[Treatment of male immune infertility by traditional Chinese medicine: A meta-analysis].

OBJECTIVE: To evaluate the efficacy and safety of traditional Chinese medicine (TCM) in the treatment of male immune infertility (MII) by meta-analysis. METHODS: We retrieved randomized controlled trial (RCT) on the treatment of male immune infertility with traditional Chinese medicine from the databases of WanFang, Chinese Biomedical Literature, Cochrane Library, Weipu, PubMed and CNKI, and performed methodological quality assessment of the RCTs identified and statistical analysis and evaluation of the publication bias using the RevMan5.4 software. RESULTS: Totally, 25 RCTs (2 563 cases) were included in this study. Compared with Western medicine alone in the treatment of MII, TCM achieved a significantly higher total effectiveness rate (OR = 6.35, 95% CI: 4.96－8.13, P<0.000 01), negative conversion rate of seminal plasma anti-sperm antibodies (OR = 4.52, 95% CI: 2.72 － 7.51, P<0.000 01), negative rate of serum anti-sperm antibodies (OR = 2.98, 95% CI: 2.23－3.96, P<0.000 01), sperm concentration (MD = 15.56, 95% CI: 11.32－19.79, P<0.000 01), grade a sperm motility (MD = 3.85, 95% CI: 1.91－5.79, P=0.000 01), grade a+b sperm motility (MD = 13.77, 95% CI: 7.06－20.48, P<0.000 1), sperm viability (MD = 10.32, 95% CI: 6.78－13.86, P<0.000 01) and pregnancy rate (OR = 3.53, 95% CI: 2.68－4.63, P<0.000 01), but a lower rate of adverse reactions (OR = 0.06, 95% CI: 0.01－0.23, P<0.000 01). There was no statistically significant difference in the percentage of morphologically abnormal sperm between TCM and Western medicine alone in the treatment of MII (MD = －7.53, 95% CI: －15.50－0.44, P = 0.06). CONCLUSION: TCM has a definite effectiveness and high safe in the treatment of male immune infertility.

Update on the research on the antigens of anti-sperm antibodies over the last decade.

This review summarizes the advancements over a decade of research on antigens of anti-sperm antibodies (ASAs), which are key to male immune infertility. Despite the progress in assisted reproductive technologies, understanding the roles and mechanisms of ASAs and their antigens remains vital for immune infertility management. We conducted a comprehensive literature search on PubMed from January 2013 to December 2023 using the following keywords: "anti-sperm antibody," "sperm antigen," and "immune infertility." In this review, we focus on the discoveries in sperm antigen identification and characterization through proteomics, gene disruption technology, and immunoinformatics, along with the development of fertility biomarkers. Here, we discuss the clinical applications of improved ASA detection methods and the progress in the development of immunocontraceptive vaccines. The intersection of advanced diagnostic techniques and vaccine development represents a promising frontier in reproductive health. The findings also highlight the need for standardized ASA detection methods and a comprehensive molecular-level approach to understanding ASA-related infertility. These insights underscore the significance of ongoing reproductive immunology research in enhancing clinical fertility outcomes and contraceptive vaccine development.

Clinical Efficacy of Traditional Chinese Medicine Suppository Combined with Yishen Tongluo Qingkang Decoction in Treatment of Immune Infertility / 中国实验方剂学杂志

ObjectiveTo evaluate the clinical efficacy and safety of traditional Chinese medicine （TCM） suppository combined with Yishen Tongluo Qingkang decoction in the treatment of immune infertility. MethodA total of 116 patients meeting the inclusion criteria of this study were randomly divided into an observation group （58 cases） and a control group （58 cases）. The observation group was treated with TCM suppository combined with Yishen Tongluo Qingkang decoction，and the control group was treated with prednisone acetate tablets. Both groups were treated for 12 weeks and followed up six months after treatment. Semen samples of the patients were collected before and after treatment，and the pregnancy status of their spouses，negative conversion rate of seminal plasma anti-sperm antibody （AsAb），sperm concentration，motility，percentage of forward motile sperm，sperm acrosin activity， and incidence of adverse reactions were compared between the two groups. ResultA total of 104 patients completed the study，including 53 cases in the observation group and 51 cases in the control group. Before treatment，the baseline data of the two groups were balanced. After treatment，the total effective rate of the observation group was 92.45%，which was higher than that of the control group （76.47%）（P<0.05），and the negative conversion rate of AsAb in the observation group was higher than that in the control group，but the difference was not statistically significant. After treatment，the sperm motility， percentage of forward motile sperm， and sperm acrosin activity increased in the two groups（P<0.05），and the sperm concentration in the observation group increased （P<0.05）. There was no significant difference in sperm concentration in the control group. After treatment，the sperm concentration，motility，percentage of forward motile sperm， and acrosin activity in the observation group were better than those in the control group （P<0.05）. During the trial，the incidence of adverse reactions in the observation group was lower than that in the control group （P<0.05）. ConclusionTCM suppository combined with Yishen Tongluo Qingkang decoction can significantly increase the negative conversion rate of AsAb and improve the quality of semen in patients with immune infertility.

Immunology in reproductive medicine: is current testing and therapy justified by science?

Immunology and reproduction are intimately combined in human physiology; however, the mechanisms whereby the uterus accepts the fetus and allows it to flourish remain unclear, at least in the human. The introduction of unproven and expensive tests and therapies to alter immune mechanisms around conception has spread throughout reproductive medicine. Specialists in this discipline need to understand more of the immune physiology of reproduction and be more conservative in the use of therapeutics until evidence-based data become available.

Xiaokang Liuwei Dihuang decoction ameliorates the immune infertility of male rats induced by lipopolysaccharide through regulating the levels of sex hormones, reactive oxygen species, pro-apoptotic and immune factors.

Male immune infertility is a kind of disease that damages family life and happiness. The development of novel methods treating male immune infertility is of great significance. This study aimed to investigate the therapeutic effects of Chinese medicine Xiaokang Liuwei Dihuang decoction on immune infertility of male rats and explored the involved mechanisms. Model rats were established by lipopolysaccharide (LPS) injection. Anti-sperm antibody (AsAb) was detected by ELISA assay and testicular cell apoptosis was evaluated by TUNEL staining to verify the successful model establishment and screen suitable doses of Xiaokang Liuwei Dihuang decoction. Thirty rats were then divided into five groups (n = 6 per group): Control, LPS, Xiaokang Liuwei Dihuang decoction (15.12 g/kg, 30.24 g/kg and 45.36 g/kg). Results of HE staining showed that compared with LPS group, Xiaokang Liuwei Dihuang decoction treatments gradually improved the morphology of seminiferous tubules and elevated the number of spermatogenic cells as the doses increased. The sperm number and the levels of testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) in the serum of 15.12 g/kg, 30.24 g/kg and 45.36 g/kg Xiaokang Liuwei Dihuang decoction groups were much higher than those in LPS group. Results of TUNEL staining, ELISA assay and western blot showed that compared with LPS group, the testicular cell apoptosis and the levels of interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), AsAb, malondialdehyde (MDA) and toll-like receptor 2 (TLR2) in the testicular tissue significantly decreased in three Xiaokang Liuwei Dihuang decoction groups. Compared with LPS group, Bax expression in the 30.24 g/kg and 45.36 g/kg Xiaokang Liuwei Dihuang decoction groups was significantly down-regulated as well. In conclusion, Xiaokang Liuwei Dihuang decoction might ameliorate the immune infertility of male rats induced by LPS through regulating the levels of sex hormones, reactive oxygen species, pro-apoptotic and immune factors.

Immune regulatory molecules as modifiers of semen and fertility: A review.

Declining fertility rates in both human and animals is a cause for concern. While many of the infertility cases are due to known causes, idiopathic infertility is reported in 30% of the infertile couples. In such cases, 18% of the infertile males carry antisperm antibodies (ASAs). Such data are lacking in livestock, wherein 20-30% of the animals are being culled due to low fertility. In males, the blood-testis barrier (BTB) and biomolecules in the semen provide an immuno-tolerant microenvironment for spermatozoa as they traverse the immunologic milieu of both the male and female reproductive tracts. For example, insults from environmental contaminants, infections and inflammatory conditions are likely to impact the immune privilege state of the testis and fertility. The female mucosal immune system can recognize allogenic spermatozoa-specific proteins affecting sperm kinematics and sperm-zona binding leading to immune infertility. Elucidating the functions and pathways of the immune regulatory molecules associated with fertilization are prerequisites for understanding their impact on fertility. An insight into biomolecules associated with spermatozoal immune tolerance may generate inputs to develop diagnostic tools and modulate fertility. High-throughput sequencing technologies coupled with bioinformatics analyses provides a path forward to define the array of molecules influencing pregnancy outcome. This review discusses the seminal immune regulatory molecules from their origin in the testis until they traverse the uterine environment enabling fertilization and embryonic development. Well-designed experiments and the identification of biomarkers may provide a pathway to understand the finer details of reproductive immunology that will afford personalized therapies.

Human MOSPD2: A bacterial Lmb mimicked auto-antigen is involved in immune infertility.

Autoantibody production is one of the leading factors of immune infertility, an autoimmune disease of the male reproductive system. The potential involvement of MHC-class II derived self-peptides against bacterial proteins in the antisperm antibody (ASA) production has been reported previously. Apparently, Streptococcus agalactiae has been considered as an important pathogen to impart infection-induced infertility in a bacteriospermia associated leukocytospermia (LCS/BS) state. Hence, the present study attempts to confirm S. agalactiae specific Laminin binding protein (Lmb) derived self-peptide ('KDSYTKKAKAFKKEA') namely human Motile Sperm domain-containing protein 2 (MOSPD2) as an auto-antigen in LCS/BS condition. Semen samples were collected from infertile men with LCS/BS (n â€‹= â€‹17) and their fertile counterparts (n â€‹= â€‹10). Gram-positive bacteria were predominantly identified in the entire 17 LCS samples using culture method followed by 16S rDNA sequencing technique. TLRs 2 and 4 expression used as markers of immune response in spermatozoa and sperm dysfunction were elevated in the LCS/BS spermatozoa as compared to their fertile counterparts. A significant increase in oxidative stress indices i.e., protein carbonylation, lipid peroxidation and acridine orange test (AOT), was also observed in the LCS/BS spermatozoa. Spermatozoa lysate (both auto and heterologous), bacterial lysate (control) and synthesized MOSPD2 self-peptide were used to test their antigenicity against the autoantibodies by rocket immunoelectrophoresis (RIEP) assay. Seminal plasma from LCS/BS patients with S. agalactiae was used as the source of autoantibodies. Spermatozoa and bacteria lysate; and MOSPD2 self-peptide were able to bind autoantibodies in the seminal plasma. Besides, the self-peptide showed a dose dependent increase in the precipitation of antibody. T-cell epitope mapping of 48 Enterococcus faecalis and 91Staphylococcus aureus surface proteins confirmed MOSPD2 as a global auto-antigen. Thus, augmentation of TLR expression in LCS/BS spermatozoa inferred MOSPD2 to be a putative immunogen. Altogether, these findings will delineate the significance of MOSPD2 auto-antigen in a bacteria derived immune infertility condition.

[Application of Tri-Jiao Theory in the treatment of male immune infertility].

Male immune infertility is a common disease with an incidence rate of about 10%. This article aimed to find some breakthrough clues to the etiology and pathogenesis of male immune infertility from years of relevant studies in traditional Chinese medicine (TCM). Some consensuses on the diagnosis, etiology and pathogenesis of the disease are based on limited and isolated understandings. With the Tri-Jiao Theory as the breakthrough point, we analyzed the three studies by the Xu Fu-song Group and discussed the causes, development and outcome of male immune infertility from the aspects of its positioning, transmission and syndrome differentiation. The Tri-Jiao Theory reflects the holistic thought of TCM and offers a comprehensive insight into the dynamic changes of the disease. As the basis for TCM understanding of male immune infertility, studies on the mucosal immune system have provided some new ideas for applying the Tri-Jiao Theory to TCM researches into the disease.

Effect of Chinese Herbal Medicine on Male Infertility.

Male infertility normally refers a male's inability to cause pregnancy in a fertile female partner after 1 year of unprotected intercourse. Male infertility in recent years has been attracting increasing interest from public due to the evidence in decline in semen quality. There are many factors contributing to the male infertility including abnormal spermatogenesis; reproductive tract anomalies or obstruction; inadequate sexual and ejaculatory functions; and impaired sperm motility, imbalance in hormone levels, and immune system dysfunction. Although conventional treatments such as medication, surgical operation, and advanced techniques have helped many male with infertility cause pregnancy in their female partners, effectiveness is not satisfactory and associated with adverse effects. Chinese herbal medicine (CHM) has been used to improve male infertility in China for a very long time and has now been increasingly popular in Western countries for treating infertility. In this chapter we summarized recent development in basic research and clinical studies of CHM in treating male infertility. It has showed that CHM improved sperm motility and quality, increased sperm count and rebalanced inadequate hormone levels, and adjusted immune functions leading to the increased number of fertility. Further, CHM in combination with conventional therapies improved efficacy of conventional treatments. More studies are needed to indentify the new drugs from CHM and ensure safety, efficacy, and consistency of CHM.

The relationship between female anti-sperm immune infertility and chronic inflammation in female reproductive tract / 中国生化药物杂志

Objective To investigate relationship between anti-sperm immune infertility and chronic inflammation in female reproductive tract.Methods80 patients of anti-sperm immunity infertility were selected, and randomly divided into the study group and the control group.The study group was treated with dexamethasone+Vitamin E+Vitamin C+roxithromycin, the control group was treated with dexamethasone+vitamin E+vitamin C, After a course of treatment, serum IL-6, TNF-α and the AsAb in serum and cervix change was detected before and after treatment.ResultsThe clinical efficacy of study group was significantly better than the control group, with statistical significance (P<0.05).the AsAb in serum and cervix in the study group was significantly lower than the control group, with a statistically significant difference (P<0.05).serum IL-6, TNF-α in the study group was significantly lower than the control group, with significant difference (P<0.05).ConclusionThe female anti-sperm immune infertility and the chronic inflammation in female reproductive tract are relational, The female anti-sperm immune infertility combined with antibiotic has a significant effect.

Anti-GAPDHS antibodies: a biomarker of immune infertility.

Numerous investigations have focused on the detection of antisperm antibodies, which have a naturally occurring impact on male and female fertility. In this study, spermatogenic glyceraldehyde-3-phosphate dehydrogenase (GAPDHS) was considered to be a candidate biomarker of immune infertility. The concentrations of anti-GAPDHS antibodies in the sera of sterile individuals and fertile couples were measured by enzyme-linked immunosorbent assay. Sera were collected from immune infertile (n = 175) and fertile (n = 237) individuals and were screened by tray agglutination tests (TAT). Infertile sera were further divided into two groups according to the serum titers obtained by TAT (titers ≤ 1:8, n = 58; titers > 1:8, n = 117). The concentrations of anti-GAPDHS antibodies were significantly higher in the immune infertile group than in the fertile group and were much higher with regard to the increased degrees of sperm agglutination (titers > 1:8). Surprisingly, we found statistically significantly higher concentrations of antibodies in the sera of infertile men than in those of infertile women, and a similar statistical result was obtained in the sera when primary infertility was compared with secondary infertility. Thus, anti-GAPDHS antibodies seem to be a sensitive parameter in immune infertile detection and might be one of the main factors causing immune infertility. This factor might be valuable as an indicator in the clinical diagnosis and monitoring treatment of infertility.

Antisperm antibodies and fertility association.

OBJECTIVE: To evaluate the relation between antisperm antibodies (ASA) and human fertility by reviewing the scientific literature of the last 45 years. METHODS: We carried out a review of scientific literature about antisperm antibodies and infertility published in spanish or english in databases as Pubmed, Medline, Scielo, some books and another gray literature include information related to this review and that is published in the last 45 years. SUMMARY OF EVIDENCE: Infertile couples suffer infertility by immunological mechanisms mainly by the presence of antisperm antibodies ASA in blood, semen or cervicovaginal secretions; the formation of ASA in men and women may be associated with disturbance in immunomodulatory mechanisms that result in functional impairment of sperm and thus its inability to fertilize the oocyte. CONCLUSION: Immunological infertility caused by ASA is the result of interference of these antibodies in various stages of fertilization process, inhibiting the ability of interaction between sperm and oocyte.