While we were taking a break before proceeding with our first IVF cycle, (aka, my in-laws were visiting when I was ovulating) I saw a newly pregnant 38 year old. She delivered her first baby about two and a half years ago, and her obstetrician had automatically registered her for an amniocentesis due to her Advanced Maternal Age (AMA) status. I informed her that our group permits patients to make their own decisions if they want to pursue any diagnostic or screening options. I won't even offer a recommendation. My role is merely to provide information regarding her risks and the benefits and limitations of each test in order to guide her decision making process.
We spent a lot of time discussing the testing options during her visit and we exchanged several emails over the next few weeks. The new Non-Invasive Prenatal Testing (NIPT) can provide results as early as 11 weeks, it only assesses the three most common trisomies (13, 18 and 21) but it also detects sex chromosome abnormalities and some common translocations, which is not covered by Full Integrated Screening (FIS). The Nuchal Translucency (NT) ultrasound is a valuable tool as a markedly abnormal NT measurement can suggest a structural defect and prompts further testing, even if a karyotype is normal. The NT scan can also be viewed as a preview for the anatomy survey, as sometimes structural abnormalities can be detected. The amniocentesis would provide the most comprehensive chromosomal analysis as well as screening for neural tube defects, but carries the risk of an invasive procedure and is usually scheduled after sixteen weeks.
Our LVN called her to follow up and spent about 45 minutes reviewing all the information I had provided as she tried to get a sense regarding the patient's concerns and priorities. At last, she had made her decision. She would just go ahead with an amnio only, just like she did with her last pregnancy. I signed the requisition and the LVN helped her schedule her procedure. A week before it was slated she came in for a routine visit with one of my colleagues. She couldn't auscultate heart tones with a doppler and even with our back office ultrasound, my colleague suspected a cystic hydroma was present. "Oh shit!" I commented "That likely would have been picked up on an NT scan..." We both noted that earlier screening wouldn't have changed the outcome, just may have provided an earlier diagnosis.
A few days earlier, I had learned that my first IVF transfer resulted in an embryonic demise. This patient and I had our D+C procedures performed on the same day and the pathology reports each confirmed a trisomy, +13 for her and +16 for me. While she was waiting to see my colleague for her follow up visit, I knocked on the door and asked if I could come in to check in on her. I wasn't intending to mention anything about her decision to skip the earlier screening options, or ask what she plans to do with a future pregnancy, as it would be obviously inappropriate at that time. However, she brought it up. "I knew all the advantages of the earlier testing. I read the brochures inside and out. I had all the forms and the requisition for the NT scan on my desk and I just didn't get around to call to schedule it. I just didn't ever think that anything would be abnormal. I thought I could rely on the amnio to give me a final piece of mind."*
As I returned to my desk, I reflected on how much my thought process differed from hers. Yes, there are a lot of AMA women who give birth to normal babies, but there are a lot who a lot of older women who miscarry due to presumed chromosomal abnormalities. The everyday woman is probably not aware of those cases in the way that I am. Additionally, as I recently saw a 30 year old woman who gave birth to a baby with Down's Syndrome, I felt reminded that despite the increased incidence that spikes after the age of 35, we can't forget that trisomies still occur in younger women. I had accepted there was a high probability that an embryo could be abnormal, perhaps reflecting a measure of my age and general bad luck. I wanted to test as soon as possible. As a blastocyst prior to transfer.
I learned about Comprehensive Chromosomal Screening (CCS) in detail while attending an infertility conference in September 2012. I still laugh as even though I was approaching the six month no conception mark, I signed up for the conference merely because I needed the credits and it would stretch my CME allotment. I actually thought I might be a few months pregnant by the time the conference commenced. Instead we were waiting to see if Clomid could improve Husband's male factor infertility before starting IUIs. My initial thoughts noted that if we had to proceed with IVF, this testing might allow us to avoid an amniocentesis. Then my eyes were opened as the speaker closed his presentation by showing pictures of five different blastocyts and he asked the embryologist in attendance to vote on which ones they would grade as being the best and worst. The embryo that everyone thought looked the best, actually had two abnormalities (45, X- +4) and the embryo voted least impressive, was completely normal.
"Why is this not a routine practice?"** I asked my RE as we were discussing details prior to my first IVF cycle. "Well studies, haven't demonstrated that it is cost effective." he replied, although he offered that he had a 40 year old patient who felt very encouraged when she had four embryos make it to the blastocyst stage. Unfortunately, all four were abnormal, so she saved herself the cost any transfers. On one hand, I concede that there probably are a lot of young women with tubal factors or unexplained infertility who will likely produce mostly normal embryos and will proceed to become a first time IVF success story. I also knew of two bloggers who conceived through IVF only to discover via a miscarriage that an aneuploid embryo was transferred. (One was in her late 20s and the other used eggs from a 32 year old donor). I thought more about the intangible emotional costs involved, and I tried to make that case to Husband, who was loathe to spend one more dollar (let alone two to three thousand of them) on this already expensive proposition.
"Are you going to do PGD testing this cycle?" the billing woman in my RE's office asked as we discussed the fees. "Well, embryo willing." I replied. "I still can't claim that it's cost effective." My RE advised, engaging in the doctor's strategy of hiding behind data. I silently sighed inside my head. A part of me wanted to tell him that I don't blame him for recommending the day 3 transfer with our ill fated embryo rather than taking the risk to see if any would survive for a biopsy on day 5. Instead I replied that I didn't need to see any population studies to demonstrate cost effectiveness. I knew it was cost effective for our situation. After a miscarriage, two failed transfers and a second fresh cycle, Husband was convinced in a way he never could have been last November.
And then there were four. Four euploid embryos. The other two were abnormal. One was 46 +20, another one 45, X- +1, +8. Yes, that is three separate chromosomal abnormalities on one single embryo. Two of my six embryos had no potential to produce a human life. Yet they were grade 1 blasts. I can only imagine the hottie embryologist telling us how perfect they looked. It would be like playing Russian Roulette, except there would be a bullet in two chambers. There was a 33.3% probability of selecting one of the lethal embryos for transfer. PGD testing merely removed the game of chance. I know it's still not a guarantee. Some women have still received a BFN after transferring a known euploid embryo and others have still suffered a miscarriage.
Once again, I know how fortunate I am to be in this position. I also appreciate that not every situation would be amenable to CCS testing. If there are fewer embryos, it may not justify the extra cost and there are concerns that the biopsy procedure may inflict damage upon the embryos. I know first hand about receiving recommendations to do a day 3 transfer because it is feared that no embryos will progress to day 5. "Make the case for the day 3 embryo." I challenged my RE, after I saw in his notes that if we were to do a fresh transfer with my recent cycle, it would be on day 3. "Easy." he replied. "Your body is a better incubator than the most state of the art lab in this world." All right then. Point made. The day after my retrieval, I received a call from New Girl who noted that we needed to sign some additional consents for the PGD testing. "I'm sorry for the inconvenience." she apologised "We don't do this very often. It's the blind leading the blind." I was really surprised to hear that. While I can appreciate that it may not be applicable to perform CCS as a routine practice, I cannot understand how (ethically seems too strong of a word) REIs in good conscience do not at least discuss and offer this option to all their IVF patients.
*That patient is currently pregnant again. This time the discussion was limited to her declaring, "I'd like to do FIS and NIPT and amnio only if those are abnormal." All fingers are crossed for normal results!
**My observation from CCRM bloggers is that CCS seems to be routinely employed for AMA and patients with egg quality issues.