We are excited to introduce a new website FertilityWire, http://fertilitywire.com.  This site is separate from our current website www.pacificfertilitycenter.com.

FertilityWire will provide access to a wealth of fertility information, news, and social content. Please take a moment to check out this exciting new resource. You can let us know what you think in the comments section.

Enjoy!

-Robb Mayberry, Director of Development

In January, Dr. Carolyn Givens and I attended a meeting in Hawaii organized by the American Board of Bioanalysts (ABB). This organization board certifies and licenses embryologists, andrologists, and a number of other laboratory specialists in the United States. Our meeting was under the direction of the College of Reproductive Biology, a special interest group within the ABB and for which I am the immediate past Chair.

The meeting was small and intimate, a situation always welcomed among reproductive biology professionals. The location allowed for good interaction with embryologists from Japan who have always been a great source of ideas and innovation within our specialty.

In fact, the highlight of the meeting was a series of videos shown by Dr. Yasuyuki Mio from the Mio Fertility Clinic in Yonago, Japan. He was able to take time-lapse cinematography of human embryos in culture, and as a result reported some novel observations on how oocytes fertilize and how embryos develop. The actual moment of sperm entry into the oocyte was recorded and it was possible to see that human oocytes form a fertilization cone (a membrane that helps bring the sperm into the oocyte), shortly after sperm entry. The events that follow (2nd polar body extrusion, which is the egg extruding a set of chromosomes, and pronuclear formation, alignment of the nuclei from the egg and sperm) occurred as expected, but for the first time the male and the female nuclei could be distinguished from each other.

After fertilization, the embryos were seen to change dramatically as they developed. In particular, they appeared more disorganized and untidy immediately after a cell division event and more symmetrical and organized several hours later. This discovery has implications for those embryos that sometimes may appear poorly. It suggests that they may look better later in the day when they are clear of the cell division process. Another important observation regarding blastocysts, is that those that develop 2 inner cell masses (ICM: the precursor cells of the fetus) do so in a predictable way. At PFC, we avoid using embryos with two ICMs whenever possible, as they are likely to lead to the formation of identical twins. A normal embryo should have only a single ICM. Currently, it is possible that one of the ICMs may be small enough to avoid detection. The observation was made that the fine cellular bridges within the embryo cavity appear to correlate to the presence of an extra ICM.

Another notable presentation was that of Dr. Tetsunori Mukaida, of Hiroshima HART Clinic, on sperm morphology. He demonstrated that observing sperm under ultra-high magnification can show structural defects that are not always visible when using standard microscopes. While magnifying sperm thousands of times has its difficulties, Dr. Mukaida reported that sperm with subtle physical defects have a much lower chance of making an embryo that can become a baby. Sperm that are close to perfect in size, shape and structure are difficult to find in any sperm sample and it can take hours just to find a few ideal sperm. However, the extra effort may be worthwhile, especially in patients that have had a previous IVF cycle where the embryos did not develop well or implant after transfer. PFC is currently looking into this technology and we will report more details in a future issue of Fertility Flash.

Attending meetings like this and keeping up with the latest developments in our field is an important part of the culture at PFC. We share the load of traveling to educational events and are always excited to bring home ideas and thoughts to share with our colleagues. PFC is committed to implementing the latest technology and innovations to maximize pregnancy rates for our patients. We will continue to stay updated with all of the research and development in our specialty.

Both Dr. Givens and Dr. Conaghan contributed to this article.

	Joe Conaghan, Ph.D., HCLD is PFC’s laboratory director. Dr. Conaghan is internationally recognized for his work on improving embryo culture conditions. His interests include developing programs for the treatment of severe male factor infertility; diagnosis of genetic disease in embryos; and improved embryo culture. See more posts
	Carolyn Givens, M.D. was the first in San Francisco to successfully initiate a pregnancy using intracytoplasmic sperm injection (ICSI). She currently co-directs the Bay Area Pre-Implantation Genetic Diagnosis Program (PGD) and is director of PFC’s PGD program. See more posts

Stress is no stranger to most of our lives. The everyday, chronic strain of a demanding job, driving in traffic, dealing with relationships, taking care of the chores of life, all leave us feeling “stressed out.” “Does stress cause infertility?” No matter what the answer to the question, it is important to look at ourselves and determine just how stressed we are. We need to then take steps to attempt to reduce the stress. One undisputable fact is that it makes good sense to reduce our stress to the lowest levels possible. At the very least, you will feel better!

To provide you with the opportunity to assess your fertility stress, we have added a Stress Test domar© to our website at www.pacificfertilitycenter.com. Click on “for patients” then “support” then “infertility stress test.” The test is brief and it generates a stress level score with comments. You can take it as frequently as you would like.

The goal of stress reduction is to reach what Harvard physician, Herbert Benson calls the “relaxation response.” It’s like stress running backwards. We can calm our racing minds. We can soften our tense bodies. The relaxation response leads to a series of changes that take place in the body and mind as you calm down. Your heart rate, muscle tension, breathing rate, and oxygen consumption fall below resting levels. Your brain wave patterns become slower. There are many ways to elicit the relaxation response. The goal is to find the one that works for you, meaning that it reduces your stress and you will take the time to practice it!

One way to learn about all of these techniques is to participate in our Mind/Body class. We discuss and practice each of the following methods; progressive muscle relaxation, breathing techniques, yoga, visualization, mindfulness meditation, and journaling. It is a wonderful day where you get to meet others going through treatment, learn some new skills, eat some excellent food and de-stress.

In addition to learning specific techniques to reduce stress, it may also be helpful to consider the following suggestions:

-Give up any and all feelings of guilt for how you are feeling. There is no right or wrong way to experience infertility. Your feelings may run the gamut from indifference to intense anger and despair and everywhere in between.

-Choose the gatherings you attend carefully. If being around children or babies upsets you, gracefully decline invitations to events where they are likely to be present. Know your limits and stick with them.

-Continue to get moderate amounts of exercise. Eat healthy and get plenty of rest. You will feel better if you treat your body with care.

-Communicate with your partner to let him/her know of your feelings. Even if you and your partner are feeling differently it may help to share. If you are single, call a friend with whom you feel safe to share your feelings.

-Meet and talk with others who are experiencing similar feelings. Finding that you are not alone helps.

We offer these stress reduction workshops every quarter. There is no charge for PFC patients to attend. Join us!

Participants in a workgroup.	Practicing micromanipulation

On November 8 th and 9 th, 2008, PFC held a training course for embryologists interested in learning the techniques associated with Preimplantation Genetic Diagnosis (PGD).

The course was organized in conjunction with the Genetics and IVF Institute (GIVF) of Fairfax, Virginia and was originally scheduled to run on the Sunday only. However, due to the overwhelmingly positive response to attend the course, PFC decided to offer the course on Saturday as well. Forty seven individuals heard excellent lectures over the 2 day period.

Dr Dagan Wells from Oxford, UK and Dr Alan Thornhill from London, UK, gave talks on current and future technologies for genetic testing on embryos. Participants were then divided into 4 working groups that spent the rest of the day rotating between activities. The activities included embryo biopsy training, cell fixation training, media and solution making and PGD troubleshooting. Lauri Black, MS, CGC, a Certified Genetic Counselor at California Pacific Medical Center and Mary Sands of GIVF gave talks on genetic counseling. The course also allowed embryologists from all over the world to view the new state of the art laboratory at PFC.

Joe Conaghan, PhD, HCLD

Pacific Fertility Center launched it’s Educational Series on July 31 st with a presentation on the “Disclosure of Use of Sperm or Egg Donors.” The speaker was Dr. Bob Nachtigall, a local Reproductive Endocrinologist, who has done much research and published numerous papers on various fertility related issues. Dr. Nachtigall addressed the difficult decisions couples face, who attempt conception with donor sperm or donor eggs. These include when to abandon medical treatment using their own gametes, whether to conceive with donor gametes over other options such as adoption, and decisions related to the selection of a donor. Yet the final decision, whether to disclose to their children the circumstances of their conception, is one of the most challenging.

He and his team, conducted research which was based on interviews with 254 parents of children conceived with donor sperm or eggs, they found that 95% of study couples came to a united disclosure after discussions that reflected a wide range of contexts and influences that included: the sociopolitical environment of the community; the couples’ friendships and support network; counseling and professional opinion; religious and cultural background; extended and immediate family structure and relationships; the child’s appearance; and the couple’s individual personal and ethical beliefs. For those couples who decided to tell their young children about their use of a donor, no parent expressed regret or reported a negative outcome after having initiated disclosure.

Dr. Nachtigall will be returning to PFC, to present his findings from a research study he did on “Frozen Embryos.” The annual number of IVF procedures performed in the U.S. has increased from less than 2,500 in 1985 to over 120,000 today. Yet the rapid growth and availability of this advanced reproductive technology has had an unforeseen consequence – the accumulation of an estimated 500,000 frozen embryos that represent the unused “leftovers” of past IVF cycles.

His presentation will address the question of what to do with frozen embryos, which is complicated by the variety and disparity of their potential uses and fates: (1) they can be used by the couple in further attempts to conceive; (2) they can be “donated” to other infertile couples who wish to have a child; (3) they can be used in stem cell research; (4) they can be destroyed; (5) they can be stored indefinitely. Dr. Nachtigall and his team interviewed over 100 couples (many of whom were PFC patients) who had undergone IVF. The team found that ambivalence, uncertainty and most significantly, feelings of deep connection to a couple’s own embryos are several factors that cause difficulty in reaching a disposition decision.

The presentation on “Frozen Embryos” has not been scheduled at this time. However, please watch for dates and times in upcoming issues of Fertility Flash.

PFC Educational Series 2008

The PFC Educational Series are presentations held the last Thursday of each month from 4:00 till 5:30 p.m. in the PFC Education Center located at 55 Francisco Street, Suite 500. The presentations address various topics, which are open to PFC staff, as well as members of the medical community. The PFC physicians found offering programs of this nature would be an ideal way to increase knowledge regarding different topics. In addition, this is a great opportunity to “reach out” to other local physicians and their staff, by offering educational resources, that they otherwise may not have access. The presentations are offered at no charge and the topics will be published in the Fertility Flash, as well as on the website www.pacificfertilitycenter.com. If you are interested in attending this presentation, please contact our Development Department directly at 415-249-3656.

For many people, the dream of having a family also includes the dream of having children of both sex. Since most families today are much smaller than in generations past, the odds of having two or three or even four children of the same sex is fairly high.

Throughout human history, there always has been interest in methods to sway the chances of conceiving a child of a particular sex. Today, in the 21 st century, it is quite clear that many of these sometimes bizarre and sometimes simple home remedies have no basis in fact.

There are ways to significantly shift the odds of having a child of one sex or another. Sex is conferred on an embryo by whether an X-bearing sperm (for a girl) or a Y-bearing sperm (for a boy) enters the egg. Unfortunately, despite highly publicized claims, there are no proven effective “at home” methods of sperm separation. Nor does timing of intercourse relative to ovulation affect the 50:50 sex ratio. By natural methods, the ratio remains a flip of the coin.

The only commercially available method for sperm separation that appears to be effective is the sperm sorting process available through Microsort.net. This method involves using a fluorescent DNA dye that attaches to either X or Y chromosomes. The sperm then passes through a cell sorter that separates the sperm based on the fluorescence. This method is still under FDA investigation for safety and efficacy but does appear to do a reasonable job in separating sperm, especially if the desired sex is female.

Mirosort reports a 90% success rate with separating X-bearing sperm and a 73% success rate in separating Y-bearing sperm. There have been only a few hundred babies born thus far, but there does not appear to be any increase in birth defects. Because this process is still considered “experimental,” couples wishing to participate, will have to travel to either Fairfax, Virginia (Microsort headquarters) or an affiliated clinic in Southern California for fresh sperm insemination.

Unfortunately, after Microsort processing, the number of sperm available for insemination is severely decreased. Freezing and thawing of sperm, which would allow the sample to be shipped to another location, reduces these numbers even further. Because sperm counts are so low after sorting, it is usually necessary to do in vitro fertilization with sperm injection (IVF-ICSI) to significantly improve the fertilization in the IVF laboratory. PFC is a participating site in the FDA investigation for Microsort. We have used sperm specimens that had been previously Micro-sorted for IVF-ICSI.

Researchers at UC Irvine recently published a study describing the use of lasers to “trap” the heavier and slower moving X-bearing sperm to separate it from the lighter Y-bearing sperm. In the future, this process may provide an alternative to Microsort. However, it is not yet commercially available.

Beyond the Microsort technique, the only way to improve the odds of selecting one sex over another at close to 100% accuracy is to undergo Pre-Implantation Genetic Screening (PGS). PGS uses a DNA-binding technique to determine if there are a correct number of chromosomes in the embryo at the time of IVF. To complete this screening, embryos on Day 3 of culture (5-10 cells) undergo a biopsy to remove a single cell. The rest of the embryo remains in culture in the IVF laboratory. The removed cells are analyzed for the correct number of chromosomes. Currently, PFC with its cytogenetic partner, Genetics and IVF Institue screen embryos for 3-12 chromosomes. This screening is called “aneuploidy screening.” We allow our patients to know and select the sex of their normal embryos for transfer if they so wish.

Although IVF with PGS is the most effective method for sex selection, it is certainly the most expensive and there is no absolute guarantee that the transfer of the screened embryos will result in pregnancy. A PFC physician can best discuss the odds of success, based on the woman’s age and the couple’s history of childbirth.

Many couples undergoing PGS are doing so to screen for specific genetic defects or are specifically undergoing sex selection because of their risks of having a genetic disease that only affects males (X-linked diseases).

On the other hand, PGS for elective sex selection, either for “family balancing” or even for having a first child of a particular sex poses difficult ethical issues. Just because we have the ability to choose the sex of a child, should we? What will the couple do with normal embryos of the undesired sex? At PFC, we do not encourage PGS for elective sex selection. However, if a couple is undergoing IVF and wishes to undergo aneuploidy screening, we do allow them to select to transfer embryos by sex. We encourage all patients to consider donating excess embryos of the undesired sex for adoption by other couples.

Women or couples interested in this procedure should discuss it with their Reproductive Endocrinologist. At PFC, we also refer our PGS patients for a special genetic counseling session at California Pacific Medical Center in preparation for this process.

Title: The Joy of Pregnancy
Subtitle: The Complete, Candid, and Reassuring Companion for Parents-to-Be
Author: Tori Kropp, R.N.

For many of our patients, who successfully conceive at PFC, a major shift in thinking follows the moment they realize that their pregnancy is viable. Shelving all the fertility literature, now it’s time to get educated about pregnancy. Hundreds of books on the subject of pregnancy can be found, but which one to read?

Finally we have a thoroughly enjoyable, informative and readable book by Tori Kropp, a labor and delivery nurse for many years at our own California Pacific Medical Center. “The Joy of Pregnancy” celebrates the miracle of pregnancy, labor, birth and brand-new parenthood. It embraces these experiences for what they should be: a time of joy and excitement, not of fear and guilt.

Tori has not only worked in Labor and Delivery at California Pacific Medical Center in San Francisco for many years, but she has also taught childbirth classes for thousands of expectant parents. As a mother herself, she has experienced pregnancy and birth first hand. She really has seen it all. Her calm, reassuring manner, helped many parents-to-be welcome the birth experience with knowledgeable assurance.

This book is written in an honest and open style. The medical terminology is minimized and practicality is emphasized. The many “Tori’s Tips” in the book are gems resulting from her knowledge and experience. They serve as little pearls of pregnancy wisdom. A glossary of medical terms at the end of the book is very useful. The questions and answers sprinkled through the book are entertaining, yet filled with practical and informed answers. Special sections for fathers are also included.

The last section of the book is one that is often missing in books about pregnancy: it is all about the first few weeks of parenthood. Breast-feeding and caring for your new baby are covered, again with an eye to being relaxed and enjoying the experiences.

We highly recommend this new book as you journey from infertility to family.

Invitation to Tour the New PFC Offices

Changes are happening at Pacific Fertility Center! If you have stopped by our office location at 55 Francisco Street lately, you’ll notice that things may not look quite the same at PFC. We recently went through a major change by relocating our administrative offices and Egg Donor Agency from the third floor to the fifth floor. What does this mean to you? By moving to the fifth floor, we have been able to consolidate all our team and deliver comprehensive services from one floor instead of two floors. The embryologists from the laboratory, the nursing staff, and administrative staff will now be able to communicate in a more timely and efficient manner. In addition, to providing a more comprehensive team approach and improving communication, relocating the organization to one floor has reduced confusion for those visiting the facility. By being on the fifth floor, patients have one site for service and immediate access to care. The move has also helped organize the PFC team for future growth and services. Overall, this move will assist PFC in providing quality patient care. If you are interested in touring our facility, please contact our New Patient Guides to arrange a day and time. You can contact the New Patient Guides by calling 415-834-3095.

Many IVF programs routinely schedule frozen embryo transfers (FET) to occur on specific days by putting their patients on estrogen and progesterone to prepare the uterine lining for implantation. This allows for a flexible schedule for the clinic and the patient, i.e. it allows the clinics to group FETs together and avoid weekend transfer procedures. However, the patient must remain on both estrogen and progesterone to support the pregnancy for up to 12 weeks.

More and more, clinics are starting to schedule FETs in natural cycles, timed to natural ovulation with minimal medications. This does mean that a transfer can occur any day of the week. Due to tradition and convenience, some clinics remain hesitant to switch to natural cycle FETs. Part of the problem is that there have been very few studies showing what the success rates were in natural vs. programmed FET cycles. The few studies that have been published have reported on a fairly limited number of cycles.

Pacific Fertility Center has always been a proponent of natural cycle FETs. Because we do about 400 FETs each year, we have been able to gather a large number of cycles to evaluate. Most of our patients we evaluated for this study were in natural cycles but some patients had to do programmed cycles because they did not ovulate regularly or because they had to travel some distance to come to PFC for their FET and needed to have the more precise scheduling that a programmed cycle affords.

In our study, we looked at 1,378 frozen embryo transfers done between 2000-2005. Of these, 934 were done in patients using embryos from their own eggs and 444 were done in patients using embryos from donor eggs. The bottom line is that there were no differences in delivered pregnancy rates within both groups of patients (own eggs and donor eggs) between those patients having a transfer timed to natural ovulation or those patients with estrogen-progesterone uterine preparation.

Because we feel that a natural cycle is less costly, requires no blood tests and (usually) fewer ultrasounds and injections, patients find this a desirable alternative to the more common, programmed FET. In addition to these patient-friendly reasons for choosing natural cycle FETs, we now feel PFC has solid data to justify this approach.

Preliminary results of this study were presented at an oral presentation at the Pacific Coast Reproductive Society meeting in Palm Springs this past April (see sidebar).

This study has just been submitted to Fertility and Sterility, the major reproductive endocrinology journal of the American Society for Reproductive Medicine. We expect full publication after the peer review process is completed.

Carolyn Givens, MD

“Outcomes of Natural Cycles vs. Programmed Cycles for 1378 Frozen Embryo Transfers” Carolyn R. Givens, M.D.a, Leslie C. Markun,b Isabelle P. Ryan, M.D.,a Philip E. Chenette, M.D.,a Carl M. Herbert, M.D.,a and Eldon D. Schriock, M.D.a Submitted July 2007 to Fertility and Sterility.

Tuesday February 1st was a busy day here at Pacific Fertility Center. The front office was busy with their usual patient appointments, comings and goings for consultations, ultrasound scans and blood draws. In the procedure area and the lab, we were having one of our busier days, with 7 retrievals, 5 fresh embryo transfers and 1 frozen embryo transfer scheduled. It’s rare for us to have so many procedures on a single day, but because the exact date of a patient’s retrieval is uncertain and depends on their response to stimulation drugs, we get a day like this a few times per year. Fortunately, PFC has an exceptionally large and well-equipped laboratory, so we can cope easily with variations in case load. Also, both our nursing and embryology staff schedules are flexible enough to allow us to schedule extra staff when necessary. On that Tuesday for example, we had 8 of our 9 embryologists on duty in the lab

Even though most patient appointments don’t happen before 8 AM, lab and nursing staff are here between 7 and 7:30 in the morning to open up the facility and perform the usual quality control (QC) checks before the work day can begin. In the lab, once all QC and start-up procedures have been completed and documented, we begin looking at embryos that are to be transferred that morning, thawing frozen embryos for transfer, evaluating fertilization for the previous day’s patients, retrieving eggs and processing sperm samples. The nursing staff is busy checking in patients for retrievals, doing all their pre-operation checks and setting up IV bags, and coordinating patients for embryo transfers. Mornings are definitely our busiest time; we do this every day (7 days a week) so we like to think that the work flows smoothly.

At approximately 8:30 AM, right in the middle of the action, the power to our building and to those in a 10-block radius, went out. When a power outage occurs, there’s a split second when everything goes dark, but before you can think about it, emergency power kicks in and we almost seamlessly continue working. However, as part of our procedures for disaster preparedness, we have protocols for working during a power outage, and these immediately become active. First we check our emergency power generator and then all vital equipment to make sure that everything has power and is functioning normally. In the lab, one of our 15 incubators reset itself and went into calibration mode, so we simply moved its contents to a new home. No other problems or incidents occurred that day. We completed all retrievals and transfers in the usual way and our biggest concern was simply wondering why the power had gone out.

On the nursing end, patients were escorted up and down 5 flights of stairs because the elevators shut down, but otherwise their day was uneventful.

Emergency procedures and back-up power are a vital part of our operation. Our emergency generator will run our facility for 36 hours, or longer with the addition of diesel to the tank. The generator gets a 30-minute test run and an inspection every week. It receives a full service a minimum of 4 times a year and immediately after any power outage. After this instance, a service technician checked the generator and refilled the tank.

In the event there is a power failure when no one is present, the system will automatically switch over to back-up power. The alarm system in the lab then proceeds to dial each embryologist in turn on his or her home and cell phones until the call is received and verified with a code. All vital equipment is alarmed which enables us to check the status of the equipment from a remote location. We also have auditory monitoring capability and can listen to the background noise in the lab (such as a fire alarm) at any time. If it is necessary, we are prepared to have an individual physically present in the lab within 30 minutes of getting an alarm call.

Embryos and sperm in freezers don’t actually need power at all, provided that we physically fill the cryo tanks with liquid nitrogen once or twice a week. The computers that usually monitor and automatically fill these tanks do need power of course, but they are not essential to maintain refrigeration.

On February 1st, power was restored after 90 minutes, however we never know the time or duration of a power outage. At Pacific Fertility Center, we remain well rehearsed and prepared, just in case it happens on the busiest morning of the year.