SALpingectomy for STERilisation (SALSTER): study protocol for a Swedish multicentre register-based randomised controlled trial.

INTRODUCTION: Salpingectomy is currently suggested as an alternative to tubal ligation for sterilisation. Precursor lesions of ovarian carcinoma can be found in the fallopian tubes; thus, salpingectomy could possibly reduce the incidence. Most of the existing trials on safety are small, on caesarean section and report on surrogate ovarian function measures. Randomised trials in laparoscopy are lacking. Well-designed trials are needed to evaluate safety of laparoscopic opportunistic salpingectomy. METHODS AND ANALYSIS: In SALSTER, a national register-based randomised controlled non-inferiority trial, 968 women <50 years, wishing laparoscopic sterilisation will be randomised to either salpingectomy or tubal ligation. The Swedish National Quality Register of Gynecological Surgery (GynOp) will be used for inclusion, randomisation and follow-up. Primary outcomes are any complication up to 8 weeks postoperatively, and age at menopause. Both outcomes are measured with questionnaires, complications are also assessed by a gynaecologist. In a nested trial, ovarian function will be evaluated comparing the mean difference of anti-Müllerian hormone (AMH), assessed preoperatively and 1 year after surgery. ETHICS AND DISSEMINATION: Performing salpingectomy for sterilisation has become increasingly common, despite the unclear risk-benefit balance. SALSTER studies the safety of salpingectomy compared with tubal ligation. Regardless of the result, SALSTER will provide gynaecologists with high quality evidence to inform women to decide on salpingectomy or not. The central ethical review board of Gothenburg, Sweden (Dnr. 316-18) approved the trial in 2018. Results will be presented at scientific congresses and published in peer-reviewed scientific journals. The results will be communicated through professional organisations and research networks. TRIAL REGISTRATION NUMBER: NCT03860805.

Physicians' assessment of complications after gynecological surgery in Sweden: The GYNCOM survey.

INTRODUCTION: Complications after gynecological surgery in Sweden are registered in the well-established Swedish National Quality Register of Gynecological Surgery, GynOp. The aim of this study was to analyze interrater reliability in assessing complications according to the methods in GynOp, and to explore physicians' perceptions of registering complications. MATERIAL AND METHODS: A digital survey was sent to gynecologists and residents in gynecology in Sweden. Participating clinics were recruited through the Swedish network for national clinical studies in Obstetrics and Gynecology, SNAKS. Twenty fictional cases, intended to represent normal postoperative course, failure to cure, and varying degrees of complications, were developed by the research group. The clinical scenarios included abdominal and laparoscopic surgery of the uterus and adnexa, vaginal hysterectomies, as well as hysteroscopy. The respondents graded each case on the presence of a complication (yes/no). Type of complication, severity, and what action the complication required according to Clavien-Dindo was registered if a complication was acknowledged, according to the method in GynOp. Interrater reliability and the opinions of the respondents were presented descriptively. More than 80% of respondents making the same assessment was considered as agreement. RESULTS: The response rate was 41%, with 104 responding physicians from 16 gynecological clinics. Type and severity of complication was considered relevant to register by 88% and 89% of respondents, respectively. Agreement on whether the case described a complication was >80% in 85% (17/20) of cases and agreement using the Clavien-Dindo classification was >90% in 80% (16/20) of cases. There was high agreement in assessments of classically severe complications, such as pulmonary embolism and ureteral damage, in both presence of complication and severity, as well as Clavien-Dindo (>90% for all methods). Cases with agreement <80% on whether the case described a complication were bordering between normal postoperative course and minor complication. CONCLUSIONS: This study provides validation for the methods used to register complications after gynecological surgery according to the GynOp register, including the use of Clavien-Dindo in gynecology. However, the results indicate a need to define what should be considered symptoms inherent to each type of surgery.

Efficacy and safety of sterilisation procedures to reduce the risk of epithelial ovarian cancer: a systematic review comparing salpingectomy with tubal ligation.

PURPOSE: The objective of this systematic review is to evaluate current literature comparing salpingectomy for sterilisation with tubal ligation, regarding the effectiveness and safety, and assess the certainty of evidence. MATERIALS AND METHODS: PubMed, Cochrane, and Embase databases were searched. Randomised (RCT) and observational studies were included. Articles were quality assessed and data extracted by two independent authors. Certainty of evidence was assessed using GRADE. RESULTS: Of 2020 articles, 17 were included. No study investigated the risk of EOC. No difference in anti-Müllerian hormone was reported in one RCT at caesarean section (CS). Two cohort studies evaluated ovarian function with surrogate measures and found no difference at caesarean section. Complications did not differ but were inconsistently reported. Laparoscopic tubal ligation was 7 min faster (95% CI 3.8-10.5). Operative time at caesarean section was dependent on the use of surgical devices. Certainty of evidence was low or very low for all estimates, indicating knowledge gaps. Reliable safety data on salpingectomy for sterilisation is lacking, and there is no effectiveness data. Presently, women cannot be properly counselled regarding salpingectomy for sterilisation.

Silencing markers are retained on pericentric heterochromatin during murine primordial germ cell development.

BACKGROUND: In the nuclei of most mammalian cells, pericentric heterochromatin is characterized by DNA methylation, histone modifications such as H3K9me3 and H4K20me3, and specific binding proteins like heterochromatin-binding protein 1 isoforms (HP1 isoforms). Maintenance of this specialized chromatin structure is of great importance for genome integrity and for the controlled repression of the repetitive elements within the pericentric DNA sequence. Here we have studied histone modifications at pericentric heterochromatin during primordial germ cell (PGC) development using different fixation conditions and fluorescent immunohistochemical and immunocytochemical protocols. RESULTS: We observed that pericentric heterochromatin marks, such as H3K9me3, H4K20me3, and HP1 isoforms, were retained on pericentric heterochromatin throughout PGC development. However, the observed immunostaining patterns varied, depending on the fixation method, explaining previous findings of a general loss of pericentric heterochromatic features in PGCs. Also, in contrast to the general clustering of multiple pericentric regions and associated centromeres in DAPI-dense regions in somatic cells, the pericentric regions of PGCs were more frequently organized as individual entities. We also observed a transient enrichment of the chromatin remodeler ATRX in pericentric regions in embryonic day 11.5 (E11.5) PGCs. At this stage, a similar and low level of major satellite repeat RNA transcription was detected in both PGCs and somatic cells. CONCLUSIONS: These results indicate that in pericentric heterochromatin of mouse PGCs, only minor reductions in levels of some chromatin-associated proteins occur, in association with a transient increase in ATRX, between E11.5 and E13.5. These pericentric heterochromatin regions more frequently contain only a single centromere in PGCs compared to the surrounding soma, indicating a difference in overall organization, but there is no de-repression of major satellite transcription.