Before I go on, I must preface everything that I am about to say with the statement that the choice we made in having this child is not necessarily the right choice for other families. It was our choice and the right one for us; however, every CAH family has to make this decision for themselves according to their cultural and religious beliefs as well as what is most comfortable for them. Therefore, I offer our story merely as another alternative for every CAH family’s consideration.

It had always been my husband’s and my 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 cost of CAH, we were not comfortable with consciously bringing another child with CAH into the world without doing everything we possibly could do to avoid this for any of our other children, especially if we were to have a girl. In discussing this with our pediatric endocrinologist, he suggested we contact Cornell University’s New York Presbyterian Hospital to learn more about genetic testing and prenatal treatment options.

From Ann Carlson at Cornell, we learned that DNA testing for CAH is available and in 95-percent of cases they are able to identify mutation(s) that result in CAH. In other words, if we sent them some of our blood, they would look at our DNA – specifically Chromosome No. 6 – and hopefully find the mutation(s) that caused our son’s CAH. Moreover, if Cornell were able to identify the mutation(s) then prenatal diagnosis would be possible for us. In any case, if we were considering another pregnancy, Ann suggested, our first step should be to meet with a genetic counselor. She gave us the names of a few such counselors in our area and our journey began.

Over the course of the next two years, we engaged in extensive pre-conception counseling to learn about our options for another child. Our genetic counselor presented us with the following:

• Not having another child
• Adoption
• Gamete donation: using the egg or sperm of someone other than my husband or myself
• Spinning of sperm: separating the boys from the girls and then choosing "male" sperm
• Prenatal treatment with Dexamethasone
• Pre-implantation genetic diagnosis

However, research at Cornell was showing this prenatal Dexamethasone treatment to be highly effective and generally safe.

Prenatal treatment with Dexmethasone clearly was an option for us. We might still have a CAH child, but at least we could do something to minimize the in-utero effects of CAH on a baby girl. However, upon learning more about Pre-implantation Genetic Diagnosis (PGD), we knew it was the way for us to go.

Our first real conversation about PGD was a telephone conference as set up by our genetic counselor with a molecular bio-chemist at Wayne State University in Detriot, Dr. Mark Hughes. Over the course of 45-minutes or so, he explained what is PGD, how it is achieved, and how it could help us to give birth to a non-CAH child.

PGD is a medical technique whereby embryos can be screened for specific genetic defects prior to transfer to the womb. It has been being done 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 a CAH child from 25-percent to less than two-percent.

A PGD cycle begins with in-vitro fertilization (IVF). This involves inducing ovulation through maternal intake of hormones, the harvesting of eggs, and the fertilization of those eggs in a culture dish. On Day 3 after retrieval, when the embryo is eight-cells or so in size, a single cell is biopsied from each embryo. These cells then are sent to Detriot where Dr. Hughes tests the single cell from each embryo for the genetic defect in question. From biopsy to diagnosis would take approximately 48 hours. In the meantime, our embryos would be sitting in their petri-dishes at the fertility center growing.

PGD can be done for any number of diseases including CAH. The only pre-condition to undergoing PGD is that the specific DNA mutation(s) that cause the disease must be known. As Dr. Hughes explained it to us, the genetic code of each of our DNA is made up of 3.3 billion "genetic letters." Sometimes, these letters or even entire paragraphs or volumes of these letters get moved around, duplicated or deleted. When this happens a genetic mutation occurs. If the mutation carried by prospective parents is known, then Dr. Hughes could test the DNA of an embryo for the same mutation simply by comparing sequences of genetic letters.

The goal? By the end of Day 5 to have at least one and hopefully two or three high-quality embryos that were either unaffected by CAH or carriers of CAH for transfer. These then would be moved from the lab to my uterus. From there, based on the fact that we have no known fertility problems and I would be 35 years of age at the time of delivery, we would have a 45-55-percent chance of having one or more embryos implant themselves in my uterine lining thereby achieving pregnancy.

"Would biopsying a cell from a Day 3 embryo cause damage?" we asked. After all, this meant removing one of only eight cells from the embryo. Dr. Hughes asked us to think about how identical twins are formed. At some point in the very early stages of development, an embryo splits in half, each half losing far more than a single cell, yet two fully formed babies result. Similarly, when a single cell is taken in the PGD process, the remaining cells merely "pick up the slack." He added, however, that it was very important that we be working with an IVF center with laboratory personnel practiced and skilled in this biopsy procedure. As we soon learned, no such center exists in our state; however, Dr. Hughes was able to provide us with the names of several IVF centers in our part of the United States that did have the proper staff and experience to take us through a PGD cycle.

cycle would cost approximately $20,000. PGD is not a procedure covered by most insurance companies; however, some will pay for it and others can be incited to do so. We were advised that if we were going to undergo a PGD cycle the insurance coverage approval process might be lengthy. If we could not wait for a final approval or denial to start our cycle, then we should plan on having to cover the full $22,800 ourselves; the majority of which is due in full in advance.

In other words, if Cornell could identify our CAH-causing genetic mutation(s), then not only was prenatal diagnosis possible but also pre-pregnancy diagnosis. PGD could reduce our risk of having a CAH child from 25-percent to less than two-percent. For us, this meant that PGD afforded us the best chance possible of giving birth to a healthy child.

We immediately had our blood drawn and sent it to Cornell. They performed their DNA test and found me to be the carrier of a heterozygous Exon 3 (8 basic pair deletion) mutation and my husband to carry a heterozygous Intron 2 (A or C to G) mutation. In short, we are carriers of CAH mutations and they are clearly identifiable; therefore, the "biomedical" path to PGD was clear.

As everyone we came in contact with while undergoing this process told us repeatedly, every PGD cycle is different. In all cases, however, it is a complicated, physically and emotionally intense, and relatively expensive procedure.

First and foremost, we had to face the fact that IVF is a prerequisite to PGD as a single cell cannot be biopsied from an embryo in-utero. Having no known fertility problems, undergoing the IVF portion of this process was a strange and often disquieting experience. It began with more genetic counseling. I explained that we had already undergone extensive genetic counseling, but the IVF center was insistent that we go through a session with their counselors. They also insisted that we do a comprehensive pre-cycle assessment including testing for sexually transmitted diseases, several ultrasounds and blood tests to determine my fertility status as well as complete analysis of my husband’s semen. Moreover, we had to send blood off to Dr. Hughes’ lab for him to create the probe that he would use to test our embryo samples. Finally, there were all sorts of forms to be read, filled out, signed and notarized.

At every step of the way, I worried that something else "wrong" with us might be found. I was now 35 as opposed to 31 like I was when my first son was conceived. In the interim had my eggs diminished in number significantly or become too old for conception or had my husband’s sperm been compromised in some way? Should we do the Tay-Sachs, Cystic Fibrosis, and other disorder testing just to be sure there is nothing else lurking in our genes? For some reason would Dr. Hughes be unable to create an effective probe? What do we want the IVF center to do with any embryos we do not transfer? If we freeze embryos – assuming we even have any to freeze – what do we want the IVF center to do with those embryos if we decide we do not want to keep paying for their cryopreservation? Would my irregular periods somehow keep us from starting a cycle?

The moment of greatest apprehension came, however, when we were told we would have to undergo not only IVF but also Intracytoplasmic Sperm Injection (ICSI). The form we were asked to sign indicated, "ICSI is a micromanipulation technique developed to help couples with severe male factor infertility…[It] involves precise maneuvers under the microscope to inject a living sperm directly into an egg to effect fertilization." In other words, my eggs would not simply be put in petri dishes with some of my husband’s sperm. Rather, a lab technician would examine my husband’s sperm and select individual ones, break the tails off them, and then inject one sperm into each egg.

"But we have no fertility problems, why would we need to do ICSI?" we asked. The purpose of this, we were told, was to avoid having more than one egg and one sperm’s DNA present in any sample sent to Dr. Hughes. In "normal" IVF conditions, it is possible for one sperm to penetrate and thereby fertilize the egg while others get stuck in the outer layers of the egg or onto the outside of a growing embryo. The presence of these "extra" sperm could interfere with Dr. Hughes’ analysis and therefore diagnosis.

general population…Babies with sex chromosome abnormalities can have a variety of symptoms, including but not limited to cardiac and other problems which may require surgery, behavioral and learning difficulties or infertility."

"Whoa!" I said. "No way. We have already done one in 15,000 [the statistical probability of having a CAH affected child]. The whole purpose of doing PGD is to reduce risk not increase it!" The genetic counselor stepped in. Explaining that the form was standard for all ICSI patients, she noted that recent data is revealing that the chromosomal problems generally show up in couples with "male factor" (low to zero sperm count/motility) infertility not couples like us with no known fertility problems. Bringing it all into perspective, she concluded, "By undergoing PGD and thereby reducing your risk of having a CAH affected child from 25 percent to less than two percent, your greatest risk of birth defects is due to your [my] age." We signed all the documents and moved on to reviewing IVF drug dosages, cycle schedules, and injection instructions.

Which IVF drugs one takes and the timing of their administration depends purely on each individual couple’s situation; therefore, I cannot say what your experience might be should you do IVF. In our case it was daily prenatal vitamins and baby aspirin and nearly three weeks of follicle stimulating hormones overlapped one week with an ovulation suppression drug for me. Then I took a single egg release trigger dose the night before our harvesting appointment. Throughout this hormonal therapy I was closely monitored as to my follicular development and reaction to the drugs via ultrasounds and blood tests. Once the embryos were transferred I also would take a uterine lining growth hormone. As for my husband, he took a single antibiotic dose the night before his sperm was needed and otherwise spent the cycle dealing with a semi-crazed woman on way too many hormones. While I did not experience sudden weight gain, I was exceedingly hungry while on these drugs, often felt heavy in the lower abdomen, and ran to the bathroom to empty my bladder constantly. Moreover, I was often queasy and not particularly pleasant to be around. It was all worth it though when 16 days after starting our cycle 15 eggs were retrieved.

The time period from retrieval to transfer was nerve-wracking. We had been forewarned by others who had undergone IVF that it was a roller coaster ride, and we had prepared ourselves for this experience both physically and emotionally well in advance. I had quit my job a month prior to the start of our cycle to remove all work related stress from my system. We had chosen an IVF center with extensive IVF and PGD experience in a location where we had a numerous family members to help us so as to reduce emotional and physical strain to a minimum. Moreover, we had spent hundreds of hours discussing our thoughts, feelings and beliefs about conception, life, birth; so as to be as clear and unified as possible when making decisions in the midst of the cycle. However, we still were not prepared for the "count down" as I called it – the race against nature and time to have unaffected viable embryos to transfer – and the inexplicable complexity of PGD.

We started with 15 eggs of which 12 achieved fertilization. All twelve were biopsied on Day 3 but really only ten of them were looking viable by Day 5 when we went in to the IVF center to hear the results of Dr. Hughes’ analysis and undergo embryonic transfer. We had spent the entire night before steeling ourselves for the momentous decisions we would have to make the next day; decisions that would have to be made within a matter of an hour or so. Would any of the "good looking" embryos be unaffected? If so, how many? How many would we ask to have transferred? Would we have any left over to freeze? Or would it turn out – as statistics predicted – half the fertilized eggs would be unviable…of those six 25 percent would be affected by CAH and another 18 percent would have ambiguous PGD results eliminating another three…and we would lose another few by the time we got to transfer day leaving us with nothing?

clear that to transfer embryos without an analysis was the same as throwing the genetic dice and conceiving naturally; so, we would not transfer without a diagnosis. But we had come this far and had viable embryos and now we might have to throw the entire cycle away because the PGD was not successful? We had no choice but to wait.

At 8:00 the next morning, our doctor at the IVF center called. She had PGD results for us: five affected, five unaffected and two carriers. Of the five unaffected, three looked good; the other two they considered poor choices for transfer. The two carriers were also candidates for transfer. In all cases, however, overnight the blastocysts had hatched – they had broken out of their protective zona pellucida shell - and rapidly were becoming too advanced in their development for transfer. As we had already agreed that "selective reduction," the removal of one or more fetuses from the womb to reduce the number of babies being carried, was out of the question for us and that we were perfectly happy with having twins, we decided to transfer the two good unaffected embryos and freeze the other unaffected and two carriers. From here on it was all up to Mother Nature and given our past history of becoming pregnant within a month of trying to conceive, we both were sure we were well on our way to a second and third child despite the statistical fact that we had only a 45 to 55-percent chance of achieving pregnancy.

Two weeks later, I had my blood draw and the next day we received a telephone call from the IVF center. My HCG levels were rising. My body was showing signs of pregnancy! I had my blood drawn again and continuing rising HCG levels confirmed what the IVF center called a "chemical pregnancy." We visited our obstetrician to get "visual" verification of pregnancy two weeks later. On the ultrasound we saw a heartbeat – "Yes!" – but only one. We asked the obstetrician to look again. No there’s only one. "It could not be hiding behind the one we see," I asked. No. As I had experienced no bleeding or cramping or any other signs of having lost one of the two, we were both surprisingly dismayed at this news. We were definitely pregnant but one of the two embryos had dissolved sometime between transfer and this first ultrasound. The uncertainty of it all suddenly hit home.

We abruptly became adverse to the idea of doing chorionic villi sampling (CVS) or amniocentesis to reconfirm Dr. Hughes’ diagnosis as well as anxiously awaited each and every ultrasound appointment so as to be sure the baby was indeed still there. In the end we did do CVS at 12 weeks – CVS can be done between 10 and 12 weeks allowing earlier detection of any problems with a fetus than amniocentisis which cannot be done before 15 weeks – as we had signed paperwork indicating that we would, but it was with great trepidation that we might be one of the one in 200 who suffer a spontaneous miscarriage therefrom.

The CVS results for Down’s Syndrome and other chromosomal abnormalities was presented to us shortly after the procedure. The baby’s chromosomes looked completely normal. It would take several weeks though for Cornell to complete their CAH analysis; so, we asked not to be told the sex of the baby until after Cornell’s report was in. In fact it was over a month before we received a call from the genetic counselor, "Great news! The baby is an unaffected carrier of the maternal mutation."

My heart stopped. We had transferred two unaffected embryos and froze the two that were carriers. Was Dr. Hughes or Cornell right? Or worse, were they both wrong? I had not taken dexamethasone as there was such a low probability of a misdiagnosis. What if the baby actually is a CAH-affected girl? We are too late to minimize or prevent virilization. I quickly asked to have the results along with the CVS analysis faxed to our home. Gender: Male. Even if they were both wrong and the baby was CAH-affected, we were definitely going through with the pregnancy. A pregnancy that was to end much sooner than we expected.

As it turns out, my placenta was low lying and anterior (in the front of the womb) and started to come apart in the fourth month of pregnancy; causing pre-term labor and the delivery of our baby boy at 31 weeks of gestation. These conflicting diagnoses became the center of attention and anxiety immediately thereafter as 17-hydroxyprogesterone levels are elevated in premature infants. Blood drawn at 60-hours after birth showed his 17OH-P to be 1841. Maybe too high; maybe not. We reran the test at 10 days of age: 382. It was going down and his electrolytes were looking really good, but we would have to do the 17OH-P again at one month of age.