Pretreatment hCG Research Articles

Readmission following methotrexate treatment for tubal pregnancy.

To identify risk factors for readmission following methotrexate treatment for tubal pregnancy. A retrospective study undertaken in two tertiary medical centers, including all individuals with medically treated tubal pregnancy (N = 511), between December 2009 and June 2021. Individuals with and without readmission following methotrexate treatment were compared. The primary outcome was the readmission rate. Secondary outcomes included the rate of post-discharge gynecological emergency department visits, tubal rupture rate, and the eventual need for surgical treatment. Readmission following methotrexate treatment occurred in 224/511 patients (43.8%). Most readmissions were due to abdominal pain or suspicion of treatment failure. Readmitted individuals were more likely to have a history of pelvic inflammatory disease and pretreatment serum human chorionic gonadotropin (hCG) >2000 mIU/mL. Both factors remained significantly associated with higher readmission rates in a logistic regression analysis (adjusted odds ratio [OR] 6.28, 95% confidence interval [CI] 1.30-30.45, and adjusted OR 2.73, 95% CI 1.83-4.07, respectively) after adjustment for age, endometriosis, tubal pathology, abdominal pain, and presence of yolk sac or embryo at diagnosis. A dose-dependent association was observed between pretreatment serum hCG levels and readmission rate (P < 0.001). Pretreatment hCG levels were also associated with tubal rupture and the eventual need for surgical treatment (P < 0.001 for both). A prediction model using hCG was not sufficiently accurate to predict readmission risk. Readmission following methotrexate treatment for tubal pregnancy was independently associated with previous pelvic inflammatory disease and pretreatment serum hCG levels. The latter was also associated with surgical intervention rate.

Analysis of Risk Factors for Intraoperative Bleeding in the Surgical Treatment of Cesarean Scar Pregnancy and Development of Predictive Models.

The objective of this study was to investigate the risk factors associated with cesarean scar pregnancy (CSP) and to develop a model for predicting intraoperative bleeding risk. We retrospectively analyzed the clinical data of 208 patients with CSP who were admitted to the People's Hospital of Leshan between January 2018 and December 2022. Based on whether intraoperative bleeding was ≥ 200 mL, we categorized them into two groups for comparative analysis: the excessive bleeding group (n = 27) and the control group (n = 181). Identifying relevant factors, we constructed a prediction model and created a nomogram. We observed that there were significant differences between the two groups in several parameters. These included the time of menstrual cessation (P = 0.002), maximum diameter of the gestational sac (P < 0.001), thickness of the myometrium at the uterine scar (P = 0.001), pre-treatment blood HCG levels (P = 0.016), and the grade of blood flow signals (P < 0.001). We consolidated the above data and constructed a clinical prediction model. The model exhibited favorable results in terms of predictive efficacy, discriminative ability (C-index = 0.894, specificity = 0.834, sensitivity = 0.852), calibration precision (mean absolute error = 0.018), and clinical decision-making utility, indicating its effectiveness. The clinical prediction model related to the risk of hemorrhage that we developed in this experiment can assist in the development of appropriate interventions and effectively improve patient prognosis.

Risk factors for methotrexate resistance in low-risk gestational trophoblastic neoplasia patients (FIGO score 0-4).

The challenge of methotrexate (MTX) resistance among low-risk gestational trophoblastic neoplasia (GTN) patients has always been prominent. Despite the International Federation of Gynaecology and Obstetrics (FIGO) score of 0-4 patients comprising the majority of low-risk GTN patients, a comprehensive exploration of the prevalence and risk factors associated with MTX resistance has been limited. Therefore, we aimed to identify associated risk factors in GTN patients with a FIGO score of 0-4. Between January 2005 and December 2020, 310 low-risk GTN patients received primary MTX chemotherapy in two hospitals, with 265 having a FIGO score of 0-4. In the FIGO 0-4 subgroup, 94 (35.5%) were resistant to MTX chemotherapy, and 34 (12.8%) needed multi-agent chemotherapy. Clinicopathologic diagnosis of postmolar choriocarcinoma (OR = 17.18, 95% CI: 4.64-63.70, P < 0.001) and higher pretreatment human chorionic gonadotropin concentration on a logarithmic scale (log-hCG concentration) (OR = 18.11, 95% CI: 3.72-88.15, P < 0.001) were identified as independent risk factors associated with MTX resistance according to multivariable logistic regression. The decision tree model and regression model were developed to predict the risk of MTX resistance in GTN patients with a FIGO score of 0-4. Evaluation of model discrimination, calibration and net benefit revealed the superiority of the decision tree model, which comprised clinicopathologic diagnosis and pretreatment hCG concentration. The patients in the high- and medium-risk groups of the decision tree model had a higher probability of MTX resistance. This study represents the investigation into MTX resistance in GTN patients with a FIGO score of 0-4 and disclosed a remission rate of approximately 65% with MTX chemotherapy. Higher pretreatment hCG concentration and clinicopathologic diagnosis of postmolar choriocarcinoma were independent risk factors associated with resistance to MTX chemotherapy. The decision tree model demonstrated enhanced predictive capabilities regarding the risk of MTX resistance and can serve as a valuable tool to guide the clinical treatment decisions for GTN patients with a FIGO score of 0-4.

PREDICT-GTN 2: Two-factor streamlined models match FIGO performance in gestational trophoblastic neoplasia

ObjectiveThe International Federation of Gynecology and Obstetrics (FIGO) scoring system uses the sum of eight risk-factors to predict single-agent chemotherapy resistance in Gestational Trophoblastic Neoplasia (GTN). To improve ease of use, this study aimed to generate: (i) streamlined models that match FIGO performance and; (ii) visual-decision aids (nomograms) for guiding management. MethodsUsing training (n = 4191) and validation datasets (n = 144) of GTN patients from two UK specialist centres, logistic regression analysis generated two-factor models for cross-validation and exploration. Performance was assessed using true and false positive rate, positive and negative predictive values, Bland-Altman calibration plots, receiver operating characteristic (ROC) curves, decision-curve analysis (DCA) and contingency tables. Nomograms were developed from estimated model parameters and performance cross-checked upon the training and validation dataset. ResultsThree streamlined, two-factor models were selected for analysis: (i) M1, pre-treatment hCG + history of failed chemotherapy; (ii) M2, pre-treatment hCG + site of metastases and; (iii) M3, pre-treatment hCG + number of metastases. Using both training and validation datasets, these models showed no evidence of significant discordance from FIGO (McNemar's test p > 0.78) or across a range of performance parameters. This behaviour was maintained when applying algorithms simulating the logic of the nomograms. ConclusionsOur streamlined models could be used to assess GTN patients and replace FIGO, statistically matching performance. Given the importance of imaging parameters in guiding treatment, M2 and M3 are favoured for ongoing validation. In resource-poor countries, where access to specialist centres is problematic, M1 could be pragmatically implemented. Further prospective validation on a larger cohort is recommended.

Expectant management of tubal pregnancies with human chorionic gonadotropin up to 2000 mIU/mL.

To describe outcomes of expectant management (EM) versus methotrexate (MTX) treatment in tubal pregnancies with pretreatment human chorionic gonadotropin (hCG) less than 2000 mIU/mL. This retrospective cohort from two tertiary hospitals included women with confirmed tubal pregnancies and pretreatment hCG <2000 mIU/mL. Exclusion criteria were unrecorded pregnancy site, unconfirmed diagnosis, and surgical treatment upon diagnosis. The primary outcome was eventual rate of surgical treatment. Between December 2009 and June 2021, 545 of 2114 (25.8%) women diagnosed with a tubal pregnancy met our inclusion criteria. We compared women who underwent EM (N = 201) with women who received MTX (N = 344). All women in the EM group had a declining trend of hCG. The MTX group had higher pretreatment hCG and higher rates of yolk sac or embryo presence on ultrasound. Eventual surgical treatment rate was higher in the MTX group compared with the EM group (39 [11.3%] vs. 9 [4.5%], P = 0.006), with no difference in the treatment failure rate or tubal rupture rate. In a subgroup analysis of women with pretreatment hCG between 1000 and 2000 mIU/mL, eventual surgical treatment, treatment failure, and tubal rupture rates did not differ between groups. Logistic regression analysis revealed that eventual surgical treatment was independently associated with hCG levels less than 1000 mIU/mL (adjusted odds ratio [aOR] 0.28, 95% confidence interval [CI] 0.14-0.56) and endometriosis (aOR 9.20, 95% CI 3.55-23.81). Expectant management of tubal pregnancies with pretreatment hCG levels less than 2000 mIU/mL and even between 1000 and 2000 mIU/mL and with a declining trend of hCG demonstrated lower or comparable rates of eventual surgical treatment, when compared with MTX treatment.

P-524 Fertility and subsequent pregnancy outcomes among women with tubal ectopic pregnancy treated with methotrexate

Abstract Study question What are the future fertility prospects and subsequent pregnancy outcomes among women with tubal ectopic pregnancy treated with methotrexate? Summary answer Pregnancy post-ectopic pregnancy occurred in 53% of women within 12 months following methotrexate treatment. Among those who became pregnant, ectopic pregnancy recurrence occurred in 16.8%. What is known already Concerns regarding ectopic pregnancy recurrence and future fertility predominate when counselling women about management options for tubal ectopic pregnancy treatment. Current UK National Institute for Health and Care Excellence guidance is based on low quality evidence and estimate long-term ectopic pregnancy recurrence rate of ∼18.5%. Further, they state that there are no differences in rates of subsequent pregnancy or ectopic pregnancy recurrence between ectopic pregnancy management methods. However, 30% of women managed with methotrexate experience treatment failure and require rescue surgery and subsequent pregnancy outcomes in this group are poorly understood. Study design, size, duration The data for this study were derived from a UK multicentre RCT of methotrexate and gefitinib versus methotrexate and placebo for treatment of ultrasound diagnosed definite or probable tubal ectopic pregnancy with pre-treatment hCG ≥1000 IU/L and ≤5000 IU/L (GEM3). The trial found adding gefitinib to methotrexate was not superior to placebo. This analysis reports trial participant follow-up data at 12-months examining post-treatment fertility, subsequent pregnancy outcomes and participant characteristics associated with ectopic pregnancy recurrence. Participants/materials, setting, methods Trial participants of GEM3 (as described above). Participants were contacted to provide follow-up data 12 months after randomisation to treatment. Where telephone contact was unsuccessful, electronic health records were reviewed to collect pregnancy outcome data. Post-treatment fertility and pregnancy outcomes were summarised using descriptive statistics and compared between groups using a chi-squared test, p&amp;lt;.05 signified statistical significance. Main results and the role of chance Pregnancy follow-up data was obtained for 283/327 trial participants. (167 participants were successfully contacted by telephone; the electronic health records were reviewed for 116 participants). 52.7% (149/283) of the trial participants became pregnant in the 12-month follow-up period. There was no difference in subsequent pregnancy rates between ‘methotrexate only’ and ‘methotrexate and rescue surgery’ groups. The surgical approach (salpingectomy vs salpingotomy) did not affect subsequent pregnancy rates. Among women who had a pregnancy in the follow-up period, a live birth was recorded in 65% of women (n = 93/142, n = 7 missing), any pregnancy loss (miscarriage, ectopic pregnancy, stillbirth, termination of pregnancy or molar pregnancy) was recorded in 43% of women (n = 59/137, n = 12 missing). Recurrent ectopic pregnancy was reported in 16.8% of women (n = 22/131, n = 18 missing). There was no difference in rates of live birth, pregnancy loss or recurrent ectopic pregnancy between methotrexate only and methotrexate and surgery groups or between type of surgical management groups (salpingectomy vs salpingotomy). Limitations, reasons for caution This study only reports on a 12-month follow-up period and this should be considered when interpreting comparatively low post-treatment pregnancy rates. We did not record which couples were trying-to-conceive post treatment and were therefore unable to stratify results by this variable or report subfertility rates. Wider implications of the findings This prospective dataset strengthens current understanding of the likelihood of ectopic pregnancy recurrence. Furthermore, it provides reassurance that women with tubal ectopic pregnancy managed with methotrexate requiring rescue surgery have similar post-treatment fertility and pregnancy outcomes to those successfully treated with methotrexate. Trial registration number ISRCTN67795930

P-467 Early (day 1–4) post-treatment serum hCG level changes predict single-dose methotrexate treatment success in tubal ectopic pregnancy

Abstract Study question How effective is the change between day 1 and 4 post-treatment serum hCG level at predicting single-dose methotrexate treatment success in tubal ectopic pregnancy (tEP)? Summary answer Any fall in day 1–4 serum hCG signifies an 85% (95%CI 76.8–90.6) likelihood of treatment success for tEP managed with single-dose methotrexate. What is known already For those with tEP managed by single-dose methotrexate, current guidelines advocate intervention if day 4–7 hCG fails to fall by ≥ 15%. The trajectory of hCG over day 1–4 has been proposed as an early indicator that predicts treatment success, allowing early reassurance for women. However, almost all prior studies of day 1–4 hCG change have been small or retrospective. Study design, size, duration This was a prospective cohort study of women with tEP (pre-treatment hCG of ≥ 1000 IU/L and ≤5000 IU/L) managed with single-dose methotrexate. The data were derived from a UK multicentre randomised controlled trial of methotrexate and gefitinib versus methotrexate and placebo for treatment of tEP (GEM3). For this analysis, we include data from both treatment arms. Participants/materials, setting, methods Participants were categorised by single-dose methotrexate treatment success or failure. Treatment success for this analysis was defined as complete tEP resolution to serum hCG &amp;lt;30 IU/L following single-dose methotrexate treatment only. Patient characteristics between groups were compared. Changes in day 1–4, 1–7 and 4–7 serum hCG were evaluated as predictors of treatment success through receiver operating characteristic (ROC) curve analysis. Test performance characteristics were calculated for percentage reduction thresholds including optimal thresholds. Main results and the role of chance A total of 322 women with tEP and hCG ≥1000 IU/L and ≤5000 IU/L were treated with single-dose methotrexate. The overall single-dose methotrexate treatment success rate was 59% (n = 189/322). Day 1–4, 1–7 and 4–7 serum hCG change predicted single-dose methotrexate treatment success with ROC area under curve 0.80 (95% CI 0.74–0.85), 0.86 (95% CI 0.81–0.91) and 0.89 (95% CI 0.85–0.93) respectively. Any fall between day 1 and day 4 hCG predicted single-dose methotrexate treatment success with a positive predictive value of 85%, negative predictive value 57%, sensitivity 58%, specificity 84%, positive likelihood ratio 3.6 and negative likelihood ratio 0.5. A less than 18% rise in day 1–4 serum hCG was identified as an optimal classification threshold and predicted treatment success with 82% positive predictive value, 69% negative predictive value, 79% sensitivity, 74% specificity, positive likelihood ratio 3.0 and negative likelihood ratio 0.3. Limitations, reasons for caution Our findings may be limited by intervention bias resulting from existing guidelines which influences evaluation of hCG changes reliant on day 7 serum hCG levels. Wider implications of the findings This large prospective cohort demonstrates the value of day 1–4 serum hCG changes in predicting single-dose methotrexate treatment success in tEP. We recommend clinicians provide early reassurance to women who have fall or modest (&amp;lt;18%) rise in day 1–4 serum hCG that their treatment will likely be effective. Trial registration number This study is a secondary analysis of the GEM3 trial (ISRCTN Registry ISRCTN67795930).

The indication and treatment outcome predictors of mifepristone treating ectopic pregnancy

Ectopic pregnancy is a life-threatening disease and is an important cause of pregnancy-related mortality. MTX is the primary conservative treatment medicine of ectopic pregnancy, and mifepristone is also a promising medicine. Through studying the ectopic cases at the third affiliated hospital of Sun Yat-Sen University, the study aims to analyze the indication and treatment outcome predictors of mifepristone. The data of 269 ectopic pregnancy cases treated with mifepristone during the year 2011-2019 were retrospectively collected. Logistic-regression analysis was used to analyze the factors affiliated with the treatment outcome of mifepristone. Then ROC curve was used to analyze the indication and predictors. Through logistic-regression analysis, HCG is the only factor related to the treatment outcome of mifepristone. The AUC of ROC curve predicting treatment outcome with pre-treatment HCG is 0.715, and the cutoff value of ROC curve is 372.66 (sensitivity 0.752, specificity 0.619). The AUC of 0/4 ratio predicting the treatment outcome is 0.886, and the cutoff value is 0.3283 (sensitivity 0.967, specificity 0.683). The AUC of 0/7 ratio is 0.947, and the cutoff value is 0.3609 (sensitivity 1, specificity 0.828). Mifepristone can be used to treat ectopic pregnancy. HCG is the only factor related to the treatment outcome of mifepristone. Patients with HCG less than 372.66U/L can be treated by mifepristone. If HCG descends more than 67.18% on the 4th day or 63.91% on the 7th day, it is more likely to have a successful treatment outcome. It is more precise to retest on the 7th day.

EMACO for treatment of gestational trophoblastic neoplasia: A multinational multicenter study

ObjectiveTo investigate the efficacy and toxicity of etoposide, methotrexate, actinomycin D alternating with cyclophosphamide, and vincristine (EMACO) for treatment of gestational trophoblastic neoplasia, and for factors independently associated with EMACO resistance and disease-specific death in an international cohort. MethodsMedical records of GTN patients who received EMACO during 1986–2019 from gestational trophoblastic disease centers from four countries including the USA, Thailand, Hungary, and Brazil, were retrospectively reviewed. Among 335 GTN patients, 266 patients who received EMACO as primary chemotherapy were included in the primary treatment group, and 69 patients who received EMACO after relapse/resistance to single-agent chemotherapy were included in the prior treatment group. ResultsThree-quarters (76.1%) of all patients achieved remission, and the survival rate was 89%. The prior treatment group had better outcomes than the primary treatment group relative to remission rate (87.0% vs. 73.3%, p = 0.014) and number of EMACO cycles to achieve remission (3 vs. 6 cycles, p < 0.001). Sustained remission increased to 87.2% in EMACO-resistant patients treated with later-line chemotherapy. Number of metastatic organs ≥2 (adjusted odds ratio [aOR]: 2.33, p = 0.049) was the only independent predictor of EMACO resistance among overall patients. Interval from index pregnancy ≥7 months (aOR: 4.34, p = 0.001), and pretreatment hCG >100,000 IU/L (aOR: 2.85, p = 0.028) were independent predictors of EMACO resistance in the high-risk subgroup. The only factor independently associated with disease-specific death was EMACO resistance (aOR: 176.04, p < 0.001). ConclusionsEMACO is an effective treatment for GTN. Number of metastatic organs and EMACO resistance were the independent predictors of EMACO resistance and disease-specific death, respectively.

Epithelioid trophoblastic tumor: A case series.

An epithelioid trophoblastic tumor (ETT) is an extremely rare gestational trophoblastic tumor. Cases of ETT present with abnormal vaginal bleeding in women of reproductive age group with marginally elevated beta human chorionic gonadotrophin (B-hCG) levels. Here, we describe a series of four patients (all were females) including histomorphology, immunoprofiles, and diagnostic difficulty of this rare entity. All cases were in their reproductive age group. The mean pre-treatment hCG level was 665.24 (mIU/mL). Microscopically, all cases had a tumor showing an epithelioid appearance arranged in large nests and sheets. Individual tumor cells were round to polygonal with abundant eosinophilic cytoplasm, with central vesicular nuclei and prominent nucleoli. Areas of hemorrhage, necrosis, and intercellular hyaline-like material deposition were identified in all cases (100%). Immunohistochemically, tumor cells in all cases showed diffuse positivity for AE1/AE3 and p63 (100%). GATA3 was available in one case (25%), which was positive in the tumor cells. In one case (25%), hPL was focally positive, and in one case (25%), it was negative. SALL4 was performed in two cases (50%) and was negative in tumor cells. The mean Ki67 labeling index was 19.2 (range 10-30%). All four patients underwent surgical intervention and were treated with hysterectomy. The mean follow-up in this series was 39.4 months (range 6-70), and all patients are alive to date with a mean survival of 32.8 months (range, 4-67).

PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n=4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P< .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.

Treatment of low-risk gestational trophoblastic neoplasia.

Low-risk gestational trophoblastic neoplasia (GTN), defined as FIGO/WHO score 0-6, is highly curable with an overall survival rate, which is approximately 100%. For most low-risk GTN patients, first-line single-agent chemotherapy with either methotrexate or actinomycin-D is recommended with overall complete human chorionic gonadotrophin (hCG) response rates of 60%-90% in mostly retrospective, non-randomised studies. The few randomised trials that exist are not appropriately powered or designed to define the optimal first-line treatment. Approximately 25%-30% of low-risk patients will develop resistance to initial single-agent chemotherapy with an increase in the FIGO score, a diagnosis of choriocarcinoma, higher pre-treatment hCG and the presence of metastatic disease being associated with an increase in the risk of resistance. The optimal treatment of patients scoring WHO 5 and 6 remains poorly defined given that approximately 70%-80% of these patients develop resistance to first-line single-agent chemotherapy, and there is an urgent need to refine the FIGO/WHO scoring system so that these patients can be identified for more intensive therapy from the outset. Despite this, almost all low-risk patients who experience treatment failure with first-line monotherapy will be cured with either sequential single-agent chemotherapy or multiagent chemotherapy with or without surgery. Given the associated increased short and longer-term toxicities associated with multi-agent chemotherapy, promising strategies to reduce the exposure of women to combination chemotherapy in low-risk disease have been investigated, including the use of carboplatin and immune check-point inhibitors. Further evaluation is required to define optimal patient selection, particularly with the use of immunotherapeutic agents given their significant increased costs and lack of longer-term safety data. Although there is a clear need to revise the FIGO/WHO (2000) scoring system, consistent international use of this is recommended to facilitate the comparison of data along with future focus in the development of international collaborative translational and clinical research, including randomised controlled trials.

The Use of Single Dose Methotrexate in the Management of Ectopic Pregnancy and Pregnancy of Unknown Location: 10 Years' Experience in a Tertiary Center.

ObjectiveTo study factors associated with the success of single dose methotrexate (MTX) treatment in women with ectopic pregnancy.MethodsThis is a retrospective study of women (n=110) with ectopic pregnancy and treated with single dose of MTX. The clinical presentations, transvaginal sonography (TVS) findings, pretreatment beta-human chorionic gonadotropin (β-HCG), and progesterone values were compared between the treatment success (Group S) and treatment failure (Group F) groups.ResultsThe overall success rate of treatment with single dose of MTX was 75.45%. The majority of patients in both groups presented with pain and bleeding (~55%), and bleeding only was the presenting symptom in about 20% of patients. Only 3 patients (3.61%) in Group S required a repeat dose of MTX. In contrast, 51.8% of the Group F patients required a repeat dose. The mean pretreatment β-HCG level was 2.3 times higher in Group F than in Group S (1734±1684 vs 4036±2940 IU/L). The data showed a β-HCG level of 3924IU/L as a suitable cut-off value with 76.19% sensitivity and 62.5% specificity to predict MTX treatment success. History of ectopic pregnancy had no relation with success/treatment failure or a repeat dose. None of the TVS findings were related to the outcome of the treatment, whereas pretreatment HCG level was a significant predictor.ConclusionThe single dose MTX treatment was successful in 75.45% (83/110) of cases, with 3.61% (3/83) requiring a repeat dose of the drug. Pretreatment β-HCG level is a significant predictor of the treatment outcome.

SUN-009 Variable Presentation of Two Patients with Gestational Trophoblastic Disease and Hyperthyroidism

Background: Gestational trophoblastic disease (GTD) represents a group of tumours caused by abnormal proliferation of trophoblastic cells, including molar pregnancy. Elevated β-hCG levels are an established marker for the presence of the disease and useful for monitoring. Due to the shared structural homology of β-hCG and TSH, hyperthyroidism can occur. Clinical Cases: We present two patients with GTD associated with hyperthyroidisim. Case 1, a 20 year old female (G1P0) presented to the emergency department complaining of vaginal bleeding associated with abdominal pain. She was estimated to be 13 weeks. Laboratory evaluation were β-hCG 648 324 IU/L, TSH 0.06 (0.35 - 4.94 mIU/L, free T4 23.2 (9.0 - 19.0 pmol/L, Hb 8.0 (11.6 - 16.4 g/dL). Ultrasound revealed molar pregnancy. She underwent uterine evacuation, thereafter complicated with thyroid storm (Burch Wartofsky score = 45). Post- operative vitals were BP 192/112, pulse rate 120 bpm and temperature 360C. She was managed in high care on labetolol, carbimazole, lugol’s iodine and hydrocortisone.She was subsequently referred to Medical Oncology for further management. Histology sample obtained in theatre confirmed complete molar pregnancy.Her staging CT scan indicated the presence of small lung nodules, suggesting metastatic disease. The patient’s FIGO/WHO score was III: 2. At the time of preparing this study, she had already received 7 weeks of methotrexate intramuscularly and still had detectable β-hCG levels.Case 2 was a 31 year old female presented similarly. This was her second pregnancy (G2P1), 12 weeks by dates. Her vitals were BP 141/74, pulse rate 110 bpm and temperature 36oC. The Ultrasound revealed larger for gestational age uterus with cystic structures in utero. Her quantitative β-hCG was significantly elevated (> 1 500 000 IU/L) she was thyrotoxic [TSH (<0.1 (0.34 - 4.94 mIU/L) free T4 (47.2 (9.0 - 19.0 pmol/L)], however did not develop thyroid storm (Burch Wartofsky score = 20). This patient also underwent uterine evacuation and did well post operatively. She was treated for her thyrotoxicosis with carbimazole, propranolol and thiamine. Further management was by Medical Oncology. Histological examination was in keeping with a partial mole.Her staging CT scan showed no metastasis, and had a FIGO/WHO score of 1: 4 due to her pre-treatment hCG of >1.5 million IU/L. She received 7 cycles of intramuscular methotrexate from which she achieved and maintained suppressed β-hCG levels (<1 IU/L). Conclusions: This study has demonstrated that the β-hCG levels may not always correlate with disease severity and prognosis.When comparing the two patients Case 1 had lower levels of β-hCG and of free T4 than Case 2, however was clinically more unwell, developed thyroid storm and had metastatic disease. Case 2 had hCG levels almost double those of Case 1, wsa stable and her levels decreased much quicker reaching undetectable levels

Gestational Trophoblastic Neoplasia: Clinical and Therapeutic Profile in Madagascar

Gestational trophoblastic disease (GTD) develops from abnormal cellular proliferation of trophoblasts following fertilization. This includes complete and partial hydatidiform mole (HM) and gestational trophoblastic neoplasia (GTN). The aim of this study was to report the epidemiological, clinical and therapeutic profile of gestational trophoblastic neoplasia (GTN) over period of ten years in the department of Oncology Radiotherapy at the University Hospital Joseph Ravoahangy Andrianavalona (HJRA) Antananarivo Madagascar. Medical records of women diagnosed with GTD in the department of Oncology Radiotherapy at HJRA from January 1st, 2007 to September 2017 were retrospectively reviewed. Only patients with the FIGO diagnosis GTN were included, while those with the histological diagnosis of hydatidiform mole (HM), also sometimes classified as GTD, were not included in this study. Also excluded were all cases with incomplete or missing data. Twenty four patients were included. Median age of patients at the time of diagnosis was 37 years (range 18 - 60). Most patients developed GTN following molar pregnancy (75%), had disease duration from antecedent pregnancy of less than 6 months (58.20%), and had the pre-treatment hCG level more than 10,000 IU/L (58.27%). At diagnosis, 14 patients (58.33%) had localized disease (M0). Most common metastatic sites at initial diagnosis were the liver and brain (20.83%). After a median follow-up from initial diagnosis of six months (range 1 - 24), 58.33% were lost to follow up. This represented an increase in the percentage of patients lost to follow up prior to completion of therapy, when compared with our previous results for an earlier time period. GTN in Malagasy woman displays an aggressive clinic profile. Finding ways to increase treatment compliance provides the best way to minimize recurrences of this potentially deadly disease.

1225 Early Prediction of Methotrexate Treatment Success by 24‐Hour Pretreatment HCG Increment and Day 1-4 HCG Ratio

Study Objective Several studies have tried to identify early markers for treatment outcome after methotrexate (MTX) treatment for an ectopic pregnancy (EP) including pretreatment and day 4 hCG levels and corresponding ratio, and hCG increment during the initial 24 hours following treatment, with conflicting results. We aim to re‐evaluate the role the aforementioned markers in the earlier identification of treatment success in a large cohort of women. Design A retrospective cohort study. Setting A tertiary medical center during 2010-2018. Patients or Participants All women diagnosed with an EP and treated by intention of single-dose regimen of intramuscular MTX. Interventions A comparison of maternal and gestation characteristics was performed between treatment success and failure groups. Measurements and Main Results 292 women treated with single-dose intramuscular MTX for EP during were included in this study. Treatment success rate with a single dose of MTX of the overall cohort was 62.7% (183/292). Only two independent determinants were significantly associated with the treatment success: initial 24 hours hCG percentage of increment (adjusted odds ratio [OR]: 1.82; 95% confidence intervals [CI]: 1.26, 2.63; p Conclusion A low rise in hCG levels 24 hours prior to treatment with MTX, alongside a decline in hCG levels from day 1 to day 4 may predict success of medical treatment of EP.

Low-risk gestational trophoblastic neoplasia outcome after treatment with VMP regimen from 2005 to 2017

ObjectiveTo evaluate the efficacy and toxicity of VMP regimen applied to the patients with low-risk gestational trophoblastic neoplasia (LR-GTN) treated in Anhui provincial hospital. Materials and methodsBetween 2005 and 2017, 87 patients with low-risk gestational trophoblastic neoplasia received VMP regimen, consisted of vincristine (VCR), methotrexate (MTX) and platinum (cisplatin, carboplatin or nedaplatin), 68 of whom received VMP as their first-line chemotherapy, and 19 methotrexate-failed patients received VMP regimen as their second-line chemotherapy. The staging and scoring system was based on International Federation of Gynecology and Obstetrics (FIGO 2000) criteria. We describe and analyze their baseline characteristics, remission/resistance/recurrence rates, adverse reactions and prognosis. ResultsThe first-line VMP protocol can achieve an 83.8% remission rate and it tended to develop resistance when the pretreatment β-hCG reaches 7503.5 IU/L, and can achieve complete remission with FAV and EMA-CO as the salvage regimen. Among the 19 methotrexate-failed patients, 2 of whom were yet resistant to VMP regimen, followed by several courses of salvage chemotherapy such as FAV and EMP, and achieved 89.5% remission rate in second-line VMP group. Resistance to this regimen was obviously related with higher pre-treatment HCG whether used as primary or salvage treatment. Severe myelosuppression (grade 3 or 4) was shown in 4 (5.9%) of 68 cases, of which none was grade 4. ConclusionFor patients diagnosed with LR-GTN VMP regimen was a safe and effective treatment with a high rate of remission.

Human chorionic gonadotropin value and its change prior to methotrexate treatment can predict the prognosis in ectopic tubal pregnancies.

PurposeTo investigate the role of beta‐human chorionic gonadotropin (HCG) level and its change prior to methotrexate (MTX) treatment as predictors of treatment success and to access the posttreatment observation period for ectopic tubal pregnancy.MethodsClinical data of 41 females treated with MTX for tubal pregnancies were reviewed and analyzed retrospectively.ResultsAmong 41 patients, 34 achieved complete resolution without surgery. No statistically significant difference was observed in the presence of hemorrhagic ascites, serum progesterone levels, or diameters of adnexal mass between the MTX success and failure groups. Serum HCG levels on the day of MTX administration (day 1) were significantly lower in the MTX success group. Moreover, % HCG change per day, which represents the increment ratio of HCG prior to MTX treatment, was significantly lower in the MTX success group. Receiver operating characteristic (ROC) curves demonstrated that the treatment success was predicted by % HCG change per day less than +12.6% per day with a sensitivity of 87% and a specificity of 71%. The duration from treatment to complete recovery was strongly correlated with day 1 HCG levels.ConclusionsPretreatment HCG change is a significant predictor of therapeutic success of MTX treatment, and the treatment period may be predicted from initial HCG levels.

Predictive factors of methotrexate treatment success in ectopic pregnancy: A single-center tertiary study.

OBJECTIVE:It is controversial whether medical or surgical treatment options have more successful results in ectopic pregnancy treatment. Although high pretreatment serum hCG levels have been known to be the most important predictor, the appropriate treatment modality for a specific range of hCG level remains unclear. Furthermore, the variables that make a patient a bad candidate for single-dose methotrexate treatment is unclear. The aim of this study was to identify predictive factors associated with the success of single-dose methotrexate treatment in women with ectopic pregnancy.METHODS:In this retrospective study, 101 women with tubal ectopic pregnancies who had been treated with single-dose methotrexate were selected. The gestational ages, pretreatment hCG values, ectopic mass size, and fluid presence in the abdomen were compared between the groups.RESULTS:The mean age of the patients was 30.6±5.8 (range, 19–42) years, and the gestational age at first injection was 7.0±2.13 (range, 2.3–13.6) weeks. The overall treatment success rate was 77.2% (n=79). The mean duration of hospital stay was 4.21±1.89 days in the successfully treated group and 6.92±2.13 days in the failure group (p<0.05). The rate of treatment failure in patients with abdominal fluid was 37.8%, and it was 12.7% in the non-fluid group (p=0.03). hCG values on days 1, 4, and 7 were significantly higher in the unsuccessful group (3887–2589 mIU/mL, 2814–1287 mIU/mL, and 1119–285 mIU/mL, respectively; p<0.05). The cutoff hCG value, which determined the failure of methotrexate treatment, was found to be 1362 mIU/mL.CONCLUSION:In present study, patients with hCG value <1362 mIU/mL were found to be good candidates for methotrexate treatment. Although not strictly decisional, this hCG threshold level can be used to decide on the likelihood of methotrexate success or failure. Detection of abdominal fluid on ultrasonography also can be assessed as a bad prognostic factor, but size of ectopic mass does not correlate with methotrexate treatment success.

Postmolar choriocarcinoma: An independent risk factor for chemotherapy resistance in low-risk gestational trophoblastic neoplasia

ObjectiveTo evaluate the effect of a clinicopathologic diagnosis of choriocarcinoma (CCA) on clinical characteristics, extent of disease, and response to chemotherapy in low-risk gestational trophoblastic neoplasia (GTN). MethodsWe reviewed the records of 678 patients with low-risk GTN (FIGO stage I and stages IIIII, score<7) treated from 1962 to 2009. Patient and disease characteristics, treatment course, as well as clinical response and survival were analyzed retrospectively. Patients with a clinicopathologic diagnosis of CCA were compared to those with a clinical diagnosis of postmolar GTN. ResultsOf 678 women with low-risk GTN, 129 (19.0%) had a clinicopathologic diagnosis of CCA. Patients with CCA had higher parity (median 1 vs. 0, p=0.003), more pretreatment human chorionic gonadotropin (hCG) levels at >100,000mIU/mL (12.7% vs. 5.9%, p=0.009), longer duration of disease (19.6 vs. 9.9weeks, p<0.001), and higher FIGO scores (median 2 vs. 1, p<0.001) compared with those with other histology; however, patients with CCA and postmolar GTN presented with similar stage of disease (stage I, 83.1% vs 88.2%, p=0.126). Although there was no difference in survival between groups, increased resistance to first-line methotrexate chemotherapy was significantly associated with a diagnosis of postmolar CCA (OR 2.67, p=0.007)), pretreatment hCG level at >10,000mIU/mL (OR 2.62, p=0.002), and higher FIGO score (3–4: OR 2.02, p=0.027; 5–6: OR 5.56, p<0.001) on multivariate analysis. ConclusionsClinicopathologic diagnosis of postmolar CCA in patients with low-risk GTN is associated with higher pretreatment hCG levels, higher FIGO scores, and increased resistance to first-line single-agent methotrexate chemotherapy.