Antiidiotypic antibodies to sperm in sera of fertile women that neutralize antisperm antibodies.

The presence of antiidiotypic antibodies (ab-2) to sperm was investigated in the sera of fertile, infertile, and virgin women using sperm-specific anti-FA-1 monoclonal antibody Fab'.ab-2 were detected in 71% (17/24) of sera from fertile women and in none (0/12) of the sera from virgin females by the enzyme-linked immunosorbent assay, Western blot procedure, and immunoprecipitation procedure. Sera from infertile women that had antisperm antibodies showed a minimal presence of ab-2, with only three sera (13%, 3/23) demonstrating the presence of low levels of ab-2. The ab-2 present in fertile women were capable of neutralizing the fertilization-inhibitory activity of anti-FA-1 antibody in a concentration-dependent manner in a human sperm penetration assay (SPA) of zona-free hamster oocytes. ab-2 were also capable of inhibiting the binding of antisperm antibodies to the sperm surface as determined by the immunobead binding technique. This is the first report demonstrating the presence of ab-2 in the sera of fertile women that are capable of neutralizing antisperm antibodies present in sera of infertile women. These findings suggest that the inability to detect antisperm antibody activity in the sera of fertile women may be due to higher levels of ab-2 present in these sera than levels found in sera of infertile women, although both groups may be producing antisperm antibody response after sexual exposure to sperm.

Assessment of sperm function and clinical aspects of impaired sperm function.

Fertility is dependent on a complex set of events, involving both male and female components. Normal sperm function involves many steps, including motility, capacitation, acrosome reactivity and, ultimately, fertilization of the oocyte. While male fertility is most often assessed by means of gross semen parameters, infertility may also be caused by abnormal sperm function, and only by performing specific tests of this function, may the reasons for infertility become evident. Specific tests which may be helpful include semen analysis, detailed sperm motility assessment, motility longevity, hypo-osmotic swelling test, mucus penetration assay, acrosome reactivity, antisperm antibody tests, sperm penetration assay and in vitro fertilization. Relatively well-defined syndromes of abnormal sperm function include immunologic infertility, immotile-cilia syndrome, anejaculation and nifedpine-associated infertility.

Monoclonal antibodies to human sperm antigens--II.

As part of our continuous effort to elucidate the biochemical and immunological nature of human sperm surface antigens, monoclonal antibodies to human spermatozoa were generated by improved hybridoma techniques. Following immunizations with the membrane fraction of human spermatozoa and cell fusions, hybrid cells were cultured in a semi-solid HAT-selection medium to maximize the number of monoclones recovered. Subcultures were made in liquid phase 7 to 10 days after cell fusions by removing colonies from the initial medium. Based on the results of screening by microplate enzyme-linked immunoassay, 143 of 552 initial clones were found to secrete antibodies to human sperm antigens. More than one-hundred independently derived hybrid cell lines were established. Using indirect immunofluorescent procedures, 62 cell lines were shown to produce antibodies to surface antigens of human spermatozoa. Unique sperm antigens that react with monoclonal antibodies were identified by the SDS gel/protein blot radioimmunobinding method. Sperm agglutinating and immobilizing antibodies were exhibited by 4 and 15 hybrid cell lines, respectively. Fourteen of the monoclonal antibodies also exhibited cross-reactivity with methanol-fixed sperm cells of the rabbit or mouse or both whereas a reaction was not seen with viable sperm of these species. Generation of monoclonal antibodies against a wide spectrum of human sperm antigens should facilitate future investigations regarding immunologic-associated human infertility and fertility control.

Reduction of fertility in female rabbits and mice actively immunized with a germ cell antigen (GA-1) from the rabbit.

Female rabbits and mice were actively immunized against germ cell antigen (GA-1) of 63 kDa molecular mass isolated from rabbit sperm and testis. There was a significant (P less than 0.05) reduction of fertility in rabbits actively immunized with GA-1 as compared to controls, as seen by the percentage of 9-day implants/corpora lutea ratio (GA-1, 36.3%; controls, 85.7%). In mice, there was again a significant (P less than 0.01) reduction in fertility as seen by mean 7-9 day implants +/- S.D. per mated mouse actively immunized with GA-1 whether through the intraperitoneal route (GA-1, 1.2 +/- 1.6; controls, 8.0 +/- 3.4) or through the subcutaneous/intramuscular route (GA-1, 3.8 +/- 3.4; controls, 10.1 +/- 3.9). The antisera from these actively immunized animals were negative for sperm agglutinating and immobilizing antibodies. In the Western blot enzyme-immunobinding procedure, the antisera showed specific binding to a single protein of 63 kDa. The incidence of fertilization of eggs recovered from rabbits inseminated with anti-GA-1 antibodies-treated sperm was not significantly different from control rabbits. The percentage of fertilized eggs obtained from rabbits inseminated with anti-GA-1 antibodies-treated sperm that reached the blastocyst stage upon in vitro incubation, however, was significantly less than that for embryos obtained from rabbits inseminated with control serum-treated sperm. Incubation of normal fertilized eggs in vitro with the antibodies did not affect development. Neither antiserum nor immune uterine fluid reacted with 4-day blastocysts in the indirect immunofluorescence technique. It is concluded that active immunization with GA-1 results in post-fertilization reduction of fertility in rabbits and mice by inhibiting early embryonic development.

Levels of interferon-gamma and tumor necrosis factor-alpha in sera and cervical mucus of fertile and infertile women: implication in infertility.

Concentrations of two immune cytokines, namely interferon-gamma (INF-gamma) and tumor necrosis factor-alpha (TNF-alpha), were determined in the sera and cervical mucus samples of fertile (n = 16), idiopathic infertile (n = 44), and immunoinfertile women (n = 45) to investigate their role, if any, in female infertility. Sera of idiopathic infertile women demonstrated significantly (P < 0.0001) higher levels of INF-gamma compared to those in fertile controls, whether expressed as pg/ml or pg/mg serum protein. Similarly, sera of immunoinfertile women demonstrated significantly (P = 0.0008) higher levels of INF-gamma compared to fertile controls and idiopathic infertile women. Cervical mucus of idiopathic infertile women also demonstrated significantly (P < 0.0001) higher concentrations of INF-gamma compared to those in fertile controls. Cervical mucus of immunoinfertile women demonstrated significantly (P < 0.0001) higher concentrations of INF-gamma compared to those in fertile controls and idiopathic infertile women. INF-gamma levels in serum did not significantly (P > 0.05) correlate (r = 0.12-0.43) with the concentrations in cervical mucus, when all the three groups were compared together. However, when the serum levels were compared with the cervical mucus concentrations by condition, only the idiopathic infertile group showed a significant (P = 0.005) correlation (r = 0.70). Serum levels of TNF-alpha did not differ significantly (P > 0.05) among three groups of women. Cervical mucus concentrations of TNF-alpha, however, varied among groups with levels being significantly (P = 0.04) higher-in idiopathic infertile women compared with fertile controls and in immunoinfertile women significantly (P = 0.0007) higher than in fertile controls as well as idiopathic infertile women. TNF-alpha levels in serum correlated (r = 0.65) significantly (P < 0.001) with the concentrations in cervical mucus when all the three groups were compared together or individually by infertility condition. These findings suggest the involvement of cytokines in infertility, and thus may have potential applications in diagnosis and treatment of female infertility.

Monoclonal antibodies to human sperm antigens.

To elucidate the molecular nature of human sperm autoantigens, attempts were made to raise monoclonal antibodies against these antigens, by hybridoma techniques. After successive immunizations with the particulate fractions of human sperm extract in BALB/c mice, the spleen cells were fused with P3-X63-Ag8 myeloma cells. Several clones and their subclones were obtained and shown by microplate radioimmunoassay to produce antibodies against human sperm antigens. When SDS gel/protein blot radioimmunobinding was used for further molecular analysis, three independently derived clones were shown to produce antibodies, all of which cross-reacted with the same two human sperm antigens with a molecular weight of about 10,000. Using an indirect immunofluorescence assay, antibodies produced by these clones were shown to react with antigens localized on the acrosomal regions of human spermatozoa. Monoclonal antibodies produced by other clones, however, showed no cross-reactivity with any of the blotted proteins from SDS gels of human spermatozoa. Some possible reasons for this are presented.

Interrelationships among semen characteristics, antisperm antibodies, and cervical mucus penetration assays in infertile human couples.

Semen characteristics, antisperm antibodies, and cervical mucus penetration studies were analyzed in 754 couples and 95 men undergoing infertility evaluation. The means for the different semen/sperm variables were within ranges published for fertile men. Ages of the men ranged from 22 to 55 years and accounted for a small amount of variation. Sperm counts were lowest in September, December, and January, and highest in April, May, October, and November. Of the sperm characteristics, morphology appeared to be associated with the most other variables. Specimens with more than 50% abnormal sperm forms were overall of significantly poorer quality in terms of sperm counts, motility, forward progression, and ability to penetrate cervical mucus. Antisperm antibodies (agglutinating and immobilizing) were detected in the serum samples of 19.0% of the men, 20.4% of the women, and 32.8% of the couples where one or both partners were positive. Agglutinating antibody titers were significantly correlated between partners. Serum titers of antisperm antibodies were associated with decreased sperm counts, motility, forward progression, and normal forms (immobilizing antibodies). Multiple correlation analysis indicated significant independent effects of sperm concentration, motility, forward progression, and antibodies on sperm-cervical mucus penetration scores of the men. In women, cervical mucus penetration was adversely affected by the presence in the serum of sperm agglutinating antibodies and of immobilizing activity in the cervical mucus.

Antisperm antibodies: origin, regulation, and sperm reactivity in human infertility.

OBJECTIVE: To follow-up and expand discussion on the action mechanisms of antisperm antibodies in human infertility, the etiology and control of antisperm antibody induction, sperm antigens involved in immunoinfertility, and strategies for therapy. DESIGN: A review of the recent literature with an emphasis on female immunoinfertility. RESULTS: The role of antisperm antibodies in clinical infertility continues to be defined. Through assisted reproductive technologies, antisperm antibodies were shown to exert detrimental effects on different prefertilization and possibly postfertilization events. The female reproductive tract is part of the common mucosal immune system and is able to mount effective immune responses against infectious agents, foreign antigens, and, occasionally, sperm cells. Sperm membranes and constituents contain numerous antigenic components foreign to the human body, and yet antisperm antibodies become problematic in few women exposed to semen. Semen and sperm cells contain immunosuppressive factors capable of inhibiting different immune cells. Fertile women apparently produce antisperm antibodies but also possess neutralizing serum anti-idiotypic antibodies that are lacking in virgin and immunoinfertile women. CONCLUSIONS: Antisperm antibodies can affect adversely human fertility but normally may be controlled by anti-idiotypic antibodies, which along with immunosuppressor factors in semen prevent their induction to a significant degree. This balance between detrimental and "beneficial" immune response to sperm may be shifted toward an antisperm antibody response by stimulatory factors such as infection. Therapies may be devised to stimulate the anti-idiotypic antibody system, to induce immune tolerance to sperm antigens, and to use antigens to adsorb antisperm antibodies from spermatozoa.

Effects of antisera on human sperm penetration of zona-free hamster ova.

Human sperm, after treatment with a 10% concentration of rabbit or rhesus monkey normal sera and antisera, were evaluated for fertilizing potential by incidence of zona-free hamster ova penetrated by the sperm as evidenced by the presence of swollen sperm heads and male pronuclei. Compared with the basic medium alone, treating sperm with normal sera tended to increase the percentage of ova penetrated whereas antisera against sperm, sperm extract, and testis caused significant decreases in ova penetrated. A Fab preparation of these antisera exhibited similar inhibitory effects. Antisera Fab treatment of the zona-free ova prior to exposure to sperm had no effect on penetration rate.

PIP: This study demonstrates that anti-sperm antibodies exert an effect on human sperm to block their penetration of zona-free ova from golden hamsters. In the experiment, human sperm, after treatment with a 10% concentration of rabbit or rhesus monkey normal sera and antisera, were evaluated for fertilizing potential as evidenced by the presence of swollen sperm heads and male pronuclei. Treating sperm with normal sera tended to increase the percent of ova from hamsters penetrated, compared with using the basic medium alone, whereas antisera against sperm, sperm extract, and testis caused significant decreases in ova penetrated. Even a Fab preparation of the antisera tested showed similar inhibitory effects. Antisera Fab treatment of the zona-free ova before exposure to sperm had no effect on penetration rate.

Immunoglobulin (Ig) G, IgA, and IgA subclass antibodies against fertilization antigen-1 in cervical secretions and sera of women of infertile couples.

OBJECTIVES: To assess the occurrence of immunoglobulin (Ig) G, IgA, and IgA subclass antibodies against human sperm fertilization antigen-1 (FA-1) in cervical mucus (CM) and serum of women of infertile couples. DESIGN: Enzyme-linked immunosorbent assay methodology was used to detect anti-FA-1 antibodies. Antisperm antibodies were detected by agglutinating, immobilizing, and indirect immunobead (IB) methods. Control samples for the ELISA were from 10 women negative in the antisperm antibody assays. PARTICIPANTS: Samples were from women of 32 infertile couples undergoing antisperm antibody analysis. RESULTS: One of 10 control CM samples was slightly positive for IgG anti-FA-1 and none for IgA. Of the 22 CM samples from antisperm antibody-positive women, 9 were positive for IgG antibodies, 9 for IgA, 7 for IgA1, and 6 for IgA2. Cervical mucus samples from eight women were positive for both IgA and IgG antibodies. Assay of 19 serum samples, including 8 controls, by ELISA, indicated 9 of 11 from antisperm antibody-positive women and none from controls were positive for IgA and IgG (7 of 9 identical women). In addition, of the nine IgA-positive sera, seven were of the A1 subclass and five were of the A2 subclass. Positive IB assays occurred more frequently in CM and serum samples positive for anti-FA-1 antibodies than in negative samples. CONCLUSION: The results suggest that cervical secretions and sera of antisperm antibody-positive women contain IgA and IgG antibodies against sperm antigen FA-1 that may be involved in antifertility effects.

Testis antigens of man and some other primates.

Rabbit antisera raised aginst testis preparations of human, chimpanzee, rhesus monkey, and baboon origin were used to study testis-specific antigens within and among the four primate species. Antisera were absorbed with serum, liver, kidney, and spleen preparations of the respective species against which they had been produced. Immunoelectrophoretic analysis of testis extracts, using the absorbed antisera, indicated the following minimum numbers of testis-specific antigens for each species: man, 10; chimpanzee, 8; rhesus monkey, 10; and baboon, 8. Most of the testis antigens were cross-reactive among species. The results suggest that human spermatozoa possess at least four to five specific antigens which originate in the testis. The antigen that induces sperm-immobilizing antibody cross-reacted among the four species of primates. Human and rhesus monkey sperm reacted equally in the immobilization system. Testis extracts from each primate species were capable of removing the sperm-immobilizing activity of human immune sera by absorption. Testis proteinase activity, as determined by using a gelatin membrane substrate, was inhibited by the gamma-glogulin fractions of rabbit and rhesus monkey antisera and also appeared to be cross-reactive among the species.

Evaluation of human sera for antibodies against sperm by immunofluorescence.

Newborn cord sera and sera from pregnant women and from couples with unexplained infertility were observed by indirect immunofluorescence for reactions against human sperm. The sera from the infertile couples had been tested for macro-agglutination and complement-dependent immobilizing antibodies as well. Nonspecific fluorescence was noted only on the quatorial segment. Acrosomes and tail end-pieces were strongly immunofluorescent (positive at a serum dilution of 1:16) with 60 to 70% and 30 to 50%, respectively, of the sera from each main group, with the exception of the nonreactive cord blood. End-piece fluorescence was primarily due to the IgM globulin fraction. It is suggested that cord serum anti-sperm antibodies, directed mainly against the tail main piece, are due to IgG passively acquired from the mother. There was no apparent difference in immunofluorescence between infertile patients and control groups (except for the acrosome and end-piece, with cord sera). However, when the sera from infertile patients were subdivided into groups containing only agglutinating antibody, only immobilizing antibody, and both types of antibody, a higher percentage of the sera from the group having only agglutinating antibody reacted with all sperm areas. This reaction seemed more uniform over the sperm and included the usually negative posnuclear cap and midpiece. The other subgroups showed no obvious trends.

Monoclonal antibodies to rabbit sperm autoantigens.

Rabbits were immunized with homologous spermatozoa to investigate their autoimmunogenic nature. Major sperm autoantigens that elicit antisperm antibodies were analyzed molecularly by the sodium dodecylsulfate (SDS) gel/protein blot radioimmunobinding method. IgG fractions of the autoimmune sera were purified by a protein A-Sepharose column, immobilized on Sepharose as affinity ligands, and utilized to purify major sperm autoantigens from rabbit testes. The autoimmunogenicity of the purified autoantigens was verified by reimmunizations in rabbits. BALB/c mice were immunized with the affinity-purified autoantigens to raise monoclonal antibodies by modified hybridoma techniques. Following fusions and clonings, we have established more than 100 hybrid cell lines that were shown to secrete antibodies to purified autoantigens and to rabbit sperm. A variety of techniques was employed to characterize these monoclonal antibodies. By the SDS gel/protein blot radioimmunobinding method, some were found to react with unique proteins of rabbit spermatozoa. By indirect immunofluorescent assay, about one third were shown to bind different cytologic regions of spermatozoa from rabbit, man, and/or mouse. Six were found to inhibit rabbit sperm binding to rat ova in vitro. In addition, agglutinating and immobilizing activities of these antibodies on live sperm were observed.

The incidence and influence of antisperm antibodies in infertile human couples on sperm-cervical mucus interactions and subsequent fertility.

Analysis of serum samples from 698 infertile couples revealed antisperm antibodies present in 16.5% of the men and 21.6% of the women. Overall, 31.1% of the couples possessed at least one individual with positive results. Sperm-immobilized activity was detected in 29.6% of the cervical mucus (CM) samples from 459 women. Reduced sperm penetration of CM was significantly associated with serum titers of antisperm antibodies in both sexes and also with immobilizing activity in CM of women. The incidence of subsequent pregnancy in 376 infertile couples was reduced significantly if one or both partners had antisperm antibodies in serum or in genital tract secretions. The latter was reflected by evaluation of the immobilization, penetration, and shaking phenomenon of sperm in CM.

PIP: Serum antisperm antibodies were analyzed for 698 human couples with primary or secondary infertility to evaluate the incidence of antisperm antibodies in the circulation of men and women and in the cervical mucus of women as well as to evaluate the association of these antibodies with sperm penetration of cervical mucus in vitro and the relationship of these factors with subsequent fertility. Questionnaires concerning fertility status were mailed to 520 couples that had been analyzed for sperm antibodies from 1-3 years earlier. Completed questionnaires were obtained from 402 couples, and 376 of these couples were suitable for inclusion in the study. The mean duration of infertility was 4.1 +or- 2.5 years, with a range of 1-15 years for all couples; for 31 couples with secondary infertility, the duration was 3.4 +or- 1.9 years, with a range of 1.5-5.5 years. 14.8% of the men 19.6% of the women had sperm-agglutinating antibodies. An examination of the type of agglutination indicated that 88% of the positive sera showed the tail-to-tail type and the remainder showed the head-to-head type. The overall incidences of immobilizing antibody were 5.6 for men and 6.4% for women. The incidence of immobilizing antibody increased significantly in both men and women with increasing agglutination titers, as reflected by the respective correlations of 0.50 and 0.34 between the 2 tests. The incidence of pregnancy was influenced significantly by the presence of circulating sperm-agglutinating and immobilizing antibodies in both sexes. Sperm-immobilizing activity was detected in 29.6% of the cervical mucus samples from 459 women. The frequency of immobilizing antibody activity was significantly greater in samples from women with positive serum samples by either the TAT or the SIT. Sperm penetration of cervical mucus was significantly affected by the presence of either type of serum antisperm antibody in men and by sperm agglutinins in women. The incidence of subsequent pregnancy among the couples was significantly associated with each of the techniques utilized to assess antisperm antibodies. The sperm shaking phenomenon showed a significant effect that was most dramatic in those couples with more than 75% of the motile sperm exhibiting shaking in which only 1 of 13 experienced a diagnosed pregnancy. Significant but low correlation coefficients were found for the occurrence of pregnancy with the results of the serum and cervical mucus techniques. Multiple partial correlation analyses of the variables with pregnancy occurrence revealed that of the serum tests, agglutinating titers had significantly greater coefficients for men and women.

Procreation after death or mental incompetence: medical advance or technology gone awry?

OBJECTIVE: To review our experience with semen retrieval in men who are incompetent or dead and to formulate general medical, legal, and ethical guidelines for practitioners. DESIGN: Case series and literature review. SETTING: Academic. PATIENT(S): Seven incompetent or neurologically dead individuals in whom sperm retrieval was requested. INTERVENTION(S): Electroejaculation. RESULT(S): Seminal emission was induced in the two men who underwent electroejaculation. Sperm suitable for cryopreservation was obtained in one of these men. Review of the legal and ethical implications of such procedures led to development of general guidelines for determining whether gamete retrieval should be performed when requested. Issues of procreational autonomy, consideration of the decedent's wishes, and assurance of the well-being of any new life created were considered most strongly in the formation of these guidelines. CONCLUSION(S): Although the retrieval of sperm from deceased or incompetent individuals may be achieved readily, it is incumbent upon the practitioner to consider the legal and moral implications of these procedures before proceeding.

Fertilization antigen-1 removes antisperm autoantibodies from spermatozoa of infertile men and results in increased rates of acrosome reaction.

OBJECTIVE: To determine if fertilization antigen (FA)-1 will remove autoantibodies from the surface of sperm cells of immunoinfertile men by immune adsorption and permit an increased acrosome reaction (AR). DESIGN: Prospective analytic study. SETTING: University medical center. PATIENT(S): Men from 18 infertile couples with autoantibodies present on their spermatozoa. INTERVENTION(S): Sperm samples after processing were examined for antibody binding and AR before and after adsorption with control medium or FA-1. MAIN OUTCOME MEASURE(S): Sperm-bound antibody was assessed by the immunobead assay (immunoglobulin [Ig] A and IgG) and the AR by induction with ionophore A23187. RESULT(S): Adsorption with FA-1 compared with control medium increased immunobead-free swimming sperm an average of 50% and 76% for IgA and IgG antisperm antibodies, respectively, with 78% and 100% of the 18 semen specimens increasing significantly. The AR rate increased an average of 10.3% compared with control medium and showed improvement in 78% of the sperm samples after FA-1 adsorption. CONCLUSION(S): The FA-1 sperm antigen appears to significantly free sperm cells coated with autoantibodies in the semen of most infertile men examined. Reducing sperm-bound antibodies that inhibited the AR allowed the sperm cells to undergo successful AR induction by calcium ionophore.

Motility longevity of sperm samples processed for intrauterine insemination.

This study demonstrates that sperm from men with male factor infertility and sperm obtained by electroejaculation have reduced motility longevity when compared with normal specimens. After 24 hours, normal samples lost only 34% of initial motility, whereas male factor patients lost 48%, and electroejaculation patients dropped 66%. Based on these data and previous clinical studies of insemination timing, it is recommended that sperm retrieval and artificial insemination for male factor infertility, especially when electroejaculation is necessary, be performed 24 to 36 hours after urinary detection of the LH surge or as close to the time of ovulation as possible.

Circulating antisperm antibodies in recurrently aborting women.

One hundred seventy-three women with a history of three or more recurrent consecutive abortions were analyzed for circulating antisperm antibodies with a radiolabeled antiglobulin assay (RAA), a modified enzyme-linked immunosorbent assay (ELISA), a tray agglutination test (TAT), and a sperm immobilization test (SIT). No pregnancies were subsequently gestated to term in women who were antisperm antibody-positive unless they were inoculated with their husband's leukocytes as treatment for an immune basis (not related to antisperm antibodies) for their recurrent abortions. In women with an immune basis for their recurrent abortions, immunization with leukocytes from their male partners increased the ability of these women previously aborting their fetuses to carry their fetuses to term, even if they had positive results in the ELISA, TAT, and SIT; women with positive results in the RAA continued to abort subsequent pregnancies, despite leukocyte immunization. Immunization of antisperm antibody-positive women with their partner's leukocytes did not incite or increase the antisperm antibody titer, with any of the assay techniques.

Allergic reactions to penicillin during in vitro fertilization and intrauterine insemination.

Two cases are reported in which hypersensitivity reactions occurred after intrauterine placement of spermatozoa or embryos. Because the cells were processed and transferred in antibiotic-containing media, these reactions were suspected to be because of penicillin allergy. One patient had no prior penicillin allergy but was found to be penicillin allergic by skin testing. The other had a history of allergy to oral penicillin. In both cases, the allergy symptoms did not occur during subsequent cycles when antibiotics were removed from the transfer media. These reports suggest that in patients known to be penicillin sensitive, penicillin should not be used during transfer of gametes and embryos for assisted reproductive procedures. In addition, the routine use of antibiotics in these procedures should be scientifically evaluated.

Electroejaculation and assisted reproductive technologies in the treatment of anejaculatory infertility.

OBJECTIVE: To determine the efficacy of electroejaculation in combination with assisted reproductive technology (ART). DESIGN: Case series. SETTING: University fertility program. PATIENT(S): One hundred twenty-one consecutive couples seeking treatment of anejaculatory infertility. INTERVENTION(S): Electroejaculation with IUI, or gamete intrafallopian transfer or IVF. MAIN OUTCOME MEASURE(S): Pregnancy and pregnancy outcome. RESULT(S): Fifty-two couples became pregnant (43%), 39 by IUI alone (32.2%). Cycle fecundity for IUI was 8.7%. No difference in cycle fecundity was seen among ovarian stimulation protocols (clomiphene citrate, 7.6%, hMG, 13.2%, and natural cycle, 11.2%). Pregnancy was unlikely when the inseminated motile sperm count was <4 million. Female management protocol and etiology of anejaculation did not affect results. Patients undergoing IVF had higher cycle fecundity (37.2%) than did those undergoing IUI. The rates of spontaneous abortion and multiple gestations were 23% and 12%, respectively. CONCLUSION(S): Electroejaculation with stepwise application of ART is effective in treating anejaculatory infertility. Intrauterine insemination with the least expensive monitoring protocol should be used for most couples, because use of more expensive monitoring did not improve results. It is cost-effective to bypass IUI and proceed directly to IVF in men who require anesthesia for electroejaculation and in those with a total inseminated motile sperm count < 4 million.