At Pacific Fertility Center we aim to help our patients build a healthy family. To build healthy families, maximum pregnancy rates are a goal, but maximum pregnancy rates must be balanced by consideration of risk, the chance of an adverse outcome. High pregnancy rates with minimal risk is PFC’s goal.
The risk of multiple pregnancy has increased as fertility therapy has improved. The wider use of gonadotropins in the 1990s to induce ovulation of multiple follicles, as well as the use of more effective laboratory and clinical IVF methods, resulted in production of more and healthier oocytes and more embryos, and increased the chances of multiple pregnancy. The very dramatic improvement in success rates over this time period resulted in many more children being delivered after fertility therapies, but also more twins, triplets, and higher order multiples.
Over the last twenty years, the incidence of multiple birth has increased nationally. According to the National Vital Statistics Report and the March of Dimes, the incidence of twins has increased by two-thirds, and the number of triplets and quadruplets has increased four-fold since 1980.
It is thought that about one-third of multiple pregnancies arise because women are waiting until later in life to conceive; age is a well-known risk factor for multiples. Another third arise from use of ovulation induction with gonadotropins (Pergonal, Follistim, Gonal-F, Repronex) alone. Less than one fifth of multiples are from assisted reproduction techniques (IVF and related procedures). Assisted reproduction in 2003 accounted for 18% of multiple pregnancies, 16% of twins and 44% of triplets 1.
The risks to the children of multiple pregnancy are numerous. Low birth weight and very low birth weight are increased in children born as multiples. The chance of low birth weight (<2500g) is increased 8 times in twins. Cerebral palsy is increased 4 times, neonatal death risk by 7 times 2, 3.
The risk to the mother from multiple pregnancy is also increased. Pre-eclampsia, high blood pressure, preterm labor, and premature rupture of membranes are all more common with multiple pregnancy 4 .
Multiple pregnancy is also expensive. It is estimated that twins alone cost the healthcare system some $600,000,000. There is clear evidence of an increase in parenting stress and divorce in families of multiples 5, 6 .
The need to assure our patients of the highest quality care requires that we bear this in mind – the healthiest pregnancy is a singleton pregnancy.
Pregnancy requires the cooperation of sperm and egg, accurate transcription of the early genetic code in the developing embryo, a fertile spot for attachment to the mother in the uterus, and a route for getting there. All other factors being equal, pregnancy rates almost double when two embryos are transferred instead of one, and increase again when a third and fourth embryo are added. The desire for high pregnancy rates has driven a desire for more embryos to be transferred 7 .
Improvements in insemination technique, embryo culture methods, and transfer efficiency have added substantially to pregnancy rates. Each embryo transferred today has a considerably higher chance of producing a pregnancy than an embryo transferred twenty years ago. Such improvements have enabled us to think about ways to reduce the risk of multiple pregnancy by transferring fewer embryos.
The development of blastocyst (day 5 embryo) culture techniques allows the selection of high quality embryos for transfer. The blastocyst stage requires advanced incubation techniques with low oxygen incubators and specialized culture media. A tight quality control system is also required. The blastocyst stage is a more advanced stage in which the genetic code of the embryo is fully activated and working. Only the healthiest of embryos can move to the more advanced stages, allowing selection of the best embryos for transfer.
In 2006 the ASRM published guidelines for number of embryos to transfer:
These guidelines encourage all of us to transfer ‘just enough’ embryos to achieve pregnancy.
Pacific Fertility Center has pioneered techniques of transferring fewer embryos. Last year, in 2007, our program of single embryo transfer in oocyte donation recipients produced a 66% pregnancy rate. The multiple pregnancy rate in this group was minimal. Utilizing a single embryo, two-thirds of patients were able to conceive a singleton pregnancy. This pregnancy rate was very similar to the overall pregnancy rates regardless of the number of embryos transferred.
Today half of our patients using oocyte donation elect to transfer a single embryo. Single embryo transfer is not always possible. Our criteria include age and embryo quality. A young woman (under age 35) with high quality blastocyst stage embryos and a healthy uterus can reliably transfer a single embryo and achieve high pregnancy rates. An older woman (over 40) may need to transfer 3 or more embryos to achieve a good pregnancy rate. Because of the higher number of embryos transferred, the risk of multiple pregnancy remains higher in these older age groups9 .
Pacific Fertility Center is very pleased to offer these techniques of single embryo transfer as some of the best and most advanced fertility treatment technology available. We are moving closer to our goal of growing families, one healthy baby at a time.  Philip Chenette, MD
- Martin, Births: Final Data for 2003. National Vital Statistics Reports, volume 54, number 2, 2005
- Scher, Ped Res, Vol. 52:671-81, 2002
- Rutter, J Child Psychol Psych, Vol. 44:326-41, 2003
- Pinborg, Human Reproduction, Vol. 18:1234-43, 2003
- Griesinger, Hum Reproduction, Vol. 19:1239-1241, 2004
- Glazebrook, Fertil Steril, Vol. 81:505-11, 2004
- Paulson RJ, Fertil Steril., Vol. 53:870-874 , 1990
- Fertil Steril, Vol. 85, Suppl. 4, 2006
- Pacific Fertility Center 2007 IVF Statistics
 Philip Chenette, M.D. has spent over a decade specializing
in the treatment of patients with
complex infertility diagnoses, especially
in women with decreased ovarian
reserve and women over 40.
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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.
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This year Pacific Fertility Center is undergoing a much anticipated structural and design change. The clinic located on the fifth floor at 55 Francisco Street was purchased in 1999 from a previous owner, and after 8 very busy years, we are ready for a facelift. The opportunity to renovate our space came last month when PFC was offered an adjacent suite vacated by another tenant. The suite, adjacent to our laboratory, was perfect for an expansion that we had been considering for some time.
While the additional space is a bonus, the major benefit of the expansion is the ability to install a state-of-the-art air handling and cleaning system for the laboratory. With the addition of special air-lock doors, the laboratory will have improved separation from the rest of the building, ensuring the highest air quality. The air inside the laboratory will have an updated purification system to remove all particles and chemicals. These combined upgrades will further protect the laboratory from outside environmental influences.
The driving force behind the current construction is the air purification system, and isolation of the lab. However with this opportunity we are also expanding our laboratory space, purchasing new equipment, redecorating and painting. In the past, our laboratory was closed for several weeks at the end of each year to allow for major maintenance, equipment servicing, and cleaning related to normal wear and tear. The use of volatile paint and certain cleaning products is prohibited during the year on the entire fifth floor to protect the delicate growing embryos The cleaning products normally used throughout the year, are ones we know do not affect our embryos.
We do have many other noticeable upgrades planned. We are taking this opportunity to update the rest of our center. The front reception and lobby are undergoing a significant renovation, as are our exam rooms and some of our offices.
All materials being used in the remodel are organic and toxin free. PFC continues to promote a safe and clean environment. Special paints will be used that are plant derived and free of volatile organic compounds (VOC’s). The chairs and furniture we purchase will also be VOC free. New carpets and flooring are already laid out in warehouses so that any chemicals used in their manufacture can dissipate before being installed.
As a further precaution, to ensure that all furniture, equipment, flooring and paint are guaranteed VOC free, we’re going to “cook-off” the lab by raising the temperature to about 120 0F continuously for 4 days prior to reopening. The high temperatures drive out any residual VOC’s and chemicals which will then be removed by the charcoal and potassium permanganate filters in the air handling system.
All of these changes will cause some minor disruption in our office during the next few weeks. To minimize the amount of disturbance we have construction crews working around the clock. In addition, we have dedicated some of our staff to assist patients in navigating the new space and construction areas.
Pacific Fertility Center is making a clean start. We look forward to welcoming you to our newly renovated clinic. We anticipate even greater success in the years to come. Thank you for your understanding. Please let us know if we can assist you in any way during this time of transition. 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.
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PFC embryologist Jean M. Popwell, Ph.D., HCLD was recognized for the outstanding oral abstract presentation at the American Association of Bioanalysts’ (ABB) 2008 Annual Meeting and Educational Conference. The annual conference was held May 15th -17th at the Flamingo Hotel in Las Vegas, Nevada.
Dr. Popwell’s abstract, Vitrification and Warming of Blastocysts Produces High Implantation and Pregnancy Rates When Compared to Slow Freezing, was selected from eight oral abstract presentations given at the Conference. Dr. Popwell’s abstract was co-authored by Erin Fischer, B.S.; Elizabeth Holmes, B.A.; Mariluz Branch, M.S., T.S.; Carolyn Givens, M.D.; Carl Herbert, M.D.; and Joe Conaghan, Ph.D., HCLD/ECLD, all from PFC.
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| An Example X-Ray of a normal HSG |
An example X-Ray of an abnormal HSG |
Infertility due to blocked fallopian tubes was a common cause of infertility in the 1970’s and 1980’s. Some textbooks from that era quote an incidence as high as 25% of all infertility causes. At Pacific Fertility Center in 2005, only 10% of our in vitro fertilization patients were noted to have a tubal factor contributing to their infertility. Fallopian tube damage is most commonly due to prior infection with a sexually transmitted disease such as gonorrhea or Chlamydia. Most chlamydial pelvic infections are relatively asymptomatic and may go unrecognized; therefore many patients with tubal obstruction are unaware they have a tubal problem. Better safe-sex practices and improved screening of young women are possible factors for the lower incidence of tubal disease we are seeing, at least in our Bay Area infertility population.
Even though there is less tubal factor infertility these days, if there is a tubal obstruction, the course of fertility treatment becomes quite definitive: in vitro fertilization. No other treatments, including surgery, are likely to result in a healthy intra-uterine pregnancy. Therefore, we are still advocating some type of screening test for tubal factor in the evaluation of infertile couples.
There are two common ways to determine whether there is tubal obstruction. One is surgery, where dye is passed through the cervix, uterus and tubes, and there is direct visualization of the flow of the dye out the ends of the tubes into the pelvis. The other is the HSG, or hysterosalpingogram. The HSG is an X-ray procedure that involves placing into the cervix a small flexible catheter with a balloon around the tip to hold the catheter in place and close off the cervical opening. Radiographic contrast dye is then instilled into the uterine cavity, using a syringe attached to the tube. Under X-ray visualization, the dye is tracked into the uterine cavity and into the tubes. Pictures are taken during this process to document the shape of the uterine cavity and whether or not the dye enters and flows through both tubes into the pelvis.
HSG procedures are usually performed by radiologists; however, if there is difficulty placing the catheter securely into the cervix, the radiologist may ask the patient’s gynecologist to assist. This test is valuable in determining tubal blockages, but it has some disadvantages. It is very important to get the balloon properly inflated in the cervix to keep enough pressure on the fluid (no back flow into the vagina) so it will enter the fallopian tubes. Unfortunately, this pressure on the walls of the uterus can cause the uterus to contract, causing the patient to experience significant cramping. For this reason, it is recommended the patient take 2 or 3 ibuprofen prior to the procedure.
In some cases, the pressure is enough to cause the smooth muscle walls of the fallopian tubes themselves to spasm, blocking any dye from entering the tube. Sometimes the dye flows so easily through one tube that there is not enough pressure generated to get the dye to fill the other tube. These are some of the drawbacks of the procedure. This is why, even when we get a report of one-sided tubal obstruction, we are often skeptical that this is really due to some abnormality of the tube.
Although there are some false positives associated with this test, if the dye fills both tubes and does not flow out the ends of the tubes, this is highly suggestive of true tubal obstruction. In this instance, IVF is indicated. 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.
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Earlier this year the PFC physicians and staff were thrilled to learn that The Turek Clinic (www.TheTurekClinic.com), a new medical center that specializes exclusively in men’s reproductive health care, would be located in the same building as PFC. The Turek Clinic is dedicated to treating the unique conditions that affect reproductive age men.
Surprisingly, reproductive age men are one of the largest medically under served populations. For example is it not widely known that widespread conditions such as erection and ejaculation problems, low testosterone, and infertility can profoundly affect a man’s self-esteem, his relationships, and even his career success.
Until now, men’s reproductive health has been divided among many different medical specialists. To remedy this situation, Dr. Paul Turek, an internationally renowned expert in male infertility and sexual health, founded The Turek Clinic. In addition to treating the conditions mentioned above, the clinic also offers vasectomies, vasectomy reversals, variocele repair and other minimally invasive procedures.
It is often the case that there is more than one person involved with infertility care. Dr. Turek sees PFC as a major collaborator in the care of the infertile couple. “There is great orchestration of care between both clinics,” says Dr. Turek. “The Turek Clinic specializes in treating all aspects of men’s reproductive health and PFC offers superb medical care for women with reproductive health problems.”
The choice of this particular location relates to Dr. Turek’s philosophy of providing care that is convenient, comfortable, and easy. “The attitude of care should be reflected in the men’s health clinic, which should be an efficient yet pleasant experience for young men” says Dr. Turek. A visit to The Turek Clinic will definitely assure you that you are not in a doctor’s office of the past. The decor is modern; surf boards and photos of vintage cars hang beside the numerous awards recognizing Dr. Turek’s achievements worldwide.
This non-traditional medical space evolved from Dr. Turek’s belief that the “experience” of receiving medical care is different for men and women of different ages. He feels that by providing an optimal environment for young men, they will feel more comfortable communicating their needs and return in the future, if other problems arise. In Dr. Turek’s words: “I really want them to feel ‘connected’ to medical care.”
Even though his clinic addresses the health needs of young men, Dr. Turek understands that the breadth of research in the field of men’s reproductive health falls short of that observed with other patient populations. For this reason, he is creating The Turek Clinic Foundation, a non-profit corporation supporting ongoing research in the field of men’s reproductive health with a focus on stem cell and regenerative medicine.
It is this visionary and disciplinary spirit that sets Dr. Turek apart from his colleagues. His attitude to “change the world, one patient at a time” is self-evident. The physicians and staff at PFC welcome The Turek Clinic to the building. We wish Dr. Turek all the best. For more information about this practice, please visit: www.TheTurekClinic.com.
Genetics and Male Factor Infertility
Approximately 40% of couples who are unable to conceive will have some degree of male factor infertility. Historically, numerous causes for male factor infertility have been recognized, including varicocele (a varicose vein in the scrotum), infection, hormonal imbalance, environmental exposures that can harm sperm production, and scarring from surgery or injury. More recently, genetic causes have become increasingly more important and are recognized as one of the most common causes of male infertility. Men, who might have had an unidentifiable reason for their infertility in the past, may now be diagnosed through genetic testing.
There are two main categories of male factor infertility that carry genetic risks: 1) sperm production problems and 2) being born without one or both vasa deferens (the tubes that allow sperm to travel out of the body during ejaculation).
Sperm production problems can be associated with chromosome differences, which can potentially impart to offspring the risk of infertility, birth defects or learning disability. In general, the lower the sperm count, the greater the chance that genetics may play a role. If a chromosome problem is identified, it may be possible to perform testing on embryos using in vitro fertilization (IVF) techniques along with preimplantation genetic diagnosis (PGD) before they are transferred back to the uterus for possible pregnancy. Alternatively, a fetus can be tested by prenatal diagnosis techniques, such as amniocentesis, once pregnancy is achieved.
Men that have been born without one or both vasa deferens, a diagnosis known as congenital absence of the vas deferens (CAVD), are at higher risk to be carriers of mutations in the cystic fibrosis genes. Cystic fibrosis (CF) is a genetic lung disease which can also affect the digestive system. Sometimes, CAVD is the only clue that an otherwise healthy man may have mutations in the CF genes. If a man is tested and found to have one or more mutations, carrier testing for the man’s partner, or an egg donor, is important to identify the level of risk to offspring. If both partners are carriers, there is a 25% risk for CF disease in offspring. Again, PGD or prenatal diagnosis may be options to consider.
If you have further questions about genetic risks and testing for a diagnosis of male factor infertility you can speak with a genetic counselor, a male infertility urologist, or reproductive endocrinologist.
Some helpful on-line resources include:
National Society of Genetic Counselors (www.nsgc.org)
American Society for Reproductive Medicine (www.asrm.org)
American Urological Association (www.auanet.org)
Lauri D. Black, MS, CGC, Certified Genetic Counselor, California Pacific Medical Center.
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Free Seminar
Overcoming Infertility:
The Next Step to Parenthood
Ask • Meet • Learn
Led by PFC’s Infertility Specialists
Dates:
December 3, 2008
Location:
Pacific Fertility Center
55 Francisco Street, 5th Floor
San Francisco, CA 94133
Contact:
Please call for reservations,
directions and parking information:
888-834-3095
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