Long-Term Effectiveness of Vestibulectomy for the Treatment of Vulvodynia: A Retrospective Cohort Study.

OBJECTIVE: To evaluate the effectiveness and complication rate of vestibulectomy for vulvodynia. METHODS: A retrospective cohort study in a teaching and university hospital analyzing patients with vulvodynia with insufficient response to conservative treatment who underwent a vestibulectomy. Data from 114 consecutive vestibulectomy procedures done between September 2009 and October 2018 were retrospectively analyzed. All procedures were performed by the same surgeon.The primary outcome was difference in pain scale (6-point Q-tip test, Nociceptive Rating Scale) between preoperative consultation, postoperative visit, and last follow-up consultation. The secondary outcome was surgical complications, such as wound dehiscence and hematoma. RESULTS: Complete data were available for 80 patients. There was a significant reduction in median pain scores of between 65% and 80% on all 6 evaluated vestibular points during Q-tip tests. The median follow-up was 21 months, ranging from 1 to 92 months (interquartile range [IQR]). Overall, 75% of patients needed no further treatment at the end of the follow-up period. In 22.6% (18/80), a limited wound dehiscence was noted. No other complications were reported nor were there any cases of worsening of the complaints. CONCLUSION/DISCUSSION: In this retrospective cohort study, a significant pain reduction occurred after vestibulectomy in patients who were not responding to conservative treatment. The complication rate of this surgical procedure is low. Vestibulectomy seems to be an effective technique for management of vulvodynia.

Effects of E4/DRSP on self-reported physical and emotional premenstrual and menstrual symptoms: data from the phase 3 clinical trial in Europe and Russia.

PURPOSE: To describe the effects of estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg on physical and emotional premenstrual and menstrual symptoms. MATERIALS AND METHODS: We used Menstrual Distress Questionnaire (MDQ) data from a phase-3 trial (NCT02817828) in Europe and Russia with participants (18 - 50 years) using E4/DRSP for up to 13 cycles. We assessed mean changes in MDQ-t-scores from baseline to end of treatment in premenstrual (4 days before most recent flow) and menstrual (most recent flow) scores for 4 MDQ domains in starters and switchers (use of hormonal contraception in prior 3 months) and performed a shift analysis on individual symptoms within each domain. RESULTS: Of 1,553 treated participants, 1,398(90.0%), including 531(38%) starters, completed both MDQs. Starters reported improvements for premenstrual Pain (-1.4), Water Retention (-3.3) and Negative Affect (-2.5); and for menstrual Pain (-3.5), Water Retention (-3.4), and Negative Affect (-2.7) (all p < 0.01). For switchers, no changes were significant except an increase in premenstrual (+1.0, p = 0.02) and menstrual (+1.5, p = 0.003) Water Retention. We observed a change in symptom intensity in >40% of participants for Cramps, Backache and Fatigue (domain Pain), Painful or Tender Breast and Swelling (domain Water Retention) and Mood Swings and Irritability (domain Negative Affect). CONCLUSION: E4/DRSP starters experienced significant improvements in the domains Pain, Water Retention and Negative Affect particularly benefiting those with more severe baseline symptoms. Switchers showed minimal changes.

A phase 3 study in Europe and Russia showed that Estetrol/Drospirenone, a new combined oral contraceptive, significantly improved the MDQ scores for domains Pain, Water Retention and Negative Affect in women starting COC use, while switchers showed minimal changes.

Reproductive and obstetrical outcomes after treatment of retained products of conception: hysteroscopic removal vs ultrasound-guided electric vacuum aspiration, a prospective follow-up study.

BACKGROUND: Traditionally, curettage has been the most widely performed surgical intervention for removing retained products of conception. However, hysteroscopic removal is increasingly performed as an alternative because of the potentially lower risk of intrauterine adhesions and higher rates of complete removal. Until recently, studies comparing curettage with hysteroscopic removal regarding reproductive and obstetrical outcomes were limited, and data conflicting. OBJECTIVE: This study aimed to assess reproductive and obstetrical outcomes in women wishing to conceive after removal of retained products of conception by hysteroscopy or ultrasound-guided electric vacuum aspiration. STUDY DESIGN: This was a prospective long-term follow-up study, conducted in 3 teaching hospitals and 1 university hospital. Patients were included from April 2015 until June 2022 for follow-up, either in a randomized controlled, nonblinded trial on the risk of intrauterine adhesions after removal of retained products of conception, or in a cohort alongside the randomized trial. Women with an ultrasonographic image suggestive of retained products of conception ranging from 1 to 4 cm were eligible. Surgical procedures in the randomized controlled trial were hysteroscopic morcellation or ultrasound-guided electric vacuum aspiration. In the cohort study, hysteroscopic treatment included hysteroscopic morcellation or cold loop resection compared with ultrasound-guided electric vacuum aspiration. RESULTS: A total of 261 out of 305 patients (85.6%) were available for follow-up after removal of retained products of conception, resulting in a cohort of 171 women after hysteroscopic removal and 90 women after removal by ultrasound-guided vacuum aspiration. Respectively, 92 of 171 women (53.8%) in the hysteroscopic removal group and 56 of 90 (62.2%) in the electric vacuum aspiration group wished to conceive (P=.192). Subsequent pregnancy rates were 88 of 91 (96.7%) after hysteroscopic removal and 52 of 56 (92.9%) after electric vacuum aspiration (P=.428). The live birth rates were 61 of 80 (76.3%) and 37 of 48 (77.1%) after hysteroscopic removal and electric vacuum aspiration, respectively (P=.914), with 8 of 88 pregnancies (9.1%) in the hysteroscopic removal group and 4 of 52 (7.7%) in the electric vacuum aspiration group still ongoing at follow-up (P=1.00). The median time to conception was 8.2 weeks (interquartile range, 5.0-17.2) in the hysteroscopic removal group and 6.9 weeks (interquartile range, 5.0-12.1) in the electric vacuum aspiration group (P=.262). The overall placental complication rate was 13 of 80 (16.3%) in the hysteroscopic removal group and 11 of 48 (22.9%) in the electric vacuum aspiration group (P=.350). CONCLUSION: Hysteroscopic removal and ultrasound-guided electric vacuum aspiration of retained products of conception seem to have no significantly different effects on subsequent live birth rate, pregnancy rate, time to conception, or pregnancy complications. Reproductive and obstetrical outcomes after removal of retained products of conception are reassuring, albeit with a high risk of placental complications.

Manually driven versus motor driven hysteroscopic tissue removal system for polypectomy: Long-term results.

OBJECTIVE: The aim of this follow-up study is to compare a manually driven hysteroscopic tissue removal system (ResectrTM 9 Fr) with a motor driven system (TruclearTM) in terms of long-term clinical outcomes such as abnormal uterine bleeding and polyp recurrence. STUDY DESIGN: This is a follow-up of a multicenter randomized controlled trial comparing a manually and motor driven hysteroscopic tissue removal system for polypectomy. This prospective cohort study was performed at Ghent University Hospital (Ghent, Belgium) and Catharina Hospital Eindhoven (Eindhoven, the Netherlands). The trial was registered at Clinicaltrials.gov (Trial ID = NCT05337605, April 2022). Seventy-five women with abnormal uterine bleeding who participated in the randomized controlled trial and had pathological confirmation of the diagnosis of an endometrial polyp, were contacted. Fifty-five women (70.67 %) were willing to participate in this follow-up study. The primary outcome was the recurrence and/or persistence of abnormal uterine bleeding and the time to the recurrence of abnormal uterine bleeding. Secondary outcomes were polyp recurrence and time to polyp recurrence, symptom relief, satisfaction score regarding symptom relief and general satisfaction score regarding the surgical procedure. RESULTS: In the manually driven group, the mean time to the recurrence or persistence of abnormal uterine bleeding was 26 months (95 % CI 20 - 32). In the motor driven group, the mean time to the recurrence or persistence of abnormal uterine bleeding was 29 months (95 % CI 23- 34). A log-rank test showed a non-significant difference between both groups (P =.77). There was no significant difference in polyp recurrence (P =.22) or symptom relief between the two groups (P =.67). Additionally, the groups did not differ in satisfaction scores regarding symptoms or polypectomy (P =.16 and P =.61, respectively). CONCLUSION: This long-term follow-up study showed no statistically significant difference in the recurrence and persistence of abnormal uterine bleeding between a manually and motor driven hysteroscopic tissue removal system for polypectomy.

Clinical Accuracy of Alinity m HR HPV Assay on Self- versus Clinician-Taken Samples Using the VALHUDES Protocol.

The VALHUDES protocol was established to evaluate clinical accuracy of human papillomavirus (HPV) assays to detect cervical precancer on first-void urine (FVU) and vaginal self-samples versus matched clinician-collected cervical samples (CCSs). Here we evaluated clinical performance of Alinity m HR HPV assay in a colposcopy referral population. Home-collected FVU (Colli-Pee FV 5020) 1 day before colposcopy (n = 492), at-clinic collected dry vaginal self-samples [multi-Collect Swab (mC; n = 493), followed by Evalyn Brush (EB; n = 233) or Qvintip (QT; n = 260)] and matched CCSs, were available for the study. Sensitivity to detect cervical intraepithelial neoplasia grade 2 or higher (CIN2+) of Alinity testing on FVU (ratio, 0.94; 95% CI, 0.85-1.03), mC (ratio, 1.00; 95% CI, 0.94-1.06), and EB/QT (ratio, 0.92; 95% CI, 0.85-1.00) was not different to CCSs. Specificity on FVU was similar to CCS (ratio, 1.02; 95% CI, 0.95-1.10), whereas specificity on mC was lower (ratio, 0.83; 95% CI, 0.76-0.90), but on EB/QT was higher (ratio, 1.08; 95% CI, 1.01-1.15) than on CCS. Accuracy on EB (sensitivity ratio, 0.96; 95% CI, 0.87-1.05; specificity ratio, 1.18; 95% CI, 1.06-1.31) was slightly better than on QT (sensitivity ratio, 0.88; 95% CI, 0.75-1.03; specificity ratio, 1.00; 95% CI, 0.92-1.09). In conclusion, clinical sensitivity of Alinity assay on all self-sample types was similar to cervical specimens. Adjustment of signal thresholds improved assay's accuracy to detect CIN2+ in all self-sample types.

Hysteroscopic morcellation vs. curettage for removal of retained products of conception: a multicenter randomized controlled trial.

OBJECTIVE: To study the comparison between hysteroscopic morcellation (HM) of retained products of conception (RPOC) with ultrasound (US)-guided electric vacuum aspiration in terms of intrauterine adhesion (IUA) formation, efficacy, and complications. DESIGN: A randomized controlled, nonblinded trial. SETTING: Three teaching hospitals and one university hospital from April 2015 to June 2022. PATIENTS: A total of 133 women with RPOC on US, ranging from 1-4 cm, were randomized to receive either HM or electric vacuum aspiration. INTERVENTION: Hysteroscopic morcellation was performed with the TruClear System (Medtronic, Minneapolis, MN, USA). Electric vacuum aspiration was performed using an 8- or 10-mm flexible plastic Karman cannula under US guidance. Women allocated to vacuum aspiration underwent the procedure as soon as possible. MAIN OUTCOME MEASURES: In the HM group, an office diagnostic hysteroscopy was planned a minimum of 6 weeks after the end of pregnancy, followed by retained product of conception removal at least 8 weeks after the end of the pregnancy. Postoperatively, an office second-look hysteroscopy was scheduled to assess the primary outcome of IUAs. RESULTS: Postoperative IUAs were seen in 14.3% (9/63) of patients in the HM group and 20.6% (13/64) of patients in the vacuum aspiration group (-6% [-19.1% to 7.1%]). Significantly more RPOC were removed completely by HM compared with vacuum aspiration (95.2% vs. 82.5% (-14% [-24.9% to -3.1%]), and additional operative hysteroscopy was less frequently necessary in the HM group (12.5%) compared with the vacuum aspiration group (31.3%) (-20.1% [-34.3% to -6%]). The median operating time was shorter for vacuum aspiration compared with HM (5.80 minutes vs. 7.15 minutes). No differences were observed between HM and vacuum aspiration for the occurrence of intraoperative or postoperative complications (5.5% vs. 5.0% and 2.7% vs. 1.3%, respectively). CONCLUSION: In our randomized controlled trial, no significant differences were found in the occurrence of IUAs and complications. However, the RPOC were more often completely removed by HM than vacuum aspiration, and the HM group required fewer additional hysteroscopic treatments. CLINICAL TRIAL REGISTRATION NUMBER: NTR4923 (https://trialsearch.who.int/Trial2.aspx?TrialID=NTR4923). Date of registration: November 23, 2014, date of initial participant enrollment: January 1, 2015.

Operative hysteroscopy versus ultrasound-guided electric vacuum aspiration for removal of retained products of conception: A prospective cohort study.

Objectives: To compare intrauterine adhesion (IUA) formation after hysteroscopic removal (HR) of retained products of conception (RPOC) with IUA formation after ultrasound-guided electric vacuum aspiration (EVA) and externally validate the outcomes of an RCT. Study design: This prospective cohort study was conducted from April 2015 until June 2022 in 2 Dutch teaching hospitals and one Belgian university hospital. Women opting for EVA underwent the procedure as soon as possible. In the HR group, the therapeutic hysteroscopy was performed at least eight weeks after the end of pregnancy. Postoperatively, an office second-look hysteroscopy was offered to all patients. Women were included if they had been diagnosed with RPOC ranging from 1 to 4 cm on ultrasound and did not want to participate in the RCT. EVA was performed using a Karman cannula. Operative hysteroscopy consisted either of hysteroscopic morcellation with the TruClear™ System or the Intrauterine BIGATTI Shaver or cold loop resection with a bipolar resectoscope. Results: Of 178 included women, 124 were treated with HR and 28 with EVA. Outcomes of HR and EVA did not differ significantly in terms of complications (5.6 % vs 3.6 %; p = 1.00). Second-look hysteroscopy showed IUAs in 14 of 91 women (15.4 %) after HR and in 1 of 16 (6.3 %) after EVA (p = .461). Completeness of removal was significantly higher (90.1 %) after HR than after EVA (68.8 %) (p = .035). Additional operative hysteroscopy was required in 14.3 % of the HR group versus 37.5 % in the EVA group (p = .036). Conclusion: In our cohort study, no significant differences in IUAs or complications were found. RPOC removal with HR was more often complete than removal with EVA, and additional therapeutic hysteroscopy was less frequently required after HR. These findings need to be correlated with those of RCTs. Clinical trial registration: The study was registered in de Dutch Trial Register (NTR4923). Date of registration 23-11-2014. Date of first enrollment 01-01-2015. https://trialsearch.who.int/Trial2.aspx?TrialID=NTR4923.

Comparison of the Clinical Accuracy of Xpert HPV Assay on Vaginal Self-Samples and Cervical Clinician-Taken Samples within the VALHUDES Framework.

The accuracy of high-risk human papillomavirus testing with the Xpert HPV assay on vaginal self-samples was compared with clinician-taken samples within the VALidation of HUman papillomavirus assays and collection DEvices for Self-samples and urine samples (VALHUDES) framework. Five-hundred and twenty-three women were recruited in five Belgian colposcopy clinics, of whom 483 (median age, 40 years; interquartile range, 31 to 49 years) were included in the main analysis (226 collected with Evalyn Brush and 257 collected with Qvintip). Cervical samples were collected with Cervex-Brush. Colposcopy and histology outcomes were considered as the reference standard. The Xpert HPV assay had similar accuracy for cervical intraepithelial neoplasia ≥2 on self-collected versus clinician-collected samples [relative sensitivity, 0.96 (95% CI, 0.91-1.02); and relative specificity, 0.96 (95% CI, 0.89-1.04)]. The relative accuracy slightly differed by vaginal collection device [sensitivity ratios of 0.98 (95% CI, 0.90-1.06) and 0.94 (95% CI, 0.87-1.02) for Evalyn and Qvintip, respectively; specificity ratios of 1.06 (95% CI, 0.95-1.19) and 0.88 (95% CI, 0.80-0.98) for Evalyn and Qvintip, respectively]. No difference in cycle threshold values was observed between vaginal and cervical samples. In conclusion, the sensitivity of Xpert HPV assay for cervical intraepithelial neoplasia ≥2 on vaginal self-samples was similar to that of cervical specimens. The clinical specificity was lower than on clinician-collected samples when self-samples were taken with Qvintip.

Integrating human papillomavirus testing as a point-of care service using GeneXpert platforms: Findings and lessons from a Kenyan pilot study (2019-2020).

BACKGROUND: Globally, cervical cancer is a major public health problem, with about 604,000 new cases and over 340,000 deaths in 2020. In Kenya, it is the leading cause of cancer deaths, with over 3,000 women dying in 2020 alone. Both the Kenyan cancer screening guidelines and the World Health Organization's Global Cervical Cancer Elimination Strategy recommend human papillomavirus (HPV) testing as the primary screening test. However, HPV testing is not widely available in the public healthcare system in Kenya. We conducted a pilot study using a point of care (POC) HPV test to inform national roll-out. METHODS: The pilot was implemented from October 2019 to December 2020, in nine health facilities across six counties. We utilized the GeneXpert platform (Cepheid, Sunnyvale, CA, USA), currently used for TB, Viral load testing and early infant diagnosis for HIV, for HPV screening. Visual inspection with acetic acid (VIA) was used for triage of HPV-positive women, as recommended in national guidelines. Quality assurance (QA) was performed by the National Oncology Reference Laboratory (NORL), using the COBAS 4800 platform (Roche Molecular System, Pleasanton, CF, USA). HPV testing was done using either self or clinician-collected samples. We assessed the following screening performance indicators: screening coverage, screen test positivity, triage compliance, triage positivity and treatment compliance. Test agreement between local GeneXpert and central comparator high-risk HPV (hrHPV) testing for a random set of specimens was calculated as overall concordance and kappa value. We conducted a final evaluation and applied the Nominal Group Technique (NGT) to identify implementation challenges and opportunities. KEY FINDINGS: The screening coverage of target population was 27.0% (4500/16,666); 52.8% (2376/4500) were between 30-49 years of age. HPV positivity rate was 22.8% (1027/4500). Only 10% (105/1027) of HPV positive cases were triaged with VIA/VILI; 21% (22/105) tested VIA/VILI positive, and 73% (16/22) received treatment (15 received cryotherapy, 1 was referred for biopsy). The median HPV testing turnaround time (TAT) was 24 hours (IQR 2-48 hours). Invalid sample rate was 2.0% (91/4500). Concordance between the Cepheid and COBAS was 86.2% (kappa value = 0.71). Of 1042 healthcare workers, only 5.6% (58/1042) were trained in cervical cancer screening and treatment, and only 69% (40/58) of those trained were stationed at service provision areas. Testing capacity was identifed as the main challenge, while the community strategy was the main opportunity. CONCLUSION: HPV testing can be performed on GeneXpert as a near point of care platform. However, triage compliance and testing TAT were major concerns. We recommend strengthening of the screening-triage-treatment cascade and expansion of testing capacity, before adoption of a GeneXpert-based HPV screening among other near point of care platforms in Kenya.

Clinical evaluation of a new hand-driven hysteroscopic tissue removal device, Resectr™ 5fr, for the resection of endometrial polyps in an office setting.

PURPOSE: A first clinical evaluation of a new hand-driven hysteroscopic tissue removal device, Resectr™ 5fr, for office polypectomy without any anesthesia. METHODS: Women with at least one small endometrial polyp were eligible. Hysteroscopic polypectomy was performed using the Resectr™ 5fr in an office setting, without any anesthesia. RESULTS: One hundred and two hysteroscopic polypectomies were included in the analysis. The median installation time was 1.9 min (95% confidence interval (CI) 1.6-2.1). The median time to complete polyp removal was 1.2 min (95% CI 0.8-1.6). The median surgeon's safety, practical, and comfort scores on a 5-point Likert scale were high (5 (5-5), 5 (4-5), and 5 (4-5), respectively). Women's pain score was low (median 1 (0-3)), whereas the satisfaction rate was high (median 5 (5-5)), both on a 5-point Likert scale. There were two conversions (hysteroscopic scissors (n = 1), a new Resectr™ 5fr device (n = 1)). There was one incomplete procedure (tissue hardness). CONCLUSION: Hysteroscopic removal of small polyps, using the [Formula: see text] 5fr in an office setting is feasible in terms of installation and resection time. Surgeon's practical, comfort, and safety scores are high, whereas women report low pain scores and high satisfaction rates.  TRIAL REGISTRATION: Dutch Clinical Trial Registry (NTR 7119, NL6923): https://www.trialregister.nl/trial/6923 . Date of registration: 27/03/2018.

Efficacy of Oral Nifedipine, Naproxen, or Placebo for Pain Relief During Diagnostic Hysteroscopy in an Office Setting: A Randomized Pilot Study.

STUDY OBJECTIVE: To compare nifedipine, naproxen, or placebo for pain relief during diagnostic hysteroscopy. DESIGN: Double-blind, randomized controlled pilot study. SETTING: University hospital. PATIENTS: Women scheduled for office diagnostic hysteroscopy (n = 60). INTERVENTIONS: Women received nifedipine (2 tablets of 10 mg), naproxen (2 tablets of 250 mg), or placebo (2 tablets of 500 mg lactose) 30 to 60 minutes prior to hysteroscopy. MEASUREMENTS AND MAIN RESULTS: Sixty patients were enrolled in the study (21 in the nifedipine group, 19 in the naproxen group, and 20 in the placebo group). The median pain scores during hysteroscope insertion, measured on a Visual Analog Scale (VAS), were 1 (interquartile range (IQR) 0-0), 2 (0-4) and 1 (0-1) in the nifedipine, naproxen and placebo group, respectively (P,14). The median VAS scores during hysteroscopy were 5 (IQR 2-7), 5 (4-8) and 5 (3-7) in the nifedipine, naproxen and placebo group, respectively (P,73). The median VAS scores immediately after hysteroscopy were 2 (IQR 0-4), 3 (0-6) and 3 (1-5) in the nifedipine, naproxen and placebo group, respectively (P,40). The median VAS scores 30 minutes after hysteroscopy were 1 (IQR 0-2), 1 (0-1) and 1 (0-2) in the nifedipine, naproxen and placebo group, respectively (P,63). Hysteroscope insertion failed in 1 case (naproxen group) because of cervica`l stenosis (P,32). Flushes, fatigue and vertigo, 30 minutes after the procedure, were significantly more prevalent in the nifedipine group compared to the naproxen (p < .001, p,03, p,03, respectively) and the placebo group (p < .001, p,01, p,01, respectively). Palpitations occurred only in the nifedipine group (p < .001). The day after the procedure, the headache was most prevalent in the nifedipine group compared to the naproxen group (p,001) and the placebo group (p,001). CONCLUSION: In our pilot study, pain relief and success rates for office diagnostic hysteroscopy were not significantly different between nifedipine, naproxen, and placebo. Nifedipine was associated with more, albeit tolerable, side-effects.

Manual morcellation (Resectr™ 9Fr) vs electromechanical morcellation (TruClear™) for hysteroscopic polypectomy: A randomized controlled non-inferiority trial.

INTRODUCTION: Meta-analyses comparing hysteroscopic electromechanical morcellation with electrosurgical resection showed a shorter operating time for electromechanical morcellation, mainly for polypectomy. The Resectr™ 9Fr is a new hysteroscopic manual morcellator, designed to simplify this procedure. We aimed to compare manual with electromechanical morcellation for hysteroscopic polypectomy. MATERIAL AND METHODS: This two-center randomized controlled non-inferiority trial was performed from 2018 to 2021 in the Catharina Hospital and the Ghent University Hospital. The study was registered at the Dutch Trial Register (NL6922; ICTRP ID: NTR7118). One hundred and forty women with polyps (between 8 and 20 mm) scheduled for hysteroscopic removal were randomized between manual (Resectr™ 9Fr) or electromechanical (TruClear™) morcellation. The primary outcome was time (instrumentation set-up, resection, and total procedure time). RESULTS: The non-inferiority margin for the primary outcome time was 1.3. Mean instrumentation set-up time was 10% shorter with the manual compared with the electromechanical morcellator (estimated mean ratio manual/electromechanical = 0.9; 97.5% confidence interval [CI] 0.8-1.1). Mean resection time was 30% longer with the manual compared with the motor-driven system (estimated mean ratio manual/electromechanical = 1.3; 97.5% CI 0.9-1.9). Mean total procedure time was 10% longer with the manual compared with the electromechanical morcellator (estimated mean ratio manual/electromechanical = 1.1; 95% CI 0.91-1.298). The estimated odds (electromechanical/manual) of better surgeon's safety, effective and comfort scores were, respectively, 4.5 (95% CI 0.9-22.1), 7.0 (95% CI 1.5-31.9), and 5.9 (95% CI 1.1-30.3) times higher with the motor-driven compared with the manual morcellator. Conversion rates and incomplete resection rates were comparable in both groups (manual vs electromechanical) (7.6% [4/66] vs 2.9% [2/68] and 6.1% [4/66] vs 3.0% [2/66], respectively). No intraoperative and postoperative complications were registered. CONCLUSIONS: The manual morcellator was non-inferior to the electromechanical morcellator for hysteroscopic polypectomy in terms of mean instrumentation set-up time and total procedure time. Results on resection time were inconclusive. Conversion and incomplete resection rates were within the range reported in the literature. Surgeon's reported rating for both devices was high, however, in favor of the motor-driven tissue removal system.

Registry of the International Society of Uterus Transplantation: First Report.

BACKGROUND: Uterus transplantation (UTx) is a novel type of transplantation to treat infertility in women with an absent or nonfunctioning uterus. The International Society of Uterus Transplantation (ISUTx) has developed a registry to monitor worldwide UTx activities while serving as a repository for specific research questions. METHODS: The web-based registry has separate data fields for donor, recipient, surgeries, immunosuppression, rejections, pregnancies with live birth(s), and transplant hysterectomies. Data are prospectively registered. RESULTS: A total of 45 UTx procedures have been registered; the majority (78%) of those procedures were live donor (LD) transplants. Median age of the LDs, deceased donors, and recipients were 50 y (range 32-62), 38.5 y (19-57), and 29 y (22-38), respectively. The duration of LD surgery was approximately twice as long as the recipient surgery. Postoperative complications of any Clavien-Dindo grade were registered in 20% of LDs and 24% of recipients. Rejection episodes were more frequent (33%) early after transplantation (months 1-5) compared with later time points (months 6-10; 21%). Healthy neonates were delivered by 16 recipients, with 3 women giving birth twice. The total live birth rate per embryo transfer was 35.8%. Median length of pregnancy was 35 gestational weeks. Twelve uteri were removed without childbirth, with 9 transplant hysterectomies occurring during the initial 7 mo post-UTx. CONCLUSIONS: A mandatory registry is critical to determine quality and process improvement for any novel transplantation. This registry provides a detailed analysis of 45 UTx procedures performed worldwide with a thorough analysis of outcomes and complications.

The use of an intrauterine balloon in preventing adhesion recurrence after hysteroscopic adhesiolysis: a feasibility study.

We aimed to evaluate the feasibility of a heart-shaped intrauterine balloon as antiadhesion method immediately after hysteroscopic adhesiolysis in terms of surgeon's and patient's experience. This feasibility study was performed at the Ghent University Hospital (Belgium) from 2018 to 2020. A heart-shaped intrauterine balloon was inserted in 10 women immediately after hysteroscopic adhesiolysis and left in place for 7 days under antibiotic prophylaxis. Insertion and removal of the balloon was easy in 7 women out of 10 (5-point Likert scale), and successful in all cases. The median pain score during balloon wearing on a visual analogue scale (VAS) was 1.7 (IQR 1.0-4.2). Seven out of 10 women were satisfied (5-point Likert scale). Eight out of 10 women would probably or certainly recommend the procedure to a friend (5-point Likert scale) and would use the balloon again. The heart-shaped intrauterine balloon as antiadhesion method is feasible in terms of surgeon's and patient's experience. Designing a proper Randomised Controlled Trial (RCT) is worth the effort. Clinical trial registration: https://clinicaltrials.gov (NCT03446755). Initial release on 27th February 2018.IMPACT STATEMENTWhat is already known on this subject? Intrauterine adhesion (IUA) reformation is high and different methods to prevent this subsequent to an operative hysteroscopy have been assessed. The use of antiadhesion gel, acting as a mechanical barrier, may decrease the occurrence of IUAs compared to no treatment or placebo. A heart-shaped intrauterine balloon is another example of a mechanical barrier. A small number of studies, of varying quality and with heterogeneous results, have been performed. A proper RCT, comparing the intrauterine balloon to no treatment or placebo, is needed.What the results of this study add? The heart-shaped intrauterine balloon as antiadhesion method is feasible in terms of surgeon's and patient's experience.What the implications are of these findings for clinical practice and/or further research? Designing a proper RCT is worth the effort.

Cervical cancer programme, Kenya, 2011-2020: lessons to guide elimination as a public health problem.

Background: Cervical cancer is the leading cause of cancer mortality in Kenya, with an estimated 3,200 deaths in 2020. Kenya has implemented cervical cancer interventions for more than a decade. We describe the evolution of the cervical cancer programme over the last 20 years and assess its performance. Methods: We searched the Ministry of Health's archives and website (2000-2021) for screening policy documents and assessed them using seven items: situational analysis, objectives, key result areas, implementation framework, resource considerations, monitoring and evaluation and definition of roles/responsibilities. In addition, a trend analysis was performed targeting screening and disease burden indicators in the period 2011-2020, using data from Kenya Health Information System and the Global Burden of Disease database. Findings: Policy guidance improved over time, but the implementation of screening was poor. Before 2016, a clear leadership and accountability structure was lacking; improvement occurred after the establishment of the National Cancer Control Program. The main health system gaps included the lack of a trained healthcare workforce and poor data collection. Annual screening coverage varied between <1% and 36% of the target population for the year for HIV-negative women and between <1% and 7% for HIV-positive women, from 2011 to 2020. Test positivity for visual inspection with acetic acid was below 5% for most of the period. Compliance to treatment of precancerous lesions ranged between 22% and 39%. The detection rate of cervical cancer ranged between 0.5% and 1.0%. The burden of invasive cervical cancer did not change significantly: world age-standardised incidence and mortality rates of 26.3-27.4 and 16.6-18.0/100,000 women-years, respectively; disability-adjusted life years of 579-624/100,000 life years. Conclusion: The Kenyan cervical cancer control programme suffered from inadequate health system strengthening and poor quality implementation. Evidence-based policy implementation and sustained health system strengthening are necessary to move towards cervical cancer elimination as a public health problem.

Tolerability and safety of the estetrol/drospirenone combined oral contraceptive: Pooled analysis of two multicenter, open-label phase 3 trials.

OBJECTIVES: To evaluate tolerability and safety of estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg oral contraceptive using pooled data from two, multicenter, phase 3 trials. STUDY DESIGN: The two trials enrolled participants aged 16-50 years with a body mass index ≤35.0 kg/m2 to use E4/DRSP in a 24/4-day regimen for up to 13 cycles. We pooled data from participants who used at least one E4/DRSP dose and had a follow-up assessment to analyze adverse events (AEs), vital signs, and laboratory parameters, including serum lipids, glucose, glycated hemoglobin, and potassium. We consolidated similar Medical Dictionary for Regulatory Activities preferred terms into groupings. RESULTS: Of 3725 participants enrolled, we included 3417 in the analyses of whom 1786 (52.3%) reported ≥1 AE. Most participants with reported AEs had AEs that investigators rated as mild or moderate (n = 1665, 93.2%); of participants reporting AEs, 1105 (61.9%) did so during cycles 1 to 3. In total, 981 (28.7%) participants experienced ≥1 treatment-related AE, most frequently related to bleeding complaints (n = 323, 9.5%), breast pain or tenderness (n = 136, 4.0%), acne (n = 113, 3.3%), and mood disturbance (n = 111, 3.2%). Discontinuation due to treatment-related AEs occurred in 272 participants (8.0%), with only bleeding complaints (n = 97, 2.8%) and mood disturbance (n = 38, 1.1%) at rates exceeding 1%. Three participants experienced serious AEs, which the site investigators considered treatment-related: one venous thromboembolism, one worsening of depression, and one ectopic pregnancy. We found no clinically relevant changes in weight, blood pressure, heart rate, or laboratory parameters during treatment. CONCLUSIONS: E4/DRSP is associated with a favorable tolerability and safety profile. IMPLICATIONS STATEMENT: Pooling data allowed for a robust assessment of tolerability and safety, including relatively infrequent events. Other than bleeding complaints and mood disturbance, no adverse event resulted in E4/DRSP discontinuation at rates >1%. Post-marketing surveillance studies are needed to evaluate long-term safety of the E4/DRSP COC and population-based venous thromboembolism risks.

Validation of BD Onclarity HPV Assay on Vaginal Self-Samples versus Cervical Samples Using the VALHUDES Protocol.

BACKGROUND: In this study, we evaluated accuracy of HPV testing on self-samples versus clinician-taken samples through the VALHUDES protocol. VALHUDES was designed as a diagnostic test accuracy study, where women referred to colposcopy collected self-samples followed by clinician-taken cervical samples. METHODS: Four hundred eighty-five women recruited in five colposcopy clinics (median age = 40 years; IQR, 31-49) with valid results for all specimens were included in the main analysis: 230 vaginal self-samples were collected with Evalyn Brush and 255 with Qvintip. Cervical samples were taken by the gynecologist with the Cervex-Brush. HPV testing was performed with BD Onclarity HPV assay (Onclarity). Colposcopy and histology were used as the reference standard for accuracy estimation. RESULTS: The sensitivity for CIN2+ on vaginal self-samples overall was not different from cervical samples (ratio = 0.96; 95% CI, 0.90-1.03), whereas specificity was significantly higher (ratio = 1.09; 95% CI, 1.02-1.16). However, the relative accuracy (self- vs. clinician sampling) differed by vaginal collection device: relative sensitivity and specificity ratios of 1.00 (95% CI, 0.94-1.06) and 1.15 (95% CI, 1.05-1.25), respectively for Evalyn-Brush; 0.91 (95% CI, 0.79-1.04) and 1.03 (95% CI, 0.95-1.13), respectively for Qvintip. CONCLUSIONS: Clinical accuracy of BD Onclarity HPV assay on vaginal self-samples was not different from cervical samples. IMPACT: VALHUDES study showed that HPV testing with Onclarity HPV on vaginal self-samples is similarly sensitive compared with cervical specimens. However, differences in accuracy by self-sampling devices, although not significant, were noted. Onclarity HPV testing on vaginal self-samples following validated collection and handling procedures may be used in primary cervical cancer screening.

Stress and rumination in Premenstrual Syndrome (PMS): Identifying stable and menstrual cycle-related differences in PMS symptom severity.

Since the inclusion of Premenstrual Dysphoric Disorder (PMDD) as a mood disorder in the DSM-5, Premenstrual Syndrome (PMS) symptoms have received more attention from researchers and clinicians. In this large-scale study, we investigated core psychological concepts relevant to mood disorder vulnerability between people with 1) no to mild, 2) moderate to severe, and 3) PMDD levels of PMS symptoms. Several trait measures related to mood disorders including depressive symptoms, feelings of stress and anxiety, and ruminative thinking were measured (single measurement, N = 380) along with state (momentary) reports of stress and stress-related perseverative thinking (measured twice, once in the follicular and once in the premenstrual/luteal phase, N = 237). We consistently observed that participants with higher severity of PMS symptoms also scored higher on depression, anxiety, stress, and rumination (trait measures). We also found consistent increases in momentary stress and stress-related perseverative ruminative thinking with increased PMS symptoms at each of our two test moments (in the middle of the follicular and premenstrual/luteal phase respectively). Interestingly, we did not find significant differences between our two test moments for any group, despite PMS being characterized by specific systems in the premenstrual/luteal phase. However, this could be due to noise surrounding the testing moments due to the temporal resolution of the questionnaires and the menstrual cycle estimation method. Nevertheless, these results suggest that stress and rumination are important psychological mechanisms to consider in PMS. Future PMS research studying stress and rumination on a day-to-day basis in combination with hormonal measures is warranted.

Clinical Performance of the RealTime High Risk HPV Assay on Self-Collected Vaginal Samples within the VALHUDES Framework.

The VALHUDES framework (NCT03064087) was established to evaluate the clinical accuracy of HPV testing on self-samples compared with HPV testing on matched clinician-taken cervical samples. Women referred to colposcopy due to previous cervical abnormalities were recruited at five Belgian colposcopy centers. A total of 486 pairs of matched cervical samples and vaginal self-samples were included in the analysis (228 collected with Evalyn Brush and 258 with Qvintip). The dry vaginal brushes were transferred into 20 mL ThinPrep PreservCyt solution. All specimens were tested with the Abbott RealTime High Risk HPV assay (Abbott RT). Testing on vaginal and cervical specimens was considered the index and comparator tests, respectively, and colposcopy and histology as the reference standard. The clinical sensitivity for CIN2+ of Abbott RT (cutoff ≤32 cycle number [CN]) on vaginal self-samples (Evalyn Brush and Qvintip combined) was 8% lower than on the cervical clinician-collected samples (ratio = 0.92 [95% CI, 0.87 to 0.98]), while the specificity was similar (ratio = 1.04 [95% CI, 0.97 to 1.12]). Sensitivity (ratio = 0.95 [95% CI, 0.89 to 1.02]) and specificity (ratio = 1.11 [95% CI, 0.995 to 1.23]) on Evalyn Brush samples was similar to cervical, while on Qvintip samples, the sensitivity was 12% lower than cervical samples (ratio = 0.88 [95% CI, 0.78 to 0.998]) with similar specificity (0.99 [95% CI, 0.90 to 1.10]). Exploratory cutoff optimization (cutoff ≤35 CN) resulted in an improvement of the relative sensitivity (self-sampling versus clinician sampling: ratio = 0.96 [95% CI, 0.91 to 1.02]) but yielded a loss in relative specificity (ratio = 0.92 [0.85 to 1.00]). The clinical accuracy of Abbott RT differed from the self-sampling device. However, after cutoff optimization, the sensitivity on self-samples taken with either of two vaginal brushes became similar to clinician-collected samples. IMPORTANCE Self-samples are becoming a crucial part of HPV-based cervical cancer screening programs to reach nonattendee women and increase screening coverage. Therefore, the VALHUDES framework was established to validate and evaluate HPV tests and devices on self-samples. Here, in the present manuscript, we evaluated the accuracy of the RealTime High Risk HPV assay (Abbott RT) on two different vaginal devices to detect cervical intraepithelial neoplasia grade two or higher (CIN2+). The study results demonstrated that the Abbott RT assay is similarly accurate on vaginal self-samples as on matched clinician-taken cervical samples after adjusting cutoff values. Moreover, we observed that some vaginal devices perform better than others in CIN2+ detection. We also underline the necessity of standardization and validation of general workflow and sample handling procedures for vaginal self-samples.

Analytical and clinical performance of extended HPV genotyping with BD Onclarity HPV Assay in home-collected first-void urine: A diagnostic test accuracy study.

BACKGROUND: Urine collection is a non-invasive self-sampling method offering the prospect of reaching women un(der)-screened for cervical cancer. The VALHUDES research framework was designed to address the lack of clinical accuracy data for high-risk (hr)HPV testing using urine samples. OBJECTIVES: Here, we report on the analytical and clinical accuracy of hrHPV testing on first-void urine, collected at home, using an extended HPV genotyping assay. STUDY DESIGN: Paired first-void urine (Colli-Pee with UCM, Novosanis; index test) and clinician-collected cervical samples (Cervex-Brush, Rovers in PreservCyt Solution, Hologic; comparator test) were collected from 492 women aged 19 to 72 years attending colposcopy (reference test, with histology if indicated) (VALHUDES; NCT03064087). Extended HPV genotyping was performed on paired samples with the BD Onclarity HPV Assay. Cut-offs defined for cervical samples were also applied for first-void urine. RESULTS: HrHPV testing in first-void urine was similarly sensitive for both CIN2+ (ratio 1.00; 95% CI: 0.93-1.07) and CIN3 (ratio 0.98; 95% CI: 0.88-1.08), and marginally less specific for