It’s always heartbreaking when an egg freezing or IVF cycle does not work, or the outcome isn’t as good as you’d hoped. Even though Ovally patients complete a battery of pre-treatment tests to make sure to the extent possible that they’re a good candidate for the procedure, these tests still cannot rule out some risks that a cycle might be unsuccessful or less successful, with either no or few mature eggs retrieved. Below are some examples of such situations that we’ve observed, backed up by scientific literature. These examples are not comprehensive, and we advise you to always ask your doctor for what risks might exist in your specific case.
1. Not enough high-quality eggs:
“Low ovarian reserve” (defined as decreased number and quality of eggs), is detected to some extent by pre-treatment tests when a physician counts your number of antral follicles (which contain eggs) during an ultrasound and measures certain hormone levels. If the follicle count and certain hormone levels are low, they indicate low ovarian reserve and low responsiveness to fertility treatment. In this case, your doctor will be able to predict that you’ll be more likely to have few eggs retrieved. Low ovarian reserve is associated with aging but can also occur in younger women, and is the most common reason for infertility in women, with the CDC mentioning it as an underlying cause in 31% of IVF cases. It’s best to complete pre-treatment tests close to your treatment start date to have a good sense of your ovarian reserve for your upcoming treatment, as it decreases over time and can sometimes do so rapidly (e.g., an almost 40% decline over 2.5 years has been observed).
Ovarian cysts are a reason the “stimulation” phase of egg freezing or IVF, when more eggs than usual are stimulated to grow, has to be postponed until they have subsided. There are different kinds of ovarian cysts – the more common are “follicular cysts” that form when the follicle contained an egg in a previous cycle but did not release it during ovulation. Another common cyst is a “corpus luteum cyst” that accumulates fluid inside the follicle. A pre-treatment ultrasound checks for enlarged cysts and if a cyst is detected, fertility treatment is typically delayed until the cyst has subsided. Another such ultrasound is performed on the first day of treatment before you’ve taken any hormones, to make sure all follicles are “dormant”, and there are no enlarged follicles. Avoiding enlarged cysts is important, as you wouldn’t want to use hormones to further stimulate cysts, which could grow even bigger and risk bursting. Taking hormonal birth control can help suppress cysts.
3. Low or no response to drugs:
Pre-treatment hormone tests give you an indication of your response to fertility drugs. For example, “Anti-Muellerian” hormone levels are associated with responsiveness to follicle-stimulating hormones. However, in some cases, “poor ovarian response” to fertility drugs cannot be predicted. In such cases, patients may have a resistance or very low response to fertility drugs. This can be the case if they have a genetic mutation that prevents their follicular receptors from responding to follicle-stimulating hormones; this is so rare that it is not screened in advance. Some patients also respond better to one kind of hormone prescription brand over another. Further, some patients don’t seem to respond well to the hormones that get their eggs to full maturity at the end of the stimulation period, when the eggs are supposed to shed 23 of their 46 chromosomes. In that case, the retrieved eggs are not fully mature (i.e., don’t have the right number of chromosomes) and cannot be fertilized.
4. Eggs developing at different rates:
Having follicles that develop at different speeds can be a frustrating experience if some of them reach mature size quickly and others lag behind significantly. If smaller follicles don’t catch up quickly enough to reach mature size, then only the follicles that are of mature size (around 18mm) will typically contain mature eggs that are retrieved.
5. Low egg quality:
Low egg quality is one of the trickiest issues underlying less successful egg freezing or IVF cycles, as egg quality cannot be tested until eggs are actually fertilized. However, we know a few things: Lower egg quality is related to aging and in some cases to polycystic ovary syndrome, especially when coupled with obesity. Lower quality eggs (e.g., eggs with chromosomal abnormalities) are less likely to grow to the size at which they can be retrieved, and to fully mature in response to the last hormone (the “trigger shot”), as discussed in 3. Even if lower quality eggs fully mature, they are less likely to fertilize and grow to be embryos later on.
6. Empty follicles:
In <2% of cases, follicles grow to be the mature size, but turn out not to contain an egg during retrieval. Given how tiny eggs are, they cannot be seen during the ultrasound, so it’s not possible to detect empty follicles in advance. Empty follicles have been found to be more likely in women with low ovarian reserve (see 1.), polycystic ovary syndrome, and those who are a little bit older. In those cases the follicles may not actually be empty, but the immature or chromosomally abnormal egg may not be deteachable from its follicle. Empty follicle syndrome is still being researched, but we know of a other underlying reasons for its occurrence if egg quality is not an issue: For some patients, there may be challenges with absorbing the “trigger shot” that gets the eggs to complete the last step of maturation (see 3.). Similarly, in some cases there are issues with the dosage and timing of this trigger shot (typically human error).
In <2% of cases, patients have an outsized response to the hormones and suffer from hyperstimulation. If this is detected and cannot be mitigated with lower hormone doses, the treatment may be stopped early to prevent further hyperstimulation and more severe symptoms. The risk of hyperstimulation is higher in patients with high levels of certain hormones. Doctors monitor the risk by checking on your progress with ultrasounds and blood tests on a regular basis.
As you can tell, some risks of a less successful or unsuccessful egg freezing or IVF cycle can be predicted, while other are only discovered during treatment or after the egg retrieval. In the above we did not go into the remainder of the IVF procedure, i.e., egg fertilization, development till embryo blastocyst stage, implantation, and pregnancy. Lower rates of success at those stages are dependent on many factors, including egg quality, but also sperm quality, other underlying fertility issues, and the capabilities of the lab. The above risks tend to be lower for younger egg freezers with no known fertility issues than for IVF patients with fertility issues, where factors like low ovarian reserve tend to be more common.
These risks are part of what make fertility treatment so emotionally challenging. By being open about some of the reasons why treatments can be less successful, we hope to prepare you better and hope to be able to support you through your journey.