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"BMC Pregnancy and Childbirth (2018) 18:289 https://doi.org/10.1186/s12884-018-1923-x  RESEARCH ARTICLE  Open Access  Management of Caesarean scar pregnancy with or without methotrexate before curettage: human chorionic gonadotropin trends and patient outcomes Sheng Wang, Rajluxmee Beejadhursing, Xiangyi Ma and Ya Li*  Abstract Background: To evaluate the effects of systemic methotrexate in cesarean scar pregnancy (CSP) patients treated with ultrasound-guided suction curettage. Methods: A retrospective review of all women presenting with CSP treated with ultrasound-guided suction curettage at Tongji Hospital, Wuhan, China, between January 1, 2013 and December 31, 2015, was conducted.",1,1,12,"1_1"
"Patients were grouped into those not treated with methotrexate before curettage (group 1), treated with methotrexate by intramuscular injection (group 2) and treated with methotrexate by intravenous injection (group 3).",1,12,12,"1_1"
"The clinical characteristics and outcomes were analyzed. Results: Among 107 patients, 47 patients were not treated with methotrexate before curettage, 46 patients had methotrexate administered by intramuscular injection and 14 patients had methotrexate injected intravenously.",1,12,13,"1_1"
"After treatment with methotrexate or curettage, the percentage changes and varied ranges of the hCG levels were also similar in all groups.",1,13,13,"1_1"
"However group 1 had significantly shorter hospital stays than the two groups that were treated with methotrexate (p<0.001). Conclusion: By grouping CSP patients who shared similar age, gravity, parity, fetal heart beat positive and gestational age at diagnosis, we found that the presence or absence of methotrexate treatment before curettage resulted in comparable outcomes and hCG levels, although patients who were not treated with methotrexate had significantly shorter stays in the hospital. Keywords: Cesarean scar pregnancy, Human chorionic gonadotropin, Methotrexate, Suction curettage, Protocol comparisons  * Correspondence: yalitjh@163.com Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China © The Author(s).",1,13,18,"1_1"
"Nevertheless, while the optimal management of CSP remains unclear, there is a variety of therapeutic strategies are currently in use, such as medical treatment with systemic MTX (methotrexate)$*, medical treatment with systemic and local MTX (methotrexate)$*, uterine curettage, hysteroscopy, resection of CSP through a transvaginal approach, uterine artery embolization, laparoscopy, and high-intensity focused ultrasound [2].",2,5,5,"1_1"
"Some complicated case may require combined application of several methods [3]. MTX (methotrexate)$* is a folic acid antagonist that inhibits the enzyme dihydrofolate reductase, thereby interfering with DNA synthesis in rapidly dividing cells such as trophoblasts.",2,5,6,"1_1"
"The first usage of MTX (methotrexate)$* in the treatment of ectopic pregnancy was reported by Tanaka et al. in an interstitial ectopic pregnancy in 1982 [4].",2,6,6,"1_1"
"Recently, MTX (methotrexate)$* has also used in treatment of cervical pregnancy, which is another form of ectopic pregnancy [5].",2,6,6,"1_1"
"CSP is a special type ectopic pregnancy and as such, some researchers have investigated the use of MTX (methotrexate)$* in conservative management or preliminary treatment of CSP prior to curettage [6, 7].",2,6,6,"1_1"
"The application of the systemic administration of MTX (methotrexate)$* in CSP is controversial.",2,6,6,"1_1"
"Semih Z. reported that systemic MTX (methotrexate)$* manifested similar results compared to local MTX (methotrexate)$* in terms of treatment success and reproductive outcomes [8].",2,6,6,"1_1"
"Some researchers have further suggested that systemic MTX (methotrexate)$* may be less effective in cases with higher serum hCG concentrations [9].",2,6,6,"1_1"
"The effects of systemic MTX (methotrexate)$* before curettage and whether it is recommended before curettage are still unknown.",2,6,6,"1_1"
"The aim of this study was to evaluate the hCG levels and outcomes in CSP patients treated with or without MTX (methotrexate)$* before curettage to assess the efficacy of MTX (methotrexate)$*. Methods This retrospective study analysed CSP patients treated at the Tongji Hospital, Wuhan, China, between 2013 and 2015.",2,6,7,"1_1"
"Patients who were unsuccessfully treated and then transferred to our hospital were excluded from this study. The protocol for treating CSP in our hospital included suction evacuation, chemotherapy with MTX (methotrexate)$*, hysteroscopy, laparoscopy, transabdominal approach or a combination of two or more treatment options.",2,9,10,"1_1"
"In this study, our aim was to only assess the effects of MTX (methotrexate)$* used before curettage.",2,10,10,"1_1"
"In the assessment of treatment outcome, we included patients who met the following criteria: (1) they were diagnosed with CSP and (2) either underwent medical treatment with MTX (methotrexate)$* by intramuscular injection, by intravenous injection or were not treated with MTX (methotrexate)$* before ultrasound-guided suction curettage.",2,10,10,"1_1"
"MTX (methotrexate)$* was administered according to the protocol originally described by Stovall et al. [11] in 1991.",2,10,10,"1_1"
"In brief, MTX (methotrexate)$* was administered intramuscularly two times (Day 0 and Day 4) or intravenously for 5 days (Day 0 to Day 5), with the same total dose of 50 mg/m2.",2,10,10,"1_1"
"Suction curettage was performed the day following MTX (methotrexate)$* treatment without awaiting a decline in serum hCG levels. The clinical characteristics of the patients, such as age, gravity, parity, and number of previous cesarean sections, were reviewed.",2,10,11,"1_1"
"Duration of hospitalisation was significantly shorter in group 1 (p<0.001). Data comparing patients who underwent MTX (methotrexate)$* therapy with patients who did not is displayed in Table 4.",3,80,81,"1_1"
"The outcomes of the treatment are the same when we further divided the MTX (methotrexate)$* group according to mode of administration; by intramuscular injection or by intravenous injection.",3,81,81,"1_1"
"There were no significant differences in intraoperative blood loss and rates of retained products of conception among MTX (methotrexate)$* patients and patients who were not treated with MTX (methotrexate)$* (p = 0.051 and p = 0.437, respectively).",3,81,81,"1_1"
"Duration of hospital stay was significantly shorter in the group that did not receive MTX (methotrexate)$* (p<0.001). Discussion In this study, the efficacy of MTX (methotrexate)$* use before curettage in managing CSP was assessed.",3,81,82,"1_1"
"We also found that using MTX (methotrexate)$* before curettage, either by intramuscular or intravenous injection, could significantly prolong the hospital-stay duration of patients.  Table 2 Human chorionic gonadotropin levels (mIU/ml) in patients not treated with MTX (methotrexate)$* (Group 1), treated with MTX (methotrexate)$* by intramuscular injection (Group 2) or treated with MTX (methotrexate)$* by intravenous injection (Group 3)  Mean ± SD/Rate  Group 1(n = 47)  Group 2(n = 46)  Group 3(n = 14)  A:Before MTX (methotrexate)$* treatment  ­  44,603.28 ± 38,615.27  25,648.86 ± 16,125.92  B:After MTX (methotrexate)$* treatment or before curettage  31,163.48 ± 28,626.86  37,712.91 ± 23,880.85  31,005.21 ± 23,029.37  C:Three days after curettage  2838.68 ± 3.10  4434.98 ± 4.90  3263.46 ± 2.93  B-A  ­  9664.21 ± 8993.10  22,506.29 ± 36,916.63  (B-A)/A  ­  0.27 ± 0.213  1.33 ± 3.451  C/B  0.085 ± 0.04  0.084 ± 0.05  0.79 ± 0.04  P value 0.080 0.196 0.077 0.219 0.273 0.674  Wang et al.",3,82,145,"1_1"
"Before curettage, some patients were treated with MTX (methotrexate)$*, either by intramuscular or intravenous injection. Systemic and local MTX (methotrexate)$* are two of the most widely used forms of management for CSP.",4,45,46,"1_1"
"Previous studies comparing the two treatments showed conflicting results likely due to differences in study design, supplementary treatments and various definitions of response [15, 16].  A recent review [2] showed that almost every fourth woman treated with systemic MTX (methotrexate)$* required additional treatment, and severe complications occurred in 13% of them.",4,46,48,"1_1"
"Therefore, one may wonder whether chemotherapy using MTX (methotrexate)$* is truly justified.",4,48,48,"1_1"
"Even though patients underoging MTX (methotrexate)$* treatment, had elevated hCG levels after the initial dose, 3 days after curettage, the hCG percentage change was also the same whether patients were treated with MTX (methotrexate)$* or not.",4,48,48,"1_1"
"In theory, MTX (methotrexate)$* may take some time to cause trophoblastic cytolysis.",4,48,48,"1_1"
"In addition, MTX (methotrexate)$* half-life is short, making it difficult for MTX (methotrexate)$* to reach the sac and embryo [17].",4,48,48,"1_1"
"Owing to of these setbacks, trophoblastic cells in CSP may be insensitive to MTX (methotrexate)$*.",4,48,48,"1_1"
"Another possibility is that not enough time was given after the MTX (methotrexate)$* treatment to observe a responsive effect.",4,48,48,"1_1"
"In consideration of these possibilities that may confound the effects of MTX (methotrexate)$*, we further analyzed the outcomes of the 3 groups. Massive hemorrhage is a major complication of CSP.",4,48,49,"1_1"
"Our hospital records have no instances where only MTX (methotrexate)$* was used to treat CSP and as a result, we could not assess the outcomes of standalone MTX (methotrexate)$* treatment.",5,5,5,"1_1"
"Hua Yang [18] reported that conservative MTX (methotrexate)$* treatment achieved satisfactory therapeutic effects, similar to uterine artery embolization (UAE) group, but the recovery time was significantly longer than that of the curettage group.",5,5,5,"1_1"
"In our study, the duration of hospitalization was also significantly longer in the MTX (methotrexate)$* groups.",5,5,5,"1_1"
"Therefore, based on our results, MTX (methotrexate)$* administration before curettage has no obvious remedial effects in patients managed with ultrasound-guided suction curettage and has an additional side effect of prolonging hospital-stay. This studying is primarily limited by its retrospective nature.",5,5,6,"1_1"
"Besides, the use of MTX (methotrexate)$* before curettage had no significant effects on intraoperative blood loss or retention of pregnancy tissue.",5,7,7,"1_1"
"Concurrently, the duration of hospital stay of patients treated with MTX (methotrexate)$* was significantly prolonged. Abbreviations CSP: Cesarean scar pregnancy; hCG: human chorionic gonadotropin; MTX: methotrexate; UAE: uterine artery embolization Availability of data and materials The datasets analyzed during the current study are available from the corresponding author on reasonable request. Authors' contributions YL conducted the experimental design.",5,7,10,"1_1"
"Combined systemic and Hysteroscopic intra-amniotic injection of methotrexate associated with Hysteroscopic resection for cervical pregnancy: a cutting-edge approach for an uncommon condition.",5,19,19,"1_1"
"Comparison of systemic and local MTX (methotrexate)$* treatments in cesarean scar pregnancies: time to change conventional treatment and follow-up protocols.",5,19,19,"1_1"
"Single-dose MTX (methotrexate)$* for treatment of ectopic pregnancy.",5,19,19,"1_1"
"Comparative efficacy and safety of local and systemic MTX (methotrexate)$* injection in cesarean scar pregnancy.",5,19,19,"1_1"
"Transvaginal ultrasound-guided local MTX (methotrexate)$* administration as the first-line treatment for cesarean scar pregnancy: follow-up of 18 cases.",5,19,19,"1_1"
"Therapeutic effects of uterine artery embolisation (UAE) and MTX (methotrexate)$* (MTX) conservative therapy used in treatment of cesarean scar pregnancy.",6,3,3,"1_1"
