Female infertility

Diagnosis and treatment of infertility

Introduction

Infertility (infertility, sterilitas - lat.) Is defined as the inability to conceive a child with regular sex without contraception for 12 months, provided the partners are of childbearing age. Infertility is not a disease, but a dysfunctional condition caused by a number of diseases in which the onset of pregnancy becomes impossible.

Infertility is one of the most important and complex modern medical and social problems. According to the WHO, 60 to 80 million couples suffer from infertility worldwide. Therefore, the problem of diagnosis and treatment of infertility is extremely urgent in obstetric and gynecological practice. According to recent studies, about 10% of married couples are infertile in Europe, up to 15% in the USA, 17% in Canada, 15.4% in Australia, 17.5% in Russia, and 15% in Belarus. There is a tendency to increase these numbers. In recent years, there has been a deterioration in reproductive health indicators for both men and women. The state of the reproductive system is negatively affected by the deterioration of the environmental situation and harmful working conditions, the widespread occurrence of sexually transmitted infections, early abortions.

In Belarus, amid falling fertility, increasing mortality, decreasing working-age population, deteriorating population health and aging, the problem of infertility is also gaining great social significance. The demographic situation in Belarus is currently characterized by a negative population growth. In this situation, it is especially important that every woman has the opportunity to get the desired pregnancy. In addition, the problem of infertility in marriage often leads to divorce, conflict, reduces social adaptation and self-realization.

In recent years, much attention has been paid to the diagnosis and treatment of infertility, however, despite the achievements of medicine in this area, many unresolved issues remain. In 5% of cases, the cause of infertility cannot be determined. Ineffective operations to restore patency of the fallopian tubes. The effectiveness of such advanced methods as in vitro fertilization, on average, is 25 - 40%. Thus, taking into account all medical, social and psychological aspects, the problem of infertility can be attributed to the main problems in modern medicine.

The purpose of this article was to systematize data on the causes of infertility, methods for their diagnosis, the main stages and methods of treatment, to highlight current trends in the tactics of infertile marriage, the latest treatment methods, the role of assisted reproductive technologies and their effectiveness.

Classification

Distinguish between female and male infertility. When a combination of female and male factors of infertility occurs, the term “combined infertility” is used. According to statistics, 40-60% of cases of infertility are caused by violations of the reproductive function of women, 5-6% are men, 27-48% are caused by violations in both spouses, and in 5% of cases it is not possible to identify the cause of infertility.

In addition, infertility is divided into primary and secondary, absolute and relative. Primary infertility is the lack of infertility from the onset of sexual activity. Secondary infertility is infertility if a woman has a history of one or more pregnancies (childbirth, abortion, ectopic pregnancy).

Absolute infertility is infertility associated with irreversible pathological changes in the genitals that exclude the possibility of conception (with the congenital absence of internal genital organs or their surgical removal). Relative infertility - a woman and a man are able to have children separately, but with a long life together, their marriage is barren.

Highlights several forms of female infertility:

• endocrine, associated with a violation of ovulation (35-40%)
• tubal peritoneal (20-30%)
• infertility associated with endometriosis (15-20%)
• uterine factor (5%)
• immunological reasons (2%);
• infertility of unknown origin (5-15%).

Endocrine female infertility

Endocrine female infertility is a violation of a woman's reproductive function caused by a lack of normal folliculogenesis and ovulation in the ovaries.

In the structure of barren marriage, endocrine female infertility occupies a significant part - 30-40%.

Despite the variety of clinical and laboratory manifestations, female endocrine infertility is always associated with a violation of the ovulation process: anovulation, luteal phase insufficiency, luteinization syndrome of a non-ovulating follicle. With anovulation, the follicle does not mature and rupture with the release of the egg. The causes of this violation are very diverse.

In case of insufficiency of the luteal phase, hypofunction of the corpus luteum occurs, a decrease in the level of progesterone in the blood plasma, insufficient secretory transformation of the epithelium, and as a result, impaired implantation of the embryo. The causes of the luteal phase deficiency can be hyperprolactinemia, hyperandrogenism, hypothyroidism, chronic inflammatory diseases of the pelvic organs, endometriosis.

With luteinization of the neovulated follicle, premature luteinization of the preovulatory follicle occurs without ovulation. The reasons for the completion are not clarified.

The mechanism of formation of these pathological conditions is a violation of the implementation of direct and feedback in the hypothalamus-pituitary-ovary system. The reasons may be damage to the reproductive system at various levels, including violation of the function of other endocrine glands. The following clinical and pathogenetic forms of endocrine (anovulatory) infertility in women are distinguished:

• hypothalamic-pituitary insufficiency (14.3%)
• hyperprolactinemia (22.3%)
• ovarian failure (5.7%)
• polycystic ovary syndrome
  • central origin (37.2%)
  • adrenal genesis (11.3%)
  • ovarian genesis (6.1%)
• hypothyroidism (3.1%)

The following methods are used to detect anovulation:

1. Sonography - allows you to detect the absence of a dominant follicle on the 11-16th day of the menstrual cycle or the absence of the corpus luteum on the 19-23rd day of the menstrual cycle.
2. Hormonal studies - determining the level of progesterone on the 18-23 day of the cycle, identifying the pre-ovulatory peak of luteinizing hormone on the 11-16th day of the menstrual cycle.
3. Measurement of basal temperature and tension of cervical mucus (now less commonly used due to the high probability of error and the availability of more reliable methods).

Diagnosis of luteal phase insufficiency is based on the identification of shortening of the second phase of the cycle (less than 10 days), a decrease in the amplitude of fluctuations in the basal temperature in the interval between the first and second phases of the cycle by less than 0.3 ° C, a decrease in progesterone in the heyday of the corpus luteum, inferiority endometrial secretion phases.

For differential diagnosis, a detailed hormonal study is carried out, as well as a wide range of additional studies. Given the form of infertility, treatment is carried out, which usually consists of three stages:

• Preparation for the induction of ovulation. At this stage, correction of endocrine disorders, preparation of the endometrium
• Controlled ovulation induction
• Hormonal support of the luteal phase of the induced cycle.

The drugs of the scheme and dose are selected depending on the form of the lesion. In the absence of a positive result, the issue of using assisted reproductive technologies is being resolved. Next, each form of infertility, its diagnosis and treatment will be examined in detail.

Hypothalamic-pituitary insufficiency

Hypothalamic-pituitary insufficiency is a disease which is based on the insufficiency of gonadotropic function, accompanied by delayed sexual development of central genesis, estrogen deficiency. It occurs in 15-20 women with amenorrhea. Among forms of secondary amenorrhea, the frequency of psychogenic amenorrhea is about 10%, amenorrhea with a decrease in body weight from 10 to 12%. The frequency of Kallman syndrome is 1 in 50 thousand women.

The etiological factor distinguishes between congenital and acquired hypothalamic-pituitary insufficiency. According to the level of damage, the hypothalamic and pituitary forms are distinguished. The severity distinguishes between mild, moderate and severe.

Congenital hypogonadism is caused by genetic causes - mutations in the gonadotropin genes of luteinizing hormone and follicle-stimulating hormone, gonadotropin receptor - releasing hormone. The most common example of this pathology is Kallman syndrome - hypogonadotropic hypogonadism, combined with anosmia.

Acquired gonadotropin deficiency is a consequence of external influences and may be reversible. This includes amenorrhea with anorexia, with a decrease in body weight, exercise amenorrhea, psychogenic amenorrhea, Sheehan syndrome.

Due to insufficiency of the hypothalamic-pituitary system, secondary ovarian failure develops, which leads to deficiency of estrogen and anovulation. At the same time, the ovaries are intact, as are the target organs.

The leading symptom is amenorrhea, which can be primary (65%) or secondary (35%) (after 2-5 spontaneous menstruation). Estagen deficiency determines the phenotype: eunuchoid physique, secondary sexual characteristics are underdeveloped, hair growth in the armpits and pubis is scarce, the mammary glands are hypoplastic. A gynecological examination reveals hypoplasia of the external and internal genital organs. The uterus is reduced in size, the ovaries are not determined. In addition, such women are prone to cardiovascular disease, osteoporosis, atrophic changes in the mucous membranes, psychoemotional and vegetovascular changes due to a lack of estrogen. The main diagnostic method is to study the concentration of gonadotropins and estradiol in blood plasma. Their decrease is noted. The test with clomiphene is negative, the cyclic hormonal test is positive. Ultrasound of the pelvic organs hypoplasia of the uterus and ovaries. Such patients are shown a consultation of genetics.

For a differential diagnosis between hypothalamic and pituitary insufficiency, tests are carried out with gonadoliberin. If, in response to the administration of a gonadoliberin agonist, there is a three-fold increase in the concentration of luteinizing hormone and follicle-stimulating hormone, then it can be concluded that there is a lesion of the hypothalamus.

Treatment is carried out in two stages:

• first stage - preparatory therapy
• second stage - ovulation induction

At the first stage, cyclic hormone replacement therapy is carried out for 3-12 months to form a female phenotype, increase the size of the uterus, and endometrial growth. At the second stage, ovulation is induced using exogenous gonadotropins (human menopausal gadotropin 225-300 IU / m once a day or follitropin-beta 300 IU + lutropin-alpha 150 IU / day under ultrasound control, then human chorionic gonadotropin 10000 IU once ) If the hypothalamus is damaged, gonadoliberins can be used (from the 3-5th day, pulsating injections of gonadorelin acetate for 20-30 days).

Recovery of a spontaneous menstrual cycle and reproductive function with congenital hypothalamic-pituitary insufficiency is unlikely. With acquired hypothalamic-pituitary insufficiency, the occurrence of spontaneous pregnancies is possible after the completion of an induced pregnancy. The effectiveness of treatment with a correctly diagnosed diagnosis reaches 80-90%.

Hyperprolactinemia

Hyperprolactinemia is a condition characterized by an increased content of prolactin in blood plasma.

When examining patients who applied for infertility, hyperprolactinemia is detected in 18-20% of cases, and with endocrine disorders of the menstrual cycle and endocrine infertility - in 40%.

Hyperprolactinemia syndrome, or persistent galactorrhea-amenorrhea syndrome, in women is a combination of hyperprolactinemia with menstrual irregularities, galactorrhea and infertility. For the first time in the literature, the clinical form of amenorrhea-galactorrhea syndrome was described more than 100 years ago, however, the cause of this condition was clarified only in the early 70s, when the hormone of the anterior pituitary gland, an increased content of prolactin, was first isolated in its pure form.

Physiological hyperprolactinemia (during pregnancy and lactation), pharmacological (when taking antipsychotics, antidepressants, antiemetics, antihypertensive drugs, oral contraceptives, narcotic drugs) and pathological hyperprolactinemia are distinguished. Pathological hyperprolactinemia can be primary, due to the pathology of the hypothalamus and pituitary, secondary, in the pathology of another organ, and idiopathic or functional.

Primary pathological hyperprolactinemia occurs with diseases and / or tumors of the hypothalamus and pituitary gland, empty Turkish saddle syndrome, pituitary leg transection syndrome. The frequency of organic hyperprolactinemia in violation of the secretion of high prolactin levels ranges from 60 to 75%. This group consists of patients with prolactin-secreting pituitary adenomas (microprolactinomas less than 1 cm and macroprolactinomas more than 1 cm), which are the most common pathology among all benign pituitary tumors. Prolactinomas are mainly localized in the lateral parts of the anterior pituitary gland. The so-called non-functioning pituitary adenomas are diagnosed in 19–27% of cases.

Secondary pathological hyperprolactinemia occurs in patients with primary hypo- and hyperthyroidism, with polycystic ovary syndrome, adrenal cortex insufficiency, congenital dysfunction of the adrenal cortex, liver cirrhosis, diabetes mellitus, chronic renal failure, hormone-active ovarian tumors producing estrogen.

Hyperprolactinemia in combination with hypothyroidism is explained by a decrease in the level of thyroid hormones, an increase in the level of thyroliberin and an increase in the sensitivity of lactotrophs to its stimulating effect.

It is believed that in 11-30% of women with polycystic ovary syndrome, increased secretion of increased prolactin levels may be associated with overproduction of estrogens, while in other patients it occurs as an independent endocrine disorder.

Violation of the secretion and metabolism of androgens is detected in 32-40% of patients with elevated levels of prolactin.

The most common clinical parameters of hyperprolactinemia are:

1. menstrual irregularities according to the type of oligomenorrhea, primary or secondary amenorrhea (62-74%);
2. galactorrhea of ​​varying degrees (30-80%);
3. infertility.

In addition, with the tumor genesis of the disease, there is a volumetric process in the area of ​​optic nerve intersection with the corresponding symptoms.

A correlative relationship has been established between the level of increased prolactin and the nature of menstrual irregularities. A significantly higher level of prolactin is diagnosed with amenorrhea compared with oligomenorrhea and a regular menstrual cycle. An assessment of the functional state of the ovaries indicates that in the vast majority of patients (84%), menstrual irregularities are accompanied by chronic anovulation. The remaining 16% are diagnosed with luteal phase insufficiency (NLF), mainly patients with oligomenorrhea or a preserved rhythm of menstruation. Most patients are characterized by a timely onset of menarche and a period of regular menstruation. Most often, the onset of the disease is associated with the onset of sexual activity, stress, childbirth, abortion, spontaneous miscarriages. Primary infertility occurs in 70% of patients.

The second characteristic clinical sign of hyperprolactinemia is galactorrhea of ​​varying degrees, which is often the first symptom of a future disease. So, in 18% of patients, galactorrhea appears a few years before a cycle disorder, in 56% - simultaneously with a cycle disorder, and in 26% of patients - a few years after a menstrual cycle disorder and going to the clinic. Distinguish galactorrhea:

• I degree - excretion of colostrum from the nipples during palpation by drops,
• II degree - the excretion of colostrum from the nipples during palpation by a stream,
• III degree - spontaneous continuous secretion of colostrum from the nipples.

Some women have hyperandrogenism, excessive hair growth, and metabolic disorders. Long-term hypofunction of the ovaries with hyperprolactinemia is accompanied by a decrease in estrogen saturation and corresponding systemic disorders.

The diagnosis of the disease is made after determining a significantly elevated level of prolactin in plasma (more than 550 mIU / l or 25 ng / ml) with several studies. Analysis of the basal concentration of elevated plasma prolactin levels indirectly suggests the cause of the disease. The level of increased prolactin content of less than 1500 mIU / L is most characteristic for a group of patients with functional hyperprolactinemia. The content of elevated prolactin 1500–4000 mIU / L is most often diagnosed with microprolactinomas, pituitary cysts and the “empty Turkish saddle”. The level of increased prolactin content of more than 4000-5000 mIU / L is characteristic for patients with pituitary macroprolactinomas.

The level of elevated prolactin levels of 1000-1500 mIU / L is mainly detected in patients with a regular rhythm of menstruation and is caused by psychogenic factors, the use of pharmacological agents, the presence of hypothyroidism, CPCR, various gynecological diseases (endometriosis, chronic inflammatory diseases of the pelvic organs, benign uterine tumors and appendages).

Hormonal screening, along with the determination of the basal level of elevated prolactin content, includes an assessment of the levels of thyroid-stimulating hormone, T4 free, antibodies to thyroglobulin, gonadotropic hormones (luteinizing hormone, follicle-stimulating hormone), E2, T, K, DGA / DGAS. Of great importance already at the stage of hormonal examination is the assessment of the functional state of the thyroid gland in order to exclude primary and secondary hypothyroidism. Patients with a dysfunction of the thyroid gland need to be consulted by an endocrinologist for the purpose of further examination and the appointment of thyroid hormone replacement therapy.

An X-ray examination of the skull and the Turkish saddle is carried out. The main objective of this stage is to clarify the nature and severity of changes in the hypothalamic-pituitary region, leading to overproduction of high prolactin levels, as well as confirmation or exclusion of the tumor (organic) origin of the disease. To this end, X-ray of the skull (craniography), computed or magnetic resonance imaging.

Craniography makes it possible to evaluate the size, configuration and features of the Turkish saddle, as well as solve a number of differential diagnostic tasks. Diagnostic signs of the pituitary gland adenoma are an increase in the size of the Turkish saddle, an expansion of the entrance to the Turkish saddle, thinning and shortening of the sphenoid processes, deepening of the bottom, straightening, and destruction of the back of the saddle. The craniogram can not only diagnose pituitary adenomas, but also determine the nature and direction of tumor growth (supra-, infra-, para- and retrocellular). An increase in the Turkish saddle without destructive changes in its walls may be due to the so-called empty Turkish saddle.

Computed tomography and magnetic resonance imaging of the brain are modern methods for diagnosing the pathology of the hypothalamic-pituitary region, in particular the pituitary microadenoma. The methods provide information on the configuration of the skull bones, the size of any intrasellar formation, and also determine the prevalence of extrasellar lesions, since these methods have the ability to differentiate soft tissues in density.

The study of the fundus and visual fields for white and color marks are carried out for all patients with hyperprolactinemia to clarify the state of the opto-chiasmal region. Tumors that extend beyond the Turkish saddle up (suprasellarly) can squeeze the optic nerve cross, causing bitepore hemianopsia. Complete bitemporal hemianopsia is rare.

The functional state of the hypothalamic-pituitary region in hyperprolactinemia is assessed in order to study the reserve capabilities of the adenohypophysis, as well as to clarify the genesis of this pathological condition.

Consultation of a neurosurgeon is necessary for all patients with macro- or microprolactinoma of the hypothalamic-pituitary region in order to determine indications for surgical treatment and discuss the possibility of drug therapy. As a result of a comprehensive, phased clinical and laboratory examination, it seems possible to determine the causes of hyperprolactinemia and identify various disorders of the hypothalamic-pituitary region, in the structure of which pituitary micro- and macroprolactinomas occupy a leading place in women of reproductive age.

Functional, or idiopathic, hyperprolactinemia is characterized by a slight increase in the level of increased prolactin, often an unspecified etiology. The diagnosis of functional hyperprolactinemia is made after exclusion of the organic pathology of the pituitary gland. The clinical picture of the disease with functional hyperprolactinemia is characterized by the presence of oligomenorrhea against the background of anovulation / NLF or a regular rhythm of menstruation with NLF.

Methods of treating patients with hyperprolactinemia depend on the form of the disease (organic or functional) and consist in removing prolactinoma and / or suppressing the secretion of increased prolactin levels, which leads to the restoration of menstrual and reproductive functions.

There are three main methods of treatment: surgical, radiation and drug. Surgical treatment is carried out in a neurochurgical hospital, this is the removal of pituitary tumors by transfenoidal access. Indications for surgical treatment are:

1. with macroadenoma - compression of the visual intersection by a tumor, hemorrhage into the tumor, cerebrospinal fluid, germination into the sphenoid sinus;
2. with microadenoma - clear boundaries of the tumor (according to CT and MRI), patient refusal from drug treatment, adenomas refractory to treatment with high doses of dopamine agonists, intolerance to dopamine agonists.

Radiation treatment is carried out with incomplete removal of the tumor during surgery, contraindications and refusal of surgical treatment, inefficiency and intolerance to drug therapy. A positive effect after treatment develops within 12 to 30 months. With radiation therapy, irradiation of the tumor is less traumatic, but also less reliable compared to surgical methods. Complications of radiation therapy are: visual field disorders, paralysis of the oculomotor muscles, the development of panhypopituitarism for several years from the moment of exposure. The level of increased prolactin in plasma as a result of these methods of treatment is normalized and persists for several years, however, restoration of menstrual and reproductive function does not occur in all patients.

Drug treatment is carried out with bromocriptine preparations. Bromocriptine (parlodel) and its analogues suppress the secretion of increased prolactin levels by stimulating DA receptors, without affecting the normal levels of other pituitary hormones and exerting a direct effect on the pituitary tumor cells. In order to reduce adverse reactions, parlodel is started from 1/4 tablet per day, increasing the dose gradually over 5-10 days to 1 tablet. In patients with functional hyperprolactinemia, the daily dose of parlodel usually does not exceed 5 mg (1-2 tablets), and the duration of treatment is 6 months. In case of microprolactinomas, the daily dose of the drug is 5–10 mg (2–4 tablets), and for macroprolactinomas it is 10–12.5 mg (4–5 tablets). Therapy is carried out in a continuous manner.

Some patients have bromocriptine resistance. In these cases, a quinagolide preparation or a cabergoline preparation is used. Cabergoline is 2 times more effective than bromocriptine, has a prolonged effect, side effects are less pronounced.

The duration of treatment is from 6 months to 2 years. Against the background of drug therapy, a decrease in the level of elevated prolactin levels should be monitored monthly: on the 5-7th day when the menstrual cycle is restored or once every 30 days in the absence of menstruation. A dynamic study of elevated prolactin levels allows you to choose the dose of the drug and determine the duration of treatment. The lack of independent menstruation in the context of drug treatment indicates the preservation of an increased level of increased prolactin and is not an indication for the additional appointment of progestogens, estrogen-progestogen drugs in order to accelerate the restoration of the menstrual cycle.

The frequency of restoration of ovulation and reproductive function in patients with hyperprolactinemia during treatment with dopamine agonists is 86 and 79%, respectively.

Additional hormonal treatment aimed at regulating the cycle (progestogens) or stimulating ovulation (clomid, clostilbegit, ChMG / HCH drugs), according to generally accepted schemes, is carried out when, against the background of a normal level of prolactin, menstrual cycles continue to remain anovulatory. Most often, this group consists of patients with hyperprolactinemia and polycystic ovary syndrome. In the presence of an increased level of prolactin and a regular rhythm of menstruation, infertility treatment should not begin with the correction of hyperprolactinemia, but with the elimination of the main cause of infertility, which is detected by the use of a comprehensive clinical and laboratory study.

Ovarian failure

Ovarian failure (hypergonadotropic amenorrhea) 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 adequately respond to stimulation with gonadotropins.

The following forms of ovarian failure are distinguished:

• ovarian exhaustion syndrome;
• resistant ovary syndrome;
• gonad dysgenesis.

Syndrome of premature ovarian exhaustion and ovarian resistance syndrome occurs in 10% of women with amenorrhea. Gonad dysgenesis occurs in 1 case in 10-12 thousand newborns.

A typical form of gonadal dysgenesis, or Shereshevsky-Turner syndrome, is characterized by the karyotype 45-X. The clinical picture is characterized by a specific appearance (“Shereshevsky-Turner phenotype”), low growth - not more than 150 cm, dysplastic physique: short neck with a low hairline, skin folds from the mastoid to acromial processes, micrognathia and high palate, low located auricles, hallux valgus deformation of the elbow and knee joints. In addition, there may be malocclusion, strabismus, and the thyroid chest. In 38% of patients there are abnormalities of the kidneys and ureters, in 16% - malformations of the cardiovascular system. There is no sexual hair growth, the mammary glands are not developed, the uterus is sharply hypoplastic, i.e. there is a pronounced genital infantilism. According to ultrasound, the sizes of the gonads in the form of connective tissue cords are 1–1.5 cm in length and 0.3–0.5 cm in width. Histological examination - stromal elements, primordial follicles and oocytes are absent.

Diagnosis is not difficult in connection with the typical appearance of the patients. The diagnosis is confirmed by ultrasound, hormonal studies, which are characterized by a sharp increase in the level of gonadotropins, especially follicle-stimulating hormone, the level of which corresponds to early postmenopause. Genetic testing includes determination of sex chromatin in buccal smears and a karyotype, in which the absence of sex chromatin and a typical karyotype, 45-X, are detected.

The erased form of gonadal dysgenesis is characterized by the variability of clinical manifestations. The karyotype has a mosaic character, often 45-X / 46-XX. In addition to the mosaic karyotype, there may be other variants of chromosomal aberrations, such as deletion of the long or short arm of the X chromosome (Xc-, Xp-), isochromosomes along the long arm X (Xc), along the short arm X (Xp), balanced translocations between X chromosome and autosome. The clinical picture depends on the percentage of normal and aberrant cell clone. The higher the percentage of clone of cells with karyotype 45-X, the more patients in appearance and clinical picture are similar to patients with Shereshevsky-Turner syndrome. Accordingly, with the prevalence of a normal clone with a karyotype 46-XX, the clinical picture can be characterized by a normal morphotype, spontaneous development of secondary sexual characteristics, and even sporadic independent menstruation. But there is always genital infantilism, elevated levels of gonadotropins, and ultrasound signs of dysgenetic gonads.

A pure form of gonadal dysgenesis is characterized by the karyotype 46-XX or 46-XY (Swyer syndrome). This form is the most rare, its frequency is 1 per 100 thousand newborns. The clinical picture has features: the appearance is characterized by normal growth, there are no somatic dysplasias, the morphotype can be eunuchoid or intersexual, with moderately expressed hirsutism (with Swyer syndrome), secondary sexual characteristics are not developed against the background of pronounced genital infantilism. Gonads - in the form of connective tissue cords, and with Swyer syndrome - with elements of testicles that can become malignant. Patients with a pure form of gonadal dysgenesis with a karyotype 46-XX are described. The causes of this form are not fully known. Description of family cases of the disease indicates the hereditary nature of the disease.

Diagnosis is based on: the data of the clinical picture, in which the main one is pronounced sexual infantilism; echoscopic signs of dysgenetic gonads; high levels of gonadotropins; determination of the karyotype and lack of sex chromatin. Laparoscopy with a gonad biopsy confirms the diagnosis.

Resistant ovary syndrome occurs in women under 36 years of age (sometimes 6 to 10 years after menarche), characterized by secondary amenorrhea, macro- and microscopically unchanged ovaries, and elevated levels of gonadotropins. The frequency of CFA is approximately 5% among all forms of amenorrhea. It is believed that its development is associated with defects in the receptor apparatus of the follicles. Possibly, resistance to gonadotropins is due to the disturbed structure of follicle-stimulating hormone or pathology of gonadotropin receptors in the ovaries. However, most researchers consider autoimmune processes to be the cause. So, anti-varial antibodies were found in the blood of these women, as well as a frequent combination with autoimmune diseases.

Depleted ovary syndrome is characterized by secondary amenorrhea with vegetovascular disorders in women aged up to 38 years old, who had normal menstrual and generative function in the past. The frequency of SIA in the population is up to 2%, and in the structure of secondary amenorrhea up to 5–6%. One of the reasons is chromosomal abnormalities, in particular the presence of three X chromosomes. It has been established that various adverse factors in both the antenatal and postnatal periods (radiation, chemicals, teratogenic drugs, influenza virus, rubella, mumps) can lead to damage to the gonads and their replacement with connective tissue. Perhaps there is an accelerated, compared with physiological, apoptosis of oocytes in the ovaries. Probably, against the background of an inferior genome, any exogenous effects (infectious diseases, intoxications, stresses, surgical interventions, chemotherapy) can contribute to the development of ovarian exhaustion syndrome. The ovaries are reduced in size, the follicular apparatus on ultrasound is not determined.

The main clinical symptom of ovarian failure of any form is hypergonadotropic amenorrhea (primary for gonadal dysgenesis and secondary for depleted and resistant ovary syndrome).

The diagnosis of ovarian failure is based on the results of hormonal studies. A high level of gonadotropic hormones, especially follicle-stimulating hormone (> 20 IU / L), hypoestrogenism (<100 pmol/ L) is characteristic. In ovarian failure, the test with gestagens is negative, the cyclic hormonal test is positive. Ultrasound of the pelvic organs shows uterine hypoplasia, a thin endometrium, ovarian ovaries in the form of cords with gonad dysgenesis, ovarian hypoplasia with ovarian depletion, lack of a follicular apparatus, and the follicular apparatus is preserved with resistant ovaries. A cytogenetic study is performed if gonad dysgenesis is suspected.

Ovulation stimulation for the treatment of infertility is not indicated. Hormone replacement therapy is carried out. To achieve pregnancy, a fertilized donor egg is transferred to the uterine cavity, followed by replacement therapy with estrogens and gestagens for up to 12 weeks.

Polycystic Ovary Syndrome

Polycystic ovary syndrome is a multifactorial heterogeneous pathology characterized by menstrual irregularities, chronic anovulation, hyperandrogenism, cystic changes in the ovaries and infertility.

The frequency of polycystic ovary syndrome among women of reproductive age is 8 - 15%, among women with endocrine infertility - up to 60%, among all causes of infertility up to 20%.

There are polycystic ovary syndrome of central, adrenal and ovarian origin.

The etiology and pathogenesis of polycystic ovary syndrome is not fully understood. Polycystic ovary syndrome is a multifactorial pathology, possibly genetically determined, in the pathogenesis of which there are central mechanisms for regulating the gonadotropic function of the pituitary gland from the puberty, local ovarian factors, extravarial endocrine and metabolic disorders that determine the clinical symptoms and morphological changes of the ovaries. The provoking factors that lead to the realization of a genetic defect can be stress, chronic infections, intoxication, obesity.

In the central form, the leading link in pathogenesis is a violation of the rhythm of the release of gonadotropin releasing hormone, and as a result, a violation of the secretion of luteinizing hormone and follicle-stimulating hormone. Insulin resistance and hyperinsulinemia are also of great importance. Dysfunction of the adrenal cortex also contributes to the violation of the hypothalamic-pituitary-ovarian system. As a result, folliculogenesis and steroidogenesis in the ovaries are disrupted. There is an increase in many follicles at different stages of development, some of them undergo atresia, some are luteinized, the capsule of the ovary thickens.

Clinical manifestations are very variable, the most persistent symptoms are menstrual irregularities, hyperandrogenism, chronic anovulation, infertility. Disorders of the menstrual cycle, as a rule, occur with menarche, are of the nature of oligomenorrhea or amenorrhea primary or secondary. Primary infertility. 30 - 50% of patients have obesity, as well as various symptoms of virilization: hirsutism, oily seborrhea, acne. On ultrasound, the ovaries are enlarged, with a large number of follicles from 2 to 9 mm, the capsule is thickened. In a hormonal study, there is an increase in the level of luteinizing hormone with normal follicle-stimulating hormone, as well as an increase in the level of free testosterone, DHEA, androstenedione. In addition, due to the constant monotonous effect of estrogens and a reduced level of progesterone in 40 - 50%, hyperplastic processes are observed in the endometrium.

Diagnosis is based on the clinical picture, the results of ultrasound and hormonal studies. In the presence of obesity, the first stage of therapy is the normalization of body weight with diet and physical activity, as well as with the help of drugs such as metformin. In the presence of high levels of luteinizing hormone, the hypothalamic-pituitary system is desensitized to completely suppress ovarian function. For this, gonadoliberin agonists are used (buserelin 0.2% 2 mg intranasally starting from 21 or 2 days of the menstrual cycle for 1-3 months). With the adrenal form of the polycystic ovary syndrome, dexamethasone is used at 0.25 mg per day for 3 months. Clomiphene ovulation stimulation starts from the 5th to the 9th day of the menstrual cycle at 50 mg per day. In the absence of ovulation, the dose of clomiphene can be increased in each subsequent cycle by 50 mg, reaching 200 mg per day. However, many clinicians believe that if there is no effect when prescribing 100-150 mg, then a further increase in the dose of clomiphene is not advisable. In the absence of ovulation at the maximum dose for 3 months, the patient can be considered resistant to clomiphene. In the presence of a dominant follicle of at least 18 mm, endometrial thickness of at least 8–10 mm. the introduction of an ovulatory dose of 7500–10,000 human chorionic gonadotropin is recommended, after which ovulation is noted after 36–48 hours. To reduce the antiestrogenic effect of clomiphene, estrogen is recommended. In case of insufficiency of the luteal phase, it is recommended to appoint progestogens in the second phase of the cycle from 16 to 25 days.

With resistance to clomiphene, gonadotropic drugs are prescribed - direct ovulation stimulants. Used menopausal human gonadotropin (pergonal, humigon, etc.). In recent years, a highly purified follicle-stimulating hormone (metrodine) preparation has been developed to stimulate ovulation in women with high luteinizing hormone. The clinical use of the recombinant follicle-stimulating hormone obtained by genetic engineering is promising.

The frequency of ovulation induction during treatment with clomiphene is approximately 60–65%, the onset of pregnancy is 32–35%, the rate of multiple pregnancy, mostly twins, is 5–6%, the risk of ectopic pregnancy and spontaneous miscarriage is not higher than in the population.

When ovulation is stimulated with gonadotropins, the pregnancy rate rises to 60%, the risk of multiple pregnancy is 10–25%, ectopic from 2.5 to 6%, spontaneous miscarriages in the cycles ending in pregnancy reach 12–30.

As a surgical stimulation of ovulation, a wedge-shaped ovarian resection is used. In recent years, interest in surgical treatment has increased due to the introduction of surgical laparoscopy, the advantages of which are minimal invasive intervention and a reduced risk of adhesions. In addition, the advantages of laparoscopic resection are: the absence of the risk of hyperstimulation, the onset of multiple pregnancy and the ability to eliminate the often associated peritoneal infertility factor. The pathophysiological mechanisms of wedge-shaped resection in stimulating ovulation are based on a decrease in the volume of steroid-producing ovarian stroma, as a result of which the pituitary sensitivity to gonadotropin-releasing hormone is normalized and the hypothalamic-pituitary-ovarian connections are restored.

In addition to wedge-shaped resection, with laparoscopy, ovarian cauterization can be performed using various energies (thermo, electro, laser), which is based on the destruction of the stroma by a point electrode. The operation is less traumatic and long in comparison with a wedge-shaped resection.

In the postoperative period, a menstrual-like reaction is observed after 3-5 days, and after 2 weeks ovulation, which is tested at basal temperature. The absence of ovulation for 2-3 cycles requires additional administration of clomiphene. As a rule, pregnancy occurs within 6-12 months, in the future, the frequency of pregnancy decreases. The absence of pregnancy in the presence of ovulatory menstrual cycles necessitates the exclusion of tubal infertility factor. The frequency of ovulation induction after surgical laparoscopy is 84–89%, pregnancy on average is 72%.

Most clinicians report a relapse of polycystic ovary syndrome and clinical symptoms after about 5 years. Therefore, after pregnancy and childbirth, prevention of relapse of polycystic ovary syndrome is necessary, which is important, given the risk of developing endometrial hyperplastic processes. For this purpose, it is most advisable to prescribe combined oral contraceptives, preferably monophasic (marvelon, femoden, diane, mercilon, etc.). If the combined oral contraceptives are poorly tolerated, as happens with overweight, gestagens in the second phase of the cycle can be recommended: Duphaston 20 mg from 16 to 25 days of the cycle, medroxyprogesterone acetate 10–20 mg from 16 to 25 days of the cycle or 17-OPK 12, 5% IM on the 16th and 21st day of the cycle of 125-250 mg.

Hypothyroidism

Hypothyroidism is a clinical syndrome that is caused by a persistent deficiency of thyroid hormones in the body. In women suffering from infertility, hypothyroidism is detected in 10-34% of cases.

Pathogenetically distinguish primary (thyroid), secondary (pituitary), tertiary (hypothalamic) and tissue (transport, peripheral). Secondary and tertiary hypothyroidism are combined under the name central, but develops as a result of a deficiency of thyroid-stimulating hormones.

According to severity, there are:

• Subclinical - the concentration of thyroid-stimulating hormone in the blood is increased, T4 is free within normal limits. There are usually no symptoms.
• Manifest - thyroid-stimulating hormone concentration is increased, free T4 is reduced, there are moderate clinical manifestations.
  • Compensated
  • Uncompensated
• Complicated - a detailed clinical picture, severe complications (polyserositis, heart failure, creatinism, myxedema). In hypothyroidism, the most common forms of reproductive function disorders are hypomenstrual syndrome, amenorrhea, anovulatory, dysfunctional uterine bleeding and infertility.

The causes of hypothyroidism are most often autoimmune thyroiditis, less commonly thyroid surgery and radioactive iodine therapy.

Deficiency of thyroid hormones leads to a change in the processes of synthesis, transport, metabolism and peripheral effects of sex hormones. Long-term deficiency of thyroid hormones leads to the development of secondary hyperprolactinemia. Hyperprolactinemic hypogonadism syndrome in primary hypothyroidism is called Van Wick-Hennes-Ross syndrome and is manifested by oligomenorrhea or amenorrhea, galactorrhea, chronic anovulation, and secondary polycystic ovary. Secondary pituitary adenoma may also develop.

The diagnosis is based on the clinical signs of hypothyroidism and the results of a thyroid function test. Study of serum levels of thyroid stimulating hormone, TK, T4, free fractions of TK, T4, thyroglobulin, antibodies to thyroid peroxidase and thyroglobulin.

Treatment is with levothyroxine preparations. When compensating for thyroid function, if pregnancy has not occurred on its own, ovulation with clomiphene, gonadotropins, and gonadotropin releasing hormone agonists is stimulated.

Endometriosis

Among fertile women, endometriosis is diagnosed in approximately 6–7%, while among patients with infertility, its frequency can reach 20–48%.

The probable causes of infertility in endometriosis include the following:

• tubal infertility: organic - in violation of the anatomy of the fallopian tubes caused by the endometriotic process; functional - due to the effects on the fallopian tubes of inflammatory mediators and cytokines formed in the foci of endometrioid heterotopia, as well as on the background of hormonal imbalance (constant relative hyperestrogenism in combination with progesterone deficiency in the 2nd phase of the cycle) accompanying endometriosis;
• peritoneal infertility - against the background of endometriosis occurs during adhesions in the pelvis under the influence of the same reasons (local inflammation in the area of ​​endometrioid heterotopies) as organic tubal infertility;
• endocrine infertility (anovulation, NLF, luteinization syndrome of the neovulating follicle against the background of inadequate functioning of the axis of the hypothalamus – pituitary – ovary)) - is caused by an imbalance in female sex steroids accompanying endometriosis (an absolute or relative increase in estrogen production) and potentiation of gonadotin formation of prolactin, and prolactin regulation ;
• immune reactions that inhibit the process of implantation of the blastocyst in the endometrium or damage to spermatozoa by activated macrophages.

An increased level of estrogen in endometriosis can provoke the hyperprolactinemia observed in individual patients. In addition, infertility in endometriosis is also facilitated to a certain extent by sexual dysfunction due to severe dyspareunia, which complicates regular sex life and / or providing a full sexual intercourse.

Depending on the localization of endometrioid heterotopia, there are:

1. genital endometriosis;
2. extragenital endometriosis.

Endometriosis of the ovaries, fallopian tube, pelvic peritoneum, rectovaginal septum and vagina are classified as external, and endometriosis of the uterus (adenomyosis) - as internal. Extragenital endometriosis is topographically not related to the genitals and can affect any organs and tissues. The introduction of endosurgical diagnostic and treatment methods has revealed the so-called small forms of external genital endometriosis, when the diameter of the focus does not exceed 5 mm, but cicatricial changes in the peritoneum can take place.

Currently, the following classification of diffuse adenomyosis (internal endometriosis) is used (V.I. Kulakov, L.V. Adamyan, 1998):

• stage I - the pathological process is limited to the mucous membrane of the uterus;
• stage II - the transition of the pathological process to the muscle layers;
• stage III - the spread of the pathological process throughout the entire thickness of the muscular wall of the uterus to its serous cover;
• stage IV - involvement in the pathological process, in addition to the uterus, parietal peritoneum of the pelvis and neighboring organs.

A modern approach to the treatment of infertility with external genital endometriosis consists in the initial attempt to restore natural fertility using drugs (surgical and / or hormonal) used to treat endometriosis itself and its complications (anemia, pain). In this case, they also provide for the elimination of the concomitant pathology that accompanies endometriosis (for example, ovulatory disorders, peritoneal adhesions, etc.). If infertility persists for 1–2 years against the background of such therapy, it is recommended to switch to treatment using in vitro fertilization. Inertial patients older than 38 years of age, in vitro fertilization should be prescribed immediately, and regardless of the form and severity of the endometriosis process. As a non-alternative method of overcoming infertility, in vitro fertilization is initially recommended for infertile patients with adenomyosis, retrocervical endometriosis and grade IV peritoneal endometriosis. Mostly, laparoscopy is used for surgical interventions, but with severe forms of endometriosis, laparotomy access is also used.

If a patient with infertility has endometrioid (chocolate) ovarian cysts, they perform economical operations that set out the task of removing cystic formations with minimal damage to healthy ovarian tissues.

With external genital (peritoneal) endometriosis of the I – II degree, intraoperative diathermo-coagulation of foci of endometriosis without subsequent hormonal therapy is sufficient. In case of external genital endometriosis of the III degree after surgical correction (laparoscopic or laparotomy access), hormonal therapy is indicated for no more than 3 months and in patients no older than 38 years. Hormone therapy is carried out by gonadotropin-releasing hormone agonists or danazol. Gonadotropin-releasing hormone agonist preparations are used in an amount of not more than 3 injections. Danazol is prescribed at a dose of 40 mg / day in continuous mode for no more than 3 months. After the surgical treatment of peritoneal endometriosis has been performed, restoration of natural fertility within 1-2 years is possible. In this period, it is advisable to conduct controlled induction of ovulation to increase the frequency of ovulatory cycles. If there is no pregnancy at the indicated time, it is necessary to refer the patient to the in vitro fertilization program.

With a combination of external (peritoneal) and internal endometriosis in infertility patients, the tactics of managing patients to achieve spontaneous pregnancy is the same as if they only have external genital endometriosis. If such treatment is ineffective, patients are referred for in vitro fertilization. In infertility associated only with adenomyosis, in vitro fertilization is initially recommended for patients, since in case of internal endometriosis, restoration of natural fertility with the help of hormonal or endosurgical treatment seems unpromising.

Articles

Women
Health

Dysfunctional uterine bleeding

Female
infertility

Female
genitals

Tubal peritoneal infertility

Tubal peritoneal infertility is the absence of pregnancy due to a violation of the patency of the fallopian tubes and an adhesion process in the pelvis. In this case, the tubular factor prevails, and the peritoneal form is less common.

The main causes of damage to the fallopian tubes and the development of adhesions are:

1. Past inflammatory diseases of the pelvic organs - (sexually transmitted infections). The largest role belongs to gonococci and chlamydia, as well as anaerobic-aerobic microbial associations and viral infections.
2. Intrauterine manipulations (intrauterine contraception, induced abortion, diagnostic curettage, tubal tubing, etc.)
3. Previous surgical operations on the pelvic organs and abdominal cavity

In the pathogenesis of infertility in inflammatory diseases of the uterine appendages, the leading role is played by functional disorders of kinetics and obstruction of the fallopian tubes, as well as violations of the immune status and ovulation process. Functional disturbances in the kinetics of the fallopian tubes may be due to inflammatory infiltration of the walls of the tubes and atrophy of the ciliary epithelium of the mucous membrane. The key point is the formation of hydrosalpinx due to increased production of mucus. Due to compression of the epithelium, necrotic changes occur, which primarily cover the ciliary epithelium, decilitation of the epithelium and a violation of the transport function of the tubes. Obstruction of the fallopian tubes occurs as a result of cicatricial sclerotic changes in the destruction of the tube epithelium by infection. After a single episode of salpingitis, obstruction of the fallopian tubes is detected in 11–13% of patients, double - in 23–36%, triple and more - in 54–75% of patients.

There is the following classification of the adhesive process (Hulka et al., 1987):

• Stage 1 - adhesions are minimal, the pipe is passable, folding is saved;
• Stage 2 - more than 50% of the ovary is free. Distal occlusion, folding is preserved;
• Stage 3 - freely less than 50% of the surface of the ovary, occlusion of the distal tube, folding is destroyed;
• Stage 4 - the surface of the ovary is not visible, hydrosalpinges (sactosalpinges), folding is destroyed.

Diagnosis includes examination for genital infections, ultrasound of the pelvic organs (large hydrosalpings can be determined). To determine the patency of the fallopian tubes is used:

• Hysterosalpingography - a contrast image of the uterine cavity and fallopian tubes using radiography. During the study, a reflex spasm of the mouths of the fallopian tubes may be observed. The diagnostic value is 60-70%. Contraindications are acute and subacute inflammatory diseases of the pelvic organs, general infectious diseases, pregnancy. This study is conducted in the luteal phase of the cycle.
• Contrast echo hysterosalpingoscopy assessment of the condition of the uterine cavity and patency of the fallopian tubes using anechoic and hyperechoic contrasts under the control of ultrasound. Diagnostic value of 80%.
• Kimographic perturbation is carried out in the first phase of the cycle using a special apparatus. Carbon dioxide, oxygen, and air are used as input gases. Evaluation of the results is carried out according to the pressure gauges, the amount of air introduced, the results of auscultation of the peritoneum, the appearance of the phrenicus symptom. The method gives an idea of ​​the patency and contractility of the fallopian tubes, however, due to the low specificity it is of little use.
• Laparoscopy allows you to get an accurate visual assessment of the condition of the pelvic organs, the prevalence of adhesions.
• Transvaginal endoscopy (hydrolaparoscopy) is performed by puncture of the posterior fornix under conditions of hydroflotation. A less aggressive method than laparoscopy, access through the posterior arch allows the most complete examination of the area of ​​the appendages.

Conservative treatment with the use of anti-inflammatory, anti-adhesion therapy, tubal hydrotubation is not promising. An alternative is laparoscopic microsurgery, but its effectiveness reaches no more than 10-45%, depending on the severity of the adhesive process. Separation of adhesions, restoration of patency of the fallopian tubes and restoration of the normal anatomy of the pelvic organs are carried out. The following types of operations are distinguished:

1. Salpingo-ovariolysis - dissection of adhesions covering the fallopian tube and ovary and isolating them from each other
2. Fimbriolysis - carried out with phimosis of fimbriae, is a separation of fimbriae in the place of their bonding
3. Salpingostomy - is performed in case of obstruction of the fallopian tube in the ampullar section
4. Salpingoneostomy - performed when restoring the patency of the fallopian tube in the ampullar section with its complete destruction
5. Tubectomy - performed with hydrosalping, is to remove the futile in relation to the restoration of the function of the fallopian tube.

The effectiveness of treatment with 1-2 degrees of severity of the adhesive process is 40-45%, with the 3rd - 15-20%, with the 4th - no more than 10%. Repeated surgical interventions are ineffective. In case of failure, the use of assisted reproductive technologies is recommended.

Uterine factor

In addition to the endocrine disorders and tubo-peritoneal changes already discussed above, the following factors can also lead to infertility:

• cervical factor - anatomical or functional changes in the cervix that impede the movement of sperm or lead to their death (endocervicitis, cervical erosion, polyps of the cervical canal, stenosis of the external pharynx);
• uterine factor - malformations of the uterus (uterine septum, uterine hypoplasia, etc.), pathological conditions of the endometrium (chronic endometritis, synechia and polyps in the uterine cavity), uterine neoplasms (fibromyomas).

The pathological condition of the cervix and cervical canal is rarely the main cause of infertility, more often they are combined with another pathology. However, in the presence of infertility and the absence of another pathology, this may be the only reason. With endocervicitis, a change in the composition of the cervical mucus and its pH occurs, the penetration of sperm into the uterine cavity is impaired. In this case, if available, appropriate anti-inflammatory treatment is carried out taking into account the etiology of the pathogen according to the results of the polymerase chain reaction - screening for (sexually transmitted infections). The polyp of the cervical canal must be removed. Stenosis of the external pharynx can develop after curettage of the cervical canal, electrocoagulation of cervical erosion, conization of the cervix. To eliminate this factor, intrauterine insemination is performed.

Infertility can be caused by various malformations of the uterus and intrauterine synechia. Intrauterine synechia is a pathology that is associated with full or partial fusion of the uterine cavity (Asherman’s disease). Synechia occurs after endometritis, curettage of the uterine mucosa or conservative myomectomy. For therapeutic purposes, a hysteroscopic separation of senechia is performed, followed by the installation of an intrauterine device and the use of combined oral contraceptives for 3-6 months.

Immunological infertility

Immunological infertility is caused by the formation of antibodies to sperm, which occur in both men and women. About 40 male ejaculate antigens are known to which antibodies are formed. Antisperm antibodies are formed in the cervix, less commonly in the endometrium or fallopian tubes. The cervix is ​​the main component of local immunity; class A immunoglobulins are formed in it, in addition, immunoglobulins of classes M G that are absorbed from plasma. The concentration of immunoglobulins changes throughout the menstrual cycle, their decrease during ovulation is noted.

For the diagnosis of immunological infertility, a postcoital test is carried out, which is based on an assessment of the number and motility of sperm in cervical mucus. A cervical mucus is taken with a pipette 2.5 hours after sexual intercourse. Normally, 10-20 sperm are detected in the field of view, if this number is less, then we can talk about immunological infertility. When gluing spermatozoa with antibodies under a microscope, instead of translational motion, oscillation and trembling can be observed. As a treatment, the method of desensitization with lymphocytes of the husband (donor) or intrauterine insemination is used.

Male infertility

Since two are involved in the process of conception, in the presence of infertility, it is necessary to exclude the male factor of infertility. In addition, it must be remembered that in 5-10% of cases combined infertility occurs.

Male infertility is a condition caused by a violation of the generative and copulative function of the male reproductive system. The main causes of male infertility are:

• Varicocele
• Infectious and inflammatory diseases of the genitals
• Pathozoospermia of unknown etiology
• Isolated violations of seminal fluid production
• Immunological infertility
• Congenital malformations (cryptorchidism, monorchism, hypospadias, epispadias, etc.)
• Systemic diseases (tuberculosis, cirrhosis of the liver, chronic renal failure, chronic respiratory diseases, diabetes mellitus, mumps, progressing with severe orchitis)
• Surgical interventions for inguinal hernia, hydrocele, urethral stricture, bladder surgery, sympathectomy, etc.
• Radiation, chemotherapy and hormone therapy, the use of tranquilizers, antihypertensive drugs, etc.
• Sexual and ejaculatory disorders
• Obstructive azoospermia
• Necrosoospermia
• Endocrine disorders (primary and secondary hypogonadism, hyperprolactinemia, testosterone-deficient conditions)
• Chromasomal pathology

In addition, fertility disorders contribute to smoking, alcohol abuse, occupational hazards, the heat factor, scrotal organ trauma, nutritional factors, and psychological disorders.

According to the mechanism of violation, they distinguish:

• Secretory infertility - insufficiency of the secretory function of the sex glands
• Excretory infertility - a violation of sperm transport along the vas deferens
• Immunological infertility
• relative infertility

Diagnostics include medical history, objective examination, spermogram, determination of sperm antibodies, assessment of acrosomal sperm reaction, screening for the presence of (sexually transmitted infections), hormonal screening, genetic counseling.

Normal sperm counts are:

• Volume - 2-5 ml
• pH - 7.2-8
• Viscosity - up to 2 cm
• Liquefaction time - up to 60 min
• Sperm count - at least 20 million / ml
• The total number of sperm is at least 60 million
• Sperm motility:
  • Fast progressive movement (A or 4) - more than 25%
  • Progressive movement (A + B or 3.4) - more than 50%
• Morphology: normal sperm - 30% -70% (according to different authors)
• Agglutination - absent
• White blood cells - not more than 10 million in ml
• Spermiogenesis cells - not more than 4% of the total
• Epithelial cells - single
• Red blood cells - none

Sperm motility is evaluated and classified according to the following criteria:

• Characterization of sperm movement (WHO, 1992)
  • A - fast progressive movement.
  • B - slow linear and non-linear progressive motion.
  • C - oscillatory or motion in place.
  • D - sperm are not motile.
• Characterization of sperm movement (AUA, 1997)
  • 0 - lack of movement.
  • 1 - sluggish movement in place.
  • 2 - slow twisty movement.
  • 3 - moderate progressive movement.
  • 4 - pronounced progressive movement.

The following terms are used to indicate sperm pathology:

1. Normozoospermia - normal sperm counts
2. Oligozoospermia - sperm concentration of less than 20 million per ml
3. Teratozoospermia - normal forms of sperm less than 30% with a normal total number and proportion of motile forms
4. Asthenozoospermia - sperm motility less than 25% of category A or less than 50% of category A + B with normal indicators of quantity and morphology
5. Oligoastenoteratozoospermia - a combination of the above three disorders
6. Azoospermia - no sperm in semen
7. Aspermia - lack of sperm per se

Treatment of male infertility may include conservative methods (anti-inflammatory treatment, hormonal correction, treatment of sexual disorders), surgical (with varicocele, cryptorchidism, obstructive disorders). And with unsuccessful conservative treatment, alternative methods are used (intracytoplasmic sperm injection, intrauterine insemination with husband's sperm, intrauterine insemination with donor sperm).

Assisted Reproductive Technologies

Currently, the term assisted reproductive technologies includes in vitro fertilization, embryo transfer, transfer of female and male gametes into the fallopian tubes under laparoscopic and ultrasound control (GIFT), transfer of zygotes into the fallopian tubes (ZIFT), in vitro fertilization using donor gametes and embryos, in vitro fertilization using micromanipulations (intracytoplasmic sperm injection or sperm injection under zona pellucida).

Using the program of assisted reproductive technologies, it is possible to treat most patients suffering from severe forms of infertility in almost any etiology. However, there are a number of contraindications to the inclusion of assisted reproductive technologies in the program. These include the presence of severe extragenital diseases in which gestation is contraindicated, the presence of mental illness, and the high risk of genetically inherited diseases in the offspring. The program (assisted reproductive technologies) provides for a preliminary examination of a married couple and determination of indications, the choice of the optimal method of assisted reproductive technologies, taking into account the existing pathology, preimplantation genetic diagnosis, management of burdens and childbirth with minimal reproductive losses.

The in vitro fertilization procedure itself involves the stimulation of superovulation to collect a sufficient number of preovulatory follicles, fertilization of the egg outside the body, and embryo transfer. Superovulation can be stimulated using clomiphene or exogenous gonadotropins (pergonal, humegon, metrodin). To increase efficiency, gonadoliberin agonists (triptorelin, buserelin, goserelin) are included in the stimulation scheme. In the process of egg fertilization in the presence of male infertility, the method of intracytoplasmic sperm injection is used. This technique allows men with severe forms of oligo-, astheno-, terato- and even azoospermia to have offspring.

The most formidable complication of stimulation of superovulation is the development of ovarian hyperstimulation syndrome. To prevent severe forms of this complication, cryopreservation of embryos is possible with their subsequent transfer in the next unstimulated cycle. The embryo cryopreservation technique is also used in the embryo donation program.

Upon pregnancy, further monitoring and treatment is aimed at reducing possible reproductive losses. One of the methods for improving the outcome for multiple pregnancies is the method of embryo reduction by administering cardiotoxic agents to the embryo in a transabdominal or transvaginal way under ultrasound guidance.

Donation and surrogacy programs are used for women who cannot receive their own oocytes or have no uterus. The first child in the world was born from a surrogate mother in 1989 in the UK, since then this program began to be widely used in many countries.

The effectiveness of assisted reproductive technology programs is currently 15-45%.

Conclusion

Despite the great success of medicine in the treatment of infertility, this problem still has many unresolved issues.

Due to worsening reproductive health, more and more couples are facing this problem. The behavioral factor also plays a large role. Women are increasingly planning their first pregnancy after 30-35 years old, which sharply reduces the chances of a favorable treatment outcome. Widespread (sexually transmitted infections) leads to chronic inflammatory diseases of the pelvic organs, which are subsequently complicated by tubal-peritoneal infertility in women and impaired spermatogenesis in men. Abortions, which lead to chronic endometritis, synechia in the uterine cavity, are extremely negative for reproductive health. Therefore, as a prophylaxis of such severe negative consequences, timely treatment of inflammatory diseases of the pelvic organs and the use of adequate methods of contraception are necessary. For a successful treatment of infertility, correct and quick diagnosis is of great importance, as well as the timely sending of couples to in vitro fertilization. Delaying the examination and treatment process reduces the likelihood of success.

By: Dr. Joan Berman