Sexually Transmitted Diseases - I. I. Mavrov 2005

Infertility
Female Infertility

There are two forms of Infertility: Primary and secondary. Primary infertility implies that a woman who is sexually active and does not use contraceptives has never been pregnant. Secondary infertility refers to a condition where one or more pregnancies have occurred in the past, but no Pregnancy has ensued for over two years. A woman's inability to conceive during her reproductive years can be absolute—when the possibility of pregnancy is entirely ruled out (malformation of the reproductive Organs, absence or extreme hypoplasia of the Uterus, absence of the Ovaries, etc.)—or relative, when pregnancy is impossible due to certain factors but becomes achievable once these factors are resolved. A special category is endocrine infertility, caused by dysfunction of one or more Endocrine glands.

A fundamental prerequisite for female fertility is normal ovulation. The condition of the reproductive tract, which ensures the movement of spermatozoa and oocytes as well as their fusion, is of vital importance. Essential conditions for this process include fallopian tube patency, the ability of the fertilized egg to implant into the uterine mucosa, and suitable conditions for fetal GROWTH AND DEVELOPMENT. Women must have regular ovulatory menstrual cycles, while post-ovulatory endocrine shifts and The properties of endocervical mucus should remain within normal limits.

For conception to occur within the fallopian tubes, favorable conditions are required to facilitate The transport of spermatozoa from the uterine cavity toward the migrating egg (tubal patency, fimbrial apparatus). The uterus and its cervix must ensure the retention of the fertilized egg and the fetus throughout pregnancy.

The primary causes of female infertility include anatomical anomalies and developmental defects of the FEMALE Reproductive System; pelvic inflammatory disease; endocrine disorders; immunological factors; Endometriosis; Genital Tuberculosis; psychiatric or neurological disorders; genetic and chromosomal abnormalities; occupational and domestic intoxications; and The Use of irrational therapies or certain medications that negatively affect conception or exert teratogenic effects on the fetus. In some cases, exact data on the Etiology of infertility are lacking (unexplained infertility). For the majority of such women, no real obstacles preventing pregnancy are identified.

Female infertility can also be physiological—caused by the absence of ovulation during childhood, advanced age, or Lactation. Evidence suggests that significant deviations in the body's physiological Functions can be triggered by psychogenic factors. For instance, ovulation disorders are observed in patients with psychogenic anorexia, in whom ovulation typically resumes once the anorexia is successfully treated.

Diagnosis. Identifying the cause of infertility generally involves examining both the man and the woman. Therefore, the physician addressing potential infertility must conduct a consultation, outline the diagnostic plan and scope, and explain its rationale. Diagnostic Procedures include gathering medical history and performing a physical examination, with primary emphasis placed on findings that could explain the causes of infertility.

The principles of taking a medical history and conducting a physical examination are identical for all couples (who should be evaluated simultaneously) regardless of their Complaints. A detailed history is taken (age, history of childbirth, duration of infertility, date of the last menstrual period, etc.), along with data on menstrual function, including menarche, cycle length, and the interval between periods. Assessing the sexual history—frequency of intercourse, use of contraceptives, and the presence or absence of dyspareunia and dysmenorrhea—is crucial for evaluating couple fertility. It is also necessary to ascertain whether there have been spontaneous abortions, induced premature births, or elective abortions, including information regarding previous sexual partners.

Inquiries are made regarding past illnesses. Special attention should be paid to pelvic infections, particularly those acquired through sexual contact (chlamydia, mycoplasmosis, Gonorrhea, Trichomoniasis, etc.). Previous surgeries (appendectomy, wedge resection of the ovaries, uterine surgeries) can also cause infertility. Furthermore, infertility may stem from harmful exposures (occupational factors, environmental hazards, alcohol abuse, drug use, tobacco smoking, etc.). To uncover the underlying cause of infertility, systemic diseases (tuberculosis, diabetes, thyroid disorders, adrenal cortex disorders, etc.) and hereditary conditions—accounting for their presence in first- and second-degree relatives—must be ruled out.

Patients are questioned about physical changes such as excessive Hair growth (facial hair, body and limb hair growth) or non-puerperal galactorrhea (breast milk discharge unrelated to nursing), which may indicate underlying endocrine disorders.

Following the medical history, a complete physical examination of the patient is performed. Particular attention is paid to secondary sexual characteristics (hair distribution pattern, breast development). Pelvic examination (including rectal examination) is conducted after the general assessment. During this exam, the physician evaluates the size of the Clitoris, vaginal rugosity, the appearance of the cervix and The Nature of the mucus, as well as the size, shape, consistency, and mobility of the uterus, ovarian dimensions, the presence of tumor-like masses in the adnexa, the condition of the uterosacral ligaments, and the presence of 'free' fluid in the pouch of Douglas.

Systemic evaluations are performed, including Blood pressure measurement, Skull and sella turcica radiography, fundoscopy, visual field testing, and assessment of Skin condition (dryness, acne, etc.).

Depending on the Anamnesis and physical examination results, a list of required diagnostic procedures is established. Functional diagnostic tests are conducted over 2–3 cycles: postcoital test (on cycle days 12–14), hysterosalpingography (on cycle days 6–8), kymopertubation (during ovulation), ultrasound biometry of follicular growth (on cycle days 8–14), laparoscopy (on cycle day 18), and hormonal assays (LH, FSH, prolactin, testosterone, dehydroepiandrosterone on cycle days 3–5, mid-cycle, and in the luteal phase; progesterone levels on cycle days 19–24; and endometrial biopsy 2–3 days before the expected onset of menstruation).

Typically, the diagnosis of female infertility is based on evaluating ovulation (it is advisable to measure basal body Temperature over several menstrual cycles prior to specialized diagnostic tests), analyzing changes in endocervical mucus mid-cycle, and verifying fallopian tube patency.

The main diagnostic procedures for patients with ovulatory menstrual cycles include the postcoital test, seminal Analysis of the partner, and periodic determination of serum progesterone levels to confirm ovulation. Regular measurement of basal body temperature throughout the evaluation period facilitates the Structure/127.html">Interpretation of Results.

According to M. K. Shepard (1985), assessing corpus luteum function should be based on basal body temperature measurements (specifically the peak thermal shift) rather than data on the average length of the Menstrual cycle. For preliminary evaluation of corpus luteum function, the author utilizes progesterone assays rather than endometrial biopsy, as the latter must be performed under strictly aseptic conditions and is less convenient for patients.

Determining the causes of female infertility requires the simultaneous evaluation of both partners. Evaluation of the male partner is typically limited to a semen analysis. If the seminal parameters are normal, a comprehensive evaluation of the female partner is carried out using standard methodologies.

Tubal and peritoneal infertility. This occurs in women with primary and secondary infertility, accounting for 50–80% of female infertility cases associated with reproductive system pathology. It results from inflammatory processes, endocrine disorders, and other factors. Inflammatory lesions of the fallopian tubes are the leading cause of infertility. They may develop following Sexually Transmitted Infections, as well as post-abortal and postpartum inflammation. Peritoneal infertility is the consequence of pelvic adhesions while tubal patency is maintained in one or both fallopian tubes.

Ascending infections of chlamydial, mycoplasmal, gonococcal, viral, or other etiologies induce adhesive and obliterative processes in the fallopian tubes, leading to luminal narrowing, peritubular and ovarian adhesions, and a reduction in the number of endosalpingeal cilia. This disrupts the tubal functions responsible for capturing and nourishing the ovum, spermatozoa, and embryo, as well as transporting Gametes and the embryo. Various infectious agents enter the fallopian tubes via the bloodstream, ascend from the lower genital tract, or hitchhike on spermatozoa. Once spermatozoa reach the fallopian tubes, they perish within 4–5 hours, whereas Bacteria actively proliferate using the glucose contained in seminal plasma, thereby triggering an inflammatory disease.

Genital tuberculosis is quite frequently associated with infertility in female patients. The primary cause in such cases is fallopian tube obstruction. In some instances, transport function and Fertilization are impaired due to the destruction of the tubal mucosa. Meanwhile, endometrial and ovarian involvement play a secondary role in the onset of infertility.

In addition to inflammatory pelvic diseases, tubal dysfunction may result from generalized or pelvic Peritonitis, appendectomy, myomectomy, ovarian resection, polyps, tubal endometriosis, or Other forms of extragenital endometriosis.

Endocrine factors can impair tubal peristalsis. Hormones such as estrogens, progesterone, and Prostaglandins participate in regulating the muscular contractions that ensure gamete transport through the fallopian tube. In the presence of hormonal imbalances, peristaltic tubal movements are either entirely absent or poorly expressed, leading to tubal infertility.

Functional tubal insufficiency can also occur despite confirmed patency. Nervous factors and stressful situations negatively affect fertilization by disrupting Muscle contractions or Ciliary movement within the fallopian tubes. Tubal muscle spasm, or hyperactive or sluggish peristalsis driven by chronic psychological stress regarding infertility, can impede conception or even cause persistent infertility. Furthermore, tubal infertility may develop secondary to uterine and ovarian tumors that disrupt tubal activity or mechanically compress the tubes.

Infertility termed 'peritoneal' can also result from inflammatory conditions of the reproductive organs following pelvic, abdominal, or gynecological surgeries. It likewise develops as a consequence of pelvic adhesions following hydrotubation. Studies have established a direct correlation between the extent of adhesions and the number of hydrotubations performed, as well as The Role of oily contrast media used in hysterosalpingography (G. V. Tuycheva, 1988).

Diagnosis. When anamnestic data or physical examination findings suggest fallopian tube pathology, tests are conducted to evaluate tubal patency, muscular contractility, and the motility of cilia and fimbriae. Fallopian tube patency testing is performed during the follicular phase of the menstrual cycle (after menstruation but prior to ovulation). This minimizes the likelihood of false-positive results caused by physiological endometrial hypertrophy, which can be misinterpreted as uterine pathology or tubal obstruction. Patency testing is undertaken only when bacteriological screening and complete blood counts rule out active inflammation and reproductive tract infections. Otherwise, patients receive appropriate antibacterial therapy prior to the Procedure.

Hysterosalpingography (HSG) is primarily used to evaluate tubal patency, providing information on pelvic adhesions. When HSG results are inconclusive and no other factors explain the infertility, laparoscopy is performed. This method is the most informative for assessing tubal patency through direct visualization of the pelvic organs. It also allows for the assessment of tubal wall condition, muscular activity, and the mobility of the tubes and cilia. Laparoscopy enables direct examination of Tissues involved in inflammatory processes and the acquisition of bacteriological or histological samples directly from the lesion site, thereby improving diagnostic accuracy. The method is indicated for patients suffering from infertility for more than two years, though it can also be used in patients with a shorter duration of the condition. It yields excellent results in cases of unexplained infertility, suspected pelvic pathology, preoperative evaluation prior to tubal reconstructive surgery, and the diagnosis of peritoneal infertility, among others.

Simultaneously with laparoscopy, hysteroscopy is also performed (if uterine cavity anomalies or other intrauterine pathology are suspected).

Treatment. Once the causes of tubal infertility have been identified, a personalized therapy plan is developed for each patient, taking into account the Nature of the fallopian tube damage and the Specific features of the pathological process. Both conservative and Surgical treatment Methods, including microsurgical techniques, are applied.

The approach to conservative treatment of inflammatory tubal diseases depends on their etiological origin. Treatment is based on the General Principles of comprehensive and individualized therapy for chronic inflammatory pelvic diseases. This comprehensive treatment combines etiotropic, pathogenetic, and symptomatic measures.

While pathogenetic and symptomatic therapy relies on the same methods and remedies used for inflammatory processes of various infectious origins, etiotropic therapy has specific features determined by the biological Properties of the CAUSATIVE AGENT OF the tubal inflammation. Once microorganisms are identified, antibiotic therapy is prescribed, taking into account the pathogens' biological characteristics, their sensitivity spectrum to various drugs, and their pharmacodynamic properties. If Chlamydia is the cause, Tetracyclines, macrolides, fluoroquinolones (ofloxacin or tarivid, ciprofloxacin), sulfonamides, and rifampicin are prescribed. In cases of mixed infections, the effectiveness of etiotropic therapy is enhanced by the rational combination of targeted antimicrobial agents capable of suppressing associated pathogens.

In addition to specific etiotropic agents, the comprehensive treatment system for patients with tubal infertility includes pathogenetic and symptomatic therapy. To this end, analgesics, tonics, desensitizing, sedative, and stimulating agents are prescribed, along with targeted local treatment. In combination with other therapies, ultraviolet blood irradiation (UVBI) autotransfusion and intravascular laser blood irradiation (ILBI) are effective; these aim to activate the body's immune system, improve microcirculation and blood rheology, stimulate hemopoiesis, promote the resorption of inflammatory infiltrates—thus ensuring better antibiotic penetration and a subsequent bactericidal effect—and accelerate tissue repair. For infertility associated with tubal obstruction, gynecological massage is indicated.

Rehabilitation measures include physical therapy and balneotherapy combined with pelotherapy (mud therapy). Muds with analgesic, resorptive, and pronounced anti-inflammatory properties are used to stimulate tissue regeneration processes. In the final stages of infertility treatment, health resort therapy is most appropriate. Rehabilitation therapy is indicated at health resorts such as Berdyansk, Yevpatoria, Yeysk, Kuyalnik, Mariupol, Pyatigorsk, Saki, Sloviansk, Stara Russa, Tskaltubo, and others.

Currently, conservative therapy for tubal infertility, tailored to the individual characteristics of each patient, yields more encouraging results compared to traditional treatment methods that ignore the nature of the pathogen, the Specifics of the pathological process, and lack a customized comprehensive therapy plan. Under METABOLISM/18.html">The Influence of this advanced, multimodal conservative treatment, the resolution of adhesions, the restoration of fallopian tube patency, and the recovery of reproductive capacity are frequently achieved.

If comprehensive conservative therapy fails within 1.5–2 years, the issue of surgical treatment for fallopian tube disorders arises. Surgery is indicated in cases of complete or partial tubal obstruction, pathological twisting, saccular dilations, or The formation of peritubular or periovarian adhesions that restrict tubal mobility. Following microsurgical Operations on the fallopian tubes, the pregnancy rate in women suffering from tubal and peritoneal infertility increases to 30–60%.

Surgery on the fallopian tubes is not performed in cases of genital tuberculosis, the presence of other insurmountable obstacles to conception (such as medically unresponsive anovulation), or when the patient's general condition or psychological factors contraindicate pregnancy. Relative contraindications for surgery include a patient age over 30, inadequate or unsuccessful conservative treatment of adnexal inflammation, and pronounced pelvic adhesions (A. N. Strizhakov et al., 1985).

Infertility treatment in patients with genital tuberculosis, which most frequently affects the fallopian tubes, yields poor results. The prevailing opinion is that surgical restoration of tubal patency should not be attempted in tuberculous lesions. Surgery is considered ineffective because tubal obstruction in such cases is accompanied by extensive damage to the mucosal lining (G. Schaefer, 1976). However, in some instances, pregnancy occurs following the lysis of adhesions caused by minor tuberculous lesions (I. Gonzales-Merlo, 1983). There is evidence that treating such patients increases the likelihood of Ectopic Pregnancy.

Treatment of infertility caused by impaired tubal function focuses primarily on eliminating the neural factors and stress states that trigger this dysfunction. Psychotherapy is one of the primary methods. The administration of sedatives, tranquilizers, and antispasmodics is indicated. In the premenstrual days of the cycle, prostaglandin blockers (such as naproxen or indomethacin) should be administered, and hormonal imbalances corrected. Physical therapy combined with appropriate local treatment (electrical stimulation of the fallopian tubes) is recommended. Physiotherapeutic procedures are alternated with hydrogen sulfide, brine, and pine-sea baths, ascending showers, and thalassotherapy.

Endocrine infertility. This is most commonly observed in patients with primary infertility. It is noteworthy that in some cases it may be of a mixed nature, where tubal damage coexists with endocrine disorders. The prevalence of endocrine infertility ranges from 5% to 40% of all cases, ranking second after tubal infertility.

Ovulatory dysfunction plays a significant role in The Development of endocrine infertility. Anovulation, one of the most frequent causes of infertility, comprises a group of pathological conditions characterized by impaired synthesis and release of releasing hormones and peripheral endocrine gland hormones. Endocrine System disorders lead to Changes in the properties of cervical mucus, preventing spermatozoa from penetrating the uterine cavity and fallopian tubes, and thus impeding egg fertilization.

Endocrine infertility is the consequence of numerous disorders. It is typically observed in women suffering from Amenorrhea due to genital hypoplasia, and may result from pituitary and hypothalamic tumors, polycystic Ovary syndrome (PCOS), or other conditions. Important, albeit less frequent, causes of anovulatory cycles (cycles lacking ovulation) include developmental defects caused by chromosomal abnormalities.

Clinical signs of endocrine infertility are diverse and do not always correlate with laboratory findings regarding ovarian hormonal and ovulatory functions. The most frequent signs include various menstrual cycle disorders (amenorrhea, Dysfunctional Uterine Bleeding, hypomenstrual syndrome, etc.), hirsutism, virilization, various endocrinopathies, and Metabolic Disorders. At the same time, clinically healthy women with regular menstrual cycles may also suffer from infertility. In patients with endocrine infertility, ovarian size varies widely (from normal to several times enlarged). Blood tests in cases of anovulation reveal either normal or elevated levels of androgens and luteinizing hormone.

Infertility is frequently accompanied by thyroid and pancreatic disorders, and in some cases by adrenal dysfunction. Disorders of the female reproductive endocrine system may be associated with chronic infections, occupational and household intoxications, significant physical and psychological stress, traumatic injuries, etc. In such cases, patients present with complaints of infertility alongside symptoms characteristic of these underlying conditions. In some instances, the clinical signs of the primary disease predominate, while in others, symptoms of reproductive dysfunction take precedence.

THE CONCEPT OF "endocrine infertility" encompasses a range of other conditions that differ etiopathogenetically, morphologically, and in their clinical course. What they share in common are infertility, amenorrhea, oligomenorrhea, and anovulatory cycles.

Typical disorders characterized by these symptoms include neuroendocrine-metabolic syndrome, which develops As a result of a neuroinfection contracted during Puberty or at the onset of sexual activity. Infertility in such patients is generally primary, manifesting as anovulation, menstrual cycle disturbances such as oligomenorrhea, progressive weight gain, hypertrichosis, striae distensae on the skin, a tendency toward Hypertension and hyperglycemia, and occasionally hypertension and Diabetes Mellitus. In some cases, signs of diencephalic disorders (polyuria, polydipsia, Sleep disturbances, hyperthermia, etc.) are present.

Another group of disorders accompanied by amenorrhea, oligomenorrhea, dysfunctional bleeding, hirsutism, and virilization includes polycystic ovary syndrome (PCOS), which manifests as infertility in 75% of cases. In some PCOS patients, Palpation reveals non-tender, firm, enlarged ovaries. Weight gain is frequently observed in this condition, with 15% to 50% of patients suffering from obesity.

Menstrual dysfunction, anovulatory cycles, and alterations in The regulation of ovarian hormonal and ovulatory functions cause infertility in patients with the postpubertal form of adrenogenital syndrome, Various Forms of hyperprolactinemia, and hyperandrogenemia. Some authors believe that hyperprolactinemia may play a decisive role in the Pathogenesis of corpus luteum insufficiency. This condition is characterized by inadequate progesterone production by the corpus luteum and a shortened luteal phase (less than 12 days) of the menstrual cycle. Luteal phase deficiency is observed in 3–5% of infertility cases (W. Andrews, 1971).

Demonstrating alterations in the regulation of hormonal and ovulatory functions is often very difficult. Therefore, various Research Methods assessing the functional state of the ovaries and ovulation are proposed for diagnosing endocrine infertility.

The simplest METHOD FOR DETERMINING ovulation is tracking basal body temperature across the dynamic course of the menstrual cycle. During the transition between the follicular and luteal phases of an ovulatory cycle, a 0.5 °C increase in body temperature is observed. This shift is caused by the thermogenic effect of progesterone and occurs immediately following ovulation. In the absence of ovulation, the basal temperature curve remains monotonously monophasic. If the temperature rise In the second half of the cycle is negligible or if body temperature drops within 3–5 days, luteal phase deficiency due to decreased progesterone production should be suspected. Due to its simplicity, this sign is widely used to confirm the occurrence of ovulation.

One of the best symptomatic indicators of ovulation is the Characteristic Properties of cervical mucus. Its production is regulated by estrogens and progesterone; it peaks during the pre-ovulatory estrogen surge and sharply declines upon progesterone secretion by the corpus luteum after ovulation. The production of cervical mucus increases during the follicular phase, reaching a maximum immediately before ovulation. Pre-ovulatory characteristics of cervical mucus include transparency, Cell-free composition, and low viscosity. At this stage, the cervical mucus of healthy women can be stretched into a thread 8–10 cm long and forms a characteristic fern-like pattern ("ferning phenomenon") upon drying on a Microscope Glass slide; it does not impede the free progression of spermatozoa through it either in vivo or in vitro. During maximal mucus secretion, the external os of the cervix is maximally open. After ovulation, it closes, and the cervical mucus drastically changes all the aforementioned properties—it is secreted in small amounts, becoming viscous and impenetrable to spermatozoa.

The ability of spermatozoa to penetrate cervical mucus is determined using tests that evaluate sperm fertilizing capacity by assessing sperm penetration into the cervical mucus (the Huhner-Sims-Schuwursky test). For this test, cervical mucus is sampled immediately after sexual intercourse during the period of ovulation (normally, the number of motile spermatozoa ranges from 5 to 20). Free progression of spermatozoa into the cervical mucus is also determined using the Kurzrock-Miller test, where cervical mucus is brought into contact with a drop of semen on a glass slide warmed to 37 °C. A positive result is recorded when spermatozoa penetrate the mucus in significant numbers and maintain their motility for more than 5 hours.

To evaluate the functional state of the ovaries, vaginal smears (colpocytological examination) are analyzed during ovulation. In smears taken from the lateral fornices near the cervix, three categories of Cells are distinguished: parabasal, intermediate, and superficial, which differ in size and the staining characteristics of their nuclei and Cytoplasm. In the absence of ovarian activity, parabasal cells predominate in the smear, whereas estrogens induce the maturation of superficial cells immediately prior to ovulation. Progesterone influences the formation of intermediate cells (luteal phase). Such smears typically also reveal A large number of polymorphonuclear cells.

To confirm whether a menstrual cycle was ovulatory, a woman's evaluation may be supplemented by an endometrial biopsy. However, this procedure is rarely performed today due to the potential risk of cervical trauma. An endometrial biopsy is recommended only when pathology, such as tuberculosis, is suspected.

Ultrasound can provide supplementary insights and contribute to a more precise diagnosis of endocrine infertility. Serial ultrasound scanning of developing follicles and the endometrium throughout the menstrual cycle can suggest a luteinizing hormone deficiency during the luteal phase. Meanwhile, a slow, gradual shrinkage of follicles serves as an echographic sign of follicle luteinization without egg release. Ultrasound imaging of the follicle at various stages of its development holds the highest diagnostic value. The absence of a follicular image in the middle of the menstrual cycle is an echographic sign of ovulation. When selecting diagnostic methods for patients with endocrine infertility, one must consider that ovarian generative dysfunction may be associated with follicular and corpus luteum cysts, as well as polycystic ovary syndrome (PCOS). These conditions present with characteristic sonograms (for instance, the primary hallmark of PCOS is altered sizing of both ovaries). The ovarian structure appears heterogeneous, marked by multiple small cystic inclusions that, unlike normal ovaries, are detected not only along the organ's periphery but also within the central regions of its parenchyma. An essential echographic indicator of polycystic ovaries is the absence of a normal maturing follicle (V. N. Demidov, B. I. Zikin, 1990).

More precise results can be achieved through diagnostic laparoscopy. This examination helps determine the time of ovulation and provides criteria against which other ovulation indicators can be compared. In certain cases of endocrine infertility where organic pathology is suspected, laparoscopy remains the sole method for establishing an accurate diagnosis.

Endocrinological investigations are among the most critical diagnostic tests, providing essential data on the hormonal and ovulatory Functions of the ovaries. Hormonal assays include measuring plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, dehydroepiandrosterone (DHEA), testosterone, and progesterone throughout the menstrual cycle (on days 3–5, mid-cycle, and during the luteal phase). Additional endocrinological assessments (evaluating thyroid and adrenal functions) are performed if the patient's history and physical examination suggest hypothyroidism or adrenal pathology.

A marked surge in serum LH levels in the mid-menstrual cycle serves as the hormonal criterion for ovulation. The mid-cycle FSH peak coincides with the LH peak, although it is of lower magnitude. In the absence of ovarian activity, normal or low levels of LH and FSH indicate hypothalamic or pituitary dysfunction, whereas high levels of LH and FSH point to a primary ovarian disorder.

Blood and urine estrogen assays can provide information on ovarian activity and pinpoint the onset of ovulation. Under normal conditions, estrogen levels fluctuate depending on the phase of the menstrual cycle. Immediately following menstruation, estrogen levels are low, rapidly rising in correlation with follicular activity. Typically, the estrogen peak coincides with the serum LH peak, though it may occur 1–2 days earlier. This is one of the earliest hormonal indicators of ovulation and generally corresponds to the onset of cervical mucus changes. The day following the estrogen peak represents the period of highest fertility.

Ovulation can also be confirmed by measuring serum progesterone or urinary pregnanediol approximately one week post-ovulation. This is a more reliable indicator that ovulation has occurred, as rises in LH and estrogen can also take place during anovulatory cycles.

Thyroid and adrenal function tests are of particular value. Thyroid function must be evaluated in all anovulatory patients, as minor disorders may present without overt clinical symptoms. It is crucial not to overlook mild hypothyroidism. Therefore, in addition to triiodothyronine (T3) and thyroxine (T4) tests, serum thyrotropin-releasing hormone (TRH), or thyroliberin, levels should be determined.

Measuring urinary 17-ketosteroids (17-KS) in patients exhibiting signs of hyperandrogenism generally helps identify infertility caused by adrenal dysfunction. In such cases, serum dehydroepiandrosterone sulfate (DHEAS) levels or a dexamethasone suppression cortisol test may be performed.

The treatment of endocrine infertility in women is tailored to each patient's individual profile and adjusted According to the character of the menstrual cycle as well as the specific factors driving reproductive dysfunction. Prior to initiating treatment, a targeted therapy plan is formulated based on the Clinical presentation, the severity of ovarian dysfunction, the level of lesion within the Hypothalamus-pituitary-ovary axis, and any concurrent disorders in other endocrine glands.

When a patient is anovulatory but exhibits adequate estrogen stimulation, normal serum prolactin levels, and normal thyroid function, direct ovulation induction is prescribed using clomiphene citrate, which exerts a stimulating effect on the Hypothalamus and Pituitary gland.

Standard treatment typically begins with clomiphene citrate at 50 mg daily for 5 days, starting on cycle day 5. Ovulation occurs 4–10 days after completing the medication course. This can be verified by a biphasic basal body temperature curve, changes in cervical mucus (which transitions from clear and watery with maximal ferning to opaque, rubbery, and non-ferning), and a unilateral increase in ovarian size that was absent during the initial baseline examination. If treatment yields no results, a subsequent course is administered with the daily dose increased by 50 mg; if still ineffective, a third course escalating the dose to 150 mg daily is recommended.

Clinical observations (I. A. Manuylova, 1980; A. Poliak et al., 1973, among others) highlight the efficacy of combining clomiphene citrate with human chorionic gonadotropin (hCG); clomiphene citrate with synthetic progestins; or clomiphene citrate, estrogens, and hCG, as combination therapy significantly enhances treatment success.

For anovulatory patients with hyperprolactinemia who have no sella turcica pathology or pituitary tumors, ovulation is stimulated using bromocriptine. The medication is prescribed at 2.5 mg daily, increasing the dose by 2.5 mg every 2 weeks until prolactin levels normalize or menstruation resumes. Bromocriptine administration at the established effective dose is continued until pregnancy is achieved.

In cases of hypothalamo-pituitary insufficiency, human menopausal gonadotropin (hMG) is recommended. Some authors (M. Shepard, 1985) prefer hMG over wedge resection in treating polycystic ovary syndrome. The hMG dosage is adjusted based on individual patient response. On the first day, the patient receives 1 ampoule to screen for potential hypersensitivity. If no reaction occurs, 2 ampoules are administered daily and continued until a 5-day course fails to produce a further increase in serum estrogen levels. The daily dose is then increased by 1 ampoule every 5 days until the desired outcome is reached. Once serum estrogen levels reach or exceed the preovulatory peak value of a normal ovulatory cycle, 10,000 IU of hCG is administered to trigger ovulation. The combination of hMG and hCG represents the concluding stage of hormone replacement therapy and yields a high rate of ovulation and pregnancy.

Currently, many specialists believe that luteal phase defects in the menstrual cycle should not be overstated. According to G. Jones (1976), this condition is observed in only 3.5% of infertile patients. Clinical observations and laboratory data indicate that luteal phase insufficiency results in inadequate follicular development, corpus luteum dysfunction, impaired interaction with structures governing prolactin synthesis, and a deficiency of endometrial progesterone receptors.

The treatment approach for this condition is guided by endometrial biopsy results, plasma progesterone levels during the luteal phase, the duration of the luteal and follicular phases, and serum prolactin levels. Specifically, patients with a shortened luteal phase are prescribed clomiphene citrate During the first 5 days of the menstrual cycle. Patients with a normal luteal phase duration but low progesterone levels are recommended progesterone suppositories. Bromocriptine is indicated for women presenting with elevated serum prolactin.

V. I. Grishchenko et al. (1983) treated various forms of endocrine infertility using allotransplantation of cryopreserved ovarian tissue enclosed in an amniotic membrane. The efficacy of this non-pharmacological therapy was noted by the authors in 20% of women who had previously undergone prolonged cyclical hormone therapy for infertility.

In cases of infertility associated with adrenogenital syndrome characterized by adrenocortical hyperfunction—which blocks gonadotropin release—the administration of cortisone, prednisone, and prednisolone is required. When hypothyroidism coexists with infertility, low doses of thyroidin are prescribed.

When cervical factors impede sperm migration and overall fertilization, the choice of treatment depends on the suspected underlying cause. Therapy for such patients includes: appropriate etiological treatment of urogenital infections causing chronic cervicitis (initiated on day 1 of menstruation); cryotherapy of affected cervical areas in patients with ectropion; correction of estrogen deficiency responsible for unfavorable cervical mucus properties (estrogens are prescribed from cycle days 8 through 12); alkalinization of acidic cervical mucus via prolonged vaginal douches with a 4% sodium bicarbonate solution; and the use of bromelain, an enzyme preparation capable of thinning cervical mucus. If anti-sperm Antibodies are suspected in the cervical mucus, barrier therapy can be employed. In such instances, condoms offer advantages over cervical caps: they completely isolate the antigenic stimulus from the entrance to the female reproductive tract, whereas cervical caps cover only the cervix.

Most authors consider the minimum adequate trial duration for treating endocrine infertility to be three ovulatory menstrual cycles, after which Conclusions regarding treatment failure are drawn. The duration of barrier therapy in the presence of immunological infertility factors is 6 months or more.

Endometriosis and Infertility. Accumulated data from recent years indicate that endometriosis is detected in 23–30% of infertile patients. The causal link between these conditions remains unclear. Several theories have been proposed to explain the etiology of primary and secondary infertility in endometriosis.

Available evidence suggests that cervical endometriosis can lead to scarring and cervical stenosis, hindering sperm transport through the cervical canal into the upper reproductive tract, and may cause extensive peritubular adhesions as well as adhesions in the pouch of Douglas, which can induce infertility.

Another probable cause of infertility in patients with endometriosis is dyspareunia resulting from involvement of the pouch of Douglas, uterosacral ligaments, and the posterior uterine wall, occasionally accompanied by uterine displacement. In some cases, intercourse-related pain is so severe that partners become unable to maintain sexual relations. However, certain authors (V. P. Baskakov, 1990) view this assertion with considerable skepticism.

A range of abnormalities is associated with the presence of anti-endometrial antibodies in the blood of patients with endometriosis, as well as a significant elevation of prostaglandins in peritoneal fluid aspirated from the pouch of Douglas during laparoscopy. The resulting autoantibodies likely play a major role in the development of infertility and an increased rate of spontaneous abortions, while the ectopically located endometrium secretes prostaglandins that disrupt ovum transport (V. I. Bodyazhina et al., 1990, et al.).

Morphological changes in the ovaries play a certain role in the genesis of infertility in patients with endometriosis. According to A. E. Koloskov (1985), The structure of the ovaries outside the endometriotic lesions is highly characteristic, manifesting as oocyte degeneration, cystic and fibrous follicular atresia, stromal thecomatosis, and the presence of follicular cysts. These disorders can also cause infertility.

One of the causes of infertility in patients with endometriosis who have a normal biphasic menstrual cycle and patent Fallopian tubes is dysfunction of the multicomponent immune system. Such patients often suffer solely from infertility, with no other symptoms present.

Modern diagnostic methods have made it clear that disorders in the hypothalamic-pituitary-ovarian system and their consequences (anovulation, luteal phase defect, altered estrogen fraction ratios) play a leading role in the development of infertility associated with endometriosis. Consequently, recent years have seen The Emergence of pathogenetically targeted approaches to treating infertility in these patients. Specifically, therapeutic measures combining comprehensive hormonal therapy with surgery and immunostimulation enable pregnancy to be achieved in more than 30% of women of fertile age.

Infertility caused by uterine pathology is attributable to impaired implantation of the fertilized egg or compromised pregnancy development. The most serious causes of these disorders include adhesions—frequently the result of inflammatory processes or trauma—as well as uterine myomatosis.

Adhesive processes and synechiae within the uterine cavity hinder ovum implantation and can cause miscarriages in the second trimester of pregnancy. Intrauterine adhesions are diagnosed via hysteroscopy, during which they are dissected using a hysteroscope. Following this procedure, a foreign body (a catheter with a balloon containing 2 cm³ of fluid) is left in the uterine cavity for 7–10 days to prevent the walls from adhering. Antibacterial therapy is prescribed until the foreign body is removed. During the first week post-surgery, patients receive 2.5 mg of conjugated estrogens daily, followed by a reduced dose of 1.25 mg maintained for the subsequent 7 weeks. In total, patients take estrogens for 2 months. It should be noted that discontinuation of estrogen therapy induces withdrawal bleeding.

Pregnancy may be hindered or its development disrupted by benign tumors originating from the uterine Muscle tissue (myomatosis). Myomectomy is the primary treatment for this condition. Although conception capacity is usually restored after tumor node removal, myomectomy recurrences are not uncommon and often necessitate repeat surgeries.

It is well established that myomatosis can alter the body's hormonal status, a factor that is crucial for the treatment and Prevention of uterine myomas. The Concept of the hormone-dependent nature of this tumor has served as the basis for developing non-surgical treatments that inhibit tumor growth. Therapy must be comprehensive, providing for the correction of neuroendocrine disorders responsible for the onset and pathogenesis of myomatosis, the treatment of extragenital and gynecological diseases that promote tumor growth, and the elimination of factors that exacerbate the course of the disease (V. I. Bodyazhina et al., 1990).

Female infertility can result from congenital morphological anomalies of various PARTS OF THE reproductive system (vaginal aplasia, septate Vagina, vaginal and uterine duplication, imperforate hymen, etc.). Developmental anomalies are typically straightforward to diagnose. Treatment aims to restore the patency of the reproductive tract; surgical dissection and septal resection are performed for an imperforate hymen and atresias.

Infertility prevention is not only a medical issue but also a significant socio-economic challenge. Preventing and timely treating diseases of various organs and systems that affect the Formation of the reproductive apparatus are vital for infertility prevention. This work should be carried out by obstetrician-gynecologists, dermatovenereologists, pediatricians, psychoneurologists, and other specialists as indicated. Special attention should be paid to organizing women's work schedules, rest, and Nutrition, as well as providing sex education and awareness campaigns about the harms of abortions and the dangers of sexually transmitted infections, which are frequently the ROOT cause of infertility. Preventive measures must be comprehensive and aligned with strategies addressing marriage and family issues.

Infertility prevention demands not only public attention and scientific analysis of the causes behind declining birth rates, but also the creation of state-level conditions that enable women to harmoniously balance motherhood

with professional pursuits. The future reproduction of the population depends on the successful resolution of these socio-economic issues.