Persistent Gestational Trophoblastic Disease Research Articles

Tetraploid Partial Hydatidiform Mole

Distinction of hydatidiform moles from nonmolar specimens and their subclassification as complete (complete hydatidiform mole) versus partial hydatidiform mole (PHM) are important for clinical practice and investigational studies to refine ascertainment of risk of persistent gestational trophoblastic disease, which differs among these entities. Immunohistochemical analysis of p57 expression, a paternally imprinted maternally expressed gene on 11p15.5, and molecular genotyping are useful for improving diagnosis. Here, we describe a first trimester abortus with morphologic features consistent with a hydatidiform mole and p57 expression pattern supporting a diagnosis of PHM. Short tandem repeat (STR) genotyping and fluorescent in-situ hybridization analysis showed tetraploidy with 3 paternal and 1 maternal chromosome complements. To our knowledge, this is the first description of a tetraploid PHM confirmed to be triandric by STR analysis, and the first description of p57 immunostaining in a confirmed triandric tetraploid PHM. This case highlights the complex nature of the genetics that can be encountered in molar specimens and illustrates that STR genotyping, in contrast to fluorescent in-situ hybridization or ploidy analysis, offers the advantage of determining the parental origin of chromosome complements for refined diagnosis of hydatidiform moles.

Diandric Triploid Hydatidiform Mole With Loss of Maternal Chromosome 11

Distinction of hydatidiform moles (HM) from nonmolar specimens and their subclassification as complete (CHM) versus partial hydatidiform mole (PHM) are important for clinical practice and investigational studies to refine ascertainment of risk of persistent gestational trophoblastic disease (GTD), which differs among these entities. Immunohistochemical analysis of p57 expression, a paternally imprinted maternally expressed gene on 11p15.5, and molecular genotyping are useful for improving diagnosis. CHMs are characterized by androgenetic diploidy, with loss of p57 expression due to lack of maternal DNA. Loss of p57 expression distinguishes CHMs from both PHMs (diandric triploidy) and nonmolar specimens (biparental diploidy), which retain expression. We report a unique HM characterized by morphologic features suggesting an early CHM, including lack of p57 expression by immunohistochemistry, but with genetic features more in keeping with a PHM. Specifically, molecular genotyping by short tandem repeat markers provided evidence to support interpretation as a PHM by demonstrating allele patterns and ratios most consistent with diandric triploidy, with evidence of loss of the maternal copy of chromosome 11 to explain the lack of p57 expression. This case illustrates the value of combined traditional pathologic and ancillary molecular techniques for refined diagnosis of molar specimens. It also raises questions regarding which modalities should be used to ultimately define the subtypes of HMs and whether chromosomal losses or gains, particularly involving imprinted genes such as p57, might play a role in modifying risk of persistent GTD.

Hyperthyroidism and human chorionic gonadotrophin production in gestational trophoblastic disease

Background:Gestational trophoblastic disease (GTD) is a rare complication of pregnancy, ranging from molar pregnancy to choriocarcinoma. Patients with persistent disease require treatment with chemotherapy. For the vast majority, prognosis is excellent. Occasionally, GTD is complicated by hyperthyroidism, which may require treatment. This is thought to occur due to molecular mimicry between human chorionic gonadotrophin (HCG) and thyroid-stimulating hormone (TSH), and hence cross-reactivity with the TSH receptor. Hyperthyroidism usually resolves as the GTD is successfully treated and correspondingly HCG levels normalise.Methods:This paper reviews cases of GTD treated over a 5-year period at one of the three UK centres and identifies the prevalence of hyperthyroidism in this population. Four cases with clinical hyperthyroidism are discussed.Results:On review of the 196 patients with gestational trophoblastic neoplasia treated with chemotherapy in Sheffield since 2005, 14 (7%) had biochemical hyperthyroidism. Of these, four had evidence of clinical hyperthyroidism.Conclusion:Concomitant biochemical thyroid disease in patients with GTD is relatively common, and measurement of thyroid function in patients with persistent GTD is, therefore, important. The development of hyperthyroidism is largely influenced by the level of HCG and disease burden, and usually settles with treatment of the persistent GTD. However, rarely the thyroid stimulation can have potentially life-threatening consequences.

Hydatidiform Moles

Distinction of hydatidiform moles from nonmolar specimens and subclassification of hydatidiform moles as complete hydatidiform mole (CHM), partial hydatidiform mole (PHM), or early CHM are important for both clinical practice and investigational studies. The risk of persistent gestational trophoblastic disease and hence, clinical management, differs for CHMs, PHMs, and nonmolar specimens. However, diagnosis based solely on morphology suffers from poor interobserver reproducibility and remains problematic even for experienced gynecologic pathologists. The unique genetic features of CHMs (androgenetic diploidy), PHMs (diandric triploidy), and nonmolar specimens (biparental diploidy) allow for certain molecular techniques, including immunohistochemical analysis of p57 expression (a paternally imprinted maternally expressed gene) and molecular genotyping, to refine the diagnosis of hydatidiform moles. Although p57 immunostaining alone can identify CHMs, which lack p57 expression because of the lack of maternal DNA, this analysis cannot distinguish PHMs from nonmolar specimens as both express p57 because of the presence of maternal DNA. Short tandem repeat genotyping, which can determine the parental source of polymorphic alleles, can distinguish among all of these entities by discerning androgenetic diploidy, diandric triploidy, and biparental diploidy to rigorously diagnose CHMs, PHMs, and nonmolar specimens, respectively. An algorithmic approach using these techniques to refine morphologic diagnosis has been developed for routine practice. This review discusses current issues in the diagnosis of hydatidiform moles, including the limitations of morphologic diagnosis, the need for refined diagnosis to assure accurate ascertainment of risk of persistent gestational trophoblastic disease associated with the different subtypes of hydatidiform moles, the use of ancillary immunohistochemical and molecular techniques for providing such refined diagnosis, and problems that can be encountered with these techniques.

Dizygotic Twin Pregnancy with a Normal Fetus and a Nodular Embryo Associated with a Partial Hydatidiform Mole

Although twin pregnancies complicated by a coexisting complete hydatidiform mole are uncommon, those with partial hydatidiform mole (PHM) are exceedingly rare; there are only several well-documented cases diagnosed antenatally. Here we present the first case of a twin placenta containing a nodular embryo associated with PHM diagnosed on routine placental examination. This dizygotic twin pregnancy featured viable embryos at 8 weeks' gestation, death of 1 embryo at 12 weeks, and delivery of a healthy infant by caesarean section at 28 weeks because of worsening maternal reflux nephropathy. Macroscopic and microscopic placental examination and fluorescence in situ hybridization showed one part of the placenta to be diploid and the other to contain a vanishing triploid embryo and a PHM, which had eluded antenatal ultrasound diagnosis. Careful pathologic examination of vanishing twins and their placentas may disclose an unexpected PHM, which can be associated, albeit infrequently, with persistent gestational trophoblastic disease or a trophoblastic tumor.

Molecular Analysis of Hydatidiform Moles

Distinction of hydatidiform moles from nonmolar specimens and subclassification of hydatidiform moles as complete hydatidiform mole (CHM), partial hydatidiform mole (PHM), or early CHM are important for both clinical practice and investigational studies. The risk of persistent gestational trophoblastic disease and hence, clinical management differs for CHMs, PHMs, and nonmolar specimens. However, diagnosis based solely on morphology suffers from poor interobserver reproducibility and remains problematic even for experienced gynecologic pathologists. The unique genetic features of CHMs (androgenetic diploidy), PHMs (diandric triploidy), and nonmolar specimens (biparental diploidy) allow for certain molecular techniques, including immunohistochemical analysis of p57 expression (a paternally imprinted maternally expressed gene) and molecular genotyping, to refine the diagnosis of hydatidiform moles. While p57 immunostaining alone can identify CHMs, which lack p57 expression due to the lack of maternal DNA, this analysis cannot distinguish PHMs from nonmolar specimens since both express p57 due to the presence of maternal DNA. Short tandem repeat genotyping, which can determine the parental source of polymorphic alleles, can distinguish among all of these entities by discerning androgenetic diploidy, diandric triploidy, and biparental diploidy to rigorously diagnose CHMs, PHMs, and nonmolar specimens, respectively. An algorithmic approach using these techniques to refine morphologic diagnosis has been developed for routine practice. This review discusses current issues in the diagnosis of hydatidiform moles, including the limitations of morphologic diagnosis, the need for refined diagnosis to assure accurate ascertainment of risk of persistent gestational trophoblastic disease associated with the different subtypes of hydatidiform moles, and the utility of ancillary immunohistochemical and molecular techniques for providing such refined diagnosis.

Placental site trophoblastic tumor presenting as an intramural mass with negative markers: an opportunity for novel diagnosis and treatment with robotic hysterectomy.

A patient presented with persistent levels of quantitative human chorionic gonadotropin despite therapy with methotrexate. A dilation and curettage procedure did not provide a pathologic diagnosis. Gestational trophoblastic disease was suspected, but serum biomarkers were unable to provide a pre-operative diagnosis. A mass was found in the uterus by ultrasound and subsequent computed tomography scans. There was no evidence of extrauterine disease, but the uterine mass was continuous with the endometrial cavity, evoking the suspicion of an invasive endometrial mass. The patient underwent robotic hysterectomy for both therapy and diagnosis of suspected gestational trophoblastic disease (GTD). The final pathologic diagnosis was placental site trophoblastic tumor. The robotic approach allows for a minimally invasive surgical procedure with thorough examination of the pelvic cavity and adnexae and does not require a uterine manipulator which may be contra-indicated in the setting of uterine GTD. For patients with suspected persistent uterine GTD who are otherwise candidates for minimally invasive surgery, a robotic procedure offers advantages when compared to traditional laparoscopy or vaginal hysterectomy.

May platelet count be a predictor of low-risk persistent gestational trophoblastic disease?

The aim of this paper was to determine whether platelet count could be used as an early marker to predict low-risk persistent trophoblastic disease (PTD) from complete hydatidiform mole (CHM). This study included 27 PTD, 30 CHM, and 30 healthy pregnant women. All patients were evaluated with respect to age, gestational age, parity, BMI, and platelet count. All women had low-risk disease using FIGO and WHO scoring systems. There were no significant differences in terms of age, gestational age, parity, BMI between the groups (P > 0.05, for all). Platelet levels were lower in patients with low-risk PTD compared with CHM and healthy pregnant group (P = 0.001 and P < 0.0001, respectively). Platelet levels were also found to be lower in patients with CHM than in healthy pregnancies (P = 0.006). There was a negative relationship between platelet count and low-risk PTD (r = 0.47, P < 0.0001) in the study. The receiver operating characteristic curve analysis revealed a high diagnostic value for platelet count with respect to low-risk PTD with an area under curve of 0.80 (95% confidence interval = 0.89-0.90), sensitivity = 77% and specificity = 75%. Platelet count was significantly decreased in low-risk PTD compared with CHM and healthy pregnant controls. Platelet count can be used as a reliable marker for the early detection of low-risk PTD.

Twin pregnancy with diploid partial hydatidiform mole and coexisting fetuses following in vitro fertilization and embryo transfer: A case report

A 24-year-old woman, gravida 1, para 0, was referred to our hospital at 14 weeks of gestation due to suspected twin pregnancy with hydatidiform mole and coexisting fetuses. The present pregnancy was achieved following in vitro fertilization and embryo transfer (IVF-ET). Ultrasound examinations at 14 weeks 3 days of gestation revealed a live fetus appropriate for assigned gestational age with a normal-looking placenta and a dead fetus with an additional echogenic mass resembling molar placenta. The patient was planned to take amniocentesis for chromosomal analysis. However, regular uterine contraction was developed and spontaneous expulsion was occurred at 14 weeks 4 days of gestation. Chromosomal analysis of twin pregnancy using normal and molar placental tissues revealed normal karyotype with 46,XY, 46,XX, respectively. Follow-up showed no progression to persistent gestational trophoblastic disease. We present a twin pregnancy with diploid partial hydatidiform mole and coexisting fetuses that occurred following IVF-ET, which was aborted spontaneously.

Analysis of risk factors for persistent gestational trophoblastic disease

Persistent disease is a serious consequence of molar pregnancies. Its early detection is critical to effective chemotherapy. Therefore, determination of risk becomes an important clinical decision. To determine the relative risk of persistent disease in a cohort of patients with partial and complete molar pregnancies by analysis of five factors derived from a database using multivariate analysis. Of 686 patients, 78 developed persistent disease which required treatment (rate of 11.3%). Risk was markedly increased when serum human chorionic gonadotrophin (HCG) failed to reach negative by 12 weeks after evacuation [hazard ratio (HR) = 120.78, P < 0.001]. Risk was markedly decreased when the interval from last pregnancy exceeded 12 months (HR = 0.24, P = 0.005). Other factors such as patient's age, stage of gestation and serum HCG level at presentation were not found to be strongly associated with risk of persistent disease. These findings support the application of the following two factors in risk prediction for molar pregnancies: > 12 weeks to become HCG negative and interval from last pregnancy < 12 months. They will contribute to a greater awareness of persistent disease and assist in early detection and effective chemotherapy.

Molecular Genotyping of Hydatidiform Moles: Analytic Validation of a Multiplex Short Tandem Repeat Assay

Distinction of hydatidiform moles from non-molar (NM) specimens, as well as their subclassification as complete (CHM) versus partial hydatidiform moles (PHM), is important for clinical management and accurate risk assessment for persistent gestational trophoblastic disease. Because diagnosis of hydatidiform moles based solely on morphology suffers from poor interobserver reproducibility, a variety of ancillary techniques have been developed to improve diagnosis. Immunohistochemical assessment of the paternally imprinted, maternally expressed p57 gene can identify CHMs (androgenetic diploidy) by their lack of p57 expression, but cannot distinguish PHMs (diandric monogynic triploidy) from NMs (biparental diploidy). Short tandem repeat genotyping can identify the parental source of polymorphic alleles and thus discern androgenetic diploidy, diandric triploidy, and biparental diploidy, which allows for specific diagnosis of CHMs, PHMs, and NMs, respectively. In this study, a retrospectively collected set of morphologically typical CHMs (n = 8), PHMs (n = 10), and NMs (n = 12) was subjected to an analytic validation study of both short tandem repeat genotyping and p57 immunohistochemistry. Several technical and biological problems resulted in data that were difficult to interpret. To avoid these pitfalls, we have developed an algorithm with quantitative guidelines for the interpretation of short tandem repeat genotyping data.

Complete Hydatidiform Mole With Retained Maternal Chromosomes 6 and 11

Distinction of hydatidiform moles from nonmolar specimens and their subclassification as complete hydatidiform mole (CHM) versus partial hydatidiform mole (PHM) are important for clinical practice and investigational studies to refine ascertainment of risk of persistent gestational trophoblastic disease which differs among these entities. Immunohistochemical analysis of p57 expression, a paternally imprinted maternally expressed gene on 11p15.5, and molecular genotyping are useful for improving diagnosis. CHMs are characterized by androgenetic diploidy, with the loss of p57 expression owing to lack of maternal DNA. Loss of p57 expression distinguishes CHMs from both PHMs (diandric triploidy) and nonmolar specimens (biparental diploidy) which retain expression. In the process of evaluating molar specimens in our laboratory with p57 immunohistochemistry and molecular genotyping, we identified a morphologically typical androgenetic diploid CHM with aberrant diffuse p57 expression. Molecular genotyping by short tandem repeat markers and genome-wide copy number analysis by single nucleotide polymorphism array established androgenetic diploidy with retained maternal copies of chromosomes 6 and 11, with aberrant p57 expression attributable to the latter. This case, only the second reported to date, illustrates the value of combined traditional pathologic and ancillary molecular techniques for refined diagnosis of molar specimens. Specimens with morphologic features suggestive of CHM yet retaining p57 expression should be subjected to molecular genotyping to establish a definitive diagnosis because misclassification as PHM underestimates the risk of persistent gestational trophoblastic disease. We recommend use of p57 immunohistochemistry and molecular genotyping to evaluate all products of conception specimens for which there is any consideration of a diagnosis of hydatidiform mole. Genome-wide analysis has the potential to assist in localizing imprinted genes critical for determining the morphologic and behavioral phenotypes of hydatidiform moles.

Complete mole coexistent with a twin fetus

Complete hydatiforme mole with coexisting live fetus (CMCF) is a rare entity. Management for this rare twin pregnancy still remains undetermined. We report the delivery of a healthy baby coexisting with complete mole as twins. There was no other complication during or after the pregnancy. A 30-year-old multiparous woman was first time assessed in the antenatal outpatient department of our hospital at 17weeks gestation for normal pregnancy control. Ultrasound examination showed a 17week and 5days viable fetus with normal anatomy and placenta. There was a second multicystic placenta located at the posterior wall of the uterus next to the normal placenta. Hydatiforme mole was suspected. The couple was informed about the possible complications but they were not willing to consider pregnancy termination or to have any invasive procedure for diagnosis. A cesarean section was performed at 33weeks gestation due to premature rupture of membranes and initiation of labor with the fetus presenting as breech. After the delivery of a live healthy female 1,950g baby, as well as the normal placenta, a second vesicular placenta was delivered. Histopathologic examination confirmed the diagnosis of complete mole. Today most of the twin pregnancies with complete mole are identified in the first or second trimester. In this case, the parents who choose continuation of pregnancy, are counseled about the increased risk of complications like preeclampsia, fetal loss, persistent gestational trophoblastic disease. Close surveillance of the woman with CMCF is mandatory during and after the pregnancy.

Triplet pregnancy with partial hydatidiform mole coexisting with two fetuses: A case report

Hydatidiform mole with a coexistent fetus is rare, but this condition has recently shown an increased incidence because of assisted reproduction technology. Herein, we report on a case of triplet pregnancy with a partial hydatidiform mole coexisting with two fetuses. It was diagnosed by p57(kip2) immunohistochemical staining which is helpful in determining histologically equivocal cases. After termination of pregnancy, the patient was diagnosed with persistent gestational trophoblastic disease. Six courses of methotrexate chemotherapy were performed. Her beta-human chorionic gonadotrophin titers then fell to a normal level.

Treatment for Low-Risk Gestational Trophoblastic Disease: Comparison of Single-Agent Methotrexate, Dactinomycin and Combination Regimens

Numerous chemotherapy regimens for treating gestational trophoblastic disease (GTD) have been described over the past 5 decades. Few studies have evaluated different chemotherapeutic agents in patients from a single center who had low-risk GTD. This retrospective review, covering the years 1980-2002, compared 3 medication regimens in 108 patients who had low-risk but persistent GTD and who received first-line chemotherapy. Forty-two patients were treated with methotrexate (MTX), 42 with dactinomycin (ACT), and 24 with a combination of MTX and ACT (MACT). Rates of complete remission were 69% in the MTX group, 61.4% in patients treated with ACT, and 79.1% in those given combination therapy. There were no significant group differences in either the duration of treatment or the number of courses of chemotherapy. Reported rates of adverse side effects were 62.5% in the MACT group, 28.6% with MTX only, and 19.1% in patients given only ACT. Grade 3 or grade 4 side effects were recorded in 2 patients in the MTX group and 2 of those given combined treatment. Hysterectomy was done in 21 patients, with no differences among treatment groups. Thirty patients required second-line chemotherapy. The investigators conclude that single-agent chemotherapy is as effective as combination chemotherapy when treating patients for low-risk GTD. Dactinomcin was the least toxic of the drugs evaluated in this study, and it might be the most cost-effective option. In areas where resources are limited, MTX-which is relatively feasible to administer-is the preferred regimen.

Twin pregnancy with a complete hydatidiform mole and surviving co-existent fetus

Twin pregnancy with complete hydatidiform mole and co-existent fetus (CHMF) resulting in a healthy take-home baby is rare, with only 30 cases documented in detail in the literature. A 29-year-old woman conceived following two cycles of ovulation induction with clomiphene citrate. Successive ultrasound examinations demonstrated a normally growing live fetus alongside a normal placenta and an additional intrauterine echogenic mass with features of hydatidiform mole. At 17 week gestation, serum beta-hCG level was 25.38 multiples of the median. Genetic amniocentesis at 18.5 week gestation showed normal fetal 46XX karyotype. A cesarean section performed at 28 week gestation resulted in the delivery of a live normal female infant and two adjoining placentas. One placenta was normal and the other placenta was composed of vesicles of various sizes. Microscopic examination of the abnormal placenta confirmed complete hydatidiform mole. The baby did well and serial maternal serum beta-hCG levels showed a declining trend and were undetectable by 7 weeks after delivery. Continuation of a twin pregnancy with CHMF is an acceptable option. There is, however, an increased risk of developing pre-eclampsia and fetal loss due to miscarriage. The chance of a live term birth is <50% with nearly 33% of the mothers developing persistent gestational trophoblastic disease after delivery. Thus, close surveillance of an ongoing twin pregnancy with CHMF is mandatory to detect potential early signs of maternal and fetal complications.

Treatment for low-risk gestational trophoblastic disease: Comparison of single-agent methotrexate, dactinomycin and combination regimens

Objectives To compare the efficacy of three different standard chemotherapy regimens for low-risk gestational trophoblastic disease according to the FIGO staging system in a single-institute setting. Methods From 1980 until 2002, we retrospectively reviewed 108 cases with low-risk persistent gestational trophoblastic disease who were treated with first-line chemotherapy. Patients were divided in three groups according to chemotherapy regimen: patients treated with methotrexate (MTX group; n = 42), patients treated with dactinomycin (ACT group; n = 42) and patients treated with methotrexate and dactinomycin in combination (MACT group; n = 24). We compared the number of chemotherapy courses for achieving remission, the duration of treatment, the adverse side effects, the efficacy of the treatment and the need for performing a hysterectomy among the groups Results The complete remission rates were 69%, 61.4% and 79.1% for methotrexate (MTX), dactinomycin (ACT) and the combination regimen (MACT) treated groups, respectively ( p = 0.7). The duration of the treatment and the number of chemotherapy courses were similar among the groups ( p = 0.2 and p = 0.4, respectively). Adverse side effects rate was reported to be 62.5% in the MACT group, 28.6% in the MTX group and 19.1% in the ACT group ( p = 0.0003). Second-line chemotherapy was indicated for 30 patients. Hysterectomy was performed in 21 patients overall, and there was no difference among the groups ( p = 0.6). Conclusion Our analysis indicates that single-agent chemotherapy regimens are as effective as combination chemotherapy for low-risk gestational trophoblastic disease. Dactinomycin is a less toxic drug and might offer the best cost-effective treatment option. Methotrexate must be considered as the regimen of choice for low resource areas because of the feasibility of its administration.

Selective uterine artery embolization: A new therapeutic approach in a patient with low-risk gestational trophoblastic disease

We report a case of persistent gestational trophoblastic disease (GTD) in which a selective uterine artery embolization instead of invasive surgery achieved both the control of pelvic hemorrhage and of disease.

Overdiagnosis of Complete and Partial Hydatidiform Mole in Tubal Ectopic Pregnancies

Partial or complete hydatidiform mole (HM) affects approximately 1 in 500 to 1,000 pregnancies. Previous small series suggest that histopathologic diagnosis of HM may be difficult in tubal ectopic pregnancies. The histopathology database of a regional Trophoblastic Disease Unit was searched to identify cases with a referral diagnosis of tubal HM, and the histopathologic findings were reviewed. During the study period (1986-2004 inclusive), there were 132 cases. After central review by specialist histopathologists, the final diagnosis was ectopic partial mole in two, ectopic complete mole in five, and ectopic hydatidiform mole (not otherwise specified) in one. The final diagnosis of definite hydatidiform mole was made in eight (6%) cases, significantly less than in referred uterine curettage specimens, in which approximately 90% have a confirmatory diagnosis of HM (Z = 12.9; p < 0.0001). No cases in this series developed persistent gestational trophoblastic disease, the human chorionic gonadotropin concentration spontaneously returning to normal. Ectopic pregnancies, where managed surgically, should be submitted for histopathologic examination; however, the pathologist should be aware that the degree of extravillus trophoblastic proliferation may appear more florid compared with evacuated uterine products of conception. Molar pregnancy should only be diagnosed when strict criteria regarding morphologic abnormalities previously described in uterine evacuation material are applied.

Experience in Treatment of Patients with Gestational Trophoblastic Disease

To determine outcome in patients with hydatidiform mole and gestational trophoblastic tumor after successful treatment. This was a retrospective review of outcome in 22 patients with gestational trophoblastic disease (GTD) who completed human chorionic gonadotropin (hCG) follow-up for 1 year or more after treatment between 1999 and 2003. The mean age of patients with GTD was 32.5 years. Sixteen patients (72.7%) with hydatidiform mole and six (27.3%) with gestational trophoblastic tumor were evaluated. One patient (4.5%) with metastatic choriocarcinoma experienced complete remission after debulking surgery followed by chemotherapy. Fifteen patients (68.2%) with persistent GTD were diagnosed by hCG follow-up. After at least 1 year, eight patients (36.4%) conceived and six (27.3%) delivered a healthy term baby. All patients experienced an excellent prognostic outcome following chemotherapy and there were no deaths. GTD exhibited an excellent response to chemotherapy and subsequent successful pregnancy was achieved in some patients 1 year or more after completion of treatment. Patients without previous childbirth desired subsequent pregnancy. Patients must be followed-up carefully after treatment and during conception.