SCIENCE PULSE    ASRM Updates

Every year, several Pacific Fertility Center professionals participate in ASRM’s national meeting. They evaluate the research and share their findings with PFC and Fertility Flash.

Among those attending the conference from PFC were Dr. Philip Chenette and Dr. Isabelle Ryan and Peggy Orlin, MFT. Their reviews cover the following topics: Update #1: Ovarian Stimulation Techniques, Update #2: PGD and Aneuploidy Screening Techniques, Update #3: Egg Freezing, Update #4: Acupuncture, and Update #5: Men and ART.

Update #1: Ovarian Stimulation Techniques: Changes in ovarian stimulation techniques evolve as a better understanding of the medications and their effects on eggs and ovaries develops.

Letrozole (Femara) is increasingly being used as a mild stimulation for ovarian follicle growth and as an additional medication with gonadotropins (e.g. Follistim). In a study on the use of letrozole in preparation for IVF in breast cancer patients, a group from New York showed that breast cancer recurrence or the incidence of invasive carcinoma in the opposite breast does not appear to be increased after stimulation using letrozole and FSH for fertility preservation.

For patients with PCOS, researchers from France compared stimulation with a GnRH agonist, similar to Lupron, with oral contraceptives plus agonist. In these preliminary results, dual suppression does not provide any obvious effect in harmonizing the group of developing follicles nor in improving the quality of oocytes and embryos. This study is still ongoing in order to test these results in a larger population.

In patients that produce an excessive number of follicles in response to stimulation, ovarian hyperstimulation syndrome (OHSS) is possible. To prevent this, the fertility drugs are sometimes stopped mid-stimulation; the follicles are “coasted” – they grow without stimulation, with a lower risk of OHSS. An alternative to “coasting” is the use of Ganirelix, a GnRH antagonist, in a “salvage protocol.” Probability of live birth with the Ganirelix salvage protocol was similar to controls. High-grade embryos were more common with this regimen, in contrast to “coasting”. The miscarriage rate was slightly higher, but not statistically significant. These results suggest that the Ganirelix salvage regimen is a superior alternative to “coasting” in women at risk for OHSS.

A group in Montpelier, France is interested in gene expression in the follicle after use of fertility drugs. Using gene chips they measured gene expression in patients exposed to urinary FSH products and recombinant FSH. Significant differences were found meaning that different genes are being expressed in follicles of women receiving pure FSH (Gonal-f or Follistim) as compared to genes being expressed in follicles of women receiving urinary FSH (Repronex or Menopur)– the meaning of these changes will have to await further study.

On the other hand, a long debate about the effectiveness of urinary and recombinant FSH products is a bit closer to resolution. A meta-analysis from a group in Egypt examined pregnancy outcomes and risks in a group of previously published studies. No significant differences were found. Their conclusion was that urinary gonadotropin (hMG) is as effective as recombinant gonadotropin with regards to clinical outcomes and patient safety.  Philip Chenette, MD

Update #2: PGD and Aneuploidy Screening Techniques

Preimplantation genetic diagnosis (PGD) has been one of the hallmark technologies of modern reproductive medicine. The ability to look inside a cell, beyond its visual appearance to the actual genes controlling the cell, has provided insight into the workings of the embryo and a valuable clinical tool to improve fertility care.

The most common use of PGD is to count chromosomes using FISH probes. Using labels that glow under ultraviolet light, a limited number of chromosomes can be identified and counted. Missing or duplicated chromosomes are indicators of abnormalities in the embryo, a condition known as “aneuploidy.” FISH has a significant error rate, and while clinically useful, results must be interpreted with caution.

A new technique discussed at the ASRM meeting is SNP analysis. SNPs are common tags in DNA that can be measured by automated systems. Microarrays of thousands of SNPs have been prepared that provide a clear picture of the chromosome structure of a cell. Microarray-based aneuploidy screening has excellent reliability and accuracy, and holds enormous promise for identifying genetically normal embryos. This study represents the first validated method of analyzing the entire set of chromosomes in a single cell. Stay tuned for more on this exciting technology.

Array CGH uses thousands of very small DNA probes along with computer software to describe the structure of DNA in a single cell. A very sensitive test, it is fast enough to be used during an IVF treatment cycle, and far more accurate than conventional fluorescent probe (FISH) analysis. Array CGH may lead to improved IVF outcomes as embryos containing an error in any chromosome can be detected, which would allow better selection of healthy embryos.

PGD has proven useful for the treatment of recurrent miscarriage. In an analysis of 279 patients with recurrent miscarriage (women who had previously experienced 3-5 miscarriages), researchers in New Jersey found an improved miscarriage rate of 19.5% after PGD versus their 40.9% expected rate.  Philip Chenette, MD

ASRM Update #3: Egg Freezing

Oocyte cryopreservation is the storage of the female gamete, the egg, prior to fertilization. Preservation of fertility for single women that must undergo cancer therapy or surgery, or that must delay or choose to delay childbearing, and donated oocyte banking are all applications of oocyte cryopreservation. The need for this technology is clear, but reports of success with oocyte cryopreservation have been limited.

Highly successful oocyte cryopreservation is now attainable. New studies are showing pregnancy rates with oocyte cryopreservation that are equal to traditional IVF techniques.

The key to this technology is oocyte vitrification – an ultrarapid cryopreservation technique. Researchers from Atlanta described their experience with vitrification. Out of 11 patients with transfers, nine conceived, with an implantation rate of 65%.

Pregnancies after oocyte cryopreservation have developed normally. An Italian study of 105 children born after oocyte cryopreservation showed no problems. A Chicago study of the genetics of oocytes, embryos, and children born after oocyte cryopreservation was reassuring. No increase rates of aneuploidy or malformations were reported, and normal development was found in post-natal follow-up.

These results are similar to those we have previously reported from our own research at Pacific Fertility Center (see December 2007 Fertility Flash). Oocytes are now cryopreserved with high success rates. Oocyte cryopreservation technology has matured, and we look forward to providing these techniques for our patients.  Philip Chenette, MD

Update #4: Acupuncture

The published study of German Paulus ⁽¹⁾ reported improved pregnancy rates with a one-time acupuncture treatment pre-and-post embryo transfer. This sparked great interest for providers of fertility treatment, in both the conventional and Chinese medicine (TMC) communities (see Fertility Flash March, 2004). A few years later, a study from Denmark ⁽²⁾ reported improved pregnancy rates in patients receiving pre-and-post transfer acupuncture, but no improvement if there were two post-transfer treatments. In both of these studies, there were no sham acupuncture (i.e. simulated but not real acupuncture) treatment controls.

Smith ⁽³⁾ and colleagues in Australia did compare acupuncture versus sham acupuncture (but did not include a no-treatment control group), using 3 treatment sessions: ovarian stimulation day 9, pre and post embryo transfer. There was no difference found in these different study groups. Interestingly, subjects in the sham control group were more likely to report relaxation as a side effect of acupuncture. Some studies indicate that sham acupuncture evokes acupressure, and in this way, may trigger physiological responses.

In all the above studies, the acupuncture treatments were performed within the IVF centers (patients did not have to travel off-site). In general, there were no more than 100 patients per treatment group.

At ASRM, Dr. Craig and colleagues reported an acupuncture study conducted in Seattle, using 3 IVF clinics. The acupuncture sessions were performed off-site by 2 acupuncturists. The patients were randomized to pre- and post-transfer acupuncture vs. no treatment. The physicians were not aware if the subjects were or were not receiving treatment. A total of 97 patients were studied (about 50 patients per treatment group). Clinical pregnancy and live birth rates were as follows: 54% and 39% for the acupuncture group, and 78% and 65% for the control group. These results were statistically significant. Of all the acupuncture studies thus far published, this is the first study to suggest a possible detriment to the use of acupuncture in IVF treatment.

One of the important differences for this study versus other randomized controlled trials is that all the patients had to go to an off-site acupuncture center for their treatment. This may be an important factor when a patient has to travel to the acupuncture clinic immediately before and immediately after an embryo transfer. Perhaps this factor would increase stress levels. Another important difference for these Seattle IVF centers was that baseline pregnancy rates are much higher than the previously-studied non-US centers. The higher the baseline pregnancy rate, the more difficult it is to show a difference in treatment results— so a statistically significant result would be more credible.

Ideally, a multi-center randomized-controlled-trial should be performed where the following comparisons can be evaluated: acupuncture pre-and-post transfer, no-acupuncture control group, sham-acupuncture control group, and these 3 groups can be compared at both on-site and off-site acupuncture centers. Each study group would require at least 100 patients, so this would require about 1000 patients total.

As we have a chance to collaborate with TCM providers, and as patients are willing to participate in these large multi-center randomized clinical trials, we will gain a better understanding about whether a mix of allopathic and TCM medicine improves overall care, and which combination of treatments may be the most beneficial for our mutual patients.  Isabelle Ryan, MD

References:

(1) Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy. Fertil Steril. 2002, Apr; 77(4):721-4.

(2) Acupuncture on the day of embryo transfer significantly improves the reproductive outcome in infertile women: a prospective, randomized trial. Fertil Steril. 2006 May; 85(5):1341-6.

(3) Influence of acupuncture stimulation on pregnancy rates for women undergoing embryo transfer. Fertil Steril. 2006 May; 85(5):1352-8.

Update #5 Men and ART

The Mental Health Professional Group (MHPG) course entitled Men and ART: The Missing Voice, blended medical, psychological, ethical and legal information relating to men who participate in Assisted Reproductive Technology (ART).

The legal issues confronting single men and gay men considering the use of egg donors and gestational surrogates continue to be controversial. Adoption legislation in many states prohibits gays and lesbians from adopting. In a study reported in 2005 by Gurmankin, et. al, 44% of ART programs responded that they would not turn away gay couples seeking surrogacy with one partner’s sperm and 48% responded that they would turn them away. This is in contrast to the higher rate of acceptance of lesbian couples. In lesbian couples seeking treatment using donor insemination, 82% of ART programs agreed to treat versus 17% who refused to treat them.

Though often presented exclusively to women, men can also benefit from the use of stress reduction strategies and following a healthy life style which includes regular exercise, normal body weight, no smoking or recreational drug use and avoidance of environmental toxins. In addition, the effects of aging and cancer on sperm quality should not be overlooked when men seek reproduction assistance. (See Sperm aging: Fertility Flash Feb. 2004, Sperm Fragmentation: Fertility Flash March 2005, October 2004 Cancer and Infertility: Fertility Flash Oct. 2004).

The psychological component of this course was compelling. Approximately 50% of cases of infertility involve at least some degree of male infertility. Why is it that most infertility references are traditionally directed at women? By definition, Infertility is “…the inability of a woman to conceive after some months (12-24) without contraception, or the inability to carry a pregnancy to term.” (Institute of Medicine and National Research Council, 1989). Ancient biblical references and popular literature focus on women’s infertility – e.g. Sarah and Hannah in the bible, Sylvia Plath’s Barren Woman, Jane Smiley’s 1000 Acres. The list is long. Google hits by gender for infertility and psychology show 542,000 for men and 700,000 for women.

The cause of this discrepancy is multifaceted. There are fewer psychological studies on men simply because men have a lower study response rate than women. A variety of successful techniques have been developed to overcome male related medical issues. Additionally, most men spend less time in treatment and experience fewer invasive procedures than women. In general, it is more socially acceptable for women to express their feelings regarding infertility. The opposite is true for men whose fertility often is a taboo topic. Furthermore, some cultures protect their men from the unacceptable stigma of infertility and even falsely describe men as having “poor” coping skills.

Despite these discrepancies, men do have feelings about infertility and may need support and assistance to better cope with the diagnosis. A study by Mason MC in 1993 found that men felt guilt, shame, anger, isolation, loss and a personal sense of failure. This is not all that different from what women feel, but each individual’s coping mechanism is unique. We all, however, find ways to protect ourselves from what we perceive as painful information.

These coping skills can be divided along gender lines. There are ways that many, but certainly not all, men commonly protect themselves from the pain related to his or his partner’s infertility diagnosis. Frequently men are able to distance themselves from the feelings. They appear to have the ability to take painful information and put it in a little box that they then file away in the back of their minds. The box stays tightly shut. Other men want to problem-solve for their partner or avoid the topic completely, throwing themselves into work or hobbies. Some men become extremely optimistic to avoid or counter their partner’s pessimism.

These are different styles- not right or wrong. For many of us, particularly women, the closed box technique does not work. The box is opened often, and feelings appear to refuse to stay tucked away. When partners have different coping styles, it’s important to both learn to tolerate and support these differences. Sometimes that is easier said than done...  Peggy Orlin, MFT

Peggy Orlin, MFT served as the 2006-7 Chair of ASRM’s Executive Committee of the Mental Health Professional Group (MHPG), is a member of Resolve’s National Mental Health Advisory Board. She co-teaches PFC’s Mind/Body@PFC workshops. (see PacificFertilityCenter.com for more information on Dr. Domar and Mind/Body@PFC Workshop.)

Isabelle Ryan, MD is recognized by prestigious medical associations for her pioneering research leading to new insight into the important clinical problem of endometriosis related infertility. At PFC she remains active in research while enjoying caring for infertile patients. Dr. Ryan has been repeatedly recognized as a “Best Doctor” in peer surveys for her expertise in the field of infertility (see www.BestDoctors.com). Dr. Ryan directs PFC’s Third Party Parenting Program and our in-house egg donor agency.

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 www.BestDoctors.com)

               
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ASK THE EXPERTS    Life Span of Frozen Sperm

   Pacific Fertility Center Team: Left to Right: Front: Philip Chenette, MD, Isabelle Ryan, MD, Carolyn Givens, MD, Back: Joe Conaghan, PhD, Carl Herbert, MD, Eldon Schriock, MD

Question: I am an educator for a human sexuality class. A student asked me an interesting question that I was unsure how to answer. Given that we know sperm can survive about 72 hours in a woman’s body, how is it possible to keep sperm viable by freezing them?

Answer: Sperm can survive for a long time under the right circumstances. In a woman’s body we think that 72 hours is approximately correct, but the data supporting this estimate is not conclusive. In the lab, sperm can live 5 days or more provided they are removed from the seminal fluid and placed in a more nurturing environment. Seminal fluid contains many enzymes that first clot and then liquefy. This change in the fluid allows the ejaculated sperm to stay in the vagina initially, but then swim out as the seminal fluid becomes more liquid. These enzymes quickly destroy any sperm that can’t swim out of the semen within a few hours.

It takes approximately 72 days for sperm to mature in the body. During the last 14 days of this process, the sperm are very much alive and swimming. They are alive a long time prior to leaving a man’s body.

During freezing, sperm are cooled to a very low sub zero temperature (minus 196 degrees Centigrade). At that temperature, all biological activity is effectively stopped. The sperm cells are not metabolizing or depleting their energy reserves. They are truly in suspended animation. Bacteria or other microbes cannot attack or degrade the sperm in any way because they are also unable to function at such a low temperature. Everything is on hold.

Biologists believe that correctly frozen cells in long term storage can literally last forever, as long as the temperature is properly maintained. It is believed that constant exposure to normal levels of background radiation is the only thing that could cause loss of viability and this effect is difficult to measure. Studies done in the 1970’s, exposing frozen mouse embryos to the equivalent of 2,000 years of background radiation, showed no measurable mutagenic effects in offspring.

Cryobiology is a relatively new science, and human fertility treatments are newer still. Consequently, in humans there are no long term results with frozen sperm or embryos. There are a handful of reports showing babies born from embryos that had been frozen for 12-15 years. A couple in New York had a child in 2005 from sperm that had been stored for 28 years. Sperm frozen for domestic animal species have a longer record because samples frozen in the 1950’s are still viable.

The process used for freezing is very precise and works best when cells exist individually (such as sperm) or in very small groups (such as an embryo). Larger masses of cells, tissues or even whole bodies cannot be frozen and subsequently thawed alive. It is not currently possible to freeze and thaw a whole ovary or kidney.

To successfully freeze cells we must remove cell water (water expansion during freezing would burst the cell) and replace the water inside the cell with antifreeze. This is done by incubating the cells in a solution of antifreeze. The water and antifreeze swap places through the process of simple osmosis. In a complex tissue like an ovary, there is no way to get all the water out of all of the cells so easily, thus a whole ovary cannot be frozen. If the ovary is chopped up into tiny pieces however, more water can be extracted. Some success has been reported with freezing ovarian pieces in this way.

               
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ANNOUNCEMENTS    New On-site Acupuncture Service

Pacific Fertility Center is pleased to announce the launch of our in-house mind-body medicine program. We are offering on-site acupuncture and mind-body groups to further support your treatment choices.

Over the years, Pacific Fertility Center (PFC) patients have elected to receive acupuncture treatment in combination with IVF and other fertility treatments. These treatments have been provided at outside facilities. We now offer acupuncture on-site, to minimize the stress of visiting numerous providers during your treatment cycle. We recognize that family building choices are diverse and want to support you throughout your important, personal decisions on your journey to parenthood.

This new service offers the expertise of acupuncturists who specialize in reproductive care. Our acupuncture team will work in close communication with the physicians of PFC. The result is a program that supports you with safe and convenient treatment. This exceptional new team is comprised of four licensed acupuncturists (LAc) who hold Masters of Science degrees in Traditional Chinese Medicine from accredited schools in California.

The medical team at Pacific Fertility Center is proud to provide this new service. While current studies do not show improved pregnancy rates with the combination of IVF and acupuncture treatment, we look forward to collaborative research studies to clarify these important questions. Together, we are launching exciting research projects that will investigate the scope and effectiveness of combined acupuncture and assisted reproductive technologies. Fertility Flash will provide readers with more information as the research program develops.

We hope you will enjoy getting to know the acupuncturists and take advantage of these new treatment options.

Pacific Fertility Center continues to offer the Mind/Body@PFC Workshop. At the workshop, our experienced, Alice Domar-taught instructors help patients learn healthy, positive ways to relax and decrease the symptoms of stress during their fertility treatments.

It is our hope that these offered services will provide a more comprehensive approach to your journey through fertility treatment with us at PFC.

Tired of traveling to an outside acupuncturist for treatments or just curious about what this new service entails? Call (415) 834-3000 for information and to schedule an appointment for acupuncture.

Stressed or anxious attempting to conceive? Attend Mind/Body@PFC workshop and re-frame your journey to pregnancy. Call (888) 834-3095 for fee and workshop information and registration forms.

Pacific Fertility's Onsite Acupuncture Team

Tiffinie McEntire, MS, LAc, has been a passionate advocate of holistic health care for more than twenty years. After completing her Bachelor of Arts degree in English Literature and Holistic Health at San Francisco State University. Ms. McEntire pursued a brief career in medical journalism before discovering her true calling, Chinese Medicine. She received her Masters of Science degree at the American College of Traditional Chinese Medicine in San Francisco. During a clinical internship at the SF Women’s Community Clinic, she was introduced to the integration of Chinese medicine and western gynecology. This experience led Tiffinie to become more involved in reproductive health care.

For entertainment, she enjoys exploring San Francisco’s culinary delights and Salsa dancing.

Jennifer Moss, MS, LAc , has received advanced training and extended education in treating infertility and obstetrics with Traditional Chinese Medicine. She has been treating couples who are trying to conceive since 2002. Ms. Moss graduated magna cum laude from the University of Vermont with a Bachelor of Science degree in 1998. In 2001, she graduated the top of her class with a Masters of Science in Traditional Chinese Medicine from the American College of Traditional Chinese Medicine in San Francisco. Jennifer is a professional member of the American Association of Oriental Medicine (AAOM).

Outside of her practice, Jennifer can usually be found on a hiking trail or a yoga mat.

Caylie See, MS, LAc , comes from a long line of chocolatiers. Her own mixing bowl combines the integration of Chinese and western medicine and the desire to create enhanced infertility care for men and women. Her undergraduate education includes classical Latin and Mandarin Chinese linguistics. She gained a Master's degree summa cum laude at Emperor's College of Traditional Oriental Medicine and completed her clinical studies at the LA Free Clinic, UCLA Arthur Ashe Center and Daniel Freeman Memorial Hospital. Her extended studies include a mentorship in gynecology and infertility. In addition, Caylie has spent time in China exploring traditional and modern uses of medicinal herbs. She balances her private practice with medical research. Caylie is a member of the American Society for Reproductive Medicine, Vice President of the American Board of Oriental Reproductive Medicine and sits on the board of OpenPath, (formerly RESOLVE of Northern CA).

In her free time, Caylie enjoys archery, violin and French cooking.

Sara Steig, MS, LAc , specializes in women’s health and reproductive medicine. Ms. Steig received her Masters of Science degree from the American College of Traditional Chinese Medicine in San Francisco. Her undergraduate education includes a Bachelors degree in psychology, Italian studies and holistic health care. She has also completed in-depth mentorships in fertility. Sara continues to develop her knowledge and the knowledge of others in the field of integrative reproductive medicine through her commitment to research and education.

Bay Area native, Sara enjoys spending time with family and friends, hiking the beautiful Marin trails, doing yoga, and traveling to tropical destinations.

               
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PATIENT EDUCATION CONFERENCE    "Family Matters San Francisco"

Pacific Fertility Center is a supporter of The American Fertility Association, (AFA), a national nonprofit organization dedicated to educating, supporting, and advocating for men and women concerned with reproductive heath, fertility preservation, infertility and all forms of family building. At the end of 2007, PFC’s Dr. Philip Chenette was honored with the presentation of the Family Building Award at the American Fertility Association’s glamorous Kokopelli Ball in New York City.

For the first time, on February 10, 2008, the American Fertility Association (AFA) will bring their annual day-long conference to the Bay Area. Pacific Fertility Center is a Platinum Sponsor of this conference and Drs. Carolyn Givens and Isabelle Ryan will be speaking at the event.

“family matters san francisco”, held at The Presidio, will provide a one-of-a-kind opportunity to attend lectures, listen to panel discussions and have questions answered during Q & A sessions.

At the conference, you will have the opportunity to meet face-to-face with an array of experts to discuss your particular concerns involving the medical, legal or emotional aspects of family building. Whether you are just beginning to consider seeing a reproductive endocrinology and infertility specialist or are deep into your treatment plan. With a special track devoted to Gay and Lesbian issues, this comprehensive event is for everyone with a passion for building their families of choice.

Pacific Fertility Center : Platinum Sponsor

Meet PFC Physicians at the conference.

ART: The Past, The Present and The Future • 9:15 AM to 10:00 AM
Carolyn Givens, MD with Special Introduction by Philip Chenette, MD

Establishing Parentage: Medical and Legal Issues for
Lesbians and Gay Men Using A.R.T. • 1:50 PM to 3:25 PM
Isabelle Ryan, MD and Deborah Wald, Esq.

Patient Education Conference Details:

The American Fertility Association’s, family matters san francisco,
Sunday February 10, 2008, 8:00 AM - 5:45 PM
The Golden Gate Club at the Presidio Trust, 135 Fisher Loop, San Francisco, CA

8:00 AM Registration and Breakfast in the Exhibit Hall

9:00 AM AFA Opening Remarks, Cypress Room

4:30 PM - 5:30 PM Wine and Cheese Reception and Special Open Session:
“Having Kids? The Environment and Your Fertility” in the Cypress Room
Moderator: The AFA National Spokesperson Brenda Strong, of the cast of Desperate Housewives.

Individual Tickets: $40.00
To register or for more information:
Call 888-917-3777 or email: [email protected]
Website: www.afafamilymatters.com

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