Chromosomal aberrations in 2000 couples of Indian ethnicity with reproductive failure

Constitutional chromosomal aberrations contribute to infertility and repeated miscarriage leading to reproductive failure in couples. These aberrations may show no obvious clinical manifestations and remain undetected across multiple generations. However, infertility or recurrent spontaneous pregnancy loss, and/or genotypic/phenotypic aberrations may be manifested in the progeny during gametogenesis. The current study was a retrospective analysis to examine the chromosomal aberrations and prevalence in 2000 couples of Indian ethnicity with reproductive failure. Cytogenetic analysis via conventional G-band karyotyping analysis was carried out on phytohaemagglutinin stimulated peripheral blood lymphocytes, cultured in RPMI1640 medium. The chromosomes were enumerated as per International System for Human Cytogenetic Nomenclature at 500–550 band resolution, and recorded in the screening sheets. Chromosomal aberrations were detected in a total of 110 (2.78%) couples, with structural chromosomal aberrations in 88 cases including reciprocal translocations in 56 cases, Robertsonian translocations in 16 cases, inversions in eight cases, deletions in three cases, derivative chromosomes in five cases and numerical chromosome aberrations in 23 cases. The study emphasizes the importance of cytogenetic work up in both the partners associated with a history of reproductive failure. Genetic counselling with an option of prenatal diagnosis should be offered to couples with chromosomal aberrations.Alteration in the number or structure of chromosomes is associated with adverse obstetric outcome in the form of infertility or recurrent miscarriages. Most of these aberrations are balanced and hence, the person does not manifest any obvious clinical signs and symptoms. However, because of the formation of abnormal gametes (i.e. the eggs and sperm), these chromosomal aberrations result in infertility and recurrent spontaneous pregnancy losses. In the present study, we studied 2000 couples of Indian ethnicity with reproductive failure. Karyotyping was done on the blood sample of these couples using standard protocols. Chromosomal aberrations were detected in a total of 110 (2.78%) couples with structural chromosomal aberrations in 88 cases including reciprocal translocations in 56 cases, Robertsonian translocations in 16 cases, inversions in eight cases, deletions in three cases, derivative chromosomes in five cases and numerical chromosome aberrations in 23 cases. Thus, our study emphasizes the importance of cytogenetic work up in both the associated partners with history of reproductive failure which would help in better patient counselling and management.     

An evaluation of cytogenetic analysis as a primary tool in the assessment of recurrent pregnancy wastage.

Cytogenetic evaluation of couples with recurrent pregnancy wastage is frequently performed only after other possible etiologic factors have been excluded. Previous reports of studies using conventional and G-banding chromosome techniques in these couples have shown a higher frequency of translocations than that found in the general population. In the study reported here, both conventional and G-banded chromosome analyses were performed as a primary method of evaluation in 34 couples with recurrent fetal loss not ascertained by the birth of a child with a diagnosed chromosome disorder. Balanced translocations were found in 5 partners of the 34 couples studied. In only 2 of these cases was the translocation detected by conventional chromosome analysis. These results suggest that G-banded chromosome analysis should be a useful tool in the initial evaluation of couples with recurrent fetal wastage, rather than being recommended only after extensive investigation of other factors is unrewarding. The reproductive counseling of couples with a translocation detected on this basis is discussed.     

Cytogenetic findings in fifty-five couples with recurrent fetal wastage

Balanced chromosomal translocations in parents and Müllerian abnormalities constitute defined causes of reproductive wastage. Fifty-nine couples with histories of recurrent abortion with or without fetal malformations were evaluated with cytogenetic studies and gynecography. In 44 of the couples with pure abortion histories of two or more spontaneous abortions, three (6.8%) balanced carrier parents were identified. In 11 couples with a mixed history of abortion plus fetal malformation, 3 (27.3%) had balanced translocations in one of the parents. The over-all incidence of Müllerian abnormalities in the group of 59 patients was 11.9%.     

Cytogenetic investigations in couples with repeated miscarriages and malformed children: report of a novel insertion

Recurrent miscarriage and the birth of a malformed child continue to be challenging problems for the patient and clinician. Often, cytogenetic studies have an important role in the evaluation of couples with a poor obstetric history. The present study deals with analysis of chromosome abnormalities in 2150 couples from India, and is the largest group ever reported in the literature. The observed incidence of chromosomal rearrangements in these couples was 3.5%. Apart from reciprocal, Robertsonian, inversions, a unique case of chromosome insertion was identified, which is perhaps only the second report in literature. Minor chromosome variants such as inv(9),inv(Y),9qh+, D/G variants were observed in 108 subjects. Cytogenetic studies should be performed for all couples with repeated miscarriages and bad obstetric history, and in cases of detected chromosomal aberration, the patient should be counselled individually according to the type of anomaly.     

Cytogenetics of recurrent abortions

Chromosome banding studies were carried out on both partners of 37 couples who had had two or more spontaneous abortions. Three patients had chromosome disorders; one was a triple-X female and the other two (one male and one female) were t(13;14) translocation carriers. Review of the literature indicates that the over-all frequency of major chromosome disorders in couples with repeated abortions is 2.6%. About three-fourths of these disorders are reciprocal and Robersonian translocations.     

Statistical analysis of possible causes of repeated spontaneous abortions]

The possible causes of early pregnancy failure in one thousand, three hundred and seventeen women (n = 1,317) with a history of repeated reproductive wastage were analysed and the results of treatment for each etiology were evaluated. Out of 1,200 hysterosalpingographies, 188 (15.7%) congenital uterine anomalies were detected and the degree of each uterine cavity deformity was evaluated by the X/M ratio. Metroplasty was performed on 71 women with no other causes of spontaneous abortion, and more than 84% of the post-operative pregnancy were successfully maintained. One hundred and four (n = 104, 5.5%) out of 949 couples with a high incidence of reproductive failure had either a chromosomal abnormality or normal variants in the wife and/or husband. Twelve cases (n = 12, 8.1%) had a positive analysis for anticardiolipin antibody among 148 women examined. Immunotherapy utilizing the husband's lymphocytes was indicated for four hundred and seventy three (n = 473) other couples with no other abnormalities likely to induce spontaneous abortions. This treatment brought approximately 80% of pregnancies to successful termination and 199 deliveries were recorded with this immunotherapy. The present study suggests that the causes of early pregnancy failure are complex, but that most of the causes of repetitive wastage are curable after exact diagnosis and appropriate treatment.     

Survey of 1120 Japanese women with a history of recurrent spontaneous abortions.

Our recent 7-year clinical survey showed that among the 1120 women with repeated spontaneous abortions registered in this clinic, 2898 out of a total of 3216 pregnancies (90.1%) had terminated in spontaneous abortion. Among these wastages, 84.2% occurred before 12 weeks of gestation, and 11.1 percent occurred between 12 and 15 weeks. Through routine examination of reproductive wastage, 82 (9.9%) of the 825 Japanese couples examined were shown to have either a chromosomal abnormality or normal variants in the wife and/or husband, thus demonstrating no racial difference in the incidence of chromosomal abnormalities in infertile patients in comparison with studies performed in other countries. One hundred and forty-seven congenital uterine anomalies (14.7%) were found in 1000 hysterosalpingographies, and 12 of 148 examined females were positive for anti-cardiolipin antibody. 393 other females with no major abnormalities likely to induce spontaneous abortions were indicated for immunotherapy. Ample time spent on genetic counseling prevented further reproductive wastage, and ideal metroplasty resulted in a successful post-operative pregnancy course in more than 85% of cases. Immunosuppressant and anticoagulant therapy decreased the serum titer of anti-cardiolipin antibody, enabling pregnancies to be maintained to term. Immunotherapy utilizing the husband's lymphocytes also brought more than 80% of pregnancies to successful completion, with 200 deliveries achieved with this therapy. In contrast, 64.1% of pregnancies again terminated spontaneously in patients who were indicated for immunotherapy but did not receive treatment. The findings of the present study suggest that the causes of reproductive wastage, especially the etiology of early recurrent spontaneous abortion, are complex.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prenatally diagnosed balanced chromosome rearrangements: eight years' experience

OBJECTIVE: To investigate the incidence and pregnancy outcome of prenatally diagnosed balanced chromosome rearrangements from amniocentesis. STUDY DESIGN: Between January 1996 and December 2003, we collected cases with balanced chromosome rearrangements from amniocentesis specimens submitted to our cytogenetics laboratory for fetal karyotyping. Data on maternal age, indication for amniocentesis, detailed anatomic sonographic findings, gestational age at delivery, newborn birth weight and infant anomalies, if any, were obtained by chart review. RESULTS: A total of 66 cases of balanced chromosomal translocations or inversions were identified from the 12,468 amniocentesis specimens. Specifically, 0.256% had a reciprocal translocation, 0.080% had a Robertsonian translocation, and 0.192% had an inversion. The incidences of de novo reciprocal translocations, Robertsonian translocations and inversions were 0.080%, 0.016% and 0.024%, respectively. Abnormal prenatal sonographic findings occurred in 2 cases, 1 in an inherited case and 1 in a de novo case. Abnormal postnatal findings occurred in 5 cases, 3 in inherited cases and 2 in de novo cases. Excluding the cases with minor congenital anomalies, the major congenital anomaly rates of inherited and de novo chromosome rearrangements were 1.96% and 6.66%, respectively. CONCLUSION: The incidences of prenatally diagnosed de novo reciprocal translocations, de novo Robertsonian translocations and de novo inversions were higher than those reported in previous, larger series. The major congenital anomaly rates for inherited and de novo chromosome rearrangements were higher than the 1.4% congenital anomaly rate in our general population. Consequently, detailed ultrasound examination and parental karyotyping should be viewed as essential measures in dealing with prenatally diagnosed balanced chromosome rearrangements.     

Cytogenetic investigation in 413 couples with spontaneous abortions.

413 couples with one or more spontaneous miscarriages were karyotyped. Observed chromosomal rearrangements were classified as major rearrangements, i.e. Robertsonian and reciprocal translocations, pericentric and paracentric inversions, supernumerary small metacentrics, and minor rearrangements, i.e. pericentric inversions of chromosome 9, and constitutional fragility of particular chromosome sites. 2.30% of the individuals were carriers of a major rearrangement, which represents a ten-fold increase when compared to the general population. The contribution of each type of rearrangement is unequal, the most important being pericentric inversions (36 times more frequent than in the general population). Contrary to data from the literature, the probability of finding a rearrangement does not seem to increase with the number of miscarriages.     

Cytogenetic study in 50 couples with recurrent abortions

The presence of chromosome abnormalities in couples with repeated spontaneous abortion is known even if the phenomenon is far from a complete assessment. A cytogenetic investigation in 50 couples with a history of two or more spontaneous abortions is referred to in this study. A peripheral blood lymphocyte culture was harvested for each subject and the slides were stained by G- and C-banding. Of the 100 individuals examined, 4 were carriers of balanced translocations, 3 of which were of the Robertsonian type. A chromosomal fragility (chromatidic and/or chromosomic gaps) was seen in 2 cases. The incidence of balanced translocations found here is 8% which is near to the mode (about 9%) observed in previous studies. Those frequencies are greater than in the general population (0.1-0.4%). This indicates that balanced translocations have some importance in causing abortion while this is not the case for other chromosomal abnormalities (e.g. pericentric inversions). Thus, cytogenetic analyses should be recommended in couples with repeated spontaneous abortions, when clinical data fail to clarify the cause.     

Cytogenetic studies in patients with reproductive failure

BACKGROUND: Cytogenetic studies in patients with reproductive failure AIM: To investigate the contribution of chromosomal abnormalities in sub fertility and in couples with repeated abortions. METHODS: Hundred and 13 couples who had at least two or more spontaneous abortions and 65 women and 63 men with infertility were analyzed cytogenetically. RESULTS: Major chromosomal rearrangements were found in 8% and minor variants in 6% in the study population. Major chromosomal aberrations were judged to explain 4.9% of recurrent abortions and 13% of infertility. Chromosomal abnormalities in infertile men occurred in 5% and in infertile women in 21.5%. The chromosomal abnormalities were structural (57%), numerical (18%) or mosaics (25%). CONCLUSIONS: Chromosomal aberrations in recurrent abortions are mostly structural ones and those in female infertility mosaicism of sex chromosomes. Turner's syndrome, Turner variants and XY females are detected as a cause of female infertility. The structural and numerical aberrations of either sex or autosomal chromosomes were found in infertile men.     

Chromosome abnormalities in 118 couples with recurrent spontaneous abortions

Cytogenetic studies were carried out on 118 couples with recurrent spontaneous abortions. Four major chromosomal abnormalities were found including two 13/14 Robertsonian translocations, one t(7;12) and one t(1;10) reciprocal translocation. The incidence of chromosomal abnormalities in this study was 3.39%, which is lower than the mean value of the published data. The clinical significance of balanced translocations in recurrent reproductive loss is discussed.     

Cytogenetic studies in couples with repeated spontaneous abortions

Chromosome studies were carried out on both partners of 509 couples with a history of two or more spontaneous abortions. 1) Twenty-six individuals (2.6%) were carriers of a major chromosome abnormality. This incidence is at least six to seven times higher than that in the general adult population. 2) Of these, 10 were reciprocal translocations, 10 robertsonian translocations and 6 numerical aberrations of gonosomes. None of the carriers showed abnormal phenotypes. 3) Chromosome aberrations were more frequent in the women than in their husbands. There were 19 abnormalities in females and 7 in males. 4) The use of banding techniques in chromosome analysis improves the detection of balanced reciprocal translocations. 5) Prenatal diagnosis was performed in 5 subsequent pregnancies of 4 balanced translocation carriers. The fetal karyotypes were 2 normal and 3 balanced translocations. It would seem reasonable to recommend chromosome analysis for couples with repeated spontaneous abortions.     

Etiologies and subsequent reproductive performance of 100 couples with recurrent abortion.

From 1958 through 1977, 100 couples with documented recurrent reproductive failure were evaluated in the reproductive endocrine unit of the Medical College of Georgia. All couples underwent cytogenetic studies, radiologic evaluation of the Müllerian system, and timed endometrial biopsy. Recurrent pregnancy wastage was found to be associated with genetic disorders in 25 couples. Müllerian anomalies in 15, endocrine anomalies in 23, and negative findings in 37. The subsequent reproductive performance of each group is reviewed.     

309对早期自然流产夫妇的染色体分析——附4例世界首报核型

目的 :分析早期自然流产与染色体异常核型的关系。方法 :检测 30 9对早期自然流产夫妇双方的外周血淋巴细胞染色体核型。结果 :早期自然流产夫妇中异常核型检出率明显高于普通人群 ,总检出率为 6 .95 %。染色体异常 2 0例 :其中平衡易位 18例 (4例为世界首报核型 ) ,增加额外小染色体 2例 ;染色体异态 2 3例 :9号染色体臂间倒位 7例 ,D、G组随体变异 2例 ,9、16号次缢痕异染色质区变异 2例 ,Y染色体异态 12例。结论 :染色体异常和异态是导致早期自然流产的重要原因之一 ,对早期自然流产夫妇进行染色体检查是必要的 ,可以寻找流产原因 ,为优生优育提供依据     

Chromosome study of couples with repeated spontaneous abortions

The incidence of chromosomal abnormalities was evaluated in couples with a history of repeated abortions. The study included 14 couples with a history of 2 or more spontaneous abortions. Chromosome analysis was carried out on both marital partners from peripheral lymphocyte cultures. In every case, 30-62 metaphases were counted, and at last 20 karyotyped. Among the 14 couples, chromosome anomaly was found in 1 of the partners in 1 case. The patient, a 29-year-old female, was admitted to the hospital in the 36th week of her 10th pregnancy. In addition to an induced abortion and a premature delivery, her history included 7 spontaneous abortions at the 1st or 2nd month. Chromosome analysis of her peripheral blood revealed neither numerical nor structural aberations. In the 38th week, the patient gave birth ato a 3990 gm healthy boy whose karyotype of the cord blood also proved to be normal. The karyotype of the patient's husband revealed 45 chromosomes in 32 observed cells, and a chromosome was missing from each of the D and G groups. It was not possible to include in any of the groups a medium-sized, subterminal chromosome, diagnosed as D/G translocation. The husband proved to be a balanced D/G translocation carrier. When the pedigree was prepared, it was found that the younger sister of the husband had given birth to a child 1 month before term. Both the sister and her child were studied. The sister proved to be a balanced D/G translocation carrier. The child had translocational Down's syndrome: the D/G translocation occured in an unbalanced form. A table lists the results of chromosome investigations of cases of repeated abortions. Of 1066 married partners, chromosome aberations or variations responsible for multiple abortions were found in 70 (6.5%). Of these, 26 proved to be translocations. This incidence, 2-4%, is higher than the .4% in the general population. The results add credence to the argument that chromosome aberation may play a role in the causal background of recurring abortions. It is possible that with special staining procedures some aberations can be demonstrated in cases hitherto considered normal. In cases of repeated abortion, cytogenetic examination of both partners is routinely justified. In cases of chromosome aberations valuable data can be gained to serve as a basis for genetic counseling. When examining women with recurrent abortions, it should be possible to select patients to whom the possibility of intrauterine cytogenetic diagnosis can be offered.     

Role of chromosome heteromorphism in early recurrent miscarriages in the Middle East.

To identify the role of chromosome polymorphism in miscarriages, an analysis was carried out on 774 couples; 391 of them with two or more miscarriages and 383 serving as control. All couples were taken from two separate ethnic groups residing in the United Arab Emirates (UAE): 199 cases and 194 controls came from the indigenous population who are UAE nationals (Arabs) whilst 192 cases and 189 controls came from the Asian expatriate population residing in the UAE (Asians). Out of 391 cases, six Arab and three Asian couples were excluded because at least one partner had a chromosomal aberration. From the control group four Arab and four Asians were excluded for similar reasons. The remaining 757 couples were analysed to detect the presence of chromosomal heteromorphism in one or both partners. The results suggest that chromosomal heteromorphism was significantly increased in the Arab study population (P < 0.05). Two heteromorphisms, 9qh and inversion (9)(p11q13) seem to be marginally related to recurrent miscarriages and only in the Arab study population. No differences were found in the distribution of chromosomal heteromorphism in couples analysed in relation to the number of miscarriages (two or more).     

Results of chromosomal studies in 270 couples with reproductive problems]

Cytogenetic study in couples with recurrent reproductive failure allows the detection of structural chromosome anomalies which don't have a phenotypic effect in carriers, but permit the explanation of the production of genetically unbalanced gametes. We present the investigation performed in 270 couples which demonstrated a chromosomal alteration in 9.2% of them. This allows genetic counselling in respect of the importance of the finding, recurrence risk and reproductive alternatives. In 8.6% we found some cellular lines with aneuploidies in sexual chromosomes, which don't represent a such concrete risk.     

502对反复自然流产夫妇的染色体研究

对反复自然流产２次或２次以上的５０２对夫妇进行外周血培养Ｇ显带染色体核型分析。发现异常核型５２例，占５．１８％；其中平衡易位３８例，占７３．０８％；染色体数目异常５例，占９．６２％；嵌合体８例，占１５．３８％；９号染色体臂间倒位１例，占１．９２％。结果表明，平衡易位携带者是反复自然流产夫妇中最常见的染色体异常，故流产史是检出人群中平衡易位携带者的重要临床指征。     

Intracytoplasmic sperm injection in infertile patients with structural cytogenetic abnormalities.

OBJECTIVE: To investigate the incidence of chromosomal aberration in men and women in an intracytoplasmic sperm injection (ICSI) program for severe male infertility as well as in conceptuses resulting from these ICSI treatments. STUDY DESIGN: We evaluated chromosomal analysis, outcome of ICSI and the conceptuses resulting from treatment of 301 couples included in ICSI program. RESULTS: Cytogenetic evaluation demonstrated structural anomalies in 11 cases (3.6%), 9 men (2.9%) and 2 women (0.7%), all consisting of balanced chromosomal translocations. There were no significant differences in the rates of developed embryos (44.2% versus 40.1%) in couples with abnormal (n = 11) and normal (n = 290) chromosomal analysis. Embryo transfer led to a similar number of newborns (15.3% versus 12.4%) per transferred embryos, without any correlation with parents' chromosomes. In 63 fetuses conceived from couples without chromosomal abnormalities, we observed one fetus affected by Patau syndrome (47,XY, + 13). Two of four (50%) fetuses conceived by couples with male balanced chromosomal defects were carriers of the chromosomal translocation inherited from their fathers. The two fetuses resulted in the birth of two infants observed to be normal at the 12-month pediatric follow-up. CONCLUSION: The offer of this treatment to infertile couples with male factor infertility should be accompanied by proper information regarding the genetic risks of this treatment. ICSI remains a good therapeutic option for infertile patients, but prenatal diagnosis is mandatory because of the potential increased aneusomic risk for the offspring conceived.