Evaluation of Chromosomal Structural Anomalies in Fertility Disorders.

Background and objectives: Reproductive disorders may occur not only due to environmental factors (air pollution, stressful lifestyle, previous abortions or the use of contraceptives) but also due to genetic factors. Materials and Methods: The aim of the study was to identify the range and frequency of chromosomal aberrations in couples (n = 99) with infertility or recurrent miscarriages in Lithuania. The data were collected from the out-patient medical histories. The couples were divided into three groups based on pregnancy, childbirth and the number of miscarriages. The Chi-square test was used to carry out the statistical analysis, and the statistical significance was (p < 0.05). Results: There were 6.6% (n = 13) structural changes observed in the karyotype tests. Chromosomal aberrations were found in 3% (n = 6) of the subjects, while 3.6% (n = 7) of them had chromosomal length polymorphisms. No difference was found between the aberration frequency in the karyotypes of men and women (p > 0.05). The most common aberrations were balanced translocations (23.1%, n = 3) which accounted for 15.4% of the reciprocal (n = 2) and 7.7% of the Robertsonian type (n = 1) of translocations. The most frequent aberrations were found in couples with the inability to conceive (42.9% (n = 3), p = 0.031). The childless couples and those with recurrent miscarriages showed an aberration rate of 8.2% (n = 5), while in the couples with at least one child it was 16.1% (n = 5). The group of couples unable to conceive had a significantly higher aberration rate of 28.6% (n = 2), p = 0.029. Miscarriages in partners' families accounted for 8.1%. Miscarriages on the female side of the family accounted for 4.5% (n = 9), on the male side it accounted for 2.5% (n = 5) and on both sides it accounted for 1.1% (n = 2). There were no statistically significant differences observed between the female and male sides (p > 0.05). The miscarriages observed in the second group of couples (childless with ≥2 miscarriages) were more frequent at 18.1% (n = 11), in the third group (having children ≥2 miscarriages) they were less frequent at 12.9% (n = 4), while no miscarriages were recorded in the first group of infertile couples. In total, 3% of the identified significant chromosomal aberrations were likely to trigger miscarriages or the inability to conceive. Conclusions: In couples with reproductive disorders, chromosomal mutations and chromosomal length polymorphisms were found at similar rates: 3% vs. 3.6%. The highest aberration rate was found in couples that were unable to conceive, a lower one was found in a group with children and ≥2 miscarriages, and the lowest one was found in a childless group of subjects with ≥2 miscarriages. The miscarriage rate in partner families was 8.1%; however, no difference was found between the male and female sides.

Recién nacida normal con sospecha prenatal de monosomía del cromosoma X debido a mosaicismo confinado a la placenta / Normal newborn with prenatal suspicion of X chromosome monosomy due to confined placental mosaicism

La reciente introducción de las pruebas prenatales no invasivas (NIPT, por sus siglas en inglés) basadas en el ADN libre ofrece un método más preciso que los métodos tradicionales de detección en el suero materno para identificar aneuploidías fetales. La eficacia de las pruebas NIPT para detectar los síndromes de Down, Edwards y Patau se ha demostrado en ensayos clínicos. Sin embargo, los enfoques de las pruebas NIPT que aprovechan la información sobre el polimorfismo de un solo nucleótido (SNP, por sus siglas en inglés) tienen el potencial de identificar triploidías, síndromes de microdeleción cromosómica y otras variantes genéticas no habituales. Para destacar este enfoque de las pruebas NIPT, se presenta un caso poco frecuente de monosomía del cromosoma X debido a mosaicismo confinado a la placenta, del que había una sospecha prenatal por el resultado de una prueba prenatal no invasiva basada en el polimorfismo de un solo nucleótido. Los resultados de las pruebas invasivas (amniocentesis) mostraron una pequeña proporción de mosaicismo del cromosoma X (45, X[5]/46, XX[95]). Después del nacimiento, el cariotipo de la niña no reveló anomalías (46 XX), lo que confirmó que el mosaicismo se limitaba a la placenta. Estos resultados ponen de manifiesto la necesidad del consentimiento informado de la paciente, y del minucioso asesoramiento anterior y posterior a las pruebas, para garantizar que comprenda las limitaciones y las ventajas de dichas pruebas, y las repercusiones de los resultados.

The recent introduction of cell-free DNA (cfDNA)-based noninvasive prenatal testing (NIPT) offers pregnant women a more accurate method than traditional serum screening methods for detecting fetal aneuploidies. Clinical trials have demonstrated the efficacy of NIPT for Down, Edwards and Patau syndromes. However NIPT approaches that take advantage of single-nucelotide polymorphism (SNP) information potentially allow the identification of triploidy, chromosomal microdeletion syndromes and other unusual genetic variants. To highlight this approach of NIPT we present a rare case of confined placental X chromosome monosomy mosaicism that was prenatally suspected with a single-nucleotide polymorphism-based noninvasive prenatal test. The results of invasive tests (amniocentesis) showed small proportion of X chromosome mosaicism (45, X[5]/46, XX[95]). After birth karyotype of the girl revealed no abnormalities (46 XX), confirming that mosaicism was limited to the placenta. These results highlight the need of patient's informed consent and thorough pretest and postest counseling to ensure that they understand the limitations and advantages of the tests and the implications of the resultss.

Normal newborn with prenatal suspicion of X chromosome monosomy due to confined placental mosaicism. / Recién nacida normal con sospecha prenatal de monosomía del cromosoma X debido a mosaicismo confinado a la placenta.

The recent introduction of cell-free DNA (cfDNA)-based noninvasive prenatal testing (NIPT) offers pregnant women a more accurate method than traditional serum screening methods for detecting fetal aneuploidies. Clinical trials have demonstrated the efficacy of NIPT for Down, Edwards and Patau syndromes. However NIPT approaches that take advantage of single-nucelotide polymorphism (SNP) information potentially allow the identification of triploidy, chromosomal microdeletion syndromes and other unusual genetic variants. To highlight this approach of NIPT we present a rare case of confined placental X chromosome monosomy mosaicism that was prenatally suspected with a single-nucleotide polymorphism-based noninvasive prenatal test. The results of invasive tests (amniocentesis) showed small proportion of X chromosome mosaicism (45, X[5]/46, XX[95]). After birth karyotype of the girl revealed no abnormalities (46 XX), confirming that mosaicism was limited to the placenta. These results highlight the need of patient's informed consent and thorough pretest and postest counseling to ensure that they understand the limitations and advantages of the tests and the implications of the resultss.

La reciente introducción de las pruebas prenatales no invasivas (NIPT, por sus siglas en inglés) basadas en el ADN libre ofrece un método más preciso que los métodos tradicionales de detección en el suero materno para identificar aneuploidías fetales. La eficacia de las pruebas NIPT para detectar los síndromes de Down, Edwards y Patau se ha demostrado en ensayos clínicos. Sin embargo, los enfoques de las pruebas NIPT que aprovechan la información sobre el polimorfismo de un solo nucleótido (SNP, por sus siglas en inglés) tienen el potencial de identificar triploidías, síndromes de microdeleción cromosómica y otras variantes genéticas no habituales. Para destacar este enfoque de las pruebas NIPT, se presenta un caso poco frecuente de monosomía del cromosoma X debido a mosaicismo confinado a la placenta, del que había una sospecha prenatal por el resultado de una prueba prenatal no invasiva basada en el polimorfismo de un solo nucleótido. Los resultados de las pruebas invasivas (amniocentesis) mostraron una pequeña proporción de mosaicismo del cromosoma X (45, X[5]/46, XX[95]). Después del nacimiento, el cariotipo de la niña no reveló anomalías (46 XX), lo que confirmó que el mosaicismo se limitaba a la placenta. Estos resultados ponen de manifiesto la necesidad del consentimiento informado de la paciente, y del minucioso asesoramiento anterior y posterior a las pruebas, para garantizar que comprenda las limitaciones y las ventajas de dichas pruebas, y las repercusiones de los resultados.