Treatments and outcomes in high-risk gestational trophoblastic neoplasia: A systematic review and meta-analysis.

BACKGROUND: High-risk gestational trophoblastic neoplasia (GTN) is rare and treated with diverse approaches. Limited published institutional data has yet to be systematically reviewed. OBJECTIVES: To compile global high-risk GTN (prognostic score ≥7) cohorts to summarise treatments and outcomes by disease characteristics and primary chemotherapy. SEARCH STRATEGY: MEDLINE, Embase, Scopus, ClinicalTrials.gov and Cochrane were searched through March 2021. SELECTION CRITERIA: Full-text manuscripts reporting mortality among ≥10 high-risk GTN patients. DATA COLLECTION AND ANALYSIS: Binomial proportions were summed, and random-effects meta-analyses performed. MAIN RESULTS: From 1137 records, we included 35 studies, representing 20 countries. Among 2276 unique high-risk GTN patients, 99.7% received chemotherapy, 35.8% surgery and 4.9% radiation. Mortality was 10.9% (243/2236; meta-analysis: 10%, 95% confidence interval [CI] 7-12%) and likelihood of complete response to primary chemotherapy was 79.7% (1506/1890; meta-analysis: 78%, 95% CI: 74-83%). Across 24 reporting studies, modern preferred chemotherapy (EMA/CO or EMA/EP) was associated with lower mortality (overall: 8.8 versus 9.5%; comparative meta-analysis: 8.1 versus 12.4%, OR 0.42, 95% CI: 0.20-0.90%, 14 studies) and higher likelihood of complete response (overall: 76.6 versus 72.8%; comparative meta-analysis: 75.9 versus 60.7%, OR 2.98, 95% CI: 1.06-8.35%, 14 studies), though studies focused on non-preferred regimens reported comparable outcomes. Mortality was increased for ultra-high-risk disease (30 versus 7.5% high-risk; meta-analysis OR 7.44, 95% CI: 4.29-12.9%) and disease following term delivery (20.8 versus 7.3% following molar pregnancy; meta-analysis OR 2.64, 95% CI: 1.10-6.31%). Relapse rate estimates ranged from 3 to 6%. CONCLUSIONS: High-risk GTN is responsive to several chemotherapy regimens, with EMA/CO or EMA/EP associated with improved outcomes. Mortality is increased in patients with ultra-high-risk, relapsed and post-term pregnancy disease.

Asbestos exposure and gestational trophoblastic disease: a hypothesis.

Among 2,968 women and girls exposed to crocidolite (blue asbestos) at Wittenoom, three cases of choriocarcinoma and three cases of hydatidiform mole have been identified (crude incidence rate of 9.9 per 1000 women and 1.7 per 1000 deliveries for choriocarcinoma and hydatidiform mole, respectively). The women with choriocarcinoma were resident at Wittenoom at the time of disease development, whereas hydatidiform mole occurred much later in women who had first been exposed to asbestos as young girls. Four of the six cases were known to have lived with asbestos company workers who brought their dusty work-clothes home for washing. Asbestos fibers have been reported in the lung, the pleural and peritoneal mesothelium, and the human ovary. They have also been detected in placental digests of live and stillborn infants. This cluster of gestational trophoblastic diseases has some biological plausibility for asbestos causation. Taking an occupational and residential history and examining pathologic specimens for asbestos fibers or bodies may prove useful in patients with gestational trophoblastic disease.

Recurrent partial hydatidiform mole, with a first twin pregnancy, after treatment with clomiphene citrate.

We present a patient, treated for 3 months with clomiphen citrate after 5 years of infertility. This treatment resulted in a twin pregnancy, one degenerated into a partial hydatidiform mole and the other into a very early embryo death. The karyotype was a mosaic one: 63% of metaphases showed triploidy - 69 XXX and 37% diploidy - 46 XX. Despite all medical advice, she returned 8 months later with a new pregnancy, which proved to be a new partial hydatidiform mole, this time a single one. Karyotype was, also, a triploidy - 69 XXX. The genetic map of both genitors was performed, showing no aberrations. Unfortunately, the patient came back, once again, 5 months later, with a new positive pregnancy test. Ultrasonography revealed a new very early embryo death, the histopathological analysis establishing to be a single 'pure' stop in evolution of the pregnancy. As all the three pregnancies obtained after treatment with clomiphene were abnormal, two being partial hydatidiform moles and one being a premature miscarriage, without any genetic aberrations of the genitors, it seems very possible that clomiphene, apart from improving fertility, also increases the risk of abnormal ovum appearance.

Review of recent Vietnamese studies on the carcinogenic and teratogenic effects of phenoxy herbicide exposure.

The methodology and results of several Vietnamese studies on the possible health effects of exposure to herbicides among the Vietnamese during the Second Indochina War are reviewed. The results of the studies appear to link either paternal or maternal exposure to herbicides to unfavorable outcomes of pregnancy. There is some evidence to suggest that the injury to reproduction diminishes over time. Two studies found statistically significant odds ratios of 4.6 and 12.0 for hydatidiform moles after exposure. One case-control study found a statistically significant odds ratio of 5.2 for liver cancer. Elevated odds ratios were also found for major externally detectable birth defects. Many of the detailed findings are in agreement with the results of animal experiments. Unfortunately, the Vietnamese do not have the resources to fully examine the health effects of phenoxy herbicides. It is our hope that recognition of the importance of the Vietnamese studies will lead to further work in this area.

Recurrent molar pregnancies associated with clomiphene citrate and human gonadotropins.

A 34-year-old patient, gravida 7, para 0, with three consecutive spontaneous abortions followed by four recurrent molar pregnancies is described. The patient conceived only with clomiphene citrate or human gonadotropin treatment. The occurrence of molar pregnancies succeeded spontaneous abortions with one remaining pregnancy progressing to gestational trophoblastic disease. The role of clomiphene citrate and human gonadotropins in the pathogenesis of this disease is discussed.

Coexistent complete hydatidiform mole and fetus after therapy with human menopausal gonadotropin. A case report.

A patient who had undergone therapy with human menopausal gonadotropin had a coexistent complete hydatidiform mole and fetus. This report is the first published account of such a case.

Clomiphene-citrate-induced hydatidiform mole.

The reported incidence of molar pregnancies induced by clomiphene citrate is 1:659. Only nine cases, including this one, were found in an extensive search of the literature. Several questions are raised regarding the true incidence of molar pregnancy in clomiphene-induced pregnancies. Evaluation of the induced pregnancy with diagnostic ultrasound is urged.

Hydatidiform mole arising twice during bromocriptine therapy. Case report.

A patient with a prolactin secreting pituitary tumour is described, in whom two pregnancies occurred during bromocriptine treatment. Both were hydatidiform moles.