The ovary has a biological age that do not always correspond to the chronological age. Knowing this may be of great
importance for Reproductive System evaluation.
Although the topic is still the subject of scientific research, I can quite reasonably described as “ovarian reserve” the ovary ability to produce follicles capable of being fertilized and give a healthy embryo. Actually it is a very important aspect of what can be considered more globally the reproductive capacity of a woman.
But why today it is talked more and more about ovarian reserve and what the patient need to know? What are its clinical implications and those on the reproductive future of women subjected to this investigation?
Undoubtedly, Reproductive Medicine and the postponed desire of reproduction (> 35 years old) have attracted the most interest, but the ovarian reserve is also being studied in very young women with otherwise unexplained infertility or who have had medical treatment, surgery, radio or chemotherapy which may have damaged the ovaries.
How evaluate it?
- FSH (Follicle Stimulating Hormone) assay
- AMH (Anti Mullerian Hormone) assay
- Ultrasound antral follicle count (AFC)
FSH is a small protein secreted by the anterior Pituitary Gland (Adenohypophysis) with a pulsatile rhythm in blood and it is essential to make ovary and ovulation work properly. Its levels are inversely related to follicular heritage. The dosage of FSH on the 3rd day of the cycle was the first and is still the most widely used method for assessing the ovary reproductive capacity. Generally recommended at least two determinations of FSH in two different menstrual cycles (even consecutive) excluding the use of drugs such as the Pill that might alter the dosage. Values less than 10 mIU / mL are considered normal, as deponents to reduced fertility between 10 and 25, and frankly ominous for reproductive purposes when more than 25 mIU / ml.
Anti Mullerian Hormone (AMH) is a Glycoprotein that belongs to the family of “transforming growth factor
beta”. Historically, the first knowledge of it is dated back to the studies on sexual differentiation (regression of the Mullerian ducts in the male), and thereafter it became clear that the AMH was also produced by preantral follicles and from small antral follicles. It is believed that the Anti Mullerian Hormone in women is an important regulator of follicular growth and it is inibitory for follicle recruitment in antagonism to the action of ‘FSH. Its deficiency then accelerate oocyte depletion.
Its production is independent from follicular growth and its blood levels are fairly stable during the menstrual cycle and can be dosed at any time. Recent studies have shown lower values in the luteal phase, but the difference is not significant. Also, for AMH determination, take care to interfering factors such as prolonged use of oral contraceptives (OC) and the pregnancy that reduce its levels.
It is also known that the patients with Polycystic Ovarian Syndrome (PCOS) typically have values from 2 to 4 times greater than in healthy women and that this correlates with a higher risk of hyperstimulation. Currently, the determination of Anti Mullerian Hormone is considered the most reliable test for evaluating ovarian reserve (directly related to the number of antral follicles) and is routinely carried out in anticipation of medically assisted reproduction treatments (PMA) for its high predictivity of follicular response (“pick up”number of recoverable oocytes) pharmacological induction. The recent overcoming difficulties of dosing and consequent differences of reading of the results has facilitated its spread and use in clinical practice, even outside of the PMA: this is the case of Occult Shortcomings Ovary. Currently 1 ng / ml seems to be the threshold limit value below which the ovarian reserve can be considered small and values below 0.5 ng / ml seem predictive of a poor ovarian response in 88% of cases.
The antral follicles count (AFC) is performed by a fairly sophisticated ultrasound technique that joins the previous evaluation of what might be called “ovarian age”, because ovarian reserve is also an expression of aging. With a transvaginal ultrasound probe (preferably a three-dimensional type) will be conducted a volumetric assessment of ovaries and then will proceed to the counting of antral follicles (2-10mm) 3-5 in the early follicular phase of the cycle; particularly the counting of follicles with a diameter between 2 and 6mm (small antral follicles) seems to correlate better with the functional ovarian reserve.
Recent histological studies show that the AFC has an accuracy identical to that of AMH. Although there is no unanimous agreement about the threshold values, we can reasonably say that a total ovarian volume greater than 6 cm and a count equal to or greater than 7 of antral follicles are considered reassuring (good reproductive chancs seem possible from counts higher than 12) .
The chronological age should however be considered in the evaluation of reproductive potential. It seems independent from the tests that I described. In fact, a whole series of data orient on the fact that after 38-40 years old there is a reduced oocyte quality independently from ovarian reserve and probably related to accumulation of oocyte damage that may be consequent to oxidative stress.
External and environmental factors: in a memorable work published in Reproductive BioMedicine Online in 2003 (Fig. 3) we demonstrated a direct damage related to smoking (cigarette smoke).
Now I would like to emphasize one very important aspect of ovarian reserve and that is its correlation with oocyte quality and fertilization capacity and have a healthy embryo which is no coincidence that we mentioned at the onset of this article. The reproductive capacity of a woman is not only related to ovulation but the ability of the oocyte to be fertilized and the low rate of miscarriage and birth defects of the products of conception (fetus). A poor ovarian reserve correlates fact also reduced fecundability rates and an increase in birth defects and miscarriage.
But when it is useful to study the ovarian reserve?
- Always when it is faced an otherwise unexplained infertility;
- When the decision to have children is postponed well over 35 years old;
- Every time a patient goes to a Reproductive Medical Center;
- When a surgery on the ovary is underwent or medical treatments, radio or chemotherapy can damage it;
- When there are endocrine and immunological diseases typically associated with reduced fertility and Premature Ovarian Failure (eg Chronic Autoimmune Thyroiditis)
- Repeated abortions;
- Fetal malformation episodes.
And now I want to focus on the more modern concept of “ovarian aging”. I said that the ovary has a biological age that do not necessarily correspond to the chronological age. Epidemiological studies have shown that about 10% of the female population goes through menopause around the age of 45 and not more typically occurs around 48-52 years old. Well these women in the acceleration of follicular decay occurs already at around 32-33 years old with infertility or subfertility hard to explain unless a study of the ovarian reserve is made.
In conclusion I would also say that all the tests which I wrote about but never express certainty and probability that in this context should be interpreted (possibly more from experienced people in the field). The ovarian reserve although important, it is certainly one of many factors contributing to reproductive potential. We have seen as well as the chronological age remains an important independent factor and how the overall reproductive potential can not be separated even by anatomical factors, metabolic, immunologic.