Monday, April 27, 2009

One Good Egg

After an increasingly agonizing six-week wait, I finally received my PBB/CGH results: out of ten embryos, there was one normal and one no result. While I wouldn't say I'm over the moon, I am very happy to have one normal. It was my first ever (to my knowledge) and my expectations had been extremely low, so it was really good news. Of course, now I sorely wish I had gone for the 5-day biopsy and that this normal were a highly-implantable blast rather than a two-day old embryo that had only been tested via polar body biopsy on the maternal side and with a long road of growth ahead of it. Nonetheless, I’m still incredibly thankful and have counted my blessings more than once. What’s most exciting is that this means I’m still producing normal eggs, and I’m doing so at a rate that is consistent with my age group despite having a translocation.

But what a difference a year makes. It’s clear to me that the translocation is actually becoming the lesser of my problems. Even without it, I would have had only two normals this cycle, as only one embryo of the abnormal bunch was discovered to have a singular chromosomal error (monosomy 14) caused by the translocation. Every other embryo displayed complex aneuploidy. The geneticist forwarded a list of the chromosome errors per embryo and it actually made me cringe. I've spent so much time cursing my translocation (with good reason), but it's hard to be angry at yourself for simply living and aging. While I had long assumed my eggs had already started feeling the inevitable effects of age, seeing the speed with which they're doing so is a bit alarming. Still, knowing that I have one good egg is an important milestone for me. If there's one, there's bound to be more, and I'm going to find them.

Monday, April 20, 2009

The Road to Discovery

More than one year after almost not finding out about a major chromosomal problem, I had the unfortunate experience of almost not finding out about something else. This time, it involved clotting.

It was January 2008 and I was about to begin my first IVF cycle with my previous clinic. Having already missed an opportunity to diagnose my translocation due to a former doctor’s less than stellar judgment, I asked the clinic to run a Thrombophilia panel. Two of my friends whom I met in an online support group had spoken of the risks of blood-clotting disorders in pregnancy, and I was a big believer in precautionary testing, particularly when embarking on as costly a procedure as IVF. I had already found myself in the 1% of the population with a translocation, so I understood that it absolutely can happen to me. And having one rare condition didn’t necessarily preclude me from having another. I called my doctor to request the test and she was, predictably, opposed to the idea. I insisted and she finally agreed to call in a script.

A week later, I called for my results and was told my blood work was normal. I was very relieved and proceeded to undergo two IVF/PGD cycles, neither of which produced any normals for transfer. It was a painfully disappointing five months. In June, while organizing a sizeable stack of paperwork -- we were taking a much-needed vacation and I like coming home to a clean house -- I came across my Thrombophilia report and began to flip through it. Within minutes, I learned that I had not one, but two clotting disorders. Each diagnosis had been underlined and initialed by the doctor. I was stunned. My own clinic -- a well-regarded one at that -- had informed me months earlier that my test results were normal, so I had assumed that to be the case. Things like this just don't happen, I thought.

Not only do they apparently happen, but they also manage to get worse. Several days later and still waiting for a return call from my doctor, I found out I was pregnant naturally. (This alone was alarming because with my translocation, getting pregnant with an untested embryo is a big gamble.) Suddenly, the recent clotting revelation was more urgent. If untreated, clotting problems can cause pregnancy loss, and if we were lucky enough to have a normal embryo, we could not afford to lose it to a blood clot. Unbelievably, despite leaving a series of increasingly frantic messages, I did not receive a call from the doctor for four days. When we finally did speak, she said she had not told me about the clotting disorders because “they weren’t that big of a deal.”

My doctor was actually admitting that she had taken note of my abnormal diagnoses yet chosen not to inform me because she considered them unimportant...despite the well-documented and well-recognized association between clotting and pregnancy loss. It was flabbergasting, to say the least, but my bewilderment would not continue for long. Six weeks later, the heartbeat had stopped and a karyotype revealed that the translocation was once again to blame.

What's most disturbing about these events is that had I not followed my own instincts to get tested, I would not be taking Folgard and baby aspirin each day (for my MTHFR) nor Lovenox when pregnant (for my anticardiolipin antibodies), two very simple treatments which can prevent very horrifying consequences.

Saturday, April 18, 2009

A Bitter Pill

One of the most unassuming yet unpleasant parts of this whole infertility business is the large amount of pills I must take on a daily basis. This might sound trivial and I know it pales in comparison to the other things I endure, but I’m just so sick of swallowing pills. I long for the day -- years from now when my pregnancy endeavors are behind me -- when I don’t have to take any sort of pill at all.

Unfortunately, that day will never actually arrive. This is because I’m on Folgard and baby aspirin for life due to my MTHFR mutation, and Calcium to prevent bone loss since I’m of “advanced age” and I suppose it’s always prudent to take a multi-vitamin. (And if my parents' vitamin baskets are any indication, I will eventually be adding a handful of cholesterol and blood pressure concoctions, and who knows what else, to the mix...but at least this won't be for a while.) Perhaps I’ll just say that I long for the day when I must take only six pills. Still much more manageable than my current routine. A sort of vacation for my esophagus.

Right now, my daily pill regimen looks like this:

This includes Estrace, DHEA, a prenatal, Folgard, DHA, L-Arginine, Caltrate, Vitamin C and a baby aspirin. I split these into two doses -- half in the morning and half in the evening. I try to assign my critical pills the morning rotation in case I get lazy and neglect to take all of my nighttimers, which I do from time to time.

I also take three daily eyedroppers-full of a Chinese herb that was highly recommended by my acupunturist. It’s an odd-tasting and pungent potion, and was almost repulsive to me when I first tried it. It's available in capsules as well, but I'll opt for the tincture any day. And I've actually come to find it quite tasty.

Friday, April 17, 2009

The Out-of-Towner

Today marks exactly five weeks since my retrieval -- 4w5d from when the biopsies would have reached the lab -- and still no word on my CGH results. I know the official wait time is six weeks, and I was thoroughly informed of this interval by the geneticist, but other people seemed to have heard within the four-to-five week range so I had hoped I would too. I've found that the two-hour time difference between CCRM (MT) and me (EDT) just adds further frustration because even though my day might start around 7 am, the relevant people in Lone Tree, CO are all still sound asleep in their beds. Now that I'm down to the finish line, I watch the clock every morning, impatiently awaiting 11 am which is the earliest I can realistically expect a call. At least I started Estrogen Priming today – a consolation of sorts since it means the ball is once again in motion.

Next come the travel arrangements. Because CCRM requires that your Day 6 ultrasound be done in their offices, I usually fly to Denver on Day 5. Hotel and rental car booking can be arranged now and based on estimated dates, but airfare will wait until I know positively what day Day 5 actually is. If things play out as expected, I will fly out on April 27 and my husband will follow five days later. Since switching to CCRM, I’ve been cycling back-to-back which means I get my post-retrieval period and then I start right up again. Each time I pull out my suitcase, I feel as if I've only just unpacked from my previous cycle -- largely because I have. Still, it’s a feeling that I’m used to and with routine (this one included) comes an odd comfort. Interestingly, as much as it’s inconvenient to be out of town for a week and half every month, I've noticed that it’s actually very healing to be away from home during my cycle. The physical separation provides a buffer that allows me to segregate IVF, if even a little, from the rest of my life.

When I first started looking into IVF in late 2007, I narrowed my search to three clinics: one local, one very local and CCRM. Even back then I viewed CCRM as the mother of all clinics, an opinion based not only on their SART stats but on a significant amount of anecdotal data -- the experiences of women who had cycled there. At the time, it was the distance that scared me off. As an IVF novice, I just couldn’t envision flying across the country to do a cycle. It seemed so extreme, so excessive...especially since I lived just outside of New York City, home to a number of well-regarded clinics. What’s more, cycling locally seemed difficult enough with the daily ultrasounds and bloodwork; how exactly would cycling 1,500 miles away work? Could it really be worth the effort? The fact that so many women were doing it should have been a big clue, but I wound up initially choosing the shorter commute over the cross-country jaunt. The great irony, of course, is that my local clinic turned out to involve a treacherous one-hour drive whereas my hotel in Colorado is a relaxing 10-minute ride from CCRM. I still kick myself for not heading to Colorado straight away, but I suppose everything’s a process, even good decision-making.

Thursday, April 16, 2009

Robertsonian Translocations 101

(Please note that I'm not a medical or genetics professional. The following is intended only to provide a basic summary and maybe a starting point for those wanting to learn more; it's not a substitute for meeting with your doctor or genetics counselor!)

Because my primary infertility problem is a translocation, I refer to it often on this blog and thought it might make sense to explain what it is. A translocation is a chromosomal rearrangement involving the exchange of material between two different chromosomes. Translocations can be balanced, where the exchange is even, resulting in no important genetic information being gained or lost; or unbalanced, where the exchange is uneven, resulting in missing or extra chromosomes. A person with a balanced translocation is phenotypically normal; thus, balanced translocations usually go undetected until a carrier tries to reproduce. People with balanced translocations are at greater risk than usual of creating unbalanced gametes (eggs/sperm), and unbalanced gametes produce unbalanced embryos.

Translocations are diagnosed through a karyotype, a map of a person's chromosomes via a simple blood test. Most doctors wait until a woman has had several miscarriages before suggesting karyotyping. (My previous OB would not test me after my first m/c.) Even in the IVF world, karotyping is not always standard testing, so many couples go through IVF cycles without knowing if they are predisposed to miscarriage and/or abnormal offspring. However, you can request to have your karyotype done and this may or may not be covered by insurance. (My feeling is that $900 is not a lot if you're shelling out $15,000 for an IVF cycle which may incorrectly assume your chromosomes are normal.)

There are two types of balanced translocations: reciprocal and Robertsonian. About 1 in 1000 people is a carrier of a Robertsonian Translocation. Because my translocation is Robertsonian, I will speak mainly about this type. Also, keep in mind that in order to make this understandable (particularly for me), I'm not addressing the major cell division events -- meiosis and mitosis -- which play a huge role in all of this.

Under normal circumstances, human beings have 46 chromosomes - 22 pairs of 'autosome' chromosomes and 1 pair of sex chromosomes. Each pair is a different size and most are comprised of a long arm and a short arm which are fused together at a joint known as a 'centromere.' Five of our chromosomes -- 13, 14, 15, 21 and 22 -- have very short arms and are known as 'acocentric.' Robertonsian translocations are translocations that occur on any of these five chromosomes.

A Robertsonian translocation occurs when one chromosome breaks apart at its centromere (joint) and the long arm fuses with the long arm of another acocentric chromosome, creating a single larger chromosome. Both short-arms are lost in the process, but because they don't contain relevant genetic information, this is uneventful. As a result, a person with a balanced Robertsonian translocation has only 45 chromosomes, but because they are not missing (and have not gained) any important genetic information, they're normal except from a reproductive perspective. Robertsonian Translocations occur in both men and women and can be spontaneous or inherited. The most common chromosomes impacted are 13 and 14, as in my case, but a person can have any of the five chromosomes affected.

This is a what normal chromosomes 13 and 14 look like:

This is what those same chromosomes look like with my translocation:

(You can see that the long arm of chromsome 14 has left its partner and fused to the long arm of the 13. )

With a Robertsonian Translocation, there are six possible outcomes for the embryo (even more in a reciprocal translocation): normal, normal/carrier, an extra 13 (Trisomy 13), a missing 13 (Monosomy 13), an extra 14 (Trisomy 14), and a missing 14 (Monosmy 14). So from an odds perspective, if nothing else played a role, a Robertsonian carrier has a 2 in 6 (33%) chance of producing a normal embryo. This in on top of the inherent rate of abnormals in young, healthy women without translocations. With the proliferation of PGS (preimplantation genetic screening), their rate of normals is now thought to be around 40%. So very roughly, 33% of 40% normals if you're young with a translocation. And if you're my doesn't look very promising.

But let me say this -- many, many people with Robertonsian translocations have several children -- although they often experience one or more miscarriages. Because I started relatively late at baby-making, it's been significantly more challenging. What doesn't have the translocation always seems to have something else. This is why I'm doing IVF -- so I can test the embryos and transfer only normal ones, hopefully saving me from yet another heartbreaking and time-consuming miscarriage. If I were 10 years younger, I might have decided to try naturally until I found a good egg, but at my age I don't have the luxury of time. Unfortunately, I have yet to know if I'm even capable of producing a normal egg, and I have to accept this as a distinct possiblity. But I suppose even if that's all I find out in the end, it's at least more than I have now.

Wednesday, April 15, 2009

Keep on Walking

I am fairly certain that my first clinic (which shall remain nameless) wanted me out of there the moment I stepped through the door. I was 41 at the time and had a balanced translocation – a double whammy. Even if I were 10 years younger, having a baby would have been substantially harder for me. Despite my FSH of 6, I was a difficult case. But isn’t this the main premise behind a fertility clinic? To help someone with lower odds of success have a baby?

This didn't seem to be true of my clinic. Perhaps they welcomed the 'slightly infertiles,' but their doors did not appear to be fully open to someone as hopeless as I. People often refer to the greedy as seeing dollar signs in their eyes; this clinic must have seen flashing red lights around a billboard that read “Danger: Will Lower Stats.” Not only did they push donor eggs in our consult and both regroups (actually, not an uncommon occurrence) before ultimately dropping me, but they were hesitant to modify my protocol or attempt to come up with anything new, even after my first failed cycle. In retrospect, I'm surprised they even agreed to cycle me in the first place. Maybe the chance of getting another over-40 pregnancy on their books was so compelling that they were willing to give it a lukewarm whirl, which they did.

My very first try was a miserable Microdose Lupron cycle in which I was over-suppressed and produced only 4 eggs. I was so disappointed. Considering it was my first cycle, I would have thought the doctor would have been somewhat open to the possiblity that my doses and/or protocol needed adjusting. (Cycling is, to some degree, trial and error.) Instead, our regroup went something like this:

ME: Is there another protocol we could try to make me respond better?
THEM: There’s not much else. Donor Egg is your best shot. I’m so sorry.

ME: There's no other protocol? No other meds? Nothing at all?
THEM: Nothing that would really change your response. I'm so sorry.
ME: I’ve heard of Antagon, what about that? Would that help?
THEM: Well, we can try it, but don't expect a big difference.

In my very next cycle, I had twice as many eggs and embryos on Antagon. I would call that a big difference. It was the same thing with Estrogen Priming (EPP), except that my doctor actually said, “Estrogen Priming hasn’t really been shown to help with poor responders.” Hmmm. Perhaps I'd been confused. She finally agreed to try it, but not without registering her irritation at being convinced to do something against her will. After EPP, my antral follicle count doubled -- something that proved to be very helpful to this poor responder.

Tuesday, April 14, 2009

Where I Am Now

I'm about to begin my seventh IVF cycle and it’s a very strange place to be. Never in my wildest (bad) dreams could I ever have imagined getting to this point. One, two cycles maybe, but never seven. Like everything else in life, I suppose, it sneaks up on you. At first, I lived normally while trying desperately for IVF success. Then, I lived IVF while trying desperately to be normal. Now, IVF is living me and I’m too indescribably drained to try much of anything at all.

Today marks four and a half weeks since my March 13 retrieval and I anxiously await my CGH results from CCRM. I produced a record-breaking (for me) 17 eggs, of which 13 were mature, and 10 embryos were vitrified after Polar Body Biopsy (PBB). I opted for PBB because I've never before made enough embryos to even try for Day 5 CGH so I never expected to have the option. It didn't help that I was dubbed a poor responder by my previous clinic; I suppose some labels are hard to shake, if even in your own mind.

Here is my history:

Previous clinic:
(E2 never above 1,300)
IVF#1 – 4 eggs, 2 mature, 2 embryos
IVF#2 – 7 eggs, 4 mature, 4 embryos
IVF#3 – 8 eggs, 5 mature, 4 embryos

(E2 up to 4,000)
IVF#4 – 13 eggs, 9 mature, 4 embryos
IVF#5 – 9 eggs, 7 mature, 5 embryos
IVF#6 – 17 eggs, 13 mature, 10 embryos

You can see that my response has improved notably since switching to CCRM. Even their basic protocol -- which includes Dexamethasone, Menopur and lower stims -- helped things along significantly, as evidenced by my first cycle there. We added Saizen in IVF#5 (bringing me one additional embryo) and then I found DHEA, which really seems to have upped the ante. I was only on it for five weeks at the time of IVF#6 (they say optimal response is reached after four months), so I can barely contain my excitement over what my upcoming cycle will bring (aside from more acne and, possibly, hair loss) after taking it for 12 weeks. It's a blatent violation of my first rule of IVF -- nothing hoped for, fewer tears -- but I just can't help myself.

Monday, April 13, 2009

My Infertility Story

I was 40 when we married in early 2007. Shortly before the wedding, I dragged us both to Cornell for a barrage of tests so we'd be ready for IVF, which I assumed I would have to endeavor due to my age. Imagine my surprise when I became pregnant naturally right after the honeymoon. Ten weeks later, the heartbeat had stopped and I had a D&C (two, actually, because the doctor missed something). I was devastated, as was my husband. My OB told us it was common and, for reasons which I still do not understand, tried to dissuade me from the "very expensive" fetal karyotype that would tell me for sure what had happened. I held my ground and Trisomy 13 was the verdict; my OB assured me that there was a 1% risk of recurrence. Fearing the worst and wanting to leave no stone unturned, I asked to have my karyotype done to rule out an inherited genetic problem. He said it was absolutely unnecessary. Still naive in many ways, I made the mistake of listening.

What followed were some of the longest and darkest days of my life. Numerous failed Clomid IUIs, a laparascopic myomectomy because "it must be the fibroids," and then the life-altering discovery that I was a carrier of a Robertsonian Translocation, a (usually) inherited chromosomal disorder which strongly impacts the ability to conceive, and, what's more, a known condition in my family of which, disturbingly, I was never aware. (Not to mention something which would have been diagnosed six months earlier had my OB actually listened to me.)

Anger and resentment ensued, and then life became even more complicated: three heartbreaking failed PGD cycles, another natural pregnancy that ended in miscarriage, my previous clinic's dangerously inaccurate communication of my blood-clotting results just before dropping me from their practice, a very close relative backing out of being my egg donor at the 11th hour, and me at the closest I've come to a true breakdown. All the while, the growing stress of buying and renovating an old home, my husband's immigration problems and his subsequent inability to find a job in a melting economy were also taking their toll.

There's been some good in this story: My husband has been extremely supportive during my infertility journey, something that perhaps has drawn us closer while giving him a sensitivity and appreciation that he would never have had otherwise...and I eventually found my way to CCRM, an incredible clinic where I re-learned the meaning of hope and where I'm currently involved in a succession of back-to-back bundled IVF cycles, each response better than the previous. I went from being dropped by my old clinic as a poor responder to producing 17 eggs and 10 good quality embryos at CCRM. Maybe there's a chance for me yet.

Sunday, April 12, 2009

In the Beginning

For better or for worse, my first attempt at blogging occurs while poised on the precipice of emotional, financial and, occasionally, marital crisis. As if two miscarriages, six IVF cycles and being 42 years old with a balanced translocation is not bad enough. But in my world, the word "crisis" continues (deep sigh) to redefine itself. I guess I should start at the beginning.

Year: 2005

Me: Living in New York City in a beautiful co-op in a beautiful neighborhood with a fairly comfortable financial situation. I was single, almost 39 and in an out-and-out panic over the future. I was moderately social and dated somewhat regularly, but was very worried about meeting someone I loved and having a baby, and I felt my chances slipping away with every breath. It didn't help that I came from a family that places its highest value on people with babies, people with spouses and just plain people, in that order. I found it nearly impossible not to feel like a social misfit being unmarried at this age, and I desperately wanted a partner. I was ready.

Him: Handsome, intelligent, funny, tough -- a sensitive heart in an armored body living in a minuscule but immaculate walk-up in Bensonhurst. He was Eastern European and looked it, and had lived a difficult life, one about as far away from mine as you could imagine. I came from a well-placed and well-off family, leaving me well-educated, well-rounded and well-mannered, albeit a bit emotionally fragile. He was raised Communist, served for years in the Special Forces, ate each meal as if he were racing back to the battlefield and had experienced his share of loss for a lifetime. He loved children and animals and they loved him back. And he cleaned up very nicely. In a way, we were the perfect match. We loved each other deeply and were prepared for the bumps along the road that our different cultures and life experiences would bring.

Little did we know that something as seemingly primitive and instinctive as wanting a baby would soon catapult us into an emotionally complex and exhausting netherworld that would grimly define the first two years of our marriage.