SCIENCE PULSE    ASRM Round Up

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

 Carolyn Givens, MD 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 Pacific Fertility Center’s PGD program. Dr. Given’s excellent care and over 12 years of experience is recognized by her peers; they repeatedly single her out as a “Best Doctor” in national surveys. (See www.BestDoctors.com)

  Joe Conaghan , PhD, HCLD, PFC's ART Laboratory Director is internationally recognized for his work with embryos. His background includes involvement in the first PGD on human embryos. His high standards and extensive experience bring national recognition to our laboratory. He also trains fellow embryologists for licensure and is an inspector for CAP, the licensing body for IVF laboratories in the USA.

PATIENT ODYSSEY    One Good Sperm

I had been trying to get pregnant for six months and didn’t want to wait any longer. In the past, my husband had gone through chemotherapy, but when we decided to begin our family, we never contemplated that his medical history would make conceiving a challenge.

Once we were ready to take the next step, our urologist recommended Pacific Fertility Center. Patients he referred to PFC had been successful, so we were very hopeful that they might be able to help us. We lived a distance from the center and had to make the 6-hour drive each way for treatments. We were determined to get the best care available.

Our cycle began way back in August of 2005. Initially we worked with Dr. Paul Turek, an urologist from UCSF in conjunction with PFC in cases like ours. He performed testicular mapping, looking for pockets of live sperm. Since only one pocket was found, Dr. Turek recommended my husband undergo FSH injections 3 months prior to our cycle, to increase sperm production. Fortunately, this experimental protocol worked better than expected and we were able to avoid invasive surgical removal of sperm. It only takes one good sperm to fertilize an egg and he was able to find more than enough.

In order to get my eggs to fertilize with my husband’s sperm, I went through IVF including FSH injections. The needles intimidated me, but I was able to get past that fear. Everything turned out OK and I made it through the procedure really well. During my retrieval they collected 20 eggs.

As it turns out, after fertilization with ICSI, we had 8 grade 1 and 2 embryos. Three of the embryos were transferred and the other five were frozen. To my pleasure, I became pregnant with a single baby girl. This was an amazing experience, especially considering the odds were not hugely in our favor. Once we got the good news, we were in an elated state of shock – we had been through a lot and finding out we were finally pregnant was wonderful news! I had an extremely easy and natural birth in May of the following year.

All in all the experience was quite a whirlwind; my husband and I had a lot of ups and downs. The assumption we had when we first decided to try to get pregnant was it would be natural and uncomplicated. However, learning we had an infertility problem was a devastating experience. What empowered my husband and me was that we started doing research about our problem. The more we learned, the more comfortable and less intimidated we felt. I would highly recommend this. In retrospect, the biggest ups and downs were when we got the reports on the good or the poor sperm samples. When they found sperm they could use, we could hardly contain our excitement.

I appreciate the care Dr. Isabelle Ryan provided. I liked her a lot and I have heard nothing but good things about all the PFC doctors. Dr. Ryan knows what she’s doing and was able to explain all the options available to us. Joe Conaghan, the lab director, was spectacular. He was able to find sperm in a sample that our local doctors could not. Being from a rural area, we didn’t have local access to PFC’s level of care and state-of-the-art technology. I absolutely trust PFC and have recommended them to others. If we decide to have another child, we will definitely come back. We love our little baby girl so much and every day is a new adventure. We can’t imagine our lives without her!

 Susie & Steven D.

CONCEPTION HEALTH    Why Minimize Multiples?

Many couples, in the midst of their struggle with infertility and who may have undergone several cycles of fertility treatment, have a hard time visualizing success. They often have an even harder time believing they could conceive a multiple gestation. On the other hand, many fertility patients may see a twin gestation as a positive thing in that they can increase their family size all at once – a bargain!

In this country, we have seen an increase in the percentage of twin births that has become phenomenal and is mostly due to an increase in the use of fertility medications and assisted reproductive treatments. Of the 35,025 babies born from IVF in the year 2000, 44% were twins and 9% were triplets or more. Nationwide, the number of twins has increased by 65% since 1980 and by 38% since 1990. These numbers have not gone unnoticed by public health officials, insurance companies and increasingly, lawmakers.

Thankfully, although in the early 1990's we saw astounding increases in the number of triplet and higher-order multiple gestations, the good news is that these numbers are falling. This change is felt to be due to increased awareness on the part of reproductive specialists and consequently better education of their patients about the desirability of avoiding triplet+ gestations.

Although most twin and even most triplet babies survive without serious problems, these pregnancies do involve significant increases in the risk for poor outcomes. This is because the gestational age at delivery (averaging 40 weeks for a singleton pregnancy) is decreased on average by 3 weeks for each additional fetus. Neonatal Intensive Care Unit admissions are significantly higher as a consequence. Only 9% of singletons end up in the NICU but 48% of twins and 78% of higher order multiples are admitted to the NICU. Intrauterine death (stillbirth) is increased 5-fold in twins. Neonatal death (death within the first month of life) is increased 7-fold for a twin as compared to a singleton. (See Table below.)

Treatment of prematurity has allowed even some of the lowest birth weight babies to survive. But survival may not mean disability-free living. Cerebral palsy is a devastating permanent brain injury that occurs either in the uterus or at the time of birth. For twins, the incidence is 4 times higher than singletons and the incidence is 17 times higher for triplets. Ultimately, the main worry is having a child with a severe handicap. This risk is 1.7 times higher for twins and 2.9 times higher for triplets. While the risks of twin gestation are definitely measurable, most high-risk pregnancy specialists do not advocate selective reduction of twin gestations. Most do advocate selective reduction of triplet+ gestations, however.

The maternal risks increase with multiple gestations and the risks rise with each additional fetus. These risks include high blood pressure, postpartum hemorrhage, excessive nausea, miscarriage, gestational diabetes, preterm labor, Cesarean section and even maternal death. Although obstetrics has come a long, long way in this country in the last 100 years, pregnancy and childbirth still pose medical risks to mothers and these risks are definitely affected by multiple gestation.

The purpose of this article is not to frighten patients considering fertility treatments. It is meant to educate our patients about these risks and to help our patients to understand why Pacific Fertility Center is doing its best to adhere to ASRM guidelines. However, we wish to retain the rights to individualize our treatments and adapt to the specific circumstances for each of our patients. We do not want to see the government interfere with medical decisions that should be made between physicians and their patients. This is why our motto is “Conception Solutions: One Healthy Baby at a Time.”

 Carolyn Givens, MD

FROM US TO YOU    2006 IVF Pregnancy Rates

  Pacific Fertility Center Team
Left to Right: Front: Philip Chenette, MD, Isabelle Ryan, MD, Carolyn Givens, MD
Back: Joe Conaghan, PhD, Carl Herbert, MD, Eldon Schriock, MD

2006 IVF Pregnancy Rates
Pacific Fertility Center is pleased to share our in vitro fertilization (IVF) pregnancy rates for 2006. Our outstanding in vitro fertilization pregnancy rates are made possible thanks to our team of ABOG board certified specialists in Reproductive Endocrinology and Infertility and highly trained embryologists.

Pacific Fertility Center’s investment in enhanced methods of embryo culture has improved outcomes with in vitro fertilization. New incubators, culture media, and procedures have increased embryo quality and embryo implantation rates. Each embryo has a higher potential to produce a pregnancy, which allows us to transfer fewer embryos, reducing the risk of higher order multiples.

Our technology offers better pregnancy rates with fewer numbers of embryos transferred. Based on this improvement we are instituting a new emphasis on single embryo transfers and expect to significantly reduce the risk of multiples and achieve our goal of “optimal” pregnancy outcomes.

2006 Highlights:
• Pregnancy Rates with Day 5 (Blastocyst Transfers) – Selecting day 5 (blastocyst) fresh embryo transfers, we achieved a 59% pregnancy rate per transfer for women under age 35 using their own oocytes. As remarkably we achieved a 49% pregnancy rate per transfer for all women under age 43 using their own eggs.

• Outstanding Oocyte Donation Pregnancy Rates – Oocyte donation pregnancy rates are one of the best indicators of an outstanding IVF laboratory. Last year we achieved a 73% pregnancy rate per transfer for fresh day 5 transfers in women using donated oocytes. As not all donor oocyte recipients used a day 5 transfer, the combined pregnancy rate for all Day 3 or Day 5 fresh embryo transfers was an outstanding 66%.

Notes on Pacific Fertility Center statistics:
1. Pacific Fertility Center does not restrict IVF to only those patients most likely to succeed, (a practice which often leads to higher pregnancy rates). Our less restrictive approach is confirmed by our high percentage of Decreased Ovarian Reserve, DOR (a basal FSH level of 10 mIU/mL or higher). As reported by SART/CDC in 2005, 24% of PFC patients were diagnosed with DOR.

2. PFC performs a substantial volume of IVF and oocyte donor cycles. This allows for better statistical accuracy of our data, (the fewer number of patients - the less statistically significant the rates become). We feel it keeps all of us well attuned to the practice of ART.

3. Although we individualize treatment to each patient’s diagnosis and prognosis, our goal is to adhere to ASRM guidelines on the maximum number of embryos to transfer, in order to lower the risk of high order multiples.

Thank you for your interest in subscribing to Pacific Fertility Center’s free monthly newsletter. In order to better protect your privacy, we have a new secure subscription/log in form. We respect your privacy: Your email remains confidential and will not be shared or sold. Please click here to change your subscription preferences.

-- Best regards from all of us at Pacific Fertility Center.