Determining the Cause of Recurrent Miscarriages in a Couple: Importance of NOR in the Era of NGS (original) (raw)
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Cytogenetic investigation of couples with recurrent spontaneous miscarriages
Cytogenetic investigation of couples with recurrent spontaneous miscarriages, 2019
Background & Objective: Spontaneous pregnancy loss has always been the frustrating experience for the couples and concern clinician. Chromosomal abnormality in either of the parent is considered to be the one of the leading cause of recurrent spontaneous miscarriages. This study was designed to evaluate the possible chromosomal etiology of miscarriage and the subsequent intimacy of maternal or paternal genetic abnormality. Methods: This case-control study was conducted between January 2016 and October 2016 at a tertiary care hospital in Karachi. A total of thirty-two couples were selected who had suffered with recurrent spontaneous miscarriages (RSM). Using conventional cytogenetic technique karyotyping was performed on all of the subjects. For the control twenty couples were also selected with no history of pregnancy loss. All the karyotypes were recorded on the standard method. Data was analyzed through SPSS version 22. Results: Among thirty-two cases nine cases were found to have abnormal karyotype. In which sex chromosomal trisomy=02 (46,XY/47,XXY), marker chromosome=01 (47,XX,+mar), Robertsonian translocation=01 (45,XY,der,(14:21),(q10;q10)), reciprocal translocation=01 (46,XX,t(11;22)(q23;q11.2)), inversion=02 (46,XX,inv(9)(p11q13)) and minor structural abnormalities=02 (46,XX,15PS+) were found. Approximately equal ratio with 1:1.25 was observed among male and female carrier respectively. Non-significant difference was found between the ages of both carriers (p=0.34). Though a significant different value was calculated in the case of number of miscarriage (p=0.004*). Moreover, no significant association was found among spontaneous miscarriage (SM) and recurrent spontaneous miscarriage (RSM) with respect to maternal age (p= 0.157). Conclusion: In the recent study possible chromosomal abnormalities suggested the evaluation of the patient with the history of recurrent spontaneous miscarriage must include conventional cytogenetic. Moreover, probe development and extended investigation can ease the prognosis among pregnancy related complication.
Fertility and Sterility, 2010
Objective: To characterize a t(2;6) by array-based comparative genomic hybridization (array-CGH) in a couple with recurrent miscarriage, to analyze the meiotic segregation of the t(2;6), and to discuss couple specific care-taking modality before intracytoplasmic sperm injection. Design: Case report. Setting: INSERM U613 in Brest, France. Patient(s): Couple consulting for infertility. Intervention(s): Array-CGH to characterize a t(2;6) and fluorescence in situ hybridization (FISH) to analyze the meiotic segregation were performed. Main Outcome Measure(s): Array-CGH, FISH with a panel of bacterial artificial chromosome clones and commercial probes. Result(s): Analyses from peripheral blood lymphocytes identified a t(2;6)(q35;q24) unbalanced reciprocal translocation with microdeletions on the der(2) and the der(6). FISH on spermatozoa found that the frequency of normal (23,X or 23,Y) or ''translocation-deletions'' (23,X,der(2),der(6) or 23,Y,der(2),der(6)) spermatozoa was 41.10%. Conclusion(s): For our 46,XY,t(2;6)(q35;q24) carrier, more than 50% of the spermatozoa are chromosomally unbalanced. Moreover, FISH does not permit a distinction between normal and ''translocation-deletion'' phenotypes. So, in the possibility of preimplantation genetic diagnosis, is it necessary to select the normal embryos to the detriment of those translocation-deletions carriers? The pathogenicity of these microdeletions not been proved. Because the family history was oriented toward a variation of genetic equipment without phenotypic consequences, the couple decided not to make a selection between the normal embryos and the translocation-deletion carrier embryos. (Fertil Steril Ò 2010;93:2075.e3-e6.
Clinical and Experimental Obstetrics & Gynecology, 2019
A pregnancy loss (miscarriage) is defined as the spontaneous demise of a pregnancy before the fetus reaches viability. The term therefore includes all pregnancy losses from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss (RPL) is defined as two or more losses of the pregnancy. There are many proposed reasons; however in a prominent portion of cases, the reason remains unclear. Chromosomal abnormalities have an important place in recurrent pregnancy loss. Numerical and structural abnormalities constitute a significant cause. The purpose of this study was to assess the chromosomal abnormality of 490 chorionic villus samples of the couples who experienced RPL and to provide data for both clinicians and genetic counsellors
Journal of Assisted Reproduction and Genetics, 2011
Purpose The purpose of the present study was to investigate the contribution of chromosomal anomalies and the frequency of a particular type of aberration in couples with recurrent miscarriages. Methods A total of 1,162 couples with recurrent miscarriages were analyzed using G-banding and Fluorescence in situ hybridization where ever necessary. Results Chromosomal anomalies were detected in 78 cases. This study describes majority of the cases with balanced reciprocal translocations. Among the abnormal karyotypes we also report for the first time three unique translocations involving (3;14), (18;22) and (X;22) chromosomes which were confirmed by molecular cytogenetic methods. Conclusions The review of literature and the overall incidence of the abnormalities suggest that chromosomal analysis in couples with recurrent miscarriages should be taken up by all the practioners at all levels. This not only helps to check the cytological abnormalities but also helps to correlate the recurrent abnormalities in a given population. Thus establishing and correlating the environmental and genetic condition of that particular phenotype and genotype.
Human reproduction is considered as the most inefficient event as ∼15–20% of human pregnancies end in miscarriage and in the product of miscarriages, chromosomal anomalies are a common occurrence. The aim of the present retrospective study was to assess the frequency of chromosomal aberrations in couples with recurrent miscarriages in the region of Punjab and to compare with worldwide frequencies. In this study, a total of 440 cases were referred between the period 1995– 2015. After lymphocyte culturing, giemsa–trypsin banding was done for each case to assess the chromosomal anomalies. The frequency of chromosomal aberrations among couples was found to be 3.41% in our study. Among these aberrations, balanced reciprocal translocations formed the largest group with 60% anomalies. We would conclude that clinicians should understand the importance of chromosomal analysis in these couples and refer them for karyotyping after two miscarriages to rule out the possible genetic cause of recurrent miscarriages. [Sudhir N., Kaur T., Beri A. and Kaur A. 2016 Cytogenetic analysis in couples with recurrent miscarriages: a retrospective study from Punjab, north India. J. Genet. 95, 887–894]
Assessment of Chromosomal Abnormalities in Couples with Recurrent Pregnancy Loss
https://www.ijrrjournal.com/IJRR\_Vol.6\_Issue.3\_March2019/Abstract\_IJRR0025.html, 2019
Previous studies have demonstrated the type of chromosomal abnormalities found among couples with recurrent pregnancy loss. But a majority of the couples show a normal karyotype. The present study was undertaken to inquire the nature of cytogenetic abnormalities by routine karyotyping and c-banding whenever required, among couples with recurrent pregnancy loss and to compare it with fertile couples. Among couples, women with the history of two or more than two spontaneous abortions ≤ 24 weeks of gestation were included and couples with the history of Diabetes mellitus, thyroid disorders and hypertension, etc. were excluded. The lymphocytes were cultured as per the standard protocol and metaphase spreads stained by GTG banding technique. The presence of chromosomal aberrations was analyzed by semi-automated karyotyping software (Ikaros). In the present study, abnormal karyotypes were found in 3 cases. All the controls had a normal karyotype.
Cytogenetic analysis of miscarriages from couples with recurrent miscarriage: a case-control study
Human Reproduction, 2002
BACKGROUND: Reproductive loss carries immeasurable human costs as well as being costly to the health care system. The objectives of this study were to determine the frequency and distribution of cytogenetically abnormal miscarriages from couples with recurrent miscarriage and to compare the results with the general population. METHODS: A total of 420 specimens, including 29 pre-clinical, 237 embryonic and 154 fetal, were successfully karyotyped from 285 couples with recurrent miscarriage. The results were stratified according to maternal age and compared with controls. RESULTS: In all, 225 specimens (54%) were euploid. A total of 195 specimens (46%) were cytogenetically abnormal, of which 131 (66.5%) were trisomic, 37 (19%) were polyploid, 18 (9%) were monosomy X, eight (4%) were unbalanced translocations and one was a combination of trisomy 21 and monosomy X. The frequency of euploid miscarriages was significantly higher in women <36 years of age with recurrent miscarriage compared with controls. The distribution of cytogenetic abnormalities in the recurrent miscarriage group was not significantly different from controls, when stratified by maternal age. CONCLUSIONS: Women <36 years of age with recurrent miscarriage have a higher frequency of euploid miscarriage. When stratified for maternal age, there is no difference in the distribution of cytogenetically abnormal miscarriages in couples with recurrent miscarriage compared with controls.
Journal of Assisted Reproduction and Genetics, 2022
Spontaneous abortion occurs in 8-20% of recognized pregnancies and usually takes place in the first trimester (7-11 weeks). There are many causes of pregnancy loss, but the most important (about 75%) is the presence of chromosomal aberrations. We present the results of oligonucleotide array application in a cohort of 62 miscarriage cases. The inclusion criteria for the study were the loss after 8th week of pregnancy and the appearance of recurrent miscarriages. DNA was extracted from trophoblast or fetal skin fibroblasts. In the 62 tested materials from recurrent miscarriages, the detection rate was 56.5% (35/62). The most commonly found were aneuploidies (65%) (chromosomal trisomy 14, 16, 18, 21, and 22), Turner syndrome, and triploidy (17.1%). Other chromosomal abnormalities included pathogenic and likely pathogenic structural aberrations: 1) pathogenic: deletion 7p22.3p12.3 and duplication 9p24.3p13.2 inherited from the normal father, deletion 3q13.31q22.2 and deletion 3q22.3q23 of unknown inheritance and duplication of 17p12 inherited from father with foot malformation; 2) likely pathogenic variants: deletion 17p13.1 inherited from normal mother, deletion 5q14.3 of unknown inheritance and de novo deletion 1q21.1q21.2. Among these aberrations, six CNVs (copy number variants) were responsible for the miscarriage: deletion 7p22.3p12.3 and duplication 9p24.3p13.2, deletion 3q13.31q22.2 and deletion 3q22.3q23, and deletion 17p13.1 and deletion 1q21.1q21.2. Other two findings were classified as incidental findings (deletion 5q14.3 and 17p12 duplication). Our research shows that 17% of the aberrations (6/35 abnormal results) that cannot be identified by the routine kariotype analysis are structural aberrations containing genes important for fetal development, the mutations of which may cause spontaneous abortion.
Chromosomal abnormalities and embryo development in recurrent miscarriage couples
Human Reproduction, 2003
BACKGROUND: Chromosomal abnormalities are an important cause of spontaneous abortion and recurrent miscarriage (RM). Therefore, we have analysed the incidence of chromosomal abnormalities and embryo development in patients with RM. METHODS: Preimplantation genetic diagnosis (PGD) was performed on 71 couples with RM and 28 couples undergoing PGD for sex-linked diseases (control group). Chromosomes 13, 16, 18, 21, 22, X and Y were analysed by¯uorescence in-situ hybridization. RESULTS: The implantation rate in RM patients was 28% and three patients (13%) miscarried. The percentage of abnormal embryos was signi®cantly increased (P < 0.0001) in RM patients compared with controls (70.7 versus 45.1%). All of the embryos were abnormal in 19 cycles (22.1%) and repeated PGD cycles yielded similar rates of chromosomal abnormalities in 14 couples. Anomalies for chromosomes 16 and 22 were signi®cantly higher (P < 0.01) in RM cases. In the RM population, euploid embryos reached the blastocyst stage more frequently than abnormal embryos (61.7 versus 24.9%; P < 0.0001). CONCLUSIONS: RM is associated with a higher incidence of chromosomally abnormal embryos, of which some are able to develop to the blastocyst stage. IVF plus PGD is an important step in the management of these couples, but the technique has to move towards a full chromosome analysis.