1/27. Molecular cloning of translocation breakpoints in a case of constitutional translocation t(11;22)(q23;q11) and preparation of probes for preimplantation genetic diagnosis.in vitro fertilization (IVF) centres with preimplantation genetic diagnosis (PGD) programmes are often confronted with the problem of identifying chromosomal abnormalities in interphase cells biopsied from preimplantation embryos of carriers of a reciprocal translocation. The present authors have developed a dna testing based approach to analyse embryos from translocation carriers, and this report describes breakpoint-spanning probes to detect abnormalities in cases of the most common human translocation (i.e. the t(11;22)(q23;q11)). Screening a yeast artificial chromosome (YAC) library for probes covering the respective breakpoint regions in the patient lead to probes for the breakpoint on chromosome 11q23. The physically mapped YAC and bacterial artificial chromosome (BAC) clones from chromosome 22 were then integrated with the cytogenetic map, which allowed localization of the breakpoint on chromosome 22q11 to an interval of less than 84 kb between markers D22S184 and KI457 and to prepare probes suitable for interphase cell analysis. In summary, breakpoint localization could be accomplished in about 4 weeks with additional time needed to optimize probes for use in PGD.- - - - - - - - - - ranking = 1keywords = preimplantation, embryo (Clic here for more details about this article) |
2/27. Preimplantation genetic diagnosis of a reciprocal translocation t(3;11)(q27.3;q24.3) in siblings.Preimplantation genetic diagnosis (PGD) was performed in two couples to avoid chromosomally unbalanced progeny in a family in which a brother and a sister carry an identical maternally inherited balanced translocation t(3;11)(q27.3;q24.3). Embryos were biopsied 3 days after fertilization and blastomeres were analysed by fluorescent in-situ hybridization (FISH). Embryos were classified as unbalanced or normal/balanced. In the first case, the male carrier and his wife underwent one IVF/PGD treatment cycle. In all, 18 embryos were analysed. Of those, 15 revealed an unbalanced karyotype. For one embryo, results were not conclusive, from one embryo results were contradictory and one embryo was classified as normal/balanced and subsequently transferred. A singleton pregnancy was achieved. The PGD analysis was confirmed at 16 weeks gestation by amniocentesis. At term, a healthy girl with a balanced karyotype was born. Pregnancy and delivery were without complications. In the second case, the female carrier and her husband underwent two IVF/PGD treatment cycles. During the first cycle, three embryos were analysed. One embryo revealed an unbalanced karyotype and two embryos were designated a normal/balanced karyotype and transferred but no pregnancy was achieved. During the second PGD cycle three embryos were analysed. Of those, none appeared suitable for transfer. The couple decided not to undergo further treatment. Our results indicate that for individuals carrying a reciprocal translocation PGD is a feasible approach to obtain embryos with a normal chromosome balance and to avoid both spontaneous and induced abortion.- - - - - - - - - - ranking = 0.069034662400053keywords = embryo (Clic here for more details about this article) |
3/27. female gamete segregation in two carriers of translocations involving 2q and 14q.FISH, using a combination of whole-chromosome painting and telomeric probes, was used to study the gamete segregation of two female carriers of translocations involving the same chromosome arms, 2q and 14q. Preimplantation genetic diagnosis of the first polar bodies of these oocytes permitted selecting normal embryos for replacement.- - - - - - - - - - ranking = 0.0076705180444504keywords = embryo (Clic here for more details about this article) |
4/27. Outcome of preimplantation genetic diagnosis of translocations.OBJECTIVE: To review 35 cases of preimplantation genetic diagnosis (PGD) of translocations with several methods, including telomeric probes. DESIGN: Retrospective study. SETTING: Clinical IVF laboratory. PATIENT(s): Thirty-five couples with one partner carrying a chromosomal translocation. INTERVENTION(s): PGD of translocation after polar-body or embryo biopsy. MAIN OUTCOME MEASURE(s): pregnancy outcome. RESULT(s): Several trends were observed. First, PGD can achieve a statistically significant reduction in spontaneous abortion, from 95% to 13%. Second, the chances of achieving pregnancy are correlated with 50% or more of the embryos being chromosomally normal. Third, patients with robertsonian translocations produced fewer abnormal gametes and more pregnancies than did patients with reciprocal translocations. Fourth, a new fluorescence in situ hybridization protocol for PGD of translocations, which involves applying telomeric probes, has proved adequately reliable with a 6% average error rate. CONCLUSION(s): PGD of translocations achieves a statistically significant reduction in spontaneous abortion, both for polar-body and blastomere biopsy cases. pregnancy outcome depended on the number of normal embryos available for transfer, with patients having <50% abnormal embryos achieving the most pregnancies. Because robertsonian translocations caused fewer abnormal embryos than reciprocal translocations, they also resulted in higher rates of implantation.- - - - - - - - - - ranking = 0.85890172681483keywords = preimplantation, embryo (Clic here for more details about this article) |
5/27. Hydatiform mole with coexisting live fetus in dichorionic twin gestation.A case of dichorionic twin pregnancy was diagnosed in a 29-year-old, on routine ultrasound at 12 weeks. Subsequent ultrasounds for persistent vaginal bleeding at 16 weeks revealed molar placenta with viable fetus in both gestational sacs. The patient declined any invasive prenatal testing to confirm the karyotype of the fetus. The pregnancy was managed expectantly until 21 weeks, when she had a spontaneous abortion of twin fetuses and separate placentae with attached molar tissue. A final karyotype on cord blood samples confirmed 46XY and 46XX for both fetuses. Histopathology of molar tissue reported complete mole, with diploid chromosomal pattern on subsequent dna flow cytometry. The clinical, ultrasound and chromosomal examination suggest that there has been a quadruplet pregnancy where two embryos developed into normal fetuses and other two degenerated to complete moles.- - - - - - - - - - ranking = 0.0076705180444504keywords = embryo (Clic here for more details about this article) |
6/27. Maternal origin of monosomy 21 derived from ICSI.With the worldwide diffusion of the intracytoplasmic sperm injection (ICSI) procedure in recent years, the issue of possible genetic risks of this new and powerful technique has attracted considerable attention. An important concern is whether ICSI facilitated the passage of genetic defects from spermatozoa to offspring. ICSI was performed with spermatozoa from a frozen-thawed sperm sample from a testicular sperm extraction (TESE) of a 38 year old man who suffered from azoospermia. His wife was 36 years old. The resulting pregnancy spontaneously aborted at 8 weeks gestation after embryo replacement. Cytogenetic investigation displayed monosomy 21. The paternal origin of the single chromosome 21 was determined by molecular analysis. The segregation error leading to loss of one chromosome 21 is likely to have occurred during oogenesis rather than as a direct consequence of ICSI. Nonetheless, monosomy 21 is extremely rare and it cannot be excluded that ICSI assisted the fertilization of an abnormal oocyte.- - - - - - - - - - ranking = 0.0076705180444504keywords = embryo (Clic here for more details about this article) |
7/27. Low incidence of UPD in spontaneous abortions beyond the 5th gestational week.Approximately 15-20% of all clinically recognised pregnancies abort, most commonly between 8-12 gestational weeks. While the majority of early pregnancy losses is attributed to cytogenetic abnormalities, the aetiology of approximately 40% of early abortions remains unclear. To determine additional factors causing spontaneous abortions we retrospectively searched for uniparental disomies (UPD) in 77 cytogenetically normal diploid spontaneous abortions. In all cases an unbalanced chromosome anomaly was ruled out by cytogenetic investigation of chorionic/amniotic membranes and/or chorionic villi. For UPD screening microsatellite analyses were performed on dna of abortion specimens and parental blood using highly polymorphic markers showing UPD in two cases. The distribution of markers analysed indicated maternal heterodisomy for chromosome 9 (UPhD(9)mat) in case 1 and paternal isodisomy for chromosome 21 (UPiD(21)pat) in case 2. The originating mechanism suggested was monosomy complementation in UPiD(21)pat and trisomy rescue in UPhD(9)mat. In the case of UPhD(9)mat purulent chorioamnionitis was noted and a distinctly growth retarded embryo of 3 cm crown-rump length showing no gross external malformations. Histological analysis in the case of UPiD(21)pat suggested a primary anlage defect. Our results indicate that less than 3% of genetically unexplained pregnancy wastage is associated with total chromosome UPD. UPD may contribute to anlage defects of human conception. Chromosome aneuploidy correction can occur in very early cleavage stages. More research, however, ought to be performed into placental mosaicism to further clarify timing and mechanisms involved in foetal UPD.- - - - - - - - - - ranking = 0.0076705180444504keywords = embryo (Clic here for more details about this article) |
8/27. cholesterol and development: the RSH ("Smith-Lemli-Opitz") syndrome and related conditions.The half-century of lipophobia in the united states may be abating with some return of sanity on the discussion of health and dietary fat [Taubes, 2001]. The youngest victims of this collective, decades long madness are those infants deprived for one reason or another of breast milk. They are unable to speak for themselves at a time of greatest need for cholesterol during growth, the most critical period of myelination of central and peripheral nervous system, formation of bone and bile, and of every steroid hormone. Some of the commercial formulas they are fed contain only 1 or 2 mg of cholesterol per 100 g edible portion contrasted with almost 14 mg in breast milk. One can only hope that the confidence in their endogenous ability to synthesize sufficient amounts of cholesterol is not misplaced. Pediatric pathology has learned that when this endogenous ability fails during embryogenesis on the basis of mutations in the postsqualene biosynthesis of cholesterol, a startling variety of developmental pathology may present itself ranging from lethal forms of "idiopathic" hydrops, microcephaly with cerebral dysgenesis and dysmyelinization, agenesis of corpus callosum, cerebellar vermis dysgenesis, cataracts, cleft palate, many different forms of congenital heart defect, pyloric stenosis and/or Hirschsprung dysganglionosis, adrenal (cortical) insufficiency, cholestatic liver disease, limb malformations, and genital ambiguity in genetic males. population genetic considerations suggest a hypothetical birth prevalence of the RSH (so-called Smith-Lemli-Opitz) syndrome, the commonest of these Garrodian errors of cholesterol biosynthesis, of 1/2500; since only about 1/15,000 to 1/20,000 homozygotes are liveborn and biochemically confirmed, over 80% prenatal or perinatal mortality must occur and deserves the most discerning of services from birth attendants, perinatologists, neonatologists, and fetal/pediatric pathologists. An easy, reliable, economical biochemical test for the presence of 7-dehydrocholesterol is available and the commonest mutation, the IVS8-1G-->C mutation, is quickly and reliably tested for molecularly. Thus, the successful diagnosis, even after death, will contribute substantially to correct genetic counseling, carrier detection, prenatal diagnosis, and treatment in those known to be affected prenatally andplanned to be liveborn. Thus, developmental pathology plays an integral, vital role in preventive medicine.- - - - - - - - - - ranking = 0.0076705180444504keywords = embryo (Clic here for more details about this article) |
9/27. Twin gestation in one horn of a bicornuate uterus.We report a rare case of twin pregnancy in the same horn of a bicornuate uterus. This patient's uterine malformation was detected for the first time when she experienced abdominal pain at 6 weeks of amenorrhea. Transabdominal and transvaginal sonographic examinations were performed. Both embryos showed cardiac motion on transvaginal sonography. The patient was re-examined monthly. Her pregnancy ended in spontaneous abortion at 22 weeks. Two live male fetuses were delivered, but they both died immediately after their birth. Sonography, particularly transvaginal sonography, is valuable for early detection of uterine abnormalities that may affect the outcome of pregnancy.- - - - - - - - - - ranking = 0.0076705180444504keywords = embryo (Clic here for more details about this article) |
10/27. Preimplantation genetic diagnosis of chromosome abnormalities: implications from the outcome for couples with chromosomal rearrangements.OBJECTIVES: Chromosomal rearrangements can lead to infertility or repeated spontaneous or induced abortions. The use of preimplantation genetic diagnosis (PGD) allows the selected transfer of chromosomally balanced embryos. The aim of this study was to carry out detailed analysis of the outcome of 11 PGD cycles for 8 patients carrying various chromosomal rearrangements. methods: patients underwent routine in vitro fertilisation with biopsy of embryos on day 3. Specific fluorescent in situ hybridisation protocols were developed for each couple. embryo transfer was possible in all 11 cycles. RESULTS: The outcome was four pregnancies, leading to three live births and one biochemical pregnancy. Post-zygotic mosaicism was detected in 75% of untransferred embryos, the majority of which were chaotic. Detailed follow-up and analysis provided evidence for the co-existence of chromosomally balanced and abnormal cells in six embryos. The mechanisms involved included chromosome breakage and loss of material. CONCLUSIONS: biopsy and analysis of two blastomeres, where possible, reduced the risk of misdiagnosis in cases of balanced/aneuploid mosaics. The three live births achieved for the eight couples treated in this series, despite the poor history in almost all cases, is further proof that a policy of biopsying two cells from embryos consisting of six or more cells and a single cell from four- or five-cell embryos is compatible with a positive outcome.- - - - - - - - - - ranking = 0.21013293558522keywords = preimplantation, embryo (Clic here for more details about this article) |
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