In Vitro Fertilization With Frozen Eggs

Unlike sperm and embryo cryopreservation, which have become routine processes in assisted reproductive technology, success with freezing eggs has historically been difficult to achieve. This is because the egg is the largest cell in the human body and contains a considerable amount of water.

When eggs are frozen, ice crystals form that can destroy the cell. To prevent this, the egg must be dehydrated prior to freezing. The water is then replaced by a special “antifreeze” that inhibits the formation of ice crystals. Because the eggshell hardens when frozen, sperm must be injected with a needle in order to fertilize the egg. This is known as ICSI (intracytoplasmic sperm injection) and is a standard technique also used in IVF.

Zygote Intra-Fallopian tube Transfer Shows Promise

Santa Monica Fertility Specialists in Santa Monica California, home to world renown Fertility Specialist Dr John Jain, recently implemented a ZIFT program for women over 40. ZIFT stands for Zygote Intra-Fallopian tube Transfer, a process where embryos are transferred to the fallopian tube soon after fertilization so that they can grow in their natural environment. The reason we offer this is that the increased rate of infertility and miscarriage seen in women over 40 years of age is primarily due to chromosomal errors that occur during egg and embryo development. Growing embryos in the artificial environment of the IVF laboratory puts further stress on developing embryos.

The results with ZIFT and early intrauterine transfer have led to ongoing pregnancies in approximately 60% of the first group of women treated in this manner. ZIFT is also a viable alternative to those women who have encountered multiple IVF failures.

Are Multiple Pregnancies Dangerous?

Over the past decade, improved fertility treatments has lead to a rise in the incidence of twins, triplets and even higher-order (Quadruplets etc.) multiple pregnancies. Although most of these multiple pregnancies are fraternal (each from one egg), the incidence of identical twinning has also increased, probably due to embryo manipulation in the laboratory.

Fertility treatments utilize hormonal injections that increase the number of eggs produced. Following hormone injections, a woman can be artificially inseminated, or undergo in-vitro fertilization whereby the eggs are fertilized in the laboratory and actual embryos are transferred into the uterus.

Multiple pregnancies are considered high-risk pregnancies. For the mother, the risks include increased chance of hypertension in pregnancy, gestational diabetes, cesarean section and hemorrhage at the time of delivery. For the babies, the main risks relate to preterm delivery and the risk of disability or death from underdeveloped organs.

Egg Donation Provides Options for Pregnancy

Egg donation allows women to become pregnant even when they lack eggs of their own, or their eggs are of poor quality. The technique is most commonly used in women who are unsuccessful after undergoing multiple cycles of in vitro fertilization (IVF), those with premature ovarian failure or elevated FSH levels, and those over the age of forty-three. The combination of young eggs and optimal preparation of both donor and recipient makes egg donation a very successful fertility procedure.

The process of egg donation requires that the components of a single IVF cycle be divided between the donor and the recipient. The donor undergoes the initial steps of IVF, including ovarian stimulation and egg retrieval, and the recipient undergoes the embryo transfer.

Both women's cycles must be synchronized using birth control pills. When the cycle begins, the donor is administered the medications required for egg follicle development, while the recipient takes a combination of estrogen and progesterone to prepare the uterine lining for implantation. Once the donor's eggs are mature, they are retrieved and fertilized in the laboratory.

Typically the embryo transfer is scheduled 3 or 5 days later. The recipient continues to take estrogen and progesterone through the end of the first trimester to mimic the hormones produced by the ovary in natural conception. At the end of the first trimester (twelve weeks gestational age, or approximately ten weeks after embryo transfer), when the placenta is producing enough hormones. Estrogen and progesterone supplementation is stopped.

Dr Jain Answers Questions About IVF and The California Octuplets

There has been intense international reaction to the birth of octuplets by a Southern California woman. While the details are not fully available, it appears that several frozen embryos were transferred to the uterus of a 33 year old woman resulting in the birth of 8 infants. Dr. Jain has been interviewed by news agencies from around the globe for his comments and perspective. The following is a summary of the most common questions and excerpts from his interviews:

Who qualifies for in-vitro fertilization?

There are no set qualifications for in-vitro fertilization services. Patients should be assessed for medical, psychological and social well-being. Unique to the specialty of fertility is the health and welfare of the unborn child or children. I try to educate and counsel my patients and make a responsible decision in partnership with the intended parents.

Since this young, single woman lives at home and already has 6 children from in-vitro, is it ethical to help her have more?

It is not my role to dictate how many children a person can have. However, since she represents a situation well outside the norm, I would have recommended psychological evaluation and evaluation of her social situation prior to assisting her with additional pregnancies.

Are fertility services regulated? As a result of this case, will there be more regulations?

There are no specific regulations dictating the practice of infertility. The American Society of Reproductive Medicine has created practice guidelines based on scientific evidence that aid practitioners in the safe and effective provision of fertility services. Most fertility doctors follow these guidelines responsibly. The case presented here is an exception and should not be used as the basis for wide-sweeping rules and regulations. Patients should not be fearful that such rogue behavior is common.

Are there guidelines on how many embryos should be transferred?

In general, for women under the age of 35, no more than 2 high-quality fresh embryos or 3 frozen embryos should be transferred. These guidelines exist to prevent multiple pregnancies which carry with them significant risk for premature birth and life long disability or death. The apparent transfer of at least 6 frozen embryos was well above the standard. I am uncertain why they were not transferred in smaller groups of 2 or 3. As a result, both the mother and the children were put at great risk.

What will happen to the fertility doctor? Will the doctor lose his/her license?

We have Medical Boards for this very purpose. They will no doubt investigate this case, gather all the facts, and determine whether sanctions are warranted. The doctor may be put on probation or have his medical license revoked.

It is important to consult with a specialist like Santa Monica Fertility Specialist Doctor John Jain, MD. Be sure to have all your questions answered and ensure you understand the egg freezing process prior to undergoing Egg Freezing and Fertility treatments.

GENETIC TESTING OF EGGS PRIOR TO FREEZING COULD BE DETRIMENTAL

Eggs are more prone to genetic abnormalities as a woman ages. These abnormalities lead to increased incidences of infertility, miscarriage and birth defects especially in women over 38 years of age. Egg freezing is a method that suspends egg aging. Since the genetic status of an egg cannot be determined solely on appearance, methods to evaluate eggs using genetic probes have developed and recently tested.

The egg discards DNA at two different times during its development, ovulation and fertilization. The reason for this is to reduce the number of chromosomes to 23 in order to match the 23 chromosomes delivered by the sperm. The discarded DNA (in the form of excess chromosomes) is jettisoned outside of the egg as a small, round pocket called the polar body. Removal of the polar body (biopsy) can provide useful information about the genetic status of the egg. For example, if 23 chromosomes are found in the polar body, the presumption is that a normal count of 23 chromosomes remains in the egg. In contrast, if a number other than 23 is found in the polar body, it implies that an abnormal count remains in the egg and suggests that the egg and ensuing embryo will be genetically abnormal.

Testing of the polar body using modern genetic techniques such as Comparative Genomic Hybridization (CGH) or Array-CGH, allows identification of abnormal eggs and can thus help determine the number of genetically normal eggs a woman has to freeze.

However, there are several important limitations to this technology. First, CGH and Array-CGH are still considered experimental, with very little clinical data available. Most clinical data is based on young egg donors and does not reflect the genetic status of eggs from women in their late 30’s.

Second, embryos may be genetically abnormal due to mistakes contributed by the egg at the time of the first polar body formation or the second polar body formation; or mistakes contributed by the sperm at the time of fertilization. Therefore, assessing only the first polar body by no means guarantees that a normal embryo will derive. Third, and perhaps most concerning, is the lack of research regarding the effects of biopsying an egg prior to freezing.

We recently completed a small clinical trial wherein we performed polar body biopsy on eggs prior to freezing. We found a high degree of egg damage. The panel of microscopic pictures above demonstrate these changes: the first picture is a normal egg with an intact first polar body (Photo #1); the next picture is an egg after the polar body was removed (Photo #2); the next two pictures show a biopsied egg after freezing and thawing demonstrating egg contents (Photos #3 & #4) extruding through the biopsy slit. These changes were found on multiple eggs from different patients. These eggs had to be discarded. In addition, many other eggs demonstrated abnormal chromosome segregation after fertilization, and none of the patients achieved a pregnancy.

We vitrified these eggs using a closed container to protect the eggs from viral or fungal contamination. This closed container method, used at the Egg Freezing Center, is currently being tested for FDA approval. Other vitrification methods (open container) expose eggs directly to liquid nitrogen and can lead to contamination. For this reason, the method in use at Egg Freezing Center, and the data presented here is very relevant for patients contemplating fertility preservation and genetic testing.

It is my recommendation that women contemplating egg freezing should not undergo genetic testing of their eggs prior to freezing, but rather use these promising technologies to test eggs in the future once they are fertilized as embryos and have all possible egg-derived and sperm-derived abnormalities present for detection.

It is important to consult with a specialist like Santa Monica Fertility Specialist Doctor John Jain, MD. Be sure to have all your questions answered and ensure you understand the egg freezing process prior to undergoing Egg Freezing and Fertility treatments.