Presence Of Sperm Antibodies Research Articles

STUDY OF THE INFLUENCE OF SPERM ANTOBODIES ON SPERM CHARACTERISTICS

Event Abstract Back to Event STUDY OF THE INFLUENCE OF SPERM ANTOBODIES ON SPERM CHARACTERISTICS Anatoliy P. Godovalov1*, Tatyana Y. Danielyan2, Liliya P. Bykova3 and Mikhail V. Smirnov1 1 Acad. E.A. Wagner Perm State Medical University, immunology, Russia 2 Ltd. Medical Studio, Russia 3 Acad. E.A. Wagner Perm State Medical University, microbiology and virology, Russia It is known that about 15% of couples suffer from infertility, with a third of cases due to male infertility (Carr, 2013). According to the observations of several authors, the quality of sperm is changing in the last decade, that is due to reduction of sperm concentration and motility (Carr, 2013). One of the factors affecting the sperm may be immune effector molecules, such as antibodies. It is shown that sperm antibodies can affect sperm parameters (Cui et al., 2015). Unfortunately, it was not possible to identify the leading antigen to which the sperm antibodies are formed, and the animal experiments showed the role of complex antigens in stimulation of antibody formation (Carr, 2013; Cui et al., 2015). Causes of these antibodies formation, as well as the mechanisms of their negative impact on sperm are understudied (Cui et al., 2015). The purpose of the research was to study the characteristics of sperm in case of sperm antibodies detection in the semen. Materials and methods. Semen samples from 71 men, mean age was 37.7±0.7 years, were analyzed. Term from onset of sexual activity without protection until the study averaged 42 months. Taking material and study of sperm was performed according standardized procedures suggested by WHO experts (2010). Determination of the concentration of sperm antibodies in semen was performed by ELISA according to the manufacturer's instructions. All the men were divided into two groups, the first one consisted of men with the presence of sperm antibodies in semen, the second one (control group) - men who had no sperm antibodies detected in semen. Statistical analysis was performed using the Student t-test. Results and discussion. In the course of studies it was found that men with sperm antibodies had reduced number of sperm. Thus, the number of cells in the control group of men was 91.41±12.53 million/ml, and men with the presence of sperm antibodies had 47.93±9.17 million/ml (p<0.05) sperm. In addition, there was a reduction of living sperm number up to 43.89±8.60 million/ml (in the control group 75.76±9.43 million/ml; p=0.05). During the study of the motility characteristics of sperm it was found that the first group had significantly fewer cells with rapid progressive motion activity, 9.91±5.67 million/ml (the control group had 30.15±4.08 million/ml; p<0.05). The number of slow-moving sperm and cells with disordered progressive activity was not significantly different in two groups. The number of fixed cells in group of men with sperm antibodies was 19.87±1.08 million/ml, and in the control group – 4.85±1.24 million/ml (p<0.05). The first group had sperm with reduced average linear velocity to 10.67±1.20 μm/s (in the control group 13.57±0.53 μm/s; p<0.05). The presence of sperm antibodies in semen does not significantly affect sperm morphology. The number of sperm with defects in the first group of men was 21.96±3.57 million/ml, and in the control group 30.92±4.10 million/ml (p>0.05). The number of leukocytes in two groups was not significantly different. Men of the first group had significantly more cells of spermatogenesis - (0.75±0.06)%, and men of the control group had (0.47±0.07)% (p<0.05). One of the factors of reproductive failure is contamination of semen by microorganisms (Weng et al., 2014). So, total bacterial count of semen in the first group of men surveyed was 5.33±0.32 log10 CFU/ml, and in the control group – 3.96±0.36 log10 CFU/ml (p<0.05). The first group predominantly had members of Enterobacteriaceae family (69.3% samples), while the control group had Gram-positive cocci (88.8% of samples). Men in the first group had no clinical symptoms associated with infectious and inflammatory diseases. However, the ultrasound examination revealed diffuse changes of the prostate by type of chronic prostatitis in more than half of the cases. It is known that microorganisms have the unique ability to adhere, including sperm cells, which promotes their penetration into the egg cell (Prabha et al., 2010). At this, microorganisms violate the fertilization process and division of the zygote. When placing the microorganisms in human cells, the antibodies form to bacterial antigens, as well as to antigens of human cells. Thus, a massive infection of sperm by opportunistic pathogens probably contributes to the increase in the number of sperm antibodies that destroy the activity of sperm. Conclusion. Studies have shown that sperm antibodies violate some quantitative characteristics of sperm, their motion activity. One possible reason for the formation of a large number of sperm antibodies is probably a massive infection of sperm by opportunistic pathogens.

Etiology of sperm immunity in women

Sperm immunity in females can reduce the likelihood of natural conception, and sperm antibodies from female sera have been shown to inhibit IVF in humans and in several animal models. The etiology of sperm immunity in human females is unknown, but several possible mechanisms have been proposed, including cross-reactivity with microbial antigens and interferon gamma-mediated potentiation of the antisperm immune response in women whose male partners have sperm autoantibodies in their semen. This article reviews these ideas and postulates a novel hypothesis based on the potential for the generation of anti-idiotype antibodies in women whose partners have sperm antibodies in their semen.

Semen culture, leukocytospermia, and the presence of sperm antibodies in seminal hyperviscosity.

Seminal hyperviscosity is generally thought to reveal genitourinary infection. The aim of the present work was to study this hypothesis. A total of 65 semen samples were obtained from males presenting for infertility screening. The samples were evaluated according to WHO criteria and microbiologically investigated, including culturing for Mycoplasma hominis and Ureaplasma urealyticum, and microscopic observation of Chlamydia trachomatis by a direct fluorescence assay. Determination of local antisperm antibodies was performed. Semen was categorized according to consistency: normal (n = 31) and high (n = 34). No difference was recorded either in the number of positive cultures, or in the number of species found in each sample. The number of white blood cells and the percentage of antibody-bound sperm showed no difference in the groups under study. There was no association between seminal hyperviscosity, positivity in semen cultures, number of species isolated in semen cultures, leukospermia, or presence of sperm antibodies. Further studies should be performed considering the evolution of the genital-infected patients to clarify the etiology of the hyperviscosity.

Sperm antibodies in rat models of male hormonal contraception and vasectomy.

The presence of sperm antibodies correlates with nearly every pathological condition of the male reproductive tract. In the seasonal breeder, mink, a decrease in gonadotrophin secretion and testicular regression also induces sperm antibodies. Because the Sertoli cells and the principal cells of the epididymis (i.e. the cells mainly responsible for protection of germ cells from autoimmune destruction) are dependent on androgens, and because the androgen concentration decreases in both the testis and epididymis during male hormonal contraception, the presence of IgG class sperm antibodies in serum was studied in rats during the suppression and recovery phases of testosterone contraception and after vasectomy. Five-centimetre long testosterone implants were placed under the dorsal skin of rats under pentobarbitone anaesthesia. The control rats received empty implants. All implants were left in the rats for 27 or 53 days. The total number of testicular antigens detected by sera from the vasectomized rats increased significantly until 66 days post-operation, and then decreased to the levels of intact rats. The number of testicular antigens detected by sera from rats receiving contraceptive doses of testosterone did not increase before the testosterone capsules were removed, but at 40 days post removal of the silastic capsules, the number of antigens detected by the sera was significantly higher than in intact rats and at 77 days post removal of the silastic capsules, the number of antigens detected by the sera was significantly higher than at 27 days after starting testosterone administration. No significant changes in the number of antigens detected by the sera could be observed after the implanting of empty capsules or after their removal. Vasectomy mostly induced antibodies against testicular antigens in the molecular ratio ranges of 70-82, 25-33 and 21-24.5 kD. Antibodies against antigens in these molecular ratio ranges were not significantly induced during or after treatment with contraceptive doses of testosterone. Cell nuclei with apoptotic morphology could be observed in the seminiferous tubules of the vasectomized rats, but DNA in situ 3'-end labelling of testes could not confirm any differences between the testes of vasectomized and sham-operated rats or between testosterone-treated and empty implant-treated rats. CD3+ T cells could not be observed in the testes of any of the treatment groups. These results suggest that the immunological conditions remain stable in the testes after vasectomy and during testosterone treatment, but that the animals are more prone to develop autoantibodies after vasectomy and during recovery from treatment with exogenous testosterone.

Presence of sperm antibodies and association with viscosity of semen.

Semen characteristics were studied in 96 men from an in-vitro fertilization and embryo transfer programme. Along with the routine semen analysis, the presence of sperm antibodies in seminal plasma was measured by an ELISA technique. Antibodies to spermatozoa (IgA and/or IgG) were present in 19 cases and 15 of these (78.95%) had abnormally high viscosity, often associated with a high percentage of particulate debris and an increased number of morphologically abnormal spermatozoa.

Treatment of refractory infertility by transcervical intrauterine insemination of washed spermatozoa

One hundred thirteen couples with either male factor, cervical factor, endometriosis, or idiopathic infertility of at least 3 years' duration were treated by intrauterine insemination (IUI) of washed motile sperm. Of the 68 women who became pregnant or completed at least three cycles of insemination, the overall pregnancy rate was 38.2%, with a mean of 1.7 treatment cycles per pregnancy. The average pregnancy rate per treatment cycle was 11.4%. Women who did not become pregnant underwent an average of 4.7 treatment cycles. Importantly, only two pregnancies occurred independent of treatment in 113 couples. In the male factor group, the pregnancy rate was 42.9% (n = 21). In women with a cervical factor, 34.5% became pregnant (n = 29); in idiopathic infertile couples or women suffering from endometriosis, there was a pregnancy rate of 38.9% (n = 18). The presence of sperm antibodies in either the male or female partner significantly lowered the pregnancy rate (6.7%) when compared with couples without sperm antibodies (50.0%). The authors conclude from these observations that IUI with washed sperm is a successful mode of therapy, especially in the case of males with asthenozoospermia.

Analysis of the action of corticosteroid treatment in immunologic infertility: a preliminary report and an alternative hypothesis.

The presence of sperm antibodies can be demonstrated in 8-10% of the male partners of infertile couples. The therapeutic schedule with which the highest pregnancy rate has been obtained in these cases is that proposed by Shulman, which uses methylprednisolone (MP). If treatment with corticosteroids (CS) is effective, the way in which it acts is not entirely clear. In this study we report the results of 16 treatment cycles with CS administered to eight male patients having sperm antibodies in their serum, in which several parameters of humoral immunity were evaluated. The results are conflicting: several parameters (such as IgG concentration) underwent only slight variations after 7 days of therapy, whereas in 12 cycles out of 16, the Tray agglutination test (TAT) indicated that a reduction or disappearance of the antibodies had been obtained. This confirms the usefulness of CS in immunological infertility, and allows us to hypothesize that the beneficial effect may be found in a reduction of inflammation rather than in a suppression of the immunological response, since CS are well known to have these two kinds of effect.

Effect of Sperm Antibodies in Males on Human In Vitro Fertilization (IVF)

The effect of sperm antibodies on the human fertilization process was evaluated by analyzing the Royal Women's Hospital in vitro fertilization (IVF) data. The results suggest that sperm autoantibodies, particularly those of IgA immunoglobulin class (determined by immunobead test (IBT] can interfere with IVF. Thus, in a group (n = 8) of couples where the male partner had 80% or more of his motile spermatozoa coated with IgG and IgA class sperm antibodies, an overall fertilization rate of only 27% (18/66 ova) was obtained. In contrast, in a group (n = 9) with positive IBT results, but with less than 80% of motile spermatozoa coated with IgA class antibodies, a normal fertilization rate of 72% (47/65 ova) was obtained. Three of these patients had 90% or more of their motile spermatozoa coated with IgG and less than 70% coated with IgA class antibodies. In this subgroup a good fertilization rate of 16/21 (76%) was obtained. Another observation derived from this investigation is that the oocytes that do fertilize in the presence of sperm antibodies can subsequently proceed with normal cleavage, implantation, and pregnancy. This provides a rationale for attempting to treat these patients by reducing the proportion of antibody-coated sperm in vitro for future IVF cycles.

Intrauterine insemination: the University of Minnesota experience

Forty-five patients initiated intrauterine insemination between October 1981 and August 1983. Indications for insemination included poor semen (count less than 20 X 10(6)/ml and/or motility less than 40%), poor cervical mucus, presence of sperm antibodies, unexplained poor postcoital tests, or various combinations of the above. During this time period, 374 inseminations were performed in 163 cycles and resulted in eight pregnancies in the 45 patients receiving artificial insemination by homologous donor, for an overall pregnancy rate of 17.4%. The fact that five of the pregnancies occurred in the first insemination cycle and two in the second cycle was felt to indicate a cause-and-effect relationship. A trial of intrauterine insemination in selected patients would appear to be warranted.

Antisperm antibodies and male infertility.

Two hundred males attending a fertility clinic and 65 men who had fathered one or more children were screened for sperm antibodies using sperm agglutination and immobilisation tests. The incidence of sperm antibodies was significantly higher in the former group. Agglutinin and immobilisin were not related to sperm concentration, morphology, ejaculate volume, seminal plasma zinc, magnesium, acid phosphatase and fructose. However, sperm motility and viability were significantly reduced in the presence of sperm antibodies. There appeared to be no relationship between the presence of antisperm antibodies and Mycoplasma, aerobic or anaerobic organisms. There was a positive correlation between agglutinating and immobilising antibodies in serum and seminal plasma. This study suggests that sperm antibodies at a significant titre may lower male fertility.

Fertility following reversal of male and female sterilization

It is estimated that 60% of Australian couples will opt for sterilization as a method of birth control. Approximately 0.5 to 1% of all sterilized males and females will request reversal. With tubal occlusion, it appears that the method used to produce occlusion, the occlusion site, the length of viable tube remaining and the time between sterilization and reversal appear to be predictive factors in producing intrauterine pregnancy. With the increasing tendency for sterilization to be performed in younger women, surgeons should consider performing surgery only on the isthmus of the tube, preserving as much undamaged tube as possible and using methods of occlusion other than diathermy to ensure adequate tubal occlusion and yet maintain optimum conditions should reversal be required. Successful pregnancy following vasovasostomy appears to be related primarily to length of time elapsed following vasectomy and to the skill of the surgeon in the use of microsurgical techniques, possibly aided by preservation of nerve supply to the vas. It is doubtful whether the presence of sperm antibodies in serum or semen will affect the return of fertility in most individuals, but further research is required to clarify this.

Infertile male mink: A naturally-occurring model of autoimmune infertility

This chapter reviews current knowledge on clinical male infertility, with emphasis on autoimmune orchitis and its pathogenetic mechanism. Male infertility associated with immunologic mechanisms may result from the presence of sperm antibodies or autoimmune disease of the testis and its excurrent ducts. In the first case, antibodies, once generated, may result in infertility by a variety of mechanisms, mainly disturbances in sperm transport or disruptions in gamete interaction. In the second case, immunopathologic damage of the testis occurs through T-cell-mediated mechanisms triggered by antigens or pathogens that disrupt testicular immunoprivilege. Male infertility may result from the binding of antisperm antibodies (ASAs) to ejaculated sperm. Importantly, data from in vitro fertilization programs indicate that a reduced fertilization rate is associated with IgA and IgG antibody binding to the head region of sperm. Moreover, the recent finding of a single gene (AIRE) defect causing a systemic human autoimmune polyglandular syndrome provides an exciting tool for exploring molecular therapy for these autoimmune diseases.

Immunological aspects of female infertility.

Summary: Results in 377 couples indicate that the sperm immobilization test provides a reliable means of detecting significant humoral anti‐sperm activity in infertile patients. Occlusion therapy in patients with sperm antibodies has proved disappointing when compared with the natural reproductive pattern in untreated patients.A continuing prospective study indicates a lower subsequent fertility rate, and a markedly higher abortion rate, in women with sperm antibodies compared with those without them. Notwithstanding this, patients with infertility of 3 or more years' duration achieved a subsequent pregnancy rate of 27%, even in the presence of sperm antibodies. The nature and significance of sperm iso‐immuniza‐tion requires much further elucidation.