ASRM 2011 Updates

In addition to the magical wonders of Disney, Orlando welcomed reproductive endocrinologists from around the world this October to attend the annual meeting of The American Society for Reproductive Medicine (ASRM).  Several members of Pacific Fertility Center were among the participants. 

Preimplantation Genetic Screening (PGS)

PGS was again a hot topic of discussion.  Multiple presentations showcased the recent technological advances in this field.  The ability to perform comprehensive chromosome analysis using microarray technology instead of the first generation method of FISH (fluorescent in situ hydridization), which could only test a selected number of chromosomes at a time, has increased the accuracy and the detection rate of embryonic aneuploidy (abnormal number of chromosomes).  Laboratory advances such as biopsy of the trophectoderm (the outer cell layer of a day 5 embryo) and vitrification (a method of rapid cooling of embryos that minimizes ice crystal formation) have further improved success.  As the result of the above-mentioned technical breakthroughs, we have seen a measurable increase in the pregnancy rate and a decrease in the miscarriage rate from IVF using PGS.  Additionally, two respected groups independently presented data supporting the use of PGS as a successful embryo selection tool to promote elective single embryo transfer (the process of transferring one embryo at a time into the uterus to reduce the risks of multiple gestation).  The pregnancy rates from a single PGS-selected euploid embryo were 58% and 60.7% compared to 42% and 40.7%, respectively, from a morphologically comparable but non-PGS-selected embryo.  Moreover, the miscarriage rates decreased to 6% and 6.3% from 12% and 12.5%, respectively.  The risk of multiple gestation was essentially eliminated (1-2% monozygotic twining).

We were excited to note the parallels between the data presented and our own work at PFC.  Several years ago, we made the commitment towards decreasing our multiple pregnancy rates by adopting a policy of encouraging elective single embryo transfer in qualified patients.  We have found that 24-chromosome aneuploidy screening (via informatics-based single nucleotide polymorphism microarray technology by Gene Security Network) of trophectoderm biopsy has significantly enhanced our ability to select the embryo with the best implantation potential.  Our improved vitrification program has also allowed us to reassure our patients that their unused embryos can be safely stored for future use, thus removing the pressure to transfer more embryos at one setting.  We are very proud of our success so far in achieving our goal as we are currently the number one ranked program in the nation of the fewest number of embryos transferred in donor cycles (1.4 embryos per fresh cycle) while maintaining a high pregnancy rate of 57% (of all programs with more than 20 donor cycles per year, 2009 SART).  For more details on our experience with single embryo transfer and its pregnancy rates, please read “What are my chances of having a baby from a single IVF cycle” by our embryologist, Erin Fischer, and laboratory director, Dr. Joe Conaghan, in this issue of Fertility Flash.

Fertility Preservation

Another interesting topic that deserves attention is fertility preservation using oocyte cryopreservation. Two centers with extensive experience in this area shared their outcome data from both methods of cryopreservation, slow freeze and vitrification.  A center in Atlanta vitrified over 2000 oocytes from donors with an average age of 26 years.  Of the 1772 oocytes rewarmed, 88% survived, 75% fertilized, and 51% resulted in viable cleavage stage (day 3) embryos.  Live birth rate per cryopreserved oocyte was 11%.  The other presentation by a group in New York reported their experience of rewarming 536 cryopreserved oocytes using both slow freeze and vitrification from non-donors with an average age of 32 years.  The overall live birth rate per rewarmed oocyte was 5.5%.  Study is ongoing to compare the efficacies of slow freeze and vitrification.     

PFC’s own data with vitrification of oocytes is comparable to, if not better than, the results presented at our national meeting by various groups across the US.  A 5-10% live birth rate per oocyte in women under the age of 35 years translates to a respectable chance of having a baby in the future from one to two treatment cycles in the present (10-20 oocytes can be expected to be cryopreserved per cycle).   As we further perfect our own techniques of vitrification, we will be increasingly more confident in our ability to offer young women with a viable option for future family planning in addition to embryo freezing and donor gametes.  Future research is needed to achieve the same type of success rates in older women.   

Participating at ASRM is always an educational experience.  We enjoyed sharing our own clinical and research endeavors with our colleagues across the US and all over the world.  Our position as the nation’s leader in many of the most cutting-edge technologies in our field is a validation of our commitment to excellence and to provide our patients with the highest quality care available.

PCRS Meeting Review

Pacific Fertility Center’s team directed the Pacific Coast Reproductive Society’s annual meeting in April this year.  Dr. Carolyn Givens was President of the Society and Dr. Joe Conaghan was Program Co-Chair at the meeting this year.  And what a meeting it was!

Optimizing success rates for patients was the focus, with presentations on “Improving Live Birth Rates”, videos on the importance of early embryo development, optimizing treatment protocols, and early embryo testing.  There were sessions on stress reduction, discussions on single embryo transfer, healthy debates between experts, and conversations about new advances that will improve patient care.

Alice Domar, Richard Tucker, Michael Alper and Richard Scott were among the luminaries presenting at the meeting.  Right alongside them was Joe Conaghan, Carolyn Givens, Lauri Black, and Paul Turek with matching skills and knowledge.  All were directed at improving care for our patients.

Pacific Coast Reproductive Society is one of the important professional organizations supporting fertility care.  Although they are a West Coast organization by title, Pacific Coast has developed national and international status in our field by focusing on the patients. As described on their website, “PCRS provides an outstanding forum for the exchange of information, and the advancement of the ideologies of reproductive medicine in a relaxed and collegial setting building relationships that foster the integration of current knowledge to ensure quality medical care for patients.”

Pacific Fertility Center is pleased to support Pacific Coast Reproductive Society.  We are looking forward to applying these advances, and already working on the new advances we will be talking about next year!

-Philip Chenette, M.D.

Pacific Coast Reproductive Society Highlights

One of the highlights of this year’s meeting was a talk by Sheryl Kingsberg, Ph.D., a Professor in the Dept. of Reproductive Biology and the Chief of the Division of Behavioral Medicine at Case Western University. Dr. Kingsberg’s area of expertise is in Human Sexuality and sexual disorders in women. She gave an excellent synopsis of “normal” sexuality in our culture and how we have come to view and define that norm. She also provided background on the physiology of sexual excitement and sexual response in women. She spoke about the different classifications of sexual disorders, which includes Hypo-active Sexual Desire Disorder (what we know as low libido), Sexual Aversion Disorder, Female Sexual Arousal Disorder, Female Orgasmic Disorder, and the Pain Disorders: Dyspareunia (painful intercourse) and Vaginismus (localized vaginal and vulvar pain).

Dr Kingsberg also covered the topic of sexual dysfunction and sexual function. One of the most valuable things she discussed was that doctors should use a sexual function checklist. Here is the checklist she presented:

Please answer the following questions about your overall sexual function in the past 3 months or more:

Please answer the following questions about your overall sexual function in the past 3 months or more:

1. Are you satisfied with your sexual function?
   • Yes
   • No              If no, please continue.
2. How long have you been dissatisfied with your sexual function?
3. The problem(s) with your sexual function is: (mark one or more):
   1. Problems with little or no interest in sex
   2. Problems with decreased genital sensation (feeling)
   3. Problems with decreased vaginal lubrication (dryness)
   4. Problems reaching orgasm
   5. Problems with pain during sex
   6. Other
4. Which problem is most bothersome?  Circle one: 1  2  3  4  5  6 
5. Would you like to talk about it with your doctor?
   • Yes
   • No

Many of us at the conference realized there is a need to identify and assist our fertility patients that also may be suffering from sexual dysfunction. We need to spend a few moments covering this topic with our patients. We will be considering how to add these types of questions to our current patient history forms. We want to identify the patients with sexual dysfunction in addition to fertility problems so we may assist them in finding the appropriate resources for treatment.

-Carolyn Givens, M.D.

Genetic Testing Breakthrough

Genetic screening techniques are a prime topic of research and dialogue in the IVF community.  We continue to seek techniques that are 1) accurate, 2) have quick turnaround times for results, and are 3) versatile enough to be able to give a breadth of testing results on one embryo, as well as 4) cost effective.

One of the exciting presentations at PCRS was by a firm called Gene Security Network (GSN), whose laboratory is in Redwood City, CA. GSN has been on the forefront of providing pre-implantation embryo genetic testing which is accurate, covers all 23 pairs of chromosomes including the sex chromosomes, and provides results within 24-48 hours post embryo biopsy (therefore negating the need to freeze embryos while waiting for the genetic results, as with the CGH technique). This technique, developed by GSN, is called Parental Support.

Parental Support is a new technology for Preimplantation Genetic Diagnosis (PGD) that tests all 24 chromosomes in a single cell from an embryo (called a blastomere) for a variety of genetic abnormalities. The test reliability typically exceeds 99% and results are returned within 24 hours in time for Day 5 embryo transfer.

Single gene mutations (such as cystic fibrosis) have been traditionally tested for as one genetic test only.  Dual testing, the ability to test for both single gene mutation and aneuploidy screening was not able to be done accurately or easily.  GSN has been working on this challenge of dual testing, and had just announced the birth of the first baby born after such dual screening—a healthy baby girl.

This announcement was also exciting for us, since the patient who is now a proud parent of a healthy baby, was a PFC patient.

We continue to collaborate with GSN on current and upcoming clinical trials, pushing the frontiers of genetic testing of embryos, and of diagnostic testing that promotes the creation of healthiest babies possible.

-Isabelle Ryan, M.D.

I had a case recently which demonstrated to me the utility of Gene Security Network’s (GSN) Microarray Chromosome Analysis with Parental Support.  A 40 year old patient had previously had a miscarriage and underwent a D&C procedure, complicated by her hemorrhage and appropriate vigorous curettage.  Following that procedure, her endometrial cavity appeared compromised with both filmy and dense adhesions found at a subsequent hysteroscopy.  Some of the adhesions were lysed but the question of the competency of her uterus remained.

She conceived again with fertility treatment but had a fetus that underwent demise between the 6 and the 7 week ultrasounds.  I really wanted to know if the pregnancy loss was due to her uterine compromise or due to fetal aneuploidy. 

We performed a suction D&C and the chorionic villi as well as a sample of maternal blood was sent to GSN for Microarray Chromosome Analysis evaluation.  The results of this testing indicated a fetal karyotype of 47,XX,+10 (Trisomy 10).  Unique to this testing, GSN was able to determine that the abnormality was of maternal origin.  Also, if the result had been 46,XX,GSN would have been able to definitively rule out maternal cell contamination (MCC). GSN provided me with a report in less than a week.

With this information, we knew we could proceed on without further treatment to her uterus.  We considered egg donation because it was likely this loss was due to the egg and subsequent embryo’s chromosomal non-disjunction and it was less likely to be a uterine issue.  GSN’s POC testing helped me guide this patient’s future treatment decisions.

-Carolyn Givens, M.D.

Having grown up in the Pacific Northwest, I have been a transplant to the Bay Area ever since starting graduate school in 1996.  I remained in the area for the fabulous professional opportunities.  It was here I met my husband and now am also blessed with a son.  I have always had a deep appreciation and love of nature.  Living in the Bay Area has allowed me to nurture this passion in the form of surfing, sailing and most recently snowshoeing.

I began my career as a practicing genetic counselor in the spring of 1998 when I accepted a position at the University of California San Francisco (UCSF) Medical Center in the Departments of Reproductive Genetics and Urology just prior to completing my graduate work at the University of California Berkeley’s Genetic Counseling Program.  It was my good fortune to begin my career with some of the most influential physicians in the field of reproductive medicine:  Eldon Schriock, Carolyn Givens, Isabelle Ryan and Paul Turek. In addition, I worked with Dr. Joe Conaghan to build the Preimplantation Genetic Diagnosis Program at UCSF.    These physicians moved from UCSF to PFC, and soon after I moved from UCSF to California Pacific Medical Center (CPMC).  I was able then to re-establish our collaborative efforts with the additional advantage of working with the experienced Drs. Carl Herbert and Philip Chenette. We have learned much from each other over the years and continue to foster wonderful professional and personal relationships. In December of 2010, I left CPMC to branch out into private practice.  I am thrilled to be working more closely with the providers and patients at PFC in my new role as an in-house genetic counselor. 

As a genetic counselor, I am a health care professional trained in human genetics and counseling. I have a Master of Science in Genetic Counseling and in 1999 was certified by the American Board of Genetic Counseling.  Genetic counselors practice in several subspecialty areas of genetics, including assisted reproduction technologies, infertility genetics, and prenatal diagnosis.  My job is to help you understand the complex information regarding your situation and enable you to make an informed decision as to what’s best for you. 

The most common reason your infertility doctor would refer you for a consultation is to discuss the testing of embryos.  There are two basic types of testing. Preimplantation genetic diagnosis (PGD) is the testing of embryos for a specific genetic disease known in the family.  Preimplantation genetic screening (PGS) is the testing of embryos for general chromosome abnormalities such as Down syndrome.

The two main objectives in a genetic consultation for PGD/S are  family history review and informed consent.  During the review of family history, I take at least a three generation family tree (pedigree) to identify any additional genetic risks.  This process helps to clarify the correct type of PGD/S being offered, as well as to identify any additional testing that might be appropriate.  Medical records may be requested for review if there is a significant family history or to document familial mutations for PGD. This part of the consultation is typically less time consuming.

The informed consent portion of the consult includes an in depth discussion of the PGD/S process, from beginning to end, and a review of the information in the consent form.  For those who have already had IVF treatment, some of this explanation may be familiar.  However, as complex as the process of IVF is, embryo testing adds yet another layer of complexity.  In addition to the steps in the IVF process, there are the biopsy procedures, the testing of a single or more cells for specific chromosome abnormalities, DNA markers, and/or gene mutations, and then the review of the PGD/S report results prior to embryo transfer.  My job is to guide you through this process mentally, prior to the actual cycle, so hopefully there are no unanticipated outcomes for you.  Even more critical is the consent form review before signing.  Consent forms are designed to inform and protect patients.  Important information is contained in the consent form, including risks and limitations of PGD/S, as well as the purpose of the procedure and the diagnostic technique.  The informed consent portion of the consultation is typically the more in depth part of the discussion and is intended to address all of your questions about this option prior to your cycle start. I am available to answer these questions and witness your signature.   The entire consultation usually lasts one and a half to two hours depending on the type of testing being discussed and the number of questions you have.

I also work with the PFC Egg Donor Agency to provide genetic risk assessment for all prospective ovum donors. The EDA has implemented this protocol to ensure that their donors have been screened in accordance to the American College of Obstetricians and Gynecologists guidelines. Any genetic risk from family history is addressed.  This screening is just one of the ways the EDA works to optimize your pregnancy outcome when using an ovum donor.

In addition, I am available on request to provide a genetic risk assessment for you, even if there is no embryo testing or ovum donor included in your treatment cycle.  Some of you may have questions concerning conditions in your families, and want to discuss what impact that history may have on your or your children’s future health.  Discuss these concerns with your infertility doctor, so they may determine whether a genetic risk assessment consultation is appropriate for you. 

I am grateful for the opportunity to work directly with PFC.  I wish all of you the best in your family building pursuits.

Most sincerely,

Lauri Black, MS, CGC

Certified Genetic Counselor

Our story began about 4 years ago, in all likelihood similar to those couples who ultimately end up seeking help from a fertility specialist.  I had just turned 36 years old and was very happily married.  My husband and I decided to put our triathlon ambitions to the side and start a family. We naively assumed after I stopped birth control pills, we would start trying and would conceive shortly after. After all, we were just in our mid 30s’ and had no underlying health issues.  Unfortunately, a few months later, I was still not having normal menstrual cycles.  But of even greater concern, we received the devastating news that both my husband and I were carriers of a rare form of muscular dystrophy, and our odds of having an affected child would be 25%. 

And so began our emotional and medical “journey”.  Through many conversations, my husband and I recognized that conceiving our own child was a dream that we were not yet ready to concede.  We also wanted to explore any possibility that would allow us to conceive an un-affected child after having seen how my niece’s life was affected by severe muscular dystrophy.  We realized that we would need to seek out the best fertility specialist possible, and thus we found our way to Dr. Givens at Pacific Fertility Center. 

As a physician myself, I had done extensive research on fertility specialists and centers and was hoping that Dr. Givens would be able to help us.  Her credentials were outstanding and were exactly what we sought – a fertility expert specializing in advanced maternal age/decreased ovarian reserve and in PGD (prenatal genetic diagnosis).  After our first meeting with her, I knew that we had made the right choice.  Dr. Givens was extremely knowledgeable, professional and most importantly caring.  She understood that this was a very challenging fertility case, but embraced the chance to help us rather than tell us we should look into adoption.

With Dr. Givens help we were able to set up PGD through a planned IVF cycle.  This treatment plan required a great deal of coordination between Dr. Givens, PFC’s dedicated staff and California Pacific Medical Center’s genetic counselor Laurie Black.  It required months of patience as we waited for “probes” to be built by the PGD center and for the IVF cycle timing to be optimized.  Unfortunately, our first PGD-IVF cycle ended in an early miscarriage.  Dr. Givens remained optimistic and with some changes in our stimulation IVF protocol and using acupuncture, my husband and I were able to conceive during our 2^nd PGD-IVF attempt. We were thrilled!! As the months went by and my belly grew, we became increasingly excited that we were indeed going to be able to have our own unaffected child! About 38 weeks later we gave birth to our beautiful healthy daughter – a gift that words cannot express, as I believe all parents can attest to.  The extreme gratitude that we felt for Dr. Given’s help, perseverance and care during this journey can not quite be expressed in words.  Without her expertise and belief in a successful outcome, we would never have been able to conceive a child.

Within 6 months of having delivered, my husband and I approached Dr. Givens and told her how happy we were as parents and how much we would love to attempt having a second child to complete our family.  We assumed that we would be able to conceive just as we had the first time, as I was only a little bit older.  Again, I was proven naïve.  I had not realized that even 1-2 years could affect my ovarian reserve as much as we soon discovered.  The stimulation protocol we had used with our first daughter’s conception, this time produced only ½ the amount of follicles and eggs.  The quality of the embryos was also clearly less. We attempted 3 additional cycles: a frozen cycle (we had one embryo left from our initial attempt) and 2 fresh cycles. Quite tragically, we felt, we lost the second conception at around 6 weeks and then lost a twin pregnancy at around 8 weeks. The loss of miscarriage is indescribable. We realized that from a financial standpoint, we would not be able to continue attempts at IVF indefinitely.

Again, Dr. Givens advice was instrumental in helping us through this difficult time.  She expressed concern that our miscarriages were from poor quality embryos (genetic trisomy/monosomy/etc) and not from my own inability to carry a pregnancy.  She recommended that we give consideration to doing full aneuploidy screening of our embryos in addition to PGD – something that had only recently been medically possible.  Thanks to her expertise and connections with other experts in the field, we were enrolled in a clinical trial with GSN.  They were able to build probes again for our specific muscular dystrophy mutation and offer aneuploidy testing on all of our embryos.  We subsequently did our last fresh IVF cycle, this time with both PGD and full aneuploidy screening. We had a total of 10 embryos and only 1 was identified as being unaffected and with a full set of chromosomes.  We prayed that this sole embryo would implant – quite skeptical admittedly given that only one was transferred and with our daughter’s conception we had put in more.  Our prayers were answered!  We are now 30 weeks pregnant and additional testing done via amniocentesis has confirmed all of the PGD/aneuploidy test results.  My husband, daughter and I are all eagerly awaiting the birth of our second daughter in early February.

I hope that our story helps those out there who may have felt any of the things we experienced in our journey to create a family.  I learned not only to “never give up” on a dream, but that being cared for by someone like Dr. Givens is the only way for such a dream to become a reality.

-Anonymous

Update: On January 27th, 2011, our patient, the fist at PFC to undergo embryo biopsy for both genetic disease risk and chromosome analysis, gave birth to a healthy baby girl.  She weighed in at 6 lbs., 6 oz. and was 19 3/4″ long.  Congratulations to everyone involved in this success story!

Andy and I married in June of 2008.  I was just turning 39 and we tried to conceive a child “the old fashioned way” for a year  before working with PFC. We didn’t expect it to be so difficult as all signs indicated that we would get pregnant.  Andy’s sperm was normal and my FSH was good.  When we moved to the IUI and IVF processes, I responded well to the drugs, produced lots of follicles and eggs, we had nice looking embryos, and we were able to do day 5 transfers.  The doctors seemed confident.  But over the course of about 15 months we experienced 2 rounds of IUI, 4 rounds of IVF, and 2 miscarriages. 

Now it is December 2010 and we’re nearing the end of a blissfully uneventful pregnancy.  Our baby boy is due to arrive on New Year’s Eve!  It looks like our story will have a happy ending, but I don’t need to tell you how difficult the journey has been.  Instead, I’m going to try to share a little bit about how we got through it all, in the hopes that it might give you some ideas or a new perspective for your own experience.

First, Andy and I knew we wanted to be parents. We absolutely knew it would happen for us, one way or another.  Although our first preference was to have “our own” child, it was only a preference.  We both knew that if IVF did not work out for us with my own eggs, we would go the route of an egg donor.  If necessary, we knew we would move to adoption.  Starting a family was our priority and our dream.  We believed that whatever baby came into our lives, that baby would undoubtedly be the baby we were meant to parent, and we would love our baby no matter what.  Have you ever heard the Buddhist saying, “Don’t be attached to any particular outcome”?  It became one of our mantras and allowed us to stay focused on the big picture plan, as opposed to the various routes or paths that might be part of that overall plan.

Teamwork was another essential element of our journey.  I’m lucky because Andy is very detail-oriented, patient, and he was completely on board with the program.  I’m more emotional. I have a short attention span, I like information in summary format, and I can manage a calendar like nobody’s business.  We make a great team because I could endure the shots and stay on top of all those doctor appointments, but keeping track of the drugs, the dosages, the ordering—that was all Andy.  At first, I worried that we would run out of a drug that we’d need, and we wouldn’t realize it until it was too late.  However, thinking like that made me nuts.  Soon we developed a system where Andy managed all the prescriptions and ordering, he prepped my needles with the right dosages, and he tracked what we were supposed to do each day.  I did my own injections and dealt with the side effects.  Those were our roles.  I didn’t want to have to think about the details.  By relying on Andy to “manage the minutia,” I was able to stay more relaxed and less stressed.

Finally, I had an epiphany that, in order for this process to be successful, I’d have to stop expecting infertility to somehow fit into my life.  I don’t know about you, but I was pretty overwhelmed by all we had on our plates.  At first, I was trying to squeeze in my appointments with PFC and with my fertility acupuncturist, while maintaining a calendar filled with dinners with friends, a busy work schedule, and a significant amount of travel. It’s no surprise that I was tired and stressed out, but I also became very resentful.  I was seeing a fertility acupuncturist on a weekly basis, yet I was annoyed that she recommended I take herbs and make changes to my diet.  I was frustrated as I tried to find time for all the appointments at PFC. Then, one night I was crying and sharing my frustrations with Andy, and he helped me see things differently.  He said that none of this was going to work if I didn’t fully embrace what we were doing.  I had to take the herbs with a positive attitude and whole-heartedly believe in the power of both eastern and western medicines.  Otherwise, what was the point in going through it all?  I realized that my bad attitude could have the power to neutralize all we were doing and I had to shift my mindset, accept that this was our path, and surrender to the process.  I created a big opening in my life so that there would be space for the infertility and all the energy it would take to tackle it.  I stopped traveling, dramatically reduced my social commitments, and spent much more time resting and “nesting” at home.  This was really difficult for me as an extrovert, but it became so much easier to make the right decisions and to more graciously accept what was required of me.

The last thing I would like to mention is that we were not secretive or private about our challenges with infertility.  I’m used to being pretty open with my friends, and I think it helped us to reach out to people for support during our ups and downs. One friend in particular, who had gone through her own IVF process, was reading some message boards online and found out about a new form of preimplantation genetic testing that she thought might be helpful to us.  We brought it up to Dr. Chenette and he was happy to give it a try since our prior IVF rounds produced seemingly good embryos, but failed to result in a viable pregnancy. So, on our 3^rd round of IVF, on day 3 we had 12 great looking embryos.  PFC biopsied all 12 and Gene Security Network ran a full analysis of all 23 sets of chromosomes.  On day 5 we showed up to transfer the best ones.  We were excited because we would know which embryos were genetically viable and which were not.  As we waited to see Dr. Givens, we wondered whether we would have 2 or 3 embryos to transfer.  But when Dr. Givens entered the procedure room, we could tell something was wrong.  We were told that all 12 of our embryos were genetically defective and none were viable for transfer.  Worse yet, because all of them possessed defects from the maternal chromosomes, it was recommended that we stop trying to conceive with my eggs and to think about alternative paths.  It seemed that this path had come to an end.  None of our embryos were good and there was no point in trying to make any more.  The news was devastating for us.

Andy and I went to a dark place for a few weeks.  But I’m happy to say that after talking and crying and praying about our situation, we came out of the darkness fully ready to embrace the process with an egg donor as soon as possible.  But first, we wanted to do the same preimplantation genetic testing on the 4 frozen embryos we had saved from our 2^nd round of IVF.  As expected, 3 of those embryos were genetically defective, just like the 12 from our 3^rd round of IVF.  But, we also experienced a miracle: one of those embryos was a genetically perfect boy.  He was my last hope to have a baby with my own genetic make-up.  Amazingly, he survived the freeze and the thaw, and survived the biopsy for the testing.  We transferred him in April and today I hit 37 weeks of pregnancy.  He is now considered full term and we are excited to meet him soon!

So, that’s our story.  I know we all have one.  Andy and I wish you the very best as you pursue parenthood and aim to build your family in whatever way makes sense for you. 

~Andy and Susan Nelson

Update:

“Our son was born on 12/30/10 at 12:20 am.  His name is Boden, he weighed 6 lbs. 15 oz. at birth, was 20” long, and is completely healthy.”

The field of Assisted Reproduction has always been one of rapidly evolving technologies, but nowhere more so than in the area of screening embryos. Screening is possible for not only genetic disease (PGD) and but also abnormal numbers of chromosomes (PGS). Along with the revolution in human DNA biotechnology, new companies such as Gene Security Network of Redwood City, California have emerged.  They are able to apply information from the Human Genome Project to the analysis of DNA from single human embryonic cells.

It is now possible to accurately diagnose most any human genetic disease in a pre-implantation human embryo. We do not even need to know the mutated sequence as long as there is DNA available from the parents that carry the mutation. By using what are called “linked markers”, we can make an analysis from the amplified DNA from a single embryonic cell and compare it to the parental DNA to determine the likelihood that any one embryo received mutated copies from either parent. This analysis is done at the time of an IVF cycle when the embryos are in the IVF laboratory. Affected embryos carrying mutations that may cause the disease, such as cystic fibrosis or muscular dystrophy, are not transplanted back into the mother’s uterus.

Until recently, a single embryonic cell could only be analyzed for either a mutated gene sequence using a limited number of markers (usually about 10) or for chromosome copy number (karyotype), but not both at the same time. In the last year, Gene Security Network has offered testing of DNA for BOTH genetic mutations (when parents are at risk for having affected offspring) AND for chromosome copy number to rule out Down Syndrome, Trisomy 18, or any other “aneuploidies” that can cause implantation failure or miscarriage. Both tests can be done on the amplified DNA from a single cell. Pacific Fertility Center has been participating in their pilot studies on this project and, due to the success of the initial group of patients PFC is now offering this type of testing routinely to couples that need this service. We welcome this change because it means we can now not only select unaffected embryos, but also have a fairly high confidence that the embryos we select for embryo transfer have normal chromosome copy numbers and will have a good chance of establishing a normal pregnancy.

Another area in which this DNA micro-array technology has found application is in the area of testing miscarriages for chromosome copy number. In the past, if we wanted to know if the reason a miscarriage had occurred was due to abnormal chromosomes, we had to do a D&C procedure, obtain placental DNA and send it to a cytogenetics lab. At the cytogenetics lab, the placental tissue had to be put into cell culture to try to capture dividing cells, which is the only way a karyotyping analysis could be performed. If the placental tissue contained no viable, living cells, the culture would fail and there would be no results. If the analysis revealed a 46 XX karyotype, we could not be sure that this was a normal female miscarried or if the cell culture was contaminated with maternal DNA. Now we can send the placental tissue with a sample of the mother’s blood, and the lab can tell if the DNA is maternal or not and the tissue does not need to be viable to get a result. This then allows us to determine if a pregnancy loss was due to abnormal fetal chromosomes, one of the most common causes of miscarriage.

There is no doubt that all of these new genetic technologies will continue to evolve over time, becoming even more rapid and accurate than they are today. It is exciting to be involved with applying the latest science and biotech has to offer to help solve clinical problems for our fertility patients.

-Carolyn Givens, M.D.

Since Pacific Fertility Center came into existence in November of 1999, we have been offering genetic pre-screening of IVF embryos for couples with recurrent miscar- riage, repeated IVF implantation failure and sex selection for family balancing. For most of the last decade, a technology known as Fluorescent In-Situ Hybridization, or FISH has been used to screen embryos. FISH is employed to probe a cell removed from a Day 3 embryo to determine the chromosomal makeup for anywhere from three to twelve of the cell’s 23 pairs of chromosomes. With time, we, as well as everyone else in the reproductive genetic world, came to realize the serious limitations of this technology.

In the last 2-3 years, as the Human Genome Project has been completed and as more DNA-related biotechnologies have emerged to evaluate human genes, these methods are being utilized to analyze human embryos. The technology now available—the ability to analyze large numbers of genetic locations on each human chromosome, and quantify that genetic material, with the previously well-established techniques to amplify a single cell’s genetic material up to hundreds of thousands of copies—has allowed PGS to take a quantum leap forward. It is now possible to more accurately analyze all 23 chromosome pairs from a single embryo; not only to determine if the correct number of copies of each chromosome is present, but also to look at single gene mutations.

At the end of 2009, Pacific Fertility Center began working with a new biotech company called Gene Security Network, located in Redwood City (genesecurity.net). This company uses gene microarray technology to analyze amplified DNA from a single cell.

It then uses microchips to analyze 30,000 genetic loci in a quantitative manner. In addition, their unique technology allows us to compare the analysis of the embryos’ cells to the parent’s chromosomes to ensure that all the genes are being properly analyzed. It does appear that the error problems that plagued FISH technology have been overcome with this new, more sophisticated, method.

In October of 2009, Dr. Conaghan and I were invited to tour the GSN laboratory and see the technology in action. We met with David Johnson, the lead scientist at GSN, who explained the cell process; from the amplification of the DNA, to arranging the chromosomes on chips, to DNA analysis, to synthesizing the data generated with the parental genetic data to come up with a full analysis of that cell’s genome. In order to process the cells between the day of embryo biopsy (Day 3) and receive the results on the day of embryo transfer (Day 5), their technicians work around the clock in shifts. GSN has a very cold, clean room to replicate the single cells into multiple copies. They cannot allow any outside contamination, not even from a single cell. They videotape the cell duplicating process so if any errors subsequently arise, they have a video record of what the laboratory technician did. We found this to be very impressive. We also saw how the chips were coated with DNA and analyzed. We were shown the sophisticated software that generates the final report detailing the genetic makeup of each embryo from the cells in which they originated. All in all, the tour gave us great confidence in the quality control and scientific integrity at GSN.

Even with this 21st century technology, we continue to biopsy Day 3 embryos because it provides us with a 48 hours window to send the cells to the lab and complete the analysis in time for transfer. However, we have not yet found a way around the problem of mosa- icism. GSN and microarray technology appears to have largely solved the resolution error problem but it can only tell us what is in the chromosomal make-up of the single cell. It cannot tell us whether or not that cell represents what is truly going on with the rest of the embryo. We are currently looking at the possibility of biopsying Day 5 embryos. The set back would result in having to freeze these embryos due to the time constraint in analyzing the genetic material in time for fresh transfer. With all of the innovation occurring daily in the genetics field, we hope that this puzzle will be resolved.

— Carolyn Givens, M.D.

Previous Fertility Flash articles about PGS:
2 Methods of Gaining Info Prior to Implantation
PGD & PGS: Why Genetic Counseling is a Prerequisite
The Benefits and Pitfalls of PGS

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.

For patient(s) who need to use an egg donor to create or expand their family, medical scrutiny is performed on the chosen egg donor before she can proceed with the IVF cycle.

The medical screening of egg donors is an important process. Here at the PFC Egg Donor Agency, we proceed with an extensive screening process PRIOR to allowing the egg donor to become eligible for choosing by the intended parent(s). This extensive screening is performed to help determine and identify any medical factors which may disqualify the donor, or to identify information which may require additional testing prior to determining donor eligibility. At PFC, our philosophy is that we want to identify any issues prior to intended parents choosing the donor, so that the risk of identifying medical issues with the donor after the start of the IVF cycle is minimized, and the risk of canceling the cycle is much reduced.

Medical screening for the donor includes an extensive review of her personal and family medical history, physical exam and pelvic ultrasound, psychological evaluation (in-person visit with our MFT Peggy Orlin),

standardized personality assessment (PAI), and blood testing including ethnic appropriate genetic testing.

The PFC Egg Donor Agency complies with current recommendations by the American College of Obstetrics and Gynecology (ACOG), and the American College of Medical Genetics (ACMG). The donor identifies her ethnic background, and based on this information, appropriate testing is performed (see article by Lauri Black, Genetic Counselor, outlining current recommendations). This testing is done and results reviewed prior to approving the egg donor as eligible to be in the donor database. If the donor is a carrier for a genetic mutation, this may disqualify her from being an egg donor; some genetic mutations may not be disqualifying, but the sperm source may need to be screened for that mutation, prior to deciding to choose that egg donor. These tested mutations are for recessive disorders, so an embryo would only be at risk of having the disorder if BOTH the egg and sperm source were carriers for the identified mutation (see above noted article).

It is important to understand that new genetic mutations are identified almost every day; so recommendations for ethnic-based testing do potentially change year by year. While many genetic mutations have been identified on the human genome, many of these are very rare, and only mutations that are more frequently seen within one’s ethnic group are those that are recommended to be tested for. It is not appropriate, nor feasible, to check for all known possible mutations. The PFC Egg Donor Agency is kept apprised of current recommendation by our affiliated genetic counselors, so that our list of genetic screening tests may change over time. Rest assured that we keep informed of these changes, and comply with up-to-date recommendations.

While all this testing may seem cumbersome, it is to help assure that once you choose your egg donor, we can proceed with the IVF cycle with minimal risk of a cancellation, and start you on your way to achieve your dream of a healthy family.