At Pacific Fertility Center, we consider very carefully the number of embryos we transfer to each patient. Our goal is to create a healthy singleton pregnancy. We do our best to avoid multiple gestations. Consequently, in many cycles where we think that the chance of pregnancy is extremely high, we transfer only a single embryo. Our outstanding and robust embryo cryopreservation program preserves all embryos that were not transferred in the fresh cycle. Patients who transfer only a single embryo can feel secure in knowing that there are frozen embryo(s) available should they be needed.

Recently, we completed our analysis of the cumulative pregnancy rates per cycle for 2007. This type of report represents the overall pregnancy chance from a single IVF treatment cycle. This data was not available previously as many patients delay their use of frozen embryos. This cumulative analysis looks at the chance of pregnancy from a single IVF cycle when using both fresh embryos and subsequent frozen embryos, if needed.

Table 1 shows the rates for patients that used their own eggs (oocytes).
Table 2 shows pregnancy rates for patients that were the recipients of donor oocytes.

Please note that these are not delivered pregnancy rates. Many of these pregnancies are ongoing. There are also some patients that have not yet achieved pregnancy, but have frozen embryos remaining.

Being a single gay dad certainly suggests that I didn’t get pregnant accidentally; my journey into parenting has been a long and deliberate one. Having my 6 month old son and daughter staring up at me all day reminds me that I really did want to do this 25 years ago, but being 50 still does not feel too late. They say it takes a village to raise a child. In my case it took a village to create a child. Thanks to a loving gestational surrogate, and longtime friends as both egg and sperm donors, my dream of parenting has come true.

A difficult pregnancy with many complications somehow made it to 36 weeks and 5 days with Ella weighing 5 lbs 12 ounces and Armstrong (Ari) weighing 5 lbs 11 ounces. Amazingly, at 6 months, they are 19 lbs each and have been sleeping 11 hours a night since week 13. For those of you who are soon to be parents, you will find that’s pretty remarkable. Having hardy and healthy babies is such a blessing. I am forever indebted to Pacific Fertility Center, and Dr. Isabelle Ryan, for their essential roles in helping me achieve parenthood and having a healthy family.

Choosing PFC was not initially an easy decision. It took accessing the CDC nationwide fertility clinic website and comparing the data from clinic to clinic to make me feel confident about picking up the phone and scheduling a first meeting. I really analyzed the data from the clinics carefully, as I was interested in high success rates achieved with high total numbers of embryo transplants.

I had also heard about specific experiences that gay men had had with other local clinics that were less than heartwarming. As an HIV-positive individual, even though I was opting to not undergo sperm-washing to utilize my own genetic material, I did want a compassionate and professional environment in which to pursue my parenting dream.

To be perfectly honest, I had been told by other parents that PFC took a “conservative” approach to achieving pregnancy. Conservative is a term that can be interpreted in many ways. For leftist liberals, like myself, it can somehow seem like a dirty word. However, I have a newfound appreciation for the term. My first surrogate was a lovely married woman with 2 children. She had been a gestational surrogate for a San Francisco couple 2 years prior. They had worked with another local fertility clinic and she got pregnant, rather quickly, with twins. She carried to week 28 and the babies were each under 3 lbs and fortunately survived. I was excited to proceed with her, as we got along splendidly and my priority was finding someone who had her own family and had previous surrogacy experience. PFC screened her and immediately determined that she had an “incompetent cervix”. I had no idea what that meant, though it seemed like the two most incongruous words to ever be placed back to back. Well, an incompetent cervix is a serious matter! I’m supposing that this was not previously diagnosed and was likely the cause of her prior preterm labor and delivery. PFC’s screening saved me a lot of heartache, money and time. I should say that 3 times in a row, to really give it the weight it deserves. I don’t think many people arrive at fertility clinics devoid of heartache, so having a clinician save you from avoidable disaster is an enormous gift.

Having now gone through a twin pregnancy, I more fully understand the roller-coaster process of which I was forewarned. Proceeding with a less than perfect surrogate would have been a tragedy. The second surrogate I found had actually conceived via PFC twice before and would have been a great surromom; but her insurance no longer covered surrogacy. I’m still in constant touch with her and she has nothing but great things to say about her experiences with PFC.

It would be easy for me to find the heart-space to simply rave about PFC. After all, I have the reward of two healthy babies to serve as living proof. For others considering parenting through assisted reproductive technology, there is so much more about my process that is crucial to know. I was insistent, from the get-go, about wanting twins. I had several discussions with Dr. Ryan about the risks that came with carrying multiples. Yes, I’d heard from many people that being a single dad with twins was going to be a “handful”, but the potential clinical complications and risks were not something I’d widely considered. I was 48 years old and didn’t want to go through the process over the course of several years and really wanted at least 2 kids.

Again, if a “conservative” approach is what I got from PFC, the counsel was so very right. My surrogate had previously carried twins and we were both confident that all would go well. We never imagined the complications that did arise during each trimester. It was a very difficult pregnancy. Even with a vaginal delivery, the recovery was tougher than I wish to describe herein. Everything I’d been told by PFC was absolutely accurate. Knowing what I know now, I would say that I, while not at all cavalier, was filled with excitement and anticipation that had me driving full speed through a string of yellow lights. Trust me; I drive now more carefully with twins on board.

Not a day goes by without my being awestruck by the wonder of my children. I have to say that, so far, this has not been a daunting experience. Maybe I have easy babies. Maybe being highly organized has provided them with the structure and consistency that I was told was essential to parental sanity. I’m not sure what it takes to be a great dad, but certainly the desire to parent was a good start towards just being a good dad. Certainly, being 50 has made me a bit more patient and knowledgeable than I might have been as a 20 or 25 year old dad. Being 50 also makes me appreciate having gotten pregnant on the first embryo transfer. At the time, every passing month was just another month of living without the children I knew I was going to have. It seemed like lost time. I heard the clock ticking; I felt the pangs of desire growing.

As crazy as it may sound, hardly a day goes by without my thinking about going back to PFC, thawing my remaining embryos and giving it another go. Through all the obstacles, PFC gave me a sense of direction, a grasp of the reality that I faced and clear information with which to proceed. Perhaps the confidence that I felt in PFC’s expertise has given me a residual optimism that makes me feel willing to try again. For the moment, Armstrong and Ella find each other in sufficient and good company; but I’d be willing to consider a special unanimous request from the two of them for another sibling. But, maybe just an old-fashioned singleton next time!

—Submitted by Gedalia (G’dali) Braverman,
Dad to Armstrong and Ella who were born November 19, 2008

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.

	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.
	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.

Question: I’m 38 years old and have been trying to get pregnant for about a year. All of my lab tests and my husband’s semen analysis have been normal. What do you think is the problem?

Answer: For women in their late 30s, it is naturally going to take longer to get pregnant. They are experiencing what I like to call “age-related sub-fertility.” Some may be lucky and become pregnant right away. However, for the majority of women, as we age fewer of the eggs we ovulate are chromosomally normal; and therefore fewer ovulations result in the release of a normal egg. It just may take more ovulations before that normal egg is released, fertilized, implants, and succeeds in becoming a baby. It is estimated that about 1 in 5 eggs are normal at age 35, about 1 in 10 at age 40, and only 1 in 25 at age 45. So, at age 38, if about 1 in 8 eggs are normal, you may have only 1 or 2 chances a year for successful conception. If your intercourse was not well-timed that cycle or there was some other subtle inefficiency, the chance for conception may be lost. The catch-22 with age-related sub-fertility is that it takes longer to get pregnant and meanwhile, you are getting older and your egg quality is also declining. For this reason, many women seek treatment with fertility medications or IVF as they get older. These treatments can increase the number of eggs produced and exposed to sperm in a single month, thus improving the odds that normal eggs will be found. The good news is that for most women still in their 30s, fertility treatments for age-related sub-fertility are often successful.

– Carolyn Givens, M.D.

We never planned nor expected to have twins, but we feel exceptionally fortunate to have the best of both worlds: a boy and a girl. It was a great hand of luck, which, minus the infertility part, has been our story from the beginning of this journey.

We knew we wanted kiddos, but like many couples wanting kids nowadays, we thought we had a good reason to postpone starting a family. Our plans were to travel the world, come back home and then grow kids. We sold everything we owned, bought two motorcycles and traveled across 30 countries over the span of three years before returning to San Francisco. Only later did we discover that infertility would be our issue.

We tried to conceive on our own for a year without luck. When we decided to get preliminary blood work to help solve our mystery, each test came back normal. Our prognosis wasn’t good: unexplained infertility.

I spent the next three weeks researching our fertility options online—looking at doctors and clinics, and comparing their success rates and patient reviews. During my research process, I learned how quickly the chances of having a family were dwindling for a couple of our age. A 40 year old healthy woman has around a 25% chance of a live birth through IVF. While a woman over 42 years of age, has a 5% or less chance of conceiving. I was almost 41 years old.

I felt very good about Pacific Fertility Center as all five of the doctors were researchers in the field of fertility with exceptional resumes. Furthermore, as practitioners, they seemed more experienced than most, in working with women past age 40. I chose the first doctor I spoke with, Doctor Ryan, based on her online profile. She was straightforward, and took the time to explain our treatment to us both verbally and visually (drawing out diagrams). She has a rare ability to conduct a professional yet personal relationship. She is genuinely warm, personable, and interested in her patients. Pierre and I knew after one meeting that we wanted to work with her.

The injections and the medications became a kind of ritual for us. The experience brought Pierre and I closer. Of the seven eggs collected, four developed into embryos. On the third day, all four were transferred and we started to wait, hopeful it would “work”. Six weeks later, late in the evening, I began to bleed and was sure I had miscarried. For the first time I realized what it meant to me to have a child. I wouldn’t let myself believe I had miscarried, but I also recognized the emotional tail-spin I’d go into if I had in fact lost the pregnancy. We both must have had the saddest night of our lives. Early the next morning, I went in for an emergency appointment. The image came up on the ultrasound screen and, within seconds, the doctor turned to me and exclaimed: “You have twins!” Pierre and I looked at each other elated. Twins! It was the best fortune imaginable.

Max and Emmanuelle are now 9 months old. We barely remember life before them. They are healthy, incredibly good-natured babies. Pacific Fertility Center was the best choice for us, but not entirely based on our (and Dr Ryan’s!) success. We knew it was a one-shot deal and the result, a girl and a boy, could not have been better.

For parents thinking about using IVF, I would recommend setting a limit in the number of attempts before you begin treatment. Knowing we were with the best doctors allowed us to approach the procedure in a more relaxed way. Knowing our odds, however, we did feel like this was our last hope. Now we find it more amusing and gratifying to find ourselves looking for our own characteristics in our kids. We see Max and Emmanuelle as little individuals who have been placed into our care, two beautiful and unique little people whose personas are going to blossom in front of our eyes.

We are incredibly grateful to Dr. Ryan and the team at PFC for allowing us to know the joy of giving birth. However, we are most grateful to be parents. Above all else, it is this unconditional love that lasts 18 years and beyond, that really defines parenthood. Even if your fertility issue doesn’t permit the use of your own genes, know that you still will be a very loving, loved and fulfilled parent.

–Submitted by Merritt Grooms

A human embryo

In 2007, PFC took the bold step of changing the way we freeze embryos. Traditionally, embryos are frozen using a “slow-freeze” protocol where they are exposed to weak concentrations of cryoprotectants before being cooled slowly (-0.3 °C/min) for 2-3 hours. This system has worked well over the years, but recent advances in an ultra-rapid freezing technology showed great promise. PFC began looking at a technology called vitrification in 2006. After seeing wonderful results from in-house trials we were able to phase vitrification into our practice in March of 2007. By June, we had stopped slowfreezing completely. In late 2008, after our 200th thawing cycle with vitrified embryos, we examined the data.

From our first 2 years of thaws, we recovered 94% (423/448) of embryos vitrified, and 94% (397/423) of these were alive when the thawing process was completed. The total number viable was 88% (397/44 8). These numbers compare well to those reported in the scientific literature, but we continue to improve the process and strive for even better results. Vitrification uses tiny straws called “cryotips” to house the embryos during the process, and uses higher concentrations of cryoprotectants than slowfreezing. These details make the procedure technically challenging, which may sometimes result in the loss of an embryo. The tiny straws can crack or break due to the extreme physical force that they endure during freezing and thawing. If this happens, the embryo in the straw cannot be recovered. This lack of recovery or survival is a complication of any freezing procedure. We continue to go to great lengths to minimize these losses, some of which are unavoidable.

Frozen embryos are stored in liquid nitrogen

We have completed 202 thawing cycles to date (A thawing cycle refers to a treatment cycle wherein a patient returns to use vitrified embryos and we thaw and transfer 1 or more to her uterus at the same time). Ninety-seven of these 202 cycles (48%) resulted in an established clinical pregnancy. The average number of embryos transferred per cycle was 1.9 and the implantation rate (embryos implanting out of embryos transferred) was 31%.

The vitrification procedure and materials continue to evolve. Irvine Scientific, the company that manufactures the cryotips, continues to improve their product. They are working extremely hard to eliminate defects that may lead to straw failure during cooling and thawing. At the same time, PFC continues to evaluate new ways to improve embryo survival and implantation rates. This year, we are investigating a process which artificially collapses blastocysts prior to vitrification. We will also be investigating the use of assisted hatching with thawed embryos. Be sure to watch these pages for exciting updates in the months to come.

The article in January’s issue of Fertility Flash, Conception at 40 and Beyond – Does IVF Help? contained some errors in the table. The following is a reprint of the article with corrections.

We all know that fertility declines with female age but what is not certain is how much does in vitro fertilization improve one’s chances of conception if a woman/couple is having problems conceiving on their own?

The table below is one I often use when counseling patients 40 and over about their chances of conception with in vitro fertilization.

This table represents pregnancy outcomes with PFC patients from January 2003 to March 2008, so most of the viable pregnancies tabulated here have been delivered.

One thing to note is that over half of the patients that get a positive beta-hCG result do not end up delivering a baby. This is consistent with the observation that most embryos from women 40 and over have abnormal numbers of chromosomes.

Another thing to note is that pregnancies after age 43 are exceedingly rare, even with IVF. We encourage most women over age 43 to strongly consider ovum donation.

World-wide, over half the babies born from assisted reproduction to women over age 40 are born from ovum donation, not from their own eggs.

—Carolyn Givens, M.D.

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.

In southern California last month, a set of octuplets were born via Cesarean section. The mother, Ms. Nadya Suleman, recently divulged that this pregnancy resulted after undergoing in vitro fertilization (IVF) treatment. Most previous cases of high-order multiple births have occurred after treatment with injectable fertility drugs combined with intrauterine insemination (IUI). This case is unusual in that the treatment was IVF, where the number of embryos transferred back to the patient is a conscious decision on the part the patient and her physician. We are reassured to hear that Ms. Suleman and the octuplets are thus far doing well, but certainly the potential complications of premature birth may not present themselves until much later in each of these octuplets’ coming days, months, or even years.

We are very concerned that such an event of a high-order multiple pregnancy has occurred, and would like to reiterate that PFC takes the issue of multiple gestation very seriously. PFC has been taking steps to minimize the risk of multiple pregnancy for several years. Balancing high pregnancy rates with low pregnancy risk improves pregnancy outcomes. Achieving that balance and reducing the risk of multiple pregnancy is our goal. In all treatment cycles that we perform here at PFC, our ultimate aim, and any recommendations we provide, are with the hope of achieving a singleton pregnancy- the safest pregnancy.

Fertility physicians are very aware that one of the most important side effects of fertility treatment is multiple gestation. Our governing organization, the American Society of Reproductive Medicine (ASRM), as well as the Society for Assisted Reproductive Technology (SART) have worked steadily to formulate evidence-based guidelines for the number of embryos to be transferred in assisted reproductive technology (ART) cycles. These guidelines were first established in 1996 and were updated in 2006 to reflect improved success rates with ART. Over the past decade we have seen a significant decrease in the number of high-order multiples in the US.

We at PFC adhere to the ASRM and SART guidelines. These guidelines provide the flexibility to give each patient treatment individualized to her needs, and her best chance to become pregnant; while minimizing the risks of a high-order multiple pregnancy.

SART member clinics are committed to following these guidelines, although it would appear that the guidelines were not followed in Ms. Suleman’s case.

In October of 2008, after many months of planning, PFC began construction on our new lab. The design called for an environmentally friendly facility that was bright, open, and efficient for our 8 embryologists and the many thousands of embryos that we care for each year. The size of the lab was doubled to allow for the addition of more embryo incubators and ensure room for future growth.

Traditionally the embryology lab is an area that is not accessible to patients or visitors, but our new design utilizes glass walls in key areas and makes our activities more transparent to the outside world. While the lab remains a secure area with limited access, the activities inside can be observed from the outside by anyone passing through our facility. This openness is important to all of us at PFC; we want to remove any mystery associated with the IVF lab, and allow patients free “visual” access. Large TV monitors are installed above several of the microscopes to further open up the world of IVF. We are proud of the work we do at PFC and we want to share.

While the glass walls are largely a cosmetic change, almost every other part of the new lab was designed with the health of our embryos in mind. The installation of a specialized and custom-designed air filtering unit consumed over 20% of the budget for the project. Our goal is to have highly purified air circulating in the lab. The new air handler achieves this goal with the use of a series of filters that remove all particles and chemicals from the air. The lab is further protected from the outside by two separate air lock doors that use positive pressure from the inside to the outside to keep unclean air out.

All supplies and consumables for the lab are handled by the embryologists only, who also take responsibility for all cleaning and other custodial functions. We empty our own trash and wash our own floors. These precautions are in place not only to keep custodians and other building staff out, but also to control the chemicals and cleaners that might con- taminate our clean environment. All com- pressed gases (which feed our incubators) and liquid nitrogen (for our frozen embryo tanks) is piped in from outside the lab, so that it is not necessary for delivery people to enter the lab.

Our incubators in which the embryos develop are fundamentally the most important pieces of equipment in the lab. These incubators are monitored, serviced, and maintained by the embryologists, who have specific training in the use of all of our equipment. Quality control checks are exhaustive and performed daily to make sure that all equipment is functioning exactly as specified. A change of even a half degree in temperature could cause problems in an incubator, so monitoring is continuous and detailed. The gases that are piped into the incubators (carbon dioxide and nitrogen) are filtered as they enter the lab to make sure that they are pure.

The laboratory is supplied with emergency power from a large dedicated back-up generator located at the side of our building. Should there be a major power outage this generator produces power for at least 36 hours before it needs additional diesel. Our generator has proved itself many times over during the years of rolling black outs and other power failures.

We continue to upgrade our facility and maintain the standards of excellence that makes PFC the choice of patients. At the time of writing, we are working toward installing a second back-up system in the event that there is a power outage and our back-up generator fails. We are also always examining new equipment that will allow us to offer new technologies to patients. As we move forward, we will report our latest developments at PFC in the Fertility Flash. In the meantime, come by and visit with the embryologists through the glass. We won’t wave at you, but we’re happy to see you checking up on us. We want you to know that your embryos are in good hands.

To schedule a tour contact one of our New Patient Coordinators at 888-834-3095.

—Joe Conaghan, Ph. D., HCLD

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.

Cutting Edge Approaches to Sex and Relationship Therapy

Presented by: Dr. Naomi O’Keefe,
Licensed Clinical Psychologist

Thursday, March 26, 2009
Time: 4:00 – 5:00 p.m.

Program will be held at the
PFC Education Center
55 Francisco St., Fifth Floor
San Francisco, CA 94133
Parking in garage will be validated.

The Educational Series is a complimentary service provided by PFC to health care professionals specializing in the field of reproductive medicine, obstetrics and/or gynecology. Please watch for future talks on a variety of topics within the field.