During embryonic development, women have around 7-8 million germ cells; by birth this has been reduced to 1-2 million, and by the time ovulatory cycles begin, there are between 300,000-400,000, of which only 400-500 will ovulate, and there will also be a percentage that is aneuploid (genetically abnormal), so we can say it is an inefficient system, but one that works.
How to assess ovarian reserve to establish an appropriate stimulation protocol in a patient?
One of the methods we use to assess ovarian reserve in women is to stratify them by age group; however, not all women of the same age have the same ovarian reserve, so it is not the only variable to consider, as a woman of any age can be a normal responder, poor responder, or hyper-responder. Therefore, when establishing the appropriate stimulation protocol in each case, in a woman with a low response we want to obtain as many follicles as possible, in a normal responder around 70-80% of them; however, in a hyper-responder the last thing we want is for all of them to develop.
We need a good idea of the reserve to determine how to stimulate. Another reason why assessing ovarian reserve is important is that it helps predict the live birth rate after an IVF cycle.
It is important to know that more than 220-230 days pass from when we have an oocyte until ovulation takes place, and during this process, only in the last 3 weeks do follicles respond to gonadotropins, meaning they can be stimulated.
What role does AMH play?
It prevents a primordial follicle from being recruited and responding to gonadotropin. The maximum expression of AMH occurs in preantral and small follicles; in the future we may use this property of AMH to antagonize it and promote follicular recruitment in poor responders.
AMH is therefore produced by follicles up to 6-7 mm, and is a good indicator of follicle count and predictor of ovarian reserve, just like the antral follicle count via ultrasound. Both therefore predict the response to gonadotropin stimulation.
AMH can also predict the age of menopause, along with other factors such as: phenotype, genotype, ethnicity…
Is there variation in AMH levels?
Today we know that variations in AMH levels are not due to technical reasons; there is biological variation, with variations within the cycle of 20.7% and between cycles of 28%. There are also isoforms of the hormone about which we know very little. We all want a good number of oocytes: the more oocytes, the greater the chance of having a live birth. AMH value is a factor that impacts not only quantity, but also oocyte survival, embryo quality, and the probability of miscarriage, regardless of age and genetic load.
A value is considered normal, and therefore a good response, if it is 2-4 ng/ml; a hyper-response if it is above 4 ng/ml, and a poor response if it is below 1 ng/ml. If the value is below 1.09 ng/ml, oocyte survival is lower, their quality is lower, and the probability of miscarriage is higher. In fact, Renato Fanchin reports that, regardless of age, the probability of miscarriage increases at lower AMH levels; the genetic load of those embryos may be affected. La Marca also reports that, regardless of age, AMH is related to the embryo’s euploidy status.
Main predictive factors for outcomes after an IVF cycle
AMH is not only a predictor of response, but also of quality, as it is related to embryo ploidy. Thus, the prognosis of a 25-year-old woman with very low AMH can end up being worse than that of a 40-year-old woman with good AMH levels.
Ideally, a thorough assessment should consider AMH levels, antral follicle count, as well as FSH and estradiol levels and the patient’s age, giving us a much more complete evaluation of each case.
As for age, it has an impact on both quantity and oocyte quality: it has a negative impact on the genetic load of the oocytes, and on the other hand, even when euploid embryos are transferred, the implantation rate still decreases with age; so genetic load is not the only thing that matters.
Regarding FSH and estradiol levels, we should not dismiss them as response markers: when measuring both hormones at the start of the cycle, we see that if estradiol is low, the higher the FSH, the poorer the oocyte quality and the lower the pregnancy and live birth rates.
The antral follicle count (AFC) via ultrasound, especially when the follicles are homogeneous in size, helps us predict the response with high reliability: “what you see is what you get.”
At Clínica Fertia, our recommendation both for starting IVF treatment and for finding out about your fertility status in order to plan for motherhood is to come in for a consultation to carry out the relevant follicle count tests and anti-Müllerian hormone level analysis. We encourage you to book an appointment at our fertility clinic and receive personalized advice for your case.
Contact us for your first consultation.
References
- Tarasconi B, Tadro T, Ayoubi JM, Belloc S, De Ziegler D, Fanchin R. Serum antimüllerian hormone levels are independently related to miscarriage rates after in vitro fertilization-embryo transfer. Fertil Steril. 2017;108:518-524.
- La Marca A, Minasi MG, Sighinolfi G, Greco P, Argento C, Grisendi V, Fiorentino F, Greco E. Female age, serum antimüllerian hormone level, and number of oocytes affect the rate and number of euploid blastocysts in vitro fertilization/intracytoplasmic sperm injection cycles. Fertil Steril. 2017;108:777-783.
