Morphological ultrasound types known as 'blob' and 'bagel' signs should be reclassified from suggesting probable to indicating definite tubal ectopic pregnancy.

OBJECTIVE: In a recent consensus statement on early pregnancy nomenclature by Barnhart, a definite ectopic pregnancy (EP) was defined morphologically on transvaginal sonography (TVS) as an extrauterine gestational sac with yolk sac and/or embryo, with or without cardiac activity, whilst a probable EP was defined as an inhomogeneous adnexal mass ('blob' sign) or extrauterine sac-like structure ('bagel' sign). This study aims to determine whether these ultrasound markers used to define probable EP can be used to predict a definite tubal EP. METHODS: This was a retrospective cohort study of women presenting to the Early Pregnancy Unit (EPU) at Nepean Hospital, Sydney, Australia between November 2006 and June 2016. Women classified with a probable EP or a pregnancy of unknown location (PUL), i.e. with no signs of extra- or intrauterine pregnancy (IUP), at their first TVS were included, whilst those with a definite tubal EP, IUP or non-tubal EP were excluded from the final analysis. The gold standard for tubal EP was histological confirmation of chorionic villi in Fallopian tube removed at laparoscopy. The performance of blob or bagel sign on TVS in the prediction of definite tubal EP was evaluated in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). This was compared with the performance of extrauterine gestational sac with yolk sac and/or embryo on TVS to predict definite tubal EP. RESULTS: During the study period, 7490 consecutive women attended the EPU, of whom 849 were analyzed. At primary TVS, 240/849 were diagnosed with probable EP, of which 174 (72.5%) were classified as blob sign and 66 (27.5%) as bagel sign. The remaining 609/849 were diagnosed with PUL, of which 47 had a final diagnosis of EP (including 24 blob sign, 19 bagel sign and four gestational sac with embryo/yolk sac). 101 of all 198 (51%) blob sign cases and 50 of all 85 (59%) bagel sign cases underwent laparoscopy and salpingectomy; histology proved a tubal EP in 98 (97%) of these blob-sign cases and 48 (96.0%) of the bagel-sign cases. The sensitivity for the blob and bagel signs in the prediction of definite tubal EP was 89.8% and 83.3%, respectively, the specificity was 99.5% and 99.6%, PPV was 96.7% and 95.2% and NPV was 98.3% and 98.6%. This was comparable to the sensitivity of extrauterine gestational sac with yolk sac and/or embryo on TVS in the prediction of definite tubal EP (sensitivity, 84.0%; specificity, 99.9%; PPV, 97.7%; NPV, 99.3% (P = 0.5)). CONCLUSIONS: Blob and bagel signs seem to be the most common presentations of a tubal EP on TVS. Although they cannot be considered as a definitive sign of EP, their PPV is very high (> 95%); such women should therefore be considered at very high risk for having a tubal EP and should be treated as such. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Molecular detection of Chlamydia trachomatis and semen quality of sexual partners of infertile women.

Chlamydia trachomatis is considered as the bacterium that is more sexually transmitted as cause of male urethritis, epididymitis, orchitis and infertility. A total of 116 semen samples of men whose couples are infertile women were analysed. The quality of the semen was measured by standard procedures recommended by WHO while C. trachomatis was detected by the PCR assay. Thirty-seven semen samples were positive for C. trachomatis (31.9%). Regarding semen analysis, no different values were observed between positive and negative samples to C. trachomatis. However, the presence of leucocytes and erythrocytes suggests an inflammatory process; however, these were high in negative samples to C. trachomatis. Furthermore, an association between low seminal volume at 1, 5 ml and the positivity to C. trachomatis was observed (OR=2, 1; CI95 % 1,16-3,07). The total semen volume is a contribution by the various accessory glands (this reflects the secretory activity of the glands); a low semen volume could be due to an obstruction of the ejaculatory duct or infection of accessory glands by C. trachomatis. More studies are necessary to identify the causes of a reduced semen volume.

Performance of ultrasound-based endometriosis staging system (UBESS) for predicting level of complexity of laparoscopic surgery for endometriosis.

OBJECTIVE: To develop and assess the performance of a preoperative ultrasound-based endometriosis staging system (UBESS) to predict the level of complexity of laparoscopic surgery for endometriosis. METHODS: This was a multicenter prospective and retrospective cohort study on consecutive women with suspected endometriosis who underwent laparoscopy between June 2009 and July 2013. Each woman underwent a systematic transvaginal ultrasound evaluation to assess the pelvis for different phenotypes of endometriosis, and the diagnostic performance of ultrasound for these different phenotypes was evaluated relative to the gold standard, laparoscopy. A three-stage preoperative UBESS was developed to assess the severity of pelvic endometriosis, based on the histological phenotypes of endometriosis, the anatomical locations of deep infiltrating endometriosis and their sonographic markers of local invasiveness. The three stages of UBESS (I-III) were then correlated with the three levels of complexity of laparoscopic surgery for endometriosis described by the Royal College of Obstetricians and Gynaecologists (Levels 1-3). The end-points were the diagnostic performance of UBESS to predict the level of complexity of laparoscopic surgery for endometriosis, i.e. UBESS stage I to predict Level-1 laparoscopic surgery, UBESS stage II to predict Level-2 laparoscopic surgery and UBESS stage III to predict Level-3 laparoscopic surgery. RESULTS: The analysis included 192 women, with a mean ± SD age at diagnosis of endometriosis of 23.7 ± 9.3 years and a mean duration of symptoms prior to presentation of 42 months. Predominant reported locations of pelvic pain were left iliac fossa (32%), right iliac fossa (29.5%) and lower abdomen (61%) and predominant symptoms included dyspareunia (57.5%), dysmenorrhea (58.5%) and dyschezia (41.5%). The accuracy, sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios of UBESS I for predicting a requirement for Level-1 laparoscopic surgery were: 87.5%, 83.3%, 91.7%, 90.9%, 84.6%, 10 and 0.182; those of UBESS II for predicting Level-2 surgery were: 87.0%, 73.7%, 90.3%, 65.1%, 93.3%, 7.6 and 0.292; and those of UBESS III for predicting Level-3 surgery were: 95.3%, 94.8%, 95.5%, 90.2%, 97.7%, 21.2 and 0.054, respectively. CONCLUSION: UBESS could be utilized to predict the level of complexity of laparoscopic surgery for endometriosis. It has the potential to facilitate the triage of women with suspected endometriosis to the most appropriate surgical expertise required for laparoscopic endometriosis surgery. UBESS needs to be validated externally in multiple centers to assess its general applicability. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Interpreting the real-time dynamic 'sliding sign' and predicting pouch of Douglas obliteration: an interobserver, intraobserver, diagnostic-accuracy and learning-curve study.

OBJECTIVE: To determine inter- and intraobserver agreement, diagnostic accuracy and the learning curve required for interpreting the 'sliding sign' and predicting pouch of Douglas (POD) obliteration. METHODS: This was an inter-/intraobserver, diagnostic-accuracy and learning-curve study involving six observers with different medical backgrounds, clinical skill sets and prior gynecological ultrasound experience: five non-specialist observers who had performed 0-750 previous gynecological scans and an expert sonologist who had performed > 15 000. Following a formal theoretical and practical training session, they each viewed 64 offline transvaginal ultrasound (TVS) 'sliding-sign' videos from two anatomical locations (retrocervix and posterior uterine fundus (PUF)) in 32 women presenting with chronic pelvic pain, interpreting the videos as positive or negative for sliding sign and predicting, on that basis, the POD status. For intraobserver agreement analysis they re-analyzed the same video sets, in a different order, at least 7 days later. The expert sonologist was the reference standard for interpreting the sliding sign and the gold standard, laparoscopy, was used for the POD analysis. Learning-curve cumulative summation (LC-CUSUM) tests were conducted to assess if observer performance reached acceptable levels, using LC-CUSUM score < -2.45 as a cut-off. RESULTS: With respect to interpretation of the sliding sign, the overall multiple-rater agreement was moderate (Fleiss' kappa, K = 0.499). Observers were more consistent in their interpretation of the second compared with the first observation set (K = 0.547 vs 0.453) and for the retrocervical compared with the PUF region (K = 0.556 vs 0.346). Regarding prediction of POD status, the accuracy, sensitivity, specificity and positive and negative predictive values for individual observers ranged from 65.4 to 96.2%, 80.0 to 100%, 64.7 to 100%, 50.0 to 100% and 94.7 to 100%, respectively. Using LC-CUSUM score < -2.45, the observer with experience of 200 previous gynecological scans reached acceptable levels for predicting POD obliteration and interpreting the sliding sign at each region (retrocervix and PUF) at 39, 54 and 28 videos and the observer with experience of 750 scans at 56, 53 and 53 videos. CONCLUSIONS: Performance of a minimum number of gynecological ultrasound examinations is necessary for interpreting offline videos of the real-time dynamic sliding sign and predicting POD obliteration. Non-specialist observers with prior experience of 200 or more gynecological scans were more consistent in interpreting the sliding sign at the retrocervix vs PUF. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Seroprevalence and risk factors associated with within-flock transmission of Leptospira interrogans in transhumant farming systems in Mexico.

A number of recent reports emphasize the risk of zoonotic diseases and the high degree of prevalence of asymptomatic animals infected with Leptospira interrogans. This report sought to assess the prevalence of antibodies to certain serovars of L. interrogans, and to describe the association between seropositivity and risk factors associated with within-flock transmission in a mountainous region of Mexico. Overall seroprevalence to L. interrogans was 54·5% (95% confidence interval 48·3-60·7); the most frequent serovar was Icterohaemorrhagiae. The accumulation of placentas and fetuses at a site close to lambing paddocks can play a significant role as a risk factor for within-flock transmission of L. interrogans in transhumant farming systems in the municipality of Xalatlaco. The high prevalence of L. interrogans antibodies supports the hypothesis that natural foci of this zoonosis are present in sheep flocks in this area. These findings emphasize the need for planning and implementation of control programmes for ovine leptospirosis in Mexico and elsewhere.

Adherence of five serovars of Ornithobacterium rhinotracheale to chicken tracheal epithelial cells.

1. Interaction between bacteria and host tissue is important, both for primary adhesion and tissue-specific colonisation, as well as for pathogen invasion for different host tissues. 2. Ornithobacterium rhinotracheale is a bacterium associated with respiratory tract infections in poultry. The mechanisms by which O. rhinotracheale causes infection are not known. To date, at least 18 serovars of this bacterium, with or without the ability to agglutinate erythrocytes of chicken and other species, have been identified. 3. The purpose of this work was to evaluate the ability of five references strains, belonging to serovars A, B, C, D and E, to adhere to a culture of primary chicken tracheal cells. 4. Serovars A and B adhered to less than 20% of tracheal cells with no specific adherence pattern. Serovars C, D and E gave adherence values greater than 70%. Serovars C and E showed a diffuse adherence pattern, while serovar D had an aggregated adherence pattern. 5. The adherence ability and pattern could be associated with different pathogenicity mechanisms in the various serovars but more studies are needed to understand the reasons for these differences.

Efficiency of aseptic open vitrification and hermetical cryostorage of human oocytes.

The present study reports, as far as is known for the first time, the safety of UV sterilization of liquid nitrogen and hermetical cryostorage of human oocytes by comparing the efficiency of fresh and vitrified sibling oocytes of infertile patients. A prospective randomized study on sibling oocytes of 31 patients was carried out. Metaphase-II oocytes were randomized for intracytoplasmic sperm injection and the supernumerary sibling oocytes were vitrified using a novel Cryotop aseptic procedure (UV liquid nitrogen sterilization and hermetical cryostorage). After unsuccessful attempts with fresh oocytes, vitrified sibling oocytes were injected. Mean outcome measures observed were fertilization, cleavage and top-quality embryo rates. No significant differences were observed between the fresh and vitrified-warmed sibling oocytes: oocyte fertilization was 88.3% versus 84.9%; cleavage 72.6% versus 71.0%; top-quality embryos 33.8% versus 26.3% and mean number of transferred embryos 2.6 ± 0.1 versus 2.5 ± 0.1, respectively. Clinical pregnancy rate per cycle with vitrified-warmed oocytes was 35.5% (implantation rate 17.1%) and seven healthy babies were born. This study demonstrated that UV liquid nitrogen sterilization and hermetical cryostorage does not adversely affect the developmental competence of vitrified oocytes, allowing safe aseptic open vitrification applicable under strict directives on tissue manipulation.

Freezing within 2 h from oocyte retrieval increases the efficiency of human oocyte cryopreservation when using a slow freezing/rapid thawing protocol with high sucrose concentration.

BACKGROUND: A number of factors influence the success of oocyte cryopreservation and subsequent ICSI. The aim of the present study is to establish the ideal time, after oocyte retrieval, for human oocyte cryopreservation via slow freezing/rapid thawing protocol with 0.3 M sucrose concentration in cryoprotectant solution (SF/RT 0.3 M). METHODS: Retrospective study with 75 patients on the clinical outcome of 93 oocyte thawing cycles divided into three groups. Group A: freezing within 2 h from oocyte retrieval. Group B: freezing between 2 and 3 h from retrieval. Group C: freezing after 3 h. RESULTS: The rate of best quality embryos was significantly higher (35.2%; P = 0.050) in Group A than in Group C (14.1%). Pregnancy and implantation rates were 39.1% (9/23) and 18.5% (10/54) in Group A. Nine clinical pregnancies per 124 thawed (7.3%) and 73 injected (12.3%) oocytes were observed in Group A versus 3 pregnancies per 174 thawed, 103 injected (1.7%, 2.9%, P = 0.046 and 0.0049) in Group B and 4 per 139 thawed, 88 injected (2.9%, 4.5%, NS) in Group C. The overall yield from oocytes cryopreserved within 2 h of retrieval was 8.1 implantations per 100 oocytes thawed. CONCLUSIONS: Embryo quality and clinical outcome of thawing cycles were significantly improved when oocyte cryopreservation by SF/RT 0.3 M was carried out within 2 h from oocyte retrieval.

Calcium absorption from milk in lactase-deficient subjects.

Intestinal calcium absorption from milk containing lactose (+) and from another containing glucose (-) was studied in eight patients with normal lactase (NL) and seven lactase-deficient (LD) subjects to determine if lactase deficiency is implicated in Ca absorption. The results were compared with data obtained from Ca ingestion in a water solution. Ca absorption was measured by a double-isotope technique and the kinetic indices were obtained by a deconvolution method. With (-), Ca absorption was identical in NL and LD subjects and slightly higher than with water solution (15%, NS). With (+), Ca absorption in NL subjects was identical with that from water solution; in LD subjects it increased (23%, p less than 0.02). These data indicate that: Ca is absorbed equally well from milk as from water solution; (+) favors Ca absorption in LD subjects, which suggests that milk ingestion might be encouraged in LD subjects to avoid Ca deficiency; and (-) should be a valuable alternative for lactose-intolerant patients.

Glycaemic response and hydrogen production to blenderised and polymeric enteral nutrition formulas.

Complete enteral nutrition preparations include blenderised formulas based on natural foods with some fibre content and also low-residue polymeric formulas. This study examines the effect of the different fibre content of two commercial formulas (6.4 g/l and 0.25 g/l) on glycaemic and insulin response and hydrogen production in the colon during constant rate administration in 11 normal subjects. No difference in serum glucose and insulin levels was found. No rise in hydrogen production was detected with either formula suggesting no carbohydrate malabsorption. The quantity or nature of fibre present in blenderised formulas does not modify the pattern of carbohydrate absorption compared to a low-residue polymeric formula. However, this does not preclude other possible physiological effects of fibre content upon gastrointestinal motility and function.

Tumor necrosis factor in peritoneal fluid from asymptomatic infertile women.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that can be found in the peritoneal fluid (PF) of patients with endometriosis and pelvic inflammatory disease (PID) as a response to inflammatory disorders and infections. The cytotoxic effect of this cytokine could be a factor participating in the pathology of various gynecological diseases, and could also be accountable for the high immunological response and damage to the tubal epithelium. The objective of this study was to establish the presence of TNF-alpha in asymptomatic infertility and its association with various isolated bacteria. METHODS: Ten milliliters of PF were collected from each of 73 patients by means of laparoscopy and cultured in synthetic medium and McCoy cells for the isolation of aerobic and anaerobic bacteria, as well as for Chlamydia trachomatis. The activity of TNF-alpha was determined by means of a bioassay using L-929 cells. RESULTS: Forty-three percent of the PFs showed positive TNF-alpha activity, while the laparoscopic evaluation showed that 32 patients had Fallopian tube occlusion (FTO), 7 had endometriosis, 30 had PID, and 4 had myomas and adhesions. TNF-alpha activity was found to be high in FTO patients (p < 0.05). Positive cultures were found in 50.7% of patients; of these, 31.5% had PID (p < 0.05), and only 20.5% of positive cultures were TNF-alpha positive. Chlamydia trachomatis (16%) was the most frequently isolated bacteria in these patients. CONCLUSIONS: The detection of TNF-alpha could be useful in the diagnosis of active infectious and inflammatory diseases in asymptomatic infertile patients.

Alaria nasuae (Trematoda: Diplostomidae) from domestic dogs.

Two stray dogs were found naturally infected with adult Alaria nasuae in Tamaulipas, Mexico. This is the first report of this species from a domestic dog, the first report of it from Mexico, and the first time the species has been recorded since its original description.

Improved immunobinding test using monoclonal antibodies for detection of Mycoplasma bovis in milk.

The aim of this study was to evaluate an improved immunobinding test (IBT) using monoclonal antibodies to identify Mycoplasma bovis in naturally infected milk. The IBT and the improved IBT were highly specific and had an immunologic sensitivity of 5 x 10(3) colony-forming units per milliliter. The results for the 2 methods agreed in the 130 milk samples tested. However, the IBT required 158 min, whereas the improved IBT required only 110 min. In addition, the improved IBT used smaller quantities of antibodies and conjugates.

Efficacy of the API Staph-Ident system for identification of Staphylococcus species from milk.

A total of 524 staphylococcal isolates from bovine milk were identified, using the API Staph-Ident system and conventional biochemical methods. The API Staph-Ident system correctly identified 192 of 201 (95.5%) Staphylococcus aureus isolates, but was correct on only 23 of 323 (7.1%) non-S aureus isolates.

Metal contamination in illicit samples of heroin.

We analyzed 198 illicit heroin samples from Andalusia (southern Spain) to determine the contents of various metals (cadmium, calcium, copper, iron, manganese and zinc) with a view to investigating a new aspect of the drug purity and the conditions under which the drugs are used by addicts. Calcium was found in 93.4% of the samples and always at high concentrations, which can be ascribed to adulteration of the heroin by addicts with thinners and excipients containing salts of this metal such as calcium bicarbonate. Also, all samples were found to contain variable amounts of zinc and substantial amounts of iron, probably because it is the most common metal found in metal containers used in the extraction of morphine from the opium poppy. Only cadmium and, to a lesser extent, zinc, copper, and iron, are among the metals detected in heroin that can increase the inherent toxicity of the drug while always taking into account the maximum values.

[Diet and cancer of the pancreas]. / Alimentation et cancer du pancréas.

A case-control study was carried out in Geneva on the basis of an interview involving 88 new cases of pancreatic cancer and 336 controls. The percentage of histologically confirmed cases was 67 p. 100. Controls were drawn at random from the general population. An excess risk was observed with increased consumption of fatty foods. This excess, however, was only significant for butter; in contrast, margarine was associated with a reduction in risk (relative risk = 0.35, p less than 0.05). Meat intake did not modify the risk, except for lean pork, for which the risk was significantly reduced. For carbohydrates, an excess risk was observed, with a dose-response effect. Fresh fruit and vegetables led to a marked and significant reduction in risk. Among beverages, beer was the only one for which consumption entailed an increased risk (RR = 2.85, p less than 0.05). The results concerning tea and coffee were not significant, but there appeared to be a trend towards an increase in relative risk.

[Evaluation of anorexia in patients with bile duct obstruction]. / Evaluación de la anorexia en enfermos con obstrucción de la vía biliar.

INTRODUCTION: Obstructive jaundice is often accompanied by protein-caloric malnutrition. The objective of the present study is to analyze the incidence and the degree of alterations in the food ingestion of patients with obstructive jaundice. MATERIAL AND METHODS: In a prospective, cross-sectional study 50 patients with obstructive jaundice (19 benign and 31 malignant) were evaluated. The anorexia was evaluated using Welch's test (subjective evaluation) and by means of quantifying the caloric ingestion. An anthropometric parameter (ideal weigh < 95%) and two biochemical ones (albumin < 3.5 g/dl and pre-albumin < 17 mg/dl) were used to define the degree of malnutrition. RESULTS: 96% of the patients presented alterations in the Welch test and in 72% of the patients the caloric ingestion was below the estimated needs. Overall, the ingestion of food was reduced by 76.3 +/- 30% of the estimated needs (84.7 +/- 28% in the benign cases and 70.9 +/- 32% in the malignant cases). Both the Welch test (r = 0.59; p = 0.01) and the caloric ingestion (r = 0.53; p < 0.001) were inversely correlated with the serum bilirubin. In patients with malnutrition criteria, the caloric ingestion was reduced by 30% against the 12% reduction in the non-malnourished patients (p < 0.05). There was a direct correlation between the two methods used in the assessment of the anorexia (r = 0.71; p < 0.001). CONCLUSIONS: Obstructive jaundice is associated with an important reduction in the caloric ingestion, and this is manifested in both biliary obstructions of a benign origin, and in those of neoplasic origins.

Induction of tumor necrosis factor-alpha by cefodizime in U-937 cells.

Cefodizime has modulating effects on the release of diverse cytokines. We determined the modulator activity of this antibiotic on the production of TNF in human monocytic U-937 cells. The measurement of TNF was carried out by ELISA test and by a L-929 cells-based citotoxic bioassay. The results showed that cefodizime alone induced the production of TNF on U-937 cells, however, the addition of LPS led to a decrease in the release of this cytokine (p < 0.05). On the other hand, the combination of cefodizime-PMA had a synergic effect (p < 0.05), while addition of LPS to this combination caused a decrease of TNF production (p < 0.05). With these results we conclude that cefodizime modulates the production of TNF in U-937 cells, which is down regulated by the addition of LPS.

[Evaluation of sensitivity and specificity of 3 reagents of direct immunofluorescence in the diagnosis of Chlamydia trachomatis]. / Evaluación de la sensibilidad y especificidad de tres reactivos de inmunofluorescencia directa para el diagnóstico de Chlamydia trachomatis.

The sensitivity, specificity, positive and negative predictive values and positive and negative false percentage of three monoclonal immunofluorescence reagents for direct diagnosis of Chlamydia trachomatis infections were evaluated, 150 cervical specimens and 50 samples of peritoneal liquid of patients with pelvic inflammatory disease, were studied. The results showed that the reagents against the main protein of external membrane of Chlamydia introduced high sensitivity but minor specificity than the reagent of immunofluorescence direct against then chlamydial lipopolysaccharide.

[Determination of the tumor necrosis factor in the peritoneal fluid of gynecologic patients with intraperitoneal infections and endometriosis]. / Determinación del factor de necrosis tumoral en líquido peritoneal de pacientes ginecológicas con infecciones intraperitoneales y endometriosis.

Tumor necrosis factor (TNF-alpha) is a cytokine which can be found in peritoneal fluid (PF) of patients with endometriosis and pelvic inflammatory disease (PID) as a response of inflammatory disorder and infections diseases. The cytotoxic effect of this cytokine could be participating in the pathology of different gynecologic problem and be accountable of the high immunological response and damage on the tubal epithelium. The objective of this study was determinate the presence of TNF-alpha in PF of endometriosis patients, fallopian tube occlusion (FTO) and PID and their correlation with different isolated bacteria. Ten mililiter PF were collected and cultured in antificial medium and Mc Coy culture cells for isolation of acrobic, and anaerobic bacteria and Chlamydia trachomatis from 73 patients by laparoscopy. The TNF-alpha activity was determined by L-929 cells endometriosis, 30 PID and 4 had miomas and adherences. The 50.7% of patients were cultive positive, fom these, 31.5% were PID. Chlamydia trachomatis (16%) was the most frecuenty isolated bacteria in these patients. 59.4% of FTO patients displayed TNF-alpha activity. However, only 4% showed positive isolation, in conclusion the detection of TNF-alpha could be useful in active infectious and inflammatory diseases in patients which not present simptomatologic characteristic of these illnesses and plus being attended at for sterility clinical as a result of their incapacity to get pregnant.