May 2023

IVF Over 40: Insights from an Embryologist

Are you interested in the challenges involved in IVF for women over 40? In our interview with the head embryologist at Gynem Clinic, RNDr. Tomáš Rieger, Ph.D. shares insights on maximizing embryo quality through innovative laboratory methods, the impact of age on egg quality and fertilization rates, the potential benefits of genetic testing, and the ideal time for egg freezing.


1. From an embryological perspective, what are the specifics of IVF in women over 40?

Given that older patients are expected to have lower egg yields and poorer quality eggs, we recommend using all available methods to maximize the chances of obtaining a good embryo. In these cases, we particularly recommend the use of the Spindle Observation System laboratory method. The Spindle method allows us to optimize the time of ICSI (a method for fertilizing the oocyte), which, according to scientific studies, maximizes the chances of obtaining a good embryo. Patients often think that the Spindle method affects the maturity of the oocyte, but unfortunately, this cannot be influenced. We also recommend extended embryo culture to the blastocyst stage while using a time-lapse incubator. In the final stage of embryo preparation for transfer, we recommend using the EmbryoGlue method, for which we see statistically positive results in women over 40.

Since creating an embryo requires not only oocytes but also sperm, we must not forget about men, regardless of their age. We recommend using the full range of possible methods to select the most suitable sperm for fertilization. These methods do not affect the quality of sperm, but only allow for the selection of the best sperm for oocyte fertilization.


2. Is there any difference in the preparation of eggs for fertilization between older and younger oocytes?

To be honest, I can't see a visual difference. If I had two photos of oocytes and was told that one photo contained oocytes from a 30-year-old patient and the other from a 40-year-old patient, I would assume that the oocytes that look worse are from the older patient. Statistics show that the quality of oocytes deteriorates with the increasing age of patients. However, the truth is that a visually beautiful oocyte may have very poor genetic quality. Unfortunately, the genetic information of an oocyte cannot be evaluated in any way, and it is precisely this internal genetic quality that is crucial for the success of treatment. In the case of photos, I would therefore assign the worse-looking oocytes to the older patient, but I would not be surprised if I made a mistake. In IVF treatment, results are often due to purely individual factors.


3. Is the chance of fertilization lower in older eggs compared to younger ones?

Statistically, yes. This is due to the genetic disadvantage of older patients' oocytes. Older patients generally have a higher chance of genetic abnormalities. Why is this so? Let me try to explain it as simply as possible:

A woman is born with a certain number of eggs. These eggs remain in their development until the girl reaches reproductive age. The eggs mature during individual menstrual cycles. Since the eggs are released gradually over the years, up to 30 years can pass between the first and last release. During the "waiting" period for the release of the egg, the genetic information inside the egg is protected by special proteins. These proteins are subject to the negative effects of oxidative stress, which is a standard part of the human body. The level of this stress is individual and can be positively influenced by antioxidants. You can imagine the negative effect of oxidative stress as imaginary bombardment of the complex genetic information and protective proteins inside the oocyte by small bombs - so-called free radicals.

Over time, under the influence of this bombardment, the proteins protecting the genetic information in the egg weaken and are damaged. Therefore, with increasing age, there is a greater likelihood of genetic abnormalities in the matured egg. This cannot be influenced or corrected by any method. This is why older eggs have a lower probability of successful fertilization, the creation of a quality embryo, and ultimately a healthy foetus. The aforementioned genetic abnormality can manifest in any stage of embryo or foetal development.


4. Do you recommend genetic testing on embryos before implantation for women over 40?

At this point, the opinions of doctors and embryologists differ. Doctors often recommend preimplantation genetic testing of embryos for women over 40 years of age. The reason is the higher chance of genetic defects in embryos. From an embryological point of view, genetic analyses are suitable for cycles in which more than one quality blastocyst can be obtained. As mentioned earlier, the chance of producing a greater number of quality eggs and subsequently embryos decreases with age. It is very likely that a woman over 40 will only produce 1 quality blastocyst. In that case, based on my experience, I see a greater benefit in a fresh transfer without biopsy than with biopsy and transfer of a frozen embryo.

I have reached this conclusion because I am aware of the complexity of the method, the associated risks of freezing embryos, and the risk of DNA analysis errors. It is not excluded that the sample taken from the embryo is not representative of the entire embryo or its larger part. In addition, self-repair mechanisms work in human embryos, and embryos can cope with small DNA errors on their own. Embryologists often agree that embryo testing is appropriate mainly for women aged 35-39, when we are able to work with a greater number of quality blastocysts and testing works as a kind of embryo selection for implantation.

To summarise: from an embryologist's point of view, when obtaining one quality embryo at the blastocyst stage, it seems more advantageous to me to transfer a fresh embryo without genetic testing. In the case of obtaining multiple quality blastocysts, it makes sense to genetically test the embryos and then select the appropriate embryo for transfer.


5. When is the ideal time to freeze eggs?

According to most studies conducted on thousands of eggs, the quality of eggs does not change until the age of 32. The ratio of good genetic information in the oocyte compared to oocytes with genetic defects is monitored. Simply put, the percentage of "defective" oocytes to "healthy" oocytes is approximately 10% in women under 32 years old. Studies then record a fairly sharp increase in the ratio of defective oocytes to good ones. Of course, everything is individual, but overall, based on known studies, it can be concluded that it is ideal to freeze eggs in women under the age of 32.