EGG FREEZING PROGRAM

Women today lead highly demanding lives and often are faced with the need to obtain advanced degrees in pursuing their careers before choosing to start a family.

However, waiting to have children exposes many women to a more difficult time in achieving a successful healthy pregnancy. Unfortunately, because of the biological clock, egg quality and quantity begin to decline when the “right time” finally arrives.

Egg freezing potentially offers women, who are planning to delay motherhood, the opportunity to beat the biologic clock and store their eggs during their optimal reproductive years for later use to either start or expand their family.

Although embryos (fertilized eggs) and sperm have been successfully frozen and thawed to create healthy children for several decades, it is only recent that egg freezing has been a successful reality.

Sperm freezing and embryo freezing are both easier to accomplish than freezing unfertilized eggs. Sperm are very small-sized (180 times smaller than the egg cell) and therefore have a low water content. Egg cells, being larger, have a higher water content and are more likely to develop ice crystal damage during freezing which will damage the egg membrane and cause rupture of the cell.

Embryo freezing, which has enabled thousands of babies to be born since 1984, is also easier because the membrane is more sturdy than that of the unfertilized egg even though they are both approximately the same size.

The first successful pregnancy from frozen eggs was reported by Chen in 1986. For the following 16 years, the success rate remained 1-3% at centers throughout the world despite numerous attempts to find a method that worked.

In 2002, the success rate jumped with reports of 20-50% per embryo transfer. The reason for this remarkable improvement in success rates was a function of improvements made in 2 areas. First, the development of better cryoprotectants – the antifreeze that protects eggs during the freezing process. And secondly, changes in the rate with which the eggs were frozen and thawed.

Because eggs are a 180 times bigger than sperm and their membrane is extremely sensitive, we realized that in order to protect the egg during the freeze / thaw process, cryoprotectants that would reduce dramatically the amount of water that remained in the egg during the freezing process would have to be modified. Secondly, the use of sucrose during the thaw process that would allow the egg to rehydrate slowly and prevent the rapid influx of water into the thawed egg which would prevent the egg from swelling and bursting was an additional improvement.

For your information, the common cryoprotectants for freezing are: a solvent (DMSO), a carbohydrate (Sucrose) and an alcohol (1,2-propanediol).

An alternative method called vitrification is an ultra rapid freezing technique where the unfertilized eggs are placed in a cryoprotectant and quickly immersed in liquid nitrogen. There have been pregnancies with this new methodology but it is still a matter of debate whether slow freeze / rapid thaw or the quick freeze method is superior.

Which individuals benefit from Egg Cryopreservation?

• individuals who anticipate are delaying motherhood until later in life but desire to    preserve their reproductive potential of when they were younger
• Women who are at risk of becoming sterile because of chemotherapy or radiation    therapy or surgical removal of their ovaries because of cancer
• Couples undergoing IVF who are morally or ethically opposed to freezing
   pre-embryos or embryos

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Who is a good candidate for egg freezing?

Egg quality differs from patient to patient so it is not feasible to advise any patient their exact chances of achieving pregnancy from a specific number of frozen eggs. In some cases, individuals will produce multiple follicles and as many 15 mature eggs can be obtained from one cycle. Other patients may require 2 or more cycles to achieve this number.

Age is an important predictor of ovarian reserve and is a useful guide to help patients assess how many eggs will be retrieved. Patients who are older than 37 will often times have less eggs and less optimal quality eggs than patients who are younger. The three most important factors that help determine new chances for success with the egg freezing are:
FSH and Estradiol
The follicle count of your ovaries during the menstrual phase
Ovarian reserve testing with the Clomid challenge test
These studies are helpful to help estimate your ability to produce healthy eggs that are of sufficient quality to be successfully frozen, thawed, fertilized and then developed into healthy embryos.

How is the Clomid challenge test done?

Some programs recommend the use of the Clomiphene citrate (Clomid) challenge test. On menstrual day 3, blood is drawn for FSH and Estradiol. Clomid 100 mg is given days 5-9 and then a repeat FSH and Estradiol level is drawn on day 10.

Additional studies

In addition to knowing the quality of the ovarian reserve, it is equally important to determine that the uterus will be able to provide the embryos resulting from cryopreserved eggs with a suitable environment. Therefore, we advise all patients considering freezing to have a hysterosalpinogram and in some cases a sonohysterogram and/ or MRI of the pelvis to be certain that there are no polyps, scar tissue within the cavity, or fibroid tumors. In addition, if a patient has a hydrosalpinx (a blocked tube that is filled with fluid), this should be removed prior to IVF embryo transfer of the cryopreserved egg. This procedure can be performed by your local obstetrician / gynecologist or fertility specialist.

Out of state patients – Coordinating Care with Your Local Fertility Specialist

Arrangements will be made through our cryopreservation egg IVF coordinator with a specialist in your local area to coordinate monitoring and stimulation of your cycle. Hormone and ultrasound data will enable us to assist your physician in regards to the dose of medications you will be taking and when it is necessary to be seen at one of our centers. In general, most patients from out of town will require you to be in New York City 3-5 days at most.

Stimulation of the Cycle

In the normal unstimulated cycle, a woman usually produces only one egg each month. In order to produce multiple eggs from the ovary, gonadotropin medication (follicle-stimulating hormone and luteinizing hormone) are given to allow multiple healthy eggs to develop and later frozen. These hormone medications are given on a daily basis for approximately 10 days.

Additionally, to monitor your response to these medications and avoid the risk of ovarian hyperstimulation, monitoring with a vaginal ultrasound and a blood Estradiol level is done frequently – everyday or almost every other day. Instructions regarding the injection of medications can be done through your local fertility specialist.

For out of town patients, the first 7 days of monitoring will usually be done with your local physician. When the follicles appear to be close to the point of maturity, we will see you at one of our centers so that Dr. Brandeis can determine the day of human chorionic gonadotropin should be administered. This medication is given when the majority of follicles are at an optimal mature stage of development. Approximately 35 hours after this medication is administered, egg retrieval is performed. IV sedation is used to avoid discomfort during the procedure.

Before your egg retrieval of eggs to be used for cryopreservation is done, you will meet with our anesthesiologist who will review your history and discuss alternative medications that can be used.

How do I prepare for my retrieval?

We ask all patients to avoid eating or drinking for at least 6 hours before any procedure that involves anesthesia. These anesthetic medications wear off quickly after the procedure. The retrieval process similar to standard IVF takes about 15 to 30 minutes, depending on the number of eggs you produce.

Removal of the eggs involves aspiration of the follicles using a vaginal ultrasound probe and a thin needle that is carefully and gently placed though the wall of the vagina. After your retrieval, you will remain in the recovery area for about an hour. Dr. Brandeis will then meet with you and provide you a complete report of the number of eggs obtained that can be used for egg freezing. We require all patients to remain the New York area for 24 hours prior to returning home.

Follow-up care for egg freezing patients will be through Dr. Brandeis and your physician.

Following the Freezing Process

Your Cryopreserved eggs will be transferred to a liquid nitrogen storage tank and they will remain stored in a frozen state until used for fertilization.

Cryopreserved eggs are stored in unique holding tanks that are filled with liquid nitrogen. Current information suggest that there is no detriment to the frozen eggs even when they are held for a extended period – but long term studies have not yet confirmed this to be absolutely true.

Thawing and using your frozen eggs

Patients must notify our center at least 3 months in advance before the time they will desire that the eggs be thawed and fertilized.

During the cycle that the Cryopreserved eggs will be thawed / fertilized to form embryos, we will recommend Estrogen patches in increasing amounts for approximately 14 days. Near the mid cycle, an ultrasound will be done on Day 13 to determine if the endometrium (inner lining of the uterus) is adequate in thickness.

Estrogen and progesterone blood levels will also be obtained the same day. If the lining is not thick enough, we will then extend the duration of treatment.

Once the endometrial thickness is acceptable, you will start progesterone. The cryopreserved eggs will be thawed and inseminated with your partner’s or a donor sperm.

The success of fertilization of cryopreserved eggs is greatly increased by the use of ICSI (Intracytoplasmic Sperm Injection).

The reason why ICSI is necessary as opposed to just exposing the sperm to the thawed eggs is that the zona pellucida (the outer membrane that covers the outside of the egg) is affected by the freezing process. The zona pellucida plays a key role in allowing the egg to fertilize. Damage to the zona makes it more difficult after eggs are thawed for sperm to naturally attach and penetrate to the zona pellucida as it normally occurs. And by injecting the sperm directly into the egg, we can overcome these changes in the zona pellucida.

Dr. Brandeis will recommend embryo transfer 2-5 days after the egg is fertilized. His decision will be based upon how the embryos produced from cryopreserved eggs are dividing and the couples’ particular concerns about multiple pregnancy. The ultimate decision is a shared decision and your particular desires and concerns are important to Dr. Brandeis.

You will continue the use of Estrogen patches and progesterone given by daily injection even after pregnancy has occurred. Dr. Brandeis will recommend estrogen replacement for the first 6 weeks and progesterone for the first 12 weeks.

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