Chromosomal abnormalities in recurrent miscarriages by conventional karyotyping analysis

Marqui, Alessandra Bernadete Trovó de

doi:10.1590/1806-93042018000200002

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Revista Brasileira de Saúde Materno Infantil

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REVIEW • Rev. Bras. Saude Mater. Infant. 18 (2) • Apr-Jun 2018 • https://doi.org/10.1590/1806-93042018000200002 copy

Chromosomal abnormalities in recurrent miscarriages by conventional karyotyping analysis

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objectives:

to describe the prevalence and types of chromosomal abnormalities in couples with recurrent miscarriage and products of conception.

Methods:

electronic searches were performed in the PubMed/Medline database and in the Portal Regional da Biblioteca Virtual em Saúde/BVS (Regional Website of the Virtual Library in Health/BVS) using the descriptors “chromosomal abnormalities and abortions and prevalence”. After applying the inclusion and exclusion criterias, 17 studies were selected.

Results:

11 studies were conducted in couples with recurrent miscarriage and six in products of conception. The main results of the couples with recurrent miscarriage were: the frequency of chromosomal abnormalities which varied from 1.23% to 12% and there was a predominance alteration of the chromosomal structures (reciprocal translocations, followed by Robertsonian). In products of conception, the results observed were: the frequency of chromosomal abnormality was above 50% in approximately 70% of the studies; there was a predominance alteration of the numerical chromosomal (trisomy - chromosomes 16, 18, 21 and 22, followed by polyploidy and monosomy X).

Conclusions:

in summary, cytogenetic alterations represent an importante cause of pregnancy loss and its detection can help couples with genetic counseling. Therefore, the value of knowledge on the prevalence of cytogenetic abnormalities in miscarriage samples is unquestionable, once it is permitted a proper genetic counseling for the couple.

Key words
Miscarriage; Chromosome abnormalities; Cytogenetics; Genetic translocation; Genetic counseling

Study	Sample	Types of chromosomal abnormalities	Prevalence
Ozawa et al.¹⁷17 Ozawa N, Maruyama T, Nagashima T, Ono M, Arase T, Ishimoto H, Yoshimura Y. Pregnancy outcomes of reciprocal translocation carriers who have a history of repeated pregnancy loss. Fertil Steril. 2008; 90 (4): 1301-4.	2324 couples had a history of two or more consecutive pregnancy loss	chromosome abnormalities: 114 couples 3.18% (74) reciprocal translocations, 0.99% (23) Robertsonian translocations (17 women, 0.73% and 6 men 0.26%), 0.43% (10) inversions and 0.39% (9) others 14 couples with normal variants (0.6%) and 81 with pericentric inversion 9 (3.49%)	4.91%
Kiss et al.¹⁸18 Kiss A, Rosa RF, Dibi RP, Zen PR, Pfeil JN, Graziadio C, Paskulin GA. Chromosomal abnormalities in couples with history of recurrent abortion. Rev Bras Ginecol Obstet. 2009; 31 (2): 68-74.	108 couples with history of two or more RMs	chromosome abnormalities: 10 cases (5 women and 5 men) woman-man ratio 1:1 chromosomal analysis (normal results): 46,XX (n=100) and 46,XY (n=103) 5 structural alterations (30% of reciprocal translocation, 20% of Robertsonian translocation, 10% of chromosome inversion) and 5 numerical alterations (50% of mosaicism - sexual chromosomes) in one of the couples, the woman presented two concomitant alterations 3 polymorphisms (1.4%)	9.3%
Pal et al.¹⁹19 Pal S, Ma SO, Norhasimah M, Suhaida MA, Siti Mariam I, Ankathil R, Zilfalil BA. Chromosomal abnormalities and reproductive outcome in Malaysian couples with miscarriages. Singapore Med J. 2009; 50 (10): 1008-12.	56 couples who had two or more miscarriages	five couples - chromosomal abnormality in one partner 4 cases - structural alterations (60% reciprocal translocations - women and 20% Robertsonian D/D translocations - men) 1 case - numerical abnormality (20% mosaic of Down syndrome - men) 60% (n=3) occurred in women and 40% (n=2) in men woman-man ratio 1.5:1	8.9%
Dutta et al.²⁰20 Dutta UR, Rajitha P, Pidugu VK, Dalal AB. Cytogenetic abnormalities in 1162 couples with recurrent miscarriages in southern region of India: report and review. J Assist Reprod Genet. 2011; 28 (2): 145-9.	1162 couples with recurrent miscarriages	chromosomal anomalies: 78 cases 1.41% (33) structural abnormalities [more frequent: 21 cases of balanced reciprocal translocations and 6 cases of Robertsonian translocations) -women (18 cases) and men (9 cases)] 1.89% (44) polymorphic variants (chromosome 9) 0.05% (1) numerical anomaly (mosaic XY/XXY)	3.35%
Niroumanesh et al.²¹21 Niroumanesh S, Mehdipour P, Farajpour A, Darvish S. A cytogenetic study of couples with repeated spontaneous abortions. Ann Saudi Med. 2011; 31 (1): 77-9.	100 couples with two or more miscarriages	chromosome abnormalities: 13 cases chromosomal abnormalities: 8% women and 5% men woman-man ratio 1.6/1 4 (30.8%) balanced reciprocal translocations 3 (23%) Robertsonian translocations (D and G groups) 3 (23%) pericentric inversions (chromosomes 7 and 9) 1 (7.7%) paracentric inversion (chromosome 16) 1 (7.7%) chromosomal marker 1 (7.7%) polymorphism 9qh+ (woman who had a history of eight miscarriages and one live birth) inv(9) - one couple with a similar chromosomal abnormality	12%
Saxena et al.²²22 Gada Saxena S, Desai K, Shewale L, Ranjan P, Saranath D. Chromosomal aberrations in 2000 couples of Indian ethnicity with reproductive failure. Reprod Biomed Online. 2012; 25 (2): 209-18.	955 couples with recurrent pregnancy loss	chromosomal abnormalities: 49 cases 63.3% (31) reciprocal translocations (18 women and 13 men), 20.4% (10) Robertsonian translocations (7 women and 3 men), 10.2% (5) inversions, 2.04% (1) derivative chromosome, 2.04% (1) aneuploidy sexual chromosome, 2.04% (1) marker chromosome	1.23%
Gonsalves et al.²³23 Gonçalves RO, Santos WV, Sarno M, Cerqueira BA, Gonçalves MS, Costa OL. Chromosomal abnormalities in couples with recurrent first trimester abortions. Rev Bras Ginecol Obstet. 2014; 36 (3): 113-7.	151 women and 94 partners (couples with two or more recur-ren t first trimester miscarriages)	chromosome abnormalities: 13 cases (11 women and 2 partners) women: 4.7% X-chromosome mosaicism (n=7), 2% reciprocal translocations (n=3) and 0.6% Robertsonian translocations (n=1) men: 1% X-chromosome mosaicism (n=1) and 1% inversions (n=1) 3.65% structural alterations (n=5) and 5.75% numerical alterations (n=8) normal variations in the chromosomes structure: 4.6% (women, n=7) and 6.4% (men, n=6), more frequent: 9qh+ (9 cases)	7.3% (woman) 2.1% (man)
Karatas et al.²⁴24 Karatas A, Eroz R, Albayrak M, Ozlu T, Cakmak B, Keskin F. Evaluation of chromosomal abnormalities and common trombophilic mutations in cases with recurrent miscarriage. Afr Health Sci. 2014; 14 (1): 216-22.	142 couples with recurrent miscarriage (≥2 pregnancy loss that occurred before the 20th gestational week)	chromosome abnormalities: 33 cases (14 women and 19 men) woman-man ratio 0.7:1 chromosomal analysis (normal results): 46,XX (n=128) and 46,XY (n=123) women: 9 polymorphisms (64.3%), 3 translocations (21.4%) and 2 trisomy X (14.3%) men: 19 polymorphisms (100%) 28 polymorphisms: more frequent 1qh+ (n=9), 9qh+ (n=4) and 16qh+ (n=3)	9.86% (woman) 13.4% (man)
Ghazaey et al.¹⁶16 Ghazaey S, Keify F, Mirzaei F, Maleki M, Tootian S, Ahadian M, Abbaszadegan MR. Chromosomal analysis of couples with repeated spontaneous abortions in north-eastern iran. Int J Fertil Steril. 2015; 9 (1): 47-54.	728 couples with history of miscarriages ranging from 1-7	chromosomal abnormalities: 85 (48 women and 37 men) woman-man ratio 1.3:1 43.5% (37) reciprocal translocations (24 women and 13 men) 9.4% (8) Robertsonian translocations (4 women and 4 men) 8.3% (7) inversions 8.3% (7) numerical abnormalities 52 structural and 7 numerical abnormalities 30.5% (26) polymorphic variants	11.7%
Fan et al.²⁵25 Fan HT, Zhang M, Zhan P, Yang X, Tian WJ, Li RW. Structural chromosomal abnormalities in couples in cases of recurrent spontaneous abortions in Jilin Province, China. Genet Mol Res. 2016; 15(1).	1948 couples with two or more recurrent miscarriages	chromosomal abnormalities: 58 cases (20 men - 34.5% and 38 women -65.5%) women-men carriers ratio - approximately 2:1 types of structural chromosomal alterations: 72.4% (n=42) reciprocal translocations, 19% (n=11) Robertsonian translocations and 8.6% (n=5) pericentric inversions 42 reciprocal translocations (15 men - 35.7% and 27 women - 64.3% 11 Robertsonian translocations (3 men - 27.3% and 8 women - 72.3%) 5 inversions (2 men - 40% and 3 women - 60%)	2.98% (structural chromosomal alterations) (1.95% woman and 1.03% man)
Sudhir et al.²⁶26 Sudhir N, Kaur T, Beri A, Kaur A. Cytogenetic analysis in couples with recurrent miscarriages: a retrospective study from Punjab, north India. J Genet. 2016; 95 (4): 887-94.	440 couples with at least two consecutive miscarriages	chromosomal abnormalities: 15 cases 53.3% (8) reciprocal translocations, 6.7% (1) Robertsonian translocation, 20% (3) duplications and inversion and 20% (3) polymorphic variants percentage of cases carrying translocations: 78% men and 22% women (man: woman ratio 1.5:1)	3.41%

Study	Sample	Types of chromosomal abnormalities	Prevalence
Teixeira et al.¹¹11 Teixeira ACZ, Oliveira ARCP de, Pereira TM, Jesus NA de, Rodrigues MG, Salvador R, Agostinho MA de B, Rodini ESO. Estudo citogenético de abortos espontâneos. Arq Ciênc Saúde. 2009; 16 (2): 59-61.	574 miscarriage materials and	Miscarriages 211 (36.76%) - no results 250 (43.55%) - normal karyotype 113 (19.69%) - abnormal karyotype [80 aneuploidias (monosomy X and trisomy 16), 23 euploidies and 10 structural alterations]	19.7% -miscarriages
	197 couples with RMs	Couples 15 (7.6%) - structural alterations in one of the partners (inversion of chromosome 9 and balanced translocations)	7.6% - couples
Rolnik et al.¹²12 Rolnik DL, Carvalho MHB, Catelani ALPM, Pinto APAR, Lira JBG, Kusagari NK, Belline P, Chauffaille M de L. Análise citogenética em material de abortamento espontâneo. Rev Assoc Med Bras. 2010; 56 (6): 681-3.	428 miscarriage materials (up to 12 weeks)	46 (10.7%) - there was no cell growth 145 (33.9%) - normal results 237 (55.4%) - abnormal results - more frequent: numerical abnormalities -trisomy 16 (17.3%), triploidy (11.3%), monosomy X (10.9%), tetraploidy (5.4%) and trisomy 15 (5.4%)	55.4%
Lopez et al.²⁷27 López AGA, Huerta SB, Gálvan RH, Posadas RA, del Ángel AG, González PG. Diagnóstico citogenético en aborto espontáneo del primer trimestre. Ginecol Obstet Mex. 2011; 79 (12): 779-84.	120 miscarriage materials	46% (55/120) - normal karyotypes 54% (65/120) - abnormal karyotypes 52.3% (34) trisomy (32.3% - trisomy 1 6, 23.4% trisomy 22, 11.7% - trisomy 18, 8.8% - trisomy 13 and 5.8% - trisomy 21) 24.6% (16) polyploidy (50% - 69,XXX and 37.5% - 69,XXY) 13.9% (9) monosomy (45,X) 9.2% (6) mosaics	54%
Salazar et al.²⁸28 Salazar A, Álamos C, Arriagada M, Selman E. Estudio Citogenético en 677 casos de aborto espontáneo. Revista Anacem. 2011; 5 (2): 74-7.	677 samples of the miscarriage tissues	38.3% (259/677) - normal karyotypes (158 - 46,XX and 101 - 46,XY) 61.7% (418/677) - abnormal karyotypes 63.4% (265) trisomies (34.4% - trisomy 16, 13.6% - trisomy 21 and 12.8% -trisomy 22) 19.8% (83) polyploidy 11.5% (48) monosomy (46 - monosomy X) 5.3% (22) structural abnormalities	61.7%
Boue et al.²⁹29 Boué J, Boué A, Lazar P. Retrospective and prospective epidemiological studies of 1500 karyotyped spontaneous human abortions. 1975. Birth Defects Res A Clin Mol Teratol. 2013; 97 (7): 471-86.	1498 miscarriages (embryo was less than 12 weeks)	38.5% (577) - normal karyotype 61.5% (921) - anormal karyotype 52% (479) - trisomy (chromosomes of D - n=109 and E groups - n=172) 19.9% (183) - triploidy 15.3% (141) - monosomy (45,X - n = 140) 6.2% (57) - tetraploidy 3.8% (35) - translocations 1.7% (16) - double trisomy 1.1% (10) - mosaicism structural abnormalities - only 3.8%	61.5%
Bastos et al.³⁰30 Bastos R, Ramalho C, Dória S. [Prevalence of chromosomal abnormalities in spontaneous abortions or fetal deaths]. Acta Med Port. 2014; 27 (1): 42-8.	333 recurrent miscarriages and 262 sporadic miscarriages )	(71 72.7% (242/333) - normal karyotype 27.3% (91/333) - abnormal karyotype 92.3% (84/91) numerical alterations, mainly trisomies (65.5%; 55/84); 30.9% (17) - trisomy 16, 21.8% (12) - trisomy 18 and 14.5% (8) trisomy 21 25% (21) - poliploidy 8.3% (7) - monosomy X 7.7% (7) - structural alterations	27.3%

Authors	Number of couples	Frequency of chromosomal abnormalities %
Azim et al.³⁵35 Azim M, Khan AH, Khilji ZL, Pal JA, Khurshid M. Chromosomal abnormalities as a cause of recurrent abortions: a hospital experience. J Pak Med Assoc. 2003; 53 (3): 117-9.	300	5.3
Rao et al.³⁶36 Rao L, Murthy K, Babu A, Venkata P, Deenadayal M, Singh L. Chromosome inversions and a novel chromosome insertion associated with recurrent miscarriages in South India. Arch Gynecol Obstet. 2005; 272 (4): 273-7.	160	11.25
Celep et al.³⁴34 Celep F, Karagüzel A, Ozeren M, Bozkaya H. The frequency of chromosomal abnormalities in patients with reproductive failure. Eur J Obstet Gynecol Reprod Biol. 2006; 127 (1): 106-9.	645	3.86
Elgehzal et al.³⁷37 Elghezal H, Hidar S, Mougou S, Khairi H, Saâd A. Prevalence of chromosomal abnormalities in couples with recurrent miscarriage. Fertil Steril. 2007; 88 (3): 721-3.	1400	6.93
Yuce et al.³⁸38 Yuce H, Tekedereli I, Elyas H. Cytogenetic results of recurrent spontaneous abortions in Turkey. Med Sci Monit. 2007; 13 (6): CR286-89.	421	3.68
Meza-Espinoza et al.³⁹39 Meza-Espinoza JP, Anguiano LO, Rivera H. Chromosomal abnormalities in couples with reproductive disorders. Gynecol Obstet Invest. 2008; 66 (4): 237-40.	542	5.7
Goud et al.⁴⁰40 Goud TM, Mohammed Al Harassi S, Khalfan Al Salmani K, Mohammed Al Busaidy S, Rajab A. Cytogenetic studies in couples with recurrent miscarriage in the Sultanate of Oman. Reprod Biomed Online. 2009; 18 (3): 424-9.	380	6.84
El Dahtory et al.⁴¹41 El-Dahtory FA. Chromosomal abnormalities as a cause of recurrent abortions in Egypt. Indian J Hum Genet. 2011; 17 (2): 82-4.	73	6.1
Kochhar & Ghosh⁴²42 Kochhar PK, Ghosh P. Reproductive outcome of couples with recurrent miscarriage and balanced chromosomal abnormalities. J Obstet Gynaecol Res. 2013; 39 (1): 113- 20.	788 individuals (including 367 couples)	6.8
Sheth et al.⁴³43 Sheth FJ, Liehr T, Kumari P, Akinde R, Sheth HJ, Sheth JJ. Chromosomal abnormalities in couples with repeated fetal loss: An Indian retrospective study. Indian J Hum Genet. 2013; 19 (4): 415-22.	4859 individuals (2428 couples and three single mothers)	3.5
Alaraji⁴⁴44 Alaraji SMH. Chromosomal abnormalities associated with recurrent spontaneous abortions in Iraqi women. Med J Babylon. 2014; 7: 2.	61	9.83
Flynn et al.⁴⁵45 Flynn H, Yan J, Saravelos SH, Li TC. Comparison of reproductive outcome, including the pattern of loss, between couples with chromosomal abnormalities and those with unexplained repeated miscarriages. J Obstet Gynaecol Res. 2014; 40 (1): 109-16.	795	3.52
Turki et al.⁴⁶46 Turki RF, Banni HA, Assidim M, Al-Qahtani MH, Abduljabbar HS, Jamel HS, Rouzi AA, Abuzenadah AM. Analysis of chromosomal and genetic disorders in patients with recurrent miscarriages in Saudi Arabia. BMC Genomics. 2014; 15 (Suppl. 2): P73.	171	6.43

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[TFN1] RMs: recurrent miscarriages.