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sperm). As we explain earlier in this chapter, knowing more about a person’s genes provides many more clues about possible diseases. In infertility, knowing about your genes can help explain key questions such as why you are not getting pregnant, why you don’t make good embryos, or why you miscarry.

      Karyotyping

      There are a number of tests that are used to gain information about a person’s genetic code. One test, called karyotyping, determines how many chromosomes are present. This can be done for people, a fetus, or embryos.

      Remember that the chromosomes are long strings of genetic code that are tightly packaged, and there are 23 sets of chromosomes. Chromosomes 1–22 are called autosomes, while 23 is the sex chromosome. Each person has one set of chromosomes from each parent so there are 46 chromosomes arranged in 23 pairs. The sex chromosomes determine the sex of the person with XX being female and XY being male.

      Until recently, testing chromosomes was laborious with cells being grown, stopped in their development, stained, photographed, and then counted. This process required a number of cells to be tested and was most commonly associated with an amniocentesis. The amniocentesis was done during the early second trimester to diagnose the presence of an abnormal number of chromosomes such as Down syndrome, which is trisomy 21, where the fetus has three copies of chromosome 21 (instead of two).

      There is controversy as to whether the use of preimplantation genetic testing for screening embryos is indicated, but many physicians and patients are opting for this diagnostic procedure. For some couples, the information from testing for chromosome number can help identify why a person has not conceived and may suggest either doing more cycles of IVF with the woman’s own eggs or may identify the need to move on to other options such as stopping treatment, adoption, or using donor eggs.

      Spotting single gene defects

      A second type of genetic testing can determine if a gene is abnormal. There may be a single nucleotide error, pieces of the gene may be missing or duplicated, or there may be other errors. The advent of next-generation sequencing has permitted easy, cost-effective testing for these errors. Genetic diseases may require that both chromosomes have the same defective gene. These diseases are called recessive. A person may have one defective gene, but the other normal gene compensates for the defective gene. Some genetic diseases require that only one chromosome have the gene defect, and these are call dominant gene diseases. One use of next-gen sequencing is for a family that has a history of a genetic disease. A person, who does not have the genetic disease or an embryo, can be tested for that disease. Since a person receives a chromosome from each parent, there is a double dose of each gene. The person who has a single gene defect is called a carrier for that gene, and the vast majority of these mutations are of the recessive type (requiring both sets of chromosomes to have the gene defect before the disease develops).

      Suppose that the gene that is responsible for cystic fibrosis is faulty in the chromosome from one parent but normal in the other. Then the normal gene compensates for the malfunction of the other gene, and the person does not develop cystic fibrosis. The child of these parents may have one abnormal gene and one normal gene and is called a carrier for that gene defect. Sometimes, having one defective gene results in a disease. An example of this is Huntington’s chorea (a dominant gene disease), a devastating neurologic disease that does not show up until later in life after the person has reproduced. Huntington’s chorea is caused by a gene defect in which too many of the codons exist — similar to the type of problem in fragile X syndrome. The genetic defect for Huntington’s and fragile X is not due to an error in the code but rather to too much code. For families with a family history of Huntington’s, it is now possible to test embryos and elect not to transfer an embryo that has the defect.

      Looking for other anomalies

      As if testing your genes is not enough, scientists are now looking at how we can change your genetic structure, or the genetic structure of your embryos! While it sounds more like science fiction than real medicine, there are some new ideas in the field of genetics that may someday help conquer infertility.

      An expanding area of research for genetic diseases focuses on how the genetic code is actually read. It turns out that while there is a core code, inherited unchanged from generation to generation, the cell is able to modify how the code is read based upon environmental and developmental conditions. Cells do this by adding molecules to the core code, which is called epigenetics. For example, one theory of how endometriosis forms is that molecules called methyl groups can either be added or removed from the core genetic code, creating new instructions from the genetic code that leads to the formation of endometriosis. Endometriosis is a very complex disease, and this is not the only reason a person develops endometriosis, but the process may add to the risk for developing endometriosis.

      A cell requires considerable energy to perform the work it does. The energy is generated by a small structure within the cell called mitochondria. Mitochondria are similar to bacteria and have their own set of chromosomes. When errors occur in these genes, the mitochondria do not perform well. This can lead to devastating diseases. One treatment that is being developed is to take normal mitochondria from an embryonic cell and transfer it into the cell from an affected embryo.

      A final advancement is the ability to genetically modify the genetic code of an embryo. The technology uses a procedure called CRISPR (technically CRISPR-Cas9). The use of this for clinical medicine is quite a ways off, but the implications are immense. In theory, it may become possible to actually alter the genetic code. This could provide a way to cure inherited diseases or reduce genetic risk factors for a number of chronic diseases. The use of genetics to improve the human condition is called eugenics. The ability to alter the genetic code elevates the field of eugenics to a new level that could challenge both ethics and the legal system. So once again, just as IVF

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