volumes were estimated using a Prader (1966) orchidometer. Testicular volume was deemed to be normal when the combined volume of both testicles equalled ...
Human Reproduction vol 11 no 12 pp 2604-2608, 1996
Mitotic chromosomal anomalies among 1210 infertile men
N.Pandiyan1'2 and Anne MJequier Department of Obstetrics and Gynecology, University of Nottingham, University Hospital, Queens Medical Centre, Nottingham NG7 2UH, UK 'Present address: Department of Obstetrics and Gynecology, Apollo Hospital, Madras, India 2
To whom correspondence should be addressed
Semen analysis Semen analyses were performed on at least two separate occasions on each patient and were earned out according to the methods described in the World Health Organization manual (1980). White blood cell karyotype Blood was drawn from the antecubital vein and transferred into hepannized plastic tubes. Karyotyping was earned out on the blood lymphocytes using the pro-metaphase banding technique (Dutrillaux and Lejeune, 1971). The Giemsa 'G' banding or the 'R' banding technique was also used
Results Introduction An association between human male infertility and chromosomal anomalies has been known for a long time (Chandley, 1979; Faed et al., 1979). The incidence of karyotype abnormalities among infertile men has been reported to range between 2.2 and 19.6% (Chandley et al., 1972; De Kretser et al, 1972). Thus, it would not be unusual to find chromosomal abnormalities in men attending an infertility clinic. Karyotyping of white blood cells of every male attending the infertility clinic would be necessary to identify those with genetic defects. However, this process is time consuming and expensive. It would be useful to find some overt clinical feature that could be readily identified with the presence chromosomal anomalies The objective of this study was to examine a large group of men from infertile marriages in an attempt to identify any clinical or seminal abnormality that could be of predictive value for chromosomal aberration(s). Materials and methods Subjects The patient population consisted of African, Asian and White British men living in an 80 km radius of Nottingham, UK, and who attended the Infertility Clinic (University of Nottingham, University Hospital, Queens Medical Centre, Nottingham, UK) between 1977 and 1986. The seminal fluid profiles for 1210 men out of a total of 1608 patients 2604
Incidence of chromosomal anomalies Abnormal karyotypes were found in 44 (3.65%) of the 1210 subjects studied. We were not aware of any data available on the rate of anomalies in an equivalent fertile population. Of these 44 subjects, 27 (61 4%) exhibited sex-chromosomal abnormalities; the remaining 17 (38.6%) had autosomal abnormalities. Of the 27 individuals with sex-chromosomal abnormalities, 18 were found to have Klinefelter's syndrome (47.XXY), three patients showed a 47.XYY configuration, and in the remaining six men the Y chromosome was abnormal. Of those nine men exhibiting autosomal anomalies, three showed inversions, three had chromosomal markers and the remaining three showed a variety of minor autosomal abnormalities (Table I). Abnormalities of the sex chromosomes 47.XXY (Klinefelter's syndrome) The 18 individuals with Klinefelter's syndrome constituted 1.5% of the total group studied; 41% of these patients were found to have an abnormal blood karyotype. Of the 18 men, 17 had a chromosomal complement (47.XXY), while one exhibited mosaicism. Of these 18 men, only one (47.XXY) had the classic features of hypo-androgenization and gynaecomastia. The remaining 17 men were, apart from the reduction in their testicular size, phenotypically normal and all appeared to be normally androgenized. All 18 men with Klinefelter's © European Society for Human Reproduction and Embryology
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Detailed medical and clinical examinations were carried out on 1608 men attending an infertility clinic to determine if any of those exhibiting abnormal semenograms also had any other readily identifiable clinical condition. In all, 1210 men showed abnormal semenograms according to World Health Organization criteria. Karyotyping of the white blood cells in these 1210 men revealed 44 (3.6%) individuals with either autosomal or sex chromosomal aberrations. However, no single characteristic feature of their semenogram or clinical condition was of any diagnostic value to predict the existence of a chromosomal anomaly. Key words: karyotype/male infertility/semen analysis
were abnormal, and their blood samples were subjected to a white cell chromosome analysis. These 1210 men constitute the subject of this study. Following detailed clinical and medical examinations, testicular volumes were estimated using a Prader (1966) orchidometer. Testicular volume was deemed to be normal when the combined volume of both testicles equalled 30 ml. The occurrence or otherwise of any other major pathology was also noted
Mitotic chromosomal anomalies in infertile men
Table I. Distribution of the different types of chromosomal abnormality among the patients with an anomaly and the study group as a whole
Table IL Testicular size and seminal profile in the three patients with the 47.XYY anomaly
Karyotypic abnormality
No of patients
% of group (n = 44)
% of total (n = 1210)
Testicular size
Sperm concentration (XlO'/ml)
% Sperm motihty
% Abnormal morphology
47.XXY (Khnefelter's syndrome) 47.XYY Abnormal Y chromosome Autosomal translocanon Autosomal inversion Autosomal markers Unclassified anomalies Total
18 3 6 8 3 3 3 44
41 7 13 18 7 7 7 100
149 025 050 066 025 025 025 3 65
Reduced Normal Normal
0 85 33 44
10 20 25
80 60 30
Abnormalities of the Y chromosome The karyotype of six patients exhibited the presence of an abnormal Y chromosome. The incidence of this anomaly in the total study group was 0.5%, while among the men shown to have an abnormal karyotype its incidence was 13.6%. All six men had primary infertility. Testicular volume was reduced in two of these patients but not in the remaining four. The abnormality of the Y chromosome was variable; in two men the Y chromosome was inverted, in another the Y chromosome was small, in another the Y chromosome showed an abnormal morphology, in another there was a partial inversion (var. 46,XYq) and in the remaining man a presumptive Y chromosome was attached to the X chromosome. Four of these individuals had azoospermia, while the remaining two were normozoospermic, with one of them exhibiting asthenozoospermia. None of these seminal abnormalities correlated with any particular Y chromosome abnormality (Table EH)
Autosomal inversions Three men showed autosomal inversions involving chromosomes 4, 9 and 10. These anomalies represented 0.3% of the total group and 6.8% of the men with chromosomal abnormalities. Testicular volume was normal in all three patients. Sperm concentration and sperm motility were reduced, and the incidence of abnormal spermatozoa was increased in the patient with a chromosome 4 inversion (Table V). Marker chromosomes Three men were found to have extra marker chromosomes. The incidence of this anomaly was therefore 0.3% of the whole study group and 6.8% of those patients with an abnormal karyotype. All three men presented with primary infertility, and two of these had testes that were reduced in size. In two of these men their semen showed a reduction in sperm concentration, but the spermatozoa from all three patients showed reduced percentage motility and an increase in the percentage of spermatozoa showing an abnormal morphology (Table VI). Uncategorized chromosomal anomalies There were three patients in this group. The chromosomal anomalies present in two of the three men were 46.XY 16qh + , 46,XY/46,XY + small fragment. In the third man there was an increase in the chromosomal breakage rate above that of the control samples. Testicular size was normal in the first of these patients but was reduced in the other two men. A semen analysis revealed oligozoospermia and asthenozoospermia m all three men. In two individuals, however, there was a marked increase in the incidence of abnormal sperm morphology (Table VII).
Abnormalities of the autosomes
Discussion
Autosomal translocations Eight patients were found to have a balanced autosomal translocation. This group of anomalies constituted 0.7% of the whole study population and 18.2% of the patients with known chromosomal abnormalities. Of these eight men, five had a 13-14 translocation, which was therefore the most common type of chromosomal rearrangement. One man had a 6-16 translocation. Testicular volume was reduced in seven of the eight men with autosomal translocations. All five patients with a 13-14 translocation and one with a 6-16 translocation were
The incidence of karyotypic anomalies amongst men also exhibiting abnormal semen was 3 65%. However, the reported incidence of karyotypic anomalies among infertile men depends on several factors. The most important of these factors is the definition of 'infertility'. The incidence of chromosomal abnormalities will also depend on patient access to chromosomal analysis techniques. Thus, climes that carry out chromosomal analyses on all men from mfertile marriages may have a lower incidence of such anomalies (Chandley et al., 1972) than those clinics that perform such analyses only on patients 2605
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syndrome showed the presence of azoospermia when their seminal fluid was examined. 48,XXXY/47,XXY Men with such karyotypes had primary infertility and the testicular volume in all of them was reduced markedly. 47,XYY The incidence of this anomaly was observed in only 0.3% (n = 3) of the total number of patients studied and in 6.8% of all men with chromosomal abnormalities. Testicular volume was reduced in one patient but was normal in the remaining two. The seminal fluid profile was abnormal m all three men. In one individual the testicular volume was reduced and his semen exhibited oligoteratoasthenozoospermia. In the remaining patients, reduced sperm motUity was the only abnormality (Table II).
found to have a reduced sperm concentration and an increased incidence of abnormal sperm morphology. One patient with a 14-22 translocation had a normal semenogram. The other individual whose karyotype showed a 14-21 translocation had severe asthenozoospermia (Table TV).
N.PandJyan and A.MJequler
Table HL Testicular size and seminal profile in the six men with abnormalities of their Y chromosome Karyotype
Tesocular size
Sperm concentration
% Monlity
46.X inv Y 46.X inv Y 46.X smaU Y 46.X unusual Y Var 46,XYq 46,XX presumptive X attached to Y
Normal Normal Normal Normal Reduced Reduced
Azoospermia 49 X lOfymJ 24 X lO'/ml Azoospermia Azoospermia Azoospermia
25 10 -
% Abnormal morphology 10 50
Table IV. Testicular size and seminal profiles in the eight men whose white cell karyotypes showed the presence of a balanced translocation Karyotype
Testicular size
45,XY,t(13q,14q) 45,XY,t(13q,14q) 45,XY,r(13q,14q) 45,XY,t(13q,14
