Chromosomal Abnormalities In Women Research Articles

Contribution of chromosomal aberrations to the pathogenesis of primary and secondary amenorrhea: A study from Western Iran.

Amenorrhea is an abnormal condition characterized by the absence of menstruation in women of reproductive age. According to the World Health Organization, amenorrhea ranks as the sixth leading cause of female infertility. Approximately 2% to 5% of women of reproductive age experience amenorrhea, which can be classified as primary amenorrhea (PA) or secondary amenorrhea (SA). Several studies have named chromosomal abnormalities among the main causes of amenorrhea, though the prevalence of these abnormalities may differ across populations. The objective of this study was to ascertain the frequency and types of chromosomal abnormalities in women with amenorrhea in Kermanshah Province, Iran. This retrospective study included patients with PA and SA who underwent standard cytogenetic analysis. We also conducted a review of the literature on chromosomal abnormalities and their prevalence in SA. Among the 137 cases of PA in this study, 22% exhibited chromosomal abnormalities. Numerical changes were the most common finding (46.6%) in this group, including 45,X, mosaic, and 47,XXX karyotypes. These were followed by the 46,XY karyotype (40%). Of the 51 cases of SA that received chromosomal analysis, abnormalities were identified in only one case. Additionally, our review of the literature revealed that chromosomal aberrations are responsible for 7% of SA cases globally. In this study, we successfully characterized the cytogenetic causes of PA and SA in a substantial population from Kermanshah Province, Iran.

The Types and Frequencies of X Chromosome Abnormalities in Women with Reproductive Problems

Introduction: X chromosome architecture and integrity are essential for normal ovarian function. Both numerical and structural X chromosome abnormalities play an important role in female infertility. This study aimed to determine the types and frequency of X chromosome aberrations detected in women referred for cytogenetic investigation due to reproductive problems. Methods: 2,936 women (average age: 37.5 years) were enrolled in the present study. Peripheral blood karyotyping was performed by conventional cytogenetic techniques. For each woman, 20 G-banded metaphases were studied and in case of suspected mosaicism, analysis was extended to 100 metaphases. Results: 2,588/2,936 (88.15%) of women had a normal karyotype (46,XX), while 348/2,936 (11.85%) had an abnormal one. Thirty-two women (1.09%) carried autosomal chromosome abnormalities and 316 (10.76%) had X chromosome rearrangements. In 311/2,936 women (10.59%), X chromosome numerical aberrations were detected (low-level mosaicism), and in 5/2,936 cases (0.17%), X structural abnormalities (two with pericentric inversion, one with Xq deletion and two 45,X mosaics, one with an Xp deletion cell line and the other with isochromosome Xq cell line). Low-level X mosaicism was a common finding in women >35 years as compared to younger ones (92.93% vs. 7.07%), a finding consistent with loss of chromosome X with aging. Other X chromosome abnormalities were detected in younger women (32.3 ± 4.13 vs. 41.04 ± 4.5 years). The mean age of women with Turner-like phenotype was 28.75 ± 6.6 years. Conclusion: The study confirms that the incidence of X chromosome abnormalities is increased in women with fertility problems and that karyotype is the gold standard for their identification. Genetic counseling is recommended in these cases to provide information concerning available treatment and fertility options.

Single nucleotide polymorphism array (SNP-array) analysis for fetuses with abnormal nasal bone.

This study aims to evaluate the prevalence of submicroscopic chromosomal abnormalities found on single nucleotide polymorphism array (SNP array) in pregnancies with either an absent or hypoplastic nasal bone. This retrospective study included 333 fetuses with either nasal bone hypoplasia or absence identified on prenatal ultrasound. SNP array analysis and conventional karyotyping were performed in all the subjects. The prevalence of chromosomal abnormalities was adjusted for maternal age and other ultrasound findings. Fetuses with either an isolated nasal bone absence or hypoplasia, those that had additional soft ultrasound markers, and those where structural defects were found on ultrasound were divided into three groups: A, B, and C, respectively. Among the total cohort of 333 fetuses, 76 (22.8%) had chromosomal abnormalities, including 47 cases of trisomy 21, 4 cases of trisomy 18, 5 cases of sex chromosome aneuploidy, and 20 cases of copy number variations of which 12 were pathogenic or likely pathogenic. The prevalence of chromosomal abnormalities in group A (n = 164), B (n = 79), and C (n = 90) was 8.5%, 29.1% and 43.3%, respectively. The incremental yields by SNP-array compared with karyotyping in group A, B, and C were 3.0%, 2.5% and 10.7%, respectively (p > 0.05). Compared to karyotype analysis, SNP array detected an additional 2 (1.2%), 1 (1.3%), and 5 (5.6%) pathogenic or likely pathogenic CNVs in groups A, B, and C, respectively. In the 333 fetuses, the prevalence of chromosomal abnormalities in women with advanced maternal age (AMA) was significantly higher than that in non-AMA women, (47.8% vs. 16.5%, p < 0.05). In addition to Down's syndrome, many other chromosomal abnormalities are present in fetuses with abnormal nasal bone. SNP array can improve the prevalence of chromosomal abnormalities associated with nasal bone abnormalities, especially in pregnancies with non-isolated nasal bone abnormalities and advanced maternal age.

P-487 Preimplantation genetic testing for aneuploidy for recurrent pregnancy loss: a systematic review and meta-analysis

Abstract Study question Can preimplantation genetic testing for aneuploidy (PGT-A) improve the live rate of recurrent pregnancy loss(RPL)? Summary answer PGT-A can improve the live birth rate and reduce the rate of miscarriages in women with RPL following in vitro fertilization-embryo transfer (IVF-ET). What is known already PGT-A has been widely used in women with RPL over the past decade. However, there is no consensus supporting this approach to the management of RPL. Study design, size, duration Systematic review and meta-analysis according to PRISMA guidelines. The research population was focused on RPL women. The intervention was PGT-A. The comparator was IVF/ICSI without PGT-A or expectant management. The primary outcome was the live birth rate per woman, and the secondary outcomes were the miscarriage rate and clinical pregnancy rate. Participants/materials, setting, methods PubMed, EMBASE, The Cochrane Library, and trial registers were searched for studies on PGT-A and RPL up to October 2022. There were no limitations regarding the year of publication or duration of follow-up but to the English language. The primary outcome was the live birth rate per woman, and the secondary outcomes were the miscarriage rate and clinical pregnancy rate. Main results and the role of chance Out of 1466 search results, 9 studies (including one RCT, one prospective pilot study, and seven retrospective cohort studies) were included in the review. Seven of these studies compared the live birth rate of RPL with PGT-A versus without PGT-A following in vitro fertilization-embryo transfer (IVF-ET). PGT-A significantly increased live birth rate (odds ratio(OR): 2.07; 95% confidence interval: 1.88 to 2.27) and lowered miscarriage rate (OR: 0.21; 95% confidence interval: 0.13 to 0.34). However, PGT-A did not improve the clinical pregnancy rate. In two studies comparing the live birth rate/ongoing pregnancy of RPL with PGT-A versus expectant management, the result shows that PGT-A did not improve the live birth rate (OR: 1.11; 95% confidence interval: 0.74 to 1.67). Limitations, reasons for caution Limitations include the retrospective design and heterogeneity of studies included, limiting comparison and pooling of data. Some studies have limited sample sizes. The data collected in the database could not exclude anatomic or chromosomal abnormalities in women with RPL. Wider implications of the findings PGT-A can improve the live birth rate and reduce the rate of miscarriages in women with RPL following IVF-ET. However, there is no evidence of a beneficial effect of PGT-A if compared with expectant management. It is important to evaluate carefully the application of PGT-A in clinical practice. Trial registration number not applicable

Recurrent pregnancy loss: fewer chromosomal abnormalities in products of conception? a meta-analysis.

To compare the prevalence of chromosomal abnormalities detected in products of conception (POCs) between recurrent pregnancy loss and sporadic pregnancy loss. A systematic search was performed in the PubMed and Embase databases from inception to December 31, 2020. Relevant studies analysing the association between the number of pregnancy losses and the incidence of chromosomal abnormalities were included. Independent data extraction was conducted and study quality was assessed. Meta-analyses were carried out to calculate odds ratios by using fixed- or random-effects models according to statistical homogeneity. A total of 8320 POCs in 19 studies were identified for the meta-analyses. The incidence of chromosomal abnormalities in sporadic pregnancy loss was significantly higher than that in recurrent pregnancy loss. In subgroup analyses, the following studies reported a high incidence of abnormal outcomes of sporadic pregnancy loss: studies with ≥ 300 samples, studies published before 2014, studies conducted in European and American countries, and studies with analyses using conventional karyotype techniques. Moreover, the incidence of chromosomal abnormalities in women with two pregnancy losses was significantly higher than that in women with three or more pregnancy losses. However, there was no difference in the distribution of abnormal types between sporadic and recurrent pregnancy loss or between two and three or more pregnancy losses. The prevalence of chromosomal abnormalities detected in POCs was lower in recurrent pregnancy loss than in sporadic pregnancy loss, and decreased with an increasing number of pregnancy losses.

Refractory Temporal Lobe Epilepsy in Patients with Mosaic Turner Syndrome

Turner syndrome (TS) is one of the most common sex chromosome abnormalities in women, but there are only a few case reports of patients with TS who have epilepsy or seizures. Here, we report two additional cases with drug-resistant temporal lobe epilepsy (TLE) and TS mosaicism. Patient #1 is a 22-year-old female with drug-resistant TLE whose karyotype analysis showed that 84% of interphase cells had (45,X) genotype and brain magnetic resonance imaging (MRI) initially reported as normal showed developmental left temporal lobe encephalocele. She underwent left temporal lobectomy, and she is seizure free for 10-year postoperative follow-up period. Patient #2 is a 49-year-old female who has TLE with normal brain MRI. The karyotype analysis showed that 2/30 of metaphase cells had (45, X) genotype. In addition, 11 cases of epilepsy associated with TS were determined through PubMed. The clinical characteristics of all are reviewed.

Increased Risk of Aortic Dissection Associated With Pregnancy in Women With Turner Syndrome: A Systematic Review.

Turner syndrome (TS) is one of the most common chromosomal abnormalities in women. The condition is characterized by gonadal dysgenesis and is associated with structural cardiac abnormalities. Assisted reproductive technology with oocyte donation may be successful but places women with TS at increased risk of aortic dissection and death. To summarize all cases of aortic dissection associated with pregnancy in women with TS and provide guidance regarding the safety of pregnancy. Systematic review of PubMed for reports of women with TS, aortic dissection, and pregnancy. There are 14 total reported cases of aortic dissection associated with pregnancy in women with TS. Ten of these cases occurred during pregnancy or in the first month postpartum. The majority of affected pregnancies resulted from oocyte donation, 2 of which were multiple gestations. Two women had a documented history of hypertension, and 3 pregnancies were complicated by preeclampsia. Bicuspid aortic valve and coarctation of the aorta were the most common associated cardiac anomalies. More than half of women had some degree of aortic dilatation. Two women had no identifiable risk factors. Women with TS who desire pregnancy must be thoroughly counseled regarding the increased risk of aortic dissection during pregnancy and postpartum. Preconception consultation with maternal-fetal medicine, reproductive endocrinology, and cardiology is necessary along with a comprehensive physical evaluation. If women with TS choose to pursue pregnancy, they require rigorous cardiac monitoring each trimester during pregnancy and postpartum.

Chromosomal aberrations in women with primary and secondary amenorrhea: A cross-sectional study.

Among women of childbearing age, about 2-5% are affected by amenorrhea that is either primary or secondary. However, there are no data regarding the frequency and type of chromosomal abnormalities associated with amenorrhea in Saudi women. The present study aims to establish the frequency and pattern of chromosomal abnormalities in primary amenorrhea (PA) and secondary amenorrhea (SA) cases in a tertiary care center, Riyadh, Saudi Arabia. This cross-sectional study was conducted between 2013 and 2016 on women referred to the Reproductive Endocrine and Infertility Medicine Department at a tertiary care center in Riyadh. Women were divided into two groups: PA and SA. After the initial diagnosis of amenorrhea based on medical history, physical examination, hormonal profile and ultrasonography, chromosome karyotype analysis was conducted on metaphase preparations following routine cytogenetics culture and harvest methods. Chromosomal tests were performed for 53 patients (42 with PA and 11 with SA) out of 79 referred patients with amenorrhea. About 19% of the 42 patients with PA and 1 patient (9.1%) diagnosed as SA showed an abnormal karyotype. The most common abnormal karyotypes observed were 46, XY and 45, X. The present study indicates that the chromosomal analysis after the exclusion of nongenetic causes should be essentially considered for the precise diagnosis and the development of more successful management for females with amenorrhea. This study also revealed that the prevalence of chromosomal abnormalities in women with PA and SA is similar to that reported in the literature.

Pregnancies and obstetrical prognosis after oocyte donation in Turner Syndrome: A multicentric study

IntroductionTurner syndrome is one of the most frequent chromosomal abnormalities in women, with a prevalence estimated to be 1 of 2500 live birth. Pregnancy in women with Turner syndrome is known to be at high risk, whether it is spontaneous or after oocyte donation, because of miscarriages and potential cardio-vascular complications which can be life-threatening. All of these patients should therefore be screened with a comprehensive cardio-vascular assessment before pregnancy, and have a close follow-up during and after pregnancy. Patients and methodsIt is a retrospective study, conducted in 10 of the 27 French oocyte donation centers between 2012 and 2016, on all the patients presenting with Turner syndrome included in an oocyte donation program. Results151 embryo transfers were realized in 73 patients, resulting in 39 pregnancies. Among these pregnancies, 24 children were born healthy, 11 spontaneous miscarriages, 3 voluntary abortions, 1 extra-uterine pregnancy and 1 maternal death from non-cardio-vascular origin occurred. Pregnancies were complicated by gravid arterial hypertension in 28.2% of cases, preeclampsia in 10.3% of cases, and gestational diabetes in 7.7% of cases. ConclusionThis study bring out obstetrical complications of the same magnitude than the ones described in the literature. Lead over a period of 4 years, in 10 French oocyte donation centers, it doesn’t reveal any cardio-vascular complications, conversely to other studies published before French and American recommendations. This study reinforces the usefulness of specific recommendations for the care of these particular patients.

Specific Chromosomal Aberrations in Primary Amenorrhoea: Study on 3776 Cases from Indian Population.

To verify the prevalence of chromosomal abnormalities in women with primary amenorrhoea in India aiming at appropriate genetic counselling. In a 16-year retrospective (2001-2016) study, 3776 women with primary amenorrhoea were evaluated. Chromosomal analysis of all the cases was done by GTG banding. Clinical history and other laboratory findings were taken into consideration to determine the diagnosis. The karyotype results revealed 31.2% cases with chromosomal abnormalities (n = 1177/3776). In patients with abnormal chromosome complement, 31.2% exhibited numerical aberrations (n = 367) and 34.9% with structural aberrations (n = 411). About 33.9% of cases were with XY male karyotype (n = 399). As per the literature till date, this study is the largest with high incidence of chromosomal abnormalities; early detection of abnormalities is necessary for guidance to reproductive management and genetic counselling.

Genetic abnormalities seen on CVS in early pregnancy failure

Objective: To determine the frequency and distribution of chromosome abnormalities in women with early pregnancy failure (EPF) detected by cytogenetic testing on chorionic villus sampling.Method: Retrospective observational cohort study of chromosomal analysis from transvaginal chorionic villus sampling (CVS) or reflex products of conception (POC) karyotype. CVS was offered as a training tool for Maternal Fetal Medicine fellows prior to manual vacuum aspiration for EPF 9-week gestation. POC were analyzed for cytogenetics if no results were obtained on CVS.Results: One hundred thirty samples were collected from December 2011 to April 2015. 33 (27.3%) cases had a normal karyotype and 88 (73.0%) cases had an abnormal karyotype. The most common group of abnormalities were trisomy, (n = 50, 41.3%), triploidy/tetraploidy, (n = 17, 14.0%), monosomy (n = 15, 12.4%), and structural rearrangements (n = 6, 5.0%). Nine (6.9%) samples were maternal decidua only. Abnormal karyotype in EPF was significantly increased in women by age group (p < .01) but not in women with a history of prior miscarriage (p = .5).Conclusion: Our cohort had a high detection rate of aneuploidy. The most common chromosomal abnormalities in EPF were: trisomy, followed by triploidy/tetraploidy, monosomy, and structural rearrangements. Maternal age had the strongest correlation with EPF associated with aneuploidy.

228: Amniocentesis with microarray versus serum screening for detection of chromosomal abnormalities in women in low-risk population

228: Amniocentesis with microarray versus serum screening for detection of chromosomal abnormalities in women in low-risk population

Cytogenetic analysis in women with primary and scondary amenorrhea in iran: retrospective study on 110 patients

The absence of menstrual periods for one or more periods is called amenorrhea. Primary amenorrhea means the lack of its occurrence until the age of 16 years. Secondary amenorrhea refers to situations that a person has experienced menstruation periods in the past and then stops its occurrence. Amenorrhea is a symptom, not a disease that can cause due to disorders of hypothalamus and pituitary glands, disorders of sexual glands and deformities of the uterus and ovaries. Due to the clinical importance of reproductive in life and non-reproductive of women amenorrhea due to ovarian function, this study has been conducted in order to determine the prevalence and type of chromosomal abnormalities in women referred to the Cytogenetic Laboratory of Cellular and Molecular Research Center, in University of Medical Sciences of Qazvin. Karyotype analysis and its relationship with phenotype were performed on 110 Iranian female patients with primary and secondary amenorrhea. Metaphase chromosomes were prepared and analyzed by G-banding technique and were evaluated to examine the mosaicism of 100 cells of lymphocytes cells. Karyotype of 91 women (82.72%) was normal and chromosomal abnormalities in 19 patients out of 110 patients (17.37%) were observed with primary and secondary amenorrhea. Primary amenorrhea was observed in 17 of these patients, two of whom also had a secondary amenorrhea. Monosomy chromosome X (6 Cases- 31.57%) and Monosomy chromosome Y (6 Cases- 31.57%) was the most common disorders observed in the women with primary amenorrhea. Monosomy mosaic and trisomy chromosome X were observed in 2 cases of women with secondary amenorrhea (21.81% of the whole statistical sample). The overall prevalence of chromosomal abnormalities was between 15.9 % and 63.3% among patients with primary amenorrhea, that our findings in chromosomal analysis of these women (19.76%) confirm it. Keywords: cytogenetic, primary amenorrhea, secondary amenorrhea, chromosomal abnormalities

Fertility and Pregnancy in Turner Syndrome.

Turner syndrome (TS) occurs in one in 2500 live female births and is one of the most common chromosomal abnormalities in women. Pregnancies in women with TS, conceived with either autologous or donated oocytes, are considered high risk because of the associated miscarriages and life-threatening cardiovascular complications (aortic dissection, severe hypertension). Therefore, it is imperative to conduct a full preconception evaluation and counselling that includes cardiac assessment with Holter blood pressure monitoring, echocardiography, and thoracic MRI. Abnormal findings, such an aortic dilatation, mandate close monitoring throughout the pregnancy and the immediate postpartum period and could possibly contraindicate pregnancy. When invitro fertilization using donated oocytes is performed in these women, only a single embryo should be transferred. Women with a Turner mosaic karyotype appear to have a lower risk of obstetrical and cardiovascular complications but should nevertheless undergo the full preconception evaluation. In this article, we offer guidelines on the management of women with TS in the preconception period, during pregnancy, and postpartum.

High frequency of X chromosome abnormalities in women with short stature and elevated liver enzymes.

Paucisymptomatic forms of Turner's syndrome (TS), in which short stature is the predominant clinical abnormality, remain underdiagnosed. Abnormal liver tests are extremely frequent in adult TS patients reflecting various types of hepatic lesions. The objective of the study was to investigate whether unexplained elevated liver enzymes in women with short stature could reveal X chromosome abnormalities of undiagnosed TS. Thirty-one consecutive short stature women displaying elevated liver enzymes and no previous diagnosis of TS were compared with 31 age-matched controls in a prospective study. Liver biopsy was performed in 26 patients. Systematic karyotype analysis and fluorescence in situ hybridization. X chromosome abnormalities were found in 27 patients and one control (87.0% vs 3.2%, P < .0001), including a 45,X/46,XX mosaicism in 24 patients and isochromosome of the long arm in three. Liver histological analysis showed architectural changes in 17 patients with nodular regenerative hyperplasia in 12. Biliary lesions were present in 13 patients and liver steatosis in 20. X chromosome abnormalities indicative of cryptic TS are extremely frequent in short-stature women with unexplained elevated liver enzymes. In short-stature women, abnormal liver tests should lead to systematic karyotype analysis.

Chromosomal abnormalities in couples with recurrent first trimester abortions.

To investigate the prevalence of chromosomal abnormalities in couples with two or more recurrent first trimester miscarriages of unknown cause. The study was conducted on 151 women and 94 partners who had an obstetrical history of two or more consecutive first trimester abortions (1-12 weeks of gestation). The controls were 100 healthy women without a history of pregnancy loss. Chromosomal analysis was performed on peripheral blood lymphocytes cultured for 72 hours, using Trypsin-Giemsa (GTG) banding. In all cases, at least 30 metaphases were analyzed and 2 karyotypes were prepared, using light microscopy. The statistical analysis was performed using the Student t-test for normally distributed data and the Mann-Whitney test for non-parametric data. The Kruskal-Wallis test or Analysis of Variance was used to compare the mean values between three or more groups. The software used was Statistical Package for the Social Sciences (SPSS), version 17.0. The frequency of chromosomal abnormalities in women with recurrent miscarriages was 7.3%, including 4.7% with X-chromosome mosaicism, 2% with reciprocal translocations and 0.6% with Robertsonian translocations. A total of 2.1% of the partners of women with recurrent miscarriages had chromosomal abnormalities, including 1% with X-chromosome mosaicism and 1% with inversions. Among the controls, 1% had mosaicism. An association between chromosomal abnormalities and recurrent miscarriage in the first trimester of pregnancy (OR=7.7; 95%CI 1.2--170.5) was observed in the present study. Etiologic identification of genetic factors represents important clinical information for genetic counseling and orientation of the couple about the risk for future pregnancies and decreases the number of investigations needed to elucidate the possible causes of miscarriages.

Non-meiotic chromosome instability in human immature oocytes

Aneuploidy has been a major issue in human gametes and is closely related to fertility problems, as it is known to be present in cleavage stage embryos and gestational losses. Pre-meiotic chromosome abnormalities in women have been previously described. The aim of this study is to assess the whole-chromosome complement in immature oocytes to find those abnormalities caused by mitotic instability. For this purpose, a total of 157 oocytes at the germinal vesicle or metaphase I stage, and discarded from IVF cycles, were analysed by CGH. Fifty-six women, between 18 and 45 years old (mean 32.5 years), including 32 IVF patients (25-45 years of age) and 24 IVF oocyte donors (18-33 years of age), were included in the study. A total of 25/157 (15.9%) of the oocytes analysed, obtained from three IVF clinics, contained chromosome abnormalities, including both aneuploidy (24/157) and structural aberrations (9/157). Independently of the maternal age, the incidence of abnormal oocytes which originated before meiosis is 15.9%, and these imbalances were found in 33.9% of the females studied. This work sheds light on the relevance of mitotic instability responsible for the generation of the abnormalities present in human oocytes.

Chromosomal abnormalities and hormonal disorders of primary amenorrhea patients in Egypt

BACKGROUND:Primary amenorrhea is defined as the absence of menstruation and secondary sexual characteristics in phenotypic women aged 14 years or older. Hormonal disorders are main causes of primary amenorrhea. Common hormonal cause of primary amenorrhea includes pituitary dysfunction and absent ovarian function. The aim of this study was to estimate the incidence and types of chromosomal abnormalities in patients with primary amenorrhea in Egypt.MATERIALS AND METHODS:Chromosomal analysis and hormonal assay were carried out on 223 patients with primary amenorrhea that were referred from different parts of Egypt to Cytogenetic laboratory of Genetic Unit, Children Hospital Mansoura University, from July 2008 to December 2010. FISH technique was carried out in some of cases to more evaluation.RESULTS:The frequency of chromosomal abnormalities was 46 (20.63%) in primary amenorrhea patients. The chromosomal abnormalities can be classified into four main types. (1) The numerical abnormalities of the X chromosome were detected in 23 (50 %). (2) Structural abnormalities of the X chromosome were detected in 11 (23.91%). (3) Mosaicism of X chromosome was found in 10 (21.74%). (4) Male karyotype 46, XY was presented in 2 (4.35%).CONCLUSION:The present study showed that karyotype and FISH are necessary to detect the causes of primary amenorrhea. This study also revealed the incidence of chromosomal abnormalities in women with primary amenorrhea in Egypt is similar to that reported in previous literatures.

Intérêt de la cytogénétique des gamètes humains : résultats et perspectives

In man, the incidence of reproductive failures is high and chromosomal abnormalities remains the major cause of pregnancy wastage. The advent of molecular cytogenetic techniques and assisted reproduction technology have brought forth new approaches for the chromosomal analysis of human oocytes and spermatozoa. The oocyte analyses have evidenced the high rate of chromosomal abnormalities in women and identified premature separation of sister chromatid as a major mechanism in aneuploidy occurrence. High frequencies of aneuploidy have been found in various groups of women, such as patients over 35 or 38 years old, patients with recurrent implantation failures or recurrent miscarriages. The polar body analysis has confirmed the major contribution of premature separation of sister chromatids in aneuploidies and the effect of maternal ageing on its occurrence. In spermatozoa, the efficient adaptation of in situ chromosomal detection techniques has facilitated the segregation analysis of chromosomal abnormalities. Despite the consensus observed in sperm studies of robertsonnian translocations and inversions, new data are required for accurate estimates of imbalances in various types of structural rearrangements. For infertile patients with normal karyotypes, there is significant increase in aneuploidy frequencies, which can be extremely elevated in some groups of subjects, such as patients with large headed spermatozoa syndrome.

Second‐trimester prenatal screening for trisomy 21 using biochemical markers: a 7‐year experience in one cytogenetic laboratory

Screening for trisomy 21 in the second trimester of pregnancy using biochemical markers is an established part of prenatal care in many developed countries. The present study was aimed at determining the incidence of trisomy 21 and other chromosomal abnormalities in women undergoing prenatal chromosome analysis after a second-trimester biochemical screening. A total of 2832 karyotypes were analyzed following a positive second-trimester maternal serum screening (risk > or = 1/250) between 1998 and 2004. Thirty-nine cases of trisomy 21 and 40 other chromosomal abnormalities were detected. The positive predictive value was 1 in 73 karyotypes for trisomy 21 and 1 in 71 for the other chromosomal abnormalities. However, a temporal decline in the detection rate of trisomy 21 was noted, from 1/63 in 1998 to 1/221 in 2004. This change was attributable to an increasing number of pregnant women having first-trimester ultrasound nuchal translucency measurement. Given the fact that nuchal translucency measurement combined with first-trimester biochemical marker screening has a positive predictive value of trisomy 21 comparable to that obtained following second-trimester biochemical screening, we should question whether to move trisomy 21 screening by maternal serum markers from the second trimester to the first trimester in conjunction with nuchal translucency measurement. Furthermore, genetic counseling prior to the amniocentesis should discuss the relatively high probability that a chromosomal abnormality other than trisomy 21 may be identified.