Rev Med UAS
Vol. 12: No. 2. Abril-Junio 2022
ISSN 2007-8013

Análisis cromosómico en parejas con abortos recurrentes: Un estudio piloto

Chromosomal analysis in couples with recurrent miscarriages: A pilot study

Picos-Cárdenas Verónica Judith1, Bernal-Ortiz María Fernanda2, Espinoza-Galván Salvador2, López-Castro Fabiola Karely2, López -Quintero Alba Esthela2, Mijangos-González Damaris Rocío2, Morgan-Ortiz Fred3, Trapero-Corona Irak Mijail4, Meza-Espinoza Juan Pablo5*

  1. Doctora en Genética Humana, Laboratorio de Genética, Facultad de Medicina, Universidad Autónoma de Sinaloa, Culiacán, Sin., México. Servicio de Medicina Genética, Hospital General de Culiacán, Culiacán, Sin., México. Núcleo Académico Básico del Programa de Posgrado de la Facultad de Ciencias de la Nutrición y Gastronomía, Universidad Autónoma de Sinaloa, Culiacán, Sin., México.
  2. Residente de especialidad de ginecología y obstetricia, Centro de Investigación y Docencia en Ciencias de la Salud-Hospital Civil de Culiacán.
  3. Coordinación de Investigación, Centro de Investigación y Docencia en Ciencias de la Salud.
  4. Médico especialista en ginecología y obstetricia. Hospital civil de Culiacán. Centro de Investigación y Docencia en Ciencias de la Salud, Universidad Autónoma de Sinaloa.
  5. Doctor en Genética Humana, Facultad de Medicina e Ingeniería en Sistemas Computacionales de Matamoros, Universidad Autónoma de Tamaulipas, Matamoros, Tamps., México.

* Correspondencia: Dr. Juan Pablo Meza-Espinoza.
Facultad de Medicina e Ingeniería en Sistemas Computacionales de Matamoros,
Universidad Autónoma de Tamaulipas, Matamoros, Tamps., México. Tel. 8682044000. E-mail: sirol1073@yahoo.com.mx

DOI http://dx.doi.org/10.28960/revmeduas.2007-8013.v12.n2.003

Texto Completo PDF

Recibido 15 de enero 2022, aceptado 15 de febrero 2022

RESUMEN
Antecedentes. El aborto recurrente impacta aproximadamente al 5% de las parejas que buscan tener hijos; una de sus principales causas es la existencia de anormalidades cromosómicas en algún miembro de la pareja, las cuales producen gametos con desbalance genómico que llevan a embarazos incompatibles con la vida y se abortan a las pocas semanas de gestación. --- Objetivo. Realizar cariotipo a todas las parejas con abortos recurrentes del servicio de ginecología del Hospital General de Culiacán en el periodo de un año. --- Material y Métodos. Se realizó cariotipo a 34 parejas cuyos estudios anatómicos y hormonales resultaron normales y el perfil TORCH negativo. El cariotipo se realizó mediante cultivo de linfocitos estimulados con fitohemaglutinina, incubados a 37ºC durante 72 h y teñidos con bandas GTG. Se analizaron 20 células por cada individuo; en pacientes en quienes se encontraron anormalidades cromosómicas se analizaron 50 células y en mosaicos 100. --- Resultados. En siete parejas (20.6%) se detectó una anormalidad cromosómica; en cinco la anormalidad se presentó en mujeres y en dos en varones. Se identificaron tres translocaciones recíprocas [t(1;14)(p36;q32), t(5;13)(p13;q34) y t(6;17)(p23;p13)], una translocación Robertsoniana [rob(15;22)(q10;q10)], una inversión [inv(20)(p12q11.2)] y dos mujeres con aneuploidías del cromosoma X en mosaico. Conclusiones. La prevalencia de anormalidades cromosómicas en este estudio es relativamente alta comparada con trabajos similares realizados en población mexicana, por lo que estos resultados resaltan la importancia de realizar análisis cromosómico a todas aquellas parejas que cursan con aborto recurrente y que aún no ha sido diagnosticada una causa específica.
Palabras clave: Aborto recurrente, cariotipo, anormalidades cromosómicas.

ABSTRACT
Background. Recurrent miscarriage impacts approximately 5% of couples trying to have children; one of its main causes is the presence of chromosomal abnormalities in one of the partners, which produce gametes with genomic imbalance that lead to pregnancies incompatible with life and are aborted within a few weeks of gestation. --- Objective. To perform karyotyping of all couples with recurrent miscarriages in the gynecology service of the General Hospital of Culiacán for one year. --- Material and Methods. Karyotyping was performed in 34 couples whose anatomical and hormonal studies were normal and TORCH profile was negative. Karyotyping was performed by culturing lymphocytes stimulated with phytohemagglutinin, incubated at 37ºC for 72 h, and stained with GTG bands. Twenty cells were analyzed for every individual; in patients in whom chromosomal abnormalities were found, 50 cells were analyzed, and in mosaics 100. --- Results. In seven couples (20.6%) a chromosomal abnormality was detected; in five this was present in females and in two in males. Three reciprocal translocations [t(1;14)(p36;q32), t(5;13)(p13;q34), and t(6;17)(p23;p13)], one Robertsonian translocation [rob(15;22)(q10;q10)], one inversion [inv(20)(p12q11.2)] and two females with mosaic X chromosome aneuploidies were identified. Conclusions. The prevalence of chromosomal abnormalities in this study is relatively high, compared with similar studies carried out in the Mexican population, therefore these results highlight the importance of performing chromosomal analysis in all those couples with recurrent miscarriage and for whom a specific cause has not yet been diagnosed.
Key words: Recurrent miscarriage, karyotyping, chromosomal abnormalities.

REFERENCIAS

  1. Brugo OS, Chillik C, Kopelman S. Definición y causas de la infertilidad. Rev Col Obstet Gin 2003;54(4):228-48.
  2. Practice Committee of the American Society for Reproductive Medicine. Evaluation and treatment of recurrent pregnancy loss: A committee opinion. Fertil Steril 2012;98(5):1103-11.
  3. Schaeffer AJ, Chung J, Heretis K, Wong A, Ledbetter DH, Martin CL. Comparative genomic hybridization-array analysis enhances the detection of aneuploidies and submicroscopic imbalances in spontaneous miscarriages. Am J Hum Genet 2004;74(6):1168-74.
  4. Stephenson M, Kutteh W. Evaluation and management of recurrent early pregnancy loss. Clin Obstet Gynecol 2007;50(1):132-45.
  5. Arias-Sosa LA, Acosta ID, Lucena-Quevedo E, Moreno-Ortiz H, Esteban-Pérez C, Forero-Castro M. Genetic and epigenetic variations associated with idiopathic recurrent pregnancy loss. Assist Reprod Genet 2018;35(3):355-66.
  6. Portnoi MF, Joye N, van den Akker J, Morlier G, Taillemite JL. Karyotypes of 1,142 couples with recurrent abortion. Obstet Gynecol 1988;72(1):31-4.
  7. Makino T, Tabuchi T, Nakada K, Iwasaki K, Tamura S, Iizuka R. Chromosomal analysis in Japanese couples with repeated spontaneous abortions. Int J Fertil 1990;35(5):266-70.
  8. Fryns JP, Van Buggenhout G. Structural chromosome rearrangements in couples with recurrent fetal wastage. Eur J Obstet Gynecol Reprod Biol 1998;81(2):171-6.
  9. Meza-Espinoza JP, Ortiz Anguiano L, Rivera H. Chromosomal abnormalities in couples with reproductive disorders. Gynecol Obstet Invest 2008;66:237-40.
  10. De la Fuente-Cortés BE, Cerda-Flores RM, Dávila-Rodríguez MI, García-Vielma C, De la Rosa Alvarado RM, Cortés-Gutiérrez EI. Chromosomal abnormalities and polymorphic variants in couples with repeated miscarriage in Mexico. Reprod Biomed Online 2009;18(4):543-8.
  11. 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.
  12. 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.
  13. Ghazaey S, Keify F, Mirzaei F, Maleki M, Tootian S, Ahadian M, et al. Chromosomal analysis of couples with repeated spontaneous abortions in northeastern Iran. Int J Fertil Steril 2015;9(1):47‑54.
  14. Tunc E, Tanriverdi N, Demirhan O, Suleymanova D, Cetinel N. Chromosomal analyses of 1510 couples who have experienced recurrent spontaneous abortions. Reprod Biomed Online 2016;32(4):414‑9.
  15. Frikha R, Kassar O, Elloumi M, Kamoun H. Cytogenetic screening in couples with recurrent pregnancy loss: A single-center study and review of literature. J Hum Reprod Sci 2021;14(2):191-5.
  16. Miller OJ, Therman E. Clinical importance of translocations, inversions, and insertions In: Human Chromosomes. Springer, fourth Ed. New York, 2001: pp. 239-254.
  17. Clouston HJ. Lymphocyte culture In: Human Cytogenetics: Constitutional analysis, a practical approach. Rooney DE (Ed.), Oxford University press, third ed. New York, 2001: pp. 33-54.
  18. ISCN 2020: An International System for Human Cytogenomic Nomenclature. McGowan-Jordan J, Hastings Simons RJ, Moore S (eds). Cytogenet Genome Res 2020;160:341-503.
  19. Kovaleva NV. Sex-specific chromosome instability in early human development. Am J Med Genet A 2005;136A(4):401-13.
  20. Antonelli A, Gandini L, Petrinelli P, Marcucci L, Elli R, Lombardo F, et al. Chromosomal alterations and male infertility. J Endocrinol Invest 2000;23(10):677-83.
  21. Ishikawa M, Hidaka E, Wakui K, Fukushima Y, Katsuyama T. Habitual abortion and high frequency of low frequent X chromosome monosomy mosaicism: detection by interphase FISH analysis of buccal mucosa cells and lymphocytes. Rinsho Byori 2000;48(10):955-9.
  22. Durmaz B, Karaca E, Durmaz A, Atik T, Akin H, Cogulu O, et al. Subtelomeric rearrangements in patients with idiopathic intellectual disabilitiy/multiple congenital anomalies and recurrent miscarriages: seven years' experience. Genet Couns 2013;24(2):167-77.
  23. Rajcan-Separovic E, Diego-Alvarez D, Robinson WP, Tyson C, Qiao Y, Harvard C, et al. Identification of copy number variants in miscarriages from couples with idiopathic recurrent pregnancy loss. Hum Reprod 2010;25(11):2913-22.
  24. Tise CG, Byers HM. Genetics of recurrent pregnancy loss: a review. Curr Opin Obstet Gynecol 2021;33(2):106-111.
  25. Kim JO, Ahn EH, Sakong JH, An HJ, Park HS, Kim YR, et al. Association of miR-27aA>G, miR-423C>a, miR-449bA>G, and miR-604A>G polymorphisms with risk of recurrent implantation failure. Reprod Sci 2020;27(1):29-38.
  26. Golestanpour H, Bahrami R, Dastgheib SA, Tabatabaei RS, Javaheri A, Karimi-Zarchi M, et al. A meta-analysis for association of eNOS VNTR 4b/a, -786 T>C and +894G>T polymorphisms with risk of recurrent pregnancy loss. Arch Gynecol Obstet 2021;304(5):1135-51.
  27. Sui Y, Chen Q, Sun X. Association of skewed X chromosome inactivation and idiopathic recurrent spontaneous abortion: a systematic review and meta-analysis. Reprod Biomed Online 2015 31(2):140-8.
  28. Bobadilla-Morales L, Cervantes-Luna MI, García-Cobián TA, Gómez-Meda BC, de la Torre CO, Corona-Rivera JR, et al. Chromosome instability in a patient with recurrent abortions. Genet Couns 2009;20(2):153-9.
  29. Toncheva D. Fragile sites and spontaneous abortions. Genet Couns 1991;2(4):205-10.