Is sperm FISH analysis still useful for Robertsonian translocations? Meiotic analysis for 23 patients and review of the literature

Abstract

BackgroundRobertsonian translocations (RobT) are common structural chromosome rearrangements where carriers display a majority of chromosomally balanced spermatozoa from alternate segregation mode. According to some monotony observed in the rates of balanced segregation, is sperm FISH analysis obsolete for RobT carriers?MethodsRetrospective cohort research study on 23 patients analyzed in our center from 2003 to 2017 and compared to the data of 187 patients in literature from 1983 to 2017.Robertsonian translocation carriers were divided in six groups according to the chromosomes involved in the translocation: 9 patients from our center and 107 from literature carrying 45,XY,der(13;14) karyotype, 3 and 35 patients respectively with 45,XY,der(14;21), 5 and 11 patients respectively with 45,XY,der(13;15), 4 and 7 patients respectively with 45,XY,der(14;15), 1 and 4 patients respectively with 45,XY,der(13;22),and 1 and 10 patients respectively with 45,XY,der(14;22).ResultsAlternate segregation mode is predominant in our group of Robertsonian translocation carriers with 73.45% ±8.05 of balanced spermatozoa (min 50.92%; max 89.99%). These results are compliant with the data from literature for all translocations types (p > 0.05) and are consistent among the different types of Robertsonian translocations (p > 0.05) except for der(13;15) that exhibit lower balanced spermatozoa rates (p < 0.05 versus der(13;14), der(14;21), (13;21) and der(15;22)). Normozoospermic patients also display a significantly (p < 0.01) higher rate of balanced sperm cells than patients with abnormal seminograms whatever the defect implied.ConclusionsAccording to the discrepancies observed between der(13;15) and all the other Rob T carriers, the differences observed among patients presenting normal and abnormal sperm parameters and the input in genetical counselling, sperm FISH does not seem obsolete for these patients. Moreover, it seems important to collect more data for rare RobT.

How much, if anything, do we know about sperm chromosomes of Robertsonian translocation carriers?

“…To date, meiotic segregation patterns have been analysed in sperm from over 200 carriers of different nonhomologous RobTs. On average, the frequency of genetically normal/balanced segregants has been found to be approximately 80% [42,43]. In contrast, in the carriers of homologous translocations, e.g., der(21;21) or der(13;13), all sperm cells show disomy or nullisomy of a particular chromosome, in agreement with theoretical expectations [44].…”

“…Values with significant differences: 1 : (p = 0.029); 2 : (p = 0.032) a References from Suppl. Table S1: [3, 43, 65, 83, 92, 132-149, 150-152, 176] b References: [43, 64-66, 77, 82, 83, 92, 132, 133, 135, 144, 146, 153-162] c References: [42,43,65,66,82,132,133,138,139,144,146,148,[162][163][164][165][166] 79.3%) for normal/balanced segregation rates was not different from that of rob(14;21) (i.e., 78.9%). Moreover, these mean values for common RobTs were not different from the mean value of the sum of rare RobTs (i.e., 79.7%).…”

Double chromosomal translocation in an infertile man: one-step FISH meiotic segregation analysis and reproductive prognosis

“…Sperm FISH is a reliable method to study the segregation of chromosomal translocations in spermatozoa and to provide accurate genetic counseling to couples, since the existence of a balanced chromosomal translocation leads to the formation of a variable percentage of chromosomally unbalanced gametes. This has been performed extensively for many years now, both in Robertsonian and reciprocal translocation carriers [2]. Typically, Robertsonian translocations are associated with a lower proportion of unbalanced spermatozoa as compared with reciprocal translocations (3-40% vs. 20-75% for reciprocal translocations; [2,5,6]).…”

“…This has been performed extensively for many years now, both in Robertsonian and reciprocal translocation carriers [2]. Typically, Robertsonian translocations are associated with a lower proportion of unbalanced spermatozoa as compared with reciprocal translocations (3-40% vs. 20-75% for reciprocal translocations; [2,5,6]). We will discuss both types in this short review, since they are both associated with the same segregation analysis issues.…”

“…Evaluating the proportion of chromosomally unbalanced spermatozoa is an important element of genetic counseling in translocation carriers since it allows affected couples to choose to have a child either by natural pregnancy with a prenatal diagnosis or by in vitro fertilization with a preimplantation genetic diagnosis (PGD). Generally, the proportion of unbalanced gametes in Robertsonian translocations is 10 to 49% according to a recent review of the literature by Lemotte et al [2]. Such an evaluation is particularly important in rare individuals who carry two different translocations.…”