The American Society for Reproductive Medicine’s (ASRM) annual meeting was held in New Orleans. It is the largest meeting for reproductive medicine specialists and scientists in the world. From our practice, Dr.s Givens, Schriock and Conaghan attended, as well as embryologists Jean Popwell, PhD and Jennifer Andres. Also, PFC nurse Allison Chamberlaine and PFC’s Marriage and Family Therapist Peggy Orlin attended. In addition, the genetics counselor with whom we work closely, Lauri Black from California Pacific Medical Center, was an attendee and active participant.

PFC’s embryologists attending ASRM’s research poster session Jean Popwell, PhD (left) and Jennifer Andres (right).

Single-Embryo Transfer: Minimizing Risks & Maximizing Outcomes
Dr. Givens attended a post-graduate course entitled “Moving Toward Single-Embryo Transfer: Minimizing Risks and Maximizing Outcomes.” This two-day course dealt with a pressing issue in assisted reproduction: the high incidence of multiple gestations. With the ever-increasing success of in vitro fertilization and the significant improvement in embryo implantation rates, the incidence of twin and higher-order pregnancies has risen dramatically in this country. Many countries now regulate the maximum number of embryos that can be transferred into the uterus at one time. The course topics included a summary of optimal medication protocols, several lectures on pre-cycle evaluation and testing and embryo transfer techniques.

Oocyte Freezing, PGS & Blastocyst Embryo Transfers
On the laboratory side, there were several talks on evaluation of eggs and embryo selection techniques, embryo freezing technology, including a debate about the usefulness of pre-implantation genetic screening (chromosome analysis of embryos) embryo selection. The combination was a fascinating mixture of new ideas, refinements in current technology, as well as a welcome opportunity to network and discuss with others the latest developments in reproductive science. Topping the list of presentations in New Orleans were those concerning the continuing refinements in oocyte freezing technologies, the more selective use of preimplantation genetic testing and the ongoing scrutiny of blastocyst stage embryo transfers.

Slow-freeze vs. Vitrification
The traditional slow-freeze technology used so successfully with embryos for many years, has essentially stalled with oocyte freezing. It appears the slow-freeze technology has finally met its successor: a process called vitrification. Slow freezing has had very limited success with oocytes due to their large size, high water content and their extreme sensitivity to cryoprotective chemicals and to changes in temperature and pH.

Vitrification, a technology that cools cells so rapidly that ice does not form, has been such a success for oocyte freezing that many labs are now abandoning slow freezing altogether. Here at PFC, we have been developing protocols for oocyte vitrification throughout 2006 and are actively working on blastocyst vitrification. It was reaffirming to see that this technology has gained wide acceptance, and is showing excellent results.

Preimplantation Genetic Screening (PGS)
While vitrification is on the rise, it was interesting to see that another technology, Preimplantation Genetic Screening (PGS), was lacking in new improvements or viable alternatives. Embryos have been screened for extra or missing chromosomes for over 15 years now, but the technology has not advanced significantly over that time. It is still possible to count only 12 chromosomes in an embryo. Although the error rate per chromosome is very low, the accumulated error rate becomes significant as we count more chromosomes. PGS was “under the microscope” in several presentations in New Orleans and it appears PFC’s limited use of genetic screening is well justified. Specifically, PGS does not improve embryo selection and pregnancy rates in younger patients. Its use is limited in older patients because there are often too few embryos available to justify testing. The patients who benefit most from PGS are the younger patients who experience recurrent miscarriages. However, unless there is evidence that previous pregnancies were genetically abnormal, PGS may provide limited benefit to this group.

Blastocyst stage embryo transfers
While younger patients (those under 35) don’t benefit from PGS, they are the patient population most likely to benefit from blastocyst transfers. Culturing embryos for 5 days to the blastocyst stage, instead of the more traditional day 3 embryo transfer, is one of the main ways in which the laboratory staff can help in selecting the “best” embryo for single embryo transfer (SET) patients. Blastocyst culture techniques are well refined now and support the commitment within the community to transfer fewer embryos at one time. Furthermore, the promise of vitrification can reassure patients that their remaining embryos can be stored indefinitely when preserved at the blastocyst stage. Several presentations showed that blastocysts which were vitrified early, before their cavity (or cyst) had expanded too much, benefited most from the technology. In more advanced blastocysts, artificial reduction of the cavity gave superior results. It may not be long before vitrification is the procedure of choice for preserving all blastocysts.

2006 ASRM guidelines for numbers of embryos to transfer
The new 2006 ASRM guidelines for numbers of embryos to transfer were presented. See Tables 1 and 2 below.

The topic of whether or not federal or state legislation should regulate the maximum number of embryos to transfer was also discussed. Many people in the general public support such legislation but those of us in the field (and most patients) are opposed to the government regulating medical practice and arbitrarily setting limits on embryo transfer. In order to forestall such legislation, it is obvious that we must decrease the number of twin gestations (the number of triplet and higher-order gestations has already dramatically decreased in the last 5-7 years). At Pacific Fertility Center we have instituted a new emphasis on single embryo transfers and expect to significantly reduce the risk of multiples and achieve our goal of “optimal” pregnancy outcomes. (See From Us to You in this issue for a discussion of our 2006 statistics and please see Conception Health in this issue for a discussion of why it is important to try to achieve single baby conceptions.

– Carolyn Givens, MD and Joe Conaghan, PhD

For those of us with an interest in human reproduction, scarcely a day goes by without us hearing or seeing something related to oocyte freezing. The topic has generated a lot of hype and it is difficult to avoid the frequent magazine and newspaper articles, advertisements and TV features that generate excitement on the subject.

We have already discussed oocyte freezing in a previous newsletter article (Keeping Egg Freezing in Perspective; January 2005) and readers unfamiliar with the technology are encouraged to visit our website where they can read this in the newsletter archive. Having already discussed the methods for freezing, and their merits, we now address the achievements of oocyte cryopreservation on this, the 20-year anniversary of the first success.

There are two technologies used in oocyte freezing, and the primary aim of each is avoiding ice formation within the cell. The first is the slow freeze method (used so successfully with embryos) that dehydrates and cools the cells gradually, over three hours. The second is an ultra-rapid procedure that is performed so quickly that the cell contents turn to a glass-like substance. This latter method is called vitrification and it is gaining in popularity for oocyte and embryo freezing. And since no ice forms, the cells are technically not frozen, but “vitrified.”

In reviewing the scientific literature since the first success in 1986, the importance of oocyte freezing is apparent by the sheer volume of publications on the subject. For the purpose of this article, the many papers that report on the technique only have been excluded, and here we will only report on the pregnancy outcome data. However, even this is difficult since some patients may have become pregnant from the first few thawed oocytes, leaving us with no data on the many oocytes still frozen on their behalf. Also, even though there are reports that detail only one or two pregnancies, there are probably many other isolated successes around the world that have gone unreported in the scientific literature.

Most of the pregnancy outcome data has been pulled together in a single review paper by Dr. K. Oktay and colleagues at Weill Medical College in New York (Fertility & Sterility, 2006, Vol 86 (1), pages 70-80). The 47 papers reporting outcome data for slow freezing were analyzed and from these, only 26 provided sound usable data. The others were excluded either because sub-optimal procedures were used, the pregnancies had not yet delivered or the authors could not be reached to clarify the data. The 26 useful papers collectively documented the freezing of 4,564 oocytes from which 4,000 had been thawed in 397 patient cycles. Out of 95 pregnancies, 76 resulted in live births, and since some of these were multiple pregnancies, the total number of children born was 97. If we add in the excluded data, the number of pregnancies becomes 170, resulting in 106 live births and 11 ongoing pregnancies. Because of ambiguities in the excluded data, a final number of children is not stated. However, the data suggest that the number of children that are alive today as a result of 20 years of slow freezing of oocytes is approximately 200. Taking all the data into account, the clinical pregnancy rate per thawed oocyte was a mere 2.3%. The live birth rate in the 26 usable papers was 1.9% per oocyte thawed.

Unfortunately it is not possible to give rates per oocyte frozen since some papers are not complete, but more importantly because many oocytes are still in the freezer.

Vitrification, which is a technology that came late to oocyte preservation, is quickly gaining ground on the slow freezing method. By June of 2005 there were only 10 reported births following oocyte vitrification, but a year later the numbers reported by Oktay are 61 pregnancies from which 42 have delivered live infants and 7 are ongoing. With limited data, vitrification appears to be a more highly efficient preservation method than slow freezing. The latest numbers, based on admittedly limited data, shows that >90% of oocytes survive and about 90% of these fertilize. Overall, 50% of vitrified oocytes make blastocysts in culture which is as efficient as fresh oocytes. These numbers are reported by Masa Kuwayama at the Kato Ladies Clinic in Tokyo. Also, from 29 embryo transfers, 12 pregnancies have yielded 7 live infants with 3 not yet delivered at publication time (Kuwayama et al., 2005, Reprod Biomed Online, Vol 11 (3) pages 300-308). We can compare this data to the latest results with slow freezing where the experience of 20 years has been incorporated. Using sodium-depleted medium, in which oocytes are slow cooled and frozen, 59% of oocytes survived and 68% of these fertilized. Nine pregnancies were established in 28 thaw cycles from which 5 delivered and 1 was ongoing (Boldt et al., 2006, Reprod Biomed Online, Vol 13 (1) pages 96-100). For those women who want to rely on oocyte cryopreservation to postpone motherhood, these data should be sobering. While we don’t expect the technology to ever be 100% successful, it currently offers no guarantees.

Expecting too much from today’s procedures could leave many women very disappointed. Further, many of the pregnancies reported in these studies were achieved by preserving the oocytes from young women. Since oocyte quality declines as a woman ages, the success rates for older women are likely to be less than reported here. Women considering oocyte preservation will need careful counseling and a good understanding of the success rates before putting their eggs in this basket.

– Joe Conaghan, PhD

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

Is the Future of Egg Freezing Here?
On the surface, it sounds remarkable that one can now shop for frozen oocytes through a start-up company called Cryo Eggs International, which offers single frozen oocytes for sale for $2,500 apiece via mail order. Based in Arizona, the company offers no guarantees whatsoever. The company claims that couples can save money and reduce their risk by choosing individual frozen eggs over the more involved and expensive process of working with a donor to produce fresh oocytes for fertilization.

Oocyte cryopreservation technologies have been evolving since 1986, and there is little doubt that there is a strong future in egg freezing. Young women are expected to have the choice of “banking” a cache of their genetic material for later use. Infertile women may indeed turn to a frozen egg bank, much the way that frozen sperm is marketed, to choose available eggs.

But is that time now?
A handful of infertility clinics are offering female patients a chance to undergo an IVF cycle and freeze their eggs for future use. Eventually PFC expects to offer this. Yet the majority of these clinics insist on prominently displaying the disclaimer that egg freezing technologies are still evolving and are highly “experimental”.

Indeed, as of early 2005, less than 1% of eggs that had been frozen and thawed had resulted in live born infants. (Keeping Egg Freezing in Perspective). Most certainly, egg-freezing technologies advancing cryopreservation of oocytes are evolving rapidly. (A Few Good Eggs). Yet the research community is still weighing the advances of different freezing mediums and methodologies, such as rapid vs slow freezing and thawing.

Responsible researchers/authors publishing their work in the global body of scientific literature are calling for several more years of studies with larger numbers of participants. Most of the current research is based on very small groups.

Cryo Eggs International attributes its success to the advances of Dr. Jeff Boldt, an associate professor of medical and molecular genetics and scientific director of Assisted Fertility Services at the Community Health Network, Indianapolis. He is also reportedly the scientific director at Cryo Eggs International. Yet Boldt’s primary published work in a scientific journal reported the results of a study that only involved 11 women. He is quoted in the media as having a larger number (33) of cycles from which results were comparable to standard IVF procedures, yet this study has not yet been published in a peer-reviewed science journal.

Can one tell if an egg is good or bad upon thawing?
Unlike sperm, of which mainly healthy ones are frozen, there is no sure way to determine quality control of a donor’s eggs short of conducting a DNA analysis of the resulting embryo. In this regard, Cryo’s customers are essentially asked to purchase single oocytes not knowing if they are viable.

Associated Costs with Frozen Eggs
After oocytes have been frozen they may have a thicker outer wall, otherwise known as the zona pellucida. This generally requires the embryologist to apply additional costly methodologies such as assisted hatching and ICSI.

Healthy Quarantine
The six months of freezing that is required before the frozen eggs can be released is no different than the six month testing requirement that a typical donor must go through to test for infectious diseases. In this regard, it is misleading for the Cryo Eggs International web site to claim that this process is any safer than conventional donor cycles.

Successful Approach
A donor cycle at Pacific Fertility Center has yielded a consistent 65% or greater success rate for many years. A key point here is this record has improved incrementally over the years after decades of experience and applying evolving technologies.

It is every physician’s wish for his/her infertile clients’ to have inexpensive choices to tackle their life dream of conceiving. It is also important for people to be as well informed as possible so their money may be spent for the most cost-effective and successful method for their particular situation.

– 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.

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.

Pacific Fertility Center is now participating in an important program that helps protect the fertility of cancer patients undergoing chemotherapy and radiation. Fertile Hope, an advocacy organization that raises awareness about fertility issues for cancer patients, is partnering with carefully selected clinics throughout the US in a program called Sharing Hope. The program will be open to those who have been diagnosed with cancer, want to preserve their fertility and have limited financial means. Sharing Hope offers qualifying cancer patients significant discounts for fertility-preservation treatments, such as embryo freezing and egg freezing before undergoing chemotherapy, radiation and/or surgery.

Cancer treatments can affect fertility in both men and women. In some cases infertility will be temporary, but in others it will be permanent. Currently, options are limited for cancer patients wishing to preserve their fertility. Men may freeze their sperm prior to cancer treatments to be used for artificial insemination or IVF. This is quite successful and in most cases at least 50% of a man’s sperm will survive freezing and thawing. The best option for women is to freeze embryos (via IVF). Yet this offers a viable solution only to women with partners or those willing to use donor sperm. What is the single woman diagnosed with cancer to do? She has not yet found Mr. Right, or even Mr. Perfect Sperm Donor, but knows she wants to have a child in the future. The bright spot may be egg freezing. Still considered experimental, egg freezing is a relatively new procedure and has much lower success rates than embryo freezing. Some say the numbers for egg freezing are around 1 live birth for every 100 eggs frozen, yet there are clinics around the world claiming to have 1 live birth for every 10 eggs frozen. The success of egg freezing will continue to improve as technology and scientific knowledge develop. PFC will offer egg freezing in the near future.

For some people, the idea of losing their fertility is as devastating as the diagnosis of cancer. Often, cancer patients have little time or opportunity to gather funds for the high cost of cancer treatment, let alone fertility preserving treatments. At PFC we hope to extend a helping hand to cancer patients unable to afford these costly treatments and to provide them with the hope of building a family.

You may find out more about Sharing Hope at Fertile Hope’s website

What might a mindful career-oriented 36-year-old woman have in common with a 22-year-old just diagnosed with an unusual cancer and scheduled for radiation or chemotherapy treatment?

• Both may want to carefully chart their course of family planning.
• Both face the loss of their ovarian egg reserves: one from the damaging chemotherapy, the other from age.
• Both may be considering oocyte (egg) freezing.

The idea that a woman can undergo a standard IVF procedure and then freeze individual eggs, instead of having her oocytes inseminated and then frozen as an embryo, is a notion that is capturing the imagination of grandmothers, women and doctors alike. So much so, dozens of infertility clinics are boasting egg cryopreservation as a new service even though most qualify it as “experimental”. Indeed, egg freezing is simply too new, and it has not shown the success rates necessary for widespread marketplace acceptance. This procedure is not a panacea or an insurance certificate for everybody. However, it can be a viable option for women who are aware of its limitations.

What is most important is a patient’s absolute understanding of the challenges of egg cryopreservation. To say women’s oocytes are much more difficult to freeze than male sperm is an understatement. A good quality female egg is essentially a pin head-sized globule of fluid plus the necessary DNA to carry new life into being. It is this sac of liquid that must be carefully drained and then filled with anti-freeze to help the egg freeze and thaw. Accomplishing this without damaging the microcosm of genetic material, as delicate as a spider web, is the main hurdle. When egg quality is compromised, a myriad of problems ensue: failure to fertilize or implant, miscarriage and birth defects.

The race to offer egg cryopreservation was initially fueled by favorable research results from a study that used subjects in their early 20s, and which resulted in >50% chance of a live birth. Yet with only 7 subjects, that study is not statistically significant. In subsequent studies that used women in their early 30s, the success rate dropped below 25%. Currently, most U.S. clinics pioneering this procedure predict only an 8-10% chance of live birth. Also, a side effect of freezing is the hardening of the egg’s outer membrane, known as the zona pellucida, making sperm penetration difficult. However, this is overcome by using ICSI (intracytoplasmic sperm injection).

Those requesting this service need to have all of the facts before making a choice. In particular women in their mid- to late-30s, who tend to be the most enthusiastic candidates, need to weigh other options with higher proven success rates. We at PFC share an understanding with much of the medical community that this procedure may be the right choice for the right person, but only with a full understanding of its limitations. This will be our approach when we start offering egg cryopreservation to our patients later in 2004.