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I2 Is there effect of controlled stimulated cycles (COS) on endometrial receptivity and aneuploidy rates
Reproductive BioMedicine Online 26 Suppl. 1 (2013) S1–S11
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ABSTRACTS OF INVITED SPEAKERS Clinical Aspects of PGD I1 Clinical challenges in application of prenatal technologies J.L. Simpson. March of Dimes Foundation, White Plains, New York, USA Multiple prenatal technologies exist, for which reason clinicians and geneticists must weigh indications, match with potential options and take into account available expertise. The first decision is whether the goal is screening (e.g. maternal serum analytes for fetal aneuploidy) or definitive testing (preimplantation genetic diagnosis, PGD). Screening with cell free fetal DNA in maternal blood might blur this distinction if high detection for trisomy rate and low false positives continue to be observed as in initial reports. The second decision involves selection of appropriate technology, a reflection of specific clinical indication and patient preferences. Preimplantation genetic diagnosis (PGD) is the only practical approach in certain circumstances. Couples wanting to avoid clinical termination can only utilize PGD. Only PGD is applicable for improving pregnancy rates, either in infertile couples or in fertile couples at exceptional statistical risk for genetically abnormal offspring (e.g., balanced translocation). The initial challenge is often cost, which is unavoidably higher than in traditional prenatal genetic methods involving analysis of chorionic villi or amniotic fluid cells. Couples with resources may be less financially stressed, but those lacking resources may not have access to PGD at all. A third decision involves whether optimal PGD can indeed be provided. As technologies advance, attractiveness of routine array CGH to assess aneuploidy will increase. This may become the standard for all couples undergoing PGD, regardless of clinical indication. If the primary indication is a single gene disorder or HLA embryo matching, transferring euploid as well as unaffected embryos will increase pregnancy rate. However, desirability of PGD aneuploidy testing to increase pregnancy rates is predicated on prowess in embryo biopsy. Without such, a given ART center might be prudent to seek referral services. Still, the future will see increased demand for PGD and, hence, necessity for ART units to adapt. PGD will also extend to analysis of cell free DNA in culture media, providing information on gene expression as well as aneuploidy. I2 Is there effect of controlled stimulated cycles (COS) on endometrial receptivity and aneuploidy rates C. Sim´ on. Fundaci´ on IVI (FIVI) Instituto Universitario IVI (IUIVI) Universidad de Valencia & IVIOMICS, Valencia, Spain Functional genomic studies have demonstrated that endometrial receptivity is altered in controlled ovarian stimulated cycles (COS) during the window of implantation (WOI) (Mirkin et al., 2004; Horcajadas et al., 2005; Sim´ on et al., 2005). We have expanded these studies by comparing the gene expression profile
of the human endometrium throughout the early-mid secretory phase in natural versus COS cycles (Horcajadas et al., 2008). We have analyzed endometrial samples collected from healthy fertile cycling ovum donors (aged 23 39), that underwent either natural cycles (n = 25) at days LH+1, LH+3, LH+5, LH +7 and LH+9 or a COH cycle (n = 25) at days hCG+1, hCG+3, hCG+5, hCG +7 and hCG+9 (n = 5 per time point). COS treatment consisted of a long protocol with leuprolide acetate and FSH/HP, hMG and hCG as described elsewhere. In natural and COS cycles, no progesterone (P) supplementation was administered in the luteal phase. RNA was extracted and labeled cDNA were hybridized onto the GeneChip HG_U133A (Affymetrix) for the comparisons. Gene expression data were analysed using different methods such as clustering or selection of differentially expressed genes, as implemented in the GEPAS (http://www.gepas.org). Results demonstrate that the endometrium from natural and COS cycles without P supplementation followed similar genomic patterns in the prereceptive phase, although hCG+7 can categorize as prerereceptive in molecular terms versus LH+7, recovering similar genomic profile thereafter at LH+9 and hCG+9. These results indicate that gene expression profiling of the endometrium at the time of implantation is different between natural and COS cycles. The functional relevance of this finding is become more evident with the use of elective deferred embryo transfer that will be analysing in this presentation. Also, evidences indicating the induction of embryo aneuploidies after different induction ovulation regimes in COS cycles will be discussed. Reference(s) Riesewijk A, Martin J, Horcajadas JA, Polman J, Pellicer A, Mosselman S, Sim´ on C (2003) Gene expression profiling of human endometrial receptivity on days LH+2 versus LH+7 by microarray technology. Mol Hum Reprod 9, 253 264. Mirkin S, Nikas G, Hsiu JG, Diaz J and Oehninger S (2004) Gene expression profiles and structural/functional features of the peri-implantation endometrium in natural and gonadotropinstimulated cycles. J Clin Endocrinol Metab 89, 5742 5752. Horcajadas JA, Riesewijk A, Polman J, van Os R, Pellicer A, Mosselman S and Sim´ on C (2005) Effect of Controlled Ovarian Hyperstimulation in IVF on Endometrial Gene Expression Profiles. Mol Human Reprod 11, 195 205. Sim´ on C, Bellver J, Vidal C, Bosch E, Horcajadas JA, Murphy C, Adams S, Riesewijk A, Obery´ e J, Mannaerts B and Pellicer A (2005) Similar endometrial development in oocyte donors treated with high- or low-dose GnRH-antagonist compared to GnRH-agonist treatment and natural cycles. Human Reprod 12, 3318 3327. Horcajadas JA, Mínguez P, Dopazo, Esteban FJ, Domínguez F, Giudice L, Pellicer A, Sim´ on C. (2008) Controlled ovarian stimulation induces a functional genomic delay of the endometrium with potential clinical implications. J Clin Endocrinol Metab; 93(11), 4500 4510.
1472-6483/$ - see front matter © 2013, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
www.sciencedirect.com www.rbmonline.com
ABSTRACTS OF INVITED SPEAKERS Clinical Aspects of PGD I1 Clinical challenges in application of prenatal technologies J.L. Simpson. March of Dimes Foundation, White Plains, New York, USA Multiple prenatal technologies exist, for which reason clinicians and geneticists must weigh indications, match with potential options and take into account available expertise. The first decision is whether the goal is screening (e.g. maternal serum analytes for fetal aneuploidy) or definitive testing (preimplantation genetic diagnosis, PGD). Screening with cell free fetal DNA in maternal blood might blur this distinction if high detection for trisomy rate and low false positives continue to be observed as in initial reports. The second decision involves selection of appropriate technology, a reflection of specific clinical indication and patient preferences. Preimplantation genetic diagnosis (PGD) is the only practical approach in certain circumstances. Couples wanting to avoid clinical termination can only utilize PGD. Only PGD is applicable for improving pregnancy rates, either in infertile couples or in fertile couples at exceptional statistical risk for genetically abnormal offspring (e.g., balanced translocation). The initial challenge is often cost, which is unavoidably higher than in traditional prenatal genetic methods involving analysis of chorionic villi or amniotic fluid cells. Couples with resources may be less financially stressed, but those lacking resources may not have access to PGD at all. A third decision involves whether optimal PGD can indeed be provided. As technologies advance, attractiveness of routine array CGH to assess aneuploidy will increase. This may become the standard for all couples undergoing PGD, regardless of clinical indication. If the primary indication is a single gene disorder or HLA embryo matching, transferring euploid as well as unaffected embryos will increase pregnancy rate. However, desirability of PGD aneuploidy testing to increase pregnancy rates is predicated on prowess in embryo biopsy. Without such, a given ART center might be prudent to seek referral services. Still, the future will see increased demand for PGD and, hence, necessity for ART units to adapt. PGD will also extend to analysis of cell free DNA in culture media, providing information on gene expression as well as aneuploidy. I2 Is there effect of controlled stimulated cycles (COS) on endometrial receptivity and aneuploidy rates C. Sim´ on. Fundaci´ on IVI (FIVI) Instituto Universitario IVI (IUIVI) Universidad de Valencia & IVIOMICS, Valencia, Spain Functional genomic studies have demonstrated that endometrial receptivity is altered in controlled ovarian stimulated cycles (COS) during the window of implantation (WOI) (Mirkin et al., 2004; Horcajadas et al., 2005; Sim´ on et al., 2005). We have expanded these studies by comparing the gene expression profile
of the human endometrium throughout the early-mid secretory phase in natural versus COS cycles (Horcajadas et al., 2008). We have analyzed endometrial samples collected from healthy fertile cycling ovum donors (aged 23 39), that underwent either natural cycles (n = 25) at days LH+1, LH+3, LH+5, LH +7 and LH+9 or a COH cycle (n = 25) at days hCG+1, hCG+3, hCG+5, hCG +7 and hCG+9 (n = 5 per time point). COS treatment consisted of a long protocol with leuprolide acetate and FSH/HP, hMG and hCG as described elsewhere. In natural and COS cycles, no progesterone (P) supplementation was administered in the luteal phase. RNA was extracted and labeled cDNA were hybridized onto the GeneChip HG_U133A (Affymetrix) for the comparisons. Gene expression data were analysed using different methods such as clustering or selection of differentially expressed genes, as implemented in the GEPAS (http://www.gepas.org). Results demonstrate that the endometrium from natural and COS cycles without P supplementation followed similar genomic patterns in the prereceptive phase, although hCG+7 can categorize as prerereceptive in molecular terms versus LH+7, recovering similar genomic profile thereafter at LH+9 and hCG+9. These results indicate that gene expression profiling of the endometrium at the time of implantation is different between natural and COS cycles. The functional relevance of this finding is become more evident with the use of elective deferred embryo transfer that will be analysing in this presentation. Also, evidences indicating the induction of embryo aneuploidies after different induction ovulation regimes in COS cycles will be discussed. Reference(s) Riesewijk A, Martin J, Horcajadas JA, Polman J, Pellicer A, Mosselman S, Sim´ on C (2003) Gene expression profiling of human endometrial receptivity on days LH+2 versus LH+7 by microarray technology. Mol Hum Reprod 9, 253 264. Mirkin S, Nikas G, Hsiu JG, Diaz J and Oehninger S (2004) Gene expression profiles and structural/functional features of the peri-implantation endometrium in natural and gonadotropinstimulated cycles. J Clin Endocrinol Metab 89, 5742 5752. Horcajadas JA, Riesewijk A, Polman J, van Os R, Pellicer A, Mosselman S and Sim´ on C (2005) Effect of Controlled Ovarian Hyperstimulation in IVF on Endometrial Gene Expression Profiles. Mol Human Reprod 11, 195 205. Sim´ on C, Bellver J, Vidal C, Bosch E, Horcajadas JA, Murphy C, Adams S, Riesewijk A, Obery´ e J, Mannaerts B and Pellicer A (2005) Similar endometrial development in oocyte donors treated with high- or low-dose GnRH-antagonist compared to GnRH-agonist treatment and natural cycles. Human Reprod 12, 3318 3327. Horcajadas JA, Mínguez P, Dopazo, Esteban FJ, Domínguez F, Giudice L, Pellicer A, Sim´ on C. (2008) Controlled ovarian stimulation induces a functional genomic delay of the endometrium with potential clinical implications. J Clin Endocrinol Metab; 93(11), 4500 4510.
1472-6483/$ - see front matter © 2013, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.