Risks of IVF

Summary

While there are many theoretical risks associated with IVF, here we will focus on four: ovarian hyperstimulation syndrome (OHSS), issues associated with twins or triplet pregnancies, birth defects in offspring, and women developing cancer after undergoing IVF.

Generally speaking, it seems reasonably clear that IVF increases the risk of OHSS and multiple pregnancies. But that doesn’t have to be the case, and treatment can actually be adjusted to nearly eliminate these risks.

As for birth defects within the children who result from IVF, it appears that IVF increases the risk, especially for boys, but the absolute increase is small and there are plausible (but not bulletproof) ways to mitigate the risk.

As for breast and ovarian cancer, it’s difficult to conclude whether the underlying infertility itself, or the IVF treatment, drives higher rates of cancer. Generally speaking, recent studies have been reassuring and pointed to the infertility, rather than IVF, as the causal factor. What’s more, the absolute incidence of both breast and ovarian cancers amongst IVF patients is low. However, whether IVF drives higher rates of cancer is unresolved and requires more study. Given the complexity of the answer, we may never arrive at a definitive conclusion.

As always, be sure to have a thorough discussion with your doctor on each of these subjects. Your circumstances may well be unique and require a deeper conversation.

IVF Risks Summary

Ovarian Hyperstimulation Syndrome (OHSS)

Most IVF patients are given gonadotropins to stimulate their ovaries to produce an abnormally high number of follicles (that house eggs) and a “trigger shot” to ensure the doctor can remove mature eggs from the follicles during retrieval.

What Causes OHSS

Women who have been “overstimulated” with gonadotropin may develop Ovarian Hyperstimulation Syndrome or OHSS. OHSS symptoms include pain, nausea, dizziness, vomiting, hospitalization, organ failure or worse. OHSS occurs in 1 - 10% of IVF patients, but that’s an average — amongst certain demographics (like younger women, women with PCOS, or those with a high AMH) the risk and incidence is higher.

OHSS is preventable and for it to transpire, two things must occur.

First, a woman must receive more gonadotropin than her body can handle, and this manifests itself in the fast growth of a high number of follicles or especially high estrogen levels. If this unfolds, the cycle can be stopped and OHSS can be avoided.

Signs of OHSS

Even if a woman is overstimulated and continues treatment, if she takes Lupron (instead of hCG) as her trigger, OHSS can be largely avoided. A powerful example of this comes from three studies of women freezing their eggs showing that when Lupron is used as a trigger, OHSS is virtually eliminated.

Lupron Eliminates OHSS

However, a Lupron trigger can only be used with an “Antagonist” protocol which must be agreed to at the outset of the cycle. Doses can be changed during a cycle, but protocols can’t be.

Issues Associated With Twin or Triplet Pregnancies

When multiple embryos are transferred, the risks that an IVF pregnancy results in a multiple gestation birth rise from 1% to as high as 30%. This results in greater risk to the mother and to the offspring, as you can see in three excellent studies below.

eDET Risk

Twins and triplets are more likely to be born prematurely, possibly missing out on a period of in-utero development critical for grey matter development in the brain. As a result, prematurity has been associated with lower cognitive function as you can see in analysis that appeared in the Journal of The American Medical Association.

Prematurity and Cognition

Much of this risk can be mitigated by transferring one embryo per transfer. While this may increase the odds the first transfer doesn’t work (requiring an additional transfer, costing $3,000 per transfer), it doesn’t lower the odds the IVF cycle itself will lead to a live birth (a cycle starts when a woman does stimulation ahead of a retrieval).

Risk of Birth Defects To Offspring

This is a difficult subject to study and summarize for two reasons. First, the definition of “birth defects” vary by type and the age of the offspring. Second, IVF patients often have fertility issues, and by definition are different from the general population. As a result, any difference in the rates of birth defects in offspring could be on account of the factors that produced infertility in the first place, the IVF process itself, or even another factor. It can be difficult to disentangle these possible factors.

Generally speaking, 1 - 3% of babies born in the general population suffer from some birth defect. When a couple has had trouble conceiving, that rate climbs to 3 - 5%. This is best evidenced by one large Finnish registry that includes nearly 30,000 offspring.

Amongst the groups needing fertility assistance (using ovulation induction, IUI, or IVF), those requiring IVF were more likely to produce a child with a birth defect, but, as you can see below, the absolute difference is rather small.

Birth Defects Amongst Finnish Offspring

When we look more closely at the Finnish data, amongst singleton births, in many categories children born from any type of fertility treatment (not just IVF) are more likely to have a birth defect than those conceived naturally. But that does not get IVF off the hook necessarily. As you can see below, babies born from IVF do have more issues than those born from IUI or ovulation induction, especially boys.

That said, one should keep straight the difference between “relative” and “absolute” risk here. In the example below, boys born from IVF are 1.6x more likely on a relative basis to have a birth defect compared to boys in the general population. But since the odds of that happening in the general population are low (~3%), the absolute risk of of boys born from IVF developing a birth defects is only about 5%.

IVF Birth Defects

Two strategies for mitigating the risk of birth defects during IVF could include:

  • Deploying more single embryo transfer, as babies born from multiple gestation pregnancies are more likely to encounter physical and cognitive challenges.

  • Only using ICSI as a fertilization technique when absolutely necessary. As one large New England Journal of Medicine study showed, the incidence of birth defects is lower when conventional insemination is deployed. However, a confounder in the data is that those IVF patients who required ICSI may be different than those who used conventional insemination (namely, having a severe male factor infertility issue).

Birth Defects and ICSI

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