Human Egg Freezing/ Preimplantation Genetic Diagnosis (PGD): Doesn’t Help Pregnancy Disorders

Human Egg Freezing/ Preimplantation Genetic Diagnosis (PGD): Doesn’t Help Pregna

The research on methods of improving the chances of pregnancy; fertilization; egg activation, maturation, and freezing; genetic diagnosis before implantation; and the development of embryonic stem cells is important hot issue today. Research on the cloning and use of oocytes without their transfer to the uterus for gestation was considered to warrant additional review. Unacceptable research included the cloning and use of oocytes followed by transfer, and cross-species fertilization.

Egg freezing is an evolving technology that preserves a woman’s fertility by literally keeping her eggs on ice until she decides to get pregnant. Egg freezing is not as simple as it sounds. Unlike freezing embryos, which has been widely available for decades, freezing human eggs is difficult. An egg is the largest cell in the body and is filled with water. When an egg is thawed, ice crystals cause damage that will prevent it from being fertilized. Preventing ice crystal formation is critical to freezing and thawing eggs successfully. Currently, egg freezing techniques have a low rate of success. However, researchers are trying to make significant progress.

Semen stored by freezing may be undertaken at a time of great emotional stress when future fertility is unlikely could be an immediate priority. Cancer treatments such as chemotherapy and radiation therapy can cause damage to a woman's reproductive system and leave her unable to have children afterward. Some women may regain their reproductive function after their treatment ends and may be able to conceive on their own, while others will become infertile. Egg cryopreservation could be insurance for those women at highest risk of fertility problems after cancer treatment. When a woman wishes to become pregnant, the vitrified eggs would be warmed and then fertilized with male sperm. The fertilized eggs would then be transferred to the uterus in the same procedure that's used successfully when couples freeze embryos.

In the United States, oocyte cryopreservation is aimed at three groups of women in particular: those diagnosed with cancer who have undergone chemotherapy or radiation, both of which are toxic to oocytes; those who do not, for moral or personal reasons, wish to freeze embryos; and those who do not currently have a partner, but would like the option of having children in the future through IVF.

Researchers led by a University of Missouri-Columbia professor of reproductive biotechnology have reported success in freezing and preserving swine embryos that were created by in vitro techniques and that carried modified genetic material. After thawing and transfer to a surrogate mother, some of the embryos went on to produce live piglets with new genetic traits.

The potential applications of preimplantation genetic diagnosis continue to expand.10 Women who have had repeated spontaneous abortions of fetuses with aneuploidy appear to be at increased risk for having live-born offspring with aneuploidy in subsequent pregnancies. This increased risk may be due to abnormal meiotic or mitotic processes.

One of the more cutting edge technologies is pre-implantation genetic diagnosis, or pre-implantation genetic screening for women getting IVF. This technology allows an individual embryo to be tested for a specific genetic disease such as cystic fibrosis or sickle cell disease in certain populations. Also, it is at times possible to screen for conditions such as Down's syndrome. The ability to test embryos prior to implantation is important for some women and is a relatively new technology.

PGD is a new option for couples at risk of transmitting genetic diseases. Instead of carrying out a prenatal diagnosis followed by a termination of pregnancy, in vitro fertilization (IVF) with intracytoplasmic sperm injection (where a sperm is injected directly into an egg) is performed, followed by genetic testing of the embryos. Only unaffected embryos are subsequently transferred to the womb.

Preimplantation genetic diagnosis (PGD) is a technique used during the IVF process to test embryos for genetic disorders. After embryos are created, they are allowed to mature in the laboratory for 3 days. After the embryos reach a certain stage of development, a single cell can be removed from the embryo and tested for the presence of certain genetic disorders. The embryos that do not contain the disorder can then be trans­ferred to your uterus or frozen for future use. The embryos that contain the genetic defect can be discarded or donated to research. Alternatively, some couples may also choose to im­plant embryos with known genetic disorders. But because there is a slim chance a genetic abnormality can cause doctors to misdiagnose embryos.

Furthermore, say the investigators, the limitation on the number of chromosomes that can be analysed could lead to the transfer of embryos that appear normal but are in fact abnormal for one or more chromosomes not tested. Finally, many embryos resulting from IVF may be mosaic, where a single cell does not properly reflect the chromosomal composition of the whole, so that chromosomal analysis may not be representative of the entire embryo; according to 23rd annual conference of the European Society of Human Reproduction and Embryology.

For patients who are undergoing preimplantation genetic diagnosis (PGD) for a homozygous recessive gene disorder (where an abnormal disease causing gene is inherited from both parents), there could be a serious misdiagnosis of a carrier as being affected if the chromosome containing the normal gene is lost in the biopsied cell through a chromosome assembly defect." On the other hand, in a dominant disorder, where one parent has a disease-causing gene that dominates its normal counterpart, loss of the affected chromosome in the biopsied cell could result in the embryo being wrongly diagnosed as normal; according to 20th annual conference of the European Society of Human Reproduction and Embryology.

While this approach to the management of Huntington disease offers enormous potential benefits, it raises several important issues. It is apparent that IVF and PGT would be offered to some couples in whom the at-risk parent was actually unaffected and this could be construed as an inefficient or "wasteful" use of an expensive technology.

In the U.S., IVF with PGT is available for about $10,000 per treatment cycle, and less in some other countries. Hence, for an average cost of about $50,000, a couple containing one member at risk for having the Huntington gene could be on average assured of having two unaffected children and the risk of the disease in all future generations would be eliminated.

For many years its not possible reliably freeze mature eggs and have them do what we wanted them to do when they were thawed - in other words, fertilize normally. Sometimes it is possible to freeze embryos for quite a long time, and that is very common but some women are unable to freeze embryos. They may not have a partner at the current time but they want to maintain their fertility potential in the future. It's been very difficult to freeze oocytes (mature eggs) but progress has been made in that area and there have been a number of human pregnancies. It is still not mainstream topics.

According to Paulson; director of reproductive endocrinology and infertility at the University of Southern California in Los Angeles: "The approach can be beneficial for women who suffer repeat miscarriages due to chromosomal abnormalities, but it has not proven its worth as a routine screening technique for all patients. Among its drawbacks, PGD can damage embryos and may not always give accurate results because one cell does not necessarily reflect the health of the entire embryo. An improvement, he says, would be a noninvasive test that would provide more precise information, perhaps using a special microscope."

Some researchers also fear PGD will be used to create “designer babies” with specific traits that have nothing to do with their health. The technology is already being used in some cases solely to choose a child’s sex. But, even if these diseases can be identified, experts say they’re still a long way from being able to “fix” embryos by altering their DNA.

Another study found that 85 percent of embryos transferred during in vitro fertilization fail to become live births, highlighting the need for improving diagnostic techniques to identify viable embryos. The study reviewed seven years of U.S. statistics from all the fertility clinics that report data on reproductive techniques. Director of the Yale Fertility Center, Pasquale Patrizio, M.D., professor in the Department of Obstetrics, Gynecology & Reproductive Sciences led the project. "Something in nature has decided that these implanted embryos are not viable"; he concluded.

Concerns have been raised that children born after PGD would face a higher risk of malformation, given that the procedure involves removing cells from an embryo. Dr. Ingeborg Liebaers of the Research Centre for Reproductive Genetics noted in an interview. However, the rate of malformations found in the group in the current study — 3.6% — was no higher than among children born after IVF who did not undergo PGD.

A randomized clinical trial of 406 patients with advanced maternal age by Mastenbroek and co-workers recently published in the New England Journal of Medicine showed a significant decrease in pregnancy outcome after preimplantation genetic screening (PGS). It is our opinion that this study suffers from a number of insurmountable inaccuracies and that these are either a direct consequence of the inexperience of the team or of a general disregard of vital guidelines reported in the literature. Most importantly, the authors show that in their hands embryo biopsy may affect as many as half the embryos.

Two experimental fertility procedures -- preserving a woman's eggs by freezing them and testing an embryo for genetic flaws by sampling a single cell -- remain unproven, the American Society for Reproductive Medicine advised Recently. The American Society for Reproductive Medicine, founded in 1944, is an organization of more than 8,000 physicians, researchers, nurses, technicians, and other professionals dedicated to advancing knowledge and expertise in reproductive biology.

Such warnings join a host of concerns -- including some raised by a recent study in the New England Journal of Medicine -- that question the usefulness of advanced fertility treatments for many patients. While such treatments are offered with all kinds of caveats that no baby is guaranteed, the marketing of them may play into the fears of patients facing an emotionally fraught decision. At their worst, critics say, some treatments may interfere with patients' goal of having a baby. And they are expensive, often costing thousands of dollars.

The group recommended comprehensive counseling for any women seeking egg-freezing services, even though some studies have shown that healthy babies have been born using frozen eggs or ovarian tissue. A few clinics are advertising these procedures and news reports have been describing them, but the group said women should know they are far from routine.

"With any new technology it is vital that patients understand completely what the process entails and the likelihood of a successful outcome," said Dr. Marc Fritz, chair of the ASRM Practice Committee. A few reports have shown that a young girl or woman can have her eggs, or in some cases ovarian tissue, frozen ahead of cancer treatment or other procedures that may destroy fertility.

But the society, which is meeting in Washington, said that the currently available data are too limited to allow egg freezing to be considered an established medical treatment. No numbers on how many women have tried the technique were available. Human eggs are more fragile than human embryos, which are now commonly frozen for years before use.

ASRM, a group that includes fertility doctors, also said a growing practice called preimplantation genetic testing remains experimental. This testing, done on embryos created in lab dishes via in vitro fertilization or IVF, involves the removal of one or more cells to check for genetic problems before the embryo is implanted in the mother's womb. It is standard for checking for genetic diseases such as cystic fibrosis, a fatal and incurable condition caused by a single mutated gene.

But the ASRM said evidence did not support the use of the procedure to improve the odds of pregnancy for an older woman, or to reduce the rate of miscarriages.” The use of preimplantation genetic screening for chromosomal problems may one day become an essential component of infertility therapy, but for now, available evidence does not support its effectiveness and common usage," ASRM president Dr. Steven Ory said in a statement.

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