Gonadotropic insufficiency

Gonadotropic insufficiency is a form of anovulatory infertility, characterized by injuries in the central parts of the reproductive system, leading to a decrease in the secretion of gonadotropic hormones.

Secretion of GnRH by the hypothalamus is the key in creating and maintaining the normal function of the gonads.

[1], [2], [3], [4], [5]

Epidemiology

Gonadotropic insufficiency occurs in 15-20% of women with amenorrhea.

[6], [7], [8], [9],

Stages

Depending on the results of hormonal research, the following severity levels of gonadotropic insufficiency are distinguished:

• light (LH 3.0-5.0 IU / l, FSH 1.75-3.0 IU / l, estradiol 50-70 pmol / l);
• average (LH 1.5-3.0 IU / l, FSH 1.0-1.75 IU / L, estradiol 30-50 pmol / l);
• severe (LH <1.5 IU / L, FSH <1.0 IU / L, estradiol <30 pmol / L).

[10], [11], [12], [13], [14]

Forms

Distinguish the following forms of gonadotropic insufficiency:

• hypothalamic;
• pituitary.

[15], [16]

Diagnostics of the gonadotropic insufficiency

The absence of the effect of estrogens on the woman's organism determines the characteristic features of the phenotype: the eunuchoid physique - high growth, long limbs, sparse hair on the pubic region and in the armpits, hypoplasia of the mammary glands, labia, reduction of the size of the uterus and ovaries. The severity of clinical symptoms depends on the degree of gonadotropic insufficiency.

Clinically, for patients with gonadotropic insufficiency, amenorrhea is characteristic: primary in 70% of cases, secondary in 30% of cases (more typical of hypothalamic form).

Special research methods

• The diagnosis is based on the results of hormonal research. Low serum levels of LH (<5 IU / L), FSH (<3 IU / L) and estradiol (<100 pmol / L) are typical for normal concentration of other hormones.
• Ultrasound of the pelvic organs (to determine the degree of hypoplasia of the uterus and ovaries).
• Lipidogram.
• Study of bone mineral density (to identify and prevent possible systemic abnormalities on the background of prolonged hypoestrogeny).
• Examination of the spermogram of the spouse and the patency of the fallopian tubes in a woman in order to exclude other factors of infertility.

[17], [18], [19], [20]

Differential diagnosis

For differential diagnosis of the hypothalamic and pituitary forms of gonadotropic insufficiency, a gonadotropin-releasing hormone (GnRH) agonist test (eg, tryptorelin IV 100 μg once) is used. The sample is considered positive if, in response to the introduction of drugs (LS) at the 30-45th minute of the study, the increase in the concentrations of LH and FSH is not less than 3-fold. With a negative sample, the pituitary form of insufficiency is diagnosed, a positive testifies to the preserved function of the pituitary gland and the damage to the hypothalamic structures.

Treatment of the gonadotropic insufficiency

Treatment of infertility in gonadotropic insufficiency is carried out in 2 stages:

• 1 st stage - preparatory;
• The second stage is the induction of ovulation.

At the preparatory stage, cyclic hormone replacement therapy is carried out to form a female phenotype, increase the size of the uterus, proliferate the endometrium, activate the receptor apparatus in the target organs, which increases the effectiveness of subsequent stimulation of ovulation. Preferably the use of natural estrogens (estradiol, estradiol valerate) and gestagen (dydrogesterone, progesterone). The duration of the preparatory therapy depends on the severity of hypogonadism and is 3-12 months.

Drugs of choice:

• 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, 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 in / m 250 mg once a day, the course of 10 days. The introduction of estrogens begins with a 3-5-day menstrual-like reaction.

Alternative preparations:

Scheme 1:

• Estradiol 2 mg once a day, course 14 days, then
• estradiol / dydrogesterone 2 mg / 10 mg once a day, the course is 14 days.

Scheme 2:

• estradiol valerate inside 2 mg once a day, course 70 days, then
• estradiol valerate / medroxyprogesterone inside 2 mg / 20 mg once a day, course 14 days, then
• Placebo 1 time per day, 7 days course. Scheme 3:
• Estradiol valerate inside 2 mg once a day, course 11 days;
• Estradiol valerate / norgestrel inside 2 mg / 500 mcg once a day, course 10 days, then break 7 days.

After the completion of the first stage, ovulation induction is conducted, the main principles of which are adequate selection of the drug and its starting dose and careful clinical and laboratory control of the stimulated cycle.

Drugs of choice at this stage are menotropins.

• Menotropins in / m 150-300 IU once a day at the same time from the 3rd-5th day of the menstrual-like reaction. The starting dose depends on the severity of gonadotropic insufficiency. The adequacy of the dose is estimated from the dynamics of follicle growth (at a rate of 2 mm / day). With slow growth of the follicles, the dose is increased by 75 IU, with too rapid growth decreases by 75 IU. The introduction of the drug continues until the formation of mature follicles with a diameter of 18-20 mm, then gonadotropin is injected chorionic IM 10 000 units once.

Following the establishment of ovulation, the luteal phase of the cycle is supported:

• dydrogesterone orally 10 mg 1-3 times a day, course 10-12 days or
• progesterone inside by 100 mg 2-3 times a day, or in the vagina for 100 mg 2-3 times a day, or in / m 250 mg once a day, the course of 10-12 days.

In the absence of symptoms of ovarian hyperstimulation, it is possible to use:

• gonadotropin chorionic in / m 1500-2500 units 1 time per day for 3.5 and 7 days of the luteal phase.

If the first course is ineffective, repeated courses of ovulation induction are performed in the absence of ovarian cysts.

An alternative scheme for induction of ovulation is the use of GnRH agonists (effective only in hypothalamic form), which are administered iv in the 3-5th day of the menstrual reaction for 20-30 days in a pulsating regime (1 dose for 1 minute every 89 min ) with the help of a special apparatus. If the first course is ineffective, repeated courses of ovulation induction are performed in the absence of ovarian cysts.

Use with gonadotropic insufficiency for the induction of ovulation antiestrogens is inexpedient.

Forecast

The effectiveness of treatment depends on the degree of gonadotropic insufficiency, the age of the woman and the adequacy of the preparatory therapy.

In the pituitary form of gonadotropic insufficiency, the induction of ovulation with menotropins leads to the onset of pregnancy in 70-90% of women.

In the hypothalamic form, induction of ovulation with menotropins is effective in 70% of women, induction by pulsating administration of the agonist GnRH - in 70-80% of women.

[21], [22], [23],