Welcome to your newly designed January issue of Connections, The American Fertility Association’s monthly e-newsletter. In this issue, you’ll find:

1. A Message from the Executive Director
2. Exciting new changes within The AFA - Press Release
3. Recurrent Pregnancy Loss: Is PGD the Answer?
4. Adoption Option - What Is Adoption Really Like?
5. Support Services
   1. Free Teleconference Coaching Sessions
   2. West Coast Programs
6. Stay Connected

Sponsored Links

BostonIVF - We Care for You
Most experienced & successful specialists - over 20,000 babies
www.bostonivf.com

Expert Fertility Therapy
Schraft's, A Walgreens Specialty Pharmacy
Phone: 800-876-4545
www.schrafts.com

Anonymous Egg Donation
Shared Donor with 100% Refund Option significantly reduces cycle costs.
www.shadygrovefertility.com

Yoga for Fertility
Reconnect to your body. Build energy/relax/renew
Yoga4Fertility.com

Interested in seeing your link here?
Please contact Corey Whelan, Director of Development at 718-853-1411 or Corey@theafa.org

A Message from the Executive Director

Pamela Madsen

Dear Friend of The AFA, Don’t know about you, but I’m getting winded trying to keep up with the rapid-fire changes and transitions reshaping the world at large and our own AFA community. Since the New Year roared in, I haven’t picked up a paper, surfed the net or turned on the tube without being bombarded with news about and controversy over reproductive medicine, fertility, eggs, embryos and sex. I mean these are The AFA’s core issues. Just this past week, the House of Representatives cast a solid majority vote in favor of federal funding of embryonic stem cell research, setting the stage for a brutal ideological and political battle with the Bush Administration. There weren’t enough yea votes to overturn an expected presidential veto, but enough to mark the beginning welcome sea change in Congressional attitudes. Immediately my phone started ringing off the hook with calls from reporters wanting to know what this would mean for the hundreds of thousands frozen embryos that belong to The AFA community. I told USA Today what I told countless reporters, federal regulators and members of the President’s Bioethics Commission—we are 100% behind the right of the people who created these embryos to donate them to this vital area of scientific research, if they so choose. Period. In the nanosecond it took to hang up the phone and turn on the Today Show, I was stunned to watch a segment about The Abraham Center of Life, a business that boasts the “first human embryo bank.” As I listened, my stomach lurched. This was a flat-out commercial venture: generating, storing and merchandising embryos for willing buyers. It infuriated me given that in excess of 400,000 embryos are already in storage precisely because disposition is such an emotionally and ethically thorny problem. It smacked of callous disregard for the lightening rod the issue has become in the “moral” debates about reproductive medicine around the country. (For a full discussion, read over our embryo disposition fact sheet posted on our site, www.theafa.org.) We’re all for people who want children to create embryos for their own use. But this? This crossed the line. We simply cannot abide any institution selling commercially produced embryos. Frankly, the demand for Abraham’s offerings has been slim so far. But the FDA has its own concerns and launched an investigation. Believe it or not, in the same week, I watched another Today Show segment discussing what every woman and man needs to know about preconception health care and the best ways to get pregnant. It was kind of gratifying since fertility preservation, safe sexual practices and reproductive health are among The AFA’s longest standing educational projects. And the capper? I’m working with staff and our board, ramping up our education initiative on the importance of sexual intimacy and pleasure, especially for couples dealing with reproductive problems. And again, the Today Show, in happy synchronicity weighed in with a tour of Toys in Babeland, an upscale sex paraphernalia emporium, while explaining to millions of Americans how to rekindle the intimate connection between partners. Like I said, the news vibrated with issues that The AFA has made the foundation of our expanded mission. Which brings me to the big news inside our own organization. We are proud and honored to welcome three new members on to the board: Drs. William Schoolcraft, Jamie Grifo and Richard Paulson. Each one is on the cutting edge of the continuing revolution in assisted reproduction and reproductive health. We are especially gratified that Dr. Schoolcraft will serve as our Medical Director and Dr. Grifo as our Scientific director. To learn more about these extraordinary men, please read on in this issue of Connections. At the same time, we bid a fond adieu to Drs. Owen Davis and Richard Scott who, respectively, served as The AFA’s first Medical and Scientific Directors. These two giants in the field of assisted reproduction generously helped us blaze a trail for a new model of patient advocacy and education. We’re eternally grateful. These remarkable additions to our board underscore The AFA’s vitality as responsive and forward-thinking group that anticipates the needs of our growing membership. We know that reproductive health and wellness encompass so much more than contraception and a PAP test. These day’s we’re talking about sexual health, wellness and, yes, even pleasure. We’re talking about how to teach young people to protect their fertility through safe sexual practices. We’re even talking about the real likelihood of women able to genuinely control their biological clocks through egg freezing. While we grapple with the ethical and moral issues of embryo freezing and stem cell research, we’re still moving hard on the most basic matters of access to safe and sound preconception health care and education people about conception. And let’s not forget we’re also supporting people who are overcoming tremendous obstacles—whether they’re physical or social in nature -- in their desire to have a child. So read on to find out about our special educational online seminar with the two authors of a much-heralded book about adoption. Check out the article on PGD and recurrent miscarriage. Look for the schedule for The AFA’s telephone support groups. Can’t wait to see what’s next. Whatever it is, we’re ready. Warm regards, Pamela Madsen Executive Director

Dr. Jamie Grifo

Dr. William Schoolcraft

Dr. Richard Paulson

####

[back to top]

Recurrent Pregnancy Loss: Is PGD the Answer?
By Serena H. Chen, MD

Serena Chen

Introduction

Preimplantation Genetic Diagnosis or PGD is an exciting new technology that can detect genetic abnormalities such as disease-causing mutations and chromosomal abnormalities to prevent the conception of abnormal pregnancies or children. PGD has made the headlines recently in some controversial cases, including the use of PGD to prevent transmission of adult-onset diseases such as Alzheimer’s; and the use of PGD to help conceive an HLA-matched child to donate bone marrow for a sibling with Fanconi’s anemia. However, what is even more exciting than these headline stories is that PGD may also be a very effective treatment option for women who suffer recurrent first trimester pregnancy loss, for women with a history of a chromosomally abnormal pregnancy, and for women with age-related infertility. PGD can be used to detect aneuploidy in a very young embryo, before the embryo attaches to the mother’s uterus. Aneuploidy is a condition in which an embryo has an abnormal number of chromosomes. Aneuploidy is the cause of 50 to 70% of first trimester miscarriages, down’s syndrome and other birth defects. By preventing the transfer of abnormal embryos, the risk for miscarriage and aneuploidy can be significantly reduced.

Dr Santiago Munne, PGD director at Reprogenetics and at IRMS at Saint Barnabas, reported the first use of PGD to detect aneuploidy and the first babies born after PGD in the early 1990’s. At this time, only a few centers have significant experience with this technique, but this technology is spreading rapidly and will likely become more routine within the next few years. This article reviews PGD and the Saint Barnabas experience with this technique.

How is PGD performed?

PGD requires the creation of embryos in the laboratory. Therefore, patients must undergo in vitro fertilization or IVF. This technique involves ovarian stimulation of multiple egg-containing follicles using injectable hormones called gonadotropins (Follistim, Gonal f, Pergonal, Repronex, etc). While the patient is under sedation or anesthesia, her eggs are retrieved through the vagina using a needle and ultrasound guidance to aspirate the eggs. The eggs are then inseminated with the husband’s sperm in the laboratory. Once fertilization occurs, embryos are allowed to grow in the laboratory for a total of 3 days after egg retrieval. After 3 days of culture, normal embryos will divide and should reach the 6 to 8 cell stage. At this stage of development, each cell has the potential to become an entire human being and removal of a single cell will not harm the embryo.

An embryo biopsy is performed by creating an opening in the zona pellucida, the “shell” around the embryo. A single cell from the embryo is removed through this opening using gentle suction and a micropipette (Figure 1). The procedure is performed using a special microscope with micromanipulators – special devices designed for delicate microscopic procedures. The cell is then fixed upon a slide and the embryos that have been biopsied are placed back into an incubator to await the results of the biopsy.

Figure 1.

Figure 2.

For the diagnosis of aneuploidy a technique called fluorescence in-situ hybridization (FISH) is used. This technique uses small pieces of DNA (probes) attached to fluorescent labels that bind to specific chromosomes in the cell. Once the probes are bound, the glow-in-the-dark signals are read under a fluorescent microscope, so that the number and type of chromosomes present in that cell can be determined (figure 2). The analysis takes approximately 1 day to accomplish. Embryos that are normal by the analysis are then transferred to the woman’s uterus on day 4 or 5 after the oocyte retrieval. Due to the limited amount of material being analyzed and the brief window of time in which to obtain a diagnosis, only 9 out of the 24 types of chromosomes can be analyzed. However, the chromosomes analyzed (13, 15, 16, 17, 18, 21, 22, X and Y) are those responsible for the majority of early pregnancy losses.

What are the results of PGD of aneuploidy?

PGD of aneuploidy can be used to reduce the chance of miscarriage. In a group of IVF patients at IRMS at Saint Barnabas, matched for maternal age, number of previous IVF cycles and response to fertility drugs, there was a significant 68% reduction in the rate of miscarriages in the group that underwent PGD compared to the group that did not (the control group). The control group experienced a 40% miscarriage rate while the PGD group experienced a 13% miscarriage rate.

Other benefits of PGD of aneuploidy: less Down’s syndrome, improved pregnancy rates and lower rates of high order multiple births.

The rate of Down’s syndrome and other abnormal pregnancies is also significantly reduced by PGD. In addition, in patients undergoing IVF, PGD for aneuploidy may improve the chance of conception by increasing embryo implantation rates. It is thought that PGD improves the process of selecting embryos for transfer, allowing embryologists to choose embryos most likely to result in a normal pregnancy. By improving embryo selection, and allowing fewer embryos to be transferred, PGD can also assist in reducing the frequency of high order multiple births after IVF.

What are the risks and limitations of PGD?

The risks of PGD include damage to the embryo during the biopsy procedure. Embryo damage is an “all or none” phenomena. If an embryo is damaged, it will stop growing. Embryos that continue to grow after the biopsy do not become abnormal as a result of the biopsy. The risk of embryo damage at our center is currently 0.9% but can vary widely depending upon the experience and skill of the person performing the biopsy. Embryo damage rates can be much higher in the hands of an inexperienced embryologist. If the embryo continues to grow after PGD, it will not sustain any injury and will not be at greater risk for miscarriage or for birth defects. In fact as stated above, if the results of the PGD are normal, these risks will be decreased.

As discussed earlier in this article, PGD of aneuploidy is currently limited to 9 out of the 24 types of chromosomes. An embryo that is deemed normal by PGD could have an abnormality in one of the other 15 types of chromosomes that were not analyzed by PGD. In addition, because the analysis is performed using FISH, the abnormalities that are detected are in chromosome number only. Other types of structural abnormalities, where the chromosome number may be correct, but the chromosome itself is abnormal, such as additions, deletions or translocations may not be detected as they would be in chorionic villus sampling (CVS) or amniocentesis. CVS and amniocentesis are tests that are performed on the fetus during early pregnancy.

Because hundreds of cells are analyzed, CVS and amniocentesis can detect conditions known as mosaicism, where some cells of the fetus are chromosomally normal and some cells are not. Since only a single cell is analyzed during PGD, mosaicism may lead to misdiagnosis. A mosaic embryo does not have the same chromosomal component for all cells, so that a single cell will not reflect the chromosomes of the entire embryo. Because of these limitations, the error rate for PGD for the chromosomes analyzed (including mosaics, false positive and false negative results) is approximately 7% at our center, while the error rate for CVS and amniocentesis is typically less than 1%. The error rate may vary between programs depending upon the experience of the personnel performing the PGD. Because of this difference in error rates, PGD cannot be considered a substitute for CVS or amniocentesis. The decision about whether or not to have CVS or amniocentesis should not be based upon whether or not PGD was performed. At this time, our center recommends that patients at high risk for abnormalities (such as patients who themselves have a chromosomal abnormality) have CVS or amniocentesis even if PGD has been performed. On the other hand, many couples who have experienced recurrent miscarriage would rather take the small risk of missing an abnormality because they did not have CVS or amniocentesis, rather than taking the small risk of losing a normal pregnancy due to complications from CVS or amniocentesis. Speaking with a genetics counselor who is familiar with PGD can be helpful in making this complex decision.

Which patients should have PGD?

Recurrent first trimester pregnancy loss

Recurrent pregnancy loss (defined as 3 or more consecutive miscarriages) affects approximately 1% of the population. However, after 2 consecutive miscarriages, it is reasonable to have a full evaluation and to consider treatment. The evaluation for recurrent miscarriage should rule out genetic, anatomic, endocrine, and immunologic causes for recurrent miscarriage. Many physicians will also rule out blood clotting disorders, although this testing remains controversial. The evaluation should be individualized, but typically includes history and physical exam, transvaginal pelvic sonogram, hysterosalpingogram or saline hysterosonogram, complete blood count, thyroid testing, antithyroid antibodies, prolactin, lupus anticoagulant, anticardiolipin and antiphosphostidylserine antibodies, karyotyping of both partners (blood chromosomal analysis) and possibly an endometrial biopsy and screening for blood clotting disorders.

Approximately 5 to 8% of couples with a history of recurrent pregnancy loss will have an abnormal karyotype or chromosomal abnormality, usually a balanced translocation. A balanced translocation means that all the normal chromosomal material is there in the right amounts (“balanced”), but it is arranged in an abnormal way (“translocated”) such that when the individual who carries the balanced translocation makes eggs or sperm, most of the eggs or sperm carry abnormal amounts of chromosomal material (are “unbalanced”). This can lead to infertility, miscarriage and birth defects depending upon the particular type of translocation. These couples can have an over 95% chance of miscarriage. PGD can be performed for couples with a balanced translocation, allowing them to implant only normal or chromosomally balanced embryos, thus dramatically reducing their risk of miscarriage (from over 95% to less than 10%). PGD for translocations is technically much more complicated than PGD of aneuploidy. Patients with a translocation should be seen by a genetics counselor to review their options. A referral for PGD at a center with experience performing this type of analysis can then be made if the couple desires it.

Once the evaluation is complete, many patients will not have an identifiable cause for their miscarriages and therefore, no obvious treatment options. Without any treatment, couples with this history have a 40 to 70% chance of a successful live birth, depending upon how many miscarriages they have had and whether they have any previous live births. Thus, doing nothing, with close follow up can be a reasonable option depending upon the couple’s preference. Some couples will feel more comfortable just having close follow up: very early, serial blood pregnancy testing; early, serial transvaginal sonograms; testing for estrogen and progesterone levels with hormone supplementation as needed. Many couples, once they know that their testing is normal will feel comfortable with this less aggressive approach. For couples that desire a more aggressive approach, IVF with PGD may be offered to significantly reduce the risk of first trimester loss due to aneuploidy. Ultimately, success rates will depend upon multiple factors including the experience and skill of the embryologist performing the biopsy, the experience and quality of the IVF laboratory and IVF program and individual patient characteristics such as maternal age and past medical history

Previous chromosomally abnormal child or pregnancy

For patients with a previous child or pregnancy with a chromosomal abnormality, PGD can reduce the risk of certain abnormalities in the patient’s next pregnancy. This may be an attractive alternative to post conception testing for patients as they may be able to avoid termination of an abnormal pregnancy.

Advanced maternal age

Figure 3.

As a woman ages, her risk for both miscarriage and chromosomally abnormal or aneuploid pregnancy increases markedly, and is the major reason why IVF success rates decline with increasing age of the female partner. The chance of embryo implantation after IVF is inversely correlated with the risk for aneuploidy. The higher the risk of aneuploidy, the lower the chance for pregnancy (Figure 3). By improving the ability to select embryos more likely to implant by eliminating embryos with some of the most common chromosomal abnormalities, PGD can improve implantation rates and ultimately live birth rates. Since the morphologic appearance of the embryo (the way the embryo looks under the microscope) is not an accurate reflection of the chromosomal make-up of the embryo, as a women ages, the ability of the embryologist to select the embryos most likely to implant decreases and the proportion of aneuploid embryos increases. So in older women, the beauty of the embryo, its “quality” or “grade” becomes disconnected from its ability to implant in the uterus. Often, it is the high quality embryos that are chromosomally abnormal, while the lower quality embryos are the ones that test normal. Without PGD, these lower quality embryos may not be the ones selected for transfer, if there are excess embryos available for transfer. For women 35 years of age and older undergoing IVF, our center has demonstrated that PGD for aneuploidy significantly improves pregnancy rates, reduces miscarriage rates and reduces trisomies if 6 or more embryos of good quality are available for analysis. This will not hold true at all centers, since the PGD pregnancy rate is a result of the individual patient characteristics, the PGD analysis, the skill and experience of the person performing the embryo biopsy and the overall success rates of the IVF program.

Summary

PGD of aneuploidy is a new and exciting technology that is becoming available at more IVF centers around the country. In order to undergo PGD, patients must conceive via in vitro fertilization. PGD of aneuploidy is a limited chromosomal analysis of early stage embryos prior to implantation. PGD of aneuploidy is an option for women with a history of recurrent first trimester loss that is unexplained or due to a chromosomal abnormality. PGD can significantly reduce miscarriage risk in these women. PGD may also improve pregnancy rates in women undergoing IVF. If a woman wants to consider PGD of aneuploidy, she should have a consultation with a genetics counselor for a more extensive discussion on the procedure and its limitations. The experience and skill of the person performing the biopsy, the experience and quality of the IVF laboratory and program and individual patient characteristics such as age and past medical history will all have an impact upon success rates. While PGD can have significant benefits, it is a limited genetic test and is not a substitute for CVS or amniocentesis.

Future Outlook

The technology is moving forward rapidly and in the near future, PGD will be able to evaluate all the chromosomes in a single cell. This will allow more accurate selection of embryos and will ultimately eliminate one of the biggest complications in IVF – multiple pregnancy - by allowing IVF programs to select and transfer the single embryo that is most likely to result in a healthy pregnancy.

Copyright Serena H. Chen, MD 2007
Director, Division of Reproductive Medicine
Director, Ovum Donation
Institute for Reproductive Medicine and Science (IRMS) at Saint Barnabas
94 Old Short Hills Road
Livingston, NJ 07039
Tel: 973 322 8286
FAX: 973 322 8890
Web sites: www.sbivf.com
www.serenachen.yourmd.com
Email: serenac@sbivf.com

[back to top]

Adoption Option

What Is Adoption Really Like? Ask Pamela Kruger and Jill Smolowe
By Carolyn Berger, LCSW

Carolyn Berger, LCSW

Jill Smolowe

Pamela Kruger

Please join The AFA on Wednesday, January 31st, 8 to 9 pm when our Online Educational Session features Pamela Kruger and Jill Smolowe, co-editors and contributors of the much talked about anthology A Love Like No Other: Stories From Adoptive Parents.

Kruger and Smolowe are not only the people who collected and edited this varied and reality steeped group of essays—they are also adoptive parents. It would be hard to find two people better equipped to tell us about adoption in all its brilliance and imperfection.

A Love Like No Other was praised by The Christian Science Monitor as “One of the most thoughtful books on adoption to come along in years, and by USA Today for its “gripping, rarely told tales.” The collection tackles head-on a variety of thorny issues—among them birth parents, race, cultural heritage, and family resistance to adoption. Kruger, a freelance writer and contributing editor at Child Magazine, and Smolowe, a People magazine senior writer and author of An Empty Lap, will discuss findings from their book—a rare glimpse into the issues that adoptive parents often discuss in private but rarely discuss in public. And, they will answer any and all questions from YOU, our online participants!

Can’t attend our Online Educational Session? Then go get a copy of this groundbreaking book! Each essay offers a vivid snapshot of a different aspect of adoptive parenting. And, because the writers explore their own feelings so honestly and express their ambivalence so bravely, they don’t stoop to offer advice or make pat generalizations about adoption.

“Post-Adoption Panic” by Melissa Fay Green is an especially powerful and poignant essay. Green shows how she struggles with an onslaught of doubts over having brought a four-year-old boy home from Bulgaria to join her husband and four kids by birth. After many sleepless nights she calls her adoption agency and whispers, “I don’t think I can do this. Is it possible to disrupt an adoption?” only to hear the voice on the other end respond, “Nobody’s ever asked me that before! Let me find somebody to ask.” Undone, Greene quickly hangs up the phone, believing her experience is somehow unacceptable.

But Greene learns that post-adoption depression is common among mothers of post-institutionalized children. She realizes that she, not her new son Jesse, is having difficulty bonding. (Jesse becomes enamored of Greene the moment she is introduced to him as “Mama”). Fortunately, Greene reaches out for help from her doctor and her friends and begins to allow herself to become Jesse’s mother by first pretending that she is his mother and treating him the way she treated her children by birth. Happily, Greene comes through this harrowing time—a time that might have been less harrowing had she been told about the realities of adopting older institutionalized children from other countries—as a parent who comes to deeply love the newest member of her family.

We who are adoptive parents or people considering adoption need many more books like A Love Like No Other. And we need to hear from many more people who have “been there” and aren’t afraid to tell their story honestly.

Please join us on January 31st for a conversation with Pamela Kruger and Jill Smolowe! Become part of the “adoptive parent-to-parent grapevine that has been silent too long.”

Carolyn Berger, LCSW
AFA Adoption Coordinator

[back to top]

Support Services

FREE TELECONFERENCE COACHING SESSIONS

Phone based tele-coaching groups provide a convenient way for you to take part in a supportive and educational group experience from the comfort of your home or work place. These groups meet for one hour via a phone bridgeline. A bridgeline allows all participants to hear and speak with each other via the telephone. No special phone is required. All groups are led by licensed mental health professionals with an expertise and often personal experience in infertility treatment and/or adoption.

TOPIC: Considering Adoption

This tele-coaching support group is for couples and individuals who are exploring the possibility and 'how to's" of building a family via adoption. During this 1 hour conference call you will have the opportunity to receive clear information regarding adoption practices and domestic/international adoption options, explore the myths and challenges of domestic and international adoption, consider which options may be right for you, and learn about the role of birthparents in the adoption process. You will receive professional and peer support as you consider and learn about the adoption option.

For further information, please contact:
Bob Bamman, LCSW - Email: BobBmmn@aol.com
Sara Barris, PsyD – Email: Sara Barris@aol.com

Bob Bamman, LCSW and Sara Barris, PsyD are trained AFA coaching group leaders, adoption specialists, and adoptive parents.

West Coast Programs

Four Seminars Offered

• EGG DONATION: WORKING WITH A THIRD PARTY
• CHOOSING SINGLE PARENTING
• CREATING A SUCCESSFUL SURROGATE ARRANGEMENT
• GAY AND LESBIAN PARENTING

The American Fertility Association is sponsoring separate discussion groups for patients considering alternative family building options. The emotional, medical and practical aspects of each of these arrangements will be explored, such that prospective parents can make an informed decision about whether these plans are the “right” choice for them.

Elaine R. Gordon, Ph.D. is a licensed clinical psychologist with a specialty in reproductive medicine. She has worked in the field for twenty years helping individuals and couples build families through non-traditional options. She is the author of “Mommy, Did I Grow in Your Tummy? Where some Babies Come From”.

Ellen Speyer, M.A., M.S., MFT. is a psychotherapist with twenty years with working with assisted reproduction, pregnancy loss, surrogacy, and adoption. She is a retired Chair of the Education Committee for the Mental Health Professional Group of the American Society for Reproductive Medicine.

[back to top]

Online Education Session Schedule—January - February 2007