Ovarian insufficiency (hypergonadotropic amenorrhea)

Ovarian insufficiency is a form of endocrine infertility characterized by primary damage to the ovaries, consisting of the absence of the follicular apparatus or a violation of its ability to adequately respond to stimulation with gonadotropins.

[ 1 ], [ 2 ], [ 3 ], [ 4 ], [ 5 ], [ 6 ], [ 7 ], [ 8 ]

Epidemiology

Premature ovarian failure syndrome and ovarian resistance syndrome occur in 10% of women with amenorrhea. Gonadal dysgenesis occurs in 1 case per 10–12 thousand newborns.

[ 9 ], [ 10 ], [ 11 ], [ 12 ]

Symptoms of hypergonadotropic amenorrhea

Patients with gonadal dysgenesis are characterized by short stature, the presence of stigmata - an arched palate, pterygoid folds on the neck, and a wide chest.

Complaints of hot flashes, menstrual dysfunction such as oligo- and amenorrhea are typical. Amenorrhea can be either primary (with gonadal dysgenesis) or secondary.

Classification

The following forms of ovarian insufficiency are distinguished:

• ovarian failure syndrome;
• resistant ovary syndrome;
• gonadal dysgenesis.

[ 13 ], [ 14 ], [ 15 ], [ 16 ], [ 17 ], [ 18 ]

Diagnosis of hypergonadotropic amenorrhea

The diagnosis of ovarian failure is established based on the results of hormonal testing. Characterized by high levels of gonadotropic hormones, especially FSH (> 20 IU/L), hypoestrogenism (< 100 pmol/L).

In case of ovarian insufficiency, the test with gestagens is negative, the cyclic hormonal test is positive.

Progesterone test: dydrogesterone is administered orally at 20 mg/day for 14 days. The test is considered positive if menstrual-like bleeding occurs after discontinuing the medication.

Test with estrogens-gestagens in a cyclic mode: estradiol valerate is prescribed orally 2 mg 2 times a day (until the endometrial thickness according to ultrasound data reaches 8-10 mm), then dydrogesterone is added orally 20 mg/day for 14 days. If the test is positive, menstrual-like bleeding occurs after the drug is discontinued.

• Ultrasound of the pelvic organs (hypoplasia of the uterus, thin endometrium, in case of gonadal dysgenesis, the ovaries are in the form of cords, in case of ovarian depletion - hypoplasia of the ovaries, absence of the follicular apparatus, in case of resistant ovaries, the follicular apparatus is preserved).
• Cytogenetic examination (if gonadal dysgenesis is suspected).
• Lipidogram.
• Bone mineral density testing (for timely prevention of systemic disorders associated with estrogen deficiency).

[ 19 ]

Treatment of ovarian failure

If the Y chromosome is present in the karyotype, laparoscopic removal of the gonads is necessary.

Stimulation of ovulation for the purpose of treating infertility is not indicated. The only method of achieving pregnancy is the transfer of a fertilized donor egg into the uterine cavity (donation).

Donation consists of 2 stages:

• preparatory stage, the purpose of which is to increase the size of the uterus, grow the endometrium, and form the receptor apparatus in the uterus;
• donation cycle.

At the preparatory stage, cyclic hormone replacement therapy is indicated:

• estradiol orally 2 mg 1-2 times a day, course 15 days, or
• estradiol valerate orally 2 mg 1-2 times a day, course 15 days, or
• EE orally 50 mcg 1-2 times a day, course 15 days, then
• dydrogesterone orally 10 mg 1-2 times a day, course 10 days, or
• progesterone orally 100 mg 2-3 times a day, or vaginally 100 mg 2-3 times a day, or intramuscularly 250 mg 1 time per day, course 10 days, or
• norethisterone orally 5 mg 1-2 times a day, course 10 days.

Estrogen intake begins on the 3rd–5th day of the menstrual-like reaction.

It is preferable to use natural estrogens (estradiol, estradiol valerate) and gestagens (dydrogesterone, progesterone). The duration of preparatory therapy depends on the severity of hypogonadism and is 3-6 months.

Donation cycle:

• estradiol orally 2 mg once a day from the 1st to the 5th day of the menstrual cycle or
• estradiol valerate orally 2 mg 1 time per day from the 1st to the 5th day of the menstrual cycle, then
• estradiol orally 2 mg 2 times a day from the 6th to the 10th day of the menstrual cycle or
• estradiol valerate orally 2 mg 2 times a day from the 6th to the 10th day of the menstrual cycle, then
• estradiol orally 2 mg 3 times a day from the 11th to the 15th day of the menstrual cycle (under ultrasound control) or
• estradiol valerate orally 2 mg 3 times a day from the 11th to the 15th day of the menstrual cycle (under ultrasound control).

With an endometrial thickness of 10–12 mm from the day of administration of menotropins to the donor:

• estradiol orally 2 mg 3 times a day;
• estradiol valerate orally 2 mg 3 times a day +
• progesterone orally 100 mg once a day.

From the day of receiving donor oocytes:

• estradiol orally 2 mg 3-4 times a day;
• estradiol orally 2 mg 3-4 times a day +
• progesterone orally 100 mg 2 times a day.

From the day of embryo transfer into the uterus:

• estradiol orally 2 mg 3-4 times a day, course 12-14 days;
• estradiol valerate orally 2 mg 3-4 times a day, course 12-14 days +
• progesterone orally 200 mg 2-3 times a day and 250-500 mg intramuscularly, course 12-14 days.

The donor superovulation stimulation schemes are similar to those used in ovulation induction cycles for polycystic ovary syndrome - pure schemes with menopausal and recombinant gonadotropins, schemes with gonadotropin-releasing hormone analogues. Treatment schemes are selected individually. If the pregnancy test is positive, replacement therapy with estrogens and gestagens is continued until 12-15 weeks of pregnancy. The doses of estrogens and gestagens are similar to those used after embryo transfer, under the control of estradiol and progesterone levels in the blood.

Forecast

The efficiency of donor embryo transfer reaches 25-30% per attempt. The efficiency does not depend on the cause of ovarian failure, but is determined by the woman's age, the quality of donor oocytes and the adequacy of endometrial preparation for implantation.

[ 20 ], [ 21 ], [ 22 ], [ 23 ], [ 24 ]