Finding Zwee

You might recall that last time we had 12 eggs retrieved, 9 off which were immature, 3 of which were mature and fertilized. By day 5, we had 1. It went for testing and came back aneuploid: 49 chromosomes.

This time we had 29 eggs retrieved, 21 of which were mature, 16 of which fertilized, 12 which survived to day 5, and are now off to testing.

At this point last time we had one, this time we have 12. So what’s the deal?

A few things:

1. Different drugs, and different doses of drugs. Last time I took 225 IUs of Follistim (which contains Follicle Stimulating Hormone, or FSH)  in both the morning and evening. This time I took 300 IUs in the evening only (about 40% more) and a different drug that does the same thing, called Menopur, in the morning. Menopur contains FSH, but it also contains Leutenizing Hormone (LH), where as Follistim does not. Don’t quote me on this, but I believe the doctor said that Menopur is derived from the urine of menopausal women.

Also this time I took a drug called Omnitrope, instead of Low Dose HCG (Human Chorionic Gonadotropin). Omnitrope is a  somatropin, and helps cells grow. Don’t ask me the difference betweeen a gonadotropin and a somatropin.

Each of these drugs (FSHs, LH, tropins) push the development of eggs.

Meanwhile, you want to prevent premature ovulation, so while we are pushing the eggs to grow, we are also pushing back with Ganirelix to ensure they don’t ovulate. Last time if I even took Ganirelix (I don’t think I did?) I took it once. This time I took it for 4 days before the retrieval.

In general I got the sense that the doctor was pushing growth harder, and pushing harder on premature ovulation. Hence, the higher numbers.

[Side note: part of the reason we went to Oregon Reproductive Medicine for round 2 is that the doctor there looked at my round 1 results and suggested these changes. Meanwhile, the doctor from round 1 suggested no changes. See lead-off quote.]

2. Additional supplements. In addition to lots of eggs, the other thing you want is high quality eggs. Dexamethazone was prescribed because it can help with that. Same with CoQ10, DHA/Omega-3’s, a baby aspirin (for more blood flow to the scene). I felt like my own private pharmacy some days, with all these pills. It appears that this helped, because of my 12 eggs, graded on 2 characteristics, 10 were graded AA, and two were graded BB. So they were high quality indeed.

3. Data from the previous round.  The value of these data  is not to be underestimated. At my day 10 ultrasound, when they would normally say, looks great, we will retrieve on day 12, what happened instead was my doctor was comparing the data from my Round 1 eggs – comparing sizes, and outcomes. What he saw was that last time my eggs were around 15mm on day 10, and 75% were immature. This time around, we were in the same place – eggs around 15mm. He made the call to hold off on the retrieval one more day – so my retrieval was day 13, rather than the more common day 12, in order to give the eggs one more day to mature. Clearly it was the right call.

4. Meditation.  I started nearly every day with a 10 minute visit to my ovaries. No joke. I brought each follicle into view in my mind’s eye, greeted it with loving kindness, thanked it for being here, and encouraged it to have the right chromosome count. I looked around and asked if there were more follicles that wanted to join the brigade, and let them know that it was safe to be part of this party and that they were most welcome to come along.

There you have it – four factors that made the difference.

I thought waiting 5 days for news would be painful, but after weeks, if not months, of heavy focus on all that needs to be done in preparation, the radio silence is a nice reprieve!

For a while, I almost forgot the rest of the world out there – news was one of the things I gave up in order to free mental bandwidth.

While I reconnect with the world and life back at home in Missoula, I have zygotes in Petri dishes in Portland. And not just a few, but sixteen. 

Zygo-whaaa? Let’s take a trip down basic biology lane.

Here’s what’s happening:

You read the post about ICSI (if not, it’s here). Once the eggs are fertilized, they are left alone to divide.

They start out with two pronuclei (one from the egg, one from the sperm), and each contains 23 chromosomes – not 23 pairs, but just one of each.

The pronuclei combine, to create a regular cell, on Day 1. That’s when it becomes a zygote.

On day 2, the cell replicates itself and divides in two.

One day 3, both cells replicate and divide, so there are four.

On day 4, same thing: 8 cells, until this point, all laying flat.

On day 5, all the cells divide again, and it turns into a ball shape. Now there are too many too count.

On day 5 or 6, the ball of cells begins to differentiate – into an outside layer called the trophodecterm, inside cells that go on to form the embryo, and inside cells that go on to form the yolk sac. (Yep, you heard that right. The yolk sac supplies nutrients to the embryo until the placenta comes online to get nutrients from the mom, which usually happens at about 8 weeks.)

At this point, the ball of differentiated cells is now called a blastocyst.

On day 6, the embryologist will laser of a few cells from the trophodecterm, and those cells will be sent to the lab for CCS – Comprehensive Chromosomal Screening.

On average, half of eggs that fertilized will survive to day 6, and of those, 30% will pass genetic screening, the results of which take a week to receive. So, more waiting.

If I think about it, my mind can get all wound up. But no amount of thinking about it will change the outcome, so I turn my attention elsewhere. No use in getting wound up! Focusing elsewhere also happens to be a convenient cover for being guarded, given our disappointing results last time. So I welcome the mental break. I’m sure that by Friday morning when I am waiting for a phone call, my mind-tricks won’t work.  And that’s ok!

 

 

Ready for some fun science?

Hold on to your chair, because this is where shit gets interesting.

Yesterday they collected the eggs from the follicles, and they fertilize them on the spot. But not by just letting them take a bath in a pool full of swimmers — nooooooooooo — that would be way to easy.

What they do for mine is ICSI – Intra-cytoplasmic sperm injection. They take a single swimmer, chop its tail off so they can aspirate it into a needle, then inject it directly into the egg. (About 75% off eggs survive this procedure.) Of the 29 eggs retrieved yesterday, 21 were mature, which is more than the 17 we had counted on the ultrasound a few days earlier. (Hooray, 4 more!)

From a pool of 85 million, the embryologist selects one swimmer for each egg.

How do they select which ones make the cut? I heard that they place the sample on a gradient, and pick from the strongest uphill swimmers. But Google reveals that they expose the sperm to Hyaluronan (not sure what that is), and those that bind well to Hyaluronan tend to have a better fertilization rate, as it is a marker for a better set of chromosomes. That’s all I can tell you on this topic, given that I just learned this. I like the gradient version of the story better, but oh well.

Why not just let the egg bathe in swimmers? You can actually do it that way, and many women do – particularly those who are younger and tend to have better chromosome counts. At 41, only 30% of my eggs have normal chromosome counts, so we want to be able to perform CCS – Comprehensive Chromosomal Screening – on them to ensure that we only put back in embryos that have a normal chromosome count. If you throw a bunch of sperm at an egg, and one sperm fertilizes, the chromosomes from the sperm that didn’t make it inside the egg will remain on the outside of the egg. At day 6, when cells from the embryo are biopsied, these chromosomes from non-successful sperm will contaminate the results. That’s why if you are doing CCS, you have to do ICSI. One egg, one sperm, and on Day 6, screen the chromosome count.

It is the end of day 1, and we just heard that we have 16 successfully fertilized eggs remaining. This too is a great start. From here, the odds are that 50% will make it to day 6 (so, down to 8) and then 30% will be genetically viable, (so, 2.4).

If we end up with 2 or 3 viable embryos, that would also be a great start. If you implant (aka: “transfer”) a viable embryo back inside, there is a 60% chance it will result in a healthy full-term live birth. Having 1 viable embryo is good, but having 2 or even 3 really raises the odds of success.

It is far too early to get my hopes up, having had them dashed last time, but last time on day 1 we were already down to 3.

There is still a long road to travel, but 16 is about as good as one could hope for. You can let go of your chair now.

I am ready.

We have packed and departed our quaint Airbnb, in hopes that I will feel well enough to do the 9 hour drive back to Missoula post-surgery. It’s a gamble, but one I am willing to take.  Portland is fun, and I have had my fill for now.

We check in to the clinic. It is Saturday morning – it is eerily quiet, yet I find it calming. The nurse brings me to my room, points me to my gown and booties, and gets me going with an IV.

While I wait for the doctor to arrive, I peruse a copy of Genome magazine – odd but befitting reading.

A young man with a baby face appears in my room to explain the procedure. He asks if I have any questions. What I really want to know is how old he is and how many times he has done this before, but asking that would be entirely inappropriate. While we make small talk, I inquire about how many women are here on an average day, and do the math in my head. At least 100+ times a year, which seems to me to be ample practice. I have assuaged my concerns.

My main fear right now is how much the anesthesia drip is going to hurt. I remember it from last time as the single most painful part of the entire experience, and the thought of having it again has been looming in the back of my mind for weeks.  “It will only burn for a few moments,” says the anesthetist, “and we will give you good happy drugs before that so you won’t feel much.”

The doctor says he will collect every last follicle, I notice a bit of burning, and then I am out. It truly seems like no time passes before I am waking up in my recovery room, and I am confused. Clearly we must be done, given I am in recovery, but since I have no feeling of time having passed, I am momentarily thrown off.

The nurse tells me they collected 29 eggs. (!!) A number of those will be immature, but 29 is a great start.  They will call tomorrow with a fertilization report.

I get dressed, and with a check out procedure that is barely more than, “Take care, have a safe drive!” we are on the road.

Enough drugs, and enough testing. We are there.

Last night I gave myself my trigger shots – (Note to self: don’t toss your medicine before you’re sure you don’t need it. Buying replacement med is expensive) – which I take at precisely 10:45pm. We pause House of Cards for the pricks, which in comparison to Frank Underwood & Co., are child’s play.

During yesterday’s scan, the nurse counted 17 mature follicles. Maturity is measured in millimeters – in this case, anything larger than 14mm. The larger ones are about 21mm.

For reference:

VIDEO: You can see them all on the right side, as the nurse scans from left to right:

Follicle Scan on Day 10  (28MBs.)

Collecting 17 eggs would be a great start. On average, it takes 9.7 eggs to get to one viable embryo.

We take advantage of the gorgeous day to do a bit of touristing. We visit the Oregon Museum of Science & Industry, along with every last young child in town, we take in one final breakfast at a hipster-loaded cafe, and get lost twice on the way to the Test Rose Garden in Washington Park. It’s nice to have a day off from shots.

I can’t and don’t really think about tomorrow. There is little I can do at this point. My only job now is to remember to show up on time in the morning. If you don’t think I’m capable of forgetting, see above note to self.

Surgery is scheduled for tomorrow morning at 9:45, so think of us while you’re having your omelette.

It was great to get out of town for… an afternoon.

We now find ourselves in a familiar routine of Get Ultrasound, Go to Pharmacy to Refill Drugs, Wander Aimlessly Until We Hatch a Plan. While hopelessly stuck waiting for a train that has parked itself on the tracks, we decide to wander out to the coastal village of Seaside, about 1.5hr’s drive from Portland.

It was a welcome reprieve from the noise and clatter. I’m already being hyper-stimulated – I don’t need to be overstimulated too.

The tide was allll the way out, the water cold, and the air grey. Perfectly somber recovery weather. It wasn’t meant to last though – we got called back for another morning (8:15am!) ultrasound.

This time the doctor counted 20 (!!) on the right and 11 on the left, though not all are mature. Many of those won’t mature, and most look to not be ready yet.

[Above: 5 bigger follicles and 2 smaller]

Last round there were 3 mature and 8 immature – not a good result. So he wants to wait one more day – until Saturday – for retrieval, in order to give the eggs more time under the grow lights. In my mind, I was ready for Thursday, delayed to Friday, pushed to Saturday.

I pull out one of the intended-to-inspire-and-let-go quotes from the waiting room:

We also learn that because my retrieval is Saturday, the doctor we have been meeting with will not be present. A different doctor will do the surgery. Everyone assures me he is great, experienced, etc, but it’s little consolation to change horses for the most important part of this thing.

I’m not sure I want to embrace the uncertainty. I want the doctor I know. I said my piece to the nurse coordinator; she frowns at me. We will see what happens.

Back on the positive mindset horse though! In the mean time, I now have 31 (!!) follicles to picture in my morning meditation. With all the bouncing around my mind does, it’s going to take a while to visit with each one! Good thing our morning ultrasound tomorrow isn’t until 9:15.

Portland traffic is a mess, and everyone is on bikes except me.

But who cares, that’s not why we are here. It’s follicle measuring time.

I have this mixed bag of emotions that I don’t know how to reconcile, and I can’t drink beer, so the next best option is to just ignore them. They will go away, and besides, they have little bearing on the outcome.

Yet, I can’t help but get excited when it’s time to count. It’s the moment where I finally get to see tangible results of all the researching, planning, waiting, and shooting.

Clearly, counting is a skill that comes with time. Below is a video for you to test your own abilities. The doctor counts 9 large and 5 smaller, though the video ends before you hear him count that far. Still, you will see him scan back and forth.

Measuring Follicles – it’s PG but if you don’t know me well you might think it’s weird. It’s a video version of the photo above.

[FYI – video is a 100MB download, until I learn how to embed it.]

If you keep an eye on the lower right corner, you will see the average of the X and Y axis measurements being calculated. The doctor wants them to be 20-22mm for retrieval, and right now the larger ones are at 15mm, the smaller ones are 7-9mm. So, more shots tonight, and back for more measuring (gladly!) tomorrow morning.

 

 

Just keep doing what you’re doing, says the nurse. It is Sunday, so the doctor is out.

I get poked – blood shows my estrogen is at 1671, progesterone is 0.9, leutenizing hormone 0.6, all good and normal.

On the right ovary (above, right) you can see 6 follicles of varying sizes – they are the black sort-of-circles. Some are big (18mm+) and others smaller (12mm). She counts a whopping 9+ 8, which means 9 look like they will grow to maturity, and there are another 8 that are growing but lagging behind and may not be fully ripe when it’s harvest time.

On the left (above, left) you can see 3 follicles on the left and what I think is a gas bubble that obscures the view. The nurse somehow manages to count 10+, which completely surprises me. I press her for more details, but she’s not into it. Just gotta wait.

If we get to harvest time (retrieval) and they pick 19 ripe follicles from the trees, that could be a really fabulous start. Yet, I find myself unable to get excited at this news, given that last time we went from twelve to none in less than 7 days. You can’t count your chicks until they hatch, so we keep doing what we’re doing. Get brunch, followed by the Portland Pride Parade. Two things we never do.

The hyper-stimulation phase is the first 14 days of a cycle – where rather than grow one egg, the idea is to grow as many eggs as possible. At my age, 10 is good, 15 is solid, 20 fantastic. On average, it takes 9.7 eggs to create one viable embryo worthy of transfer – putting it back inside.

More on these stats later, but the idea right now is “make as many high-quality eggs as possible.” You need two things with IVF: lots of eggs, and good quality eggs. The more of both you have, the better your chances.

It’s all done with shots – mostly sub-cutaneous in belly fat – some in the morning, and some at night.

The shots do a few different things.

Menopur and Follistim are Gonadotropins – natural hormones that stimulate the ovary to promote the maturation of several eggs at once. These shots also contain some follicle stimulating hormone (FSH), a hormone that will stimulate the growth of the follicles themselves. So these shots are doing two things at once: increase the number of follicles, and helping grow the follicles.

Omnitrope is a growth hormone that helps with egg quality.

Those three drugs I take for the first 8 days. On day 6, I add Ganirelix, a Gonadotropin-releasing antagonist – it prevents premature ovulation.

On days 8 – 12, it’s a game of grow the eggs, but watch out to not grow them to fast. Hence the push-pull of the drugs.

Think of the eggs like the runners in a 100-meter dash: all the runners are in the starting blocks for the 3 weeks before starting injections. You want them all to relax in the starting blocks and not do any false-starts. On day 1, the gun goes off – injections start – and the runners start out altogether.  You’re giving everyone the gonadotropins to help speed them along. Some of the runners run at exactly the same pace – and some start to spread apart. You don’t want a Usain Bolt in your pack – he gets out too far ahead. You’d give him the Ganirelix to slow him down. You also don’t want anyone lagging far behind. If so, they may not be mature at retrieval – you want them to get across the finish line with everyone else.

By Day 12, the follicles are about 18mm across – about the size of a ping-pong ball. The ones out ahead could be 22-24mm, and the ones that are lagging could be 12mm or smaller. All of these eggs will be retrieved, but the smaller ones may not be mature and won’t hatch. (Yep, that’s what they call it.)

That’s hyper-stimulation in a nutshell. Or, an eggshell, hahah.