SCIENCE PULSE    Fertility for Cancer Patients

Introduction

Sara (a hypothetical patient) found a breast lump. 36 years of age, she was a single active professional, otherwise healthy, careful about her diet, and carefully evaluating her options after a diagnosis of breast cancer. Along with the discussion on surgery, chemotherapy, and radiation therapy came the question “Were you planning to have children?”

A diagnosis of cancer presents many decisions that must be made quickly. Confirming the diagnosis and planning therapy will be the primary concerns, but the implications of therapy on long-term quality of life must be assessed. One of the primary issues facing women with a diagnosis of cancer is future fertility.

Candidates

Cancer treatment can interfere with future fertility. Toxicity varies by treatment. Cyclophosphamide, an alkylating agent used in many chemotherapy regimens, is highly toxic to sperm and eggs; methotrexate and 5-flouro-uracil (5FU) are not. Medications used for longer time intervals create a higher risk of fertility problems than shorter time intervals; effects on women in older age groups are more severe than younger. Radiation therapy, in high doses, can have effects on eggs and sperm. Surgery and anesthesia are not known to have direct effects.

It is difficult to give specific fertility risks for chemotherapeutic regimens, since studies are not yet definitive. Among the more toxic treatments are stem cell transplantation for leukemia in which total body irradiation and cyclophosphamide are used, beam radiation to a field that includes the ovaries, and extended chemotherapy of up to 6 cycles using cyclophosphamide in combination with other agents. After conventional chemotherapy for breast cancer for women under 40, the chance of infertility is roughly 50%, in older women the risk is over 80%.

Treatment options

What are the options for fertility in patients diagnosed with cancer? The best choices are available to those that have not yet initiated treatment and involve cryopreservation. During treatment, the risk of problems rises, and after treatment, there may not be adequate recovery of fertility to achieve pregnancy.

Cryopreservation allows cells to be stored with great stability for long periods of time. The record time from sperm cryopreservation to pregnancy is 28 years; there probably is no real limit to the time that cells can be stored. To store cells requires technology that reduces the formation of ice crystals, which disrupt cells, and prevents the rapid rise in salt concentration that occurs as water freezes. Cryopreservatives and management of temperature changes (slow freeze or vitrification) are used to reduce the risk of these problems.

Male

The option for fertility preservation in men is straightforward, cryopreservation of sperm. Sperm is obtained by masturbation and frozen in multiple vials in liquid nitrogen. 2-3 sperm samples can be obtained per week, with 2-4 vials stored per ejaculate; two weeks worth of donations could yield 8-24 vials of sperm. Costs vary widely, but would range from $1500-$3000 for processing and 3 years of storage.

Testicular sperm extraction is an option for individuals with azoospermia. Testicular tissue cryopreservation remains a theory that has not yet produced a human pregnancy. It has been proposed as an option for preservation of fertility in children, but has yet to be proven in clinical practice.

Female

Women have the option of cryopreservation of oocytes or embryos. For women without a partner, oocyte cryopreservation holds promise as a means to preserve fertility potential without committing to a specific sperm source or partner. For women with a partner or sperm donor, embryo cryopreservation is a proven technology.

To create cryopreserved oocytes, Follicle Stimulating Hormone (FSH) is administered over a ten day time period to stimulate ovarian follicles. The oocytes are retrieved under sedation with a needle guided by ultrasound and then stored in liquid nitrogen.

Newer techniques of oocyte vitrification secure good pregnancy rates for those with good oocyte quality. Traditional oocyte cryopreservation is performed using a slow freeze technique, but more rapid vitrification procedures optimize results. The trick with cryopreservation is to lower the temperature while avoiding ice crystals that disrupt cell membranes and proteins. Vitrification, an ultrarapid freezing process utilizing a minimal fluid volume, reduces the risk of these problems and optimizes cell quality.

For those women with a partner, or that are willing to commit to a specific sperm donor, embryo cryopreservation is an excellent option. After stimulation and retrieval, oocytes are inseminated and cultured in an incubator for 1-5 days, followed by cryopreservation. The embryos can be thawed and transferred at a later date, after clearance from the oncologist. Embryo cryopreservation is the best established of the fertility preservation techniques, with years of experience in its applications. Good pregnancy rates can be anticipated.

Ovarian tissue cryopreservation, the cryopreservation of whole pieces of the ovary, as opposed to cells, remains experimental. Complex tissues are more difficult to cryopreserve than cells, though rare success has been reported.

Cancer recurrence

Is there risk to the use of fertility drugs in patients with cancer? It does not appear in studies to date that breast or ovarian cancer risk is affected by use of fertility drugs. Studies indicating an increased risk are balanced by other studies indicating a reduction in risk. Studies to date have been limited, and treatment decisions still must be individualized.

Does pregnancy increase the risk of cancer recurrence? In theory, certain types of cancer could be aggravated by the hormones of pregnancy, but studies have not confirmed an overall risk. Certain types of cancer are less common in women that have delivered a pregnancy. Treatment decisions must be individualized, as future studies gather more information.

Pregnancy

Certain cancer treatments create organ toxicity that must be evaluated in considering patients for pregnancy. Heart output is limited in patients that have received doxorubicin. Uterine irradiation is associated with miscarriage and pre-term labor.

Children

Children born after fertility preservation procedures do not carry any increased risk for birth defects. There are hereditary syndromes that can be associated with cancer that could be transmitted to children, but there does not appear to be any other increased risk for cancer or genetic disease in children of cancer survivors.

Patients contemplating conception must consider life span expectations as part of their decision on whether to conceive. Such considerations are not, however, a reason to withhold treatment, and are ultimately the individual and family should decide.  Philip E. Chenette, MD

Resources:

www.fertilehope.org Fertile Hope

www.livestrong.org Lance Armstrong Foundation     

www.cryobank.com California Cryobank                   

www.PacificFertilityCenter.com Pacific Fertility Center               

Philip E. Chenette, MD 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. As a member of the International Society for Stem Cell Research, he is working to apply the concepts of stem cell therapy to help couples have healthy children. His expertise is recognized by peers who repeatedly select him as “Best Doctor” in peer surveys.(see BestDoctor.com)

OB/GYN GRAND ROUNDS at California Pacific Medical Center
Date: Tuesday, October 30, 2007
Time: 8:00 AM to 9:00 AM
Topic: Fertility Options for Cancer Patients Presented by Dr. Philip Chenette for the Department OB/GYN Grand Rounds
Location: California Pacific Medical Center: California West Campus at 3700 California Street
Bothin Auditorium, basement level

               
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ASK THE EXPERTS   IUI vs IVF

Question: I am 38 years old with age-related infertility (at least that is what my doctor, a Reproductive Endocrinology and Infertility Specialist (REI), thinks). It has been suggested that I undergo super-ovulation with injectable Follicle Stimulating Hormone (FSH) along with intrauterine insemination. I really don’t want to have twins, if possible, and certainly not triplets or more! But ideally, I would like to have more than one child. Even if I am successful in having one baby now, I am worried about trying to have a second child when I am 40 or more. What do you suggest?

Answer: We agree that having one baby at a time is the safest thing for you and your family. However, undergoing FSH super-ovulation is intended to create more eggs in one cycle in order to increase the odds that one or two will fertilize and implant. This helps to overcome the relative inefficiency of conception for women in their late 30’s. The risks are as you stated, twins or more. Luckily, the risks that a woman undergoing this treatment will get triplets or more is really fairly low – on the order of less than 10% of all pregnancies, with careful monitoring. The risk of twins is higher – on the order of 20% of such pregnancies.

If a woman at 38 years old has no identifiable cause for infertility, the goal is usually to get 3-6 follicles. Most of the time, if the treatment is successful, the pregnancy will be a singleton pregnancy (one baby). Your issue of wanting to have a second child and concern for difficulties beyond age 40 is a real one. You may want to discuss with your REI the option of in vitro fertilization. If your doctor thinks you may be a good responder to fertility medications, you could have extra embryos to freeze, which provides some back-up and allows you to preserve some embryos from 38 year old eggs for down the road.

Patients contemplating conception must consider lifespan expectations as part of their decision on whether to conceive. Such considerations are not, however, a reason to withhold treatment, and are ultimately the individual and family should decide.  Carolyn Givens, MD

               
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PFC SPOTLIGHT     New Director of Development

   Pacific Fertility Center continues to expand and grow. You may wonder what is needed to expand a medical practice? We are excited to introduce one of many new faces that are providing a new direction to PFC. We asked our new Director of Development to tell us about himself and about his role at Pacific Fertility Center. Here’s what he shared:

Hello my name is Robb Mayberry. I was recently hired as the Director of Development for Pacific Fertility Center. While I have always considered California my home, I am actually the product of a military family. Being a member of my family meant adapting to frequent moves. I was born in Seattle, Washington, the eldest of three children and the only son. Early in my childhood I have had the opportunity to live overseas in Madrid, Spain, then back to the US in Colorado, and ultimately in Northern California. Most of my important developing years were spent right here in the Bay Area, with brief stints of living as far south as San Diego, as far north as Redding and as central as Sacramento. So, I have definitely seen all corners of our beautiful state. Experiencing the world this way at a very young age has given me an appreciation and desire to travel, something I love to do when I’m not at home or at a San Francisco Giants game.

Struggling with which career path to take while in college, I dabbled a little in political science, theater and drama, and some psychology. While they were all fun or interesting, they weren’t really for me. At the suggestion of my father, I enrolled in a communications course, which I thoroughly enjoyed. The communications courses I explored, seemed to be the perfect fit, so I went on to receive my Bachelor of Arts degree in Communications with an emphasis on Public Relations and Broadcasting.

After college, I spent a brief period of my career in the hospitality industry as a concierge with a few upscale hotels in Colorado and here in California. During this time I had the opportunity to meet some interesting people including presidents, celebrities, and even a ghost from time to time. You see, some of the hotels had a reputation for being haunted and being that it is October, I thought it appropriate to mention.

Eventually, I chose to move from the hotel industry into healthcare and soon discovered I enjoyed working for and communicating with physicians. I have spent almost 20 years in the healthcare industry and have worked in small and large medical groups, Healthcare Maintenance Organizations, and hospital systems. While each organization operates a little differently, one goal has always been prevalent: the patient’s outcome is the most important, true measure of success.

Throughout my career, one of the most common questions I have been asked is: “Why do physicians or medical organizations need someone to engage in marketing or public relations?” My usual response is, “The healthcare industry, as with most industries, has drastically changed over the past 20 years. There is more competition, new technological developments, and customer expectations are higher. Physicians have studied for many years to learn how to serve the needs of the patient, not to how to write press releases.” As the Director of Development for Pacific Fertility Center my responsibilities will include assisting in the branding and image development of the organization; overseeing all Pacific Fertility Center publications; fielding all media inquiries; orchestrating press conferences and press releases; coordinating trade shows and educational seminars; and serving as the liaison for our referring physician’s offices.

I am excited to be a part of a team where the physicians are not only respected experts in their specialty, but compassionate human beings. The staff at Pacific Fertility Center is truly the most professional and caring. I am looking forward to a rewarding and challenging experience with my new family, as we work to build healthy new families. Robb Mayberry

               
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FROM US TO YOU     New PFC Offices

Invitation to Tour the New PFC Offices
  

Changes are happening at Pacific Fertility Center! If you have stopped by our office location at 55 Francisco Street lately, you’ll notice that things may not look quite the same at PFC. We recently went through a major change by relocating our administrative offices and Egg Donor Agency from the third floor to the fifth floor. What does this mean to you? By moving to the fifth floor, we have been able to consolidate all our team and deliver comprehensive services from one floor instead of two floors. The embryologists from the laboratory, the nursing staff, and administrative staff will now be able to communicate in a more timely and efficient manner. In addition, to providing a more comprehensive team approach and improving communication, relocating the organization to one floor has reduced confusion for those visiting the facility. By being on the fifth floor, patients have one site for service and immediate access to care. The move has also helped organize the PFC team for future growth and services. Overall, this move will assist PFC in providing quality patient care. If you are interested in touring our facility, please contact our New Patient Guides to arrange a day and time. You can contact the New Patient Guides by calling 415-834-3000 and pressing option 12.

               
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ANNOUNCEMENTS    PFC Medical Team Honors

AFA 2007 Family Building Award to be Presented to Dr. Philip Chenette
Pacific Fertility Center is proud to announce that Dr. Philip E. Chenette will be honored, along with five other physicians, with the Family Building Award at the American Fertility Association's glamorous Kokopelli Ball in New York City on November 5, 2007. Brenda Strong of the cast of Desperate Housewives will present the award.

Joe Conaghan, PhD, HCLD, Named Chair of the College of Reproductive Biology
Pacific Fertility Center's Laboratory Director Joe Conaghan, PhD, HCLD, has been elected as the Chair of the College of Reproductive Biology (CRB). CRB is a special interest group within the American Board of Bioanalysts (ABB). In addition to his new responsibilities, Dr. Conaghan remains an active member of the ABB Board of Directors from whom embryologists and andrologists receive their certification and licensure.

We are proud to announce that once again all physicians at Pacific Fertility Center have been singled out by their peers as *Best Doctors (see www.bestdoctors.com) .

Our doctors are internationally recognized specialists in reproductive endocrinology and infertility. They have completed top-level medical education, published groundbreaking professional papers, and held positions on the faculty of leading research universities. They continue to participate in reproductive research. All MDs are Board Certified by ABOG as Reproductive Endocrinology and Infertility Specialists. Our state-of-the-art laboratory has one of the most highly trained teams in the country.

*Continuous peer-to-peer surveys help bestdoctors.com identify specialists who are considered by fellow physicians to be the most skilled in their fields and most qualified for reviewing and treating complex medical conditions. The polling process is anonymous and confidential, qualitative and quantitative. It provides detailed profiles of each physician, including his or her practice, research programs and diagnostic and treatment procedures. They survey doctors in more than 400 subspecialties of medicine.

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