scispace - formally typeset
Search or ask a question
Author

Jan W.A de Vries

Bio: Jan W.A de Vries is an academic researcher from University of Amsterdam. The author has contributed to research in topics: Population & Copy-number variation. The author has an hindex of 10, co-authored 10 publications receiving 1422 citations.

Papers
More filters
Journal ArticleDOI
TL;DR: Preimplantation genetic screening did not increase but instead significantly reduced the rates of ongoing pregnancies and live births after IVF in women of advanced maternal age.
Abstract: BACKGROUND Pregnancy rates in women of advanced maternal age undergoing in vitro fertilization (IVF) are disappointingly low. It has been suggested that the use of preimplantation genetic screening of cleavage-stage embryos for aneuploidies may improve the ef- fectiveness of IVF in these women. METHODS We conducted a multicenter, randomized, double-blind, controlled trial comparing three cycles of IVF with and without preimplantation genetic screening in women 35 through 41 years of age. The primary outcome measure was ongoing pregnancy at 12 weeks of gestation. The secondary outcome measures were biochemical preg- nancy, clinical pregnancy, miscarriage, and live birth. RESULTS Four hundred eight women (206 assigned to preimplantation genetic screening and 202 assigned to the control group) underwent 836 cycles of IVF (434 cycles with and 402 cycles without preimplantation genetic screening). The ongoing-pregnancy rate was significantly lower in the women assigned to preimplantation genetic screen- ing (52 of 206 women (25%)) than in those not assigned to preimplantation genetic screening (74 of 202 women (37%); rate ratio, 0.69; 95% confidence interval (CI), 0.51 to 0.93). The women assigned to preimplantation genetic screening also had a significantly lower live-birth rate (49 of 206 women (24%) vs. 71 of 202 women (35%); rate ratio, 0.68; 95% CI, 0.50 to 0.92). CONCLUSIONS Preimplantation genetic screening did not increase but instead significantly reduced the rates of ongoing pregnancies and live births after IVF in women of advanced maternal age. (Current Controlled Trials number, ISRCTN76355836.)

640 citations

Journal ArticleDOI
TL;DR: It is suggested that the existence of this deletion as a polymorphism reflects a balance between haploid selection, which culls gr/gr-deleted Y chromosomes from the population, and homologous recombination, which continues to generate newgr/gr deletions.
Abstract: Many human Y-chromosomal deletions are thought to severely impair reproductive fitness, which precludes their transmission to the next generation and thus ensures their rarity in the population. Here we report a 1.6-Mb deletion that persists over generations and is sufficiently common to be considered a polymorphism. We hypothesized that this deletion might affect spermatogenesis because it removes almost half of the Y chromosome's AZFc region, a gene-rich segment that is critical for sperm production. An association study established that this deletion, called gr/gr, is a significant risk factor for spermatogenic failure. The gr/gr deletion has far lower penetrance with respect to spermatogenic failure than previously characterized Y-chromosomal deletions; it is often transmitted from father to son. By studying the distribution of gr/gr-deleted chromosomes across the branches of the Y chromosome's genealogical tree, we determined that this deletion arose independently at least 14 times in human history. We suggest that the existence of this deletion as a polymorphism reflects a balance between haploid selection, which culls gr/gr-deleted Y chromosomes from the population, and homologous recombination, which continues to generate new gr/gr deletions.

428 citations

Journal ArticleDOI
TL;DR: Preimplantation genetic screening did not increase but instead significantly reduced the rates of ongoing pregnancies and live births after IVF in women of advanced maternal age.
Abstract: Both in vitro fertilization (IVF) and preimplantation genetic screening are being increasingly used, the latter for women of advanced maternal age. Observational studies show that, when screening is added to IVF, implantation rates increase but rates of ongoing pregnancies do not. Some researchers believe that preimplantation genetic screening of cleavage-stage embryos for aneuploidies may make IVF more effective. The present multicenter, randomized, double blind, controlled trial compared 3 cycles of IVF with embryo selection based either on preimplantation genetic screening or on the morphologic features of the embryo. Of the 408 participants, all women ranging in age from 35 through 41 years, 206 were assigned to preimplantation genetic screening. Screening accompanied 434 of 836 cycles of IVF. Screening began 3 days after follicular aspiration by biopsying a single blastomere on all embryos having 4 or more blastomeres. Compared with control women, those having preimplantation genetic screening had a significantly lower rate of ongoing pregnancy (25% vs. 37%). The rate ratio was 0.69, with a 95% confidence interval (CI) of 0.51-0.93. Biochemical and clinical pregnancy rates also were significantly lower in the screened group, but there was no significant difference in rates of miscarriage. Women assigned to genetic screening had a significantly lower rate of live births than control subjects (24% vs. 35%). The rate ratio was 0.68, with a 95% CI of 0.50-0.92. Not only did preimplantation genetic screening fail to increase rates of ongoing pregnancy and live births following IVF in this population of older women, but observed rates were lower than in control (unscreened) women. At present, preimplantation genetic screening should not be routinely performed in women of advanced maternal age who undergo IVF. It is not clear whether different results would be obtained in women with indications for genetic screening other than advanced maternal age.

196 citations

Journal ArticleDOI
TL;DR: Phenotypic differences between patients with different deletions suggest a dose effect of the DAZ genes, and two different partial deletions were found that were not detected by PCR with conventional markers.

54 citations

Journal ArticleDOI
TL;DR: The use of both models, one before start of the IVF cycle and one at the time of OPU, allows an accurate prediction of the chance of TFF and is useful in counseling patients on whether to opt for IVF or ICSI.

53 citations


Cited by
More filters
Journal ArticleDOI
TL;DR: Rapidly accumulating evidence indicates that structural variants can comprise millions of nucleotides of heterogeneity within every genome, and are likely to make an important contribution to human diversity and disease susceptibility.
Abstract: The first wave of information from the analysis of the human genome revealed SNPs to be the main source of genetic and phenotypic human variation. However, the advent of genome-scanning technologies has now uncovered an unexpectedly large extent of what we term 'structural variation' in the human genome. This comprises microscopic and, more commonly, submicroscopic variants, which include deletions, duplications and large-scale copy-number variants - collectively termed copy-number variants or copy-number polymorphisms - as well as insertions, inversions and translocations. Rapidly accumulating evidence indicates that structural variants can comprise millions of nucleotides of heterogeneity within every genome, and are likely to make an important contribution to human diversity and disease susceptibility.

1,804 citations

Journal ArticleDOI
01 Dec 2007-Diabetes
TL;DR: The strength of the GWA is that it has the potential to identify genes of high genetic effect that were previously unsuspected as candidates, and is not biased by a priori assumptions based on prior observations of the phenotype.
Abstract: It has long been appreciated that there is a genetic component to type 2 diabetes, but progress in gene finding has been slow because the genetic component is complex. Accumulating data on various diabetes-related phenotypes suggest that so-called “type 2 diabetes” is likely a collection of many diseases due to varying but often overlapping underlying mechanisms. As such, the search for the once hoped-for simple genetic basis of type 2 diabetes has proved elusive. This year marks the application of the next gene-finding tool to the study of type 2 diabetes, the genome-wide association study (GWA). This type of study is the logical extension of the candidate gene association study, an approach in which a few (1–20 or so) single nucleotide polymorphisms (SNPs) within a single gene are tested for association with the phenotype of interest. By that approach, the candidate gene is chosen based on biochemistry or physiology related to that phenotype. The candidate gene approach has identified some genes but has not yielded the definitive picture of the genetic contribution to type 2 diabetes (Table 1; reviewed in [1]). In contrast, the GWA approach tests every gene by testing the association of SNPs in every known gene (∼100,000 SNPs) or in both known genes and in regions outside of genes throughout the genome (∼300,000 to 1 million). The GWA is therefore not biased by a priori assumptions based on prior observations of the phenotype (e.g., kinetics of insulin signaling, glucose-mediated insulin secretion, etc). Therefore, the strength of the GWA is that it has the potential to identify genes of high genetic effect that were previously unsuspected as candidates. The latter might be because little was known about the genes previously or because investigators simply had not addressed the action of the products of these genes …

1,110 citations

Journal ArticleDOI
TL;DR: The past six years have witnessed a virtual explosion in the identification of gene mutations or polymorphisms that cause or are linked to human infertility, but translation of these findings to the clinic remains slow, however, as do new methods to diagnose and treat infertile couples.
Abstract: Reproduction is required for the survival of all mammalian species, and thousands of essential 'sex' genes are conserved through evolution. Basic research helps to define these genes and the mechanisms responsible for the development, function and regulation of the male and female reproductive systems. However, many infertile couples continue to be labeled with the diagnosis of idiopathic infertility or given descriptive diagnoses that do not provide a cause for their defect. For other individuals with a known etiology, effective cures are lacking, although their infertility is often bypassed with assisted reproductive technologies (ART), some accompanied by safety or ethical concerns. Certainly, progress in the field of reproduction has been realized in the twenty-first century with advances in the understanding of the regulation of fertility, with the production of over 400 mutant mouse models with a reproductive phenotype and with the promise of regenerative gonadal stem cells. Indeed, the past six years have witnessed a virtual explosion in the identification of gene mutations or polymorphisms that cause or are linked to human infertility. Translation of these findings to the clinic remains slow, however, as do new methods to diagnose and treat infertile couples. Additionally, new approaches to contraception remain elusive. Nevertheless, the basic and clinical advances in the understanding of the molecular controls of reproduction are impressive and will ultimately improve patient care.

840 citations

Journal ArticleDOI
TL;DR: A multivariable model is proposed based on the findings to classify embryos according to their probability of implantation and it is proposed that the image acquisition and time-lapse analysis system makes it possible to determine exact timing of embryo cleavages in a clinical setting.
Abstract: background: Time-lapse observation presents an opportunity for optimizing embryo selection based on morphological grading as well as providing novel kinetic parameters, which may further improve accurate selection of viable embryos. The objective of this retrospective study was to identify the morphokinetic parameters specific to embryos that were capable of implanting. In order to compare a large number of embryos, with minimal variation in culture conditions, we have used an automatic embryo monitoring system. methods: Using a tri-gas IVF incubator with a built-in camera designed to automatically acquire images at defined time points, we have simultaneously monitored up to 72 individual embryos without removing the embryos from the controlled environment. Images were acquired every 15 min in five different focal planes for at least 64 h for each embryo. We have monitored the development of transferred embryos from 285 couples undergoing their first ICSI cycle. The total number of transferred embryos was 522, of which 247 either failed to implant or fully implanted, with full implantation meaning that all transferred embryos in a treatment implanted. results: A detailed retrospective analysis of cleavage times, blastomere size and multinucleation was made for the 247 transferred embryos with either failed or full implantation. We found that several parameters were significantly correlated with subsequent implantation (e.g. time of first and subsequent cleavages as well as the time between cleavages). The most predictive parameters were: (i) time of division to 5 cells, t5 (48.8–56.6 h after ICSI); (ii) time between division to 3 cells and subsequent division to 4 cells, s2 (≤0.76 h) and (iii) duration of cell cycle two, i.e. time between division to 2 cells and division to 3 cells, cc2 (≤11.9 h). We also observed aberrant behavior such as multinucleation at the 4 cell stage, uneven blastomere size at the 2 cell stage and abrupt cell division to three or more cells, which appeared to largely preclude implantation. conclusions: The image acquisition and time-lapse analysis system makes it possible to determine exact timing of embryo cleavages in a clinical setting. We propose a multivariable model based on our findings to classify embryos according to their probability of implantation. The efficacy of this classification will be evaluated in a prospective randomized study that ultimately will determine if implantation rates can be improved by time-lapse analysis.

738 citations

Journal ArticleDOI
TL;DR: There is an urgent need to prioritize research in reproductive physiology and pathophysiology, particularly in highly industrialized countries facing decreasing populations, because environmental exposures arising from modern lifestyle, rather than genetics, are the most important factors in the observed trends.
Abstract: It is predicted that Japan and European Union will soon experience appreciable decreases in their populations due to persistently low total fertility rates (TFR) below replacement level (2.1 child ...

631 citations