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Objective: Although preimplantation genetic diagnosis (PGD) is offered to an increasing number of patients as an alternative to conventional prenatal diagnosis, very little is known about the attitudes of potential consumers of the technique. The main objective of this study was to investigate their reproductive behaviour and to assess the opinions of carriers and patients with haemophilia (HA) and cystic fibrosis (CF) about PGD and to elucidate the possible impact of PGD on future reproductive behaviour in carriers. Materials/Methods: The survey was performed as a part of a comprehensive Health Technology Assessment analysis comparing PGD with conventional prenatal diagnosis in terms of technological aspects, ethics, cost-effectiveness and organizational aspects. Two populations with hereditary disease in the family were investigated. One group was families with cystic fibrosis (members of the Danish Cystic Fibrosis Association) and the second group was people treated and advised about haemophilia A or B at the Centre for Haemophilia and Thrombosis at Aarhus University Hospital, Denmark. The survey was done with postal questionnaires, answers to which were anonymous. A total of 298 carriers of HA and haemophiliacs and 561 patients with CF and parents of children with CF were surveyed with a questionnaire pertaining to reproductive behaviour, their perception of the severity of the disease and future priorities regarding reproductive choices if offered PGD. The questionnaire offered a short description of PGD, sex selection in the HA group and specific gene diagnosis in the CF group. Results: Almost two-thirds of parents of haemophiliacs and 42% of parents of a child with CF had avoided having more children because of the risk of having another affected child. Most (78%) carriers of HA had accepted prenatal diagnosis when offered, but only a few (24%) had had a therapeutic abortion if the test proved positive. Prenatal diagnosis was accepted significantly more often by parents of children with CF (89%): 94% had an abortion if the test was positive, According to 77% of the HA group and 94% of CF carriers, PGD should be offered in the public health care system. More CF carriers (54%) than HA carriers (18%) would opt for PGD if available in the public health care system. Preference for PGD was positively correlated with the severity of HA, but not with the severity of CF. In the subgroup of severe haemophiliacs, PGD was the most common priority (28%). Among the subgroup of 11 carriers of CF who had rejected prenatal diagnosis, four opted for PGD if possible. None of 12 carriers of HA who had rejected prenatal diagnosis would have PGD of gender if possible. Conclusions: The birth of a genetically affected child has a major impact on reproductive behaviour. PGD is widely demanded by carriers of CF and, for a minority. PGD is the only acceptable reproductive technique to have unaffected children. PGD of gender is only of interest in carriers of severe haemophilia. Whether specific gene diagnosis in HA, rather than sex determination, might change the acceptance of PGD in haemophilia remains to be examined. [ABSTRACT FROM AUTHOR]

The fusion of non-Abelian anyons is a fundamental operation in measurement-only topological quantum computation 1 . In one-dimensional topological superconductors (1DTSs) 2-4 , fusion amounts to a determination of the shared fermion parity of Majorana zero modes (MZMs). Here we introduce a device architecture 5 that is compatible with future tests of fusion rules. We implement a single-shot interferometric measurement of fermion parity 6-11 in indium arsenide-aluminium heterostructures with a gate-defined superconducting nanowire 12-14 . The interferometer is formed by tunnel-coupling the proximitized nanowire to quantum dots. The nanowire causes a state-dependent shift of the quantum capacitance of these quantum dots of up to 1 fF. Our quantum-capacitance measurements show flux h/2e-periodic bimodality with a signal-to-noise ratio (SNR) of 1 in 3.6 μs at optimal flux values. From the time traces of the quantum-capacitance measurements, we extract a dwell time in the two associated states that is longer than 1 ms at in-plane magnetic fields of approximately 2 T. We discuss the interpretation of our measurements in terms of both topologically trivial and non-trivial origins. The large capacitance shift and long poisoning time enable a parity measurement with an assignment error probability of 1%., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Study Question: Does the metabolomic profile, obtained with nuclear magnetic resonance (NMR), of spent culture media from human embryos correlate with reproductive potential in a cohort of good prognosis patients?, Summary Answer: In a large cohort of single transferred blastocysts from a homogeneous group of good prognosis patients, we find a high degree of individual variation in the metabolome that, however, has no relation to pregnancy outcome., What Is Known Already: Differences among various specific metabolites have been linked to reproductive potential. Although results from retrospective near infrared (NIR) spectroscopy analyses of spent culture medias from transferred embryos were promising, randomized controlled trials were unable to demonstrate that NIR analysis improved pregnancy rates. Therefore, a more detailed investigation of the relation between embryo metabolism and reproductive potential is required. NMR is a powerful technique that provides detailed structural and dynamic information., Study Design, Size, Duration: A prospective cohort study was conducted at the Fertility Clinic, Aarhus University Hospital between February 2011 and July 2012. Infertile patients aged <38 years without endometriosis were offered participation and their embryos were included if greater than or equal to eight oocytes were retrieved. In total, 161 infertile patients were included in the cohort., Participants/materials, Setting, Methods: Spent culture media was collected on Days 3 and 5 after oocyte retrieval from 148 single transferred embryos. NMR spectra were obtained from 12 µl of spent media. Data were quantitatively analysed using multivariate analysis with respect to pregnancy outcome, defined as a live fetus by ultrasound in gestational Week 8, along with patient and treatment related variables such as embryo score, age, BMI, fertilization method and cause of infertility., Main Results and the Role of Chance: A total of 148 cycles were included in the analysis [embryo transfer cancelled (n = 12), no media collected (n = 1)]. Clinical pregnancy was confirmed in 47 patients (32%). We obtained high quality NMR spectra for 141 Day 3 and 137 Day 5 samples. Our spectra show a high degree of individual variation. Multivariate data analysis was performed on spectral data with several different pre-processing combinations, i.e. binning, alignment, normalization and scaling in the attempt to develop a valid prediction model. Different strategies of multivariate analysis showed, however, no correlation between the NMR profiles and pregnancy outcome, patient or treatment characteristics. No model could therefore be developed for prediction of pregnancy outcome. We conclude that within this group of good prognosis patients, large-scale metabolic variations between embryos detected with NMR have no apparent association with pregnancy outcome., Limitations, Reasons for Caution: Although this study is the largest we know of using NMR to investigate metabolomic profiles of single-transferred embryos, there may be differences that would be detected with a larger study. When analysing such a small sample volume, even small variations in the amount of media and dilution may introduce a large uncertainty in the results., Wider Implications of the Findings: Our study questions the usefulness of the entire metabolome for embryo selection, which should direct the search for viability markers in the culture media towards individual components., Study Funding/competing Interests: Funding was provided by Aarhus University, the Lippert Foundation, the Toyota Foundation, the Aase og Einar Danielsen foundation. Research at the Fertility Clinic, Aarhus Universtity Hospital is supported by an unrestricted grant from MSD and Ferring. The authors declare no competing interest., Trial Registration Number: NCT01139268., (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: A number of studies have investigated the relationship between psychological factors such as stress and distress (measured as anxiety and depression) and outcomes of assisted reproductive technology (ART). The results, however, are inconsistent, and the strength of any associations remains to be clarified. We conducted a systematic review and meta-analysis of the results of studies reporting on the associations between stress, anxiety, and depression and ART outcomes., Methods: Prospective studies reporting data on associations between stress or distress in female patients and ART outcome were identified and evaluated by two independent researchers according to an a priori developed codebook. Authors were contacted in cases of insufficient data reporting. Stress was defined as perceived stress, work-related stress, minor life events or major life events, and distress was defined as anxiety or depression., Results: A total of 31 prospective studies were included. Small, statistically significant, pooled effect sizes were found for stress [ESr, effect size correlation) = -0.08; P = 0.02, 95% confidence interval (CI): -0.15, -0.01], trait anxiety (ESr = -0.14; P = 0.02, 95% CI: -0.25, -0.03) and state anxiety (ESr = -0.10, P = 0.03, 95% CI: -0.19, -0.01), indicating negative associations with clinical pregnancy rates. A non-significant trend (Esr = -0.11, P = 0.06) was found for an association between depression and clinical pregnancy. For serum pregnancy tests and live birth rates, associations between trait anxiety or state anxiety were not significant. The fail safe number did not exceed the suggested criterion in any analyses, between-study heterogeneity was considerable and the mean age, mean duration of infertility and percentage of first time ART attenders in the study samples were found to moderate several of the associations., Conclusions: Small but significant associations were found between stress and distress and reduced pregnancy chances with ART. However, there were a limited number of studies and considerable between-study heterogeneity. Taken together, the influence of stress and distress on ART outcome may appear somewhat limited.

The parr-smolt transformation involves complex modulation of immune parameters, affecting both cell populations and humoral factors. The expression of cytokines was studied in salmon cells and tissues during this period using an anadromous and a landlocked freshwater resident dwarf strain of Atlantic salmon (Salmo salar L.). The constitutive activity of three immunoregulatory genes encoding the cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) and the cyclo-oxygenase (COX) isoform COX-2 was investigated in head kidney, spleen and gill tissue from healthy, unvaccinated fish by real-time PCR. The TNF-alpha gene was generally lower expressed than COX-2 and IL-1beta1, which were approximately expressed at equal levels and constitutive expression was seen for COX-2 and IL-1beta1 in all tissues examined and at all sampling dates. The expression of all three genes in head kidney and spleen tissue seemed to be highest at the sampling in May for both strains around the time of seawater transfer suggesting an influence of smolting related hormones on cytokine expression. The gill tissue experienced the highest expression of IL-1beta1 and COX-2 at all sampling dates indicating that this organ is immunologically important.

Introduction: Preimplantation genetic diagnosis (PGD) is a possible alternative to prenatal diagnosis, whereby families with serious inherited diseases can avoid having children with the disease. The genetic diagnosis is performed on embryos before implantation and therefore implies IVF. Hence, PGD offers the possibility of transferring embryos without disease, thereby avoiding termination of pregnancy owing to an affected fetus., Material and Methods: Activities at the Centre for Preimplantation Genetic Diagnosis at Aarhus University Hospital since its opening in February 1999 are described. The fluorescent in situ hybridisation (FISH) technique was used for sex selection (hemophilia A and Duchenne's muscular dystrophy) and translocations. The polymerase chain reaction (PCR) was used for cystic fibrosis., Results: Of 20 PGD cycles started, 15 were successful in terms of transference of healthy or carrier embryos. A positive pregnancy test was found after six of 15 embryo transfers (40%) with two subsequent clinical pregnancies., Conclusions: The present pregnancy rates with PGD are comparable to those following IVF; the clinical pregnancy rate may seem low, but the cycle numbers are small. Preimplantation genetic diagnosis seems to be a realistic alternative for selected genetic diseases, in cases where the couple find abortion unacceptable.

Purpose: The aim of this study was to develop a multiplex PCR protocol, which could be suitable for screening of microdeletions in the three azoospermia factor (AZF) regions on the Y chromosome., Methods: In the screening protocol, 36 known sequence tagged site (STS) primer pairs were first tested in single PCR reactions and thereafter combined in multiplex PCR to test for specificity and sensitivity in order to develop a stable and reliable multiplex PCR assay to detect Y microdeletions., Results: Of the 36 primers tested, 11 turned out not to be specific or produced PCR products that were too weak, and they were therefore not used in the multiplex PCR. The remaining 25 STSs were selected on the basis of their ability to be reproducibly amplified with each other using identical amplification conditions. Five multiplex sets, each consisting of five primer pairs, were established in the multiplex PCR setup., Conclusion: The multiplex PCR protocol presented in this study is an easy and reliable method for detection of Y chromosome microdeletions and could be used for screening of infertile men to allow genetic counseling about the risk of transmitting infertility from father to son.

Polycystic ovary syndrome (PCOS) is probably the most prevalent endocrinopathy in women and the most common cause of menstrual disturbances during the reproductive age. It is characterised by the presence of polycystic ovaries on ultrasound examination together with clinical and biochemical signs of hyperandrogenaemia. The majority of patients will seek medical advice because of menstrual disturbances, infertility or signs of hyperandrogeneamia (hirsutism, acne, alopecia). In obese patients the therapeutic mainstay is weight reduction. Anovulatory infertility is treated by stimulation of ovulation, laparoscopic electrocautery or IVF, while patients with menstrual disturbances without a wish to conceive should be treated with cyclic gestagen therapy or oral contraceptives in order to reduce the increased life-long risk of endometrial cancer. Additionally, hirsutism may be treated by epilation or antiandrogen therapy. PCOS is a common disease with an increased risk of NIDDM, hypertension, cardiovascular disease and endometrial cancer. Polycystic ovary syndrome is thus a disease which needs attention from the health system.

The polycystic ovary syndrome (PCOS) is diagnosed by the simultaneous presence of polycystic ovaries by ultrasound together with clinical and biochemical signs of hyperandrogenaemia. Recently, it has been shown that a majority of PCO patients exhibit metabolic abnormalities, i.e. android obesity, insulin resistance and dyslipidaemia, all of which dispose to "civilized" life-style diseases such as cardiovascular disease and non-insulin dependent diabetes. PCOS is therefore not merely a gynaecological curiosity, but an endocrinopathy with multisystem sequelae. The endocrinological and metabolic aspects of the disease are discussed.

During investigations for infertility azoospermia was diagnosed in two men who were concomitantly using anabolic steroids for body-building. Following cessation of anabolic steroid use the semen quality was normalized. Suppression of spermatogenesis during treatment with testosterone and derivatives hereof is wellknown. Usage of anabolic steroids should be remembered as a cause of oligo- and azoospermia and asked about in cases of sperm counts approaching or at zero.

In Denmark, legislation has made cryopreservation of human oocytes and embryos possible since October 1992. The legislation is reviewed. Cryopreservation of embryos constitutes a significant improvement of infertility treatment. The number of oocyte pick-ups and the number of embryos transferred can be reduced without compromising the total likelihood of success of in-vitro fertilization (IVF) treatment. According to Danish law, frozen embryos can only be stored for one year. This limit will interfere with patient expectations in numerous cases, and the time limit should be expanded. Moreover, freezing of embryos should be allowed in connection with oocyte donation programmes.

Medical indications for in vitro fertilization and embryo transfer (IVF-ET) internationally and in Denmark are reviewed. Reports from large international centres document that tubal infertility, unexplained infertility, endometriosis and male infertility are equally good indications for IVF. Traditionally, tubal infertility has been the only medical indication qualifying for IVF treatment within the National Health Service in Denmark. Thus, in this country, couples with unexplained and male infertility and with endometriosis have to pay up to 25,000 D.Kr. per IVF-ET treatment in private fertility clinics. Since there is no scientific basis for this discrimination, it is urged that the present rules are changed, so that couples with unexplained and male infertility and endometriosis are also allowed IVF treatment free of charge in the public fertility clinics.

The most common indication for oocyte donation is ovarian insufficiency due to premature menopause or resistant ovarian syndrome and ovarian dysgenesis with either normal or abnormal (e.g. Turner's syndrome) karyotype. In Denmark, oocyte donation must be anonymous, and the donors have to be other infertile patients undergoing in vitro fertilisation (IVF), treatment. It is suggested, that the National Health Service offers oocyte donation to hypergonadotropic women with ovarian insufficiency, as well as to a few other groups who fulfil the criteria for IVF treatment, but where this treatment cannot be completed. Oocyte donors must be less than 35 years old, physically and mentally healthy and without major genetic diseases in the family. The donor must be screened for HIV, hepatitis, syphilis, chlamydia and gonorrhoea. We propose that those patients who have more than six oocytes aspirated, allowing "surplus" oocytes to be donated. It is also proposed that the departmental order from the Ministry of Health be changed, so that normally fertile women are allowed to donate oocytes. Oocyte donation should be reported to a central authority.

Immunohistological demonstration of human placental lactogen (hPL) in non-villous, mononuclear intermediate trophoblastic cells may be of routine diagnostic value, when chorionic villi are absent in endometrial curettings from patients suspected of miscarriage of an intrauterine pregnancy. The histological presence and distribution of hPL was investigated in endometrial curettings from 90 patients studied retrospectively (47 had ectopic pregnancies, 14 miscarriages, and 29 legal abortions), and a consecutive, prospective series of 50 patients (40 had miscarriages and 10 had ectopic pregnancies) without chorionic villi in their endometrial curettings. Non-specific background staining was not a problem. The retrospective survey disclosed that hPL was a highly sensitive marker of intrauterine pregnancy (sensitivity = 0.98). In the prospective series, the predictive value of positive staining for hPL for intrauterine pregnancy was 1.00, and the sensitivity of hPL, as an indicator of uterine gestation, was 0.62. In absence of specific hPL-staining, the risk of ectopic pregnancy was about 50%. The immunohistochemical demonstration of hPL is a useful tool for identifying patients who are suspected of having had a miscarriage, but for whom evidence in the form of chorionic villi in endometrial curettings is lacking.

Failure of the testes to descend is probably mostly due to dysfunction of the hypothalamo-pituitary-testis axis. The primary treatment of testicular non descent should therefore be pharmacological in the form of HCG injections or LH-RH intranasally. Contraindications for hormonal therapy are coexistent inguinal hernia or hydrocele testis or previous inguinal operations. HCG and LH-RH treatment lead to testicular descent with about the same frequency, 20-50% in boys above five years of age, whereas HCG therapy before this age results in 10-20% success only. Reversible androgenic side effects are described in approximately 30% following HCG treatment, but only limited side effects are seen in less than 10% after LH-RH therapy. Because of the non-invasive mode of administration, the good response to treatment in the age of 2-5 years and the very limited side effects, LH-RH is recommended as the primary treatment of testicular nondescent.

In a double-blind, placebo-controlled study, 118 boys, aged 2-12 years, with 161 undescended testes were treated with luteinising-hormone releasing-hormone (LH-RH), 1.2 mg daily intranasally for four weeks. According to randomization, 60 boys with 85 undescended testes received LH-RH and 58 boys with 76 undescended testes received the placebo. 17 testes (20%) in 12 boys (20%) descended in the LH-RH group and 2 testes (3%) in 2 boys (3%) descended in the placebo group. This difference is statistically significant (chi 2, 0.01 greater than p greater than 0.001). A second LH-RH course, offered three months later to the boys who did not respond to the first LH-RH course, increased the success rate to 35%. The primary location of the testis was a significant factor for the effect of treatment. The highest success rate (63%) was registered in testes located in a high scrotal position. There was no significant difference in success of treatment between unilateral and bilateral cryptorchidism, nor between age groups. No serious adverse effects of treatment were noted. It is concluded, that LH-RH administered intranasally can be used in the treatment of boys with unilateral and bilateral cryptorchidism.

Sperm agglutinins detectable by a tray agglutination technique in sera from women from infertile couples were characterized. Preparative zone electrophoresis of seven head-to-head-agglutinating sera revealed two patterns. In two sera sperm agglutinins were obtained in the gamma-globulin fraction, whereas in five sera the agglutinating activity was detected in the beta-globulin fraction only. By immunoaffinity chromatography, IgM and IgG sperm antibodies were demonstrated in the former two sera and also in two tail-to-tail-agglutinating sera. The beta"sperm agglutinin was not found to share physicochemical or immunological characteristics with beta-lipoprotein in the present investigation by ultracentrifugation, by precipitation of beta-lipoprotein with heparin and MnCl2, by absorption of beta-lipoprotein with colloidal silic acid, or by affinity chromatography on an anti-beta-lipoprotein column. An apparent neutralizing effect of anti-beta-lipoprotein by simple addition of antiserum to sera containing the beta-sperm agglutinin was shown to be due to a reaction with sperm components released from the spermatozoa by which the antiserum had been absorbed before use. These sperm components were found to neutralize the activity of the beta-sperm agglutinin only, whereas no effect was observed in sera containing sperm antibodies. By Sephadex G-200 fractionation the beta-sperm agglutinin was shown to have a high molecular weight (MW greater than or equal to 600,000). Ultrafiltration and dialysis experiments gave no evidence of involvement of low-molecular compounds in head-to-head agglutination.

The centralization of treatment for functional masticatory disturbances by the Copenhagen Municipality Children's Dental Service has made possible the present survey of symptoms and results of treatment in a child population. Over a period of four years, a total of 366 children, aged six to sixteen (two thirds girls), were referred for treatment. Their symptoms differed from those reported by adult patients by a marked attrition of the mandibular incisors and concomitant sensitivity to thermal and mechanical stimulation. Other symptoms of functional disturbance, such as reduced mandibular mobility and muscle tenderness, were similar to those reported for adult subjects. Treatment conformed to conventional principles with widespread use of soft bite-splints (Figure 5). Both symptoms and signs were eliminated in about 60 percent of the patients, while 34 percent were essentially symptom-free at the conclusion of treatment. The survey showed that functional disturbances in the mandibular apparatus occur in children, and that many can be treated with good results. The symptomatology, however, resembles that of a wide range of other ailments, especially with respect to headache and facial pain, necessitating a careful differential diagnosis before functional corrective treatment is started.

The present report describes microbial, serological, and histological findings in chlamydial endometritis. Irregular bleeding, frequently seen in salpingitis patients, suggests endometritis, being a common manifestation of that disease. Chlamydia trachomatis is known to be a principal etiological agent of acute salpingitis. Chlamydiae can be recovered from the uterine cavity of such patients. A dense plasma-cell infiltration is seen in patients in whose endometrial epithelial cells chlamydial inclusions are found. A significant antibody response may be demonstrated in such patients. In acute salpingitis, the presence of chlamydial endometritis supports evidence from experimental animal studies that indicate a canalicular spread of chlamydiae from the cervix to the fallopian tubes.

Treatment of tubal infertility with in vitro fertilization and embryo transfer (IVF-ET) was introduced in the gynaecological/obstetric department of Arhus Municipal Hospital in February 1988. The principles of treatment are described. During the first ten months, 305 therapeutic cycles were carried out and clinical pregnancy occurred in 20.2% of the cycli after transfer of pre-embryos.

Fertility after late spontaneous descent of the testes in 45 men with previous bilateral undescended testes was evaluated on the basis of seminal analysis and concentrations of follicle-stimulating hormone (FSH) in serum. Only 15 (33 per cent) were found to have a normal fertility as estimated from the results of the total semen analysis, whereas 21 (47 per cent) were classified as being sterile or having severely reduced fertility. Elevated serum FSH concentrations in the majority of men with subnormal sperm densities supported the results of the semen analysis, indicating impaired spermatogenesis. These findings suggest that the expectant attitude in the treatment of cryptorchidism does not seem to be justified in terms of fertility and combined with recent histomorphological studies favour a more active and early treatment of undescended testes.

The association between acute epididymitis and development of antisperm antibodies was investigated by the gelatin agglutination technique in prospectively collected serum samples from 27 patients. Agglutinating antisperm antibodies, mainly of the IgG class, were detected in seven men (27 per cent), a significantly increased frequency compared to prevalences previously found among blood donors and men from infertile couples. The antibodies developed de novo in four patients (15 per cent). The increased incidence of positive sera and the kinetics of the antibody responses strongly indicate a causal link between acute epididymitis and autoimmunization against spermatozoa. In the majority of the patients the antibody titers were low, being of only theoretical importance in respect to later fertility.

Metal workers exposed to trichloroethylene for the degreasing of metals were studied to evaluate the genotoxicity of this exposure. For 15 workers presently exposed to high doses of trichloroethylene there was no difference from unexposed persons with respect to sperm count and morphology, and a small increase of two fluorescent bodies (YFF%) in spermatozoa. In contrast, there was a highly significant increase in frequency of structural aberrations (breaks, gaps, translocation, deletions, inversions) and hyperdiploid cells in cultured lymphocytes from trichloroethylene degreasers. As control groups, physicians from chemically non-exposed surroundings and a concurrently sampled reference from cytogenetic investigations were used. This study indicates positive correlations between exposure to trichloroethylene and somatic chromosome aberrations, whereas no effect on male germ cells could be demonstrated.

A fetal tibia was removed from the uterus of a woman who had had a legal abortion 8 years earlier, followed by tubal sterilization. Because of irregular vaginal bleeding she was hysterectomized and no sign of recanalization of the Fallopian tubes was seen peroperatively.

Incubation of cervical mucus with the proteolytic enzyme bromelin is known to result in complete liquefaction of the gel. This effect has been used in the detection spermagglutinating antibodies in cervical mucus. However, the well-known papain-like effect of bromelin on human immunoglobulin G (IgG) might be expected to lead to an underestimation of the sperm antibody activity in cervical mucus. This possibility was investigated by studying the effect of bromelin on known amounts of purified IgG from four spermagglutinating sera. Serologic testing of bromelin-treated samples of cervical mucus mixed with purified IgG revealed no effect on spermagglutinin titers, whereas a significant effect was observed on purified IgG alone. Inert proteins in cervical mucus seem to protect the antibodies against degradation, apparently by substrate competition. Liquefaction of cervical mucus by bromelin seems to be a better basis for the assessment of the sperm antibody content of the mucus than extraction procedures, which have been shown to give a deficient yield.

Sera from five groups of women were investigated by the tray agglutination technique for the presence of spermagglutinins: (1) 326 women from infertile couples, (2) 51 women in early pregnancy, (3) 65 women in advanced pregnancy, (4) 41 oral contraceptive users, and (5) 109 presumably fertile, nonpregnant women. By absorbing spermagglutinating sera with a cell-free eluate from spermatozoa, agglutination disappeared when due to a high-molecular weight compound with beta-mobility in preparative zone electrophoresis (denoted beta-spermagglutinin), whereas activity due to sperm antibodies was unchanged. Spermagglutinating sera occurred with comparable frequency among women from infertile couples, women in advanced pregnancy, and oral contraceptive users. The absorption study revealed agglutinating antibodies in a significantly higher frequency and in higher titers among women of infertile couples than among fertile women, in whom beta-spermagglutinins were found almost exclusively. These results demonstrate the importance of discriminating between sperm antibodies and beta-spermagglutinins in studies of sperm antibodies as a cause of infertility in women.

By immunoaffinity chromatography using anti-IgG, anti-IgM, and anti-IgA coupled to CNBr-activated sepharose 4B, the immunoglobulin class of sperm-agglutinating antibodies was investigated in cervical mucus from four infertile women. In all patients, it was found that the sperm antibodies in cervical mucus belonged to the IgA class, whereas in serum, which was studied in two of the patients, IgG sperm antibodies were demonstrated. Absorption of the four cervical mucus samples with anti-secretory component sepharose 4B revealed that the IgA antibodies in at least two of the samples were SC-IgA antibodies. Investigation of a third sample by sucrose gradient ultracentrifugation revealed that the IgA sperm antibodies were characterized by a sedimentation coefficient between 9S and 13S, strongly suggesting the presence of SC-IgA antibodies. Accordingly, the sperm-agglutinating antibodies were SC-IgA antibodies in at least three of the four samples studied.

Spermagglutinins were demonstrated by the tray agglutination technique in cervical mucus collected during presumably-ovulatory cycles in 8 women among 21 patients with spermagglutinating antibodies in serum treated for infertility. A "poor" sperm penetration test was recorded exclusively in women with spermagglutinins in cervical mucus, and the results of the sperm-cervical mucus contact test were significantly correlated to the spermagglutinin titers in cervical mucus. The incidence of spermagglutinating antibodies in cervical mucus from infertile women was estimated to be 2.2% on the basis of the results in the present study. However, an inhibiting effect on sperm penetration in cervical mucus by spermagglutinins is expected to occur in less than 1% of women from infertile couples. A decrease in spermagglutinin titers in cervical mucus observed during estrogen medication was significantly associated with improved sperm penetration in vitro. The latter results may indicate a new approach to the treatment of infertility due to the presence of spermagglutinating antibodies in cervical mucus.

The association between clinical findings and the occurrence of spermagglutinating antibodies was investigated in serum from women in 326 consecutive infertile couples. No relationship was found between unexplained infertility and the occurrence of sperm antibodies as detected by the tray agglutination technique. The occurrence of pregnancy at follow-up was the same in women with and without circulating sperm antibodies. However, the cumulative probability of conception per year was significantly lower in women with spermagglutinating antibodies than in women without such activity (0.005 greater than 2 P greater than 0.001), and the results showed a positive correlation between the duration of infertility and the occurrence of sperm antibodies. The latter findings may either reflect a fertility-reducing effect of the sperm antibodies or represent a time-related increasing tendency to develop sperm antibodies secondarily to the infertility.

In a series of 545 boys with undescended testis, 91 had bilateral spontaneous descent after the age of 10. Forty-five accepted to take part in an investigation of their fertility based on history, clinical examination, sperm analysis and estimation of serum FSH levels. In the majority, the volume of the testis was below normal and the sperm concentration was below the lower limit of the normal range. It is concluded that late spontaneous bilateral descent of the testis carries a serious risk of later impaired spermatogenesis.