Prediction of sperm extraction in non-obstructive azoospermia patients: a machine-learning perspective.

STUDY QUESTION: Can a machine-learning-based model trained in clinical and biological variables support the prediction of the presence or absence of sperm in testicular biopsy in non-obstructive azoospermia (NOA) patients? SUMMARY ANSWER: Our machine-learning model was able to accurately predict (AUC of 0.8) the presence or absence of spermatozoa in patients with NOA. WHAT IS KNOWN ALREADY: Patients with NOA can conceive with their own biological gametes using ICSI in combination with successful testicular sperm extraction (TESE). Testicular sperm retrieval is successful in up to 50% of men with NOA. However, to the best of our knowledge, there is no existing model that can accurately predict the success of sperm retrieval in TESE. Moreover, machine-learning has never been used for this purpose. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study of 119 patients who underwent TESE in a single IVF unit between 1995 and 2017 was conducted. All patients with NOA who underwent TESE during their fertility treatments were included. The development of gradient-boosted trees (GBTs) aimed to predict the presence or absence of spermatozoa in patients with NOA. The accuracy of these GBTs was then compared to a similar multivariate logistic regression model (MvLRM). PARTICIPANTS/MATERIALS, SETTING, METHODS: We employed univariate and multivariate binary logistic regression models to predict the probability of successful TESE using a dataset from a retrospective cohort. In addition, we examined various ensemble machine-learning models (GBT and random forest) and evaluated their predictive performance using the leave-one-out cross-validation procedure. A cutoff value for successful/unsuccessful TESE was calculated with receiver operating characteristic (ROC) curve analysis. MAIN RESULTS AND THE ROLE OF CHANCE: ROC analysis resulted in an AUC of 0.807 ± 0.032 (95% CI 0.743-0.871) for the proposed GBTs and 0.75 ± 0.052 (95% CI 0.65-0.85) for the MvLRM for the prediction of presence or absence of spermatozoa in patients with NOA. The GBT approach and the MvLRM yielded a sensitivity of 91% vs. 97%, respectively, but the GBT approach has a specificity of 51% compared with 25% for the MvLRM. A total of 78 (65.3%) men with NOA experienced successful TESE. FSH, LH, testosterone, semen volume, age, BMI, ethnicity and testicular size on clinical evaluation were included in these models. LIMITATIONS, REASONS FOR CAUTION: This study is a retrospective cohort study, with all the associated inherent biases of such studies. This model was used only for TESE, since micro-TESE is not performed at our center. WIDER IMPLICATIONS OF THE FINDINGS: Machine-learning models may lay the foundation for a decision support system for clinicians together with their NOA patients concerning TESE. The findings of this study should be confirmed with further larger and prospective studies. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Division of Obstetrics and Gynecology, Soroka University Medical Center, there are no potential conflicts of interest for all authors.

Testicular tissue cryopreservation: 8 years of experience from a coordinated network of academic centers.

STUDY QUESTION: Is it feasible to disseminate testicular tissue cryopreservation with a standardized protocol through a coordinated network of centers and provide centralized processing/freezing for centers that do not have those capabilities? SUMMARY ANSWER: Centralized processing and freezing of testicular tissue from multiple sites is feasible and accelerates recruitment, providing the statistical power to make inferences that may inform fertility preservation practice. WHAT IS KNOWN ALREADY: Several centers in the USA and abroad are preserving testicular biopsies for patients who cannot preserve sperm in anticipation that cell- or tissue-based therapies can be used in the future to generate sperm and offspring. STUDY DESIGN, SIZE, DURATION: Testicular tissue samples from 189 patients were cryopreserved between January 2011 and November 2018. Medical diagnosis, previous chemotherapy exposure, tissue weight, and presence of germ cells were recorded. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human testicular tissue samples were obtained from patients undergoing treatments likely to cause infertility. Twenty five percent of the patient's tissue was donated to research and 75% was stored for patient's future use. The tissue was weighed, and research tissue was fixed for histological analysis with Periodic acid-Schiff hematoxylin staining and/or immunofluorescence staining for DEAD-box helicase 4, and/or undifferentiated embryonic cell transcription factor 1. MAIN RESULTS AND THE ROLE OF CHANCE: The average age of fertility preservation patients was 7.9 (SD = 5) years and ranged from 5 months to 34 years. The average amount of tissue collected was 411.3 (SD = 837.3) mg and ranged from 14.4 mg-6880.2 mg. Malignancies (n = 118) were the most common indication for testicular tissue freezing, followed by blood disorders (n = 45) and other conditions (n = 26). Thirty nine percent (n = 74) of patients had initiated their chemotherapy prior to undergoing testicular biopsy. Of the 189 patients recruited to date, 137 have been analyzed for the presence of germ cells and germ cells were confirmed in 132. LIMITATIONS, REASONS FOR CAUTION: This is a descriptive study of testicular tissues obtained from patients who were at risk of infertility. The function of spermatogonia in those biopsies could not be tested by transplantation due limited sample size. WIDER IMPLICATIONS OF THE FINDINGS: Patients and/or guardians are willing to pursue an experimental fertility preservation procedure when no alternatives are available. Our coordinated network of centers found that many patients request fertility preservation after initiating gonadotoxic therapies. This study demonstrates that undifferentiated stem and progenitor spermatogonia may be recovered from the testicular tissues of patients who are in the early stages of their treatment and have not yet received an ablative dose of therapy. The function of those spermatogonia was not tested. STUDY FUNDING/COMPETING INTEREST(S): Support for the research was from the Eunice Kennedy Shriver National Institute for Child Health and Human Development grants HD061289 and HD092084, the Scaife Foundation, the Richard King Mellon Foundation, the Departments of Ob/Gyn & Reproductive Sciences and Urology of the University of Pittsburgh Medical Center, United States-Israel Binational Science Foundation (BSF), and the Kahn Foundation. The authors declare that they do not have competing financial interests.

Risk of major congenital malformations following first-trimester exposure to vaginal azoles used for treating vulvovaginal candidiasis: a population-based retrospective cohort study.

OBJECTIVE: To evaluate the risk for major malformations following first-trimester exposure to vaginal azoles. DESIGN: A population-based retrospective cohort study of women exposed to vaginal azoles from the first day of the last menstrual period until the 90th gestational day. SETTING: A combination of four computerised databases: medications, birth, infant hospitalizations, and pregnancy terminations. POPULATION: All women who gave birth or underwent a pregnancy termination at Soroka Medical Center, Beer-Sheva, Israel, between 1999 and 2009. METHODS: Crude and adjusted relative risks for major congenital malformations and for specific malformations according to organ systems were calculated using a multivariate negative binomial regression. Potential confounders were assessed and controlled for included parity, maternal age, ethnicity, maternal diabetes, smoking, and year of birth or pregnancy termination. Additional analysis using propensity score matching was performed for selected malformations. MAIN OUTCOME MEASURES: Major malformations as well as specific malformations according to organ systems. RESULTS: Of 101 615 pregnancies, 1993 (1.96%) were exposed to clotrimazole vaginal tablets and 313 (0.31%) to miconazole vaginal tablets during the first trimester of pregnancy. No association was found between first-trimester exposure to clotrimazole and major or specific malformations. An association was found between miconazole exposure and musculoskeletal malformation in general and other congenital musculoskeletal anomalies in particular. However, no association was detected when propensity score matching was used. CONCLUSIONS: Intrauterine exposure to vaginal azoles during the first trimester of pregnancy was not associated with either major or specific malformations according to organ systems. TWEETABLE ABSTRACT: First-trimester exposure to vaginal azoles is not associated with either major or specific malformations.

The fetal safety of clomiphene citrate: a population-based retrospective cohort study.

OBJECTIVE: To evaluate whether exposure to clomiphene citrate (CC) for ovulation induction is associated with major malformations overall or with specific fetal anomalies. DESIGN: We conducted a population-based retrospective cohort study. Exposure was defined as CC dispension from 2 months before conception through the first month of pregnancy. SETTINGS: Four databases were combined: medication, birth, hospitalization, and terminations of pregnancy. POPULATION: The study included all women in southern Israel who gave birth or underwent termination of pregnancy at Soroka Medical Center, from 1998 to 2009. METHODS: The rates of major malformations overall and six different subcategories of anomalies were evaluated. The crude odds ratio (OR) was calculated with a 95% confidence interval (95% CI). Subsequently the adjusted odds ratio (aOR) was calculated using multiple logistic regression models controlling for maternal age, pre-pregnancy diabetes, parity, ethnicity, the calendar year in which the birth/termination of pregnancy took place, smoking, and the use of gonadotropins and progesterone. MAIN OUTCOME MEASURES: Major malformations overall and specific fetal malformations by organ systems. RESULTS: Of 114 961 pregnant women, 1872 were exposed to CC. No association was detected between exposure to CC and rates of major malformations overall (aOR 1.08, 95% CI 0.88-1.32) or rates of subcategories of malformations. Exposure was not associated with anencephaly (aOR 2.27, 95% CI 0.44-11.71) or oesophageal atresia (aOR 3.681, 95% CI, 0.65-20.76). CONCLUSIONS: In this large population-based retrospective cohort study, exposure to CC was not associated with an increased risk of either rates of major malformations overall or rates of specific malformations. TWEETABLE ABSTRACT: An observational study: no increased risk for fetal malformations following exposure to clomiphene citrate.

Cell-free DNA and telomere length among women undergoing in vitro fertilization treatment.

PURPOSE: The current research is aimed at finding potential non-invasive bio-markers that will help us learn more about the mechanisms at play in failed assisted reproduction treatment. This exploratory pilot study examined the relationship between cell-free DNA (CFD) in plasma and telomere length in lymphocytes among women undergoing in vitro fertilization (IVF) and compared telomere length and CFD levels to a healthy control group. METHODS: Blood of 20 women undergoing IVF was collected at three time points during the IVF cycle. We assessed the relationship between CFD and telomere length as well as controlling for morning cortisol levels. We also collected blood of 10 healthy controls at two time points (luteal and follicular phases of the menstrual cycle) and compared mean telomere length, CFD, and cortisol levels between the IVF patients and healthy controls. RESULTS: The results revealed an inverse relationship between CFD levels and telomere lengths at several time points that remained significant even after controlling for cortisol levels. Women undergoing IVF had statistically significant higher levels of CFD and shorter telomeres compared to healthy controls. CONCLUSIONS: The relationship between telomere length and CFD should be further explored in larger studies in order to uncover potential mechanisms that cause both shortened telomere length and elevated CFD in women undergoing IVF.

Glial cell line-derived neurotrophic factor (GDNF) induced migration of spermatogonial cells in vitro via MEK and NF-kB pathways.

Glial cell line-derived neurotrophic factor (GDNF) regulates spermatogonial stem cell (SSC) maintenance. In the present study, we examined the levels and the cellular origin of GDNF in mouse testes during age-development, and the capacity of GDNF to induce migration of enriched GFR-α1 positive cells in vitro. The involvement of MAP kinase (MEK) and NF-kB signal pathways were examined. Our results show high levels of GDNF in testicular tissue of one-week-old mice which significantly decreased with age when examined by ELISA, real time PCR (qPCR) and immunofluorescence staining (IF) analysis. GDNF receptor (GFR-α1) expression was similar to GDNF when examined by qPCR analysis. Only Sertoli cell cultures (SCs) from one-week-old mice produced GDNF compared to SCs from older mice. However, peritubular cells from all the examined ages did not produce GDNF. The addition of recombinant GDNF (rGDNF) or supernatant from SCs from one-week-old mice to GFR-α1 positive cells induced their migration in vitro. This effect was significantly reduced by the addition of inhibitors to MEK (PD98059, U0126), NF-kB (PDTC) and IkB protease inhibitor (TPCK). Our results show for the first time the capacity of rGDNF and supernatant from SCs to induce migration of enriched GFR-α1 positive cells, and the possible involvement of MEK, NF-kB and IkB in this process. This study may suggest a novel role for GDNF in the regulation SSC niches and spermatogenesis.

Interleukin-1 receptor antagonist is produced by sertoli cells in vitro.

The interleukin-1 (IL-1) system has been suggested to be involved in the cell-to-cell cross-talk within the testis. To identify a testicular cell source of IL-1 receptor antagonist (IL-1ra), mouse Sertoli cells were isolated, purified, cultured, and examined for IL-1ra. Our investigation revealed that Sertoli cells produce large amounts of immunoreactive IL-1ra under basal culture conditions, as examined by enzyme-linked immunosorbent assays. Its expression can be induced, showing maximum concentrations after 8 h of stimulation. Lipopolysaccharide, as well as IL-1alpha and -beta, were found to stimulate IL-1ra production in Sertoli cells. FSH is capable to induce IL-1ra production in Sertoli cells in a dose-dependent manner. Immunocytochemical staining confirmed the presence of IL-1ra in the cytoplasma of Sertoli cells. The presence of IL-1ra messenger RNA was demonstrated by RT-PCR analysis. Our results may help to better evaluate the IL-1 activity in the testis and may indicate the involvement of IL-1ra in the autocrine and paracrine regulation of testicular cell function.

Distinct expression levels of cytokines and soluble cytokine receptors in seminal plasma of fertile and infertile men.

OBJECTIVE: To compare the levels of interleukin (IL) 1 beta, IL-6, tumor necrosis factor (TNF) alpha, and soluble TNF (sTNF) receptors types I and II, and IL-1 receptor antagonist in seminal plasma of fertile and infertile men. DESIGN: Prospective and comparative study. SETTING: Andrology clinic of a university hospital. PATIENTS: Four groups of normogonadotropic men: group 1, donors with proven fertility (controls, n = 15); group 2, azoospermic men (n = 12); group 3, infertile men with oligoteratoasthenospermia (n = 20); and 11 men with oligoteratoasthenospermia and genital infection (n = 11). INTERVENTIONS: None. MAIN OUTCOME MEASURE: Measurement of cytokines and cytokine-soluble receptors in the semen by specific commercial kits. RESULTS: The levels of IL-1 beta, TNF-alpha, and IL-6 were similar in seminal plasma of controls and infertile men. The mean level of sTNF-I receptor in the seminal plasma of group 4 was 2.4 +/- 0.2 ng/mL, which was significantly lower than observed in seminal plasma of group 1 (3.88 +/- 0.5 ng/mL), the group 3 (4.1 +/- 0.4 ng/mL), or group 2 (3.03 +/- 0.35 ng/mL). The soluble receptor of TNF-II could not be detected in any group. Interleukin 1ra was 120 +/- 10 pg/mL in seminal plasma of group 1, but increased levels were detected in group 2 (420 +/- 180 pg/mL), group 3 (480 +/- 90 pg/mL), and even higher (760 +/- 120 ng/mL) in group 4 patients. CONCLUSIONS: During genital infection cytokines and various soluble receptors of immunoregulatory cytokines are expressed distinctly in seminal plasma. These factors also may be involved in the regulation of sperm cell functions and thus may affect male fertility. Our results may indicate local production of these factors in the secondary sex glands, independently of spermatogenesis.

Obstetric outcome of singleton pregnancies conceived by in vitro fertilization and ovulation induction compared with those conceived spontaneously.

OBJECTIVE: To compare the obstetric characteristics of singleton pregnancies conceived by IVF and ovulation induction with those conceived spontaneously. DESIGN: Case-control study. SETTING: Tertiary care medical center. PATIENT(S): All singleton pregnancies that were achieved by IVF (n = 169) and ovulation induction (n = 646) and were delivered from January 1989 through December 1994 were evaluated. Each group was compared with a separate control group that conceived spontaneously (n = 469 and n = 1,902 for the IVF and ovulation induction groups, respectively) and delivered during the same period and was matched in terms of maternal age, gestational age, and parity. INTERVENTION(S): Ovulation induction, IVF-ET. MAIN OUTCOME MEASURE(S): Obstetric complications. RESULT(S): Multivariate analysis showed that patients who conceived by IVF and ovulation induction had a significantly higher risk for gestational diabetes mellitus (odds ratio [OR] = 2.0; 95% confidence interval [CI] = 1.23-3.30 and OR = 1.9, 95% CI = 1.09-1.79, respectively), pregnancy-induced hypertension (OR = 2.1, 95% CI = 1.04-4.10 and OR = 1.5, 95% CI = 1.04-2.02, respectively), and cesarean section (OR = 3.6, 95% CI = 2.44-5.29 and OR = 1.4, 95% CI = 1.09-1.79, respectively) compared with their matched controls. CONCLUSION(S): After controlling for maternal age, gestational age, and parity, we demonstrated that singleton pregnancies conceived by IVF and ovulation induction are at increased risk for maternal gestational diabetes mellitus and pregnancy-induced hypertension, and at greater risk for delivery by cesarean section.

Efficacy of kallikrein in the treatment of oligozoospermia and asthenozoospermia: a double-blind trial.

OBJECTIVE: To assess the effect of kallikrein on sperm motility and sperm count in infertile oligozoospermic and asthenozoospermic men. DESIGN: Double-blind placebo-controlled clinical trial. SETTING: Multicenter trial in three andrologic clinics. PATIENTS: Infertile men with < 20 x 10(6) total sperm count and > 3 x 10(6) sperm cells/mL and/or sperm motility of < 30%. INTERVENTIONS: One hundred fourteen men received either placebo or 600 kallikrein units of kallidinogenase by mouth daily for 12 weeks. Semen analyses were performed before and at 6-week intervals during the trial. Compliance and incidence of adverse effects were assessed. RESULTS: The incidence of adverse effects was similar under placebo and under kallidinogenase treatment, usually mild, transient, and did not require the cessation of treatment in any patient. Kallidinogenase was not superior to placebo in improving sperm count and sperm motility. CONCLUSIONS: At the doses and for the duration given, our results were disappointing. The absence of a therapeutical effect, as evidenced in the present study may be due to the very low absorption rate of kallidinogenase after oral administration. Probably a much higher dose of kallidinogenase should be used to achieve a therapeutic affect.

Sperm quality of subfertile males before and after treatment with human follicle-stimulating hormone.

OBJECTIVE: To assess the potential of short-term systemic administration of FSH for improving sperm quality, including ultrastructure, in teratozoospermic patients having normal endocrine profiles. DESIGN: Semen parameters were assessed prospectively using light microscopy (LM), biochemical analysis, and quantitative ultramorphological analyses within 2 months before FSH administration and within 5 days after the end of treatment. SETTING: Samples were collected from patients who were referred to the male fertility clinic at Bar-Ilan University. PATIENTS: Thirty-one patients with teratozoospermia who exhibited normal hormonal profiles and who failed to fertilize their wives in at least two previous IVF attempts (n = 17) or who had wives with apparent normal fertility unable to conceive for > or = 5 years (n = 14) were classified as subfertile. One hundred one males with no previous history of infertility, whose wives conceived after < or = 12 months of pregnancy expectation, served as the control group. INTERVENTION: Treatment was 75 IU FSH administered daily for 30 days. MAIN OUTCOME MEASURES: Pretreatment and post-treatment sperm evaluation of basic and quantitative ultramorphological analyses parameters. The hypothesis was FSH treatment may improve spermatid morphogenesis by its multiple actions on the Sertoli-gamete cell compartment without interfering with the testicular hormonogenic function. RESULTS: A significant improvement in agenesis of the acrosome and in the amorphous heads was observed, reaching normal values after treatment with FSH. The axonema deteriorated. No significant changes were observed in basic semen analysis parameters. CONCLUSIONS: Because malformations of the fine structure of the sperm head subcellular organelles seem to be prerequisites for the success of FSH treatment, ultramorphological examination of the sperm may serve as an indication for the probability of success of this treatment.

Production of interleukin-1-like molecules by human sperm cells.

OBJECTIVE: To characterize and localize interleukin (IL)-1alpha and IL-1beta in human sperm cells. DESIGN: Prospective and comparative study. SETTING: Andrology clinic of a university hospital. PATIENT(S): Two groups of normogonadotropic men: 17 fertile men (donors with proved fertility) and 8 oligoteratoasthenospermic infertile men. INTERVENTION(S): None. MAIN OTUCOME MEASURE(s): Evaluation of IL-1alpha and IL-1beta levels and expression in sperm cells by immunohistochemical staining, immunoassay, and Western blot analysis. RESULT(S): Both types of IL-1-like molecules (IL-1alpha and IL-1beta) were expressed in the tail, neck, and head of sperm cells of fertile men and patients with oligoteratoasthenospermia. Swim-up sperm cells from fertile men and patients with oligoteratoasthenospermia secreted similar levels of IL-1-like molecules. The levels of IL-1beta-like molecules were higher than those of IL-1alpha-like molecules in both groups. The expressed IL-1-like molecules were characterized by the presence a 60-kd protein for both IL-1alpha-like and IL-1beta-like molecules. In some samples of both fertile men and infertile men with oligoteratoasthenospermia, 17-kd, 33-kd, and 45-kd IL-1beta-like molecules were detected. Impairment of sperm function, such as decreased sperm count and motility and/or impaired morphology, was not related to the capacity of sperm cells to produce IL-1-like molecules. CONCLUSION(S): IL-1 molecules originating in sperm cells may play a role in the physiologic functions of sperm cells (autocrine effect) and/or in cell-cell interactions within the testis (paracrine effect).

Fertility drugs and the risk of breast and ovarian cancers: results of a long-term follow-up study.

OBJECTIVE: To investigate a possible linkage between the use of fertility drugs for infertility and the risk of breast and ovarian cancers. DESIGN: Long-term, historic-prospective study. SETTING: Fertility clinic in a university hospital. PATIENT(S): Files of 1,197 infertile women with a mean (+/- SD) follow-up of 17.9+/-5 years (21,407 person-years) were reviewed. Diagnoses, number of courses, and dosage of fertility drugs were extracted from the files. INTERVENTION(S): Cancers were identified by record linkage to the National Cancer Registry. Histopathologic reports and data on estrogen and progesterone receptors in breast cancer tissue were also reviewed. MAIN OUTCOME MEASURE(S): Standardized incidence ratio with 95% confidence interval (CI) were used for risk assessment. RESULT(S): Of 20 breast cancers (standardized incidence ratio, 1.40 [95% CI, 0.83-2.10]), 16 were detected among 780 women who had been exposed to 3,978 cycles of clomiphene citrate (CC) and/or hMG (standardized incidence ratio, 1.65 [95% CI, 0.94-2.68]). The standardized incidence ratio for this cancer was significantly increased only in patients with one or two CC treatments and a dose of < or =1,000 mg (2.6 [1.19-5.0] and 2.52 [1.21-4.64], respectively). Two cases of ovarian cancer (1 patient unexposed) were observed with no evidence of excessive risk. Six of the eight patients with data on estrogen and progesterone receptors were exposed to CC, and all tested positive for these receptors. CONCLUSION(S): An association between the use of fertility drugs and an increased risk of breast and ovarian cancers has not been confirmed.

Treatment outcome in women with a single ovary versus patients with two ovaries undergoing in vitro fertilization and embryo transfer (IVF/ET).

OBJECTIVE: To compare ovarian response and pregnancy rate between women with one and two ovaries undergoing in vitro fertilization and embryo transfer (IVF/ET). STUDY DESIGN: 20 IVF/ET treatment cycles in ten women with a single ovary were compared with 60 IVF/ET cycles in 47 women with two ovaries. Both groups were matched for age and treated for mechanical infertility. In both groups treatment protocol included gonadotropin releasing hormone/human menopausal gonadotropin/human chorionic gonadotropin (GnRH/hMG/hCG). RESULTS: Effective daily dose of gonadotropins (3.7+/-0.7 vs. 3.6+/-1.0), mean 17beta-estradiol levels on day of hCG administration (1136+/-467 vs. 1343+/-776), number of retrieved oocytes (6.4+/-3.7 vs. 8.3+/-4.2) and number of embryos per transfer (3.0+/-0.7 vs 2.9+/-1.2) were not statistically different between the groups. A significantly higher pregnancy rate was observed among women with one ovary (52.9%) as compared with those with two ovaries (20.8%), (P=0.015). Multivariate logistic regression analysis demonstrated an odds ratio of 5.73 for patients with a single ovary. CONCLUSION: Treatment outcome in patients with a single ovary undergoing IVF/ET is comparable to those with two ovaries. The unexpected significantly higher pregnancy rate observed among these patients need to be further evaluated.

Chlamydial IgG and IgA in serum and follicular fluid among patients undergoing in vitro fertilisation.

The point prevalence of IgG and IgA antibodies to Chlamydia was analyzed in serum and follicular fluid in 63 patients undergoing in vitro fertilisation (IVF) in comparison to sera of 298 healthy women by the single serovar (L2) inclusion immunoperoxidase assay (IPA). The presence of specific IgG and IgA to Chlamydia in follicular fluid was demonstrated. No statistical association was found between the presence of specific Chlamydia IgG and IgA in serum and follicular fluid to oocyte fertilization. The positive predictive value for mechanical infertility of Chlamydia IgG at titers of greater than or equal to 128 and IgA titers at greater than or equal to 16 was 91 and 92%, respectively, in this high-risk group for mechanical infertility. Multiple regression analysis singled out Chlamydia IgG levels as a major contributor to the variance between the groups of infertile patients.

[Beta-interferon for labial and genital herpes virus infection].

19 women and 9 men, aged 15-59 (mean, 35.1), who had had recurrent lip or genital infections with herpes virus (HSV) for from 1-38 years, were treated with beta-interferon gel (100,000 IU/g), self-administered 4 times daily to the affected areas. In half the patients the drug and a placebo were given in a double-blind, cross-over study. The trial lasted 30 months. Frequency of attacks, length of each attack and its severity, and the presence of itching were noted. If there was improvement in at least 2 parameters treatment was considered successful. This was the case in about 75% of the patients. The mean number of attacks per year before and during treatment with interferon was 6.8 and 3.0, respectively (p less than 0.003) and the mean length of attacks 8.2 and 4.7 days, respectively (p less than 0.001). Results of the double-blind, cross-over test were also significant, and were similar to those for the total group. These results clearly indicate that local interferon is effective treatment for genital and labial HSV infections.