SCIENCE PULSE    ASRM 2005 Roundup

This past fall, over 6000 of the world’s leading researchers in reproductive medicine gathered in Montreal, Canada to participate in the annual conference of The American Society for Reproductive Medicine (ASRM). ASRM is an organization of 8,500 physicians, researchers, nurses, technicians, and professionals dedicated to advancing knowledge and expertise in reproductive biology.

PFC partners Eldon Schriock, Isabelle Ryan and Joe Conaghan attended the conference this year. Here they share with Fertility Flash readers highlights from a chosen handful of the presentations.

Nicotine Damage to Sperm Better Understood

An experiment led by researchers from the State University at Buffalo School of Medicine revealed that chronic male smokers could experience a reduction in their fertility of up to 75% as compared to non-smokers. Lani Burkman led the study to provide more details on past research, which had shown that when nicotine and its by-product, cotinine, were added to sperm in the lab, these chemicals changed the way the sperm moved.

In this recent research, sperm from both smokers and non-smokers were combined in two different Petri dishes with oocytes derived from one source. The sperm’s ability to bind to and penetrate the zona pellucida (outer shell) was carefully observed. In summary, the smokers' sperm were less effective in binding to the zona pellucida. The sperm of chronic smokers - people who have smoked a minimum of four cigarettes a day for at least two years – maintained an average of 75% less capacity to fertilize compared to nonsmokers. The researchers also discovered that light smokers’ sperm performed better than chronic smokers’, suggesting that men trying to start a family will have better results even by cutting back on the smoking.

Knowledge of Egg Freezing Advancing Rapidly

Fourteen papers on the topic of oocyte cryopreservation were presented. Some focused on studying overall results since egg freezing was first introduced in the late 1980s, while other presentations reported on testing specific methodologies, such as slow vs rapid freeze and thaw techniques, or the use of different cryoprotectants. Results continue to bode well but specifically for women who are relatively young.

In what the media hailed as a breakthrough, one research team presented what could be the highest success rate for oocyte cryopreservation to date. Led by John Jain, MD, an associate professor of Reproductive Endocrinology at University of Southern California, the team’s egg-freezing protocol involves the use of slow freezing and fast thawing, in addition to a specific culture medium that applies choline for stabilizing the egg’s membrane.

The research was derived from a small study involving only eight infertile women with tubal factors, all around the age of 31. Out of the eight women trying to conceive, five achieved pregnancies with their own previously frozen oocytes. For the particular study group, this translates into a 62% success rate per patient, which is comparable to fresh embryo transfers. However, Dr. Jain stressed that considerably more research needs to take place before egg freezing should be used in standard clinical practice.

More good news for oocyte cryopreservation came out of a research team from McGill University in Montreal, Canada. This team applied a proprietary blended cryoprotectant formula and used only the vitrification (rapid freeze) method in contrast to the more standard slow freeze protocol. In this case, 180 oocytes that were derived from 15 women of mean age 31.7 were vitrified. Out of these, 169 survived the fast freeze process (93.9%), and 126 oocytes fertilized normally (74.6%). Out of the original 15 patients, 4 are currently showing signs of successful pregnancies and one has already delivered.

More Worries About Multiples

Ongoing research continues to identify problems with multiple gestation births, some involving assisted reproduction, some not.

Genetic Testing Important for Twins: Researchers at UCLA’s School of Medicine working with the Cedars-Sinai Medical Center identified higher rates of cytogenetic abnormalities in the first trimester of twin gestations conceived through IVF compared to spontaneously conceived twins.

The team set out to discover whether the previously suggested increased incidence of aneuploidy in twins might be related to IVF. This retrospective case-controlled study analyzed women at least 35 years of age carrying dizygotic twins who underwent chorionic villus sampling (CVS) at these institutions between 2000 – 2004. The average age of the patients carrying twins from IVF was slightly higher (2 years) than those with twins who conceived naturally.

Out of the 27 women carrying twins conceived through IVF, the incidence of aneuploidy was 14.8%. Out of the 14 women carrying twins conceived spontaneously the aneuploidy incidence was 0%. Because genetic abnormalities can be identified through CVS early in the pregnancy, the paper points to the importance of counseling. (Note: Those who require IVF may already have an increased incidence of genetic abnormalities unrelated to the IVF process. Continued study is needed.)

Vanishing Twins Provide Clues: A research team at UCSF studied the gestational sacs of 244 births resulting from IVF/ICSI and found that singletons born with a so-called vanishing twin were more likely to have adverse perinatal outcomes including low birth weight, premature birth and stillbirth incidences, suggesting abnormalities start in early placentation. They are now calling for a larger sample size to confirm the data. Female Twins Reach Early Menopause: Weill Medical College of Cornell University researchers presented data suggesting that female twins are more likely to undergo premature menopause. Although identical twins showed a higher incidence than non-identical twins, both groups showed significantly higher rates than their non-twin counterparts from the general population. Statistically speaking, only about 1% of women reach menopause by age 40. The twins from this study revealed that about 5% reached premature ovarian failure and showed menopausal symptoms by age 40. In some cases, only one twin out of a pair entered early menopause. This joint study involved a survey of 850 women from different twin populations around the world collected by the Queensland Institute of Medical Research in Brisbane, Australia; St. Thomas's Hospital in London and St. Luke's Hospital in St. Louis, Missouri.

Infertile Women Want Twins: While the news about multiple gestations continues to raise concerns, a group out of the University of Iowa, Carver College of Medicine confirmed earlier research indicating that infertile women desire twins at twice the rate of their fertile counterparts. This research team used a questionnaire-based prospective study to survey over 1000 maternity patients and found that 20% of infertile women conveyed a preference for twins compared to 10% of fertile women.

Pollution Has Impact in Brazil

Two research groups from the School of Medicine at the University of São Paulo in São Paulo, Brazil are studying the impacts of air pollution on reproductive health. One study group focused on early miscarriage by exposing mice to ambient air pollution from rush hour traffic, compared to a control group placed in a less polluted environment. The exposed mice group had 80% of the early gestational miscarriages recorded out of the combined set. Specific pollution types and quantities were not listed in this study.

The other study analyzed the possible impact of increased ambient air pollution on gender outcome of live births of both humans and mice. In this study the researchers correlated live birth data to 15 air pollution monitoring stations in the city of São Paulo. They analyzed birth registries between January 2001 and December 2003, and correlated conception dates to the pollution levels of each station. In the least polluted area the sex ratio was 51.7% males for 34,795 births recorded, and for the most polluted area the proportion decreased to 50.7% for 48,023 births recorded, indicating a difference of 1% in total male births. Similar findings were observed in the experimental study involving mice placed in polluted vs filtered chambers. In the filtered chamber the male/female ratio was 1.34 opposed to 0.86 in the non-filtered chamber.

Left to right: Front row: Carl Herbert, MD, Isabelle Ryan, MD Back row: Joe Conaghan, PhD, Eldon Schriock, MD, Carolyn Givens, MD, Philip Chenette, MD

The physicians at Pacific Fertility Center 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.

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PFC SPOTLIGHT    My Journey to PFC

When I was in high school my mother said I should go to a finishing school where I might meet a nice man. I never quite got that connection and instead went to Washington D.C. to study design. I graduated and worked as an interior designer for 5 years. My design career began during the Vietnam years. Interior design did not feel sincere or altruistic enough for me at the time. I yearned to make a real difference in peoples lives.

In 1968 I moved to Cambridge, marched for women's rights and generally became more of an activist. I took a job for two years at the local state mental institution and worked as an attendant on a locked ward for chronically ill women. By the summer of 1969 I had moved further from the mainstream, became a “hippie” and among other things, hitchhiked back from Woodstock.

It soon became clear to me that if I were to be of service to others in the way that I envisioned, a nursing degree would help. So off I went, traveling from one coast to the other to live in Southern California near family members. After 2 years I began nursing school.

Why the delay? Well I met a nice man and had a baby. That was a slight detour from my plan, but it only served to steady my goal. After graduating from nursing school I began working in an OB/GYN‘s office. The routine work was not what I was looking for.

I later took a course at UCLA studying Lamaze and taught classes for a while at Cedars Sinai. I enjoyed teaching, however at the time I was also undergoing fertility treatment. Teaching pregnant couples, being genuinely happy for them, yet yearning for my own pregnancy made for a very bittersweet experience. It's something that those of us who have lived with infertility cannot easily explain to others. How can I explain what it feels like to see pregnant women or women strolling with their babies along Montana Avenue? My family thought I was crazy to work so hard to get pregnant saying things like “just be happy with the one child you have”. It was my second marriage and I truly wanted to share a family with him.

After 2 years of IUI's every other month, we went through an IVF cycle. We borrowed money from his grandmother and gave it our all. Alas, it was not to be. Needless to say I was heartbroken. I wanted to move on to an ovum donor cycle, but my husband didn't. I struggled to accept that we were finished trying. In time, I came to know what it takes to make peace with that part of myself that yearned for the experience of family as I hoped it would be. We gave it our best and the outcome was out of our control.

A few months later a friend told me about a job working in a fertility office coordinating cycles for couples going through infertility. After a bit of reflection, I knew this was what I was meant to do. The nurse who had coordinated my cycle was compassionate, strong and encouraging, all qualities that I admired.

My daughter was in her teens when I was trying to get pregnant. When she reached 19 she announced to the family she was going to be an egg donor. She knew how hard it was for me not to be able to conceive and she wanted to help others in a similar situation. We said, “No, wait a few more years.” At 21 she became an egg donor and went through three egg donation cycles. Now she has her own family. She has kept the thank you cards from each of her couples and continues to feel that she contributed something very special to those who were in need of help.

For me, it has been at least 15 years since I became a coordinator. I am just as engaged in the process and cherish the relationships with patients that have come my way. I continue to wish them all happiness and success along their journey. I am also so grateful to have two grandsons who are the light and joy of my life. • Allison Chamberlaine, RN

Allison Chamberlaine, RN is a registered nurse with 15 years of experience in the field of infertility. Her depth of experience provides her valuable insight into caring for those experiencing infertility. She has been affiliated with Pacific Fertility Center since 1996. Ms. Chamberlaine currently coordinates care for individuals involved in third party family building at Pacific Fertility Center and co-leads stress reduction classes for Mind/Body@PFC. Ms. Chamberlaine's professional associations include the American Society for Reproductive Medicine and RESOLVE. She has been a speaker at the Resolve Symposiums. In addition to her infertility nursing, Ms. Chamberlaine enjoys the practice of Tai Chi and Hatha yoga and gardening. She has been involved with Siddha Yoga meditation for 22 years, has participated in 4 retreats with The Dali Lama and has taught meditation and relaxation techniques for over 20 years. In line with her long history of teaching meditation and relaxation techniques, and her belief that emotional support and self-nurturing activities are important for those experiencing infertility, she has received Mind/Body Teacher Training with Alice Domar, PhD. (Dr. Alice Domar, a pioneer in the development of mind/body programs for infertility.)

CONCEPTION HEALTH    Safe Lubrication

It has been known for quite some time that many lubricants used to facilitate intercourse or as an aid in masturbation for sperm collection may actually be toxic to sperm. A new study presented at the American Society for Reproductive Medicine 2005 conference confirmed this through a more rigorous study analyzing sperm motility and DNA damage after exposure to four brands: FemGlide, Replens, Astroglide and Pre-Seed.

Although no single product left the sperm completely free of damage, the research identified the Pre-Seed product as causing considerably less motility and DNA damage than the others.

The company that distributes this product claims that Pre-Seed is of the same osmolarity (salt density) and pH as seminal fluid. They further claim that it contains a plant sugar that acts as an anti-oxidant.

The study was jointly conducted without funding from any of the lubricant companies by researchers at Cleveland Clinic Foundation in Cleveland, Ohio; South Dakota State University in Brookings, South Dakota; and Washington State University in Spokane, Washington.

In the first experiment, sperm from 13 different donors was analyzed for progressive motility after 30 minutes of exposure to each lubricant while compared to a control batch from the same sperm donors with no lubricant exposure.

The results showed that sperm activity ranged from a high of 66 percent in untreated sperm, followed by 64 percent with sperm treated with Pre-Seed, followed by 51 percent with FemGlide and 25 percent with Replens. The lowest reported sperm motility was 2 percent in a solution containing Astroglide.

In a second experiment, spermatozoa was exposed for 4 hours and then evaluated for sperm chromatin integrity and then analyzed for percentage of DNA fragmentation, and then compared to non-exposed sperm. Again, the results indicated that Pre-Seed was associated with the smallest amount of sperm DNA damage at 7 percent more than untreated sperm, followed by KY at 10 percent and FemGlide at 15 percent.

Besides the brands tested, it is also thought that KY Jelly, Vaseline, and even saliva can have a negative impact on sperm. (One of the least toxic substances is pure mineral oil but it is generally not advised that women use lipid-based products in the vagina. Mineral oil remains an excellent choice for lubrication for masturbation.)

We welcome the news that a product that is backed by independent laboratory analysis is now available that can make vaginal intercourse more comfortable as well as acting as a promoter of fertility.  • Carolyn Givens, MD

ASK THE EXPERTS    Follicles and Fertility

Answer:
Women are born with all of the eggs (oocytes) that they will ever have. This is a set number, which is determined before birth. This pool of eggs is never replenished. A female fetus will have the greatest number of eggs around 16-20 weeks of pregnancy (6-7 million); at birth this number decreases to about 2 million; and by puberty to about 300,000. This constant and dynamic process of decline continues until menopause and is not interrupted by birth control pills, pregnancy, or ovulation. From this reservoir of eggs, fewer than 500 eggs will ovulate during a woman's reproductive life.

There is a continuous process occurring in the ovaries, where eggs are constantly being prepared for the maturation process. It takes 3-6 months for eggs to develop and mature. As the eggs are developing, they transition from a primordial, to preantral, to then antral follicle. Antral follicles are visible by vaginal ultrasound. Antral follicles therefore represent the reserve of eggs in our ovaries and those that are candidates for selection and growth by fertility stimulation medications (gonadotropins).

When assessing one's ovarian reserve (potential for a successful pregnancy), a number of parameters are evaluated. One of these is called the “antral follicle count” (AFC). An antral follicle count is typically done during the 2nd-4th days of menstrual flow, though it can probably be as accurately done during other times of the menstrual cycle. Studies show that the AFC is predictive of the expected ovarian response to gonadotropins. An AFC less than 6 total (between both ovaries), predicts a poor stimulation response. For those undergoing IVF, a similarly low AFC will be associated with a higher cancellation rate. As women approach their 40s, and as day-3 FSH results rise above 10 mIU/ml, this typically correlates with fewer eggs overall in our ovaries, and therefore a low AFC. Indirectly, a low AFC can correlate with diminished ovarian reserve.

In the same way that there can be monthly variability in day-3 FSH test results, there can be monthly variability in the AFC. More variability is observed in the AFC of young infertile women than in older women. However, overall a single AFC is still quite predictive of ovarian response under gonadotropin stimulation, and there is fairly good agreement between repeated AFC over consecutive cycles. In conclusion, doing an AFC is an adjunct to the day 3-FSH test to predict ovarian reserve and ovarian response to fertility medications. • Isabelle Ryan, MD

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CRITICAL REVIEW:    "A Few Good Eggs"

A Few Good Eggs; Two Chicks Dish on Overcoming the Insanity of Infertility is one of the best books about infertility written from the patients’ perspective. Julie Vargo and Maureen Regan have written a very readable and entertaining book presenting the entire gamut of the infertility experience covering diagnosis, procedures and the psychological challenges faced by patients – mainly women - facing infertility.

The book is organized chronologically starting from the early disbelief after realizing that one might be infertile, through the testing procedures, physician diagnosis and ultimately treatments.

Back-up options for those women and couples for whom treatments are unsuccessful are also explored. Along the way, the authors provide stories of their own experiences as well as the experiences of other women with whom the authors have met and talked in order to write the book. These two women personally went through many of the procedures and shared the same emotions that most fertility patients experience, their unique perspective brings a human touch to their writing. This is a refreshing contrast to the books written for the consumer by physicians or other health care professionals that work in the field.

However, because the book is written by patients and not reproductive endocrinologists (REs), there are some areas that not all REs will agree with, such as their perspective on immunology and infertility. The authors also seem to have gone through their treatments some years ago as the list of drugs is not current with some of the drugs now commonly used for ovulation induction. For example, they mention Pergonal, which is not currently available and do not cover the recombinant FSH medications most commonly used today, Gonal-f and Follistim. Plus, I doubt that a reproductive endocrinologist proofread the chapter on medications because they misnamed Repronex as “Repromax.” I also think their description of the side effects of these drugs is frightening and not typical of the side effects experienced by most women using them in treatment.

The book does provide a lot of useful information in a personal and accessible fashion. Most of the facts are correct. And most of all, the publication encourages women not to wait to get help if they think they may be infertile. • Eldon Schriock, MD

SEMINARS:   Dr. Phil

Overcoming Infertility: The Next Step to Parenthood: Led by PFC's Infertility Specialists

NEW San Francisco LOCATION!
Holiday Inn San Francisco - Fisherman's Wharf at 1300 Columbus Avenue
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2006 Dates: Wednesday from 6:30 to 8:30 PM (Registration begins at 6:15 PM)
January 18th
February 15th
March 15th

Special Event!
January 28, 2006 at HEALTHetc in the Moscone Center.
Family Building Basics: Need help building your family? For many, advanced reproductive technology is the answer. Learn from Pacific Fertility Center's Board Certified physicians who will discuss state-of-the-art infertility treatments such as in-vitro fertilization (IVF). We encourage those trying to build a family to attend this session—whether you're a couple, individual, man or woman. PFC will present a workshop at this one-day health event.

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