- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05825183
Study of Product of Conception Derived From Ultrasound-guided Manual Vacuum Aspiration
Early pregnancy loss is very common, approximately one in four women will experience a miscarriage in their lifetime. The etiology of pregnancy loss remains largely unknown, although genetic, anatomical, endocrinological and immunological abnormalities have been implicated.
It is known that embryonic/fetal chromosomal aberrations contributed to approximately 50% of early pregnancy loss, among which 60-70% were aneuploidies, largely can be detected by the current gold standard karyotyping approach recommended by various international societies. However, the drawbacks of conventional karyotyping include the risk of culture failure, maternal cell contamination (MCC), limited detection resolution (5-10 Mb), and differential growth of specific cell lineages which could hinder the diagnosis of genetic abnormalities, particularly mosaicisms. Additional genetic factors beyond the resolution of karyotyping are not well studied.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Early pregnancy loss is very common, approximately one in four women will experience a miscarriage in their lifetime. The etiology of pregnancy loss remains largely unknown, although genetic, anatomical, endocrinological and immunological abnormalities have been implicated.
It is known that embryonic/fetal chromosomal aberrations contributed to approximately 50% of early pregnancy loss, among which 60-70% were aneuploidies, largely can be detected by the current gold standard karyotyping approach recommended by various international societies. However, the drawbacks of conventional karyotyping include the risk of culture failure, maternal cell contamination (MCC), limited detection resolution (5-10 Mb), and differential growth of specific cell lineages which could hinder the diagnosis of genetic abnormalities, particularly mosaicisms. Additional genetic factors beyond the resolution of karyotyping are not well studied.
Next-generation sequencing (NGS) has brought genetic testing to new frontiers, expanding the scope of detectable genomic variants. Moreover, its significant reduction in costs over the years has facilitated the implementation of genetic diagnostic testing. Our customized shallow read-depth genome sequencing analytical pipeline, namely low-pass genome sequencing (GS), enables efficient and cost-effective detection of genome-wide copy-number variants (CNVs, >50 kb) and low-level chromosomal mosaicisms (as low as 10%). Furthermore, the roles of cryptic structural rearrangements, absence of heterozygosity (AOH), and single-nucleotide variant (SNV) were less understood in current studies.
Various versions of sequencing platforms targeting at different variants were already established and validated in the Prenatal Genetic Diagnostic Laboratory, The Chinese University of Hong Kong, including FetalSeq, ChromoSeq, and 30xWGS.
Human endometrial and decidual tissues, containing a myriad of immune and inflammatory populations, are immunologically dynamic. In the early proliferative phase of the menstrual cycle, T-cells are the most abundant leukocyte population in the endometrium, but they decrease to 20% of all stromal leukocytes during early pregnancy. Macrophages are also present in endometrial tissues during all phases of the menstrual cycle, but are most abundant in late secretory endometrium and in decidual tissues during early pregnancy. The most abundant population (70%) of stromal leukocytes observed in late secretory endometrium and in the decidua during early normal pregnancy are large granular lymphocytes (LGL) bearing the unique phenotype: CD56++, CD16-, CD57-, CD2±, CD38±, CD3-, CD4-, CD8-. Increased mean numbers of CD56+ cells have been reported in secretory endometrium of women with recurrent miscarriages.
The hypothesis that the balance between T-cell subsets (i.e. CD4+ and CD8+ cells) plays a role in maintaining successful pregnancy is controversial. Some studies have reported no difference between the proportions of T-cell subsets in either secretory endometrium or first trimester decidua from women with a history of recurrent pregnancy loss compared with normal controls; while others have described a shift towards a higher ratio of CD8+ T-cells in endometrial biopsies from women with a history of recurrent pregnancy loss.
The activation status of T-cell populations may provide another indicator of cellular immunity potentially involved in pregnancy loss. The IL-2 receptor has been reported to be absent on T-cells in normal first trimester decidual tissues using immunohistochemical techniques; however, using flow cytometry, CD3+CD25+ activated T-cells have been identified in decidual tissue. CD69 is another early activation marker expressed on the surface of T-cells. A proportion of T-cells constitutively expresses this marker throughout the menstrual cycle and in normal early pregnancy.
Approximately 60% of spontaneous abortions are attributable to numerically abnormal chromosomes in the developing conceptus, yet limited data to date addressing immunological phenomena in the decidua of miscarried women has compared their data relative to well-defined chromosomal abnormalities belonging to conceptuses. This is important since the chromosome abnormality trisomy 16, which occurs in 26% of all spontaneous abortions, is incompatible with life and would thus be an undisputed cause of spontaneous abortion. Therefore, the purpose of our study was to determine whether decidual leukocyte subpopulations and their associated activation markers were different between women having miscarriage of either a trisomy 16 conceptus (47XY+16 or 47XX+16) compared with a chromosomally normal male conceptus (46XY) and compared with gestationally age-matched decidual tissues. Samples from presumably normal female conceptuses (46XX) were not chosen for study because of the inability to accurately differentiate from possible maternal cell contamination.
For managing with miscarriage or termination of pregnancy (TOP) in first trimester loss, ultrasound-guided manual vacuum aspiration (USG-MVA) is one of the treatment options. USG-MVA for the treatment of early pregnancy loss has been used for many decades. It had been reported that USG-MVA is safer, more cost-effective, and is associated with shorter hospitalization time and cost than surgical evacuation under general anesthesia . USG-MVA is a surgical technique of suction curettage. It is performed by using a hand held vacuum source (a syringe with barrel and plunger) attached to a uterine cannula. The USG-MVA device works by aspirating the uterine content via the cannula into the syringe. Furthermore, product of conception derived from USG-MVA can be sent for karyotyping analysis.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Pui Wah Jacqueline Chung
- Phone Number: 35051537
- Email: jacquelinechung@cuhk.edu.hk
Study Contact Backup
- Name: Mandie Ho
- Phone Number: 35051764
- Email: mandieho@cuhk.edu.hk
Study Locations
-
-
-
Hong Kong, Hong Kong
- Recruiting
- Prince of Wales Hospital
-
Contact:
- Jacqueline Pui Wah CHUNG, MBBS
- Phone Number: 30501537
- Email: jacquelinechung@cuhk.edu.hk
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Women 18 years old or above
Women with miscarriage or TOP who are suitable candidates for MVA
- first trimester miscarriage or TOP
- No fetal heart beat or TOP in those with CRL 25mm
- incomplete miscarriage or TOP with POG <5cm
- hemodynamically stable,
- tolerates well with speculum examination
Exclusion Criteria:
Women who are not feasible for the MVA procedure
- cervical stenosis
- fibroid uterus >12 weeks in size
- known uterine malformation
- bleeding disorder
- clinically sepsis
- inability to tolerate pelvic examination
- History of psychological/ psychiatric problem
- Patient refusal
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Histopathologic diagnosis of chorionic villi
Time Frame: 31 May 2028
|
Detecting site-to-site heterogeneity and detecting cryptic structural rearrangements, absence of heterozygoisity (AOH), and single-nucleotide variant (SNV).
|
31 May 2028
|
Immunohistochemistry staining
Time Frame: 31 May 2028
|
immunoassay of maternal decidua
|
31 May 2028
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Pui Wah Jacqueline Chung, Prince of Wales Hospital
Publications and helpful links
General Publications
- WARBURTON D, FRASER FC. SPONTANEOUS ABORTION RISKS IN MAN: DATA FROM REPRODUCTIVE HISTORIES COLLECTED IN A MEDICAL GENETICS UNIT. Am J Hum Genet. 1964 Mar;16(1):1-25. No abstract available.
- Klentzeris LD, Bulmer JN, Warren MA, Morrison L, Li TC, Cooke ID. Lymphoid tissue in the endometrium of women with unexplained infertility: morphometric and immunohistochemical aspects. Hum Reprod. 1994 Apr;9(4):646-52. doi: 10.1093/oxfordjournals.humrep.a138564.
- Bulmer JN, Morrison L, Longfellow M, Ritson A, Pace D. Granulated lymphocytes in human endometrium: histochemical and immunohistochemical studies. Hum Reprod. 1991 Jul;6(6):791-8. doi: 10.1093/oxfordjournals.humrep.a137430.
- Bulmer JN, Sunderland CA. Immunohistological characterization of lymphoid cell populations in the early human placental bed. Immunology. 1984 Jun;52(2):349-57.
- Starkey PM, Sargent IL, Redman CW. Cell populations in human early pregnancy decidua: characterization and isolation of large granular lymphocytes by flow cytometry. Immunology. 1988 Sep;65(1):129-34.
- Hill JA, Melling GC, Johnson PM. Immunohistochemical studies of human uteroplacental tissues from first-trimester spontaneous abortion. Am J Obstet Gynecol. 1995 Jul;173(1):90-6. doi: 10.1016/0002-9378(95)90175-2.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2023.095
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Genetic Anticipation
-
Shanghai High Myopia Study GroupEye & ENT Hospital of Fudan UniversityRecruiting
-
Evidence Based Cataract Study GroupEye & ENT Hospital of Fudan UniversityRecruitingVisual Outcome | Congenital Cataract | Traumatic Cataract | Pediatric Cataract | Genetic AnticipationChina
-
National Human Genome Research Institute (NHGRI)CompletedGenetics | Birth Defects | Genetic Disease | Genetic Linkage | Genetic VariationUnited States
-
Children's Hospital Medical Center, CincinnatiUniversity of CincinnatiRecruitingAdolescent | Knowledge, Attitudes, Practice | Shared Decision Making | Genetic Testing | Genetic Screening | Genetic ChangeUnited States
-
Central Hospital, Nancy, FranceCompletedGenetic Disease | CNV | Genetic Counseling | Array CGHFrance
-
University of Illinois College of Medicine at PeoriaRady Children's Institute of Genomic MedicineActive, not recruitingGenetic Disease | Genetic SyndromeUnited States
-
Nicklaus Children's Hospital f/k/a Miami Children...Rady Pediatric Genomics & Systems Medicine InstituteRecruiting
-
Boston Children's HospitalNational Human Genome Research Institute (NHGRI)Active, not recruitingGenetic Disease | Genetic PredispositionUnited States
-
Vanderbilt University Medical CenterRecruitingGenetic DiseaseUnited States
-
Rady Pediatric Genomics & Systems Medicine InstituteActive, not recruiting
Clinical Trials on Ultrasound-guided manual vaccum
-
Marmara UniversityCompletedAdhesive Capsulitis of the ShoulderTurkey
-
University of FloridaNot yet recruiting
-
Abant Izzet Baysal UniversityRecruiting
-
Tri-Service General HospitalCompleted
-
Alabama Physical Therapy & AcupunctureUniversidad Rey Juan CarlosRecruitingEpicondylalgiaUnited States
-
Jose Antonio Garcia VidalUniversidad de MurciaCompleted
-
University of PalermoCompleted
-
Bracco Diagnostics, IncBracco Imaging S.p.A.TerminatedProstate CancerItaly, Austria, France, Netherlands, Belgium, Germany, United Kingdom
-
University of AlcalaActive, not recruiting
-
University of California, San FranciscoCompletedUterine FibroidsUnited States