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Deep Dive

Medical Risks of ICSI

For many IVF patients, deciding to fertilize eggs using ICSI is an elective choice. For male factor patients, where ICSI is most effective, it improves success rates by about 3 – 7% on average. And for patients without male factor, ICSI likely doesn’t improve success rates at all.

While patients are aware of ICSI’s financial cost (around $1,687), most have little understanding of the potential medical risks it carries along the way.

Natural Fertilization vs. ICSI

In traditional IVF, fertility clinics try and recreate the natural selection process by surrounding an egg with sperm in a petri dish. Presuming the semen sample has sufficient concentration of sperm, and the speed (motility) and shape (morphology) fall within normal ranges, the egg should be fertilized naturally by the healthiest available sperm.

ICSI is a procedure whereby an embryologist selects an individual sperm from a sample, and injects the sperm directly into the egg, essentially end-running the natural fertilization process. When embryologists select sperm, they are able to choose one that can swim and has a normal shape, but beyond that the methods for selecting sperm are not very sophisticated — it’s not possible for them to select the “best” sperm verses a decent one. At the selection phase embryologists don’t know, for example, the DNA makeup of the sperm.

ICSI is an incredibly delicate procedure, and typically an embryologist needs training, skill, and practice to master the technique and to keep their skills fresh.

Risks of ICSI

Egg Damage

The most immediate concern with ICSI is that in the process of trying to fertilize an egg, some eggs will be damaged. Today, good labs manage to achieve fertilization in 70 – 80% of eggs inseminated with ICSI, and likely about 5% of good quality eggs will be damaged in the process.

For patients who have male factor infertility and would derive an absolute 3 – 7% higher rate of success (and in the context of 34 – 37% success rates, a 10 – 20% improvement), losing 5% of eggs is likely a good trade off. For others, the reward may not counterbalance the risk of egg loss.

Risks to Offspring

The longer term, and murkier, question, is whether using ICSI impacts offspring, either as babies or later in life. A 300,000 patient study in Australia investigated rates of birth defects comparing children born naturally (5.8%) versus through IVF (8.3%). When the authors disaggregated the “IVF” bucket, birth defects without ICSI were 7.7%, and 9.9% with ICSI. Women undergoing IVF with ICSI typically were older and had other risk factors, which the authors tried to account for.

Below you can see the results comparing the rate of birth defects in children born via IVF with no ICSI, or children born via IVF with ICSI, with children born naturally. After correcting for a number of factors, children born through IVF with ICSI were deemed to be statistically more likely to have a birth defect than those who were not born through IVF.

On the other hand, when a group of researchers did their best to pool all of the studies comparing birth defect rates of IVF with and without ICSI (which requires a fair amount of interpretation), they determined children born using IVF with ICSI carried no statistically higher risk of birth defects compared to children born using IVF with no ICSI.

In reality, much of this analysis required a fair amount of interpretation from the authors and statisticians, and the field is still at odds trying to determine if ICSI increases risk to offspring.

Importantly, it’s impossible to know if the increased rate of defects found by some studies are actually caused by the ICSI procedure, or if they’re related to the underlying conditions that caused its use in the first place.

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