How can we predict IVF outcome in poor ovarian responders?

In this webinar session, Dr Ángela Llaneza, Fertility Specialist at Clinica Tambre shared her expertise on the intriguing topic of predicting IVF outcomes in poor ovarian responders. Poor ovarian response, also known as low ovarian reserve, poses a significant challenge in fertility treatments. However, with advancements in reproductive medicine, there have been promising developments in identifying markers and predictors that can assist in determining the success rates of IVF in such cases.

Woman’s physiology & age

In essence, the production of oocytes occurs during fetal development when our mothers were pregnant with us. Even then, the ovaries were capable of producing millions of follicles. At birth, there are already millions of oocytes present, but by the time puberty begins, this number decreases to around 400,000-600,000. From that point onward, there is a constant loss of oocytes until menopause. This loss is initially slow but accelerates significantly after the age of 35.

Nowadays, due to various reasons, women often postpone their plans for motherhood, leading to situations where there are not enough retrievable oocytes in the ovaries to achieve a good prognosis and high success rates during IVF treatments. Some women may experience premature ovarian failure, where there is a loss of menses and a lack of follicles in the ovaries before the age of 40. On the other hand, some women may have a slower decline in ovarian reserve and still have a good number of follicles in their ovaries, even at unexpected ages.

Assessing the ovarian reserve, which refers to the reproductive potential of the ovaries, is crucial before starting any IVF treatment. It helps us understand the status of the ovaries and their ability to respond to ovarian stimulation. It’s important to note that ovarian reserve is not very useful in predicting pregnancy rates, but is valuable in predicting the response to ovarian stimulation.

Ovarian stimulation is the process we use to maximize the number of growing follicles in the ovaries. In a natural cycle, only one dominant follicle is typically selected for ovulation, while the others undergo atresia (follicular death). However, with ovarian stimulation, we create conditions that allow multiple follicles to continue growing, thereby saving them from atresia. It’s essential to dispel any myths or misinformation surrounding ovarian stimulation, as it does not trigger early menopause or lead to a premature loss of follicles. We are merely utilizing the follicles that would have been lost otherwise.

Before starting the IVF process and ovarian stimulation, it’s crucial to have an idea of the number of oocytes that can be obtained. The more oocytes, the greater the potential for producing more embryos during the culture process. Studying the ovarian reserve can be done through two accepted methods: measuring anti-Mullerian hormone (AMH) levels and performing a transvaginal ultrasound scan in the first days of the menstrual cycle to assess the ovaries and count the follicles.

Ovarian reserve

Follicles are an important indicator of ovarian reserve. Typically, we consider ovarian reserve to be normal when the AMH (anti-Mullerian hormone) level is higher than 1.1 nanograms per millilitre or when there are between 6 and 10 follicles. If both the AMH level and the antral follicle count are normal, it suggests that the patient will likely have a normal response to ovarian stimulation. This means we could potentially retrieve between 10 and 15 oocytes, which is considered within the normal range. On the other end of the spectrum, a high ovarian reserve indicates a higher response to stimulation, with more than 15 oocytes. However, today we will focus on a lower ovarian reserve, which poses significant challenges.

A low ovarian reserve refers to a situation where the reproductive potential is diminished due to a decrease in the number of remaining follicles in the ovary. This results in a lower number of retrievable oocytes. We diagnose a low ovarian reserve when the AMH level is below 5.5 pmol or 1.1 ng/mL. The units used may vary depending on the country or laboratory. Additionally, an AFC below 5 is also an indicator of low ovarian reserve. There are other criteria to diagnose and classify patients with lower ovarian reserve, such as the Poseidon criteria, which consider age (above or below 35 years) and past response to previous cycles of ovarian stimulation.

When we face a low ovarian reserve, we are concerned because it means the response to ovarian stimulation will likely be low. A lower response means having fewer than four oocytes retrieved. This could be due to a lack of follicular growth or even when follicles grow, none of the oocytes are collected. It’s worrisome because the first step to having embryos is having oocytes, and the more oocytes we have, the more chances and embryos we could have at the end of the embryo culture.

Ovarian reserve & age

Age does make a difference. There’s an ongoing discussion regarding the causes behind the low reserve. After the age of 40, there is a natural decrease in the number of follicles. However, the process can occur earlier or later for different patients, even without chromosomal or genetic abnormalities explaining the low reserve.

We cannot predict individual outcomes accurately. Success rates and statistics can give us an idea, but the results vary from person to person. We can’t say with certainty how many oocytes will be retrieved or how many will result in viable embryos. It’s a challenge, but we always strive to maximize our chances and provide the best care.

Using up-to-date, individualized protocols and an experienced medical team and lab can make a difference in the ovarian response. Each extra oocyte counts. While we cannot perform miracles or dramatically increase the number of available follicles, every additional oocyte contributes.
It’s essential, to be honest with patients and not discourage them, even if the chances are low. Each patient is unique, and each ovary responds differently. Second opinions are valuable if there are doubts or hesitations about the treatment or expectations.

Conclusion

In conclusion, do not be discouraged before consulting with fertility specialists. Knowledge and experience of the centre make a difference when it comes to the number of potential oocytes that can be retrieved. Beware of false promises and seek reputable centres with the latest knowledge and technology.