Local production of 17ß-oestradiol in the endometrium during the implantation window: a pilot study.

Abstract: Sex steroids are converted to bioactive metabolites and vice versa by endometrial steroid-metabolising enzymes. Studies indicate that alterations in this metabolism might affect endometrial receptivity. This pilot study determined whether the endometrial formation and inactivation of 17ß-oestradiol differed between the supposedly embryo-receptive endometrium and non-receptive endometrium of women undergoing IVF/intracytoplasmic sperm injection (ICSI). Endometrial biopsies were obtained from IVF/ICSI patients 5-8 days after ovulation in a natural cycle, prior to their second IVF/ICSI cycle with fresh embryo transfer (ET). Endometrial biopsies from patients who achieved clinical pregnancy after fresh ET (n = 15) were compared with endometrial biopsies from patients that did not conceive after fresh ET (n = 15). Formation of 17ß-oestradiol (oxidative 17ß-hydroxysteroid dehydrogenases (HSDs)), oestrone (reductive HSD17Bs) and inhibition of HSD17B1 activity were determined by high-performance liquid chromatography. The endometrial transcriptome was profiled using RNA sequencing followed by principal component analysis and differentially expressed gene analysis. The false discovery rate-adjusted P < 0.05 and log fold change >0.5 were selected as the screening threshold. Formation and inactivation of 17ß-oestradiol resulted similar between groups. Inhibition of HSD17B1 activity was significantly higher in the non-pregnant group when only primary infertile women (n = 12) were considered (27.1%, n = 5 vs 16.2%, n = 7, P = 0.04). Gene expression analysis confirmed the presence of HSD17B1 (encoding HSD17B1), HSD17B2 (encoding HSD17B2) and 33 of 46 analysed steroid metabolising enzymes in the endometrium. In the primary infertile subgroup (n = 10) 12 DEGs were found including LINC02349 which has been linked to implantation. However, the exact relationship between steroid-metabolising enzyme activity, expression and implantation outcome requires further investigation in larger, well-defined patient groups. Lay summary: Sex hormones are produced and broken down by enzymes that can be found in the endometrium (the inner lining of the womb). This enzyme activity might influence the chances of becoming pregnant. We compared (i) enzyme activity in the endometrium of 15 women who did and 15 women who did not become pregnant in their second in vitro fertilisation attempt, (ii) how enzyme activity can be blocked by an inhibitor, and (iii) differences in gene expression (the process by which instructions in our DNA are converted into a product). Enzyme activity was similar between groups. We found that in women who have never been pregnant in the past, inhibition of enzyme activity was higher and found differences in a gene that has been linked to the implantation of the embryo, but future studies should be performed in larger, well-defined patient groups to confirm these findings.

Efficacy of eye movement desensitization and reprocessing therapy for fear of cancer recurrence among cancer survivors: a randomized single-case experimental design.

Background: Fear of cancer recurrence (FCR) is one of the greatest problems with which cancer survivors have to deal. High levels of FCR are characterized by intrusive thoughts about cancer-related events and re-experiencing these events, avoidance of reminders of cancer, and hypervigilance, similar to post-traumatic stress disorder (PTSD). Eye movement desensitization and reprocessing (EMDR) therapy focuses on these images and memories. It is effective in reducing PTSD and may be effective in reducing high levels of FCR.Objective: The aim of the present study is to investigate the effectiveness of EMDR for severe FCR in breast and colorectal cancer survivors.Method: A multiple-baseline single-case experimental design (n = 8) was used. Daily repeated measurements for FCR were taken during the baseline phase and treatment phase, post-treatment, and at the 3 month follow-up. Participants answered the Cancer Worry Scale (CWS) and the Fear of Cancer Recurrence Inventory, Dutch version (FCRI-NL) five times, i.e. at the start and at the end of each phase (baseline, treatment, post-treatment, and follow-up). The study was prospectively registered at clinicaltrials.gov (NL8223).Results: Visual analysis and effect size calculation by Tau-U were executed for the daily questionnaire on FCR. The weighted average Tau-U score was .63 (p < .01) for baseline versus post-treatment, indicating large change, and .53 (p < .01) between baseline and follow-up, indicating moderate change. The scores on the CWS and FCRI-NL-SF decreased significantly from baseline to follow-up.Conclusion: The results seem promising for EMDR therapy as a potentially effective treatment for FCR. Further research is recommended.

Patients who experience high fear of cancer recurrence (FCR) often have intrusive memories and images about (future) cancer-related events.Eye movement desensitization and reprocessing (EMDR) therapy can focus on these intrusions.EMDR therapy is found to be a promising therapy for patients experiencing high FCR.

Endometrial scratching in women with one failed IVF/ICSI cycle-outcomes of a randomised controlled trial (SCRaTCH).

STUDY QUESTION: Does endometrial scratching in women with one failed IVF/ICSI treatment affect the chance of a live birth of the subsequent fresh IVF/ICSI cycle? SUMMARY ANSWER: In this study, 4.6% more live births were observed in the scratch group, with a likely certainty range between -0.7% and +9.9%. WHAT IS KNOWN ALREADY: Since the first suggestion that endometrial scratching might improve embryo implantation during IVF/ICSI, many clinical trials have been conducted. However, due to limitations in sample size and study quality, it remains unclear whether endometrial scratching improves IVF/ICSI outcomes. STUDY DESIGN, SIZE, DURATION: The SCRaTCH trial was a non-blinded randomised controlled trial in women with one unsuccessful IVF/ICSI cycle and assessed whether a single endometrial scratch using an endometrial biopsy catheter would lead to a higher live birth rate after the subsequent IVF/ICSI treatment compared to no scratch. The study took place in 8 academic and 24 general hospitals. Participants were randomised between January 2016 and July 2018 by a web-based randomisation programme. Secondary outcomes included cumulative 12-month ongoing pregnancy leading to live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with one previous failed IVF/ICSI treatment and planning a second fresh IVF/ICSI treatment were eligible. In total, 933 participants out of 1065 eligibles were included (participation rate 88%). MAIN RESULTS AND THE ROLE OF CHANCE: After the fresh transfer, 4.6% more live births were observed in the scratch compared to control group (110/465 versus 88/461, respectively, risk ratio (RR) 1.24 [95% CI 0.96-1.59]). These data are consistent with a true difference of between -0.7% and +9.9% (95% CI), indicating that while the largest proportion of the 95% CI is positive, scratching could have no or even a small negative effect. Biochemical pregnancy loss and miscarriage rate did not differ between the two groups: in the scratch group 27/153 biochemical pregnancy losses and 14/126 miscarriages occurred, while this was 19/130 and 17/111 for the control group (RR 1.21 (95% CI 0.71-2.07) and RR 0.73 (95% CI 0.38-1.40), respectively). After 12 months of follow-up, 5.1% more live births were observed in the scratch group (202/467 versus 178/466), of which the true difference most likely lies between -1.2% and +11.4% (95% CI). LIMITATIONS, REASONS FOR CAUTION: This study was not blinded. Knowledge of allocation may have been an incentive for participants allocated to the scratch group to continue treatment in situations where they may otherwise have cancelled or stopped. In addition, this study was powered to detect a difference in live birth rate of 9%. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study are an incentive for further assessment of the efficacy and clinical implications of endometrial scratching. If a true effect exists, it may be smaller than previously anticipated or may be limited to specific groups of women undergoing IVF/ICSI. Studying this will require larger sample sizes, which will be provided by the ongoing international individual participant data-analysis (PROSPERO CRD42017079120). At present, endometrial scratching should not be performed outside of clinical trials. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by ZonMW, the Dutch organisation for funding healthcare research. J.S.E. Laven reports grants and personal fees from AnshLabs (Webster, Tx, USA), Ferring (Hoofddorp, The Netherlands) and Ministry of Health (CIBG, The Hague, The Netherlands) outside the submitted work. A.E.P. Cantineau reports 'other' from Ferring BV, personal fees from Up to date Hyperthecosis, 'other' from Theramex BV, outside the submitted work. E.R. Groenewoud reports grants from Titus Health Care during the conduct of the study. A.M. van Heusden reports personal fees from Merck Serono, personal fees from Ferring, personal fees from Goodlife, outside the submitted work. F.J.M. Broekmans reports personal fees as Member of the external advisory board for Ferring BV, The Netherlands, personal fees as Member of the external advisory board for Merck Serono, The Netherlands, personal fees as Member of the external advisory for Gedeon Richter, Belgium, personal fees from Educational activities for Ferring BV, The Netherlands, grants from Research support grant Merck Serono, grants from Research support grant Ferring, personal fees from Advisory and consultancy work Roche, outside the submitted work. C.B. Lambalk reports grants from Ferring, grants from Merck, grants from Guerbet, outside the submitted work. TRIAL REGISTRATION NUMBER: Registered in the Netherlands Trial Register (NL5193/NTR 5342). TRIAL REGISTRATION DATE: 31 July 2015. DATE OF FIRST PATIENT'S ENROLMENT: 26 January 2016.

Editor's Choice - Nationwide Analysis of Patients Undergoing Iliac Artery Aneurysm Repair in the Netherlands.

OBJECTIVE: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR). METHODS: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests. RESULTS: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively). CONCLUSION: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair.

Treatment effect of oil-based contrast is related to experienced pain at HSG: a post-hoc analysis of the randomised H2Oil study.

STUDY QUESTION: Does pain or volume of used contrast medium impact the effectiveness of oil-based contrast during hysterosalpingography (HSG)? SUMMARY ANSWER: In women who report moderate to severe pain during HSG, the use of oil-based contrast resulted in more ongoing pregnancies compared to the use of water-based contrast, whereas in women who reported mild or no pain, no difference in ongoing pregnancies was found. WHAT IS KNOWN ALREADY: We recently showed that in infertile women undergoing HSG, the use of oil-based contrast results in more ongoing pregnancies within 6 months as compared to the use of water-based contrast. However, the underlying mechanism of this fertility-enhancing effect remains unclear. STUDY DESIGN, SIZE, DURATION: We performed a post-hoc analysis of the H2Oil study, a multicentre randomised controlled trial (RCT) evaluating the therapeutic effect of oil- and water-based contrast at HSG. Here, we evaluated the impact of pain experienced at HSG and volume of used contrast media during HSG on ongoing pregnancy. PARTICIPANTS/MATERIALS, SETTING, METHODS: In a subset of 400 participating women, pain during HSG by means of the Visual Analogue Scale (VAS) (range: 0.0-10.0 cm) was reported, while in 512 women, we registered the volume of used contrast (in millilitres). We used logistic regression analyses to assess whether pain and volume of used contrast media modified the effect of oil-based contrast on ongoing pregnancy rates. Data were analysed according to intention-to-treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: In 400 women in whom pain scores were reported, the overall median pain score was 5.0 (Interquartile range (IQR) 3.0-6.8) (oil group (n = 199) 4.8 (IQR 3.0-6.4); water group (n = 201) 5.0 (IQR 3.0-6.7); P-value 0.28). There was a significant interaction between pain (VAS ≤5 versus VAS ≥6) and the primary outcome ongoing pregnancy (P-value 0.047). In women experiencing pain (VAS ≥6), HSG with oil-based contrast resulted in better 6-month ongoing pregnancy rates compared to HSG with water-based contrast (49.4% versus 29.6%; RR 1.7; 95% CI, 1.1-2.5), while in women with a pain score ≤5, 6-month ongoing pregnancy rates were not significantly different between the use of oil- (28.8%) versus water-based contrast (29.2%) (RR 0.99; 95% CI, 0.66-1.5). In the 512 women in whom we recorded contrast, median volume was 9.0 ml (IQR 5.7-15.0) in the oil group versus 8.0 ml (IQR 5.9-13.0) in the water group, respectively (P-value 0.72). Volume of used contrast was not found to modify the effect of oil-based contrast on ongoing pregnancy (P-value for interaction 0.23). LIMITATIONS, REASONS FOR CAUTION: This was a post-hoc analysis that should be considered as hypothesis generating. The RCT was restricted to infertile ovulatory women, younger than 39 years of age and with a low risk for tubal pathology. Therefore, our results should not be generalised to infertile women who do not share these features. WIDER IMPLICATIONS OF THE FINDINGS: The underlying mechanism of the fertility-enhancing effect induced by HSG with the use of oil-based contrast remains unclear. However, these findings suggest a possible mechanistic pathway, that is increasing intrauterine pressure occurring prior to dislodging pregnancy hindering debris or mucus plugs from the proximal part of otherwise normal fallopian tubes. This information might help in the search of the underlying fertility-enhancing mechanism found by using oil-based contrast during HSG. STUDY FUNDING/COMPETING INTEREST(S): The original H2Oil RCT was an investigator-initiated study that was funded by the two academic institutions (AMC and VUmc) of the Amsterdam UMC. The funders had no role in study design, collection, analysis and interpretation of the data. K.D. reports consultancy for Guerbet. H.V. reports consultancy fees from Ferring. C.B.L. reports speakers' fees from Ferring and research grants from Ferring, Merck and Guerbet. V.M. reports receiving travel and speakers fees as well as research grants from Guerbet. B.W.M. is supported by an NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck KGaA and Guerbet and travel and research grants from Merck KGaA and Guerbet. The other authors do not report conflict of interests. TRIAL REGISTRATION NUMBER: The H2Oil study was registered at the Netherlands Trial Registry (NTR 3270). TRIAL REGISTRATION DATE: 1 February 2012. DATE OF FIRST PATIENT'S ENROLMENT: 3 February 2012.

Does endometrial scratching increase the rate of spontaneous conception in couples with unexplained infertility and a good prognosis (Hunault > 30%)? Study protocol of the SCRaTCH-OFO trial: a randomized controlled trial.

BACKGROUND: In the Netherlands, couples with unexplained infertility and a good prognosis to conceive spontaneously (i.e. Hunault > 30%) are advised to perform timed intercourse for at least another 6 months. If couples fail to conceive within this period, they will usually start assisted reproductive technology (ART). However, treatment of unexplained infertility by ART is empirical and can involve significant burdens. Intentional endometrial injury, also called 'endometrial scratching', has been proposed to positively affect the chance of embryo implantation in patients undergoing in vitro fertilization (IVF). It might also be beneficial for couples with unexplained infertility as defective endometrial receptivity may play a role in these women. The primary aim of this study is to determine whether endometrial scratching increases live birth rates in women with unexplained infertility. METHOD: A multicentre randomized controlled trial will be conducted in Dutch academic and non-academic hospitals starting from November 2017. A total of 792 women with unexplained infertility and a good prognosis for spontaneous conception < 12 months (Hunault > 30%) will be included, of whom half will undergo endometrial scratching in the luteal phase of the natural cycle. The women in the control group will not undergo endometrial scratching. According to Dutch guidelines, both groups will subsequently perform timed intercourse for at least 6 months. The primary endpoint is cumulative live birth rate. Secondary endpoints are clinical and ongoing pregnancy rate; miscarriage rate; biochemical pregnancy loss; multiple pregnancy rate; time to pregnancy; progression to intrauterine insemination (IUI) or IVF; pregnancy complications; complications of endometrial scratching; costs and endometrial tissue parameters associated with reproductive success or failure. The follow-up duration is 12 months. DISCUSSION: Several small studies show a possible beneficial effect of endometrial scratching in women with unexplained infertility trying to conceive naturally or through IUI. However, the quality of this evidence is very low, making it unclear whether these women will truly benefit from this procedure. The SCRaTCH-OFO trial aims to investigate the effect of endometrial scratching on live birth rate in women with unexplained infertility and a good prognosis for spontaneous conception < 12 months. TRIAL REGISTRATION: NTR6687 , registered August 31st, 2017. PROTOCOL VERSION: Version 2.6, November 14th, 2018.

Endometrial scratching in women with implantation failure after a first IVF/ICSI cycle; does it lead to a higher live birth rate? The SCRaTCH study: a randomized controlled trial (NTR 5342).

BACKGROUND: Success rates of assisted reproductive techniques (ART) are approximately 30%, with the most important limiting factor being embryo implantation. Mechanical endometrial injury, also called 'scratching', has been proposed to positively affect the chance of implantation after embryo transfer, but the currently available evidence is not yet conclusive. The primary aim of this study is to determine the effect of endometrial scratching prior to a second fresh in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle on live birth rates in women with a failed first IVF/ICSI cycle. METHOD: Multicenter randomized controlled trial in Dutch academic and non-academic hospitals. A total of 900 women will be included of whom half will undergo an endometrial scratch in the luteal phase of the cycle prior to controlled ovarian hyperstimulation using an endometrial biopsy catheter. The primary endpoint is the live birth rate after the 2nd fresh IVF/ICSI cycle. Secondary endpoints are costs, cumulative live birth rate (after the full 2nd IVF/ICSI cycle and over 12 months of follow-up); clinical and ongoing pregnancy rate; multiple pregnancy rate; miscarriage rate and endometrial tissue parameters associated with implantation failure. DISCUSSION: Multiple studies have been performed to investigate the effect of endometrial scratching on live birth rates in women undergoing IVF/ICSI cycles. Due to heterogeneity in both the method and population being scratched, it remains unclear which group of women will benefit from the procedure. The SCRaTCH trial proposed here aims to investigate the effect of endometrial scratching prior to controlled ovarian hyperstimulation in a large group of women undergoing a second IVF/ICSI cycle. TRIAL REGISTRATION: NTR 5342 , registered July 31st, 2015. PROTOCOL VERSION: Version 4.10, January 4th, 2017.

Stimulation of the ovaries in women with breast cancer undergoing fertility preservation: Alternative versus standard stimulation protocols; the study protocol of the STIM-trial.

BACKGROUND: Chemotherapy for breast cancer may have a negative impact on reproductive function due to gonadotoxicity. Fertility preservation via banking of oocytes or embryos after ovarian stimulation with FSH can increase the likelihood of a future live birth. It has been hypothesized that elevated serum estrogen levels during ovarian stimulation may induce breast tumour growth. This has led to the use of alternative stimulation protocols with addition of tamoxifen or letrozole. The effectiveness of these stimulation protocols in terms of oocyte yield is unknown. METHODS/DESIGN: Randomized open-label trial comparing ovarian stimulation plus tamoxifen and ovarian stimulation plus letrozole with standard ovarian stimulation in the course of fertility preservation. The study population consists of women with breast cancer who opt for banking of oocytes or embryos, aged 18-43years at randomisation. Primary outcome is the number of oocytes retrieved at follicle aspiration. Secondary outcomes are number of mature oocytes retrieved, number of oocytes or embryos banked and peak E2 levels during ovarian stimulation. DISCUSSION: Concerning the lack of evidence on which stimulation protocol should be used in women with breast cancer and the growing demand for fertility preservation, there is an urgent need to undertake this study. By performing this study, we will be able to closely monitor the effects of various stimulation protocols in women with breast cancer and pave the way for long term follow up on the safety of this procedure in terms of breast cancer prognosis. TRIAL REGISTRATION: NTR4108.

The SUPER study: protocol for a randomised controlled trial comparing follicle-stimulating hormone and clomiphene citrate for ovarian stimulation in intrauterine insemination.

OBJECTIVE: To study the effectiveness of four cycles of intrauterine insemination (IUI) with ovarian stimulation (OS) by follicle-stimulating hormone (FSH) or by clomiphene citrate (CC), and adherence to strict cancellation criteria. SETTING: Randomised controlled trial among 22 secondary and tertiary fertility clinics in the Netherlands. PARTICIPANTS: 732 women from couples diagnosed with unexplained or mild male subfertility and an unfavourable prognosis according to the model of Hunault of natural conception. INTERVENTIONS: Four cycles of IUI-OS within a time horizon of 6 months comparing FSH 75 IU with CC 100 mg. The primary outcome is ongoing pregnancy conceived within 6 months after randomisation, defined as a positive heartbeat at 12 weeks of gestation. Secondary outcomes are cancellation rates, number of cycles with a monofollicular or with multifollicular growth, number of follicles >14 mm at the time of ovulation triggering, time to ongoing pregnancy, clinical pregnancy, miscarriage, live birth and multiple pregnancy. We will also assess if biomarkers such as female age, body mass index, smoking status, antral follicle count and endometrial aspect and thickness can be used as treatment selection markers. ETHICS AND DISSEMINATION: The study has been approved by the Medical Ethical Committee of the Academic Medical Centre and from the Dutch Central Committee on Research involving Human Subjects (CCMO NL 43131-018-13). Results will be disseminated through peer-reviewed publications and presentations at international scientific meetings. TRIAL REGISTRATION NUMBER: NTR4057.

Extended use of endovascular aneurysm sealing: Chimneys for juxtarenal aneurysms.

Hostile infrarenal aortic neck anatomy presents a challenge for the endovascular treatment of abdominal aortic aneurysm. Open surgical repair has been seen as the gold standard treatment for juxtarenal abdominal aortic aneurysm; however, endovascular techniques are now becoming more prevalent, particularly in patients deemed high risk for morbidity and mortality with open repair. The morphology of an aneurysm is a determinant of long-term outcomes, and short aneurysm necks are associated with poorer outcomes and a higher rate of secondary reinterventions. Parallel grafts have been used in combination with endovascular aneurysm repair to elongate the sealing zone into the paravisceral segment of the aorta. This technique is associated with a risk of proximal Type I endoleak due to "guttering." This risk may be decreased when parallel grafts are used in combination with endovascular aneurysm sealing and, as such, this technique may represent an alternative to current techniques for the treatment of juxtarenal abdominal aortic aneurysm, such as the use of conventional bifurcated grafts (with or without parallel grafts) and fenestrated endovascular stent grafts.

The Endovascular Sealing Device in Combination with Parallel Grafts for Treatment of Juxta/Suprarenal Abdominal Aortic Aneurysms: Short-term Results of a Novel Alternative.

BACKGROUND: The chimney technique using parallel grafts offers an alternative to fenestrated or branched endovascular solutions for juxtarenal and suprarenal aneurysms. Endograft deployment proximal to the renal or visceral ostia is combined with parallel stents to the aortic side branches. Application of the chimney technique using the Nellix device (Ch-EVAS) may offer some potential advantages with respect to the seal between the endograft and the parallel grafts. This study aimed to investigate the feasibility and efficacy of the Nellix endovascular aneurysm sealing (EVAS) system in conjunction with parallel grafts for the treatment of juxtarenal and suprarenal aneurysms. METHODS: A prospective evaluation of patients treated for juxtarenal and suprarenal non-ruptured aortic aneurysms using Ch-EVAS was undertaken in a single vascular unit. Patients were treated with this technique if they were unsuitable for either open repair or a custom-made complex branched/fenestrated endograft. Procedural, postoperative morbidity, and mortality data were recorded. RESULTS: Between March 2013 and April 2015, 28 patients were treated with Ch-EVAS. The median age was 75 years (range 60-87 years) and the median aneurysm diameter 66 mm (IQR 60-73 mm). Eight patients underwent suprarenal aneurysm repair including parallel grafts in the superior mesenteric artery and renal arteries. Five patients had a double chimney configuration; all the other patients were treated with a single chimney configuration. There was one 30-day or in-hospital mortality in a patient with a symptomatic aneurysm (4%) and three further deaths within 1 year of follow-up. One proximal type I endoleak and one type II endoleak occurred. Four patients underwent a reintervention. One patient experienced a transient ischemic attack and two patients suffered from a minor stroke (7%), therefore the total number of cerebrovascular complications was 11%. No patient required postoperative renal replacement therapy. CONCLUSIONS: Ch-EVAS appears to offer a feasible solution for juxtarenal and suprarenal aneurysms with adverse morphology. In this short-term follow-up endoleak rates were low and re-intervention rates were acceptable. Outcomes over extended follow-up will determine the application of this novel technique and better define which patients and aneurysm morphology can be treated effectively.

Quality of life from a randomized trial of open and endovascular repair for abdominal aortic aneurysm.

BACKGROUND: Long-term survival is similar after open or endovascular repair of abdominal aortic aneurysm. Few data exist on the effect of either procedure on long-term health-related quality of life (HRQoL) and health status. METHODS: Patients enrolled in a multicentre randomized clinical trial (DREAM trial; 2000-2003) in Europe of open repair versus endovascular repair (EVAR) of abdominal aortic aneurysm were asked to complete questionnaires on health status and HRQoL. HRQoL scores were assessed at baseline and at 13 time points thereafter, using generic tools, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36®) and EuroQol 5D (EQ-5D™). Physical (PCS) and mental component summary scores were also calculated. Follow-up was 5 years. RESULTS: Some 332 of 351 patients enrolled in the trial returned questionnaires. More than 70 per cent of questionnaires were returned at each time point. Both surgical interventions had a short-term negative effect on HRQoL and health status. This was less severe in the EVAR group than in the open repair group. In the longer term the physical domains of SF-36® favoured open repair: mean difference in PCS score between open repair and EVAR -1·98 (95 per cent c.i. -3·56 to -0·41). EQ-5D™ descriptive and EQ-5D™ visual analogue scale scores for open repair were also superior to those for EVAR after the initial 6-week interval: mean difference -0·06 (-0·10 to -0·02) and -4·09 (-6·91 to -1·27) respectively. CONCLUSION: In this study EVAR appeared to be associated with less severe disruption to HRQoL and health status in the short term. However, during longer-term follow-up to 5 years, patients receiving open repair appeared to have improved quality of life and health status.

Endovascular aneurysm sealing for infrarenal abdominal aortic aneurysms: 30-day outcomes of 105 patients in a single centre.

OBJECTIVE: Endovascular aneurysm sealing (EVAS) has been proposed as a novel alternative to endovascular aneurysm repair (EVAR) in patients with infrarenal abdominal aortic aneurysms (AAA). The early clinical experience, technical refinements, and learning curve of EVAS in the treatment of AAA at a single institution are presented. METHODS: One-hundred and five patients were treated with EVAS between March 2013 and November 2014. Prospective data were recorded on consecutive patients receiving EVAS. Data included demographics, preoperative aneurysm morphology, and 30-day outcomes, including rates of endoleak, limb occlusion, reintervention, and death. Postoperative imaging consisted of duplex ultrasound and computed tomographic angiography. RESULTS: The mean age of the cohort was 76 ± 8 years and 12% were female. Adverse neck morphology was present in 72 (69%) patients, including aneurysm neck length <10 mm (20%), neck diameter >32 mm (18%), ß-angulation >60° (21%), and conical aneurysm neck (51%). There was one death within 30 days. The incidence of Type 1 endoleak within 30 days was 4% (n = 4); all were treated successfully with transcatheter embolisation. All four proximal endoleaks were associated with technical issues that resulted in procedure refinement, and all were in patients with adverse proximal aortic necks. The persistent Type 1 endoleak rate at 30 days was 0% and there were no Type 2 or Type 3 endoleaks. Angioplasty and adjunctive stenting were performed for postoperative limb stenosis in three patients (3%). CONCLUSIONS: EVAS appears to be associated with reasonable 30-day outcomes despite the necessity of procedural evolution in the early adoption of this technique. EVAS appears to be applicable to patients with challenging aortic morphology and endoleak rates should reduce with procedural experience. The utility of EVAS will be defined by the durability of the device in long-term follow-up, although the absence of Type 2 endoleaks is encouraging.

International validation of a risk score for complications and reinterventions after endovascular aneurysm repair.

BACKGROUND: Lifelong surveillance is considered mandatory after endovascular repair (EVAR) of abdominal aortic aneurysms to detect endograft complications and prevent aneurysm rupture. Current protocols are not cost-effective or clinically effective. The international validity of the St George's Vascular Institute (SGVI) score for EVAR complications was examined. METHODS: The ENGAGE registry recruited patients undergoing EVAR at 79 centres in 30 countries. Reinterventions and endograft complications were recorded for up to 3 years after surgery. Preoperative aneurysm morphology was extracted from the registry database, and used to predict whether patients would be at low or high risk of complications after EVAR based on the SGVI score. Kaplan-Meier analysis was used to compare the incidence of endograft complications and reinterventions in patients predicted to be at low risk compared with those predicted to be at high risk. RESULTS: Some 1207 patients underwent EVAR, with follow-up of up to 3 years. The SGVI score accurately discriminated freedom from reinterventions (90·5 versus 79·3 per cent in low- versus high-risk patients; P < 0·001), freedom from endograft complications (77·9 versus 69·6 per cent in low- versus high-risk patients; P = 0·012), and freedom from a composite outcome measure of reinterventions or endograft complications (75·0 versus 66·1 per cent in low- versus high-risk patients; P = 0·006) during mid-term follow-up. CONCLUSION: This study has provided international validation of a morphological risk score that predicts mid-term reinterventions and endograft complications. The results may enable risk-stratified surveillance after EVAR.

Current endovascular management of acute type B aortic dissection - whom should we treat and when?

Aortic dissection is the most common of the acute aortic syndromes, once initiated, intimal disruption can propagate in an anterograde or retrograde fashion, and the resulting false lumen may compress the ostia of aortic branches or cause aortic expansion and eventual rupture. Acute complicated type B dissection most often requires immediate interventional treatment, whereas uncomplicated dissection has classically been managed with medical therapy alone. The first line management of complicated acute and aneurysmal chronic type B dissections has shifted toward minimally invasive endovascular treatment. To give an overview of the contemporary management of acute type B dissection, clinical manifestations, aims of management, and therapeutic options are discussed in the context deciding which patients require intervention and when.

Renal function 5 years after open and endovascular aortic aneurysm repair from a randomized trial.

BACKGROUND: Deterioration of renal function after major vascular surgery is an important complication, and may vary between patients undergoing endovascular (EVAR) or open surgical (OR) repair of an abdominal aortic aneurysm (AAA). The objective was to determine the impact of OR and EVAR on renal function after 5 years. METHODS: This was a post hoc analysis of data collected prospectively from the Dutch Randomized Endovascular Aneurysm Management (DREAM) trial. Five years after surgery, creatinine levels were available for 189 patients (94 after OR and 95 after EVAR). The severity of renal disease was staged using the chronic kidney disease classification of the US National Kidney Foundation clinical guidelines. RESULTS: Using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, the estimated glomerular filtration rate (eGFR) for the entire group declined over time, with a mean(s.d.) preoperative value of 80·0(7·6) ml per min per 1·73 m(2) compared with 75·7(9·7) ml per min per 1·73 m(2) after 5 years (mean difference 4·2 (95 per cent confidence interval 3·2 to 5·3) ml per min per 1·73 m(2) ; P < 0·001). Five years after surgery, the mean eGFR (CKD-EPI equation) was not significantly different between the OR and EVAR groups: 76·3(9·3) versus 75·1(10·0) ml per min per 1·73 m(2) (mean difference 1·2 (-1·6 to 3·9) ml per min per 1·73 m(2) ; P = 0·410). CONCLUSION: Renal function 5 years after OR and EVAR for AAA was similar. Neither surgical procedure accelerated the loss of renal function.

Decision making in AAA repair in 2012: open or endo?

With data from four randomized trials on elective endovascular abdominal aortic aneurysm repair and many more additional post-hoc publications, the evidence can be somewhat overwhelming for the surgeon, let alone the patient. This chapter aims to present the most recent and relevant data for decision making in abdominal aortic aneurysm (AAA) repair in a comparative and concise format. After a comparison of the short- and long-term survival data of the randomized trials, the following post-hoc analyses of the four randomized trials will be presented: causes of death, reinterventions, renal function, prediction of complications, and quality of life. When both open and endovascular repair are a reasonable option for an individual patient, we need to objectively inform our patient about the available evidence from the trials. The three-fold reduction of operative mortality with endovascular repair as compared to open repair should be presented. Next, the convergence of the overall survival curves should be discussed as a key factor in the decision process. The counterintuitive observation may be considered that if endovascular repair is better for any specific subgroup it is for younger patients with low surgical risks. Finally, the patient needs to understand that the risks of reintervention and complications are higher after endovascular than after open repair and that this is even more relevant in older patients with larger aneurysms. The information that the quality of life advantage of endovascular repair is only short lived and for several domains surpassed by open repair is most likely not suitable for direct discussion with the individual patient, but it may put the procedures in the right perspective for the physician and health care managers.

Residual infrarenal aortic neck following endovascular and open aneurysm repair.

BACKGROUND: The effectiveness of open and endovascular aneurysm repair of aortic abdominal aneurysms (AAAs) can be jeopardised by deterioration of the residual infrarenal neck of the aneurysm. OBJECTIVE: The study aims to determine the length of the residual infrarenal aortic segment after endovascular and open aneurysm repair. METHODS: In a multicentre randomised controlled trial comparing open and endovascular AAA repair, 165 patients were discharged after open AAA repair (OR) and 169 after endovascular repair (EVAR). Immediately after the operation, surgeons were asked to enter in the case record form whether the level of their anastomosis after open repair was within or beyond 10 mm of the caudal renal artery. Postoperative computed tomography (CT) scans that were obtained within 6 months after surgery were used for comparative analysis. The distance between the caudal renal artery and the proximal anastomosis of the (endo-) graft was measured using axial CT slices and a standardised protocol. CT images were available and suitable for analysis in 156 (95%) of 165 OR patients and in 160 (95%) of 169 EVAR patients. Data are presented as median (range). Differences were analysed using the Mann-Whitney test. RESULTS: The distance from the caudal renal artery to the proximal anastomosis was 24 mm (16-30 mm) in the OR group versus 0 mm (0-6 mm) in the EVAR group (p < 0.0001, Mann-Whitney). In 140 of 156 (90%) patients, at least 1 cm of untreated infrarenal neck persisted after OR and in 17 of 160 (10%) after EVAR. In 84 of the 156 open repair patients (54%), the surgeon had indicated that the proximal anastomosis was within 10 mm of the caudal renal artery. Only five surgeons (6%) were accurate in this respect. CONCLUSION: After open repair, a longer segment of the infrarenal aortic neck is left untreated compared with endovascular repair and this length is underestimated by most surgeons. Long-term studies are required to determine the consequences of this difference.

Is the fertility treatment itself a risk factor for early pregnancy loss?

This longitudinal multicentre cohort study aimed to identify the role of the conception mode in infertile couples with an early pregnancy loss (EPL). All couples referred to the fertility clinic for the first time in the period 2002-2006 because of infertility were followed up to their first clinical pregnancy (n=1809). EPL was the outcome of 286 (15.8%) pregnancies. EPL rates for the different conception modes were as follows: spontaneous 14.5% (125/864), ovulation induction 15.8% (42/266), intrauterine insemination 25.0% (5/20), intrauterine insemination combined with ovarian stimulation 18.2% (37/203), IVF 16.3% (31/190), intracytoplasmic sperm injection (ICSI) 14.9% (30/202) and frozen embryo transfer (FET) 26.2% (16/61). After adjusting for female age, male age, hospital, obstetric history, female smoking habit, male alcohol use, menstrual cycle type and infertility diagnosis, the EPL rate after FET was significantly increased (odds ratio 2.2, 95% CI 1.14-4.19) compared with spontaneous conception. Embryo quality was comparable in fresh and frozen embryos. Other fertility treatments showed no increased miscarriage rate. Therefore, it is concluded that even after adjustment for confounding factors conception through FET remained an independent risk factor for EPL. Other modes of conception were not related with EPL.

The role of dysregulated glucose metabolism in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer and also one of the most poorly understood. Other health issues that are affecting women with increasing frequency are obesity and diabetes, which are associated with dysglycemia and increased blood glucose. The Warburg Effect describes the ability of fast-growing cancer cells to preferentially metabolize glucose via anaerobic glycolysis rather than oxidative phosphorylation. Recent epidemiological studies have suggested a role for hyperglycemia in the pathogenesis of a number of cancers. If hyperglycemia contributes to tumour growth and progression, then it is intuitive that antihyperglycemic drugs may also have an important antitumour role. Preliminary reports suggest that these drugs not only reduce available plasma glucose, but also have direct effects on cancer cell viability through modification of molecular energy-sensing pathways. This review investigates the effect that hyperglycemia may have on EOC and the potential of antihyperglycemic drugs as therapeutic adjuncts.