High-intensity focused ultrasound as a pretreatment combined with hysteroscopic resection for gestational trophoblastic neoplasia with chemotherapy intolerance: a case report.

BACKGROUND: Due to resistance and intolerance to chemotherapy, localized lesion resection may be required in some patients with Gestational trophoblastic neoplasia (GTN), which may lead to massive bleeding. In this case report, we describe the successful use of high-intensity focused ultrasound (HIFU) as an effective pretreatment method for surgical procedure in a patient with GTN to reduce the perioperative risk and the impact on fertility. CASE PRESENTATION: A 26-year-old woman was diagnosed with high-risk GTN (FIGO Stage III: 12 prognostic scores) after a hydatidiform mole. The fifth chemotherapy cycle was interrupted due to severe chemotherapy toxicity. However, the uterine lesion was still present and the beta-human chorionic gonadotropin (ß-hCG) level was not restored to normal. Therefore, ultrasound-guided HIFU was performed as a pretreatment method to shrink the lesion and prevent massive bleeding during localized lesion resection. The effectiveness of ablation was evaluated immediately using contrast-enhanced ultrasound and Color Flow Doppler ultrasonography. One month after HIFU treatment, the uterine lesion was completely resected under hysteroscopic surgery. During the surgery, HIFU was found to have shrunk the lesion and there was minimal bleeding (5 mL). The uterine cavity morphology and menstruation returned to normal after surgery. The patient has showed no signs of recurrence as of one-year follow-up. CONCLUSION: Ultrasound-guided HIFU ablation may be a new choice for high-risk GTN patients with chemoresistance or chemo-intolerance. As a noninvasive pretreatment method, HIFU can shrink the uterine lesion, and reduce the risk of bleeding with no obvious effect on fertility.

Intrauterine hydatidiform mole complicated with tubal ectopic pregnancy: a case report.

Heterotopic pregnancies are rare pathological pregnancy disorders in clinical practice. However, the number of cases has increased with the widespread use of ovulation induction drugs in recent years. The clinical manifestations of heterotrophic pregnancies are diverse and easy to missed or misdiagnosed. A 33-year-old married Gravida1 Para 0 + 0 patient was admitted on December 8, 2020 with intermittent abdominal pain 18 days after uterine curettage for complete hydatidiform mole of 8 weeks gestation. She had ovulation-promoting drugs prior to the index pregnancy. Hysteroscopic-directed endometrial biopsy and laparoscopic left tubal surgery were offered to her; and she is being followed up with serial pelvic ultrasounds and ß-Human Chorionic Gonadotrophin (ßHCG) assays. This case study presents a case of intrauterine hydatidiform mole complicated with tubal pregnancy to highlight the problems associated with its diagnosis and treatment.

Laparoscopic Management of Partial Molar Caesarean Scar Ectopic Pregnancy.

STUDY OBJECTIVE: To demonstrate laparoscopic management of a molar scar ectopic pregnancy. DESIGN: Stepwise demonstration of the technique with narrated video footage. SETTING: Cesarean scar ectopic pregnancy and molar pregnancy are 2 separate extremely rare pathologies with an incidence range from 1/1800 to 1/2500 of all pregnancies for the former [1,2]. The concurrence of both cesarean scar ectopic and molar pregnancy is furthermore exceptionally rare, and there are only 8 reported cases of cesarean scar molar pregnancy in literature till date [3]. There is a high risk of uterine rupture, uncontrolled hemorrhage, hysterectomy, and significant maternal morbidity owing to thin myometrium and fibrous scar after cesarean section [4,5]. Knowledge and awareness about this clinical condition aid in early diagnosis and reduced morbidity. Here, we present a rare case of cesarean scar ectopic pregnancy that was operated for failed medical management and diagnosed to be molar scar ectopic pregnancy intraoperatively. INTERVENTIONS: Total laparoscopic approach to molar scar ectopic pregnancy excision involved the following steps, strategies to minimize blood loss, and complete enucleation of tissue: (1) Hysteroscopy to localize the scar ectopic and its type and size (2) Bladder dissection to expose scar (3) Intramyometrial injection of vasopressin (4) Use of harmonic scalpel to delineate the gestational sac (5) Complete evacuation of products of conception (6) Excision of scar tissue (7) Uterine repair in 2 layers CONCLUSION: There are only 8 reported cases of cesarean scar molar pregnancy in literature till date, and all patients had at least 2 previous uterine curettages with abnormally increased ß-hCG levels. The clinical manifestations were varied, the most common symptom being vaginal bleeding for a period >1 month, including our case [3]. Considering the limitations of ultrasound, magnetic resonance imaging, and serum hCG levels in the differential diagnosis of molar cesarean scar pregnancy from normal cesarean scar pregnancy, postoperative specimen should be sent for histologic examination [6]. As seen in our case, the possibility of molar pregnancy at cesarean scar ectopic site should be kept in mind in cases with rising ß-hCG levels despite continuous medical interventions, which was being medically managed for 3 months. Our case is the first to be successfully managed with laparoscopic surgery as the previously reported cases were managed with suction evacuation, chemotherapy, laparotomy, or hysterectomy [3].

A Rare Case of Large Hydatidiform Mole Mimicking a Term Pregnancy.

Molar pregnancy is a type of abnormal pregnancy that usually presents with amenorrhea, vaginal bleeding and elevated serum ß-hCG levels. We report a rare case of complete hydatidiform mole occurring in a 46-year-old P2L2 lady who presented with a term size uterus and elevated serum ß-hCG level (> 15,00,000 per deciliter, anemia (hemoglobin: 8.1 g/dL), difficulty in breathing and minimal vaginal bleeding. During the course of her evaluation, she had profuse vaginal bleeding, she underwent suction and evacuation, but bleeding was not controlled despite measures to control it. She was given uterotonics and antifibrinolytic agents and uterine artery ligation. But was proceeded with emergency hysterectomy for uncontrolled hemorrhage. The content of suction and evacuation was vesicles with blood clots and histopathology was reported as complete hydatidiform mole. The patient received a total of 4 units of packed red blood cells. She was discharged from hospital on 5th postoperative day and was followed up serial serum ß-hCG level. Therefore, complete mole can present with enlarged uterus, vaginal bleeding and anemia. It is also important to note that intractable bleeding following suction and evacuation not being controlled with uterotonics and antifibrinolytic agents and uterine artery ligation may require hysterectomy to save the patient's life.

Immune cell composition in the endometrium of patients with a complete molar pregnancy: Effects on outcome.

OBJECTIVE: In 15% of patients with complete hydatidiform mole (CHM), disease progresses to post-molar gestational trophoblastic neoplasia (GTN) after curettage. Tumor infiltrating lymphocytes (TILs) are essential in overcoming disease in many tumors. Infiltrating lymphocyte composition and density may influence trophoblast regression and development of post-molar GTN. We analyzed immune cell composition and density in curettaged endometrium of patients with CHM which spontaneously regressed, and of patients with CHM which progressed to post-molar GTN. METHODS: Sixteen patients with CHM and spontaneous regression, and 16 patients with CHM which progressed to post-molar GTN were selected. Immune cell composition and density of natural killer (NK) cells, natural killer T (NKT)-like cells, Cytotoxic T cells, T-Regulatory and T-Helper cells, were determined by multiplex immunohistochemistry (mIHC). RESULTS: Curettaged endometrium of patients with CHM and spontaneous regression contained a slightly higher number of immune cells compared to patients with CHM which progressed to post-molar GTN. NKT-like cell density was significantly higher in patients with spontaneous regression compared to patients with CHM which progressed to post-molar GTN (483 ± 296 vs.295 ± 143 (mean ± SD), p = 0.03) respectively. NKT-like cell density in the spontaneous regression group was split in 'high' and 'low' (i.e. above and below the median number of NKT-like cells). In patients with high NKT-like cell density, hCG normalized earlier than in patients with low NKT-like cell density (9.5 weeks, (range 3.7-14) vs. 12.9 weeks, (range 8.6-17.9), p = 0.05). CONCLUSION: A high number of NKT-like cells in the endometrium of CHMs may contribute to spontaneous regression of molar trophoblast cells.

Assessment of current follow-up for complete molar pregnancies: A single centre review.

BACKGROUND: Current guidelines recommend that resolution of a complete molar pregnancy (CMP) can only be confirmed once a negative ß-human chorionic gonadotropin (ß-hCG) has been maintained for six months following uterine surgical evacuation. However, multiple studies have found that the risk of developing gestational trophoblastic neoplasia (GTN) once a negative ß-hCG had been obtained is negligible, which suggests that a shorter follow-up may be reasonable. AIM: To determine the trend in ß-hCG following diagnosis of a CMP and the incidence of GTN, in a single unit. MATERIALS AND METHODS: All patients presenting to the tertiary hospital, Royal Prince Alfred Hospital Early Pregnancy Assessment Service (RPAH EPAS), with a histopathological diagnosis of a CMP between 2010 and 2017 were included. Data collected included age, parity, ß-hCG at diagnosis, subsequent ß-hCG levels, incidence of GTN and treatment required. RESULTS: Sixty-seven patients were diagnosed with CMP between January 2010 and July 2017 through RPAH EPAS. The mean age of women diagnosed with a CMP was 33 years. None of the 40 patients who spontaneously achieved a negative ß-hCG and completed their six months follow-up had a subsequent rise in ß-hCG. The median number of days from surgical evacuation to normalisation of ß-hCG was 55.5 days. Sixteen out of 67 patients who had a CMP required further management for persistent GTN. None of these patients achieved a negative ß-hCG prior to further management. CONCLUSIONS: Consideration could be made to decreasing the period of ß-hCG monitoring for women who achieve a spontaneous negative ß-hCG following surgical evacuation of a CMP.

Histological Examination of Tissue Obtained in Early Pregnancy Loss.

Background It is a routine practice to send histological sample after surgical evacuation of early pregnancy loss. Objective This study was carried out to see the justification of regular histological study by carrying out the histological study of early pregnancy loss and to find the prevalence of gestational trophoblastic disease in early pregnancy loss. Method It was a descriptive prospective study, conducted in Nepal medical college teaching hospital from February to October 2020 in Obstetrics and Gynaecology department. Clinical data such as age, parity, gestational age and diagnosis were collected of 130 patient of early pregnancy loss. Then histological study were sent after surgical evacuation. Result Among the age group, 21-30 age group was maximum. (64.61%), more than half of the patient was primigravida (53.07%) and most of the cases were between 6 to 9 weeks of gestation. Incomplete abortions were maximum (43.07%), missed abortions 38.46%, blighted abortions 16.15%, enevitable abortions 1.53% and septic abortion was 0.76%. Among histological finding, 72.30% were product of conception, 15.38% of the cases had no product of conception, decidual tissue only in 6.92%, partial mole in one case (0.76%), complete mole in one case (0.76%) and hydrophic changes in one case (0.76%). The total cases of Gestational trophoblastic diseases (GTD) were 3(2.30%). Conclusion In our study we found 2.3% of cases of GTD, which was quite high in compare to Western word. So it is a good practice to do histological study of all cases of EPL in our country to detect GTD, determining cause for recurrent pregnancy loss and detecting unexpected fetal pathology.

The impact of previous cesarean section (C/S) on the risk for post-molar gestational trophoblastic neoplasia (GTN).

OBJECTIVE: To investigate the relationship between previous cesarean section (C/S) and risk for post-molar gestational trophoblastic neoplasia (GTN). METHODS: Data from patients who were treated for hydatidiform moles between 1995 and 2016 were retrospectively reviewed. Patient age, gravidity, parity, abortion history, gestational age, pretreatment beta-human chorionic gonadotropin (HCG), previous molar pregnancy, clinical symptoms, enlarged uterus, theca lutein cyst, type of GTN, World Health Organization risk score, chemotherapy, and mode of delivery were recorded. Hazard ratios (HR) and 95% confidence intervals (CI) for variables associated with the occurrence of post-molar GTN and invasive mole were estimated by univariate and multivariate Cox proportional hazards models. RESULTS: From 1995 to 2016, 182 patients were diagnosed with molar pregnancy and underwent treatment. Patients with previous C/S (C/S group) had higher age (37.0 vs 32.8. p = 0.004), gravidity (3.1 vs 2.0, p < 0.001), and parity (1.6 vs 0.9, p < 0.001) than patients without previous C/S (non-C/S group). Post-molar GTN (43.5 vs 26.5%, p < 0.001), invasive mole (21.7 vs 3.7%, p < 0.001), hysterectomy (28.3 vs 6.6%, p < 0.001), and chemotherapy (45.7 vs 28.7%, p = 0.03) were more frequent in the C/S group. In multivariate analysis, independent risk factors for post-molar GTN were previous C/S (HR 5.1, 95% CI 2.1-12.7), abortion history (HR 6.3, 95% CI 2.5-15.6), and pretreatment ß-hCG (HR 1.3, 95% CI 1.1-1.6). CONCLUSIONS: In this study, C/S was a strong risk factor for occurrence of post-molar GTN and invasive mole. Aggressive treatment, such as multi-agent chemotherapy or hysterectomy, can be considered for hydatidiform moles in patients with a C/S history.

Evaluation of a routine second curettage for hydatidiform mole: a cohort study.

OBJECTIVE: The aim of this study was to evaluate routine second curettage for hydatidiform mole (HM) by comparing the characteristics and outcomes of developing gestational trophoblastic neoplasia (GTN). STUDY DESIGN: This was a cohort study including 173 patients diagnosed with HM between January 2002 and August 2019 who were followed up at Nagoya University Hospital, Japan. After an evacuation, 105 and 68 patients were managed with the routine method (routine group) and elective method (elective group) for a second curettage, respectively. The routine second curettage was performed around 7 days after the first evacuation. Patients in the elective group underwent a second curettage if there was ultrasonographic evidence of molar remnants in the uterine cavity. Socio-clinical factors were retrospectively compared between the routine and elective groups, and between patients showing regression and those who developed GTN. RESULTS: The incidence of GTN was 15.2% in the routine group and 20.6% in the elective group, and the difference was not significant (P = 0.364). The median GTN risk score was significantly higher in the routine group than in the elective group (P = 0.033). Presence of a complete HM, gestational age, and a pre-treatment human chorionic gonadotropin level of ≥ 200,000 mIU/mL were independent risk factors for GTN in molar patients. CONCLUSION: The incidence of GTN was unchanged but the risk score of GTN was higher in the routine group than in the elective group. Routine second curettage may not be necessary, but further study will be needed to confirm this.

Pre-operative classification of molar pregnancy: How good is ultrasound?

BACKGROUND: Histopathology is the reference standard for diagnosing hydatidiform molar pregnancy (HMP). AIM: To assess the performance of pre-operative transvaginal ultrasound (TVS) to predict HMP. MATERIALS AND METHODS: A retrospective diagnostic accuracy study was performed on women who had both TVS and histopathological examination of uterine curettings between January 2011-February 2017. TVS diagnosis of partial MP (PMP) included assessment of fetal parts and/or empty gestational sac with small cystic spaces adjacent to gestational sac. TVS diagnosis of complete MP (CMP) included assessment of complex, echogenic intra-uterine mass(es) containing multiple small cystic areas. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive and negative likelihood ratios (PLR/NLR) for TVS were reported. Reference standard was histology. RESULTS: There were 4917 consecutive women who underwent TVS; 1636 underwent surgical curettage for miscarriage. Forty out of 4917 (0.6%) had HMP histologically; 25/40 (62.5%) had suspected HMP and 15/40 (37.5%) did not; 24/40 (60.0%) had CMP of which 19/24 (79.1%) were suspected on TVS and 5/24 (20.8%) were not; 16/40 (40.0%) had PMP of which 6/16 (37.5%) were suspected on TVS and 10/16 (62.6%) were not. The sensitivity, specificity, PPV, NPV, PLR and NLR of pre-operative TVS to predict HMP were: 60.0, 99.1, 63.2, 99.0% 68.4, 0.4; for CMP: 79.2, 99.8, 86.3, 99.6%, 421.7, 0.2; for PMP: 37.5, 99.3, 35.3, 99.4%, 54.3, 0.6. CONCLUSION: Histology remains the gold standard for diagnosing HMP. TVS is an acceptable diagnostic tool for HMP. When there are no ultrasound features of HMP, almost all these women will not have an underlying HMP.

[Clinical characteristics and diagnosis of early hydatidiform mole].

Objective: To evaluate the clinical characteristics and diagnostic strategies of early hydatidiform mole. Methods: A retrospective cohort study was conducted of 526 women with hydatidiform mole who underwent suction curettage and were confirmed by histopathology in Dalian Maternal and ChildHealth Care Hospital from Feb. 2013 to Feb. 2018, including 484 women with gestational age less than or equal to 12 weeks (the early group) and 42 women with gestational age greater than 12 weeks (the late group). The clinical characteristics between the two groups were compared, and the pathological diagnosis and pre-evacuation ultrasound examination of the early group were further discussed. Results: Compared with the late group, the clinical characteristics of the early group tended to be atypical, and the incidence of vaginal bleeding, excessive uterine size, theca lutein cysts (>6 cm) and pregnancy complications decreased significantly (all P<0.05). The serum level of ß-hCG in the early group was significantly lower than that in the late group (Z=-2.382, P=0.017). While there was no significant difference in the pre-evacuation ultrasound detection rate between the two groups (53.5% vs 66.7%; χ(2)=2.697, P=0.101). Five hundred and fifteen patients completed the follow-up, and 38 patients with post-mole neoplasia were all cured. There was no significant difference in the malignant transformation rate of hydatidiform mole between the two groups (7.0% vs 11.9%; χ(2)=0.745, P=0.388). In the early group, 302 cases of complete hydatidiform mole (CHM), 179 cases of partial hydatidiform mole (PHM) and 3 cases of unclassified hydatidiform mole (UHM) were histologically diagnosed, according to pathological morphology combined with p57(KIP2) immunohistochemical staining. Compared with pathological diagnosis, the overall pre-evacuation ultrasound detection rate in the early hydatidiform mole was 53.5% (259/484), which was significantly better for complete (78.1%, 236/302) versus partial (11.7%, 21/179) hydatidiform moles (χ(2)=199.224, P<0.01). There was significantly weak negative correlation between the overall ultrasound detection rate and gestational age of hydatidiform mole (r=-0.211, P<0.01). The gestational age of early PHM was significantly longer than that of CHM (68.0 vs 58.5 days; Z=-8.048, P<0.01). Conclusions: The clinical presentations of early hydatidiform mole are not typical. Although ultrasound examination identifies only about half of hydatidiform moles, ultrasonography is still an important auxiliary examination method. Morphological examination combined with p57(K)IP2 immunohistochemical staining could effectively diagnose early hydatidiform mole, so as to reduce the missed diagnosis of hydatidiform mole.

Invasive molar pregnancy in rudimentary uterine horn.

OBJECTIVE: Incidence of molar pregnancy is 1-3/1000 pregnancies. Invasive mole is a local invasive form of gestational trophoblastic neoplasias which is mostly seen in reproductive age and usually follows a molar pregnancy and rarely has an initial presentation. Ectopic pregnancy in rudimentary uterine horn is extremely rare and is seen in 1/100,000 - 140,000 pregnancies. Invasive mole has seldom been reported in ectopic localizations but not in a patient with Müllerian duct anomaly. Here we represent a case of invasive mole in a reproductive age patient with unicornuate uterus and rudimentary communicating uterine horn. Invasive mole presented initially, mimicking ectopic pregnancy. The patient underwent diagnostic laparoscopy and resection of rudimentary uterine horn was performed. The pathology result was reported as an invasive mole. Serum b-hCG levels normalized on post-operative first month and no additional chemotherapy was needed.

Human Chorionic Gonadotropin Regression Curves after Partial or Complete Molar Pregnancy in Flanders: Are They Different from Regression Curves from the Eighties?

BACKGROUND/AIMS: We updated human chorionic gonadotropin (hCG) regression curves created in the eighties after evacuation of complete and partial molar (CM and PM, respectively) pregnancies using modern hCG assays. We created similar curves for patients in need of chemotherapy (gestational trophoblastic neoplasia [GTN]). METHODS: A total of 126 patients who were diagnosed with gestational trophoblastic disease from 1990 to 2014 were included. We compared curves from 2 groups, CM and PM, with historical ones. The third group was a comparison of GTN patients receiving first-line chemotherapy and patients in need of a switch of chemotherapy. RESULTS: The regression curves were comparable to historical ones. According to the latter, mean time to normalization was 14-15 weeks after evacuation. We observed a normalization within 12 (CM) and 12.7 (PM) weeks. In addition, a remarkable but not statistically significant vertical shift (20 IU/L higher) was observed prior to day 60 compared with historical curves. The comparison in GTN patients showed a statistical significant difference, even at day 7. CONCLUSION: The presented hCG regression curves in the Flemish region were comparable with the ones of the eighties but with a vertical shift, hypothetically due to more sensitive assays. In addition, regression curves in GTN patients receiving chemotherapy can be used to evaluate response.

Removal of retained products of conception showing marked vascularity without uterine artery embolization: Two case reports.

Retained products of conception with marked vascularity can cause massive postabortal or post-partum bleeding. Uterine artery embolization is effective for uterus preservation but does not assure fertility preservation. Thus, the optimal treatment for retained products of conception with marked vascularity is uncertain. Here, we report two cases of retained products of conception with marked vascularity: one early abortion and one hydatidiform mole, which were successfully resolved by dilation and removal of the retained products, without uterine artery embolization. We pretreated the cervical dilation using two or more laminaria tents and named this technique the 'maximum laminaria procedure'. We observed that the vascularity disappeared just after the laminaria tents were removed, and subsequently, we could remove the retained products with minimal bleeding, without uterine artery embolization. This protocol might become a standard treatment for retained products of conception with marked vascularity.

ANTEMORTEM DIAGNOSIS AND SUCCESSFUL TREATMENT OF A COMPLETE MOLAR PREGNANCY IN A GERIATRIC BONOBO ( PAN PANISCUS).

A 47-yr-old multiparous female bonobo ( Pan paniscus) tested positive for pregnancy on a routine urine test. Because this geriatric animal was considered postreproductive, oral contraception had been discontinued. Sequential transabdominal ultrasound evaluations were performed under voluntary behavior and revealed that the uterus contained a mass of heterogenous tissue which was rapidly increasing in size. Due to a lack of normal fetal development and the ultrasonographic appearance of the uterine tissue, a molar pregnancy was suspected. Ovariohysterectomy was performed, and a complete hydatidiform mole was confirmed through human chorionic gonadotropin levels as well as gross and histological examination of the uterus. To the authors' knowledge, this is the first time a complete molar pregnancy has been reported antemortem in a nonhuman great ape, although a single case of partial hydatidiform mole was previously documented in a chimpanzee on postmortem examination. This case describes the successful medical and surgical management of complete molar pregnancy in a bonobo and provides support for extending the age range of birth control recommendations in geriatric captive great apes that exhibit active breeding behavior.

Does hormonal contraception during molar pregnancy follow-up influence the risk and clinical aggressiveness of gestational trophoblastic neoplasia after controlling for risk factors?

OBJECTIVE: To evaluate the influence of hormonal contraception (HC) on the development and clinical aggressiveness of gestational trophoblastic neoplasia (GTN) and the time for normalization of human chorionic gonadotropin (hCG) levels. METHODS: A retrospective cohort study was conducted with women diagnosed with molar pregnancy, followed at the Rio de Janeiro Trophoblastic Disease Center, between January 2005 and January 2015. The occurrence of postmolar GTN and the time for hCG normalization between users of HC or barrier methods (BM) during the postmolar follow-up or GTN treatment were evaluated. RESULTS: Among 2828 patients included in this study, 2680 (95%) used HC and 148 (5%) used BM. The use of HC did not significantly influence the occurrence of GTN (ORa: 0.66, 95% CI: 0.24-1.12, p=0.060), despite different formulations: progesterone-only (ORa: 0.54, 95% CI: 0.29-1.01, p=0.060) or combined oral contraception (COC) (ORa: 0.50, 95% CI: 0.27-1.01, p=0.60) or with different dosages of ethinyl estradiol: 15mcg (ORa, 1.33, 95% CI 0.79-2.24, p=0.288), 20mcg (ORa: 1.02, 95% CI: 0.64-1.65, p=0.901), 30mcg (ORa: 1.17, 95% CI: 0.78-1.75, p=0.437) or 35mcg (ORa: 0.77, 95% CI: 0.42-1.39, p=0.386). Time to hCG normalization ≥10weeks (ORa: 0.58, 95% CI: 0.43-1.08, p=0.071) or time to remission with chemotherapy≥14weeks (ORa: 0.60, 95% CI: 0.43-1.09, p=0.067) did not significantly differ among HC users when compared to patients using BM, when controlling for other risk factors using multivariate logistic regression. CONCLUSIONS: The use of HC during postmolar follow-up or GTN treatment does not seem to increase the risk of GTN or its severity and does not postpone the normalization of hCG levels.

A Novel Prediction Model for Postmolar Gestational Trophoblastic Neoplasia and Comparison With Existing Models.

OBJECTIVE: The aim of this study was to comparatively study a novel model and existing models of predicting postmolar gestational trophoblastic neoplasia (GTN). METHODS: Two hundred twenty-two patients with complete hydatidiform moles were enrolled retrospectively. A natural regression was noted in 195 patients (spontaneous regression group), whereas the remaining 27 patients entered postmolar GTN (postmolar GTN group). The upper limits of the 95% confidence interval of human chorionic gonadotropin (hCG) values and hCG regression rates were calculated aggregately from the spontaneous regression group. The 4 prediction models (weekly hCG regression curve and weekly hCG regression rate curve reported by previous studies; daily hCG regression curve and daily hCG regression rate curve pioneered by us) were then plotted. The individual hCG curve of the postmolar GTN group was plotted and compared with the prediction models, respectively. The individual hCG curve superimposing the prediction curve was considered showing an elevated risk of GTN. RESULTS: All patients with postmolar GTN were preidentified by daily hCG regression rate curve. The other 3 prediction models had a considerable rate of failure in identification. Mean diagnosis time of daily hCG regression rate curve was significantly lower (P = 0.008), with an average of 15.3 days gained compared with International Federation of Gynecology and Obstetrics criteria. Cochran Q test showed that daily hCG regression rate curve produced a significantly better performance in predicting postmolar GTN than weekly hCG regression curve (P = 0.01). CONCLUSIONS: Our data showed that daily hCG regression rate curve gives a better prediction of postmolar GTN and might potentially enhance the monitoring of patients with molar pregnancy, especially those who could not adhere to International Federation of Gynecology and Obstetrics protocols. However, this preliminary research should not change current clinical practice until further validation is carried out.

Role of Surgery in the Management of Hydatidiform Mole in Elderly Patients: A Single-Center Clinical Experience.

OBJECTIVE: Women older than 40 years develop gestational trophoblastic neoplasia (GTN) after a hydatidiform mole (HM) more often than do younger women. Therefore, in elderly women, primary hysterectomy has been advocated as first-line treatment. The aim of the present study was to evaluate whether hysterectomy could reduce the incidence of GTN after a diagnosis of HM. METHODS: Seventy-six of 442 patients referred to our unit for an HM between 1994 and 2015 were older than 40 years old. Among these, 12 patients were treated by primary hysterectomy. We compared clinical features, serum human chorionic gonadotrophin (hCG), incidence of GTN, and further treatments in these patients and in those who underwent evacuation and serum hCG monitoring, using univariate and multivariate analyses. RESULTS: Patients treated by primary hysterectomy all had a diagnosis of a complete or invasive HM, had more hyperemesis than did control subjects (82% vs 37%, P = 0.008), and had an increased uterine volume (100% vs 41%, P = 0.001). Seven of them developed a subsequent GTN, whereas 5 patients achieved complete remission of disease after surgery (58% vs 30%, P = 0.094). All the patients who developed a GTN after surgery showed lower hCG levels than did control subjects (mean, 671.4 [SD, 1178.4] IU/L vs 23,919.4 [SD, 34,284.9] IU/L; P = 0.005), but there were no significant differences in the amount and type of chemotherapy needed to achieve remission. CONCLUSIONS: Primary hysterectomy after 40 years old in women affected by HM does not reduce the incidence of GTN and amount of chemotherapy. Although further studies are needed to confirm these results, a careful hCG monitoring should be recommended in these high-risk patients.

Case Report of an Ectopic Molar Pregnancy in the Presence of an Intrauterine Device.

BACKGROUND: Ectopic molar pregnancy is a rare phenomenon and has not been reported in the presence of an intrauterine device (IUD). Clinical diagnosis of molar pregnancy is challenging and requires careful follow-up. CASE: A 25-year-old woman (gravida 2, para 0) with a copper IUD in place presented with a positive pregnancy test. Diagnosis of the complete hydatidiform mole was pathologically confirmed after surgery following clinical and sonographic investigations that identified a left-sided ectopic pregnancy. CONCLUSION: Gestational trophoblastic disease (GTD) presenting as an ectopic pregnancy is a very rare occurrence. This patient recovered without event through a combined management and follow-up for ectopic pregnancy and gestational trophoblastic disease. Appropriate identification and management of this clinical problem is essential in order to prevent initial complications as well as subsequent malignant sequelae.

Early diagnosis of gestational trophoblastic neoplasia based on trajectory classification with compartment modeling.

BACKGROUND: In randomized clinical trials or observational studies, it is common to collect biomarker values longitudinally on a cohort of individuals. The investigators may be interested in grouping individuals that share similar changes of biomarker values and use these groups for diagnosis or therapeutic purposes. However, most classical model-based classification methods rely mainly on empirical models such as splines or polynomials and do not reflect the physiological processes. METHODS: A model-based classification method was developed for longitudinal biomarker measurements through a pharmacokinetic model that describes biomarker changes over time. The method is illustrated using data on human Chorionic Gonadotrophic Hormone measurements after curettage of hydatidiform moles. RESULTS: The resulting classification was linked to the evolution toward gestational trophoblastic neoplasia and may be used as a tool for early diagnosis. The diagnostic accuracy of the pharmacokinetic model was more reproducible than the one of a purely mathematical model that did not take into account the biological processes. CONCLUSION: The use of pharmacokinetic models in model-based classification approaches can lead to clinically useful classifications.