Progress has been steady at the Center this week. From last Sunday up until this coming Saturday we will do 13 egg retrievals, 14 fresh embryo transfers, 6 frozen embryo transfers and one hysteroscopy. It looks to be a fairly typical week.

Last Saturday I attended an investigators’ meeting, along with our lab director, Dr. Joe Conaghan, for a new clinical research study that we may be undertaking with Gene Security Network (GSN). GSN is one of the pre-implantation genetic diagnosis/screening (PGD/PGS) laboratories with which we work. I really can’t discuss the details of the study at this time, as we have signed a standard non-disclosure agreement with GSN, but this will be a big study to investigate how useful PGS will be to the average IVF patient.

This leads me to the topic of today’s blog: clinical research. Although PFC is not an academic institution, we are still interested in research because this is how the field of reproductive medicine advances. In fact, since there are so many private IVF clinics, much of the research on IVF is currently being done in the private sector. We would not have the field of assisted reproduction today if it were not for clinical research and for the thousands of patients who have participated in this research to this point. I’d like our readers to know that participation in research is not taken lightly by anyone conducting the studies. As investigators, we all have to be trained in the ethical conduct of research, to make sure the risks of participation are minimized and that there is potential benefit to patients from participation. Our number one goal is still to get our patients a healthy pregnancy. We will not compromise that goal for the sake of a clinical study. The study protocols are carefully reviewed by an independent Institutional Review Board (IRB), tasked with ensuring there is no harm or undue coercion to participants. In most good studies, the design of the study includes a “control arm” and the patients who are randomized into this arm receive current standard treatment. The patients randomized to the “treatment arm” receive the treatment under investigation. It is very important that the patients in the treatment arm should be expected to be at least as successful, if not more so, than the patients in the control arm.

This year, PFC is participating in at least 4 clinical studies. Some, like our acupuncture study, are designed by PFC and are only being done at our facility. Some, like the GSN study, are being designed by the company and will be done at multiple IVF centers, then GSN will pool the data.  If you are interested, please let us know. I will be posting more details very soon to our PFC website.

UPDATE: Research web page is live

It’s looking to be another typically busy week at the Center. Although the overall patient volume at PFC in 2009 was down about 10% from 2008, 2008 was a record year, so 2009 was more typical of the volume in the last 10 years. So far in 2010, we are up over this time in 2009. Many clinics in California and around the country are seeing decreased demand for IVF services, likely due to the poor economy. I heard on the radio the other day that the number of vasectomy procedures was up sharply in 2009 as well. A sign of the tough economic times, I suppose.

In 2007, the last year for which U.S. IVF clinics have official results tabulated from mandatory reporting to the CDC, the total number of  fresh IVF cycles performed in 430 reporting clinics was 142,435 resulting in 43,412 live births and 57,569 infants*. It is estimated that in western countries, about 1% of babies born are now from assisted reproductive technologies. Overall, about 36% of embryo transfers resulted in a live birth. This number continues to climb nationwide, at the same time the number of triplets and more is dropping (now at only 1.8% of live births, which is excellent). The twin percentage is still too high at 30% but we hope to also see this number declining in the coming years as overall success rates improve and we continue to emphasize to our patients the  much better outcomes of singleton pregnancy as compared to twin pregnancy.

Delayed childbearing still continues to be the biggest issue for human reproduction and fertility in the post-industrial world. This is especially true in the San Francisco Bay Area. The median age for women doing IVF in the U.S. was less than 35 but at PFC it is age 39. This may partly to do with the fact that in California, insurance coverage for fertility treatment is not mandatory, like it is in some states like Massachusetts and Illinois. Therefore, couples wait longer before availing themselves of the most effective treatment for infertility. This is also why the proportion of women undergoing IVF nationwide diagnosed with decreased ovarian reserve (i.e. diminished egg quality, a diagnosis that tracks with female age) is 10.3% but this diagnosis represents 31% of the patients at PFC.

*2007 Assisted Reproductive Technology Success Rates National Summary and Fertility Clinic Reports U.S. Dept. of Health and Human Services Centers for Disease Control and Prevention www.cdc.gov/ART/

It’s been another busy week at Pacific Fertility Center. Since Monday, we have done 13 egg retrievals, 11 embryo transfer procedures and one hysteroscopy. One thing is certain – our lab is very hard working. I’m really proud of our embryologists. We have 8 embryologists, including 2 PhDs. They are very enthusiastic and never complain about the work load. They put in the hours and virtually never make mistakes. They really are professionals.

Many people wonder why IVF is so expensive. One reason is that, unlike other medical procedures, it’s often not covered by insurance, so patients have to pay out of pocket and that can hurt. If you were undergoing, say, a kidney transplant procedure, with the attendant technological and complicated procedures involved, no one really questions the costs, mainly because medical insurance covers so much of it. Until infertility is seen as a medical condition for which treatment should be universally covered, we are unlikely to see a change in the perception of the high expense. Although IVF does cost about $15-20K for one cycle, with all possible expenses included, the increase in costs over the last 20 years have not risen to anywhere near the extent that other medical services have risen in this time period. This is because we all try to do what we can to be as efficient as possible, mindful of what it costs patients out of their own bank accounts.

Last night, the MDs and PFC managers met for our monthly meeting (usually a 3-4 hour marathon meeting!). We have managers for the following departments: nursing, billing, IT, medical records, the Egg Donor Agency, HR, clinical research and our Laboratory Director. One of the topics under consideration is how we are going to wire the Center to accommodate a large diesel generator we just purchased. We never really use the generator, it’s only there for emergency power losses. Yet we must have a functioning generator to keep the Center running in case of minor power losses, or heaven forbid, the big quake that damages significant infrastructure. We decided last night to go with the “Cadillac” plan for re-wiring, allowing us to run the entire Center for several days off the generator and allowing for flexible allocation of the electricity to some or all areas. The difference in cost was $25K for basic wiring and $39K for the most extensive and flexible arrangement. Along with rent, salaries for 70+ employees, including some very highly educated staff, these are some of the “hidden” expenses that are essential to running a world-class IVF center.

UPDATE: This study is currently on hold while we attend to some administrative details. Please check back to this blog often, as we will keep our readers updated.  You may also call the New Patient Coordinators at 415 834-3095 for more information.

PREVIOUSLY: 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.

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.

Pacific Fertility Center and The Fertility Flash would like to invite you to a special Valentine’s Day event.
Do You Love Your Genes? Tweetup/Meetup (a Valentine’s Day event)
Thursday February 11, 2010 at 5:30pm
Pacific Fertility Center’s Education Center
55 Francisco St., Suite 550
San Francisco, California 94133 Get Directions

Please join us for genes, love, award-winning wine, chocolate, and tasty, healthy appetizers!

To view the invitation, click here

This is an in-person and virtual event for all who would like to participate and learn about the leading edge of genetics and fertility. We will also be tweeting live during the event to communicate with and connect tweeters.

Genes are an important part of life, especially for those who are struggling to conceive a child.  At this event we will celebrate these building blocks of life in all forms, whether they come from biological parents, birth parents, or donors.

We will also be joined by representatives from Counsyl and the Gene Security Network (GSN) to speak about their cutting edge genetic testing technologies.

For more details on our presenters see:

Pacific Fertility Center: http://pacificfertilitycenter.com
Counsyl: http://counsyl.com
GSN: http://genesecurity.net

**

Please RSVP at rsvp@fertilitywire.com or on Facebook at http://bit.ly/bopZUZ

FertilityWire is a source of real-time fertility information and
insights founded by fertility doctors. Visit us: http://fertilitywire.com

Follow us on Twitter at http://twitter.com/fertilitywire
Become a fan on Facebook at http://bit.ly/dB7ewl

Thank you for your interest in subscribing to Pacific Fertility Center’s free monthly newsletter. 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.

This year’s flu season is certainly not your standard flu season. 2010 brings not only the current seasonal flu variety, but also the pandemic H1N1 virus, commonly known as Swine Flu. These are two separate viruses. H1N1 is not only of great concern for all members of the population, but also of particularly serious concern for pregnant women.

The single most important action, strongly recommended by the Centers for Disease Control (CDC), is for pregnant women to be vaccinated against both the seasonal flu and, most importantly, H1N1. Both the seasonal flu vaccine and the H1N1 vaccine can be administered at the same time, at separate injection sites. There are two methods of dispensing the flu vaccine; either by injection or by a nasal spray (Flu Mist).

For immunization of pregnant women, only the injectable vaccine should be administered. Ob/Gyn practices will be the first to receive the vaccine. Patients should plan to be vaccinated at their Ob office.

Above: Tis the season to be conscious about germs

In addition to the flu vaccines, there is medication available to treat those with symptoms of the flu or those who have been exposed to someone with the flu. Symptoms of the flu can include: cough, sore throat, runny or stuffy nose, body aches, headache, chills, fatigue, and sometimes diarrhea and vomiting. Fever is common, but it is important to note that not everyone with flu will have a fever. If you have symptoms or if you have been exposed to someone who has the flu, call your doctor right away.

Pregnant women with suspected influenza, or experiencing more severe symptoms such as evidence of lower respiratory tract infection or clinical deterioration should receive prompt empiric antiviral therapy, regardless of previous health or age. Most healthy persons who develop an illness consistent with uncomplicated influenza, or persons who appear to be recovering from influenza, do not need antiviral medications for treatment or prophylaxis.

Pregnant women exposed to someone with influenza should consider antiviral chemoprophylaxis. Chemoprophylaxis should generally be reserved for persons at higher risk for influenza-related complications who have had contact with someone likely to have been infected with influenza. However, early treatment is an emphasized alternative to chemoprophylaxis after a suspected exposure. Household or close contacts (with risk factors for influenza complications) of confirmed or suspected cases can be counseled about the early signs and symptoms of influenza, and advised to immediately contact their healthcare provider for evaluation and possible early treatment if clinical signs or symptoms develop. Early recognition of illness and treatment when indicated is preferred to chemoprophylaxis for vaccinated persons after a suspected exposure.

Go to the emergency room immediately if you have difficulty breathing, or shortness of breath, pain or pressure in your chest or abdomen, sudden dizziness or severe or persistent vomiting. Prevention is certainly the best defense–and there are a number of things we can all do to minimize the spread of flu this season.

Wash your hands! Frequent hand washing or use of alcohol-based hand sanitizers is a major preventative measure. Carry a hand sanitizer in your purse, in the car, even a small bottle in your pocket. You can use them just about anywhere at any time.

Cough into your elbow! This helps to keep your germs to yourself.

Keep your hands away from your face! You will not be infected with the flu by touching a contaminated surface — unless you then touch your eyes, nose, or mouth.

Stay away from sick people if you are healthy and from healthy people if you are sick! You do not want to knowingly expose yourself, but remember, if it does happen, call your doctor straight away.

You do not want to spread the flu if you have it. Stay home and stay away from other family members as much as possible and make sure to call your doctor as soon as you have symptoms.

The CDC will continue to update their website as there is new information:

For general information on 2009 H1N1 flu go to:
cdc.gov/h1n1flu/qa.htm

For more information on flu shots go to:
cdc.gov/h1n1flu/vaccination

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.

Imagine a website that allows you to search for the very latest information on fertility. Well, it’s here and it’s called fertilitywire.com.

PFC is proud to present fertilitywire.com as a completely unique website that offers real-time and fresh information on fertility and infertility related topics. It’s a resource for people engaged in the process of becoming pregnant through fertility treatments or people studying this field who want to explore it.

And, it’s a unique resource in that it’s powered by a type of search called “browsing or universal search,” which is how we’re able to pull together all of the content for any given search term you see. You are able to see, in one place, the latest fertility related news, blogs, tweets, videos, images, articles and books.

We are excited by the positive feedback we have been receiving about fertilitywire.com. Here is one testimonial that sums up the experience very well:

“This website has a friendly approachable tone. It also covers so much, by the time I was done navigating, fertility issues seemed not intimidating but manageable and that there is a world that one could enter, (your center) and not be a stranger. At the same time, it seems like there is hope; if not here and now–it is being developed right around the corner.”

— Michael Lynn, PFC Patient

Visit fertilitywire.com. We hope you find everything you are searching for!

Ovarian reserve is an expression of the number and quality of eggs available for conception. As a parameter for predicting pregnancy, ovarian reserve testing is often part of a fertility evaluation. Such testing requires specific measurement, and clinical judgment to interpret the results.

Egg numbers are at a maximum before birth, at around 20 weeks gestation. After birth, there is a progressive decline in the number of eggs from roughly one million at birth to 300,000 at puberty. Through the reproductive years the remaining eggs are lost, with the rate accelerating around the mid-30s, resulting in few eggs left at menopause, around age 50-52. The number of eggs available for reproduction at a certain age is the ovarian reserve, which is the target of the diagnostic tests described here.

Age is the most accurate predictor of egg health, but within age groups, there is considerable variation in the number of eggs remaining for reproduction. Age alone as a predictor of ovarian reserve is not sufficient, since, for individuals, fertility may be better or worse than the average for that age. Extreme examples of this variability include the teenager in menopause and the 59 year-old that delivered a natural pregnancy in 1997. This variability in pregnancy rates within an age group is present in all reproductive age groups.

To predict an individual woman’s fertility rate, in addition to her age, both clinical and laboratory methods are available to evaluate ovarian reserve. The best tests are direct measures of the ovary, such as the Antral Follicle Count (AFC) and Anti-mullerian Hormone (AMH) level; indirect measures, such as clinical history and levels of pituitary hormones, are common tools for prediction of ovarian reserve.

The simplest method of predicting fertility rates is clinical history, of both the individual and her closely related family. The number of months spent attempting to conceive predicts fertility. A couple that has been trying for some time will naturally have a lower fertility rate than a woman that has not had unprotected intercourse. Response to ovarian stimulation can also be used as a marker, as it is fairly consistent between cycles. Family history, i.e., the fertility of the woman’s mother or sisters reflected in age at menopause and age at conception are useful predictors. Such factors from clinical history can help define the risk of a problem with ovarian reserve.

Ultrasound is a useful tool for predicting ovarian reserve, as in measuring the Antral Follicle Count (AFC). Antral follicles are the smaller follicles, visible on ultrasound, between 2 and 10 mm, that are lost as a woman ages. In younger women, the AFC is 10-20, declining by 5% per year through age 37, and then accelerating to a loss of 10% per year thereafter. Women show a fairly consistent AFC loss rate of one follicle every two years.

AFC predicts the response to ovarian stimulation at least as well as blood tests, but its ability to predict pregnancy outcomes is limited, particularly when low. A woman with a higher AFC will show a better response to fertility drug treatments. A high AFC seems to predict pregnancy rates, but data remains limited, as there are no prospective studies published. A low AFC seems to be a less accurate predictor of ovarian reserve, particularly in older age groups. AFC may help predict outcomes, but should not be used to exclude patients from treatment.

Anti-mullerian hormone (AMH) is a blood test that directly measures ovarian reserve. Produced directly by early stage ovarian follicles, high levels (over 1.0) are favorable, while low levels (less than 1.0) indicate decreased ovarian reserve. AMH may be the best measure of the menopausal transition and ovarian age. It may also be useful in predicting ovarian hyperstimulation syndrome, the effects of chemotherapy, and in determining the treatment of PCOS.

AMH seems a superior predictor of ovarian response compared to other markers, including age, and day 3 FSH and estradiol. It offers similar predictive value compared to AFC. AMH can be drawn at any time in the menstrual cycle, and is not affected by hormonal therapy, including oral contraceptives.

AMH still requires further study. The range of normal variation is still being determined, and the true predictive value of the test requires a great deal more analysis. The specific range of reliability and predictive value by age is yet to be established.

Cycle day three FSH and estradiol, and, to a lesser extent, the clomiphene challenge test, remain viable tests for estimating ovarian reserve. These tests are established as predictors of response to ovarian stimulation. Prediction of pregnancy rates is more difficult. Recent studies concentrating on the predictive value of these tests have shown that they cannot be used to determine which patients cannot conceive, but are useful for screening and counseling.

All in all, these tests are only rough predictors of ovarian reserve. They are moderately good predictors of ovarian response to stimulation, and relatively poor predictors of pregnancy outcome. In a particular patient, the tests can be used to counsel about potential response to ovulation induction, but it remains difficult to predict pregnancy outcome based on the test results.

The ultimate test of ovarian reserve is response to treatment and whether a pregnancy results from that treatment. Stay tuned as we evaluate further research to establish the validity of ovarian reserve testing methods.