Resolution Of Ectopic Pregnancy Research Articles

Developing and Implementing a Core Outcome Set for Ectopic Pregnancy

Background: Diagnosis of ectopic pregnancy (EP) has improved significantly in the last few decades, and RCTs remain the mainstay of assessing the effectiveness and safety of treatments. The pooling of individual RCT data is likely to provide the best evidence to inform clinical practice. However, currently published data in ectopic pregnancy has reported many different outcomes, which are themselves often defined and measured in distinct ways. The lack of consensus and level of variation results in an inability to compare the results of individual RCTs, and consequently directly impacts the usefulness of research to inform patients and clinicians in clinical practice. Aim: The development of a core outcome set to ensure outcomes important to key stakeholders are collected consistently will guide future research in ectopic pregnancy. Methods and Analysis: We have established an international steering group of stakeholders, including healthcare professionals, researchers, and individuals with lived experience with EP. We have identified potential outcomes from a comprehensive literature review of published randomised controlled trials. We have utilised a modified Delphi method to prioritize outcomes. Results: Key stakeholders have been invited to score potential core outcomes on a nine-point Likert scale, ranging from 1 (not important) to 9 (critical). 424 enrolled participants, with 86% completing round 1, comprising of 117 (32%) healthcare professionals, 237(64%) individuals with lived experience, 14(4%) researchers. Highly rates outcomes included the resolution of EP, psychological impact, and future fertility outcomes. Conclusion: Repeated reflection and rescoring should promote whole and individual stakeholder group convergence towards consensus ‘core’ outcomes over 3 rounds. Implementation of a core outcome set will enable collection and reporting of data in a standardised fashion. This will allow standardisation of research to guide and inform clinical practice and enhance patient centred care.

Efficacy and safety of expectant management in the treatment of tubal ectopic pregnancy: a systematic review and meta-analysis.

STUDY QUESTIONIs expectant management (EM) of tubal ectopic pregnancy (EP) an effective and safe treatment strategy when compared to alternative interventions?SUMMARY ANSWERThere is insufficient evidence to conclude EM yields a difference in the resolution of tubal EP, the avoidance of surgery or time to resolution of tubal EP when compared to intramuscular methotrexate in stable patients with β-hCG <1500 IU/l.WHAT IS ALREADY KNOWNThe utilisation of medical and surgical management for EP is well established. EM aims to allow spontaneous resolution of the EP without intervention.STUDY DESIGN, SIZE, AND DURATIONWe performed a systematic review and meta-analysis, searching Ovid MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, OpenGrey.eu, Google Scholar, cross-referencing citations and trial registries to 15 December 2019. There were no limitations placed on language or publication date. Search terms included tubal EP and EM as well as variations of these terms.PARTICIPANTS/MATERIALS, SETTING AND METHODWe considered studies that included patients with tubal EP, EM as a comparator, and that were randomised controlled trials (RCTs). The primary outcome was resolution of tubal EP. Secondary outcomes included avoidance of surgery and the time to resolution of EP. Two reviewers independently selected the studies, assessed bias and extracted data. Relative risk (RR) and mean difference with 95% CI were assessed using a random effects model. The certainty of evidence was scored according to Grading of Recommendations Assessment, Development and Evaluation guidelines.MAIN RESULTS AND THE ROLE OF CHANCEIn total, 920 studies were screened. Five studies were eligible for inclusion in the systematic review. Two RCTs comparing methotrexate to EM were identified as being eligible for inclusion in meta-analysis. No RCTs comparing surgery to EM were identified. Compared with EM, there was insufficient evidence that methotrexate yields a difference on resolution of tubal EP (RR 1.04, 95% CI 0.88–1.23, P = 0.67; two RCTs, moderate-certainty evidence), avoiding surgery (RR 1.10, 95% CI 0.94–1.29, P = 0.25; two RCTs, low-certainty evidence) or the time to resolution of tubal EP (−2.56 days (favouring EM), 95% CI −7.93–2.80, P = 0.35; two RCTs, low-certainty evidence).LIMITATIONS, REASONS FOR CAUTIONOnly two RCTs with a total of 103 patients were eligible for inclusion in this meta-analysis. Further RCTs comparing EM to medical and surgical management are needed and these should also report adverse events. Patient preference should also be evaluated.WIDER IMPLICATIONS OF THE FINDINGSWe found insufficient evidence of differences in terms of resolution, avoidance of surgery and time to resolution between expectant and medical management. Given the imprecision in the effect estimates as demonstrated by the wide CIs, resulting in the downgrading of certainty of evidence for all outcomes in this meta-analysis, larger RCTs comparing interventions for tubal EP are needed. Caution should be exercised when trying to decide between EM and methotrexate to treat tubal EP.STUDY FUNDING/COMPETING INTEREST(S)There was no funding for this study. NICM receives funding from various sources; none specifically supported this research. M.L. reports grants from Australian Women and Children's Research Foundation, outside the submitted work. M.A.: As a medical research institute, NICM Health Research Institute receives research grants and donations from foundations, universities, government agencies and industry. Sponsors and donors provide untied and tied funding for work to advance the vision and mission of the Institute. This systematic review was not specifically supported by donor or sponsor funding to NICM. M.A. reports a partnership grant with Metagenetics outside the submitted work. G.C. reports grants from Australian Women and Children's Research Foundation, personal fees from Roche and GE Healthcare, outside the submitted work. The remaining authors report no conflicts of interest.PROSPERO REGISTRATION NUMBERCRD42020142736

Prognostic accuracy of a novel methotrexate protocol for the resolution of tubal ectopic pregnancies

ObjectiveTo evaluate if a decreasing human chorionic gonadotropin (hCG) between day (D) 1 and D7 is an equal or better predictor of tubal ectopic pregnancy (EP) resolution following methotrexate (MTX) treatment than the current standard of care. Study designThis was a retrospective cohort prognostic accuracy study of women with a transvaginal ultrasound (TVS)-confirmed tubal EP (November 2006–December 2015). After single-dose MTX treatment, D4/7 hCG ratios were compared with that of D1/D7 in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) to predict EP resolution. ResultsTubal EP was diagnosed in 301/7350 (4.1%) women who underwent TVS for early pregnancy-related complaints. The patients were managed accordingly: expectant, 84/301 (27.9%); MTX, 65/301 (21.6%); surgery, 152/301 (50.5%). A D1/D7 hCG ratio ≤0.85 predicted successful resolution of tubal EPs (P < 0.001) treated with MTX with sensitivity 0.84 [95% confidence interval (CI), 0.69–0.94]), specificity 0.71 [95%CI, 0.48–0.89], PPV 0.84 [95%CI, 0.69–0.94], NPV 0.84 [95%CI, 0.69–0.94], which is comparable to the prognostic performance of the D4/7 protocol. ConclusionIn patients with tubal EP carefully selected for and treated with MTX, it may be reasonable to eliminate the D4 hCG in the follow-up algorithm.

Uterine Artery Embolization and Methotrexate Infusion as Sole Management for Caesarean Scar and Cervical Ectopic Pregnancies: A Single-Center Experience and Literature Review

IntroductionThe incidence of caesarean scar pregnancy (CSP) and cervical pregnancy (CP) has increased significantly in recent years. The related hemorrhage can be lethal and often needs hysterectomy. This study aims to assess the technical and clinical results of uterine artery embolization (UAE) combined with intra-arterial methotrexate (MTX) infusion for CSP and CP. MethodsA retrospective study was conducted for 11 patients (age range from 25–40 years, mean; 31.8 y) with CSP (7/11) and CP (4/11). The diagnosis was confirmed by elevated b-hCG levels (mean 31.245 mIU/mL) with sonography and/or magnetic resonance imaging. They were treated with UAE using particulate embolic material. In all patients, the infusion of MTX (50 mg/m2) was performed before UAE. Follow-up periods after UAE ranged between 6-24 months included weekly sonography and b-hCG level assessment. A literature review was performed using standard online search tools. ResultsIn 10 patients, UAE controlled active vaginal bleeding and reduced post-procedural b-hCG levels significantly by the second week. One patient presented with persistent elevated b-hCG level and vaginal rebleeding. The rebleeding was successfully controlled by second UAE procedure. The ectopic pregnancies were resolved, and the uterus was preserved in all patients. No major complications were detected. Normal menses resumed within 2 months after UAE. Two patients had subsequent natural successful intrauterine pregnancies. ConclusionUAE combined with intra-arterial MTX infusion resulted in resolution of ectopic pregnancies with control of hemorrhage and without hysterectomy in this small group of patients.

Comparison of Four Methods of Treating Ectopic Pregnancy: A Retrospective Cohort Study.

Objective To compare the results of expectant management, single and multidose methotrexate (MTX) and surgical management of ectopic pregnancy (EP). Materials and Methods In this retrospective cohort study, the original files of 233 patients who were treated for EP between May 2009 and December 2016 were analyzed. The patients were assigned to the following groups based on the applied treatment methods: Group 1, expectant management (n = 24), Group 2, single-dose MTX (n = 144), Group 3, multiple-dose MTX (n = 25), and Group 4, surgical intervention (n = 40). The following parameters were recorded and assessed: sociodemographic characteristics, pelvic ultrasonography findings (gestational sac, ectopic mass appearance, positive fetal cardiac activity), serum beta-human chorionic gonadotropin (β-hCG) levels on Day 0, Day 4, and Day 7, and surgical procedures in women that underwent surgical interventions. Results The sociodemographic characteristics were similar in all four groups. The percentage of ectopic mass and positive fetal cardiac activity was greater and the diameter of the mass was larger in Group 4 than in the other groups. The β-hCG values on Day 0, Day 4, and Day 7 were statistically different between the groups (p < 0.001). The cutoff value for the β-hCG change for EP resolution was 18% between Day 0 and Day 4 (AUC = 0.726, p < 0.001) and 15% between Day 4 and Day 7 (AUC = 0.874, p < 0.001). The probability of the requirement for an additional dose of MTX was 0.78 (95% CI 0.71 – 0.87; p < 0.001) times lower in patients who had a > 18% decrease in β-hCG levels from Day 0 to Day 4 in comparison to those who had a decrease < 18% from Day 0 to Day 4. The probability of the requirement for an additional dose of MTX was 1.64 (95% CI 1.25 – 2.16; p < 0.001) times greater in patients whose reduction in β-hCG levels from Day 4 to Day 7 was < 15% in comparison to those who had > 15% reduction from Day 4 to Day 7. Conclusions Additional dose requirements for patients with EP may be predicted early in the changes in β-hCG levels between Day 0 and Day 4. Further prospective studies are required to elucidate this issue.

Embarazo ectópico: Tratamiento médico

Objetivo: Evaluar la respuesta al metotrexato (MTX)en el tratamiento del embarazo ectópico no complicado. Diseño: estudio observacional prospectivo. Lugar: Instituto Latinoamericano de Salud Reproductiva. Participantes: Mujeres con embarazo ectópico no complicado. Intervenciones: entre loa os 1998 y 2005, 21 casos tuvieron diagnóstico ecográfico de tumoración anexial menor de 30 mm, ausencia de actividad embrionaria, ausencia de evidencia clínica y7o ecográfica de hemorragia interna y gonadotropina coriónica subunidad beta (hCG-β) menor de 3000 mUI/mL. tres paceintes tenían una sola trompa; en una de ellas se realizó tratamiento con MTX en un embarazo ectópico previo. El tratamiento lo realizó el oncólogo, por vía endovenosa u oral, utilizando 1 mg/kg de peso de MTX. El seguimiento fue clínico, ecográfico (que incluía estudio Doppler color) y hCG-β semanal. La autorización para recibir tratamiento con MTX fue por medio del consentimiento informado. principlaes medidas de resultados: Resolución del embarazo ectópico. Resultados: En 19 casos se resolvió satisfactoriamente el embarazo ectópico (90,9%), con una sola dosis de MTX, y en un caso se repitió la dosis a los 7 días. Un caso requirió tratamiento quirúrgico al tercer día de recibir MTX. En 9 pacientes (42,8%) hubo información de embarazos posteriores; uno de ellos correspondió al caso de embarazo ectópico recurrente. Conclusiones: El tratamiento con MTX, en casos seleccionados de embarazo ectópico, es una buena opción terapéutico, con 95,2% de resultados satisfactorios. La aceptación al tratamiento fue adecuada y no hubo efectos secundarios.

Triple tubal ectopic pregnancy resolution with medical management and outcome

Ectopic pregnancy is a life-threatening condition and is rising in incidence due to assisted reproductive techniques in the present era. Three simultaneous implantations in the fallopian tubes is very rare. A 39-year-old G4 A3 was diagnosed to have ectopic pregnancy 42 days after embryo transfer done elsewhere. She had recurrent early pregnancy losses of previous three pregnancies. The first two conceptions were after IUI for prolonged unexplained infertility, and the third pregnancy was spontaneous conception. On the day of admission, she was diagnosed to have two extra uterine gestational sacs of <2 cm on TVS and a β HCG of 4539 mIU/mL. Medical management with variable dose methotrexate was instituted after counseling. Her β HCG rose to 16,125 mIU/L and a review TVS revealed three gestational sacs, two on right side and one on the left side. The third sac measured 1.7 cm × 2.2 cm with small fetal elements after two doses of methotrexate and it was 16,102 mIU/L after completion of one course of methotrexate. She was treated with two doses of 200 mg of mifepristone and was given 2nd course of variable dose of methotrexate and followed by single dose of mifepristone. Her β HCG was 624 mIU/L after 76 days of ET and 33 days of starting therapy. She had spontaneous conception after 2 months of stopping therapy and delivered a healthy baby of 3 kg normally at term.

Single-dose methotrexate injection for treatment of ectopic pregnancy in women with relatively low levels of human chorionic gonadotropin

ObjectiveTo evaluate potential risk factors at admission for failed single-dose methotrexate injection in women with ectopic pregnancy. MethodsFile review of a tertiary medical center in Israel yielded 102 consecutive patients with ectopic pregnancy initially treated with single-dose methotrexate. Overall successful treatment was defined as normalization of human chorionic gonadotropin (hCG) levels after the first or second injection. ResultsThe mean pretreatment hCG level for the whole cohort was 2350±2955mIU/mL (median, 1187mIU/mL; 90th percentile, 5000mIU/mL). Resolution of ectopic pregnancy was achieved after a single injection in 76/102 (74.5%) women and after a second dose in 16/21 (76.2%) women. The remaining 10 (9.8%) patients were treated surgically after the first (5/76) or the second (5/26) dose. The overall success rate for methotrexate treatment was 90.2%. On multivariate stepwise logistic analysis, fetal cardiac activity was an independent predictor of a failed first methotrexate injection, and presence of a yolk sac and mass size were independent predictors of overall methotrexate failure and need for secondary surgery. ConclusionIn patients with ectopic pregnancy and relatively low levels of serum hCG, the most important predictors of overall failure of methotrexate injection were the presence of a yolk sac and mass size.

Manejo actual del embarazo ectópico en la paciente estéril y en la que se desea conservar su fertilidad futura. Actualización

This article aims to provide an update on the most effective treatment of ectopic pregnancy (EP) in patients wishing to preserve future fertility. We reviewed the literature on the topic and the results of our experience of the management of women with EP wishing to conserve future fertility. A brief historical overview of treatments for EP is provided and the main features of this entity (incidence, predisposing factors, current types of treatment, etc.) are analyzed. The diagnostic procedures and the advantages of early detection are described. Several treatment modalities (medical, surgical and combined) are outlined and their advantages and disadvantages and results in relation to resolution of EP, subsequent fertility and the possibility of EP recurrence are discussed. The prognostic factors indicating favorable results are reviewed. Reflections are provided on why conservative treatment (surgical and especially medical) has become the most widely accepted option. In conclusion, EP is increasingly frequent; early diagnosis is essential; whenever possible, conservative (especially medical) treatment is preferred since the results are excellent.

P437 Ultrasound follow up on ectopic pregnancy treated with multiple doses of methotrexate: a case report of ultrasonographic monitoring in the resolution of ectopic pregnancy

P437 Ultrasound follow up on ectopic pregnancy treated with multiple doses of methotrexate: a case report of ultrasonographic monitoring in the resolution of ectopic pregnancy

Single Dose Methotrexate In Treatment Of Ectopic Pregnancy: Review Of 32 Cases

Objective: To evaluate the efficacy of single dose intramuscular methotrexate in the treatment of ectopic pregnancy. Material and Methods: 32 patients who matched the inclusion criteria were enrolled. Success of treatment was defined as a resolution of ectopic pregnancy without performing surgical intervention. The cases in whom the treatment was successful and those that were not were compared for b-hCG values and clinical features. Results: b-hCG at diagnosis averaged 1293.9 mIU/ml. Of the 32 patients who received methotrexate, 26 were successfully treated. 23 patients (71.8%) received a single dose of methotrexate, 3 patients (9.3%) received an additional dose of methotrexate, 6 patients (18.7%) who had failed methotrexate required surgery for cure. The success rate of single-dose methotrexate was 79.3%. Conclusion: Our study shows that single dose systemic methotrexate treatment can be used as an option in unruptured pregnancies.

Enzymatic removal of asparagine-linked carbohydrate chains from heterodimer human chorionic gonadotrophin and effect on bioactivity

The native form of human chorionic gonadotropin (hCG) is a heterodimer protein with two asparagine (Asn)-linked carbohydrate chains on each subunit. Removal of the Asn-linked carbohydrate chains from hCG has resulted in hCG variants with consistent antagonistic properties on isolated murine cells. Specific and direct enzymatic removal of these carbohydrate chains from native hCG with resultant antagonistic properties has not been reported. An antagonist to the hCG/luteinising hormone (LH) receptor could be used as an anticancer therapy, emergency contraceptive or for therapeutic resolution of ectopic pregnancies. Therefore, our aim was to use enzymes to specifically remove Asn-linked carbohydrate chains from hCG in the heterodimer form and analyse the resultant bioactivity. Native hCG was treated with endoglycosidases, carbohydrate removal was analysed with electrophoresis and the hCG variants were tested for altered bioactivity with human and murine cells. Endoglycosidases were able to cleave most of the Asn-linked carbohydrate chains from the native hCG. The deglycosylated hCG demonstrated a 75% reduction in bioactivity on a murine Leydig cell line and a 65% reduction in bioactivity on human granulosa cells. These results exemplify a simple and efficient method for creating deglycosylated hCG and provide the most direct evidence for the importance of Asn-linked carbohydrate chains in maintaining hCG bioactivity.

Conservative management of live tubal pregnancies by ultrasound guided potassium chloride injection and systemic methotrexate treatment

Unruptured live tubal ectopic pregnancies are often managed surgically. Significantly elevated beta-hCG levels in these patients make treatment with methotrexate ineffective. However, achieving cardiac asystole via sonographically guided injection of potassium chloride (KCl) along with systemic methotrexate can improve treatment outcome. We describe the successful conservative management of 3 cases of unruptured tubal pregnancy with cardiac activity and significantly elevated beta-hCG levels. Under sonographic guidance, KCl was injected into the fetal heart to achieve cardiac asystole, and patients concurrently received a systemic methotrexate injection. The resolution of ectopic pregnancy was achieved and surgery was avoided in all 3 cases. Conservative management may thus be an option for patients with live ectopic pregnancies.

Serum human chorionic gonadotropin dynamics during spontaneous resolution of ectopic pregnancy

To study serum hCG dynamics in patients with ectopic pregnancy (EP) selected for expectant management. A prospective observational study. Helsinki University Central Hospital, Helsinki, Finland. One hundred eighteen patients, who were selected for expectant management among 493 patients with EP. Patients were examined every 1 to 3 days using transvaginal sonography and serum hCG determinations until hCG values < 10 IU/L (conversion factor to SI unit, 1 IU/L = 2.93 pmol/L) were reached. Laparoscopy was performed if the patient developed abdominal pains or intra-abdominal hemorrhage as revealed by sonography. Serum hCG level. The median gestational age at the start of follow-up in patients with a spontaneous resolution was 44 days and in patients requiring laparoscopy was 48 days. The success rate for a spontaneous resolution was 88% when the initial hCG level was < 200 IU/L but only 25% at levels > 2,000 IU/L. In the 77 patients with a spontaneous resolution, the initial median hCG concentration was 374 IU/L (range, 20 to 10,762 IU/L) and it decreased to normal in 4 to 67 days (mean, 20 days). In the 41 patients requiring laparoscopy the median initial hCG concentration was 741 IU/L (range, 165 to 14,047 IU/L); a normal level was reached in 3 to 43 days (mean, 12 days) after operation. Follow-up period before operation was 1 to 24 days (mean, 9 days). Laparoscopy was indicated in two thirds of the patients with a serum hCG level > 64% of the initial value after 7 days of follow-up. Spontaneous resolution of EP correlated with a low and rapidly decreasing hCG level.

Spontaneous resolution of ectopic pregnancy: initial appearance and evolution at transvaginal US.

Spontaneous resolution of ectopic pregnancy (EP) diagnosed with transvaginal ultrasound (US) was confirmed in 13 patients from May 1990 to December 1991. These cases accounted for 24% of the total number of EPs seen in our institution during the same period. These EPs ranged in size from 1 to 3.5 cm, and the beta subunit of human chorionic gonadotropin (beta-hCG) level was less than 1,000 IU/L in all patients. The serum beta-hCG levels became undetectable in 3-45 days (mean, 15.8 days). All EPs had completely resolved at follow-up transvaginal US performed 10-63 days (mean, 30 days) after initial examination. A gestational sac was present in three of these patients, and various degrees of vascularity were detected in four. Four of the resolving EPs increased in size. Four of the nine EPs without detectable flow initially became mildly vascular during the course of resolution. The authors concluded that spontaneous resolution of EP is not an uncommon phenomenon and occurs more commonly in patients with less advanced and less vascular EPs and serum beta-hCG levels less than 1,000 IU/L. EPs can increase in size and become more vascular during their course of resolution.

Spontaneous resolution of ectopic pregnancy

Spontaneous resolution of ectopic pregnancy

Spontaneous Resolution of Ectopic Pregnancy

Spontaneous Resolution of Ectopic Pregnancy

Nonsurgical therapy to preserve oviduct function in patients with tubal pregnancies

Surgical treatment for tubal pregnancies greatly impairs the subsequent fertility of patients because of salpingectomy and its complicated adhesions. Nonsurgical methotrexate therapy was developed to avoid such complications. Although early detection was of prime importance, resolution of ectopic pregnancy was obtained in 22 patients (95.7%) with methotrexate administration alone. Patency of the oviducts was evaluated with hysterosalpingography and/or laparoscopy in 19 patients after termination of methotrexate treatment. In 10 of 19 patients (52.6%), complete patency of the involved oviduct confirmed the validity of this regimen. Severe side effects were not observed in any of the 23 patients.