Ovarian insufficiency (hypergonadotropic amenorrhea)

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

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

Epidemiology

The syndrome of premature ovarian depletion and ovarian resistance syndrome occurs in 10% of women with amenorrhea. Gonadal dysgenesis occurs in 1 case for 10-12 thousand newborns.

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

Symptoms of hypergonadotropic amenorrhea

For patients with gonadal dysgenesis, low growth is characteristic, the presence of stigma is the arcuate sky, the pterygopal folds on the neck, and the broad chest.

Characterized by complaints of hot flashes, menstrual irregularities in the type of oligo- and amenorrhea. Amenorrhea can be either primary (with gonadal dysgenesis) or secondary.

Classification

There are following forms of ovarian failure:

• syndrome of ovarian malnutrition;
• syndrome of resistant ovaries;
• gonadal dysgenesis.

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

Diagnosis of hypergonadotropic amenorrhea

Diagnosis of ovarian failure is established on the basis of the results of hormonal research. A high level of gonadotropic hormones, especially FSH (> 20 IU / L), hypoestrogenia (<100 pmol / L) is characteristic.

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

Progesterone test: dydrogesterone is administered orally at 20 mg / day for 14 days. The sample is considered positive if menstrual bleeding occurs after the abolition of the drugs.

A test with estrogens-progestins in a cyclic mode: prescribe estradiol valerate inside 2 mg 2 times a day (until the thickness of the endometrium is reached according to ultrasound of 8-10 mm), then add dydrogesterone inside 20 mg / day for 14 days. With a positive sample, menstrual bleeding occurs after the drug is discontinued.

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

[19]

Treatment of ovarian failure

In the presence of Y-chromosome in karyotype, laparoscopic removal of gonads is necessary.

Stimulation of ovulation for the purpose of treating infertility is not indicated. The only way to achieve pregnancy is to transfer a fertilized donor egg to the uterus (donation).

Donation consists of 2 stages:

• preparatory stage, whose goal is to increase the size of the uterus, the growth of the endometrium, the formation of the receptor apparatus in the uterus;
• cycle of donation.

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

• Estradiol inside 2 mg 1-2 times a day, course 15 days, or
• Estradiol valerate inside 2 mg 1-2 times a day, course 15 days, or
• EE inside by 50 mcg 1-2 times a day, course 15 days, then
• dydrogesterone orally 10 mg 1-2 times a day, 10 days course, or
• progesterone inside by 100 mg 2-3 times a day, or in the vagina 100 mg 2-3 times a day, or / m 250 mg once a day, a course of 10 days, or
• norethisterone orally 5 mg 1-2 times a day, a course of 10 days.

Admission of estrogens begins with a 3-5-day menstrual-like reaction.

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

Donation cycle:

• Estradiol inside 2 mg once a day from the 1st to the 5th day of the menstrual cycle or
• Estradiol valerate inside 2 mg once a day from the 1st to the 5th day of the menstrual cycle, then
• Estradiol inside 2 mg twice a day from the 6th to the 10th day of the menstrual cycle or
• Estradiol valerate inside 2 mg 2 times a day from the 6th to the 10th day of the menstrual cycle, then
• Estradiol inside 2 mg 3 times a day from the 11th to the 15th day of the menstrual cycle (under ultrasound guidance) or
• Estradiol valerate inside 2 mg 3 times a day from the 11th to the 15th day of the menstrual cycle (under the supervision of ultrasound).

When the thickness of the endometrium is 10-12 mm from the day of administration of the menotropins to the donor:

• Estradiol inside 2 mg 3 times a day;
• Estradiol valerate inside 2 mg 3 times a day +
• progesterone inside 100 mg once a day.

From the day of receipt of donor oocytes:

• Estradiol inside 2 mg 3-4 times a day;
• Estradiol inside 2 mg 3-4 times a day +
• progesterone inside by 100 mg 2 times a day.

Since the day of embryo transfer to the uterus:

• Estradiol inside 2 mg 3-4 times a day, the course of 12-14 days;
• estradiol valerate inside 2 mg 3-4 times a day, the course of 12-14 days +
• progesterone inside by 200 mg 2-3 times a day and 250-500 mg IM, the course of 12-14 days.

Schemes of stimulation of superovulation in the donor are similar to those used in ovulation induction cycles in the syndrome of polycystic ovaries - pure schemes with menopausal and recombinant gonadotropins, schemes with analogues of gonadoliberin. Schemes of treatment are selected individually. With a positive pregnancy test, estrogen and gestagen replacement therapy continues until 12-15 weeks of gestation. Doses of estrogen and gestagen administration are similar to those used after embryo transfer, under the control of estradiol and progesterone levels in the blood.

Forecast

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

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