We are the parents of a little boy with a rare, life-threatening, enzymatic disorder. He inherited this condition through genetic mutations passed along to him by us. Caused by a recessive genetic defect, neither of us is affected in anyway as we are simply “carriers” of this disease. Once we were determined to be carriers, however, we learned that should we conceive another child naturally, there is a 25-percent chance that we will have another affected child.

It had always been our plan to have more than one child. However, as we began to discuss the possibility of having a second baby, we both realized that given the physical, emotional and financial costs of being affected by this disorder, we were not comfortable with consciously bringing another child into the world without doing everything we possibly could do to avoid this for any other child.

Embryo Biopsy

After two years of extensive pre-conception counseling, we decided in-vitro fertilization (IVF) with pre-implantation genetic diagnosis (PGD) through Pacific Fertility Center would give us the best possible chance of giving birth to an unaffected child.

A medical technique whereby embryos can be screened for specific genetic defects prior to transfer to the womb, PGD has been performed for over 10 years and has proven to be a most effective method of diagnosing embryos for known genetic mutations. To-date there have been over 2500 PGDs performed around the world resulting in over 1600 children born without the disease for which they were screened. The error rate for PGD is less than two-percent; therefore, PGD would reduce our chance of having an affected child from 25% to less than 2%.

A little over a year ago we began our IVF with PGD Embryo Biopsy cycle. On Day 3 after retrieval, when our embryos were eight-cells or so in size, a single cell was biopsied from each embryo. These cells then were sent to a lab where the single cell from each embryo was tested for the genetic defect in question. We then transferred two embryos pre-determined to be unaffected by the disorder. In October of last year, we welcomed to the world our miraculous bundle of joy, an – unaffected – little boy.

– Name withheld upon request

Preimplantation genetic diagnosis (PGD) is a technique used to identify many inherited diseases. PGD uses DNA amplification to identify embryos with specific mutations of single genes, which may have been acquired from the mother, or father or both.

What PGD can do:
1. PGD can diagnose embryos at risk for some specific genetic diseases if the parent(s) are known to be carriers, and the molecular genetic basis of that disease is known.
2. PGD identification enables elimination of those embryos carrying the genetic mutation that causes the disease in question. It cannot repair those mutations.

What PGD cannot do:
1. PGD cannot guarantee that the baby will be free of all diseases or birth defects because the genetic basis for many defects is unknown. At this time, it is impractical or impossible to screen for most diseases, such as diabetes and cancer, or birth defects such as cleft lip and palate.
2. PGD cannot diagnose all diseases, even if the genetic basis is known, because some of the rarer diseases do not yet have available DNA probes.
3. PGD cannot determine traits, such as eye color, height, intellectual or athletic abilities.
4. PGD is not perfect, despite how sophisticated it is. Errors in diagnosis can occur, albeit at a very low rate. Confirmation of the correct diagnosis should be done by chorionic villus sampling (CVS) or amniocentesis, once the pregnancy is established.

The second type of genetic analysis is what we like to call Preimplantation Genetic Screening (PGS) to look for abnormalities in entire chromosomes missing or extra chromosomes or multiple complex abnormalities in chromosome numbers.

What PGS can do:
1. PGS can screen for abnormalities in 9 out of the 23 chromosome pairs. Currently it is not technically possible to screen for abnormalities in the other 14 chromosome pairs.
2. PGS can help to reduce the risks of miscarriage, commonly due to Monosomy X (one X chromosome) or Trisomy 16 (three of chromosome 16).
3. PGS can help to significantly decrease the risk of Down Syndrome (Trisomy 21) and Trisomy 18, as well as abnormalities in numbers of sex chromosomes (X and Y) (These are among the few abnormalities in fetuses that can survive to the time of amniocentesis and birth).
4. PGS can reduce the number of embryos one must transfer to find the embryos most likely to succeed.
5. PGS may help couples experiencing multiple IVF failures to determine if the failed implantations may be due to aneuploidy (chromosomal abnormalities).
6. PGS can determine the gender of the embryo.

What PGS cannot do:
1. PGS cannot screen for specific genetic diseases couples at risk need PGD.
2. PGS cannot guarantee that the baby will be free of all diseases or birth defects.
3. PGS is not perfect. The detection rate is between 90-93% for the chromosomes analyzed, which is why we still recommend CVS or amnio as a confirmation of PGS findings.

Couples who are at risk of passing on an inherited disease are probably familiar with genetic counselors. However, those who have decided to undergo IVF with Preimplantation Genetic Diagnosis (PGD) will need to see a genetic counselor who is specialized in the procedure of PGD itself. It is important to make sure that the mutation in question can be diagnosed by PGD since not all heritable diseases have DNA probes. And sometimes there are other means of using PGD to determine mutation likelihood.

In cases where there is concern about chromosomal abnormalities rather than single gene defects, Preimplantation Genetic Screening (PGS) is another option that requires a genetic counseling session. The genetic counselor can help patients understand the basics of chromosomes, how they affect the health of embryos and what this testing conveys about the embryos.

Some of the common reasons why patients undergo PGS include:
1. Age (eggs of women >35 years old have a higher risk for chromosome abnormalities),
2. Unexplained recurrent pregnancy loss,
3. Gender selection for genetic disease,
4. History of unexplained unsuccessful IVF cycles.

Who Are Genetic Counselors?
Genetic counselors are health care professionals with graduate degree training in genetics and counseling, and 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. Because your genetic counselor can see you to discuss PGD or PGS, as well as prenatal testing options once you are pregnant, you will receive continuity of care. He/she will help you understand the complex information involved in your PGS cycle, and encourage your own decision making according to your needs. He/she will also serve as a liaison between you, your fertility doctors, and the PGD/PGS laboratory.

What Happens During A Genetic Counseling Visit?
There are two main objectives:
1. Family History Review: Your genetic counselor will take a three generation family tree (pedigree) to identify any additional genetic risks. This process ensures that the type of screening being offered is correct, and to identify any additional testing needed. Medical records may be requested for review.
2. Informed Consent: Informed consent includes an in depth discussion of the PGD/PGS process, from beginning to end, and a review of the information in the consent form, which is designed to inform and protect patients. Important information contained in the consent form includes risks and limitations of PGD/PGS, as well as the purpose of the procedure and the diagnostic technique. Your genetic counselor is available to answer questions regarding its content and to help you thoroughly understand it before signing. For those who have already gone through IVF, the beginning of the IVF with PGD/PGS cycle will be familiar. However, as complex as IVF is, embryo testing adds yet another layer of complexity. Additional steps include biopsy procedures, screening of a single cell for specific chromosome abnormalities or DNA mutations, and reviewing the results prior to embryo transfer. Only a genetic counselor is especially trained to mentally guide you through this process before you are actually in cycle so that, hopefully, there are no unanticipated outcomes.

How Can I Find Out More?
Please contact the Certified Genetic Counselor working with Pacific Fertility Center: Lauri Black at (415) 600-6371.

– Carolyn Givens, MD and Lauri Black, MS, CGC contributed to this article

My husband and I were married for 6 years before we started trying to have a baby, and essentially got pregnant on the first attempt. Unfortunately, I miscarried in the second month. Our doctor told us not to worry; we tried again, got pregnant again, and miscarried early again. We still weren’t particularly worried, but had some tests performed and nothing in particular seemed to be inhibiting fertility. Over the next 5 years we went through phases of trying and not trying as we moved twice to accommodate dual careers, worked with 3 different fertility specialists in 2 states, negotiated a variety of insurance policies, endured the gamut of fertility tests, and suffered 3 more early miscarriages. Along the way I also struggled with mild depression, and guilt that perhaps the stress and travel associated with my job was the culprit, but we generally remained optimistic that we would someday have a baby.

Gradually we attempted more intense treatments, from Clomid to ovulation induction injections to intrauterine insemination (IUI). When our second IUI attempt failed last spring, our hopes really started to fade. I was 36, and while my husband and I are blessed with the resources to try several assisted fertility cycles, there were limits to what we could withstand financially and emotionally. Although I liked my doctor (a specialist at a teaching hospital), the support staff seemed to be in flux, the office environment had a high chaos factor, and I didn’t feel as though my particular case was significant to them.

On the recommendation of my primary care physician, I set up a consultation with Pacific Fertility Center and met with Dr. Ryan. I was immediately encouraged by the thorough review of my history and finally felt that someone was really listening to me, unfortunately this is not a given with all practices. After discussing a range of options it was crystal clear to me that we should try IVF with PGD, in order to screen the embryos (since we had experienced so many early miscarriages). We figured even if PGD told us that none of the embryos were viable, at least we would have valuable information about our next steps.

We embarked on a cycle of IVF this past winter, and with each successful step of the cycle, were amazed and encouraged. When the results of PGD came in we found that the majority of our embryos had a chromosomal abnormality, but several also appeared perfectly normal. We transferred 3 embryos, and I’m delighted to report that I’m now in the 5th month of my pregnancy (one baby, a boy, due in August). So 6 years after we began our quest for a baby we see the proverbial light at the end of the tunnel, and it is an amazing feeling. We can’t thank PFC enough for their combination of expertise and compassion. They restored our confidence and hope.

– Name withheld upon request

Several years ago I received a call that would change my life forever. My mother was diagnosed with Huntington’s Disease, an inherited neuropsychiatric disease that affects mind and body – (imagine Parkinson’s and Alzheimer’s combined). The chances of passing on the disease are 50/50, and symptoms usually appear between ages 35 and 50. Because there is no cure, many “at risk” for the disease choose not to learn if they have inherited the HD gene.

Living at risk with HD has altered my life completely. Every choice I make is influenced by the possibility I have inherited the HD gene. And no choice is more affected than that of bringing a child into the world.

As I grappled with my mother’s news, two facts became certain: I wanted children and I did not want to know if I would someday get HD. Given this, my husband and I sought advice on how to have a healthy baby. Our genetics counselor outlined two viable options: Once pregnant I could have a “non-disclosing” CVS that would indicate if the fetus had inherited the chromosome from either my mother or my father, thereby not revealing if I had HD. The second option was a cutting-edge process through IVF called pre-implantation genetic diagnosis (PGD). This involves testing each embryo for the HD gene at the cellular level when the blastocyst is only 5 days old. Only healthy embryos are implanted.

After having experienced a failed pregnancy, CVS had no appeal. That left IVF/PGD. Yet in order to maintain my status as a non-disclosing patient, I arranged NOT to be told any details throughout the IVF cycle. Even knowing how many eggs were harvested or how many embryos were implanted; I could surmise my status. (Imagine: if none of the embryos were healthy, my doctors would stage a fake embryo transfer so I wouldn’t suspect anything.) As such, it was important for all PFC doctors and staff not to reveal any information to me. Doing this meant putting total trust in everyone.

Trying to get pregnant through IVF is a costly endeavor: emotionally, physically and financially. I believed it would be easy because I had gotten pregnant so quickly before. Consequently, I was devastated when our first two attempts failed. In retrospect, I am amazed at how my husband and I endured, despite days when I had almost given up all hope.

After an exhausting six months and three attempts, I was finally pregnant. While overjoyed, I was still hesitant to believe it would go to term. Furthermore, I was required to have an amnio to ensure no errors were made, although given my non-disclosing status, I would not learn the results of that testing. It was only after my fifth month into pregnancy, that I believed I would have a healthy baby.

Our son is a miracle and my husband and I cherish him beyond belief. We are eternally grateful to the people who supported our choice to conceive a healthy baby using PGD.

–Patient’s name withheld upon request

PGD FISH (Fluorescent in situ hybridization) Photo: An embryo with normal chromosomes

We are looking here at the DNA from a cell taken from a human embryo. It has been stained green, and colored fluorescent probes have been applied, which are specific to individual chromosomes. This allows us to count the number of chromosomes and tell if the embryo is normal or not for those chromosomes tested. For the chromosomes that we are interested in counting, we should see 2 brightly colored spots, since we have 2 copies of each chromosome. In this picture, we see 2 red spots (= 2 copies of chromosome 13), 2 yellow (chromosome 22), 2 light blue (chromosome 18), 2 dark blue (chromosome 16) and 2 green (chromosome 21). This embryo has the correct number of these chromosomes. Note that one of the green spots and one of the yellows are very close together in the picture, but they are definitely there.

Q:
I am 40 years old and have been experiencing unexplained infertility for about 2 years. I have been reading that PGD may help to improve my chances of success with IVF. Is this true?

A:
PGD, or Pre-implantation Genetic Diagnosis is a technique, when used in combination with IVF, that can help to determine if the embryos have what it takes to successfully establish a pregnancy. As women get older, there are more errors in the chromosomal make-up of eggs. The most well-known of these defects is Down Syndrome or Trisomy 21, a condition in which the fetus or baby has an extra chromosome number 21. Having a missing or an extra chromosome may make the embryo unable to develop much past a few days of life or may result in a first trimester miscarriage. PGD uses a DNA-binding technique to determine if there are a correct number of chromosomes in the embryo. To do this, embryos on Day 3 of culture (5-10 cells) undergo a biopsy to remove a single cell. The rest of the embryo remains in culture in the IVF laboratory. The biopsy cell is analyzed for the correct number of chromosomes. Currently, PFC with its cytogenetic partner, St. Barnabas Medical Center, tests for 9 chromosome pairs which represent the most common abnormalities seen and some of the most serious in terms of a potential birth defect. As this technology continues to evolve, we expect to be able to assess all 23 pairs. IVF with PGD cannot correct defects in chromosomes. It can only diagnose whether an embryo is abnormal for these 9 chromosomes. The embryo could still be abnormal for one of the other 14 pairs. PGD may decrease the possibility of a miscarriage due to abnormal chromosomes. It may allow for the selection of the embryos most likely to implant and cause a normal pregnancy. If a woman has a good number of fertilized eggs to work with, it may eliminate having an excess number of embryos returned to the uterus at any one time and may eliminate having frozen embryos that really are not genetically normal. Because the embryos will have been screened for some of the major chromosomal abnormalities, theoretically, the remaining embryos should provide a patient who is older a better chance at a viable pregnancy. Some studies have shown that the implantation rates (chance that any one embryo will successfully implant) can be doubled with IVF/PGD. Also, miscarriage rates have been reduced by one-half and the delivered pregnancy rate is increased. Women or couples interested in this procedure should discuss it with their Reproductive Endocrinologist. At PFC, we also refer our PGD patients for a special genetic counseling session in preparation for this process.