Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vaginal swabs of women with acute SARS-CoV-2 infection: a prospective study.

OBJECTIVE: To determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is present in the vaginal secretions of both reproductive-aged and postmenopausal women during acute SARS-CoV-2 infection. DESIGN: Prospective study. SETTING: A single tertiary, university-affiliated medical centre in Israel. Time period, 1 June 2020 through to 31 July 2020. POPULATION: Women who were hospitalised in a single tertiary medical centre, who were diagnosed with acute SARS-CoV-2 infection by a nasopharyngeal RT-PCR test. METHODS: Women were diagnosed with acute SARS-CoV-2 infection by a nasopharyngeal RT-PCR test. Vaginal RT-PCR swabs were obtained from all study participants after a proper cleansing of the perineum. MAIN OUTCOME MEASURES: Detection of SARS-CoV-2 in vaginal RT-PCR swabs. RESULTS: Vaginal and nasopharyngeal swabs were obtained from 35 women, aged 21-93 years. Twenty-one women (60%) were in their reproductive years, of whom, five were in their third trimester of pregnancy. Most of the participants (57%) were healthy without any underlying medical conditions. Of the 35 patients sampled, 2 (5.7%) had a positive vaginal RT-PCR for SARS-CoV-2, one was premenopausal and the other was a postmenopausal woman. Both women had mild disease. CONCLUSION: Our findings contradict most previous reports, which did not detect the presence of viral colonisation in the vagina. Although passage through the birth canal exposes neonates to the vaginal polymicrobial flora, an acquisition of pathogens does not necessarily mandate neonatal infection or clinical disease. Nevertheless, when delivering the infant of a woman with acute SARS-CoV-2 infection, a clinician should consider the possibility of vaginal colonisation, even if it is uncommon. TWEETABLE ABSTRACT: When delivering the infant of a woman with acute SARS-CoV-2 infection, a clinician should consider the possibility of vaginal colonisation.

Molecular epidemiology of silent introduction and sustained transmission of wild poliovirus type 1, Israel, 2013.

Poliovirus vaccine coverage in Israel is over 90%. The last nine birth cohorts have been vaccinated exclusively with inactivated polio vaccine (IPV). However, between February and July 2013 type 1 wild poliovirus (WPV1) was detected persistently in 10 and intermittently in 8 of 47 environmental surveillance sites in southern and central Israel and in 30 stool samples collected during July from healthy individuals in southern Israel. We report results of sequence and phylogenetic analyses of genes encoding capsid proteins to determine the source and transmission mode of the virus. WPV1 capsid protein 1 nucleotide sequences were most closely related to South Asia (SOAS) cluster R3A polioviruses circulating in Pakistan in 2012 and isolated from Egyptian sewage in December 2012. There was no noticeable geographical clustering within WPV1-positive sites. Uniform codon usage among isolates from Pakistan, Egypt and Israel showed no signs of optimisation or deoptimisation. Bayesian phylogenetic time clock analysis of the entire capsid coding region (2,643 nt) with a 1.1% evolutionary rate indicated that Israeli and Egyptian WPV1-SOAS lineages diverged in September 2012, while Israeli isolates split into two sub-branches after January 2013. This suggests one or more introduction events into Israel with subsequent silent circulation despite high population immunity.

Intensified environmental surveillance supporting the response to wild poliovirus type 1 silent circulation in Israel, 2013.

An emergency response was triggered by recovery of wild poliovirus type 1 (WPV1) of the South Asia (SOAS) lineage from sewage in southern Israel in April 2013 during routine environmental surveillance. Public health risk assessment necessitated intensification of environmental surveillance in order to facilitate countrywide monitoring of WPV1-SOAS circulation. This involved increasing sampling frequency and broadening the geographical area, for better coverage of the population at risk, as well as modifying sewage testing algorithms to accommodate a newly developed WPV1-SOAS-specific quantitative real-time RT-PCR assay for screening of RNA extracted directly from sewage concentrates, in addition to standard virus isolation. Intensified surveillance in 74 sites across Israel between 1 February and 31 August 2013 documented a sustained high viral load of WPV1-SOAS in sewage samples from six Bedouin settlements and two cities with Jewish and Arab populations in the South district. Lower viral loads and intermittent detection were documented in sampling sites representing 14 mixed communities in three of the five health districts in central and northern Israel. Environmental surveillance plays a fundamental role in routine monitoring of WPV circulation in polio-free countries. The rapid assay specific for the circulating strain facilitated implementation of intensified surveillance and informed the public health response and decision-making.

Silent reintroduction of wild-type poliovirus to Israel, 2013 - risk communication challenges in an argumentative atmosphere.

Israel has been certified as polio-free by the World Health Organization and its routine immunisation schedule consists of inactivated poliovirus vaccine (IPV) only. At the end of May 2013, the Israeli Ministry of Health (MOH) has confirmed the reintroduction of wild-type poliovirus 1 into the country. Documented ongoing human-to-human transmission necessitated a thorough risk assessment followed by a supplemental immunisation campaign using oral polio vaccine (OPV). The unusual situation in which ongoing poliovirus transmission was picked up through an early warning system of sewage monitoring without active polio cases, brought about significant challenges in risk communication. This paper reviews the challenges faced by the MOH and the communication strategy devised, in order to facilitate and optimise the various components of the public health response, particularly vaccination. Lessons learned from our recent experience may inform risk communication approaches in other countries that may face a similar situation as global polio eradication moves towards the 'End game'.

Insidious reintroduction of wild poliovirus into Israel, 2013.

Israel was certified as polio-free country in June 2002, along with the rest of the World Health Organization European Region. Some 11 years later, wild-type polio virus 1 (WPV1) was isolated initially from routine sewage samples collected between 7 and 13 April 2013 in two cities in the Southern district. WPV1-specific analysis of samples indicated WPV1 introduction into that area in early February 2013. National supplementary immunisation with oral polio vaccine has been ongoing since August 2013.

Placenta/birthweight ratio and perinatal outcome: a retrospective cohort analysis.

OBJECTIVE: The placenta weight/birthweight (PW/BW) ratio has been shown to be associated with certain long-term fetal outcomes; however, its association with short-term outcomes has not received much attention. Our aim was to assess the correlation between the PW/BW ratio and short-term adverse obstetrics outcomes in full-term, appropriate-for-gestational-age (AGA) newborns. DESIGN: Retrospective cohort study analysis using data from the McGill Obstetrical and Neonatal Database. SETTING: McGill University Health Centre in Montreal Canada. POPULATION: AGA neonates. METHODS: Three groups of full-term AGA neonates were created, according to their PW/BW ratio (high, normal and low), to be compared. Our primary outcome was the admission rate to the neonatal intensive care unit (NICU), and secondary outcomes included an Apgar score < 7 at 5 minutes, cord PH < 7.0, cord base excess (BE) ≤ 12, respiratory distress syndrome (RDS), patent ductus arteriosus (PDA), occurrence of apnoea episodes, breech presentation at delivery, caesarean section rate and status in discharge home. A logistic regression model was instituted to investigate the predictors for adverse obstetrics outcomes. MAIN OUTCOME MEASURE: Admission to the NICU. RESULTS: Compared with the group with normal PW/BW ratios, the high PW/BW ratio group was associated with increased rates of admission to the NICU, of Apgar scores < 7 at 5 minutes, of breech presentation and caesarean section. On the contrary, the low PW/BW ratio group showed decreased rates of NICU admission, breech presentation and caesarean section. CONCLUSIONS: A high PW/BW ratio is significantly correlated with short-term adverse perinatal outcomes. This ratio may be used as a new and simple warning sign to predict the possibility of short-term health risks for newborns.

Management of Kell isoimmunization--evaluation of a Doppler-guided approach.

OBJECTIVE: To assess the role of peak systolic velocity in the middle cerebral artery (MCA-PSV) in the management of pregnancies complicated by Kell isoimmunization. METHODS: Sixteen fetuses were monitored by conventional protocol (Group 1) and eight fetuses by an MCA-PSV-guided protocol (Group 2). The conventional protocol included a weekly ultrasound evaluation and measurement of maternal anti-Kell titers every 4-6 weeks. In Group 2 Doppler assessment of the MCA-PSV was performed at intervals of 4 to 7 days and MCA-PSV>1.5 multiples of the median (MoM) was considered as an indication for fetal blood sampling (FBS). RESULTS: No parameter emerged as a reliable predictor of isoimmunization severity in Group 1. In Group 2, no FBS was necessary in one case since the MCA-PSV values obtained during the follow-up were <1.29 MoM. In two cases the first FBS was already indicated after 1 week of follow-up, but five other fetuses were followed for 3-9 weeks before FBS was indicated. All fetuses with MCA-PSV>1.5 MoM prior to intrauterine transfusion (IUT) had severe fetal anemia on FBS. In fetuses with severe anemia on the first FBS, the MCA-PSV values 7 days before the first FBS were <1.29 MoM (four cases), between 1.29 and 1.5 MoM (two cases) and >1.55 MoM (one case). CONCLUSIONS: In the management of Kell isoimmunization invasive procedures may be avoided by implementing MCA-PSV measurements. Delineation of appropriate intervals between reassessments, the reliability of MCA-PSV following repeated IUTs, and cut-off values for FBS await further study.

Development of the human fetal pons: in utero ultrasonographic study.

OBJECTIVES: To examine the ultrasonographic feasibility of imaging the fetal pons and to construct a reference chart for its normal development during gestation. METHODS: A cross-sectional, prospective study on 293 healthy fetuses of low-risk pregnancies between 19 and 34 weeks was performed. The transfontanel approach, via the abdominal or vaginal routes, was used to evaluate the fetal metencephalon (pons and cerebellum). The anteroposterior diameter of the fetal pons was measured in a mid-sagittal plane. The longitudinal diameter of the cerebellar vermis was measured at the same plane and the vermis-pons ratio (VPR) was established. RESULTS: One hundred and forty-four fetuses were in vertex position. In 140 (97.2%) satisfactory visualization and measurements of the pons and cerebellar vermis were obtained. One hundred and forty-nine fetuses were breech presentations and measurements were successfully performed in 147 (98.6%). The pons anteroposterior and vermis longitudinal diameters showed a linear correlation with gestational age (GA) (r = 0.95 for both measurements; P < 0.001). The mean VPR was 1.5 (+/-0.1 SD) and did not change in the gestational interval that was considered. CONCLUSION: By using the transfontanel approach, evaluation of the fetal pons is feasible via the mid-sagittal plane. The nomograms developed and the ratio to fetal vermis provides reference data that may be helpful when evaluating anomalies of the brainstem.

Increased erythrocyte aggregation in ovarian hyperstimulation syndrome: a possible contributing factor in the pathophysiology of this disease.

BACKGROUND: Many theories regarding the pathophysiology leading to ovarian hyperstimulation syndrome (OHSS) have been proposed and tested. Increased erythrocyte aggregation is associated with capillary slow flow and tissue hypoxaemia. We performed this study in order to assess the degree of erythrocyte aggregation in the peripheral blood of individuals with OHSS and undergoing controlled ovarian stimulation (COH). METHODS: Twenty women with severe OHSS, 20 women undergoing COH under IVF protocol, and 20 healthy matched controls were recruited for this prospective study. Blood samples were drawn for determination of erythrocyte aggregation as well as haematological indices. The percentage of slide covered by the cells ('erythrocyte percentage': EP) was determined using a simple slide test and image analysis. Lower EP values correspond to higher degrees of aggregation. RESULTS: The respective measures of EP were 59.2 +/- 3.0, 42.0 +/- 3.0 and 35.0 +/- 2.4% micro m for the controls, women with COH and OHSS (P < 0.01 between controls and the two stimulation groups). CONCLUSIONS: The degree of erythrocyte aggregation is enhanced in the peripheral venous blood of patients with both COH and OHSS. This finding, known to cause capillary leak, may contribute to the pathophysiology of the OHSS.

Seasonal variations in pre- and post-thaw donor sperm quality.

BACKGROUND: The present study was conducted to evaluate seasonal variability in the quality of pre- and post-thaw semen parameters among sperm bank donors. METHODS: The first two consecutive ejaculates during the months March (spring, 92 males), June (summer, 97 males), September (autumn, 81 males) and December (winter, 97 males) were analysed. A comparison was made between sperm parameters from the same sperm donor at different seasons. Only males who donated semen samples during at least two seasons were enrolled in the study group (n = 103). Sperm specimens were cryopreserved in aliquots with fixed range of 8-12 x 10(6)/ml of progressive motile sperm concentration after thawing. RESULTS: Differences between months were found in sperm concentration (P = 0.030) and normal morphology (P = 0.038); highest values were found in March and December, and the lowest in September. Mean specimen volume and percent of motile sperm cells did not vary throughout the seasons. The freezability of the donors' sperm dropped dramatically from March to September, as determined by the number of straws (fixed aliquots of 0.5 ml) and total thawed progressive motile sperm that were cryopreserved for each male (P = 0.017 and P = 0.002, respectively). CONCLUSIONS: Cryopreservation of donor sperm is more effective during winter and spring than during the rest of the year.

Clinical and economic benefit of HPV-load testing in follow-up and management of women postcone biopsy for CIN2-3.

This study aimed to evaluate the clinical and economic implications of integrating human papilloma virus (HPV) load testing into the follow-up and management protocol of women postconisation for high-grade cervical intraepithelial neoplasia (CIN2-3). We evaluated 130 suitable women: 63 were screened biannually by Pap smears ('conventional approach') and 67 also had HPV-load testing ('HPV approach'). More stringent criteria for undergoing colposcopy or reconisation were observed by the former group compared to the latter. Both approaches were analysed for cost effectiveness. There were 33 out of 67 (49.2%) colposcopic referrals and 24 out of 67 (35.8%) reconisation/hysterectomies with the 'conventional approach' compared to 9 out of 63 (14.2%) and 7 out of 63 (11.1%) with the 'HPV approach'. Cervical intraepithelial neoplasia 2-3 residual disease was detected in 7 out of 67 (10.5%) and 7 out of 63 (11.1%) women. The 'conventional approach' had more negative colposcopic biopsies and more negative reconisation/hysterectomy histologies than the 'HPV approach'. The respective cost per detection of one case of residual disease was US$3573 and US$3485. The 'HPV approach' required fewer colposcopic and reconisation procedures to detect one case of residual CIN2-3. Its higher positive predictive value than that of cytology provided a significant decrease in false positive rates and a reduction of US$88 per detected case.

The progestative effect of the levonorgestrel-releasing intrauterine system--when does it manifest?

The objective of the study was to evaluate, clinically and sonographically, the time required for the progestative effect of the levonorgestrel-releasing intrauterine system (IUS, Mirena) to be manifested. Doppler flow of the cervical branch and spiral artery of the uterine artery, as well as the endometrial width (up to day 10 of the cycle), were evaluated in 36 women carrying levonorgestrel-releasing IUS 1-2 months after insertion of the device compared to 4-6 months after insertion. The rate of intermenstrual bleeding was reduced from 44% during the first 2 months, to only 8% of women after 4-6 months of use. Complete cessation of menstrual bleeding occurred in 5% after 2 months and in 66% after 4-6 months following insertion. While there was no change in the Doppler flow in the cervical branch of the uterine artery between both groups, there was a significant reduction in the subendometrial flow in the spiral artery. This observation was reinforced by the demonstration of significant reduction in endometrial thickness in the following 4 months of use. The present study has demonstrated that the local progestative effect of the levonorgestrel-releasing IUS on the endometrium is already manifested within a period of 3 months and over after insertion.

In-utero development of the fetal colon and rectum: sonographic evaluation.

OBJECTIVE: To construct a normal range for the internal diameter of the fetal descending colon and rectum during gestation. SUBJECTS AND METHODS: This was a prospective, cross-sectional study including 379 healthy pregnant women with normal singleton pregnancies at 19-40 weeks of gestation. Measurements of the fetal descending colon (maximum internal diameter) and the fetal rectum (at the level of the bladder, measuring the anteroposterior diameter), were performed by high-resolution transabdominal sonography. RESULTS: Adequate bowel measurements were obtained in all 379 fetuses. The diameter of the descending colon and rectum plotted as a function of gestational age had a sigmoid curve; the curve estimation was expressed by a cubic regression equation with R(2) of 0.848 and 0.831, respectively (P < 0.0001). The normal mean and the 95% prediction limits were defined. CONCLUSION: The present data provide a normal range of fetal bowel (descending colon and rectum) diameters from the early second trimester of pregnancy onwards. They may allow intrauterine assessment of the development of the fetal colon and may serve as reference values in the detection of anomalies of the fetal bowel.

The expression of mannose-ligand receptor is correlated with sperm morphology.

The objective of the present study was to evaluate the association between the expression of sperm mannose-ligand receptors and sperm morphology. Sperm samples were obtained from 45 men, 30 fertile sperm donors and 15 infertile men. Sperm concentration, motility and morphology were evaluated and then incubated with control medium (Ham's F-10 + 1% HSA) for 4 h. Expression of mannose-ligand receptors was evaluated by mannosylated-BSA-FITC (subdivided into 3 patterns: I, for uncapacitated sperm; II, for capacitated; and III, for acrosome-reacted sperm). The mean (+/- SE) frequencies of sperm cells of the total sperm population that expressed patterns I, II, and III were 88 +/- 2.1%, 7 +/- 1.6%, and 5 +/- 0.8%, respectively, for fertile men, and 90 +/- 2.1%, 7 +/- 1.3%, and 3 +/- 0.5%, respectively, for infertile men. The rate of pattern III expression of mannose-ligand receptors was significantly higher in the fertile group compared to the infertile patients (p <.01). A poor but significant correlation was observed between the rate of pattern III and the percentage of normal-forms sperm cell in the ejaculate (r =.35, p =.018). Fertile sperm samples express more advanced patterns of mannose-ligand receptors compared to infertile men. This phenomenon is related to the morphology of human sperm cell in the ejaculate more than to any other basic sperm characteristics.

The local progestational effect of the levonorgestrel-releasing intrauterine system: a sonographic and Doppler flow study.

BACKGROUND: We aimed to evaluate the effect of the levonorgestrel-releasing intrauterine system (LNG-IUS) on the uterine vasculature and the endometrium. METHODS: The study was a prospective controlled study evaluating the local effects of LNG-IUS compared with the copper intrauterine device (IUD). Forty-seven women carrying LNG-IUS (group A) were compared with 35 women carrying copper IUD in a control group (group B). Clinical measures of menstrual bleeding, endometrial thickness and Doppler flow of the cervical branch of the uterine artery and spiral artery were evaluated and compared between the two groups. RESULTS: Doppler flow in the cervical branch of the uterine artery did not reveal any changes between the groups (resistance index = 0.6 +/- 0.01 in both groups). Endometrial width was significantly thinner in group A (4.1 +/- 0.2 mm) compared with group B (7.3 +/- 0.2 mm) (P < 0.0001). Subendometrial flow in the spiral artery was significantly reduced in 35 women of group A (75%) and in none of group B (P < 0.0001). CONCLUSIONS: The present study offers an explanation for the oligomenorrhoea in LNG-IUS users, i.e. a local progestational effect on the endometrium with no change in the blood flow in the uterine artery. This should be presented to the women in the pre-contraceptive counselling in order to lessen the discontinuation rate.

Probability of sperm detection in nonobstructive azoospermic men undergoing testicular sperm extraction procedures unrelated to clinical parameters.

The study was conducted to evaluate the significance of preoperative clinical parameters for detection of mature testicular sperm cells in nonobstructive azoospermic men. Sixty-five consecutive men with nonobstructive azoospermia underwent testicular sperm extraction procedures. Testicular samples were analyzed histologically with patterns classified as mature spermatogenesis (normal or partial), arrest of spermatogenesis, and Sertoli cell only. Testicular sperm cells were isolated for use in an IVF/ICSI program. Histologic patterns and detection rate of sperm cells were correlated to clinical characteristics. Mature sperm cells were found in all levels of serum FSH. The men were divided into 3 groups based on their clinical characteristics (serum FSH level and testicular size). The distribution of the different testicular histologic patterns, as well as detection rate of sperm cells, was similar in all groups. No correlation was found between serum levels of FSH, LH, prolactin, or testosterone and sperm presence. None of these parameters, nor the testicular size and consistency, can serve as predictive variables of the histological pattern or the presence of mature sperm cells in the testicular biopsies in cases of nonobstructive azoospermia. Until an effective predictive tool is available, a trial of sperm retrieval is recommended for all azoospermic men independent of their clinical characteristics.

Placental apoptosis in discordant twins.

OBJECTIVE: To investigate placental apoptosis in discordant dichorial twins. METHODS: Placental samples were obtained from 7 third-trimester suitable twins. Discordancy was defined as a >25 per cent difference in newborn birth weight. Light microscopy using hematoxylin and eosin (H&E)-stained paraffin slides and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling (TUNEL) methods were used to confirm the incidence of apoptosis. Investigators were blinded to pregnancy outcome. RESULTS: Both methods revealed that the incidence of apoptosis in the placentas of the smaller fetuses was significantly higher than in placentas of the larger fetuses. The incidence of TUNEL-positive cells in the former was 1.4+/-0.26 per cent: this was significantly higher than the incidence of apoptosis in the placental specimens of the latter (0.9+/-0.07 per cent, P< 0.02 Wilcoxon rank test). The same results were obtained with H&E: the incidence of apoptosis detected in placentas from the former was 1.07+/-0.1 per cent compared to 0.72+/-0.08 per cent in those of the latter (P< 0.02 Wilcoxon rank test). CONCLUSIONS: Despite similar environment conditions, placental apoptosis is increased in the smaller fetus and thus might play a role in discordancy between twins. Since increased placental apoptosis has also been found in singleton intrauterine growth restriction, this supports the hypothesis that the smaller twin is selectively growth restricted.

High levels of catecholamines in human semen: a preliminary study.

The objective of this study was to determine the seminal concentrations of four different catecholamines and their association with semen quality. Seminal concentrations of adrenaline, noradrenaline, 3,4-dihydroxy-phenylalanine (DOPA), and 3,4-dihydroxy-phenyl acetic acid (DOPAC) were determined in 13 healthy volunteers, using high-performance liquid chromatography with an electrochemical detector. In addition, semen analysis was performed. Noradrenaline and DOPA were present in all specimens with a concentration of 15 181+/- 2951 pg ml(-1) and 4023 +/- 429 pg ml(-1) (mean +/- SE), respectively. These concentrations are respectively 19 times (range: 3-44) and twice (range: 1-3) as high as the maximal normal concentration in plasma. Adrenaline was present in 10 and DOPAC in seven of 13 specimens. No correlation was found between the concentration of any of the catecholamines evaluated and semen characteristics. In conclusion, noradrenaline and DOPA are present in human semen at concentrations that are much higher than maximal normal values in plasma. Adrenaline and DOPAC were also found in some of the samples. The concentrations of catecholamines in semen are not associated with semen quality.

Results of 6139 artificial insemination cycles with donor spermatozoa.

BACKGROUND: Artificial insemination by donor spermatozoa (AID) can prove a valuable treatment for a number of male factor disorders, although its success rate is variable. METHODS: Retrospective analysis of the results of 6139 cycles performed in 1001 women during an 18 year period is presented. Pregnancy rates per cycle are presented as a function of: female fertility history, treatment modalities, medication used for induction of ovulation, female age, year of treatment, consecutive cycle effect and the use of fresh versus frozen-thawed spermatozoa. RESULTS: Overall pregnancy rate of 12.6% and cumulative pregnancy rate after 12 months of treatment of 75% were achieved. Age was found to be the most important determinant for success rate. CONCLUSIONS: Since the establishment of AID treatments, the mean age of the population of women receiving treatment has increased each year. Consequently, success rate did not improve, even with the use of more sophisticated medical modalities.