23. Lobo, R. A. N Engl J Med 2005;353:64-73 Decline in the Number of Oocytes from Birth to Menopause
24. Heffner, L. J. N Engl J Med 2004;351:1927-1929 Fertility and Miscarriage Rates as a Function of Maternal Age
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80. Van Voorhis B. N Engl J Med 2007;356:379-386 The Process of IVF
81. Rebar, R. W. et al. N Engl J Med 2004;350:1603-1604 Embryos and Blastocysts during Assisted Reproduction (x20)
82. Van Voorhis B. N Engl J Med 2007;356:379-386 Biopsy and Preimplantation Genetic Diagnosis of a 3-Day-Old (Eight-Cell) Embryo
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84. Braude P. N Engl J Med 2006;355:541-543 In Vitro Fertilization and Preimplantation Genetic Haplotyping
85. Elias S. N Engl J Med 2001;345:1569-1571 Analysis by Comparative Genomic Hybridization of a Blastomere Obtained by Biopsy of a Six-to-Eight-Cell Embryo
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11/04/09 Figure 1. Decline in the Number of Oocytes from Birth to Menopause. Data provided in Panel A are adapted from Faddy et al.1 The images in Panel B -- which shows histologic specimens of oocytes (arrows) taken from patients at birth, at the age of 25 years, and at the age of 50 years -- are adapted from Erickson8 and are reprinted with the permission of the publisher.
11/04/09 Figure. Fertility and Miscarriage Rates as a Function of Maternal Age. Adapted from Menken et al.1 and Anderson et al.2
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11/04/09 Figure 1. The Process of IVF. The ovaries are stimulated by daily injections of gonadotropins to optimize follicular development, which is monitored by means of transvaginal ultrasonography. Ultrasonography of an unstimulated ovary shows a small antral follicle (Panel A, arrow). The same ovary has multiple growing follicles after gonadotropin stimulation. One follicle is shown with measurements in two dimensions (Panel B). After ovarian stimulation, eggs are retrieved by means of ultrasound-guided transvaginal aspiration of follicular fluid (Panel C). A mature human egg is recovered from the aspirated fluid (Panel D). Recovered eggs are often fertilized in vitro by culturing eggs with many motile sperm (Panel E); in this image, multiple sperm are attached to the egg's zona pellucida (arrows point to three of the sperm). Eggs can also be fertilized by means of intracytoplasmic sperm injection, a technique in which a single sperm is injected into the egg with the use of a thin glass pipette (Panel F). This technique was developed to facilitate fertilization in cases of male-factor infertility but is now used in a majority of IVF cycles. Multiple embryos are cultured, often for 3 days (an eight-cell embryo, shown in Panel G) or 5 days (a blastocyst embryo, shown in Panel H, with the inner cell mass indicated by the arrow) before selected embryos are transferred back to the uterus (Panel I). Good-quality, excess embryos are often cryopreserved.
11/04/09 Figure. Embryos and Blastocysts during Assisted Reproduction (x20). Panel A shows two embryos in the pronuclear stage, approximately 18 hours after insemination. Panel B shows two eight-cell embryos three days after insemination. Panel C shows a blastocyst five days after insemination. Panel D shows a blastocyst hatching from the zona pellucida six days after insemination.
11/04/09 Figure 3. Biopsy and Preimplantation Genetic Diagnosis of a 3-Day-Old (Eight-Cell) Embryo. One or two blastomeres are removed from the embryo, as shown in Panel A, for preimplantation genetic diagnosis. Fluorescence in situ hybridization (FISH) is used to identify and count individual chromosomes. Panel B shows a blastomere with trisomy 21 detected by means of FISH (red probe). With current techniques, up to 10 chromosomes in a single cell can be evaluated, although techniques that allow more comprehensive evaluation are being developed.
11/04/09 In Vitro Fertilization and Preimplantation Genetic Haplotyping. Embryos are created with the use of in vitro fertilization. On the third day after fertilization, a single cell is removed from each embryo for genetic testing. After whole-genome amplification, the DNA is tested for the presence of a large series of specific short-tandem-repeat loci closely linked to the mutation causing the susceptibility. This testing will reveal contamination by extraneous DNA and provide sufficient information for a diagnosis to be made with the use of genetic-linkage analysis, even without precise knowledge of the mutation sequence. Up to two mutation-free embryos are considered for transfer back to the uterus.
11/04/09 Figure 1. Analysis by Comparative Genomic Hybridization of a Blastomere Obtained by Biopsy of a Six-to-Eight-Cell Embryo. Comparative genomic hybridization simultaneously evaluates all chromosomes from a single cell for aneuploidy. Selected results from chromosome 10, which is euploid, and chromosome 21, which is aneuploid, are shown in the boxes. See figure 2 of Wilton et al.9 for an explanation of the chromosomal diagram.
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11/04/09 Figure 1. Blastocyst Apposition and Adhesion. The diagram shows a preimplantation-stage blastocyst (approximately six to seven days after conception) and the processes thought to be necessary for uterine receptivity and blastocyst apposition and adhesion. COX-2 denotes cyclooxygenase-2, EGF epidermal growth factor, and LIF leukemia inhibiting factor.
11/04/09 Figure 2. Blastocyst Implantation. The diagram shows an invading blastocyst (about 9 to 10 days after conception) and the processes necessary for trophoblast invasion.
11/04/09 Figure 3. Maintenance of Early Pregnancy. The diagram shows an implanted embryo (approximately 14 days after conception) and the processes necessary for the maintenance of an early pregnancy. VEGF denotes vascular endothelial growth factor, and hCG human chorionic gonadotropin.