If you’re headed to a fertility clinic for IVF this year, the odds are high that your doctor will suggest using a technique called ICSI during insemination. ICSI is crucial for success in some cases, but that’s not true for everyone, and the costs of performing ICSI are non-trivial. There are different scenarios that make ICSI more, and less, necessary.
ICSI is Spectacular for Male Factor Infertility
ICSI was originally designed to help in cases of male factor infertility, and patients with a male factor issue are still those who see the greatest benefit from ICSI.
Male factor infertility impacts 30 – 50% of couples suffering from infertility. By injecting a single sperm directly into an egg, ICSI helps sperm overcome many of the natural barriers they would encounter when fertilizing an egg. For example, if a man has bad sperm motility, meaning his sperm aren’t swimming well, ICSI helps bypass that issue in fertilization. Likewise, if a man suffers from a low sperm count, where there would be a low likelihood of fertilization taking place, as long as an embryologist is able to find and select a single good sperm, she is able to perform ICSI to fertilize an egg.
So ICSI is enormously effective in treating male factor infertility: it cuts down on the percentage of failed fertilizations by more than half from 14% to 6% (with "cancelled cycles after egg retrieval but before transfer", as a proxy). A canceled cycle is heartbreaking for patients, and often means enduring the cost and aggravation of additional cycles, and if the problem persists, the prospect of using a sperm donor, foregoing the father’s biological tie to the child.
Here we should state that “male factor” is a broadly-defined term and that some patients with this diagnosis more sorely need to use ICSI than others. For instance, patients with azoospermia must use ICSI with IVF to have any chance at success. On the other hand, there is a fair amount of debate as to whether patients with a poor morphology (but an otherwise sufficient concentration and motility) truly need ICSI. Below is one study from NYU that looked at patients who suffered from poor morphology, but no other issues identified on the semen analysis.
Is ICSI Helpful for Couples Without Male Factor Issues? Usually Not.
When ICSI is used in IVF procedures with no male factor infertility, it appears there is no benefit. You’ll recall that ICSI’s primary purpose is to increase fertilization rates and decrease the number of cycles cancelled between retrieval and transfer. As you can see below, using ICSI in non-male factor patients ultimately generates no better outcomes.
So is ICSI Being Overused? Maybe.
Despite this, ICSI use has skyrocketed for patients without male infertility, reaching rates between 60 – 80%, depending on the type of patient and their IVF treatment protocol. Most clinicians will tell you that ICSI is the best way to assure fertilization, and for some patients, such as those with unexplained infertility, there are genuine concerns that fertilization may be challenging. If fertilization does not happen, that of course is devastating to the patient.
The reality is that in most circumstances, ICSI may slightly improve fertilization rates, but it does not improve the end outcome. So patients might not have to receive that devastating phone call informing them of failed fertilization, but that doesn’t mean their cycle is more likely to be successful in the end.
We often hear doctors say ICSI is necessary in “poor prognosis” cases, especially in circumstances where there is a low egg count. The data simply doesn't support this. The one counter-example, not captured here, is that when a woman has historically had a low percentage of eggs fertilized in the past, ICSI should be used. But again, in most “poor responders”, ICSI is of no help.
ICSI and PGS
One subject we need to consider is whether doing Preimplantation Genetic Screening (PGS) of embryos makes ICSI a necessity.
PGS theoretically helps doctors determine whether an embryo is chromosomally normal, and select which embryos should be transferred. If you’re interested, we’ve done a lot more work on the details of PGS, and what the data says specifically about PGS and ICSI.
At a high level there are a few quick things to know about PGS. First, its proponents deeply believe that it cuts down on the risk of both miscarriage (by transferring the embryos most likely to work) and twin pregnancies (by allowing them to select a single good embryo). Second, PGS is growing like crazy. According to our data, 35% of IVF cycles incorporate PGS, and that number will top 50% in 18 months.
So how does ICSI fit in here? Many clinics strongly suggest that patients use ICSI if they are planning to use PGS testing. The argument is that ICSI makes PGS testing more accurate.
As you can see below, use of ICSI in conjunction with PGS has exploded.
Your doctor may say that they would otherwise not use ICSI, but because they want to use PGS, they feel compelled to. The reality is that many of these doctors were ordering ICSI well before PGS was popular.
But that does not necessarily settle the debate as to whether ICSI is necessary if we want to use PGS. Back to the main argument for using it – ICSI makes PGS more accurate. If we believe that to be the case, then we would assume that ICSI-inseminated embryos would have a higher likelihood of being correctly identified as chromosomally normal, so there would be a higher birth rate when those embryos were transferred, compared to PGS tested embryos that didn’t use ICSI.
The reality is that when PGS is used to test embryos for IVF the live birth rates are virtually identical regardless of whether ICSI is used or not.
Many of the third-party laboratories that run the PGS analysis do not require that the embryo was fertilized using ICSI, though they may be slow to admit it for fear of upsetting the referring clinics who are eager to perform ICSI.
In Contrast, PGD Testing
While the acronyms are confusing, and the tests do have similarities, PGD, or preimplantation genetic diagnosis, is different from PGS. With PGD, doctors are using a biopsy of an embryo's cells to test that embryo for specific genetic diseases – these single gene disorders can be life threatening to a child. When PGD testing is being used, there is no argument: ICSI is absolutely necessary to ensure the test’s accuracy.
ICSI Use by Region and Clinic Type
ICSI is regarded, and deployed, differently across regions. For instance, a review of the publicly-available CDC data reveals ICSI is used far more often in the Southeast, and in Southern California, than in New England. And while initially it was the larger clinics that adopted ICSI more quickly, today it’s smaller clinics who use ICSI in a more aggressive fashion.
Costs and Downsides
In a field where patients are desperate for good outcomes, many doctors think it is a mistake not to employ every weapon in their arsenal. Especially when they believe the costs and risks of using treatments like ICSI are relatively harmless. Of course, most doctors will acknowledge that their perception of cost may not be in line with that of their patients, and many patients, when making such an emotionally-charged decision, have trouble calibrating risk rationally.
ICSI costs today are approximately $800 - $2,500 depending on where you live and it should be said, typically those costs represent a fraction of the cost of doing a single IVF cycle. As for the medical risks, most studies indicate the impact of employing ICSI are small on an absolute basis, but since ICSI is a delicate procedure and bypasses natural selection, employing ICSI carries more risk than utilizing natural insemination.
Given the additional costs and potential downsides, it’s crucial that patients understand whether or not ICSI will help them achieve success in their individual case.