Negative Postcoital Test Research Articles

Prevalence of anti-sperm antibodies and relationship of degree of sperm auto-immunization to semen parameters and post-coital test outcome: a retrospective analysis of over 10 000 men.

What is the prevalence and the relationship of anti-sperm antibodies (ASA), screened by means of IgG-mixed anti-globulin reaction (MAR) test, to semen quality and post-coital test (PCT) outcome? A 100% positive IgG-MAR test, detected in 2% of the study population, was associated with lower sperm output and progressive motility, and was the sole determinant of higher prevalence of a negative PCT outcome. Although ASA may affect sperm fertilizing ability and the IgG-MAR test is recommended by the World Health Organization (WHO) as an integral part of semen analysis for screening the occurrence of ASA, the prevalence and clinical relevance of positive MAR test results remain controversial. A retrospective analysis of 12 296 consecutive men who attended a university/hospital andrology clinic for the evaluation of fertility potential was carried out. Immunological screening with the IgG-MAR test was performed on all ejaculates as an integral part of semen analysis. Positive samples (≥10%) were further tested for IgA-ASA. The prevalence of positive IgG-MAR tests results, along with the relationship of the degree of sperm auto-immunization to semen parameters and PCT outcome, were analyzed. After excluding semen samples showing azoospermia or severe oligo-asthenozoospermia, the prevalence of a positive IgG-MAR test in the remaining 10 025 men was 4%, 3.4% and 2%, with 10%, 50% and 100% thresholds, respectively. The 100%-positive MAR tests exhibited significantly higher consistency over time, and were significantly associated with higher prevalence of a mixed pattern (i.e. when the majority of sperm exhibited beads attached on both the head and along the tail) of positivity as well as with the concomitant occurrence of IgA-ASA. Additionally, the 100%-positive MAR tests were significantly associated with a lower median value of the total number of spermatozoa and progressive motility, compared to samples with a lower degree of positivity or negative samples. In the PCT performed in 120 couples, where ASA were detected in the male partner, the 100%-positive MAR tests were significantly associated with a higher prevalence of negative PCT outcome, in comparison to the lower degree of positivity, independent of, and without any significant contribution from, other determinants (semen and cervical mucus quality). Only surrogate infertility-related end-points were analyzed in the present study. However, since the impairment of sperm penetration through the cervical mucus represents the primary mechanism of ASA-interference with fertility, PCT outcome may represent a suitable clinical end-point. The present study, being the largest reported to date, provides a reliable estimate of ASA prevalence. Moreover, it indicates that a 50%-positive MAR test, which is suggested by WHO as the clinically-relevant threshold, also includes patients with a degree of sperm auto-immunization that contributes to couple infertility only in the presence of other causal factors; conversely, the 100%-positive MAR test can represent the sole determinant of couple infertility, as it was the sole significant predictor of the highly prevalent negative PCT outcome. The study was supported by the University of L'Aquila, Italy. The authors declare no competing interests. N/A.

Does the postcoital test predict pregnancy in WHO II anovulatory women? A prospective cohort study

ObjectiveTo assess the capacity of the postcoital test (PCT) to predict pregnancy in WHO II anovulatory women who are ovulatory on clomiphene citrate (CC). In these women, an abnormal PCT result could be associated with lower pregnancy chances, but this has never been proven or refuted. Study designProspective cohort study was performed between December 2009 and September 2012 for all women who started ovulation induction with CC in one university clinic and two teaching hospitals in the Netherlands. A PCT was performed in one of the first three ovulatory cycles. Ovulation induction with CC was continued for at least six cycles. The PCT was judged to be positive if at least one progressive motile spermatozo was seen in one of five high power fields at 400× magnification. The primary outcome was time to ongoing pregnancy, within six ovulatory cycles. ResultsIn 152 women the PCT was performed. 135 women had a reliable, well-timed PCT. The ongoing pregnancy rate was 44/107 (41%) for a positive and 10/28 (36%) for a negative PCT. The hazard rate for ongoing pregnancy was 1.3 (95% CI 0.64–2.5) for a positive versus a negative PCT.Thirty five of 77 (46%) women with clear mucus had an ongoing pregnancy versus 12 of 45 (27%) women in whom the mucus was not clear (HR 2.0; 95% CI 1.02–3.84, p=0.04). ConclusionThe present study suggests that the outcome of the postcoital test in women with WHO-II anovulation that undergo ovulation induction with CC does not have a large effect on ongoing pregnancy chances over time.

Long-term ongoing pregnancy rate and mode of conception after a positive and negative post-coital test.

Many fertility clinics have decided to abolish the post-coital test. Yet, it is a significant factor in prognostic models that predict the spontaneous pregnancy rate within one year. The aim of this study was to evaluate (1) the long-term outcome of infertile couples with a positive or a negative post-coital test during their fertility work-up and (2) the contribution of the different modes of conception. Retrospective cohort study. Three fertility clinics in the Netherlands, of which two are secondary care training hospitals and is a one tertiary care academic training hospital. 2476 newly referred infertile couples, where a post-coital test was performed in 1624 couples. After basic fertility work-up, couples were treated according to the national treatment protocols. Spontaneous and overall ongoing pregnancy rate. The spontaneous and overall ongoing pregnancy rates after three years were 37.7 and 77.5% after a positive post-coital test compared with 26.9 and 68.8% after a negative test (p<0.001). Even in couples with severe male factor infertility (total motile sperm count <3) (p=0.005) and mild male factor infertility (total motile sperm count 3-20) (p<0.001), there was a significantly higher spontaneous ongoing pregnancy rate, justifying expectant management. After a follow-up of three years a positive post-coital test is still associated with a higher spontaneous and a higher overall ongoing pregnancy rate, even in couples with severe male factor infertility.

Presence of interleukin-8 and the IL-1 receptor antagonist in the cervical mucus of fertile and infertile women

Cytokines are involved in almost every aspect of reproduction, and recent studies suggested a relationship between cytokines and male/female infertility. In the present study, the levels of interleukin-8 (IL-8) and interleukin-1 receptor antagonist (IL-1Ra) were determined in the cervical mucus of fertile and infertile women. Groups of patients were formed according to the results of the standard procedure for infertility investigation, including postcoital test and the presence of antispermatozoid antibodies in the sera of both partners and in seminal plasma, by mixed antiglobulin reaction (MAR) test and Kibrick agglutination test. IL-8 and IL-1Ra levels were determined in solubilized (ultrasonographic sonication) cervical mucus sampled in the midcycle by commercial ELISA kits and expressed as pg/mg proteins. The groups were designated as fertile (n=20) and infertile (n=48). The latter was divided into two subgroups, one consisting of infertile women with positive postcoital test and without antispermatozoid antibodies (n=30), and the other designated as infertile women with negative postcoital test (n=18). This subgroup was composed of women with negative postcoital test and without antibodies (n=10) and the women with negative postcoital test with antibodies (n=8). Similar levels of IL-8 and IL-1Ra were noted in the cervical mucus of infertile women and women with positive postcoital test and without antispermatozoid antibodies. A tendency of decrease (p=0.052) and significant decrease in IL-8 levels (p<0.05) was noted in negative postcoital test group and negative postcoital test group without antibodies, respectively, compared to the levels in the fertile examinees. A significant rise in IL-1Ra levels (p<0.05) was detected in the mucus of negative postcoital test group with further increase in negative postcoital test group with antibodies (p<0.02). Changes in IL-8 and IL-1Ra levels in the cervical mucus of infertile patients with negative postcoital test suggested the existence of the relationship between cervical cytokines and infertility in these women.

Anticardiolipin Antibodies in Women with Unexplained Infertility.

Concept of autoimmune basis of infertility is still controversial, particularly regarding the presence of non-organ specific autoantibodies. Non-organ specific anticardiolipin (aCL) and antithyroglobulin (TgAt) antibodies were detected in infertile women. Both partners were evaluated according to the criteria of The American Society for Reproductive Medicine. All the results were normal in cases of unexplained infertility. Antisperm antibodies (ASA) were determined by a mixed antiglobulin reaction (MAR) and the Kibrick agglutination assay, aCL by commercial ELISA, TgAt by commercial RIA. Fertile women had children. Subjects were grouped in fertile (n=27), infertile (n=65), and cases of unexplained infertility (n=42). In fertile women, aCL was below the negative cut-off value (100 %), while women with unexplained infertility were positive in 23.8 %. Anticardiolipin (aCL) antibodies were detected in 21.5 % of infertile patients, most of them with unexplained infertility (15.4 %). Other positive women had partners with ASA (4.6 %), or exhibited a negative postcoital test (1.5 %). In this study aCL were not detected in women with ASA. TgAt incidence was increased in infertile (20 %) and unexplained infertility group (21.4 %) compared to the fertile controls (18.5 %). Increased incidence of aCL and TgAt in infertile women supports the contention that these autoantibodies contribute to the infertility

Management of assisted reproductive technologies in women with cystic fibrosis

Management of assisted reproductive technologies in women with cystic fibrosis

Value of the hamster oocyte test and computerised measurements of sperm motility in predicting if four or more viable embryos will be obtained in an IVF cycle.

The experimental group consisted of men from 81 couples waiting for in vitro fertilization (IVF), about half of whom had sperm dysfunction defined by a negative post-coital test. A diagnostic semen sample was subjected to a hamster oocyte penetration test (HOPT) after stimulation of the acrosome reaction with A23187 +/- pentoxifylline and to computerized sperm motility measurements (CASA) as well as conventional semen analysis according to the WHO protocol. Logistic regression was used to identify parameters that predicted the probability of achieving four or more viable embryos at IVF among the 65 couples from whom four or more oocytes were collected. The number of oocytes available and whether the woman had previously been pregnant (ever pregnant) were important factors but once these had been taken into account a number of sperm parameters had additional predictive power. The most useful of these were the percentage sperm static (CASA) or the percent sperm progressively motile (conventional semen analysis) in the Percoll preparation. A model incorporating the number of oocytes collected, ever pregnant and percentage sperm static achieved 85% correct prediction of outcome in the experimental dataset but only 62% correct prediction in an independent set of 280 IVF cycles. The percentage of hamster oocytes penetrated was a significant predictor but had no advantage over simple motility measurements. The results illustrate the difficulty of basing a prognosis for achieving satisfactory fertilization in IVF on the properties of spermatozoa.

The prognostic power of the post-coital test for natural conception depends on duration of infertility.

Controversy about the value of the post-coital test (PCT) has prompted us to re-analyse data from 207 couples, originally studied between 1982 and 1983, with at least 12 months' infertility at presentation, complete diagnostic information and exclusion of female factors, to clarify the effect of duration of infertility on the prediction of conception. In couples with less than 3 years infertility and a positive PCT, 68% conceived within 2 years compared with 17% of those with a negative result. After 3 years, corresponding rates were 14% and 11%. The relative risks of conception [95% confidence interval (CI)] calculated using the Cox's proportional hazards model were 0.23 (0.12-0.43) for a negative PCT (reference positive PCT) and 0.25 (0.13-0.51) for more than 36 months infertility (reference 12-23 months). Semen analysis had no extra predictive power given the duration of infertility and the PCT. The PCT is an effective predictor of conception where defined female causes of infertility are absent and duration of infertility is less than 3 years. Once infertility is prolonged (beyond 3 years) the conception rate is low even with a positive test because a large proportion of couples remaining childless so long have true unexplained infertility. Use of the PCT will enable clinicians to allocate scarce, expensive and invasive resources effectively.

Antisperm antibodies in cervical mucus in an unselected subfertile population*

To determine the incidence and the clinical significance of antisperm antibodies (ASA) in cervical secretions in an unselected subfertile population, cervical mucus samples of 192 patients with long-standing infertility were screened by means of the indirect mixed antiglobulin reaction (MAR) test allowing differentiation for immunoglobulin (Ig)A and IgG in a parallel test setting. In addition, the indirect MAR IgG test in cervical mucus was evaluated by means of IgG coated latex particles instead of sensitized erythrocytes as the indicator system. All cervical mucus samples were taken under standardized conditions. Results of ASA determination were related to microbial findings in the cervix and the outcome of sperm-mucus interaction testing in vivo and in vitro, and the subsequent fertility in a prospective study. The total incidence of cervical mucus ASA within this population was low (< 2%). A significant correlation was found between sperm antibodies of the IgG and IgA class and of IgG ASA, determined with the standard MAR and testing with latex microspheres as indicator particles. Results were not influenced by microbial colonization of the cervix and were not markedly related to lymphocytes subset testing. All ASA positive women had a negative outcome of the post-coital test, but the majority of negative post-coital tests was not caused by local mucus antibodies of the IgG and/or IgA class. In patients with positive indirect MAR testing in cervical mucus, there was no pregnancy within an observation period of > 12 months. In conclusion, the results indicate the ASA in cervical secretions are not frequent but nevertheless are a severe cause of infertility when present.(ABSTRACT TRUNCATED AT 250 WORDS)

Improvement of cervical mucus viscoelasticity and sperm penetration with sodium bicarbonate douching

The aim of the study was to evaluate the influence of vaginal douching with sodium bicarbonate (NaHCO3) upon cervical mucus viscoelasticity and sperm penetration in vitro and in vivo. Twenty-five couples with primary infertility for greater than 12 months participated in the study. The selection criteria were: (i) semen quality compatible with conception, (ii) regular ovulatory cycles and (iii) repeated negative post-coital test (PCT). After at least one inventory cycle, three consecutive cycles were studied. In the second and third cycles, vaginal douching was performed with either 1.5% (w/v) NaHCO3 or 0.9% (w/v) NaCl (randomized procedure). The viscoelasticity of the cervical mucus, sperm penetration tests (SPT) and PCTs were analysed. The viscoelasticity of mucus samples after NaHCO3 douching was significantly lower than the viscosity after NaCl douching (P less than 0.001, n = 16) and in the control cycles (P = 0.003). The SPT scores were significantly higher in the NaHCO3 cycles than in the NaCl cycles (P = 0.004, n = 22) and in the control cycles (P less than 0.001). The PCT scores proved to be significantly higher after NaHCO3 douching than after NaCl douching (P = 0.002, n = 21). Comparison of NaHCO3 and control cycles also showed a significant improvement of the PCT score after NaHCO3 douching (P less than 0.001).

Effects of Kallikrein on Sperm Motility, Capillary Tube Test, and Pregnancy Rate in an Aih Program

From 1984 to 1986, 172 couples were enrolled in an artificial insemination homologous (AIH) program, because of negative postcoital test, fair PT, positive PT with unexplained infertility, and impotentia coeundi. Patients were randomly assigned to the following procedures: AIH with native semen (N, n = 68), washed sperm (V, n = 50), semen mixed with kallikrein (K, 5 IE/ml semen, n = 45), and timed intercourse. The overall pregnancy rate (PR) was 22% per couple (13% inseminations, 9% spontaneous). PR from insemination (spontaneous) was 13% (8), 13% (13), 23% (0) in PT negative, fair, and positive patients, respectively, and 18% (9), 13% (7), and 11% (9) in AIH groups N, V, and K. Among in vitro studies with K added semen, an improvement of sperm motility was demonstrated in half of the specimens. In the capillary tube test (CTT), with wives' cervical mucus, a deterioration was more frequently seen than an improvement after 2 h, independent of the early effect of K in semen, K induced changes of CTT were less pronounced when donors' cervical mucus was used. The results of the in vitro studies offer an explanation for the low PR in the AIH program with K.

Improved penetration of spermatozoa into uterine fluids of women with abnormal postcoidal tests

Cervical mucus-uterine fluid cross-penetration of husbands' and control sperm was assessed in 13 couples with poor or negative postcoital tests. Cervical mucus scoring and tray agglutination test identified six women with sperm-agglutinating antibodies and seven women with cervical dysmucorrhea. All males were normozoospermic, with penetration into control cervical mucus and control uterine fluids. Control sperm penetrated into cervical mucus and uterine fluids of three and five of the women with sperm-agglutinating antibodies and cervical dysmucorrhea, respectively. Penetration of husbands' spermatozoa into uterine fluids of patients with sperm-agglutinating antibodies was lower than that of control semen (P less than .05). Control and husbands' sperm penetration into uterine fluids of women with cervical dysmucorrhea were identical. In both groups, husbands' and control sperm penetrated uterine fluids more frequently than cervical mucus (75 versus 12%; P less than .001). On a six-month follow-up and midcycle intrauterine inseminations, six patients (46%) conceived. We conclude that uterine fluids of patients with sperm-agglutinating antibodies and cervical dysmucorrhea may provide a better milieu for spermatozoa than cervical mucus. This observation suggests a rationale for intrauterine inseminations to achieve pregnancy.

The treatment of infertility by the high intrauterine insemination of husband's washed spermatozoa.

A total of 345 couples with non-tubal infertility on an IVF waiting list underwent 702 treatment cycles involving daily intrauterine inseminations of husband's washed spermatozoa (AIH) over 3 days of the periovulatory period, following ovarian stimulation. Pregnancy rates achieved were dependent upon the underlying infertility disorder, with similar rates noted in those with a negative post-coital test (15.8%) or where antispermatozoal antibodies were present in either the male (18.5%) or female (17.1%) partner. These rates were significantly higher than for couples with poor cervical mucus (4.7%), asthenozoospermia (0%), endometriosis (mild, 7.7%; severe, 4.1%) or unexplained infertility (8.5%), while discrete oligozoospermia showed mid-range results (10.3%). Pregnancy outcome revealed a high level of early wastage (33.3%), mainly in the blighted ovum category, however congenital abnormalities (5.6%) were not significantly increased. It is concluded that the procedure of AIH should be considered for infertility due to poor sperm--mucus interaction, antispermatozoal antibodies and simple oligozoospermia, prior to IVF-related treatments.

An evaluation of the role of relaxin in the penetration of cervical mucus by spermatozoa.

Relaxin-like immunoreactivity was measured in seminal plasma from men who were separated into two groups, on the basis of a previous positive or negative result in a postcoital cervical mucus penetration test. There was no difference in the relaxin concentration between the groups. The effect of exogenous porcine relaxin (0, 10 or 100 ng/ml) on human cervical mucus penetration in vitro by washed human spermatozoa was studied using a capillary tube preparation. In the positive postcoital test group the highest relaxin concentration (100 ng/ml) tended to inhibit cervical mucus penetration, although this effect was only significant for one of the parameters measured (number of spermatozoa penetrating to the 10-mm mark). The same trend was apparent for the negative postcoital test group, but no differences were significant. The results are in direct contrast to previous reports that relaxin can stimulate human spermatozoa motility and cervical mucus penetration.

Sperm penetration through cervical mucus in infertile couples in relation to selected cervical factors.

One-hundred-and-fourteen women of infertile marriages with negative post-coital test (PCT) results were studied. The women were divided into three groups: those with anatomical anomalies of the cervix, abnormalities of the cervical mucus and a negative PCT and normal parameters in cervical mucus. Patients were treated with mestranol when the physicochemical characteristics of the cervical mucus were impaired. Those with antispermatozoal antibodies found by means of the Katsh test were treated with desensitizing therapy, condoms and homologous artificial insemination (AIH). Among all the patients therapy resulted in 23 pregnancies. After applying these treatments to women, 49 of them (43%) had positive PCT results.

The sperm-mucus interface: patterns of disorder in the diagnosis of specific causes of penetration failure causing infertility.

In 94 infertile couples with negative postcoital tests (PCTs) the results of an in-vitro sperm-mucus invasion test (SMIT) were compared with seminal analysis (excluding sperm density less than 1 x 10(6)/ml) and agglutination assays for antisperm antibodies in semen (MAR, TAT) and in mucus (TAT). Abnormalities at the sperm-mucus interface were classed into three types. (i) Failure to form semen clefts and of spermatozoa to colonize the clefts was closely correlated with oligo-asthenoteratozoospermia, and vice versa, the two tests agreeing in 90% of cases (P less than 0.001). Most of the discrepancies, in which sperm-dense clefts developed despite low sperm counts, were due to antisperm antibodies in semen. (ii) Failure of spermatozoa to invade mucus, despite normal sperm colonization of clefts, was closely correlated with the presence of antisperm antibodies in semen (positive MAR or TAT), and vice versa, the tests agreeing in 81% of cases (P less than 0.001). (iii) Failure of sperm survival after normal invasion of mucus could not be correlated significantly with the TAT results on mucus, but more extensive study of this question is needed. Finally a normal SMIT result was associated with a significantly improved chance of conception (39 versus 10% at 12 months), particularly with artificial insemination, suggesting undisclosed coital failure as the cause of the negative PCT. In conclusion, the invasion test, when assessed in the foregoing detail, offers a reliable and simple substitute for laboratory assessment of both seminal quality and the presence of antisperm antibodies in semen, and would be applicable in general infertility practice everywhere.

The value of artificial insemination with husband's semen in infertility due to failure of postcoital spermmucus penetration—controlled trial of treatment

Artificial insemination with husband's semen into the cervical canal and uterine cavity (high AIH) was assessed by a randomized controlled prospective study in 46 couples whose infertility was due to failure of sperm mucus penetration, as defined by negative postcoital tests, after excluding all interfering female factors and men with sperm density less than 1 x 10(6)/ml. Seminal analysis was abnormal in 18 of the 46 men and sperm antibodies in semen were detected in 19 of the remaining 28 with normal seminal analysis. Overall, the cumulative conception rate after 6 months with AIH was 4.7 (SE 3.8)% and without treatment was 6.6 (SE 3.9)%. The results were unaffected by the findings on seminal analysis or by the presence or absence of sperm antibodies in semen. AIH appeared to be of no benefit.

The value of the postcoital test in predicting the fertilization of human oocytes.

The relevance of the postcoital test (PCT) in relation to the fertilization rate of oocytes was determined in an analysis of 66 couples in an in vitro fertilization (IVF) program. The test is routinely performed in the workup of all IVF patients and is accurately timed to the immediate preovulatory period by daily hormonal, cervical mucus, and ultrasound monitoring. Cases demonstrating antispermatozoal antibodies in the serum of either partner, in cervical mucus, or in semen were excluded. There was no significant difference in the fertilization rate of oocytes whether the PCT result was negative, equivocal, or positive, and the finding was the same in both normospermic and oligospermic groups. It is concluded that the PCT is of no value in predicting the outcome of IVF and, conversely, IVF should be considered as a therapeutic option for couples with a negative PCT.

Intrauterine insemination for infertility due to cystic fibrosis

Mild CF is not associated with increased obstetric risk to patients or offspring. These patients can be identified on the basis of Shwachman-Kulczycki scores, nutritional status, normal chest x-ray and pulmonary function tests, normal lung volumes, and mild to moderate airway obstruction. Spontaneous pregnancy has been achieved in women with CF, but they appear to have a decreased fertility. One possible cause in mild disease is a cervical factor due to abnormal viscous mucus. This mucus has been shown to fail to hydrate, and at midcycle contains less than 80% water, whereas 93% to 96% hydration appears to be necessary for sperm migration. Cyclic electrolyte changes in cervical mucus are not noted in CF patients, and sodium concentration in dry residue at midcycle is 10% of normal. Intrauterine insemination with a washed sperm fraction offers a theoretically safe method of bypassing this barrier. Preliminary data have revealed that this may be a useful therapy in other cases of infertility in which the abnormality is an unexplained, negative postcoital test. CF patients should be carefully evaluated and advised of risks before becoming pregnant. In cases of mild CF in which no factor for infertility exists other than consistently abnormal cervical mucus, intrauterine insemination with washed motile sperm may be beneficial. We believe this to be the first case of a CF patient successfully treated in this manner.

Postcoital recovery of sperm in Douglas pouch aspirates of infertile patients

Tubal dysfunction is certainly involved in some cases of infertility. Clinical diagnostic procedures for tubal patency are occasionally misleading and contradictory. Moreover, they provide no information on tubal function. The recovery of viable sperm in Douglas pouch aspirates (DPA) was used to evaluate tubal function in 94 infertile patients with different tubal findings at hysterosalpingography (HS) and laparoscopy. Sperm recovery in DPA of ten infertile patients with poor or negative postcoital Sims-Huhner test results demonstrated the limitation of this test for evaluation of sperm transport in the female genital tract. Laparoscopic aspiration of DP may be performed in infertile patients under-going chromosalpingoscopy as a part of their infertility investigation. The procedure should be supplementary to other available diagnostic parameters.