Contrast media for hysterosalpingography: systematic search and review providing new guidelines by the Contrast Media Safety Committee of the European Society of Urogenital Radiology.

OBJECTIVES: Hysterosalpingography (HSG) is widely used for evaluating the fallopian tubes; however, controversies regarding the use of water- or oil-based iodine-based contrast media (CM) remain. The aim of this work was (1) to discuss reported pregnancy rates related to the CM type used, (2) to validate the used CM in published literature, (3) to discuss possible complications and side effects of CM in HSG, and (4) to develop guidelines on the use of oil-based CM in HSG. METHODS: A systematic literature search was conducted for original RCT studies or review/meta-analyses on using water-based and oil-based CM in HSG with fertility outcomes and complications. Nine randomized controlled trials (RCTs) and 10 reviews/meta-analyses were analyzed. Grading of the literature was performed based on the Oxford Centre for Evidence-Based Medicine (OCEBM) 2011 classification. RESULTS: An approximately 10% higher pregnancy rate is reported for oil-based CM. Side effects are rare, but oil-based CM have potentially more side effects on the maternal thyroid function and the peritoneum. CONCLUSIONS: 1. HSG with oil-based CM gives approximately 10% higher pregnancy rates. 2. External validity is limited, as in five of nine RCTs, the CM used is no longer on the market. 3. Oil-based CM have potentially more side effects on the maternal thyroid function and on the peritoneum. 4. Guideline: Maternal thyroid function should be tested before HSG with oil-based CM and monitored for 6 months after. CLINICAL RELEVANCE STATEMENT: Oil-based CM is associated with an approximately 10% higher chance of pregnancy compared to water-based CM after HSG. Although side effects are rare, higher iodine concentration and slower clearance of oil-based CM may induce maternal thyroid function disturbance and peritoneal inflammation and granuloma formation. KEY POINTS: • It is unknown which type of contrast medium, oil-based or water-based, is the optimal for HSG. • Oil-based contrast media give a 10% higher chance of pregnancy after HSG, compared to water-based contrast media. • From the safety perspective, oil-based CM can cause thyroid dysfunction and an intra-abdominal inflammatory response in the patient.

Treatment of gastric varices with cyanoacrylate complicated by systemic embolization / Tratamiento de várices gástricas con cianoacrilato complicado con embolización sistémica

ABSTRACT Acute gastric variceal bleeding is a life-threatening condition that could be effectively treated with endoscopic cyanoacrylate injection diluted with lipiodol. The mixture acts as a tissue adhesive that polymerizes when in contact with blood in a gastric varix. This work reports a patient that presented to the emergency department with upper gastrointestinal bleeding due to acute variceal bleeding, who developed systemic embolization following cyanoacrylate injection therapy. This complication culminated in cerebral, splenic and renal infarctions with a fatal outcome. Systemic embolization is a very rare, but the most severe complication associated with endoscopic cyanoacrylate injection and should be considered in patients undergoing this treatment.

RESUMEN La hemorragia digestiva por várices gástricas es una afección potencialmente mortal que puede tratarse eficazmente con la inyección endoscópica de cianoacrilato diluida con lipiodol. La mezcla actúa como un adhesivo tisular que se polimeriza cuando entra en contacto con la sangre de la várice gástrica. Este trabajo nos reporta un paciente que acudió al servicio de urgencias con hemorragia digestiva alta debido a hemorragia aguda por várices, que desarrolló embolización sistémica después de la terapia con inyección de cianoacrilato. Esta complicación culminó en infartos cerebrales, esplénicos y renales con desenlace fatal. La embolización sistémica es una complicación muy rara, pero con alta mortalidad, asociada con la inyección endoscópica de cianoacrilato y debe considerarse en pacientes sometidos a este tratamiento.

Assessment of contrast intravasation in patients investigated by fluoroscopic hysterosalpingograms: A two-year retrospective audit in Western Australia.

INTRODUCTION: Intravasation on hysterosalpingogram (HSG) is defined by the flow of injected contrast from the uterine cavity into adjacent myometrial vessels. Evidence suggests intravasation can result in consequences such as pulmonary and cerebral embolisms. However, adverse events are poorly reported across published studies. Reported intravasation ranges from 0.0% to 13%, with higher rates attributed to oil-soluble contrast medium (OSCM) use. Recent reviews of OSCM's fertility-enhancing benefits have prompted rapid clinical uptake by fertility specialists worldwide. This instigates increased concern for intravasation and its associated sequelae. We aim to assess the prevalence of intravasation in fluoroscopic HSGs and its reporting in Western Australia (WA). METHODS: A two-year retrospective analysis of all fluoroscopic HSGs in one public teaching hospital within WA was conducted. All HSGs were retrieved from the public radiology information system and a blinded method was utilised to verify the presence and grading of intravasation in captured HSG images. Grading of intravasation was attributed by anatomical spread: 1 to myometrium, 2 to parametrium and 3 to para-iliac vessels. Results were subsequently compared with reported intravasation to assess for discrepancies. RESULTS: Of 308 successful HSGs, an intravasation rate of 7.1% was identified. Of these cases, 45% were reported and 32% were graded. Majority (73%) of intravasation events were classified as grade 1, with 9.0% and 18% of cases classified as grade 2 and 3, respectively. CONCLUSION: Under-reporting of intravasation emphasises a need for increased vigilance of radiologists. Standardised classification can provide interpretational consistency and should be considered to improve safety in future practice.

Genicular artery embolization for knee osteoarthritis: Results of the LipioJoint-1 trial.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of transient genicular artery embolization (GAE) using an ethiodized oil-based emulsion for the treatment of knee osteoarthritis (KOA). MATERIALS AND METHODS: This prospective, single-arm, open-label, multicenter, first-in-human cohort trial was registered on ClinicalTrials.gov (NCT04733092). The main inclusion criterion was diagnosis of KOA according to a visual analogue scale (VAS) pain score ≥ 40 mm (score range: 0-100 mm), despite conservative treatment for at least three months. Treatment efficacy was assessed using changes in VAS pain score, Mean Western Ontario & McMaster Universities osteoarthritis (WOMAC) function score (normalized to 100; score ranging from 0 to100) and outcome measures in rheumatoid arthritis clinical trials (OMERACT)-Osteoarthritis Research Society (OARSI) set of responder criteria. RESULTS: Twenty-two consecutive participants (13 women; mean age, 66 ± 9 [standard deviation (SD)]) were included and underwent GAE. Emulsion consisted in a mixture of ioversol and ethiodized oil (ratio 1:3, respectively) prepared extemporaneously. The rate of serious adverse events attributed to GAE within one month was 5% (1/22), corresponding to reversible worsening of renal function. Immediate technical success rate was 100%. Mean VAS pain score dropped from 74.4 ± 16.5 (SD) mm at baseline to 37.2 ± 26.7 (SD) mm at three months (P < 0.001). Mean WOMAC function score (normalized to 100: score ranging from 0 to 100) decreased from 57.3 ± 17.1 (SD) at baseline to 33.5 ± 25.9 (SD) at three months (P < 0.001). At three months, 16 out of 22 participants (73%) were considered responders according to the OMERACT-OARSI set of responder criteria, including high improvement in either pain or WOMAC function, or improvement in both pain and WOMAC function. CONCLUSION: GAE using an ethiodized oil-based emulsion is safe and improves pain and function in participants with KOA for at least three months.

Ethiodized oil as an imaging biomarker after conventional transarterial chemoembolization.

Conventional transarterial chemoembolization (cTACE) utilizing ethiodized oil as a chemotherapy carrier has become a standard treatment for intermediate-stage hepatocellular carcinoma (HCC) and has been adopted as a bridging and downstaging therapy for liver transplantation. Water-in-oil emulsion made up of ethiodized oil and chemotherapy solution is retained in tumor vasculature resulting in high tissue drug concentration and low systemic chemotherapy doses. The density and distribution pattern of ethiodized oil within the tumor on post-treatment imaging are predictive of the extent of tumor necrosis and duration of response to treatment. This review describes the multiple roles of ethiodized oil, particularly in its role as a biomarker of tumor response to cTACE. CLINICAL RELEVANCE: With the increasing complexity of locoregional therapy options, including the use of combination therapies, treatment response assessment has become challenging; Ethiodized oil deposition patterns can serve as an imaging biomarker for the prediction of treatment response, and perhaps predict post-treatment prognosis. KEY POINTS: • Treatment response assessment after locoregional therapy to hepatocellular carcinoma is fraught with multiple challenges given the varied post-treatment imaging appearance. • Ethiodized oil is unique in that its' radiopacity can serve as an imaging biomarker to help predict treatment response. • The pattern of deposition of ethiodozed oil has served as a mechanism to detect portions of tumor that are undertreated and can serve as an adjunct to enhancement in order to improve management in patients treated with intraarterial embolization with ethiodized oil.

Transarterial chemoembolization for advanced hepatocellular carcinoma without macrovascular invasion or extrahepatic metastasis: analysis of factors prognostic of clinical outcomes.

Objectives: To evaluate the safety and efficacy of TACE and factors predicting survival in patients with advanced hepatocellular carcinoma (HCC) without macrovascular invasion (MVI) or extrahepatic spread (EHS). Methods: This single-center retrospective study included 236 treatment-naïve patients who underwent TACE as first-line treatment for advanced HCC without MVI or EHS between January 2007 and December 2021. Results: Following TACE, the median overall survival (OS) was 24 months. Multivariate Cox regression analyses revealed that tumor number ≥4 (risk point: 3), maximal tumor size >10 cm (risk point: 2), Child-Pugh class B (risk point: 2), alpha-fetoprotein (AFP) concentration ≥400 ng/mL (risk point: 2), and presence of HCC rupture (risk point: 2) were risk factors significantly associated with OS. The expected median OS among patients with <2, 2-4, and 5-9 risk points were 72, 29, and 12 months respectively. The major complication rates were significantly lower in patients with maximal tumor size ≤10 cm than in those with maximal tumor size >10 cm (4% [5/138] vs 21% [21/98], p = 0.001). Conclusion: TACE may be safe and effective in selected patients with advanced HCC without MVI or EHS, with a median OS of 24 months. Patients with limited tumor burden, compensated liver function, absence of HCC rupture, and favorable biologic markers may benefit the most from TACE. TACE is not recommended for patients with huge HCCs (>10 cm) because of its high rate of major complications (21%).

CT-guided biopsies of unspecified suspect intrahepatic lesions: pre-procedure Lipiodol-marking improves the biopsy success rate.

BACKGROUND: While computed tomography (CT)-guided liver biopsies are commonly performed using unenhanced images, contrast-enhanced images are beneficial for challenging puncture pathways and lesion locations. This study aimed to evaluate the accuracy of CT-guided biopsies for intrahepatic lesions using unenhanced, intravenous (IV)-enhanced, or intra-arterial Lipiodol-marked CT for lesion marking. PATIENTS AND METHODS: Six-hundred-seven patients (men: 358 [59.0%], mean age 61 years; SD ±12.04) with suspect hepatic lesions and CT-guided liver biopsies were retrospectively evaluated. Successful biopsies were histopathological findings other than typical liver tissue or non-specific findings. Data was ascertained regarding the use of contrast medium for the biopsy-planning CT, unenhanced (group 1) vs. Lipiodol (group 2) vs. IV contrast (group 3). Technical success and influencing factors were insulated. Complications were noted. The results were analyzed using the Wilcoxon-Man-Whitney t-test, Chi-square test, and Spearman-Rho. RESULTS: Overall lesion hitting rate was 73.1%, with significantly better rates using Lipiodol-marked lesions (79.3%) compared to group 1 (73.8%) and group 3 (65.2%) (p = 0.037). Smaller lesions (<20 mm diameter) benefited significantly from Lipiodol-marking with 71.2% successful biopsy rate compared to group 1 (65.5%) and group 3 (47.7%) (p = 0.021). Liver cirrhosis (p = 0.94) and entity of parenchymal lesions (p = 0.78) had no impact on the hitting rate between the groups. No major complications occurred during the interventions. CONCLUSIONS: Pre-biopsy Lipiodol marking of suspect hepatic lesions significantly increases the lesion-hitting rate and is especially beneficial for biopsy of smaller targets below 20 mm diameter. Further, Lipiodol marking is superior to IV contrast for non-visible lesions in unenhanced CT. Target lesion entity has no impact on the hitting rate.

Iodine-Induced Hypothyroidism After Chemoembolization With Ethiodized Oil: A Case of Failure to Escape From Wolff-Chaikoff Effect (WCE).

Wolff-Chaikoff effect (WCE) is an acute physiologic response of the thyroid gland to high levels of iodine. The WCE is usually temporary, and the thyroid gland adjusts to high iodine levels within days or weeks. It is a protective mechanism and a failure to escape from it can result in thyroid dysfunction. Hypothyroidism is rare but more likely in patients who have had thyroid disease, are under stress, or are exposed to high iodine concentrations for a long time. The use of iodinated contrast media in radiologic studies or invasive medical procedures is a common source of excessive iodine exposure and can lead to thyroid disfunction. Despite the frequent use of contrast media in health care, the thyroid dysfunction associated with their use is poorly recognized. We report a patient who developed iodine-induced hypothyroidism after chemoembolization of recurrent chylothorax with ethiodized oil (Lipiodol®, Villepinte, France). This case report raises awareness of the importance of the physiologic WCE as well as the relevance of monitoring thyroid function when using iodinated contrast media in patients with specific risk factors.

Chemical Shift MRI Monitoring of Chemoembolization Delivery for Hepatocellular Carcinoma: Multicenter Feasibility of Initial Clinical Translation.

Purpose To demonstrate the feasibility of using chemical shift fat-water MRI methods to visualize and measure intrahepatic delivery of ethiodized oil to liver tumors following conventional transarterial chemoembolization (cTACE). Materials and Methods Twenty-eight participants (mean age, 66 years ± 8 [SD]; 22 men) with hepatocellular carcinoma (HCC) treated with cTACE were evaluated with follow-up chemical shift MRI in this Health Insurance Portability and Accountability Act-compliant prospective, institutional review board-approved study. Uptake of ethiodized oil was evaluated at 1-month follow-up chemical shift MRI. Measurements of tumor size (MRI and CT), attenuation and enhancement (CT), fat content percentage, and tumor:normal ratio (MRI) were compared by lesion for responders versus nonresponders, as assessed with modified Response Evaluation Criteria in Solid Tumors and European Association for the Study of the Liver (EASL) criteria. Adverse events and overall survival by the Kaplan-Meier method were secondary end points. Results Focal tumor ethiodized oil retention was 46% (12 of 26 tumors) at 24 hours and 47% (18 of 38 tumors) at 1 month after cTACE. Tumor volume at CT did not differ between EASL-defined responders and nonresponders (P = .06). Tumor ethiodized oil volume measured with chemical shift MRI was statistically significantly higher for EASL-defined nonresponders (P = .02). Doxorubicin dosing (P = .53), presence of focal fat (P = .83), and a combined end point of focal fat and low doxorubicin dosing (P = .97) did not stratify overall survival after cTACE. Conclusion Chemical shift MRI allowed for assessment of tumor delivery of ethiodized oil out to 1 month after cTACE in participants with HCC and demonstrated tumor ethiodized oil volume as a potential tool for stratification of tumor response by EASL criteria. Keywords: MRI, Chemical Shift Imaging, CT, Hepatic Chemoembolization, Ethiodized Oil Clinicaltrials.gov registration no.: NCT02173119 Supplemental material is available for this article. © RSNA, 2023.

Therapeutic lymphangiography with ethiodized oil for the management of lymphoceles and chylous ascites.

PURPOSE: The purpose of this study was to analyze the safety, technical success and clinical outcome of percutaneous intranodal ethiodized oil (Lipiodol®) based lymphangiography (L-LAG) for the management of refractory pelvic lymphoceles or chylous ascites using high doses of ethiodized oil. MATERIALS AND METHODS: Thirty-four patients presenting with symptomatic, refractory postoperative pelvic lymphocele or chylous ascites referred for theranostic, inguinal, intranodal L-LAG treatment between May 2018 and November 2021 were retrospectively included. There were 21 men and 13 women, with a mean age of 62.7 ± 16.2 (standard deviation) years (age range: 9-86 years), who underwent a total of 49 L-LAG for the management of lymphoceles (n = 14), chylous ascites (n = 18) or a combination of lymphocele and chylous ascites (n = 2). Clinical and radiological pre-interventional, procedural and follow-up data up to January 2022 were collected from patients' electronic medical records and imaging files. RESULTS: Technical success was obtained in 48 out of 49 L-LAG (98%). No complications related to L-LAG were noted. After one or more L-LAG, clinical success was obtained in 30 patients (88%) with a mean of 1.4 interventions per patient and mean intranodal injected volume of 29 mL of ethiodized oil per session. The remaining four patients (12%), with one or more failed L-LAG, underwent additional surgical intervention to definitively treat the postoperative lymphatic leakage. CONCLUSION: L-LAG using high doses of ethiodized oil is a minimally invasive, safe and effective treatment of postoperative pelvic lymphocele or chylous ascites. Multiple sessions may be needed to obtain a meaningful clinical result.

Facilitating combined biopsy and percutaneous microwave ablation of pulmonary ground-glass opacities using lipiodol localisation.

OBJECTIVES: Whether preoperative localisation is necessary and valuable for the microwave ablation (MWA) of small pulmonary lesions with ground-glass opacity (GGO) remains unclear. This study aimed to explore the role of the Chiba needle and lipiodol localisation techniques in facilitating MWA and biopsy. METHODS: This retrospective before-after study included patients with GGOs who underwent conventional MWA and biopsy treatment in our hospital between January 2018 and December 2019 (group A) or who underwent the Chiba needle and lipiodol localisation treatment before MWA and biopsy between January 2020 and December 2020 (group B). The characteristics of each patient and GGO lesion were collected and analysed to evaluate the safety and effectiveness of the localisation technique. RESULTS: A total of 122 patients with 152 GGOs and 131 patients with 156 GGOs underwent MWA and biopsy in groups A and B, respectively. The primary technique efficacy rate of MWA differed significantly between the two groups (A vs. B: 94.1% vs. 99.4%; p = 0.009). The positive biopsy rate in the two groups was determined by the difference (A vs. B: 93.4% vs. 98.1%; p = 0.042). The incidence of complications did not increase in group B. CONCLUSIONS: Compared with the unmarked group, the Chiba needle and lipiodol localisation technique improved the positive rate of biopsy and the initial effective rate of MWA, without significantly increasing the complication rate. KEY POINTS: • The localisation of the Chiba needle and lipiodol could improve the positive biopsy rate and the initial effective rate of MWA. • The localisation of the Chiba needle and lipiodol does not affect the subsequent MWA and biopsy and does not increase the incidence of pneumothorax and haemorrhage.

Balloon-occluded transarterial chemoembolization versus conventional transarterial chemoembolization for the treatment of single hepatocellular carcinoma: a propensity score matching analysis.

OBJECTIVES: To compare the safety and efficacy of balloon-occluded transarterial chemoembolization (B-TACE) and conventional TACE (C-TACE) in treating single hepatocellular carcinoma (HCC). METHODS: This single-center retrospective study included 523 patients who underwent C-TACE and 44 who underwent B-TACE as first-line treatment for single HCCs between November 2017 and December 2019. After propensity score matching (PSM), initial tumor response rates, local tumor progression (LTP), and major complication rates were evaluated in the 32 pairs of PSM matched population. RESULTS: In the 32 pairs of PSM cohort, B-TACE showed distinct superiority over C-TACE in treating single HCCs, with significantly higher initial complete response (CR) rates (93.8% vs. 62.5%, p = 0.005). During a median follow-up of 37 months (range, 12.7-46.5 months), 13 patients (40.6%) who underwent B-TACE and 16 (50%) who underwent C-TACE showed LTP of treated lesions. Size-based sub-group analysis showed that the median times to LTP in patients with medium- to large-sized tumors (> 3 cm) were significantly longer in the B-TACE (27 months; 95% confidence interval [CI], 19.7-34.3 months) than in the C-TACE (13 months; 95% CI, 3.9-22.1 months) group (p = 0.019). The major complication rate was similar between the two groups. CONCLUSIONS: B-TACE had a higher initial CR rate than C-TACE in treating single HCCs. Moreover, size-based subgroup analysis showed that time to LTP was significantly longer in patients with medium- to large-sized HCCs (> 3 cm) who underwent B-TACE rather than C-TACE. KEY POINTS: • B-TACE was superior to C-TACE in treating single HCC, with a significantly higher initial complete response rate after one session of treatment. • In size-based subgroup analysis, time to LTP was significantly longer in patients with medium- to large-sized HCCs (>3 cm) who underwent B-TACE rather than C-TACE. • B-TACE should be considered an alternative treatment option for medium- to large-sized single HCCs (>3 cm) in patients with a nonresectable condition and those who prefer nonsurgical treatment.

Conventional or Drug-Eluting Beads? Randomized Controlled Study of Chemoembolization for Hepatocellular Carcinoma: JIVROSG-1302.

Introduction: With the advent of effective systemic therapy, transarterial chemoembolization (TACE) is established as a highly effective locoregional treatment modality for carefully selected patients with hepatocellular carcinoma (HCC). This randomized controlled trial was conducted to clarify whether selective TACE with drug-eluting beads (DEB-TACE) loaded with epirubicin or selective conventional TACE (cTACE) with epirubicin-ethiodized oil might be more effective for obtaining complete response(CR) in patients with HCC. Methods: Between March 2016 and May 2019, Child-Pugh class A or B patients with unresectable HCC who were scheduled to receive selective TACE were randomly assigned at a 1:1 ratio to the DEB-TACE arm or the cTACE arm. The primary endpoint was the CR rate at 3 months, as evaluated according to the modified Response Evaluation Criteria in Solid Tumors by an independent review committee, and the secondary endpoints were the CR rate at 1 month and incidences of adverse events. Results: A total of 200 patients (DEB-TACE, 99 patients; cTACE, 101 patients) were enrolled in the study. The CR rates at 3 months and 1 month were significantly higher in the cTACE arm (75.2%, 84.2%) as compared with the DEB-TACE arm (27.6%, 35.7%). However, the frequencies of adverse events of any grade, including pyrexia (DEB-TACE vs. cTACE, 19.4% vs. 45.5%, p = 0.0001), fatigue (5.1% vs. 15.8%, p = 0.0194), malaise (11.1% vs. 25.7%, p = 0.0103), appetite loss (12.1% vs. 28.7%, p = 0.0048), abdominal pain (12.1% vs. 23.8%, p = 0.0423), increased serum bilirubin (22.2% vs. 48.5%, p = 0.0002), hypoalbuminemia (43.4% vs. 60.3%, p = 0.0154), increased serum aspartate aminotransferase (35.7% vs. 81.2%, p < 0.0001), and increased serum alanine aminotransferase (35.7% vs. 77.2%, p < 0.0001), were also significantly higher in the cTACE arm than in the DEB-TACE arm. Conclusions: Selective cTACE appeared to have higher CR rates for local tumor control as compared to selective DEB-TACE for HCC. However, the frequency of postembolization syndrome was also significantly higher in the cTACE group than in the DEB-TACE group. Thus, to achieve CR, cTACE may be selected over DEB-TACE in patients who can be expected to tolerate postembolization syndrome.

Usefulness of ethiodized oil and gelatin sponge particles for delaying the washout of indocyanine green from the liver in swine.

PURPOSE: To assess the effect of ethiodized oil (EO) and gelatin sponge particles (GS) on delaying the washout of indocyanine green (ICG) from the liver in swine. METHODS: Fifteen swine were divided into 3 groups: injection of a mixture of ICG and water-soluble contrast medium (CM) followed by embolization with GS (group A), injection of a mixture of ICG and EO (group B) and injection of a mixture of ICG and EO followed by embolization with GS (group C). The liver surface was observed using an infrared camera system during and at 1, 2, 3, and 6 h after the procedure to measure ICG contrast. Livers were removed at 6 h for histopathological examination. RESULTS: The contrast ratio between injected and non-injected regions at 6 h was 1.45 ± 0.44 in group A, 1.89 ± 0.37 in group B, and 3.62 ± 0.76 in group C. The contrast ratio in group C was significantly greater than that in groups A and B (P = 0.032 and 0.033, respectively). CONCLUSIONS: EO and GS delayed the washout of ICG from the liver in swine and may extend intraoperative navigation in clinical use. Indocyanine green (ICG) mixed with ethiodized oil (EO) was injected into the left hepatic artery in swine, and the artery was embolized with gelatin sponge particles (GS). We confirmed that ICG remained in the liver parenchyma up to 6 h after the procedure. EO and GS delayed the washout of ICG from the liver in swine.

Corrigendum: Preliminary Exploration of Transpedal Lymphangiography With High-Dose Ethiodized Oil Application in the Treatment of Postoperative Chylothorax.

[This corrects the article DOI: 10.3389/fmed.2021.754781.].

Oil-based versus water-based contrast media for hysterosalpingography in infertile women of advanced age, with ovulation disorders or a high risk for tubal pathology: study protocol of a randomized controlled trial (H2Oil2 study).

BACKGROUND: In women with unexplained infertility, tubal flushing with oil-based contrast during hysterosalpingography (HSG) increases ongoing pregnancy and subsequent live birth rates when compared to tubal flushing with water-based contrast. It is currently unclear whether an HSG with oil-based contrast also results in more ongoing pregnancies and live births in women of advanced age, women with ovulation disorders, and women with potential tubal pathology when compared to an HSG with water-based contrast. METHODS: We plan an international, multicentre, open-label, randomized controlled trial (RCT) studying three groups of infertile women who have an indication for tubal patency testing according to their treating physician and additionally; (1) are 39 years of age or older, (2) have an ovulation disorder or (3) have a high risk for tubal pathology based on their medical history. Women with an allergy for iodinated contrast medium are excluded, as are women with diabetes, hyperprolactinemia or untreated hyper- or hypothyroidism, and women with a partner with severe male infertility. After informed consent, women will be randomly allocated to the intervention, tubal flushing with the use of oil-based contrast during HSG or the control group, tubal flushing with the use of water-based contrast during HSG in a 1:1 ratio by the web-based system Castor. The primary endpoint will be ongoing pregnancy leading to live birth with conception within six months after randomization. Secondary outcomes are other pregnancy outcomes, used fertility treatments, adverse events and cost-effectiveness. Based on the expected ongoing pregnancy rate of 17% in the control group and 27% in the intervention group, the sample size will be 930 women (465 per group). Study inclusion is expected to be complete in four years. DISCUSSION: This multicentre RCT will establish whether, for women of advanced age, women with ovulatory disease, and women who have a high risk for tubal pathology, there is a fertility enhancing effect of tubal flushing with oil-based contrast during HSG and whether the use of this contrast medium is cost-effective. Trial Registration The study was prospectively registered in the Netherlands Trial Register on August 1st 2019 as 'H2Oil2' (reference number NL7925, https://www.trialregister.nl/trial/7925 ).

Immunology and Immunotherapy of Endometriosis.

Endometriosis is one of the most common gynecological and systemic diseases, with a remarkable immune background. Patients suffer from pain and fertility reduction. Due to the distinct immune component, an immunotherapeutic approach may gain importance in the future. In endometriosis, shifts in the cell fractions of the immune system are well known. Moreover, hypoxia concomitant with inflammation causes a disturbed immune response. The removal of endometriosis has a therapeutic effect, normalizes the immune disorders, and remains the most effective causative treatment in terms of pain and infertility. A key issue is whether a similar effect can be achieved for fertility with non-invasive immunotherapy where surgery is inadvisable or cannot be performed for various reasons. Numerous immunotherapy trials, including vaccines, were conducted on animals only, although the research is encouraging. Among the promising methods of non-specific immunotherapy is the administration of an ethiodized oil contrast. Moreover, due to the significant successes of immunotherapy in oncology, the possibility of immunotherapy affecting NK cells has been postulated. NK cells are responsible for the surveillance and apoptosis of ectopic cells. Expanding the arsenal of endometriosis treatment by immunotherapy is promising due to the significant contribution of immunological factors and the limitations of current treatment methods.