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:ImportanceVacuum aspiration is commonly used to remove retained products of conception in patients with incomplete spontaneous abortion. Scarring of the uterine cavity may occur, potentially impairing future fertility. A procedural alternative, operative hysteroscopy, has gained popularity with a presumption of better future fertility.ObjectiveTo assess the superiority of hysteroscopy to vacuum aspiration for subsequent pregnancy in patients with incomplete spontaneous abortion who intend to have future pregnancy.Design, setting, and participantsThe HY-PER randomized, controlled, single-blind trial included 574 patients between November 6, 2014, and May 3, 2017, with a 2-year duration of follow-up. This multicenter trial recruited patients in 15 French hospitals. Individuals aged 18 to 44 years and planned for surgery for an incomplete spontaneous abortion with plans to subsequently conceive were randomized in a 1:1 ratio.InterventionsSurgical treatment by hysteroscopy (n = 288) or vacuum aspiration (n = 286).Main outcomes and measuresThe primary outcome was a pregnancy of at least 22 weeks' duration during 2-year follow-up.ResultsThe intention-to-treat analyses included 563 women (mean [SD] age, 32.6 [5.4] years). All aspiration procedures were completed. The hysteroscopic procedure could not be completed for 19 patients (7%), 18 of which were converted to vacuum aspiration (8 with inability to completely resect, 7 with insufficient visualization, 2 with anesthetic complications that required a shortened procedure, 1 with equipment failure). One hysteroscopy failed due to a false passage during cervical dilatation. During the 2-year follow-up, 177 patients (62.8%) in the hysteroscopy group and 190 (67.6%) in the vacuum aspiration (control) group achieved the primary outcome (difference, -4.8% [95% CI, -13% to 3.0%]; P = .23). The time-to-event analyses showed no statistically significant difference between groups for the primary outcome (hazard ratio, 0.87 [95% CI, 0.71 to 1.07]). Duration of surgery and hospitalization were significantly longer for hysteroscopy. Rates of new miscarriages, ectopic pregnancies, Clavien-Dindo surgical complications of grade 3 or above (requiring surgical, endoscopic, or radiological intervention or life-threatening event or death), and reinterventions to remove remaining products of conception did not differ between groups.Conclusions and relevanceSurgical management by hysteroscopy of incomplete spontaneous abortions in patients intending to conceive again was not associated with more subsequent births or a better safety profile than vacuum aspiration. Moreover, operative hysteroscopy was not feasible in all cases.Trial registrationClinicalTrials.gov Identifier: NCT02201732.
Project description:BackgroundPost-vasectomy pain syndrome (PVPS) is difficult to treat. Direct damage to the vas deferens, inflammation, compression of nerves through fibrotic adhesions, and congestion of the epididymis are known to cause PVPS. The purpose of this study was to evaluate whether the application of anti-adhesion agents after vasectomy can reduce the degree of adhesion and fibrosis in a rat model.MethodsIn the study, 11 Sprague-Dawley rats (22 vas deferens) from each group were evaluated. In the experimental group, surgery was terminated after applying the anti-adhesion agent; this was not applied in the control group. After 14 days of vasectomy, the scrotum was dissected to evaluate the degree of gross adhesion at the vasectomy site. Histological examination of the surrounding tissues, including the vas deferens and the spermatic cord, was also performed.ResultsAdhesions were not observed in 72.73% (16/22) rats from the experimental group, in which the anti-adhesion agent was applied; in contrast, the incidence of adhesions in the control group was 100%. There was a statistically significant relationship between the distribution of grades for adhesion and anti-adhesion agent (chi-square, P<0.001). On classification of fibrosis and inflammation, application of the anti-adhesion agent was significantly associated with lower grade inflammation and fibrosis compared to that of the control group (chi-square, P=0.001). The rate of intact muscle structure was 90.91% (20/22) in the experimental group, and 36.36% (8/22) in the control group, and the application of the anti-adhesion agent demonstrated significant association with preservation of intact muscle structure (chi-square, P<0.001).ConclusionsThe application of an anti-adhesion agent after vasectomy prevented the development of adhesion, fibrosis, and inflammation reaction and further reduced structural destruction.
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:PurposeSpontaneous oocyte activation (SOA) is a recently classified phenomenon characterized by the presence of a single pronucleus immediately following oocyte retrieval, without the apparent involvement of sperm. SOA currently remains poorly understood in humans, with no clear genetic or pathological factor(s). Herein, we report two separate cases of recurrent spontaneous oocyte activation, investigating potential avenues to identify causative etiology.MethodsTwo patients with several cycles with SOA have undergone further genetic and embryologic investigation to reveal underlying causes for SOA and provide a treatment if possible.ResultsOne case was a patient with recurrent pregnancy loss and the other was diagnosed as unexplained infertility. In the first case, 61 out of 69 oocytes retrieved exhibited SOA in five cycles while in the second case 44 out of 49 oocytes exhibited SOA in five cycles. Oocytes were injected with sperm; embryo development and presence of paternal contribution were investigated. No pregnancy is ensued following embryo transfer in both patients. Time-lapse imaging of embryogenesis from the second case did not reveal even momentary second pronucleus appearance. We also performed clinical whole exome sequencing for both patients but did not identify any disease-causing variant.ConclusionPatients with SOA suffer from infertility. Our results indicate that more investigation is required to understand the etiology of SOA in humans concentrating on the molecular mechanisms that underpin regulation of oocyte activation and calcium dynamics need to be investigated to fully understand, and perhaps in the future rectify, recurrent SOA.