In-vitro-fertilisation (IVF) is a type of Assisted Reproductive Therapy (ART) that has helped millions of couples around the world conceive and have the families they desire.

The first live birth using IVF occurred in England in 1978, and since then, the procedure has been credited with over 8 million babies born over the last 4 decades [1, 2].

Fertility experts widely agree that children born through IVF grow up just as healthy as those that are naturally conceived [3], an assessment strongly supported by the high number of IVF babies leading normal lives today. However, some studies point to an increased risk of health issues among IVF babies, although there is no definitive conclusion linking these risks to the use of IVF and other ART [4].

So what exactly are the health risks that IVF babies may face, and what do we know so far? 

Let’s start by taking a closer look at IVF, and why it may contribute to increased health risks in babies. 

In an IVF treatment cycle, eggs are harvested from the mother’s ovaries just before ovulation occurs. They are then mixed with sperm from the father, and kept in the laboratory for observation, and to check for fertilisation and optimal growth [5].

Similar to what happens in the body, having the egg and sperm in close proximity allows fertilisation to occur. Having said that, this depends on the sperm’s ability to penetrate the outer layer of the egg and reach the cytoplasm inside. 

If the sperm is unable to do this, an intracytoplasmic sperm injection (ICSI) may be performed to ensure fertilisation. This is where a micropipette is used to insert a single sperm into the centre of the egg [5]. Whether naturally, or through ICSI, successfully fertilised eggs (now called embryos) are allowed to grow in the lab for up to 5 days, where it is then reintroduced into the mother’s body to continue the gestation process [5]. 

How, then, does IVF and ICSI introduce increased health risks to the resulting embryos? The reason is not yet fully understood, but there are 2 prevailing theories.

One is epigenetics, which may be thought of as ‘switches’ that govern the expression of genes, turning them on or off. Biological events in embryonic and early development can potentially influence health outcomes in later life, and epigenetics plays an important role in this process. It is thought that IVF could theoretically impact epigenetic gene expression and bring about certain health issues [6]. 

Another theory states that ICSI evades natural selection at the oocyte membrane, allowing both genetically and structurally abnormal sperm to fertilise eggs, which may pass abnormal genetic materials to the children [4]. 

Other factors may also have an impact. 

For instance, to increase the chances of success, multiple embryos are implanted in IVF. This increases the chances of multiple pregnancies, which is associated with higher risk of prematurity and low birth weight [4].

Additionally, couples who turn to IVF are often older (and would thus have accumulated epigenetic modifications), could have poorer sperm quality, or may have other health conditions that increase the health risks of the child [6]. 

Babies conceived through IVF and other ART have an increased risk of premature birth, low birth weight and younger gestational age. It is important to note that these issues are common in multiple pregnancies, which - as mentioned earlier - becomes more likely due to transferring multiple embryos to encourage successful pregnancy.

These issues are also observed among singleton pregnancies achieved via ART, but it is unclear that ART alone is the culprit — or if it even plays a part at all. Other studies suggest that the infertility of parents may be the main factor influencing these neonatal outcomes. 

A study involving infants born in California between 2007 and 2008 found that IVF babies had a higher chance of birth defects, particularly of the eyes, heart, reproductive organs and urinary system. After controlling for maternal characteristics (mother’s age, race, birth history, the infant’s gender and whether it was a multiple pregnancy etc.), it was found that overall, IVF infants' odds of having birth defects were 1.25 times greater than those of naturally conceived infants.

Furthermore, an increased risk of cancer in IVF babies who have birth defects has also been observed, with the study stating that such babies are 6.8 times more likely to develop the disease in childhood. 

Despite the significant association, incidences remain low with the authors of the cancer study noting that numbers in absolute terms are small. 

Another study found that IVF babies also have an increased risk of high blood pressure in adolescence, underpinned by premature vascular ageing. This unusual pathology was found when comparing IVF babies at adolescence (mean age = 16 years old) with their age-matched naturally conceived counterparts. 

While this is a concerning finding, the study’s sample size is very small, involving only 54 IVF-born subjects. Nevertheless, it might be prudent for parents of IVF babies to be more vigilant in imparting healthy lifestyle choices.

While the findings above may sound alarming, researchers stress that there is no definite conclusion so far that IVF babies face increased health links. 

A 2012 review published by the University of Zhejiang concludes that ART children are generally healthy, and while there are risks of poorer perinatal outcome, birth defects, and epigenetic disorders, it is still unclear whether ART procedures or subfertility itself is the cause [4]. 

Additionally, some of these studies have small sample sizes which may result in skewed results, while changing attitudes - such as a preference for singleton IVF babies, instead of multiple implantations - may also lower associated risks. 

It is clear that more and better studies are required before we can draw any definite conclusions regarding the health outcomes of IVF babies. Despite the concerns raised, IVF remains a popular and safe solution for couples finding difficulty in conceiving. Just be sure to have a frank discussion with your ob-gyn on the potential risks involved. 

Thankfully, there are many other options out there like the twoplus Applicator. An at-home intravaginal insemination device of sorts, it allows sperm to bypass the acidic vaginal tract and brings them closer to the cervical opening, thereby increasing chances of conception.