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Objective: To evaluate the incidence, diagnostic management strategies and clinical outcomes of women with spontaneous haemoperitoneum in pregnancy (SHiP) and reassess the definition of SHiP., Design: A population-based cohort study using the Netherlands Obstetric Surveillance System (NethOSS)., Setting: Nationwide, the Netherlands., Population: All pregnant women between April 2016 and April 2018., Methods: This is a case study of SHiP using the monthly registry reports of NethOSS. Complete anonymised case files were obtained. A newly introduced online Delphi audit system (DAS) was used to evaluate each case, to make recommendations on improving the management of SHiP and to propose a new definition of SHiP., Main Outcome Measures: Incidence and outcomes, lessons learned about clinical management and the critical appraisal of the current definition of SHiP., Results: In total, 24 cases were reported. After a Delphi procedure, 14 cases were classified as SHiP. The nationwide incidence was 4.9 per 100 000 births. Endometriosis and conceiving after artificial reproductive techniques were identified as risk factors. No maternal and three perinatal deaths occurred. Based on the DAS, adequate imaging of free intra-abdominal fluid, and identifying and treating women with signs of hypovolemic shock could improve the early detection and management of SHiP. A revised definition of SHiP was proposed, excluding the need for surgical or radiological intervention., Conclusions: SHiP is a rare and easily misdiagnosed condition that is associated with high perinatal mortality. To improve care, better awareness among healthcare workers is needed. The DAS is a sufficient tool to audit maternal morbidity and mortality., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: Spontaneous Haemoperitoneum in Pregnancy (SHiP) is a rare, but life-threatening complication of pregnancy that occurs predominantly in the third trimester of pregnancy and is associated with adverse pregnancy outcomes. Recently the largest case series in literature was published describing 11 Dutch cases of SHiP in women with endometriosis., Purpose: To investigate experiences, psychological impact, and quality of life after SHiP., Methods: A mixed-methods study was performed in women with a history of SHiP and their partners, including all known cases in the Netherlands between 2007 to 2015. Semi-structured in-depth interviews were organized between 2016 and 2017 and analysed thematically with a framework approach. Participants were asked to complete questionnaires investigating the impact of the event (Impact of Event Scale) and Quality of Life (RAND-36)., Results: Out of a total of 11 known cases, 7 women agreed for be individually interviewed. From these, all women described a freeze response at the moment of SHiP, combined with either an anxious reaction or a survival mode mind-set. All women received psychological help after SHiP. Still, the feeling of not being heard by the medical staff was present in all women. Other themes such as postpartum period, bonding with their child, effect on daily life, reviving the event, and future pregnancies were also identified in the interviews. In regard to their partners, 3 were interviewed, hence no saturation was achieved. Finally, the questionnaires showed lower Quality of Life and an impact score of ≥ 8/10., Conclusion: SHiP had a profound impact on women and their partners. Dedicated psychological help should be offered to all women after experiencing SHiP.

Study Question: What is the effect of uterine bathing with sonography gel prior to IVF/ICSI-treatment on live birth rates after fresh embryo transfer in patients with endometriosis?, Summary Answer: After formal interim analysis and premature ending of the trial, no significant difference between uterine bathing using a pharmacologically neutral sonography gel compared to a sham procedure on live birth rate after fresh embryo transfer in endometriosis patients (26.7% vs. 15.4%, relative risk (RR) 1.73, 95% confidence interval (CI) 0.81-3.72; P- value 0.147) could be found, although the trial was underpowered to draw definite conclusions., What Is Known Already: Impaired implantation receptivity contributes to reduced clinical pregnancy rates after IVF/ICSI-treatment in endometriosis patients. Previous studies have suggested a favourable effect of tubal flushing with Lipiodol ® on natural conceptions. This benefit might also be explained by enhancing implantation through endometrial immunomodulation. Although recent studies showed no beneficial effect of endometrial scratching, the effect of mechanical stress by intrauterine infusion on the endometrium in endometriosis patients undergoing IVF/ICSI-treatment has not been investigated yet., Study Design Size Duration: We performed a multicentre, patient-blinded, randomised controlled trial in which women were randomly allocated to either a Gel Infusion Sonography (GIS, intervention group) or a sham procedure (control group) prior to IVF/ICSI-treatment. Since recruitment was slow and completion of the study was considered unfeasible, the study was halted after inclusion of 112 of the planned 184 women., Participants/materials Setting Methods: We included infertile women with surgically confirmed endometriosis ASRM stage I-IV undergoing IVF/ICSI-treatment. After informed consent, women were randomised to GIS with intrauterine instillation of ExEm-gel ® or sonography with gel into the vagina (sham). This was performed in the cycle preceding the embryo transfer, on the day GnRH analogue treatment was started. The primary endpoint was live birth rate after fresh embryo transfer. Analysis was performed by both intention-to-treat and per-protocol., Main Results and the Role of Chance: Between July 2014 to September 2018, we randomly allocated 112 women to GIS (n = 60) or sham procedure (n = 52). The live birth rate after fresh embryo transfer was 16/60 (26.7%) after GIS versus 8/52 (15.4%) after the sham (RR 1.73, 95% CI 0.81-3.72; P -value 0.147). Ongoing pregnancy rate was 16/60 (26.7%) after GIS versus 9/52 (17.3%) in the controls (RR 1.54, 95% CI 0.74-3.18). Miscarriage occurred in 1/60 (1.7%) after GIS versus 5/52 (9.6%) in the controls (RR 0.17, 95% CI 0.02-1.44) women. Uterine bathing resulted in a higher pain score compared with a sham procedure (visual analogue scale score 2.7 [1.3-3.5] vs. 1.0 [0.0-2.0], P  < 0.001). There were two adverse events after GIS compared with none after sham procedures., Limitations Reasons for Caution: The study was terminated prematurely due to slow recruitment and trial fatigue. Therefore, the trial is underpowered to draw definite conclusions regarding the effect of uterine bathing with sonography gel on live birth rate after fresh embryo transfer in endometriosis patients undergoing IVF/ICSI-treatment., Wider Implications of the Findings: We could not demonstrate a favourable effect of uterine bathing procedures with sonography gel prior to IVF/ICSI-treatment in patients with endometriosis., Study Funding/competing Interests: Investigator initiated study. IQ Medical Ventures provided the ExEm FOAM ® kits free of charge, they were not involved in the study design, data management, statistical analyses and/or manuscript preparation, etc. C.B.L. reports receiving grants from Ferring, Merck and Guerbet, outside the submitted work. C.B.L. is Editor-in-Chief of Human Reproduction . V.M. reports grants and other from Guerbet, outside the submitted work. B.W.M. reports grants from NHMRC (GNT1176437), personal fees from ObsEva, Merck and Merck KGaA, Guerbet and iGenomix, outside the submitted work. N.P.J. reports research funding from Abb-Vie and Myovant Sciences and consultancy for Vifor Pharma, Guerbet, Myovant Sciences and Roche Diagnostics, outside the submitted work. K.D. reports personal fees from Guerbet, outside the submitted work. The other authors do not report any conflicts of interest. No financial support was provided., Trial Registration Number: NL4025 (NTR4198)., Trial Registration Date: 7 October 2013., Date of First Patient’s Enrolment: 22 July 2014., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: For surgical endometriosis, treatment key is to properly identify the peritoneal lesions. The aim of this clinical study was to investigate if advanced imaging improves the detection rate by comparing narrow-band imaging (NBI), near-infrared imaging with indocyanine green (NIR-ICG), or three-dimensional white-light imaging (3D), to conventional two-dimensional white-light imaging (2D) for the detection of peritoneal endometriotic lesions., Methods: This study was a prospective, single-center, randomized within-subject, clinical trial. The trial was conducted at Amsterdam UMC-Location VUmc, a tertiary referral hospital for endometriosis. 20 patients with ASRM stage III-IV endometriosis, scheduled for elective laparoscopic treatment of their endometriosis, were included. During laparoscopy, the pelvic region was systematically inspected with conventional 2D white-light imaging followed by inspection with NBI, NIR-ICG, and 3D imaging in a randomized order. Suspected endometriotic lesions and control biopsies of presumably healthy peritoneum were taken for histological examination. The pathologist was blinded for the method of laparoscopic detection. Sensitivity and specificity rates of the enhanced imaging techniques were analyzed. McNemar's test was used to compare sensitivity to 2D white-light imaging and Method of Tango to assess non-inferiority of specificity., Results: In total, 180 biopsies were taken (117 biopsies from lesions suspected for endometriosis; 63 control biopsies). 3D showed a significantly improved sensitivity rate (83.5% vs. 75.8%, p = 0.016) and a non-inferior specificity rate (82.4% vs. 84.7%, p = 0.009) when compared to 2D white-light imaging. The single use of NBI or NIR-ICG showed no improvement in the detection of endometriosis. Combining the results of 3D and NBI resulted in a sensitivity rate of 91.2% (p < 0.001)., Conclusion: Enhanced laparoscopic imaging with 3D white light, combined with NBI, improves the detection rate of peritoneal endometriosis when compared to conventional 2D white-light imaging. The use of these imaging techniques enables a more complete laparoscopic resection of endometriosis.

Background: The best surgical technique for managing ovarian endometriomas is still widely debated, though the current standard is stripping cystectomy. The use of plasma energy as a treatment option is a relatively new concept and little data is currently available on this method. The aim of this study was to determine the feasibility of the use of plasma energy in our daily clinical practice by looking at various postoperative outcomes., Methods: Twenty-one women previously diagnosed with uni- or bilateral ovarian endometriomas by transvaginal ultrasound, associated with pelvic pain and/or infertility, were included in this retrospective cohort study performed in a tertiary endometriosis referral centre. All women underwent endometriotic cyst ablation using plasma energy. At follow up postoperative pain, number of days until return to work following surgery, postoperative pregnancy rate and recurrence rate were determined., Results: This study demonstrates a significant decrease in the proportion of patients reporting pain postoperatively when comparing the number of patients with dysmenorrhoea, dyspareunia, and chronic pelvic pain pre- and postoperatively. In addition, the median number of days until women returned to work postoperatively was 9 days (interquartile range (IQR) 8-11 days). The postoperative pregnancy rate was 46.2% (6 of 13 women wishing to conceive) and the recurrence rate was 9.5%., Conclusions: In conclusion, plasma energy is a promising alternative to stripping cystectomy, as comparable results for postoperative pregnancy and recurrence rates can be observed. However, further research is necessary to draw firm conclusions when comparing these two techniques., (Copyright © 2019 Facts, Views & Vision.)

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.

Background: Tubal pathology is a causative factor in 20% of subfertile couples. Traditionally, tubal testing during fertility work-up is performed by hysterosalpingography (HSG). Hysterosalpingo-foam sonography (HyFoSy) is a new technique that is thought to have comparable accuracy as HSG, while it is less expensive and more patient friendly. HyFoSy would be an acceptable alternative for HSG, provided it has similar effectiveness in terms of patient outcomes., Methods/design: We aim to compare the effectiveness and costs of management guided by HyFoSy or by HSG. Consenting women will undergo tubal testing by both HyFoSy and HSG in a randomized order during fertility work-up. The study group will consist of 1163 subfertile women between 18 and 41 years old who are scheduled for tubal patency testing during their fertility work-up. Women with anovulatory cycles not responding to ovulation induction, endometriosis, severe male subfertility or a known contrast (iodine) allergy will be excluded. We anticipate that 7 % (N = 82) of the participants will have discordant test results for HyFoSy and HSG. These participants will be randomly allocated to either a management strategy based on HyFoSy or a management strategy based on HSG, resulting in either a diagnostic laparoscopy with chromopertubation or a strategy that assumes tubal patency (intrauterine insemination or expectant management). The primary outcome is ongoing pregnancy leading to live birth within 12 months after randomization. Secondary outcomes are patient pain scores, time to pregnancy, clinical pregnancy, miscarriage rate, multiple pregnancy rate, preterm birth rate and number of additional treatments. Costs will be estimated by counting resource use and calculating unit prices., Discussion: This trial will compare the effectiveness and costs of HyFoSy versus HSG in assessing tubal patency in subfertile women., Trial Registration: Dutch Trial Register (NTR 4746, http://www.trialregister.nl ). Date of registration: 19 August 2014.

Spontaneous Hemoperitoneum in Pregnancy (SHiP), an unprovoked (nontraumatic) intraperitoneal bleeding in pregnancy (up to 42days postpartum), is associated with serious adverse pregnancy outcomes. To evaluate the clinical consequences of SHiP and its association with endometriosis, a systematic review was conducted according to the PRISMA guidelines. PubMed, Embase.com and Thomson Reuters/Web of Science were searched for articles published since the latest review (August 2008) until September 2016. After assessment for eligibility, forty-four articles were included in this systematic review, describing 59 cases of SHiP. Endometriosis was present in 33/59 cases (55.9%), most often diagnosed prior to pregnancy. An association between the severity of SHiP and the stage of endometriosis could not be found. In the majority of cases, SHiP occurred in the third trimester of pregnancy (30/59 cases (50.8%)); women presented with (sub)acute abdominal pain (56/59 cases (94.9%)), hypovolemic shock (28/59 cases (47.5%)) and/or a decreased level of hemoglobin (37/59 cases (62.7%)). Signs of fetal distress were observed in 24/59 cases (40.7%). Imaging confirmed free peritoneal fluid in (37/59 cases (62.7%)). At time of surgery active bleeding was revealed in 51/56 cases (91,1%), originating from endometriotic implants (11/51 cases (21.6%)), ruptured utero-ovarian vessels (29/51 cases (56.8%)), hemorrhagic nodules of decidualized cells (1/51 cases (2.0%)) or a combination (10/51 cases (19.6%)). Median amount of hemoperitoneum was 1600mL (IQR 1000mL-2500mL). From the 45/59 cases (76.3%) in which surgical interventions was carried out during pregnancy, 7/45 cases (15.6%) reported a successful continuation of pregnancy. 5/59 cases reported recurrence of SHiP (recurrence rate 8.5%). The perinatal mortality rate was 26.9% (18/67 fetus), one maternal death was reported (1/59 cases (1,7%)). In conclusion, SHiP is a very serious complication of pregnancy, highly associated with adverse pregnancy outcomes and particularly relevant to women with endometriosis. Currently preventive measures are lacking, therefore increasing the awareness and recognition of SHiP is crucial to improve pregnancy outcomes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aim: Surgical management of patients with deep endometriosis (DE) of the rectum is difficult. Inflammation and subsequent adhesions due to DE impede access to the lower pelvis and may lead to complications during laparoscopic low anterior resection (LAR). Transanal minimally invasive surgery (TAMIS) is an alternative to an abdominal approach with potential advantages. The aim of this study was to provide a description of the TAMIS technique and to present the perioperative results of TAMIS and of conventional LAR in patients with DE., Method: A prospective consecutive cohort of patients undergoing rectal resection for DE had either conventional laparoscopic LAR or TAMIS rectal excision. Pre-, intra- and postoperative parameters, such as patient symptomatology, operating time and postoperative complications were compared between the groups. Quality of life was assessed using the EORTC-QLQ-29/30 questionnaires., Results: Between May 2014 and March 2016 a total of 11 rectal resections were performed, including five TAMIS procedures. No differences were found in the pre-, intra- or postoperative parameters. Two major complications occurred after conventional LAR and none after TAMIS. No differences in quality of life were found between the groups., Conclusion: Transanal minimally invasive surgery for DE of the rectum is feasible. Potential advantages include better surgical access to the pelvis, possibly fewer complications than LAR and no extraction incision with no difference in quality of life. Larger prospective studies are required to compare TAMIS with conventional rectal resection., (Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.)

Objective: To report pregnancy outcomes of SHiP (spontaneous haemoperitoneum in pregnancy) and the association with endometriosis., Design: Retrospective case note review., Setting: Dutch referral hospitals for endometriosis., Sample: Eleven women presenting with 15 events of SHiP., Methods: In collaboration with the Dutch Working Group on Endometriosis, unpublished cases of SHiP that occurred in the Netherlands between 2010 and 2015 were retrieved., Main Outcome Measures: Maternal and perinatal mortality and morbidity., Results: SHiP occurred predominantly in the second and third trimester of pregnancy. The earliest and major presenting symptom was an acute onset of abdominal pain, often combined with low haemoglobin levels or signs of fetal distress. Imaging was a diagnostic tool when free peritoneal fluid could be observed. For surgical treatment of the bleeding site, a midline laparotomy was mostly needed, the median estimated amount of blood loss was 2000 mL. No fetomaternal or perinatal mortality was reported, despite a high rate of preterm births (54.5%). In all women, endometriosis was diagnosed at a certain moment in time and therefore was probably involved in the pathogenesis of SHiP. Four women showed recurrence of SHiP. In one of these cases the second event of SHiP occurred in a subsequent pregnancy., Conclusion: Pregnancy outcomes of SHiP are improving when compared with previous reports, with absent fetomaternal and perinatal mortality in this recent series. Growing knowledge and adequate multidisciplinary intervention may have contributed to these favourable results. Increasing awareness of this serious complication of pregnancy is advocated, especially in women diagnosed with endometriosis., Tweetable Abstract: Growing awareness of SHiP is advocated, especially in women diagnosed with endometriosis., (© 2016 Royal College of Obstetricians and Gynaecologists.)

Background: Spontaneous hemoperitoneum in pregnancy (SHiP) is a rare, life-threatening event, particularly relevant to women with endometriosis or deciduosis., Methods: To determine the type of lesions leading to SHiP, a literature search was conducted among all published SHiP cases. From a total of 1,339 publications, information on pathological findings at the bleeding site with histological data was found in 24 case reports (16 pregnant, 8 postpartum)., Results: Among pregnant women (81% primigravida), 75% had a diagnosis of endometriosis and 25% of deciduosis. Among postpartum women (38% primiparous), 63% had a diagnosis of deciduosis and 25% of endometriosis. In all cases except one, decidual cells, with or without glandular structures, were present at the bleeding site. Decidual vessels were described in 7 cases and all exhibited vascular changes, including distension of the lumen, medial disorganization, or loss of vascular integrity. These vessels were significantly different from arteries seen in the secretory endometrium, showing that structural modifications take place during the initial stage of the remodelling of placental bed spiral arteries., Conclusions: During pregnancy, a link seems to exist between ectopic decidualization, particularly that occurring in endometriotic foci, and occurrence of SHiP. In addition, subclinical decidual bleeding may be a potential risk factor for preterm labour., (© 2017 S. Karger AG, Basel.)