Autoimmune oophoritis is a pathological destruction of the ovaries caused by exposure to antiovarial antibodies. It is manifested by disorders of menstrual function (oligomenorrhea, amenorrhea), primary and secondary infertility. When the disease is combined with inflammatory processes, patients complain of pain in the lower abdomen. Gynecological ultrasound, determination of the content of sex hormones, antiovarial antibodies, interleukins, interferon and TNF are used for diagnosis. The treatment is complex with the appointment of glucocorticoid, antibacterial, hormonal drugs and antagonists of interleukin receptors. With persistent infertility, IVF is indicated.
General information
Although autoimmune oophoritis is a relatively rare pathology, it is this disease that often provokes the development of resistant forms of amenorrhea and infertility. Hereditary forms of the disease are extremely rare and are part of the polyglandular syndrome, in which a pathological autoimmune process affects other organs of internal secretion (thyroid gland, adrenal glands, islets of Langerhans, etc.). Usually this variant of oophoritis complicates the course of chronic inflammation of the internal genitalia. Patients over 30 years of age with genital infections, invasive diagnostic and therapeutic interventions in the anamnesis are more likely to become ill. The importance of timely detection of the disease is associated with a rapid and pronounced decrease in the number of viable follicles, which means a decrease in the likelihood of pregnancy.
Causes
Damage to ovarian tissue during the autodestructive process is caused by the formation of autoantibodies to ovarian tissue. The failure of the protective reaction occurs under the influence of factors that lead to local pathohistological changes in the cortical substance, glandular part and stroma of the genital glands, and also affect the elements of cellular and humoral immunity. According to experts in the field of gynecology, autoimmune ovarian inflammation is caused by:
- A genetic defect. Pathology is observed in the structure of autoimmune polyglandular syndrome of the 1st and 2nd types. The first of the variants is autosomal recessive, occurs with a defect of the AIRE gene located on the 21st chromosome. The second is polygenic pathology associated with haplotypes HLA-B8, -DR4, -DR5, -R3, which usually develops in several generations of families with hereditary predisposition.
- Inflammation of the reproductive organs. The probability of an autoimmune reaction increases in patients with chronic course of endocervicitis, endometritis, salpingitis, adnexitis with a disease duration of more than 5 years, as well as in patients with appendicular-genital syndrome. Auto-destruction of the ovaries is more often diagnosed in women who have had curettage, abortions, laparotomy interventions.
The results of clinical studies show that patients who have an inflammatory process in the pelvic organs caused by microbial associations that are part of the causative agents of genital infections are more prone to autoimmune damage to the ovaries. Thus, a higher incidence was found in groups of women with gonorrhea, genital chlamydia and trichomoniasis. From non-specific microbial agents, Corynebacteria and Enterobacteria are most often determined.
Pathogenesis
The mechanism of development of autoimmune oophoritis depends on the causes that caused it. In hereditary forms of the disease, antibodies to enzymes that provide steroidogenesis and active cells of glandular tissue are formed due to a DNA defect. In patients with chronic gynecological pathology, prolonged exposure to microbial antigens activates the proinflammatory cytokine cascade. In addition, inflammatory destruction of ovarian tissue leads to the formation of ovarian antigens and the development of antiovarial antibodies in response to them. The most sensitive to damage are growing follicles in the recruitment stage with a size of more than 6 mm.
In contrast to the cyclic changes characteristic of physiological ovulation, autoimmune variants of oophorites have a constant high activity of T-lymphocytes that produce interleukin-1. Due to this, resident ovarian macrophages are activated, the secretion of γ-interferon, transforming α- and β-growth factors, α-tumor necrosis factor, fibroblast growth factor and other cytokines affecting follicular tissue atresia increases. The involvement of an increasing number of maturing follicles in the process leads to a decrease in the synthesis of estrogens, a violation of the luteal phase, the emergence of hyper- and normogonadotropic primary ovarian insufficiency.
Symptoms
The symptoms of the disease increase gradually, determined by the degree of damage to the follicular and glandular tissue of the ovaries. The most characteristic manifestation of autoimmune oophoritis is a violation of the ovarian-menstrual cycle. At the initial stages, the amount of spotting decreases. Then the duration of menstruation is shortened, and the time interval between individual periods is lengthened to 42-60 days or more. The cycle becomes irregular. With significant destruction of ovarian tissue, menstruation stops completely.
Pain syndrome with autoimmune damage to the ovaries appears only in cases when the pathology develops against the background of exacerbation of inflammatory gynecological diseases. Patients usually complain of dull aching pain in the lower abdomen and above the pubis. Painful sensations can be given to the rectum, perineum, occur or increase during sexual intercourse. Algodismenorrhea may develop. With a prolonged course of the disease, the reproductive function of patients worsens, which is manifested by the inability to get pregnant with regular sexual activity without protection.
Complications
The most serious consequence of autoimmune oophoritis is infertility associated with primary ovarian insufficiency. Fertility can be impaired both in women who have never been pregnant before, and in patients who have already given birth to children. The immediate cause of infertility is the absence of ovulation. According to the results of studies, in 30-69% of cases of hypergonadotropic amenorrhea and approximately one third of patients with the normogonadotropic variant of ovarian insufficiency, antibodies to ovarian tissue are present in the blood. The situation is aggravated due to an increase in the content of antisperm antibodies (ASAT) in this autoimmune disorder. In 10-15% of patients, early menopause may occur in the long-term period.
Diagnostics
The presence of autoimmune oophoritis can be suspected in patients with persistent menstrual disorders and therapy-resistant infertility, other causes of which have not been reliably established. During the diagnosis, laboratory and instrumental methods are used to obtain data on the patient’s immune status, morphological structure and secreting function of the ovaries. They are the most informative in diagnostic terms:
- Determination of the level of antiovarial antibodies. The content of antibodies to follicular cells, granulosa cells and ovarian stroma with their autoimmune damage is on average increased by 2.5 times. Approximately 11-12% of the subjects have antibodies to Zona Pellucida (the shiny shell of the egg).
- Assessment of the immune status. The concentration of interleukins-1, 4, 6 is increased in the blood. At the same time, the level of interleukins-10 and 12 is slightly reduced. The content of TNF (tumor necrosis factor) is sharply increased. The level of gamma interferon also increases, reflecting the activity of nonspecific immunity.
- The content of sex hormones. The suppression of ovarian secretory function is manifested by a decrease in the level of estrogens and progesterone. In 2/3 of patients, there is an increase in the production of pituitary gonadotropins, primarily FSH. However, the level of gonadotropins may not be impaired.
- Ultrasound of the pelvic organs. The results of sonographic examination in the autoimmune form of oophoritis indicate morphological changes in the organ. The ovaries are usually reduced in size. At the initial stages of the disease, multiple follicular cysts can be detected in them.
If the pathology is associated with the presence of genital infections, it is important to determine the causative agent of the inflammatory process in order to choose an antibacterial drug. Usually, PCR diagnostics, RIF, ELISA, bacterial culture of a smear from the cervical canal are used for this purpose. The autoimmune variant of oophoritis is differentiated with infectious oophoritis, endometriosis, ovarian benign and malignant tumors, ovarian depletion syndrome, adhesions in the pelvis, other diseases that lead to menstrual dysfunction, endocrine and tubal infertility. If necessary, the patient is examined by an endocrinologist, immunologist, oncologist, surgeon, reproductologist.
Treatment
Medical tactics in destructive processes caused by antiovarial antibodies are aimed at correcting the immunological status, maintaining the secretion of sex hormones, and preserving the ovulatory cycle for as long as possible. Like other autoimmune processes, oophoritis is highly resistant to therapy, requires a comprehensive approach to treatment. Usually, schemes are used that affect different links of pathogenesis and have the following effects:
- Antibacterial effect. If oophoritis has arisen due to an infectious lesion of the reproductive organs, antibiotic therapy is recommended. When choosing a drug or a combination of antibiotics, the sensitivity of pathogens is taken into account.
- Immunosuppressive effect. Glucocorticoid hormones are considered the drugs of choice. Their appointment is most effective in the early stages of the process, however, such drugs depress all parts of the immune system and have a number of side effects.
- Anti-interleukin effect. In the treatment of autoimmune forms of oophoritis, receptor antagonists of interleukin 1L-1, which is one of the key links in the pathogenesis of the disease, are increasingly used to obtain a stable remission.