Our frozen embryo transfer

Some of you may remember that the fresh embryo transfer after our recent donor egg IVF cycle was a bit of a disaster. Out of 15 fertilized eggs that had been developing well as of day 3, we only had a single 5-day blastocyst, and it was not the best quality (4BC, where the number is the stage of development and the letters are the quality of the components). When I asked the doctor about the potential for the remaining embryos to catch up, he was a massive dick. And to top it off, I hadn’t properly timed my water consumption to fill my bladder, meaning that my uterus wasn’t visible on the ultrasound screen, and the embryo transfer had to be done ‘blind’.

It was not the best ending to our first donor egg IVF attempt, which had been going so well up until that point.

Well lo-and-behold, five more blastocysts ended up making it to freeze on day 6, and I’ve spent the last few weeks growing an exceptionally cushy uterine lining for a frozen embryo transfer (FET) attempt. I say ‘attempt’ because there’s always the possibility that the embryo will fail to defrost. Unfortunately, you don’t know if this is the case until the day of your appointment. Since our appointment was first thing in the morning in Belgium, we made our way there the night before without knowing if there’d even be anything to transfer.

The call

We were still at our Airbnb the next morning when we got the call: the embryo survived defrost! We were thrilled, and we vowed that this transfer would go better than the last. I immediately chugged twice as much water as I had the last time (followed by another 500mL for good measure), and I vowed that under no circumstances would I ask the grumpy doctor any questions. (“I’ll just nod mutely to whatever he says, scout’s honor!”) We also expected the embryo to be better quality (4BB), since we knew we had at least one of those in the freezer.

You can imagine our surprise, then, when we showed up at our appointment to learn the embryo was only a 3CC — i.e., not as developed and poorer quality than our best frozen embryo (Strike 1). I couldn’t fully take in what he was saying and immediately asked a question (Strike 2) about why we were transferring this poor-quality embryo, to which he responded that the defrosted embryo is chosen randomly (Whaaaaaat??)

IMG_3992
The 3CC blastocyst that we transferred on Thursday.

I kept a brave face and we went ahead with the transfer. There was a big screen where we watched a magnified video of them sucking the embryo up into the transfer device thingy (that’s the technical term), and then the technician handed it to the doctor through the window in the wall. My bladder was full enough to see my uterus on the ultrasound screen (though at 17mm, it’s probably hard to miss). After the transfer, we saw a new white mark where the liquid containing the embryo had been successfully deposited.

PUPO, but not hopeful

This all went down last Thursday, which means I am once again Pregnant Until Proven Otherwise (PUPO). But despite what my well-meaning friends/family keep assuming, I am neither excited nor hopeful. The thing is, once you’ve gone through multiple failed transfers, it becomes hard to imagine any other outcome, particularly when the doctor says the embryo ‘isn’t the best quality’. I understand that poor-quality embryos can still result in beautiful babies, but I have also seen the statistics on implantation rates as a function of embryo grade. I’m not being negative — just realistic.*

With that said, I am still extremely grateful to our egg donor, Marie, for giving us the chance to make it this far. I’m also grateful for the four more embryos (‘frosties’) still in the freezer. And I’m happy to report that we had to stop three separate times for me to pee on the 2-hour drive home from our transfer. So, you know, at least I’ve finally got the full-bladder part down for the next try.

xx

*Ok, maybe I’m being a bit negative, but I recently read that IVF is as stressful as divorce or cancer in the family, so it’s bound to happen. (The progesterone shoved up my hoo-ha probably isn’t helping either.)

What causes Premature Ovarian Failure?

Premature ovarian failure (POF) is a devastating diagnosis for the 1% of women it affects. In medical-speak, it’s a gynecological endocrine disease characterized by the exhaustion of ovarian follicles before the age of 40. In normal person-speak, it’s when your ovaries decide to throw in the towel and simply stop producing eggs.

Women with this disease have a very low chance of ever having biological children, even with the help of in-vitro fertilization (IVF). This is why, after my diagnosis at 34 — including three failed IVF attempts — we’re currently preparing to use donor eggs from my friend Marie. But how did I happen to win this infertility lottery in the first place? In other words, what actually causes premature ovarian failure?

The short answer is that medical professionals usually have no idea. The long answer is that there are a number of possible causes for the disease*. These include (but are not limited to):

  • Genetic disorders: Chromosomal defects from certain genetic disorders can cause POF. Examples include Fragile-X syndrome, where a woman’s X chromosomes are fragile and break, and Turner’s syndrome, where the second X chromosome is partially or completely missing. (Fragile-X syndrome is also one of the diseases that they screen for in potential egg donors.)

  • Cancer treatments: Common cancer treatments like chemotherapy and radiation therapy can damage the genetic material in cells, causing POF in cancer survivors. POF is already a terrible thing to face on its own, much less after battling cancer. If there’s any kernel of goodness hidden in there, it’s that this particular cause of POF is becoming more common as cancer survival rates increase.

  • Psychological stress: Studies have shown that psychological stress, like experiencing a trauma or chronic anxiety, can cause changes in reproductive endocrinology. This cause is difficult to identify if you’re trying to self-diagnose, particularly because POF itself can also cause anxiety, leading to a chicken-or-egg scenario where it’s difficult to tell what came first.

  • Autoimmune disease: In a small minority of cases, a woman may have an autoimmune disease that produces antibodies against her ovarian tissue. This can harm the follicle and permanently damage the eggs contained within. It’s not known what triggers such an immune response, but exposure to a virus is one possibility.

How often is the cause identified?

While the issues listed above are known to cause POF, the truth is that the vast majority of cases (90%) are idiopathic, which is a fancy way of saying that we have no freaking clue what causes it. This is also the case for me. It is estimated that 40% of cases are genetic, and with my mother’s history of Hashimoto’s (an autoimmune disease), and my grandmother’s thyroid issues (plus my recent hypothyroid diagnosis), I wonder if there isn’t some connection there. But while I can speculate all I want (and believe me — I do), I have also resigned myself to the fact that I will likely never know.

*Disclaimer: Please keep in mind that while I am a doctor, I’m not one of the medical variety. The information here comes from personal experience and hours of sleepless googling.

What does donor egg IVF entail?

I’ve been busily blogging these last few weeks about our current donor egg in-vitro fertilization (IVF) attempt, just naively assuming that everyone else already knows what that means. Then last week, two friends (and avid blog readers) asked me who will carry the baby if we get to that stage. Great question! And one I should have addressed earlier. Sometimes I forget that other people don’t also spend their every waking hour reading about, preparing for, or talking about IVF. With three failed ‘normal’ attempts under my belt, as well as our latest foray into donor egg IVF, I’m basically an expert. So please allow me to explain what donor egg IVF is, and how it differs from regular IVF.*

So in a regular IVF cycle, you only need two people: a man and a woman. It begins with the woman taking medication to stimulate follicle growth (‘stims’ if you want to be hip with the IVF lingo). This comes in the form of a liquid that is injected into the thigh or (if you’re super hardcore) the stomach. The woman also takes a medication to suppress ovulation, so that it can be triggered at exactly the right time. This may be a nose spray which makes one feel like one has continuous post-nasal drip, or it may be another injection which needs to be mixed first by breaking a glass vial, because obviously that’s very safe and I’ve definitely never cut myself doing that.**

The woman does these ‘stimming’ injections every day for around two weeks, depending on the specific protocol. After the first ~5 days, she needs to have a blood test and a vaginal ultrasound every couple days. The ultrasound technician will check how the uterine lining is developing, as well as how many follicles are growing in each ovary, if there are any. (Normally only one follicle will develop to maturity in a non-IVF cycle, but the idea of the ‘stims’ is to increase the odds by growing multiple follicles.) The technician will record the number of follicles in each ovary and, if any are larger than 10mm, they will record the size. Or, if you’re like me and don’t grow (m)any follicles, this may turn into a game of ‘find the ovary’.

Once the biggest (‘lead’) follicle reaches a size of around ~20mm, the doctor will have the woman ‘trigger’ ovulation by taking another medication. This is also an injection, again administered in the thigh or stomach (because the woman probably hasn’t had enough needles poked into her recently). This must be taken exactly 36 hours before the egg retrieval surgery, so that the follicles will be nice and mature, but not yet bursting.

The man’s big moment to shine comes the next morning, when he deposits a sperm sample at the hospital. Then, exactly 36 hours after the trigger injection, the woman has the egg retrieval surgery. This is a relatively minor surgery (though it does involve more needles), and I will describe it in more detail in another post.

How does donor egg IVF differ?

In the case of donor egg IVF, you need an additional woman: the egg donor. The main difference is that almost all of the steps I’ve described so far then apply to the woman who is donating eggs, rather than the hopeful mother. The other difference is that the hopeful mother also takes medication (but in this case, to inhibit follicle growth) and has regular ultrasounds to check her uterine lining, since it is she who will (hopefully) carry the baby — not the donor. That means that after the egg retrieval, the donor’s part is done.

All of the subsequent steps (waiting to hear how many eggs are mature, waiting to hear how many eggs fertilize, waiting to hear how many embryos develop, and more waiting to hear if there are any to be placed back in and any extras to be frozen) are the same for both normal and donor egg IVF. If an embryo makes it to transfer, then it is placed in the hopeful mother with what is essentially a high-tech turkey baster. That kicks off the final stage of waiting: waiting to see if the embryo sticks and develops into a baby.

*Note that I’m only referring to actual in-vitro fertilization (IVF) here, not intra-uterine insemination (IUI), a less invasive procedure which is often tried before resorting to IVF.

**I’ve definitely cut myself twice breaking the glass vial. I can’t imagine this is legal in the US…

What are the odds of this donor egg IVF cycle working?

Some people we’ve told about our current donor egg IVF attempt automatically assume that this cycle will work — that we will walk away with a baby. While we are certainly way more optimistic about this cycle than our previous three (non-donor-egg) cycles, unfortunately, the odds are still not 100%…not even close. So in the interest of managing everyone’s expectations, what are the odds of this donor egg IVF cycle working?

I won’t leave you in suspense: the answer is 25%.

Yep. 25%. Depressing, right?

Of course, the exact value will depend on the quality and quantity of eggs they get from our egg donor, Marie. But given her age and the number of eggs they aim for, we are going through all of this effort — multiple international flights, daily injections, disrupting four peoples’ work schedules, and spending thousands of euros — for a one-in-four shot. In other words, don’t get out your baby booty knitting pattern just yet.

So how is this value calculated? As I said above, the two main factors are egg quality and egg quantity. Egg quality decreases with age, where the AMH level can give a rough indication. Marie has a fairly normal AMH level for her age (even a bit above average), but she is still 36. So as high-quality as her eggs may be, we can’t expect them to compare with those of an 18-year-old.

By egg quantity, I mean the number of eggs that Marie grows during the stimulation cycle. I had previously read that they aimed for 10-12 eggs in an IVF cycle. However, apparently 15 eggs is already getting into the territory of ovarian hyper-stimulation syndrome (OHSS), which can cause complications for the donor (in addition to decreasing the quality of the resulting eggs). In order to steer clear of those complications (and since it’s not a very exact science), our clinic will aim for 6 eggs in this cycle. Combining this number of eggs with Marie’s age, we arrive at a 25% chance of it working.

All of this is nicely summarized by this chart from my doctor, which I snapped a (poor-quality) picture of at our last appointment. It shows the predicted live birth rate as a function of age and egg number. The important thing to notice is how the live birth rate starts decreasing again above 15 eggs. Even with a younger donor, this would limit our success rate to 30% (for 6 eggs) or 40% in the very best case of exactly 15 eggs.

IVF live birth rate
Chart from our clinic showing predicted live birth rate as a function of number of eggs and donor age. Note that the success rate starts decreasing again for a large number of eggs, where ovarian hyper-stimulation syndrome (OHSS) can cause complications for the donor and affect egg quality.

In summary, not only are the odds not 100%, but it’s actually likely that this cycle won’t result in a baby. We will continue to be cautiously optimistic, but don’t expect me to be googling gender-reveal cake recipes quite yet.

Thanks

The response to this blog has been overwhelming, so I just wanted to take a moment and thank everyone for reading it.

I know that for many of you, reading a blog about infertility is not exactly how you’d normally choose to spend your leisure time. Then again, I never thought I’d be writing a blog about infertility, and yet here we are

For those of you who don’t know our donor, Marie, I want you to know that she’s totally on board with me writing about all of this. She even gave me the push to finally start it. I’d been thinking about starting a blog for a while, but until recently, it would have been all too doom-and-gloom. Obviously we’re still grieving that ‘natural’ IVF didn’t work out for us, but we’re also hopeful that this new path — egg donation — will be more successful. After all, Marie had both her kids on the first try, so her eggs are clearly top-quality. (If you could buy them at the grocery store, they would be those expensive cage-free organic ones.)

Just to be clear, Marie and I are also both chronic over-sharers, which Marie calls a ‘personality flaw’ and I call a ‘character asset’.

I also want to be clear that I don’t think I’m the first person in the world who has ever had this idea. When I told a (similarly fertility-challenged) friend about the blog, she said “Great, I’ll add it to my Saturday morning infertility reading list”, and she wasn’t even being sarcastic. There are many other great infertility blogs already out there written by fellow ‘IVF warriors’, like The Infertility Voice, Life Without Baby, Dreaming of Diapers, and (my personal favorite for best title) The Impregnable Woman.

There’s also a ‘National Infertility Awareness Week’, which, by coincidence, was this week. #NIAW

I’m really hoping this blog will be a short-lived pursuit, only necessary to keep our family/friends in the loop during this (last??) crazy leg of the journey. But I’m also a scientist — I understand the statistics — and I fully understand that it very well may not be. So thank you again for reading & following — your support means the world to us.