Correlation between quantitative antibody titers of sperm immobilizing antibodies and pregnancy rates by treatments

Immunological infertility in women who possessed sperm immobilizing (SI) antibodies made it very difficult to conceive using the usual treatments. We examined SI antibodies by the quantitative Sperm Immobilization Test and found the antibody titers (50% sperm immobilization unit: SI50 unit) associated with pregnancy rates. Patients with high SI50 titers (greater than 10 units) did not conceive by ordinary or repeated artificial inseminations with husband's semen (AIH) except when treated with in vitro fertilization (IVF) and embryo replacement. Patients with relatively low SI50 titers (less than 10 units) could conceive either by repeated or ordinary AIH, though the success rates were lower than by IVF-embryo replacement. It is important to assess the SI50 titers by the quantitative method to select treatments for infertile women with SI antibodies. In follow-up studies of the patients who conceived successfully, it was found that SI50 titers tended to decline as pregnancy proceeded.     

An endometrial antibody assay in the clinical diagnosis and management of endometriosis

Coded serum samples from 11 normal fertile men and 17 fertile women without endometriosis (control groups) and 41 women with endometriosis were tested blindly for the presence of endometrial antibodies by use of a passive hemagglutination assay. Endometrial antibodies were either absent or present in low baseline titers in the serum samples from the control group. In contrast, 17 of the 23 (74%) patients with untreated endometriosis had elevated titers of endometrial antibodies in their serum. Of the 18 patients treated with danazol, endometrial antibodies were absent in 7 women who showed a good response at repeat laparoscopy, whereas 4 of 5 women with a poor response had significantly positive titers of antibodies. Six patients treated with danazol did not have repeat laparoscopy, but were found to have endometrial antibody titers in the baseline control range. Endometrial antibody titers in women with a good response to danazol were significantly lower than those in women with untreated endometriosis or with a poor response to danazol (P = 0.003). No correlation was observed between the antibody titers and the stage of endometriosis. The results suggest that the assay for serum endometrial antibodies may prove to be a clinically useful, noninvasive aid in the diagnosis of endometriosis. Sequential determination of endometrial antibody titers may be helpful in assessing the efficacy of pharmacologic therapy for endometriosis and evaluating the cases of patients with possible recurrence of the disease.     

Prednisone does not prevent recurrent fetal death in women with antiphospholipid antibody

Effects of therapy, antibody titer, and pregnancy history on pregnancy outcome were evaluated in pregnancies of women with antiphospholipid antibody. Prior fetal death and a high antiphospholipid antibody titer (greater than 40 IgG phospholipid units) contributed independently, in an additive manner, to current fetal loss. Twenty-one pregnancies occurred in asymptomatic women who had both prior fetal death and a high IgG antiphospholipid antibody titer. In this very high-risk group, 9 of 11 (82%) of pregnancies treated with prednisone, 10 to 60 mg/day, ended in fetal death, compared with 5 of 10 (50%) not treated with prednisone (p approximately 0.01, life-table analysis). Of pregnancies treated with aspirin, 80 mg/day, 9 of 14 (64%) treated and 5 of 7 (71%) not treated with prednisone had a fetal death (difference not significant). Prednisone does not improve, and may worsen, current fetal outcome in asymptomatic pregnant women with a high antiphospholipid antibody titer and prior fetal death.     

A comparison of ovulation suppression and ovulation stimulation in the treatment of endometriosis-associated infertility.

This study compares ovulation stimulation or suppression with the pregnancy rate among infertile couples with endometriosis. The design is a nonrandomized, prospective, multicentered cohort analytic study. Two hundred and ninety-seven couples with laparoscopy-proven endometriosis were analyzed: 68 received no therapy, 42 received clomiphene and 74 received danazol. Forty patients (22%) conceived and pregnancy rates were similar in each treatment group. The relative likelihood of pregnancy associated with clomiphene was 2.9 (95% confidence limits 1.2-7.1); the relative likelihood of pregnancy with danazol was 1.02 (95% confidence limits 0.5-2.3). This study suggests that pregnancy rates during clomiphene treatment could be superior to expectant therapy, while pregnancy rate after danazol is similar to no treatment.     

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.     

Active immunization of female rabbits with purified rabbit acrosin and effect on fertility.

Acrosin immunogen was purified from rabbit testes by sequential acid extraction, ammonium sulfate fractionation, cation-exchange, and affinity chromatography. Twelve females received intradermal injections of purified acrosin in Freund's complete adjuvant followed by a booster injection 6 weeks later. A radioimmunoassay for rabbit acrosin was developed and used to monitor the immune response of the recipients. The females were mated at the time when serum titers of acrosin antibodies were maximal. Four of the animals did not become pregnant, and three of these had the highest antibody titers in the total group. The remaining eight rabbits delivered normal litters at term. Of four control females (immunized with bovine serum albumin), one did not become pregnant. The pregnancy rates for the control and acrosin-immunized rabbits were 75% and 67%, respectively. It is concluded that, although active immunization with acrosin had no significant effect on fertility, the antibody titer produced may be a factor.     

Prognosis of fertility in women with unexplained infertility and sperm agglutinins in the serum

From 1967 to 1973 serum samples of 1709 infertile women were tested for antispermatozoal antibodies with the gelatin agglutination test. In 110 cases sperm agglutinins were demonstrated in titers ranging from 4 to 1024. The clinical data of 99 couples were evaluable, and in 65 there appeared to be unexplained infertility. Out of these 65 women, 44 became pregnant in the posttesting follow-up period of 6 to 13.5 years (median, 10 years). With increasing titers there was a significant decrease in the probability of becoming pregnant. Of the women who became pregnant, in general, those with higher titers had to wait longer for their pregnancy than those with lower titers. Moreover, with increasing titers there was a tendency toward a longer duration of infertility before the serum was tested. This latter observation supports the contention that the agglutinin titer influences the fecundability rate. The titers of those becoming pregnant and those remaining infertile, however, showed considerable overlap. Favorable results in the postcoital test were associated with a better prognosis, but this was independent of the titers.     

A prospective study on the lack of development of antisperm antibodies in women undergoing intrauterine insemination

To test the hypothesis that intrauterine insemination with washed spermatozoa induces antisperm antibody formation, we measured serum antisperm antibody levels by the Immunobead technique in a population of women receiving exogenous gonadotropins. Antibody levels were measured before therapy (baseline) and then serially during subsequent stimulation cycles, for a maximum of six cycles. Twenty-eight patients underwent intrauterine insemination; each patient served as her own control. An additional 25 patients were treated with exogenous gonadotropins but did not undergo intrauterine insemination; they served as external controls. Antisperm antibody levels in women who underwent concomitant intrauterine insemination were compared with levels in those who did not. Of the 53 enrolled patients, 18 completed six treatment cycles, and 35 achieved pregnancy before six cycles. Forty-five patients (85%) had less than 10% Immunobead binding, six (11%) had binding between 10% and 25% (mean 16%, range 14% to 20%), and two had binding greater than 25% (28% and 42%, respectively). Mean binding was similar (less than 10%) in the intrauterine insemination and external control groups. Eighteen patients conceived in the intrauterine insemination group and seventeen in the control group. Of patients who conceived, all but one had less than 10% Immunobead binding at the time of conception (mean 1.6 months). In patients who did not conceive, there was no difference in Immunobead binding between control and intrauterine insemination groups after 6 months of therapy. Our data do not support the hypothesis that serum antisperm antibody levels, as detected by Immunobead binding, will increase in menotropin-stimulated women undergoing intrauterine insemination over a prolonged treatment period.     

Pregnancy after treatment in patients with prolactinoma: operation versus bromocriptine

Prolactinoma was diagnosed in 190 women of the same age range, among whom 88 were treated with transsphenoidal microadenectomy and 102 with bromocriptine. The purpose of this study was to compare the two groups according to classification of the adenomas by size and invasiveness, pregnancy rates, prolactin levels after pregnancy, sella turcica changes after pregnancy, and serum prolactin levels and radiologic changes in patients who were operated on but did not become pregnant or did not desire pregnancy. In the group with operation, 91% of patients who had microadenoma and 88% of those with diffuse adenoma conceived, but none who had invasive tumors did so. In the bromocriptine-treated group, among patients with no visible microadenoma or with microadenoma seen radiologically 56% conceived; among those with diffuse adenoma 66% conceived; no patients with invasive adenoma were in this group. In the group with operation, 21% had higher serum prolactin levels and amenorrhea after pregnancy, compared with 19% in the medical treatment group and 19% in the group with operation who did not conceive. Of all patients studied, radiologic changes in the pituitary fossa were seen in only one patient undergoing operation.     

Factors affecting pregnancy rates in a donor insemination program using frozen semen

The results of therapy of 226 women receiving frozen and fresh donor semen are reported. Overall, 45.6% of patients conceived with a monthly fecundability of 0.102. The effect of a variety of factors on fertility rates was analyzed in life-table analysis of 1000 cycles. Optimal pregnancy rates were obtained in couples with azoospermia (0.17) or no female infertility factors (0.2). Patients with ovulatory dysfunction treated with clomiphene also had optimal pregnancy rates (0.17 per cycle). Endometriosis reduced fecundability significantly (0.04 per cycle). There was no significant difference in pregnancy rates per cycle between fresh (0.12) and frozen (0.09) semen. Acceptable pregnancy rates were obtained with frozen semen therapy and in patients with treated ovulatory dysfunction.     

Treatment of refractory infertility by transcervical intrauterine insemination of washed spermatozoa

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

An in vivo technique for screening immunologic factors in the etiology of the unexplained poor postcoital test

A study was designed to determine the incidence and etiology of the unexplained poor postcoital test. An in vivo comparison of sperm penetration by husband's versus donor sperm in the wife's estrogen-stimulated mucus was performed. The 8 of 30 women showing improvement of husband's penetration in mucus (group 1) were treated with high-dose estrogen (HDE) and hMG, and 4/8 conceived. Anti-sperm antibodies (ASA) were insignificant in this group. In group 2, in which donor sperm penetrated but husband's sperm did not, 8 men of 17 were found to have an ASA level over 50% on the sperm surface; 6/8 treated with high-dose methylprednisolone (MP) had an improved postcoital test, and 5 achieved a pregnancy. Two patients with levels under 50% were still treated with MP, and one achieved a pregnancy. In five group-3 couples, positive ASA were found in the cervical mucus of two women; and one woman improved on the postcoital test and conceived following MP therapy. The 30 unexplained poor postcoital tests occurred in 5,000 couples evaluated. In general, those patients considered to have significant clinical antibody had levels over 50%. Because side effects of MP may be severe, and positive ASA may be found in normal donors, it is important to use a comparison penetration test to help determine if treatment with corticosteroids seems reasonable.     

Cytotoxic sperm antibodies and in vitro fertilization of mature oocytes: A preliminary report

The fertilization rates of mature oocytes during in vitro fertilization and embryo transfer (IVF-ET) using fetal cord serum-supplemented insemination media were 57% for five infertile couples without sperm antibodies (group 1). But they were 50% for four of nine infertile couples (group 2) with cytotoxic sperm antibodies in both partners (n=6) or the husband alone (n=3). Two women in group 1 were successful in achieving normal, full-term pregnancies with the delivery of normal infants (²=4.2, P < 0.05, by chi-square analysis). One of them consistently tested negative for sperm antibodies, while her husband was previously treated with antibiotics for infection and transient sperm antibodies in the seminal plasma. Subsequently, antibody liters in the husband were in the normal range when the successful IVF-ET was performed. One woman in group 2, with antibodies to her autoimmune husband's sperm but not control sperm and with a long-standing poor postcoital test sperm motility, conceived through artificial insemination with donor sperm (AID) after failing to conceive with her husband through IVF-ET. These data suggest that the presence of cytotoxic sperm antibodies in the serum and/ or secretions of both partners reduces the rates of fertilization of mature oocytes in spite of using fetal cord serum in the IVF media. Pregnancy achievement is impaired in this group.     

Causes and outcome of infertility in previously unexamined couples

The etiology of infertility was evaluated in 98 previously unexamined couples at Helsinki University Central Hospital. Female endocrine disturbances (33%) and male causes (26%) were the most common factors of infertility. Two or more causes were found in 28 couples (29%). Both female and male factors were involved in 8% of cases. Eighteen of 98 women became pregnant during the infertility evaluation before any treatment was given. At four years the cumulative pregnancy rates were 65% for all couples and 60% and 51% for couples with single-factor and multifactorial infertility, respectively. The mean age was significantly higher (p less than 0.05) among those who failed to conceive than among those who conceived. Ovulatory disturbances and multiple causes are common factors in reproductive failure, but even in the presence of multifactorial infertility the primary referrals have good chances of achieving pregnancy.     

Artificial insemination with fresh donor semen

One hundred and thirty-four patients received artificial insemination with fresh donor semen (AID). Using the life-table method of analysis, 72 pregnancies occurred, yielding a crude conception rate of 53.7%. The 134 women received an average of three inseminations per cycle for a total of 1,282 inseminations near the day of ovulation. The majority of pregnancies occurred by the seventh cycle. Forty-two pregnancies were achieved using a single donor; 30 pregnancies required changing the donor once, twice, or more. Among 42 patients who subsequently were treated with clomiphene citrate, 16 conceived. Two of these patients became pregnant after receiving hMG and hCG additionally. The life-table analysis of cumulative pregnancy rates following infertility therapy provides a relatively simple, powerful, and reliable tool for evaluating the effectiveness of therapy and its benefits. Patients should be advised that their chances of conception with AID approach that of normal fertile couples, provided that these patients persist in their treatment.     

The cervical cap for home artificial insemination

The cervical cap was used in artificial insemination (husband) in the home by 63 couples. An overall pregnancy rate of 19% occurred regardless of the duration of use, and a rate of 44% was associated with use for at least six months or until pregnancy occurred. Comparison of pregnancy rates between those in the program and those who dropped out and conceived without therapy revealed no statistical difference.     

Antisperm antibodies in infertility: the role of condom therapy

Condom therapy has been widely used in the treatment of infertility to counteract the supposed harmful effects of antisperm antibodies. From an immunologic point of view this approach, although it may work, is illogical. Cortisone has been used experimentally on 4 of 6 couples selected from 257 patients with elevated titers of antisperm antibodies; spontaneous disappearance of antisperm antibodies occurred, followed by pregnancy, in the 2 control couples who did not receive cortisone. Only 2 of the 4 couples treated with cortisone became pregnant, although antisperm antibodies disappeared in all of them because of the treatment. It is possible that pregnancies occur in marriages that are barren due to the presence of antisperm antibodies, but it often occurs when these antibodies disappear spontaneously. A programmed schedule of the gradual decrease of coitus with condoms after a period of normal sexual intercourse has theoretic immunologic merit in bringing about normal pregnancies in previously infertile couples.     

Effect of Chlamydial antibodies on the outcome of in vitro fertilization (IVF) treatment

Objective Our objective was to study the relationship between the presence of Chlamydia trachomatisantibodies and the success of IVF treatment.Design We evaluated 118 in vitro fertilization and embryo transfer (IVF-ET) treatment cycles from 51 couples with a history of infertility lasting for at least 2 years. All women starting a treatment cycle had their serum chlamydial antibody titers measured by indirect immunofluorescent technique. All patients received similar ovarian stimulation regimens and the oocytes collected were inseminated with similar concentrations of motile sperm. Clinical data from couples where the female partner had C. trachomatisab titers 40 have been compared with the equivalent data from couples where the female partner had C. trachomatisab titers <40.Results There was no statistically significant difference between the two groups concerning age, infertility period, oocytes collected, oocytes fertilized, and fertilization rate, and the pregnancy rates were comparable.Conclusion Previous exposure to C. trachomatisdid not alter the success rate of IVF-ET.     

Early conception in patients with untreated mild endometriosis

The purpose of this paper is to report the reproductive experience in 31 infertile patients with mild endometriosis who were not treated by surgery or medication. A series of 31 cases of laparoscopically diagnosed mild endometriosis were followed up without therapy for a period of 36 months. Ten patients received artificial insemination by donor (AID) because of male-related infertility; 21 patients had well-timed postcoital tests and monitored ovulation cycles. Life-table analysis of conceptions was used for presentation of the pregnancy rate. The group of patients whose husbands were azoospermic had a 90% pregnancy rate within 18 months, with a mean of 3.5 treatment cycles for pregnancy. The nonazoospermic couples had a 47.6% pregnancy rate within 18 months, with a mean of 7.2 monitored cycles for pregnancy. The calculated median delays for the series of patients who conceived were 1.9 cycles. The whole series (n = 31) of patients with mild endometriosis had an 8.3% monthly pregnancy rate within 18 months and a 61.2% cumulative pregnancy rate within 18 months. We have come to the conclusion that mild endometriosis does not interfere with female fertility, and patients with this extent of disease should not be treated for a trial period of at least 18 months as an alternative to more aggressive therapy.     

Circulating sperm antibodies: indications for testing in infertile couples

Sperm antibody titers were evaluated in the serum of 73 infertile couples by the F-D and Kibrick agglutination tests, to study the relationship of the quality of post-coital tests and semen analysis. Thirty-eight couples had poor post-coital tests, fifteen couples had normal post-coital tests, and twenty couples revealed abnormal semen pictures of the males. In the first two groups, semen analysis was normal. The incidence of sperm antibodies was 10.5%, 6.6% in men, and 18.4%, 20.0% in women, with poor and normal post-coital tests, respectively. This suggests that sperm antibody testing is equally indicated in infertile couples with poor post-coital tests. In addition, there was no difference in the incidence of sperm antibodies in men with poor semen pictures and those with normal semen analysis in this infertile population. This suggests the significance of sperm antibody testing in infertile men with abnormal and normal semen pictures after correcting other infertility factors, in order to detect those patients who could benefit from treatment of such immunologic problems.