Portal de Periódicos da CAPES

Cytogenetic Study in Cases with Recurrent Abortion in Saudi Arabia

2000; King Faisal Specialist Hospital and Research Centre; Volume: 20; Issue: 3-4 Linguagem: Inglês

10.5144/0256-4947.2000.233

0975-4466

M. Hussain, Lulu Al‐Nuaim, Zainab Abu Talib, Osama K. Zaki,

Congenital Anomalies and Fetal Surgery

Original ArticlesCytogenetic Study in Cases with Recurrent Abortion in Saudi Arabia Muneera Al Hussain, MBBS, ABP Lulu Al-Nuaim, MBBS, MRCOG Zainab Abu Talib, and MBBS, MRCOG Osama K. ZakiMBBCh, MS, MD Muneera Al Hussain From the Departments of Pediatrics, Obstetrics & Gynecology, and the Cytogenetic Unit, King Khalid University Hospital and King Saud University, College of Medicine, Riyadh, Saudi Arabia , Lulu Al-Nuaim From the Departments of Pediatrics, Obstetrics & Gynecology, and the Cytogenetic Unit, King Khalid University Hospital and King Saud University, College of Medicine, Riyadh, Saudi Arabia , Zainab Abu Talib From the Departments of Pediatrics, Obstetrics & Gynecology, and the Cytogenetic Unit, King Khalid University Hospital and King Saud University, College of Medicine, Riyadh, Saudi Arabia , and Osama K. Zaki Address reprint requests and correspondence to Dr. Zaki: 8 Kamal Raslan St., Heliopolis, Cairo 11771, Egypt. From the Departments of Pediatrics, Obstetrics & Gynecology, and the Cytogenetic Unit, King Khalid University Hospital and King Saud University, College of Medicine, Riyadh, Saudi Arabia Published Online:1 May 2000https://doi.org/10.5144/0256-4947.2000.233SectionsPDF ToolsAdd to favoritesDownload citationTrack citations ShareShare onFacebookTwitterLinked InRedditEmail AboutAbstractBACKGROUND:A proportion of cases with repeated abortion are caused by chromosomal abnormality in one of the parents. Several studies have been done to determine the role of chromosomal abnormalities in couples with repeated fetal loss in various countries. None of these studies was done in the Arab Peninsula.MATERIAL AND METHODSCytogenetic study was done for 193 consecutive Saudi couples who presented with repeated abortion at the King Khalid University Hospital in Riyadh, Saudi Arabia.RESULTS:We found that the frequency of chromosomal abnormalities was not significantly different from that reported worldwide. The nature of those abnormalities and their relation to the obstetric history of cases were discussed.CONCLUSION:This study should help physicians working in the region to realize the contribution of chromosomal abnormalities to cases of repeated fetal loss. It should also help in setting priorities of cytogenetic screening in individual cases.IntroductionApproximately 15%-20% of clinically recognizable pregnancies end in spontaneous abortion.1,2 The incidence of chromosomal abnormalities in those abortions is as high as 50%.3 A modest but clinically important proportion of spontaneous abortions is caused by a balanced chromosomal aberration in one of the parents.4–8 This results from the production of gametes and embryos with unbalanced chromosome sets.9,10 The clinical consequences of such abnormal gametes include sterility, repeated abortions, and giving birth to malformed children.11,12Several studies have been done in various countries to determine the contribution of chromosome abnormalities in parents with fetal wastage.13 To our knowledge, no such studies have been done in the Arabian Peninsula. The aim of this study was to assess the frequency and nature of chromosomal aberrations that contribute to the occurrence of repeated abortions in Saudi Arabia. This should assist physicians in Saudi Arabia and other neighboring countries by increasing their awareness of the frequency of cytogenetic abnormalities in cases with repeated abortions. It also provides figures for comparison with other countries and research centers.MATERIALS AND METHODSThis study included all Saudi couples with repeated abortions who were referred for cytogenetic studies between December 1994 and December 1998 at King Khalid University Hospital in Riyadh, Saudi Arabia. All cases were ascertained to have had two or more spontaneous abortions. Couples who were referred because of having previous children with congenital anomalies and abortions were not included in the study. The obstetric history of couples was either recorded on the request form or retrieved from the files of patients.For routine cytogenetic analysis, 0.3 mL of peripheral blood was incubated in complete lymphocyte culture medium (10% fetal bovine serum in RPMI 1640, with 0.15% phytohemagglutinin and 1% Penstrept in 5% CO2 incubator at 37°C for three days). Metaphases were harvested by adding colcemid for 20 minutes, followed by hypotonic KCl treatment for 5 minutes and fixation, using standard 3:1 methanol-acetic fixative (all the reagents were from GIBCO Life Technologies Ltd., Paisley, Scotland). The high-resolution study was done by synchronization, using methotrexate (10-7M) for 17 hours, and thymidine (10-5 M) for 5.5 hours before harvesting, as mentioned elsewhere.14Microscopic examination of 15-20 cells and photography of two cells were done after standard trypsin-Wright G-banding (GTW) and/or Quinacrine Q-banding (QFQ). Chromosomes were visually analyzed and abnormalities were detected during microscopy in all cases. Microscopic photography and karyotype were done for documentation in abnormal cases.The correlation between the obstetric history of cases with and without abnormal karyotype was computed using the Spearman test for correlation using the SPSS program.15 The frequencies of chromosomal abnormalities were compared to similar studies using Z-test for comparison of two frequencies with unequal variance.RESULTSA total of 193 Saudi couples with history of repeated abortions were examined. The age of the referred wives ranged from 16 to 50 years, with a mean of 30.31 years (SD=6.78). The number of previous deliveries ranged from 0 to 13 (mean 2.1; SD=2.4511). The number of previous abortions varied from 2 to 16 abortions (mean 4.2 abortions/couple; SD=2.1801).Eleven females (5.7%) and four males (2.07%) were found to have abnormal karyotypes. These abnormalities included 10 balanced reciprocal translocations, one Robertsonian translocation, two inversions and two cases of mosaic X-chromosome monosomy (Table 1). Examples of the encountered chromosomal abnormalities are shown in Figures 1 and 2.Figure 1. Female karyotype showing a small paracentric inversion of chromosome 8:46, XX, inv (8) (p12 p23).Download FigureFigure 2. Male karyotype showing a reciprocal translocation between the short arms of chromosomes 2 and 6:46, XY, t (2; 6) (p13; p21.3).Download FigureTable 1. Cytogenetic findings, parity, number of abortions and maternal age in cases with abnormal karyotype.Table 1. Cytogenetic findings, parity, number of abortions and maternal age in cases with abnormal karyotype.Among cases with abnormal karyotype, the mean maternal age was 28.8 (SD=5.78). The mean number of previous deliveries was 1.4667 deliveries/couple (SD= 2.0307), and the mean number of abortions was 5.73 per couple (SD=2.4631).The Spearman test for correlation showed that older maternal age, the average gestational age at time of abortion, and the number of previous deliveries were not statistically associated with the occurrence of chromosomal aberrations. However, the number of previous abortions showed a significant influence on the possibility of having a chromosomal abnormality (P=0.005).DISCUSSIONSchmidt (1962) was the first to report the results of cytogenetics analysis in patients with a history of two or more spontaneous abortions. This was followed by a series of cytogenetic studies of couples with a history of repeated pregnancy loss.16 The incidence of chromosomal abnormalities among those cases varied in different studies, from none17 to as high as 21.4%.18 The variations in the size of the sample, the criteria used for ascertainment of cases, and the technique of cytogenetic study have contributed to these wide differences between various studies.19 It is also possible that different populations vary in the incidence of carriers of chromosomal aberrations.Several studies have been carried out to determine the prevalence of chromosomal aberrations among couples with repeated fetal loss. This was found to be 5.8%, 5% and 4.7% in three of the largest reviews that were reported by Tharapel et al.,19 Campana et al.20 and Braekeleer and Dao,16 respectively. In this study, we found that the incidence of chromosomal abnormalities among couples with repeated abortions was 7.7% (SD=1.92), which is not significantly different from the global incidence.We found that 11 women and four men had chromosomal abnormalities, which was a ratio of 2.75:1. A similar male to female ratio has been found in most of the reported studies. This predominance of females appears to be due to the fact that chromosomal abnormalities that are compatible with fertility in females may be associated with sterility in males.11,16The structural chromosomal abnormalities that we encountered were divided into balanced reciprocal chromosomal translocations (10/15), Robertsonian translocation (1/15), and inversions (2/15). Table 2 shows that the distribution of structural chromosomal rearrangements in our study is similar to that reported worldwide.Table 2. Structural chromosome rearrangements found in couples with recurrent abortions compared to similar studies.5,22,23Table 2. Structural chromosome rearrangements found in couples with recurrent abortions compared to similar studies.5,22,23Numerical chromosomal aberrations are less frequently encountered among couples with repeated abortions. Those aberrations are usually in the form of sex chromosomal aneuploidy, and they occur in a low frequency (<0.15% of cases).20 We encountered two cases with X-chromosome mosaicism. Reviewing the clinical features in both cases showed that none of them had the features of Turner syndrome. The two cases showed a low level of monosomic cells (Table 1). However, the X monosomy could not be ascribed to a normal background level of monosomic cells, as the level of X-chromosome monosomy in our laboratory never exceeded 0.5% in other groups of referrals. The low level of mosaicism and/or confinement of the aneuploid cell line to genital organs may explain the normal phenotype of both cases.Regarding the relation of the obstetric history to the frequency of chromosomal aberrations, no statistically significant correlation was found between the number of deliveries or gestational age and the occurrence of chromosomal abnormalities. However, a statistically significant correlation was found between the number of previous abortions and the occurrence of chromosomal abnormalities (P=0.005). Thus, in cases of paucity of resources and the need to limit cytogenetics study to a fraction of cases, those with a larger number of abortions should be given priority for screening, even if they had previously normal deliveries.This study has shown that the incidence and distribution of chromosomal abnormalities among Saudi couples with repeated fetal loss is comparable to that reported worldwide. Physicians in charge of clinics for repeated fetal loss should bear in mind that in at least 5% of the couples they examine, chromosomal abnormality is the cause of abortions. Those cases have to be detected as early as possible to arrange for adequate genetic counseling and to allow parents to make an informed reproductive decision regarding subsequent pregnancies.Cytogenetics studies should be offered to all couples with more than two spontaneous abortions. However, in cases where cytogenetic studies are not freely available, priority should be given to cases with larger numbers of abortions.ARTICLE REFERENCES:1. French FE, Bierman JM. "Probabilities of fetal mortality" . Publ Hlth Rep. 1967; 77:835–47. Google Scholar2. Dejmek J, Vojtassak J, Malova J. "Cytogenetic analysis of 1508 spontaneous abortions originating from South Slovakia" . Eur J Obstet Gynecol Reprod Biol. 1992; 46:129–36. Google Scholar3. Boue A, Boue J, Gropp A. Cytogenetics in pregnancy wastage. In: Harris H, Hirschhorn K, editors. Advances in human genetics. New York: Plenum Press, 1985; 14:1–57. Google Scholar4. Heritage DW, English EC, Young RB, Chen ATL. "Cytogenetics of recurrent abortions" . Fertil Steril. 1978; 29:414–7. Google Scholar5. Boue A, Boue J. Chromosome structural rearrangements and reproductive failure. In: Bennett MD, Bobrow M, Mewitt CM, editors. Chromosomes today. London: Allen and Unwin, 1981; 7:282–90. Google Scholar6. Husslein P, Huber J, Wagnbichler P, Schnedl W. "Chromosome abnormalities in 150 couples with spontaneous abortions" . Fertil Steril. 1982; 37:379–83. Google Scholar7. Schwartz S, Palmer CG. "Chromosomal findings in 164 couples with repeated spontaneous abortions: with special consideration to prior reproductive history" . Hum Genet.. 1983; 63:28–34. Google Scholar8. Wolstenholme J, Faed MJW, Robertson J, Lamont MA. "Chromosome abnormality in couples with histories of multiple abortions. The outcome of pregnancies subsequent to ascertainment and a study of familial translocation carrier" . Hum Genet. 1983; 63:45–7. Google Scholar9. Lindenbaum RH, Bobrow M. "Reciprocal translocations in man: 3:1 meiotic disjunction resulting in 47-45 chromosome offspring" . Med Genet. 1975; 12:29–43. Google Scholar10. Stene J, Stengel-Rutkowski S. "Genetic risks for familial reciprocal translocations with special emphasis on those leading to 9p, 10p, 12p, trisomies" . Ann Hum Genet. 1982; 46:41–7. Google Scholar11. Chandley AC, Edmond P, Christie S, Gowans L, Fletcher J, Frackievicz A, et al. "Cytogenetics and infertility in man. I: karyotype and seminal analysis: results of a five-year survey of men attending a subfertility clinic" . Ann Hum Genet. 1975; 39:231–54. Google Scholar12. Neri G, Serra A, Campana M, Tedeschi B. "Reproductive risks for translocations: cytogenetic study and analysis of pregnancy outcome in 58 families" . Am J Med Genet. 1983; 16:535–61. Google Scholar13. Campana M, Serra A, Neri G. "Role of chromosome aberrations in recurrent abortion: a study of 269 balanced translocations" . Am J Med Genet. 1986; 24:341–65. Google Scholar14. Yunis JJ. "High resolution of human chromosomes" . Science. 1976; 191:1268–70. Google Scholar15. Norusis MJ. SPSS/PC Advanced statistics 4.0 for the IBM PC/XT/ZT and PS/2. Chicago: SPSS Inc., 1990. Google Scholar16. Braekeleer MD, Dao TN. "Cytogenetic studies in couples experiencing repeated pregnancy losses" . Hum Reprod. 1990; 5:519–28. Google Scholar17. Rowley PT, Marshall R, Ellis JRA. "Genetic and cytological study of repeated spontaneous abortion" . Ann Hum Genet. 1963; 27:78–100. Google Scholar18. Khudr G. "Cytogenetics of habitual abortion: a review" . Obstet Gynecol Surv. 1974; 29:299–310. Google Scholar19. Tharapel AT, Tharapel SA, Bannerman RM. "Recurrent pregnancy losses and parental chromosome abnormalities: a review" . Br J Obstet Gynecol. 1985; 92:899–914. Google Scholar20. Campana M, Serra A, Neri G. "Role of chromosome aberrations in recurrent abortion: a study of 269 balanced translocations" . Am J Med Genet. 1986; 24:341–56. Google Scholar21. Hamamah S, Fingnon A, Lansac J. "The effect of male factors in repeated spontaneous abortion: lesson from in vitro fertilization and intracytoplasmic sperm injection" . Hum Reprod Update. 1997; 3:393–400. Google Scholar22. Butler M, Hamill T. "Blood specimens from patients referred for cytogenetic analysis: Vanderbilt University Experience" . South Med J. 1995; 88:309–14. Google Scholar23. Chandley AC. Infertility and recurrent abortions. In: Emery A, Rimoin D, editors. Principles and practice of medical genetics. London: Churchill Livingstone, 1990;313–9. Google Scholar Previous article Next article FiguresReferencesRelatedDetails Volume 20, Issue 3-4May-July 2000 Metrics History Received1 August 1999Published online1 May 2000Accepted3 June 2000 KeywordsCytogeneticsabortionschromosomal aberrationsACKNOWLEDGEMENTSWe would like to thank Mr. Mohamed Seraj and Mr. Joseph Nestor Beleno for their kind help in the Cytogenetics Unit.InformationCopyright © 2000, Annals of Saudi MedicinePDF download