A statistic that we follow closely at PFC is our cumulative pregnancy rate in a given year.  This is defined as a patient’s chance of taking home a baby after one IVF cycle, but it includes the fresh embryo transfer and any frozen embryo transfers resulting from that one cycle.  These rates are shown in the table and are broken down into maternal age groups.  The numbers are calculated by looking at how many patients delivered a baby from their fresh transfer (43% of patients under age 35) and then adding in pregnancies achieved from the frozen embryos for patients that did not get pregnant in the fresh cycle (totals 64% of patients in this group).  So in this age group, 2 out of every 3 patients had a baby from just one IVF cycle.  Similarly, for patients doing a single cycle with donor oocytes, 74% had a baby.

Cumulative pregnancy rates have special importance since PFC is a national leader in reducing the number of embryos transferred at one time while still maintaining exceptionally high overall pregnancy rates.  One healthy baby at a time is the goal of fertility treatment at PFC and for every patient, a singleton pregnancy is the safest and most likely way to have a healthy baby.  At PFC we work carefully with every patient to reduce their exposure to a multiple pregnancy and all its risks for mother and baby.  And a big part of our strategy involves freezing embryos successfully so that we can use embryos conservatively and efficiently to generate more singleton pregnancies, and fewer multiples. Multiple pregnancies are a complication of IVF treatment, and we strive to avoid them. 

Patients with the highest risk for multiple pregnancy are those where maternal age is <35, doing their 1^st or 2^nd IVF cycle or those patients using donor eggs.  We encourage these individuals to transfer just a single embryo during their IVF cycle and to freeze their surplus embryos for use later.  The frozen embryo program has been so successful here at PFC that it provides very high pregnancy rates for those patients that need to use their embryos from the freezer.  It also means that we don’t have to risk transferring many embryos in the fresh IVF cycle because we have the frozen embryos as a back-up. And most patients that are doing elective single embryo transfer qualify for one of PFC’s financial plans (e.g. the refund plan) that include the cost of frozen embryo transfer cycles in the original price.

We believe that using embryos conservatively is the safest treatment.  And we don’t see big differences in pregnancy rates between patients that transferred just one embryo vs. those that transferred 2.  In fact, patients that received donor eggs and transferred 1 or 2 embryos had the same delivery rates, but those transferring 2 had a 35% twin rate.  In our efforts to reduce this twin rate, we are now transferring 1 embryo 60% of the time in the donor egg program, and 40% of the time in patients aged less than 35.

We want our patients to have healthy babies and we are working to make this possible while still maintaining high success rates.  Our goal is one healthy baby at a time.

 - Joe Conaghan, Ph.D., HCLD & Embryologist Erin Fischer

Infertility & Reproductive News featured Pacific Fertility Center and interviewed Dr. Herbert for their August newsletter issue. 

Click here to read the article in Infertility & Reproductive News.

Every year thousands of families are created with the assistance of in-vitro fertilization. Many of those newborns are twins. While some may see this as a double blessing, it is important to understand that there are many potential risks associated with multiple gestation. Statistics show that a higher percentage of twins are born prematurely compared to singleton pregnancies. Premature birth can cause complications resulting in physical impairment, learning disabilities, and even death. In addition to the increased risk to the children born from a multiple pregnancy, there is also an increased risk for the pregnant woman of complications associated with carrying multiples.

Pacific Fertility Center (PFC) has been taking steps to minimize the risk of multiple gestation for several years. “We have worked actively to increase pregnancy rates and decrease the number of multiples,” comments Carolyn Givens, M.D. “Balancing high pregnancy rates with low pregnancy risk improves pregnancy outcomes. Our goal is to achieve this balance and reduce the risk of multiple gestation.”

PFC recently completed the analysis of our Elective Single Embryo Transfer (eSET) program for 2009. The twin rate was significantly lower, and, triplets were eliminated entirely. 79 patients underwent an embryo transfer procedure where they elected to transfer only one embryo created from their own eggs; these 79 transfers resulted in 38 pregnancies, two of which were identical twin pregnancies (the embryo split from one into two) and NO triplets. Compare this statistic to patients choosing to transfer two embryos: 159 patients, with embryos derived from their own eggs, transferred two embryos resulting in 80 pregnancies, of which 31% were non-identical twins and two triplet pregnancies (again from one of the embryos splitting).

Patients that choose eSET have excellent pregnancy rates with a single embryo. eSET embryos are grown for 5 days in the lab to the blastocyst stage, which allows for selection of the healthiest embryos for transfer. The transfer of fewer embryos provides for the healthiest outcomes; eSET produces high pregnancy rates while minimizing the risk of multiple pregnancy. “For many patients, there is no advantage to transferring more than one embryo. It is all about educating our patients. Given this information, these numbers and the potential risks of twin pregnancies, many will choose to transfer only one embryo,” says Carolyn Givens, M.D.

At PFC, careful consideration is given to the number of embryos transferred to each patient. Our goal is to create healthy singleton pregnancies. Utilizing advanced embryo culture techniques, the highest quality embryos can be selected for transfer. Special environmental conditions, advanced culture media, and the delicate handling of gametes and embryos is required; these efforts result in better embryos, with higher implantation and pregnancy rates.

In addition, PFC has developed an outstanding and robust program for freezing embryos not transferred in the fresh cycle. Using a technology called vitrification, we have been able to achieve pregnancy rates with frozen embryos that are very similar to those using fresh embryos. “The outstanding success of our freezing program has allowed us to be confident in transferring just one embryo at a time, which all but eliminates the risk of triplets or higher pregnancy,” says Dr. Joe Conaghan, PFC Lab Director. He adds, “We have been so successful with embryo freezing over the last 3 years that our embryologists are in high demand to provide training across the country and around the world. Our goal is to help our patients overcome infertility and build their family; one healthy baby at a time.”

Question: I am 38 years old with age-related infertility (at least that is what my doctor, a Reproductive Endocrinology and Infertility Specialist (REI), thinks). It has been suggested that I undergo super-ovulation with injectable Follicle Stimulating Hormone (FSH) along with intrauterine insemination. I really don’t want to have twins, if possible, and certainly not triplets or more! But ideally, I would like to have more than one child. Even if I am successful in having one baby now, I am worried about trying to have a second child when I am 40 or more. What do you suggest?

Answer: We agree that having one baby at a time is the safest thing for you and your family. However, undergoing FSH super-ovulation is intended to create more eggs in one cycle in order to increase the odds that one or two will fertilize and implant. This helps to overcome the relative inefficiency of conception for women in their late 30’s. The risks are as you stated, twins or more. Luckily, the risks that a woman undergoing this treatment will get triplets or more is really fairly low – on the order of less than 10% of all pregnancies, with careful monitoring. The risk of twins is higher – on the order of 20% of such pregnancies.

If a woman at 38 years old has no identifiable cause for infertility, the goal is usually to get 3-6 follicles. Most of the time, if the treatment is successful, the pregnancy will be a singleton pregnancy (one baby). Your issue of wanting to have a second child and concern for difficulties beyond age 40 is a real one. You may want to discuss with your REI the option of in vitro fertilization. If your doctor thinks you may be a good responder to fertility medications, you could have extra embryos to freeze, which provides some back-up and allows you to preserve some embryos from 38 year old eggs for down the road.

Patients contemplating conception must consider lifespan expectations as part of their decision on whether to conceive. Such considerations are not, however, a reason to withhold treatment, and are ultimately the individual and family should decide.

– Dr. Carolyn Givens

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

This past fall, over 6000 of the world’s leading researchers in reproductive medicine gathered in Montreal, Canada to participate in the annual conference of The American Society for Reproductive Medicine (ASRM). ASRM is an organization of 8,500 physicians, researchers, nurses, technicians, and professionals dedicated to advancing knowledge and expertise in reproductive biology.

PFC partners Eldon Schriock, Isabelle Ryan and Joe Conaghan attended the conference this year. Here they share with Fertility Flash readers highlights from a chosen handful of the presentations.

Nicotine Damage to Sperm Better Understood

An experiment led by researchers from the State University at Buffalo School of Medicine revealed that chronic male smokers could experience a reduction in their fertility of up to 75% as compared to non-smokers. Lani Burkman led the study to provide more details on past research, which had shown that when nicotine and its by-product, cotinine, were added to sperm in the lab, these chemicals changed the way the sperm moved.

In this recent research, sperm from both smokers and non-smokers were combined in two different Petri dishes with oocytes derived from one source. The sperm’s ability to bind to and penetrate the zona pellucida (outer shell) was carefully observed. In summary, the smokers’ sperm were less effective in binding to the zona pellucida. The sperm of chronic smokers – people who have smoked a minimum of four cigarettes a day for at least two years – maintained an average of 75% less capacity to fertilize compared to nonsmokers. The researchers also discovered that light smokers’ sperm performed better than chronic smokers’, suggesting that men trying to start a family will have better results even by cutting back on the smoking.

Knowledge of Egg Freezing Advancing Rapidly

Fourteen papers on the topic of oocyte cryopreservation were presented. Some focused on studying overall results since egg freezing was first introduced in the late 1980s, while other presentations reported on testing specific methodologies, such as slow vs rapid freeze and thaw techniques, or the use of different cryoprotectants. Results continue to bode well but specifically for women who are relatively young.

In what the media hailed as a breakthrough, one research team presented what could be the highest success rate for oocyte cryopreservation to date. Led by John Jain, MD, an associate professor of Reproductive Endocrinology at University of Southern California, the team’s egg-freezing protocol involves the use of slow freezing and fast thawing, in addition to a specific culture medium that applies choline for stabilizing the egg’s membrane.

The research was derived from a small study involving only eight infertile women with tubal factors, all around the age of 31. Out of the eight women trying to conceive, five achieved pregnancies with their own previously frozen oocytes. For the particular study group, this translates into a 62% success rate per patient, which is comparable to fresh embryo transfers. However, Dr. Jain stressed that considerably more research needs to take place before egg freezing should be used in standard clinical practice.

More good news for oocyte cryopreservation came out of a research team from McGill University in Montreal, Canada. This team applied a proprietary blended cryoprotectant formula and used only the vitrification (rapid freeze) method in contrast to the more standard slow freeze protocol. In this case, 180 oocytes that were derived from 15 women of mean age 31.7 were vitrified. Out of these, 169 survived the fast freeze process (93.9%), and 126 oocytes fertilized normally (74.6%). Out of the original 15 patients, 4 are currently showing signs of successful pregnancies and one has already delivered.

More Worries About Multiples

Ongoing research continues to identify problems with multiple gestation births, some involving assisted reproduction, some not.

Genetic Testing Important for Twins: Researchers at UCLA’s School of Medicine working with the Cedars-Sinai Medical Center identified higher rates of cytogenetic abnormalities in the first trimester of twin gestations conceived through IVF compared to spontaneously conceived twins.

The team set out to discover whether the previously suggested increased incidence of aneuploidy in twins might be related to IVF. This retrospective case-controlled study analyzed women at least 35 years of age carrying dizygotic twins who underwent chorionic villus sampling (CVS) at these institutions between 2000 – 2004. The average age of the patients carrying twins from IVF was slightly higher (2 years) than those with twins who conceived naturally.

Out of the 27 women carrying twins conceived through IVF, the incidence of aneuploidy was 14.8%. Out of the 14 women carrying twins conceived spontaneously the aneuploidy incidence was 0%. Because genetic abnormalities can be identified through CVS early in the pregnancy, the paper points to the importance of counseling. (Note: Those who require IVF may already have an increased incidence of genetic abnormalities unrelated to the IVF process. Continued study is needed.)

Vanishing Twins Provide Clues: A research team at UCSF studied the gestational sacs of 244 births resulting from IVF/ICSI and found that singletons born with a so-called vanishing twin were more likely to have adverse perinatal outcomes including low birth weight, premature birth and stillbirth incidences, suggesting abnormalities start in early placentation. They are now calling for a larger sample size to confirm the data. Female Twins Reach Early Menopause: Weill Medical College of Cornell University researchers presented data suggesting that female twins are more likely to undergo premature menopause. Although identical twins showed a higher incidence than non-identical twins, both groups showed significantly higher rates than their non-twin counterparts from the general population. Statistically speaking, only about 1% of women reach menopause by age 40. The twins from this study revealed that about 5% reached premature ovarian failure and showed menopausal symptoms by age 40. In some cases, only one twin out of a pair entered early menopause. This joint study involved a survey of 850 women from different twin populations around the world collected by the Queensland Institute of Medical Research in Brisbane, Australia; St. Thomas’s Hospital in London and St. Luke’s Hospital in St. Louis, Missouri.

Infertile Women Want Twins: While the news about multiple gestations continues to raise concerns, a group out of the University of Iowa, Carver College of Medicine confirmed earlier research indicating that infertile women desire twins at twice the rate of their fertile counterparts. This research team used a questionnaire-based prospective study to survey over 1000 maternity patients and found that 20% of infertile women conveyed a preference for twins compared to 10% of fertile women.

Pollution Has Impact in Brazil

Two research groups from the School of Medicine at the University of São Paulo in São Paulo, Brazil are studying the impacts of air pollution on reproductive health. One study group focused on early miscarriage by exposing mice to ambient air pollution from rush hour traffic, compared to a control group placed in a less polluted environment. The exposed mice group had 80% of the early gestational miscarriages recorded out of the combined set. Specific pollution types and quantities were not listed in this study.

The other study analyzed the possible impact of increased ambient air pollution on gender outcome of live births of both humans and mice. In this study the researchers correlated live birth data to 15 air pollution monitoring stations in the city of São Paulo. They analyzed birth registries between January 2001 and December 2003, and correlated conception dates to the pollution levels of each station. In the least polluted area the sex ratio was 51.7% males for 34,795 births recorded, and for the most polluted area the proportion decreased to 50.7% for 48,023 births recorded, indicating a difference of 1% in total male births. Similar findings were observed in the experimental study involving mice placed in polluted vs filtered chambers. In the filtered chamber the male/female ratio was 1.34 opposed to 0.86 in the non-filtered chamber.

Left to right: Front row: Carl Herbert, MD, Isabelle Ryan, MD
Back row: Joe Conaghan, PhD, Eldon Schriock, MD, Carolyn Givens, MD, Philip Chenette, MD

The physicians at Pacific Fertility Center are internationally recognized specialists in reproductive endocrinology and infertility. They have completed top-level medical education, published groundbreaking professional papers, and held positions on the faculty of leading research universities. They continue to participate in reproductive research. All MDs are Board Certified by ABOG as Reproductive Endocrinology and Infertility Specialists. Our state-of-the-art laboratory has one of the most highly trained teams in the country.

Patrick and I began a cycle of IVF in July of 2003 and by that September we were pregnant with twins. Our entire experience, from the time that we first met with Dr. Schriock to the actual confirmation of our pregnancy was positive. Everything was explained to us from the percentages of success to the risks associated with IVF in the initial consultation and follow-up meetings. We both went into it optimistically and decided to deal with any issues as they came up, and tried not to worry about the maybes.

Because both Patrick and I were fine with the possibility of having twins, the decision to implant more than one embryo in order to increase our chances was never an issue. Dr. Schriock was comfortable with me carrying twins, but in the small chance that more embryos did in fact attach, he strongly recommended reducing. The day of the transfer, we were told that we had seven viable fertilized eggs and the recommendation was to transfer up to three of them. I actually wanted to transfer four in the hopes of having an even greater chance of conceiving, but was overruled not only by the doctor but my husband who was terrified that all four may actually attach. A few weeks later, after having my blood drawn, my numbers were so high that I was sure I was carrying triplets. It was such a relief to finally have an ultra-sound and see two tiny heartbeats. We were both so happy to have finally been able to conceive and I was especially thankful to have avoided a decision on what to do if I was carrying three babies. My biggest concern throughout my pregnancy was to carry two babies to full term. There seemed to be a lot of “negative material” out there to be read. The biggest cause of concern seemed to be of multiples being born prematurely. After reading a lot of baby books, I finally found one that became the positive influence I was searching for: When You’re Expecting Twins, Triplets, or Quads. It shows that having multiples does not necessarily mean that you will have a difficult pregnancy or that your babies are destined to be born weighing only a few pounds. Rather it encourages you to think beyond the 35-37 week time frame that most twins are usually born and to try for the full 40 weeks if possible. One thing that I really liked about the book is that it encourages you to eat. The suggestions to eat double cheeseburgers and milk shakes definitely made my pregnancy a little more fun. I exercised 6 days a week just like I did pre-pregnancy but instead of running I used pregnancy exercise videos. I continued to exercise up until my 37th week, three weeks before I delivered. Ashley Jordan and Janelle Patrice were born on May 6, 2004, forty minutes past Cinco De Mayo. We went 40 weeks and one day before having to be induced. Because I wanted to have them vaginally and hadn’t experienced any complications, my doctor allowed me to carry them past the normal 37 weeks. In the end though, they were delivered by cesarean. Life with twins is wonderful. They actual help with entertaining each other and it is fascinating to watch them develop skills at different rates. They did start to crawl one day apart just after turning 6 months, but Janelle can already walk with a walker while Ashley has just learned how to pull herself up. For me, I sometimes wish I could have a little more one-on-one with each but I don’t think they notice. We all play together and they are used to being a twosome. There is nothing like watching them laugh hysterically with each other when playing and they seem to already have their own secret language. We are glad that at 36 years of age, we have two beautiful, healthy babies and they have each other to play and grow up with. We still have three frozen embryos and are considering trying to do it again down the road. I encourage everyone I know that is having difficulty in getting pregnant to go to PFC before any other clinic. There is no way we can thank Dr. Schriock and his team enough for giving us our beautiful girls.

– Jana

Twin pregnancies are common in women undergoing IVF and we congratulate Jana on her very successful experience as a mother of twins. Most twin pregnancies have good outcomes, however, the chance of having a healthy baby is much higher in singleton pregnancies. At Pacific Fertility Center, a singleton pregnancy is our preferred outcome. Prior to transfer, the risks and benefits of transferring one or more embryos are discussed. The patients’ final decision is made in partnership with the physician. Multiple pregnancy is risky for both the mother and infant. Premature birth occurs in over 50% of twin pregnancies. A twin is seven times more likely to die in the first month of life. Preeclampsia occurs three to five times more frequently. Prolonged bed rest and hospitalization for preterm labor is common and cesarean section is often needed for delivery. Patients may wish to refer to Patient’s Fact Sheets from the American Society of Reproductive Medicine: “Complications of Multiple Gestation” and “Challenges of Parenting Multiples”. It is very important for patients to realize that excellent pregnancy rates can be maintained while controlling the rate of multiple pregnancy. More than one study has shown that transferring one embryo at a time can be as effective and more economical than transferring two embryos. Embryo freezing is now very successful. As preimplantation genetic diagnosis improves, it may also be helpful in selecting which single embryo to transfer. With improvements in the laboratory such as embryo isolettes, refinement of medications, improved freezing techniques, and preimplantation genetic diagnosis, we are closer to our goal of all singleton births.

– Eldon Schriock, MD

Q. Considering how much trouble we’re going through to get pregnant, I don’t mind if we have twins, or even triplets. What do you think?

A. Many parents undergoing infertility treatment are open to, or even welcome the idea of having more than one baby without fully understanding the risks that a multiple gestation pregnancy poses to the mother and infants. You are wise to research this thoroughly before entering into your cycle.
Let’s first look at the facts:
– Over 50% of twin pregnancies result in preterm births;
– Over 90% of triplet pregnancies result in preterm births;
– Virtually all pregnancies of quadruplets (and greater) result in premature labor;
– Compared to a singleton pregnancy, a twin is seven times more likely, and a triplet is
over 20 times more likely to die in the first month of life.

Even with medical advances to handle early birth trauma, premies are more likely to suffer from respiratory distress syndrome, intra-cranial hemorrhage, cerebral palsy, blindness and neonatal morbidity. These stark statistics and more have been compiled by the American Society for Reproductive Medicine (www.asrm.org), and distributed in a patient’s fact sheet.

Because these facts are undisputed, infertility specialists with the help of our professional associations began a campaign to actively educate couples about the risks of multiple gestations, and to make responsible decisions. Fortunately, this work is now showing results. Research published in the April 14th 2004 New England Journal of Medicine revealed a drop since 1997 in the number of high-order multiple pregnancies. In 1997, women under 35 faced nearly a 14 percent chance of having triplets or more! Today that figure has dropped to 8.1 percent, which is still higher than the natural incidence of multiple gestation.

Couples who share the goal of conceiving a single, healthy child generally end up as happy, and with far fewer complications, as those couples that have more. If the embryos are of good quality, our doctors will transfer no more than two embryos in a first IVF cycle for women under 35. Bear in mind that identical twins are possible, since an embryo can split in two. If a couple is opposed to selective reduction, a single embryo transfer is sometimes the best choice, especially if a young donor’s eggs are used.

With our guidance and your understanding, we trust you will make the right decision for your health and the health of your baby.