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In Vitro Fertilization—Update and Advances
structural appearance of each embryo, a technique that, although (e.g. Tay-Sachs disease, cystic fibrosis) to avoid conception of an affected
somewhat predictive, remains inadequate. It has been proposed embryo. In this situation, genetic analysis of one of the cells or polar bodies
that much greater information could be obtained prior to transfer of the embryo or oocyte in question is performed by polymerase chain
by assessing markers of the metabolic activity of each embryo, perhaps reaction (PCR) amplification and gene sequencing or single nucleotide
in conjunction with accurate genetic analysis, thus providing an polymorphism (SNP) typing. In addition, embryos can be screened for more
embryo ‘fingerprint.’ routine chromosomal abnormalities (pre-implantation aneuploidy
screening). This latter approach has been used to evaluate patients with
A fascinating series of studies has correlated the secretion of specific recurrent miscarriages, advanced maternal age, and repetitive IVF failure, as
molecules by individual embryos with their viability. Proteins evaluated to well as carriers for sex-linked disorders. In this circumstance, fluorescent in
date in this regard include plasminogen-activating factor (paf), HOXA 10, situ hybridization (FISH) assays are employed.
and human leukocyte antigen (HLA) 6.
19-21
Aneuploidy screening has been shown to be beneficial in reducing
A novel field of medicine, proteomics, focuses on the analysis of pregnancy losses in patients with recurrent miscarriage.
23
However, this
expression of specific proteins by individual embryos through the approach has not, as yet, been shown to improve live birth rates in the
application of non-invasive mass spectrometry. In a recent publication, general population of women over 35 years of age. One of the problems
Katz-Jaffee et al. have identified novel specific biomarkers that reflect with aneuploidy screening at this time is the fact that current FISH analysis
normal embryo development and viability.
22
This technology possesses provides information regarding only nine of the 23 human chromosome
incredible potential to allow for enhanced characterization of the pairs. Exciting new technologies involving microchip array platforms will
likelihood that any one embryo might result in a viable pregnancy allow for analysis of all 23 chromosome pairs as well as global gene
without adverse effect. expression profiling. If proven to be accurate and reproducible, this
approach could dramatically enhance the accuracy and potential
Advances in IVF—Pre-implantation Genetic applications of embryo analysis and perhaps even take the place of fetal
Diagnosis and Screening analysis by amniocentesis and chorionic villus sampling (CVS).
19
Significant progress has been made in the ability to evaluate the genetic
make-up of embryos prior to transfer. As this procedure is most commonly Conclusions
performed, a single cell from each viable cleavage-stage embryo is removed In a short period of time, IVF has progressed from a controversial curiosity
using micromanipulation techniques and subsequently fixed and stained for with limited successes to a highly efficient and well accepted approach
analysis (see Figure 3). While genetic analysis of this one cell is performed, to the management of infertility. Advances in embryo culture techniques
the embryo remains in culture. Embryo transfer typically occurs at the have made it possible to consider drastically reducing the associated risks
blastocyst stage of development once the results of the analysis are of multiple pregnancy by allowing efficient elective single blastocyst-
obtained. Less commonly, the oocyte (polar body biopsy) or cells from the stage embryo transfer. The concept of sequential embryo assessment will
blastocyst can also be evaluated. allow analysis of genetics, metabolism, and precise quantitative
expression of secretory factors of each embryo in a non-invasive fashion.
Pre-implantation genetic diagnostic techniques were initially performed in With these applications, the likelihood of conception can be maximized
conjunction with IVF for patients who are carriers of single gene disorders with risks minimized. ■
1. Schutz RM, Williams CJ, The Science of ART, Science, 2002;296: 9. Practice Committee of the American Society for Reproductive Technology and the American Society for Reproductive Medicine,
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transfers, Clin Obstet Gynecol, 2006;49:85–92. embryos for transfer after IVF and ICSI: a Cochrane review, Hum 20. Sher G, Koskintepe L, Fisch J, et al., Soluble human leukocyte
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US OBSTETRICS AND GYNECOLOGY 2007 47
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