New Developments In Assisted Reproductive Medicine

By Gad Lavy, MD, FACOG

The success of IVF (in vitro fertilization) has risen dramatically over the past two decades.  The increase in success can be attributed to better understanding of various conditions leading to infertility and to development in cell biology in our understanding of egg and sperm interaction, embryo development, and implantation. At the same time, the IVF procedure has been simplified. Egg retrieval, once requiring laparoscopic surgery and general anesthesia, is now done in an office setting using ultrasound.  The increase in success combined with the ease of use has made IVF accessible and applicable to more couples.

However, despite these significant improvements, IVF success is still limited by factors such as age and the accompanying reduction in egg quality. Additionally, standard IVF requires the use of ovulation drugs with the potential of side effects and serious complications.

In this review we will address three emerging technologies aimed at addressing the above issues and making IVF easier and more effective.   These include:

1. PGD: Pre-Implantation Genetic Diagnosis

2)   Egg Freezing

3)   IVM: In Vitro Maturation

PGD: Pre-Implantation Genetic Diagnosis

PGD has joined amniocentesis and CVS (chorionic villi sampling) and is becoming an important addition to our prenatal testing (tests done prior to birth). In contrast to the other two, PGD provides information on the developing embryo, allowing the diagnosis to be made prior to implantation. This allows us to prevent a variety of abnormal pregnancies, miscarriages, and birth defects.

PGD was pioneered in the early 1980’s as a genetic testing tool to help identify healthy embryos in couples that were carriers of debilitating and even fatal genetic disorders such as cystic fibrosis and muscular dystrophy. These conditions involve a specific defect in a single gene. More recently it has become possible to use PGD to diagnose a different class of problems, those involving an abnormal number of chromosomes (aneuploidy). Those problems can lead to conditions such as Down’s syndrome and are much more prevalent in the infertile population than the gene disorders. These abnormalities are generally linked to poor egg (or sperm) quality and are often a result of aging.

Indications for PGD:

1. Known carriers of genetic defects
2. Older couples undergoing IVF
3. Couples with repeated IVF failures
4. Couples with a history of miscarriages
5. Couples with severe male factor infertility

In those cases, PGD can:

1. Improve the odds of a successful outcome
2. Lower the risk of miscarriage
3. Lower the risk of various birth defects
4. Allow the couple to understand the cause of their infertility and “move on”

The PGD procedure is highly complex and requires the coordinated efforts of the entire IVF team, the physician, nurse, embryologist, geneticist, and psychological counselor.

Two technologies have made PGD possible:  micromanipulation and genetic diagnosis.  Following fertilization and embryo growth, a single cell is removed from an eight-cell embryo.  Micromanipulation allows the “biopsy” to be done without damage to the embryo. The cell is then analyzed using modern genetic testing to allow the information to be available in time for the embryo transfer 24-48 hours later.  The information is then used to determine which and how many embryos will be transferred.  At the present time our ability to use PGD for diagnosis is limited by the fact that not all disease-causing genes have been identified and by the fact that we are still unable to count all the chromosomes in a single cell using the available techniques. However, these issues are currently being studied and will likely be remedied in the near future.

To date over 20,000 births have been reported following IVF/PGD. There appears to be no impact of PGD on the embryo’s ability to implant and grow into a healthy baby.

The future of PGD appears promising. It is very possible that it will become an integral part of the IVF procedure. At our center we explain PGD to all patients who are undergoing IVF. Any patient who thinks she may be a PGD candidate should ask her reproductive endocrinologist to do the same.  We use the indications listed above to recommend the procedure to an individual couple.

Egg Freezing

Freezing of sperm and eggs has been available for quite some time and is used routinely with good results. The success of egg freezing however has been limited.

The potential applications of egg freezing can be far-reaching and include:

1. Single women who are diagnosed with cancer and are about to have surgery or chemotherapy, which is likely to damage their ovaries.
2. Single women who are concerned about the effect of aging on the quality of their eggs and their chances of achieving a successful pregnancy.
3. Creating egg donor banks similar to sperm banks, providing couples in need of egg donors a wider choice and simplifying the procedure.
4. A way to limit the number of embryos created during standard IVF.

Recent developments in the field of cryobiology have made egg freezing a reality. Cryobiology involves the study of the freezing of cells and biological material. During freezing, ice crystals form within the cell and can damage essential structures leading to cellular abnormalities or cell death. In order to minimize cell injury during the freezing process, special “anti-freeze” solutions are used. Each cell has its own special characteristics, which need to be addressed in order to achieve success. The egg cell, the largest cell in the body, is especially sensitive to the damage caused by freezing.

Recently, better understanding of the egg cell has led to successful freezing. Experience is still limited. Only 300 births have been reported thus far worldwide with no evidence of birth defects resulting from the procedure.  The process involves the use of ovulation drugs similar to those used for standard IVF. Eggs are retrieved and frozen prior to being fertilized. The eggs can then be kept for prolonged periods without any deterioration.  When needed, the eggs are thawed, fertilized, and transferred, again the same as with standard IVF.

In Vitro Maturation of Eggs (IVM)

The IVF procedure includes the use of ovulation drugs in order to help develop and mature a large number of eggs. Those eggs are then retrieved and fertilized. There are certain drawbacks to the fertility drugs, particularly the gonadotropins that are used for IVF.  The drugs have to be administered by injection; side effects are not uncommon and on occasion can be serious (hysperstimulation). In addition, there is some theoretical concern of long-term side effects with prolonged exposure to these drugs.

The idea of performing IVF without drugs is therefore very attractive.  In IVM, egg retrieval is performed using a minimal dose of medications or no drugs at all. In most cases up to 10 eggs can be retrieved. Those eggs are immature and need to be treated with the same fertility drugs in order to achieve maturation. Only then can they be fertilized and grown into healthy embryos. Despite repeated attempts over the years, the success of this procedure is still limited, probably due to gaps in our understanding of the normal process of egg maturation. It remains, however, a very promising technique.

Summary

IVF is rapidly evolving. Major improvements have been made but apparently much remains to be learned.  For the infertile couple, these advancements can mean easier access to therapy and better outcomes.  The key to success is proper diagnosis of the cause of infertility and the application of new technology when appropriate.

Dr. Gad Lavy, MD, FACOG, is the founder and

Medical Director for New England Fertility Institute and

Lifeline Cryogenics.  Dr. Lavy can be reached

at GLavy @nefertility.com or 203-325-3200.