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.

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.