Fertility Estimation (ovarian reserve testing)
When compared to a healthy man whose sex cells (sperm) are created all of their life, healthy women are already born with all the egg cells they will ever have. After birth, a woman’s egg number can only be reduced so in puberty it drops down from 6 to 7 million (number of egg cells in a fetus) to around 300.000. Clinically significant fertility decline starts already in early thirties.
Each of approximately 400 menstrual cycles in a woman’s lifetime uses around 1.000 eggs, in order to choose a single egg that will ovulate in that cycle. This happens due to a complex mechanism of choosing that one egg. Apart from this, there are other factors that can influence the number and quality of woman’s eggs. They are usually found in genetics, lifestyle, environment or medical conditions such as endometriosis, ovarian surgery, chemotherapy and radiation. All of this eventually leads to complete non-responsiveness of the ovaries and menopause.
Ovarian reserve denotes the ability of ovaries to create eggs which, when fertilized, result in a healthy and successful pregnancy. Nowadays, we have tests telling us of the ovarian reserve. These tests use the information on number and quality of remaining eggs. Different tests can be done separately, but only combined they provide complete information on woman’s reproductive potential.
An ovarian reserve test in BetaPlus Center includes the following:
– Follicle stimulating hormone (FSH),
– Anti-Mullerian hormone (AMH)
– antral follicle count (AFC)
Follicle stimulating hormone (FSH)
FSH is a hormone synthesized and secreted by the anterior pituitary gland situated in the brain. In women it stimulates the growth and maturing of ovarian follicles resulting in a mature egg ready to ovulate and to be fertilized. FSH is secreted throughout a woman’s life, but in non-responsive ovaries it can no longer stimulate follicular growth, and as the result FSH levels increase.
During menstruation, FSH stimulates the ovary to produce follicles. If the ovary no longer has follicles capable of growing, FSH value will increase, trying to make the ovary react by overstimulating it. For this reason, FSH value is at its peak during menstrual period, which is the optimal time for testing (day 2-5 of period). Increased basal FSH value (higher than 10-20IU) indicates reduced ovarian reserve which results in low response to possible ovulation stimulation.
Anti-Mullerian hormone (AMH)
AMH is a glycoprotein, which in women is a product of granulose cells of primary, preantral and antral follicles in ovary. Therefore, AMH values directly depend on the number of remaining follicles in the ovary. Due to small follicles that secrete AMH its concentration is stabile within a cycle and can be measured throughout the entire cycle. As AFC (number of follicles) decreases with age, it causes lowering of AMH levels, which is one of the indicators of the remaining ovarian reserve.
In IVF procedures AMH is linked with the number of retrieved eggs. High AMH suggests woman will overreact to stimulation and have ovarian hyperstimulation syndrome (OHSS), and low AMH suggest a woman will have a poor response to ovulation stimulation. AMH levels are a good indicator of the quantity and number of eggs, but not of their quality. Therefore, young woman with low AMH level may have a reduced egg number, but good egg quality with relatively good chances of getting pregnant.
AMH values as fertility indicators in women under the age of 38 are approximately:
0.0-2.2 Very low concentration
2.2-15.7 Reduced fertility
15.7-28.6 Satisfactory fertility
28.6-48.5 Optimal fertility
>48.5 Increased concentration
Many labs will not use the table above, but will read AMH levels according to age-connected reference values which creates feelings of false security in women. In older women reference values are narrowed so that an AMH result of 20 pmol/l in a 40-year-old woman, whose reference values are 1-25 pmol/l), represents a far better result than in a young woman, whose reference values range from 1 to 75 pmol/l. However, chances for pregnancy are better in younger woman.
Laboratories use different units to express AMH levels. If your result is expressed in μg/L, you can use the following formula to get a pmol/l result:
x (level on the test result) x 7,14 = level in pmol/L
Lately, it has been found that the AMH levels in a population of women are similar in women of the same age, i.e. that an equal number of women with low AMH can be found in women of the same age in both fertile and infertile population of women.
Antral follicle count – AFC
Transvaginal ultrasoound is used to count antral follicles 2-10 mm in diameter on both ovaries. The number of antral follicles directly indicates ovarian reserve.
A infertility specialist can predict ovarian response to ovulation stimulation and probabilities of number of eggs retrieved in an IVF procedure based on AFC.
Total number of antral follicles (expected ovulation stimulation medication response and success probability)
< 4 (Extremely low count, poor response to stimulation. Possible cancelling the procedure)
4 – 7 (Low count, probably poor response to stimulation. High doses of gonadotropins needed)
8 – 10 (Moderately low count, slightly reduced chances of pregnancy)
11 – 14 (Normal count, good response to stimulation, good chances of pregnancy)
15 – 26 (Excellent response to mild stimulation, best number of expected pregnancies)
> 26 (High count, very high risk of OHSS and high probability of pregnancy)
Biochemical tests and ultrasound can be used to estimate ovarian reserve. Since no ovarian reserve estimation has 100% sensitivity or specificity, tests are combined in order to get clearer results. AMH and AFC are the best indicators.
Other tests such as estradiol and inhibin B levels, clomiphene citrate challenge test or ultrasound measurement of ovarian volume do not exert enough sensitivity and specificity and are no longer recommended for ovarian reserve estimation.
Ovarian reserve estimation (testing) is recommended:
– to women planning to postpone pregnancy beyond the age of 30 or 35,
– to all women in ART procedures,
– for genetic reasons (e.g. 45X mosaicism),
– to women with family history of premature ovarian insufficiency,
– to women who may have ovarian damage (endometriosis, pelvic inflammatory disease, cyst, ovary removal, results of gonadotoxic medication treatment and/or pelvic carcinoma irradiation),
– to women smokers.
The primary goal of these tests is to identify women with low ovarian reserve and then adjust treatment accordingly, to all women who are in need of treatment.
We would like to stress that ovarian reserve testing only indirectly indicates fertility reserve in women. Young women with low ovarian reserve can be entirely fertile while women in their forties with high ovarian reserve may be less fertile.