I am very excited because this is my first blog entry. The world of social networking and blogging is new to me and I really like new things. That is why the field of assisted reproductive medicine is so fascinating. There is still so much to learn about human reproduction and we are finally getting the tools to crack open this black box. I’ve given a lot of thought as to what I’d like to accomplish with this blog. Pacific Fertility Center already has a very informative website and we do a good job covering scientific topics related to fertility very well in our Fertility Flash newsletter. So I think in this blog, I’d really like to focus on the day-to-day happenings in the Center. I’d like to give followers a picture of the goings-on in the office and what kind of daily challenges we face as we try to provide the absolute best technology and personalized care to our patients as they go through the infertility treatment process. Of course, readers, your feedback will be very important and I hope to address your comments as I present a day in the life of PFC….

Today all 5 doctors are in the office seeing patients. It’s a bit of a slow day in the Procedure Area and IVF Lab – only one egg retrieval and two embryo transfers are planned. We usually have about 4-6 egg retrievals and as many embryo transfer procedures but we do these procedures 7 days a week, 365 days a year, so anything can happen on any given day. Some days are crazy busy and some days, we can all take a collective breath and re-energize. For me as well, it’s also a slow day, which is giving me time to write this entry. I have 7 ultrasound appointments, one IUI (intrauterine insemination), one follow up in-person consultation and 6 scheduled telephone consultations.
We do free telephone calls and it really works out well for both patients and for us. We like to stay connected with our patients by phone and e-mail so their questions and problems can be addressed fairly immediately. We are having to transition away from standard e-mail to a new communication system because although we have a secure server, it’s still not really compliant with federal guidelines on privacy. So very shortly, we’ll be moving to a new system in our new EMR (electronic medical record) which will use a web-based patient portal through which we can have dialog and share lab results with our current patients.
We also have a two hour meeting amongst the 5 physicians and our Executive Director. We are going to be discussing changes in our protocol for our acupuncture in IVF study and also a potential opportunity to set up a collaboration to bring patients from China to PFC for IVF.

See article about fertility problems in China.

So, a bit of a slow day at the Center for my first blog entry but hopefully, there will be more exciting stuff to report on in the days to come. Stay tuned!

Carolyn Givens, M.D. was the first in San Francisco to successfully initiate a pregnancy using intracytoplasmic sperm injection (ICSI). She currently co-directs the Bay Area Pre-Implantation Genetic Diagnosis Program (PGD) and is director of PFC’s PGD program.

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.

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

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—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

– Karen Volpe, Director of Nursing

R.N., Karen Volpe, Director of Nursing has been a Registered Nurse since 1979. She started working in the hospital operating Room and first worked in the IVF clinic in 1986. Karen set up one of the earliest clinic based procedure suites. She became the Director of Nursing at PFC in 1999.

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.

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.

— Philip Chenette, M.D.

Microarray Preimplantation Diagnosis (MA-PGD) created much excitement and interest at three recent meetings attended by Dr. Schriock; Pacific Coast Reproductive Society, The Midwest Reproductive Symposium, and the IVF Comprehensive Update.

PGD is a technique used to diagnosis genetic disorders by performing a biopsy of the embryo on day 3 or 5. PGD can diagnose single gene or chromosomal defects. PFC has been doing embryo biopsy for over 10 years. During this time the major method of diagnosing chromosomal disorders has been fluorescent in situ hybridization, FISH. FISH uses a fluorescent color to label individual chromosomes. This technique lacks accuracy and is now seldom used to screen embryos for the presence of missing or extra chromosomes. (refer to Fertility Flash Vol. 5 Issue 2). This technique, however, is still valid for identifying the gender of the embryo. MA-PGD uses a new technology, Single Nucleotide Polymorphisms (SNPs). SNPs are single bases, the building blocks of DNA, which can be in a different sequence in different individuals. Six to ten million SNPs have been characterized. This is the technology used in DNA fingerprinting in criminal or forensic work. Compared to FISH, where only one color marker identifies the chromosome, SNPs havethousands of markers per chromosome.

FISH can only identify 8-12 of the 24 unique chromosomes; MA-PGD will identify all 24 chromosomes, similar to amniocentesis. Identifying both single gene defects and chromosome abnormalities from one embryo cell was not possible with the older techniques, but can be done with MA-PGD. MA-PGD will identify whether the abnormal chromosome came from the mother or father. If from the mother, it will determine if the error was in meiosis I or II, or mitosis. In other words, it can identify in which stage of early cell division the genetic error occurred. Using MA-PGD, it may be possible to determine which embryo produced the baby when more than one embryo is transferred. The most important advance, however, will be the accuracy of the result. New research using MA-PGD shows that FISH is inaccurate over 40% of the time. MA-PGD appears to be nearly 100% accurate in diagnosing abnormal embryos.

This new technology is also helping to answer scientific questions. 50 – 70% of embryos with one missing or extra chromosome still develop to a healthy-looking day 5 blastocyst. This helps explain why beautiful blastocysts do not always turn into healthy pregnancies. MA-PGD will also raise new questions: Only 55% of chromosomally normal embryos turn into successful pregnancies in 30-year-olds, only 25% in 40-year-olds. Why do these embryos with a normal number of chromosomes fail? There is more to the embryo than chromosomes and more research is needed to determine what factors allow an embryo to develop into a healthy baby. Current areas of investigation include RNA production (transcriptomics), protein production (proteomics), and metabolic by products (metabolomics).

We will continue to update readers on PFC’s experience with MA-PGD in future Fertility Flash issues.

— Eldon Schriock, M.D.

Eldon Schriock, M.D. has been at the forefront of A.R.T. since 1981 and was a member of the medical team that performed the first IVF treatment in Northern California. In addition, Dr. Schriock is keenly attuned to the psychological repercussions of those undergoing A.R.T. treatments.