Association between benzodiazepine receptor agonist use and mortality in patients hospitalised for COVID-19: a multicentre observational study.

AIMS: To examine the association between benzodiazepine receptor agonist (BZRA) use and mortality in patients hospitalised for coronavirus disease 2019 (COVID-19). METHODS: A multicentre observational study was performed at Greater Paris University hospitals. The sample involved 14 381 patients hospitalised for COVID-19. A total of 686 (4.8%) inpatients received a BZRA at hospital admission at a mean daily diazepam-equivalent dose of 19.7 mg (standard deviation (s.d.) = 25.4). The study baseline was the date of admission, and the primary endpoint was death. We compared this endpoint between patients who received BZRAs and those who did not in time-to-event analyses adjusted for sociodemographic characteristics, medical comorbidities and other medications. The primary analysis was a Cox regression model with inverse probability weighting (IPW). RESULTS: Over a mean follow-up of 14.5 days (s.d. = 18.1), the primary endpoint occurred in 186 patients (27.1%) who received BZRAs and in 1134 patients (8.3%) who did not. There was a significant association between BZRA use and increased mortality both in the crude analysis (hazard ratio (HR) = 3.20; 95% confidence interval (CI) = 2.74-3.74; p < 0.01) and in the IPW analysis (HR = 1.61; 95% CI = 1.31-1.98, p < 0.01), with a significant dose-dependent relationship (HR = 1.55; 95% CI = 1.08-2.22; p = 0.02). This association remained significant in sensitivity analyses. Exploratory analyses indicate that most BZRAs may be associated with an increased mortality among patients hospitalised for COVID-19, except for diazepam, which may be associated with a reduced mortality compared with any other BZRA treatment. CONCLUSIONS: BZRA use may be associated with an increased mortality among patients hospitalised for COVID-19, suggesting the potential benefit of decreasing dose or tapering off gradually these medications when possible.

Efficacy of assisted reproductive technology after ovarian tissue transplantation in a cohort of 11 patients with or without associated infertility factors.

PURPOSE: IVF treatment in women with grafted frozen-thawed ovarian tissue is associated with poor reproductive outcomes. The aim of this study was to evaluate the efficacy of ovarian tissue transplantation (OTT) followed by assisted reproductive technology (ART) in women with or without associated infertility factors. METHODS: This is a prospective cohort study with retrospective data collection including eleven women, four of whom having an infertility factor (IF), who had undergone OTT in one university center between 2005 and 2017, followed by ART in six in vitro fertilization (IVF) centers. RESULTS: In total, 25 of the 85 cycles initiated (29%) were canceled, resulting in 60 oocyte retrievals. Ninety-five oocytes were retrieved: 36 were abnormal or immature, 29/39 fertilized (74%) after ICSI and 13/20 (65%) after IVF. Thirty-five embryos were transferred in seven patients (5/7 patients without IF and 2/4 patients with IF). After ART, one patient with IF experienced two pregnancies, one resulting in a live birth. For all patients, pregnancy rates and live birth rates were 7.4% and 3.7% per embryo transfer, respectively. Nine pregnancies and four live births occurred after spontaneous conception in five patients without IF, none in the infertility group. CONCLUSION: This study confirms that IVF treatment in women with grafted frozen-thawed ovarian tissue is associated with poor outcomes. However, the chances of natural conception are high in women without IF. Patients with IF, without the possibility of spontaneous pregnancy, should be informed of poor reproductive outcomes after OTT followed by ART. TRIAL REGISTRATION NUMBER: NCT02184806.

A report on the large measles outbreak in Lyon, France, 2010 to 2011.

In 2010 and 2011, the city of Lyon, located in the Rhône-Alpes region (France), has experienced one of the highest incidences of measles in Europe. We describe a measles outbreak in the Lyon area, where cases were diagnosed at Lyon University hospitals (LUH) between 2010 and mid-2011. Data were collected from the mandatory notification system of the regional public health agency, and from the virology department of the LUH. All patients and healthcare workers who had contracted measles were included. Overall, 407 cases were diagnosed, with children of less than one year of age accounting for the highest proportion (n=129, 32%), followed by individuals between 17 and 29 years-old (n=126, 31%). Of the total cases, 72 (18%) had complications. The proportions of patients and healthcare workers who were not immune to measles were higher among those aged up to 30 years. Consequently, women of childbearing age constituted a specific population at high risk to contract measles and during this outbreak, 13 cases of measles, seven under 30 years-old, were identified among pregnant women. This study highlights the importance of being vaccinated with two doses of measles vaccine, the only measure which could prevent and allow elimination of the disease.

[Risks in medically-assisted procreation in case of positivity for HIV, hepatitis C virus or hepatitis B virus. The French law at the end of 2001]. / Risques de l'assistance médicale à la procréation en cas d'infection par le VIH, les virus des hépatites C ou B. Qu'apporte la loi française par l'arrêté de 2001?

Inclusion of HIV+, HCV+ or HBV+ couples in medically assisted procreation has been allowed by the French law since the publication of some legal texts dates January 12th 1999 and May 2001. This article tries to identify the viral risks of such inclusion and to analyse the answers given by the French law to eliminate these risks.

Hepatitis C virus detection in follicular fluid and culture media from HCV+ women, and viral risk during IVF procedures.

BACKGROUND: Hepatitis C virus (HCV) has been detected in sperm, but no data are available on follicular fluid (FF) collected on IVF procedures. The aim of this study was to: (i) search for HCV RNA in FF and in culture media at each step of IVF undergone by HCV(+) women; (ii) investigate the impact of blood contamination of FF induced by vascular injury associated with transvaginal ovarian puncture; (iii) assess risk for the embryo and the impact on the contamination rate of the newborn; and (iv) determine the viral risk presented by these fluids in order to define guidelines for the laboratory. METHODS: FF from 22 IVF procedures performed in 17 HCV(+) women were classified as either clear, lightly bloody or bloody FF. Oocytes from each FF were washed and incubated in separated fertilization media. At 20 h after puncture (day 1), the fertilized oocytes were washed and transferred to fresh media until embryo transfer. HCV RNA was detected and quantified in FF and media using Cobas Amplicor and Cobas Monitor HCV RNA kits. RESULTS: HCV RNA was positive in 39 of 44 FF samples, and viral loads increased with blood contamination. At day 1, after rinsing of oocyte-cumulus complexes, only 8 of 44 media were still positive. Viral loads were quantified in 5 of 8 positive media, were below the test sensitivity threshold in 4 of 5 HCV RNA-positive media, and just above it in the fifth medium. The day of transfer HCV RNA was undetectable in all media. CONCLUSIONS: HCV RNA was detected in 89% of FF irrespective of the degree of blood contamination, and in 25% of the media at day 1. FF must be considered as potentially infected. Blood contamination increases HCV load in the FF. Rinsing oocytes seems significantly to discard the HCV RNA. It is too early to assess the impact of IVF on the contamination rate of HCV mothers' offspring. After counselling, attempting IVF in HCV(+) women is justified. Universal guidelines prevent nosocomial infection, and IVF does not specifically increase the professional risk.

A modified RT-PCR technique to screen for viral RNA in the semen of hepatitis C virus-positive men.

BACKGROUND: Our objective was to use an adapted RT-PCR technique to assess the presence of hepatitis C virus (HCV) in semen and also in different density gradient semen fractions collected from men with chronic viral hepatitis participating in an assisted reproduction programme. METHODS: This study included 50 semen samples from 35 HCV(+) men, with active viral replication assessed by RT-PCR, collected the day of oocyte retrieval and used for assisted reproduction. These samples were subjected to standard assisted reproduction sperm preparation conditions, using density-gradient centrifugation with 45 and 90% layers. Aliquots of semen, 45 and 90% fractions, and embryo culture media were frozen at -80 degrees C for subsequent virological analyses. All aliquots were tested with a commercially available HCV RNA assay, adapted for use with semen after a number of technical changes. This assay yielded a sensitivity of 50-100 HCV RNA copies/ml and strongly diminished the effect of seminal amplification inhibitors. RESULTS: HCV RNA was detected in 7/50 (14%) semen samples tested, 5/35 (14.3%) men. HCV RNA was found in only 1/50 45% fractions but never in the 90% fraction or embryo culture media. Sera from 3/5 men contained 3.19-7.40 x 10(5) IU/ml, while the two others had 4.5 and 11.7 x 10(6) IU/ml. However, HCV RNA was quantified at <600 IU/ml in the HCV(+) semen of these five patients. The ongoing pregnancy rate was of 20% (10/50) with one delivery at the time of the present report. No anti-HCV antibody was found in any of the women or the newborn. CONCLUSIONS: Although HCV is present at low concentrations in the semen of a few HCV(+) patients, no purified sperm fraction (i.e. 90% fraction) used in assisted reproduction was HCV(+) and no seroconversion was observed in the women and the newborn, thereby suggesting a very low risk of virus transmission. Nevertheless, because the presence of HCV in semen implies a possible risk of nosocomial contamination, safety regulations must be strictly applied in assisted reproduction laboratories.

[Ovarian hyperstimulation syndrome and thrombosis. Apropos of a case of thrombosis of the internal jugular vein. Review of the literature]. / Syndrome d'hyperstimulation ovarienne et thrombose. A propos d'un cas de thrombose de la veine jugulaire interne. Revue de la littérature.

Thrombosis of the internal jugular vein was associated with a severe syndrome of ovarian hyperstimulation. After in vitro fertilization, a twin pregnancy was obtained in a 31-year-old patient with severe endometriosis. On the day of follicle collection, plasma oestradiol was 3050 mg/ml. Ten ovocytes were collected and 3 embryos were implanted. A syndrome of severe ovarian hyperstimulation (ascites, pleural effusion) developed 3 weeks later and symptomatic treatment was given. Phlebitis of the upper left limb was diagnosed at 9 weeks amenorrhoea and echo-Doppler confirmed the diagnosis of subclavian and internal jugular venous thrombosis. Search for a cause was negative excepting a frank drop in protein S activity to 35%. Post-partum assay and assay in family members confirmed that the deficiency was acquired during pregnancy. The clinical course was favourable with anticoagulant therapy (heparin, then low-molecular weight heparin). Intra-uterine death of one of the fetuses occurred at 21 weeks amenorrhoea and a 2,550 g girl was born by vaginal delivery at 36 weeks. The Apgar score at birth was 10/10. In a review of the literature on vascular events in fertilization, programmes showed that severe syndromes of ovarian hyperstimulation, endogenous hyperestrogenism, multiple pregnancy and predominance of upper limb are the most frequently observed criteria. We emphasize the importance of preventing these thromboembolic events with subcutaneous heparin during the first trimester of pregnancy followed by low-molecular weight heparin, particularly in patients with a history of thromboembolism and/or patients with severe ovarian hyperstimulation.