Despite the develepmont of ART techniques, the results of previous studies on the obstetric, perinatal, and neonatal outcomes following ART are not conclusive, partly because of different study designs, populations and countries. The present hospital-based cohort study containing 330 subjects was carried out from April 2016 to October 2017 to investigate pregnancy complications, prenatal and neonatal outcomes related to ART. A 33% increased incidence of multiple gestations in ART pregnancies compared with NC group was found. Compared to the NC group, neonates in ART group were more delivered by a C/S, were more premature with a peak at GA 32-34 weeks, had a higher risk of IUGR, had a lower birth weight, had a higher hospitalization duration and had a higher risk of NEC and RDS. Besides a higher prenatal complications, maternal complications of pregnancy was higher in ART group compared to NC group. A 3-fold increase in incidence of pre-eclamsia in ART pregnancies compared with NC pregnancies was found. Following up the patients for one year showed that infants of ART group are more prone to need to admit at ward and also having a body weight < 5% percentile; implying a retarded growth and higher vulnerability to the diseases compared to their NC counterparts.
Previous studies have suggested an increased risk of preterm delivery and IUGR in children conceived by ART (15-18). A recent meta-analysis analyzed data of 27,819 IVF/ICSI pregnancies and found a higher risk of preterm delivery in IVF/ICSI conceived children compared to NC children (18). A prospective cohort study found that the OR for preterm delivery in IVF was 2.19 (95%CI:1.59–3.02) (17). Similarily, the results of the current study showed a higher risk of pre-term delivery especially at GA 32-34 weeks and IUGR. However, some obstetrical or gynecological variables such as multiple gestation may confound the association between ART and pre-term delivery and IUGR suggesting the need for adjusting them in future studies (16).
Besides the pre-term labor, the ART group was more prone to have a low birth weight (<2500 gr) compared to NC group in this study. This result is consistent with previous studies thatfound An increased risk of LBW among children conceived by ART compared to those conceived without medical assistance (18). Supraphysiological hormonal environment of the IVF cycle may be a significant cause of LBW in ART conception (16). However a Dutch population-based study showed that the birth weight of siblings conceived with IVF was not significantly different from their NC conceived siblings (19). This finding suggest the importance of consideration of maternal infertility as a factor that may contribute to the risk of LBW.
Consistent to our results, previous studies have demostrated that ART pregnancies are associated with a greater risk of cesarean sections (15, 20, 21). This is not only due to the higher risk of multiple pregnancy in ART, but ART pregnancies were associated with a greater risk of cesarean sections in singleton births (20). Moreover, both elective and emergency cesarean sections are more common among ART pregnancies (20). However, A population-based Swedish study over a 25 year period showed a gradual decline in this increased risk of cesarean section rate (which nonetheless remains elevated compared to non-IVF pregnancies) impying that development of the ART techniques has resulted a lower risk of C/S (21).
AER appears to be associated with known risks associated with prematurity (22). Our results showed that both RDS and NEC are more prevalent in ART concieved neonates compared to NC neonates. However Turker et al (22) reported that IVF is associated with RDS, but not NEC; similarly, Ahmad et al study showed similar prematurity-related complications for IVF-conceived preterm infants compared to matched controls with the exception of bronchopulmonary dysplasia and respiratory medication exposure (23). The discrepancy between our results and those of Turker et al and Ahmad et al may be related to inclusion of both IVF and IUI concieved neonates in our study, implying the need for investegation of prematurity-related complications in IUI conceived neonates. Moreover, ART and NC group were not matched for prematurity in this study.
Besides prenatal outcomes, ART has adverse obstetric outcomes. In the present study, we found that a 3-fold increase in incidence of pre-eclampsia was associated with pregnancies conceived by ART. Different previous studies have reported a higher risk of pre-eclampsia in ART conceived women (12, 24-26). Pre-eclampsia is a significant cause of maternal and perinatal mortality and morbidity. The mechanisms by which ART leads to pre-eclampsia are not clear yet. Defective placental vascular remodeling is a suggested mechanism of pre-eclamspsia (27) so further studies to delineate placental development in ART births are needed to understand the underlying mechanisms.
The main driver for adverse prenatal and obstetric outcomes in ART pregnancies is the higher risk of multiple gestations in ART. Moreover, singleton ART pregnancies still have a higher incidence of adverse outcomes compared to naturally conceived pregnancies (16). Infertility itself and epigenetic changes in genes involved in growth and development during the hormonal stimulation and embryo culture may be independent risk factors (16). The results of this study support previous reports on the association between increased obstetrical and perinatal morbidity and mortality and ART. Also, our fingidngs showed infants of ART group are more prone to need to admit at ward and also having a body weight < 5% percentile; implying a retarded growth and higher vulnerability to the diseases in a one year follow up. It should be noted that based on the previous reports, twins or early preterm neonates conceived via ART compared to non-ART counterparts had similar neonatal outcomes (28, 29) and no additonal management may be needed in them.