Association of unexplained infertility with gonadotropin and ovarian antibodies

PROBLEM: To determine the prevalence and characteristics of gonadotropin autoantibodies (GAB) associated with unexplained infertility, and to assess the relationship between ovarian autoantibodies (OVAB) and GAB. METHOD OF STUDY: Ovarian antibodies and GABs in sera of patients with unexplained infertility (n = 53) and a comparison (population) group from a blood bank (n = 40) were detected by immunoassay. Patients with unexplained infertility had either no prior gonadotropin treatment (n = 15) or two or more gonadotropin cycles to induce ovulation (n = 38). RESULTS: The GABs were detected in 67% of women with treatment, 27% of women without treatment and 8% of women in the population. The GABs recognized follicle stimulating hormone (FSH) and luteinizing hormone (LH) and their alpha and beta subunits and to a lesser extent thyroid stimulating hormone (TSH) and prolactin. There was no significant difference in OVAB prevalence between gonadotropin treated or untreated women while GABs were significantly more frequent in gonadotropin treated women (P < or = 0.01). CONCLUSION: Gonadotropin antibodies may represent a separate marker of ovarian autoimmunity in unexplained infertility as they are correlated with OVAB and are present in patients not treated with gonadotropin. However, as a higher frequency of GAB is associated with gonadotropin treatment, patients with ovarian autoimmunity may tend to have an immune response to gonadotropins in addition to an endocrine response.     

Ovarian antibodies, FSH and inhibin B: independent markers associated with unexplained infertility

Premature menopause and unexplained infertility are associated with ovarian antibodies, a marker of ovarian autoimmunity. In premature menopause, FSH is also elevated while in unexplained infertility FSH concentrations are often normal. The relationship of ovarian antibodies and FSH and inhibin B, as markers of follicle function, was investigated in unexplained infertility. Ovarian antibodies were determined by immunoassay in comparison to normal controls (n = 12); 51.9% were positive at two SD (P < 0.05) and 38.5% were positive at three SD above the control mean (P < 0.01). In this study three SD above the control mean was considered positive. In unexplained infertility, three out of 10 (30%) had elevated day 3 FSH (>10 mIU/ml) and ovarian antibodies, while 17/42 (40%) had normal FSH (<10 mIU/ml) and ovarian antibodies. In women with normal FSH, two out of seven (29%) had low inhibin B concentrations (<33 pg/ml) and ovarian antibodies, and 15/35 (43%) had normal inhibin B concentrations (> 33 pg/ml) and ovarian antibodies. Similarly, when women with and without ovarian antibodies were compared there was no difference in mean FSH or mean inhibin B concentrations. Thus, unlike other endocrine autoimmune disorders, hormone concentrations are not predictors of potential ovarian autoimmunity. This suggests that in unexplained infertility ovarian antibodies are an independent marker of potential ovarian failure, and may precede changes in regulatory hormones.     

Pregnancy outcome and ovarian antibodies in infertility patients undergoing controlled ovarian hyperstimulation

PROBLEM: Several endocrine markers are well-established, but not absolute, predictors of successful outcomes following controlled ovarian hyperstimulation. Another potential predictor for success may be a marker of ovarian autoimmunity. Ovarian antibodies (OVAB) are detected in women with unexplained infertility. We tested the hypothesis that women with OVAB have a poorer pregnancy outcome in in vitro fertilization (IVF). METHOD OF STUDY: Serum samples (n = 47) were assessed by a previously described immunoassay for OVAB in a cross-sectional, retrospective study design. RESULTS: Women who became pregnant had a lower frequency of OVAB than women who did not become pregnant (25.0% [4/16] vs. 58.1% [18/31], respectively; P = 0.03). There was no significant difference in day 3 estradiol, amount of human menopausal gonadotropin given, peak estradiol, the number of follicles observed, or the number of eggs retrieved between women who achieved pregnancy and those who did not. CONCLUSIONS: Together with other information such as reproductive hormone levels and measures of follicle growth, OVAB may contribute additional information for prediction of successful IVF outcomes.     

The Presence of Antithyroid Antibodies in Euthyroid Patients With Unexplained Infertility and Tubal Obstruction

PROBLEM: The presence of antithyroid antibodies in euthyroid patients with unexplained infertility and tubal obstruction. METHOD: The presence of antithyroid autoantibodies (microsomal and thyroglobulin) was measured in 40 patients with unexplained infertility, and 40 patients with tubal obstruction infertility, and compared to 40 healthy nulligravidae. RESULTS: Eight patients (20%) in the unexplained infertility study group, seven (17.5%) in the tubal obstruction group and two (5%) in the healthy nulligravida group, were positive for antithyroid autoantibodies: five (12.5%) were positive for antimicrosomal antibodies, two (5%) were positive for antithyroglobulin antibodies, and one patient (2.5%) was positive for both. The tubal obstruction group comprised seven (17.5%) patients positive for antithyroid autoantibodies: four (10%) for antimicrosomal antibodies, two (5%) for antithyroglobulin antibodies, and one patient (2.5%) was positive for both. In the healthy nulligravidae group only two patients (5%) were positive for antithyroid antibodies: one for antimicrosomal and one for antithyroglobulin. No significant differences were found in the presence of antithyroid antibodies between patients with unexplained infertility and those with tubal obstruction infertility. Both groups differed significantly from the healthy controls with regard to the presence of antithyroid antibodies (P < 0.05). CONCLUSION: Subclinical presence of antithyroid autoantibodies is characteristic of both unexplained and mechanical infertility, as opposed to healthy controls. Further investigation of larger groups is needed to determine the prevalence of antithyroid antibodies in the unique population of infertile women.     

The contribution of subtle oocyte or sperm dysfunction affecting fertilization in endometriosis-associated or unexplained infertility: a controlled comparison with tubal infertility and use of donor spermatozoa

This study aims to determine the relative contribution of oocyte and/or sperm dysfunction to the reduction of fertilization rates in vitro in cases of minor endometriosis and prolonged unexplained infertility. The results of in-vitro fertilization (IVF) treatment with ovarian stimulation have been compared between couples with the above conditions and women with tubal infertility (as control for oocyte function) and the use of donor spermatozoa (as control for sperm function). Fertilization and cleavage rates using husband's spermatozoa were significantly reduced in endometriosis couples (56%, n = 194, P < 0.001) and further significantly reduced in couples with unexplained infertility (52%, n = 327, P < 0.001) compared with tubal infertility (60%, n = 509). Using donor spermatozoa the rates were the same as using husband's spermatozoa in tubal infertility (61%, n = 27) or endometriosis (55%, n = 21) but significantly though only partly improved with unexplained infertility (57%, n = 60, P < 0.02). In unexplained infertility, a significantly increased proportion of couples experienced complete failure of fertilization and cleavage in a cycle (5-6% versus 2-3%). However, complete failure was not usually repetitive, and the affected couples did not account for the overall reduction in fertilization and cleavage rates, which remained significantly lower in the rest of the unexplained and endometriosis groups. Implantation and pregnancy rates appeared similar in all groups. The benefit of IVF treatment in cases of minor endometriosis and prolonged unexplained infertility is due to superabundance of oocytes obtained by stimulation. The reduction in natural fertility associated with endometriosis appears to be at least partly due to a reduced fertilizing ability of the oocyte. In unexplained infertility, there is distinct impairment due to otherwise unsuspected sperm dysfunction but probably also oocyte dysfunction.      

Cumulative pregnancy rates in couples with anovulatory infertility compared with unexplained infertility in an ovulation induction programme

Using a retrospective analysis, we compared cumulative pregnancy rates, early pregnancy failure rates and multiple pregnancy rates in couples with polycystic ovarian syndrome (PCOS) (n = 148), hypogonadotrophic or eugonadotrophic hypogonadism (n = 91) and unexplained infertility (n = 117), who were treated in an ovulation induction clinic between January 1991 and December 1995. The women were treated with either human menopausal gonadotrophin (HMG) or purified follicle stimulating hormone (FSH). The cumulative pregnancy rate (derived from life-table analysis) after four ovulatory treatment cycles was 70% in the PCOS group, 74% in the hypogonadism group and 38% in the unexplained infertility group. The cumulative pregnancy rate in the unexplained infertility group was significantly lower than the other groups (P < 0.001) but there was no significant difference between PCOS and hypogonadism using the log rank test. The early pregnancy failure rate was 25% in the PCOS group, 27% in the hypogonadism group and 26% in the unexplained infertility group (chi(2) = 0.132, not significant). The multiple pregnancy rate was 20% in the PCOS group, 30% in the hypogonadism group and 17% in the unexplained infertility group (chi(2) = 2.105, not significant). Treatment of anovulatory infertility using HMG or FSH is effective irrespective of the cause. Couples with unexplained infertility are less successfully treated using HMG: correction of unexplained infertility may involve more than simple correction of possible subtle ovulatory defects.      

Cost-effectiveness of aromatase inhibitor co-treatment for controlled ovarian stimulation

BACKGROUND: To compare the clinical results and the cost-effectiveness of using the aromatase inhibitor, letrozole, in conjunction with FSH and FSH alone for controlled ovarian stimulation (COS) in patients undergoing intrauterine insemination (IUI) for a variety of indications. METHODS: Four hundred and thirty-two consecutive patients who underwent 872 IUI cycles were included. The study population was composed of two groups. Group I included 308 patients who underwent 589 IUI cycles with letrozole and FSH for the following indications: anovulation (143 cycles), male factor infertility (147 cycles), unexplained infertility (250 cycles), endometriosis (18 cycles) and combined indications (31 cycles). Group II included 124 patients who underwent 283 IUI cycles who received FSH only for the following indications: ovarian factor infertility (82 cycles), male factor infertility (66 cycles), unexplained infertility (114 cycles), endometriosis (13 cycles) and other indications (8 cycles). Main outcome measures included number of mature follicles >16 mm in diameter, dose of FSH used per cycle, clinical pregnancy rate and cost-effectiveness ratio per pregnancy. RESULTS: FSH dose required for ovarian stimulation was significantly lower when letrozole was used (P < 0.0001). Although a significantly higher number of follicles >16 mm and endometrial thickness at the day of hCG administration (P < 0.0001) were observed in Group II, pregnancy rate per started (14.4 versus 15.9%) and per completed cycles (15.77 versus 18.07%) was the same in Group I and Group II, respectively. IUI cancellation rate was significantly lower with letrozole treatment (P = 0.05%). The cost per cycle was significantly lower in Group I versus Group II (468.93 Can dollars +/- 418.18 versus 1067.28 +/- 921.43; P < 0.0001). The cost-effectiveness ratio was 3249.42 dollars in the letrozole group and 6712.00 dollars in the FSH-only group. CONCLUSION: A letrozole-FSH combination could be an effective ovarian stimulation protocol in IUI cycles. Such a protocol may be more cost-effective than FSH alone because of the difference of FSH dose and cost. A randomized controlled trial is needed to further substantiate this finding.     

Relationship of antibodies to sperm head to etiology of infertility in patients undergoing in vitro fertilization/embryo transfer

Antibodies to sperm head (ASA-H) are believed to impair reproduction, probably because of a reduction in fertilization of human oocytes. However, the incidence of ASA-H in couples with different etiologies of infertility undergoing in vitro fertilization/embryo transfer (IVF/ET) is unestablished. To examine this question, the semen, serum, and follicular fluid of 11 couples with unexplained infertility and 25 couples with tubal infertility undergoing IVF/ET were tested with the immunobead binding assay to identify ASA-H of IgA, IgG, and IgM isotypes. Comparing couples with unexplained vs. tubal infertility, 46% vs. 4% had ASA-H of at least one isotype in female serum (P = .006), 36% vs. 4% had ASA-H in follicular fluid (P = .023), 27% vs. 0% had ASA-H in semen (P = .023), and 18% vs. 4% had ASA-H in male serum (P = .022), respectively. ASA-H were present in one or more fluids tested in 55% of patients with unexplained infertility, compared to 8% of patients with tubal infertility (P = .005). Of the six women with ASA-H in their serum, 83% (5/6) were undergoing IVF/ET for unexplained infertility compared to 17% (1/6: P = .08) undergoing IVF/ET for tubal infertility. In summary, clinically significant ASA-H are present in a substantial number of infertile women undergoing IVF/ET, particularly those whose infertility is unexplained. Based on these findings, we conclude that it is efficacious to screen all women with unexplained infertility undergoing IVF/ET for ASA-H.     

Evidence for different aetiologies of low estradiol response to FSH: age-related accelerated luteinization of follicles or presence of ovarian autoantibodies

BACKGROUND: We found granulosa cells of low responders (LR) expressed more LH receptors, suggesting that follicles were more luteinized than normal responders (NR). The objectives were to test the hypothesis that follicles of LR were more luteinized than follicles of NR, and to determine if LR with (LR+) and without (LR-) ovarian antibodies differed. METHODS: Hormone levels and ovarian autoantibodies (OVAB) were measured in follicular fluid from mature follicles (>17 mm), and in serum obtained on the day of oocyte retrieval during controlled ovarian stimulation. The gonadotrophin response was defined as a ratio of peak estradiol/number of FSH ampoules. RESULTS: NR (32.5 +/- 4.6 years; n = 11) were similar in age to LR+ (33.4 +/- 4.2 years; n = 9) and were younger than LR- (37.1 +/- 3.8 years; n = 12) (P = 0.03). Likewise, dehydroepiandrosterone sulphate was lower in LR- compared with LR+ or NR (P < 0.01). FSH, progesterone, inhibin-A and vascular endothelial growth factor levels were higher in follicular fluid of LR than NR. LR- and LR+ differed. For example, the follicular fluid progesterone/estradiol ratio was similar in NR (11.1 +/- 8.9) and LR+ (9.8 +/- 6.6) but was lower than LR- (22.9 +/- 19.6) (P = 0.05). Serum hormone levels did not reflect follicular fluid hormone profiles. CONCLUSIONS: In the absence of ovarian antibodies, low responses are associated with higher age and accelerated luteinization of mature follicles, rather than diminished responsiveness. Ovarian antibody may be an additional tool to predict and individualize treatment regimens in poor responders.     

Laboratory Evaluation of Women Experiencing Reproductive Failure

Reproductive life table analysis indicates that the majority of reproductive failures result from post fertilization failures, whether before or after implantation. It is important to have a set of tests to clarify the diagnosis of the reproductive failure so that appropriate therapy can be instituted. To determine the frequency of abnormal immunologic tests among women experiencing reproductive failure, 108 patients were evaluated for the presence of antiphospholipid antibodies (APA); lupus anticoagulant (LA); thyroid-thyroglobulin and microsomal antibodies (TGT); embryotoxic factor (ETA); and systemic CD56+/CD16- cells. The frequency of abnormal results obtained from testing for APA, LA, TGT, ETA, and CD56+/CD16- cells among 108 patients with diagnoses of recurrent pregnancy loss (RPL)(n=45), unexplained infertility (n=45) including IVF failure (n=10), endometriosis (n=10), premature ovarian failure (n=5), and polycystic ovaries (n=3) were compared with 15 normal controls. Seventy of one hundred eight (65%) women experiencing reproductive failure had at least one positive test, compared to 1 of 15 (7%) controls (P=0.0001). Presence of phospholipid antibodies was the most frequently abnormal result followed by elevated CD56+/CD16 cells. The prevalence of a particular abnormal test varied among the diagnoses. The most frequent abnormal test among women with RPL was an increased percentage of CD56+/CD16- cells (40%), followed by APAs (29%), TGT (9%), and ETA (7%). The most frequent abnormal result among women with unexplained infertility was the presence of APAs (42%), followed by CD56+/CD16- cells (16%), ETA (16%), and TGT (9%). APA, CD56+/CD16- cells, ETA, and TGT are useful tools to assist in the diagnosis of reproductive failure.     

Humoral immune response to the chlamydial heat shock proteins hsp60 and hsp70 in Chlamydia -associated chronic salpingitis with tubal occlusion

The aim of this study was to evaluate the prevalence of serumimmunoglobulin (Ig) G and IgA antibodies to recom-binant chlamydial60 kDa heat shock protein (C-hsp60) and to assess the prevalenceof serum IgG antibodies to recombinant chlamydial 70 kDa heatshock protein (C-hsp70) in Chiamydia-associated chronic salpingitisand/or salpingitis isthmica nodosa with tubal occlusion. Infertilepatients (n = 34) with Chlamydia-associated, histologicallydocumented chronic salpingitis and/or salpingitis isthmica nodosaand bilateral tubal occlusions (group I) were compared withinfertile patients (n = 19) without tubal occlusions (groupII). The prevalence of chlamydial antigen in endocervical, urethraland urine samples was low in both groups. The median chlamydialserum IgG and IgA antibody titres were significantly higherin group I than in group II (P < 0.0001 and P = 0.0002 respectively).Serum IgG antibodies to C-hsp60 and C-hsp70 were detected in24 out of 34 patients (71%) in group I compared with 10 outof 19 (53%) and nine out of 19 (47%) patients in group II (notsignificantly different). There was a significant difference(P = 0.035) between the prevalences of serum IgA antibodiesto C-hsp60 in groups I (seven out of 34 patients; 21%) and II(none of the 19 patients). The association between the presenceof serum IgA antibodies to C-hsp60 and Chlamydia-ossocmted chronicsalpingitis and/or salpingitis isthmica nodosa with tubal occlusionunderlines the significance of chlamydial 60 kDa heat shockprotein in the pathogenesis of tubal infertility.     

Follicular density in ovarian biopsy of infertile women: a novel method to assess ovarian reserve

The ageing ovary appears to be characterized by depletion of primordial follicles. The relationship between infertility and the number of follicles in the ovarian cortex is not known. Moreover, there are no accurate markers or clinical methods to predict the decline in ovarian reserve. This study investigates the correlation between early follicular follicle stimulating hormone, ovarian size and follicular density in 60 infertile women aged 19-45 years (mean = 34.4 +/- 5.5). An ovarian biopsy was taken from each patient while performing diagnostic laparoscopy (n = 28) or laparotomy for tubal surgery or myomectomy (n = 32). The median number of follicles was similar in tubal and unexplained infertility patients (9.5 versus 5.5). Increasing age showed a significant negative correlation with follicular density and ovarian volume (r = -0.46, P = 0.0003;. r = -0.43, P = 0.0016, respectively). In women > or = 35 years of age the ovarian volume showed a strong correlation with follicular density (r = 0.71, P < 0.0001). Our results indicate that infertile women in their late thirties and over have a decreased ovarian reserve which could possibly be predicted by ovarian volume measurement. Ovarian biopsy may have a place as part of infertility evaluation in older women.      

Antithyroid antibodies do not affect pregnancy outcome in women undergoing assisted reproduction.

The purpose of this study was to determine the association of antibodies to thyroglobulin and thyroid peroxidase and pregnancy outcome in women undergoing assisted reproductive techniques. The study included three centres and retrospectively evaluated patient sera for antithyroid antibodies, then related the results to pregnancy outcome. Enzyme-linked immunosorbant assays for thyroglobulin and thyroid peroxidase antibodies were performed using two different commercially available kits. Controls included 200 healthy women of reproductive age. Women (n = 873) who were undergoing assisted reproductive techniques for pelvic adhesions, endometriosis, ovarian dysfunction, or unexplained/other were included. All women utilized a standard regimen of gonadotrophin releasing hormone agonist down-regulation followed by ovulation induction. Embryos were cultured for 3 days, at which time embryo transfer occurred. Statistical analysis utilized the two-tailed Fisher's exact test. Antithyroid antibodies were positive in 143 of 873 (16.4%) women undergoing assisted reproductive techniques while 29 of 200 (14.5%) normal controls were positive (not significant). Deliveries were achieved in 396 of 730 (54.2%) of women who had no thyroid antibodies versus 78 of 143 (54.5%) of women who had thyroid antibodies (not significant). No difference in biochemical pregnancies (not significant) or clinical pregnancy losses (not significant) were detected. Antithyroid antibodies were found no more frequently in women undergoing assisted reproductive techniques than in normal controls. There were no differences in pregnancy outcome based on antithyroid antibody positivity in women undergoing assisted reproductive techniques. These data do not support the testing or treatment for antithyroid antibodies of women undergoing assisted reproductive techniques.     

Controlled ovarian hyperstimulation changes the prevalence of serum autoantibodies in in vitro fertilization patients

PROBLEM: Autoimmune mechanisms are involved in etiology of female infertility, the medical problem frequently treated by in vitro fertilization (IVF). Controlled ovarian hyperstimulation (COH) with supraphysiological levels of sex hormones is achieved by IVF. METHODS OF STUDY: Anti-human-ovary and eight common autoantibodies [nuclear (ANA-H, ANA-R on human HEp-2 cell line and rodent antigen, respectively), smooth muscle (SMA), parietal cell, thyroid microsomal, mitochondrial, beta2-glycoprotein-I, cardiolipin antibodies] found in IVF patients (n = 129) were analyzed with regard to the number of previous IVF procedures and the age of the patient. The changes in autoimmune reactions caused by the COH were determined. RESULTS: Endometriosis and polycystic ovary syndrome were associated with a higher number of common serum autoantibodies compared with the tubal factor infertility (Proportion test, P < 0.05). ANA-R was associated with unexplained infertility [adjusted odds ratio (aOR) 8.79, P = 0.038]. SMA correlated with endometriosis (aOR 37.29, P = 0.008), male factor infertility (aOR 20.45, P = 0.018) and with the previous IVF procedures (aOR 2.87, P = 0.013). There was an overall decrease in the number of detectible autoantibodies after COH (Proportion test, P < 0.05). CONCLUSION: COH may have a suppressive effect on the humoral immunity by the time of embryo transfer but more conclusive studies are needed.     

Association between infertility and spontaneous abortion.

Women experiencing recurrent spontaneous abortion have a higher frequency of infertility than that expected in the general population. To further define the relationships between infertility and spontaneous abortion, the obstetrical histories of 43 women with unexplained secondary infertility were evaluated for the frequency of spontaneous abortion. Of the 88 pregnancies studied, 39 (44%) resulted in spontaneous abortion. Women with unexplained secondary infertility experienced a three-fold increase (P less than 0.0001) in the frequency of spontaneous abortions and half the number of live births (P less than 0.0001) compared with the general population. We conclude that the association between infertility and spontaneous abortion includes a higher frequency of spontaneous abortion among infertile couples as well as a higher prevalence of infertility among recurrent spontaneous aborters compared with the general population.     

A randomized study comparing IVF in the unstimulated cycle with IVF following clomiphene citrate

The efficiency of IVF in unstimulated cycles was compared with that following ovarian stimulation with clomiphene citrate in a simple protocol with ultrasound monitoring only. A total of 132 couples with no previous IVF attempts, selected by female age <35 years, indication for intracytoplasmic sperm injection or infertility caused by tubal factor or unexplained infertility were randomized to the two protocols. Randomization yielded two comparable groups. The clomiphene group (68 couples) performed significantly better than the unstimulated group (64 couples) in terms of number of cycles with oocyte harvest (90/111 or 81% versus 65/114 or 57%; chi(2) = 9.21, P < 0.002), embryo transfers per started cycle (59/111 or 53% versus 29/114 or 25%; chi(2) = 18.14, P < 0.0001), live intrauterine pregnancy rate per started cycle (20/111 or 18% versus 4/114 or 4%; chi(2) = 12.42, P < 0.0001), live intrauterine pregnancy rate per embryo transfer (20/59 or 34% versus 4/29 or 14%; chi(2) = 3.96, P = 0.047), but not in terms of implantation rate (22/85 or 26% versus 4/29 or 14%; chi(2) = 1.65). Only two twin pregnancies occurred. Modest side-effects were recorded following clomiphene. Accordingly, a simple clomiphene citrate protocol, but not IVF in unstimulated cycles, seems compatible with the concept of 'friendly IVF', yielding a fair pregnancy rate both per cycle started and per embryo transfer in selected patients. The results do not substantiate any important negative anti-oestrogenic effects of clomiphene.     

Previously undetected Chlamydia trachomatis infection, immunity to heat shock proteins and tubal occlusion in women undergoing in-vitro fertilization.

The relationship between a previously undetected Chlamydia trachomatis infection, tubal infertility, immunity to heat shock proteins and subsequent in-vitro fertilization (IVF) outcome was evaluated. Women with tubal occlusion, with or without hydrosalpinges, and no history of C. trachomatis infection were tested for circulating antibodies to the human 60-kDa heat shock protein (Hhsp60), the C. trachomatis 10-kDa heat shock protein (Chsp10) and C. trachomatis surface antigens prior to their initial IVF cycle. Sera were obtained from 50 women whose male partners were infertile, 58 women with tubal occlusion but no hydrosalpinx and 39 women with tubal occlusions plus hydrosalpinx. Clinical pregnancies were documented in 68% of the women with male factor infertility. This was higher than the 43.1% rate in women with tubal occlusions (P = 0.04) and the 41% rate in women with hydrosalpinx (P = 0.02). C. trachomatis antibodies were present in one (2%) women with male factor infertility as opposed to 15 (25.9%) women with tubal occlusion (P = 0.003) and 13 (33%) with hydrosalpinx (P < 0.0001). Antibodies to Chsp10 were more prevalent in women with hydrosalpinx (46.8%) than in women with male factor infertility (P < 0.0001, 6%) or tubal occlusion (P = 0.0009, 15.5%). Hhsp60 antibodies were equally more prevalent in women with tubal occlusion plus (46.8%) or minus hydrosalpinx (41.4%) than in women with male factor infertility (P < 0.0002). Hhsp60 was more prevalent in those women positive for Chsp10 (P = 0.02) or C. trachomatis (P = 0.04) antibodies than in women lacking these antibodies. There was no relationship between any of the antibodies measured in sera and IVF outcome.     

Association of Sperm Antibodies With Other Autoantibodies in Infertile Men

PROBLEM: In many autoimmune diseases there is an increased incidence of other autoantibodies. However, the incidence of other autoantibodies in patients with seminal sperm antibodies is unknown. The most widely used tests to detect seminal and serum sperm antibodies are the mixed antiglobulin reaction (MAR) and the Tray agglutination test (TAT). METHOD: We therefore determined the incidence of antinuclear, antimitochondrial, thyroid peroxidase, and thyroglobulin antibodies, and rheumatoid factor in 147 patients investigated with MAR and 157 patients investigated with TAT. RESULTS: TAT positive patients had a significantly elevated incidence of antinuclear antibodies (χ² test, P < 0.005) and thyroglobulin antibodies (χ² test, P < 0.001). Thyroglobulin antibodies were increased in patients with MAR IgG > 40% and also significantly (χ² test, P < 0.05) increased in MAR IgA positive patients. Furthermore, thyroid peroxidase antibodies were only found in TAT positive patients. CONCLUSIONS: The consistently increased incidence of thyroid autoantibodies in infertile patients with sperm antibodies may indicate an increased risk for the development of autoimmune thyroid disease. This finding therefore suggests screening of patients with immunologic infertility for autoimmune thyroid disease and a further evaluation of the prognostic and pathophysiologic significance of thyroid autoantibodies in immunologic infertility.     

Fertilization rate in couples with unexplained infertility.

A group of 24 couples with unexplained infertility was scheduled for in-vitro fertilization and tubal embryo transfer between May 1989 and September 1990. In the same period, in-vitro fertilization and intrauterine transfer of embryos was planned in a control group of 44 women with tubal infertility. The mean age and duration of infertility were similar in both groups and the same scheme of ovarian stimulation was used. No statistically significant difference was obtained comparing oestradiol levels and numbers of mature oocytes retrieved between the group of patients with unexplained infertility and those with tubal infertility. The fertilization rate of the oocytes obtained from women with unexplained infertility (60.4%) was significantly lower (P less than 0.001) than that of the oocytes obtained from patients with tubal infertility (87.3%). There was no statistically significant difference in the cleavage rates between patients with unexplained infertility and those with tubal infertility. It is concluded that lack of fertilization is an unexplored cause of infertility in couples with unexplained infertility.     

Anti-Endometrial Autoantibodies in Women with a Diagnosis of Infertility

PROBLEM: The purpose of this study was to investigate the frecuency of anti-endometrial antibodies (AEA) in infertile women. METHOD OF STUDY: Sera from fertile women (n = 6), and from patients with ovulatory dysfunction (n = 11), tubal obstruction (n = 9) and unexplained infertility (n = 5) were investigated for the presence of anti-endometrial membrane antibodies. We used two human endometrial cancer cell lines and human endometrial cells from gynecological biopsies as an antigenic source for analysis. The immunoenzymatic assay (ELISA) was performed with cultured endometrial cells in monolayers. Immunoblot analysis was performed with these two cell lines. RESULTS: A good correlation between the response with each cell line and with human endometrial cells was obtained, indicating that the antigens analyzed were probably similar. Endometrial antibodies were detectable in a high percentage of women with tubal obstruction (77.8 and 66.7%, respectively) and ovulatory dysfunction (54.5 and 45.5%, respectively). Unexplained infertility showed anti-endometrial immunological response (40 and 60%, respectively). Some endometrial antigens in infertile women are the target for autoimmune response. The serum from a patient with tubal obstruction and ovulatory dysfunction showed two antigens by immunoblot, with molecular weights of 97 and 50 kDa. CONCLUSION: The presence of anti-endometrial antibodies, detected by ELISA, is associated with infertility, mainly with ovulatory dysfunction and tubal obstruction. Some endometrial antigens may be involved in these two pathologies.