Septum resection versus expectant management in women with a septate uterus: an international multicentre open-label randomized controlled trial.

STUDY QUESTION: Does septum resection improve reproductive outcomes in women with a septate uterus? SUMMARY ANSWER: Hysteroscopic septum resection does not improve reproductive outcomes in women with a septate uterus. WHAT IS KNOWN ALREADY: A septate uterus is a congenital uterine anomaly. Women with a septate uterus are at increased risk of subfertility, pregnancy loss and preterm birth. Hysteroscopic resection of a septum may improve the chance of a live birth in affected women, but this has never been evaluated in randomized clinical trials. We assessed whether septum resection improves reproductive outcomes in women with a septate uterus, wanting to become pregnant. STUDY DESIGN, SIZE, DURATION: We performed an international, multicentre, open-label, randomized controlled trial in 10 centres in The Netherlands, UK, USA and Iran between October 2010 and September 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with a septate uterus and a history of subfertility, pregnancy loss or preterm birth were randomly allocated to septum resection or expectant management. The primary outcome was conception leading to live birth within 12 months after randomization, defined as the birth of a living foetus beyond 24 weeks of gestational age. We analysed the data on an intention-to-treat basis and calculated relative risks with 95% CI. MAIN RESULTS AND THE ROLE OF CHANCE: We randomly assigned 80 women with a septate uterus to septum resection (n = 40) or expectant management (n = 40). We excluded one woman who underwent septum resection from the intention-to-treat analysis, because she withdrew informed consent for the study shortly after randomization. Live birth occurred in 12 of 39 women allocated to septum resection (31%) and in 14 of 40 women allocated to expectant management (35%) (relative risk (RR) 0.88 (95% CI 0.47 to 1.65)). There was one uterine perforation which occurred during surgery (1/39 = 2.6%). LIMITATIONS, REASONS FOR CAUTION: Although this was a major international trial, the sample size was still limited and recruitment took a long period. Since surgical techniques did not fundamentally change over time, we consider the latter of limited clinical significance. WIDER IMPLICATIONS OF THE FINDINGS: The trial generated high-level evidence in addition to evidence from a recently published large cohort study. Both studies unequivocally do not reveal any improvements in reproductive outcomes, thereby questioning any rationale behind surgery. STUDY FUNDING/COMPETING INTEREST(S): There was no study funding. M.H.E. reports a patent on a surgical endoscopic cutting device and process for the removal of tissue from a body cavity licensed to Medtronic, outside the scope of the submitted work. H.A.v.V. reports personal fees from Medtronic, outside the submitted work. B.W.J.M. reports grants from NHMRC, personal fees from ObsEva, personal fees from Merck Merck KGaA, personal fees from Guerbet, personal fees from iGenomix, outside the submitted work. M.G. reports several research and educational grants from Guerbet, Merck and Ferring (location VUMC) outside the scope of the submitted work. The remaining authors have nothing to declare. TRIAL REGISTRATION NUMBER: Dutch trial registry: NTR 1676. TRIAL REGISTRATION DATE: 18 February 2009. DATE OF FIRST PATIENT'S ENROLMENT: 20 October 2010.

The randomised uterine septum transsection trial (TRUST): design and protocol.

BACKGROUND: A septate uterus is a uterine anomaly that may affect reproductive outcome, and is associated with an increased risk for miscarriage, subfertility and preterm birth. Resection of the septum is subject of debate. There is no convincing evidence concerning its effectiveness and safety. This study aims to assess whether hysteroscopic septum resection improves reproductive outcome in women with a septate uterus. METHODS/DESIGN: A multi-centre randomised controlled trial comparing hysteroscopic septum resection and expectant management in women with recurrent miscarriage or subfertility and diagnosed with a septate uterus. The primary outcome is live birth, defined as the birth of a living foetus beyond 24 weeks of gestational age. Secondary outcomes are ongoing pregnancy, clinical pregnancy, miscarriage and complications following hysteroscopic septum resection. The analysis will be performed according to the intention to treat principle. Kaplan-Meier curves will be constructed, estimating the cumulative probability of conception leading to live birth rate over time. Based on retrospective studies, we anticipate an improvement of the live birth rate from 35% without surgery to 70% with surgery. To demonstrate this difference, 68 women need to be randomised. DISCUSSION: Hysteroscopic septum resection is worldwide considered as a standard procedure in women with a septate uterus. Solid evidence for this recommendation is lacking and data from randomised trials is urgently needed. TRIAL REGISTRATION: Dutch trial registry ( NTR1676 , 18th of February 2009).

Prediction of successful revision surgery for mesh-related complaints after inguinal hernia and pelvic organ prolapse repair.

PURPOSE: With this retrospective case series, we aim to identify predictors for reduction of pain after mesh revision surgery in patients operated for inguinal hernia or pelvic organ prolapse with a polypropylene implant. Identifying these predictors may aid surgeons to counsel patients and select appropriate candidates for mesh revision surgery. METHODS: Clinical records before and after mesh revision surgery from 221 patients with chronic postoperative inguinal pain (CPIP) and 59 patients with pain after pelvic organ prolapse (POP) surgery were collected at two experienced tertiary referral centers. Primary outcome was patient reported improvement of pain after revision surgery. A multivariable logistic regression model was used to specify predictors for pain reduction. RESULTS: The multivariable logistic regression was performed for each patient group separately. Patients with CPIP had higher chances of improvement of pain when time between mesh placement and mesh revision surgery was longer, with an OR of 1.19 per year. A turning point in chances of risks and benefits was demonstrated at 70 months, with improved outcomes for patients with revision surgery ≥ 70 months (OR 2.86). For POP patients, no statistically significant predictors for reduction of pain after (partial) removal surgery could be identified. CONCLUSION: A longer duration of at least 70 months between implantation of inguinal mesh and revision surgery seems to give a higher chance on improvement of pain. Caregivers should not avoid surgery based on a longer duration of symptoms when an association between symptoms and the location of the mesh is found.

Are polypropylene mesh implants associated with systemic autoimmune inflammatory syndromes? A systematic review.

PURPOSE: The surgical implantation of polypropylene (PP) meshes has been linked to the occurrence of systemic autoimmune disorders. We performed a systematic review to determine whether PP implants for inguinal, ventral hernia or pelvic floor surgery are associated with the development of systemic autoimmune syndromes. METHODS: We searched Embase, Medline, Web of Science, Scopus, Cochrane library, clinicaltrialsregister.eu, clinicaltrails.gov and WHO-ICTR platform. Last search was performed on November 24th 2021. All types of studies reporting systemic inflammatory/autoimmune response in patients having a PP implant for either pelvic floor surgery, ventral or inguinal hernia repair were included. Animal studies, case reports and articles without full text were excluded. We intended to perform a meta-analysis. The quality of evidence was assessed with the Newcastle-Ottawa Scale. This study was registered at Prospero (CRD42020220705). RESULTS: Of 2137 records identified, 4 were eligible. Two retrospective matched cohort studies focused on mesh surgery for vaginal prolapse or inguinal hernia compared to hysterectomy and colonoscopy, respectively. One cohort study compared the incidence of systemic conditions in women having urinary incontinence surgery with and without mesh. These reports had a low risk of bias. A meta-analysis showed no association when comparing systemic disease between mesh and control groups. Calculated risk ratio was 0.9 (95% CI 0.82-0.98). The fourth study was a case series with a high risk of bias, with a sample of 714 patients with systemic disease, 40 of whom had PP mesh implanted. CONCLUSION: There is no evidence to suggest a causal relationship between being implanted with a PP mesh and the occurrence of autoimmune disorders.

Metroplasty versus expectant management for women with recurrent miscarriage and a septate uterus.

BACKGROUND: The prevalence of recurrent miscarriage in women with a septate uterus has increased. Restoration of the morphology of the uterus can hypothetically increase live birth rate and subsequent pregnancies in women with a septate uterus and recurrent miscarriage. OBJECTIVES: To determine whether hysteroscopic metroplasty in women with a septate uterus and two or more preceding miscarriages improves pregnancy outcomes. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register (inception to August 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (inception to August 2010),  MEDLINE (1950 to August 2010), EMBASE (1980 to August 2010). PSYCHINFO (1806 to August 2010). In addition we searched trial registers for ongoing and registered trials, conference abstracts and OpenSigle and sources of Grey literature. SELECTION CRITERIA: Only randomised controlled trials (RCTs) that assess the effect on reproductive outcome of hysteroscopic metroplasty in women with a history of two or more preceding miscarriages and a septate uterus were eligible for inclusion. DATA COLLECTION AND ANALYSIS: If there had been data to include, two authors would have independently assessed trial quality and extracted data. They would have also contacted study authors for additional information. We collected adverse effects information from the trials. MAIN RESULTS: No randomised controlled trials were identified for inclusion. AUTHORS' CONCLUSIONS: Hysteroscopic metroplasty in women with recurrent miscarriage and a septate uterus is being performed in many countries to improve reproductive outcomes in women.This treatment has been assessed in non-controlled studies, which suggested a positive effect on pregnancy outcomes. However, these studies are biased due to the fact that the participants with recurrent miscarriage treated by hysteroscopic metroplasty served as their own controls. Until now, the effectiveness and possible complications of hysteroscopic metroplasty have never been considered in a randomised controlled trial.Taking this into account there is insufficient evidence to support this treatment in these women. A randomised controlled trial is urgently needed and currently underway (www.studies-obsgyn.nl/trust NTR 1676).