Continuous oral contraceptives versus long-term pituitary desensitization prior to IVF/ICSI in moderate to severe endometriosis:study protocol of a non-inferiority randomized controlled trial

STUDY QUESTIONS: The primary objective is to investigate if continuous use of oral contraceptives is non-inferior compared to long-term pituitary desensitization with a GnRH agonist prior to IVF/ICSI in patients with moderate to severe endometriosis with regard to treatment efficacy. Secondary objectives concern treatment safety and cost-effectiveness. WHAT IS KNOWN ALREADY: Long-term pituitary desensitization with a GnRH agonist for 3-6 months prior to IVF/ICSI improves clinical pregnancy rates in women suffering from endometriosis. However, discussion about this treatment strategy exists because of its uncomfortable side effects. Alternatively, IVF/ICSI pre-treatment with continuously administered oral contraceptives may offer fewer side-effects and lower (in)direct costs, as well as encouraging IVF outcomes in women with endometriosis. To date, these two different IVF/ICSI pre-treatment strategies in women with endometriosis have not been directly compared. STUDY DESIGN SIZE DURATION: An open-label, parallel two-arm randomized controlled multicenter trial is planned, including patients with moderate to severe endometriosis. To demonstrate an absolute difference of 13% (delta of 10% with non-inferiority margin of 3%) with a power of 80% 137 patients per group are sufficient. Taking into account a withdrawal of patients of 10% and a cancelation rate of embryo transfer after ovarian pick up of 10% (for instance due to fertilization failure), the sample size calculation is rounded off to 165 patients per group; 330 patients in total will be included. After informed consent, eligible patients will be randomly allocated to the intervention or reference group by using web based block randomization stratified per centre. Study inclusion is expected to be complete in 3-5 years. PARTICIPANTS/MATERIALS SETTING METHODS: The research population consists of patients with moderate to severe endometriosis (ASRM III/IV) who are scheduled for their first, second or third IVF/ICSI treatment attempt. Women aged over 41 years, younger than 18 years, with a known contraindication for the use of oral contraceptives and/or GnRH agonists or with severe male factor infertility will be excluded from participation. After informed consent patients are allocated to the intervention group (one-phase oral contraceptive continuously during three subsequent months) or the reference group (three Leuprorelin 3.75 mg i.m./s.c. depot injections during three subsequent months). Tibolon 2.5 mg can be given daily as add-back therapy in the reference group. After 3 months of pre-treatment the IVF/ICSI stimulation phase will be started. The primary outcome is live birth rate after fresh embryo transfer. Secondary outcomes are cumulative live birth rate after one IVF/ICSI treatment cycle (including fresh and frozen embryo transfers up to 15 months after randomization), ongoing pregnancy rate and time to pregnancy. In addition, treatment outcome parameters, adverse events, side-effects during the first 3 months, complications, recurrence of endometriosis (complaints), quality of life, patient preferences, safety and costs effectiveness will be reported. Measurements will be performed at baseline and at 3, 6, 9, 12 and 15 months after randomization. STUDY FUNDING/COMPETING INTERESTs: All authors have no conflict of interest related to this manuscript. The department of reproductive medicine of the Amsterdam UMC location VUmc has received several research and educational grants from Guerbet, Merck and Ferring not related to the submitted work. TRIAL REGISTRATION NUMBER: The trial is registered as the COPIE trial (Continuous use of Oral contraceptives as an alternative for long-term Pituitary desensitization with a GnRH agonist prior to IVF/ICSI in Endometriosis patients) in the Dutch Trial Register (Ref. No. NTR6357, http://www.trialregister.nl). TRIAL REGISTRATION DATE: 16 March 2017. DATE OF FIRST PATIENT’S ENROLMENT: Enrollment is planned for November 2018

Cost analysis and cost-effectiveness of open versus laparoscopic versus robot-assisted versus transanal total mesorectal excision in patients with rectal cancer:a protocol for a systematic review

INTRODUCTION: Nowadays, most rectal tumours are treated open or minimally invasive, using laparoscopic, robot-assisted or transanal total mesorectal excision. However, insight into the total costs of these techniques is limited. Since all three techniques are currently being performed, including cost considerations in the choice of treatment technique may significantly impact future healthcare costs. Therefore, this systematic review aims to provide an overview of evidence regarding costs in patients with rectal cancer following open, laparoscopic, robot-assisted and transanal total mesorectal excision. METHODS AND ANALYSIS: A systematic search will be conducted for papers between January 2000 and March 2022. Databases PubMed/MEDLINE, EMBASE, Scopus, Web of Science and Cochrane Library databases will be searched. Study selection, data extraction and quality assessment will be performed independently by four reviewers and discrepancies will be resolved through discussion. The Consensus Health Economic Criteria list will be used for assessing risk of bias. Total costs of the different techniques, consisting of but not limited to, theatre, in-hospital and postoperative costs, will be the primary outcome. ETHICS AND DISSEMINATION: No ethical approval is required, as there is no collection of patient data at an individual level. Findings will be disseminated widely, through peer-reviewed publication and presentation at relevant national and international conferences. TRIAL REGISTRATION NUMBER: CRD42021261125

Comparison of proactive and conventional treatment of anastomotic leakage in rectal cancer surgery:a multicentre retrospective cohort series

Purpose: Comparative studies on efficacy of treatment strategies for anastomotic leakage (AL) after low anterior resection (LAR) are almost non-existent. This study aimed to compare different proactive and conservative treatment approaches for AL after LAR. Methods: This retrospective cohort study included all patients with AL after LAR in three university hospitals. Different treatment approaches were compared, including a pairwise comparison of conventional treatment and endoscopic vacuum-assisted surgical closure (EVASC). Primary outcomes were healed and functional anastomosis rates at end of follow-up. Results: Overall, 103 patients were included, of which 59 underwent conventional treatment and 23 EVASC. Median number of reinterventions was 1 after conventional treatment, compared to 7 after EVASC (p &lt; 0.01). Median follow-up was 39 and 25 months, respectively. Healed anastomosis rate was 61% after conventional treatment, compared to 78% after EVASC (p = 0.139). Functional anastomosis rate was higher after EVASC, compared to conventional treatment (78% vs. 54%, p = 0.045). Early initiation of EVASC in the first week after primary surgery resulted in better functional anastomosis rate compared to later initiation (100% vs. 55%, p = 0.008). Conclusion: Proactive treatment of AL consisting of EVASC resulted in improved healed and functional anastomosis rates for AL after LAR for rectal cancer, compared to conventional treatment. If EVASC was initiated within the first week after index surgery, a 100% functional anastomosis rate was achievable.</p

Comparison of proactive and conventional treatment of anastomotic leakage in rectal cancer surgery:a multicentre retrospective cohort series

Purpose: Comparative studies on efficacy of treatment strategies for anastomotic leakage (AL) after low anterior resection (LAR) are almost non-existent. This study aimed to compare different proactive and conservative treatment approaches for AL after LAR. Methods: This retrospective cohort study included all patients with AL after LAR in three university hospitals. Different treatment approaches were compared, including a pairwise comparison of conventional treatment and endoscopic vacuum-assisted surgical closure (EVASC). Primary outcomes were healed and functional anastomosis rates at end of follow-up. Results: Overall, 103 patients were included, of which 59 underwent conventional treatment and 23 EVASC. Median number of reinterventions was 1 after conventional treatment, compared to 7 after EVASC (p &lt; 0.01). Median follow-up was 39 and 25 months, respectively. Healed anastomosis rate was 61% after conventional treatment, compared to 78% after EVASC (p = 0.139). Functional anastomosis rate was higher after EVASC, compared to conventional treatment (78% vs. 54%, p = 0.045). Early initiation of EVASC in the first week after primary surgery resulted in better functional anastomosis rate compared to later initiation (100% vs. 55%, p = 0.008). Conclusion: Proactive treatment of AL consisting of EVASC resulted in improved healed and functional anastomosis rates for AL after LAR for rectal cancer, compared to conventional treatment. If EVASC was initiated within the first week after index surgery, a 100% functional anastomosis rate was achievable.</p

Comparison of laparoscopic versus robot-assisted versus transanal total mesorectal excision surgery for rectal cancer:a retrospective propensity score-matched cohort study of short-term outcomes

BACKGROUND: Laparoscopic total mesorectal excision (TME) surgery for rectal cancer has important technical limitations. Robot-assisted and transanal TME (TaTME) may overcome these limitations, potentially leading to lower conversion rates and reduced morbidity. However, comparative data between the three approaches are lacking. The aim of this study was to compare short-term outcomes for laparoscopic TME, robot-assisted TME and TaTME in expert centres. METHODS: Patients undergoing rectal cancer surgery between 2015 and 2017 in expert centres for laparoscopic, robot-assisted or TaTME were included. Outcomes for TME surgery performed by the specialized technique in the expert centres were compared after propensity score matching. The primary outcome was conversion rate. Secondary outcomes were morbidity and pathological outcomes. RESULTS: A total of 1078 patients were included. In rectal cancer surgery in general, the overall rate of primary anastomosis was 39.4, 61.9 and 61.9 per cent in laparoscopic, robot-assisted and TaTME centres respectively (P < 0.001). For specialized techniques in expert centres excluding abdominoperineal resection (APR), the rate of primary anastomosis was 66.7 per cent in laparoscopic, 89.8 per cent in robot-assisted and 84.3 per cent in TaTME (P < 0.001). Conversion rates were 3.7 , 4.6 and 1.9 per cent in laparoscopic, robot-assisted and TaTME respectively (P = 0.134). The number of incomplete specimens, circumferential resection margin involvement rate and morbidity rates did not differ. CONCLUSION: In the minimally invasive treatment of rectal cancer more primary anastomoses are created in robotic and TaTME expert centres

Конференции

STUDY QUESTION: What is the cost-effectiveness of in vitro fertilization(IVF) with conventional ovarian stimulation, single embryotransfer (SET) and subsequent cryocycles or IVF in a modified natural cycle (MNC) compared with intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH) as a first-line treatment in couples with unexplained subfertility and an unfavourable prognosis on natural conception?. SUMMARY ANSWER: Both IVF strategies are significantly more expensive when compared with IUI-COH, without being significantly more effective. In the comparison between IVF-MNC and IUI-COH, the latter is the dominant strategy. Whether IVF-SET is cost-effective depends on society's willingness to pay for an additional healthy child. WHAT IS KNOWN ALREADY: IUI-COH and IVF, either after conventional ovarian stimulation or in a MNC, are used as first-line treatments for couples with unexplained or mild male subfertility. As IUI-COH is less invasive, this treatment is usually offered before proceeding to IVF. Yet, as conventional IVF with SET may lead to higher pregnancy rates in fewer cycles for a lower multiple pregnancy rate, some have argued to start with IVF instead of IUI-COH. In addition, IVF in the MNC is considered to be a more patient friendly and less costly form of IVF. STUDY DESIGN, SIZE, DURATION: We performed a cost-effectiveness analysis alongside a randomized noninferiority trial. Between January 2009 and February 2012, 602 couples with unexplained infertility and a poor prognosis on natural conception were allocated to three cycles of IVF-SET including frozen embryo transfers, six cycles of IVF-MNC or six cycles of IUI-COH. These couples were followed until 12 months after randomization. PARTICIPANTS/MATERIALS, SETTING, METHODS: We collected data on resource use related to treatment, medication and pregnancy from the case report forms. We calculated unit costs from various sources. For each of the three strategies, we calculated the mean costs and effectiveness. Incremental cost-effectiveness ratios (ICER) were calculated for IVF-SET compared with IUI-COH and for IVF-MNC compared with IUI-COH. Nonparametric bootstrap resampling was used to investigate the effect of uncertainty in our estimates. MAIN RESULTS AND THE ROLE OF CHANCE: There were 104 healthy children (52%) born in the IVF-SET group, 83 (43%) the IVF-MNC group and 97 (47%) in the IUI-COH group. The mean costs per couple were (sic)7187 for IVF-SET, (sic)8206 for IVF-MNC and (sic)5070 for IUI-COH. Compared with IUI-COH, the costs for IVF-SET and IVF-MNC were significantly higher (mean differences (sic)2117; 95% CI: (sic)1544-(sic)2657 and (sic)3136, 95% CI: (sic)2519-(sic)3754, respectively). The ICER for IVF-SET compared with IUI-COH was (sic)43 375 for the birth of an additional healthy child. In the comparison of IVF-MNC to IUI-COH, the latter was the dominant strategy, i.e. more effective at lower costs. LIMITATIONS, REASONS FOR CAUTION: We only report on direct health care costs. The present analysis is limited to 12 months. WIDER IMPLICATIONS OF THE FINDINGS: Since we found no evidence in support of offering IVF as a first-line strategy in couples with unexplained and mild subfertility, IUI-COH should remain the treatment of first choice

SELECTED ORAL COMMUNICATION SESSION, SESSION 21: FEMALE FERTILITY AND ART, Monday 4 July 2011 15:15 - 16:30

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Contemporary snapshot of tumor regression grade (TRG) distribution in locally advanced rectal cancer: a cross sectional multicentric experience.

Pre-operative chemoradiotherapy (CRT) followed by surgical resection is still the standard treatment for locally advanced low rectal cancer. Nowadays new strategies are emerging to treat patients with a complete response to pre-operative treatment, rendering the optimal management still controversial and under debate. The primary aim of this study was to obtain a snapshot of tumor regression grade (TRG) distribution after standard CRT. Second, we aimed to identify a correlation between clinical tumor stage (cT) and TRG, and to define the accuracy of magnetic resonance imaging (MRI) in the restaging setting. Between January 2017 and June 2019, a cross sectional multicentric study was performed in 22 referral centers of colon-rectal surgery including all patients with cT3-4Nx/cTxN1-2 rectal cancer who underwent pre-operative CRT. Shapiro-Wilk test was used for continuous data. Categorical variables were compared with Chi-squared test or Fisher's exact test, where appropriate. Accuracy of restaging MRI in the identification of pathologic complete response (pCR) was determined evaluating the correspondence with the histopathological examination of surgical specimens.In the present study, 689 patients were enrolled. Complete tumor regression rate was 16.9%. The "watch and wait" strategy was applied in 4.3% of TRG4 patients. A clinical correlation between more advanced tumors and moderate to absent tumor regression was found (p = 0.03). Post-neoadjuvant MRI had low sensibility (55%) and high specificity (83%) with accuracy of 82.8% in identifying TRG4 and pCR.Our data provided a contemporary description of the effects of pre-operative CRT on a large pool of locally advanced low rectal cancer patients treated in different colon-rectal surgical centers

Use of fluorescence imaging and indocyanine green during colorectal surgery: Results of an intercontinental Delphi survey

BACKGROUND: Fluorescence imaging with indocyanine green is increasingly being used in colorectal surgery to assess anastomotic perfusion, and to detect sentinel lymph nodes. METHODS: In this 2-round, online, Delphi survey, 35 international experts were asked to vote on 69 statements pertaining to patient preparation and contraindications to fluorescence imaging during colorectal surgery, indications, technical aspects, potential advantages/disadvantages, and effectiveness versus limitations, and training and research. Methodological steps were adopted during survey design to minimize risk of bias. RESULTS: More than 70% consensus was reached on 60 of 69 statements, including moderate-strong consensus regarding fluorescence imaging's value assessing anastomotic perfusion and leak risk, but not on its value mapping sentinel nodes. Similarly, although consensus was reached regarding most technical aspects of its use assessing anastomoses, little consensus was achieved for lymph-node assessments. Evaluating anastomoses, experts agreed that the optimum total indocyanine green dose and timing are 5 to 10 mg and 30 to 60 seconds pre-evaluation, indocyanine green should be dosed milligram/kilogram, lines should be flushed with saline, and indocyanine green can be readministered if bright perfusion is not achieved, although how long surgeons should wait remains unknown. The only consensus achieved for lymph-node assessments was that 2 to 4 injection points are needed. Ninety-six percent and 100% consensus were reached that fluorescence imaging will increase in practice and research over the next decade, respectively. CONCLUSION: Although further research remains necessary, fluorescence imaging appears to have value assessing anastomotic perfusion, but its value for lymph-node mapping remains questionable