Treatment of refractory infertility by transcervical intrauterine insemination of washed spermatozoa

Transcription

1 FERTILITY AND STERILITY Copyright c 1987 The American Fertility Society Printed in U.S.A. Treatment of refractory infertility by transcervical intrauterine insemination of washed spermatozoa William Byrd, Ph.D.*t Gary E. Ackerman, M.D.t Bruce R. Carr, M.D.t Clare D. Edman, M.D.t David S. Guzick, M.D., Ph.D.t John D. McConnell, M.D.:\: University of Texas Health Science Center, Dallas, Texas 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 (lui) 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 lui with washed sperm is a successful mode of therapy, especially in the case of males with asthenozoospermia. Fertil Steril 48:921, 1987 Artificial insemination by husband (AIH) has been used as a treatment modality for infertile couples for many years. Indications for AIH include abnormal semen parameters, abnormal or hostile cervical mucus, immunologic infertility, unexplained infertility, and physiologic or psychological dysfunction in the male. AIH has been performed using intravaginal, intracervical, or intrauterine insemination (lui). Received March 27, 1987; revised and accepted August 4, Reprint requests: William Byrd, Ph.D., Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, University of Texas Health SCience Center, Dallas, Texas t Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology. * Department of Surgery, Division of Urology. lui using washed spermatozoa has been used extensively only in recent years. The rationale for this approach involves bypassing the cervical barrier and depositing large numbers of washed, motile spermatozoa directly into the uterus. Theoretically, this method should enhance the fertilization and pregnancy rates over intravaginal or intracervical techniques. However, the success and benefits of using lui to treat certain types of infertility have been questioned. 1 Allen et al. 2 recently reviewed the results from 18 articles published between 1957 and 1984 in which lui was used singularly and found that the mean pregnancy rate for this method was 28% (range, 0% to 62%) in 714 patients. The discrepancies in pregnancy rates found among the various published studies are due, in part, to the selection of patient populations to be treated, the duration of infertility of the different Byrd et al. Intrauterine insemination 921

2 patient populations, and the type and severity of infertility. The purpose of this study is to review our experience with lui using washed spermatozoa in 113 couples. Patient Selection MATERIALS AND METHODS All couples who entered this program had at least 3 years of infertility prior to entry and an extensive infertility evaluation. They agreed to undergo at least three cycles of insemination with washed spermatozoa. All women had at least one patent fallopian tube and were able to ovulate spontaneously or with medication. No limits were placed on male semen parameters for entry into the study other than the presence of motile sperm in the ejaculate. While the cause of infertility was often multifactorial, the study population was divided into three categories based on the following criteria. Male factor patients were defined as males with <20 X 10 6 sperm/ml and <50 X 10 6 total sperm in the ejaculate and/or <40% sperm motility in the ejaculate in at least three semen analyses. Morphologic features of sperm in the ejaculate were determined by examination of fixed-stained slides. Except for males classified as oligoasthenospermic, all sperm samples had >50% normal forms. Other patients placed in the male factor category included men who had undergone a vasovasotomy and demonstrated high levels of sperm antibodies (IgA and IgG) in their serum and on their sperm. In these males, testing with rabbit antihuman IgA and IgG Immunobeads (BioRad, Richmond, CA) demonstrated that at least 80% of the motile sperm were coated with IgA and IgG antibodies. Two patients, one who underwent surgical correction for obstructed ducts (vasoepididyostomy) with subsequent repeated abnormal semen analyses and one patient with retrograde ejaculation, were also included in the male factor group. A second category of patients included in the study consisted of women with a cervical factor due to an anatomic disorder (cervical stenosis) or a functional disorder. Cervical stenosis was defined as a structuring of the exocervical canal so that a 3-mm uterine sound could not be passed through it. A functional disorder was defined as at least three abnormal postcoital tests (PCT) that were performed during the appropriate part of the menstrual cycle. A normal PCT was defined as more 922 Byrd et ai. Intrauterine insemination than one motile sperm per high-power field. Only women with an abnormal PCT whose husband had normal semen analyses were included in this group. In some cases, the husband of a woman with repeated abnormal PCT had an abnormal semen analyses. These patients were placed in the male factor group. A third category of subjects included women with minimal to moderate endometriosis or idiopathic infertility. Ovulation Monitoring The timing of ovulation was monitored by measuring urinary luteinizing hormone (LH) levels beginning 2 to 3 days before the expected date of ovulation based on previous basal body temperature (BBT) charts. Urinary LH levels were measured in our laboratory using urine samples collected during the midmorning, late afternoon, and early evening (when possible), and determined by a monoclonal antibody technique using the Ovustick kit (Urine LH 100 kits; Monoclonal Antibodies, Inc., Palo Alto, CA). Inseminations were performed on the day of the LH peak and on the following day, when possible. Sperm Preparation Fresh ejaculates were allowed to liquefy for 30 minutes at 37 C before processing. After a semen analysis, the ejaculate was transferred to a 15-ml conical centrifuge tube and 3 volumes of sperm wash and incubation medium was added to each volume of ejaculate and mixed by pipetting. The medium used for sperm washing and incubation consisted of Ham's F -10 medium (Gibco Laboratories, Grand Island, NY) supplemented with 25 mm sodium bicarbonate, 1.6 mm calcium lactate, 75 mg of penicillin (1650 U/mg), and 0.3% human serum albumin (Fraction V, Sigma Chemical Corporation, St. Louis, MO). All processing was performed using tissue culture tubes, flasks, and pasteur pipettes that had been cleaned, sterilized, and prepared for tissue culture. The mixture was centrifuged for 6 minutes at 200 X g and the supernatant discarded. The pellet was resuspended in 3 ml of medium and centrifuged again. Following the second centrifugation, the pellet was resuspended in 0.5 to 1.0 ml of medium and incubated for 90 to 120 minutes at 37 C in a 95% atmosphere:5% CO 2 incubator. After incubation, the supernatant (0.5 to 0.8 ml) containing motile sperm was carefully aspirated into a new tube and analyzed for count and motility be- Fertility and Sterility

3 fore insemination. In the case of males with severe oligospermia and asthenozoospermia, the entire sperm suspension was used for insemination. Insemination and Monitoring The sperm suspension was aspirated into a metal cannula (14-gauge animal feeding tube), which was connected to a 3-ml syringe. With the patient in Trendelenburg position, a speculum was placed in the vagina and the cervix cleaned with a cotton swab. The metal cannula was gently passed through the cervical canal and internal os into the uterine cavity and the contents of the syringe were slowly injected over 5 minutes. In patients with cervical stenosis a tenaculum was applied to the cervix to straighten the canal of the cervix and the small rigid catheter then was passed into the uterine cavity. After 15 minutes of resting in the supine position, the patients resumed normal activity. If the next menstrual period was delayed more than 14 days after the insemination, a quantitative beta human chorionic gonadotropin (ij-hcg) determination was performed on serum. If the ij-hcg was positive, an ultrasound confirmation of pregnancy was obtained after 6 weeks of gestation. Sperm Antibody Assay Immunoglobulins were assayed on the surface of spermatozoa with rabbit-antihuman Immunobeads using the procedure of Bronson et al. 3 The presence of antisperm antibodies in serum and cervical mucus was tested by incubating heat-inactivated serum or solubilized-heat-inactivated cervical mucus with antibody-free control sperm for 1 hour at 37 C before processing, as described by Bronson et al. 3 The extent of immunoglobulin in the sample was judged by the percentage of motile spermatozoa following incubation that bound Immunobeads complexed to rabbit-antihuman IgA, IgG, or IgM. Couples were categorized into two groups: (1) antibody-positive, defined as having at least one partner positive for sperm antibodies IgA, IgG, or IgM (>30% binding), or (2) antibody-negative, defined as both partners who had less than 30% of the motile sperm bound with Immunobeads. RESULTS A total of 68 patients underwent 229 insemination cycles (Table 1). The overall pregnancy rate was 38.2%, with a pregnancy rate per treatment cycle of 11.4%. While 113 patients began treat- Table 1 Results of Intrauterine Insemination Number of patients entering program 113 Number of spontaneous pregnancies 2 Number of patients completing three cycles of insemination or becoming pregnant 68 Number of cycles of treatment 229 Number of patients achieving pregnancy 26 Pregnancy rate per patient 38.2% Pregnancy rate per treatment cycle 11.4% Pregnancy outcome Live birth or ongoing pregnancy 22 Spontaneous abortions 4 ment, some dropped out of the program, 2 women became pregnant independent of treatment during the 24-month interval this study has been in progress, and the rest are still undergoing treatment. Only those couples who completed at least three cycles of lui (the minimum number of treatment cycles required in our protocol) or became pregnant were included in this study. The overall spontaneous abortion rate was 15.3%. Additionally, there were no ectopic pregnancies or infections related to lui treatment cycles. The average number of treatment cycles for patients achieving pregnancy was 1.7 versus 4.7 cycles of treatment for nonpregnant patients. The outcome of each pregnancy based on the type of infertility is shown in Table 2. For couples with a primary diagnosis of male factor, 9 of 21 couples (42.9%) achieved pregnancy. The highest pregnancy rate (83.3%) was seen in couples in which the male had isolated asthenozoospermia (less than 40% motility in the ejaculate, n = 6). While no pure oligospermic males are represented in this study, in couples in which the husband had both oligospermia and asthenospermia, the overall pregnancy rate was 33.3%. The four males who underwent a vasovasotomy all had greater than 80% binding of IgA and IgG rabbit-antihuman Immunobeads on their motile sperm. None of these men impregnated his spouse. Of the couples with cervical factor alone, the pregnancy rate was 34.5% (n = 29). Couples with unexplained infertility due to idiopathic causes or women with minimal to mild endometriosis had a pregnancy rate of 38.9% (n = 18). A wide variation in the semen parameters between the different categories was observed in the original ejaculates and following sperm processing (Table 3). As expected, males with asthenozoospermia or oligoasthenozoospermia exhibited abnormal semen parameters. Pregnancies were achieved with luis of sperm ranging from a low of Byrd et al. Intrauterine insemination 923

4 Table 2 Summary of Intrauterine Insemination Based on Primary Etiology Cause patients pregnant treatment cycles in pregnant patients" treatment cycles in nonpregnant patients" (%) Male factor Asthenospermia Asthenospermia and oligospermia Sperm antibodies Anatomic disorder (83.3) 3 (33.3) o 1 (50) 9 (42.9) 1.2 ± ± ± ± ± ± 1.0 Cervical factor Anatomic Functional o 10 (38.5) 10 (34.5) 2.1 ± ± ± ± ± 1.4 Other factors Endometriosis Idiopathic infertility (25) 6 (42.8) 7 (38.9) ± ± ± ± ± 1.3 " Mean ± standard deviation. 300,000 motile sperm in one severely oligoasthenozoospermic male to a high of 94 X 10 6 motile sperm in a male with retrograde ejaculation. The average number of motile sperm inseminated that resulted in a pregnancy was much lower in the male factor groups (with one exception) than in other patient groups, although male factor couples achieved a higher pregnancy rate than did those from the other categories. While all couples suspected of having immunologic infertility were tested before entry into the program, sperm antibody testing was not performed initially on all couples entering the program. To date, only one couple who tested positive by our criteria (>30% binding of motile sperm with Immunobeads, see Methods and Materials) has achieved pregnancy by lui (Table 4). We have examined 45 of the 68 couples for antibodies and have Table 3 Semen Parameters Based on Etiology Parameters of sperm used for insemination Cause sperm (X10 6 ) Ejaculate" Percent motile motile sperm (X10 6 ) Pregnant b motile sperm (XI0 6 ) Nonpregnant' Range (X10 6 ) Male factor Asthenozoospermia Asthenozoospermia and oligospermia Sperm antibodies Anatomic disorder Cervical factor Anatomic Functional Other factors Endometriosis Idiopathic " Mean of all ejaculates used for insemination. b Mean of all motile cells used in cycles when pregnancy oc- curred., Mean of all motile cells used in cycles with no pregnancy. 924 Byrd et al. Intrauterine insemination Fertility and Sterility

5 Table 4 Immunologic Infertility positive negative (percent (percent Cause tested pregnant) pregnant) (%) (%) Male factor 9 5 (20.0) 4 (50.0) Cervical factor 22 7 (0) 25 (46.6) Other 14 3 (0) 11 (54.5) (6.7) 30 (50.0) found that 15 couples tested positive for sperm antibodies. The pregnancy rate in these 15 couples was 6.7%. If the sperm antibody testing was negative in both partners, the pregnancy rate was 50.0% (n = 30). While all patients were encouraged to complete at least three treatment cycles, some discontinued therapy after one cycle when pregnancy did not occur. If all 113 patients are considered, the cumulative pregnancy rate reached a maximum after 5 months oftreatment (30.8%, Table 5). There is no significant difference between the pregnancy rate at 3 months and 5 months. From these data, we conclude that all patients should undergo at least three cycles of treatment, but no more than six cycles without being re-evaluated. DISCUSSION The use of lui for the treatment of infertile couples is predicated on the assumption that bypassing the cervical barrier and increasing the number of motile sperm in the upper reproductive tract will lead to enhanced pregnancy rates over that which would occur from natural intercourse or intracervical insemination. We offered lui to patients with specific indications and a prolonged history of infertility who had failed other forms of conventional therapy. This report describes our findings in 68 patients. The overall pregnancy rate in all groups was 38.2% and a pregnancy rate per treatment cycle was 11.4%. In contrast to many other published reports,1,2 we observed a high pregnancy rate (42.9%) in those couples with a primary male factor (n = 21). One of the major difficulties in trying to compare the efficacy of lui in this study with other studies is the absence of a control group of patients. In the absence of a control group, it is necessary to establish what the incidence of spontaneous pregnancy would be during months in which no treatment occurs. There is no question that spontaneous pregnancies (8% to 25 %) of infertile patients occur over extended periods. 4-6 However, the occurrence of a spontaneous pregnancy during a nontreatment cycle is much lower in several recent studies 7-15 compared with earlier studies. 4-6 The average spontaneous pregnancy rate (during the months in which lui was not done) reported in these studies and in our study using washed spermatozoa is 1.3% (N = 386). In our protocol, there were 26 pregnancies during 229 treatment cycles in 68 couples, but no pregnancies occurred during the 88 menstrual cycles in which these couples did not undergo treatment. Only 2 out of a total of 113 patients beginning lui have achieved pregnancy after dropping out of our protocol. We assume that the low spontaneous pregnancy rate in our study and other studies is due, in part, to selection of patients with at least 3 or more years of infertility. Since the average number of treatment cycles required for patients to achieve pregnancy was fewer than two cycles (n = 140),7-15 this would support a causeand-effect relationship and suggest that spontaneous pregnancies playa limited role, if any, here. There have been four recent studies7,15-17 using lui with appropriate controls in which only one pregnancy occurred in the control groups. Kerin et al.7 reported a 57.1% pregnancy rate in an lui-treated group with male factor couples compared with no pregnancies in a control group when LH timing of ovulation was used in combination with natural intercourse. Quagliarello and Arny15 reported a 30% pregnancy rate in women with cervical factor treated by lui as compared with no pregnancies in women with a cervical factor treated by intracervical insemination. Baerthlein et al. 16 compared a group of 26 couples who had failed three cycles of intravaginal and intracervical insemination who then underwent lui and 29 couples who were inseminated intravaginally and intracervically. They reported a 42% pregnancy rate in lui-treated patients, but no pregnancies in the other group. In a Table 5 Cumulative Pregnancy Rate per Treatment Cycle Percent Cumulative patients pregnant probability cycles treated pregnancies in cycle of pregnancy Byrd et al. Intrauterine insemination 925

6 prospective study, Cruz et aly compared the effectiveness of lui with that of intracervical insemination in 49 couples in which the male partner suffered from oligoasthenospermia. Patients were assigned randomly to either lui or intracervical insemination, and subsequent inseminations were alternated. The pregnancy rate in lui patients was 14.3%, while the pregnancy rate with intracervical insemination was 2%. These studies suggest that lui with washed spermatozoa offers a greater likelihood of success and that, while inclusion of control groups who receive no treatment is valid in controlled studies, it may be inappropriate to deny such treatment to patients with protracted infertility. Recently, lui has been used extensively for the treatment of patients with male factor, cervical factor, immunologic infertility, or unexplained infertility. This study and others using washed spermatozoa8-11,14,15 have shown that, when fresh washed spermatozoa are used in patients with documented cervical factors, the pregnancy rate following lui is 29.4% (range, 15.7% to 66.7%; n = 103). Thus, it would appear that lui does improve the chances of pregnancy in these individuals. Patients with male factor constitute the second major indication for lui. However, there is considerable disagreement as to the effectiveness of such therapy for this indication. In this study, we have shown a 42.9% success rate (n = 21) in all male factor patients and a 53.3% success rate in males with asthenozoospermia or oligoasthenospermia (n = 15). In other studies using fresh, washed sperm 7,8,10,18 the pregnancy rate in this group ranged from 0% to 57%; the average was 20.3% (n = 123). This discrepancy in pregnancy rates may be due to the criteria used to define the patients for this category, the processing techniques used, timing of insemination, and associated disease in the female partner. Since some males have a single defect (Le., oligospermia) while others have multiple defects, the efficacy of lui in treatment of male factor patients has been questioned on the basis of a poor pregnancy rate.1 The spontaneous pregnancy rate in the male factor group is often reported to be high (25%).4 However, this study included only 16 patients. In a larger study of 584 male factor couples, Aafjes et al. 6 found a 10.2% spontaneous pregnancy rate in patients with 2 to 4 years of infertility with a male factor. In this same study, if the male had experienced 6 years or more of infertility, the spontaneous pregnancy rate dropped to 2.2%. Thus, the likelihood of pregnancy appears to diminish as the duration of infertility lengthens. The optimal number of washed sperm that are required to be inseminated for maximal pregnancy rates remains to be determined. In our study, a successful pregnancy was established with an insemination of 300,000 motile sperm in one severely oligoasthenospermic male. A second pregnancy occurred with only 700,000 motile sperm. Bohrer et al. 19 found no correlation between the number of sperm inseminated during lui and the pregnancy rate per treatment cycle when the concentrations of sperm used was between 1 and 30 million. No pregnancies were observed when the number of sperm per transfer was less than 1 million. While the minimal number of sperm to be transferred remains to be determined, these findings would suggest that lui is a valid treatment option for severe male factor couples before in vitro fertilization-embry transfer (IVF -ET), artificial insemination by donor, or adoption is considered. Although some pregnancies do occur in couples using lui for immunologic infertility,2 lui as a treatment method for this type of infertility remains controversial. Sperm antibodies may be bound to the sperm, produced systemically in the female and diffuse into the reproductive tract or be produced locally within the female reproductive tract.20 The identification of sperm antibodies is further complicated by the various types of sperm antibody assays available. If sperm antibodies are bound to the sperm surface, simple washing prior to insemination will not remove the antibodies.21 In such cases, even if the cervix is bypassed, the presence of antibodies on sperm is known to interfere with the binding of sperm to the zona pellucida22 and with sperm-egg membrane fusion in the sperm penetration assay.23,24 The presence of sperm antibodies in the male or female also has been shown to lower the fertilization of human eggs in vitro.25 Thus, reduced fertility in couples with sperm antibodies appears to be dependent upon the site and synthesis of the antibodies, the type of antibodies present, the site of binding to the sperm, and the levels of antibodies present. We would like to emphasize that all of the foregoing results concerning "pregnancy rates" must be evaluated in the context of the methodology used. If all 113 patients in our sample were used to calculate the raw pregnancy rates (Table 5), there would be an underestimation of the true probability of pregnancy since some proportion of the Byrd et al. Intrauterine insemination Fertility and Sterility

7 patients left the program after one or two failed cycles or are still undergoing treatment and would have conceived in a subsequent cycle. This problem was circumvented by the use of life-table analysis (Table 5), which showed a cumulative probability of pregnancy of 27.2% after three cycles of treatment. For the detailed analysis of subgroups, however, where the sample size was smaller, we chose to include patients as "failures" only if they completed three or more cycles. This led to some overestimate of the true probability of pregnancy. It would have been preferable to do cumulative pregnancy curves for each subgroup, but the sample size was not sufficient for reliable life-table estimates. The results of this study would indicate that lui with washed sperm can result in viable pregnancies in patients with varying causes of infertility. We recommend that this procedure be considered in all suitable patients as a final treatment prior to IVF ET, gamete intrafallopian transfer, or artificial insemination by donor. REFERENCES 1. Moghissi KS: Some reflections on intrauterine insemination. Fertil Steril 46:13, Allen NC, Herbert CM III, Maxson WS, Rogers BJ, Diamond MP, Wentz AC: Intrauterine insemination: a critical review. Fertil Steril 44:569, Bronson R, Cooper G, Rosenfeld D: Ability of antibodybound human sperm to penetrate zona-free hamster ova in vitro. Fertil Steril 36:778, Glass RH, Ericsson RJ: Spontaneous cure of male infertility. Fertil Steril 31:305, Nachtigall RD, Faure N, Glass RH: Artificial insemination of husband's sperm. Fertil Steril 32:141, Aafjes JH, Vijver JCM, Schenck PE: The duration of infertility: an important datum for the fertility prognosis of men with semen abnormalities. Fertil Steril 30:423, Kerin JFP, Kirby C, Peek J, Jeffrey R, Warnes GM, Matthews CD, Cox LW: Improved conception rate after intrauterine insemination of washed spermatozoa from men with poor quality semen. Lancet 1:533, Sher G, Knutzen VK, Stratton CJ, Montakhab MM, Allenson SG: In vitro sperm capacitation and transervical intrauterine insemination for the treatment of refractory infertility: phase 1. Fertil Steril 41:260, Tollie RC, Nagel TC, Tagatz GE, Phansey SA, Okagaki T, Wavrin CA: Intrauterine insemination: the University of Minnesota experience. Fertil Steril43:743, Wiltbank MC, Kosasa S, Rogers B: Treatment of infertile patients by intrauterine insemination of washed spermatozoa. Andrologia 17:22, Confino E, Friberg J, Dukiewicz AB, Gleicher N: Intrauter- ine inseminations with washed human spermatozoa. Fertil Steril 46:55, DiMarzo SJ, Rakoff JS: Intrauterine insemination with husband's washed sperm. Fertil Steril46:470, Hoing LM, Devroey P, Van Steirteghem AC: Treatment of infertility because of oligoasthenoteratospermia by transcervical intrauterine insemination of motile spermatozoa. Fertil Steril 45:388, Hull ME, Magyar DM, Vasquez JM, Hayes MF, Moghissi KS: Experience with intrauterine insemination for cervical factor and oligospermia. Am J Obstet Gynecol 154:1333, Quagliarello J, Arny M: Intracervical versus intrauterine insemination: correlation of outcome with antecedent postcoital testing. Fertil Steril 46:870, Baerthlein WC, Muechler EK, Chaney K: Intrauterine insemination with washed semen and AIH: a comparison utilizing urinary LH determinations (Abstr). Presented at the forty-second annual meeting of The American Fertility Society and the eighteenth annual meeting of the Canadian Fertility and Andrology Society, September 27 to October 2, 1986, Toronto, Ontario, Canada. Birmingham, The American Fertility Society, 1986, p Cruz RI, Kemmann E, Brandeis VT, Becker KA, Beck M, Beardsley L, Shelden R: A prospective study of intrauterine insemination of processed sperm from men with oligoasthenospermia in superovulated women. Fertil Steril 46:673, Harris SJ, Milligan MP, Masson GM, Dennis KJ: Improved separation of motile sperm in asthenospermia and its application to artificial insemination homologous (AIH). Fertil Steril 36:219, Bohrer M, Kemmann E, Pasquale S, Shelden RM: The significance of the total number of motile sperm delivered with intrauterine insemination (lui) in menotropin treated women (Abstr). Presented at the forty-second annual meeting of The American Fertility Society and the eighteenth annual meeting of the Canadian Fertility and Andrology Society, September 27 to October 2, 1986, Toronto, Ontario, Canada. Birmingham, The American Fertility Society, 1986, p Moghissi KS: The function of the cervix in human reproduction. Curr Probl Obstet Gynecol 7:4, Bronson RA, Cooper GW, Rosenfeld DL: Autoimmunity to spermatozoa: effect on sperm penetration of cervical mucus as reflected by postcoital testing. Fertil Steril 41:609, Bronson RA, Cooper GW, Rosenfeld DL: Sperm-specific isoantibodies and autoantibodies inhibit the binding of human sperm to the human zona pellucida. Fertil Steril 38:724, Haas GG, Sokoloski JE, Wolf DP: The interfering effect of human IgG antisperm antibodies on human sperm penetration of zona-free hamster eggs. Am J Reprod Immunol1:40, Alexander NJ: Antibodies to human spermatozoa impede sperm penetration of cervical mucus or hamster eggs. Fertil Steril 41:433, Clarke GN, Lopata A, McBain JC, Baker HWG, Johnston WIH: Effect of serum antibodies in males on human in vitro fertilization (IVF). Am J Reprod Immunol Microbiol 8:62, 1985 Byrd et a1. Intrauterine insemination 927