SCIENCE PULSE    Synchronizing Cycles

Pacific Fertility Center takes great pride in its pregnancy success rates resulting from oocyte donations to women who are unable to provide their own high-quality eggs. An oocyte donation procedure involves much more than screening and scheduling. Both the donor and the recipient’s bodies have to be “synchronized” carefully and deliberately, matching the donor's oocytes to the recipient's uterus, as if there were one body making the egg and growing the embryo. This article describes the synchronization steps that match the oocyte to the uterus.

After all parties have completed the required screening, the donor and recipient are typically started on low-dose oral contraceptive pills. While the menstrual cycles of donor and recipient may begin on different days, the pills cause the ensuing menstrual flows to match. Depending on how far apart their menstrual cycles occur, it can take up to two weeks for their respective cycles to be synchronized. Additionally, the pills help prevent the women from developing ovarian cysts, fluid sacs in the ovary, which can delay the start of the cycle.

After a minimum time of at least 14 days of the pill a medication called "Lupron" or "Synarel" is prescribed for both parties. These medications turn off the fertility hormones produced by the pituitary gland and, in essence, shut down the ovaries. Lupron is taken as a subcutaneous injection. Synarel is administered as a nasal spray. Once it is determined that both women’s pituitary glands are adequately suppressed, stimulation of the donor’s ovaries and the recipient’s endometrium may be initiated respectively. Both donor and recipient continue with Lupron injections or Synarel sprays to help prevent early ovulation.

As the donor is initiating stimulation of her ovaries, the recipient starts taking estrogen to prepare the endometrium or uterine lining. The lining is very thin after the menstrual flow. Estrogen stimulates the thickening and development of the lining in preparation for implantation of the future embryo. In a natural cycle, estrogen comes from the follicle developing in the ovary. Since the recipient's ovaries are suppressed, the estrogen comes from medication. An ultrasound will determine the thickness of the uterine lining and some supplementation may be administered to ensure the best possible environment for implantation. She will have between 10 days and two weeks before the implantation.

High tech methods of administering estrogen have been developed. Pure estradiol is very similar to cholesterol, and is very poorly absorbed when taken orally. Injectable estradiol is closest to natural estrogen. It is most easily administered in an oil base, as estradiol valerate. Small amounts of estrogen can also be given through a patch, since estradiol can be absorbed through the skin. Vivelle and Estraderm are examples of estrogen patches. While oral estrogen is not easily absorbed, special manufacturing tricks can improve absorption. Estrace is a pill form in which the estradiol is specially manufactured in microcrystals that have a higher surface area to improve absorption through the intestinal tract.

The donor will begin intramuscular injections of fertility medications that gradually stimulate the growth of numerous follicles on her ovaries. This process is known as controlled ovarian hyperstimulation.

While the donor is administering the fertility medications, she begins to be monitored by routine blood tests that determine estradiol levels to monitor the development of the follicles.

At the same time, the recipient is being monitored by periodic estradiol levels and ultrasound evaluations for endometrial thickness.

After five to seven days of stimulation the donor’s follicles are measured. In a typical stimulation, both the left and right ovaries reveal multiple maturing follicles. Ideally the eggs mature at the same rate so they are all about the same size and have similar capacity to be fertilized.

When the physician determines the optimal timing of the egg retrieval, the donor will receive a final injection called hCG, which will mature the eggs for retrieval.

On the morning of egg retrieval, the male finally comes into play. Ideally a fresh collection of sperm by the recipient's male partner or sperm donor is produced to fertilize the retrieved eggs. A masturbated sperm sample is enhanced by a highly specialized process prior to being placed with the eggs, generally involving washing of the sperm to remove the less viable ones.

Approximately 72 hours following ovum retrieval, selected embryo(s) are transferred to the recipient's uterus. If there are embryos of sufficient quality remaining, they may be cryopreserved for subsequent transfers.

The embryo transfer procedure into the recipient usually requires no anesthesia. A catheter is inserted through the cervix into the uterus, and the embryos are gently and carefully placed into the uterine cavity. The recipient is maintained in a recumbent position for approximately five minutes and then discharged. The recipient will need to take daily progesterone hormone injections in order to sustain an optimal environment for the embryo implantation. This post-implantation or post embryo transfer time is called the luteal phase. Ideally, the embryo begins developing and implants in the lining of the uterus.

Approximately two weeks after the embryo transfer a pregnancy test is performed. If the pregnancy test is negative, all hormonal treatments are discontinued and menstruation will usually ensue within two weeks. If the Beta-hCG titer is rising, as determined by a second test, this indicates that implantation has taken place. Hormone injections will then be continued until 12 weeks of gestation at which time the placenta will supply all the hormones necessary to sustain the pregnancy. In the interim, ultrasound examination(s) will be performed to definitively diagnose pregnancy between 5 to 6 weeks after the embryo transfer.

The donor by this time will begin to return to her regular cycle, and will most likely have her period about 10 days after retrieval.

CRITICAL REVIEW    Egg Freezing’s Future

Oocyte cryopreservation technologies have been evolving since 1986, and there is little doubt that there is a strong future in egg freezing. Young women are expected to have the choice of “banking” a cache of their genetic material for later use. Infertile women may indeed turn to a frozen egg bank, much the way that frozen sperm is marketed, to choose available eggs.

But is that time now?
A handful of infertility clinics are offering female patients a chance to undergo an IVF cycle and freeze their eggs for future use. Eventually PFC expects to offer this. Yet the majority of these clinics insist on prominently displaying the disclaimer that egg freezing technologies are still evolving and are highly “experimental”.

Indeed, as of early 2005, less than 1% of eggs that had been frozen and thawed had resulted in live born infants. (Keeping Egg Freezing in Perspective). Most certainly, egg-freezing technologies advancing cryopreservation of oocytes are evolving rapidly. (A Few Good Eggs). Yet the research community is still weighing the advances of different freezing mediums and methodologies, such as rapid vs slow freezing and thawing.

Responsible researchers/authors publishing their work in the global body of scientific literature are calling for several more years of studies with larger numbers of participants. Most of the current research is based on very small groups.

Cryo Eggs International attributes its success to the advances of Dr. Jeff Boldt, an associate professor of medical and molecular genetics and scientific director of Assisted Fertility Services at the Community Health Network, Indianapolis. He is also reportedly the scientific director at Cryo Eggs International. Yet Boldt’s primary published work in a scientific journal reported the results of a study that only involved 11 women. He is quoted in the media as having a larger number (33) of cycles from which results were comparable to standard IVF procedures, yet this study has not yet been published in a peer-reviewed science journal.

Associated Costs with Frozen Eggs
After oocytes have been frozen they may have a thicker outer wall, otherwise known as the zona pellucida. This generally requires the embryologist to apply additional costly methodologies such as assisted hatching and ICSI.

   Healthy Quarantine
The six months of freezing that is required before the frozen eggs can be released is no different than the six month testing requirement that a typical donor must go through to test for infectious diseases. In this regard, it is misleading for the Cryo Eggs International web site to claim that this process is any safer than conventional donor cycles.

   Successful Approach
A donor cycle at Pacific Fertility Center has yielded a consistent 65% or greater success rate for many years. A key point here is this record has improved incrementally over the years after decades of experience and applying evolving technologies.

It is every physician’s wish for his/her infertile clients’ to have inexpensive choices to tackle their life dream of conceiving. It is also important for people to be as well informed as possible so their money may be spent for the most cost-effective and successful method for their particular situation.

PFC SPOT LIGHT    My Journey to PFC

   I grew up in Southern Mindanao, Philippines as one of five children. My parents were important role models in my life. As you can imagine, having ambitious career goals was essential where I came from, as both parents were educators. I wanted to be an accomplished professional just like them. When it came time to choosing a career, I chose medicine. While in the Philippines, I attended medical school and practiced as a primary care physician in a rural area, delivered babies and performed minor surgeries.

The 1980s marked significant change in my life—none bigger than having two children. During this time I also moved from the Philippines to the United States. Although I was no longer taking on duties as a physician, my career in women’s medicine was just taking off. My first job in the states was at an OB/GYN’s office in Oakland followed by an IVF clinic in Berkeley. These experiences were enjoyable and once the wonderful twin doctors I worked for retired, I longed for the opportunity to work at a bigger practice. A bigger practice affords more specific, systematic job responsibilities. While at the IVF clinic in Berkeley, I became acquainted with Pam Reck. Pam took a job at Pacific Fertility Center (PFC) as a clinical coordinator and I eventually followed suit. When I joined PFC in 2002, I worked at the Laurel Ave. office, and, in 2003, joined the PFC family on Francisco St., coordinating IVF cycles.

My experience here at PFC has been highly rewarding. In particular, being an IVF coordinator allows you to have ongoing patient contact. You feel like you’re a part of the entire treatment process—coordinating cycles, preparing patients to get ready for their IVF by overseeing pre-cycle requirements, and working out schedules. I think patients also find it helpful to know they have someone dedicated to ensuring their experience at PFC runs smoothly. Patients undergoing an IVF cycle have a lot on their minds. They need and deserve comprehensive care. PFC nurse coordinators perform an important role. In fact, PFC has nurse coordinators for different infertility treatments—be it third party coordinators, IUI coordinators, and IVF coordinators. Clearly, patients are a priority here, not a number.

I must say that there’s never a dull moment at Pacific Fertility Center. The innovation is constant. Over the years, I’ve seen enormous improvements in assisted reproductive technology (ART). This keeps me on my toes. Boredom is non-existent.

I continue to be impressed by the technology and people at PFC. Our doctors do a great job of helping staff and patients understand the technical aspects of ART. They also work well collaboratively. There’s very much a team environment without a lot of hierarchy. We have ongoing staff and laboratory meetings, which keep the communication open. They also allow you to learn about the different departments, thereby improving our working relationships.

The beauty about PFC is that we make a difference. It’s heartwarming to see how much patients appreciate our care. This experience also provides a different perspective into fertility. I, like a lot of people, once thought that individuals who didn’t have children did so by choice. Sometimes that’s the case. Sometimes it isn’t. Having this perspective is helpful with respect to being sensitive to different patient emotions.

By working at PFC, things have come full circle. I cherish my friends and family more than ever. My husband and I have been married for 20 years. We have a 19 year-old son in college and 15-year-old daughter in high school. Both bring us never-ending joy. It’s amazing to see how quickly they’ve grown up. I truly wish every patient who comes to PFC has a successful outcome and experiences the joy a child brings.

Appreciating family, however, doesn’t make me unique to PFC. After all, family is our specialty.

Doris Dalida, one of Pacific Fertility Center’s IVF Coordinators, assists patients through the entire IVF treatment cycle. Her extensive background working in OB/GYN offices and IVF clinics provides a valuable role in the care IVF patients receive. She currently resides in Richmond, California with her husband and two children.

FROM US TO YOU    New Clinical Study: New Technique for Egg Freezing

   PFC continues to be at the forefront of pioneering research in assisted reproductive technology and was the recipient of the 2005 California Pacific Medical Center (CPMC) Foundation Wishes for Wellness Grant. Through this grant, PFC will embark on a research project assessing the efficacy of a new IVF egg freezing method, vitrification.

The CPMC Foundation selects outstanding CPMC physicians in the fields of obstetrics and gynecology and pediatrics to be honored at their event Wishes for Wellness. PFC's Eldon Schriock, MD and Carl Herbert, MD were among those selected in 2005. These honored physicians have the privilege of identifying needs and/or directing purchases and programs which will be funded by the Wishes for Wellness Grants.

Egg freezing has been successful in creating a handful of pregnancies, but the process is still very inefficient. Many eggs do not survive the freezing process. While the technology for freezing sperm and embryos has been used for decades and is very successful, the technology for egg freezing is still emerging.

The key to successful egg freezing is determining a technique that will not damage the fragile chromosomes of the egg. The eggs in the ovaries are held in “suspended animation”, until they are stimulated to grow and ovulate. During this state, the chromosomes of the egg are vulnerable to damage, including damage from the exertion of the freezing and thawing process. Past freeze/thaw techniques have been very inefficient because of the chromosomal damage incurred. The vitrification freezing technique seems to be a gentler technique, and therefore leads to less chromosomal damage. This then improves efficiencies in the thawing, fertilization and embryo development steps; and ultimately better pregnancy rates.

Our study is designed to study whether vitrification can improve the efficacy of freezing eggs. The study is designed is such a way that results should be obtained in a timely manner. Egg donors who have had previous IVF cycles resulting in pregnancy will be recruited to have eggs frozen. The results of fertilization, embryo development, implantation and pregnancy rates using the embryos resulting from egg vitrification will be compared to the pregnancy rates obtained in previous cycles using embryos obtained from fertilized fresh eggs.

PFC is excited and honored to be involved in this research. The potential benefits of egg freezing are substantial and our research team looks forward to sharing results with you, as soon as they are available.

PFC EVENTS:    Health Etc. and "Dr. Phil"

   With the onset of New Years resolutions, particularly those relating to healthy living, the timing of the January 2006 HEALTH Etc. conference was ideal. Approximately 4,000 people attended the Moscone Center-based conference. The event provided a forum for the general public to learn about numerous health and wellness topics via breakout sessions and exhibits.

Pacific Fertility Center (PFC) was involved in the conference, sharing important information about infertility diagnosis and treatment. Our participation included a 45-minute infertility breakout session. PFC’s Drs. Philip Chenette and Carolyn Givens discussed some of the latest advancements in infertility diagnosis and treatment followed by a Question and Answer session. PFC’s informational booth provided literature and advice to those interested in learning more about infertility.

One of the highlights of the conference was a motivating keynote address from TV personality “Dr. Phil” McGraw.

In recent years there has been a newfound emphasis on health and wellness with the general public taking a more proactive role in their own personal well being. PFC continues its commitment to educate those who are contemplating parenthood. After all, when it comes to health and wellness, building healthy families is often at the forefront.

For other events involving PFC, click here: Events Calendar

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-- Best regards from all of us at Pacific Fertility Center.