Anti-adhesion Gel versus No gel following Operative Hysteroscopy prior to Subsequent fertility Treatment or timed InterCourse (AGNOHSTIC), a randomised controlled trial: protocol.

STUDY QUESTIONS: Does 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 ALREADY: Intrauterine 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 DURATION: This 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 METHODS: Women 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 INTERESTS: This 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.

The rationale of opportunistic bilateral salpingectomies (OBS) during benign gynaecological and obstetric surgery: a consensus text of the Flemish Society of Obstetrics and Gynaecology (VVOG).

Ovarian cancer (OC), is a disease difficult to diagnose in an early stage implicating a poor prognosis. The 5-year overall survival in Belgium has not changed in the last 18 years and remains 44 %. There is no effective screening method (secondary prevention) to detect ovarian cancer at an early stage. Primary prevention of ovarian cancer came in the picture through the paradigm shift that the fallopian tube is often the origin of ovarian cancer and not the ovary itself. Opportunistic bilateral salpingectomy (OBS) during benign gynaecological and obstetric surgery might have the potential to reduce the risk of ovarian cancer by as much as 65 %. Bilateral risk-reducing salpingectomy during a benign procedure is feasible, safe, appears to have no impact on the ovarian function and seems to be cost effective. The key question is whether we should wait for a RCT or implement OBS directly in our daily practice. Guidelines regarding OBS within our societies are therefore urgently needed. Our recommendation is to inform all women without a child wish, undergoing a benign gynaecological or obstetrical surgical procedure about the pro's and the con's of OBS and advise a bilateral salpingectomy. Furthermore, there is an urgent need for a prospective registry of OBS. The present article is the consensus text of the Flemish Society of Obstetrics and Gynaecology (VVOG) regarding OBS.

Recommendations for a standardised educational program in robot assisted gynaecological surgery: Consensus from the Society of European Robotic Gynaecological Surgery (SERGS).

BACKGROUND: The Society of European Robotic Gynaecological Surgery (SERGS) aims at developing a European consensus on core components of a curriculum for training and assessment in robot assisted gynaecological surgery. METHODS: A Delphi process was initiated among a panel of 12 experts in robot assisted surgery invited through the SERGS. An online questionnaire survey was based on a literature search for standards in education in gynaecological robot assisted surgery. The survey was performed in three consecutive rounds to reach optimal consensus. The results of this survey were discussed by the panel and led to consensus recommendations on 39 issues, adhering to general principles of medical education. RESULTS: On review there appeared to be no accredited training programs in Europe, and few in the USA. Recommendations for requirements of training centres, educational tools and assessment of proficiency varied widely. Stepwise and structured training together with validated assessment based on competencies rather than on volume emerged as prerequisites for adequate and safe learning. An appropriate educational environment and tools for training were defined. Although certification should be competence based, the panel recommended additional volume based criteria for both accreditation of training centres and certification of individual surgeons. CONCLUSIONS: Consensus was reached on minimum criteria for training in robot assisted gynaecological surgery. To transfer results into clinical practice, experts recommended a curriculum and guidelines that have now been endorsed by SERGS to be used to establish training programmes for robot assisted surgery.

Influence of contraceptive choice on vaginal bacterial and fungal microflora.

The influence of contraception on vaginal microflora can have a major impact on the risk of developing acute or recurrent vaginal infections, but also may influence the risk of acquiring sexually transmissible infections (STI) such as HIV. A cohort of 248 women presenting for levonorgestrel-releasing intrauterine system (LNG-IUS) insertion or reinsertion were stratified according to their current contraceptive method. Information concerning their menstrual pattern and data about the medical history were collected. The composition of their vaginal microflora was studied by detailed phase contrast microscopy of fresh vaginal fluid, and aerobic cultures were taken to detect enteric bacterial growth and fungal colonisation. LNG-IUS and progesterone-only-pill (POP) users had significantly lower blood loss (p < 0.001) than other women. Regardless of the type of contraception used, all women reported similar rates of symptomatic lower genital tract infection during the preceding year. Women using combined oral contraception (COC) and long-term LNG-IUS had the same bacterial composition of vaginal microflora as non-contraceptive users, even when infections were combined. Both hormonal and non-hormonal intrauterine device users had an increased tendency to have more vaginal colonisation with Candida. Women on POPs or subcutaneous implants had a tendency towards increased vaginal atrophy, but had a lower Candida carriage rate compared to IUCD users (LNG-IUS and Copper-IUCD, p = 0.037). Women with an increased risk of acquiring STIs or recurrent BV could benefit from LNG-IUS or COC due to a well-preserved vaginal bacterial flora. Women with a susceptibility for RVVC should prefer POPs, and avoid intrauterine contraception.

[The use of intrauterine device in nulliparous over 18 years: a Belgian consensus]. / La contraception intra-utérine chez la nultlipare de plus de 18 ans: vers un consensus belge.

Under the presidency of prof. H. Depypere (UZ Ghent) and Prof. P. Simon (ULB Erasme) a Belgian panel of thirteen experts (gynecologists, representatives of universities and scientific associations for gynecology-obstetrics) reached a consensus on the use of intrauterine systems, both copper IUDs as hormone IUDs, in nultiparous women.

Cholangiocarcinoma presenting as uterine metastasis.

Metastases to the female genital tract are rare, with metastatic disease restricted to the uterus being even less frequent. The primary tumor is most often intragenital rather than extragenital. The diagnosis is usually made after occurrence of gynecological symptoms. We describe the case of a 26-year-old female, in whom a curettage for menorrhagia revealed a uterine malignancy, at first thought to be a carcinosarcoma. Biochemistry only showed iron deficiency anemia. Imaging showed discrepant results with liver lesions, suspect of neoplastic or inflammatory disease. She underwent an abdominal hysterectomy and, peroperatively, a frozen section of a mass in the liver hilus demonstrated a cholangiocarcinoma. The diagnosis of a uterine metastasized cholangiocarcinoma was made. We emphasize the fact that uterine metastases have to be excluded in every woman with abnormal uterine bleeding and a personal history of malignancy. However, our case also indicates that gynecological metastatic disease may be the first presentation of an extragenital primary neoplasm.

Normative data for uterine size according to age and gravidity and possible role of the classical golden ratio.

OBJECTIVES: To document normal measurements (length, width, anteroposterior (AP) diameter) and proportions of the non-pregnant uterus according to age and gravidity. We hypothesized that uterine proportions conform to the classical 'golden ratio' (1.618). METHODS: This was a retrospective study of ultrasonographic measurements of the length, width and AP diameter of non-pregnant uteri recorded in our database between 1 January 2000 and 31 July 2012. All patients for whom abnormal findings were reported were excluded and only the first set of measurements for each patient was retained for analysis. Loess (local regression) analysis was performed using age and gravidity as explanatory variables. RESULTS: Measurements of 5466 non-pregnant uteri were retrieved for analysis. The mean length was found to increase to 72 mm at the age of 40 and decrease to 42 mm at the age of 80 years. Gravidity was associated with greater uterine length, width and AP diameter. Mean length/width ratio was found to be 1.857 at birth, decreasing to 1.452 at the age of 91 years. At the age of 21 years, the mean ratio was found to be 1.618, i.e. equal to the golden ratio. Increasing gravidity was associated with lower mean length/width ratio. CONCLUSIONS: Uterine size in non-pregnant women varies in relation to age and gravidity. Mean length/width ratio conformed to the golden ratio at the age of 21, coinciding with peak fertility.

Accuracy of peritoneal fluid measurements by transvaginal ultrasonography.

OBJECTIVE: To assess the accuracy of the assessment of peritoneal fluid volumes of up to 1 L by transvaginal ultrasonography and to re-evaluate the formula used to calculate total volume from the dimensions of the largest pocket. METHODS: Patients (n = 13) enrolled for a minor laparoscopic procedure were prospectively recruited. At the end of the procedure, with the patient in the 30 degrees anti-Trendelenburg position, Ringer's lactate was instilled into the abdomen in discrete steps up to 1 L. Following equilibration the diameters of the single pocket of fluid were measured by transvaginal ultrasonography in order to calculate the volume, and regression models were used to determine the relationship between this and the instilled volume. The body mass index (BMI) of the patient was evaluated as a parameter for predicting the instilled volume more accurately. RESULTS: The intra-abdominal fluid volume could be calculated from the measured volume using a quadratic regression equation with an overall coefficient of variation of 19%. In individual patients, changes in volume could be assessed with a coefficient of variation of 7.3%. BMI was not found to be a significant parameter in relating the measured to the instilled volume. CONCLUSION: Transvaginal ultrasound in a standardized setting can accurately estimate the volume of peritoneal fluid, with the accuracy consistent for small and large volumes. Changes in peritoneal fluid volume over time in the same individual can be measured more accurately than the total volume present.

Pregnancy outcome after cervical conisation: a retrospective cohort study in the Leuven University Hospital.

OBJECTIVE: To assess pregnancy outcome after conisation. DESIGN: Retrospective cohort study. SETTING: Belgium, data from a university hospital. POPULATION: Fifty-five pregnancies in 34 women after conisation, and 55 pregnancies in 54 women without a history of conisation or cervical intraepithelial neoplasia (CIN). METHODS: Hospital data were reviewed and questionnaires were collected from 599 women who had a conisation in a 5-year period, among whom subsequent pregnancies were identified. The control group consisted of matched pregnancies of women without a history of conisation. MAIN OUTCOME MEASURES: Gestational age at delivery, neonatal biometry, neonatal condition at birth. RESULTS: Numbers of sexual partners (4.6 +/- 3.4 SD versus 2.5 +/- 2.5 SD) and ex-smokers were significantly higher in the study group compared with the control group. Gestational age at delivery (266 +/- 2 days versus 274 +/- 9 days), neonatal head circumference (33.9 +/- 2.5 cm, versus 34.6 +/- 2.5 cm) and birthweight (3088 +/- 754 g versus 3381 +/- 430 g) were significantly lower in the study group compared with the control group. Numbers of preterm [<37 weeks; 14/55 (25%) versus 2/55 (4%); P = 0.002] and severe preterm (<34 weeks; 6/55 (11%) versus 0/55 (0%); P = 0.031] deliveries in the study group were significantly higher. There were no cases of perinatal mortality. CONCLUSIONS: Conisation affects obstetrical outcome after conisation for CIN. Babies tend to be born earlier and are smaller. It is not clear whether this is related to the procedure or to factors linked with CIN.

[Pregnancy and childbirth in a patient with a spinal cord lesion]. / Zwangerschap en partus bij een patiënte met een dwarslaesie.

A 37-year-old woman with a spinal cord lesion at the level of TvIII due to a car-accident, became pregnant. She had posttraumatic syringomyely at Cv-TvIII, for which she underwent syringo-arachnoidal drainage. At approximately six weeks of amenorrhoea she presented at the emergency room with vaginal bleeding. She was treated with dalteparine 5000 IU once daily given by intramuscular injection until 6 weeks post partum. Weekly urine checks were advised. At 36 6/7 weeks of pregnancy, the patient was admitted to hospital for daily cardiotocography and 4-hourly contraction monitoring. After spontaneous rupture of the membranes she went into labour and had a vaginal delivery of a son weighing 3320 g. His Apgar score was 6 after 1 min and 9 after 5 min; arterial pH was 7.31. For three months after giving birth she received specialist care at home as well as help and counselling from a rehabilitation centre. In pregnant women with a spinal cord lesion, special attention should be paid to urinary tract infections, pressure areas, anaemia and thrombo-embolic symptoms. During partus, cardiotocographic monitoring should be carried out, also in patients with TvI-Tx lesions regularly from 36 weeks. In pregnant women with lesions from TvI, medical attendants should be aware of the possibility of autonomous dysreflection. Epidural anaesthesia should be administered and episiotomy or rupture avoided. Post partum, the bladder should always be completely emptied and pressure areas and signs ofthrombo-embolic complications monitored. A urological bladder function consultation should be requested, and, ifepisiotomy or rupture does occur, extra care should be taken to avoid infection. The ergonomic situation at home should be evaluated to ensure that any ergonomic changes necessary for the care of the patient and her newborn, take place in time.

Pain experienced during transvaginal ultrasound, saline contrast sonohysterography, hysteroscopy and office sampling: a comparative study.

OBJECTIVE: To evaluate and compare the pain experienced by women during transvaginal ultrasound, saline contrast sonohysterography (SCSH), diagnostic hysteroscopy and office sampling. METHODS: This was a descriptive study of 402 consecutive patients presenting at a 'one-stop' Bleeding Clinic between October 2004 and November 2006. Thirty-nine percent of the patients were postmenopausal. The patients underwent the following examinations transvaginally: first ultrasound with color Doppler, second SCSH, third diagnostic hysteroscopy and fourth endometrial biopsy. After completion of the examinations the patients were asked to complete a questionnaire including a visual analog scale (VAS) about their subjective appreciation of all four examinations. Two-hundred and ninety-three (72%) patients returned the questionnaire. RESULTS: The median (range) VAS scores for transvaginal ultrasound, SCSH, diagnostic hysteroscopy and endometrial sampling were 1.0 (0-8.1), 2.2 (0-10), 2.7 (0-10) and 5.1 (0-10), respectively (P < 0.0001). The patients' answers to the other questions about the pain experienced, including comparison with other minor procedures such as venous blood sampling, were all concordant with the VAS scores. CONCLUSIONS: Transvaginal ultrasound was the procedure best accepted, followed by SCSH, hysteroscopy and endometrial sampling. These results suggest that patients would prefer SCSH over hysteroscopy as an initial diagnostic approach in the evaluation of abnormal uterine bleeding.

HPV induced ovarian squamous cell carcinoma: case report and review of the literature.

BACKGROUND: Ovarian squamous cell carcinoma is usually derived from a teratoma, a Brenner tumour or endometriosis. Association with an HPV infection is rare. CASE: A fourth case of ovarian squamous cell cancer associated with HR-HPV is presented. Debulking for stage IIIc ovarian squamous cell cancer was performed and she received adjuvant combination chemotherapy. She developed bone metastases and received radiotherapy. The Progression of these metastases and the newly developed metastases did not respond to an oral tyrosine kinase inhibitor (gefitinib). CONCLUSION: The development of bone metastases in association with an ovarian squamous cell carcinoma is a rare finding, and it did not respond to treatment with a tyrosine kinase. A review of literature is presented.

Prediction of recurrence after treatment for high-grade cervical intraepithelial neoplasia: the role of human papillomavirus testing and age at conisation.

OBJECTIVES: The aim of this study was to examine the accuracy of the presence of high-risk human papillomavirus (HR-HPV) DNA (HR-HPV DNA test) postconisation as prediction of recurrent or residual cervical intraepithelial neoplasia (CIN) after treatment of high-grade cervical intraepithelial lesions (CIN2+) in a prospective study and to compare this with follow-up cytology and the marginal status of the excised tissue. DESIGN: Prospective follow-up study. SETTING: Unselected women presenting at colposcopy clinic of University Hospital Gasthuisberg, Leuven. POPULATION: Seventy-two women treated with conisation for CIN2 or CIN3. METHODS: Women were followed by HR-HPV DNA test (Hybrid Capture II test of Digene) every 3 to 6 months. The same vial was used for cytology and the HR-HPV DNA test (SurePath). All women were further followed by colposcopy and cytology for 24 months at 6-month intervals. The outcome of the study was presence of >CIN2, proven with colposcopy-directed biopsy occurring within 24 months after treatment. HR-HPV status was correlated with recurrent or residual CIN2+. MAIN OUTCOME MEASURES: Sensitivity, specificity, predictive values and diagnostic odds ratios to predict treatment failure or cure were computed for HR-HPV testing, marginal status and follow-up cytology. HR-HPV status was also correlated with section margins postconisation and with the first cervical smear. RESULTS: In 6 of the 72 treated women (8%), residual or recurrent CIN occurred. Women with recurrence were significantly older than women without a recurrence (51.5 +/- 9.6 versus 39.8 +/- 12.2 years, P= 0.007). All six women with recurrence were HR-HPV positive, four had a positive follow-up smear (>or=atypical squamous cells of uncertain significance = ASCUS+) and only two had involved section margins. Among the 66 cured women, 15 were HR-HPV positive, 6 had an abnormal smear and 12 had positive section margins. Sensitivity of cytology, positive section margins and HR-HPV DNA positivity was 66.7, 33.3 and 100% to predict treatment failure. Specificity of the three tests was, respectively, 90.9, 81.8 and 77.3%. Women with HR-HPV DNA at 3 to 6 months showed recurrent or residual CIN in 15% (2/13) if they had normal follow-up Pap smears and in 50% (4/8) if they had abnormal Pap smears. Margin status was not statistically significantly associated with human papillomavirus status. CONCLUSION: Persistence or clearance of HR-HPV DNA is an early valid prognostic marker of failure or cure after treatment for CIN2+ and is more accurate than cytology or section margin status at the time of conisation. The absence of HR-HPV DNA has a 100% negative predictive value. Higher age at conisation may be a previously unrecognised risk factor for recurrence.

The pedicle artery sign based on sonography with color Doppler imaging can replace second-stage tests in women with abnormal vaginal bleeding.

OBJECTIVE: Unenhanced transvaginal sonography is not accurate in the detection of endometrial polyps. Currently, second-stage tests such as saline contrast sonohysterography and office hysteroscopy are used to diagnose endometrial lesions, but both have limitations and side effects. We proposed visualization of the pedicle artery on color Doppler imaging as a sign of polyps. METHODS: This was a prospective observational study involving 3099 consecutive patients referred for assessment of the endometrium and myometrium. The uterus was assessed in sagittal and coronal planes using color Doppler sonography. Patients with suspected endometrial pathology on sonography were noted and the volume of the focal lesion was calculated. Patients with a clearly visible pedicle artery reaching the central part of the endometrium were regarded as test-positive. The gold standard was defined as the presence or absence of an endometrial polyp at hysterectomy, hysteroscopy and/or endometrial histology on dilatation and curettage within 1 year of sonography. RESULTS: Of the 3099 women, no gold standard was available in 2230. Only 28 of the 199 patients who were test-positive did not have a gold standard. In the 869 patients in whom a gold standard was available, 182 had one or more endometrial polyps. The pedicle artery test had an apparent sensitivity for detection of endometrial polyps of 76.4%, specificity of 95.3%, positive predictive value (PPV) of 81.3%, and negative predictive value of 93.8%. When extending the test to the prediction of any focal intracavitary pathology the PPV was 94.2%. CONCLUSIONS: The pedicle artery test has a very high PPV for intracavitary pathology. We expect that in the majority of patients with an endometrial polyp this test may replace more invasive established second-stage tests, such as saline contrast sonohysterography and office hysteroscopy.