Spontaneous haemoperitoneum in pregnancy: Nationwide surveillance and Delphi audit system.

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.

Comparison of enhanced laparoscopic imaging techniques in endometriosis surgery: a diagnostic accuracy study.

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.

The FOAM study: is Hysterosalpingo foam sonography (HyFoSy) a cost-effective alternative for hysterosalpingography (HSG) in assessing tubal patency in subfertile women? Study protocol for a randomized controlled trial.

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.

Decidual Bleeding as a Cause of Spontaneous Hemoperitoneum in Pregnancy and Risk of Preterm Birth.

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.

Patient-Controlled Remifentanil Analgesia as Alternative for Pethidine with Midazolam During Oocyte Retrieval in IVF/ICSI Procedures: A Randomized Controlled Trial.

BACKGROUND: Pethidine with midazolam-induced conscious sedation for pain relief during transvaginal oocyte retrieval for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) procedures is associated with residual pain and oversedation. Patient-controlled analgesia (PCA) with remifentanil may serve as an alternative for pethidine. We investigated whether PCA remifentanil with diclofenac was associated with improved periprocedural pain relief than pethidine analgesia during IVF/ICSI procedures, with sedation scores, safety profiles, and patient satisfaction as secondary endpoints. METHODS: Seventy-six women were randomized to receive pethidine (2 mg/kg i.m.) and midazolam (7.5 mg)-induced conscious sedation (n = 40) or PCA with remifentanil and diclofenac (50 mg; n = 36). The Numeric Rating Scale, McGill Pain Questionnaire (MPQ), Ramsey Sedation Scale, and a 5-day pain-and-discomfort diary were used to evaluate pain and sedation levels. RESULTS: There were no differences in baseline characteristics and reproductive outcomes between both groups. Periprocedural pain scores were comparable for remifentanil and pethidine groups (4 [3 to 7] vs. 6 [4 to 8]; P = 0.13). Pain scores in the pethidine group were significantly lower at 30 minutes after the procedure (1 [0 to 3] vs. 2 [1 to 5]; P = 0.016), but at cost of higher sedation levels when compared to remifentanil (4 [2 to 4] vs. 2 [2 to 2]; P < 0.001). Patient satisfaction was higher, and MPQ scores were lower in the remifentanil group. There were no differences in safety profiles between both analgesics. CONCLUSIONS: Patient-controlled analgesia with remifentanil showed a similar reduction in pain scores than pethidine with midazolam during oocyte retrieval, while pethidine induced the highest pain relief after the procedure. However, PCA remifentanil was associated with less sedation and a better patient satisfaction profile than pethidine.

Spontaneous hemoperitoneum in pregnancy (SHiP) and endometriosis - A systematic review of the recent literature.

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.

Severe spontaneous hemoperitoneum in pregnancy may be linked to in vitro fertilization in patients with endometriosis: a systematic review.

OBJECTIVE: To evaluate existing evidence of a possible association in women with endometriosis between controlled ovarian hyperstimulation plus embryo transfer (COH-ET) and the occurrence of spontaneous hemoperitoneum in pregnancy (SHiP). DESIGN: Comprehensive review. SETTING: Not applicable. PATIENT(S): None. INTERVENTION(S): An electronic literature search up to February 2016 was conducted using Scopus and PubMed. MAIN OUTCOME MEASURE(S): The role of COH-ET in SHiP. RESULT(S): Controlled ovarian hyperstimulation plus embryo transfer may increase the severity or incidence of the rare condition known as SHiP. An analysis of published cases shows that bleeding often occurs from multiple or diffuse sites, mainly situated in the posterior pelvic cavity, making it difficult to control without interfering with the pregnancy itself. Spontaneous hemoperitoneum in pregnancy is linked to adverse perinatal outcomes, including stillbirth, neonatal mortality, and very low or low birth weight. In 14 cases a biopsy of the bleeding site was obtained, and in all cases, even in the absence of visible endometriosis, decidualization was documented. At present, the relatively small number of cases published prevents firm conclusions, although they are highly suggestive of a link between COH-ET in women with endometriosis and the occurrence and seriousness of SHiP. CONCLUSION(S): Spontaneous hemoperitoneum in pregnancy is a rare but potentially fatal complication for the pregnant woman and her unborn child. In vitro fertilization in women with severe endometriosis may be a risk factor for SHiP.