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.

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.

p>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.

Our 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.

For more information about this new procedure or about Santa Monica Fertility Specialists, email me at info@santamonicafertility.com. You can also visit http://santamonicafertility.com/ for more information.

http://news.bbc.co.uk/2/hi/health/7494772.stm

Fertility preservation treatment prior to chemotherapy or radiation remains the most effective way to safeguard future fertility for women facing a cancer diagnosis. For this reason a frank discussion of fertility preservation options should occur prior to cancer treatment. Here, Dr. John Jain discusses one option—cryopreservation—and one patient’s journey of hope.

When I first met with Susan,* a 33-year-old married woman, she had recently found a lump in her right breast and had been diagnosed with Stage I invasive breast cancer. Due to the small size of her breasts, she had undergone a right mastectomy and was set to begin adjuvant chemotherapy in six weeks.

When Susan and I had our initial meeting, we discussed the fact that several important issues must be evaluated before any cancer patient could initiate a program of fertility preservation. These issues include the age of the patient as well as the stage and the type of the cancer. Fertility preservation options are best suited to women under 40, as this represents the most fertile period, when viable egg count is still sufficient. In Susan’s case I was able to tell her that she was a good candidate for cryopreservation (freezing of eggs or embryos) because of both her age and the fact that her Stage I diagnosis did not require immediate therapy, which would have precluded egg harvesting.

Though Susan and her husband were counseled on both egg and embryo cryopreservation, they ultimately decided to proceed with egg freezing because they had ethical concerns about the disposition of embryos should Susan not survive her cancer. Although egg freezing is still considered an investigational procedure, results indicate that it may be as effective as freezing embryos. As we discussed the couple’s options, I was clear about the fact that, generally speaking, in cases where either eggs or embryos are preserved, clear advance directives are imperative to avoid future conflict.

Having made the decision to move ahead with egg freezing, Susan began the process of ovarian stimulation. Typically, for egg or embryo cryopreservation, ovarian stimulation is initiated at the start of a menstrual period, although more-rapid methods can be utilized to accommodate cancer treatment schedules. Daily injections of medications are required for ovarian stimulation to induce multiple eggs. These medications are administered for approximately 10 days, followed by ultrasound-guided egg retrieval under anesthesia. The eggs can then be frozen or fertilized with sperm and frozen as embryos.

An important factor that Susan had to consider as the couple moved forward was the fact that the daily injections she was required to undergo would cause elevated circulating levels of estrogen. This increased estrogen exposure is a particular concern for women with estrogen-sensitive cancers, such as breast cancer. One method to lower this risk is to use an aromatase inhibitor, a drug that lowers the amount of estrogen produced. This method yields fewer eggs and embryos than traditional egg stimulation, however, and the ultimate effect of low estrogen production on egg and embryo quality has yet to be fully determined. The effect of one to two weeks of elevated estrogen on cancer risk is not known.

Taking the risk of increased levels of estrogen into account, and considering Susan’s breast cancer characteristics, she and I discussed the option of an aromatase inhibitor protocol versus a traditional protocol. Because the couple wanted to maximize the yield of eggs, they chose a traditional protocol, which was modified with the addition of an aromatase inhibitor administered after the eggs were removed. This worked to stop further production of estrogen. Given Susan’s good prognosis, her oncologist supported this approach.

Ultimately, the cycle yielded 20 mature eggs for cryopreservation. Now, a year later, Susan and her husband have not yet attempted to conceive but feel very fortunate to have made the choice they did. Their decision provided them with a sense of hope and the ability to focus on Susan’s treatment at the time. And now, although Susan may very well conceive naturally, the couple feels that concerns about diminished egg counts and a possible increase in birth defects following cancer therapy make the frozen eggs they were able to secure a priceless gift.

* This patient’s name has been changed to protect her privacy.

John K. Jain, MD, FACOG, is a board-certified reproductive endocrinologist and a pioneer in the field of reproductive medicine. He is the founder of Santa Monica Fertility Specialists, a world-class fertility center offering a comprehensive range of care from basic testing to advanced in vitro fertilization techniques, including egg freezing, tubal embryo transfer, egg donation, and gestational surrogacy. Dr. Jain completed his medical training at the University of Southern California, where he was a tenured professor of obstetrics and gynecology. His egg-freezing work has earned him international recognition, and he is one of only four reproductive endocrinologists to be named to the National Scientific Advisory Council of Fertility Preservation by the National Institutes of Health. In addition to his many important publications, he is the author of the most current and complete scientific review article on egg freezing. In 2006 his work earned him the Pacific Coast Reproductive Society’s top research prize. Dr. Jain can be reached at info@eggfreezingcenter.com.

On June 17 and 19, 2008, McGill University released the results of a study that showed the safety of an advanced egg freezing technique. In one of the most exhaustive studies yet of children born after the freezing procedure, the researchers found that children conceived by egg freezing were as healthy as those conceived by IVF or conceived naturally.  The advanced egg freezing technique in the study and the method used at Egg Freezing Center, is vitrification, a method that rapidly freezes eggs to prevent ice crystals from forming, which can damage the cells.  

I applaud Dr. Chian and colleagues for providing a registry of birth information following egg vitrification. As we continue to refine methods of egg freezing, it is paramount that we monitor birth outcomes to assure safety. It is reassuring to see that Chian and colleagues demonstrated no increase in the rate of birth defects from vitrification, as similar registries in Europe have indicated the same following slow-freeze methods.

We have commenced an organization to create a US national registry of births from egg freezing. We hope to report the results of that registry early next year.

More information about the study and vitrification can be found at the links below.

http://www.mcgill.ca/newsroom/news/item/?item_id=100649  

http://news.bbc.co.uk/2/hi/health/7458415.stm  

http://www.timesonline.co.uk/tol/life_and_style/health/article4152437.ece  

http://www.mcgill.ca/newsroom/news/item/?item_id=100710  

http://www.thestar.com/article/445806  

http://eggfreezingcenter.com/