Causality and functional relevance of BRCA1 and BRCA2 pathogenic variants in non-high-grade serous ovarian carcinomas.

The identification of causal BRCA1/2 pathogenic variants (PVs) in epithelial ovarian carcinoma (EOC) aids the selection of patients for genetic counselling and treatment decision-making. Current recommendations therefore stress sequencing of all EOCs, regardless of histotype. Although it is recognised that BRCA1/2 PVs cluster in high-grade serous ovarian carcinomas (HGSOC), this view is largely unsubstantiated by detailed analysis. Here, we aimed to analyse the results of BRCA1/2 tumour sequencing in a centrally revised, consecutive, prospective series including all EOC histotypes. Sequencing of n = 946 EOCs revealed BRCA1/2 PVs in 125 samples (13%), only eight of which were found in non-HGSOC histotypes. Specifically, BRCA1/2 PVs were identified in high-grade endometrioid (3/20; 15%), low-grade endometrioid (1/40; 2.5%), low-grade serous (3/67; 4.5%), and clear cell (1/64; 1.6%) EOCs. No PVs were identified in any mucinous ovarian carcinomas tested. By re-evaluation and using loss of heterozygosity and homologous recombination deficiency analyses, we then assessed: (1) whether the eight 'anomalous' cases were potentially histologically misclassified and (2) whether the identified variants were likely causal in carcinogenesis. The first 'anomalous' non-HGSOC with a BRCA1/2 PV proved to be a misdiagnosed HGSOC. Next, germline BRCA2 variants, found in two p53-abnormal high-grade endometrioid tumours, showed substantial evidence supporting causality. One additional, likely causal variant, found in a p53-wildtype low-grade serous ovarian carcinoma, was of somatic origin. The remaining cases showed retention of the BRCA1/2 wildtype allele, suggestive of non-causal secondary passenger variants. We conclude that likely causal BRCA1/2 variants are present in high-grade endometrioid tumours but are absent from the other EOC histotypes tested. Although the findings require validation, these results seem to justify a transition from universal to histotype-directed sequencing. Furthermore, in-depth functional analysis of tumours harbouring BRCA1/2 variants combined with detailed revision of cancer histotypes can serve as a model in other BRCA1/2-related cancers. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Outcome and Prognostic Impact of Surgical Staging in Serous Tubal Intraepithelial Carcinoma: A Cohort Study and Systematic Review.

The optimal management of breast cancer susceptibility gene (BRCA)1/2 carriers with isolated serous tubal intraepithelial carcinoma (STIC) found at risk-reducing salpingo-oophorectomy (RRSO) is unclear. The prevalence of occult carcinoma and STIC in a consecutive series of BRCA1/2 carriers undergoing RRSO is reported. The outcome of staging procedures in BRCA1/2 carriers with isolated STIC at RRSO as well as the relationship between staging, chemotherapy treatment and risk of recurrence was assessed via a systematic review of the literature. Our series included 235 BRCA1/2 carriers who underwent RRSO. Federation of Gynaecology and Obstetrics stage IA carcinoma or STIC was found at RRSO in three (1.3%) and two (0.9%) patients, respectively. A systematic review of the literature included 82 BRCA1/2 carriers with isolated STIC found at RRSO. In 13/82 (16%) cases with STIC, staging was reported. In none of these cases staging revealed more advanced disease. Recurrent disease was found in four of 36 patients with reported follow-up. The estimated risk of recurrence in patients with isolated STIC at RRSO was about 11% (95% confidence interval 3-26%) after a median follow-up of 42 months (range 7-138). No recurrences were reported in those patients with STIC at RRSO who underwent staging or received chemotherapy. We found 1.3% occult carcinoma and 0.9% STIC at RRSO in our cohort of BRCA1/2 carriers. A systematic review of the literature suggests that additional treatment after RRSO, i.e. staging and/or chemotherapy, is associated with a lower risk of recurrence. However, data on staging and follow-up are limited.

Neoadjuvant chemotherapy or primary debulking surgery in FIGO IIIC and IV patients; results from a survey study in the Netherlands.

INTRODUCTION: Primary debulking surgery (PDS) followed by adjuvant chemotherapy is historically recommended as first line treatment for advanced stage ovarian cancer. Two randomized controlled trials, however, showed similar efficacy and reduced toxicity with neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS). Nevertheless, uptake of NACT-IDS varies widely between hospitals, which cannot be explained by difference in patient populations. In this survey, we therefore aimed to evaluate the views on NACT-IDS among all Dutch gynaecologists and medical oncologists involved in the treatment of ovarian cancer. STUDY DESIGN: An e-mail link to the online questionnaire was sent to all medical oncologists and gynaecologists in the Netherlands, regardless of their (sub)specializations. The data was analysed using descriptive statistics and chi-square tests were used to analyse differences between groups. RESULTS: Three-hundred-forty physicians were invited to fill out the questionnaire. After two reminders, 167 of them responded (49%). Among the responders, 82% of the gynaecologists versus 93% of the medical oncologists considered the available evidence sufficiently convincing to treat advanced stage ovarian cancer patients with NACT-IDS (p = 0.076). Moreover, 33% of gynaecologists and 62% of medical oncologists preferred NACT-IDS to PDS as first line treatment (p = 0.001). While most responders (86%) indicated that selecting the right patients for NACT-IDS is difficult, those with bulky disease, FIGO stage IV or metastases near the porta hepatica were most likely to undergo NACT-IDS. CONCLUSION: The majority of Dutch gynaecologists and medical oncologists adopted NACT-IDS as an alternative treatment approach for advanced stage primary ovarian cancer. About two-thirds of medical oncologists and one-third of gynaecologists prefer NACT-IDS to PDS as first line treatment in this setting. Improving patient selection is considered of paramount importance.

Linking uterine serous carcinoma to BRCA1/2-associated cancer syndrome: A meta-analysis and case report.

BACKGROUND: Uterine serous carcinoma (USC) shows greater morphological, clinical and molecular similarities to high-grade ovarian tubal serous carcinoma than to other types of endometrial cancer. As high-grade ovarian tubal serous carcinoma is known to be associated with BRCA1/2 pathogenic germline mutations (PMs), we aimed to explore whether USC is also a constituent of hereditary breast and ovarian cancer syndrome. METHODS: Pubmed, EMBASE and Web of Science were searched in July 2016 for articles assessing the association between USC and germline BRCA1/2-PMs. Pooled analysis and comparisons were performed using a random effects logistic model, stratifying for ethnicity (Ashkenazi versus non-Ashkenazi). In addition, tumour tissue from an USC case with a hereditary BRCA1-PM was analysed for loss of heterozygosity at the BRCA1 locus and was functionally analysed for homologous recombination proficiency. RESULTS: The search yielded 1893 citations, 10 studies were included describing 345 USC patients. For Ashkenazi Jews, the pooled odds ratio of having a germline BRCA1/2-PM was increased in USC patients compared with the general Ashkenazi population: odds ratio 5.4 (95%confidence interval: 2.2-13.1). In the patient with USC, we identified the known germline BRCA1-PM in the tumour DNA. Furthermore, we showed both loss of heterozygosity of the wild-type allele and a deficiency of homologous recombination. CONCLUSION: This study suggests that USC may be an overlooked component of BRCA1/2-associated hereditary breast and ovarian cancer syndrome. Screening for germline BRCA1/2-PMs should be considered in patients diagnosed with USC, especially in cases with a positive first-degree family history for breast and/or ovarian cancer.

The identification of patients at high risk for recurrent disease after treatment for early-stage cervical cancer.

OBJECTIVE: To investigate prognostic factors in patients with recurrent cervical cancer after treatment of early-stage disease in order to identify high-risk patients who might benefit from alternative treatment strategies. STUDY DESIGN: The authors retrospectively analyzed clinical and pathology data from 130 recurrent cervical cancer patients after surgical treatment for early-stage disease. Patients were compared with a recurrence-free control group matched for age, FIGO Stage, and adjuvant treatment. Univariate and multivariate Cox regression analyses were performed to determine prognostic factors for recurrence and survival. RESULTS: Of 889 patients, 130 (14.6%) developed recurrent disease after primary treatment for early-stage cervical cancer. Local or loco-regional metastasis was observed in 45%, distant metastasis in 31%, and combined pelvic and distant metastasis in 24%. Median survival after recurrence was 12 months (range 1-107 months). Median five-year survival was 96% in the control group and 29% in the recurrence group. Tumor size ≥ 40 mm and lymph node metastasis were independent unfavorable prognostic factors for overall survival (OS) and disease-free survival (DFS). The number of positive lymph nodes (≥ one) and bilateral occurrence of pelvic lymph node metastasis were associated with adverse clinical outcome. CONCLUSIONS: Tumor size ≥ 40 mm and lymph node metastasis were independent unfavorable prognostic factors in surgically treated, early-stage cervical cancer patients. The combination of these factors was particularly associated with recurrence. Future trials should focus on the role of alternative adjuvant treatment strategies in patients at high risk of recurrent disease (e.g., by chemotherapy, immunotherapy or combinations thereof).

A nurse-led sexual rehabilitation intervention after radiotherapy for gynecological cancer.

PURPOSE: Although vaginal dilator use after combined pelvic radiation therapy and brachytherapy (RT/BT) is recommended to prevent vaginal shortening and stenosis, women fail to use them and experience sexual problems. A nurse-led sexual rehabilitation intervention targeting sexual recovery and vaginal dilatation was developed. Its feasibility was investigated during a prospective, longitudinal, observational pilot study. METHODS: Four oncology nurses were specifically trained to conduct the intervention. Gynecologic cancer patients treated with RT/BT were assessed using (i) questionnaires on frequency of dilator use (monthly), sexual functioning, and sexual distress (at baseline and 1, 6, and 12 months) and psychological and relational distress (at 1, 6, and 12 months); (ii) semi-structured interviews (between 6 and 12 months); and (iii) consultation recordings (a random selection of 21 % of all consults). RESULTS: Twenty participants were 26-71 years old (mean = 40). Eight participants discontinued participation after 3 to 9 months. At 6 months after RT, 14 out of 16 (88 %), and at 12 months 9 out of 12 (75 %), participants dilated regularly, either by having sexual intercourse or by using dilators. Sexual functioning improved between 1 and 6 months after RT, with further improvement at 12 months. Most participants reported that the intervention was helpful and the nurses reported having sufficient expertise and counseling skills. CONCLUSIONS: According to the pilot results, the intervention was feasible and promising for sexual rehabilitation and regular dilator use after RT. Its (cost-)effectiveness will be investigated in a randomized controlled trial.

Nerve-sparing radical hysterectomy versus conventional radical hysterectomy in early-stage cervical cancer. A systematic review and meta-analysis of survival and quality of life.

BACKGROUND AND AIMS: Survival after radical hysterectomy (RH) for early-stage cervical cancer is good. Hence quality of life (QOL) after treatment is an important issue. Nerve-sparing radical hysterectomy (NSRH) improves QOL by selectively sparing innervation of bladder, bowel and vagina, reducing therapy-induced morbidity. However, the oncological outcome and the functional outcome after NSRH are subjects of debate. We aim to present the best possible evidence available regarding both QOL and survival after NSRH in early-stage cervical cancer. METHODS: Systematic review and meta-analysis on studies comparing NSRH and RH. RESULTS: Forty-one studies were included, and 27 were used for the meta-analysis. There was no difference in 2-, 3- and 5-year overall survival: the risk ratios (RRs) were respectively 1.02 (95% CI 0.99-1.05, n=879), 1.01 (95% CI 0.95-1.08, n=1324) and 1.03 (95% CI 0.99-1.08, n=638). No difference was found in 2-, 3- and 5-year disease-free survival: RR 1.01 (95% CI 0.95-1.05, n=1175), 0.99 (95% CI 0.94-1.03, n=1130) and 1.00 (95% CI 0.95-1.06, n=933) respectively. Post-operative time to micturition was significantly shorter in the NSRH group: standardized mean difference (SMD) -0.84 (CI 95% -1.07 to -0.60). CONCLUSIONS: NSRH can be considered safe and effective for early-stage cervical cancer since short- and long-term survival do not differ from those of conventional RH, while bladder function after NSRH is significantly less impaired.

Near-infrared fluorescence sentinel lymph node biopsy in vulvar cancer: a randomised comparison of lymphatic tracers.

This study aims to confirm the feasibility of near-infrared (NIR) fluorescence imaging for sentinel lymph node (SLN) biopsy in vulvar cancer and to compare the tracer indocyanine green (ICG) bound to human serum albumin (HSA) versus ICG alone. Women received 99mTc-nanocolloid and patent blue for SLN detection. Subsequently, women randomly received ICG:HSA or ICG alone. In 24 women, 35 SLNs were intraoperatively detected. All SLNs detected were radioactive and NIR fluorescent and 27 (77%) were blue. No significant difference was found between ICG:HSA and ICG alone. This trial confirms the feasibility of NIR fluorescence imaging for SLN mapping in vulvar cancer.

Vaginal cuff dehiscence in laparoscopic hysterectomy: influence of various suturing methods of the vaginal vault.

Vaginal cuff dehiscence (VCD) is a severe adverse event and occurs more frequently after total laparoscopic hysterectomy (TLH) compared with abdominal and vaginal hysterectomy. The aim of this study is to compare the incidence of VCD after various suturing methods to close the vaginal vault. We conducted a retrospective cohort study. Patients who underwent TLH between January 2004 and May 2011 were enrolled. We compared the incidence of VCD after closure with transvaginal interrupted sutures versus laparoscopic interrupted sutures versus a laparoscopic single-layer running suture. The latter was either bidirectional barbed or a running vicryl suture with clips placed at each end commonly used in transanal endoscopic microsurgery. Three hundred thirty-one TLHs were included. In 75 (22.7 %), the vaginal vault was closed by transvaginal approach; in 90 (27.2 %), by laparoscopic interrupted sutures; and in 166 (50.2 %), by a laparoscopic running suture. Eight VCDs occurred: one (1.3 %) after transvaginal interrupted closure, three (3.3 %) after laparoscopic interrupted suturing and four (2.4 %) after a laparoscopic running suture was used (p = .707). With regard to the incidence of VCD, based on our data, neither a superiority of single-layer laparoscopic closure of the vaginal cuff with an unknotted running suture nor of the transvaginal and the laparoscopic interrupted suturing techniques could be demonstrated. We hypothesise that besides the suturing technique, other causes, such as the type and amount of coagulation used for colpotomy, may play a role in the increased risk of VCD after TLH.

The value of hysteroscopy in the diagnostic approach to a rudimentary horn pregnancy.

A 33-year-old woman presented with an ectopic pregnancy without any complaints. Laparoscopy was performed since a tubal pregnancy was expected. However, both fallopian tubes appeared normal and it was not possible to differentiate accurately between a pregnancy in a non-communicating horn and a pregnancy in a bicornuate uterus. We therefore performed MRI which showed a thin myometrium around the pregnancy. In order to differentiate between a communicating and a non-communicating uterine horn the authors performed a hysteroscopy. Since there was only one cervical os, and an entrance to the second uterine cavity was not seen along the cervical canal, it was concluded that this pregnancy was situated in a non-communicating rudimentary horn. The non-communicating uterine horn, with the pregnancy in situ, was completely removed. Since a pregnancy in a bicornuate uterus is viable in contrast to a pregnancy in a non-communicating horn, accurate diagnosis is important.

[Plea for more attention to the importance of gender during medical training]. / Pleidooi voor artsenopleiding met aandacht voor gender.

Gender is an important factor in disease and health. Male and female patients with the same disease may present with different complaints. This is especially true in cardiology. Basic medical training should specifically address this topic. Moreover, the gender of the physician is an important factor in patient care. Physicians are unaware of the influence of their gender on their performance. Reflective practice is an essential educational tool in modern specialist training. As medical specialist training in The Netherlands is being modernized at present, this may be the perfect time for physicians to become aware of their gender and its impact on their performance. This will improve medical care for both male and female patients by male and female doctors.

A randomised comparison of vaginoscopic office hysteroscopy and saline infusion sonography: a patient compliance study.

OBJECTIVE: The purpose of this study was to compare patient discomfort during saline infusion sonography (SIS) and office hysteroscopy performed according to a vaginoscopic approach. DESIGN: Randomised controlled trial. SETTING: University hospital. POPULATION: Women with an indication for further investigation of the uterine cavity. METHODS: A total of 100 women randomly allocated to either SIS or vaginoscopic office hysteroscopy in an outpatient clinic. MAIN OUTCOME MEASURES: Scores on a visual analogue scale (VAS) for pain and a present pain intensity (PPI) scale, conclusiveness and success rate. RESULTS: The patients' pain scores on both the VAS and the PPI were lower for SIS when compared with office hysteroscopy (P < 0.05). However, in cases of severe pain (VAS > 7 or PPI > 2), there was no statistically significant difference between both groups. The success rate, defined as adequate inspection of the cervical canal and uterine cavity, was 94% for SIS compared with 92% for office hysteroscopy (P = 0.633). SIS, multiparity, shorter procedure time and position of the uterus in anteversion decreased pain scores among women studied. CONCLUSIONS: Both SIS and office hysteroscopy are successful procedures and well tolerated by women. SIS induces significantly less discomfort than office hysteroscopy and should therefore be considered the method of choice.

Diagnostic hysteroscopy in abnormal uterine bleeding: a systematic review and meta-analysis.

BACKGROUND: This study was conducted to assess the accuracy and feasibility of diagnostic hysteroscopy in the evaluation of intrauterine abnormalities in women with abnormal uterine bleeding. SEARCH STRATEGY: Electronic databases were searched from 1 January 1965 to 1 January 2006 without language selection. The medical subject heading (MeSH) and textwords for the following terms were used: hysteroscopy, diagnosis, histology, histopathology, hysterectomy, biopsy, sensitivity and specificity. SETTING: University Hospital. SELECTION CRITERIA: The inclusion criteria were report on accuracy of diagnostic hysteroscopy in women with abnormal uterine bleeding compared to histology collected with guided biopsy during hysteroscopy, operative hysteroscopy or hysterectomy. DATA COLLECTION AND ANALYSIS: Electronic databases were searched for relevant studies and references were cross-checked. Validity was assessed and data were extracted independently by two authors. Heterogeneity was calculated and data were pooled. Subgroup analysis was performed according to validity criteria, study quality, menopausal state, time, setting and performance of the procedure. The pooled sensitivity, specificity, likelihood ratios, post-test probabilities and feasibility of diagnostic hysteroscopy on the prediction of uterine cavity abnormalities. Post-test probabilities were derived from the likelihood ratios and prevalence of intrauterine abnormalities among included studies. Feasibility included technical success rate and complication rate. MAIN RESULTS: One population of homogeneous data could be identified, consisting of patients with postmenopausal bleeding. In this subgroup the positive and negative likelihood ratios were 7.9 (95% CI 4.79-13.10) and 0.04 (95% CI 0.02-0.09), raising the pre-test probability from 0.61 to a post-test probability of 0.93 (95% CI 0.88-0.95) for positive results and reducing it to 0.06 (95% CI 0.03-0.13) for negative results. The pooled likelihood ratios of all studies included, calculated with the random effects model, were 6.5 (95% CI 4.1-10.4) and 0.08 (95% CI 0.07-0.10), changing the pre-test probability of 0.46 to post-test probabilities of 0.85 (95% CI 0.78-0.90) and 0.07 (0.06-0.08) for positive and negative results respectively. Subgroup analyses gave similar results. The overall success rate of diagnostic hysteroscopy was estimated at 96.9% (SD 5.2%, range 83-100%). CONCLUSIONS: This systematic review and meta-analysis shows that diagnostic hysteroscopy is both accurate and feasible in the diagnosis of intrauterine abnormalities.

[The practice guideline 'pelvic inflammatory disease' (first revision) from the Dutch College of General Practitioners; a response from the perspective of gynaecology]. / De standaard 'pelvic inflammatory disease' (eerste herziening) van het Nederlands Huisartsen Genootschap; reactie vanuit de gynaecologie.

In 2005, the Dutch College of General Practitioners revised their guideline on pelvic inflammatory disease (PID). It is difficult to diagnose PID because of the variability in the presentation of the disease. The revised guideline is a solid guide in the diagnostic process. History taking and physical examination are the most important diagnostic techniques, but require experience. Any diagnostic uncertainty justifies the consultation ofa specialist. The value ofsupplementary diagnostics in a specialist setting is limited. In case of suspected PID, cervical material should always be cultured for Chlamydia trackomatis and Neisseria gonorrhoeae, even if treatment has already been started. Laparoscopy is considered to be the gold standard in the diagnosis of PID. but is only performed if other methods do not suffice. Fast and adequate treatment considerably decreases the risk of serious complications, such as fertility disorders. Therefore, adequate antibiotic therapy covering at least the above-mentioned pathogens should be started if other causes of abdominal pain, such as ectopic pregnancy, appendicitis and torsion of the adnexal mass, have been excluded.

Sonographic assessment of non-malignant ovarian cysts: does sonohistology exist?

BACKGROUND: Transvaginal ultrasound (TVU) is feasible and accurate in the differentiation between non-malignant and malignant ovarian abnormalities. However, despite the clinical relevance, the accuracy of TVU in the differentiation between the many different non-malignant cysts is unknown. METHODS: Between 1992 and 2002, all women who had surgery at our centre because of a non-malignant ovarian cyst were included prospectively in this study. The sonographic characteristics as well as the expected histological diagnosis (the 'sonohistological diagnosis') were evaluated pre-operatively. This diagnosis was compared with the histopathological diagnosis, and diagnostic parameters [with 95% confidence interval (CI)] of the sonohistological diagnosis were calculated. Logistic models, with the sonographic characteristics as variables, were constructed for each histopathological diagnosis. RESULTS: A total of 406 women were included consecutively. The overall diagnostic accuracy of the sonohistological diagnosis was 60% (95% CI 0.56-0.65). Only in cases of simple ovarian cysts did the diagnostic accuracy of the respective logistic model exceed that of the sonohistological diagnosis (0.88 versus 0.81, P < 0.01). The diagnostic accuracy of the sonohistological diagnosis for endometriotic and dermoid ovarian cysts was significantly better compared with the respective logistic model (0.84 versus 0.71, P < 0.01 and 0.87 versus 0.82, P = 0.03, respectively). CONCLUSION: In approximately half of the non-malignant ovarian cysts, TVU is capable of distinguishing between the different histopathological diagnoses of non-malignant ovarian masses. Only in the diagnosis of simple ovarian cysts might use of the logistic models be helpful.

The value of transvaginal ultrasound to monitor the position of an intrauterine device after insertion. A technology assessment study.

BACKGROUND: The intrauterine device (IUD) is an effective contraceptive method. The contraceptive power as well as the side-effects of IUD are thought to relate to the position of the IUD in the uterine cavity. We assessed the accuracy of clinical evaluation of IUD position. METHODS: A prospective comparative study was performed. The clinical evaluation was compared with the TVU measurement of IUD position both immediately after insertion and 6 weeks after insertion. The primary outcome measures were the positive and negative predictive values (PPV and NPV) of the clinical evaluation of IUD position. RESULTS: 195 women were included consecutively, 181 women (92.8%) were available for follow-up. The PPV and NPV of clinical evaluation of IUD position immediately after insertion were respectively 0.60 (95% CI: 0.39-0.81) and 0.98 (95% CI: 0.96-1.0). The prevalence of an abnormally positioned IUD was 7.7% (95% CI: 3.9-11.4). The PPV and NPV of the clinical evaluation at follow-up were respectively 0.54 (95% CI: 0.26-0.81) and 1.0 (95% CI: 0.98-1.0). The prevalence of abnormal position was 4.0% (95% CI: 1.7-7.1). CONCLUSION: Clinical evaluation is an excellent test for the evaluation of the position of an IUD and routine TVU is not indicated for this purpose.

[Efficiency of saline contrast hysterosonography for evaluating the uterine cavity]. / Doelmatigheid van watercontrastechografie ter beoordeling van het cavum uteri.

Diagnostic hysteroscopy is the standard investigation performed in the case of abnormal vaginal blood loss. More recently there has been increasing interest for minimal invasive saline contrast hysterosonography (SCHS) as this technique is less painful and less expensive. SCHS is indicated in case of abnormal uterine bleeding (premenopausal and postmenopausal), bleeding while using tamoxifen, suspicion of a congenital uterine abnormality and Asherman's syndrome. As well as intracavity abnormalities (polyps and myomas) SCHS can also be used to evaluate the intramural extension of myomas, which is necessary to assess whether hysteroscopic resection is possible. The sensitivity and specificity of SCHS for demonstrating intracavity abnormalities (with a prevalence of 54%) are 94% (95%-CI; 91-97) and 89% (95%-CI: 85-94) respectively. The positive and negative predictive values are 91% (95%-CI: 87-95) and 92% (95%-CI: 89-97) respectively. SCHS has a short learning curve and can be performed in an outpatient setting. SCHS fails more frequently in postmenopausal women than premenopausal women (12.5% vs. 4.7%; p = 0.03). The chance of a non-conclusive SCHS is 7.6% and is higher if the uterine volume is greater than 600 cm3 (relative risk: 2.63; 95%-CI: 1.05-6.60) and if two or more myomas are present: (RR 2.65; 95%-CI: 1.16-6.10). SCHS is 2 to 9 times cheaper than diagnostic hysteroscopy. It can replace 84% of the diagnostic hysteroscopies. SCHS, in combination with endometrial sampling, whenever indicated, might be able to replace diagnostic hysteroscopy as gold standard in the evaluation of the uterine cavity.