In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI),represent the mainstay of treatment for many infertile couples. Since 1978, the year of the first baby born after IVF in the UK, the number of pregnancies and births after IVF has been increasing exponentially. After the first birth of an infant by ICSI in 1992, ICSI was increasingly used for couples with severe male infertility disease, and the scope of ICSI application has expanded greatly to patients without male factor infertility. More than five million children have been born after IVF or ICSI cycles.
Birth defects (also called congenital anomalies or congenital malformations),the major cause of death and disability in infants, is a severe global public health problem. Congenital birth defects and preterm/preterm births are common and complex conditions associated with perinatal/infant mortality and morbidity worldwide.
Studies have shown that infertile patients have a higher risk for birth defects in their children even if they conceive on their own. This is because couples with unexplained reasons may have unknown problems with the quality and functionality of the egg or sperm which can result in increased risk of fetal abnormality even though they conceived naturally.
Parental health and lifestyle characteristics may also contribute to the excess risk of birth defects in infertile couples. Compared with the fertile population, infertile female women are more likely to be older, obese, and have metabolic disease and chronic health conditions, including pre-existing diabetes and hypertension, each of which is an independent risk factor for birth defects.
The risk of birth defects after IVF is still a debated and controversial issue.
The effect of assisted reproduction procedures on the health of children born using IVF is not fully understood and infertility in itself is a risk factor for congenital anomalies given the equal rate of anomalies recorded in infertile patients conceiving spontaneously. As a result of the contribution of parental health and lifestyle characteristics to infertility, studies have been largely unable to differentiate between the influence of IVF Treatment and parental characteristics on birth defects when comparing outcomes with a fertile population.
Some studies focusing on birth defects among children after IVF report that infants conceived with the use of IVF was associated with an increased risk for birth defects compared to those conceived naturally. These studies concluded that the causal pathways that underlie these associations are not definitively understood in humans, although specific laboratory factors may contribute, including the embryo culture media, ICSI gamete manipulation, and returning embryos to the uterus soon after ovarian stimulation.
On the other hand most of the studies published until now show no statistically significant differences in the rates of anomalies between babies born after IVF/ICSI transfer and infertile patients conceiving spontaneously without any treatment. No significant differences are found in the incidence of major anomalies between single and multiple pregnancies in IVF versus spontaneous conceptions.
In a study published in Journal of Assisted Reproduction and Genetics in 2016 it is found that, although babies born after IVF treatments and from spontaneous conception in infertile couples had rates of congenital anomalies higher than those non infertile couples recorded by the European Surveillance of Congenital Anomalies (EUROCAT) classification, the rates of anomalies were not different within the infertile population whether conceived by IVF or spontaneously. These data suggest that the diagnosis of infertility in itself is the common denominator for the increase in the rates of anomalies seen in both IVF and spontaneous conceptions.
Published data show that in pregnancies after IVF, both the early and late abortion rates as well as the incidence of therapeutic abortions and ectopic pregnancies are comparable with that observed in controls of infertile patients after spontaneous conceptions.
Some studies reported that infants conceived by ICSI had a 1.5–4 times increased risk for chromosomal abnormalities, imprinting disorders, and other birth defects compared to those conceived by IVF. This can be explained as ICSI is done in severe male factor infertility. Male sub-fertility even with low sperm count is associated with higher risk of chromosomal abnormality to passed on offspring.
In a Japan study published in 2019 investigated 59,971 IVF-ICSI patients’ results (singleton live births, still births, or selective terminations) treated between 2007 and 2014. Among IVF cycles, male subfertility was associated with significantly greater risks of hypospadias (0.09% vs 0.01%),and atrial septal defects in heart (0.13% vs 0.03%),compared with fertile men. Subgroup analysis using sperm parameters showed that oligozoospermia (sperm concentrations < 15 million/mL) was significantly associated with a greater risk of ventricular septal defects in heart compared with normal sperm concentrations in IVF pregnancies (0.58% vs 0.21%),and severe oligozoospermia (sperm concentrations < 5 million/mL) was significantly associated with an increased risk of hypospadias compared with normal sperm concentrations in ICSI pregnancies (0.16% vs 0.03).
Most parents who conceive a child without medical assistance are between 18 and 34 years old, while the majority who use IVF are 35 and older. Women undergoing IVF are often older and therefore at a plausible increased risk of producing abnormal gametes responsible for poorer obstetrical and perinatal outcomes.
A study published in British Journal of Obstetrics and Gynaecology in 2017 examined the results of 2211 IVF, 1399 ICSI, and 301 060 naturally conceived births. The prevalence of any birth defect was 7.1, 9.9, and 5.7% in the IVF, ICSI, and natural conception groups, respectively. As expected, the risk of birth defects increased with maternal age among the natural conceptions. They observed a very low prevalence of birth defects in IVF births to women aged 40+ years (3.6%),compared with their fertile age‐matched peers (8.2%).
The authors’ comment was although aneuploidy increases with age, some presently unknown but common factor related to diminished fertility in older women may be strongly protective against birth defects should fertilisation occur. The inferences made by the authors are hard to be substantiated based on a relatively small number of births in the over age 40 group.
The risks of birth defects and pregnancy complications are expected to decrease further by taking antioxidants, vitamin D and folic acid supplements, and by avoiding smoking, alcohol and drugs. Advances in genetic and chromosomal testings to detect abnormalities early are the biggest modality to prevent birth defects. Couples considering IVF should discuss their genetic testing options with their doctor.