Monozygotic Triplets Research Articles

Monozygotic triplets and monozygotic twins after ICSI and transfer of two blastocysts: case report.

There are data regarding the possible influences of extended embryo culture to the blastocyst stage as well as zona pellucida manipulation on the incidence of monozygotic multiples. This is interesting, as one aim of extended culture with embryo selection is to minimize the multiple pregnancy rate. We report, to our knowledge, on the first case of monozygotic twins and monozygotic triplets after ICSI and the transfer of two blastocysts. Monozygotic multiples after ICSI and blastocyst transfer and the resulting problems are another reason to encourage the transfer of only one blastocyst. Theories about risk factors and the pathophysiology of monozygotic multiples will be discussed both in terms of this case report and of the literature. In our opinion, the incidence of 5.9-8.9% monozygotic multiple occurrence after ICSI and blastocyst transfer reported in the literature requires that patients are informed of the uncertainties until this phenomenon and its risk factors are better understood.

Mitochondrial DNA control region diversity in hairs and body fluids of monozygotic triplets.

Length heteroplasmy of the homopolymeric cytosine stretch in the hypervariable region II of the mitochondrial D-loop was investigated in blood, buccal cells and hair shafts of monozygotic triplets. The proportions of length heteroplasmy were determined by cloning and sequencing of multiple independent clones. Blood and buccal cells showed an accumulation of molecules with one and two insertions of cytosine residues in relation to the Cambridge Reference Sequence (CRS). The results did not show statistically significant differences between blood and buccal cells of one and the same individual and also not between the three monozygotic brothers. In the hair samples a loss of cytosine residues was established in all three monozygotic individuals compared to blood and buccal cells, suggesting that this must be a regular process. Furthermore, the hair shaft samples showed significant differences between the frequencies of 7, 8 or 9 Cs in the poly C region comparing the three individuals (p<0.008) and in addition there were highly significant differences (p<0.0001) when comparing the results for six different hairs of each individual separately. From these results it can be assumed that besides a common genetic bottleneck during embryonic development, a post-embryonic bottleneck seems to exist in each hair follicle.

Different expressions of X-linked cardiomyopathy in monozygotic triplets with Becker's dystrophy.

Cardiac involvement is common in skeletal muscles disorders associated with dystrophin defect. It has been suggested however, that X-linked dilated cardiomyopathies with minimal or absent skeletal disease are distinct entities, resulting from mutations in cardiac-specific regions of dystrophin gene. This study presents a unique observation of phenotypic variability in monozygotic triplets with Becker's muscular dystrophy. The expressions of the disease range from severe peripheral myopathy to severe congestive heart failure. No deletion in dystrophin gene was observed and the mechanisms responsible for selective impairment of morphologically and functionally different muscles in three monozygotic siblings remain unclear.

Pre-natal, Clonal Origin of Acute Lymphoblastic Leukaemia in Triplets

A unique case of ALL in three monozygotic triplets diagnosed at the age of 24, 27 and 37 months is described. Archived bone marrow smears were available for molecular analysis of immunoglobulin heavy chain (IGH) and IGK genes and T-cell receptor (TCR)-delta and gamma gene rearrangements. A shared IGH rearrangement was found in triplets "A" and "B", and an identical rearrangement of TCR-delta in triplets "B" and "C". These data suggest a common, monoclonal initiation of ALL in one of these three triplets, followed by dissemination of clonal progeny to the other twins via vascular anastomoses within the single, monochorionic placenta that they shared in utero. Differences in IGH rearrangements in diagnostic samples also indicates divergent subclonal evolution of the original "pre-leukaemic" clone.

Anti-neutrophil cytoplasmic autoantibody (ANCA) profiles in propylthiouracil-induced lupus-like manifestations in monozygotic triplets with hyperthyroidism

We describe the ANCA profile of two monozygotic triplets (A and B) treated with propylthiouracil (PTU) for hyperthyroidism who developed LE-like manifestations. Triplet C also developed hyperthyroidism but was not treated with PTU and never experienced LE-like symptoms. Triplet A and B showed a marked rise in P-ANCA titer to 1:1280 after PTU was introduced whereas triplet C never had a titer higher than 1:80. Consecutive sera were investigated for ANCA to six different neutrophil granule proteins. Triplet A and B, but not C, both developed a strongly positive elastase-ANCA. Our results confirm the importance of a genetic factor influencing the susceptibility to drug-induced LE.

Increase in the monozygotic twinning rate after intracytoplasmic sperm injection and blastocyst stage embryo transfer

Increase in the monozygotic twinning rate after intracytoplasmic sperm injection and blastocyst stage embryo transfer

Frequency of monozygotic twinning associated with in vitro fertilization and embryo transfer (IVF-ET).

Objective: To assess the frequency of monozygotic twinning after IVF-ET. Design: A retrospective review of all in vitro fertilization procedures resulting in an embryo transfer procedure from January 1, 1997 through December 31, 2000. Materials/Methods: One thousand and sixty five IVF-ET records were reviewed. Each record was classified as to day of transfer (day 3 vs. day 5/6). Ultrasound data confirming an intrauterine gestational sac was used to determine intrauterine pregnancy (IUP). Number of documented beating hearts was compared to number of gestational sacs to indicate the presence of a monozygotic twin. Data were analyzed by Fisher’s Exact Test. Results: Six hundred and six transfers were performed on day 3, resulting in 213 (36%) IUPs. Four hundred and fifty nine transfers were performed on day 5/6, resulting in 236 (51%) IUPs. There was only one documented monozygotic twin amongst pregnancies established with day 3 transfer as compared to 16 monozygotic pregnancies resulting from day 5/6 transfer (p < .01). One of the 16 monozygotic pregnancies involved a monozygotic triplet. Day 5/6 transfers which included at least one top quality blastocyst had a higher (p < .01) pregnancy rate (112/168; 66%) as compared to day 5/6 transfers with no top quality blastocysts (102/206; 49.5%). Monozygotic twin rates tended (p < .06) to be lower when the transfer included a top quality blastocyst (4/112; 3.5%) as compared to transfers with no top quality blastocysts (11/202; 10.7%). Day 5/6 transfers with no blastocysts had a lower pregnancy rate (22/85; 26% IUP) with one (1/22;4.5%) monozygotic pregnancy. Tabled 1IVF-ETIUPMonozygotic twinningDay 3696213 (36%)1 (0.5%)Day 5/6459236 (51%)16 (6.7%) Open table in a new tab Conclusions: These data suggest that current practice involving day 5/6 embryo transfer may have a greater risk for monozygotic pregnancies. Each program should rigorously evaluate their own data in order to best counsel patients for risks associated with multiple pregnancy.

Prospective identification of an in vitro-assisted monozygotic pregnancy based on a double-inner-cell-mass blastocyst.

Prospective identification of an in vitro-assisted monozygotic pregnancy based on a double-inner-cell-mass blastocyst.

Estimated number of multiplets under 16 years using two sets of census data in Japan: 1990 and 1995.

Data for sets of multiples under 16 years of age were obtained from the population censuses of Japan in 1990 and 1995. These numbered 147,188 twin pairs, 1410 sets of triplets, 59 sets of quadruplets, and 3 sets of quintuplets in 1990, with the corresponding numbers in 1995 being 141,354, 2,211, 136 and 12, respectively. The total number of sets of multiples was 148,660 in 1990 and 143,713 in 1995. Twinning, triplet, quadruplet and quintuplet rates were estimated for each age. Rates of monozygotic twins and triplets remained constant age by age up to 15 years, while the dizygotic twinning rate, and rates of di- and tri-zygotic triplets decreased over the same period. Quadruplet and quintuplet rates also decreased. The accuracy of estimating number of multiples from census data is discussed using data on vital statistics.

Estimated Number of Multiplets Under 16 Years Using Two Sets of Census Data in Japan: 1990 and 1995

AbstractData for sets of multiples under 16 years of age were obtained from the population censuses of Japan in 1990 and 1995. These numbered 147,188 twin pairs, 1410 sets of triplets, 59 sets of quadruplets, and 3 sets of quintuplets in 1990, with the corresponding numbers in 1995 being 141,354, 2,211, 136 and 12, respectively. The total number of sets of multiples was 148,660 in 1990 and 143,713 in 1995. Twinning, triplet, quadruplet and quintuplet rates were estimated for each age. Rates of monozygotic twins and triplets remained constant age by age up to 15 years, while the dizygotic twinning rate, and rates of di- and tri-zygotic triplets decreased over the same period. Quadruplet and quintuplet rates also decreased. The accuracy of estimating number of multiples from census data is discussed using data on vital statistics.

Two identical triplet sisters carrying a germline BRCA1 gene mutation acquire very similar breast cancer somatic mutations at multiple other sites throughout the genome.

Monozygotic twins, each of whom has breast cancer, offer a natural study population for gene-environmental interactions as causation of cancer, because they are genetically identical. If heritable factors play a large role in the origin of a neoplasm, disease concordance should be significant in monozygotic twins. Two monozygotic triplet sisters carrying a germline BRCA1 gene mutation (5382insC) who both developed breast cancer at early ages were studied for loss of heterozygosity (LOH) in their microdissected, paraffin-embedded tumors along with control blood and stromal breast tissue at 19 chromosomal arms using 161 microsatellite markers. Microdissected areas of normal lobular and ductal epithelium and ductal in situ carcinoma were also studied for LOH using a subset of microsatellite markers. The mother's DNA (extracted from peripheral blood lymphocytes) was analyzed to determine the parental allele under LOH in each case. Both tumors demonstrated similar histologic features suggestive of a secretory variant of ductal carcinoma. The tumors from both sisters had similar overall LOH frequency expressed by the fractional allelic loss (FAL) indices (0.56 vs. 0.60) and demonstrated concordance for loss or retention at 82 of 97 informative markers (85% correlation). In addition, detailed mapping analysis of several chromosomal arms revealed that identical breakpoints were detected in both tumors at several chromosome regions. Finally, in both sisters' tumors, when a chromosome exhibited allelic loss, all of the markers exhibited LOH of the same parental allele even when there were intervening regions of retention of heterozygosity. In contrast, 17 archival sporadic breast carcinomas demonstrated a wide range of FAL indexes and highly individual patterns of LOH. Our findings support the hypothesis that inherited factors play a role in the development of the multiple somatic deletions occurring in breast carcinomas. Whether one of these factors is the mutant BRCA1 allele or some other gene(s) remains to be determined. Genes Chromosomes Cancer 28:359-369, 2000.

Constant multiple birth rates in the Czech Republic and the Slovak Republic until recently, 1972-1995.

Using vital statistics, yearly changes in the twinning and triplet rates by zygosity were investigated in the Czech Republic and the Slovak Republic during the period 1972-1995. Monozygotic (MZ) twinning rates in both countries had remained nearly constant (about 3 per 1000 total births) during that period. With a few exceptions, the dizygotic (DZ) twinning rates remained constant from 1972 to 1994, and increased in 1995 for both countries. MZ twinning rates for both countries were the lowest in Europe. As for triplet rates, overall rates increased significantly year by year in the Czech Republic, but not in the Slovak Republic. The triplet rate was significantly higher in 1995 than in the period 1972-1982 for both countries. The MZ triplet rate remained constant during that period in the Czech Republic. The trizygotic (TZ) triplet rates increased 3-fold for the Czech Republic and 4-fold for the Slovak Republic in 1972-1976 and 1992-1995. In the later period, the TZ rate was 1.5-fold higher in the Czech Republic than in the Slovak Republic. The quadruplet rate increased 2.3-fold from 2.9 per million births in 1982-1986 to 6.7 in 1992-1995 in the Czech Republic. The corresponding values were 2.7, 2.20 and 5.9-fold in the Slovak Republic. Both the Czech and the Slovak Republics were not affected by fertility drugs and assisted reproductive techniques until recently.

Constant multiple birth rates in the Czech Republic and the Slovak Republic until recently, 1972–1995

AbstractUsing vital statistics, yearly changes in the twinning and triplet rates by zygosity were investigated in the Czech Republic and the Slovak Republic during the period 1972–1995. Monozygotic (MZ) twinning rates in both countries had remained nearly constant (about 3 per 1000 total births) during that period. With a few exceptions, the dizygotic (DZ) twinning rates remained constant from 1972 to 1994, and increased in 1995 for both countries. MZ twinning rates for both countries were the lowest in Europe. As for triplet rates, overall rates increased significantly year by year in the Czech Republic, but not in the Slovak Republic. The triplet rate was significantly higher in 1995 than in the period 1972–1982 for both countries. The MZ triplet rate remained constant during that period in the Czech Republic. The trizygotic (TZ) triplet rates increased 3-fold for the Czech Republic and 4-fold for the Slovak Republic in 1972–1976 and 1992–1995. In the later period, the TZ rate was 1.5-fold higher in the Czech Republic than in the Slovak Republic. The quadruplet rate increased 2.3-fold from 2.9 per million births in 1982–1986 to 6.7 in 1992–1995 in the Czech Republic. The corresponding values were 2.7, 2.20 and 5.9-fold in the Slovak Republic. Both the Czech and the Slovak Republics were not affected by fertility drugs and assisted reproductive techniques until recently.

A spare or an individual? Cloning and the implications of monozygotic twinning.

The creation of Dolly, the cloned sheep, raises the scenario of cloning in humans. Neither the case for, nor against, the ethics of cloning in humans is discussed in this paper. Instead, it considers the neglected issue of the likely happiness or otherwise of the resulting children if they are born as monozygotic twins or triplets. The advantages and disadvantages of twinship are discussed in detail, and it is concluded that recognized medical risks, and incompletely understood psychological effects, should be given serious consideration.

Nuclear-cytoplasmic interaction and development of goat embryos reconstructed by nuclear transplantation: production of goats by serially cloning embryos.

The time of pronuclear formation of in vivo-matured oocytes was examined. Maturation-promoting factor (MPF) activity in enucleated and electrically activated oocytes was checked by assessment of nuclear envelope breakdown (NEBD) of fused blastomeres. The effect of stage of the cell cycle of donor cells and recipient oocytes on DNA synthesis and development of reconstructed embryos was studied. MPF activity declined rapidly to approximately 63.2% at 1 h, to 9.7% at 5 h, and to the level at which NEBD cannot occur at 7 h postactivation. All blastomeres that were fused at the time of recipient cytoplasm activation underwent NEBD and subsequent DNA synthesis. However, when blastomeres were fused to enucleated oocytes at 7 h postactivation, no NEBD was observed; DNA was replicated in nuclei at the G1/S border, but in G2 nuclei no DNA replication was observed. The proportion of development to blastocysts of reconstructed goat embryos increased with the decline in MPF activity in fused recipient cytoplasm when reconstruction took place at 0-6 h postactivation of enucleated oocytes. Generations 1, 2, 3, 4, 5, and 6 of cloned goat embryos were produced by a combination of nuclear transplantation and in vitro techniques. After transfer to recipients, 45 kids were obtained, including three pairs of monozygotic twins, three series of monozygotic triplets, two series of monozygotic quadruplets, three series of monozygotic quintuplets, and one series of monozygotic heptaplets. The present study indicates that normal DNA replication of goat blastomere nuclei can be accomplished in enucleated oocytes when MPF activity is low, regardless of the stage of the cell cycle of donor nuclei; induction of NEBD and prematuration chromosome condensation is not essential for further development of reconstructed goat embryos.

Rising trizygotic triplet rates in Japan, 1975-1994.

Zygosity of triplet births in Japan was estimated by Allen's equation with the assumption that the rate of dizygotic (DZ) triplets reflects that of twins. Whereas the DZ triplet rate increased during the period from 1975 to 1994, reflecting the increase in the DZ twinning rate in the period, monozygotic (MZ) triplet rates remained constant from 1975 (28 per million births) to 1994 (23). The trizygotic (TZ) triplet rate gradually increased from 1975 (18) up to 1985 (29), and rapidly increased thereafter to 1994 (202). The higher TZ triplet rate since 1986 is most likely attributed to the higher proportion of mothers treated with ovulation-inducing hormones and partially to in-vitro fertilization in Japan. As for maternal age, MZ triplet rates remained nearly constant for all the maternal age groups except the youngest and the oldest ones. On the other hand, TZ triplet rates increased up to the age group of 30-34 years and decreased thereafter in almost every year. The TZ rate in the age group of 30-34 years slowly increased from 1975 to 1988 (63 per million births) and rapidly increased thereafter (314 in 1994). The TZ rate was statistically significantly higher in the period 1986-1994 than in the period 1975-1985 in each of the nine districts in Japan. Geographical variations in the TZ rates in the latest period have drastically changed from those during the period from 1955-1959 and in 1974.

Agenesis of the corpus callosum: female monozygotic triplets

A case of identical (monozygotic) triplets, two of whom have agenesis of the corpus callosum, is presented. Prenatal ultrasonography and magnetic resonance imaging revealed two of the triplets to have agenesis of the corpus callosum and the third triplet to have an intact corpus callosum. No such case has been reported in the literature. Theories of the etiology and pathogenesis of corpus callosum agenesis are discussed. In this case, unequal X-inactivation as related to the twinning process is implicated as the cause of the agenesis.

X‐chromosome inactivation is mostly random in placental tissues of female monozygotic twins and triplets

X‐chromosome inactivation is mostly random in placental tissues of female monozygotic twins and triplets

Monozygotic triplets in the mare

Monozygotic triplets in the mare

Tonsillar ectopia and Chiari malformations: monozygotic triplets

A unique case of monozygotic triplets, each of whom exhibits variable degrees of tonsillar ectopia, is reported. Patient X presented with a Chiari I malformation and associated syringomyelia; examination of patients Y and Z showed 4 mm and 2.5 mm of tonsillar ectopia, respectively. No such case has been reported in the literature. The discussion defines the current magnetic resonance criteria for diagnosis of hindbrain malformations and addresses the question of whether these disorders represent a spectrum or separate disease entities, with specific emphasis on genetic predisposition. Due to the 100% concordance in this case the presence of a common hereditary factor in the etiology of these malformations is highly suggested.