IVF / Genetic Testing Procedures
What is In vitro fertilization (IVF)
In vitro fertilization (IVF) is the fertilization of eggs by sperm in a dish (outside the woman’s body). The embryos which result are transferred back into the woman’s body (Embryo Transfer; ET). Although it is technically possible to perform IVF without the use of fertility drugs, only one egg would be collected and the chance for pregnancy would be low. With the use of fertility drug, many eggs (ova) are retrieved, improving the chances of success.
Injectable gonadotropins are used for most IVF procedures. In order to arrive at an ideal starting point, a cycle of oral contraceptive pills is often prescribed prior to beginning gonadotropin injections. In addition, many patients are pretreated with a gonadotropin releasing hormone (GnRH) agonists, for example Lupron, drugs that turns off a patient’s own luteinizing hormone (LH).
 The GnRH agonist down-regulation allows injectable gonadotropins to synchronize the development of multiple follicles. GnRH agonists also prevent a woman from releasing LH and triggering her ovulation prematurely (before the eggs can be collected). Alternatively, a GnRH-antagonist medication may be utilized beginning a few days before oocyte collection in order to prevent premature LH surge and egg release.
In a typical IVF cycle the woman begins a package of oral contraceptive pills on or before the fifth days of her period. On the 18th day of that cycle injections of Lupron begin. A period is expected around day 26. An ultrasound and blood tests are then performed to verify that the woman is ready to receive the injectable gonadotropin drugs.
The dose of gonadotropins ( taken daily or twice daily) is adjusted with hopes of obtaining 12 to 15 oocytes (eggs) for use during the IVF procedure. Progress towards ovulation is monitored every few days with ultrasound and blood tests. If she has not been treated with Lupron, the woman will begin the medication Ganerelix after ultrasound has determined that her leading follicle is 12-14mm. in size. When the patient’s follicles are of sufficient size, ovulation is triggered with an injection of human chorionic gonadotropin (hCG).
Thirty-six to 37 hours after the hCG injection, eggs are retrieved by passing a needle through the vaginal wall into the ovaries to remove the eggs from the ovarian follicles. Intravenous sedation assures that the patient feels no pain. As the patient’s follicles are aspirated by the physician, an embryologist identifies eggs within the follicle fluid. The eggs are placed in a dish in an incubator, and they are later inseminated with sperm that the husband or partner produced around the time of the procedure.
On the day after the retrieval the embryologist evaluates the number and quality of newly fertilized embryoes. Sometimes, embryos are frozen the day after IVF for use in future cycles. The remaining embryos are cultured for transfer back into the woman’s uterus between three and six days in culture in the laboratory. In special situations the growing embryos are biopsied so that genetically abnormal embryos may be excluded by preimplantation genetic diagnosis (PGD).
The embryo transfer (ET) is a simple procedure which requires no anesthesia. The number of embryos transferred back into the patient is chosen in a way to balance the risk of multiple gestation against the risk of not conceiving. Injections of progesterone are taken daily to “support” the implantation process. About two weeks after the eggs were retrieved, blood tests are performed to determine whether or not pregnancy has successfully occurred. The early pregnancy will be followed with blood tests and ultrasounds in order to be sure it is progressing normally.
Preimplantation Genetic Diagnosis
What are Chromosomes?
Chromosomes are string-like structures found in the center of every cell (the nucleus). Chromosomes contain genes that are made of DNA. Therefore, our inherited information is housed on the chromosomes. Normal human cells (embryo, fetus, baby or adult) contain 46 Chromosomes or 23 pairs. We receive 23 chromosomes from each parent. The first 22 pairs of are the same for men and women and labeled largest to smallest: 1 through 22. The 23 rd pair determines our sex. To test for a chromosome abnormality such as Down syndrome, the chromosomes are studied.
Chromosomal Aneuploidy
Spermatozoa or eggs that have extra or missing chromosomes will pass this problem on to the embryo after fertilization. This situation is known as aneuploidy. There can be extra (trisomy) or missing (monosomy) chromosomes. Both conditions are a problem. If the aneuploidy involves the larger chromosomes, the embryo may not attach to the wall of the uterus or may stop developing soon after and miscarry. In some cases, however, the aneuploidy may cause the fetus to be abnormal but carry to birth. Down syndrome is an example of this, but there are several other types. The features of the chromosome condition depend upon which chromosome is extra or missing, but can include physical abnormalities and mental retardation.
Avoiding Transfer of Chromosomally Abnormal Embryos
Aneuploid embryos are mostly indistinguishable morphologically and developmentally from chromosomally normal ones, thus, without genetically testing them, the embryologists doing your IVF procedure cannot recognize them and may transfer chromosomally abnormal embryos to you.
The PGD Procedure
A technique called Preimplantation Genetic Diagnostics (PGD) has been developed to test your embryos prior to the transfer of the embryos to the uterus. This technique consists of the removal (biopsy) of one cell of each embryo, followed by a very fast genetic analysis using a technique called fluorescence in situ hybridization (FISH), and the subsequent replacement of those embryos identified as normal. Normal embryos have a higher chance of implanting, resulting in pregnancy and not miscarrying, than abnormal embryos.
The cells to be analyzed are either polar bodies or blastomeres. The ripening egg produces two small cells called polar bodies that degenerate after fertilization. The chromosomal or genetic content of these cells allows us to infer the chromosomal content of the egg. If one is testing the polar body, an opening is made in the zona pellucida, the covering of the egg, and the polar body is removed via aspiration with a pipette, a very thin glass tube. The polar body is then analyzed while the egg is placed in an incubator. By analyzing polar bodies, we obtain information from only the mother.
Paternal or sperm genetic information or chromosome abnormalities that may occur after fertilization will not be detected. At least one third of abnormalities occur during or after fertilization and are not found in the egg. That is why we prefer to biopsy cells from the embryo. A blastomere is a cell from an embryo. To obtain the blastomere, an opening is made in the covering of the embryo during its third day of development when the embryo has 6 to 10 cells. A blastomere is removed by gentle suction. The embryo is placed in an incubator while the cell is analyzed. Chromosomal disorders are tested by direct study of the chromosomes.
Not all genes or chromosomes can be studied by PGD and one cannot test for both genes and chromosomes from the singles cell concurrently. Neither test is 100% accurate because we can only biopsy a single cell from the embryo, thus follow-up prenatal testing via chorionic villous sampling (CVS) or amniocentesis is highly recommended.
Risks of the PGD Procedure
While PGD is a relatively new procedure in IVF, the micromanipulation or biopsy techniques required to perform the procedure have been in use for many years. The risk of accidental damage to an embryo during the removal of the cell(s) is less than 1% in experienced fertility centers. Additionally, no part of the future fetus will be lacking because of the removal of a cell. There is no clear evidence that biopsy of one cell is a problem for the developing embryo later on.
The test may occasionally classify an abnormal embryo as normal. Very few of such pregnancies have occurred. The reverse may happen, too - a normal embryo that is tested may be classified as abnormal by mistake, though the chance of this is also small. Again, due to the small chance of misdiagnosis as well as the presence of conditions not tested for via PGD, prenatal testing is still recommended.
How Can You Have PGD?
PGD is usually preformed in a very specialized genetics center. Your IVF center will arrange for or perform the biopsy and process the cell and then send it to Reprogenetics. Reprogenetics scientists developed the first tests for PGD of aneuploidy, and therefore, are one of the PGD centers with the most experience in this technique. For more information regarding Reprogenetics, please check www.reprogenetics.com. If you are interested in PGD through PRS, please email us info@prsfertility.com.
What About Cost?
As you might expect, this technology doesn't come cheaply. This procedure may add close to $6,000 to the cost of IVF. Few insurance policies cover the expense.
We are here to answer any questions you might have about our services, procedures, making an appointment for treatment or consultation. Please contact us today by calling (215) 822-8400 or filling out the contact form on our website for more information. Or if you are ready to schedule an appointment, you can do so right here.
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