Risk of abnormal pregnancy completing chemotherapy for gestational trophoblastic tumor

doi:10.1016/S0090-8258(02)00071-9

Gynecologic Oncology

Volume 88, Issue 2, February 2003, Pages 104-107

https://doi.org/10.1016/S0090-8258(02)00071-9 Get rights and content

Abstract

Objective

This study analyzed the outcome of the first pregnancy following chemotherapy for gestational trophoblastic tumor (GTT).

Methods

A total of 387 patients with GTT (85 patients with high-risk GTT and 302 patients with low-risk GTT) underwent chemotherapy at Chiba University Hospital between 1974 and 2000. Of these patients, 130 women (18 with high-risk GTT and 112 with low-risk GTT), who achieved remission and had at least one conception following chemotherapy, were included in the study.

Results

The outcomes of all the first subsequent pregnancies in women treated with methotrexate, actinomycin-D, or etoposide (including those switched to other regimens), or combination therapy, were comparable to those in the Japanese general population. However, the incidence of abnormal pregnancies (spontaneous abortion, still birth, repeat mole) was significantly higher in women who conceived within 6 months of completing chemotherapy (4/15; 40%) than in those who conceived after the recommended waiting period of more than 12 months (10/95; 10.5%) (P = 0.028).

Conclusion

Patients with GTT who achieved remission after chemotherapy with methotrexate, actinomycin-D, or etoposide, or combination therapy, may anticipate a normal future reproductive outcome. As pregnancies occurring within 6 months following remission are at risk of abnormalities, a waiting period of at least 6 months after chemotherapy for GTT is suggested.

Introduction

More than 90% of patients with gestational trophoblastic tumor (GTT) have been successfully treated with chemotherapy alone [1], [2]. Since this tumor occurs most frequently among women in their twenties and thirties, most of the patients at reproductive ages desire future pregnancy after the completion of chemotherapy. Therefore, the patients and their partners should receive counseling concerning subsequent pregnancy outcome after chemotherapy.

Many previous studies and our recent report have confirmed that patients with persistent GTT may anticipate normal reproductive outcomes except the risk of repeat molar pregnancy [3], [4], [5], [6], [7], [8], [9]. However, there were limited data concerning the first subsequent pregnancy, which might be at greatest risk of genetic damages or teratogenic effects induced by the anticancer drugs [7].

In this article, we studied the outcome of the first pregnancies in patients who achieved remission from GTT after receiving methotrexate (MTX), actinomycin-D (Act-D), or etoposide (including those switched to other regimens), or combination therapy.

Section snippets

Materials and methods

From 1974 to 2000, 387 consecutive patients with GTT (85 patients with high-risk GTT and 302 patients with low-risk GTT) underwent chemotherapy at Chiba University Hospital. Low-risk GTT was diagnosed on the basis of modified Hammond’s criteria [10] as follows: antecedent molar pregnancy, short disease duration (under 4 months), no brain or liver metastasis, and no treatment history.

Patients with low-risk GTT were initially treated with single-agent chemotherapy of MTX, Act-D, or etoposide.

Treatment outcome

Of 387 patients with GTT, 42 (10.9%) patients (5 with high-risk GTT and 37 with low-risk GTT) were lost to follow up. Twenty-two (6.4%) deaths occurred among 345 patients available for follow-up (follow-up period: 25 years to 9 months). Twenty patients died of GTT (widespread disease in 5, relapse in 4, refractory disease in 9, treatment-related in 1, and treatment refusal in 1), and the remaining two patients with high-risk GTT died of other causes (lung cancer in one and traffic accident in

Discussion

Anticancer drugs are preferentially toxic to rapidly dividing cells, such as cell of the oral epithelium, bone marrow, and gonads. Since many primordial to Graafian follicles have a high growth rate and the full span of follicle growth is estimated to be longer than 6 months [12], theoretically these developing follicles are particularly susceptible to the toxic effects of anticancer drugs. In addition, infertility associated with Act-D and vincristine treatment [4], and specific toxicities to

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Investigation and treatment of patients with persistent gestational trophoblastic disease and gestational trophoblastic tumours in the United Kingdom
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Comparison of chemotherapies with methotrexate, VP-16 and actinomycin-D in low-risk gestational trophoblastic diseaseremission rates and drug toxicities
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Cited by (18)

Perinatal outcomes of first pregnancy after chemotherapy for gestational trophoblastic neoplasia: a systematic review of observational studies and meta-analysis
2022, American Journal of Obstetrics and Gynecology
Citation Excerpt :
We intended to evaluate the time 1between the end of chemotherapy and the occurrence of the new pregnancy. Although 15 of the studies did not provide this information,17,27–30,32–37,39,41,43,44 5 studies presented data on outcomes 12 or more months after chemotherapy,19,20,31,40,45 3 presented data on outcomes between 6 and 12 months after chemotherapy,19,20,33 and only 2 studies presented data on outcomes <6 months after chemotherapy.19,20 A quantitative analysis was done taking into account the outcome of interest, spontaneous abortion, malformation, prematurity, and stillbirth.
To assess perinatal outcomes of first pregnancy after remission from gestational trophoblastic neoplasia and the impact of the time between the end of chemotherapy and the subsequent pregnancy.
The Medical Subject Headings related to perinatal outcomes, chemotherapy, and gestational trophoblastic neoplasia were used alone or in combination to retrieve relevant articles. We searched all references registered until April, 2019 in Embase, LILACS, MEDLINE, the Cochrane Central Register of Controlled Trials, and Web of Science.
We included any observational or interventional studies that evaluated perinatal outcomes of first pregnancy after chemotherapy for gestational trophoblastic neoplasia. Animal studies, narrative reviews, expert opinions, and previous treatments with potential risks for future perinatal outcomes which may introduce confounding bias were excluded.
Two reviewers independently screened all identified references for eligibility and data extraction. Methodological quality and bias of included studies were assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies from the National Institutes of Health. For the meta-analysis, the measures of association were calculated using bivariate random-effects models. Statistical heterogeneity was evaluated with I² statistics and explored through sensitivity analysis. Publication bias was assessed by visual inspection of the funnel plot or Egger’s test, according to the number of articles included. For all analyses, a P value of <.05 indicated statistical significance. This study was registered on PROSPERO (CRD42018116513).
A total of 763 studies were identified after literature search and 23 original studies were included in the systematic review and in the meta-analysis. The combined data from the subgroup meta-analysis (outcome vs time after chemotherapy) showed an incidence of spontaneous abortion of 15.28% (95% confidence interval, 12.37–18.74; I²=73%), 3.30% of malformation (95% confidence interval, 2.27–4.79; I²=31%), 6.19% of prematurity (95% confidence interval, 5.03–7.59; I²=0), and 1.73% of stillbirth (95% confidence interval, 1.17–2.55; I²=0%). These results were not influenced by the time between the end of chemotherapy and the subsequent pregnancy in most of the studied outcomes, including malformation (P=.14, I²=31%), prematurity (P=.46, I²=0), and stillbirth (P=.66, I²=0). However, there was a higher occurrence of spontaneous abortion (P<.01, I²=73%) in pregnancies that occurred ≤6 months after chemotherapy.
Chemotherapy for gestational trophoblastic neoplasia does not appear to increase the chance of unfavorable perinatal outcomes, except for the higher occurrence of spontaneous abortion in pregnancies occurring ≤6 months after chemotherapy.
Gestational trophoblastic disease
2012, Best Practice and Research: Clinical Obstetrics and Gynaecology
Most women with gestational trophoblastic disease are of reproductive age. Because the disease is readily treatable with favourable prognosis, fertility becomes an important issue. Hydatidiform mole is a relatively benign disease, and most women do not require chemotherapy after uterine evacuation. A single uterine evacuation has no significant effect on future fertility, and pregnancy outcomes in subsequent pregnancies are comparable to that of the general population, despite a slight increased risk of developing molar pregnancy again. If women develop persistent trophoblastic disease, single or combined chemotherapy will be needed. Although ovarian dysfunction after chemotherapy is a theoretical risk, a term live birth rate of higher than 70% has been reported without increased risk of fetal abnormalities. Successful pregnancies have also been reported after choriocarcinoma. Only a few case reports have been published on fertility-sparing treatment in placental-site trophoblastic tumour, and the successful rate is about 67%. Women are advised to refrain from pregnancy for at least 6 months after a molar pregnancy, and at least 12 months after a gestational trophoblastic neoplasia. Most of the contraceptive methods do not have an adverse effect on the return of fertility. Finally, at least one-half of these women suffer from some form of psychological or sexual problems. Careful counselling and involvement of a multi-disciplinary team are mandated.
Reproductive outcome after discharge of patients with high-risk hydatidiform mole with or without use of one bolus dose of actinomycin D, as prophylactic chemotherapy, during the uterine evacuation of molar pregnancy
2009, Gynecologic Oncology
Citation Excerpt :
Many previous studies confirmed that patients with GTN may anticipate normal reproductive outcomes except for the risk of repeat molar pregnancies [8,15,16]. In the series studied by Kim et al. [10] and Matsui et al. [41], the rate of newborns in the first pregnancy after cure was 80% and 78.1%, respectively. In a large series of pregnancies after GTD studied in the New England Trophoblastic Center (NETC), Garner et al. [11] found a percentage of 76% of newborns in 916 pregnancies to 1205 patients that had HM and 74.5% in 313 pregnancies to 420 patients treated for GTN.
To evaluate whether prophylactic chemotherapy (P-chem) with one bolus dose of actinomycin D (Act-D) during the uterine evacuation of patients with high-risk hydatidiform mole (Hr-HM) affects reproductive outcomes in subsequent pregnancies.
From 1987 to 2006, 1090 patients with gestational trophoblastic disease (GTD) were evaluated at a Trophoblastic Disease Center in southern Brazil; 265 with Hr-HM were selected and retrospectively analyzed. From 1996 to 2006, 163 received one bolus dose of Act-D at the time of uterine evacuation (Hr-HM-chem group); 102 with the same risk factors did not get P-chem (Hr-HM-control group). In March 2009, the number of pregnancies, progression of first pregnancy, and association of low age and low parity with subsequent pregnancy were evaluated.
The percentage of patients that became pregnant was similar in both groups (Hr-HM-control: 59.5%; Hr-HM-chem group: 45.7%; p = 0.069) and independent of HM progression. Percentages of no pregnancies because of age (≥ 40 years) or hysterectomy were also similar. Type of subsequent pregnancy was not statistically different between groups, and the rate of live births associated with pregnancies for which US showed a live fetus was high. Frequency of repeat GTD was unexpectedly high in both groups (4.2% and 6.3%; p = 1.00).
P-chem did not affect reproductive outcomes for patients with Hr-HM. Patients allowed to become pregnant again in both groups had high rates of live births associated with normal pregnancies. Chances of a subsequent pregnancy were higher in the low age and low parity subgroups.
Maternal and perinatal outcomes of first pregnancy after chemotherapy for gestational trophoblastic neoplasia in Brazilian women
2009, Gynecologic Oncology
To evaluate maternal and perinatal outcomes of first pregnancy after chemotherapy for gestational trophoblastic neoplasia (GTN) in Brazilian patients.
This study included 252 subsequent pregnancies after chemotherapy for GTN treated between 1960–2005. Correlations of maternal and perinatal outcomes with chemotherapy regimen (single or multiagent) and the time interval between chemotherapy completion and first subsequent pregnancy were investigated.
There was a significant increase in adverse maternal outcomes in women who conceived < 6 months than 6–12 months (76.2% and 19.6%; p < 0.0001; OR = 13.12; CI 95% = 3.87–44.40) and > 12 months (76.2% and 21.7%; p < 0.0001; OR = 11.56; CI 95% = 3.98–33.55) after chemotherapy. Spontaneous abortion frequency was higher < 6 months (71.4%) than 6–12 months (17.6%; p < 0.0001; OR = 11.66; CI 95% = 3.55–38.22) and > 12 months (9.4%; p < 0.0001; OR = 23.97; CI 95% = 8.21–69.91) after chemotherapy. There was no difference in adverse perinatal outcomes (stillbirth, fetal malformation, and preterm birth) related to the interval after chemotherapy and subsequent pregnancy. The overall occurrence of adverse maternal and perinatal outcomes did not significantly differ between patients on single or multiagent regimens.
Adverse maternal outcomes and spontaneous abortion were more frequent among patients who conceived within 6 months of chemotherapy completion. In these cases, careful prenatal monitoring and hCG level measurement 6 weeks after the completion of any new pregnancy are recommended.
Gestational trophoblastic disease
2003, Reviews in Gynaecological Practice
Gestational trophoblastic disease composed of a spectrum of abnormal trophoblastic proliferation. The benign end is molar pregnancy. Changes in the incidence, clinical presentation and criteria for ultrasonic diagnosis were observed over the years. With the help of cytogenetics, differentiation of hydropic degeneration, partial and complete mole is possible but still confined to research setting. Suction evacuation remained the main stay of treatment. Serum human chorionic gonadotrophin (hCG) monitor has to be performed in all post-molar pregnancy and the right choice of assay kit is mandatory to avoid false negative or positive results. The criteria for diagnosing persistent gestational trophoblastic neoplasia (GTN) has been agreed and reported in the FIGO 2000 Gynecologic Oncology Committee Report. Investigative tools were also recommended in the same report. The revised FIGO 2000 staging and classification in GTN has incorporated both anatomical staging and risk score classification modified from WHO. A cutoff of six inclusive was recommended to allocate patients into low and high risk groups. Appropriate treatment using single agent such as methotrexate in low risk group and multiple agents such as EMA-CO in high risk group usually resulted in a high cure rate. In drug resistant disease, multiple agents chemotherapy with and without adjuvant surgery or radiotherapy can salvage over 80% of patients. However, patients with both liver and brain metastasis stands a lower chance of survival. To achieve the best outcome for patients with gestational trophoblastic disease, patients should be managed in centers with experience.
Fertility and pregnancy outcome in gestational trophoblastic disease
2021, International Journal of Gynecological Cancer

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Regular articleRisk of abnormal pregnancy completing chemotherapy for gestational trophoblastic tumor

Abstract

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Materials and methods

Treatment outcome

Discussion

Gynecol Oncol

Am J Obstet Gynecol

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

Investigation and treatment of patients with persistent gestational trophoblastic disease and gestational trophoblastic tumours in the United Kingdom

Comparison of chemotherapies with methotrexate, VP-16 and actinomycin-D in low-risk gestational trophoblastic diseaseremission rates and drug toxicities

Gynecol Obstet Invest

Reproductive performance after molar pregnancy and gestational trophoblastic tumors

Clin Obstet Gynecol

Regular article
Risk of abnormal pregnancy completing chemotherapy for gestational trophoblastic tumor