Abstract of evidence	Conclusion
Birth defects	Systematic review analysis was performed by Lacamara et al.[5] to indicate that the use of ICSI increases the risk of congenital malformation in children born from singleton pregnancies versus naturally conceived children	Marginal increase in birth defects has been seen in ART children, cannot be directly correlated to ART
	Twenty-one of the 104 publications listed in the literature search were included in the analysis
	Observational studies reported mostly an increased risk for congenital malformation; the risk of congenital defects is 7.1% in ICSI and 4.0% in the general population (OR 1.99, 95% CI [1.87-2.11]).
	However, attributing higher risk solely to ICSI might seem far-fetched, as in vitro and simulation procedures, patient diseases, and ICSI indication may also be associated with a higher risk of malformation
Developmental delays	The outcome of the pregnancy and the developmental well-being of children conceived from 12,866 consecutive ICSI cycles were assessed. A total of 3277 couples delivered 5891 neonates. There was a higher than normal incidence of de novo chromosomal abnormalities in a small sample of ICSI offspring. Controlling for maternal age showed that the frequency of low-birth weight and gestational length were comparable with the naturally conceived counterpart. Rates of malformation in ICSI offspring ranged from 3.5% to 6.2%. At 3 years of age (n=811), the proportion of children at risk for developmental delays was 10.4% in ICSI and	No conclusive data on Indian ART babies and their developmental milestones. There is a need to monitor and setup registry for ART babies
	10.7% in IVF singletons. However, high-order gestations were characterized by 19.4% of the children having compromised development. Epigenetic analysis of assisted reproductive technique concept uses found minor imprinted gene expression imbalances. ICSI offspring presented with genetic defects that were inherited or arose de novo. Obstetric and neonatal outcomes of singleton pregnancies appeared to be dependent upon maternal age. ICSI and IVF seemed to exert a negative effect on the well-being of offspring mainly because of the association with multiple gestations. All assisted reproduction procedures should be monitored for the eventual effect of environmental aggressors on offspring epigenesis[6]
Bodyweight	A multicenter, double-blind RCT comparing the use of embryo culture media in IVF. Between July 2010 and May 2012, 836 couples (419 in the HTF group and 417 in the G5 group) were included. The allocated medium (1:1 allocation) was used in all treatment cycles a couple received within 1 year after randomization, including possible transfers with frozen-thawed embryos[4]	Culture media could affect birth weight; and needs to be monitored
	In this trial, birth weight data from 380 children: 300 singletons (G5: 163, HTF: 137) and 80 twin children (G5: 38, HTF: 42) were retrieved[4]
	Birth weight was significantly lower in the G5 group compared with the HTF group, with a mean difference of 158 g (P=0.008). More singletons were born preterm in the G5 group (8.6% [14/163] vs. 2.2% [3/137]), but singleton birth weight adjusted for gestational age and gender (Z-score) was also lower in the G5 than in the HTF group (−0.13±0.08 vs. 0.17±0.08; P=0.008)[4]
Asthma, blood pressure, blood sugar	A significantly increased risk for asthma, albeit small, was found in children conceived by IVF (aOR 1.28, 95% CI 1.23-1.34), increasing the absolute risk from 4.4% to 5.6%[7]	No conclusive data on Indian ART babies to establish a direct correlation with ART
	The risk increase for asthma was the same in boys and girls, in singletons and twins, and after caesarean section and vaginal delivery. The risk was higher for preterm than term singletons. For children with a low Apgar score, respiratory diagnoses, mechanical ventilation, continuous positive airway pressure or neonatal sepsis, the effect of IVF on asthma risk was low and statistically nonsignificant[7]
	Adjustment for the length of involuntary childlessness eliminated the effect, and removal of infants whose mothers had used anti-asthmatics in early pregnancy reduced the risk[7]
	This study verifies an association between IVF and asthma in children. This can be partly explained by neonatal morbidity and by maternal asthma acting as mediators, but the leading risk factor is parental subfertility[7]
Neurological dysfunction	Research on cognitive and behavioral development of children born after assisted conception is inconsistent	No direct association to ART
Cancers	Recently, the report of an increased risk of childhood cancers after ART (IVF/ICSI) has generated considerable concerns	No direct association to ART
De novo mutations	A significantly higher rate of de novo, noninherited chromosomal abnormalities in children born after ICSI was observed compared with the rate in the general population (1.6 vs. 0.5%), especially with the associated male factor. This finding was related to sperm concentration and motility. The significantly higher rate of observed inherited anomalies (1.4 vs. 0.3%-0.4% in prenatal tests in the general population; P<0.001) was related to a higher rate of constitutional chromosomal abnormalities, mainly in the fathers[8]	Babies born through ICSI need to be monitored

ICSI=Intracytoplasmic sperm injection, ART=Assisted reproductive technology, OR=Odds ratio, CI=Confidence interval, IVF=In-vitro fertilization, RCT=Randomized controlled trials, aOR=Adjusted OR, HTF=Human tubal fluid