Pacific Fertility Center is pleased to announce that as of October 1st we are enrolling patients into a groundbreaking research study to determine the value of combining acupuncture with IVF. Traditional

Chinese medicine has been practiced in throughout Asia for thousands of years:in the last decade, the west has been following suit.

There have been sufficient peer reviewed studies to warrant a clinical trial in which there are predictable parameters of patient involvement. One of the first studies involving acupuncture and IVF was published by Paulus et al in the journal Fertility Sterility in 2002. The Paulus study reported the influence of acupuncture on the pregnancy rate in patients who undergo assisted reproductive therapy. Clinical pregnancies were documented at 42.5% of patients in the acupuncture/IVF group, whereas pregnancy rates were 26.3% in the control group, using IVF alone. In this study, the acupuncture was performed before and after embryo transfer only.

How does acupuncture affect fertility? A review article in Alternative Therapies (Anderson 2007) suggested four possible mechanisms by which acupuncture could improve the outcome of IVF: modulatingneuroendocrine factors; increasing blood flow to the uterus and ovaries; modulating cytokines; and reducing stress, anxiety, and depression.

The participants of our study will be randomly separated into two groups. One group will have acupuncture along with their IVF cycle and the other group will continue with their regular IVF cycle without acupuncture. Both groups will have the majority of their IVF medication provided for them at no charge. Those in the acupuncture group will also have their acupuncture treatments at no charge.

We are very excited about this study. It is the first of its kind involving extensive, onsite acupuncture treatment pre and post IVF. As a study participant, you have the opportunity to help us determine with greater certainty the influence of acupuncture on fertility. We hope to better understand its mechanism and use; thus assisting others in achieving their dream of having children.

If you are interested in finding out if you are eligible to participate in our study please call 415-834-3000 and ask to speak to the Patient Care Coordinator.

Stillbirth, loss of a baby at delivery, is a painful challenge.  The suffering associated with the loss of a child, even before birth, can be overwhelming.  Especially acute for women that have conceived utilizing assisted reproduction, the loss of a pregnancy fought through reproductive technology can overwhelm a couple.  Stillbirth is a rare risk of pregnancy; the challenge facing us as reproductive medicine experts and obstetricians is how to reduce that risk.

The technologies of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) have enabled pregnancy for thousands of families with sperm, egg, and uterine problems.  With IVF, egg quality can be optimized using fertility drugs to produce more eggs.  Blocked fallopian tubes can be bypassed.  Weak sperm can achieve pregnancy by ICSI, where, using a microscopic needle, the sperm cell can be introduced into the egg.

No-one should expect these techniques to be foolproof.  While mechanical problems can be improved, other weaknesses in the reproductive system cannot.  Small deviations in the genetic code of the sperm or egg, missing chromosomes, aging, uterine defects, etc cannot be fixed by treating the sperm cell or embryo.

Thus the problem – these pregnancies established by high technology, are at higher risk.

A recent study from Denmark looked at stillbirth in children born after IVF/ICSI  and found that the risk was higher in children born after IVF/ICSI than natural pregnancy.  Out of 16,525 births to fertile women the chance of stillbirth was 0.37%, that is, 3.7 out of 1000 births.  Out of 742 babies born to women after IVF/ICSI there were 12 stillbirths, 1.62%, that is 16.2 out of 1000 births.

But more importantly to our patients, the liveborn baby rate after a successful IVF/ICSI treatment  and pregnancy is 98.4%.  The liveborn baby rate after a successful natural conception and pregnancy is 99.6%.  Almost all of the successful pregnancies after IVF/ICSI are liveborn.

Reproductive technologies, like IVF and ICSI, are enabling pregnancy and family building where it was not possible before.  All of our patients must be informed of and recognize the risks associated with fertility treatment.  These risks should not, however, dissuade anyone from considering these therapies.  On the contrary, the overwhelming likelihood is that, once a pregnancy is established, it will progress successfully to delivery and a healthy child.

We need to recognize these risks to provide help understand and take measures to reduce the risks to all children.  We will continue to watch these studies carefully in our ongoing effort to assure our patients of excellent pregnancy rates, at low risk.

Footnote:

1. K. Wisborg, H.J. Ingerslev, and T.B. Henriksen  IVF and stillbirth: a prospective follow-up study  Hum. Reprod. Advance Access published on February 23, 2010.

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.

Q.
We recently had PGD performed, and it revealed that two abnormal embryos were developing beautifully and two genetically normal embryos had ceased developing. Why would the genetically normal embryos not develop in comparison to the genetically abnormal embryos? Would this be due to egg quality? Would the same results be expected for a future PGD procedure? Is it unlikely that a six-cell embryo that had not developed in two days would result in a pregnancy?

A.
I don’t have all the information needed to give you a complete answer but I’m going to assume that you are a typical IVF patient (in your late 30’s) and were doing PGD to eliminate embryos with chromosomal abnormalities or aneuploidy. During your IVF cycle the eggs that were harvested from your ovaries were inseminated and those that fertilized and continued to develop were analyzed genetically. Depending on your (maternal) age, somewhere around 50% of your eggs would have been genetically abnormal. The genetically abnormal embryos look and behave in the same way as normal embryos.

Most genetic abnormalities cause an embryo to fail at the time of implantation (5 or 6 days old) or cause a pregnancy to fail early (miscarriage). When we look at embryos under the microscope in the days leading up to transfer, there is no way of knowing which are genetically normal or abnormal. Both types of embryos grow and develop similarly. In fact, some embryos that we know are abnormal (e.g. resulting from an egg that is fertilized by 2 sperm) often develop faster and look more beautiful than normally fertilized embryos.

The egg is a very large cell and when it is released from the ovary it has already been programmed to develop for 3 or more days after fertilization. Mom pre-loads her eggs with the necessary information for this early development. In most cells, including sperm, there are internal checks to make sure that the cell is functioning normally and that it is genetically normal. Cells that are abnormal, commit suicide in a process that we call apoptosis. Eggs however, seem to have a very poor internal surveillance mechanism, and even those that are grossly abnormal (e.g. with a whole extra chromosome) can fertilize and develop even to the point of giving you a live child. Down syndrome is the classic example, although at least 75% of embryos affected with this condition miscarry early in pregnancy.

So, eggs are endowed at ovulation with the necessary information to keep them going and looking normal for days, regardless of their genetic constitution. There is no relationship between their genetic status and how beautiful they look in our petri dish. If there were, we wouldn’t need to do PGD. We can keep embryos alive in the laboratory for 5 or 6 days and some of the abnormal embryos might stop developing by that time. However, our experience with PGD over the years tells us that about 50% of the genetically abnormal embryos will still look beautiful on their 5th day of life.

The pattern of development that we see with human embryos, regardless of their genetic status, is extremely variable. As you have witnessed first hand, normal embryos often arrest for reasons that we don’t always understand. This is true, regardless of whether the embryos are growing inside of you or in our lab, and this leads to a very inefficient process of reproduction in human females because she only ovulates one egg per month. We do know that the younger a woman is, the better the chance that the embryo will continue to grow. Embryos are more likely to fail in older women. In very young women, over 50% of embryos will implant in the uterus, but in women over age 40 less than 10% will implant. Although we can’t fully explain this phenomenon, a major contributing factor is egg age. Since women have all the eggs they will ever have when they are born, a 40-year-old woman is trying to get pregnant with a 40-year-old egg. And 40-year-old eggs just don’t perform as well as younger eggs.

Are PGD results consistent from one cycle to the next? The PGD technicians tell me that they get similar results for a patient 2 out of every 3 times.

Any embryo that has not developed in 2 days will not get you pregnant. If an embryo is to be ready for implantation, it must be alive and increasing its cell number every day. We expect a full round of cell division (e.g. from 4 to 8 cells) every 16 hours. Further, an embryo transferred to your uterus on day 4 or day 5, following your PGD analysis, should have enough cells to begin forming a placenta. It sounds like your embryo had arrested (i.e. it was dead).

Human reproduction is a very complex undertaking, and often patients feel like they’re left with more questions than answers after their fertility treatment. Don’t be afraid to ask your questions, no matter how simple or complicated they might be. Chances are, we’ve encountered your situation before. - Joe Conaghan, PhD, HCLD

By the end of the year we will have started a new and very exciting research project in our lab. We have partnered with a company called Incept Biosystems (www.inceptbio.com) to do a clinical trial of a new embryo culture system called microfluidics.

The traditional culture dish with medium droplets under oil as described by Brinster, R.L., 1963, Exp. Cell Res., Vol. 32

This involves culturing embryos in very small volumes of culture media inside a chip specifically designed for this purpose. Tiny pumps regulate the flow of culture medium in and out of the chip without causing the embryos to move around.

The traditional vessel for embryo culture is the petri dish, where small droplets of culture medium are overlain with a highly purified mineral oil. The culture medium, regulated in much the same way as pharmaceuticals, is one of the most highly tested and expensive components of the IVF laboratory operation. We typically make droplets of medium that are in the 50-200µl size range, and the oocytes or embryos are placed in the droplets for 24-48 hours at a time. This is a static culture system where nutrients are depleted by the developing embryos and waste products (e.g. ammonia from amino acid breakdown) accumulate over time. The droplets are large enough to make sure that the supply of nutrients is more than adequate and that waste is diluted to the point of not harming the embryo in any way. The embryos are changed into fresh medium at least every 48 hours.

This system for embryo culture has been in use since human IVF began in the late 1970’s and early 1980’s. It was actually developed in the early 1960’s by a pioneer of mouse embryo culture, Dr Ralph Brinster, at the University of Pennsylvania. Some early human embryologists cultured embryos in small test tubes without the mineral oil, but nowadays, despite the age of this technique, it is very unusual to find a facility that does not use the droplets under oil method. After 45 years, perhaps it is time for a change?

A microfluidic system for embryo culture has been in development for over 5 years at the University of Michigan in Ann Arbor. Professor Gary Smith combined the talents of his graduate students in physiology with those of engineering students and came up with a device that has had outstanding results with growing mouse embryos. Professor Smith is no stranger to IVF, as he was the director of the University’s IVF Laboratory for many years and he was instrumental in designing and testing the vitrification system that we now use to preserve oocytes and embryos. He solicited venture capital to start Incept Biosystems with the intent to bring microfluidics into human IVF labs. Incept Biosystems were onsite at PFC during the last week of October to train our embryologists on the use of the system. We did several trials with mouse embryos to achieve proficiency with the system and then we will actively recruit patients to enroll in a clinical trial using the system.

The clinical trials are being run at 3 centers in the US. In addition to PFC, patients will participate at the Fertility Center of San Antonio and at Southeastern Fertility Center in Charleston, South Carolina.

A schematic of a microfluidic embryo culture device with fresh medium in blue and spent medium in red. The embryo is contained at the base of the chamber, where the blue medium ends.

Patients that are asked to participate will have to consent to the study, where their embryos will be divided into 2 groups for culture in the microfluidic device and in the traditional petri dish. The culture media will be the same for all the embryos, but half will be in a replenishing media current (microfluidics) and half will be in our traditional static culture.

Microfluidics has had impressive results with mouse embryos where it significantly increased rates of development and implantation over those for embryos grown in static culture. Cell numbers for the microfluidic embryos were almost twice as high as for traditional culture (110 vs. 65), and pregnancy rates from transferred embryos were increased by 22%. Incept Biosystems have tested the new technology extensively and have been able to obtain surplus IVF embryos donated for research for human trials. There are some nice videos on their website that showcase the equipment and procedure, and detail the mouse embryo results. Professor Smith presented the results and won the prize paper at the 2008 American Society for Reproductive Medicine (ASRM) meeting (Smith et al., 2008, Fertility and Sterility, Vol 90, pages S1-S2), and these results will soon be published in a peer reviewed journal.

We will be asking for participants to join the study, beginning in November and continuing for 2-3 months. This is a short study requiring enrollment of only 20 patients, but a larger study is planned for next year subject to favorable outcomes here. If you are interested in the study and would like more information, please ask your physician at your next visit.

–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.

Many populations of the world have specific genetic conditions that are prevalent within their ethnic group. Consequently, numerous medical organizations have recommended that genetic screening for these conditions should be offered when women are either planning for, or are currently pregnant. We are all carriers of genetic conditions: generally this is of little concern, as it is highly unlikely that we would have children with a partner who is a carrier for the same condition.

The genetic conditions listed in the table below are recessive. A recessive gene mutation is “carried” by someone who is unaffected by the disease, and thus unaware of their carrier status. Men and women have equal potential to be carriers for recessive conditions. Even if someone is a carrier, we would not expect to see a family history of the disease. If there is a family history, the likelihood of being a carrier of that condition is generally greater than in the general population. Being a carrier for a genetic condition typically has no impact on the carrier’s health and development. However, if a carrier has a child with another carrier of the same genetic disease, the chance that the child will be affected with the disease is 1 in 4 (25%).

If only one partner is a carrier, and the other tests negative, then the risk of an affected child is low, but not zero (a result of the limited ability to test for all defects that would make one a carrier; see table). These genetic screening tests are typically performed on a blood sample.

Below is a table listing the minimum number of tests for various ethnic groups recommended by the physicians at Pacific Fertility Center prior to starting assisted reproduction treatment. Additional genetic tests may be considered after a discussion with your physician.

If you know that both you and your partner are carriers of the same genetic defect, you may be able to have embryos created in an IVF cycle and tested for their status. Preimplantation genetic diagnosis (PGD) is a technology that allows embryos to be tested for specific disease causing mutations. PGD can identify unaffected embryos for transfer back to the uterus or freezing.

—Guest Contributor – Certified Genetic Counselor Lauri Black, M.S., C.G.C

*See lab specific accuracies on test result

Assisted reproductive technology (ART) has been a part of modern medicine now for over 30 years and in the US alone over 132,000 IVF cycles were performed in 2007. All birth outcomes are reported to the Centers for Diseases Control but there is no mechanism for long-term follow-up of IVF births.

Well over a million babies have been born world wide through IVF and new data are emerging about reproductive birth outcomes after conception. Some countries, particularly the Scandinavian countries, do an excellent job on gathering data for all births, including IVF-conceived births. One of the greatest risks of ART is prematurity from multiple gestation. From several of these databases, it has become apparent that even singleton IVF births are statistically associated with poorer birth outcomes. Lower birth weights, pre-term delivery and infants small for gestational age (i.e. lower weight than expected for number of weeks in utero) are some of the findings from follow up of IVF babies.

These findings beg the question: is it something about IVF, namely the culture of the early embryo in a lab for the first three to five days of life, that results in these poorer outcomes, or is it something about the couples that need IVF to conceive that is associated with them? This can be a difficult issue to sort out because relatively few people undergo IVF who are not infertile.

A recent study from Norway was published in the British medical journal Lancet that tried to address this question by comparing IVF babies with their spontaneously-conceived siblings. The study compared 1,200,922 spontaneously-conceived live births and compared them with 8,229 live births after ART between January 1984 and June 2006. Of those women who had given birth to a singleton infant after ART, 2,456 also delivered a singleton infant after spontaneous conception. In 56% of the cases, the ART baby was born first and in 44% the ART baby was conceived after the birth of the spontaneously-conceived infant. The researchers looked at birth weight, gestational age as well as a number of other factors.

Compared with women in the general population that delivered a spontaneously-conceived birth, the women that delivered after IVF were older, less likely to smoke and had fewer previous births. Induced labor and cesarean section were more common in the IVF moms. The difference in birth weight between ART and non-ART babies was 131 grams (4.6 ounces). That is, the ART babies weighed, on average, 4.6 ounces, or about 3/4 pound less than the spontaneously-conceived babies. After statistical adjustment for gestational age, maternal age, prior births, year of birth, the difference in birth weight between ART and non-ART babies was 25 grams (0.88 ounces). The ART babies were born, on average, 3.7 days earlier than the controls. After statistical adjustment, the number of days of total gestation was 2 fewer days. Because of the large sample size, these were statistically significant differences but realistically, they were probably not clinically significant.

In comparing the sibling relationship ART vs. non-ART births, the differences were even smaller. The difference in birth weight was only 87 grams (about 3 ounces) for the ART babies as compared to their spontaneously-conceived siblings. The gestational age differences at birth were 1.3 days less for ART. After adjustment, these differences were only 9 grams and 0.6 days. These differences were not even statistically significant.

From these data, we can see that ART births do show statistical differences in some birth outcomes as compared to spontaneously conceived births. However, none of the differences seem are to an extent that would have any real clinical meaning. These differences tend to disappear to a large extent when comparing siblings from both spontaneous and IVF conception, suggesting that it is something about the families that utilize ART, rather than the technique itself that may be associated with the outcome differences.

News broke earlier today about the death of a 69 year old mother who had undergone fertility treatment at age 66. She gave birth to twins in December 2006.

This is a very unfortunate incident and we express condolences to the loved ones, especially the children who are left behind. However, it is necessary to clarify that Pacific Fertility Center was not involved in the treatment of this patient. The AP article printed the name of the clinic as “Pacific Fertility Center”, which is an error of ambiguity since there are two fertility clinics with similar names. The fertility clinic where this woman received services was Pacific Fertility Center-Los Angeles. Our center, which is located in San Francisco, has no affiliation with the clinic in Los Angeles. While our names are similar, our standards of practicing medicine are much different. To begin, here at Pacific Fertility Center in San Francisco, it is standard procedure to verify the identity and age of the persons being treated at every visit.  Our physicians would not have treated a woman at the age of 66, since we believe this to be unethical. At Pacific Fertility Center in San Francisco, we believe it is our foremost and ethical responsibility to assure the children that are a result of our services are provided loving and caring families.

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.

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