratio aHR = 0.70, 95% CI = 0.39–1.27, p = 0.243; multiple-birth group aHR = 0.77, 95% CI = 0.43–1.35, p = 0.853). In the single-birth group, multivariate analyses showed that male sex (aHR = 1.81, 95% CI = 1.29–2.54, p < 0.001), and intensive care unit (ICU) admission (aHR = 3.10, 95% CI = 1.64–5.86, p < 0.001) were risk factors for neurodevelopmental disorders. In the multiple-birth group, multivariate analyses demonstrated that ICU admission (aHR = 3.58, 95% CI = 1.82–7.04, p < 0.001), was risk factor for neurodevelopmental disorders.ConclusionOur study indicated that the use of ICSI does not associated with higher risk of neurodevelopmental disorders in the offspring. But male sex, and ICU admission do have increased risk of neurodevelopmental disorders. However, long term follow up of this cohort on health outcomes in adolescence and adulthood will strengthen the conclusions that ICSI is safe regarding offspring long term outcome.

O-076 Neurodevelopmental morbidity in children born after ART: a Nordic register study from the Committee of Nordic ART and Safety (CoNARTaS) group

Abstract Study question Does the risk of neurodevelopmental disorders differ between singletons born after various assisted reproductive techniques (ART) and spontaneous conception (SC) until young adulthood? Summary answer ART children had a slightly increased rate of learning and motor functioning disorders, autism spectrum disorders (ASD), and ADHD and conduct disorders. What is known already Studies on the impact of ART on offspring have reported both increased risk and comparable incidences of neurodevelopmental disorders between ART and SC offspring. The most studied neurodevelopmental disorders with ART are autism spectrum disorders (ASD.) There is, however, no consensus on the risk of ASD for ART children. The risk for other neurodevelopmental disorders, like attention-deficit hyperactivity disorders (ADHD) or tic disorder among ART children, is also a debated issue, as studies are scarce. Study design, size, duration A Nordic register-based cohort study including all singleton live births (N = 5 076 444) after ART (n = 116 909) or SC (n = 4 959 535) between 1995 and 2014 in Denmark and Finland, 1995 and 2015 in Sweden; and 2005 and 2015 in Norway. Children with intellectual disability (ICD-10: F70-F79) are excluded. The children are followed up to young adulthood (the year 2014 in Denmark and Finland, and 2015 in Norway and Sweden). Participants/materials, setting, methods Offspring outcomes were defined as following ICD-10 diagnoses: learning and motor functioning disorders (F80-83), ASD (F84), ADHD and conduct disorders (F90-F92), and tic disorders/Tourette (F95). We calculated crude and adjusted hazard ratios (HR) for neurodevelopmental diagnoses using Cox regression. Adjustments were made for the country, maternal age at the delivery, parity, smoking, and maternal psychiatric morbidity. Main results and the role of chance The cumulative incidences of neurodevelopmental disorders in the cohort were 1.74% for F90-F92, 1.40% for F80-83, 0.66% for F84, and 0.22% for F95. In crude Cox-regression ART children had an increased likelihood during the follow-up of being diagnosed with F84 (HR 1.12 [95% CI 1.04-1.21]) and F95 (HR 1.21 [95% CI 1.06-1.38]), but not with F80-83 (HR 1.01 [95% CI 0.96-1.07]) or F90-92 (HR 0.82 [95% CI 0.77-0.86]). After adjustments the likelihood was increased for F80-83 (HR 1.20 [95% CI 1.13-1.27]), F84 (HR 1.12 [95% CI 1.03-1.24]), and F90-92 (HR 1.09 [95% CI 1.04-1.19]), but nor for F95 (HR 1.13 [95% CI 0.99-1.30]). After adjustments, intracytoplasmic sperm injection children compared with in vitro fertilization children had similar likelihood during follow-up for F80-83 (1.06 [95% CI 0.89–1.25]), for F84 (HR 0.92 [95% CI 0.76–1.11]), for F90-92 (HR 0.96 [95% CI 0.83–1.12]), and for F95 (HR 1.16 [95% CI 0.83–1.63]). After adjustments, frozen embryo transfer children compared with fresh embryo transfer children had similar likelihood during follow-up for F80-83 (HR 1.11 [95% CI 0.90–1.37]), F84 (HR 0.98 [95% CI 0.76–1.27]), F90-92 (HR 0.96 [95% CI 0.78–1.19]), and F95 (HR 0.83 [95% CI 0.51–1.35]). Limitations, reasons for caution There may be residual confounding by unknown or unmeasured confounders. We lack information on possible confounders like the reason and length of infertility, maternal substance use other than self-reported smoking status, paternal age, and parental somatic morbidity. Additional limitations are differences in registration practice and data availability between study countries. Wider implications of the findings This is the largest singleton cohort and the first multinational study on the risk for neurodevelopmental disorders among ART children. While the rate of some neurodevelopmental disorders was increased among ART children, the absolute risk was moderate. The type of ART did not associate with the incidence of neurodevelopmental disorders. Trial registration number ISRCTN11780826

SUN-076 Somatic and Neurodevelopmental Outcome and Muscle Tone in 5 to 9 Year Old Children Born After Intracytoplasmic Sperm Injection

Introduction: Assessing the development and health status of children born after assisted reproductive techniques is very important. This also applies to somatic and neurological development. Little is known on the development of muscle tone in children. Aim of our study was to evaluate the somatic and neurological development in children born after intracytoplasmic sperm injection (ICSI) with special focus on proximal muscle tone. Material and methods: A group of 82 singletons (ICSI) aged 5–9 years (42 M, 40 F) and a control group of 82 singletons spontaneously conceived (SC), all with low morbidity, were compared by age and sex. Comprehensive assessment by endocrinologist, clinical anthropologist and pediatric neurologist was performed. Results: Both ICSI and SC children had normal somatic development. In the standard neurological testing, motor development did not differ significantly in ICSI children compared with the general population. Nevertheless, some coordination abnormalities tested by diadochokinesis and by the finger-nose test, were found in all but 7 ICSI children (ICSI in 91 % versus SC in 9 %; p<0.001). A prominent hypotonia of upper girdle muscles tested by the scarf sign was found in all but 4 ICSI children (ICSI in 95 % versus SC in 61 %; p<0.001). In the contrary, no difference was found for lower girdle muscle tone in ICSI versus SC children. Any of the factors tested for possible relationship to upper girdle muscle hypotonia was not found to be significant. Conclusions: As far as we know, this study is the first evaluation of proximal muscle tone in ICSI children aged 5 - 9 years. Subtle changes in the neurological status were revealed comparing ICSI and SC children, i. e. the prominent upper girdle muscle hypotonia and the coordination changes. The hypotonia can be explained by a slight change in the muscle tone maturation and movement coordination. The ICSI method very likely does not have any negative effect on the neurodevelopmental outcome of children. Nevertheless, the development of muscle tone and coordination in ICSI children should be monitored. Early diagnosis of these abnormalities helps to early initiation of appropriate therapy and thus avoids possible complications.

Long-term follow-up of ICSI-conceived offspring compared with spontaneously conceived offspring: a systematic review of health outcomes beyond the neonatal period.

A significant increase in the use of intracytoplasmic sperm injection (ICSI) since its introduction in 1992 has been observed worldwide, including beyond its original intended use for severe male factor infertility. Concerns regarding ICSI include the effects of poor quality spermatozoa on offspring health and future fertility, and of the technique itself. The health and development of ICSI-conceived children beyond early infancy have not been comprehensively assessed. A systematic review of health outcomes of ICSI-conceived offspring beyond the neonatal period compared to spontaneously conceived (SC) offspring. PubMed, OVID Medline/Embase, InformIT, Web of Science, and ProQuest databases were searched for studies reporting on health outcomes in ICSI-conceived offspring beyond 28days after birth. Physical and psychosocial health. The search strategy yielded 2826 articles. Of these, 2580 were not relevant or did not meet inclusion criteria and 138 were duplicates. One hundred and eight full-text papers were evaluated further, and 48 satisfied the inclusion criteria. Most studies reported on neurodevelopment during early infancy and childhood with reassuring results. 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. The clinical significance of many findings, however, remains unclear, and further prospective, large, and good quality studies with a focus on all these health outcomes in ICSI-conceived young adults are required.

Proteomics of Children Born After Intracytoplasmic Sperm Injection Reveal Indices of an Adverse Cardiometabolic Profile.

Context:Assisted reproduction technologies (ART), classic in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI) are increasingly used. Several studies have demonstrated an unfavorable cardiometabolic profile of the ART offspring. Proteomics is a state-of-the-art technology used for the identification of early biomarkers of disease.Objectives:To investigate the proteomic profile of children born after ICSI compared with naturally conceived (NC) controls in search of cardiometabolic risk markers.Design:Cross-sectional case-control study: qualitative, comparative proteomic plasma analysis.Setting:Pediatric Endocrinology and IVF Outpatient Clinics, University of Athens and the Biomedical Research Foundation of the Academy of Athens.Participants:Forty-two sex- and age-matched couples of ICSI and NC children were assessed. Ten pairs additionally matched for birth weight and twin/single pregnancies were submitted to proteomic analysis.Intervention:Medical history, clinical examination, and blood biochemical, hormonal, and proteomic analyses.Main Outcome Measures:(1) Differences in auxological and laboratory data between groups. (2) Differences in plasma proteomic profile in 10 individual pairs and pooled samples.Results:The ICSI group had shorter gestation, more cesarean sections, smaller birth weight/length, and advanced maternal age. No major differences were observed regarding biochemical markers. Proteomic analysis revealed 19 over- and three underexpressed proteins in ICSI. Most overexpressed proteins are implicated in acute-phase reaction, blood coagulation, complement pathway activation, and iron and lipid metabolism, suggesting a subclinical unfavorable cardiometabolic profile.Conclusions:This study applies proteomics in ICSI-conceived children, providing evidence for an early adverse cardiometabolic profile and supporting the necessity of their long-term monitoring.

Are children born through Intra-Cytoplasmic Sperm Injection (ICSI) having a lower intelligence quotient?

Abstract Background: There is still concern about delayed mental development for children born through Intra-Cytoplasmic Sperm Injection (ICSI). In the present study, the intelligence quotient (IQ) of ICSI children at the age of 5–6 years was compared with that of the control group of naturally born (NB) children. Outcome measure: Full-scale IQ of the mental development in children born through ICSI in 5–6 years. Design: Cross-sectional study. Setting: Fatemehzahra Infertility and Reproductive Health Research Center of Babol – Iran. Participants: 28 live-birth singleton children 5–6 years of the first generation born after ICSI treatment. Methods: The mental development of 28 born through ICSI children at 5–6 years compared with 32 naturally born children as control using intelligence quotient (IQ) test obtained from the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) (Iranian version). Results: The mean full-scale IQ was 105.9 ± 14 for ICSI and 107.2 ± 12.9 for NB children which showed no significant difference. The only significant possible predictors of slightly lower full-scale IQ in ICSI children were lower parental education level and longer childcare in day center. Conclusion: Our finding provides some reassurance for parents of children born through ICSI regarding the child’s preschool IQ.

To ICSI or Not to ICSI.

Intracytoplasmic sperm injection (ICSI) is the most effective assisted reproductive procedure enabling fertilization in severe forms of male factor indications and male gamete dysfunction. Reliability of ICSI has allowed the expansion of its application to other forms of infertility rendering it the most popular assisted reproduction technology (ART) insemination method worldwide. The concern related to the invasiveness of ICSI together with the arbitrary selection of the inseminating spermatozoon has induced the execution of studies to compare the performance of ICSI in non-male factor infertility with standard in vitro insemination approach. Not surprisingly, the outcome has evidenced that ICSI does not yield higher pregnancy rates than in vitro fertilization but functions invariably as a normalizer of fertilization mollifying the absent or low fertilization. The follow-up studies on ICSI children have evidenced that the procedure is safe and the slightly higher incidences of neonatal malformations or de novo gonosomal abnormalities are related to the genetics of the infertile couples. Furthermore, ICSI is accepted for some specific indications such as low number and poor morphology oocytes, thicker zona, excess polyspermia, PGD/PGS/PGT (preimplantation genetic diagnosis/preimplantation genetic screening/preimplantation genetic testing), discordant HCV/HIV (hepatitis C virus/human immunodeficiency virus) couples, in vitro maturation (IVM), and oocyte cryopreservation. Only the advent of new biomarkers in combination with routine semen analysis capable of identifying the fertilization competence of the spermatozoon can guide the reproductive physician toward the proper insemination method.

An overview of studies on psychological well-being in children born following assisted reproductive technologies

Over the course of the past 35 years, assisted reproductive technologies (ARTs) have been increasingly used worldwide, while debates on their safety have been generated. Birth defects and imprinting disorders were reported in previous research. Thus, the psychological development of children born following ARTs has become a major concern nowadays. This review gives a systematic view of psychological well-being of children conceived by different types of ART, including in vitro fertilization, intracytoplasmic sperm injection (ICSI), preimplantation genetic diagnosis/screening, and in vitro maturation. The previous studies are analyzed in three sections: (1) cognitive, motor, and language developments, (2) behavior problems and socio-emotional development, and (3) parent-child relationship. We conclude that although the majority of the studies on cognitive, motor, and language developments reported comparable achievements in the ART group vs. the naturally conceived group, lower intelligence quotient (IQ) scores, worse visual-motor ability or locomotor development, and delayed receptive language competence were found in the ART group. The results on the socio-emotional development were reassuring. As for the behavior problems, a higher prevalence of behavior problems existed in ART children; moreover, ICSI children were found to be at a higher risk of autism than the general population. Meanwhile, ART parents tended to have positive parental attitudes and be more protective of their children. Some suggestions for further research are also given in this review.

Gender-Specific Alterations in Salivary Cortisol Levels in Pubertal Intracytoplasmic Sperm Injection Offspring

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.

Follow-up of children born after intracytoplasmic sperm injection with epididymal and testicular spermatozoa

Background To evaluate the safety of intracytoplasmic sperm injection (ICSI) with epididymal or testicular sperm, this study compared children born after ICSI treatment with epididymal or testicular sperm with children conceived after ICSI with ejaculated sperm. Methods This retrospective study included 317 children born after ICSI with percutaneous epididymal sperm aspiration (PESA), 103 children born after ICSI with testicular sperm aspiration (TESA), and a control group of 1008 children born after ICSI with ejaculated sperm. All of the patients received their assisted reproductive treatment in the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2004 to December 2011. Data,such as the rate of stillbirths, perinatal mortality, gestational age, birth weight, and the rate of congenital malformations of the three groups, were compared. Results PESA and TESA children were not different from ICSI children in the rate of stillbirths, perinatal mortality infant mortality rate, gestational age, the rate of prematurity, and the rate of malformations (P&gt;0.05). A slight increase in birth defects was reported in the TESA group compared with those in the control group, but there was no significant difference between the groups (P&gt;0.05). Conclusion ICSI with epididymal or testicular sperm does not lead to more stillbirths or congenital malformations compared with ICSI using ejaculated sperm.

Comparison of brain apparent diffusion coefficient value in naturally and assisted conceived newborns

Background: Our aim was to assess the value of brain apparent diffusion coefficient (ADC) in Intra Cytoplasmic Sperm Injection (ICSI) and spontaneously conceived preterm singletons. Methods: Twenty ICSI-conceived preterm singletons and 20 gestational age matched spontaneously conceived preterm singletons were studied. All subjects underwent diffusion-weighted imaging (DWI). The main outcome measure was the brain ADC value in the in ICSI-conceived and naturally conceived newborns. Results: Children born after ICSI had an increased ADC value than the controls. The ADC values of ICSI-conceived singletons were higher than those of spontaneously conceived singletons at cerebellum, corpus striatum, frontal lobe, occipital lobe, and temporal lobe white matter. The mean Apgar score, birth weight, height, and head circumference of ICSI children were found to be similar to naturally conceived children. Conclusions: Measuring ADC value may be a promising marker in identifying neurological outcome of ICSI-conceived newborns.

Spermatozoa DNA damage measured by sperm chromatin structure assay (SCSA) and birth characteristics in children conceived by IVF and ICSI

High levels of spermatozoa DNA damage hinder fertility in vivo but not in vitro. It is a source of worry that following in vitro fertilization (IVF) spermatozoa DNA damage, if not repaired by the oocyte, might have a negative impact on the offspring. The aim of this study was to assess if a high spermatozoa DNA Fragmentation Index (DFI) is associated with alterations in birthweight (BW) and/or gestational length in IVF children. One hundred and thirty-one singleton pregnancies established by standard IVF or intracytoplasmic sperm injection (ICSI) were included in the study. DFI was measured by sperm chromatin structure assay (SCSA) in semen samples used for fertilization. DFI was categorized as low and high, using 20, 30, 40 and 50% as cut-off levels. Birthweight, gestational age, as well as gestational age adjusted BW score were used in a linear regression model as end points For none of the tested birth characteristics, statistically significant differences between the groups with low and high DFI were seen regardless of whether 20, 30, 40 or 50% were used as cut-off levels, both when the IVF and ICSI data were merged or analysed separately. Spermatozoa DNA damage as assessed by SCSA is not associated with BW or gestational length in IVF and ICSI children.

Medical, Psychological and Intellectual Development of 5-Year-Old Children Born after Intracytoplasmic Sperm Injection

The neurodevelopmental outcome of children born after intracytoplasmic sperm injection (ICSI) is controversial. Thus, we compared the medical and developmental outcome at a mean age of 5 years and 6 months of 35 singletons born after an ICSI procedure performed at the Tübingen Medical Center with those of 37 naturally conceived (NC) matched control singletons born at the Tübingen Medical Center. Children with congenital anomalies which could interfere with mental development were excluded, these were reported earlier. Each child was assessed neurologically and physically. Cognitive function was assessed using the Kaufman assessment battery for children (K-ABC). Behaviour was tested using a German behavioural questionnaire for preschoolers (VBV). Medical and cognitive outcome, and behaviour pattern were similar in both groups. Nevertheless, there were sex-related differences in favour of ICSI children: ICSI boys had better social competence than the control boys, while ICSI girls had less emotional problems than the control girls. Once severe congenital anomalies were excluded, there were no differences in physical and neurodevelopmental outcome of 5-year-old ICSI children compared with controls.With regard to behaviour and emotional development, ICSI children seem to be similar or might be even more stable and socially competent than the control children. As our study is limited by the small sample size, further research is needed to confirm our results.

A follow-up study on children conceived through intracytoplasmic sperm injection

To investigate the perinatal complications, birth defects and growth of children conceived through intracytoplasmic sperm injection (ICSI). A total of 575 children conceived by ICSI in our reproductive medical center, were studied. The follow-up study would include items as pregnant complications, neonatal complications, birth defects in perinatal period, subsequently detected birth defects, body weight and body length/height growth. Prematurity and low birth weight of ICSI children were higher in the multiple births than in the singleton births. The rates of materal gestational hypertension, neonatal asphyxia, respiratory distress syndrome, infection diseases were higher in the multiple pregnancies than in the singleton pregnancies (P < 0.05). Eleven ICSI children had died. Ten of them died in the neonatal period and they were preterm infants. One fullterm singleton ICSI child died of hepatoblastoma at the age of 2. The rate of birth defects in perinatal period was higher in ICSI children of multiple pregnancies than in the general population (P < 0.05). The body weight and body length/height of most ICSI children had obtained the standard range between 1 to 3 year-olds. The higher rates of perinatal complications in ICSI children were closely related to multiple pregnancies.

Report on a Consecutive Series of 581 Children Born After Blastomere Biopsy for Preimplantation Genetic Diagnosis

The aim of preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS) is to prevent the transmission of a genetic condition before pregnancy in couples at high risk. Healthy children have been born following PGD/PGS, but no large prospective studies have investigated the safety of embryo biopsy performed for PGD/PGS in fetuses or newborns. This observational prospective cohort study of children born after embryo biopsy for PGD or PGS was conducted between 1992 and 2005 to determine the possible risk of embryo biopsy at day 3 after intracytoplasmic sperm injection (ICSI) to the health of the fetus or offspring. Data on 581 post-PGD/PGS children were compared with historical data of 2889 children conceived through the use of ICSI technology. Physicians and parents completed questionnaires at conception and at delivery. Two-months after delivery, the babies were examined at an outpatient clinic by trained clinical geneticists. There were no statistically significant differences between the post-PGD/PGS and ICSI children with respect to gestational ages or birth weight. No major differences were found in rates of major malformation between the 2 groups of children (post-PGD/PGS: 2.13% vs. ICSI: 3.38%); the odds ratio (OR) was 0.62, with exact 95% confidence limits (CL) of 0.31–1.15. The overall perinatal death rate, however, was significantly higher in post-PGD/PGS children in comparison to ICSI children (4.64% vs. 1.87%); the OR was 2.56, with a 95% CL of 1.54–4.18. Stratification for multiple births showed that the difference between the 2 groups in perinatal deaths was a reflection of a marked increase in such infant deaths in multiple pregnancies: Although perinatal death rates among PGD/PGS and ICSI singleton children were similar (1.03% vs. 1.30%; OR: 0.83; 95% CL: 0.28–2.44), these rates were significantly higher among post-PGD/PGS multiple pregnancies compared with ICSI multiple pregnancies (11.73% vs. 2.54%; OR: 5.09; 95% CL: 2.80–9.90). The misdiagnosis rate was less than 1%. The investigators conclude from these findings that embryo biopsy is not an additional risk factor in singleton newborn PGD/PGS children and that multiple pregnancies should be avoided because of the increased rate of perinatal deaths.

Karyotyping and neurodevelopmental follow-up of intracytoplasmic sperm injection children up to 4years of age

Abstract Objectives The aim of this work is to study ICSI babies, singleton and twins and compare them with singleton naturally conceived children from the genetic and neurodevelopmental point of view. Materials and methods This is a prospective study performed on 120 children born to 100 mothers after the successful treatment of male infertility by intracytoplasmic sperm injection (ICSI). Obstetric history and Neonatal examinations were done. Developmental assessment using Denver Developmental Screening Test was done at 1, 2, 3, and 4years of age. Karyotype was done to all babies. The babies were divided into three study groups; group 1 single ICSI, group 2 twin ICSI, and group 3 normally conceived control group. Results We found no statistically significant difference when we correlated outcome of DDST to gender, mode of delivery, smoking habits of mother, maternal illnesses, paternal smoking, Apgar score, congenital anomalies or type of feeding. There was significant statistical difference between the results of DDST follow-up and gestational age, birth weight and NICU admission. Our developmental assessment using DDST reported that ICSI children in both groups do not display any significant developmental delay when compared with naturally conceived children. Conclusion Developmental assessment performed in this study revealed reassuring findings, no important differences between ICSI and NC children were noticed indicating that infertility treatment by ICSI technique does not appear to affect the development of child. It also highlights the need for continuous follow-up to evaluate whether ICSI children continue to show satisfactory development later in life.

Perturbations in finger length and digit ratio (2D:4D) in ICSI children

Intracytoplasmic sperm injection (ICSI) is used to overcome severe male-factor infertility where males are azoospermic or have poor quality spermatozoa. Perturbations of finger length (short finger length adjusted for height and high second-to-fourth digit ratio, or 2D:4D) have been described in azoospermic men and men who are rated as having low sexual attractiveness. High 2D:4D has been described in women with high fecundity. Such perturbations may be related to endocrine regulation of some homeobox genes. This study compared finger length and 2D:4D in singleton children conceived with the help of ICSI with those in naturally conceived singleton controls. Participants were recruited from centres in Germany and the UK. There were 211 children conceived by ICSI and 195 controls. Finger length was measured from photocopies of the ventral surface of the hand. In comparison to controls, male and female ICSI children had shorter fingers after correction for height. There was also evidence that female ICSI children may have higher 2D:4D than female controls. Perturbations in finger length in ICSI children may be inherited from their fathers and, in the case of boys, could be associated with lower fertility and reduced sexual attractiveness. For ICSI females, increased 2D:4D may be associated with increased fertility.

Growth of children conceived by IVF and ICSI up to 12years of age

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 prospective match-controlled study was performed to investigate the growth of children born in the UK following standard 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.

Growth and health outcome of 102 2-year-old children conceived after preimplantation genetic diagnosis or screening

Objective The major objective of this study was to determine whether the embryo biopsy procedure might cause growth restriction or affect health outcome of children. Study design Auxological data and physical findings were compared at birth and age 2 for 102 children (70 singletons and 32 twins) born after PGD/PGS and 102 matched children born after intracytoplasmic sperm injection (ICSI) in a prospective study. Results No statistically significant differences regarding weight, height and head circumference standard deviation scores (SDS) at birth and at age two years were observed. At two years of age the mean BMI SDS tended to be lower in PGD/PGS children ( p = 0.058). PGD/PGS babies had been more often breastfed ( p = 0.013), but mostly during a shorter time. The prevalence of major as well as minor congenital anomalies, hospital admissions and surgical interventions was similar. Conclusion Children born after embryo biopsy applied in PGD/PGS present similar prenatal and postnatal growth and health outcome in the first two years of life compared to ICSI children. Up till now, PGD and PGS appear not to be associated with a higher risk for health problems.

Report on a consecutive series of 581 children born after blastomere biopsy for preimplantation genetic diagnosis

Preimplantation genetic diagnosis (PGD) and subsequently preimplantation genetic screening (PGS) have been introduced since 1990. The difference from the already existing in vitro fertilization (IVF) technology, using intracytoplasmic sperm injection (ICSI), was the embryo biopsy at day 3 after fertilization. Although healthy children post-PGD/PGS have been born, the question of whether embryo biopsy could have any harmful effects has to be studied on large series in a prospective manner. A prospective cohort study was undertaken from 1992 until 2005, using the same approach as for the follow-up of IVF and ICSI children conceived in the same centre. Questionnaires were sent to physicians and parents at conception and at delivery. Children were examined at 2 months of age by trained clinical geneticists whenever possible. Data collected on 581 post-PGD/PGS children showed that term, birthweight and major malformation rates were not statistically different from that of 2889 ICSI children, with overall rates of major malformation among these post-PGD/PGS and ICSI children being 2.13 and 3.38%, respectively (odds ratio [OR]: 0.62; exact 95% confidence limits [95% CL]: 0.31-1.15). However, the overall perinatal death rate was significantly higher among post-PGD/PGS children compared with ICSI children (4.64 versus 1.87%; OR: 2.56; 95% CL: 1.54-4.18). When stratified for multiple births, perinatal death rates among PGD/PGS singleton and ICSI singleton children were similar (1.03 versus 1.30%; OR: 0.83; 95% CL: 0.28-2.44), but significantly more perinatal deaths were seen in post-PGD/PGS multiple pregnancies compared with ICSI multiple pregnancies (11.73 versus 2.54%; OR: 5.09; 95% CL: 2.80-9.90). The overall misdiagnosis rate was below 1%. Embryo biopsy does not add risk factors to the health of singleton children born after PGD or PGS. The perinatal death rate in multiple pregnancies is such that both caution and long-term follow-up are required.