Deep Dive

The Risks of Egg Freezing

Egg freezing is typically an elective procedure, and there is no guarantee it will “work”, so it’s important to digest the medical risks (namely ovarian hyperstimulation syndrome, OHSS) and how they sit with you. We think about these as “short-term knowns” and “longer-term unknowns.” Most of the concern around egg freezing stems from the drugs, so let’s start there.

Natural vs. Stimulated Cycles

During a woman’s natural, monthly cycle, she will produce a hormone called follicle-stimulating hormone (FSH), which signals a follicle or two in her ovaries to begin growing eggs. Weeks later, the body emits another hormone, luteinizing hormone, that instructs these follicles to release that egg (aka ovulation). In a typical, natural cycle, the ovary releases a single egg that ultimately travels down the fallopian tubes to either be fertilized, or released.

In the case of IVF and egg freezing (which is the same process as IVF, minus the insemination and transfer), the ovaries are stimulated to release far more eggs than the single egg they would naturally produce. During a stimulated cycle, you will inject yourself with hormones called gonadotropins, with the goal of encourage follicle growth to derive as many eggs as possible. During this period, you’ll regularly return to the clinic where they will check your follicle growth, monitor your hormone levels, and make dose adjustments. Ultimately, your doctor will decide when to have you inject a “trigger shot" to release the eggs and 36 hours later your doctor will retrieve those eggs with a needle and mini-vacuum.

Near-Term Knowns

The chief near-term risk during an egg freezing cycle is overstimulating your ovaries - ovarian hyperstimulation syndrome. This happens in approximately 5% of IVF and egg freezing cycles. In severe forms it can be dangerous, with symptoms that include shortness of breath, gastric reflux, pain and vomiting.

For OHSS to occur, two things must have gone awry. First, your doctor will have prescribed a protocol that was too aggressive for your body to handle. During your monitoring appointments this should become apparent. If the patient has 25 or more follicles over 14mm in diameter, and elevated amounts of estrogen in her blood (>2,500 pg/ml), that is a warning sign. As the estradiol level climbs, so too does the OHSS risk, and by 6,000 pg/ml, patients run an 80% risk of developing the syndrome.

The next required step for OHSS to occur, is for your doctor to order the “trigger shot” despite the warning signs. Frankly, we just don’t know which doctors routinely overstimulate their patients, but we do know which patients are most susceptible: namely women with PCOS, and younger patients. Given the younger profile of most egg freezing patients, it’s plausible they suffer a greater degree of overstimulation than the headline 5% rate.

Longer-Term Unknowns: Does Egg Freezing Cause Cancer?

A concern that has dogged fertility treatment for years is that the hormone treatment raises the risk of cancer. Hormone therapy typically raises a patient’s estrogen levels, and estrogen can abet the growth of ovarian and breast cancers specifically.

Before we dive into the data, a few notes. First, these studies focus on IVF patients, who may be subjected to a similar course of hormone treatment as egg freezers, but are often older and suffering from underlying conditions, making it a different patient population.

Second, these studies follow women from a geography (Europe) and an era (10 – 30 years ago), that may not reflect how you would be treated today. The flip side is that the study sizes are large and have respectable lengths of follow-up duration. In the US, we are simply not organized or equipped to run such disciplined studies. Thus, they’re the best we have.

Ovarian Cancer

Probably the best study on the role of hormone therapy and ovarian cancer comes from a British registry of 233,000 patients where those receiving IVF recorded a small absolute increased incidence (15 vs. 10 cases for every 10,000 patients) of ovarian cancer. Whether the underlying causes of infertility, or the IVF treatment itself, drove those incremental 5 / 10,000 cases is hard to say, as there is evidence in both directions.

Evidence to suggest the underlying infertility (rather than the drugs) is the link to cancer are that women who suffered from female infertility saw an increased rate of ovarian cancer, but not women where male factor infertility caused their need for IVF. Likewise, women who did not end up with a child saw an increased incidence in ovarian cancer (inferring their underlying issues might be the culprit) and it does not appear that there was a link between increased hormone treatment and increased incidence. On the other hand, younger women who underwent IVF did suffer a greater incidence of ovarian cancer, which is unnerving given egg freezing patients are younger.

Breast Cancer

The data on breast cancer is even less conclusive. Studies have cropped up that suggest IVF patients (some older, some younger may suffer from an increased risk, but just as many studies find no correlation.

The most recent data comes from a 25,000 patient study out of Holland, which, like the ovarian cancer study, was large and had superb follow-up, but was focused on treatments from a different era. The data showed no increased risk for IVF patients compared with women of a similar profile, and most encouragingly, no dose-related increased risk. Said differently, women who were given greater amounts of hormones did not have higher rates of cancer.

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