She should not become pregnant until she has undergone regular check-ups and one year has passed with negative beta-HCG levels. Patients will be monitored weekly with hCG dosing until it becomes undetectable, for three consecutive times. After that the monitoring will be monthly for six months and then every two months for another six months before a new pregnancy.

A 24-year-old woman, primigestation, suffers a spontaneous abortion at 7 weeks gestation. The anatomopathological study of the abortive remains indicates molar disease. We should inform you that:

The risk of a new molar gestation in a future pregnancy is 50%.

She should not become pregnant until periodic check-ups and after one year with negative BHCG levels.

Subsequent controls are not necessary if the evacuation of the trophoblastic tissue was complete.

Periodic check-ups are necessary since 40% of cases will develop gestational trophoblastic neoplasia.

Gestational trophoblastic disease

In the past, it was seen as important not to get pregnant straight away after a GTD. Specialists recommended a waiting period of 6 months after the hCG levels become normal. Recently, this standpoint has been questioned. New medical data suggest that a significantly shorter waiting period after the hCG levels become normal is reasonable for approximately 97% of the patients with hydatidiform mole. Risk of a repeat GTD The risk of a repeat GTD is approximately 1 in 100, compared with approximately 1 in 1000 risk in the general population. Especially women whose hCG levels remain significantly elevated are at risk of developing a repeat GTD. Persistent trophoblastic disease The term «persistent trophoblastic disease» (PTD) is used when after treatment of a molar pregnancy, some molar tissue is left behind and again starts growing into a tumour. Although PTD can spread within the body like a malignant cancer, the overall cure rate is nearly 100%.

Persistence of gestational trophoblastic disease for longer than 1 year following evacuation of hydatidiform mole.

A spontaneous fall in the radioimmunoassay for the beta subunit of hCG to less than 2 mIU/mL documents regression of hydatidiform mole following evacuation of a molar pregnancy. Continued negative hCG levels for the year after evacuation indicates the absence of risk for persistent gestational trophoblastic disease. This report describes an unusual case of recurrent nonmetastatic gestational trophoblastic disease 16 months after initial evacuation. A 29-year-old woman presented at 19 weeks' gestation with severe preeclampsia and vaginal bleeding. Pelvic ultrasonography demonstrated a molar pregnancy. Pathology following uterine evacuation confirmed a hydatidiform mole. Serial hCG levels fell progressively to less than 2 mIU/mL over the following 25 weeks. She remained compliant with oral contraceptive pills despite having no sexual activity. Sixteen months after uterine evacuation, recurrence of gestational trophoblastic disease was documented by a rising beta-hCG, negative pelvic ultrasound, normal liver function tests, and normal computed tomography of the head. Endometrial curettage showed no chorionic villi or molar tissue. She was treated with five courses of actinomycin D and has remained disease-free for the following 5 years. This late recurrence of gestational trophoblastic disease suggests that those with a molar pregnancy may benefit from surveillance beyond 1 year after uterine evacuation.

[Gestational trophoblastic tumors and recent clinical information].

Recent clinical advances in the field of gestational trophoblastic diseases are described. WHO modified its risk factor scoring system. This change was proposed to combine both the basic FIGO anatomic staging with the modified WHO risk factor scoring system. Patients who score as low-risk are treated with single agent chemotherapy, such as methotrexate (MTX), and patients refractory to MTX are treated with a combination chemotherapy, EMA/CO. Patients who score as high-risk are treated with EMA/CO, and patients refractory to the first line chemotherapy may be successfully treated with EP/EMA. Recent epidemiological data showed that women with complete hydatidiform moles could anticipate normal reproduction in the future. Studies found that pregnancies after treatment of molar pregnancy resulted in 69% full-term, live births; 8% premature deliveries; 1% ectopic pregnancies, and 0.5% stillbirths. First-trimester spontaneous abortions occurred in 17% of pregnancies, and major and minor malformations were detected in 0.4% of infants. Patients with hydatidiform mole were at increased risk of developing molar pregnancy in subsequent conceptions. After having one molar pregnancy, the risk of having molar disease in a future gestation was about 1%. The risk of persistent gestational trophoblastic tumors was increased by long-term oral contraceptive use before conception. In a large, multicenter, case-control study, the risk was shown to be increased in women who had ever used oral contraceptives, but was highest for women taking oral contraceptives during the cycle in which they became pregnant. Partial hydatidiform moles were never previously proven to transform into choriocarcinoma; however, a recent study with molecular techniques clearly showed that partial moles could transform into choriocarcinoma. All patients with suspected partial moles should be reviewed centrally and require hCG follow-up.

Low risk of relapse after achieving undetectable HCG levels in women with complete molar pregnancy.

Complete hydatidiform molar pregnancies occur in approximately 1 of 1,000 conceptions. After uterine evacuation of the trophoblastic tissue, women are followed up with serial serum human chorionic gonadotropin (hCG) measurements. Patients are considered to have attained remission when their hCG level spontaneously declines to an undetectable level and remains there during a 6-month follow-up period. This standard effectively detects all disease recurrence; however, it is resource intensive, delays child bearing, and is subject to significant noncompliance. Our objective was to determine the risk of disease recurrence after hCG spontaneously declines to undetectable levels. We used a database from the New England Trophoblastic Disease Center to analyze hCG levels in patients with complete molar pregnancies. Among 1,029 women with complete molar pregnancy and complete data, 15% developed persistent gestational trophoblastic neoplasia. The rate of persistent neoplasm among those whose hCG level fell spontaneously to undetectable levels was 0.2% (2/876, 95% confidence interval 0-0.8%). No women developed persistent gestational trophoblastic neoplasia after their hCG level fell to undetectable levels using an assay with a sensitivity of 5 mIU/mL (n = 82, 95% confidence interval 0-4.5%). Based on our experience with women with complete hydatidiform molar pregnancies whose hCG values spontaneously fell to undetectable levels after molar evacuation, we conclude that the risk of recurrent neoplasm after hCG levels fall to less than 5 mIU/mL approaches zero.

Placental site trophoblastic tumor arising from antecedent molar pregnancy.

Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic disease. Little is known about its pathogenesis and natural history. This report describes two cases that arose in patients with documented complete hydatidiform moles and summarizes the antecedent prenatal histories of PSTTs based on a detailed Medline literature analysis. A 28-year-old, G(2)P(2) female had a live, 12-week gestation fetus and a coexisting molar pregnancy. Her hCG levels dropped promptly from 1.5 million to 23,273 IU/ml after termination, but rose shortly thereafter together with the onset of recurrent vaginal bleeding. Curettage revealed persistent mole. Persistently elevated hCG led to hysterectomy disclosing a fundal PSTT. The second case was that of a 48-year-old, G(2) woman who presented with symptoms of preeclampsia, hyperthyroidism, and elevated hCG. Curettage yielded a complete hydatidiform mole. Although the hCG level decreased for a short period, it soon increased despite treatment with methotrexate. A second curettage revealed a PSTT. A Medline literature analysis of PSTT, which consists almost entirely of individual cases and several small series, disclosed that PSTT is preceded in 61% of cases by normal term pregnancy, 12% molar pregnancy, 9% spontaneous abortion, 8% therapeutic abortion, and 3% with ectopic pregnancy, stillbirths or preterm delivery. No information is known in 7%. This report describes two additional cases of PSTT preceded by complete molar pregnancy. PSTT is a well recognized, but uncommon form of gestational trophoblastic disease. Although little is known about its pathogenesis, it is preceded not uncommonly by an abnormal pregnancy, including a molar pregnancy.

[Studies on the viability of trophoblast after termination of various kinds of pregnancies (author's transl)].

Although normal value of hCG (LH level) does not necessarily indicate eradication of viable trophoblast, its confirmation has been demonstrated as a clinically useful guide for the probable prevention of choriocarcinoma after hydatidiform mole by Takeuchi et al. Choriocarcinoma preceded by other pregnancies than hydatidiform mole which has the highest risk for choriocarcinoma has drawn more attention than before in connection with the decrease of postmolar choriocarcinoma. So that I have studied the regression rate of urinary gonadotropin (hCG) after the termination of various kinds of pregnancies. In 2,433 cases of induced abortion, 695 cases of spontaneous abortion, 1,724 cases of term delivery and 43 cases of hydatidiform mole, their urinary hCG were determined to the level of physiological range of LH. The rate of hCG regression was in the order of term delivery, spontaneous abortion, induced abortion and hydatidiform mole. The younger was the gestational age of trophoblast, the slower was the regression of hCG. At one month after the termination of pregnancy, 80.1%, 11%, 0.3%, 8% and 4.1%, and at two month 55.8%, 1.6%, 0.5%, 4% and 0.5% for hydatidiform mole, induced abortion of less than 12 week of gestation, spontaneous abortion of less than 12 week of gestation, spontaneous abortion of between 13 and 20 week of gestation respectively still showed abnormal hCG value. One percent of induced abortion at 5 month, 4% of spontaneous abortion at 3 month, 0.3% of term delivery at 4 month still maintained abnormal titer. No malignant sequelae in patients under the investigation have ever been observed in the follow up period between 3 and 8 years.

Postevacuation hCG levels and risk of gestational trophoblastic neoplasia in women with complete molar pregnancy.

Women diagnosed with complete hydatidiform molar pregnancy are at 15% to 28% risk of developing persistent gestational trophoblastic neoplasia (GTN) requiring further management with chemotherapy. Our objective was to develop human chorionic gonadotropin (hCG) criteria that establish a patient's risk of developing persistent GTN or achieving remission from their baseline risk within a few weeks of molar evacuation. We used a database from the New England Trophoblastic Disease Center to analyze hCG levels from 1,029 women with complete molar pregnancies. We conducted a retrospective cohort study using data from 1973 to 2001. Women whose hCG level declined below 50 mIU/mL during their follow-up were found to be at no more than 1.1% risk for developing persistent GTN, irrespective of when this level was reached. Women whose hCG levels was below 200 mIU/mL in the fourth week after evacuation (59.8% of all women), or below 100 mIU/mL in the sixth week after evacuation (65.8% of all women), had a risk of persistence below 9%. hCG levels above 2,000 mIU/mL in the fourth week after evacuation (13.3% of women) were associated with a 63.8% risk of developing persistent disease. These data may allow clinicians to evaluate the risk of persistence that their patients with complete molar pregnancy have based on early hCG results after molar evacuation. In the fourth week after molar evacuation, 59.8% of women may be counseled that their risk of developing persistent GTN is substantially reduced from their baseline, whereas 13.3% of women may be warned that their risk of developing persistent GTN is greater than 50%. II-2.

[Reservation of fertility for seventeen patients with placental site trophoblastic tumor].

To approach the efficiency and feasibility of preserving the fertility for patients with placental site trophoblastic tumor (PSTT). Totally 2 086 cases of gestational trophoblastic neoplasm (GTN) patients registered in Peking Union Medical College Hospital between 1998 and 2013. Fifty-seven of them were PSTT patients, 40 cases of which suffered hysterectomy, the rest 17 PSTT patients who preserved their fertility were analyzed retrospectively. The computerized database of clinical and pathological reports was reviewed in this cohort. The clinical manifestation of PSTT was not specific compared to other types of GTN. The average age of the 17 patients was 29.5 years old (range 22-39 years). The most common antecedent pregnancy was term birth (8 cases), the others were spontaneous abortion in 4 case, artificial abortion in 3 cases and molar pregnancy in 2 cases. The baseline serum β-hCG was slightly elevated and 12 patients (12/15) were less than 1 000 U/L. In this cohort, nine of the patients were in stage I, while the other eight cases were in stage III . The patients suffered conservative surgery, including dilation and curettage of uterus in 7 cases, open abdomen uterine lesion excision in 4 cases, laparoscopic uterine lesion excision in 3 cases, hysteroscopic uterine lesion excision in 1 case, and pulmonary lobectomy in 2 cases. Two of the patients didn't received chemotherapy, while the other 15 cases suffered combination chemotherapy. Compared with 40 patients who suffered hysterectomy during the same interval, fertility preservation group did not result in poor outcomes or high risk of relapse rate. Six subsequent pregnancies happened after the therapy, two of them were during their second-trimester, while four patients had healthy babies by vaginal delivery in two and cesarean section in two. The scar of the uterus was fairly well during the cesarean sections. Reservation of fertility therapy could be considered in highly-selected patients for young women who strongly desired to preserve their fertility and with localized lesion. Exactitude follow-up after therapy should be recommended. Contraception should also be recommended for at least one year after the chemotherapy. Vaginal delivery could be an option for the future pregnancies.

Pregnancy outcomes of patients who conceived within 1 year after chemotherapy for gestational trophoblastic tumor: a clinical report of 22 patients.

The aim of this study was to explore the risk of pregnancy of patients who conceived within 1 year after successful chemotherapy for gestational trophoblastic tumor (GTT). From 1966 to 1996, 22 patients who conceived within 1 year after chemotherapy were followed up and analyzed retrospectively. Among 22 patients, 9 had term deliveries and 1 had a premature birth, 6 had induced abortion at the patient's request, and 6 had therapeutic abortion because of various indications such as repeated hydatidiform mole (1 case), intrauterine death (1 case), inevitable abortion (1 case), and threatened abortion (3 cases). The fetal loss rate was 27.1% (6/22). The incidence rate of gestational trophoblastic disease (GTD) was 9.1% (2/22). The incidence rate of GTT was 4.5% (1/22). The average interval between completion of chemotherapy and pregnancy was 10.25 months in the group of term pregnancies and 5.86 months in that of fetal loss (P < 0.05), indicating that the longer the interval, the lesser the risk of GTD. The results suggest that contraception for 1 year is necessary in patients with GTT after successful chemotherapy. However, in the case of a patient who conceives within 1 year, it is not necessary to terminate pregnancy, but the pregnancy must be carefully watched.

Gestational trophoblastic disease

The use of a reliable contraception method is very important during the entire follow up period, as patients are strongly advised against pregnancy at that time. If a reliable contraception method is not used during the follow-up, it could be initially unclear to clinicians as to whether a rising hCG level is caused by the patient becoming pregnant again, or by the continued presence of GTD. In women who have a malignant form of GTD, hCG concentrations stay the same (plateau) or they rise. Persistent elevation of serum hCG levels after a non molar pregnancy (i.e., normal pregnancy [term pregnancy], or preterm pregnancy, or ectopic pregnancy [pregnancy taking place in the wrong place, usually in the fallopian tube], or abortion) always indicate persistent GTD (very frequently due to choriocarcinoma or placental site trophoblastic tumour), but this is not common, because treatment mostly is successful.

Gestational trophoblastic diseases - clinical guidelines for diagnosis, treatment, follow-up, and counselling.

Hydatidiform mole is treated with surgical uterine evacuation with suction and blunt curettage (D). Medical uterine evacuation should not be used (C). On clinical suspicion of hydatidiform mole, one representative sample of the evacuated tissue is fixed for histopathologic investigation and one is forwarded unfixed for genetic analysis (D). Serum hCG is measured on suspicion of hydatidiform mole. At the time of the uterine evacuation, the initial hCG is measured (A). After a hydatidiform mole that is both triploid and partial, serum hCG is measured weekly until there are two consecutive undetectable values (< 1 or < 2), after which the patient can be discharged from follow-up (C). After a diploid hydatidiform mole, a complete mole, or a hydatidiform mole without valid ploidy determination, serum hCG is measured weekly until the value is undetectable (< 1 or < 2). If serum hCG is undetectable within 56 days after evacuation, the patient can be discharged from follow-up after an additional four monthly measurements. If serum hCG is first normalised after 56 days, the patient is follow-up with monthly serum hCG measurement for six months. Safe contraception should be used during the follow-up period (A). If hCG stagnates (less than 10% fall over three measurements), increases, or if hCG can be demonstrated for longer than 6 months, the patient by definition has persistent trophoblastic disease (PTD). A chest X-ray should be taken and a gynaecologic ultrasound scanning performed. The patient is referred to oncologic treatment (A). Uterine re-evacuation as a treatment for PTD can, in general, not be recommended because the rate of remission is low, and there is the risk of perforation of the uterus (C). In all following pregnancies, the woman is offered an early ultrasound scan, e.g. in gestational week eight (D). Eight weeks after termination of all future pregnancies, serum hCG is measured (D). In PTD and invasive hydatidiform mole, the primary treatment is MTX, either orally every third week or IV every week (B). In MTX-resistant PTD, IV act D is added (or replaces the MTX) (B). Third line chemotherapy is BEP or EP, alternatively EMA-CO (B). Choriocarcinoma is primarily treated with chemotherapy. Hysterectomy and/or resection of metastases are possible treatments (A). Placental site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT) are primarily treated with hysterectomy. In the case of disseminated disease, chemotherapy is considered (A). The risk of reoccurrence after trophoblastic disease treated with chemotherapy is approximately 3%. Most reoccurrences are seen within 12 months, and for this reason monitoring of hCG is recommended for one year, the first third months once or twice a month, thereafter every second to third month. Patients with PSTT and ETT are monitored with measurement of hCG throughout their lifetimes (C). In genetically verified twin pregnancy with hydatidiform mole and a living foetus, the pregnancy can continue if serum hCG is monitored and ultrasound scans regularly performed, and possible obstetric complications dealt with (C). In the case of recurrent hydatidiform mole and/or familial hydatidiform mole, patients should be referred to genetic workup and counselling (C). Women with a hereditary disposition to hydatidiform mole because of a mutation in NLRP7 should be informed of the possibility of becoming pregnant via egg donation (C).

Misdiagnosis of gestational trophoblastic neoplasia as ectopic pregnancy: A 15-year retrospective study.

Gestational trophoblastic neoplasia is an uncommon disease, whose clinical manifestations are similar to ectopic pregnancy, thus some rare pelvic lesion can be misdiagnosed as ectopic pregnancy. This study was presented to investigate the characteristics of gestational trophoblastic neoplasia misdiagnosed as ectopic pregnancy and reduce the misdiagnosis. The clinicopathological data for 14 cases of gestational trophoblastic neoplasia misdiagnosed as ectopic pregnancy at West China Second Hospital Sichuan University from January 2006 to December 2020 were retrospectively analyzed. The main clinical manifestations were amenorrhea, abnormal vaginal bleeding, and abdominal pain. At initial diagnosis, the serum hCG level was >10,000 mIU/mL in 5 patients and <10,000 mIU/mL in 7 patients, and a positive urine pregnancy test alone was found in 2 patients. Vaginal ultrasonography showed no abnormalities in 7 cases, adnexal mass in 5 cases, and tubal thickening in 2 cases. The patient's previous pregnancy was an abortion in 7 cases, full-term in 4 cases, and a hydatidiform mole in 3 cases. Clinical stage: 3 cases were stage I, 3 were stage II, 7 were stage III, and 1 case was stage IV (liver and spleen metastases). The median FIGO prognostic score was 13.5 points (12-21 points), with 9 cases having a score >13 points (very high risk). From 14 patients, only 3 had molar pregnancy previously. Only 3 patients had no metastasis at GTN diagnosis (from these 3, only one after molar pregnancy). After chemotherapy alone or in combination with surgery, all patients survived, with a median follow-up of 84 months (23-102 months). If we have positive hCG, without a sonographic topic gestation confirmation, associated with metastatic lesions, the GTN diagnosis should be considered instead of ectopic pregnancy, if the patient have had a pregnancy once during her life.

Outcome of subsequent pregnancy after treatment for persistent gestational trophoblastic tumour.

This study analysed subsequent pregnancy outcome in patients treated for persistent gestational trophoblastic tumour (GTT). Between 1974 and 1999, a total of 378 patients with GTT (83 patients with high-risk and 295 patients with low-risk GTT) were treated at Chiba University Hospital, Japan. Of these 378 patients, 363 (96.0%) achieved primary remission and 315 survivors have been followed at our hospital. To date, 129 patients have had 243 subsequent conceptions. While pregnancy outcome was comparable with that of the general Japanese population, the incidence of repeat molar pregnancy (2.1%) was approximately seven times higher than that of the general population. During the mandatory HCG follow-up period of 1 year, 15 patients conceived within 6 months of completion of chemotherapy. The incidence of spontaneous abortion in these 15 patients was significantly higher than that in patients who conceived after a waiting period of >6 months (P = 0.0053). Patients treated for GTT may anticipate a normal future reproductive outcome, although it would be better to avoid pregnancy for at least 6 months after completion of chemotherapy.

Occurrence of molar pregnancy in patients undergoing elective abortion: comparison with other clinical presentations.

Clinical data of molar pregnancies found in women undergoing elective abortion (group 1, n = 39) were compared to those of molar pregnancies in women who experienced spontaneous abortions (group 2, n = 157) and women in whom molar pregnancy was discovered before symptoms of spontaneous abortion were evident (group 3, n = 209). Group 1 women were younger and experienced uterine evacuation at an earlier stage of amenorrhea than groups 2 and 3. Group 3 had larger uteri at evacuation and longer intervals of positive tests for the beta-subunit of human chorionic gonadotropin during the postmolar phase as compared with groups 1 and 2. On the basis of available provincial data for the number of elective abortions, the estimated incidence of molar pregnancies in this population was 1:2,699. The presence of malignant gestational trophoblastic neoplasia was documented in a single patient in group 1. The incidence of malignant gestational trophoblastic neoplasia in this group was not significantly different from that in groups 2 and 3. Routine pathologic examination of the products of conception in women undergoing elective abortion coupled with routine assays of the beta-subunit of human chorionic gonadotropin when molar pregnancy is found can identify both noninvasive and invasive trophoblastic disease in these women.

Gestational trophoblastic disease

However, the incidence of rare diseases (such as GTD) is difficult to measure, because epidemiologic data on rare diseases is limited. Not all cases will be reported, and some cases will not be recognised. In addition, in GTD, this is especially difficult, because one would need to know all gestational events in the total population. Yet, it seems very likely that the estimated number of births that occur at home or outside of a hospital has been inflated in some reports. Terminology Gestational trophoblastic disease (GTD) may also be called gestational trophoblastic tumour (GTT). Hydatidiform mole (one type of GTD) may also be called molar pregnancy. Persistent disease; persistent GTD: If there is any evidence of persistence of GTD, usually defined as persistent elevation of beta hCG (see «Diagnosis» below), the condition may also be referred to as gestational trophoblastic neoplasia (GTN). See also Trophoblastic neoplasms References External links

Gestational trophoblastic neoplasia: A 6 year retrospective study.

To study the clinical presentations of gestational trophoblastic neoplasia and its response to chemotherapy. This is a retrospective study of 28 women of gestational trophoblastic neoplasia evaluated over a period of 6 years from January 2004 to December 2009. Patients were evaluated on the basis of their age, number of deliveries, history of abortion or molar pregnancy, and the treatment received. All patients were scored on the basis of WHO scoring system. Patients with low risk (score </=6) received single agent chemotherapy with methotrexate or actinomycin D. Patients with high risk (score >/=7) received multiple agent chemotherapy with EMACO regimen. After completion of chemotherapy patients were followed for a minimum of 2 years. The response to treatment was evaluated during follow-up by clinical examination, beta hCG levels and imaging as and when required. Out of 28 women only 27 could be evaluated, because 1 patient was lost to follow-up. Out of 27 patients, 18 patients (66.67%) achieved complete remission with the first-line chemotherapy and additional 25.92% (7/27) achieved complete remission with second line chemotherapy resulting in complete remission of 92.5% (25/27). Gestational trophoblastic neoplasia is curable if patient is properly evaluated and scored. It shows good response to chemotherapy.

Gestational trophoblastic neoplasia after spontaneous human chorionic gonadotropin normalization following molar pregnancy evacuation.

To evaluate the risk of gestational trophoblastic neoplasia (GTN) after spontaneous human chorionic gonadotropin normalization in postmolar follow-up. Retrospective chart review of 2284 consecutive cases of hydatidiform mole with spontaneous normalization of hCG following uterine evacuation treated at one of five Brazilian reference centers from January 2002 to June 2013. After hCG normalization, GTN occurred in 10/2284 patients (0.4%; 95% CI 0.2%-0.8%). GTN developed in 9/1424 patients (0.6%; 95% CI 0.3%-1.2%) after a complete hydatidiform mole, in 1/849 patients (0.1%; 95% CI<0.01%-0.7%) after a partial hydatidiform mole, and in 0/13 patients (0%; 95% CI 0%-27%) after a twin molar pregnancy. The median time to GTN diagnosis after hCG normalization was 18months, and no diagnoses were made before six months of postmolar surveillance. Patients who required more than 56days to achieve a normal hCG value had a ten-fold increased risk of developing GTN after hCG normalization (9/1074; 0.8%; 95% CI 0.4%-1.6%) compared to those who reached a normal hCG level in fewer than 56days (1/1210;0.08%; 95% CI<0.01%-0.5%; p=0.008). All patients presented with symptoms at the time of GTN diagnosis. GTN after spontaneous hCG normalization following molar pregnancy is exceedingly rare, and the few patients who do develop GTN after achieving a normal hCG value are likely to be diagnosed after completing the commonly recommended six months of postmolar surveillance. Current recommendations for surveillance after hCG normalization should be revisited.

Trophoblastic neoplasm

Management of GTN requires pathology review, treatment options and monitoring of hCG. Therefore, it can be treated with curettage, hysterectomy and single agent or multi agent chemotherapy. Although this group of diseases are highly susceptible to chemotherapy, prognosis depends on the type of GTN and whether the tumor has spread to other areas of the body. Cause and Risk factors The exact cause of gestational trophoblastic neoplasia (GTN) is unknown. GTN often arises after molar pregnancies but can also occur after any gestation including miscarriages and term pregnancies. Although risk factors may impact on the development of the tumor, most do not directly cause of disease. According to the some studies, the risk of complete molar pregnancy is highest in women over age 35 and younger than 20. The risk is even higher for women over age 45. Signs and Symptoms The symptoms of GTN will vary from person to person. People with the same disease may not have all the symptoms listed.

Gestational trophoblastic disease

In this scoring system, women with a score of 7 or greater are considered at high risk. It is very important for malignant forms of GTD to be discovered in time. In Western countries, women with molar pregnancies are followed carefully; for instance, in the UK, all women who have had a molar pregnancy are registered at the National Trophoblastic Screening Centre. There are efforts in this direction in the developing countries too, and there have been improvements in these countries in the early detection of choriocarcinoma, thereby significantly reducing the mortality rate also in developing countries. Becoming pregnant again Most women with GTD can become pregnant again and can have children again. The risk of a further molar pregnancy is low. More than 98% of women who become pregnant following a molar pregnancy will not have a further hydatidiform mole or be at increased risk of complications.

Postmolar gestational trophoblastic neoplasia: beyond the traditional risk factors.

To investigate the slope of linear regression of postevacuation serum hCG as an independent risk factor for postmolar gestational trophoblastic neoplasia (GTN). Multicenter retrospective cohort study. Academic referral health care centers. All subjects with confirmed hydatidiform mole and at least four measurements of β-hCG titer. None. Type and magnitude of the relationship between the slope of linear regression of β-hCG as a new risk factor and GTN using Bayesian logistic regression with penalized log-likelihood estimation. Among the high-risk and low-risk molar pregnancy cases, 11 (18.6%) and 19 cases (13.3%) had GTN, respectively. No significant relationship was found between the components of a high-risk pregnancy and GTN. The β-hCG return slope was higher in the spontaneous cure group. However, the initial level of this hormone in the first measurement was higher in the GTN group compared with in the spontaneous recovery group. The average time for diagnosing GTN in the high-risk molar pregnancy group was 2 weeks less than that of the low-risk molar pregnancy group. In addition to slope of linear regression of β-hCG (odds ratio [OR], 12.74, confidence interval [CI], 5.42-29.2), abortion history (OR, 2.53; 95% CI, 1.27-5.04) and large uterine height for gestational age (OR, 1.26; CI, 1.04-1.54) had the maximum effects on GTN outcome, respectively. The slope of linear regression of β-hCG was introduced as an independent risk factor, which could be used for clinical decision making based on records of β-hCG titer and subsequent prevention program.

How long should patients be followed after molar pregnancy? Analysis of serum hCG follow-up data.

We analyzed human chorionic gonadotropin (hCG) follow-up data of patients with molar pregnancy. Women often do not complete recommended post-disease screening. Our purpose was to determine if continuing follow up of uncomplicated molar cases beyond attaining undetectable hCG levels is necessary for detecting relapse of gestational trophoblastic disease. One hundred fifty patients treated at Hungarian National Health Center were analyzed. Those who developed persistent disease before hCG had become undetectable were excluded from further analysis (n=24; 16%). Among 126 uncomplicated cases, 72 patients (57%) completed follow up, and 54 (43%) discontinued their protocol before it had been completed. Of 120 patients who achieved at least one undetectable hCG level, none had any evidence of relapse. In uncomplicated hydatidiform mole, our analysis indicates that once undetectable serum hCG levels are attained, relapse is unlikely. Although further monthly checks are advisable, the likelihood of recurrence appears very low.

Clinical features of early-stage nonhydropic mole for diagnosis of persistent trophoblastic disease.

To characterize the clinical features of "nonhydropic" hydatidiform mole and to investigate regression of serum human chorionic gonadotropin (hCG) as an aid in detecting persistent trophoblastic disease after nonhydropic hydatidiform mole. Our study included women with histologically diagnosed nonhydropic molar pregnancies. Women did not exhibit macroscopic or characteristic ultrasonographic appearances specific to hydatidiform mole. Regression of serum hCG levels was compared with abortions of nonmolar pregnancies, which were histologically confirmed. Among 34 nonhydropic molar pregnancies, 32 complete hydatidiform moles were analyzed, excluding two partial hydatidiform moles. Compared with nonmolar aborted pregnancies, pre-evacuation hCG levels were significantly higher in the 32 complete hydatidiform moles. The 32 molar pregnancies progressed to 24 cases of spontaneous remission and eight cases of persistent trophoblastic disease. Among patients with spontaneous remission, the time at which serum hCG levels became undetectable and the onset of first postabortion menstruation were similar to those in patients who had nonmolar abortions. In all patients who experienced regression, serum hCG was undetectable after the third postabortion menstruation. In all patients with persistent trophoblastic disease, serum hCG levels exceeded 25 milli-international units/mL 4 weeks after evacuation. Without histological confirmation, it is difficult to diagnose nonhydropic molar pregnancy based solely on clinical presentation. Follow-up studies of serum hCG levels 4 weeks after abortion and after the third postabortion menstruation may aid in detecting impending persistent trophoblastic disease. II.

Postevacuation hCG levels and risk of gestational trophoblastic neoplasia among women with partial molar pregnancies.

To develop human chorionic gonadotropin (hCG) criteria that determine a patient's risk of developing persistent gestational trophoblastic neoplasia (GTN) or achieving remission after partial mole evacuation. We used a database from the New England Trophoblastic Disease Center to analyze hCG levels from 284 women with partial molar pregnancies diagnosed between 1973 and 2003. An hCG level >199 mIU/mL in the third through eighth week following molar evacuation was associated with at least a 35% risk of GTN. Women with partial mole who have elevated hCG levels within the first few weeks after molar evacuation are at increased risk for developing GTN.

Guidelines following hydatidiform mole: a reappraisal.

The aim of this study was to determine how often patients with complete hydatidiform mole (CHM) who spontaneously achieve normal human chorionic gonadotrophin (hCG) levels subsequently develop persistent or recurrent gestational trophoblast disease. Four hundred and fourteen cases of CHM registered at the Hydatidiform Mole Registry of Victoria were reviewed retrospectively after molar evacuation. Maternal age, gestational age, gravidity and parity were determined for each patient, as well as the need for chemotherapy. Among the 414 patients, 55 (13.3%) required chemotherapy for persistent trophoblastic disease. None of the patients whose hCG levels spontaneously fell to normal subsequently developed persistent molar disease. Weekly hCG measurements are recommended for all patients until normal levels are achieved. For patients who attain normal hCG levels within 2 months after evacuation, it seems safe to discontinue monitoring once normal levels are achieved. Patients who fail to achieve normal hCG levels by 2 months after evacuation should be monitored with monthly hCG measurements for 1 year after normalisation to assure sustained remission.

Persistent trophoblast disease following partial molar pregnancy.

Human chorionic gonadotrophin (hCG) follow-up data were analysed retrospectively in all patients registered in the Hydatidiform Mole Registry at the Royal Women's Hospital, Melbourne from January 1992 to January 2001 to determine the risk of persistent trophoblast disease following partial molar pregnancy and to review the present follow-up protocol of patients suffering from partial hydatidiform molar pregnancy (PHM). Demographic factors were determined for all 344 cases with a review diagnosis of PHM, included age, history of previous hydatidiform mole, gestation length, hCG levels and compliance with follow-up. Six of the 344 patients diagnosed with PHM required treatment with single-agent methotrexate and folinic acid rescue. All six patients achieved and maintained a complete biochemical remission after chemotherapy. hCG regression assays were analysed for 235 patients: 225 patients had at least one normal hCG measurement during follow-up, of whom 152 (64.7%) patients obtained normal values within 2 months after evacuation. All patients obtained normal levels within 32 weeks after evacuation of the partial hydatidiform mole. Only 63 (25.6%) patients completed the recommended follow-up program. No patient who achieved normal hCG levels required chemotherapy because of a recurrent gestational trophoblastic tumour. This study indicates that 1.7% of all partial mole pregnancy patients needed treatment for malignant sequelae. In contrast, no patient diagnosed with partial mole had a biochemical or clinical relapse after achieving normal levels of hCG, consistent with previous studies. Patients who have had a partial hydatidiform mole should be followed by hCG assays until normal levels are achieved and then follow-up can be safely discontinued.

Gestational trophoblastic disease: is intensive follow up essential in all women?

To determine the timescale of the registration process for gestational trophoblastic disease and its impact on hCG level at registration and subsequent need for chemotherapy. A prospective observational study using a standardised protocol for registration, assessment and treatment for molar pregnancy. A supra-regional tertiary referral centre for gestational trophoblastic disease. A total of 2046 consecutive women registered between January 1994 and December 1998 with a diagnosis of molar pregnancy. Data at and after registration, collected prospectively on a computerised database, were statistically analysed (by multiple logistic regression and ANOVA). Relationship between length of time to and hCG value at registration; also the subsequent need for chemotherapy. A total of 2046 women with a diagnosis of molar pregnancy were registered in the study period. The mean time interval between first evacuation and registration at the referral centre was 47 days (median 37, range 0-594). One hundred and five out of 2046 (5.1%) women needed chemotherapy. Sixty-three precent of the women (1296 out of 2046) had a normal level of urinary hCG (less than 40 IU/24 hours) at the time of registration and only one (0.08%) needed chemotherapy. Binary logistic regression analysis showed a statistically significant relationship between time to registration, hCG value, histology, pretreatment risk score and decision to administer chemotherapy. Women with gestational trophoblastic disease who were registered late were significantly more likely to have normal levels of hCG and were less likely to need chemotherapy. A less intensive follow up may be justified in women with gestational trophoblastic disease who are registered with a normal hCG level.

Late spontaneous resolution of persistent molar pregnancy.

To determine the outcome of women with persistently raised but falling human chorionic gonadotrophin (hCG) levels 6 months after surgical evacuation of a molar pregnancy. An 11-year retrospective review. The United Kingdom supra-regional trophoblastic disease treatment centres at Weston Park Hospital (Sheffield) and Charing Cross Hospital (London). Women with raised but falling serum human chorionic gonadotrophin (hCG) levels 6 months after evacuation of a molar pregnancy. Retrospective case note review of eligible women identified by the electronic databases held at each supra-regional centre. The proportion of women that attain normal hCG levels spontaneously without chemotherapy. In addition, rates of gestational trophoblastic neoplasia (GTN), drug resistance, disease relapse and overall survival are reported. Thirty-five women with molar pregnancy and raised but falling serum hCG levels continued surveillance 6 months after evacuation. Levels of hCG in 30 of the patients (86%) fell to normal levels spontaneously. One woman defaulted follow up prior to hCG normalisation (3%) and the remaining four women (11%) were treated with chemotherapy due to a plateau or rise in serum hCG levels indicating GTN. All treated women were successfully salvaged by either first (n = 1) or second line (n = 2) chemotherapy or found to have persistently raised low level hCG of uncertain clinical relevance (n = 1). No women developed relapsed disease and overall survival was 100%. Women with a molar pregnancy and a raised but falling hCG level beyond 6 months from uterine evacuation can be safely observed with regular hCG monitoring and can usually avoid potentially toxic chemotherapy. Women with treated molar pregnancy may avoid chemotherapy if 6-month hCG levels are raised but falling.

Expression of c-erb B-2 oncogene product in persistent gestational trophoblastic disease.

Much debate exists on the initiation of chemotherapy for women at risk for persistent gestational trophoblastic disease. This is a result of a lack of early predictors for the development of persistent gestational trophoblastic disease after evacuation of a complete hydatidiform mole, because the only current reliable method of detection and diagnosis lies in persistent or rising postmolar beta-human chorionic gonadotropin values. We used immunocytochemical techniques to retrospectively study the expression of the c-erb B-2 oncogene product in formalin-fixed, paraffin-embedded trophoblastic tissues as a potential indicator of the development of persistent gestational trophoblastic disease. In this retrospective study 56 trophoblastic tumors were examined by means of immunocytochemical techniques to stain for the oncogene product for evidence of c-erb B-2 expression. Our 56 cases included original tissue from 20 cases of complete mole that progressed to persistent gestational trophoblastic disease, seven cases of choriocarcinoma after term pregnancy or abortion, and 29 cases of hydatidiform mole representing postevacuation, spontaneously regressing disease (including one partial mole). We also studied 11 cases of first-trimester trophoblast and 15 cases of term placenta as additional controls. Our results showed positive immunostaining for c-erb B-2 gene product in one case of persistent gestational trophoblastic disease, with negative staining in all other cases in the study groups and controls. Analysis for the significance of c-erb B-2 expression in persistent gestational trophoblastic disease showed that this correlation between c-erb B-2 expression and persistent gestational trophoblastic disease is not significant, suggesting that future efforts should be directed at the involvement of different oncoproteins.

Gestational trophoblastic disease

All five closely related tumours develop in the placenta. All five tumours arise from trophoblastic cells. The trophoblast is the membrane that forms the wall of the blastocyst in the early development of the fetus. In a normal pregnancy, trophoblastic cells aid the implantation of the fertilised egg into the uterine wall. But in GTD, they develop into tumour cells. Cause Two main risk factors increase the likelihood for the development of GTD: 1) The woman being under 20 years of age, or over 35 years of age, and 2) previous GTD. Although molar pregnancies affect women of all ages, women under 16 and over 45 years of age have an increased risk of developing a molar pregnancy.Being from Asia/of Asian ethnicity is an important risk factor. Hydatidiform moles are abnormal conceptions with excessive placental development. Conception takes place, but placental tissue grows very fast, rather than supporting the growth of a fetus.

Outcome of pregnancies occurring before completion of human chorionic gonadotropin follow-up in patients with persistent gestational trophoblastic tumor.

To determine the outcome of pregnancies occurring before completion of human chorionic gonadotropin follow-up in patients treated with chemotherapy for gestational trophoblastic tumor. Retrospective record review of patients with gestational trophoblastic tumor who conceived before standard hCG follow-up was completed during 1973-1998. Forty-three patients treated for gestational trophoblastic tumors conceived before human chorionic gonadotropin follow-up was completed. The antecedent pregnancy was complete mole in 31 (72.1%) and partial mole in 12 (27. 9%) patients. Of the 43 patients, 39 (90.7%) had stage I, 1 had stage II, and 3 had stage III disease. The mean interval from human chorionic gonadotropin remission to new pregnancy was 6.3 months (range 1-11 months). Ten patients underwent elective termination and four patients were lost to follow-up. Of the remaining 29 patients, 22 (75.9%) had term live births, 3 (10.3%) had preterm delivery, 3 had spontaneous abortion, and 1 (3.5%) had a repeat mole. Two cases of fetal anomalies were detected; one was inherited polydactyly and the other was hydronephrosis. One patient developed choriocarcinoma with lung involvement and underwent cesarean section at 28 weeks; a normal fetus was delivered and no choriocarcinoma was detected in the placenta. Pregnancies occurring in patients treated for gestational trophoblastic tumor before standard human chorionic gonadotropin follow-up is completed may continue under close clinical surveillance since the majority have a favorable outcome. However, patients should also be advised of the low but important risk of delayed diagnosis in case tumor relapse develops during early subsequent pregnancy.

Gestational Trophoblastic Disease -- Epidemiology

Risk factors for molar pregnancy include extremes of age, ethnicity, and a prior history of a HM, suggesting a genetic etiology. The risk of a complete mole is higher for women older than 35 years and younger than 21 years and 7.5 times higher for women older than 40 years. The risk of repeat molar pregnancy in women with a history of molar pregnancy is approximately 1% which is 10 to 20 times the risk in the general population. [1] Interestingly, a history of prior spontaneous abortion has been reported to confer a 2- to 3-fold increased risk of molar pregnancy compared to women without a history of spontaneous abortion. [3] Following 2 molar gestations, the risk of having a third mole is > 10%. [7] It is also important to note that malignant transformation such as choriocarcinoma or placental-site trophoblastic tumor can occur following any pregnancy.

Shortened duration of human chorionic gonadotrophin surveillance following complete or partial hydatidiform mole: evidence for revised protocol of a UK regional trophoblastic disease unit.

Following hydatidiform mole, women are at increased risk of persistent gestational trophoblastic neoplasia (pGTN) and are therefore monitored using serum human chorionic gonadotrophin (hCG) concentration measurements. We retrospectively evaluated the policy of extended (2 year) follow up for women with hCG concentrations returning to normal >56 days after evacuation. Of 6701 women registered for hCG follow up, 422 (6%) developed pGTN, 412 (98%) of these women presented within 6 months after evacuation. Three developed pGTN at 402, 677 and 1267 days after evacuation following spontaneous normalisation of hCG levels. Only one woman was detected by routine extended follow up. Prolonged surveillance after molar pregnancy causes significant anxiety and is not cost-effective. Therefore, the current revised protocol comprises hCG follow up for 6 months after spontaneous return of hCG levels to normal for all women.