While most IVF pregnancies will progress normally and without any increased risk to mother or baby, there is little doubt that women who conceive in this manner as well as their babies are potentially at increased risk. In fact, women who give birth after IVF treatment are several times as likely to suffer from significant complications such as miscarriage, pregnancy induced hypertension, premature separation of the placenta, complicated labor, post-partum bleeding and infection and are about twice as likely to give birth to underweight babies due to premature delivery or intrauterine growth retardation (IUGR) with placental insufficiency. There is also a slight but significantly increase in the risk of birth defects. Why is this so and what should be done about it?
The hundreds of thousands of babies born and the growing worldwide demand for access to this technology clearly indicate that IVF is here to stay. It is thus incumbent on those of us that provide such services, to track the long-term development of babies born by this method, so that we can rationally strategize on how to improve safety along with outcome. It is also appropriate that we are open and forthcoming in addressing related concerns expressed by the patients we are privileged to serve, thereby empowering them to make informed decisions.’
Why is it that women who conceive following IVF and their babies are at “higher risk” and what are the contributing factors?
Age of the female partner: It is not that IVF in older women causes genetic and chromosomal defects that lead to miscarriage and birth defects, it is more accurate to say that fact that advancing age increases the risk and that women undergoing IVF tend to be older than those who conceive spontaneously. By way of example, chromosomal birth defects such as Down syndrome (and perhaps also, autism) in the new born. In fact, the miscarriage rate which for women under 35Y is about 10-15% increases to above 60% by the mid-forties, and the risk of chromosomal birth defects such as Down syndrome increases from approximately 1/1000 for women under 30Y to 1:40 by age 45Y. In both cases, this is primarily due to an increase in egg aneuploidy (numerical chromosomal defects) with advancing maternal age. There is, in addition, an independent (but less marked) increase in certain genetic defects in the offspring of older women
With increasing maternal age also comes a greater risk of pregnancy-induced complications such as hypertension (preeclampsia), diabetes, intrauterine growth retardation due to placental insufficiency, premature delivery, the need for cesarean delivery, bleeding prior to, during and after delivery and infection. Thus older pregnant women (over 35 years) who conceive following IVF should probably be under the care of a high-risk obstetrician (someone boarded in Maternal-Fetal medicine) or at the very least see such a specialist intermittently while under the care of their regular obstetrician.
Age of the male partner: There is some evidence to suggest that the older the father, the greater the risk of autism in the offspring. But if this is indeed the case, it is a small increase and should not (in my opinion) be a reason to avoid parenting through IVF.
Multiple Pregnancies: IVF remains a major cause of multiple births with incumbent increased risks to both mother and babies. This is primarily the result of multiple embryos being transferred indiscriminately in order to improve the chance of success. While twin pregnancies are associated with increased perinatal morbidity and mortality (largely due to premature delivery), high-order multiple pregnancies (triplets or greater) are disproportionately hazardous. Not only does this impact the well being of the mother and the children so born, but it has serious family, social and societal consequences
On the positive side, the fact that the number of embryos being transferred at a time is going down and with it the incidence of IVF multiple pregnancies is declining. Nevertheless, we must do better because the only way to fix this problem is to transfer fewer embryos. With the possible exception of IVF performed in older women (over 35Y), there is rarely a justification to transfer more than two embryos at a time and with the advent of full chromosome preimplantation genetic sampling (PGS) using techniques such as next generation gene sequencing (NGS) and comparative genomic hybridization to identify “competent” embryos that that are most likely to propagate a baby, we can now, regardless of the age of the egg provider, confidently transfer up to 2 embryos at a time with a high expectation of a live birth.
Does the cause of Infertility play a role?
- Uterine defects. Women undergoing IVF often have uterine pathology (e.g., fibroids, uterine septum, intrauterine scarring, and adenomyosis) that increase the risk of poor intrauterine growth as well as premature labor.
- Pelvic pathology. Conditions such as endometriosis, inflammatory and non-inflammatory pelvic adhesions, can result in pelvic pain and restrict uterine growth. This can lead to premature labor.
- Implantation dysfunction: Implantation dysfunction, whether due to uterine pathology, a thin endometrial lining or immunologic implantation dysfunction all can result in poor placental development and compromised intrauterine growth? This in turn can result in miscarriage, intrauterine growth retardation, or intrauterine death. Surviving babies can suffer occurs too early, the baby might suffer the effects of prematurity and if too late, the long term physical and neurologic effects of prolonged intrauterine deprivation.
Does IVF treatment per se increase the risk of Birth defects? Between 3% and 5% of all infants are diagnosed with congenital birth defects. There have been numerous studies done to determine whether IVF treatment per se increases the risk of birth defects. Some suggest an increase incidence this is likely attributable to the underlying infertility or its determinants, since couples who take longer than a year to conceive have a similar increased risk of having babies that exhibit birth defects. Simply stated, women undergoing IVF tend to be older and/or have other independent factors that might play a role and it is difficult to reliably correct for these variables.
So should couples contemplating IVF treatment think again? The answer is “not really” because the risk of birth defects is still very small. Either way, even if the incidence of birth defects were slightly increased, many are detectable early during pregnancy, providing the woman/couple with the opportunity to decide whether to terminate.
Clearly, IVF pregnancies are at increased risk of adverse outcomes and as such require careful prenatal oversight. However, the fact remains that the vast majority of the children born following IVF will have a good outcome. Given the known risks associated with IVF pregnancies and the fact that multiple pregnancy (albeit on the decline)remains one of the most important negative factors, strong emphasis needs to be placed on the avoidance of transferring more than two embryos at a time, with the ultimate goal being single embryo transfers. Finally, most IVF patients require very diligent prenatal care which (in my opinion) should include the involvement of a specialist in Maternal Fetal Medicine (a “high risk obstetrician”) whenever possible.