The question of the health of children born after advanced fertility treatments is one that has great importance both to patients and fertility physicians alike. In general, the data regarding the outcomes for children born after IVF, either with or without the use of ICSI, have been extremely reassuring.

The problem with these studies is the identification of an appropriate control group with which to compare the rate of problems found in the children conceived with advanced fertility techniques. Overall, most studies suggest a background risk of birth defects in naturally conceived children of approximately 4% to 5%. However, these couples tend to be younger than the couples undergoing IVF and, by definition, do not suffer from infertility. Although the vast majority of studies suggest no increased risk of anomalies in children conceived after IVF, few of these studies have looked at the rate of congenital anomalies in children conceived naturally but born to parents who suffered infertility that spontaneously resolved without treatment. This group of patients clearly represents a more appropriate control group with which to compare patients who seek out advanced fertility treatments. The few studies that have looked at this question have noted that although patients who suffered from infertility have a higher rate of anomalies and pregnancy related complications, the means by which these couples eventually conceived (spontaneously or with IVF) did not influence the rate of these problems. Therefore, it may not be the IVF process per se that is the issue here but rather the underlying infertility that matters.

Recently, in Australia, a systematic review was conducted of all studies that had previously examined the possible increased risk to children conceived after treatment with IVF and/or ICSI (Hansen, M. et al., Human Reproduction. 20 (2):328–338, 2005). However, many of these studies compare the rate of congenital abnormalities in children conceived spontaneously with the rate in children who were born to older couples undergoing IVF and/or ICSI. In many studies, the rate of congenital anomalies in the control group has been around 4%, whereas the rate of congenital anomalies in the group of couples undergoing IVF and ICSI has been 6% or greater. The difference between 4% and 6% is statistically significant and suggests that there may be an increased risk to children conceived through the use of advanced reproductive techniques. However, the question still remains as to whether this is a problem related to IVF itself or to the underlying infertility that leads to the use of IVF. In any case, most patients accept an increased absolute risk of 2% as being reasonable, especially given that their options for spontaneous conception may be significantly limited.

The greatest risk to the children conceived after fertility treatment is that of prematurity related to multiple pregnancy. Several strategies are used to reduce the rate of multiple gestations (see Question 50). The risks of prematurity associated with twins are significant and should not be discounted quickly, especially given that 50% of twins deliver a month or more before their due date.

In addition, the question has been raised as to whether even IVF singleton pregnancies are at higher risk for low birth weight and prematurity. If true, the cause of this increased risk may be difficult to determine. Patients undergoing IVF suffer from infertility, so any increased rate of adverse pregnancy outcome might not be so much a result of the IVF process as it is related to the couple’s underlying problem of infertility. Several studies have suggested that women who conceive spontaneously, but who have a preceding history of infertility, have a significantly increased rate of prematurity and pregnancy-related complications such as placenta previa, abruption, and low-birth-weight infants.

Another way to look at the question of whether any risk is related to the process of IVF itself versus the patient population undergoing IVF is to examine the pregnancy outcomes in women who undergo IVF but use a gestational carrier (carriers usually have an excellent reproductive history). A study of these pregnancies found there was no increased risk of prematurity or low birth weight in the children conceived and carried in this way. This reassuring outcome would suggest that the problem lies not so much with the IVF process but, unfortunately, with the patients who require IVF to conceive.

The impact of new and emerging technologies on the rate of congenital anomalies in children born after fertility treatment remains a subject of ongoing debate. The potential risks inherent in micromanipulation of the embryo prior to embryo transfer—like that required for preimplantation genetic diagnosis (PGD)—remain unknown. Although more than 4 million IVF babies have been delivered worldwide to date, only a relatively small number of children have been delivered after the use of PGD or following unusual situations such as “rescue ICSI” performed on the day following egg collection because of unanticipated failed fertilization. When considering such novel treatments, the physician needs to inform the patient/couple of any known or suspected risks. Currently, several studies are under way in this country and throughout the world to continue to monitor the health of those children delivered following advanced fertility treatments.

Carol comments:

Although this question is focused on the “physical normalcy” of IVF babies, I would like to comment on the “perceived normalcy” of IVF babies. I do understand that a large percentage of people will never have to deal with this challenge, and that ignorance is bliss, but I am still surprised by how commonplace the misperceptions related to ART are. I’ll never forget a comment that a woman made to me during my first pregnancy. I was flying back from a visit with my extended family during which we had announced the long-awaited news that I was pregnant. My husband and I struck up a conversation with the woman sitting next to us. As what now seems inevitable, the subject of IVF came up. I confirmed that my pregnancy was, indeed, a result of IVF. Without missing a beat, the woman looked at me and said, “I’ve never seen one of those babies.” I was astounded.

Luckily, my husband was there to help me regain my composure and politely explain to the woman that, in fact, IVF babies are not from Mars. Long story short, it’s hard to anticipate what people might say to you, so be prepared.