Postcoital Test Research Articles

Improvement of cervical microenvironment after treatment of chronic cervicitis with focused ultrasound in infertility women

To investigate the effects of focused ultrasound (FUS) treatment on cervical microenvironment in infertility women with chronic cervicitis. A total of 10 women treated in Infertility Clinic of Obstetrics and Gynecology Hospital of College of Medicine of Zhejiang University were assessed. The women aged from 25 to 34 with normal menstrual cycles had moderate or severe cervical erosion. Ultrasound showed they had normal ovulation. The sperms of their husbands had normal motility and number. The FUS they received had a focal depth range of 4 - 6 mm, a resonant frequency of 9 - 11 MHz, and an output power of 3.5 W. The follow-up time was three months. The changes of cervical mucus and the results of postcoital test were evaluated. The clinical effects on cervical erosion and complications were also evaluated. In 6 cases of severe cervical erosion, 2 were cured, 2 were improved significantly (more than 50 % reduction of erosion area) and 2 were improved (less than 50 % reduction of erosion area). In 4 cases of moderate cervical erosion, 2 were cured, 2 were improved significantly. After the treatment, the median of cervical mucus score during LH peak were increased from 11 to 13 (Wilcoxon test, P=0.014). Postcoital test showed that the median of highly motile sperm (grade III and grade II) of 5 high-power field were increased from 22 to 52 (Wilcoxon test, P=0.015). Mild side effects without medical intervention included vaginal fluid in all 10 women, vaginal spotting in 2 women. No serious side effects were observed. The focused ultrasound therapy can help to improve the cervical microenvironment for infertility women with moderate or severe cervical erosion without serious side effects.

The additional value of ovarian hyperstimulation in intrauterine insemination for couples with an abnormal postcoital test and a poor prognosis: a randomized clinical trial

To assess the effectiveness of controlled ovarian hyperstimulation (COH) in intrauterine insemination (IUI) for subfertile couples with an abnormal postcoital test and a poor prognosis. Randomized clinical trial. Twenty-four fertility centers in the Netherlands. Subfertile couples with a well-timed nonprogressive PCT and additional factors that reduce fertility. Couples were randomly allocated to three cycles of IUI with COH or three cycles of IUI without COH. Ongoing pregnancy within three IUI cycles. We randomly allocated 132 couples to IUI with COH, and 133, to IUI without COH. We observed 33 pregnancies (25%) in the couples allocated to IUI with COH, of which 28 were ongoing (21%), vs. 28 pregnancies (21%) in the couples allocated to IUI without COH, of which 23 were ongoing (17%; relative risk of an ongoing pregnancy, 1.2; 95% confidence interval, 0.75 to 2.0). Two multiple pregnancies occurred in the IUI with COH group, and one, in the IUI without COH group. In couples with an abnormal PCT and a poor prognosis, IUI with COH leads to pregnancy rates comparable to those for IUI without COH. We propose to perform IUI without COH in couples with an abnormal PCT.

Effectiveness of intrauterine insemination in subfertile couples with an isolated cervical factor: a randomized clinical trial

After randomization of subfertile couples with an isolated cervical factor to intrauterine insemination for 6 months or expectant management for 6 months, 26 women (51%) vs. 16 women (33%) conceived, respectively. Of these pregnancies, 22 (43%) vs. 13 (27%) were ongoing (relative risk, 1.6; 95% confidence interval, 0.91 to 2.8). There was one multiple pregnancy in the group that was allocated to intrauterine insemination. This trial suggests a beneficial effect of IUI in couples with an isolated cervical factor.

The length of the fertile window is associated with the chance of spontaneously conceiving an ongoing pregnancy in subfertile couples

The period in each menstrual cycle during which sexual intercourse can result in conception is called the "fertile window". Although the fertile window closes on the day of ovulation, little is known about the moment it opens. We defined the first day of normal sperm-mucus interaction as the opening of the fertile window. We hypothesized that length of the fertile window varies between couples and that the number of days the fertile window is "open" is related to the time to spontaneous conception. METHODS Serial post-coital tests and sperm-mucus penetration tests were performed to detect the first normal sperm-mucus interaction day. Ovulation was confirmed by serial ultrasound. Using Cox' regression analysis, we determined whether the fertile window length was associated with time to ongoing pregnancy. This association was expressed in fecundability ratios (FR). RESULTS The fertile window length was determined in 410 subfertile couples. The fertile window length varied among couples from <1 to >5 days. The FR increased with increasing fertile window length and varied between 0.11 (95% CI: 0.03-0.45) for a fertile window of 1 day, to 2.4 (95% CI: 1.1-5.2) for a fertile window of 5 days or more. CONCLUSIONS The longer the fertile window in subfertile couples, the higher is the probability of spontaneously conceiving an ongoing pregnancy.

Relationship Between Level of Serum Sperm Immobilizing Antibody and Its Inhibitory Effect on Sperm Migration through Cervical Mucus in Immunologically Infertile Women

Sperm immobilizing antibodies often interfere with the penetration of sperm through the cervical mucus. However, the relationship between sperm immobilizing antibody titer and the result of the post-coital test (PCT) has not yet been clarified. The aim of this study was to investigate whether the 50% sperm immobilization unit (SI50) titer, a quantitative measure of sperm immobilizing antibody, in patients' sera was correlated with the result of PCT. The sperm immobilization test (SIT) was performed for 2834 infertile women in two university hospitals. The SI50 titers were evaluated by quantitative SIT. In some cases with sperm immobilizing antibody, PCT was carried out before ovulation and assessed according to the criteria of World Health Organization (1992). Infertile couples with abnormal semen characteristics were excluded. Seventy-four of 2834 women had sperm immobilizing antibodies in their sera, giving a positive rate of 2.6%. Twenty-four (77.4%) of 31 women with sperm immobilizing antibodies and 28 (20.4%) of 137 women without the antibody had abnormal PCT results. There was a significant difference between the two groups (P<0.0001). When patients with sperm immobilizing antibodies were divided into two groups according to the SI50 titers, the abnormal result of PCT was obtained in all 10 patients with high (>10) SI50 titers, while that was 14 (66.7%) in 21 patients with low (10) SI50 titers. There was a significant difference between the two groups (P=0.04). The SI50 titer in the serum can predict inhibitory effects on sperm migration through cervical mucus in immunologically infertile women. Evaluation of the SI50 titers in patients' sera seems to be useful for decision-making in infertile women with sperm immobilizing antibodies regarding whether they have the possibility of conceiving by timed intercourse.

Hotchkiss and MacLeod: An Historical Perspective

Hotchkiss and MacLeod: An Historical Perspective

Do clinical prediction models improve concordance of treatment decisions in reproductive medicine?

To assess whether the use of clinical prediction models improves concordance between gynaecologists with respect to treatment decisions in reproductive medicine. We constructed 16 vignettes of subfertile couples by varying fertility history, postcoital test, sperm motility, follicle-stimulating hormone level and Chlamydia antibody titre. Thirty-five gynaecologists estimated three probabilities, i.e. the 1-year probability of spontaneous pregnancy, the pregnancy chance after intrauterine insemination (IUI) and the pregnancy chance after in vitro fertilisation (IVF). Subsequently they proposed therapeutic regimens for these 16 fictional couples, i.e. expectant management, IUI or IVF. Three months later, the participant gynaecologists again had to propose therapeutic regimes for the same 16 fictional cases but this time accompanied by pregnancy chances obtained from prediction models: predictions on spontaneous pregnancy, IUI and IVF. Thirty-five gynaecologists working in academic and nonacademic hospitals in the Netherlands. Setting section. Main outcome measures The concordance between gynaecologists of probability estimates, expressed as interclass correlation coefficient (ICC) and the concordance between gynaecologists of treatment decisions, analysed by calculating Cohen's kappa (kappa). The gynaecologists differed widely in estimating pregnancy chances (ICC: 0.34). Furthermore, there was a huge variation in the proposed therapeutic regimens (kappa: 0.21). The treatment decisions made by gynaecologists were consistent with the ranking of their probability estimates. When prediction models were used, the concordance (kappa) for treatment decisions increased from 0.21 to 0.38. The number of gynaecologists counselling for expectant management increased from 39 to 51%, whereas counselling for IVF dropped from 23 to 14%. Gynaecologists differed widely in their estimation of prognosis in 16 fictional cases of subfertile couples. Their therapeutic regimens showed likewise huge variation. After confrontation with prediction models in the same 16 fictional cases, the proposed therapeutic regimens showed only slightly better concordance. Therefore a simple introduction of validated prediction models is insufficient to introduce concordant management between doctors.

Intrauterine Insemination versus Timed Intercourse for Cervical Hostility in Subfertile Couples

The postcoital test has poor diagnostic and prognostic characteristics. Nevertheless, some physicians believe it can identify scanty or abnormal mucus that might impair fertility. One way to avoid "hostile" cervical mucus is intrauterine insemination. With this technique, the physician injects sperm directly into the uterine cavity through a small catheter passed through the cervix; the theory is to bypass the "hostile" cervical mucus. Although most gynecologic societies do not endorse use of intrauterine insemination for hostile cervical mucus, some physicians consider it an effective treatment for women with infertility thought the result of cervical mucus problems. The aim of this review was to determine the effectiveness of intrauterine insemination with or without ovarian stimulation in women with cervical hostility who failed to conceive.We searched Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library Issue 2, 2005, MEDLINE (1966 to June 2005), EMBASE (1980 to June 2005), POPLINE (to June 2005), and LILACS (to June 2005). In addition, we contacted experts and searched the reference list of relevant articles and book chapters. We included randomized and quasirandomized, controlled trials comparing intrauterine insemination with intercourse timed at the presumed fertile period. Participants were women with cervical hostility who failed to conceive for at least 1 year. We assessed the titles and abstracts of 386 publications and 2 reviewers independently abstracted data on methods and results from 5 studies identified for inclusion. The main outcome is pregnancy rate per couple. We did not pool the outcomes of the included 5 studies in a meta-analysis resulting from the methodological quality of the trials and variations in the patient characteristics and interventions. Narrative summaries of the outcomes are provided. Each study was too small for a clinically relevant conclusion. None of the studies provided information on important outcomes such as spontaneous abortion, multiple pregnancies, and ovarian hyperstimulation syndrome. There is no evidence from the published studies that intrauterine insemination is an effective treatment for cervical hostility. Given the poor diagnostic and prognostic properties of the postcoital test and the observation that the test has no benefit on pregnancy rates, intrauterine insemination (with or without ovarian stimulation) is unlikely to be a useful treatment for putative problems identified by postcoital testing. Obstetricians & Gynecologists, Family Physicians. After completion of this article, the reader should be able to recall that there is a lack of adequate studies that support that intrauterine insemination (IUI) is an effective treatment of cervical hostility, explain that the postcoital test has poor diagnostic and prognostic properties, and state that the use of both tests has no benefit on pregnancy rates. Although many assisted reproductive technology (ART) programs no longer perform postcoital tests, many perform intrauterine insemination (IUI), often with gonadotropins or clomiphene citrate, in their subfertile patients. Therefore, this review article will be of value to our readers who treat subfertile patients with IUI, whether or not they perform postcoital tests. For additional explanations of the statistical tests employed in this review, see D. Grimes, KF Schulz, Obstetrical and Gynecologic Survey, 57; Supplement 3: S35, September 2002; and D. Grimes, KF Schulz, Obstetrical and Gynecologic Survey, Supplement 2, S53-S69, September 2005.-RBJ.

Vaginal safety after use of a bioadhesive, acid-buffering, microbicidal contraceptive gel (ACIDFORM) and a 2% nonoxynol-9 product

Background ACIDFORM is a microbicidal and contraceptive candidate with strong buffering capacity. Methods This was a Phase I blinded, randomized and crossover clinical study on two products, ACIDFORM and a commercial nonoxynol-9 (N-9) product (2%), evaluating their vaginal safety in 20 couples aged between 19 and 45 years. The women had regular menses, underwent previous tubal ligation, were not breast-feeding, had no vaginal sign and symptom and were in a stable partnership; both partners had no previous STI. Colposcopy, vaginal microbiology, inflammation markers and subject complaints were studied after coitus. Women were randomly assigned sequentially to receive ACIDFORM 0–30 min (0–30 min before intercourse), ACIDFORM 8–10 h (8–10 h before intercourse) or N-9 0–30 min after a control cycle. Results Mild/moderate vulvar irritation was observed in five postcoital test colposcopies, burning and pruritus were reported in six treated cycles and non-irritation-related symptoms were found in five cycles with different treatments. No difference in vaginal pH, Nugent scores, H 2O 2-producing lactobacillus or leukocytes and interleukin 6 in the cervicovaginal lavage was found between the treatment and control cycles. Conclusions ACIDFORM appears to be safe for clinical use once a day. There is a potential spermicidal–microbicidal role for ACIDFORM as a vaginal flora helper or as a vehicle for products, except N-9.

Place actuelle du test de Hühner dans l'exploration de la stérilité conjugale

The interest of the postcoital test (PCT) has been subject to debate in the last ten years. In France, it is considered as part of the basic fertility work-up, since it is no longer recommended as routine investigation in English literature. However, there is no evidence-based demonstration to support the test being ostracized. PCT is still useful as a diagnostic tool to control intercourse, quantify sperm concentration and evaluate sperm mobility in the cervical mucus.

Letrozole induction of ovulation in women with clomiphene citrate–resistant polycystic ovary syndrome may not depend on the period of infertility, the body mass index, or the luteinizing hormone/follicle-stimulating hormone ratio

Letrozole induction of ovulation in clomiphene citrate-resistant women with polycystic ovary syndrome is associated with an ovulation rate of 54.6% and pregnancy rate of 25%. There was no significant difference between letrozole responders and nonresponders in age, period of infertility, body mass index, waist circumference, LH, FSH, or LH/FSH ratio.

Which factors play a role in clinical decision-making in subfertility?

Sixteen vignettes of subfertile couples were constructed by varying fertility history, post-coital test, sperm motility, FSH concentration and Chlamydia antibody titre (CAT). Thirty-five gynaecologists estimated probabilities of treatment-independent pregnancy, intrauterine insemination (IUI) and IVF. Thereafter, they chose IUI, IVF or no treatment. The relative contribution of each factor to probability estimates and to subsequent treatment decisions was calculated. Duration of subfertility and maternal age were the most important contributors for gynaecologists’ estimates of treatment-independent pregnancy [relative contribution (RC) 41, 26%]. Maternal age and FSH concentration were the most important contributors in the estimates for IUI (RC: 51, 25%) and for IVF (RC: 64, 31%). The decision to start IVF was mainly determined by maternal age, duration of subfertility, FSH concentration and CAT. The relative contribution of maternal age and duration of subfertility was in concordance with existing prediction models, whereas previous pregnancy and FSH concentration were under- and overestimated respectively. In conclusion, maternal age, duration of subfertility and FSH concentration are the main factors in clinical decision-making in subfertility. Gynaecologists overestimate the importance of FSH concentration, but underestimate that of a previous pregnancy, as compared with their importance reported in prediction models and guidelines.

Intra-uterine insemination versus timed intercourse for cervical hostility in subfertile couples.

The postcoital test has poor diagnostic and prognostic characteristics. Nevertheless, some physicians believe it can identify scanty or abnormal mucus that might impair fertility. One way to avoid 'hostile' cervical mucus is intrauterine insemination. With this technique, the physician injects sperm directly into the uterine cavity through a small catheter passed through the cervix; the theory is to bypass the "hostile" cervical mucus. Although most gynaecological societies do not endorse use of intrauterine insemination for hostile cervical mucus, some physicians consider it an effective treatment for women with infertility thought due to cervical mucus problems. The aim of this review was to determine the effectiveness of intrauterine insemination with or without ovarian stimulation in women with cervical hostility who failed to conceive. We searched Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library Issue 2, 2005, MEDLINE (1966 to June 2005), EMBASE (1980 to June 2005), POPLINE (to June 2005) and LILACS (to June 2005). In addition, we contacted experts and searched the reference list of relevant articles and book chapters. We included randomized and quasi-randomized controlled trials comparing intrauterine insemination with intercourse timed at the presumed fertile period. Participants were women with cervical hostility who failed to conceive for at least one year. We assessed the titles and abstracts of 386 publications and two reviewers independently abstracted data on methods and results from five studies identified for inclusion. The main outcome is pregnancy rate per couple. We did not pool the outcomes of the included five studies in a meta-analysis due to the methodological quality of the trials and variations in the patient characteristics and interventions. Narrative summaries of the outcomes are provided. Each study was too small for a clinically relevant conclusion. None of the studies provided information on important outcomes such as spontaneous abortion, multiple pregnancies, and ovarian hyperstimulation syndrome. There is no evidence from the published studies that intrauterine insemination is an effective treatment for cervical hostility. Given the poor diagnostic and prognostic properties of the postcoital test and the observation that the test has no benefit on pregnancy rates, intrauterine insemination (with or without ovarian stimulation) is unlikely to be a useful treatment for putative problems identified by postcoital testing.

The Value of the Post-Coital Test in the Basic Fertility Work-Up: A Nationwide Cohort Study and Decision Analysis

The Value of the Post-Coital Test in the Basic Fertility Work-Up: A Nationwide Cohort Study and Decision Analysis

Potential New Prognostic Factors In The Prediction Of Treatment Independent Pregnancy

Prognostic models for treatment-independent pregnancy might be a useful tool to prevent unnecessary treatment of subfertile couples, thus reducing unnecessary costs and multiple pregnancies. At present, three models for prediction of treatment-independent pregnancy have been developed (Eimers, 1994; Collins, 1995 and Snick, 1997). These models have recently been integrated in one prediction model (Hunault model). That model contained woman’s age, duration and type of subfertility, sperm motility and referral status, and was presented either with or without the post-coital test (PCT). The aim of the present study is to evaluate whether other factors are potentially useful in the prediction of treatment independent pregnancy. Potential new prognosticators were basal FSH-level, cycle length, body mass index (BMI), Chlamydia antibody test (CAT), one-sided tubal pathology confirmed by hysterosalpingography or laparoscopy, male age and male family fertility history. Nation wide prospective cohort study in The Netherlands. Between January 2002 and February 2004, we performed a multi-center prospective cohort study in 33 hospitals in the Netherlands. We included consecutive subfertile couples in whom the woman had a regular cycle, and who underwent a basic fertility work-up. All couples were followed until the occurrence of treatment-independent ongoing pregnancy, or until the start of treatment. Couples of whom the female partner had two-sided tubal pathology or the male partner had azoospermia were excluded. Potential prognosticators were related to the prediction of treatment-independent ongoing pregnancy using Cox’ proportional hazard analysis. Time to ongoing pregnancy was the primary outcome, expressed as hazard rate ratios (HRR). First, we constructed a model containing all the factors of the Hunault model. We added new potential variables and evaluated their contribution and whether variables of the Hunault model were forced out. In the latter analysis, we used a P-value of .50 as entry criterium and a P-value of .20 as a criterium to stay in the model. We included 4.950 consecutive couples. Until March 2005 we completed follow up of 4.561 couples, of whom 728 (16.0%) had an ongoing pregnancy within 12 months. The model of Hunault without a postcoital test had an area under the ROC-curve of .66 (95% CI .64-.68), whereas the model without the PCT had an area of .64 (95% CI .62-.66). Potential new prognosticators selected from the model were cycle length (HRR per extra cycle/year .84 (95% CI .72-.97)), BMI over 30 kg/m2 (HRR .44 (95% CI .23-.84)), male family fertility history (HRR .38 (95% CI .10-1.6)) and one-sided tubal pathology (HRR .40 (95% CI .21-.78)). Male age, basal FSH and the CAT were not selected. In the semen-analysis, total motile count was a stronger predictor than the semen motility. The PCT remained of prognostic value in the new model. This study demonstrates that the variables present in current prediction models for treatment independent pregnancy appear of importance at external validation. Moreover, cycle length, BMI, male family fertility history and one-sided tubal pathology are of importance for treatment-independent pregnancy. These factors should be incorporated in future prediction models for treatment-independent pregnancy.

A Randomized Clinical Trial Assessing The Additional Value of Ovarian Hyperstimulation in Intrauterine Insemination for Couples With an Abnormal Post-coı̈tal Test

At present, there is only one non-randomised study that assesses the effectiveness of controlled ovarian hyperstimulation (COH) in intrauterine insemination (IUI) for subfertile couples with a cervical factor. We evaluated the contribution of COH in couples with an abnormal post-coital test (PCT) undergoing IUI. Randomized clinical trial. We performed a randomised clinical trial in 24 Fertility Centers in The Netherlands. Couples were eligible if they had an abnormal PCT, either due to cervical hostility diagnosed by a well-timed, non-progressive PCT with normal semen parameters or due to a poor semen quality. These couples were randomly allocated to three cycles IUI with COH or three cycles IUI without COH. The primary endpoint was ongoing pregnancy within three IUI cycles. The treatment effect was expressed as a relative risk and 95% confidence interval (CI). The analysis was performed according the intention to treat principle. In a subgroup-analysis, we evaluated the follicular growth patterns in relation to the occurrence of pregnancy. We assumed an equal effect in both groups with an ongoing pregnancy rate of 18% after 3 cycles. To show this equavalence with a maximum difference of 12%, an alpha of 5% and a power of 80%, 117 couples were required in each group. At present, 250 couples have been included, and follow up for three cycles is available for 205 couples. In the IUI without COH group, 20 couples (19%) became pregnant of which 18 had an ongoing pregnancy (17%). In the IUI with COH group, 25 couples (26%) became pregnant, of which 23 had an ongoing pregnancy (24%). The relative risk of an ongoing pregnancy was 1.4 (95% CI 1.0 to 1.9). Two multiple pregnancies occurred in the IUI with COH group (8.7% of the ongoing pregnancies). The fraction of IUI cycles with multifollicular growth was 43% in IUI with COH versus 3% in IUI without COH. Pregnancy rates with or without multifollicular growth were 9.5% and 11% per cycle, respectively, with ongoing pregnancy rates of 6.8% and 10% per cycle. This trial suggest that COH has an additional effect to IUI in couples with an abnormal PCT.

A Randomized Clinical Trial Assessing the Effectiveness Of Intrauterine Insemination For Couples With an Isolated Cervical Factor

To assess the effectiveness of intrauterine insemination (IUI) in cervical factor subfertility. The effectiveness of IUI is well established for male and unexplained subfertility. Data on IUI for cervical factor subfertility from five small clinical trials are conflicting. Randomized clinical trial. We performed a randomized clinical trial in 17 Fertility Centers in The Netherlands. Couples were eligible if they had a cervical factor, diagnosed by a well-timed, non-progressive post-coital test (PCT) with normal semen parameters and otherwise no factors that reduced fertility. These couples were randomly allocated between expectant management or IUI for six months. In the first three IUI cycles no controlled ovarian hyperstimulation (COH) was given. If these attempts failed subsequent IUI cycles were performed with COH. The primary endpoint was ongoing pregnancy within 6 months. The treatment effect was expressed as a relative risk and 95% confidence interval (CI). The analysis was performed according the intention to treat principle. We assumed a three times higher pregnancy rate in the couples treated with IUI. To detect this anticipated difference in ongoing pregnancy rates after 6 months, with an alpha of 5% and a power of 80%, 55 couples were required in each group. At present, 98 couples have been included (89%) and six months follow-up is available for 77 couples. In the expectant management group, 11 couples (31%) became pregnant of which 9 had an ongoing pregnancy (26%). In the IUI group, 18 couples (43%) became pregnant of which 16 had an ongoing pregnancy (38%). The relative risk of an ongoing pregnancy was 1.5 (95% CI 0.99 to 2.2). This trial suggest a beneficial effect of IUI in couples with an isolated cervical factor. This effect should be considered by those who plea against performance of the post-coital test.

Efficacy of Assisted Rupture and Intrauterine Insemination in Infertile Patients With Luteinized Unruptured Follicles

Efficacy of Assisted Rupture and Intrauterine Insemination in Infertile Patients With Luteinized Unruptured Follicles

Diagnosis and treatment of immunologically infertile males with antisperm antibodies.

The presence of antisperm antibodies (ASA) can reduce fecundity in both males and females. The present review describes a strategy, established by investigations of the diverse inhibitory effects of ASA on fertility, for the appropriate diagnosis and treatment of infertile males with ASA. For infertile males with ASA, diagnosis using the direct-immunobead test (D-IBT), the postcoital test (PCT) and the hemizona assay (HZA) should be carried out as the basis for decision-making. If the patient with ASA has an abnormal hemizona index, it seems reasonable to advise selecting intracytoplasmic sperm injection-embryo transfer (ICSI-ET) as a primary treatment. However, it has been shown that some immunologically infertile males with normal fertilizing ability established pregnancy by timed intercourse (TI) or intrauterine insemination (IUI). In such patients with ASA having normal hemizona index, TI or IUI can be selected based on the PCT result. Therefore, the treatment strategy for males with ASA is similar to that for infertile males with oligozoospermia or asthenozoospermia. In conclusion, it should be emphasized that a diversity of ASA exists and their effects on fertility in infertile males. Although there is an argument that routine testing for ASA in males is not always necessary, one should be aware that in some cases of failed IUI or IVF, ICSI is selected afterward because of the diagnosis of ASA. (Reprod Med Biol 2005; 4: 133-141).

Surrogate End Points in Clinical Research: Hazardous to Your Health

Surrogate end points in clinical research pose real danger. A surrogate end point is an outcome measure, commonly a laboratory test, that substitutes for a clinical event of true importance. Resistance to activated protein C, for example, has been used as a surrogate for venous thrombosis in women using oral contraceptives. Other examples of inappropriate surrogate end points in contraception include the postcoital test instead of pregnancy to evaluate new spermicides, breakage and slippage instead of pregnancy to evaluate condoms, and bone mineral density instead of fracture to assess the safety of depo-medroxyprogesterone acetate. None of these markers captures the effect of the treatment on the true outcome. A valid surrogate end point must both correlate with and accurately predict the outcome of interest. Although many surrogate markers correlate with an outcome, few have been shown to capture the effect of a treatment (for example, oral contraceptives) on the outcome (venous thrombosis). As a result, thousands of useless and misleading reports on surrogate end points litter the medical literature. New drugs have been shown to benefit a surrogate marker, but, paradoxically, triple the risk of death. Thousands of patients have died needlessly because of reliance on invalid surrogate markers. Researchers should avoid surrogate end points unless they have been validated; that requires at least one well done trial using both the surrogate and true outcome. The clinical maxim that "a difference to be a difference must make a difference" applies to research as well. Clinical research should focus on outcomes that matter.