Comparative phase I randomized open-label pilot clinical trial of Gynophilus® (Lcr regenerans®) immediate release capsules versus slow release muco-adhesive tablets.

Gynophilus® (Lcr regenerans®) is a live biotherapeutic product (LBP) that contains the live biotherapeutic microorganism Lactobacillus rhamnosus Lcr35®, which is indicated to restore vaginal health. The aim of the study was to compare the safety, ease of use, and compliance of two formulations (immediate release: IR capsule and slow release: SR muco-adhesive tablets) as well as the colonization of Lcr35® in healthy women. This phase I study (Comprigel) is a parallel, randomized, 4-arm, and open-label clinical trial evaluating an IR daily capsule formulation vs. a SR tablet administered every 3, 4, or 5 days for 21 days. Self-collected vaginal swabs were used to quantify Lcr35® and characterize the composition and structure of the vaginal microbiota. Both LBPs were well-tolerated, and no severe adverse effects were reported. All groups had Lcr35® vaginal concentrations over 107 colony forming unit per milliliter of vaginal secretion on each day in the study. The new Gynophilus® slow release tablets administered either every 3, 4, or 5 days provided vaginal concentrations that were not significantly different from those of classic Gynophilus® (capsule) once-a-day regimen. The LBPs and the different regimens did not adversely influence the abundance of native Lactobacillus spp. and indeed tended to favor their growth and reduce colonization by non-Lactobacillus spp. This study illustrates that the SR muco-adhesive LBP tablet (Gynophilus® SR) administered every 3 or 4 days as a safe, well-tolerated, and efficacious alternative to a more demanding IR daily capsule and could protect women's healthy vaginal microbiome by promoting endogenous Lactobacillus spp.

Papillomavirus and cancers: should we extend vaccination to boys in France?

Background: In 2006, the HPV (Human papillomavirus) 6/11/16/18 quadrivalent vaccine was approved by the European Medicines Agency and obtained its marketing authorization in both girls and boys. Currently, the French guidelines recommend and refund vaccination of girls aged 11 to 14 with a catch-up program for females from 15 to 19 years old. Discussion: In France, HPV vaccination coverage tends to decrease. At the end of 2015, the vaccination coverage with three doses reached only 14% in 16-year-old girls (three doses). Although men are also affected by HPV-related diseases such as anal cancer, ano-genital warts, penile cancer or upper aerodigestive tract cancer, vaccine recommendations in France are for girls only. To face the high prevalence of anal cancer and related diseases, the best option is vaccination. Moreover, by offering men a way to prevent diseases against which they do not have any protection yet, universal vaccination could better take into account the ethical issues of prevention. In this paper, we present the point of view of different medical specialties concerning the potential benefit of extending vaccination to boys. Conclusion: HPV vaccination of both genders could benefit from a better public acceptance and contribute to a better coverage, especially in countries with low vaccination rates.

Current concepts in managing pelvic inflammatory disease.

PURPOSE OF REVIEW: The management of pelvic inflammatory disease (PID) has significantly changed during the last two decades. Moreover, some recent bacterial findings have led to recent changes in this management. RECENT FINDINGS: Most cases of PID are mild-to-moderate uncomplicated forms that can be treated as outpatients. Apart from Chlamydia trachomatis and Neisseria gonorrhoeae, other pathogens such as Mycoplasma genitalium and bacterial vaginosis (BV)-associated bacteria are playing a significant role in PID and thus must be reckoned with. Moreover, gonococci have increasingly become resistant to the majority of antibiotics. This has led to a universal recommendation to treat N. gonorrhoeae infections with ceftriaxone. A few recent clinical trials have shown that quinolones and azithromycin (with metronidazole) are the best therapeutic options to treat uncomplicated PID. SUMMARY: The management of PID nowadays must take into account the role of pathogens such as M. genitalium, BV-associated bacteria and multiresistant gonococci.

ISIDOG Recommendations Concerning COVID-19 and Pregnancy.

Providing guidelines to health care workers during a period of rapidly evolving viral pandemic infections is not an easy task, but it is extremely necessary in order to coordinate appropriate action so that all patients will get the best possible care given the circumstances they are in. With these International Society of Infectious Disease in Obstetrics and Gynecology (ISIDOG) guidelines we aim to provide detailed information on how to diagnose and manage pregnant women living in a pandemic of COVID-19. Pregnant women need to be considered as a high-risk population for COVID-19 infection, and if suspected or proven to be infected with the virus, they require special care in order to improve their survival rate and the well-being of their babies. Both protection of healthcare workers in such specific care situations and maximal protection of mother and child are envisioned.

Radiofrequency driven cord occlusion for selective termination of pregnancy: evaluation in the fetal sheep.

OBJECTIVE: This study was designed to assess the ability of an ultrasound-guided radiofrequency (RF)-driven procedure to induce complete and irreversible cord occlusion using a 90 days fetal sheep model. STUDY DESIGN: Twenty 90 days gestation sheep underwent general anesthesia. The first ten fetuses were exposed under hysterotomy, and RF electrode was inserted visually in the middle of the umbilical cord and deployed. Fetuses were then replaced into the amniotic fluid and RF procedure (average target temperature of 100 degrees C during 10 minutes) was applied. For the next ten fetuses, RF electrode was inserted into the cords under trans-parietal ultrasound guidance and the same RF procedure was applied. Cord occlusion was assessed by Doppler examination (absence of cordonal flows at the end of the procedure and until fetal heart failure occurred) and by subsequent histopathological analysis. RESULTS: Cord occlusion was always complete at Doppler examination at the end of RF procedure for the ten experiments realized under hysterotomy. No cordonal reperfusion was observed until fetal heart failure. Histopathological analysis confirmed cordonal occlusion at the site of impact. Neither cordonal rupture nor cordonal bleeding was observed for any of the ten experiments. When RF electrode was inserted under ultrasound guidance, complete occlusion could be obtained only for 6 of the ten experiments. CONCLUSION: Our results suggest that RF might be an appropriate method for selective termination of pregnancy. Yet, optimal insertion of the electrode is required to engender a complete and irreversible cord occlusion, and ultrasound-guidance training seems necessary before current human application.

European guideline for the management of pelvic inflammatory disease.

Pelvic inflammatory disease (PID) remains one of the most important consequences of sexually transmitted infections (STIs) resulting in severe morbidity and acting as the economic justification for STI screening programmes. Early and appropriate therapy has the potential to significantly reduce the long-term complications of PID, and these evidence-based guidelines provide advice on the management of pelvic infection including the use of appropriate antimicrobial regimens.

Early screening for Chlamydia trachomatis in young women for primary prevention of pelvic inflammatory disease (i-Predict): study protocol for a randomised controlled trial.

BACKGROUND: Genital infection with Chlamydia trachomatis (Ct) is the most common bacterial sexually transmitted infection, especially among young women. Mostly asymptomatic, it can lead, if untreated, to pelvic inflammatory disease (PID), tubal factor infertility and ectopic pregnancy. Recent data suggest that Ct infections are not controlled in France and in Europe. The effectiveness of a systematic strategy for Ct screening in under-25 women remains controversial. The main objective of the i-Predict trial (Prevention of Diseases Induced by Chlamydia trachomatis) is to determine whether early screening and treatment of 18- to-24-year-old women for genital Ct infection reduces the incidence of PID over 24 months. METHODS/DESIGN: This is a randomised prevention trial including 4000 eighteen- to twenty-four-year-old sexually active female students enrolled at five universities. The participants will provide a self-collected vaginal swab sample and fill in an electronic questionnaire at baseline and at 6, 12 and 18 months after recruitment. Vaginal swabs in the intervention arm will be analysed immediately for Ct positivity, and participants will be referred for treatment if they have a positive test result. Vaginal swabs from the control arm will be analysed at the end of the study. All visits to general practitioners, gynaecologists or gynaecology emergency departments for pelvic pain or other gynaecological symptoms will be recorded to evaluate the incidence of PID, and all participants will attend a final visit in a hospital gynaecology department. The primary endpoint measure will be the incidence of PID over 24 months. The outcome status (confirmed, probable or no PID) will be assessed by two independent experts blinded to group assignment and Ct status. DISCUSSION: This trial is expected to largely contribute to the development of recommendations for Ct screening in young women in France to prevent PID and related complications. It is part of a comprehensive approach to gathering data to facilitate decision-making regarding optimal strategies for Ct infection control. The control group of this randomised trial, following current recommendations, will allow better documentation of the natural history of Ct infection, a prerequisite to evaluating the impact of Ct screening. Characterisation of host immunogenetics will also allow identification of women at risk for complications. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02904811 . Registered on September 14, 2016. World Health Organisation International Clinical Trials Registry, NCT02904811. AOM, 15-0063 and P150950. Registered on September 26, 2016. A completed Standard Protocol Items : Recommendations for International Trials (SPIRIT) Checklist is available in additional file 1.

Potential impact of the human papillomavirus vaccine on the incidence proportion of genital warts in French women (EFFICAE study): a multicentric prospective observational study.

UNLABELLED: Background The objective was to evaluate the effect of a HPV vaccination program on the incidence proportion of a proxy, genital warts (GW), in women in France. METHODS: The number of primary GW cases was prospectively recorded over two 4-month periods before (T0: Dec 2008 to March 2009) and after (T1: Dec 2011 to March 2012) a HPV vaccination program. A total of 160 gynaecologists participated in T0 and 189 in T1. Primary genital herpes (HSV) infection was used as a control. RESULTS: During T0, 39190 15- to 26 year-old women were seen, of whom 176 were diagnosed with GW (incidence proportion: 0.45%) and 155 with primary HSV infection (incidence proportion: 0.39%). During T1, 45628 females were seen [229 with GW (incidence proportion: 0.50%) and 202 with HSV (incidence proportion: 0.44%)]. In the 15-20 years age category, the incidence proportion of primary GW decreased from 0.41% to 0.30% (P=0.128) between T0 and T1, and the proportion of women newly diagnosed with primary genital herpes diseases slightly increased from 0.34% to 0.38% (P=0.620). In the 15-18 years age group, this decrease became significant (0.34% to 0.18%; P=0.048). CONCLUSIONS: A trend for a non-significant decreased incidence proportion of GW was observed in young women below 20 years who are more frequently vaccinated. This may be the result of HPV vaccination and suggests that a substantial increase in vaccine coverage could lead to a more pronounced decreased incidence proportion of GW in the future.

Updated French guidelines for diagnosis and management of pelvic inflammatory disease.

BACKGROUND: Pelvic inflammatory disease (PID) is commonly encountered in clinical practice. OBJECTIVES: To provide up-to-date guidelines on management of PID. SEARCH STRATEGY: An initial search of the Cochrane database, PubMed, and Embase was performed using keywords related to PID to identify reports in any language published between January 1990 and January 2012, with an update in May 2015. SELECTION CRITERIA: All identified reports relevant to the areas of focus were included. DATA COLLECTION AND ANALYSIS: A level of evidence based on the quality of the data available was applied for each area of focus and used for the guidelines. MAIN RESULTS: PID must be suspected when spontaneous pelvic pain is associated with induced adnexal or uterine pain (grade C). Pelvic ultrasonography is necessary to exclude tubo-ovarian abscess (grade B). Microbiological diagnosis requires vaginal and endocervical sampling for molecular and bacteriological analysis (grade B). First-line treatment for uncomplicated PID combines ofloxacin and metronidazole for 14days (grade B). Treatment of tubo-ovarian abscess is based on drainage if the collection measures more than 3cm (grade B), with combined ceftriaxone, metronidazole, and doxycycline for 14-21days. CONCLUSIONS: Current management of PID requires easily reproducible investigations and treatment, and thus can be applied worldwide.

2012 European guideline for the management of pelvic inflammatory disease.

This guideline was produced by the European region of the International Union against sexually transmitted infections (IUSTI) and refers to ascending infections in the female genital tract unrelated to delivery and surgery and does not include actinomyces-related infection.

Safety and efficacy of an intravaginal prebiotic gel in the prevention of recurrent bacterial vaginosis: a randomized double-blind study.

Objective. This study was performed to evaluate the efficacy and safety of a prebiotic treatment in the balance recovery of the vaginal flora in subjects previously treated for bacterial vaginosis (BV). Study Design. A randomized trial was carried out on 42 subjects with an active prebiotic group compared to a placebo group. The main evaluation criterion was the quantification of the vaginal flora measured by the Nugent score. Secondary criteria included vaginal pH and BV recurrence. Results. After 8 days of treatment, all subjects who received the prebiotic had a normal Nugent score, whereas 33% of the subjects treated with placebo had an intermediate or positive Nugent score. After 16 days of application, a normal Nugent score was maintained in all subjects treated with the prebiotic, whereas in the placebo group 24% of the subjects still had an elevated Nugent score. Moreover, the maintenance of (or reversion to) a normal flora was associated with the maintenance of (or reversion to) physiological pH values. Conclusions. The intravaginal gel treatment improves the recovery of a normal vaginal flora after the treatment of a BV episode, which should warrant a reduction in the risk of further recurrences.

Levofloxacin plus metronidazole in uncomplicated pelvic inflammatory disease: a preliminary study.

OBJECTIVE: Uncomplicated pelvic inflammatory disease (PID) is a common disease caused by numerous pathogens: sexually transmitted infections (such as Chlamydia trachomatis, Neisseria gonorrhoeae and Mycoplasma genitalium), anaerobes, and other organisms from the vaginal flora. It is currently treated by oral route and most present protocols recommend ofloxacin plus metronidazole (MET). The CDC 2006 Guidelines suggested that levofloxacin (LEV) can be a substitute for ofloxacin. This study aimed to evaluate the efficacy and safety of LEV-MET in the treatment of uncomplicated PID. STUDY DESIGN: The first 40 cases of uncomplicated PID were prospectively evaluated (June 2006 to December 2007). Diagnosis was based on the clinical signs and microbial findings. If present (N=8), IUD were removed and cultured. Treatment consisted of LEV 500mg OD+MET 500mg BID by oral route for 14 days. Visits took place at the end of therapy (EOT) and at follow-up (FU) 4-6 weeks later. The endpoints were clinical resolution (at the EOT and FU) and bacteriological eradication (at the EOT). RESULTS: 10 cases of bacterial vaginosis were found and 35 pathogens (E. coli: 12, anaerobes: 5; C. trachomatis: 5; M. hominis: 5; U. urealyticum: 3; others: 5) were isolated in the cervix. 37 patients were evaluable at the EOT: 27 were clinically cured and 10 significantly improved; all pathogens were eradicated. At FU, all 35 evaluable patients were clinically cured. Drug-related adverse events (AEs) occurred in 9 cases: 1 patient discontinued (myalgia and tendonitis) while other AEs consisted of nausea or diarrhea. CONCLUSION: This preliminary study has shown that a 14-day course of oral LEV-MET is effective and well-tolerated in the treatment of outpatients with uncomplicated PID.

[Herpes as viewed by the French: result of a survey conducted on 10,000 persons]. / L'herpès vu par les Français: résultat d'une enquête portant sur 10,000 personnes.

Herpes is a viral infection which increases, specifically genital herpes. The aim of this survey was to assess the perception of herpes in the general population and in patients with herpes in France using a self-administered questionnaire. A total of 10,000 persons answered the questionnaire among which 128 patients presented herpes. This study showed that only 5% of the French population knew that herpes was a viral infection, and 7% a sexually transmitted disease. Among patients with genital herpes only 34% indicated a sexual relationship and a mode of contamination. The interference with sexual and social life is important. Development of information and communication on herpes appears crucial.