Immunological infertility is a hyperimmune condition of the female or male body, accompanied by the secretion of specific antisperm antibodies. Immunological infertility is manifested by the failure of conception and pregnancy with regular sexual activity without contraception in the absence of other female and male factors of infertility. Diagnosis of immunological infertility includes examination of spermogram, plasma antisperm antibodies, postcoital test, MAR test and other studies. In immunological infertility, corticosteroids, immunization methods and assisted reproductive technologies are used.
Immunological infertility is the presence of pathological antisperm immunity that prevents the process of fertilization of an egg and implantation of an embryo. In immunological infertility, antibodies to spermatozoa – antisperm antibodies (AST) can be synthesized by both female and male organisms and are present in cervical and intrauterine mucus, blood serum, seminal plasma, vas deferens. The immunological factor turns out to be the cause of infertility in 5-20% of married couples under the age of 40, while AST can be detected only in one spouse or both at once. Specialists in the field of reproductive medicine (gynecologists, reproductologists, andrologists) are engaged in studying the problem of immunological infertility.
AST may be present in a minimal amount in fertile men and women, but their fixation on the membranes of most spermatozoa dramatically worsens the prognosis for pregnancy. This is due to a violation of the quality and fertility of sperm – damage to the structure and a sharp decline in sperm motility, a decrease in their ability to penetrate the cervical mucus, blockade of the preparatory stages (capacitation and acrosomal reaction) and the process of fertilization of the egg itself. In the presence of AST, the quality of embryos is significantly reduced, the processes of their implantation into the uterus, the formation of fetal membranes and development are disrupted, which leads to the death of the embryo and termination of pregnancy at the earliest stages.
According to their antigenic structure, spermatozoa are foreign to the female and to the male body. Normally, they are protected by mechanisms of suppression of the immune response: in men – by the hemato-testicular barrier in the testicle and its appendage, the immunosuppressive factor of spermoplasm and the ability of spermatozoa to mimicry (to sorption and desorption of surface antigens); in women – by a decrease in the level of T-helpers, Ig and C3 components of the complement system, an increase in the number of T-suppressors during ovulation.
Under the influence of certain adverse factors, the violation of protective mechanisms makes it possible for sperm antigens to contact the immune system and leads to the development of immunological infertility. The reasons for the production of autoantibodies to spermatozoa and spermatogenesis cells in men can be:
- acute and blunt scrotal injuries and testicular surgery;
- infections and inflammatory processes of the urogenital tract (gonorrhea, chlamydia, herpes, HPV, orchitis, epididymitis, prostatitis);
- congenital or acquired defects of the genitals (cryptorchidism, testicular torsion, varicocele, funiculocele, etc.), oncopathology.
Failure of intrauterine immune tolerance and the appearance of AST in women during the preimplantation period may be triggered by:
- infectious and inflammatory diseases of the reproductive tract;
- an increased level of leukocytes in the partner’s ejaculate (with nonspecific bacterial prostatitis);
- contact with the partner’s immunogenic spermatozoa already associated with his autoantibodies;
- ingestion of semen into the gastrointestinal tract during oral / anal sex;
- the use of chemical contraceptives;
- coagulation of cervical erosion in the anamnesis;
- violations of intrauterine insemination;
- hormonal “blow” when trying IVF;
- injury during egg collection.
Other isoantigens contained in the partner’s ejaculate can indirectly stimulate the production of AST in the female body – enzymes and intracellular antigens of spermatozoa, HLA antigens; incompatibility in ABO, Rh-Hr, MNSs systems.
The degree of sperm damage depends on the class (IgG, IgA, IgM) and AST titer, the place of their fixation, the level of occurrence of an immune reaction. AST, connecting to the tail of the sperm, complicate their movement, and fixed to the head – block fusion with the oocyte.
Immunological infertility outwardly proceeds asymptomatically, having no visible manifestations in both partners. Men with autoimmune infertility usually retain active spermatogenesis, erectile function and the fullness of sexual intercourse. Gynecological examination of a woman does not reveal uterine, tubal-peritoneal, endocrine and other factors that prevent conception.
At the same time, a married couple of childbearing age, under the condition of a normal menstrual cycle of a woman and regular sexual life without protection, has no pregnancy for a year or more. With AST in women, due to an implantation defect and a violation of embryo development, its death and rejection are observed, termination of pregnancy at very early stages, usually before a woman can detect it.
In case of infertility, a comprehensive examination must be carried out by both a woman and a man – by a gynecologist and an andrologist, respectively. The immunological nature of infertility is diagnosed according to the results of laboratory studies: analysis of ejaculate, special biological samples – postcoital test (Shuvarsky–uner in vivo and Kurzrock–Miller in vitro), MAR test; 1W test, FC. determination of plasma antisperm antibodies. Hormonal and other medications are interrupted for the duration of diagnostic tests.
The presence of the male factor of immunological infertility can be assumed with a violation of the spermogram (a sharp drop in the number, distortion of the shape, agglutination and weak sperm activity, low sperm survival, complete absence of live sperm). The data of the main postcoital test help to identify AST in cervical mucus by its effect on the motility and viability of spermatozoa in the contents of the cervical canal. Spermatozoa connected to AST are characterized by low mobility and adynamy, pendulum-like movements and the phenomenon of “trembling in place”.
Simultaneously with the spermogram, a MAR test is performed that determines the number of AST-positive motile spermatozoa (with MAR IgG >50%, the diagnosis of “male immune infertility” is obvious). The 1W test establishes the localization of AST on the surface of the sperm and the percentage of AST-bound sperms. By the method of flow cytofluorometry (FC), the concentration of AST on one sperm, spontaneous and induced acrosomal reaction are evaluated. If abnormalities are detected in the spermogram and postcoital test, ELISA is indicated to determine the AST spectrum in blood serum. Additionally, a PCR study can be performed for urogenital infections (chlamydia, mycoplasma, HSV, HPV, etc.), determination of autoantibodies to phospholipids, DNA, cardiolipin, thyroid hormones, HLA typing. Immunological infertility must be differentiated from female and male infertility of a different genesis.
With immunological infertility, a woman’s immune status is corrected with long courses or shock doses of corticosteroids, antihistamines and antibacterial drugs are prescribed. In the case of autoimmune processes (antiphospholipid syndrome), treatment is supplemented with low doses of aspirin or heparin. The use of a barrier method of contraception (condoms) for 6-8 months with the exception of contact of spermatozoa with the immune cells of a woman’s genitals can reduce the sensitization of her body. Suppression of immunity increases the chances of conception in 50% of cases. To normalize the immune mechanisms in the female body, subcutaneous injection of allogeneic lymphocytes (husband /donor) before conception or intravenous administration of gamma globulin – a mixture of plasma proteins from different donors is proposed.
The elimination of the male component of immunological infertility is based on the treatment of the background pathology that led to the formation of AST, and may include surgical interventions correcting abnormalities of the reproductive tract and blood circulation. It is possible to prescribe proteolytic enzymes, cytostatics and corticosteroids.
The main ones in the treatment of immunological infertility are assisted reproductive technologies, which require careful examination and preparation of spouses. With artificial insemination, the husband’s sperm is injected directly into the uterine cavity, bypassing the cervical canal, in the ovulatory period of a woman. In the presence of spermatozoa capable of fertilization, but not reaching the egg, the method of artificial insemination is used. With a low fertilizing potential, a higher frequency of pregnancy is achieved by ICSI – intracytoplasmic injection of one high-quality sperm into the cytoplasm of the egg, followed by embryo insertion into the uterine cavity.
For the release of a full-fledged egg, hormonal stimulation of superovulation is carried out. Sperm production in men is performed by ejaculation, testicular biopsy (TESA, TESE, Micro-TESE) or testicular appendage biopsy (PESA, MESA). In severe cases of male immunological infertility, donor sperm is used. The presence of a high AST titer in a woman’s blood is a contraindication for insemination, ICSI and IVF and requires prolonged treatment until their level normalizes. The use of higher-quality morphologically selective or genetically healthy and functionally active spermatozoa (IMSI and PIXIE) and preimplantation culling or embryo processing (assisted hatching) is promising in the treatment of immunological infertility. To increase the probability of pregnancy, preimplantation cryopreservation of embryos is performed.
Immunological infertility has a rather specific character: AST is produced on the spermatozoa of a particular man, and when a partner changes, the possibility of pregnancy appears. With full-fledged treatment using modern ART, immunological infertility can be overcome in most non-severe cases.