The "unexplained" poor postcoital test.

In 30 or 32 infertile couples with an unexplained negative or bad in vivo and in vitro sperm penetration test, we obtained a strongly positive Sperm Cervical Mucus Contact test (SCMC-test) and demonstrated the presence of antisperm antibodies in the male or female partner. In these 30 couples 25 of the male partners had a sperm-agglutination titre of at least 32 in the serum and at least 4 in the seminal plasma. In the five remaining couples the female partner showed a minimum sperm-agglutination titre of 16 in the serum and a cervical mucus titre of at least 128. In 48 couples with a fair or good sperm penetration in cervical mucus, in vivo and in vitro, we never found a strongly positive SCMC-test. In 43 of these couples the SCMC-test was negative. Only one man in the latter group had sperm-agglutinating activity in the semen. In a group 32 couples, with a negative SCMC-test, there was no or only weak sperm-agglutinating activity in the cervical mucus, although 2 women had moderate sperm-agglutinating activity in the blood serum. Based on these data we conclude that the so called "unexplained" poor postcoital test is almost always due to the presence of antisperm antibodies in the semen or in the cervical mucus. We consider the SCMC-test not only to be a simple and reliable technique for detecting the presence of these antisperm antibodies, but also a method of demonstrating the mechanism by which antisperm antibodies decrease the chance of conception.     

Effect of antisperm antibodies in males on in vitro fertilization

To investigate the effect of antisperm autoantibodies on the process of in vitro fertilization, sperm immobilization test and sperm agglutination test with serum, and direct immunobead test with semen were conducted on the male partners of 101 infertile couples. Fourteen patients were positive in at least one of these three antisperm antibody tests. Six of them were associated with a low fertilization rate (= LFR group, less than 50% of mature oocytes were fertilized), while the other 8 patients had a normal fertilization rate (= NFR group). The spermatozoa in the LFR group were bound to immunobeads of both IgG and IgA classes. In contrast, the spermatozoa in the NFR group were not bound to IgA. The results of the tests with serum were not related to the outcome of fertilization. By rapid dilution and washing of the semen containing antisperm autoantibodies, the percentage of spermatozoa bound to IgG decreased significantly. However, the rate of fertilization was not improved. Six pregnancies were achieved after 13 embryo transfers in the 14 patients. We conclude that the fertilization rate is reduced when spermatozoa are bound to both IgG and IgA antisperm autoantibodies, or to IgA alone. Antisperm autoantibodies do not seem to hamper embryonal development and implantation.     

Treatment of infertility caused by antisperm antibodies.

Twenty infertile couples with antisperm antibodies in the male or in the female partner were scheduled for treatment. In 15 couples the male and in 5 couples the female partner was the antisperm antibody carrier. In all the couples the result of the in vivo and in vitro sperm-penetration test was negative or poor. The SCMC-test was strongly positive in each of the couples. In all the couples IgG and IgA antisperm antibodies could be demonstrated on the spermatozoa or in the cervical mucus. It was postulated that antisperm IgA and not antisperm IgG is responsible for the penetration reduction of spermatozoa in cervical mucus and for the "shaking phenomenon" in the SCMC-test. Intrauterine inseminations, performed in 20 couples, resulted in four pregnancies. Condom therapy in three couples, for at lest 6 months, had no result. Two men were treated with 96 mg methylprednisolone per day for 7 days; this resulted in a slight decrease of the sperm-agglutination titre, but no pregnancy occurred.     

Relation between antisperm antibodies and the rate of fertilization of human oocytes in vitro

To clarify further the role of antisperm antibodies in in vitro fertilization, the occurrence of antisperm antibodies on ejaculated sperm and in sera was determined by the immunobead binding assay in 67 couples after an unsuccessful in vitro fertilization cycle. Antisperm antibodies in maternal sera were associated with a failure of oocyte fertilization (P <0.02) or with fertilization of only 9–19% of the oocytes (P <0.01) in vitro. Antisperm antibodies were detected in sera from 13 of 24 women (54.2%) where no fertilization occurred, 9 of 14 women (64.3%) where less than 20% of the oocytes fertilized, and 3 of 19 women (15.8%) where greater than 40% of the oocytes fertilized. Antisperm antibodies in these sera were mostly IgG and directed against the sperm tail. Antibodies on the surface of ejaculated motile sperm were also associated with a low (9–19%) fertilization rate (P <0.01). Sperm-bound antibodies were detected in 2 of 24 men (8.3%) where no fertilization occurred, 5 of 14 men (35.7%) where less than 20% of the oocytes fertilized, and 0 of 19 men where fertilization was greater than 40%. Sperm-bound antibodies were mainly IgA and were tail-directed. Antisperm antibodies in sera of males were not related to the rate of fertilization. Antisperm antibodies were detected in female partners of 21 of 46 couples (45.7%) with unexplained infertility, 2 of 12 women (16.7%) with blocked tubes, 4 of 7 women (57.1%) with endometriosis, and 0 of 2 women with adrenal hyperplasia. There was no relation between the fertilization rate and the maternal age, number of oocytes harvested, or semen quality. We conclude that antisperm antibodies are present in sera from a high percentage of women with unexplained infertility and that antibodies reacting with sperm tails may directly interfere with fertilization in vitro or may be a surrogate marker for another factor that interferes with this event.     

Assisted procreation in the presence of a positive direct mixed antiglobulin reaction test

Twenty-five infertile couples in which the male had antisperm antibodies were treated by in vitro fertilization (IVF), zygote intrafallopian transfer, or gamete intrafallopian transfer in 38 cycles. In 10 females a tubal pathology was present, and in the normal female patients repeated intrauterine insemination with husband sperm had failed. The presence of an andrological factor in 17 male patients did not influence the fertilization and the cleavage of the retrieved oocytes. Although the fertilization rate of 45.8% was significantly lower than in patients with tubal pathology, the pregnancy rate was 34.2% per started cycle and 44.8% per replacement. Furthermore, the embryos were of lesser quality than in couples with tubal and idiopathic infertility. This study suggests that IVF could be considered as a useful therapeutic approach for couples with a positive direct mixed antiglobulin reaction test before advising them the use of heterologous sperm.     

An ELISA for antisperm antibody detection in serum: comparison with TAT and SIT in serum, with MAR-test, immunobead-test and TAT in semen and with micro-SIT in cervical mucus

16 couples belonging to couples with negative or doubtful PCT were selected according to the presence of antisperm immunization. 12 patients, 5 male and 7 female, showed both localized and generalized immunization. The former was diagnosed by means of a positive IgG MAR-Test, direct IgG Immunobead-Test, direct IgG Immunobead-Test and seminal TAT in the male patients, and Micro-SIT in the cervical mucus of the female patients, while for the latter there was simultaneous positivity of both serum TAT and SIT, except for two cases, in which the SIT only was positive. The 4 remaining patients, 2 male and 2 female, did not show any signs of antisperm immunization. The evaluation of the antisperm antibodies by means of the ZER ELISA Antisperm Kit in the serum of the 16 patients examined showed that there were no significant statistical differences between the serum TAT and the SIT. The former showed agreement of the results in 93.75% of the cases, and the latter in 81.25%. A strict correlation was observed between the ELISA for serum antisperm antibodies (ELISA-AS-Abs) and the local immunitary situation, with agreement in 93.75% of the cases. The ELISA-AS-Abs seems to bring the advantage of eliminating the need for fresh semen for antibody titration and also means that there is no subjective interference with the evaluation of the results.     

IUI in male subfertility: are we able to select the proper patients?

There is at this time no indication as to which semen parameters from the fertility work-up discriminate between couples with male subfertility who will and will not benefit from intrauterine insemination (IUI). This study evaluated the predictive capacity of semen parameters (both pre- and post-wash) and antisperm antibodies (ASA) obtained during the fertility workup on IUI outcome in couples with male subfertility in a retrospective cohort study. It included 290 couples, who underwent 722 IUI cycles. The overall ongoing pregnancy rate was 9% per cycle. Model I, with female age, duration of subfertility, secondary subfertility, the presence of anovulation, cervical hostility and cycle number had an area under the curve (AUC) of 0.59. Adding the presence of ASA to this model improved the AUC to 0.65 (model II). Further addition of the post-wash total motile count (TMC) to the model with ASA (model III) improved the AUC to 0.67. Using the models to exclude couples from IUI due to low expected pregnancy rates would increase the pregnancy rate to 11% per cycle with model I, and to 14% per cycle for model II and for model III. In conclusion, in the selection of patients with male subfertility for IUI, the use of prediction models including ASA can increase the efficiency of IUI.     

The lack of influence of age on male fertility

OBJECTIVE: This study was undertaken to determine the effect of male aging on sperm quality as determined by semen analysis, the fertilization rate of human oocytes in vitro, and live birth rates. STUDY DESIGN: Retrospective analysis correlating outcome measures with male age was performed for 558 oocyte donation cycles in 441 couples. The oocyte donation model was chosen because it controls for oocyte quality and endometrial receptivity, which allows variations in sperm quality as a function of male age to be the only dependent variable. Outcome measures analyzed were semen analysis, fertilization rates in vitro, pregnancy rates, live birth rates, and cumulative live birth rates by life-table analysis. RESULTS: There was a negative correlation between male age and total sperm count, but there was no correlation between male age and any of the other parameters in the semen analysis. There was no association between male age and the fertilization rate of donated oocytes in vitro, pregnancy rates, or live birth rates. Recipient couples were grouped by quartiles of male age, and cumulative live birth rates were the same in the 4 groups. CONCLUSION: Whereas male aging is associated with a significant decline in total sperm count, this change is not reflected in a decreased fertilization rate or a decreased live birth rate in the oocyte donation model.     

Cryopreserved/thawed semen for in vitro fertilization: results from fertile donors and infertile patients

We evaluated the in vitro fertilization (IVF) outcome in 54 cycles using cryopreserved/thawed semen from fertile donors. Controls were other IVF patients matched by time frame, female age, stimulation protocol, number of pre-embryos transferred, and absence of a male factor using freshly ejaculated normal semen samples. In the study group and controls, respectively, post-thaw swim-up motility was 83.1% and 89.5%; fertilization rate of preovulatory oocytes (91.8%, 95.7%) and ongoing pregnancy rate (PR) per transfer (21.1%, 25.0%) were similar. The excellent fertilization rate with frozen/thawed semen was achieved through high-concentration insemination (0.5 x 10(6) motile sperm/mL). With use of frozen/thawed samples from infertile men (normal and subfertile samples), PR was similar but fertilization rate was lower. Cryopreserved semen is a valuable option for infertile couples in IVF therapy.     

Failure of intrauterine insemination in male immunological infertility in cases in which all spermatozoa are antibody-coated.

OBJECTIVE: To determine if the overcoming of the cervical mucus barrier removes the interference of sperm-bound antibodies with fertility. DESIGN: Prospective case series. SETTINGS: University-based intrauterine insemination (IUI) homologous program. PATIENTS: Nineteen patients with all spermatozoa in the ejaculate coated by antisperm antibodies. As control group, 86 consecutive patients without antisperm antibodies, treated for oligoasthenozoospermia or mucus hostility. INTERVENTIONS: Intrauterine inseminations (at least 3 attempts per couple). MAIN OUTCOME MEASURES: The outcome of IUIs, demographic, and seminal parameters were compared between the two groups. RESULTS: No pregnancy occurred in the couples with male immunological infertility, treated by 110 IUIs. Twenty-three pregnancies occurred in 22 (25.6%) of the control group couples who were treated by 411 IUIs. In the group of patients without antisperm antibodies, we demonstrated that the pregnancy rate (PR)/couple in oligoasthenozoospermia without teratozoospermia was similar to that achieved in normozoospermia (35% versus 38.9%), whereas it was significantly affected by teratozoospermia (3.6%). Only three patients with antisperm antibodies had teratozoospermia. Comparing the PR per couple and per cycle between the two groups of patients (with and without antisperm antibodies), excluding the patients with teratozoospermia, significant differences resulted (P less than 0.005 and P less than 0.005, respectively). The motile sperm count was not significantly different between the two groups, which also resulted to be homogeneous for demographic data. Moreover, the motile sperm count was not different between the patients with and without antisperm antibodies, who had successful IUI. CONCLUSIONS: The analysis of this trial suggests that the failure of IUI in the treatment of male immunological infertility is imputable to antisperm antibodies when they involve all spermatozoa, regardless of semen quality.     

The fertilization of human oocytes by spermatozoa from men with antispermatozoal antibodies in semen

Seventy-two couples, including 15 with antispermatozoal antibodies in the male partner's semen, were studied in a program of in vitro fertilization and embryo transfer. Cases were further subclassified as normospermic or oligospermic and antispermatozoal antibodies were assessed with categorization into the respective human immunoglobulin classes as determined using the indirect immunobead test. The study reveals that fertilization is significantly reduced (P<0.001) only if both IgA and IgG antibodies are present in semen but there is no reduction if either class is present alone. The fertilization rate of oocytes is significantly reduced (P<0.001) by sperm from oligospermic samples, and there is a further reduction in those cases with combined IgA/IgG antispermatozoal antibodies.     

A prediction model for ongoing pregnancy after in vitro fertilization in couples with male subfertility

OBJECTIVE: To assess the predictive capacity of male and female characteristics on in vitro fertilization (IVF) outcome in couples with male subfertility and to construct an IVF prediction model. STUDY DESIGN: We performed a cohort study including all couples with male subfertility undergoing IVF. The main outcome measure was an ongoing pregnancy after IVF. The baseline characteristics from a couple including parameters of the semen-analysis were included in a univariable and multivariable analysis to construct a prediction model (model I). The addition of antisperm antibodies (ASA) and post-wash total motile count (TMC) to models I, II and III, respectively, were analyzed. RESULTS: We included 275 couples with male subfertility who underwent 473 IVF cycles with an ongoing pregnancy rate of 19% per cycle. A prediction model containing female age, secondary subfertility, percentage progressively motile sperm, percentage sperm with normal morphology, prewash total motile sperm count, bilateral tubal pathology, history of intrauterine insemination and cycle number was constructed (model I). Prediction with model I resulted in the selection of 95 couples, of whom 55 conceived (pregnancy rate of 28% per cycle). Use of the model with n ASA (Model II) resulted in the selection of 79 couples, of whom still 55 conceived (30% per cycle). CONCLUSION: In couples with male subfertility, the use of a prediction model including ASA improves the efficiency of IVF.     

A new technique for intrauterine insemination.

The 5-cm long endpiece of a soft Nelaton's catheter, ch 6-8, splinted with a rigid polyethylene cannula, proved to be a suitable instrument for intrauterine homologous inseminations. Sixty couples were treated; indications for intrauterine insemination were subfertile semen, poor postcoital test, antisperm antibodies in male or female, and unexplained infertility of more than 5 years. Seventeen pregnancies occurred, that is 28%. The best results were obtained in the group with unexplained infertility and in the group with poor postcoital tests, combined with a good result of the in vitro sperm penetration tests. Complications of the inseminations were rare. The method did not elicit sperm agglutinins in the female; however, if sperm agglutinins were already present in the female, the titre level increased after the intrauterine inseminations.     

Chlamydial infection--a female and/or male infertility factor?

After screening a large series (n = 491) of asymptomatic males of infertile partnerships for chlamydial immunoglobulin (Ig) G antibodies (Chlam AB), no significant influence of past chlamydial infection was found with regard to semen analysis, postcoital testing, in vitro sperm-cervical mucus penetration tests with hormonally standardized cervical mucus, circulating antisperm antibodies (detected with three different methods), local IgG and IgA antibodies (detected by means of the mixed antiglobulin reaction test) on the sperm surface, the sperm-cervical mucus contact test, and a microbial screening of semen samples for mycoplasmas and other potentially pathogenic micro-organisms. However, when the findings were correlated with infertility factors of patients' female partners and the subsequent pregnancy rate in a prospective study, a significant positive correlation of male Chlam AB with a tubal factor in their wives as cause of the couple's infertility was found. The results suggest that the main influence of Chlamydia trachomatis on male fertility is based on sexual transmission and negative influence on tubal function of female partners, but not on reduced sperm functional capacity.     

Relationship of antisperm antibodies to oocyte fertilization in in vitro fertilization-embryo transfer

Antisperm antibodies (ASA) appear to impair reproduction; however, their clinical significance in in vitro fertilization-embryo transfer (IVF-ET) is unestablished. For examination of this question, the immunobead binding technique was used to identify IgA, IgG, and IgM ASA in the serum, semen, and follicular fluid (FF) of 40 couples undergoing IVF-ET. ASA binding to sperm tail tip did not predict the fertilization rate of uniformly inseminated mature oocytes. Similarly, ASA binding to sperm head in semen and male serum did not predict fertilization. However, the fertilization rate in couples with ASA to sperm head (ASA-H) of at least one isotype in female serum (n = 6) was significantly less than in those without ASA-H (n = 34; 34% versus 74%, P less than 0.01). Among these women, oocyte fertilization rates were 33% versus 71% (P less than 0.001). Sixty percent of women whose ova did not fertilize (n = 5) had ASA-H in their serum versus 6% of those whose ova did (n = 35; P less than 0.05). The presence of ASA-H in FF also correlated with fertilization. ASA-H in female serum reduced the zygote cleavage rate from 91% to 67% (P = 0.51). We conclude that the presence of ASA-H in female serum and FF is associated with reduced fertilization in IVF-ET.     

Quality of embryo does not affect the implantation rate of IVF-ET in infertile women with antisperm antibody

Objective: To determine whether low quality score of embryos and advanced maternal age affect the implantation rate in infertile women with sperm-immobilizing antibody.

Design: A retrospective study.

Setting: The IVF Unit of the Department of Obstetrics and Gynecology at Tokushima University Hospital.

Patient(s): Four infertile groups were studied: 20 women with sperm-immobilizing antibodies; 169 with tubal; 129 with male factor; and 72 with unexplained etiology.

Intervention(s): All women were hyperstimulated with GnRH analogue and scheduled ovarian stimulation with FSH and hMG for oocyte retrieval.

Main Outcome Measure(s): Relationship of quality of transferred embryos, implantation rate and maternal age among four groups of infertile couples.

Result(s): In the antisperm group, the fertilization rate (57.6%) and mean (±SD) score of transferred embryos (5.4 ± 1.9) were significantly lower than those in the tubal group (72.4% and 6.2 ± 1.9, respectively). However, the implantation rate in the antisperm group (23.6%) was significantly higher than those in other three groups (tubal, 8.6%; male factor, 9.5%; unexplained, 7.6%). With advancing maternal age, the implantation rate decreased in the three comparative groups. In contrast, the implantation rate in the antisperm group did not decrease with advancing maternal age.

Conclusion(s): Women with antisperm antibodies have several disadvantages to overcome in order to achieve successful IVF-ET, such as a low fertilization rate and poor quality of transferred embryos. However, a high implantation rate was observed in this group, even in women at advanced age. The occurrence of a cellular or humoral immune reaction against sperm may augment the uterine receptivity for the implantation of fertilized ova or blastocyst.     

Anti-sperm antibody levels are not related to fertilization or pregnancy rates after IVF or IVF/ICSI

Seminal antisperm antibodies (ASAs) have been associated with male infertility and a reduced probability of achieving a spontaneous pregnancy. However, the impact of ASAs on reproductive outcomes after assisted reproductive technologies (ARTs) remains controversial. We sought to further examine the relationship between ASAs and reproductive outcomes after in vitro fertilization (IVF) or IVF with intracytoplasmic sperm injection (ICSI). We conducted a retrospective study of consecutive IVF and IVF/ICSI cycles where the male partner had had direct ASA testing in the six months preceding the ART cycle. We examined the relationship between semen parameters (sperm concentration, motility, strict morphology, ASA levels [by direct mixed agglutination reaction and expressed as the percentage of spermatozoa with IgG or IgA antibodies]) and reproductive outcomes (fertilization and clinical pregnancy rate) after IVF and IVF/ICSI. There was no significant relationship between direct ASA levels and reproductive outcomes after IVF and IVF/ICSI. Similarly, we found no significant relationships between sperm parameters (concentration, motility, strict morphology) and reproductive outcomes after IVF and IVF/ICSI. Clinical pregnancy rates were not significantly different in ASA-positive (>50% of sperm coated with ASAs) compared with ASA-negative samples (42% vs. 52% respectively, odds ratio: 1.45 (95% CI 0.63, 3.30, P>0.05). The data indicate that ASAs in semen are not associated with reproductive outcomes (fertilization and clinical pregnancy rate) after IVF or IVF/ICSI.     

Effect of the number of inseminating sperm and the follicular stimulation protocol on in vitro fertilization of human oocytes in male factor and non-male factor couples

The effect of sperm concentration and follicular stimulation protocol on in vitro fertilization of human oocytes is not well established. Comparison was made of three inseminating concentrations (250,000, 375,000, and 500,000 progressively motile sperm/oocyte) and three protocols (human menopausal gonadotropin [hMG], clomiphene citrate [CC], and combination hMG/CC) on the fertilization rate of mature and immature oocytes in couples with male factor and non-male factor infertility. In non-male factor couples, total fertilization rates for CC, hMG, and hMG/CC were 70.3%, 54.5%, and 68.8%, respectively, while total fertilization rates at the varying number of inseminating sperm were not significantly different. Mature oocytes were more likely than immature oocytes to fertilize. Among semen male factor couples, there was no difference in fertilization by stimulation protocol; however, insemination with the higher number of inseminating sperm resulted in an increased fertilization rate.     

The impact of spermatic vein ligation on the male factor in in vitro fertilization-embryo transfer and its relation to testosterone levels before and after operation

Criteria for improved semen quality after varicocele operations are not clear, as they do not express sperm fertilization capacity, its most important qualification. Twenty-two couples, 12 with mechanical female infertility (group I) and 10 with normal female fertility (group II), in whom the husband had subfertile semen in the presence of varicocele, and who had failed preoperative in vitro fertilization-embryo transfer (IVF-ET) attempts, were readmitted for the IVF-ET procedure following the repair of varicocele. In group I, a 20% pregnancy rate was achieved after the operation, while no pregnancies occurred before surgery. In group II, four pregnancies (40%) were achieved after operation. Plasma testosterone (T) levels demonstrated a significant increase in 50% of the patients in both groups after surgery, resulting in a concurrent improved fertilization, cleavage, and pregnancy rates.     

An evaluation of the effect of pentoxifylline on sperm function and treatment outcome of male-factor infertility: A preliminary study

Objective Our objective was to study the effect of pentoxifylline (PF) on fertilization rates in couples with previous failure of fertilization and male-factor infertility and to determine the predictive value of conventional semen analysis parameters in selecting the couples who would benefit from the elective use of PF in IVF.Design This prospective controlled study was conducted in an assisted conception unit.Methods Sixty-nine couples with previous failed IVF cycle, who had a low fertilization rate and/or male-factor infertility, were recruited to the study. Multiple follicular development was induced using the same protocol of human menopausal gonadotropin and gonadotropin releasing hormone analogue in both cycles. The oocytes were inseminated with spermatozoa treated with PF. The fertilization rates in the PF cycle were compared to the reference cycle based on semen analysis parameters and previous fertilization rates.Results In couples with male infertility, the fertilization rate improved significantly, from 17 to 50% in PF cycles (P<0.001). A significant improvement in fertilization rate was also demonstrated in couples with previous poor fertilization. <30% (P<0.01). particularly in those with a very low fertilization rate, <20% (P<0.001). Although there was an overall improvement in fertilization rates in couples with male-factor infertility, there was no cutoff value in sperm motility that would make a significant difference in the impact of PF on fertilization rates.Conclusion Couples with poor fertilization rates in vitro benefit with a significant improvement in fertilization by the elective use of PF. The improvement is most significant in couples with previous complete failure of fertilization and poor fertilization rates, <30%.