Chromosomal Aberrations in 224 Couples with Recurrent Pregnancy Loss

Abstract

Background: Recurrent pregnancy loss (RPL) is a major reproductive health issue, affecting 2%–5% of couples. Genetic factors, mainly chromosomal abnormalities, are the most common cause of early miscarriage accounting for 50%–60% of first trimester abortion. Aim: To estimate the prevalence and nature of chromosomal anomalies in couples with recurrent miscarriage. Patients and Methods: This study included 224 couples with a history of 2 or more abortions. Both partners were karyotyped as part of the primary investigation. Cytogenetic analysis was carried out using the standard method. Results: A total of 224 couples with a history of two or more recurrent abortions were enrolled in this study. Chromosomal abnormalities were detected in 26 couples (11.6%) and 28 individuals (6.25%). We found a structural chromosome abnormality in 17/28 patients (60.7%); 12 patients had a reciprocal translocation (42.9%) including one patient with an additional inversion of the Y chromosome, 4 (14.3%) had a Robertsonian translocation, and one patient (3.6%) carried a paracentric inversion of chromosome 2. Numerical chromosome aberrations were detected in 5 patients; three patients (10.7%) with sex chromosome abnormalities and two (7.1%) with a marker chromosome. Six patients (21.4%) showed a heteromorphic variant involving chromosome 9. Conclusion: The prevalence of chromosomal abnormalities in couples with RPL is within the range reported worldwide. Cytogenetic analysis should become an integral part of the investigations of couples with at least two pregnancy losses of undetermined etiology.

The spectrum of chromosomal translocations in the Arab world: ethnic-specific chromosomal translocations and their relevance to diseases

“…of patients/No. screened Clinical phenotype Primary mutation/associated with other abnormalities Consanguinity Reference RPL with birth deformities Egypt Rec † Rec † Rec † t(3;8)(p25;p11) t(4;6)(p24;q25) t(7;21)(p11;p11) De novo - - 30y/M 22y/F 22y/F 1/- 1/- 1/- Repeated abortions, stillbirth, fetal malformation, and birth of mentally handicapped children - - Gaboon et al 2015 ) RPL Rec Rec Rec Rec t(1;15)(p35;q15) t(3;15)(p23;q26.2) t(3;7)(p26;p15) t(4;6)(q25;q26) Fam 23-50y/ 7F, 5 M 12/224 Recurrent abortions and the birth of dysmorphic/mentally handicapped infants Primary Consanguineous couple involving translocation in chromosomes 11 and 12 Elhady et al 2020 ) Therapy-related acute myeloid leukemias Rec t(v;11q23) De novo Median: 37y/ 46 M, 28F 6/120 Poor topoisomerase II inhibitor treatment outcome Primary - Mosad et al 2012 ) Down syndrome Rec t(4;21)(q25;q22) Mat 8y/F 1/1 Severe growth retardation, microcephaly, hearing impairment, and specific facies Associated with partial trisomy 4q25-qter and 21(pter-q22) - El-Ruby et al 2007 ) ...…”

“…Most of the unique CTs were identified in Egypt, which were mostly cases of RPL. Consanguinity was reported in only five cases (Elhady et al 2020 ; AbouEl-Ella et al 2018 ). However, it is most likely that consanguinity is underreported in these cases and could possibly be a significant contributor in RPL.…”

Patterns of Cytogenomic Findings from a Case Series of Recurrent Pregnancy Loss Provide Insight into the Extent of Genetic Defects Causing Miscarriages

“…Consistent with our result, cytogenetic analysis on peripheral blood specimens from 570 and 224 couples with RPL showed a detection rate of 3% (18/57) and 7% (16/224) for parental carriers of a balanced translocation and 0.3% (2/570) and 2% (4/224) for carriers of a Robertsonian translocation, respectively, which provides cytogenetic etiology of consecutive two to nine abortions in these couples. 28,29 A recent meta-analysis focused on CMA results from large cases series of POC indicated a detection rate of approximately 3% for pCNVs and 1% for genomic disorders; the risk of pregnancy loss by pCNVs of 16p11.2 duplication, 17q12 deletion, Xp22.3 deletion, and 7q11.23 deletion was estimated in the range of 21 to 50%. 18 The detection rate of 1% for pCNVs in this case series was most likely an underestimation due to the incomplete implementation of CMA on POC specimens.…”

Implicaciones causadas por la presencia y segregación de translocaciones robertsonianas. Su diagnóstico y efectos en la población

“…Por otro lado, en Egipto se realizó un estudio estadístico enfocado en parejas que habían sufrido al menos dos abortos espontáneos recurrentes. De 224 parejas, se encontró que 28 individuos tenían una anormalidad cromosómica, cuatro de ellos (0.89%) con una translocación robertsoniana (44). En Monterrey, México con el objetivo de estimar la prevalencia de anormalidades cromosómicas y variantes poliformes en 158 parejas con historial de abortos espontáneos repetidos, se realizaron estudios cromosómicos y se encontró translocación robertsoniana en dos (1.27 %), además se observó https://doi.org/10.32776/revbiomed.v33i1.910 que la prevalencia de anormalidades cromosómicas en mujeres dividida entre la prevalencia en hombres resulta en una razón de 1.4:1 (45).…”