Cytogenetic analysis of the retained products of conception after missed abortion following blastocyst transfer: a retrospective, large-scale, single-centre study

Abstract

Cytogenetic analysis of the retained products of conception (POC) is the most effective test for identifying miscarriage causes. However, there has been no large-scale study limited to blastocyst transfer. This study retrospectively reports the findings of 1030 cases in which POC analysis was performed after missed abortion following single blastocyst transfer performed at the Shinbashi Yume Clinic. We identified 19.4% as normal karyotypes and 80.6% as aneuploid. These cases broke down into: 62.3% trisomy; 7.8% double trisomy; 0.5% triple or quadruple trisomy; 1.3% monosomy 21; 3.2% monosomy X; 0.1% 47,XXY; 1.0% polyploidy; 1.0% mixed; 1.1% embryonic mosaicism; and 2.4% structural anomalies. In samples with normal karyotypes, 49.5% were female while 50.5% were male. The occurrence of trisomy and double trisomy were both significantly more frequent in the ≥38 years group than in the ≤37 years group (P < 0.01). Trisomy was significantly more frequently associated with fetal heartbeat (P < 0.01); double trisomy, polyploidy and normal karyotype were significantly more frequent with no fetal heartbeat (P < 0.01). There was no significant difference in the frequency of chromosomal abnormalities between the number of miscarriages or blastocyst quality. Thus, POC cytogenetic testing is highly valuable for ascertaining the cause of miscarriage.

Cytogenetic Analysis of Spontaneous Miscarriages Using Long-Term Culturing of Chorionic Villi

“…Mosaics of the normal karyotype and chromosomal aberrations were observed in 15.7% of the cases, and double trisomy was observed in 1.1% of the cases. Comparable proportions have been reported in previous studies [27,28].…”

Development of a Chromosomal Microarray Test for the Detection of Abnormalities in Formalin-Fixed, Paraffin-Embedded Products of Conception Specimens

“…18 This case received an increased risk of recurrence from the FISH result of trisomy 22, and the identification of a double trisomy is thought to carry the same maternal age-related risk of recurrence as a single trisomy. It has been noted, however, that double trisomy is found more frequently with increased maternal age (34.1 AE 5.7 years), 19,20 and our patient was 38 years old. Sample 17 had a triploid result by FISH which would not indicate an increased recurrence risk; however, CMA also identified an additional copy of chromosome 16.…”

Whole‑exome sequencing analysis of products of conception identifies novel mutations associated with missed abortion

“…Previous studies suggest that chromosomal abnormalities account for 60–80% of MA cases ( 4 – 8 ). However, to the best of the authors' knowledge, no studies have been performed on POC using NGS technology to elucidate single gene defects.…”

“…Multiple epidemiological factors, including parental or embryonic chromosomal abnormalities, infection, immunological factors, hereditary thrombophilia, uterine abnormalities, endocrinological disorders, and nutritional and environmental factors have been associated with miscarriage ( 2 , 3 ). Cytogenetic analysis of the retained POC is thought to be the most effective test for identifying the cause of MA ( 4 ). Chromosomal abnormalities are the primary cause of MA, with errors in chromosome number, copy number variations and abnormalities resulting in structural defects accounting for 60–80% of MAs ( 4 – 8 ).…”

“…Cytogenetic analysis of the retained POC is thought to be the most effective test for identifying the cause of MA ( 4 ). Chromosomal abnormalities are the primary cause of MA, with errors in chromosome number, copy number variations and abnormalities resulting in structural defects accounting for 60–80% of MAs ( 4 – 8 ). However, the cause of 20–40% of MAs remains unknown, despite current detection methods.…”