gestational trophoblastic disease ( gtd ) is a rare event , up to 8 per 1000 pregnancies ( 1 ) . this term includes hydatidiform mole ( hm ) ( either complete or partial ) and malignant forms ( persistent gtd ) , comprising invasive mole , choriocarcinoma and placental site trophoblastic tumor . although hm is often treated with suction evacuation , about 15% of complete hm and 0.5% of partial hm transform into malignant forms ( 1 - 3 ) . serial assessment of serum human chorionic gonadotropin ( hcg ) titers is a standard method to identify post molar malignancy . however , in the first weeks , -hcg test has not the capability for early detection of high - risk patients . it had been shown than prophylactic chemotherapy significantly decreases the rate of persistency in this group ( 4 , 5 ) . transvaginal ultrasonography is a noninvasive and inexpensive medical imaging tool used for diagnosis of various diseases . using other imaging modalities , like computed tomography , magnetic resonance imaging ( mri ) and positron emission tomography is limited for detection of metastasis or locoregional spread ( 1 , 6 , 7 ) . mri is useful for detecting myometrial invasion , but not performed routinely for the assessment of persistent disease . several studies were performed to evaluate the roles of multiple prognostic factors , as ultrasound gray scale , doppler features , patient 's history ( as maternal age , gestational age , previous molar pregnancy and prolonged oral contraceptive use ) and lab tests ( 6 , 8 - 13 ) . because of early detection of molar pregnancy with ultrasound , some of these features ( as theca lutein cysts , larg uterine volume ) are not encountered as common as previously . in this study , we examined several predictive factors of persistency , and mainly focus on ultrasound results during follow - up courses . some ultrasound findings were determined to be effective in prediction and diagnosis of post evacuation malignancy as well as selecting high - risk patients . during the study period ( september 2009 to march 2011 ) , 19 patients were included , and 130 sonographic exams were performed . seventy - eight examinations were relevant to patients with spontaneous remission ( from the least 4 to 10 exams ) and 52 exams to patients with persistent gtd ( from the least 4 to 10 exams ) . all patients with molar pregnancy who did not perform evacuation before starting the study were included . in addition , histopathologic examination was performed for all patients after evacuation and any pathology other than molar pregnancy was excluded . patient 's history and laboratory data such as maternal age , gestational age , new hyperthyroidism and -hcg titer were recorded . the radiologist was blinded to patient s -hcg titers , and all titers were checked in one biochemistry laboratory . all patients were evaluated with transvaginal ultrasound and data about uterine volume , ovarian theca lutein cysts and uterine artery doppler indices were collected . sonographic examination was performed by duplex ultrasound machine ( medison accuvix v20 prstige ) using 7.5 mhz endovaginal probe . sample volume size was set as 2 mm , and angle between the doppler beam and the vessel was set as low as possible . doppler indices , including systolic to diastolic ratio ( s / d ) , resistive index ( ri ) and pulsatility index ( pi ) were calculated for each uterine artery by ultrasound machine software . at least two waveform samples in each side were obtained and the lowest value was used , then mean of both sides was measured as well . after evacuation , serum -hcg titers were controlled weekly and follow - up ultrasound was performed in the following manner ; one week after the evacuation , then every two weeks until 9th week and once a month , thereafter until sixth month . however , sometime patients with suspicious sonographic findings ( as endometrial retained tissue , indistinct junctional zone and focal increased vascularity in the uterus ) or abnormal -hcg titer were followed weekly . patients with rising or plateauing -hcg titers was considered persistent , and before starting chemotherapy their follow - up program was stopped . uterine artery doppler indices , any obvious increased vascularity or abnormal echo in the endometrium or myometrium and any new changes in the follow - up exams were evaluated carefully . 17 ( spss inc . , 233 south wacker drive , 11th floor , chicago , il 60606 - 6412 ) . paired t - test , based on -hcg titer during the follow - up course , patients were divided into two groups ; patients experienced persistent gtd ( group a ) , including eight ( 42% ) patients and another group ( group b ) , including 11 ( 58% ) patients who had spontaneous remission . mean follow - up assessments in group a was 6.5 and in the other group was seven . the first rise or plateauing of -hcg in patients of group a occurred at the range of 2 to 10 weeks ( mean : 4.56  2.8 weeks ) . the mean value of maternal age in patients with persistent gtd of group a was 26.3 and the other group was 25 years . in addition , past history of molar pregnancy was not seen in any of patients . eight ( 72.7% ) patients with spontaneous remission and 6 ( 75% ) patients in the other group had histologic confirmation of complete mole and other patients in the both groups had a partial mole . data from patient history , -hcg , and sonographic findings are depicted in table 1 . only existence of a theca lutein cyst was statistically significant ( p = 0.018 ) . however , there were delicate points that should be noticed : first , three of four patients , who had theca lutein cysts , had multiple bilateral cysts , and new hyperthyroidism and uterine volume  1000 cm were only seen in these patients . another patient had a few unilateral cysts with normal thyroid function test and uterine volume < 1000 cm . second , only two patients of group b had new hyperthyroidism , which was very faint and only one of them had uterine volume  1000 cm . patients with spontaneous remission were 11 cases and patients with persistent gtd were 8 cases , but hyperthyroidism evaluated in 10 patients with spontaneous remission and 7 cases in another group . findings of pulsed doppler ultrasound from the both groups are presented in table 2 . in the group with spontaneous remission , doppler indices ( s / d , ri and pi ) of uterine arteries showed a significant increase during 9 weeks follow - up course after evacuation ( p = 0.02 , p = 0.04 and p = 0.01 , respectively ) ( figure 1 ) . in contrast , no significant changes were seen in patients of group b ( p = 1 , p = 0.6 and p = 0.7 , respectively ) ( figure 2 ) . abbreviations : gtd , gestational trophoblastic disease ; hcg , human chorionic gonadotropin ; s / d , systolic to diastolic ratio ; ri , resistive index ; pi , pulsatility index . since the mean follow - up course in patients of group b was about 5.5 weeks , the data from another group in the 5th week was also analyzed to make a better comparison . besides , changes of ri and s / d were statistically significant ( p = 0.06 and p = 0.09 , respectively ) . pre - evacuation doppler indices of both groups were not significantly different ( p = 0.56 , p = 0.6 and p = 0.7 , respectively ) . hypervascularity of endometrium or myometrium , was seen in 2 ( 18% ) patients of group b , and 7 ( 87.5% ) of the other group . although subtle rising in doppler indices of patients of group b and mild decrease in the other group existed , these changes were not significant . eight ( 72.7% ) patients of group b did not have any abnormality ( as any retained tissue in the endometrium or any abnormal echo or focal hypervascularity in the myometrium ) in the uterus on the first ultrasound exam or on other follow - up visits . in the other group , the first examination was normal in only one ( 12.5% ) patient ( p = 0.02 ) , who had small polypoid lesions on the endometrial surface before -hcg rise . in five ( 62% ) patients of group a myometrial involvement , as a new nodule ( in 2 patients ) or a deep invasion ( 3 other patients ) was observed in follow - up visits after evacuation ; 2 patients had deep invasion in the first follow - up visit ( their first -hcg rise was detected at the second week of follow up visit in one patient and in fourth week of follow up visit in the other patient ) , other three patients had new nodule or deep invasion at the same time of first rising of -hcg titer ( in two patients at seventh week and one patient at third week ) . in contrast , none of these myometrial findings were observed in group b. this difference was highly significant ( p = 0.005 ) . focal indistinct junctional zone solely , without deep invasion into myometrium , was seen in two ( 18% ) patients with spontaneous remission , and in two ( 25% ) patients of the other group . one patient of group a had a retained tissue , which became progressively enlarged and hypervascular during the follow - up ( from 15.2  12 mm in the first week to 45.8  31.9 mm in 5.5th week ) ; figure 3 . the mean value of maternal age in patients with persistent gtd of group a was 26.3 and the other group was 25 years . in addition , past history of molar pregnancy was not seen in any of patients . eight ( 72.7% ) patients with spontaneous remission and 6 ( 75% ) patients in the other group had histologic confirmation of complete mole and other patients in the both groups had a partial mole . data from patient history , -hcg , and sonographic findings are depicted in table 1 . only existence of a theca lutein cyst was statistically significant ( p = 0.018 ) . however , there were delicate points that should be noticed : first , three of four patients , who had theca lutein cysts , had multiple bilateral cysts , and new hyperthyroidism and uterine volume  1000 cm were only seen in these patients . another patient had a few unilateral cysts with normal thyroid function test and uterine volume < 1000 cm . second , only two patients of group b had new hyperthyroidism , which was very faint and only one of them had uterine volume  1000 cm . patients with spontaneous remission were 11 cases and patients with persistent gtd were 8 cases , but hyperthyroidism evaluated in 10 patients with spontaneous remission and 7 cases in another group . findings of pulsed doppler ultrasound from the both groups are presented in table 2 . in the group with spontaneous remission , doppler indices ( s / d , ri and pi ) of uterine arteries showed a significant increase during 9 weeks follow - up course after evacuation ( p = 0.02 , p = 0.04 and p = 0.01 , respectively ) ( figure 1 ) . in contrast , no significant changes were seen in patients of group b ( p = 1 , p = 0.6 and p = 0.7 , respectively ) ( figure 2 ) . abbreviations : gtd , gestational trophoblastic disease ; hcg , human chorionic gonadotropin ; s / d , systolic to diastolic ratio ; ri , resistive index ; pi , pulsatility index . since the mean follow - up course in patients of group b was about 5.5 weeks , the data from another group in the 5th week was also analyzed to make a better comparison . besides , changes of ri and s / d were statistically significant ( p = 0.06 and p = 0.09 , respectively ) . pre - evacuation doppler indices of both groups were not significantly different ( p = 0.56 , p = 0.6 and p = 0.7 , respectively ) . hypervascularity of endometrium or myometrium , was seen in 2 ( 18% ) patients of group b , and 7 ( 87.5% ) of the other group . although subtle rising in doppler indices of patients of group b and mild decrease in the other group existed , these changes were not significant . eight ( 72.7% ) patients of group b did not have any abnormality ( as any retained tissue in the endometrium or any abnormal echo or focal hypervascularity in the myometrium ) in the uterus on the first ultrasound exam or on other follow - up visits . in the other group , the first examination was normal in only one ( 12.5% ) patient ( p = 0.02 ) , who had small polypoid lesions on the endometrial surface before -hcg rise . in five ( 62% ) patients of group a myometrial involvement , as a new nodule ( in 2 patients ) or a deep invasion ( 3 other patients ) was observed in follow - up visits after evacuation ; 2 patients had deep invasion in the first follow - up visit ( their first -hcg rise was detected at the second week of follow up visit in one patient and in fourth week of follow up visit in the other patient ) , other three patients had new nodule or deep invasion at the same time of first rising of -hcg titer ( in two patients at seventh week and one patient at third week ) . in contrast , none of these myometrial findings were observed in group b. this difference was highly significant ( p = 0.005 ) . focal indistinct junctional zone solely , without deep invasion into myometrium , was seen in two ( 18% ) patients with spontaneous remission , and in two ( 25% ) patients of the other group . one patient of group a had a retained tissue , which became progressively enlarged and hypervascular during the follow - up ( from 15.2  12 mm in the first week to 45.8  31.9 mm in 5.5th week ) ; figure 3 . according to figo , the sequential rise ( more than 10% ) of -hcg for  2 weeks or plateauing ( changes less than  10% ) for  3 weeks are indications for starting chemotherapy ( 13 ) . although serum -hcg titer is a powerful test and not yet replaced by other modalities , complementary method is needed : since either the entire or the maximum of tumoral tissue is evacuated , the first post evacuation titer of -hcg usually reveals a decreasing trend . thus , -hcg rise or plateauing needs more than one titer ( 14 ) and , in turn , it can not be helpful in early detection of high risk patients . sometime its titers are not available at the time of ultrasound exam , and isolated sonographic criteria are helpful ( 12 ) . several consecutive titers are needed to detect persistent disease and in high - risk patients when -hcg titer is unavailable , can lead to a delay in diagnosis that increases patient 's risk score and morbidity . despite controversy , investigations indicated that prophylactic chemotherapy reduces the incidence of persistent disease in high - risk patients in this state and are useful ( from 50% to 10 - 15% ) . however , chemoprophylaxis does not obviate the need for -hcg follow - up courses ( 4 , 5 ) . several studies were performed on different predictive factors till now ( 9 , 12 , 13 , 15 ) . in this article , among different pre - evacuation factors , the theca lutein cyst is found to be a useful parameter . its close association with new hyperthyroidism and uterine volume  1000 cm emphasizes that if a patient with gtd had new hyperthyroidism , multiple bilateral theca lutein cysts and large uterine volume , is very high - risk for further development of malignancy . however , in some previous studies it was shown that other factors had an association with persistent gtd ( 1 , 16 - 18 ) . in a study on 189 patients with gtd , only uterine size was significant among pre - evacuation factors ( maternal age , gestational age , blood group , vaginal bleeding , uterine volume , theca lutein cysts ) ( 13 ) . in addition , the early detection of molar pregnancy by ultrasound may be another reason , we did not see these features as common as previous exams . in an evaluation of doppler characteristics of the uterine arteries , we observed that the doppler index values significantly increased in patients of group b during the follow - up , but did not in another group . other studies revealed similar findings that changes in doppler indices inversely correlated with -hcg titers ( 8 - 10 , 19 ) . however , p value of these changes during 9 weeks follow - up course was not as significant as another similar investigation performed by abd el aal et al . in their study , p value of doppler index changes in each visit was about 0.0005 . nevertheless , in this study , weekly changes in doppler values were not significant in any of patients . there was no significant difference in pre - evacuation doppler results of the both groups . although , changes were faint and occasionally unpredictable in each follow - up exam . as it is shown in figures 1 and 2 , weekly changes at least for a short period did not obey the usual rule , for example in some patients of group b ( as shown in figure 1 ) , after rising doppler values for weeks , sudden decline occurred and so on in group a ( as shown in figure 2 ) . therefore , it can be suggested that doppler study is not a practical prognostic factor to differentiate these two groups . in this study , any abnormal finding in the uterus at the first follow - up examination was more related with persistent mole ; in 7 ( 87.5% ) patients of group a versus 3 ( 27.3% ) patients of the other group ( p = 0.02 ) . any abnormal echo in the myometrium or retained tissue in the endometrium at the first follow - up examination is predictive of a high - risk state . on the other hand , pre - evacuation prognostic factors therefore , ultrasound , which can accurately diagnose high - risk patients in the first week , when -hcg test is not helpful , has a worthful role in selecting patients who need closer follow - up . focal indistinct junctional zone with hypervascularity in this area was observed nearly similar in the both groups , and did not increase the risk of persistent disease . the most statistically significant ultrasound findings in this examination were myometrial involvement as deeply invasion to myometrium and new myometrial nodule ( p = 0.005 ) . these findings were observed in two patients in the first follow - up ( before rising of -hcg titer ) and in other three patients at the first rising of -hcg titer . this confirms the recent investigations . in the study of garavaglia et al . at multivariate analysis , only endometrial and myometrial involvement among different prognostic factors ( maternal and gestational age , uterine size , theca lutein cyst , etc . ) was significant ( p = 0.0001 ) ( 13 ) . compared gtd with retained product of conception . in this study , myometrial epicenter , deep invasion to myometrium , . rapid growth of endometrial retained tissue was observed in one patient with persistent disease . although it was not statistically significant , it is not considered a usual finding and suggests persistent disease . many patients with gtd are from low socioeconomic class and do not follow perfectly their post evacuation -hcg tests . thus , in high - risk patients who do not perform -hcg test at all or consecutively , observation of myometrial involvement or rapid growth of uterus mass is helpful to make a decision regarding the start of chemoprophylaxis . despite the small sample size , several factors were evaluated in this prospective study in a serial manner and our follow - up examinations started at the first post evacuation week . however , in our review of literature , the most investigations on gtd were either retrospective or started several weeks after evacuation and none of them emphasized the role of first week ultrasound . this research indicated that in patients with gtd showing no pre - evacuation prognostic factors , first week ultrasound could detect high - risk patients . when -hcg titer is not available in high - risk patients , ultrasound is an effective and useful method to make a decision of starting prophylactic chemotherapy and can be relied on as a powerful adjuvant to serum -hcg test .
background : transvaginal ultrasonography is a noninvasive and inexpensive medical imaging tool used for the diagnosis of various diseases.objectives:to identify an effective method to identify high - risk patients for developing malignancy after molar evacuation.patients and methods : a prospective serial assessment of 19 patients with gestational trophoblastic disease was performed . 
 clinical and laboratory data , transvaginal ultrasound and doppler findings were evaluated the day before evacuation . 
 they were followed - up in the first week after evacuation and every two weeks during the next two months , then every month until the sixth month.results:ovarian theca lutein cysts ( p = 0.018 ) ( among pre - evacuation factors ) and first week ultrasound ( p = 0.02 ) can help in detecting high - risk patients . even though , when -hcg titer is not available in a high - risk patient , post evacuation myometrial involvement ( p = 0.005 ) is a useful sign for detecting persistency.conclusions:some ultrasonographic features of molar pregnancy have capability to predict malignancy in the course of disease .