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• W2144012824 abstract "The aim of this work is to analyze, using the comparative genomic hybridization technique, the frequencies and the mechanisms involved in the production of aneuploidy events in donor oocytes. The results showed that 32.1% of them were aneuploid, with 51.7% of those originating from first meiotic division errors and 48.3% from the presence of aneuploid oogonium. The aim of this work is to analyze, using the comparative genomic hybridization technique, the frequencies and the mechanisms involved in the production of aneuploidy events in donor oocytes. The results showed that 32.1% of them were aneuploid, with 51.7% of those originating from first meiotic division errors and 48.3% from the presence of aneuploid oogonium. Aneuploidy is one of the main causes behind low pregnancy rates in humans (1Bahçe M. Cohen J. Munne S. Preimplantation genetic diagnosis of aneuploidy: were we looking at the wrong chromosomes?.J Assist Reprod Genet. 1999; 16: 176-181Crossref PubMed Scopus (81) Google Scholar). Chromosome abnormalities are found in both early cleavage stage embryos and first trimester, spontaneously aborted fetuses (2Munne S. Alikani M. Tomkin G. Grifo J. Cohen J. Embryo morphology, developmental rates, and maternal age are correlated with chromosome abnormalities.Fertil Steril. 1995; 64: 382-391Abstract Full Text PDF PubMed Google Scholar, 3Boue A. Boue J. Gropp A. Cytogenetics of pregnancy wastage.Adv Hum Genet. 1985; 14: 1-57PubMed Google Scholar). Most of the aneuploidy is due to errors in the female first meiotic division (4Hassold T. Hunt P. To err (meiotically) is human: the genesis of human aneuploidy.Nat Rev Genet. 2001; 2: 280-291Crossref PubMed Scopus (1715) Google Scholar, 5Nicolaidis P. Petersen M.B. Origin and mechanisms of non-disjunction in human autosomal trisomies.Hum Reprod. 1998; 13: 313-319Crossref PubMed Scopus (196) Google Scholar); therefore, the cytogenetic study of oocytes may provide useful data. To describe the aneuploidy rate in oocytes, several groups have analyzed the first polar body (1PB) and its corresponding metaphase II (MII) stage oocyte. Most of the studies were performed using discarded oocytes, generally MI immature oocytes, from IVF patients that were in vitro matured (IVM) until they reached the MII stage. Different investigators describe an aneuploidy rate of around 50%, analyzing IVM-MII oocytes from IVF patients with a mean age of 40 (6Fragouli E. Wells D. Whalley K.M. Mills J.A. Faed M.J. Delhanty J.D. Increased susceptibility to maternal aneuploidy demonstrated by comparative genomic hybridization analysis of human MII oocytes and first polar bodies.Cytogenet Genome Res. 2006; 114: 30-38Crossref PubMed Scopus (56) Google Scholar, 7Gutierrez-Mateo C. Benet J. Wells D. Colls P. Bermudez M.G. Sanchez-Garcia J.F. et al.Aneuploidy study of human oocytes first polar body comparative genomic hybridization and metaphase II fluorescence in situ hybridization analysis.Hum Reprod. 2004; 19: 2859-2868Crossref PubMed Scopus (84) Google Scholar, 8Gutierrez-Mateo C. Wells D. Benet J. Sanchez-Garcia J.F. Bermudez M.G. Belil I. et al.Reliability of comparative genomic hybridization to detect chromosome abnormalities in first polar bodies and metaphase II oocytes.Hum Reprod. 2004; 19: 2118-2125Crossref PubMed Scopus (74) Google Scholar, 9Pellestor F. Anahory T. Hamamah S. The chromosomal analysis of human oocytes. An overview of established procedures.Hum Reprod Update. 2005; 11: 15-32Crossref PubMed Scopus (56) Google Scholar, 10Wells D. Alfarawati S. Fragouli E. Use of comprehensive chromosomal screening for embryo assessment: microarrays and CGH.Mol Hum Reprod. 2008; 14: 703-710Crossref PubMed Scopus (134) Google Scholar, 11Pellestor F. Andreo B. Arnal F. Humeau C. Demaille J. Maternal aging and chromosomal abnormalities: new data drawn from in vitro unfertilized human oocytes.Hum Genet. 2003; 112: 195-203PubMed Google Scholar). The considerably high aneuploidy rate found in this population of patients is concordant with their low pregnancy expectations; in addition, it must also be taken into consideration that they are patients who are participating in an IVF program and for the most part they have an advanced maternal age indication. In contrast, oocytes from young women without a clinical history of fertility problems are expected to have a low aneuploidy rate and, therefore, a high pregnancy rate. As it is difficult to assess the aneuploidy rate in oocytes of young control women, discarded eggs from donors have been used in this proposal. Since donor oocytes are very appreciated in IVF clinics, the immature oocytes, which are mostly discarded for clinical use due to they require an IVM process, are generally available for research. Several groups, after analyzing these IVM donor oocytes, have obtained aneuploidy rates that vary between 5% and 23%, depending upon the study (7Gutierrez-Mateo C. Benet J. Wells D. Colls P. Bermudez M.G. Sanchez-Garcia J.F. et al.Aneuploidy study of human oocytes first polar body comparative genomic hybridization and metaphase II fluorescence in situ hybridization analysis.Hum Reprod. 2004; 19: 2859-2868Crossref PubMed Scopus (84) Google Scholar, 11Pellestor F. Andreo B. Arnal F. Humeau C. Demaille J. Maternal aging and chromosomal abnormalities: new data drawn from in vitro unfertilized human oocytes.Hum Genet. 2003; 112: 195-203PubMed Google Scholar, 12Fragouli E. Delhanty J.D. Wells D. Single cell diagnosis using comparative genomic hybridization after preliminary DNA amplification still needs more tweaking: too many miscalls.Fertil Steril. 2007; 88 (author reply 8–9): 247-248Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar) but that in any case are, as expected, lower than the aneuploidy rates observed in the IVF patient's IVM oocytes. Other studies have used donor oocytes at the MII stage after follicular puncture (i.e., fresh), which are much more difficult to obtain from IVF centers. In these studies, the obtained aneuploidy rate was unexpectedly high, between 29% and 65%, considering the origin of these oocytes and compared with the lower rates found in IVM donor oocytes (13Keskintepe L. Sher G. Keskintepe M. Reproductive oocyte/embryo genetic analysis: comparison between fluorescence in-situ hybridization and comparative genomic hybridization.Reprod Biomed Online. 2007; 15: 303-309Abstract Full Text PDF PubMed Scopus (19) Google Scholar, 14Sandalinas M. Marquez C. Munne S. Spectral karyotyping of fresh, non-inseminated oocytes.Mol Hum Reprod. 2002; 8: 580-585Crossref PubMed Scopus (113) Google Scholar, 15Sher G. Keskintepe L. Keskintepe M. Ginsburg M. Maassarani G. Yakut T. et al.Oocyte karyotyping by comparative genomic hybridization [correction of hybrydization] provides a highly reliable method for selecting “competent” embryos, markedly improving in vitro fertilization outcome: a multiphase study.Fertil Steril. 2007; 87: 1033-1040Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar). The aim of this work is to perform a complete aneuploidy screening of fresh and IVM oocytes in both cells of the doublet (MII oocyte and its 1PB) by comparative genomic hybridization (CGH) to contribute more data to this field, since CGH has also been a helpful tool for single-cell cytogenetic analysis in very different issues (6Fragouli E. Wells D. Whalley K.M. Mills J.A. Faed M.J. Delhanty J.D. Increased susceptibility to maternal aneuploidy demonstrated by comparative genomic hybridization analysis of human MII oocytes and first polar bodies.Cytogenet Genome Res. 2006; 114: 30-38Crossref PubMed Scopus (56) Google Scholar, 7Gutierrez-Mateo C. Benet J. Wells D. Colls P. Bermudez M.G. Sanchez-Garcia J.F. et al.Aneuploidy study of human oocytes first polar body comparative genomic hybridization and metaphase II fluorescence in situ hybridization analysis.Hum Reprod. 2004; 19: 2859-2868Crossref PubMed Scopus (84) Google Scholar, 8Gutierrez-Mateo C. Wells D. Benet J. Sanchez-Garcia J.F. Bermudez M.G. Belil I. et al.Reliability of comparative genomic hybridization to detect chromosome abnormalities in first polar bodies and metaphase II oocytes.Hum Reprod. 2004; 19: 2118-2125Crossref PubMed Scopus (74) Google Scholar, 16Fragouli E. Wells D. Thornhill A. Serhal P. Faed M.J. Harper J.C. et al.Comparative genomic hybridization analysis of human oocytes and polar bodies.Hum Reprod. 2006; 21: 2319-2328Crossref PubMed Scopus (117) Google Scholar, 17Voullaire L. Wilton L. Slater H. Williamson R. Detection of aneuploidy in single cells using comparative genomic hybridization.Prenat Diagn. 1999; 19: 846-851Crossref PubMed Scopus (106) Google Scholar, 18Wells D. Sherlock J.K. Handyside A.H. Delhanty J.D. Detailed chromosomal and molecular genetic analysis of single cells by whole genome amplification and comparative genomic hybridisation.Nucleic Acids Res. 1999; 27: 1214-1218Crossref PubMed Scopus (255) Google Scholar, 19Obradors A. Fernandez E. Oliver-Bonet M. Rius M. de la Fuente A. Wells D. et al.Birth of a healthy boy after a double factor PGD in a couple carrying a genetic disease and at risk for aneuploidy: case report.Hum Reprod. 2008; 23: 1949-1956Crossref PubMed Scopus (37) Google Scholar, 20Obradors A. Fernandez E. Rius M. Oliver-Bonet M. Martinez-Fresno M. Benet J. et al.Outcome of twin babies free of Von Hippel-Lindau disease after a double-factor preimplantation genetic diagnosis: monogenetic mutation analysis and comprehensive aneuploidy screening.Fertil Steril. 2009 Mar; 91 (e1–7. Epub 2009 Jan 10): 933Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar). A total of 84 oocytes were obtained from 53 IVF egg donors with a mean age of 26.1 by using an antagonist-stimulation protocol as described elsewhere (21Galindo A. Bodri D. Guillen J.J. Colodron M. Vernaeve V. Coll O. Triggering with HCG or GnRH agonist in GnRH antagonist treated oocyte donation cycles: a randomised clinical trial.Gynecol Endocrinol. 2009; 25: 60-66Crossref PubMed Scopus (68) Google Scholar). On the day of the follicular puncture, the recovered oocytes were classified into two groups according to their meiotic stage. Twenty-eight of them were in the MII stage, displaying a visible 1PB, and were categorized as fresh MII oocytes. The remaining 56 oocytes were characterized as IVM oocytes. All of them came from either MI or germinal vesicle stages, in all of which, after having been kept in IVF medium (IVF, Vitrolife; Gothenburg, Sweden) at 37°C for approximately 20 hours, the extrusion of the 1PB had been produced. The 28 fresh oocytes were donated by 19 donors with a mean age of 26.7, and the 56 IVM oocytes were donated by 35 donors with a mean age of 24.2. The donors signed an authorization in the IVF center to allow the donation of the rejected oocytes for basic research studies. The samples were obtained from the Clínica EUGIN, Instituto de Reproducción CEFER, and the IVF center of the Hospital Valle d'Hebrón, all of which are in Barcelona, Spain. The CGH of the 1PB and MII doublet were processed as described elsewhere (7Gutierrez-Mateo C. Benet J. Wells D. Colls P. Bermudez M.G. Sanchez-Garcia J.F. et al.Aneuploidy study of human oocytes first polar body comparative genomic hybridization and metaphase II fluorescence in situ hybridization analysis.Hum Reprod. 2004; 19: 2859-2868Crossref PubMed Scopus (84) Google Scholar, 8Gutierrez-Mateo C. Wells D. Benet J. Sanchez-Garcia J.F. Bermudez M.G. Belil I. et al.Reliability of comparative genomic hybridization to detect chromosome abnormalities in first polar bodies and metaphase II oocytes.Hum Reprod. 2004; 19: 2118-2125Crossref PubMed Scopus (74) Google Scholar). The chromosomes that are most frequently gained or lost artifactually (i.e., chromosomes 17, 19, and 22) were discarded from analysis when all three chromosomes were simultaneously gained or lost in the same cell; if not, they were considered as real aneuploidies (8Gutierrez-Mateo C. Wells D. Benet J. Sanchez-Garcia J.F. Bermudez M.G. Belil I. et al.Reliability of comparative genomic hybridization to detect chromosome abnormalities in first polar bodies and metaphase II oocytes.Hum Reprod. 2004; 19: 2118-2125Crossref PubMed Scopus (74) Google Scholar). In our hands, the distinction between chromosome or chromatid gain or loss by CGH is doubtful because after analyzing 1PBs by CGH and their corresponding MII using fluorescence in situ hybridization (FISH), some CGH loss or gain profiles on the 1PBs were indistinguishably equivalent to losses or gains of either chromosome or chromatid in the MIIs (7Gutierrez-Mateo C. Benet J. Wells D. Colls P. Bermudez M.G. Sanchez-Garcia J.F. et al.Aneuploidy study of human oocytes first polar body comparative genomic hybridization and metaphase II fluorescence in situ hybridization analysis.Hum Reprod. 2004; 19: 2859-2868Crossref PubMed Scopus (84) Google Scholar). Conclusive and informative cytogenetic results were obtained from all the CGH profiles of a total of 84 doublets of them, giving a CGH efficiency rate of 100%. Fifty-seven out of the 84 doublets presented euploid profiles (MII: 23,X; and 1PB: 23,X); therefore the euploidy rate was 67.9%. The other 27 analyzed doublets were aneuploidy; thus the global aneuploidy rate was 32.1% (Fig. 1A ). The incidence of aneuploidy observed in the fresh and in IVM oocytes that were analyzed (17.85%, five out of 28; and 39.2% 22 out of 56, respectively) were different but without significant differences. In previously published results on the aneuploidy incidence in fresh oocytes from donors, the aneuploidy rate range from 29% aneuploid oocytes using the SKY approach (14Sandalinas M. Marquez C. Munne S. Spectral karyotyping of fresh, non-inseminated oocytes.Mol Hum Reprod. 2002; 8: 580-585Crossref PubMed Scopus (113) Google Scholar) to 56% (13Keskintepe L. Sher G. Keskintepe M. Reproductive oocyte/embryo genetic analysis: comparison between fluorescence in-situ hybridization and comparative genomic hybridization.Reprod Biomed Online. 2007; 15: 303-309Abstract Full Text PDF PubMed Scopus (19) Google Scholar) or 65% (15Sher G. Keskintepe L. Keskintepe M. Ginsburg M. Maassarani G. Yakut T. et al.Oocyte karyotyping by comparative genomic hybridization [correction of hybrydization] provides a highly reliable method for selecting “competent” embryos, markedly improving in vitro fertilization outcome: a multiphase study.Fertil Steril. 2007; 87: 1033-1040Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar) using the CGH approach. Our value of 17.85% is considerably lower than these, even considering the studies in which CGH was also used. The use of multiple displacement amplification instead of Degenerate Oligonucleotide-Primed-polymerase chain reacion (DOP-PCR) in these studies could have introduced some bias into the results, as has been suggested elsewhere (12Fragouli E. Delhanty J.D. Wells D. Single cell diagnosis using comparative genomic hybridization after preliminary DNA amplification still needs more tweaking: too many miscalls.Fertil Steril. 2007; 88 (author reply 8–9): 247-248Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar). Referring to aneuploidy incidence in IVM donor oocytes, the previously published aneuploidy rates range from 7.8% aneuploid oocytes (11Pellestor F. Andreo B. Arnal F. Humeau C. Demaille J. Maternal aging and chromosomal abnormalities: new data drawn from in vitro unfertilized human oocytes.Hum Genet. 2003; 112: 195-203PubMed Google Scholar) using R-banding or from 4.54% (12Fragouli E. Delhanty J.D. Wells D. Single cell diagnosis using comparative genomic hybridization after preliminary DNA amplification still needs more tweaking: too many miscalls.Fertil Steril. 2007; 88 (author reply 8–9): 247-248Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar) to 23% aneuploid oocytes (8Gutierrez-Mateo C. Wells D. Benet J. Sanchez-Garcia J.F. Bermudez M.G. Belil I. et al.Reliability of comparative genomic hybridization to detect chromosome abnormalities in first polar bodies and metaphase II oocytes.Hum Reprod. 2004; 19: 2118-2125Crossref PubMed Scopus (74) Google Scholar) with the addition of CGH. The incidence of aneuploid IVM oocytes described in our sample is much higher, 39.3% (22 out of 56 IVM oocytes). This variation may be explained by intrinsic differences existing between the groups of donors, the size of the sample analyzed, the IVM procedure used, and the consequence of different analysis criteria used by the research group using different CGH software systems (Cytovision, Milton, NH; Metasystem Altlussheim, Germany; or Vysis, Downers Grove, IL). A total of 17.8% of the oocytes (15 out of 84) have complementary aneuploid events, that is, gain or loss of a chromosome in one of the cells of the doublet (MII or 1PB) and for the same chromosome a complementary loss or gain CGH profile in the other cell of the doublet (Fig. 1B). On the other hand, 15.5% of the oocytes (13 out of 84) had noncomplementary aneuploidy, that is, the gained or lost CGH profile for one chromosome was observed in one of the cells of the doublet (1PB or MII), but a normal CGH profile for the same chromosome was clearly observed in the other cell of the doublet (MII or 1PB). In the present work, 20 (37.7%) out of 53 donors produced at least one aneuploid oocyte. In eight of the donors, the aneuploidies found were complementary, whereas in other eight donors they were noncomplementary. Four other donors generated aneuploid oocytes containing both categories of alterations. Therefore, the incidence of donors that produced aneuploid oocytes with complementary aneuploid oocytes was 22.6% (12 out of 53), and the incidence of donors that produced noncomplementary aneuploid oocytes was also 22.6% (12 out of 53). The complementary aneuploid events observed should be considered as having originated from errors in the first meiotic division, a consequence of bivalents/homologous chromosome nondisjunction or sisters chromatid predivision produced in a euploid oogonium. The noncomplementary aneuploid events can only be understood if the doublet originated from an aneuploid oogonium, which contained aneuploidies itself before the first meiotic division. Therefore, after the first meiotic division, the aneuploidy present in the oogonium is included in one of the cells (MII or 1PB), leaving the other cell euploid and thus generating a noncomplementary aneuploidy. The aneuploid oogonium mentioned had to be produced during the early oogenesis, while the donor was still a fetus. Most probably it was during the proliferative stage of oogenesis, when multiple, consecutive mitotic divisions occur and, as a consequence of an abnormal mitotic segregation, the corresponding aneuploid oogonium was produced. So meiotic errors were observed in 17.8% of the oocytes (15 out of 84), while mitotic errors were observed in 15.5% of the oocytes (13 out of 84). Herein, the incidence of donors producing aneuploid oocytes due to segregation errors in the early mitotic stage of oogenesis or due to errors in the first meiotic stage is, in both cases, 22.6%. Even with this high frequency of alterations, all of the donors with more than one oocyte analyzed had some euploid oocytes, except Donor TA and Donor SA, who had the two oocytes that were analyzed as aneuploid. The presence of mitotic errors during oogenesis was first described after analyzing the oocytes of a patient with four previous pregnancies affected by Down syndrome (22Cozzi J. Conn C.M. Harper J. Winston R.M. Rindl M. Farndon P.A. et al.A trisomic germ cell line and precocious chromatid segregation leads to recurrent trisomy 21 conception.Hum Genet. 1999; 104: 23-28Crossref PubMed Scopus (45) Google Scholar). Other studies on oocytes from IVF patients using FISH have found errors due to aneuploid oogonia, which affect 33.3% (23Mahmood R. Brierley C.H. Faed M.J. Mills J.A. Delhanty J.D. Mechanisms of maternal aneuploidy: FISH analysis of oocytes and polar bodies in patients undergoing assisted conception.Hum Genet. 2000; 106: 620-626Crossref PubMed Scopus (67) Google Scholar), 20% (24Cupisti S. Conn C.M. Fragouli E. Whalley K. Mills J.A. Faed M.J. et al.Sequential FISH analysis of oocytes and polar bodies reveals aneuploidy mechanisms.Prenat Diagn. 2003; 23: 663-668Crossref PubMed Scopus (65) Google Scholar), or 25.7% (25Pujol A. Boiso I. Benet J. Veiga A. Durban M. Campillo M. et al.Analysis of nine chromosome probes in first polar bodies and metaphase II oocytes for the detection of aneuploidies.Eur J Hum Genet. 2003; 11: 325-336Crossref PubMed Scopus (60) Google Scholar) of the aneuploid oocytes. Moreover, studies using CGH to analyze MII-1PB also detected 11.9%–20% of aneuploidies that were due to mitotic errors (7Gutierrez-Mateo C. Benet J. Wells D. Colls P. Bermudez M.G. Sanchez-Garcia J.F. et al.Aneuploidy study of human oocytes first polar body comparative genomic hybridization and metaphase II fluorescence in situ hybridization analysis.Hum Reprod. 2004; 19: 2859-2868Crossref PubMed Scopus (84) Google Scholar, 8Gutierrez-Mateo C. Wells D. Benet J. Sanchez-Garcia J.F. Bermudez M.G. Belil I. et al.Reliability of comparative genomic hybridization to detect chromosome abnormalities in first polar bodies and metaphase II oocytes.Hum Reprod. 2004; 19: 2118-2125Crossref PubMed Scopus (74) Google Scholar), and a further CGH study concluded that 22.2% of the aneuploid oocytes originated by aneuploid oogonia (16Fragouli E. Wells D. Thornhill A. Serhal P. Faed M.J. Harper J.C. et al.Comparative genomic hybridization analysis of human oocytes and polar bodies.Hum Reprod. 2006; 21: 2319-2328Crossref PubMed Scopus (117) Google Scholar). In oocytes from donors, as far as we know, this type of aneuploidy has never been described before. It could probably be due to the fact that in previously published works just one of the cells of the doublet from the whole-chromosome complement (MII oocytes or their 1PB) was analyzed, and, consequently, it was not possible to distinguish between meiotic or mitotic segregation errors (13Keskintepe L. Sher G. Keskintepe M. Reproductive oocyte/embryo genetic analysis: comparison between fluorescence in-situ hybridization and comparative genomic hybridization.Reprod Biomed Online. 2007; 15: 303-309Abstract Full Text PDF PubMed Scopus (19) Google Scholar, 14Sandalinas M. Marquez C. Munne S. Spectral karyotyping of fresh, non-inseminated oocytes.Mol Hum Reprod. 2002; 8: 580-585Crossref PubMed Scopus (113) Google Scholar, 15Sher G. Keskintepe L. Keskintepe M. Ginsburg M. Maassarani G. Yakut T. et al.Oocyte karyotyping by comparative genomic hybridization [correction of hybrydization] provides a highly reliable method for selecting “competent” embryos, markedly improving in vitro fertilization outcome: a multiphase study.Fertil Steril. 2007; 87: 1033-1040Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar). Our results suggest that it is probably time to consider that gonadal aneuploidy is much more frequent in the general population than was expected. The presence of aneuploid oogonia has been recently assessed by Hulten et al. after analyzing eight euploid fetuses and finding in all of them an average incidence of 0.54% (range between 0.20% and 0.88%) of trisomic 21 oogonia in ovarian cells, which suggests that it is a normal situation in normal female fetuses (26Hulten M.A. Patel S.D. Tankimanova M. Westgren M. Papadogiannakis N. Jonsson A.M. et al.On the origin of trisomy 21 Down syndrome.Mol Cytogenet. 2008; 1: 21Crossref PubMed Google Scholar). The fact that the incidence of mitotic errors observed in our group of donors (22.6%) is very close to the incidence observed in previous reports in patients from different groups using CGH (11.9%–22.5%) is in agreement with this suggestion. All of the 15 (100%) oocytes with complementary aneuploidy involved only a single chromosome, while only four out of 13 (30.7%) oocytes with noncomplementary errors involved only a single chromosome. The incidences observed were very significantly different (Fisher's test P<.0001). That fact would suggest that the chromosome segregation errors could be caused by different types of failures depending on the origin. Early in the proliferative phase of oogenesis, failures could be involved in the cell-cycle checkpoint mechanisms that would affect the whole chromosome segregation (27Barlow A.L. Hulten M.A. Combined immunocytogenetic and molecular cytogenetic analysis of meiosis I oocytes from normal human females.Zygote. 1998; 6: 27-38Crossref PubMed Scopus (26) Google Scholar, 28Tease C. Hartshorne G.M. Hulten M.A. Patterns of meiotic recombination in human fetal oocytes.Am J Hum Genet. 2002; 70: 1469-1479Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar), whereas synaptic errors between specific homologous chromosomes, or reduction in the number of chiasmata because of a low recombination rate, could subsequently affect the segregation of particularly unstable bivalents that are responsible for the aneuploidies produced during the first meiotic division (4Hassold T. Hunt P. To err (meiotically) is human: the genesis of human aneuploidy.Nat Rev Genet. 2001; 2: 280-291Crossref PubMed Scopus (1715) Google Scholar, 5Nicolaidis P. Petersen M.B. Origin and mechanisms of non-disjunction in human autosomal trisomies.Hum Reprod. 1998; 13: 313-319Crossref PubMed Scopus (196) Google Scholar, 29Wolstenholme J. Angell R.R. Maternal age and trisomy—a unifying mechanism of formation.Chromosoma. 2000; 109: 435-438Crossref PubMed Scopus (86) Google Scholar). This nonnegligible aneuploidy rate in donors may explain the different clinical outcomes of donor egg-sharing recipients (30Bodri D. Colodron M. Vidal R. Galindo A. Durban M. Coll O. Prognostic factors in oocyte donation: an analysis through egg-sharing recipient pairs showing a discordant outcome.Fertil Steril. 2007; 88: 1548-1553Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar, 31Garcia-Velasco J.A. Isaza V. Caligara C. Pellicer A. Remohi J. Simon C. Factors that determine discordant outcome from shared oocytes.Fertil Steril. 2003; 80: 54-60Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar) and could be in agreement with the 57% of aneuploid embryos detected from donor oocyte cycles using eight-chromosome FISH (32Munne S. Ary J. Zouves C. Escudero T. Barnes F. Cinioglu C. et al.Wide range of chromosome abnormalities in the embryos of young egg donors.Reprod Biomed Online. 2006; 12: 340-346Abstract Full Text PDF PubMed Google Scholar). In conclusion, according to the results obtained in the present work, oocytes from young women are not free of aneuploidies, and, therefore, they could also benefit from a comprehensive Preimplantation Genetic Screening (PGS) protocol, as CGH, to avoid aneuploid pregnancies and increase their implantation rate. The manuscript was read and corrected by Mr. Chuck Simmons, a native English speaking instructor of English at the authors' university." @default.
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• W2144012824 title "Errors at mitotic segregation early in oogenesis and at first meiotic division in oocytes from donor females: Comparative genomic hybridization analyses in metaphase II oocytes and their first polar body" @default.
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• W2144012824 doi "https://doi.org/10.1016/j.fertnstert.2009.08.050" @default.
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