Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Rare Diseases

Hydatidiform Mole

Nevus

Gestational Trophoblastic Disease

Trophoblastic Neoplasms

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Pregnancy Complications

Pregnancy Complications, Neoplastic

Urogenital Diseases

Female Urogenital Diseases

Female Urogenital Diseases and Pregnancy Complications

Vasodilator Agents

All Drugs and Chemicals

Nitroglycerin

In single evacuation group women will be treated by suction evacuation and curettage is performed at the end of evacuation in one sitting. An ultrasound will be done later to examine completeness of evacuation. If there is significant amount of residual molar tissue or persistence of heavy bleeding a repeat curettage will be done . Women will be followed up with serum beta hcg 1 week after the evacuation and then weekly till the titer is negative. After three consecutive negative titre beat HCG estimation will be done at two weekly interval.

Suction and evacuation

In double evacuation group , women will be treated by suction evacuation and a thorough curettage will be avoided. A second evacuation with thorough curettage will be performed after 5 - 7 days of first evacuation.

Snehamay Chaudhuri, MD, DNB

Hydatidiform mole is a common complication of pregnancy with an incidence of 1in 400 pregnancies in India. Although this is a benign condition , it is having the malignant potential too. A repeat curettage after evacuation of hydatidiform mole was generally advocated till 1990s. A thorough curettage at the time of initial evacuation was not performed because of larger size of uterus and risk of perforation. Subsequently a number of studies assessed the usefulness of repeat curettage and found it was unnecessary and not cost effective . However all these studies are retrospective in design and conducted in developed countries where hydatidiform mole is diagnosed earlier because of wider use of ultrasonography. Thus there is a need to perform a well designed prospective study to compare the effectiveness of single evacuation with double evacuation in treatment of hydatidiform mole for prevention of Gestational Trophoblastic Neoplasia.This study compares the effectiveness of single evacuation versus double evacuation for treatment of hydatidiform mole for prevention of gestational trophoblastic neoplasia .

A Comparison of Single Versus Double Evacuation for Treatment of Hydatidiform Mole

A Comparison of Single Versus Double Evacuation for Treatment of Hydatidiform

Nilratan Sircar Medical College

Associate Professor,Obstetrics and Gynecology, NRS Medical College

Symptoms and General Pathology

Recurrence

Recurrent Hydatidiform Mole

Individuals with recurrent or sporadic hydatidiform moles and their first-degree family members. Sometimes additional family members are also enrolled.

Ignatia B Van den Veyver, MD

The researchers' laboratory is studying a rare class of highly recurrent hydatidiform moles. These are usually complete hydatidiform moles (CHM), but sometimes they are partial hydatidiform moles PHM). With sporadic moles, the difference between CHMs and PHMs is that with CHMS, there is not typically an embryo or fetus at the time of diagnosis but with a PHM there may be a fetus. Also, CHMs have 46 chromosomes in each cell. While this is the number of chromosomes that should be found, the problem is that all the chromosomes come from the father. Normally, half the chromosomes should come from the mother and half should come from the father. Unlike CHMs, PHMs have 69 chromosomes. This means that PHMs have three copies of each chromosome when they should only have two. The extra copy comes from the father.

The researchers' study focuses on moles that are genetically different from these sporadic moles in that they have 23 chromosomes from the mother and 23 chromosomes from the father - just like a normally developing pregnancy. These are called biparental moles because the mutation that causes the mole comes from both parents. This mutation occurs in a gene called NLRP7. The researchers' team is working to understand how mutations in NLRP7 leads to CHMs and how these mutations may lead to other types of pregnancy loss. The researchers are also trying to discover other genetic and epigenetic factors that may lead to moles.

Hydatidiform mole (HM) is the product of an aberrant human pregnancy in which there is abnormal embryonic development and abnormal proliferation of placental villi. The incidence of HM varies between ethnic groups, and occurs in 1 in every 1500 pregnancies in the USA. All HM cases are sporadic except for extremely rare familial cases. The exact mechanisms leading to molar pregnancies are not known. Hydatidiform moles are classified based on histology and karyotype data into two types:

complete hydatidiform moles (CHM) and partial hydatidiform moles (PHM). The complete forms are characterized by general trophoblastic proliferation and absence of an embryo and amniotic membranes. In most of the cases, CHM have a diploid genome, and are androgenetic with two identical sets of paternal chromosomes. Partial hydatidiform moles are characterized by focal trophoblastic proliferation. Embryos and amniotic membranes are usually present in these molar pregnancies. Partial hydatidiform moles are mostly triploid with two sets of paternal chromosomes and one set of maternal chromosomes. The comparison of findings in androgenetic CHM and PHM indicate that both maternally (under) expressed and paternally (over) expressed genes play a role in the pathophysiology of molar pregnancies. Very few genetic studies have been performed on molar pregnancies or the patients who carry these pregnancies. A few studies have looked at the over- or underexpression of genes that may play a role in the progression or invasiveness of hydatidiform moles; however none have addressed the underlying genetic etiology. We have been able to study an inbred family of which several female members have had recurrent hydatidiform moles and have now genetically mapped the defective gene responsible for the molar pregnancies in this family. We then worked towards refined characterization of the genetic locus containing the mutated gene and analysis of candidate genes in this region for mutations leading to molar pregnancy. Because the hydatidiform moles in these patients have abnormal genetic imprinting, we believe that this candidate gene is important for establishment of genetic imprinting in the maternal germline. Recently, another group of investigators studying this condition identified mutations in a gene, NALP7 (now renamed to NLRP7), in some of the affected women. We confirmed this in other subjects studied by us. This is the first identified gene, but there is genetic heterogeneity and other genes still remain to be found. In addition, the normal function of this gene in reproduction and how it leads to recurrent moles when mutated remains to be determined. To study both of these, it will be very important to collect as many molar pregnancy tissue samples as possible, as well as blood samples and/or other non-invasively obtained samples, such as buccal swabs and saliva, from affected patients and their families. Recent evidence suggests that mutations in NLRP7 might cause other forms of reproductive failure, such as triploid spontaneous abortions. It has further been proposed that the mutation status of NLRP7 in women with recurrent reproductive loss is an important predictor of the outcome of Assisted Reproductive Technologies. Therefore, we are carrying out mutation analysis of NLRP2 and NLRP7 in women with unexplained infertility and other forms of reproductive failure.

Study of the Genetic and Epigenetic Causes of Recurrent Hydatidiform Moles

Genetic Studies in Gestational Trophoblastic Disease

The study is aimed to find the genetic cause of a rare condition, hydatidiform moles. Patient data with no identifying information will be published in aggregate following peer review in journals and/or presented at scientific meetings.

The researchers will isolate genetic material from blood of women with recurrent hydatidiform molar (RHM) pregnancies, their RHM pregnancies, and for some first-degree relatives. DNA sequencing along with bioinformatic analysis will be used to find changes in the genetic code unique to individuals with RHM. When a new gene is found that shows variants that are deleterious to its function in at least 3 unrelated women with RHM, but not in healthy pregnant women, the outcome (finding a new genetic cause of RHM) will be achieved. RHM are very rare and only 70% have a known cause (known gene), thus the researchers will continue recruitment and enrollment of rare undiagnosed individuals when they are referred to the study. A key finding in one individual can provide the clue for a new disease gene in others. It cannot be predicted when this will happen, thus enrollment and data collection will continue as long as the protocol is open.

The researchers will isolate genetic material from blood of women with recurrent unexplained reproductive failure (RF), their miscarried pregnancies if possible, and for some from first-degree relatives. DNA sequencing and bioinformatic analysis will be used to find changes in the genetic code unique to individuals with unexplained RF. When a new gene is found that shows variants that are deleterious to its function in at least 3 unrelated women with unexplained RF, but not in healthy pregnant women, the outcome (finding a new genetic cause for RF) will be achieved. Unexplained RF is relatively rare and many causes are not yet known, thus the researchers will continue recruitment and enrollment of rare undiagnosed individuals when they are referred to the study. A key finding in one individual can provide the clue for a new disease gene in others. It cannot be predicted when this will happen, thus enrollment and data collection will continue as long as the protocol is open

Baylor College of Medicine

Professor

Gestational Trophoblastic Tumor

Micronutrients

Antineoplastic Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Hematinics

Anti-Infective Agents

Vitamins

Leucovorin

Levoleucovorin

Methotrexate

Cisplatin

Folic Acid

Dactinomycin

Folinic Acid

Folate

Vitamin B9

Patients allocated to receive conventional chemotherapy will be treated with methotrexate (1 mg/kg intramuscular) with rescue of folinic acid (15mg orally). In cases of chemoresistance, second-line chemotherapy will be performed with actinomycin-D (Act-D) 1.25 mg intravenous pulse every 14 days. The third line of chemotherapy will be the EMA/CO regimen (reserving the EP / EMA regimen (E, cisplatin, MTX / Act-D) for the fourth line.

Patients randomized to undergo a second curettage will undergo manual or electronic vacuum aspiration under ultrasound guidance. Following discharge after the second curettage patients will return to weekly hCG monitoring. If hCG levels are decreasing, patients will remain on weekly hCG follow-up until the first normal hCG (\<5 IU/L) is achieved. Then they will have monthly hCG monitoring for 12 months. If patients do not attain remission and develop persistent GTN as established by FIGO 2000, the tumor will be re-staged and appropriate chemotherapy will be initiated.

Manual or electric vacuum aspiration under ultrasound guidance.

Uterine curettage

conventional chemotherapy will be treated with MTX (1 mg/kg intramuscular) with rescue of FA (15mg orally). In cases of chemoresistance, second-line chemotherapy will be performed with actinomycin-D (Act-D) 1.25 mg intravenous pulse every 14 days. The third line of chemotherapy will be the EMA/CO regimen (, reserving the EP / EMA regimen (E, cisplatin, MTX / Act-D) for the fourth line.

Chemotherapy

MARCIO BARCELLOS, MD

Izildinha Maestá

Daniela A Yela

José Mauro Madi

Cecília Maria Ponte

Elza -Maria Hartmann

Rodrigo Bernardes Cardoso

Marcio Barcellos, MD

Antonio Braga, MD

Sue Yazaki Sun

Marcia Marcelino Ishigai

Gustavo Rubino Focchi

Antonio Braga, MD, PhD

To evaluate the efficacy and safety of second uterine curettage in patients with low-risk non-metastatic GTN.

This is a randomized, multicenter clinical trial including patients seen at one of 13 gestational trophoblastic disease reference centers in Brazil. Subjects are eligible if they have low-risk gestational trophoblastic neoplasia according to FIGO 2000 criteria and the FIGO/WHO prognostic risk score. The study includes two treatment arms: immediate treatment with single-agent chemotherapy (center choice of agent) or second uterine curettage. The primary outcome is the rate of primary remission. Secondary outcomes are the number of chemotherapy cycles required to achieve remission, rate of primary chemotherapy resistance, rate of relapse, and overall survival.

Treatment assignments are made by a remote investigator not involved in the clinical care of the patient using a coded key with random block sizes.

Second Uterine Evacuation for Low-risk Gestational Trophoblastic Neoplasia

Impact of Second Uterine Evacuation in Women With Non-metastatic, Low-risk Gestational Trophoblastic Neoplasia: A Phase III Trial

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Comparison of Single Versus Double Evacuation for Treatment of Hydatidiform Mole	NCT01630954	Hydatidiform Mo...	Suction and eva... Suction and eva...	15 Years - 45 Years	Nilratan Sircar Medical College
Study of the Genetic and Epigenetic Causes of Recurrent Hydatidiform Moles	NCT01008501	Hydatidiform Mo...		-	Baylor College of Medicine
Study of the Genetic and Epigenetic Causes of Recurrent Hydatidiform Moles	NCT01008501	Hydatidiform Mo...		-	Baylor College of Medicine
Study of the Genetic and Epigenetic Causes of Recurrent Hydatidiform Moles	NCT01008501	Hydatidiform Mo...		-	Baylor College of Medicine
Second Uterine Evacuation for Low-risk Gestational Trophoblastic Neoplasia	NCT04756713	Gestational Tro... Molar Pregnancy Gestational Tro...	Uterine curetta... Chemotherapy	-	Brigham and Women's Hospital
A Comparison of Single Versus Double Evacuation for Treatment of Hydatidiform Mole	NCT01630954	Hydatidiform Mo...	Suction and eva... Suction and eva...	15 Years - 45 Years	Nilratan Sircar Medical College
Second Uterine Evacuation for Low-risk Gestational Trophoblastic Neoplasia	NCT04756713	Gestational Tro... Molar Pregnancy Gestational Tro...	Uterine curetta... Chemotherapy	-	Brigham and Women's Hospital

Spots Global Cancer Trial Database for molar pregnancy