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.

– Eldon Schriock, MD

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

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.

Pacific Fertility Center is pleased to be involved in a six month study that will provide research data comparing two different methods of delivering enhanced progesterone to women after in vitro fertilization. Progesterone is a hormone that is produced by the ovaries after ovulation. Progesterone support is important for initiating implantation and supporting the embryo through the first months of growth.

Some women benefit from direct delivery of progesterone to enhance the implantation process.

The current protocol for direct progesterone application is via vaginal suppositories. Endometrin is an effervescent tablet that is inserted vaginally and absorbed locally to provide progesterone to the developing uterine lining and to provide support of pregnancy. The study aims to demonstrate the equivalence in maintaining pregnancy of the new medication to an existing FDA approved medication.

PFC is currently recruiting up to 25 women experiencing infertility to take part in this clinical research study.

The participants must be non-smokers between the ages of 18 and 42, with two functioning ovaries and a Body Mass Index of 34 or below. Additional screening will be conducted to determine if a patient is eligible to participate. Women who qualify and undergo an IVF treatment cycle will receive free medications and a reduction in IVF fees. Individuals interested in participating are invited to contact Dr. Philip Chenette at (415) 834-3000, or (888)-834-3095.

– Philip Chenette, MD

Mary Croughan, PhD is a Professor in the Departments of Obstetrics, Gynecology, and Reproductive Sciences and in Epidemiology and Biostatistics at the University of California, San Francisco. In 1999 her research team received funding from the National Institute of Child Health and Human Development to examine the health outcomes of infertility treatment for both mothers and children. Two thousand women who conceived after a history of infertility or after receiving infertility treatment are being compared to 2,000 women without infertility from the general population. Dr. Croughan is comparing the frequency of pregnancy complications, neonatal complications, and childhood outcomes up to six years of age in both groups. • All our physicians at PFC have supported Dr. Croughan’s research efforts for over a decade both at San Francisco Center for Reproductive Medicine and at UCSF. As a result, many of our patients have participated in her studies. We continue our research support as a participating clinic in this current study. Those women and children who are part of this or any other study must provide their consent. Under no circumstances will a patients’ chart or personal information be provided for a study without their permission.

Q. In layman’s terms, what makes your study so significant?
A. First, there hasn’t been that much research in the field of infertility or assisted reproductive technologies looking at long-term outcomes. Most studies have focused on very early pregnancy losses or the newborn period with no long term follow-up. Our study is examining children up to 6 years of age who were born as a result of either infertility treatment or following a history of infertility, and comparing them to children born to women without infertility in the general population.

We are currently interviewing women for this study and abstracting information from their medical records. We are recording detailed information regarding each woman’s infertility history, her medical history, her pregnancies, and her labor and delivery. We also are recording information about any conditions the child may have or any special services they might have received. We are particularly interested in looking at neurodevelopmental outcomes in the children.

Q. How is the study structured and what milestone have you reached?
A. In a previous study, we had gathered minimal information on a group of 52,000 patients who sought infertility services in California many years ago. Since we wanted to examine recent pregnancies in these women, we linked this existing information to birth certificates and fetal death certificates to determine which of these women had experienced a stillbirth or live birth between 1994-1998. We also selected a matched set of women from the general population using the same birth certificate and fetal death certificate database. We then mailed these women letters inviting them to participate in the current study. We are now in the process of interviewing these women and abstracting their medical records. We are about 60% complete in gathering our data. We hope to analyze it next summer.

Q. When do you expect to announce results?
A. In April 2006 we expect to be done with data collection. By June of next year we hope to see results completed. We are now nearly done with data collection for the infertile women in this study and we’re interviewing women from the general population comparison group. (Article continued-back page)

Q. It is interesting that standard comparative data for common medical conditions are not already known.
A. While we do know the incidence rates for many conditions in the general population, these numbers refer to everyone. In other words, the general population numbers include cases among children conceived using infertility treatments. In order to have comparative data, it is important to look at the groups separately.

Q. What do you mean by “examining infertility etiology?”
A. In trying to determine if there is an increased incidence of any adverse outcomes in these pregnancies or in the children, it is important to be able to tease out the effects of infertility per se from infertility treatments, other medical conditions, and advanced parental age. By looking at the reason(s) for infertility (the etiology) in combination with different treatment modalities and different conception methods, we can begin to tease out the independent effects of each.

Q. Is there any accounting for multiples vs singletons?
A. We are examining both singleton gestations and multiple gestations in this study. It is important to compare these two groups to each other, and to compare them across fertility groups (e.g., infertile vs. fertile). In a previous study I did with Dr. Rebecca Jackson here at UCSF, we performed a meta-analysis of singleton children conceived using IVF. These children had a significantly increased risk of low birth weight and prematurity as compared to singleton children in the general population. In our current study, we will be able to examine the same outcomes for multiple gestations.

Q. Why did you choose to identify patients from 11 different clinics?
A. By using many different institutions, we can examine different protocols and different types of patients. We are examining IVF with and without ICSI, IUI with and without ovarian hyperstimulation, as well as natural conceptions in infertile women and men. By including four Kaiser facilities, we also are able to look at a more diverse patient population. This is in contrast to the majority of other studies in Europe, Israel, and Australia that have focused solely on outcomes following IVF.

Q. Nine months ago a journalist revealed in an article that you already identified increased autism and ADD in children conceived using assisted reproductive technologies. Is this accurate?
A. No. The data was misinterpreted from a talk I gave at a professional meeting, and it was published without permission. We still have a lot of work left to do in this study and I don’t know what the final results will indicate.

Q. What led you to such a specialized field?
A. I have been interested in reproductive and perinatal epidemiology since high school, and have worked in it ever since. But having gone through infertility treatment myself, I was frustrated by the lack of information available to help me make decisions. I knew that I could help other women by providing information to help them make the best decisions possible.

Q. Can you comment on your ideas for future studies?
A. We just submitted a grant application for our next study. In this study, we hope to have the children and their parents come to UCSF to be evaluated in person. The children in our study are now between 10-12 years of age, so it will be important to follow these children through adolescence and adulthood. Of particular interest is looking at the children’s reproductive outcomes.

From time to time, PFC conducts clinical research aimed at improving IVF outcomes. Our newest clinical study involves the use of a new contraceptive device for ovum donors. Currently, we prescribe birth control pills to our ovum donors in the month preceding their IVF stimulation. We do this for several reasons.

First, we want to make sure the donor cannot get pregnant in the month prior to IVF at the time she needs to start Lupron. Also, hormonal contraceptives will usually prevent ovulation so that when the donor starts Lupron, there is less of a chance of inducing a cyst from the ovulation follicle. We also use birth control pills to get the donor’s and the recipient’s cycles in sync. Donors must remember to take one pill every day for anywhere from 14 to 35 days (usually 21 days).

A new contraceptive device manufactured by Organon is called NuvaRing. It is already FDA approved for contraception but to our knowledge, has not yet been used in ovum donors prior to IVF. This is a soft silastic ring containing estrogen and progesterone analogs. The patient places the ring in the vagina and removes it after 21 days. The potential advantage is that the donors will not have to remember to take a pill every day and therefore, help avoid any errors in a cycle.

We will be assessing by questionnaire whether or not the donor found the ring to be easy to use and whether or not they would consider using this method for future contraception. Because this is a randomized clinical trial, 15 donors will be randomly assigned to use the ring and 15 will be on our usual birth control pills. Organon will provide the pills or rings free of charge for donors in the study. For more information on NuvaRing and an interactive example of the ring’s flexibility go to www.nuvaring.com

Almost 20 years ago, a paper in a British medical journal Lancet announced the arrival of a new technology: Oocyte Cryopreservation (Chen, C., 1986, Vol 1, Page 884). What was initially thought to be a landmark paper turned out to be the poster child for the procedure, as Chen himself and many others were unable to repeat the process with consistency. Although it is difficult to open any magazine today without reading about this wonderful new technology, less than 1% of eggs that have been frozen and thawed have resulted in live born infants.

We have learned much about the freezing of human oocytes over the years, yet despite a massive and consistent effort by the scientific community, a reliable method to freeze eggs with the same success as embryos and sperm remains elusive.

Our ability to freeze any cell depends on many factors, but most significantly on how much water the cell contains. Because water expands in volume as it turns to ice, cells must be dehydrated prior to freezing to prevent the cell from rupturing. The addition of a cryoprotectant, which does not expand upon freezing, can greatly reduce the risk of cell rupture.

Scientists have been freezing and thawing sperm with good success for over 100 years. In many ways, sperm are ideal for freezing as they exist as individual cells, they are the smallest human cells and they contain very little water. It is thought that sperm can be stored perhaps indefinitely after being added to a solution of cryoprotectant, and then frozen to minus 1960C.

In contrast to the sperm, the oocyte is the largest human cell and it contains much more water. The oocyte is also much more sensitive and is very intolerant of the chemical and physical stresses that are created during freezing and thawing. Further, the availability of oocytes is much more limited. When an oocyte is ovulated, or retrieved from the ovary during an IVF cycle, ideally it is ready to be fertilized by a single sperm. In anticipation of fertilization, the oocyte prepares to discard half of its DNA – a process called meiosis. Any changes in the physical or chemical environment around the oocyte can disrupt meiosis, leading to an oocyte with too much or too little DNA. Even after we overcome the hurdles of sensitivity and cell water content, there are other obstacles to freezing and thawing oocytes successfully.

In scientific literature, most papers that report success with egg freezing involve very few patients and therefore even fewer pregnancies and deliveries. Porcu et al., 1997, Tucker et al., 1998 and Young et al., 1998 are typical examples of papers that report successful deliveries from just one patient’s frozen oocytes. Between them, these authors froze 34 eggs, of which 15 survived thawing. In larger studies, Porcu et al., 2000 and Fabbri et al., 2001 were able to obtain large numbers of oocytes for freezing (1502 and 1769 respectively), resulting in overall survival after freezing at just over 50% for both studies. Just over half of the oocytes that survived freezing fertilized, and about half of these made good quality embryos. Yet the number of babies delivered reported by Porcu was low (9 births plus 7 ongoing pregnancies). Fabbri reported only fertilization and embryo development rates as a measure of success in his study and has not yet reported on pregnancies and births.

Wider application and success with oocyte freezing depends on continued improvements with the technology and on careful selection of oocytes to freeze. While many researchers are continuing to improve the freezing process, much of the success so far has been with the use of good quality or young oocytes. In the Porcu study, most of the oocytes were collected from young women who would presumably have good quality oocytes. We would expect results to be worse if the eggs were from older women, although no such studies have been undertaken. • Despite all the hype, oocyte freezing will fall short of mainstream therapy in the near future until new technologies improve the process. Oocyte cryopreservation may be an especially disappointing prospect for older women. With this in mind, this year PFC will take part in a large scale study involving Japanese IVF centers and other US centers on an alternative technology called vitrification. This involves an ultra-rapid freezing process that we hope will allow more oocytes to be frozen before they are compromised by the effects of the physical and chemical stresses indicative of typical slow freezing methods. Vitrification has shown good success with human oocytes and embryos in recent Japanese studies.

Each year physicians and staff of Pacific Fertility Center attend the annual conference of the American Society for Reproductive Medicine (ASRM), a non-profit member-based organization established for the advancement of reproductive medicine. This gathering draws thousands of professionals from around the world to share advances in the field. Over 1600 abstracts were submitted for inclusion in the 2004 program. Our physicians Drs. Schriock and Chenette, and Lab Director Joe Conaghan have summarized a few topics here, based on the research’s relevance to clinical practice.

Same Success for Single Embryo Transfer
Some countries have mandated single embryo transfers (SET) in order to reduce the high rate of multiple-births from IVF treatment. Sweden’s rule was set into place January 1, 2003. A retrospective study has examined 1664 fresh IVF/ICSI/ET cycles before, during and after the transition to the new policy. Patients were of similar maternal age (mean 33.3-33.4), similar demographic characteristics and embryo quality scores.

The study revealed no difference in overall clinical pregnancy rate (33.3%, 32.8%, 33.8%) among those women studied. (Note that their mean age is less than the average age of PFC’s patients. Age is a key factor in the success or failure of IVF.) But the rate of twinning drastically reduced as a result of the new law prohibiting more than one embryo transfer (8.8% vs. 22.6% prior, and 16.3% during transition to the new policy). Sweden’s new policy appears to be resulting in a significant reduction of multiple births in young patients, while not impacting the overall clinical pregnancy rate.

Obesity Reduces Pregnancy Outcome
An extensive study has revealed that patients with a high body mass index (BMI), the method of measuring normal weight range, face a significant obstacle to getting pregnant. Specifically, researchers at the Beth Israel Deaconess Medical Center in Boston identified a 60% reduction in pregnancy rates in those with high BMI, or very obese, compared to those with a moderate to low BMI.

Researchers analyzed the records of 6,827 fresh non-donor cycles in which patients’ BMI had been recorded. The group was divided into five different weight categories, the maximum being a BMI 35 -39 kg/m2- considered obese. Researchers found no significant difference among participants with respect to the number of mature follicles observed, oocytes retrieved, mature oocytes produced, cycle number per patient and number of embryos transferred. However, they noticed significantly lower implantation rates and clinical pregnancy rates in those with a BMI >35 kg/m2 compared to all other BMI groups.

Progesterone Supplementation Not Needed
A group of researchers at the Carolinas Medical Center in Charlotte examined two groups of IVF patients to determine significant difference in pregnancy rates between those who continued progesterone supplements into the 12th week of pregnancy vs. those who had not. 237 patients categorized as the “long group” received 25mg intramuscular dose of progesterone the day of retrieval followed by a daily dose of 50mg IM until the pregnancy test and then daily through the first trimester. Another group of 121 patients, the “short group” continued same dose progesterone but only until the pregnancy test.

The study revealed similar conception rates for both groups. There was no significant difference in delivery rates when comparing all patients with a positive pregnancy test. However, both groups showed a similar degree of pregnancy loss, but at different times. Researchers concluded that long progesterone supplementation may support early pregnancy development through viability at 7 weeks but does not improve overall survival through the first trimester, showing more of a trend of delaying, not preventing miscarriage. For this reason, progesterone support of early pregnancy does not appear to be justified.

FDA Changes Ahead
Starting in May 2004, the Food and Drug Administration will be taking an active role in overseeing all aspects of health and safety of IVF clinical laboratory procedures, which are currently regulated by states. The changes are expected to increase the number of, and frequency of tests that patients will be required to undergo. Fertility Flash will publish a more extensive summary of this topic and how it will impact rates/procedures at PFC in one of our Spring 2005 issues. If you have any questions in the meantime, feel free to email us.

Drs. Chenette and Schriock attended the 2004 ASRM convention along with Lab Director Joe Conaghan and other PFC staff members. PFC’s medical team is continually evaluating the latest research. Our patients’ welfare is PFC’s first priority. With this in mind, be assured we do not include new technologies and treatments unless they are backed with solid, evidenced-based research.

Each year physicians and staff of Pacific Fertility Center attend the annual conference of the American Society for Reproductive Medicine (ASRM), a non-profit member-based organization established for the advancement of reproductive medicine. This gathering draws thousands of professionals from around the world to share advances in the field. Over 1600 abstracts were submitted for inclusion in the 2004 program. Our physicians Drs. Schriock and Chenette, and Lab Director Joe Conaghan have summarized a few topics here, based on the research’s relevance to clinical practice.Same Success for Single Embryo Transfer
Some countries have mandated single embryo transfers (SET) in order to reduce the high rate of multiple-births from IVF treatment. Sweden’s rule was set into place January 1, 2003. A retrospective study has examined 1664 fresh IVF/ICSI/ET cycles before, during and after the transition to the new policy. Patients were of similar maternal age (mean 33.3-33.4), similar demographic characteristics and embryo quality scores.

The study revealed no difference in overall clinical pregnancy rate (33.3%, 32.8%, 33.8%) among those women studied. (Note that their mean age is less than the average age of PFC’s patients. Age is a key factor in the success or failure of IVF.) But the rate of twinning drastically reduced as a result of the new law prohibiting more than one embryo transfer (8.8% vs. 22.6% prior, and 16.3% during transition to the new policy). Sweden’s new policy appears to be resulting in a significant reduction of multiple births in young patients, while not impacting the overall clinical pregnancy rate.

Obesity Reduces Pregnancy Outcome
An extensive study has revealed that patients with a high body mass index (BMI), the method of measuring normal weight range, face a significant obstacle to getting pregnant. Specifically, researchers at the Beth Israel Deaconess Medical Center in Boston identified a 60% reduction in pregnancy rates in those with high BMI, or very obese, compared to those with a moderate to low BMI.

Researchers analyzed the records of 6,827 fresh non-donor cycles in which patients’ BMI had been recorded. The group was divided into five different weight categories, the maximum being a BMI 35 -39 kg/m2- considered obese. Researchers found no significant difference among participants with respect to the number of mature follicles observed, oocytes retrieved, mature oocytes produced, cycle number per patient and number of embryos transferred. However, they noticed significantly lower implantation rates and clinical pregnancy rates in those with a BMI >35 kg/m2 compared to all other BMI groups.

Progesterone Supplementation Not Needed
A group of researchers at the Carolinas Medical Center in Charlotte examined two groups of IVF patients to determine significant difference in pregnancy rates between those who continued progesterone supplements into the 12th week of pregnancy vs. those who had not. 237 patients categorized as the “long group” received 25mg intramuscular dose of progesterone the day of retrieval followed by a daily dose of 50mg IM until the pregnancy test and then daily through the first trimester. Another group of 121 patients, the “short group” continued same dose progesterone but only until the pregnancy test.

The study revealed similar conception rates for both groups. There was no significant difference in delivery rates when comparing all patients with a positive pregnancy test. However, both groups showed a similar degree of pregnancy loss, but at different times. Researchers concluded that long progesterone supplementation may support early pregnancy development through viability at 7 weeks but does not improve overall survival through the first trimester, showing more of a trend of delaying, not preventing miscarriage. For this reason, progesterone support of early pregnancy does not appear to be justified.

FDA Changes Ahead
Starting in May 2004, the Food and Drug Administration will be taking an active role in overseeing all aspects of health and safety of IVF clinical laboratory procedures, which are currently regulated by states. The changes are expected to increase the number of, and frequency of tests that patients will be required to undergo. Fertility Flash will publish a more extensive summary of this topic and how it will impact rates/procedures at PFC in one of our Spring 2005 issues. If you have any questions in the meantime, feel free to email us.

Drs. Chenette and Schriock attended the 2004 ASRM convention along with Lab Director Joe Conaghan and other PFC staff members. PFC’s medical team is continually evaluating the latest research. Our patients’ welfare is PFC’s first priority. With this in mind, be assured we do not include new technologies and treatments unless they are backed with solid, evidenced-based research.


Each year physicians and staff of Pacific Fertility Center attend the annual conference of the American Society for Reproductive Medicine (ASRM), a non-profit member-based organization established for the advancement of reproductive medicine. This gathering draws thousands of professionals from around the world to share advances in the field. Over 1600 abstracts were submitted for inclusion in the 2004 program. Our physicians Drs. Schriock and Chenette, and Lab Director Joe Conaghan have summarized a few topics here, based on the research’s relevance to clinical practice.Same Success for Single Embryo Transfer
Some countries have mandated single embryo transfers (SET) in order to reduce the high rate of multiple-births from IVF treatment. Sweden’s rule was set into place January 1, 2003. A retrospective study has examined 1664 fresh IVF/ICSI/ET cycles before, during and after the transition to the new policy. Patients were of similar maternal age (mean 33.3-33.4), similar demographic characteristics and embryo quality scores.

The study revealed no difference in overall clinical pregnancy rate (33.3%, 32.8%, 33.8%) among those women studied. (Note that their mean age is less than the average age of PFC’s patients. Age is a key factor in the success or failure of IVF.) But the rate of twinning drastically reduced as a result of the new law prohibiting more than one embryo transfer (8.8% vs. 22.6% prior, and 16.3% during transition to the new policy). Sweden’s new policy appears to be resulting in a significant reduction of multiple births in young patients, while not impacting the overall clinical pregnancy rate.

Obesity Reduces Pregnancy Outcome
An extensive study has revealed that patients with a high body mass index (BMI), the method of measuring normal weight range, face a significant obstacle to getting pregnant. Specifically, researchers at the Beth Israel Deaconess Medical Center in Boston identified a 60% reduction in pregnancy rates in those with high BMI, or very obese, compared to those with a moderate to low BMI.

Researchers analyzed the records of 6,827 fresh non-donor cycles in which patients’ BMI had been recorded. The group was divided into five different weight categories, the maximum being a BMI 35 -39 kg/m2- considered obese. Researchers found no significant difference among participants with respect to the number of mature follicles observed, oocytes retrieved, mature oocytes produced, cycle number per patient and number of embryos transferred. However, they noticed significantly lower implantation rates and clinical pregnancy rates in those with a BMI >35 kg/m2 compared to all other BMI groups.

Progesterone Supplementation Not Needed
A group of researchers at the Carolinas Medical Center in Charlotte examined two groups of IVF patients to determine significant difference in pregnancy rates between those who continued progesterone supplements into the 12th week of pregnancy vs. those who had not. 237 patients categorized as the “long group” received 25mg intramuscular dose of progesterone the day of retrieval followed by a daily dose of 50mg IM until the pregnancy test and then daily through the first trimester. Another group of 121 patients, the “short group” continued same dose progesterone but only until the pregnancy test.

The study revealed similar conception rates for both groups. There was no significant difference in delivery rates when comparing all patients with a positive pregnancy test. However, both groups showed a similar degree of pregnancy loss, but at different times. Researchers concluded that long progesterone supplementation may support early pregnancy development through viability at 7 weeks but does not improve overall survival through the first trimester, showing more of a trend of delaying, not preventing miscarriage. For this reason, progesterone support of early pregnancy does not appear to be justified.

FDA Changes Ahead
Starting in May 2004, the Food and Drug Administration will be taking an active role in overseeing all aspects of health and safety of IVF clinical laboratory procedures, which are currently regulated by states. The changes are expected to increase the number of, and frequency of tests that patients will be required to undergo. Fertility Flash will publish a more extensive summary of this topic and how it will impact rates/procedures at PFC in one of our Spring 2005 issues. If you have any questions in the meantime, feel free to email us.

Drs. Chenette and Schriock attended the 2004 ASRM convention along with Lab Director Joe Conaghan and other PFC staff members. PFC’s medical team is continually evaluating the latest research. Our patients’ welfare is PFC’s first priority. With this in mind, be assured we do not include new technologies and treatments unless they are backed with solid, evidenced-based research.

As fertility care providers, a frequent question we are asked is “Does stress affect my chances of a successful outcome?” This is a difficult question to answer, because few substantial studies have been conducted. However, some viable data is starting to trickle in.

Researchers from the UC San Diego Dept. of Family and Preventive Medicine, working with a number of IVF centers, tried to assess the impact of patient worries on their IVF outcomes Konoff-Cohen et al, Fert Ster: Vol 81, No 4, 982-988). In this prospective study, 151 women completed questionnaires pre and post IVF or GIFT treatment regarding their concerns about medical aspects of their treatment (not achieving desired results, side effects, surgery, anesthesia, not enough information, pain, recovery) and financial aspects (missing work, finances). It is important to note that only the questionnaires completed pre-treatment provided data for this study, since not enough post-treatment questionnaires were returned.

Women who were concerned about the medical aspect of the procedures had 20% fewer eggs retrieved and 19% fewer fertilized, than women who were less inclined to worry about it. Women who were concerned about missing work had 30% fewer eggs fertilized. Those who were very concerned about the financial implications of their treatment cycle had a greater risk of not achieving a live birth. These results were adjusted for different variables that could also affect success rates such as age, race, smoking, type of infertility, previous treatment attempts, and prior live births. However, other important predictors of outcome were not adjusted for, such as FSH and antral follicle count.

While these findings may appear to show dramatic differences, it is important to note that these differences (20-30% fewer eggs, 19% fewer fertilized) clinically represented a decrease of only ONE fewer embryo transferred. The greatest decrease was seen in women > 35 yrs old, and those who had already done a treatment cycle.

This study represents an interesting look at the issues of personal concerns and IVF/GIFT outcomes, and calls for further studies to understand the potential physiological effects that may mediate these outcomes. Other related studies are also worth noting.

For instance, a well-done study (Domar), which we described in the November/December 2003 issue of Fertility Flash, has shown that women participating in support groups while in IVF treatment seem to have increased pregnancy rates. A recently published study (Facchinetti) has looked at changes in physiological markers (heart rate, blood pressure, cortisol levels) in women undergoing IVF treatment and participating in support groups, showing evidence of physiological changes for those in support groups. These physiological changes are consistent with those seem in lower stress situations.

These collective studies suggest that one can best prepare for IVF by being as informed as possible about expectations of one’s treatment cycle (treatment procedures and financial impact). It may also be helpful to consider joining a support group. Fertility clinics can help patients by trying to alleviate patient’s concerns and making the IVF experience as smooth as possible.

We occasionally get asked by same sex couples if it is possible to create an embryo, and hence a baby, by using the DNA either from 2 sperm or 2 eggs, instead of the DNA from a sperm and an egg. In mammals, such a feat hasn’t been possible until recently. A paper in the scientific journal Nature (22nd April 2004) reports the birth of 2 mice; each created using the DNA from 2 eggs and with no sperm.

Creating offspring using only female genes and with no paternal contribution is a common phenomenon in nature and in fact is a method of reproduction employed by almost all plants and animals. Mammals however have not been able to reproduce in this way. This impediment is attributed in large part to a process called genomic imprinting.

Experimentally, when mouse embryos are created using only the DNA from 2 eggs, the resulting fetus is well formed, but only a rudimentary placenta develops and the pregnancy fails. This is because the placenta is created mainly by paternal genes, and without the involvement of a sperm, we can’t get a normal placenta.

But if we have 2 copies of almost every gene (one from Mom and one from Dad), why can’t the maternal genes make a placenta? Biologists think that it’s a conflict of interest for Mom’s genes to make the placenta. Since the placenta in many ways is a parasite that fights for Mom’s resources, Mom’s placental genes are deliberately inactivated or switched off and it’s left to Dad to make the placenta. This process of deliberately inactivating a set of genes from one parent, so that the other parent’s genes are left to do the work is called imprinting. These genes carry with them a history of their origin because they are endowed at conception with a maternal or paternal imprint.

One negative consequence of imprinting is that when an imprinted gene is defective or otherwise does not work, the inactive, but perfectly good gene from the other parent can’t be called upon to help out. Diseases like Prader-Willi syndrome and Angelman’s syndrome which have variable physical, mental and behavioral effects on afflicted individuals are caused by defective imprinted genes.

So what happens when an embryo is created using 2 sperm and without maternal DNA? In this instance, as would be expected, the placenta is normal and fully formed, but the fetus is typically deformed and most notably lacks a head. It could be said that without a Mom, mammals lose their heads.

In the Nature paper, the mice without a father were created after exhaustive attempts: 2 live born from 457 reconstructed eggs. And the researchers used a trick to get around the imprinting issue. To make each embryo they used a mature (ovulated) egg and an immature egg from a newborn mouse in which the genomic imprint had not been established (imprinting occurs as eggs grow and mature). This allowed them to overcome the absence of the paternal imprinted genes since there were few or no imprinted (and therefore inactive) genes in the DNA from the immature eggs. The process was not very efficient in creating live offspring, but one of the resulting mice reproduced normally after reaching adulthood. The second mouse was used in tests to determine its DNA normalcy.