Anti-Müllerian Hormone (AMH): Know the age of your ovary

What is Anti-Müllerian hormone?

It is a protein that plays a key role in sexual differentiation during the foetal stage. In males, it is produced by a specific type of testicular cell (Sertoli cells). In the presence of this hormone, the development of the male phenotype begins. However, when the Anti-Müllerian hormone is absent, the differentiation of certain female structures such as Mullerian ducts in the uterus, one third of the vagina and oviduct occurs.

Independently of its role in foetal development, in the context of assisted reproduction it provides information about a woman’s ovarian reserve.

In women, where is it synthetized?

Antimullerian hormone is produced by the granulosa cells of the small (antral and preantral) follicles of the ovary from 36 weeks of foetal development until the menopause starts.

These levels decrease progressively until the age of about 35, after which they decrease much faster and become almost undetectable with the onset of menopause.

What is the ovarian reserve?

The ovarian reserve is a widely used concept in assisted reproduction but patients are not always aware of its meaning and clinical implications. Currently, the ovarian reserve of a woman refers to both the quantity and quality of the oocytes she has in her ovaries.

For this reason, it provides us with information about a woman’s reproductive future and possibilities of reproduction.

The ovarian reserve is inversely proportional to the woman’s age, i.e. the older the woman, the lower the ovarian reserve and the lower the egg quality, and therefore her fertility is reduced.

At present, the most appropriate way to establish the ovarian reserve is through the determination of blood levels of Anti-Müllerian hormone and the performance of an ultrasound scan under basal conditions (between day 3 and day 5 of the menstrual cycle) to count the number of antral follicles present in both ovaries.

The results of both tests must be interpreted jointly by a specialist gynaecologist, who will inform the patient of her situation from the reproductive point of view and advise her on the most appropriate treatment.

What is the most reliable AMH analysis method?

At the analytical level, it is important to note that the results may vary from one laboratory to another. Basically, there are two techniques most used at present: ELISA (enzyme immunoassay) which is a manual technique (therefore more susceptible to errors) and automated immunoassays. At Instituto Bernabeu we use the Roche automated immunoassay which, in our opinion, offers the following advantages:

• To have a more specific technique that helps us to guide and make safer decisions for diagnosis and treatment.
• Carrying out the analysis in our laboratories gives us greater control over the handling and conservation of the sample.
• The result of the analysis is available in a few days, which allows us to schedule the next consultation with the gynaecologist in the shortest time possible, reducing the anxiety of the couple.
• Being a reference centre in reproductive medicine, we have the information of the assisted reproduction treatments of our patients, carried out after the evaluation of the Anti-Müllerian hormone. This way, this monitoring will allow us to apply our experience to future patients with the continuous aim of improving our work day by day.

What level of Anti-Müllerian hormone is considered normal?

Despite the fact that there is no clear consensus on this and there is a clear influence of age, in general, levels above 1 ng/ml (7.14 pmol/l) are considered normal.

High Anti-Müllerian hormone – what does it mean assisted reproduction?

Since this hormone is synthesized by the granulose cells of the small (antral and preantral) follicles, women diagnosed with polycystic ovary will present elevated levels.

On the other hand, high levels in the blood before starting ovarian stimulation have been associated with an increased risk of ovarian hyperstimulation syndrome (Lee et al., 2008; Nelson et al., 2007).

Low Anti-Müllerian hormone – can I get pregnant?

In order to answer this question we rely on two most recent studies published in the field.

First of them, published in 2017 (Steiner et al.), included 750 women with low levels of Anti-Müllerian hormone (<0.7 ng/ml; <5 pmol/l) and concluded that these women had the same cumulative probability of conceiving in 6 or 12 months as women with normal values of this hormone.

The second study, published in 2019 (Zhang et al), included 9431 women divided into two age groups (over 35 and under 35). In patients under 35 years of age with low levels of Anti-Müllerian hormone, it was established that after three good quality embryo transfers, the results of the in vitro fertilization treatment were optimal. However, in women over 35 years, even with normal and high levels of Anti-Müllerian hormone, the rate of clinical pregnancy and live birth was lower and the miscarriage rate was higher than in the group of younger women. This fact underscores the importance of maternal age in achieving an ongoing pregnancy.

Therefore, the fact that a woman presents low levels of Anti-Müllerian hormone, can be translated to obtaining a low number of oocytes after an ovarian stimulation and egg collection, but it does not mean in any case that she cannot achieve an ongoing gestation.

According to these results, knowing the level of the Anti-Müllerian hormone is useful for the gynaecologist to individualize the pharmacological treatment for ovarian stimulation but not to know the reproductive potential of the patient.

What options do I have if I have low level of Anti-Müllerian hormone?

As we have already explained, in the presence of low levels of antimullerian hormone and low antral follicle count, it is to be expected that a low ovarian reserve will be found and a low number of oocytes will be obtained after ovarian stimulation. In view of this situation, it is important to individualize and optimize the ovarian stimulation process, so that we can obtain the best possible performance from a woman’s ovaries.

With this objective in mind, Instituto Bernabeu created the Low Response Unit. Designed protocols aim to obtain maximum number of oocytes that guarantee an optimal number of good quality embryos in order to increase the probability of success.

In the event of low ovarian reserve/response, what options do I have if I have not yet considered the maternity?

We consider three possible options:

• Seek pregnancy as soon as possible if there is a stable partner.
• In case of having a stable couple but not wanting to consider the option of motherhood yet, there is an option of carrying out an assisted reproduction treatment, obtaining embryos and freezing them by means of vitrification while waiting for the moment the couple considers appropriate to transfer them and give rise to pregnancy.
• If there were no stable couple and we wanted to postpone our maternity, it would also be possible to carry out one or more assisted reproduction treatments to obtain and vitrify the oocytes while waiting for the right moment to fertilize them (with our partner’s sperm if there is one or with donor sperm if the woman wishes to become a single parent) and then transfer the embryos obtained to achieve pregnancy.

Bibliography

• Nelson SM., Yates RW., Fleming R. Serum anti-Müllerian hormone and FSH: prediction of live birth and extremes of response in stimulated cycles. Implications for individualization of therapy. Hum Reprod. 2007; 22:2414-21.
• Lee TH., Liu CH., Huang CC. Serum anti-Müllerian hormone and estradiol levels as predictors of ovarian hyperstimulation síndrome in assisted reproduction technology cycles. Hum Reprod. 2008; 23:160-7.
• Zhang B., Meng Y., Jiang X. IVF outcomes of women with discrepancies between age and serum anti-Müllerian hormone levels. Reproductive Biology and Endocrinology 2019; 17:58
• Steiner A., Pritchard D., Stanczyk F. Association between biomarkers of ovarian reserve and infertility among older women of reproductive age. JAMA 2017; 318: 1333-1334.

Dr Ana Fabregat, Pharmacist at Instituto Bernabeu