Project description:Study questionsDoes the application of anti-adhesion gel, compared to no gel, following operative hysteroscopy to treat intrauterine pathology in women wishing to conceive increase the chance of conception leading to live birth?What is known alreadyIntrauterine adhesions (IUAs) following operative hysteroscopy may impair reproductive success in women of reproductive age. Anti-adhesion barrier gels may decrease the occurrence of IUAs, but the evidence on their effectiveness to improve reproductive outcomes is sparse and of low quality.Study design size durationThis multicentre, parallel group, superiority, blinded and pragmatic randomised controlled trial is being carried out in seven participating centres in Belgium. Recruitment started in April 2019. Women will be randomly allocated to treatment with anti-adhesion gel (intervention group) or no gel (control group). Sterile ultrasound gel will be applied into the vagina as a mock-procedure in both treatment arms. The patient, fertility physician and gynaecologist performing the second-look hysteroscopy are unaware of the allocated treatment. Power analysis, based on a target improvement of 15% in conception leading to live birth using anti-adhesion gel, a power of 85%, a significance level of 5%, and a drop-out rate of 10%, yielded a number of 444 patients to be randomised. The baseline rate of conception leading to live birth in the control group is expected to be 45%.Participants/materials setting methodsWomen of reproductive age (18-47?years), wishing to conceive (spontaneously or by fertility treatment) and scheduled for operative hysteroscopy to treat intrauterine pathology (endometrial polyps, myomas with uterine cavity deformation, uterine septa, IUAs or retained products of conception) are eligible for recruitment. Women may try to conceive from 3 to 6?weeks after receiving allocated treatment with follow-up ending at 30?weeks after treatment. If the woman fails to conceive within this timeframe, a second-look hysteroscopy will be scheduled within 2-6?weeks to check for IUAs. The primary endpoint is conception leading to live birth, measured at 30?weeks after randomisation. The secondary endpoints are time to conception, clinical pregnancy, miscarriage and ectopic pregnancy rates, measured at 30?weeks after receiving allocated treatment. The long-term follow-up starts when the patient is pregnant and she will be contacted every trimester.Study funding/competing interestsThis work is funded by the Belgian Healthcare Knowledge Centre (KCE). The anti-adhesion gel is supplied at no cost by Nordic Pharma and without conditions. Dr. Tomassetti reports grants and non-financial support from Merck SA, non-financial support from Ferring SA, personal fees and non-financial support from Gedeon-Richter, outside the submitted work. None of the other authors have a conflict of interest.
Project description:Infertility is a significant clinical problem. It affects 8-12% of couples worldwide, about 30% of whom are diagnosed with idiopathic infertility (infertility lacking any obvious cause). In 2010, the World Health Organization calculated that 1.9% of child-seeking women aged 20-44 years were unable to have a first live birth (primary infertility), and 10.5% of child-seeking women with a prior live birth were unable to have an additional live birth (secondary infertility). About 50% of all infertility cases are due to female reproductive defects. Several chromosome aberrations, diagnosed by karyotype analysis, have long been known to be associated with female infertility and monogenic mutations have also recently been found. Female infertility primarily involves oogenesis. The following phenotypes are associated with monogenic female infertility: premature ovarian failure, ovarian dysgenesis, oocyte maturation defects, early embryo arrest, polycystic ovary syndrome and recurrent pregnancy loss. Here we summarize the genetic causes of non-syndromic monogenic female infertility and the genes analyzed by our genetic test.
Project description:About 10% of women of reproductive age are unable to conceive or carry a pregnancy to term. Female factors alone account for at least 35% of all infertility cases and comprise a wide range of causes affecting ovarian development, maturation of oocytes, and fertilization competence, as well as the potential of a fertilized egg for preimplantation development, implantation, and fetal growth. Genetic abnormalities leading to infertility in females comprise large chromosome abnormalities, submicroscopic chromosome deletion and duplications, and DNA sequence variations in the genes that control numerous biological processes implicated in oogenesis, maintenance of ovarian reserve, hormonal signaling, and anatomical and functional development of female reproductive organs. Despite the great number of genes implicated in reproductive physiology by the study of animal models, only a subset of these genes is associated with human infertility. In this review, we mainly focus on genetic alterations identified in humans and summarize recent knowledge on the molecular pathways of oocyte development and maturation, the crucial role of maternal-effect factors during embryogenesis, and genetic conditions associated with ovarian dysgenesis, primary ovarian insufficiency, early embryonic lethality, and infertility.
Project description:Surgery is performed to treat various diseases. During the process, the surgical site is healed through self-healing after surgery. Post-operative or tissue adhesion caused by unnecessary contact with the surgical site occurs during the normal healing process. In addition, it has been frequently found in patients who have undergone surgery, and severe adhesion can cause chronic pain and various complications. Therefore, anti-adhesion barriers have been developed using multiple biomaterials to prevent post-operative adhesion. Typically, anti-adhesion barriers are manufactured and sold in numerous forms, such as gels, solutions, and films, but there are no products that can completely prevent post-operative adhesion. These products are generally applied over the surgical site to physically block adhesion to other sites (organs). Many studies have recently been conducted to increase the anti-adhesion effects through various strategies. This article reviews recent research trends in anti-adhesion barriers.
Project description:Hydrogels have gained tremendous attention due to their versatility in soft electronics, actuators, biomedical sensors, etc. Due to the high water content, hydrogels are usually soft, weak, and freeze below 0°C, which brings severe limitations to applications such as soft robotics and flexible electronics in harsh environments. Most existing anti-freezing gels suffer from poor mechanical properties and urgently need further improvements. Here, we took inspirations from tendon and coniferous trees and provided an effective method to strengthen polyvinyl alcohol (PVA) hydrogel while making it freeze resistant. The salting-out effect was utilized to create a hierarchically structured polymer network, which induced superior mechanical properties (Young's modulus: 10.1 MPa, tensile strength: 13.5 MPa, and toughness: 127.9 MJ/m3). Meanwhile, the cononsolvency effect was employed to preserve the structure and suppress the freezing point to -60°C. Moreover, we have demonstrated the broad applicability of our material by fabricating PVA hydrogel-based hydraulic actuators and ionic conductors.
Project description:BackgroundIncomplete spontaneous abortions are defined by the intrauterine retention of the products of conception after their incomplete or partial expulsion. This condition may be managed by expectant care, medical treatment or surgery. Vacuum aspiration is currently the standard surgical treatment in most centers. However, operative hysteroscopy has the advantage over vacuum aspiration of allowing the direct visualization of the retained conception product, facilitating its elective removal while limiting surgical complications. Inadequately powered retrospective studies reported subsequent fertility to be higher in patients treated by operative hysteroscopy than in those treated by vacuum aspiration. These data require confirmation in a randomized controlled trial comparing fertility rates between women undergoing hysteroscopy and those undergoing vacuum aspiration for incomplete spontaneous abortion.MethodsAfter providing written informed consent, 572 women with incomplete spontaneous abortion recruited from 15 centers across France will undergo randomization by a centralized computer system for treatment by either vacuum aspiration or operative hysteroscopy. Patients will not be informed of the type of treatment that they receive and will be cared for during their hospital stay in accordance with standard practices at each center. The patients will be monitored for pregnancy or adverse effects by a telephone conversation or questionnaire sent by e-mail or post over a period of two years. In cases of complications, failure of the intervention or diagnosis of uterine cavity disease, patient care will be left to the discretion of the medical center team.DiscussionIf our hypothesis is confirmed, this study will provide evidence that the use of operative hysteroscopy can increase the number of pregnancies continuing beyond 22 weeks of gestation in the two-year period following incomplete spontaneous abortion without increasing the incidence of morbidity and peri- and postoperative complications. The standard surgical treatment of this condition would thus be modified. This study would therefore have a large effect on the surgical management of incomplete spontaneous abortion.Trial registrationClinicalTrials.gov Identifier: NCT02201732 ; registered on 17 July 2014.
Project description:The high energetic demand of parental care requires parents to direct their resources towards the support of existing offspring rather than investing into the production of additional young. However, how such a resource flow is channelled appropriately is poorly understood. In this study, we provide the first comprehensive analysis of the physiological mechanisms coordinating parental and mating effort in an insect exhibiting biparental care. We show a hormone-mediated infertility in female burying beetles during the time the current offspring is needy and report that this temporary infertility is communicated via a pheromone to the male partner, where it inhibits copulation. A shared pathway of hormone and pheromone system ensures the reliability of the anti-aphrodisiac. Female infertility and male sexual abstinence provide for the concerted investment of parental resources into the existing developing young. Our study thus contributes to our deeper understanding of the mechanisms underlying adaptive parental decisions.
Project description:Based on recent, historical, and circumstantial evidence, we present a multifactorial hypothesis that has potential direct implications on the epidemiology and management of chlamydial infection and disease in humans. We propose that (1) like its veterinary relatives, the oculogenital pathogen Chlamydia trachomatis evolved as a commensal organism of the human gastrointestinal (GI) tract primarily transmissible via the fecal-oral route; (2) in the modern era, C. trachomatis causes "opportunistic" infection at non-GI sites under conditions driven by improved sanitation/hygiene and reduced fecal-oral transmission; and (3) the rise in the practice of oral sex is contributing to the increased prevalence of C. trachomatis in the human GI tract. Infectious organisms produced in the GI tract and reaching the rectum may then chronically contaminate and infect the female urogenital tract, thereby potentially contributing to the most serious sequelae of chlamydial infection in women: pelvic inflammatory disease, ectopic pregnancy, and tubal factor infertility.