Population genetic study of differential fertility in man (illustrated by habitual abortion). IV. Distribution of blood groups and frequency of incompatible marriages

Hereditary variation of 5 immunological systems coded by 8 loci was compared in 148 couples and 100 women with repeated spontaneous abortions in anamnesis (experimental group) and 141 couples and 100 women with normal fertility (control group). Marked differences in distributions of genotypes and frequencies of 3 systems (MNSs, Rhesus, Duffy) and frequency of AB0-incompatible couples were found between control and experimental groups. An average value of observed heterozygosity in experimental group was lower, as compared to the expected value. Possible influence of immunological factors on recurrent fetal wastage is discussed.     

Population genetics study of differential fertility in humans (based on an example of habitual abortion). III. Distribution of individual heterozygosity and genotype combinations for 9 polymorphic loci

Distribution of individual heterozygosity (the number of heterozygous loci per individual), wife/husband genetical differences and frequencies of genotypes formed by paired combination of eight polymorphic loci were studied in a group of couples and single women with repeated spontaneous abortions, and in a group of couples with normal fertility. No statistically significant differences were found for the first two parameters. Marked increase of genetical variability was shown for the women with repeated spontaneous abortions, as consequence of elevation of frequency of rare genotypic paired combinations. Therefore, differential fertility, as a component of stabilizing selection, alters the distribution of complex genotypes in human populations.     

Population genetics study of differential fertility in humans (based on an example of habitual abortion). II. Distribution of genotypes and heterozygosity levels for a variety of biochemical markers

Hereditary variation of 21 blood proteins coded by 22 monomorphic and 9 polymorphic loci was compared in 171 couples and 120 women with repeated spontaneous abortions in anamnesis (experimental group) and 183 couples with normal fertility (control group). Significant elevation of frequency of rare protein electrophoretic variants, marked deviation in distribution of genotypes for polymorphic loci, alteration in observed heterozygosity level were not found in experimental group. Statistically significant decrease in average value of D index (D = (hobs-hexp)/hexp; hobs, hexp--observed and expected heterozygosity per locus) was found in women of experimental group.     

A cytogenetic study of repeated spontaneous abortions.

During a cytogenetic study of spontaneous abortions, successive abortions from 40 couples were karyotyped. The chromosome constitutions of the first and second abortions were found to be highly correlated. In each of 21 instances in which the first abortion was chromosomally normal, the subsequent abortion(s) was normal as well. In nine cases, the two abortions were chromosomally abnormal, and in four of these, both abortions were trisomic. Combined with findings from other studies of consecutive spontaneous abortions, the present data indicate that certain couples are at an increased risk for either repeated chromosomally normal abortions or for repeated trisomic conceptions. The increased risk of trisomy does not seem to be restricted to a particular chromosome, and the magnitude of the risk increase appears to be independent of maternal age.     

Fragile sites and spontaneous abortions.

In this report we present the cytogenetic findings of the expression of fragile sites in 10 couples with two or more spontaneous abortions. These findings were compared with the results in a control group of 15 subjects with two normal offsprings. Individuals of couples experiencing early fetal losses carry fragile sites with significant higher frequency, moreover this frequency is markedly influenced by the number of spontaneous abortions. Eight fragile sites were significantly more expressed in individuals with miscarriages than in the controls. These eight fragile sites correspond with cancer breakpoints or sites of oncogenes. Hypothesis on the role of oncogene mutations in spontaneous abortions is proposed, based on the results of the nonrandom distribution of fragile sites on human chromosomes.     

Cytogenetic findings in 122 couples with recurrent abortions

Summary R-banded chromosome complements were analysed from 122 couples who had experienced three or more spontaneous abortions. Five women and one man were found to be carriers of translocations t(2;17), t(5;9), t(11;22), t(17;22), and t(13q14q). Two other karyotypes were abnormal: 46,XXq- and 47,XXX. Banded chromosome studies are recommended for couples with repeated abortions.     

High resolution cytogenetic evaluation of couples with recurring fetal wastage

Summary Both high resolution and routine chromosome analyses were used to study couples with a history of two or more spontaneous abortions in early pregnancy. In the 20 couples studied, two of the women were found to have an inversion. One paracentric inversion, (13)(q13.1q22.3), was apparent on routine analysis. The small pericentric inversion (11)(p11.12q12.3), was only detected by high resolution techniques. Given the low yield and increased cost and effort involved, we do not believe that high resolution studies are justified for screening couples with repeated abortions.     

Human chromosome polymorphism and disordered reproductive function. I. Routine chromosome variants]

Routine polymorphic variants of chromosomes of 58 married couples with reproductive failure (two or more spontaneous abortions, stillbirths and malformed children) and 48 control couples, having two or more normal children and no spontaneous abortions and stillbirths, were investigated by conventional staining technique. Extreme variants of chromosomes 1, 9, 16, 17, 13--15, 21--22 and Y were found in 17.2% of subjects with reproductive loss and in 15.6% of control individuals. No significant differences in frequencies of scored routine variants were noted between married couples with reproductive failure and couples with normal reproduction.     

Quantitative analysis of C-segments of chromosomes 1, 9, 16 and Y in couples with reproductive disorders

A comparative analysis of structural variability of C-bands on chromosomes 1, 9, 16 and Y was conducted in 50 phenotypically normal adults and 25 couples with repeated spontaneous abortions. Reduction of both the total amount of heterochromatin in the cell and the lengths of these regions on chromosomes 1, 9, and 16 is revealed in the group of pathology. No differences were found in the lengths of C-bands on Y chromosome.     

Population genetic study of differential fertility in man (illustrated by habitual abortion). V. Distribution of individual heterozygosity and parameters of genotypic variability for a set of immunological genetic markers

Distribution of individual heterozygosity (the number of heterozygous loci per individual), frequencies of genotypes formed by paired combinations of 5 loci and values of linkage disequilibrium between 6 blood group loci were studied both in a group of couples and single women with recurrent abortions in anamnesis, and in a group of couples and single women with normal fertility. Statistically significant deficit of highly heterozygous individuals was found in the experimental group. Marked increase of genetical variability was shown for the women with repeated abortions, as a consequence of elevation of rare genotypic paired combination frequency. Therefore, differential fertility as a component of stabilizing selection alters the distribution of complex genotypes in human populations. Differences in values of linkage disequilibrium between women with repeated abortions and those of normal fertility were not found.     

Parental HLA compatibility, fetal wastage and neural tube defects: evidence for a T/t-like locus in humans

To test the hypothesis that a locus in or near the human major histocompatibility complex (HLA) contributes to both involuntary fetal loss and neural tube defects (NTD), we evaluated sharing of antigens of the HLA-A, HLA-B, or HLA-DR loci of couples who had three or more first-trimester spontaneous abortions or who had a child with an NTD (myelomeningocele or anencephaly). HLA-A antigen sharing was increased in couples with three or more spontaneous abortions and in couples who had an anencephalic fetus, when compared with couples who had three or more pregnancies and no fetal loss. Increased sharing of antigens at the HLA-A and B loci was not seen in the entire group of couples with children with myelomeningocele, but was found in the subgroup of 36 couples whose child had a lumbar myelomeningocele. An increase in HLA-DR sharing was not seen in any group or subgroup when compared with the control couples. Among the aborting couples, increased sharing was not restricted to the couples who had no term pregnancies, but was also found in the couples whose fetal losses occurred after one or more normal term pregnancies. These results are consistent with the hypothesis that a locus on the HLA-A side of the HLA-DR locus contributes to some fetal loss and susceptibility to NTD. This model is proposed as an alternative to the hypothesis that the maternal immune response to paternal major histocompatibility complex (MHC) antigens is the basis for increased HLA sharing in couples with fetal wastage.     

Population genetics study of the differential fertility in urban populations

In an urban population with widespread birth control practice the distribution of the number of pregnancies, births and abortions was studied in a cohort of women of completed fertility. The mean number of pregnancies per woman was 4.03 +/- 0.08 (sigma = = 2.98); the mean number of births - 1.12 +/- 0.02 (sigma = 0.77). 7.4% of women which had completed their reproductive performance had no pregnancies and 19.5% - no births. The Crow's Index of the Opportunity for Selection and its components connected with differential fertility and differential mortality were estimated. In the population under study two components of selection - selection at the prenatal stages and selection associated with infertility - are shown to be still significant. Such type of selection is exemplified by investigation of couples suffering from repeated spontaneous abortions.     

罗伯逊易位分子机理初探

目的：探讨复发性自然流产与染色体罗伯逊易位间的关系。方法：采用人外周血淋巴细胞培养,常规G显带技术行染色体核型检查,并结合临床资料对其进行分析。结果：57对复发性自然流产夫妇中,检出罗伯逊易位染色体核型4例,检出率3.51%。结论：罗伯逊易位是导致复发性流产的重要原因之一,对复发性自然流产患者进行常规的染色体检查及遗传咨询具有一定的临床意义。     

Q-band chromosome polymorphism in couples with reproductive disorders

A comparative analysis of Q-band polymorphisms was conducted in phenotypically normal individuals and couples with repeated spontaneous abortions. In the group of pathology reduction of the following phenomena was found: frequencies of brilliant fluorescence in bands 4p11q11, 14p11, 14p13, 15p11, 21p13; the mean numbers of the brilliant fluorescent segments per cell per individual; frequencies of extremely large ("marker") Q-bands. All these findings coincided with our earlier published data on reduction of the C-heterochromatin amount in the same group of pathology.     

Analysis of translocations observed in three different populations. II. Robertsonian translocations

A sample of 229 Robertsonian translocations was classified into three groups according to the method of their ascertainment (Group I = couples with repeated abortions; Group II = karyotypically unbalanced probands; Group III = balanced translocation heterozygotes). Statistical analysis showed that the distributions of Robertsonian translocations differed significantly from random in all three groups. Additionally, the distributions were significantly different between couples with repeated abortions and karyotypically unbalanced probands and between unbalanced probands and balanced translocation heterozygotes.     

Cytogenetic studies in 100 couples with recurrent spontaneous abortions.

The reported incidence of translocations in couples with recurrent spontaneous abortions ranges from 3% to 31% (average 9.3%). We report 100 couples in whom no reciprocal translocation carriers were ascertained.     

Human chromosome polymorphism and disordered reproductive function. II. C-variant chromosomes]

C-stained polymorphic variants of chromosomes 1, 9, 13--16, 21, 22 and Y were studied in married couples with reproductive failure (200 individuals) and in control couples having normal children and no spontaneous abortions and stillbirths. Location of heterochromatic segments, their size and heteromorphism of homologues were estimated. The individuals with reproductive failure were carriers of variants of chromosomes 9 and acrocentrics with higher content of heterochromatic material as well as with heterochromatic chromosome 9 significantly more frequently as compared with control individuals.     

Prenatal selection and fetal development disturbances occurring in carriers of G6PD deficiency

Summary The incidence of spontaneous abortions in women with glucose-6-phosphate dehydrogenase (G6PD) deficiency was studied. In 78 families where the wife was a heterozygous carrier of G6PD deficiency the percentage of unsuccessful pregnancies with spontaneous abortions occurring in the first trimester was higher (21.7%, calculated from 258 pregnancies) than in the control group (9.3%), calculated from 678 pregnancies.     

Rates and outcome of pregnancies achieved in the first 4 years of an in-vitro fertilization program.

Between Feb. 1, 1984, and Dec. 31, 1987, 578 couples were treated in the in-vitro fertilization (IVF) program at University Hospital, London, Ont. The 160 confirmed pregnancies resulted in 86 deliveries and the birth of 108 babies. There were 20 spontaneous abortions, 12 ectopic pregnancies, 11 presumptive pregnancies, 4 neonatal deaths and 1 stillbirth. At the time of writing, 41 pregnancies of 20 weeks'' gestation or more were in progress. Except for a high cesarean section rate the obstetric outcome of pregnancies achieved with IVF does not appear to be different from that expected for a group of infertile couples treated with conventional therapies. The pregnancy rates varied according to the denominator used.     

A new case of Y to X translocation in a female

Summary Cytogenetic investigation of married couples with the history of two or more recurrent abortions or unsuccessful pregnancies was carried out. The study concerns the occurrence of reciprocal translocations in regard to spontaneous miscarriages. In 115 examined couples 9 reciprocal translocations were observed, i.e., in 7.8%.