Tactics of preparation for pregnancy in patients with hyperandrogenism

In case of unclear clinical data, if hyperandrogenism is suspected, it is necessary to conduct a test with ACTH (Synacthen-depot). Inadequate increase in the content of cortisol, DHEA and 17OP indicates a latent, non-classical form of adrenogenital syndrome.

Adrenal hyperandrogenism

According to functional diagnostic tests:

• NLF alternating with anovulation;
• Infection as a cause of miscarriage and NLF is excluded;
• No intrauterine adhesions;
• Karyotype features may or may not be present;
• There is no HLA compatibility;
• No autoimmune disorders;
• According to ultrasound data, the ovaries are unchanged;
• There is an android type of body structure, broad shoulders, narrow hips, there is hirsutism;
• Hormonal parameters reveal an increase in the level of 17KS (sometimes only in the second phase of the cycle), DHEA-S, 17OP are elevated or these indicators are at the upper limit of the norm;
• History of non-viable pregnancies.

In such a situation, it is necessary to clarify the source of hyperandrogenism. Conduct a dexamethasone test - a decrease in the levels of 17KS, 17-OP and DHEA-S by 80-90% means that the source of androgens is the adrenal glands.

When diagnosing adrenal hyperandrogenism, preparation for pregnancy consists of prescribing dexamethasone in a dose of 0.125 mg to 0.5 mg under the control of 17KS in urine or 170P and DHEA-S in the blood. In most patients, after starting to take dexamethasone, the menstrual cycle is normalized, normal ovulation and pregnancy are observed (often against the background of a dexamethasone test). Simultaneously with dexamethasone, metabolic therapy complexes or vitamins for pregnant women with an additional folic acid tablet are prescribed.

If pregnancy does not occur within 2-3 cycles, ovulation can be stimulated with clostilbegid or clomiphene at a dose of 50 mg from day 5 to day 9 of the cycle while taking dexamethasone.

An alternative method of preparing for pregnancy may be to give a contraceptive with an antiandrogenic effect - Diana-35 for two or three cycles. And in the cycle when pregnancy is planned - dexamethasone from the 1st day of the cycle.

According to research data, 55% of patients with adrenal hyperandrogenism became pregnant only while receiving dexamethasone treatment. The duration of rehabilitation therapy averaged 2.4 cycles. During pregnancy, all patients with adrenal hyperandrogenism should continue taking dexamethasone in an individually selected dose, which, as a rule, does not exceed 0.5 mg (usually 1/2 or 1/4 of a tablet).

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Preparation for pregnancy in patients with ovarian hyperandrogenism

• History: late menarche, menstrual cycle disorders such as primary or secondary oligomenorrhea, often secondary amenorrhea. Pregnancies are rare and are interrupted by non-viable pregnancy, with long periods of infertility between pregnancies;
• According to functional diagnostic tests, mainly anovulation and very rarely ovulatory cycles with NLF;
• Hirsutism, acne, striae, pigmentation features, voice timbre, morphometric features, and high body mass index are noted;
• Hormonal testing reveals elevated testosterone levels, often elevated LH and FSH levels, the LH/FSH ratio is greater than 3; the 17KS level is elevated;
• Ultrasound reveals polycystic ovaries;
• Infection is excluded or cured. Considering that 2/3 of patients with hyperandrogenism have isthmic-cervical insufficiency during pregnancy, the issue of endometrial infection is extremely relevant for them;
• No autoimmune disorders;
• No HLA compatibility;
• Karyotype features may or may not be present.

To clarify the genesis of hyperandrogenism, it is advisable to conduct a combined functional test with dexamethasone and hCG. The test is based on direct stimulation of the ovarian function by chorionic gonadotropin, which produces androgens, with the simultaneous effect of dexamethasone on the pituitary-adrenal system. Dexamethasone is prescribed at 0.5 mg 4 times a day for 3 days from the 6th day of the menstrual cycle. Then, in the following 3 days, chorionic gonadotropin is administered intramuscularly at a dose of 1500-3000 IU simultaneously with dexamethasone in the same dose. Androgen levels are determined on the 5th day of the cycle (baseline), the 8th day after dexamethasone administration, and the 11th day of the cycle after the administration of chorionic gonadotropin. In the ovarian form of hyperandrogenism, an increase in androgen levels is noted after the administration of chorionic gonadotropin.

Preparation for pregnancy begins with the administration of gestagens in the second phase of the cycle. Since Duphaston and Utrozhestan do not suppress their own ovulation, their use is preferable to other gestagens. According to research, gestagens, by suppressing LH, reduce the level of androgens. Another opinion is expressed by Hunter M. et al. (2000) - that gestagens do not reduce the level of androgens, but promote secretory transformation of the endometrium.

Duphaston at a dose of 10 mg 2 times a day, Utrozhestan 100 mg 2 times a day are prescribed from the 16th day of the cycle for 10 days, 2-3 cycles in a row under the control of basal temperature charts. Then, dexamethasone is prescribed at a dose of 0.5 mg until the level of 17 KS is normalized. It should be noted that the testosterone level does not change when dexamethasone is prescribed. Dexamethasone reduces the level of adrenal androgens, reducing their total effect. In the next cycle (if pregnancy has not occurred), ovulation is stimulated with clostilbegid at a dose of 50 mg from the 5th to the 9th day of the cycle. In the next cycle, if pregnancy has not occurred, the dose can be increased to 100 mg and stimulation can be repeated for 2 more cycles. In this case, progesterone derivatives are prescribed again in phase II of the cycle. When treating with clostilbegid, folliculogenesis must be monitored:

• during ultrasound on the 13-15th day of the cycle, a dominant follicle is noted - not less than 18 mm, the thickness of the endometrium is not less than 10 mm;
• according to the rectal temperature chart - a two-phase cycle and the second phase is at least 12-14 days;
• progesterone level in the middle of the second phase is more than 15 ng/ml.

Preparing patients with mixed hyperandrogenism for pregnancy

The mixed form of hyperandrogenism is extremely similar to the ovarian form of hyperandrogenism, but during hormonal testing, the following is determined:

• elevated DHEA levels;
• moderate hyperprolactinemia;
• there is no reliable increase in 17OP;
• the level of 17KS was increased in only 51.3% of patients;
• increased LH level, decreased FSH level;
• ultrasound examination revealed a typical picture of polycystic ovaries in 46.1%, and microcystic changes in 69.2%;
• with an elevated level of 17KS, hirsutism and excess body weight are observed (BMI - 26.5+07);
• In the dexamethasone test with hCG, a mixed source of hyperandrogenism is noted, a tendency towards an increase in 17KS, a reliable increase in testosterone and 17OP after stimulation with hCG against the background of suppression with dexamethasone.

Patients with a mixed form of hyperandrogenism have a history of stressful situations, head injuries, and encephalograms often reveal changes in the bioelectrical activity of the brain. These patients are characterized by hyperinsulinemia, lipid metabolism disorders, and increased blood pressure.

Hyperinsulinemia often leads to the development of type II diabetes (diabetus mellitus).

Preparation for pregnancy in women with mixed genesis of hyperandrogenism begins with weight loss, normalization of lipid and carbohydrate metabolism, diet, fasting days, physical exercises, and sedatives (peritol, diphenin, rudotel). Acupuncture sessions are useful. During this stage of preparation for pregnancy, it is advisable to prescribe oral contraceptives such as Diana-35 and treat hirsutism.

With normal levels of glucose, insulin, and lipids, it is advisable to prescribe gestagens in the second phase of the cycle against the background of taking 0.5 mg of dexamethasone, then stimulate ovulation with clostilbegid. With an elevated level of prolactin, we include parlodel in the ovulation stimulation scheme from day 10 to day 14 of the cycle at a dose of 2.5 mg 2 times a day. If there is no effect from the therapy, in the event of failure to conceive, similar therapy is carried out for no more than 3 cycles, and then surgical treatment of polycystic ovaries may be recommended.

When preparing for pregnancy, regardless of the form of hyperandrogenism, it is recommended to prescribe metabolic therapy complexes. This is necessary due to the fact that glucocorticoids, even in small doses, have an immunosuppressive effect, and most patients with habitual miscarriage, regardless of its genesis, are virus carriers. To prevent exacerbation of a viral infection while taking dexamethasone, it is advisable to use metabolic therapy complexes, which, by relieving tissue hypoxia, prevent virus replication. According to our data, as a result of preparation, pregnancy occurred in 54.3% of patients. The duration of preparation was on average 6.7 cycles.