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1.
Cell Death Dis ; 11(8): 658, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32814763

RESUMO

Complete hydatidiform mole (HM) is a gestational trophoblastic disease resulting in hyperproliferation of trophoblast cells and absence of embryo development. Mutations in the maternal-effect gene NLRP7 are the major cause of familial recurrent complete HM. Here, we established an in vitro model of HM using patient-specific induced pluripotent stem cells (iPSCs) derived trophoblasts harboring NLRP7 mutations. Using whole transcriptome profiling during trophoblast differentiation, we showed that impaired NLRP7 expression results in precocious downregulation of pluripotency factors, activation of trophoblast lineage markers, and promotes maturation of differentiated extraembryonic cell types such as syncytiotrophoblasts. Interestingly, we found that these phenotypes are dependent on BMP4 signaling and BMP pathway inhibition corrected the excessive trophoblast differentiation of patient-derived iPSCs. Our human iPSC model of a genetic placental disease recapitulates aspects of trophoblast biology, highlights the broad utility of iPSC-derived trophoblasts for modeling human placental diseases and identifies NLRP7 as an essential modulator of key developmental cell fate regulators.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteína Morfogenética Óssea 4/metabolismo , Trofoblastos/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Proteína Morfogenética Óssea 4/fisiologia , Diferenciação Celular/genética , Células Cultivadas , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Mola Hidatiforme/genética , Mola Hidatiforme/fisiopatologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Modelos Biológicos , Placenta/metabolismo , Gravidez , Transdução de Sinais/fisiologia , Transcriptoma/genética
2.
Sci Rep ; 10(1): 3614, 2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-32109236

RESUMO

In humans, parthenogenesis and androgenesis occur naturally in mature cystic ovarian teratomas and androgenetic complete hydatidiform moles (CHM), respectively. Our previous study has reported human parthenogenetic induced pluripotent stem cells from ovarian teratoma-derived fibroblasts and screening of imprinted genes using genome-wide DNA methylation analysis. However, due to the lack of the counterparts of uniparental cells, identification of new imprinted differentially methylated regions has been limited. CHM are inherited from only the paternal genome. In this study, we generated human androgenetic induced pluripotent stem cells (AgHiPSCs) from primary androgenetic fibroblasts derived from CHM. To investigate the pluripotency state of AgHiPSCs, we analyzed their cellular and molecular characteristics. We tested the DNA methylation status of imprinted genes using bisulfite sequencing and demonstrated the androgenetic identity of AgHiPSCs. AgHiPSCs might be an attractive alternative source of human androgenetic embryonic stem cells. Furthermore, AgHiPSCs can be used in regenerative medicine, for analysis of genomic imprinting, to study imprinting-related development, and for disease modeling in humans.


Assuntos
Células-Tronco Pluripotentes Induzidas/citologia , Herança Paterna , Diferenciação Celular , Células Cultivadas , Metilação de DNA , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Impressão Genômica , Humanos , Mola Hidatiforme/genética , Mola Hidatiforme/metabolismo , Mola Hidatiforme/fisiopatologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino , Gravidez , Reprodução Assexuada
3.
Sao Paulo Med J ; 137(3): 278-283, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31411244

RESUMO

BACKGROUND: Gestational trophoblastic diseases (GTDs) are treatable rare tumors with wide distribution. The estimated incidence of GTDs varies dramatically between different regions globally. In early pregnancy, there may be high human chorionic gonadotropin (HCG) concentrations, normal or slightly increased free T4 (fT4) and subnormal thyroid-stimulating hormone (TSH), causing hyperthyroidism ranging from subclinical to severe. Beta-HCG causes thyrotoxicosis through thyroid stimulation in patients with trophoblastic tumors. OBJECTIVE: To assess thyroid function among patients diagnosed with complete or partial hydatidiform mole, within the GTD spectrum. DESIGN AND SETTING: Cross-sectional study based on patients' medical records at Van University Hospital, Van, Turkey. METHODS: 50 patients monitored due to diagnoses of hydatidiform mole were included and were examined regarding thyroid function. Thyroid gland size and volume were measured using thyroid ultrasonography. Beta-HCG, TSH, fT4, free T3 (fT3), total T4 (TT4), total T3 (TT3), anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG) and thyroglobulin levels were measured. RESULTS: Among these patients, 15 (30%) were diagnosed with complete hydatidiform mole and 35 (70%) with partial hydatidiform mole, according to pathology results. Those with complete hydatidiform mole were older (P = 0.003), with higher number of pregnancies (P = 0.032), lower TSH level (P = 0.011) and higher fT4 and TT4 levels (P = 0.04; P = 0.028), compared with partial hydatidiform mole patients. CONCLUSION: In hydatidiform mole patients, thyroid disease severity increases with age, parity, beta-HCG level and mole size. However, prospective multicenter studies on this topic are needed, with larger numbers of patients and closer monitoring.


Assuntos
Doença Trofoblástica Gestacional/fisiopatologia , Glândula Tireoide/fisiopatologia , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Mola Hidatiforme/fisiopatologia , Pessoa de Meia-Idade , Gravidez , Neoplasias Uterinas/fisiopatologia , Adulto Jovem
4.
São Paulo med. j ; 137(3): 278-283, May-June 2019. tab
Artigo em Inglês | LILACS | ID: biblio-1020957

RESUMO

ABSTRACT BACKGROUND: Gestational trophoblastic diseases (GTDs) are treatable rare tumors with wide distribution. The estimated incidence of GTDs varies dramatically between different regions globally. In early pregnancy, there may be high human chorionic gonadotropin (HCG) concentrations, normal or slightly increased free T4 (fT4) and subnormal thyroid-stimulating hormone (TSH), causing hyperthyroidism ranging from subclinical to severe. Beta-HCG causes thyrotoxicosis through thyroid stimulation in patients with trophoblastic tumors. OBJECTIVE: To assess thyroid function among patients diagnosed with complete or partial hydatidiform mole, within the GTD spectrum. DESIGN AND SETTING: Cross-sectional study based on patients' medical records at Van University Hospital, Van, Turkey. METHODS: 50 patients monitored due to diagnoses of hydatidiform mole were included and were examined regarding thyroid function. Thyroid gland size and volume were measured using thyroid ultrasonography. Beta-HCG, TSH, fT4, free T3 (fT3), total T4 (TT4), total T3 (TT3), anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG) and thyroglobulin levels were measured. RESULTS: Among these patients, 15 (30%) were diagnosed with complete hydatidiform mole and 35 (70%) with partial hydatidiform mole, according to pathology results. Those with complete hydatidiform mole were older (P = 0.003), with higher number of pregnancies (P = 0.032), lower TSH level (P = 0.011) and higher fT4 and TT4 levels (P = 0.04; P = 0.028), compared with partial hydatidiform mole patients. CONCLUSION: In hydatidiform mole patients, thyroid disease severity increases with age, parity, beta-HCG level and mole size. However, prospective multicenter studies on this topic are needed, with larger numbers of patients and closer monitoring.


Assuntos
Humanos , Feminino , Gravidez , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Glândula Tireoide/fisiopatologia , Doença Trofoblástica Gestacional/fisiopatologia , Neoplasias Uterinas/fisiopatologia , Mola Hidatiforme/fisiopatologia , Estudos Transversais
5.
J Assist Reprod Genet ; 36(4): 667-671, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30612209

RESUMO

INTRODUCTION: The use of assisted reproduction techniques (ART) is increasing; however, reports of molar pregnancy following ART remain scarce. Currently, the Human Fertility and Embryology Authority (HFEA) collates data on the molar pregnancies that have resulted through the use of ART. Recently, they have indicated that they will no longer collect these data. AIM: This paper aimed to examine the incidence of molar pregnancy amongst patients undergoing assisted reproduction. METHODS: We contacted HFEA and placed a request under the Freedom of Information Act (2000) for the number of molar pregnancies that resulted from fresh/frozen embryo transfer since HFEA started collecting data in 1991 to February 2018. We also asked how many patients who had suffered a molar pregnancy went on to have a normal pregnancy and how many had subsequent molar pregnancies, in subsequent treatment cycles. RESULTS: Between 68 and 76 molar pregnancies occurred within this period using ART (n = 274,655). The incidence of molar pregnancy using fresh intracytoplasmic sperm injection (ICSI) (1/4302) and fresh in vitro fertilisation (IVF) (1/4333) was similar. The risk of recurrence of molar pregnancy following a previous molar was higher following ART compared to spontaneous conceptions. CONCLUSION: The use of ICSI should be protective against triploidy; however, the retrospective data suggests that molar pregnancy is not eliminated with the use of ART. It is pertinent to continue to record this data, through the gestational trophoblastic disease centres, in order to ensure no further increase in incidence, appropriate follow-up, and transparency in communication.


Assuntos
Vilosidades Coriônicas/fisiopatologia , Doença Trofoblástica Gestacional/epidemiologia , Mola Hidatiforme/epidemiologia , Técnicas de Reprodução Assistida/efeitos adversos , Adulto , Feminino , Fertilização In Vitro/efeitos adversos , Doença Trofoblástica Gestacional/fisiopatologia , Humanos , Mola Hidatiforme/fisiopatologia , Masculino , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas/efeitos adversos , Triploidia
8.
Eur J Hum Genet ; 26(7): 1007-1013, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29693651

RESUMO

Recurrent hydatidiform moles (RHM) are aberrant human pregnancies characterized by absence of, or abnormal, embryonic development, hydropic degeneration of chorionic villi, and hyperproliferation of the trophoblast. Biallelic mutations in two maternal-effect genes, NLRP7 and KHDC3L, underlie the causation of RHM in 60% of patients. We performed exome sequencing on a patient with six pregnancy losses, two miscarriages and four HM, and found no variants that affect the functions of the known genes. We found biallelic missense variants that affect conserved amino acids in PADI6 and segregate with the disease phenotype in the family. PADI6 is another maternal-effect gene and a member of the subcortical maternal complex that has been shown to have recessive variants that affect the gene function in four unrelated women with infertility who also experienced early embryonic arrest during preimplantation development after IVF. We demonstrated that PADI6 co-localizes with NLRP7 in human oocytes and preimplantation embryos and reviewed the morphology and genotypes of four products of conception from our patient. Our data expand the involvement of PADI6 to other forms of reproductive loss and highlight the commonality between infertility, miscarriages, and molar pregnancies, in some cases.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Mola Hidatiforme/genética , Infertilidade/genética , Desiminases de Arginina em Proteínas/genética , Proteínas/genética , Aborto Espontâneo/genética , Aborto Espontâneo/fisiopatologia , Adulto , Vilosidades Coriônicas/patologia , Feminino , Genótipo , Humanos , Mola Hidatiforme/fisiopatologia , Infertilidade/fisiopatologia , Mutação , Oócitos/patologia , Gravidez , Proteína-Arginina Desiminase do Tipo 6 , Sequenciamento do Exoma
9.
Arkh Patol ; 79(5): 43-48, 2017.
Artigo em Russo | MEDLINE | ID: mdl-29027529

RESUMO

The paper describes a case of twin pregnancy with complete hydatidiform mole (CHM). According to the data available in the literature, the concurrence of CHM with a normal placenta and a viable fetus occurs in 1 per 20,000-100,000 pregnancies, requires a differential diagnosis with partial hydatidiform mole and placental mesenchymal dysplasia, and is characterized by a high rate of complications. In this concurrence, the frequency of persistent trophoblastic disease is as high as 50%. In this case, the pregnancy ended in a spontaneous abortion at 16-17 weeks of pregnancy. A morphological examination determined the fetus without congenital malformations with normal placental weight and structure and the adjacent intact placental tissue with the macro- and microscopic signs of CHM. The diagnosis was confirmed by the lack of р57 expression in the villous trophoblast and stroma in the tissue of the hydatidiform mole. The patient was diagnosed with persistent trophoblastic disease at 2 months after the abortion.


Assuntos
Doença Trofoblástica Gestacional/fisiopatologia , Mola Hidatiforme/fisiopatologia , Complicações Neoplásicas na Gravidez/fisiopatologia , Gravidez de Gêmeos , Aborto Espontâneo/fisiopatologia , Adulto , Feminino , Feto/fisiopatologia , Doença Trofoblástica Gestacional/complicações , Humanos , Mola Hidatiforme/complicações , Placenta/fisiopatologia , Gravidez
10.
Clinics (Sao Paulo) ; 72(5): 284-288, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28591340

RESUMO

OBJECTIVES:: Doppler ultrasonography can be used to assess neoangiogenesis, a characteristic feature of postmolar gestational trophoblastic neoplasia. However, there is limited information on whether uterine artery Doppler flow velocimetry parameters can predict gestational trophoblastic neoplasia following a complete hydatidiform mole. The purpose of this study was as follows: 1) to compare uterine blood flow before and after complete mole evacuation between women who developed postmolar gestational trophoblastic neoplasia and those who achieved spontaneous remission, 2) to assess the usefulness of uterine Doppler parameters as predictors of postmolar gestational trophoblastic neoplasia and to determine the best parameters and cutoff values for predicting postmolar gestational trophoblastic neoplasia. METHODS:: This prospective cohort study included 246 patients with a complete mole who were treated at three different trophoblastic diseases centers between 2013 and 2014. The pulsatility index, resistivity index, and systolic/diastolic ratio were measured by Doppler flow velocimetry before and 4-6 weeks after molar evacuation. Statistical analysis was performed using Wilcoxon's test, logistic regression, and ROC analysis. RESULTS:: No differences in pre- and post-evacuation Doppler measurements were observed in patients who developed postmolar gestational trophoblastic neoplasia. In those with spontaneous remission, the pulsatility index and systolic/diastolic ratio were increased after evacuation. The pre- and post-evacuation pulsatility indices were significantly lower in patients with gestational trophoblastic neoplasia (odds ratio of 13.9-30.5). A pre-evacuation pulsatility index ≤1.38 (77% sensitivity and 82% specificity) and post-evacuation pulsatility index ≤1.77 (79% sensitivity and 86% specificity) were significantly predictive of gestational trophoblastic neoplasia. CONCLUSIONS:: Uterine Doppler flow velocimetry measurements, particularly pre- and post-molar evacuation pulsatility indices, can be useful for predicting postmolar gestational trophoblastic neoplasia.


Assuntos
Doença Trofoblástica Gestacional/diagnóstico por imagem , Doença Trofoblástica Gestacional/fisiopatologia , Mola Hidatiforme/cirurgia , Ultrassonografia Doppler/métodos , Artéria Uterina/diagnóstico por imagem , Artéria Uterina/fisiopatologia , Neoplasias Uterinas/cirurgia , Adolescente , Adulto , Velocidade do Fluxo Sanguíneo/fisiologia , Gonadotropina Coriônica/sangue , Feminino , Idade Gestacional , Doença Trofoblástica Gestacional/irrigação sanguínea , Humanos , Mola Hidatiforme/complicações , Mola Hidatiforme/fisiopatologia , Modelos Logísticos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Risco , Fatores de Tempo , Neoplasias Uterinas/complicações , Neoplasias Uterinas/fisiopatologia , Útero/irrigação sanguínea , Útero/fisiopatologia , Adulto Jovem
11.
Indian J Med Res ; 145(1): 133-137, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28574027

RESUMO

BACKGROUND & OBJECTIVES: There is considerable inter-observer variability in the diagnosis of molar pregnancies by histomorphological examination of products of conception (POC). The p57KIP2 gene is paternally imprinted and expressed from the maternal allele. On immunohistochemistry (IHC) with p57, complete mole (CM) shows absent staining whereas hydropic abortus (HA) and partial mole (PM) show positive staining. This study was undertaken to evaluate the role of p57 IHC along with histomorphology in differentiating between CM, PM and non-molar or HA. METHODS: This was a cross-sectional study over a period of three and a half years on archival material. Detailed histomorphological review along with p57 IHC was carried out in 28 diagnosed cases (23 CM, 4 PM and 1 molar pregnancy not categorized) and 25 controls of four normal placentas and 21 POC (8 non-hydropic and 13 HA). RESULTS: In 14.8 per cent (4/27) cases, there was discordance in accurate subtyping of molar pregnancy. One case of CM showed inconsistent IHC pattern. In 15.4 per cent (2/13) HA, molar pregnancy was final diagnosis. After final review, there were 25 CM, five PM, 22 non-molar controls including 10 HA and one not assigned (PM/HA). IHC with p57 was negative in 96 per cent CM and positive in 100 and 95 per cent PM and non-molar controls, respectively. INTERPRETATION & CONCLUSIONS: This study showed that negative p57KIP2 immunostaining reliably identified CM and could be used in association with the histological findings to distinguish CM from its mimics.


Assuntos
Biomarcadores Tumorais/genética , Inibidor de Quinase Dependente de Ciclina p57/genética , Mola Hidatiforme/diagnóstico , Mola Hidatiforme/genética , Adulto , Feminino , Citometria de Fluxo , Humanos , Mola Hidatiforme/fisiopatologia , Imuno-Histoquímica/métodos , Herança Paterna/genética , Gravidez
12.
Clinics ; 72(5): 284-288, May 2017. tab
Artigo em Inglês | LILACS | ID: biblio-840073

RESUMO

OBJECTIVES: Doppler ultrasonography can be used to assess neoangiogenesis, a characteristic feature of postmolar gestational trophoblastic neoplasia. However, there is limited information on whether uterine artery Doppler flow velocimetry parameters can predict gestational trophoblastic neoplasia following a complete hydatidiform mole. The purpose of this study was as follows: 1) to compare uterine blood flow before and after complete mole evacuation between women who developed postmolar gestational trophoblastic neoplasia and those who achieved spontaneous remission, 2) to assess the usefulness of uterine Doppler parameters as predictors of postmolar gestational trophoblastic neoplasia and to determine the best parameters and cutoff values for predicting postmolar gestational trophoblastic neoplasia. METHODS: This prospective cohort study included 246 patients with a complete mole who were treated at three different trophoblastic diseases centers between 2013 and 2014. The pulsatility index, resistivity index, and systolic/diastolic ratio were measured by Doppler flow velocimetry before and 4-6 weeks after molar evacuation. Statistical analysis was performed using Wilcoxon’s test, logistic regression, and ROC analysis. RESULTS: No differences in pre- and post-evacuation Doppler measurements were observed in patients who developed postmolar gestational trophoblastic neoplasia. In those with spontaneous remission, the pulsatility index and systolic/diastolic ratio were increased after evacuation. The pre- and post-evacuation pulsatility indices were significantly lower in patients with gestational trophoblastic neoplasia (odds ratio of 13.9-30.5). A pre-evacuation pulsatility index ≤1.38 (77% sensitivity and 82% specificity) and post-evacuation pulsatility index ≤1.77 (79% sensitivity and 86% specificity) were significantly predictive of gestational trophoblastic neoplasia. CONCLUSIONS: Uterine Doppler flow velocimetry measurements, particularly pre- and post-molar evacuation pulsatility indices, can be useful for predicting postmolar gestational trophoblastic neoplasia.


Assuntos
Humanos , Feminino , Gravidez , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Doença Trofoblástica Gestacional/diagnóstico por imagem , Doença Trofoblástica Gestacional/fisiopatologia , Mola Hidatiforme/cirurgia , Ultrassonografia Doppler/métodos , Artéria Uterina/diagnóstico por imagem , Artéria Uterina/fisiopatologia , Neoplasias Uterinas/cirurgia , Velocidade do Fluxo Sanguíneo/fisiologia , Gonadotropina Coriônica/sangue , Idade Gestacional , Doença Trofoblástica Gestacional/irrigação sanguínea , Mola Hidatiforme/complicações , Mola Hidatiforme/fisiopatologia , Modelos Logísticos , Valor Preditivo dos Testes , Estudos Prospectivos , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Risco , Fatores de Tempo , Neoplasias Uterinas/complicações , Neoplasias Uterinas/fisiopatologia , Útero/irrigação sanguínea , Útero/fisiopatologia
13.
J Obstet Gynaecol Res ; 41(6): 985-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25510265

RESUMO

Ectopic molar pregnancy is a rare occurrence and consequently not often considered as a diagnostic possibility. We report two cases of molar hydatidiform tubal pregnancy. Diagnosis of ectopic pregnancy was confirmed on clinical biological and sonographic investigations. Diagnosis of molar pregnancy was done on histopathology. The clinical course was favorable for both patients. Although rare, molar changes can occur at any site of an ectopic pregnancy. Clinical diagnosis of a molar pregnancy is difficult but histopathology is the gold standard for diagnosis.


Assuntos
Mola Hidatiforme/diagnóstico , Gravidez Ectópica/diagnóstico , Dor Abdominal/etiologia , Dor Abdominal/prevenção & controle , Adulto , Diagnóstico Diferencial , Feminino , Hospitais Urbanos , Humanos , Mola Hidatiforme/patologia , Mola Hidatiforme/fisiopatologia , Mola Hidatiforme/cirurgia , Dor Pélvica/etiologia , Dor Pélvica/prevenção & controle , Gravidez , Gravidez Ectópica/patologia , Gravidez Ectópica/fisiopatologia , Gravidez Ectópica/cirurgia , Salpingectomia , Resultado do Tratamento , Tunísia , Ultrassonografia Pré-Natal
14.
J Obstet Gynaecol Res ; 40(7): 1894-900, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25056468

RESUMO

AIM: To assess the use of magnetic resonance imaging (MRI) for prenatal differentiation between complete hydatidiform mole with a twin live fetus (CHMTF) and placental mesenchymal dysplasia (PMD). METHODS: Three CHMTF cases and three PMD cases, from two institutions over a 6-year period, were retrospectively included in this study. Clinical findings including age, pregnancy history, serum hCG level, ultrasonography findings, complications of the mother, outcome of the fetus, and results of chromosomal study of fetus, amniotic fluid and lesion, if possible, were noted. MRI findings were evaluated by two radiologists with respect to the location of the disease (intra- or extra-fetal sac), the presence of multicystic component, and presence of intra- or extra-lesional hemorrhage. RESULTS: In all six cases, the diseases were recognized as multicystic lesions by ultrasonography and MRI. In two of three CHMTF cases, patients continued with the pregnancy, which resulted in spontaneous abortion. In one case of CHMTF, the patient underwent artificial abortion, after which the mole progressed into an invasive mole with lung metastases. All three PMD patients had live births, and two of the three babies had fetal growth restriction. By MRI, CHMTF was located within an extra-fetal sac accompanied by intra- and/or extra-lesional hemorrhage, while PMD was located within the placenta in the fetal sac without hemorrhage. CONCLUSION: MRI could provide important information about the prenatal differential diagnosis of CHMTF and PMD, based on the pathophysiology and characteristics of the diseases.


Assuntos
Transição Epitelial-Mesenquimal , Mola Hidatiforme/diagnóstico , Doenças Placentárias/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Complicações Neoplásicas na Gravidez/diagnóstico , Gravidez de Gêmeos , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Mola Hidatiforme/fisiopatologia , Japão , Imageamento por Ressonância Magnética , Doenças Placentárias/fisiopatologia , Lesões Pré-Cancerosas/fisiopatologia , Gravidez , Complicações Neoplásicas na Gravidez/fisiopatologia , Resultado da Gravidez , Diagnóstico Pré-Natal , Estudos Retrospectivos
15.
Gynecol Endocrinol ; 30(4): 287-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24479884

RESUMO

INTRODUCTION: The effect of a hyperthyroid or euthyroid state on liver function tests in patients with hydatidiform moles (HM) is not known. The aim of this study was to determine the effect of hyperthyroidism on liver transaminases in HM. PATIENTS AND METHODS: We retrospectively reviewed aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in 80 patients with HM (23 complete moles and 57 partial moles). RESULTS: Of the 80 HM patients, 52 (65%) were euthyroid and 28 (35%) were hyperthyroid. The number of gravida and the levels of serum ß-human chorionic gonadotropin (ß-HCG), AST, and ALT were significantly higher in the hyperthyroid state than in the euthyroid state (p = 0.033, p = 0.001, p = 0.001 and p = 0.001; respectively). Number of gravida, serum TSH and total T4 were significantly higher in complete HM than partial HM (p < 0.05, p < 0.001, p < 0.05; respectively). CONCLUSIONS: Our results demonstrated that HM-related ß-HCG may activate thyroid cells via TSH-related signalling, resulting in the release of high levels of FT4, FT3, TT3 and TT4, and a subsequent decrease in TSH.


Assuntos
Mola Hidatiforme/fisiopatologia , Hepatopatias/fisiopatologia , Neoplasias Uterinas/fisiopatologia , Adolescente , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Distribuição de Qui-Quadrado , Gonadotropina Coriônica Humana Subunidade beta/sangue , Feminino , Humanos , Mola Hidatiforme/sangue , Mola Hidatiforme/enzimologia , Hepatopatias/sangue , Hepatopatias/enzimologia , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Glândula Tireoide/patologia , Hormônios Tireóideos/sangue , Neoplasias Uterinas/sangue , Neoplasias Uterinas/enzimologia , Adulto Jovem
16.
J Obstet Gynaecol Res ; 40(4): 1154-6, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24428592

RESUMO

A 23-year-old woman, gravida 1, para 1, was transferred to our hospital with acute lower abdominal pain and vital signs consistent with shock. Her urine concentration of human chorionic gonadotrophin was 8000 mIU/mL. Transvaginal ultrasound revealed an echo-free space with mosaic echo pattern in the right adnexal area and no gestational sac in the uterus. With a preoperative diagnosis of ruptured ectopic pregnancy, emergency laparotomy was performed. The rectouterine pouch was filled with many clots containing small amounts of villous tissue. After removal of the conceptus, which was infiltrating into the peritoneum of the Pouch of Douglas, bleeding was controlled by Argon laser. Histological examination of the conceptus by immunohistochemical staining with p57(kip2) showed features of complete hydatidiform mole. This case demonstrates that the peritoneum in the Pouch of Douglas is a possible site of ectopic complete hydatidiform mole occurrence and that immunohistochemical stain is useful to confirm the diagnosis of ectopic complete hydatidiform mole.


Assuntos
Mola Hidatiforme/diagnóstico por imagem , Neoplasias Peritoneais/diagnóstico por imagem , Dor Abdominal/etiologia , Adulto , Diagnóstico Diferencial , Escavação Retouterina , Feminino , Humanos , Mola Hidatiforme/fisiopatologia , Mola Hidatiforme/cirurgia , Neoplasias Peritoneais/fisiopatologia , Neoplasias Peritoneais/cirurgia , Gravidez , Gravidez Abdominal/diagnóstico por imagem , Choque/etiologia , Resultado do Tratamento , Ultrassonografia Pré-Natal , Neoplasias Uterinas/diagnóstico por imagem , Adulto Jovem
17.
Pathol Biol (Paris) ; 61(5): 178-83, 2013 Oct.
Artigo em Francês | MEDLINE | ID: mdl-23647696

RESUMO

Gestational trophoblastic disease (MGT) includes a wide spectrum of pathologies of the placenta, ranging from benign precancerous lesions, with gestational trophoblastic tumors. Metastases are the leading causes of death as a result of this tumor. They represent a major problem for obstetrics and for the public health system. To date, there is no predictor of the progression of molar pregnancies to gestational trophoblastic tumor (GTT). Only an unfavorable plasma hCG monitoring after evacuation of hydatidiform mole is used to diagnose a TTG. The causes of the development of this cancer are still poorly understood. Increasing data in the literature suggests a close association between the development of this tumor and poor placental vascularization during the first trimester of pregnancy. The development of the human placenta depends on a coordination between the trophoblast and endothelial cells. A disruption in the expression of angiogenic factors could contribute to uterine or extra-uterine tissue invasion by extravillous trophoblast, contributing to the development of TTG. This review sheds lights on the phenomenon of angiogenesis during normal and abnormal placentation, especially during the MGT and reports preliminary finding concerning, the variability of expression of "Endocrine Gland-Derived Vascular Endothelial Growth Factor" (EG-VEGF), a specific placental angiogenic factor, in normal and molar placentas, and the potential role of differentiated expressions of the main placental angiogenic factors in the scalability of hydatidiform moles towards a recovery or towards the development of gestational trophoblastic tumor. Deciphering the mechanisms by which the angiogenic factor influences these processes will help understand the pathophysiology of MGT and to create opportunities for early diagnosis and treatment of the latter.


Assuntos
Doença Trofoblástica Gestacional/fisiopatologia , Fator de Crescimento do Endotélio Vascular Derivado de Glândula Endócrina/fisiologia , Gonadotropina Coriônica/sangue , Feminino , Doença Trofoblástica Gestacional/patologia , Doença Trofoblástica Gestacional/terapia , Humanos , Mola Hidatiforme/fisiopatologia , Neovascularização Patológica/fisiopatologia , Neovascularização Fisiológica/fisiologia , Placenta/irrigação sanguínea , Gravidez , Neoplasias Uterinas/fisiopatologia
18.
Int J Gynecol Pathol ; 32(2): 199-214, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23370656

RESUMO

Recent studies have demonstrated the value of ancillary techniques, including p57 immunohistochemistry and short tandem repeat genotyping, for distinguishing hydatidiform moles (HM) from nonmolar specimens and for subtyping HMs as complete hydatidiform moles (CHM) and partial hydatidiform moles (PHM). With rare exceptions, CHMs are p57-negative and androgenetic diploid; partial hydatidiform moles are p57-positive and diandric triploid; and nonmolar specimens are p57-positive and biparental diploid. Androgenetic/biparental mosaic/chimeric conceptions can have morphologic features that overlap with HMs but are genetically distinct. This study characterizes 11 androgenetic/biparental mosaic/chimeric conceptions identified in a series of 473 products of conception specimens subjected to p57 immunohistochemistry and short tandem repeat genotyping. Fluorescence in situ hybridization was performed on 10 to assess ploidy. All cases were characterized by hydropically enlarged, variably sized and shaped villi. In 5 cases, the villi lacked trophoblastic hyperplasia, whereas in 6 there was a focal to extensive villous component with trophoblastic hyperplasia and features of CHM. The villi lacking trophoblastic hyperplasia were characterized by discordant p57 expression within individual villi (p57-positive cytotrophoblast and p57-negative stromal cells), whereas the villous components having trophoblastic hyperplasia were uniformly p57-negative in both cell types. Short tandem repeat genotyping of at least 2 villous areas in each case demonstrated an excess of paternal alleles in all regions, with variable paternal:maternal allele ratios (usually >2:1); pure androgenetic diploidy was identified in those cases with a sufficiently sized villous component having trophoblastic hyperplasia and features of CHM. Fluorescence in situ hybridization demonstrated uniform diploidy in 7 cases, including 4 of 5 tested cases with trophoblastic hyperplasia and 3 of 5 cases without trophoblastic hyperplasia. Two cases without trophoblastic hyperplasia had uniformly diploid villous stromal cells but 1 had triploid and 1 had tetraploid cytotrophoblast; 1 case with trophoblastic hyperplasia had uniformly diploid villous stromal cells but a mixture of diploid, triploid, and tetraploid cytotrophoblast. In 3 cases with a CHM component, persistent gestational trophoblastic disease developed. These results indicate that androgenetic/biparental mosaic/chimeric conceptions are most often an admixture of androgenetic diploid (p57-negative) and biparental diploid (p57-positive) cell lines but some have localized hyperdiploid components. Recognition of their distinctive p57 expression patterns and genotyping results can prevent misclassification as typical CHMs, PHMs, or nonmolar specimens. The presence of androgenetic cell lines, particularly in those with a purely androgenetic CHM component, warrants follow-up because of some risk of persistent gestational trophoblastic disease.


Assuntos
Quimera/genética , Inibidor de Quinase Dependente de Ciclina p57/análise , Doença Trofoblástica Gestacional/genética , Mola Hidatiforme/química , Mola Hidatiforme/genética , Mosaicismo , Adolescente , Adulto , Diploide , Feminino , Genótipo , Humanos , Mola Hidatiforme/fisiopatologia , Hiperplasia , Imuno-Histoquímica , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Gravidez , Triploidia , Trofoblastos/patologia
19.
Eur J Obstet Gynecol Reprod Biol ; 167(2): 194-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23274042

RESUMO

OBJECTIVE: The loss of primordial follicles from gonadal damage caused by chemotherapy results in decreased ovarian reserve. To assess the impact of chemotherapy for patients with gestational trophoblastic neoplasia (GTN) on the ovarian reserve, we evaluated the post-chemotherapy serum anti-Müllerian hormone (AMH) levels. STUDY DESIGN: In 22 patients with GTN receiving chemotherapy, serum AMH levels were measured after the administration of chemotherapy and compared with serum AMH levels measured in patients with hydatidiform mole who did not receive chemotherapy, as a control. We also analyzed differences in the serum AMH levels following the administration of different anti-cancer agents. RESULTS: The serum AMH levels measured in the GTN group after chemotherapy was administered (median 1.18, range 0.32-3.94 ng/mL) significantly decreased in comparison to those measured in the control group (median 4.22, range 0.77-6.53 ng/mL, P=0.002). Serum AMH levels were significantly lower in the patients who had received a regimen including etoposide than in the patients who had not received treatment with etoposide (0.71 vs. 1.30 ng/mL, P=0.027). CONCLUSION: Our results suggest that chemotherapy administered to treat GTN does indeed affect the ovarian reserve, especially in patients who receive a medication regimen that includes etoposide. Measuring their serum AMH levels might therefore be helpful for counseling GTN patients regarding their ovarian reserve.


Assuntos
Hormônio Antimülleriano/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doença Trofoblástica Gestacional/tratamento farmacológico , Ovário/efeitos dos fármacos , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Biomarcadores/sangue , Dactinomicina/administração & dosagem , Dactinomicina/efeitos adversos , Dactinomicina/uso terapêutico , Dilatação e Curetagem , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Etoposídeo/uso terapêutico , Feminino , Seguimentos , Doença Trofoblástica Gestacional/sangue , Doença Trofoblástica Gestacional/fisiopatologia , Humanos , Mola Hidatiforme/sangue , Mola Hidatiforme/fisiopatologia , Mola Hidatiforme/terapia , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Ovário/fisiopatologia , Gravidez , Adulto Jovem
20.
BMC Res Notes ; 5: 621, 2012 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-23126487

RESUMO

BACKGROUND: Complete hydatiform mole and coexistent viable fetus is very rare. The use of a cervical cerclage for cervical indications in the presence of this condition has never been reported. Although the diagnosis was made postnatal, the objective is to present a case with good neonatal outcome. CASE PRESENTATION: A patient presented with vaginal spotting around 23 weeks. She has a history of four preterm deliveries. Her cervix was dilated and a cerclage was placed. She presented again with PPROM around 25 weeks. She went into spontaneous preterm labor and delivered a viable fetus that is a healthy girl today. Eventually the pathology of the placenta showed a complete hydatidiform mole. CONCLUSION: It is necessary to inform patients about the potential risks and poor outcomes of this condition. For those who desire all potential interventions, cerclage placement could be considered.


Assuntos
Cerclagem Cervical , Mola Hidatiforme/fisiopatologia , Resultado da Gravidez , Feminino , Humanos , Recém-Nascido , Gravidez
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