| 1. |
- Bache, Iben, et al.
(author)
-
An excess of chromosome 1 breakpoints in male infertility.
- 2004
-
In: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 12:12, s. 993-1000
-
Journal article (peer-reviewed)abstract
- In a search for potential infertility loci, which might be revealed by clustering of chromosomal breakpoints, we compiled 464 infertile males with a balanced rearrangement from Mendelian Cytogenetics Network database (MCNdb) and compared their karyotypes with those of a Danish nation-wide cohort. We excluded Robertsonian translocations, rearrangements involving sex chromosomes and common variants. We identified 10 autosomal bands, five of which were on chromosome 1, with a large excess of breakpoints in the infertility group. Some of these could potentially harbour a male-specific infertility locus. However, a general excess of breakpoints almost everywhere on chromosome 1 was observed among the infertile males: 26.5 versus 14.5% in the cohort. This excess was observed both for translocation and inversion carriers, especially pericentric inversions, both for published and unpublished cases, and was significantly associated with azoospermia. The largest number of breakpoints was reported in 1q21; FISH mapping of four of these breakpoints revealed that they did not involve the same region at the molecular level. We suggest that chromosome 1 harbours a critical domain whose integrity is essential for male fertility.
|
|
| 2. |
- Bonduelle, Maryse, et al.
(author)
-
Prospective follow-up of 838 fetuses conceived after ovarian stimulation with corifollitropin alfa: comparative and overall neonatal outcome.
- 2012
-
In: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 27:7, s. 2177-85
-
Journal article (peer-reviewed)abstract
- STUDY QUESTION Is treatment with corifollitropin alfa, a new recombinant gonadotrophin with sustained follicle-stimulating activity, safe in terms of perinatal complications and birth defects in infants conceived following corifollitropin alfa treatment for contolled ovarian stimulation (COS)? SUMMARY ANSWER In terms of neonatal outcome and risk of malformations, treatment with a single dose of corifollitropin alfa during COS is as safe as treatment with daily recombinant FSH (rFSH). WHAT IS KNOWN AND WHAT THIS PAPER ADDS This is the first pooled analysis of individual safety data in terms of neonatal outcome and major and minor congenital malformations collected following intervention trials of corifollitropin alfa. DESIGN Pregnancy and follow-up studies were conducted prospectively and data were collected from all Phase II and III trials with corifollitropin alfa intervention, including two comparative randomized controlled trials (RCTs) in which patients received either a single dose of corifollitropin alfa or daily rFSH for the first 7 days of COS. Patients with ongoing pregnancies at 10 weeks after embryo transfer were followed up to labour and the health of the offspring was assessed up to 4-12 weeks after birth. PARTICIPANTS AND SETTING Following corifollitropin alfa treatment prior to IVF or ICSI, the health of 677 pregnant women, 838 fetuses and 806 live born infants was evaluated. MAIN RESULTS AND THE ROLE OF CHANCE Among 440 fetuses in the corifollitropin alfa arm and 381 fetuses in the rFSH arm of the two RCTs, there were 424 (96.4%) and 370 (98.7%) live births, respectively. Neonatal characteristics, the frequency of premature births and the incidence of infant adverse events were similar in both treatment arms. The overall incidence of any congenital malformations in live born infants was 16.3 and 17.0%, with major malformation rates of 4.0 and 5.4% in the corifollitropin alfa and rFSH groups, respectively [odds ratio (OR) for major malformations, 0.71; 95% confidence interval, 0.36-1.38]. From 838 fetuses assessed in all corifollitropin alfa intervention trials, there were 806 (96.2%) live births with a major malformation rate of 4.5% in live born infants. BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION Both RCTs had a double-blind and active-controlled design and the adjudication of congenital malformations was also performed in a blinded fashion. As the total number of major malformations was limited (37), the confidence interval around the OR was rather wide. GENERALISABILITY TO OTHER POPULATIONS The similarity of corifollitropin alfa and rFSH with respect to the incidence of congenital malformations was consistent across the RCTs and pregnancy type (singleton, multiple). This suggests that this similarity could hold in general. Overall incidences, however, may depend on the definitions of malformations and rules to adjudicate these events as major or minor. STUDY FUNDING/COMPETING INTERESTS Financial support for this study was provided by Merck, Sharp & Dohme Corp. (a subsidiary of Merck & Co. Inc., Whitehouse Station, NJ, USA). TRIAL REGISTRATION NUMBERS NCT00703014, NCT00702624, NCT 00702195, NCT 00702195, NCT 00702988, NCT 00702520, NCT 00702338and NCT 00702234.
|
|
| 3. |
- Ponjaert-Kristoffersen, Ingrid, et al.
(author)
-
Psychological follow-up study of 5-year-old ICSI children
- 2004
-
In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 19:12, s. 2791-2797
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The developmental outcomes of children born after ICSI are still a matter of concern. The purpose of the present study was to investigate psychological outcomes for 5-year-old children born after ICSI and compare these with outcomes for children born after spontaneous conception (SC). METHODS: Three hundred singleton children born after ICSI in Belgium, Sweden and the USA were matched by maternal age, child age and gender. Outcome measures included the Wechsler Preschool and Primary scales of intelligence (WPPSI-R), Peabody Developmental Motor Scales, Parenting Stress Index and Child Behaviour Checklist. RESULTS: Regarding cognitive development, no significant differences were found on WPPSI-R verbal and performance scales between ICSI and SC children. However, some differences were noted on subtests of the Performance Scale. ICSI children more often obtained a score below 1 SD of the mean on the subtests: Object Assembly, Block Design and Mazes (all P < 0.05). Significant differences by site (i.e. Belgium, Sweden and New York) were found on subtests related to parenting stress, child behaviour problems and motor development (all P < 0.05). These findings can probably be explained by variables other than conception mode, such as cultural differences and selection bias. CONCLUSIONS: Although the finding that a higher proportion of ICSI children obtained scores below the cut-off on some of the visual–spatial subscales of the WPPSI-R warrants further investigation, ICSI does not appear to affect the psychological well-being or cognitive development at age 5.
|
|
| 4. |
- Renard, Marjolijn, et al.
(author)
-
Novel MYH11 and ACTA2 mutations reveal a role for enhanced TGF beta signaling in FTAAD
- 2013
-
In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 165:2, s. 314-321
-
Journal article (peer-reviewed)abstract
- Background: Thoracic aortic aneurysm/dissection (TAAD) is a common phenotype that may occur as an isolated manifestation or within the constellation of a defined syndrome. In contrast to syndromic TAAD, the elucidation of the genetic basis of isolated TAAD has only recently started. To date, defects have been found in genes encoding extracellular matrix proteins (fibrillin-1, FBN1; collagen type III alpha 1, COL3A1), proteins involved in transforming growth factor beta (TGF beta) signaling (TGF beta receptor 1 and 2, TGFBR1/2; and SMAD3) or proteins that build up the contractile apparatus of aortic smooth muscle cells (myosin heavy chain 11, MYH11; smooth muscle actin alpha 2, ACTA2; and MYLK).Methods and result: In 110 non-syndromic TAAD patients that previously tested negative for FBN1 or TGFBR1/2 mutations, we identified 7 ACTA2 mutations in a cohort of 43 familial TAAD patients, including 2 premature truncating mutations. Sequencing of MYH11 revealed an in frame splice-site alteration in one out of two probands with TAA(D) associated with PDA but none in the series of 22 probands from the cohort of 110 patients with non-syndromic TAAD. Interestingly, immunohistochemical staining of aortic biopsies of a patient and a family member with MYH11 and patients with ACTA2 missense mutations showed upregulation of the TGF beta signaling pathway.Conclusions: MYH11 mutations are rare and typically identified in patients with TAAD associated with PDA. ACTA2 mutations were identified in 16% of a cohort presenting familial TAAD. Different molecular defects in TAAD may account for a different pathogenic mechanism of enhanced TGF beta signaling.(C) 2011 Elsevier Ireland Ltd. All rights reserved.
|
|
