Endocrine infertility is a complex of hormonal disorders leading to irregular ovulation or its absence in women and impaired sperm quality in men. It is characterized by the absence of a desired pregnancy in combination with menstrual disorders. Diagnosis of the causes involves a gynecological examination, hormonal examination, carrying out separate diagnostic curettage (SDC) with a study of endometrial scraping. Treatment is aimed at correcting the identified hormonal abnormalities by therapeutic or surgical methods. In cases that cannot be treated, IVF is indicated.
The concept of “endocrine infertility” is collective, including various disorders of the mechanisms of hormonal regulation of the menstrual cycle: at the hypothalamic-pituitary-ovarian level, in the systems of TSH-thyroid gland, ACTH – adrenal cortex, etc. Regardless of the causes of endocrine infertility, its development is based on a violation of ovarian function, manifested by persistent anovulation (lack of ovulation) or its irregularity.
Normalization of impaired functions leads to pregnancy in 70-80% of cases of endocrine infertility. In other cases, the elimination of endocrine infertility by IVF is currently considered promising. In every third infertile woman, the cause of infertility lies in the pathology of the endocrine system.
Anovulation can occur with the interest of the central nervous and immune systems, endocrine glands, reproductive organs-“targets”. Anovulation leading to an endocrine form of infertility may develop as a result of:
- Hypothalamic-pituitary dysfunction. It is usually observed after traumatic brain injuries and chest injuries, with tumors of the hypothalamic-pituitary region and is accompanied by hyperprolactinemia. An increase in prolactin secretion leads to inhibition of cyclic production of LH and FSH by the pituitary gland, suppression of ovarian functions, rare menstruation (by the type of oligo- and opsomenorrhea), the development of persistent anovulation and endocrine infertility.
- Hyperandrogenism of ovarian genesis. The presence in a woman’s body of a small amount of androgens – male sex hormones is necessary for puberty and proper functioning of the ovaries. Increased androgen secretion can be carried out by the ovaries or adrenal glands, and sometimes both glands at the same time. Most often, hyperandrogenism in women accompanies polycystic ovary syndrome, causing endocrine infertility, obesity, hirsutism, bleeding, oligo- and amenorrhea, bilateral ovarian damage with a change in their morphological structure.
- Adrenal hyperandrogenism. It develops more often as a result of hyperplasia of the adrenal cortex with secondary involvement of the ovaries (secondary polycystic ovaries).
- Disorders of thyroid function. The course of hypothyroidism and diffuse toxic goiter is often accompanied by anovulation, secondary hyperprolactinemia, endocrine infertility, miscarriage, fetal abnormalities.
- Deficiency of estrogens and progesterone (with insufficiency of the luteal phase). The lack of female sex hormones causes an incomplete secretory transformation of the endometrium, a change in the function of the fallopian tubes, prevents the attachment of the fetal egg in the uterine cavity. This leads to miscarriage or endocrine infertility.
- Severe somatic pathologies (cirrhosis, hepatitis with severe damage to liver cells, tuberculosis, autoimmune and systemic connective tissue diseases, malignant neoplasms of various localization, etc.).
- Obesity or lack of adipose tissue. Adipose tissue in the body also performs an endocrine function, influencing metabolic processes in tissues, including the reproductive system. Excess body fat causes hormonal imbalance, menstrual dysfunction and the development of endocrine infertility. At the same time, limiting fat intake or a sharp loss of body weight disrupts the normal functioning of the ovaries.
- Resistant ovarian syndrome (Savage syndrome). The syndrome is based on a violation of the pituitary-ovarian connection – insensitivity of the ovarian receptor apparatus to gonadotropins that stimulate ovulation, which is manifested by amenorrhea, endocrine infertility with normally developed sexual characteristics and a high level of gonadotropins. Damage to the ovaries can cause infection with rubella viruses, influenza, pathology of a previously developed pregnancy, vitamin deficiency, starvation, stressful situations.
- Premature menopause (syndrome of depleted ovaries). Secondary amenorrhea, which occurs in young women up to 35-38 years old, causes changes characteristic of menopausal syndrome and leads to endocrine infertility.
- Diseases associated with mutations of sex chromosomes. In pathologies caused by chromosomal abnormalities, there is a lack of female sex hormones, sexual infantilism, primary amenorrhea and endocrine infertility (Marfan, Turner syndromes).
The main manifestations of endocrine infertility are the impossibility of pregnancy and deviations in the menstrual cycle. Menstruation may occur with delays of varying severity (from a week to six months), accompanied by soreness and copious discharge, or absent altogether (amenorrhea). Spotting spotting in the intermenstrual period is often noted.
In 30% of patients with endocrine infertility, menstrual cycles are anovulatory in nature and in their duration correspond to the normal menstrual cycle (21-36 days). In such cases, we are not talking about menstruation, but about menstrual-like bleeding.
Patients have pain in the lower abdomen or lower back, discharge from the genital tract, dyspareunia, cystitis. There may be tension and heaviness in the mammary glands, galactorrhea (colostrum discharge from the nipples) associated with an increase in prolactin levels. The syndrome of premenstrual tension is characteristic – deterioration of the condition on the eve of menstruation. With hyperandrogenism accompanying endocrine infertility, acne, hirsutism or hypertrichosis, alopecia develop. There are fluctuations in blood pressure, the development of obesity or weight loss, the formation of striae on the skin.
When collecting anamnesis in patients with endocrine infertility, the time of the onset of menstruation, their abundance, soreness, the presence in the anamnesis (including the patient’s mother) of menstrual function disorders, the presence and duration of the absence of pregnancies, if present, the outcome and complications of pregnancies are specified. It is necessary to find out whether gynecological operations and manipulations have been performed before, the type and duration of contraception use. The general examination includes an assessment of the patient’s height, the presence of obesity, virilism, the development of mammary glands and secondary sexual characteristics.
- Consultation of a gynecologist. During a gynecological examination, the shape and length of the vagina and uterus, the condition of the cervix, parametria and appendages are found out. According to general and gynecological examinations, such causes of endocrine infertility as sexual infantilism, polycystic ovaries, etc. are being investigated.
- Functional diagnostic tests. The assessment of the hormonal function of the ovaries and the presence of ovulation in endocrine infertility is determined using functional tests: construction and analysis of the basal temperature curve, urinary ovulation test, ultrasound monitoring of follicle maturation and ovulation control.
According to the basal temperature chart, the presence or absence of ovulation is determined. The basal temperature curve reflects the level of postovulatory production of progesterone by the ovaries, which prepares the endometrium of the uterus for implantation of a fertilized egg. The basal curve is based on the morning temperature measured daily at the same time in the rectum. During the ovulatory cycle, the temperature graph is two-phase: on the day of ovulation, the rectal temperature drops by 0.2-0.3 ° C, and in the second phase of the cycle, lasting from 12 to 14 days, it rises by 0.5-0.6 ° C compared to the temperature of the first phase. The anovulatory menstrual cycle is characterized by a monophasic temperature curve (persistently below 37 ° C), and the insufficiency of the luteal phase is manifested by shortening the second phase of the cycle for less than 11-12 days.
- Ovulation monitoring. You can confirm or deny the fact of ovulation by determining the level of progesterone in the blood and pregnanediol in the urine. With the anovulatory cycle, these indicators are extremely low in the second phase, and with an insufficient luteal phase, they are reduced in comparison with the ovulatory menstrual cycle. Conducting an ovulation test allows you to determine an increase in the concentration of LH in the urine 24 hours before ovulation. Ultrasound monitoring of folliculogenesis makes it possible to trace the maturation of the dominant follicle in the ovary and the release of an egg from it.
- Examination of endometrial scraping. A reflection of the functioning of the ovaries is the state of the endometrium of the uterus. In a scraping or biopsy of the endometrium taken 2-3 days before the expected menstruation, with anovulation and endocrine infertility, hyperplasia of varying severity (glandular cystic, glandular, polyposis, adenomatosis) or secretory insufficiency is detected.
- Hormonal studies. To find out the causes of endocrine infertility, the levels of FSH, estradiol, LH, prolactin, TSH, testosterone, T3, T4, DEA-C (dehydroepiandrosterone sulfate) are determined on the 5th-7th day during several menstrual cycles.
- Hormonal tests. Carrying out hormonal tests allows you to clarify the state of various parts of the reproductive system in endocrine infertility. The mechanism of these tests is to measure the level of the patient’s own hormones after taking certain stimulating hormonal drugs.
- Instrumental diagnostics. If it is necessary to clarify the causes of endocrine infertility, skull x-ray, ultrasound of the thyroid gland, ovaries, adrenal glands, diagnostic laparoscopy is performed.
The diagnosis of endocrine infertility for a woman is established only after the exclusion of the male factor of infertility (the presence of a normal spermogram), as well as pathology on the part of the uterus, immunological and tubal forms of infertility.
The first stage of treatment of endocrine infertility includes normalization of impaired functions of the endocrine glands (correction of diabetes mellitus, obesity, adrenal gland activity, thyroid gland, removal of tumors, etc.). In the future, hormonal stimulation of maturation of the dominant follicle and ovulation is carried out. To stimulate ovulation, the drug clomiphene citrate is prescribed, which causes an increase in the secretion of follicle-stimulating hormone by the pituitary gland. Of the pregnancies that occurred after clomiphene citrate stimulation, 10% were multiple pregnancies (more often twins and triplets).
In the absence of pregnancy during 6 ovulatory cycles, when stimulated with clomiphene citrate, gonadotropins are resorted to: HMG (human menopausal gonadotropin), r-FSH (recombinant follicle-stimulating hormone), and hCG (human chorionic gonadotropin). Treatment with gonadotropins increases the frequency of multiple pregnancies and the development of side effects.
In most cases, endocrine infertility is amenable to hormonal correction, in others surgical intervention is indicated. With polycystic ovary syndrome, they resort to their wedge-shaped resection by laparoscopic method or laparoscopic thermocouterization. After laparoscopic thermocouterization, the highest percentage of pregnancies is observed – from 80 to 90% of cases, since the formation of adhesions in the pelvis is excluded.
In case of endocrine infertility, burdened with tubal-peritoneal factor or a decrease in sperm fertility, the method of in vitro fertilization (IVF) with the transfer of embryos ready for development into the uterine cavity is shown. To achieve the onset and gestation of pregnancy in women with endocrine infertility is possible only with a comprehensive solution to this problem.
Today, endocrine infertility is not a verdict. Modern gynecology and endocrinology jointly successfully treat 80% of patients using only medical methods. If ovulation has been restored and there are no other infertility factors, more than 50% of women become pregnant during the first six cycles of stimulating hormone therapy. Less favorable results from drug therapy in endocrine infertility caused by dysfunction of hypothalamic-pituitary regulation.
Immediately after the onset of pregnancy, careful monitoring of its development is established, the patient is hospitalized with signs of spontaneous termination of pregnancy. Discoordination and weakness of labor activity are often noted.
It is necessary to take care of the prevention of endocrine forms of infertility from childhood. Reducing and preventing childhood infections, chronic tonsillitis, rheumatism, influenza, toxoplasmosis in childhood and adolescence will help to avoid violations of ovarian function and processes of hypothalamic-pituitary regulation.
The correct emotional and physical education of girls is of preventive importance, because the function of the ovaries often suffers due to mental overstrain, psychological and sexual trauma. It is an undeniable fact that endocrine infertility often develops after pathological childbirth, termination of pregnancy, intoxication, inflammatory infections of the female reproductive sphere, therefore, attention should be paid to the prevention of these conditions.
Proper management of pregnancy, reasonable use of certain medications, especially hormones during pregnancy, will help to avoid congenital hypofunction of the ovaries and hyperplasia of the adrenal cortex in girls.