Ectopic pregnancies: Catch them early, treat them wisely!

INTRODUCTION: Ectopic pregnancy (EP) is a common condition encountered in Obstetrics and Gynecology. Different management protocols are currently available for haemodymanically stable patients but definitive recommendations is yet to be established, especially in developing countries with limited resources. AIM: To determine the outcome of EP in patients who are haemodynamically stable and to evaluate the factors that would predict success of specific management protocols in them. METHODOLOGY: Haemodynamically stable patients with HCG levels <1500 mIU/ml were recruited for expectant management, 1500-5000 mIU/ml were given MTX and those with >5000 mIU/ml were managed surgically. RESULTS: The overall success rate for expectant management was 92.7% and that with MTX was 80%. Baseline HCG values was found to be the only significant factor for predictor of success of treatment in the expectant group (P 0.05). The size of mass seen on USG did not have a significant correlation with beta HCG values (P 0.257). CONCLUSION: Of all the predictors for success of treatment that have been studied, the initial HCG value alone remains of paramount importance. Women with initial values of HCG <1500 mIU/ml can be offered expectant management, with a much better assurance of success for those with values <1000 mIU/ml. Those with values <5000 mIU/ml can be given MTX, with single dose being sufficient most often for <3000 mIU/ml. The presence of fluid restricted to the pelvis on USG can be managed non-surgically. One should not opt for surgical management only on the basis of size of the adnexal mass on USG.

Pristimerin Suppresses Trophoblast Cell Epithelial-Mesenchymal Transition via miR-542-5p/EGFR Axis.

BACKGROUND: Ectopic pregnancy (EP) is an ectopic embryo implantation occurred outside the uterine cavity. Nowadays, more attention have garnered in fast and effective treatment with less side effects. Pristimerin is known as the clinical application for anti-cancer, and the effect on EP therapy is still unclear. MATERIALS AND METHODS: Trophoblast cell line HTR-8/SVneo was used; then, we performed cell counting kit-8 assay, wound healing assay, flow cytometry and real-time polymerase chain reaction analysis (RT-PCR) to detect the cell viability, migration ability, apoptosis and epithelial-mesenchymal transition (EMT) under pristimerin treatment. In addition, public bioinformatic database was used to discover the connection between molecular and genes. Finally, we used miRNA transfection and RT-PCR techniques to determine the underlying molecular mechanism. RESULTS: We revealed that pristimerin inhibited trophoblast cells proliferation, migration and EMT, while induced trophoblast cell apoptosis. Furthermore, expression of miR-542-5p, AGO2 and EGFR was suppressed in HTR-8/SVneo cells post pristimerin treatment, and miR-542-5p silence showed the same effect. Combing pristimerin treatment and miR-542-5p silence showed a synergistic action. CONCLUSION: Pristimerin could be an effective treatment to block embryo implantation by miR-542-5p and EGFR down-regulation.

Shikonin suppresses trophoblast cell growth via regulation of GLI1, and p62 mediated caspase 8 activation.

Unruptured ectopic pregnancy (UEP) is a common cause of morbidity and, occasionally, of mortality in women of reproductive age. Pharmacological intervention is a common therapeutic approach for early-stage UEP. Herein, we investigated the cytotoxic effect and novel mechanism of shikonin, a natural naphthoquinone pigment purified from Lithospermum erythrorhizon, in human trophoblast cells. These data demonstrated that shikonin suppressed proliferation and induced apoptosis in a time-dependent manner in HTR-8/SVneo cells. Shikonin blocked autophagic flux and promoted p62 interaction with caspase 8, resulting in caspase 8 activation. Moreover, shikonin suppressed GLI1 expression, and GLI1 overexpression attenuated shikonin-induced cell apoptosis. Although silencing GLI1 slightly promoted cell apoptosis, p62 overexpression enhanced GLI1 silencing-induced cell apoptosis by activating caspase 8. Furthermore, rapamycin increased shikonin-induced cell apoptosis in HTR-8/SVneo cells, whereas 3-MA attenuated the cytotoxic effect of shikonin. In conclusion, shikonin suppressed trophoblast cell growth by silencing GLI1 and increasing p62 co-mediated activation of caspase 8, which suggested a potential novel therapeutic target for UEP.

Comparison of blood methotrexate level according to the route of administration in non-surgical treatment of ectopic pregnancy / 대한산부인과학회지

OBJECTIVE: This study was performed to compare the pharmacokinetics of methotrexate (MTX) in unruptured ectopic pregnancy according to the injection route. METHODS: Between May 2005 and August 2009, thirty-five patients of unruptured ectopic pregnancy in Chungbuk National University Hospital were treated medically either by intramuscular (IM) or intraamniotic (IA) injection of MTX according to the presence of fetal heart beat. Serum concentration of MTX was measured by fluorescent immunoassay using the blood samples withdrawn serially after its injection. RESULTS: The peak plasma MTX level was achieved at the 30-minute after injection sample in both groups. The mean peak plasma level of MTX in IM group was significantly higher than that of IA in 60-minute (2.296+/-0.64 umol/L vs 1.535+/-0.31 umol/L; p<0.006), 90-minute (1.9+/-0.51 umol/L vs 1.225+/-0.21 umol/L; p<0.002), and 240-minute (1.443+/-0.33 umol/L vs 1.077+/-0.18 umol/L; p<0.011) samples. The mean pretreatment plasma beta-hCG level was significantly higher in IA group, both tubal pregnancy (48,405+/-37,811.7 IU/L vs 18,452.05+/-19,205.34 IU/L; p<0.007) and cervical pregnancy (94,574.2+/-45,037.1 IU/L vs 42,446+/-34,778.12 IU/L; p<0.037), than those of IM group. But neither plasma MTX level nor pretreatment beta-hCG level were related to the treatment outcome. CONCLUSION: The plasma level of MTX increased rapidly in both IM and IA groups; the peak level reached at 30 minutes, and decreased to less than 1 umol/L after 240 minutes. Moreover, it was higher in IM group than IA group. Nevertheless, IA injection may be useful in patients who had high beta-hCG level or fetal heart beat, which are not usually indicated to medical treatment.

A Clinical Study of Unruptured Ectopic Pregnancies with the Treatment of Systemic or Local Methotrexate Injecton / 대한산부인과학회잡지

OBJECTIVE: To evaluate safety and efficacy of systemic or local methotrexate(MTX) injection to patients with unruptured ectopic pregnancy METHODS: From October 1995 to October 1999, 35 unruptured ectopic pregnancies were eligible for the conservative management. 25 tubal pregnancies, 4 cervical pregnancies, 4 pregnancies of previous cesarean section scar, and 2 cornual pregnancies diagnosed by ultrasonography & serumbeta-hCG were evaluated. Patients were treated with one of following three protocols : (1) A single-dose of 50mg/m2 of intramuscullar(IM) MTX(7 cases) (2) Two to four doses of 1.0mg/kg of IM MTX with citrovorum rescue(20 cases) (3) Transvaginal ultrasonogram-guided intra-amniotic instillation of 50mg methotrexate (8 cases) The mean age of these patients was 30.8 yrs (range 24-42) and gestational age at diagnosis ranged from 22-75 days (mean 47). Initial level of serumbeta-hCG ranged from 166.4-55363.8 mIU/mL (mean 9069.2). Patients were monitored with serumbeta-hCG titers three times per week ,and then weekly until the serumbeta-hCG level was less then 10 mIU/mL. RESULT: 31 of 35 patients (88.6%) were successfully treated and remaining 4 patients failed conservative therapy and so required surgery. Mean duration of resolution was 38.5 days (range 11-105). Side effect rate was 45.7% but severity of symptoms were so mild that no treatment was needed in most cases. CONCLUSION: Nonsurgical conservative management of MTX appears to be effective and safe treatment modality for some selected unruptured ectopic pregnancy. But further comparative studies and long-term follow-up are needed to evaluate reproductive outcome and reduce side effects of MTX.