Diagnosis and treatment of immunologically infertile women with sperm-immobilizing antibodies in their sera.

Detection of sperm-immobilizing antibodies in women may have relevance for diagnosis of immunological infertility. Infertile women in whom sperm-immobilizing antibodies are detected can be refractory to conventional treatments such as timed intercourse or intrauterine insemination (IUI) because the antibodies secreted in the female reproductive tract might impair sperm passage, inhibit fertilization, and prevent normal post-fertilization processes. Hence, manipulation of gametes and embryos from patients with sperm-immobilizing antibodies should be carried out with additional care to avoid fertilization failure resulting from the presence of antibodies during in vitro fertilization (IVF). Moreover, the reasons for the why majority of women do not develop sperm-immobilizing antibodies on exposure to sperm is not clear. The production of sperm-immobilizing antibodies is likely to occur in women with particular HLA haplotypes after repeated exposure to sperm. Characterization of sperm-immobilizing antibodies may help in the identification and characterization of sperm specific antigens that can be used as candidate antigens for the development of sperm based contraceptive vaccines.

Incidence of antisperm antibodies in males with systemic autoimmune diseases.

PROBLEM: To investigate if systemic autoimmune diseases could be one of the risk factors for developing antisperm antibodies (ASA) in males. METHOD OF STUDY: Antisperm antibodies in the sera of 70 males with systemic autoimmune diseases and 80 healthy controls were examined, by using the indirect-immunobead test (I-IBT). The sperm immobilization test (SIT) was also performed to detect sperm immobilizing antibodies to the patients who were positive in I-IBT. RESULTS: Among 70 males with systemic autoimmune diseases, five were I-IBT positives, with incidence of 7.1%. However, no positives existed in 80 healthy males. Compared with the healthy controls, the incidence of ASA in males with systemic autoimmune diseases was significantly higher (P = 0.020). None of these five ASA-positive patients had sperm immobilizing antibodies. CONCLUSION: The incidence of ASA in males with systemic autoimmune diseases was significantly higher than in the healthy controls. Systemic autoimmune diseases may be one of the risk factors for developing ASA in men.

Relationship between level of serum sperm immobilizing antibody and its inhibitory effect on sperm migration through cervical mucus in immunologically infertile women.

PROBLEM: Sperm immobilizing antibodies often interfere with the penetration of sperm through the cervical mucus. However, the relationship between sperm immobilizing antibody titer and the result of the post-coital test (PCT) has not yet been clarified. The aim of this study was to investigate whether the 50% sperm immobilization unit (SI50) titer, a quantitative measure of sperm immobilizing antibody, in patients' sera was correlated with the result of PCT. METHOD OF STUDY: The sperm immobilization test (SIT) was performed for 2834 infertile women in two university hospitals. The SI50 titers were evaluated by quantitative SIT. In some cases with sperm immobilizing antibody, PCT was carried out before ovulation and assessed according to the criteria of World Health Organization (1992). Infertile couples with abnormal semen characteristics were excluded. RESULTS: Seventy-four of 2834 women had sperm immobilizing antibodies in their sera, giving a positive rate of 2.6%. Twenty-four (77.4%) of 31 women with sperm immobilizing antibodies and 28 (20.4%) of 137 women without the antibody had abnormal PCT results. There was a significant difference between the two groups (P<0.0001). When patients with sperm immobilizing antibodies were divided into two groups according to the SI50 titers, the abnormal result of PCT was obtained in all 10 patients with high (>10) SI50 titers, while that was 14 (66.7%) in 21 patients with low (10) SI50 titers. There was a significant difference between the two groups (P=0.04). CONCLUSION: The SI50 titer in the serum can predict inhibitory effects on sperm migration through cervical mucus in immunologically infertile women. Evaluation of the SI50 titers in patients' sera seems to be useful for decision-making in infertile women with sperm immobilizing antibodies regarding whether they have the possibility of conceiving by timed intercourse.

Effects of in vivo exposure to eggs with sperm-immobilizing antibodies in follicular fluid on subsequent fertilization and embryo development in vitro.

Aims: It has been shown that supplementation of patients' sera that contains sperm-immobilizing antibodies results in failure of fertilization and embryo development in vitro. The present study was carried out to investigate if exposing retrieved eggs to a high number of sperm-immobilizing antibodies in the follicular fluid (FF) in vivo affected subsequent fertilization and embryo development in vitro, even if they were washed with an antibody-free culture medium. Methods: Patients' sera and their FF were collected in 15 in vitro fertilization-embryo transfer (IVF-ET) or intracytoplasmic sperm injection-embryo transfer (ICSI-ET) treatment cycles from 11 infertile women with sperm-immobilizing antibodies in their sera. Quantitative sperm-immobilizing antibody titers (SI50 titers) in the sera and FF were evaluated. The fertilization rate, good-quality embryo rate and implantation rate by IVF-ET were compared between infertile patients having higher (10≤) SI50 titers and lower (<10) SI50 titers in their FF. Results: There was a significant correlation in the SI50 titers between the patients' sera and their FF (P < 0.0001). After thoroughly washing the collected eggs in culture medium without the patient's serum before IVF, there was no difference in the fertilization rate in the patients with high (10≤) and low (<10) SI50 titers in their FF (P = 0.62). However, the good-quality embryo rate in the patients with a high SI50 titer was significantly lower than patients with a low antibody titer (P < 0.05). There was no significant difference in the implantation rate between the two groups (P = 0.33). Conclusions: Similar amounts of sperm-immobilizing antibodies existed in the patients' FF and in their sera. ICSI did not seem to be necessary in patients having the antibodies if their sera were not supplemented in the culture media. Even with careful manipulation of eggs, it might be suggested that the harmful effects of sperm-immobilizing antibodies on embryo development cannot be completely avoided, especially in patients with high SI50 titers in the FF. (Reprod Med Biol 2006; 5: 137-143).

Diagnosis and treatment of immunologically infertile males with antisperm antibodies.

The presence of antisperm antibodies (ASA) can reduce fecundity in both males and females. The present review describes a strategy, established by investigations of the diverse inhibitory effects of ASA on fertility, for the appropriate diagnosis and treatment of infertile males with ASA. For infertile males with ASA, diagnosis using the direct-immunobead test (D-IBT), the postcoital test (PCT) and the hemizona assay (HZA) should be carried out as the basis for decision-making. If the patient with ASA has an abnormal hemizona index, it seems reasonable to advise selecting intracytoplasmic sperm injection-embryo transfer (ICSI-ET) as a primary treatment. However, it has been shown that some immunologically infertile males with normal fertilizing ability established pregnancy by timed intercourse (TI) or intrauterine insemination (IUI). In such patients with ASA having normal hemizona index, TI or IUI can be selected based on the PCT result. Therefore, the treatment strategy for males with ASA is similar to that for infertile males with oligozoospermia or asthenozoospermia. In conclusion, it should be emphasized that a diversity of ASA exists and their effects on fertility in infertile males. Although there is an argument that routine testing for ASA in males is not always necessary, one should be aware that in some cases of failed IUI or IVF, ICSI is selected afterward because of the diagnosis of ASA. (Reprod Med Biol 2005; 4: 133-141).

Charles Bonnet syndrome and visual acuity--the involvement of dynamic or acute sensory deprivation.

A 61-year-old patient suffered from Charles Bonnet syndrome (CBS) while his visual acuity declined, whereas CBS subsided after he became blind. These findings suggest that reduction of visual acuity (dynamic or acute impairment) has a greater impact on the onset of CBS than low visual acuity (static or chronic impairment) per se in some patients. They may also explain why patients with low visual acuity do not always suffer from CBS. Although further studies are required, the present case highlights the importance of the differentiation between lowering and low visual acuity in the etiology of CBS.

The rarity of Charles Bonnet syndrome.

Charles Bonnet syndrome (CBS) is characterized by complex visual hallucinations in otherwise psychologically normal people. Estimates of the prevalence of CBS in different samples vary from a small percentage (around 1%), to a relatively large percentage (about 10%). The purpose of the present study is to determine whether CBS is rare or not. One-thousand ophthalmologic and optometric outpatients at a university hospital were consecutively screened by a questionnaire to identify patients possibly experiencing visual hallucinations. The mean corrected visual acuity in the best eye was 1.1. Those who positively responded to the questionnaire were further investigated to determine whether their symptoms were consistent with CBS. As a result, the prevalence of CBS was 0.5% (5/1000). In subclass analyses, the prevalence was 3 of 372 (0.8%) in the low vision group, 2 of 346 (0.6%) in the elderly, and 1 of 120 (0.8%) in both conditions. These were not significantly different from each other or from the overall prevalence (0.5%). This low prevalence of CBS in our subjects may be due to their relatively good visual acuity because previous studies with high prevalence of CBS investigated patients with a visual acuity of less than 0.3. The prevalence of CBS may be low in patients with these particular characteristics, and this syndrome seems to be rare in even ophthalmologic and optometric patients if they do not have seriously low vision. Further studies are needed to investigate the prevalence of CBS in general population.

Diversity of the inhibitory effects on fertilization by anti-sperm antibodies bound to the surface of ejaculated human sperm.

BACKGROUND: The presence of anti-sperm antibodies (ASA) in males can reduce fecundity. However, it has been shown that there is a diversity of ASA bound to the sperm surface. This study was performed to investigate the inhibitory effects on fertilization by ASA in males. METHODS: ASA were detected using the direct-immunobead test (D-IBT) in 509 semen samples. In some cases, the direct-sperm immobilization test (D-SIT) was carried out. The fertilizing ability of infertile males with ASA was determined as follows; (i) an IVF fertilization rate of >/=50%, (ii) a hemizona index (HZI) of >/=50%, and (iii) pregnancy established without the use of ART. RESULTS: In total, 18 (3.54%) infertile males had ASA on the sperm surface. Except for one male with an absolute indication for ICSI because of severe asthenozoospermia and two males who dropped out of this study, fertilizing ability in 15 males could be determined. Four (26.7%) men did not satisfy the criteria. The existence of sperm immobilizing antibodies on the surface of ejaculated sperm had no impact on fertilization. In four (57.1%) of seven patients who had IB-bound sperm of >/=80%, fertilizing ability was inhibited, while none of the eight patients who had <80% IB-bound sperm had an inhibitory effect on fertilization. There was a significant difference between the two groups (P = 0.01). CONCLUSIONS: Some sperm-bound antibodies are related to the inhibitory effects on fertilization, indicating that a diversity of sperm-bound antibodies exists in males. This result might be one of the reasons for the controversy of the relationship between ASA and male immunological infertility. Based on the present study, a sperm-zona pellucida binding assay should be performed for appropriate decision making in infertile males with ASA.

Infertile women without sensitization to an appropriate amount of sperm do not produce sperm-immobilizing antibodies in their sera.

Background and Aim: The factors that affect sperm immobilizing antibody production in some women are not fully understood. This study was performed to investigate if production of sperm immobilizing antibodies in women is associated with their husbands' sperm count. Methods: The sperm immobilization test (SIT) was performed on 221 infertile women whose husbands had normal semen characteristics according to the criteria by WHO; 160 patients were treated by intracytoplasmic sperm injection (ICSI) because of poor semen characteristics, and 1013 virgin female children acted as the controls. Results: A significant difference of the incidence in SIT was observed between the virgin female children and the women whose husbands had a normal sperm count (P < 0.0001). There was also a significant difference of the incidence in SIT between the women treated by intracytoplasmic sperm injection (ICSI) because of a severe male factor and those whose husbands had a normal sperm count (P < 0.05). Conclusions: These results indicate that production of sperm immobilizing antibodies in women begins after they have been exposed to a large enough amount of sperm. However, the precise amount of sperm required to produce the antibodies is not clarified by the present study. (Reprod Med Biol 2003; 2: 105-108).