SCIENCE PULSE    Fertility Preservation

Empowering a woman’s choice using fertility preservation: Protecting and preserving fertility is a new way of empowering reproductive choice. The fertility of youth is no longer a limited resource, constrained by age. Women can now pursue their reproductive lives at their own pace, rather than according to the obligations of biology. Reproductive choice means having children when you want them, rather than when you must have them.

Cryopreserved eggs can be stored and saved for later use.

The potential of fertility preservation replaces the tick of the biological clock: The tick-tock of the biological clock influenced reproductive choice in the last decades. The sacrifice of delaying family while assembling a career, home, and relationship worked in an economic sense. It did not, however, fit well with the designs of biology.

Eggs work best at a young age, when there are more of them, and they are more vital. The best pregnancy rates occur in women ages 18-30. With declining egg numbers and egg quality, pregnancy rates are lower in older age groups, while miscarriage rates and chromosome defects become more common.

Biology wastes eggs: The limit of egg quantity and quality is a consequence of our biology. From mid-gestation through menopause, there is a continuous stream of egg follicles that grow to a certain stage and then are lost. This pool of eggs is never replenished. Each woman is born with a set number of eggs (over a million), and by puberty perhaps 300,000 remain. Ovulation will happen only 500 times in a woman’s reproductive years. and will result in a child less than 1% of the time. From start (gestation) to finish (menopause), 1 in a million eggs results in a child. This constant and dynamic process of decline continues through the reproductive years, uninterrupted by birth control pills, pregnancy or ovulation.

Fertility preservation offers insurance against infertility: Fertility preservation is a relatively simple process. The first step is for a woman to see her fertility doctor for an ultrasound and physical exam. On ultrasound the ovaries are measured and the number of follicles determined. A treatment calendar with a schedule of injectable fertility drugs is initiated.

Using fertility medications for approximately ten days, multiple eggs begin to mature in the ovaries. Under sedation, the eggs are retrieved, a process that takes about 10-15 minutes. The eggs are then cryopreserved and placed in frozen storage.

At a later time, the eggs can be thawed, inseminated with sperm (ICSI is recommended), and the embryo(s) created transferred back into the uterus to develop into a pregnancy.

Technology of Fertility Preservation is improving: We are continuing to optimize the outcomes of oocyte cryopreservation. In a series of women under age 30 where eggs were cryopreserved, egg survival was 88%. Over half of the eggs fertilized, and two thirds of transfers resulted in pregnancy. As of January 2011 Pacific Fertility Center has 8 delivered babies from cryopreserved eggs.

The limits of biology continue to constrain outcomes of those eggs that survive. Not all eggs have the capacity to produce a viable embryo. This variable is very age dependent. In a healthy woman under the age of 30, approximately one third of her eggs(33%) are capable of producing a viable embryo. In women over the age 40, this ratio changes to one in twenty (5%).

Fertility Preservation: reproductive choice: The message is this: Fertility is optimal in your youth. If you have not started your family, you should consider freezing your eggs as insurance for the future.

Philip Chenette, M.D. has spent over a decade specializing in the treatment of patients with complex infertility diagnoses, especially in women with decreased ovarian reserve and women over 40.

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FROM US TO YOU Take the Time

Each Thursday evening we offer you time to further reduce your stress. Join us to talk with others on a similar journey. Learn mini-relaxation techniques. Brush up on the skills you learned in the mind/body class.

Led by Mind/Body teachers, Allison Chamberlaine, RN and Peggy Orlin, MFT

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PERSONAL ODYSSEY Dr. Ryan’s Biography

I was born in the Lower East side of New York City, my father’s hometown, to quite young parents. At six months of age, we moved to Paris, my mother’s hometown, and I played in the streets and parks of Paris until I was 9. I spent every Wednesday with my maternal grandmother (schools were in session Saturday to Tuesday, and Thursday to Sat), often spending hours in the Bois de Boulogne (a park along the western edge of Paris). We spent quite a few summers in the South of France where we would raise small chicks and rabbits, which became dinner at the end of our vacation. I am the oldest of five children.

Dr. Ryan, her husband and three daughters in Paris.

My parents later divorced, and my father moved all 5 of us children to the States. First, we lived in Washington DC, where I attended the French school for one year, and then soon enrolled in the local parochial school. My childhood included ballet lessons, camping trips, art projects, and lots of neighborhood adventures with my best friend Lucia.

In high school, our family moved to Boston after my father changed jobs. I spent 3 years at Brookline High School, where I was exposed to a broad palette of academic topics. I knew that I loved science, so my father recommended I study Latin (the root of many scientific words). However, I was also fascinated by Asian philosophy and art, so I started studying Mandarin. I studied both for 3 years.

I applied to college knowing that I wanted not only a strong scientific program, but also the opportunity to continue my Mandarin studies. Bridging both these diverse interests lead me to the University of Massachusetts at Amherst, where I majored in Microbiology. My work-study job later evolved into a research opportunity that developed into my Honors thesis. At the same time, I was also pursuing a minor in Asian Studies, and the opportunity came to be a member of the first group of ten American exchange students to attend Beijing Normal University (teaching university). This was truly my dream come true, going to mainland China, as the country was slowly allowing westerners to visit. I spent the summer in Taiwan to further improve my language skills, and then lived in Beijing at the University for one school year. I jumped on every travel opportunity that presented itself, and had some amazing experiences exploring parts of China where no foreigners had been to in many decades. My language skills truly allowed me to have personal contact with the local Chinese which would otherwise not have been possible. As the cliché goes, I learned more about myself in China than I did about the Chinese themselves, but this is the beauty of travel and stepping outside of one’s cultural comfort zone. I turned 21 years old in China.

Once I returned to the States, I matriculated and decided that I needed to spend some time with my French family. I worked in Paris for a year, and traveled extensively throughout Europe. I then returned to the States and lived in Palo Alto, doing research with a biotech startup company. During this time I was deciding what my next career steps would be. Should I pursue medicine and apply for an MD, or should I pursue research and apply for a PhD? Pursuing an MD was more in line with my overall goals, and two years later I was bound for medical school at UC Davis.

I knew that I wanted to pursue women’s health care. I also was fascinated with the growing field of fertility treatment because it was a triumvirate of scientific, ethical and surgical frontiers, all of which resonated for me. When I applied for residency, my mentor encouraged me to consider a new program at UCSF, which was a combination of residency and Reproductive Endocrinology (REI) fellowship. While this was a very big commitment to seven years of training, I knew after interviewing that this was a perfect combination for me. Fortunately, I was accepted, and thus embarked on a long career at UCSF.

Dr. Ryan and her family.

I completed my residence, fellowship, and was on faculty at UCSF for a few years. During this time, I was very active in basic science research investigating the role of endometriosis and fertility. In 2000, I left UCSF and joined my 4 current partners at PFC. We now have created a most unique fertility center, with a state of the art laboratory, dedicated and devoted staff, acupuncture center, research center, and a special combination of personal care with the benefit of input from the five MDs who are seasoned fertility providers.

While I was a resident at UCSF I met my husband, who himself was an Internal Medicine resident. After his Chief Residency year, he did a fellowship in Gastroenterology. Fortunately we were both able to complete all of our training while staying in San Francisco, the city we call home. We have three wonderful daughters who love adventure, travel, playing sports...and while none of them will become doctors like their parents, all three have a giving heart and are involved in careers and activities of giving back to their communities.

When not at work, I enjoy time with my family, as well as good food and wine, foreign films, reading, photography, yoga, and just quiet times.

I am privileged to be in a profession where I touch so many people’s lives and dreams. Every birth announcement is a reminder of this privilege, and every failed treatment cycle is a new commitment to do my best.

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FROM US TO YOU Advances in research and development

Advances in research & development bring a deeper understanding of infertility: Modern fertility science is changing treatment, enabling better pregnancy rates. A healthy child for every person suffering from fertility problems remains Pacific Fertility Center’s goal. Through a better understanding of the egg and embryo we are closer to delivering on that promise of one healthy baby at a time.

The problem of the aging egg: The aging egg remains a very basic problem in fertility. As a woman ages, her eggs do not work as well, resulting in embryos that do not develop or implant. Mistakes in early cell division, chromosomes, and development become common. With an aging egg, pregnancy rates are lower and miscarriage risk higher.

Finding that healthy egg can be a problem. For a twenty year old, roughly 1 in 3 of her eggs will be healthy. For a woman over forty, less than 1 in 20. This continues to be a real and ongoing challenge for our patients.

One way to work around this problem is to increase the number of eggs. Starting with more eggs gives a better chance of finding at least one that is healthy. Once we have a batch of eggs, the problem emerges of trying to choose the best out of the group. Which egg is most likely to achieve pregnancy?

Research of early egg and embryo development: We are excited to share that we are currently working with a privately held medical technology company, along with several other centers in the Bay Area, on a new investigational imaging device in the early stages of development. We can now observe, using a video microscope, the early stages of embryo development.

Knowledge of the way an embryo develops, the early cell division, when and how, promises to improve selection of embryos. Over a several year period at Stanford Institute for Stem Cell Biology & Regenerative Medicine, Dr. Renee Pera, in collaboration with Stanford colleagues, Dr. Barry Behr (Associate Professor and IVF Lab Director), Dr. Thomas Baer (Executive Director of the Stanford Photonics Research Center), and post-doctoral fellows Dr. Connie Wong and Dr. Kevin Loewke, conducted ground-breaking research into early human embryo development. Looking at embryos in their first few days of development, the team identified an elegant set of imaging parameters by day 2 that accurately identified embryos that develop to the blastocyst stage.

Through the use of precision imaging technology coupled with novel measurements, embryologists may be able to choose the best embryos more accurately and consistently. Published last year in Nature Biotechnology, Time magazine named the discovery one of the 10 medical breakthroughs of 2010.

Dr. Renee Reijo Pera, Ph.D.: is a leader of the team that published this study, understands these problems, working with them in a research lab for the last twenty years. She is now bringing that knowledge to clinical medicine.

Dr. Pera received her PhD from Cornell University, and later worked in David Page’s lab at the Whitehead Institute. While working with Dr. Page, she discovered a gene on the Y chromosome that was involved in male fertility called the DAZ (Deleted in AZospermia) gene. As it turns out, the gene accounts for a significant proportion of male infertility and tests for this gene are now routine for men with low sperm counts.

Now, as Director of Stanford University’s Center for Human Embryonic Stem Cell Research and Education, Dr. Pera’s focus is on understanding issues related to human reproductive failure. The questions she and her team are addressing encompass issues such as Egg formation and development, as well as what triggers cell division and formation of a healthy embryo.

Fertility care will change based on Dr. Pera’s research on early development of eggs and embryos. This work has vast implications for the future of treatment and prevention of infertility. In her exploration, she is finding new ways of thinking about old fertility problems. Dr. Pera’s work will strongly influence medicine and clinical realm for years to come.

At Pacific Fertility Center we are committed to bringing advanced science to the clinic. We are finding major changes in our understanding of early egg and embryo development and anticipate continuing to lead the way in bringing these advances to help our patients have one healthy baby at a time.

Philip Chenette, M.D. has spent over a decade specializing in the treatment of patients with complex infertility diagnoses, especially in women with decreased ovarian reserve and women over 40.

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PATIENT ODYSSEY Our Story

I was 39 when my husband and I married. We had tried for many months to get pregnant, and finally sought infertility treatment from Kaiser. Three miscarriages followed, and we decided to stop treatment. Shortly after that, much to our amazement, a month-long vacation in Indonesia turned out to be the fertility treatment we needed I was 41, and the amniocentesis said all was well. Our son, all 10.5 pounds of him, was born in 1999, when I was 42.

Kelly is now two years old.

When no other children made their appearance the old-fashioned way, we turned to Dr. Schriock at PFC, and found an egg donor. Despite having only three embryos, my husband and I were optimistic. We were delighted when I became pregnant with the last embryo. It was a tremendous relief for us to get past the first three months of the pregnancy, when most miscarriages occur. When my husband suggested I have an amniocentesis, I wondered why, since the egg donor was 26 and my husband was 39. He said he would be more comfortable if we were certain all was well with the baby, so we had the amnio performed when I was about four months along.

This time the results were not good; the geneticist called on a Thursday evening and told me that the baby had Down syndrome. The odds of this happening with a 26 year old egg donor were about 1 in 1,000. We were just unlucky. My husband and I had agreed in advance of the test that we would not bring a special needs child into the world. Grief-stricken, we ended the pregnancy.

Our IVF miracle had become a tragedy. Not only had we ended a much-wanted pregnancy, but as this was our last embryo, we had reached the end of the line in our quest for a second child. It was unbelievably painful to have come so close, and then have the outcome we did. When we had decided to pursue egg donation, I knew it was far from certain that we would come home with a baby, but I had felt that it would work out all right for us. To have spent such a tremendous amount of time, money, and emotion, and have it end the way it had was almost too much to bear.

Mourning the unborn is a lonely business, especially when you have made the decision to end the pregnancy because of a poor pre-natal diagnosis. We received a number of e-mail condolence notes, a handful of cards, and a couple of calls. We were very glad for these, but they came to a close quickly, and soon we were alone with our grief.

I found comfort in the A Heartbreaking Choice website http://www.aheartbreakingchoice.com/, and in a Kaiser support group for families who had ended pregnancies because of poor pre-natal diagnosis.

Friends advised me to move on; they pointed out that I had put a tremendous amount of time and effort into expanding our family, and now I needed to decide what else to do with that energy. I rejected that line of thought. I had always felt, after our first child, that I had one more good baby left in me, so I broached to my husband the idea of getting another egg donor and trying again. We are not a wealthy couple; my husband works for a non-profit, and I run a small business. We live in a small, old house. Our cars are old. The thought of starting afresh with the payments for another egg donor and the clinical care seemed impossible.

I approached Dr. Schriock at PFC, and asked if there was help for a couple like us. He replied that PFC offered closed embryo donations; meaning that we could be put in a queue to receive donated embryos, but we would not meet the donors. This didn’t feel right to my husband and I. Subsequently, the doctors at PFC offered to treat us at a reduced fee, and the embryo donation agency we had used the first time (Jackie Gorton) did the same.

We chose another donor, and I became pregnant on the first transfer. My son and I had always been extremely close, and I was a little worried during the pregnancy that, perhaps, I wouldn’t love this child as much as I loved my son. I didn’t want the fact that she didn’t share my genes to matter, but would it?

A family photograph.

The pregnancy was easy, and the day after Christmas, our daughter was born in a lovely natural birth. Kelly weighed in at eleven and a half pounds (making her the biggest non-caesarean baby born at Kaiser Walnut Creek in 2008!)

My worries were unfounded; my husband and I both feel we got the child that was meant for us. We loved her the instant we saw her, and my husband, son, and I enjoy every minute we have with her. Kelly is now two, and she is much like her brother: fun, funny, affectionate, bright, and coordinated.

We went down a long, hard road to build our family; four embryo transfers, three miscarriages, two egg donors, and one ended pregnancy. But after it all, we got our two beautiful children, and life would be so less rich without them.

Here is a little information about our children. They are both tall for their age, blonde-haired, blue-eyed, and fair-skinned. Their ancestry is Dutch, Scottish, French, Irish, Swedish, and Norwegian. The mental and physical health histories of the biological parents are good.

If you are interested in seeing if your family and ours might be a match, please send information about yourselves to mkdonation@gmail.com.

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