| 1. |
- Ginström Ernstad, Erica, et al.
(författare)
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Preimplantation genetic testing and child health: a national register-based study
- 2023
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 38:4, s. 739-750
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION Is preimplantation genetic testing (PGT) associated with adverse perinatal outcome and early childhood health? SUMMARY ANSWER Children born after PGT had comparable perinatal outcomes to children born after IVF/ICSI and comparable findings regarding early childhood health. WHAT IS KNOWN ALREADY PGT is offered to couples affected by monogenic disorders (PGT-M) or inherited chromosomal aberrations (PGT-SR), limiting the risk of transferring the disorder to the offspring. PGT, an invasive technique, requires genetic analysis of one or up to ten cells from the embryo and is combined with IVF or ICSI. Several studies, most of them small, have shown comparable results after PGT and IVF/ICSI concerning perinatal outcome. Only a few studies with limited samples have been published on PGT and childhood health. STUDY DESIGN, SIZE, DURATION We performed a register-based study including all singletons born after PGT (n = 390) in Sweden during 1 January 1996-30 September 2019. Singletons born after PGT were compared with all singletons born after IVF/ICSI (n = 61 060) born during the same period of time and with a matched sample of singletons (n = 42 034) born after spontaneous conception selected from the Medical Birth Register. Perinatal outcomes, early childhood health, and maternal outcomes were compared between pregnancies after PGT and IVF/ICSI as well as between pregnancies after PGT and spontaneous conception. Primary outcomes were preterm birth (PTB) and low birthweight (LBW) whereas childhood morbidity was the secondary outcome. PARTICIPANTS/MATERIALS, SETTING, METHODS Data on women who went through PGT and gave birth were obtained from the local databases at the two PGT centres in Sweden, whereas data on IVF treatment for the IVF/ICSI group were obtained from the national IVF registers. These data were then cross-linked to national health registers; the Medical Birth Register, the Patient Register, and the Cause of Death Register. Logistic multivariable regression analysis and Cox proportional hazards models were performed with adjustment for relevant confounders. MAIN RESULTS AND THE ROLE OF CHANCE The mean follow-up time was 4.6 years for children born after PGT and 5.1 years for children born after spontaneous conception, whereas the mean follow-up time was 9.0 years for children born after IVF/ICSI. For perinatal outcomes, PTB occurred in 7.7% of children after PGT and in 7.3% of children after IVF/ICSI, whereas the rates were 4.9% and 5.2% for LBW (adjusted odds ratio (AOR) 1.22, 95% CI 0.82-1.81 and AOR 1.17, 95% CI 0.71-1.91, respectively). No differences were observed for birth defects. In comparison to spontaneous conception, children born after PGT had a higher risk for PTB (AOR 1.73, 95% CI 1.17-2.58). Regarding early childhood health, the absolute risk of asthma was 38/390 (9.7%) in children born after PGT and 6980/61 060 (11.4%) in children born after in IVF/ICSI, whereas the corresponding numbers were 34/390 (8.7%) and 7505/61 060 (12.3%) for allergic disorders. Following Cox proportional hazards models, no significant differences were found for these outcomes. Sepsis, hypothyroidism, attention deficit hyperactivity disorder, autism spectrum disorders, mental retardation, cerebral palsy, and epilepsy were diagnosed in a maximum of three PGT children. No PGT children died during the follow-up period. Regarding maternal outcomes, the rates of placenta praevia and caesarean delivery were significantly higher after PGT in comparison to spontaneous conception (AOR 6. 46, 95% CI 3.38-12.37 and AOR 1.52, 95% CI 1.20-1.92, respectively), whereas no differences were seen comparing pregnancies after PGT and IVF/ICSI. LIMITATIONS, REASONS FOR CAUTION The rather small sample size of children born after PGT made it impossible to adjust for all relevant confounders including fertilization method and culture duration. Moreover, the follow-up time was short for most of the children especially in the PGT group, probably lowering the absolute number of diagnoses in early childhood. WIDER IMPLICATIONS OF THE FINDINGS The results are reassuring and indicate that the embryo biopsy itself has no adverse effect on the perinatal, early childhood, or maternal outcomes. Although the results are comparable to IVF/ICSI also regarding early childhood outcome, they should be taken with caution due to the low number of children with diagnoses and short follow-up time. Long-term follow-up studies on children born after PGT are scarce and should be conducted considering the invasiveness of the technique. STUDY FUNDING/COMPETING INTEREST(S) The study was financed by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (LUA/ALF 70940), the Board of National Specialised Medical Care at Sahlgrenska University Hospital and Hjalmar Svensson Research Foundation. There are no conflicts of interest to declare.
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| 2. |
- Landin-Wilhelmsen, Kerstin, 1952, et al.
(författare)
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Spontaneous pregnancies in a Turner syndrome woman with Y-chromosome mosaicism.
- 2004
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Ingår i: Journal of assisted reproduction and genetics. - 1058-0468. ; 21:6, s. 229-30
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To present a case involving pregnancies in a Turner woman with Y-chromosome mosaicism. METHOD: A descriptive case report of a single patient. RESULTS: A 39-year-old woman was admitted to the endocrine clinic due to fatigue and premature menopause. She had tried in-vitro fertilization and oocyte donation twice without pregnancies but became spontaneously pregnant at age 36 and 37 and delivered two girls. During the seventh month of the second pregnancy, a dissecting aortic aneurysm, a coarctation, and subsequently a pheochromocytoma were detected and repaired. Hypothyroidism developed. Turner syndrome was diagnosed. Fluorescence in situ hybridization (FISH) analysis of lymphocytes revealed 31% XY cells and 4% XYY cells, while 66% of buccal cells had an XY constitution. Oophorectomy revealed no malignancy. FISH revealed 54% XY cells in the left gonad and 38% XY cells in the right. CONCLUSION: Turner syndrome should be suspected in women with aortic dissection, in general, but especially in those with additional features such as horseshoe kidney, coarctation, and infertility.
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| 3. |
- Aguilar, Ximena, et al.
(författare)
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Myofibroblasts in the normal conjunctival surface.
- 2010
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Ingår i: Acta ophthalmologica. - : Wiley. - 1755-3768 .- 1755-375X. ; 88:4, s. 407-12
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate the occurrence of myofibroblasts (MFBs) in the normal conjunctival surface and to evaluate any anatomical and time-related variations. METHODS: MFBs were screened among healthy individuals (35 eyes) by collecting impression cytology (IC) samples from the bulbar conjunctiva. A cohort of volunteers (12 eyes) was followed for 1 year by taking two to five imprints every month. MFBs were identified by immunohistochemical localization of the MFB marker alpha-smooth-muscle actin (alpha-SMA). RESULTS: Using a filter imprint technique, MFBs were found consistently in 94% of samples from the conjunctival surface of participating individuals. The overall MFB levels, expressed as percentage of all cells on the filter, were highest in March-May [mean 4.1%, standard deviation (SD) +/- 1.5] and lowest in December-February (mean 1.2%, SD +/- 0.5). The difference was statistically significant [p < 0.0005, Friedman test, one-way repeated measures analysis of variance (anova)]. Moreover, there was a clear divergence of MFB density between the nasal, temporal, superior and inferior bulbar conjunctiva (mean 1.7%, 1.9%, 22% and 9.7%, respectively). CONCLUSION: MFBs, known as a cellular constituent of granulation tissue in wound healing, occur in the normal conjunctival surface, which is a novel finding. Our results also show that MFB level follows a seasonal variation pattern in a temperate climate, increasing in April-September and decreasing in October-March. This variation might reflect a degree of a transient or ongoing state of tissue repair after conjunctival trauma or stress caused by exposure to environmental factors.
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| 4. |
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| 5. |
- Barrenäs, Marie-Louise, 1952, et al.
(författare)
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Ear and hearing in relation to genotype and growth in Turner syndrome.
- 2000
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Ingår i: Hearing research. - 0378-5955. ; 144:1-2, s. 21-8
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Tidskriftsartikel (refereegranskat)abstract
- Hearing loss, auricular anomalies and middle ear infections are common findings in many genetic disorders, but the mechanisms have remained unknown. We studied ear and hearing problems in Turner's syndrome (TS) in relation to the degree of X chromosome loss (i.e. degree of mosaicism) and growth. One hundred and nineteen girls and women with TS were studied regarding audiometry, fluorescent in situ hybridisation, serum concentration of insulin-like growth factor-1 (IGF-1) and body height. It was found that sensorineural hearing loss and occurrence of auricular anomalies were significantly increased the greater the proportion of 45,X cells in a particular individual (P<0.05 and P<0.001, respectively). Middle ear infections and sensorineural hearing loss were negatively correlated with IGF-1 (P<0.05 and P<0.001, respectively). Hearing correlated positively with height (P<0.01) and IGF-1 independently of age (P<0.05). Height correlated positively with IGF-1 (P<0.001). Auricular malformations, middle ear infections and hearing impairment in TS were interpreted as due to growth disturbances during development. A new hypothesis on the pathophysiology of external, middle and inner ear disorders due to a delayed cell cycle caused by chromosomal aberrations per se and not only to the specific X chromosome deletion is presented.
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| 6. |
- Bryman, Inger, et al.
(författare)
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Pregnancy rate and outcome in Swedish women with Turner syndrome
- 2011
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 1556-5653 .- 0015-0282. ; 95:8, s. 2507-2510
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Tidskriftsartikel (refereegranskat)abstract
- Pregnancies occurred in 57 (12%) of 482 Swedish women with Turner syndrome with a liveborn rate of 54% in 124 pregnancies. Spontaneous pregnancies occurred in 40%, mainly in women with 45,X/46,XX mosaicism, and oocyte donation in 53% where miscarriages were less frequent, odds ratio 0.43 (95% confidence interval 0.17-1.04). (Fertil Steril (R) 2011; 95: 2507-10. (c) 2011 by American Society for Reproductive Medicine.)
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| 7. |
- Caisander, Gunilla, et al.
(författare)
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Chromosomal integrity maintained in five human embryonic stem cell lines after prolonged in vitro culture
- 2006
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Ingår i: Chromosome Res. ; 14:2, s. 131-7
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Tidskriftsartikel (refereegranskat)abstract
- There have been recent reports of human embryonic stem cell (hESC) lines developing chromosomal aberrations after long-term culture, indicating an unstable genomic status due to the in vitro milieu. This raises concern, since it would limit their use in therapeutics. In this study the chromosomal status of five well-characterized hESC lines, SA002, SA002.5, AS034.1.1, SA121 and SA461, was monitored during long-term in vitro culture. The criteria of defined hESCs were met by all of the five hESC lines (four diploid and one trisomic for chromosome 13). The genomes were screened for chromosomal aberrations and rearrangements using comparative genomic hybridization (CGH), interphase fluorescence in situ hybridization (FISH) and traditional karyotyping on several occasions while in culture. The genomic integrity was shown to be maintained after repeated freeze-thaw procedures and continuous culture in vitro for up to 22 months (148 passages). We discuss the most common de novo chromosomal aberrations reported in hESCs, as well as their possible origin.
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| 8. |
- Denes, Anna-Maria, 1988, et al.
(författare)
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The Proportion of Diploid 46,XX Cells Increases with Time in Women with Turner Syndrome-A 10-Year Follow-Up Study
- 2015
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Ingår i: Genetic Testing and Molecular Biomarkers. - : Mary Ann Liebert Inc. - 1945-0265 .- 1945-0257. ; 19:2, s. 82-87
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Tidskriftsartikel (refereegranskat)abstract
- In the normal population, loss of one of the sex chromosomes leading to monosomy (45,X) is a part of the aging process. In Turner syndrome (TS), the classic karyotype 45,X is found in up to 50% at birth, and others have a second cell line; mosaicism. The aim was to study if the chromosomal pattern in TS women changes over time. Fluorescence in situ hybridization was performed on buccal smear cells obtained twice, 10 years apart, from 42 women with TS aged 26-66 years (mean +/- standard deviation: 42.0 +/- 11.6). DNA probes specific for chromosomes X (DXZ1) and Y (DYZ3) were used and >100 cells were analyzed/patient. Nineteen women had monosomy (45,X) (<10% 46,XX), nine had 45,X/46,XX mosaicism, and 14 had iso, ring, or a marker chromosome at baseline. At 10 years, the percentage of diploid cells had increased in 29 of 42 women (69%), with an average increase of 5.7 +/- 13.0%. There was a positive correlation between age and % change in diploid 46,XX or 46,XY cells (r=0.38, p=0.023). This new finding might have relevance for the life expectancy in TS.
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| 9. |
- Egarth, M, et al.
(författare)
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Longterm survival of transplanted corneal epithelial cells and corneal stem cells.
- 2005
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Ingår i: Acta Opthalmologica Scandinavica. - 1395-3907. ; 83, s. 456-61
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate the survival of donor-derived epithelial cells in conventional penetrating keratoplasty (PKP) and in homologous penetrating central limbal keratoplasty (HPCLK). METHODS AND PATIENTS: Epithelial cells from 26 eyes of 26 patients were analysed. All cases were sex-mismatched (i.e. the transplant and patient were of different genders). At suture removal more than 1 year post surgery, epithelial cells were obtained by gently wiping the removed sutures on glass slides. The cell samples were analysed using fluorescent in situ hybridization (FISH) of the sex chromosomes. This technique makes it possible to allocate the origin of each cell nucleus to either the donor or the recipient. RESULTS: All 19 conventional PKPs were clear and seven had donor-derived epithelial cells at suture removal. Five of the seven HPCLK grafts were clear at the time of investigation (365--1355 days post surgery), and donor-derived epithelial cells were found in two grafts. CONCLUSION: Harvesting cells from removed sutures in combination with FISH enables the clinical study of cell survival in corneal transplants without jeopardizing functioning grafts. From the limited sample investigated, the following tentative conclusions can be made. Donor-derived epithelial cells can remain in conventional PKP for over 1 year. In combined stem cell and corneal grafts (HPCLK), donor-derived epithelial cells may also be retrieved at 1 year or beyond following surgery but the correlation between their presence and a remaining clear graft is uncertain.
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| 10. |
- El-Mansoury, Mohamed Mostafa, 1953, et al.
(författare)
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Chromosomal mosaicism mitigates stigmata and cardiovascular risk factors in Turner syndrome.
- 2007
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Ingår i: Clinical endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 66:5, s. 744-51
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study genotype-phenotype correlations in Turner syndrome (TS) regarding body composition, cardiovascular risk factors, stigmata and age at diagnosis vs. degree of mosaicism estimated as the percentage of 45,X and 46,XX cells. METHODS: One hundred and twenty-six TS women, mean age 31 years, were examined by three specialists, who reported stigmata independent of each other. Dual energy X-ray absorptiometry (DXA) was used to measure bone mineral density (BMD). The karyotype was blinded. Fluorescence in situ hybridization (FISH) was performed on buccal cells. A random population sample served as controls. RESULTS: Forty-four per cent exhibited a 45,X karyotype and 56% a second-cell line, while 27% of all had a 45,X/46,XX mosaicism. Five 45,X cases with a conventional karyotype were 45,X/46,XX mosaic according to FISH. At diagnosis, 45,X cases were younger (P < 0.05) and had more stigmata per person (P < 0.01) than the mosaics. TS with marker chromosome X or Y, iso or ring, did not differ from 45,X in this aspect. The mosaics had higher BMD and SHBG and lower total cholesterol and FSH than TS with 45,X and did not differ compared with controls in terms of body mass index (BMI), waist/hip ratio, BMD, blood pressure, cholesterol, triglycerides, SHBG, diabetes or osteoporosis. The number of stigmata correlated positively to BMI, waist/hip ratio, cholesterol and %45,X and inversely to height and %46,XX according to FISH. CONCLUSIONS: Mosaicism seems to mitigate the TS phenotype and the cardiovascular risk factor profile. Mosaics were diagnosed 8 years later than 45,X cases. This emphasizes the necessity for a stricter genotype categorization not only in the clinic but also in research on TS than previously adopted.
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