What did you decide to do if you’ve gone this route? How did you make that decision?

Many important convos will be had this week as we make this choice for the third time. Last time we didn’t have any embryos to freeze, so the choice turned out to be correct for us (saved us some money this way, as you have to pay up front for the PGT cycle vs not, on top of the fee per embryo at our clinic). This time, on a different protocol I really have no idea what the right choice will be.

Here’s some of the info I have found which I’ll dump on you all so you can make informed choices. For every study for, there’s a study against. (actually for every “for, there were 2+ against, despite PGT-A being so popular in North American clinics).

Studies against:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607878/
https://www.statnews.com/2021/11/26/ivf-pregnancy-pgta-genetic-testing/
https://academic.oup.com/humupd/article-pdf/29/3/291/50276439/dmad001.pdf
https://brieflands.com/articles/zjrms-121265

According to an analysis by Kemper, Wang, Rolnik, Mol:

“The biopsy may inflict direct damage on the embryo; the results of the biopsy, namely false positives and negatives, may be an indirect avenue of ‘damage’ to the embryo, or may reflect differences in the molecular technique utilized. Furthermore, examination of the results of only the first embryo transfer is likely to cover both indirect and direct forms of harm, as there is likely to be an increase in pregnancy rates due to the better selection of embryos. If the first embryo transferred is successful, then perhaps these harms are mitigated for the patient, but this relies on a relatively small first transfer success rate.

Mosaicism (the presence of two or more different sets of genetic material within the same embryo) may lead to potentially good quality embryos being discarded; by this mechanism, PGT-A actually removes these potentially viable embryos, whereas morphological assessment alone would allow these embryos the chance to produce an ongoing pregnancy. The reporting of embryos with a PGT-A plot falling in the mosaic range continues to be an issue, not because of the mosaicism per se, but due to the absence of solid unbiased evidence to counsel couples on the nature and destiny of these embryos. A mosaic result may be irrelevant, being confined to the placenta, or may represent true foetal mosaicism, with various degrees of clinical manifestations and significance (Kemper et al., 2019b; Popovic et al., 2020). This nuance is missed when analysing only the first embryo transfer; the first embryo will likely have the highest ‘purity’ and may well not be mosaic; it is only when cumulative rates are analysed that the potential impact of mosaicism is revealed.”

Studies for: (I’ll admit these were harder to find… if anyone has any to share, feel free in the comments)
This one shows no benefit for younger IVF patients, but positive benefits for older patients:
https://jamanetwork.com/journals/jama/article-abstract/2790646
https://www.frontiersin.org/articles/10.3389/fendo.2023.1020055/full

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When you have repeat failure to conceive there are lots of weird things that start to become triggers – and now that I’ve been through it, rightfully so. Here are a few things to never say to someone struggling with infertility or loss:

⁃ “But at least…” – sure, there are silver linings. It’s easy to want to look for them when talking to someone about infertility, but nothing fills the void in your heart that not having a wanted child of your own does.

⁃ “Just relax…” – followed by anecdotes about how xyz person got pregnant only when they stopped trying. (Here’s a secret, you never truly stop trying, or thinking about it every time you await your period). If relaxing was the cure for this medical condition, doctors would be out of work.

⁃ “Try to enjoy the process…” – especially during trying to conceive the old fashioned way. Nothing kills your libido and the mood more than timed intercourse and the pressure that comes with that. It’s the last thing you want to do when you’ve been timing it for 15 months+.

⁃ “Your time will come” – I sure frickin hope so! But it’s not guaranteed whatsoever.

⁃ “Congrats on doing IVF!” – the number of people who have congratulated me on my infertility journey and the need to spend tens of thousands of dollars on treatment is astounding.

⁃ Following miscarriage, “at least you know you can get pregnant!”… sure, but it’s not working. Something is clearly not working and I might never carry a baby to live birth.

I’ve had a close friend tell me that they really don’t know what the proper thing TO say to me is, as I experience the ups and downs over and over again. And to be honest, there isn’t really anything right to say. It’s a crapshoot that I wouldn’t wish on my worse enemy.

What helps me, is knowing I still have people in my corner. Still being invited to things, despite sometimes having to bail due to IVF commitments or a medication schedule. Having people simply ask how I’m doing and being open to a potential not so great response. Hearing me out when I need someone to talk to about how much the process sucks or hurts or is unfair. Just don’t stop checking in with your people. Don’t leave them to suffer through it alone. I’ve had a number of friends disappear through this journey and it’s hard. People stopped inviting us out, asking how life is going, shooting the shit. But I have also had people I never expected come out of the woodwork to pick me up and help me keep going when it feels like the universe is not on my side. A big thank you to all of you. We don’t feel like ourselves when we go through the rollercoaster of infertility. It’s not easy to be our support. But we will remember your kindness for a lifetime.

This third transfer preparation was aided by some gracious humans who offered to transport donated meds and who drove miles and miles to make it happen, who offered a place to stay or a ride to and from the ferry if we needed it. My heart felt full going into the FET prep.

Transfers after a miscarriage are a bit of a pain. You have to wait for your cycle to come and go, so it’s about a month waiting from your loss until your next cycle day 1. From March 10 until April 16. Then, priming began. More Estradiol, more visits with Wanda. More progesterone up the hooha.

Lots of things can happen in a frozen transfer to delay your cycle. From ovulating through the meds to thin endometrial lining issues. I suffer from the latter, and every time I try to grow my lining using medication, it takes its sweet time. More delays. Woohoo.

The first baseline ultrasound happens generally 2-3 weeks following priming beginning. Mine was May 5 on CD20. Too thin. I went a few more times around 2-3 days apart, and then finally on May 12, cycle day 27, I was finally ready.

They ask for a minimum lining thickness of 7-8mm before proceeding. Sometimes, you don’t get there and the cycle gets cancelled. But I got there. My frozen transfer would be scheduled a week later on May 19. We would finally get to meet our last normal embryo.

May long weekend was chaos for travelling from our island to our clinic – they had recently stopped offering transfers at our local clinic, so now we’d have to travel for any procedure larger than monitoring. Booking a ferry was nearly impossible and I had to work the following day, but we somehow managed to get on it that very morning at 7am. We anxiously anticipated our last shot from this retrieval.

The transfer went as expected, short and sweet. A new doctor we hadn’t met did the procedure (no meds this time whatsoever but no pain), and we were sent off again to suffer through the two week wait (9 days for us technically). That very day I had mild cramps, and in the days to follow they continued. My fingers and toes were crossed. The symptom spotting ramped up. Nausea, headache, back ache, fatigue, twinges, tender breasts. The whole gamut. I was 95% sure this was it for us. I had a feeling in my gut, again.

Earlier that month we decided to take a vacation – it had been about a year since we got the chance to relax and explore. Yolo. Especially during fertility treatment when so much gets pushed to the back burner – both time wise, mentally and financially. We booked a 9 day trip to NYC and we couldn’t be more excited.

Our significant transfer delays due to my lining were unexpected, so my beta tests fell on the days I’d be out of the country. Because of this I decided to test on May 26. 7 days post transfer, or 12dpo. This would give us a fairly definitive result. We left for the ferry and drive to the city where we’d overnight until our morning flight the next day. So I could test that day and the morning before we departed (8dpt by then). I packed all my injection meds, suppositories and supplies just in case. Then I took the pregnancy test.

It was negative.

I tested the next morning in a frenzy. It had to be wrong. Too early. Something. Stark white.

Our last normal embryo failed to implant. My body failed me. My symptoms failed me (I read into this further and apparently the high doses of progesterone I was on can mimic pregnancy symptoms 100%, great to know). I was angry, and I’d be stuck on a plane for 6 hours to stew in my thoughts. The idea of a relaxing vacation was out the window. Now WTF were we going to do? By this point, 30k in the hole with nothing but pain and suffering to show for it. A failed egg retrieval cycle, 3 failed transfers of 2 normal embryos. 7 total embryos gone.

I heard those phrases I knew all too well echoing in my mind. “Try to relax”, “At least…”, “your time will come…”. All I wanted to do was cry on that plane.

Lost was an understatement – but damn was I glad I had 8000 distractions in NY to take my mind off of it. At least to an extent.

We had the trip of our lives. I connected with family randomly in NYC that I hadn’t seen in many years (they just happened to be there the same week as us from the UAE). We ate at a 3 Michelin star restaurant, we saw Ray Ramano perform at the comedy cellar, we went to two wonderful broadway shows.

All I can say is book the damn vacation. Nothing is guaranteed. Life is too short. We can always make more money, but time is finite. Living our lives, finally, was the best medicine for the loss we felt deep in our hearts. It brought back our connection we felt got buried during all the trauma and all the loss. It healed us just enough to keep moving forward.

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The hardest part of IVF is the waiting game. The complete unknown and it feels like every appointment is one where you’ll hold your breath. Maybe for 10 mins, maybe for 2 weeks. The lack of control you have over your actual body and its responses can be very frustrating and discouraging. It takes a lot of getting used to, especially for control freak me.

We went into the clinic locally this time. And this was the first time until now that we had actually seen our doctor’s face. We had only spoken to him twice in 6 months. A different doctor did the last transfer and our retrieval.

The local clinic where we live is lacklustre. For how much money you toss into IVF out of pocket, you’d expect more from the digs. It felt like going into an abandoned office building when we ventured into this part of our clinic. Until now, I had only been in the monitoring rooms – also lacklustre but pretty generic with dim lighting so not as shocking.

This transfer threw me for a loop initially. We walked into a waiting area, and I had asked for Ativan again because I didn’t know how my body would react to the catheter. Better safe than risking major uterus cramping. I went in early like they asked but they never passed the message along that I was waiting to take the medication in office (thanks receptionist). So they pushed our transfer back 20 minutes and bumped the next person into our spot. The kicker… they had the same birthday as me. Flash back to the 800 times they verify your embryo is yours using the birthday. Well, I got super worried they’d mix us up due to the schedule change, and the same birthday. Stress isn’t fun when you’re about to meet your embryo. I reiterated that I was worried about a mix up to every single person I spoke to after that. All I can say is speak up! Advocate, advocate, advocate.

The meds kicked in and I got changed into my pantsless getup while my husband donned his white space suit and we were escorted into the transfer room. This time, instead of an operating room it was a cramped clinic office with barely any room to roll the equipment around. The radio was playing in the background. We met the doctor and in no time it was done. I didn’t feel much besides the speculum. We got our little ultrasound photo, I got dressed and we departed.

My husband went back to work for the day and I took it easy. It was February 1, 2023.

I’ll get into more about chronic testing and testing culture one day, but let’s just say until now I was more than slightly OCD about testing. February marked 13 months of trying. 13 months of two week waits, testing, disappointment. It had been 9 months since my chemical pregnancy. Since my last positive test. I don’t know how I did it, but I managed to wait SEVEN days before I caved and got the urge to test.

On day 6 I started feeling some stuff, but after so many failed months of trying and ghost symptoms for absolutely no reason, I learned I couldn’t trust my body to indicate either way. I did get some pretty awful back pain on day 6, which would be the equivalent of 11dpo for those trying unassisted. The pain persisted and I had a gut feeling. I couldn’t wait any longer. Not even the two days until my beta blood work.

It was positive!!!! And not super faintly positive squinter like before. It was actually positive. I was soooo very cautious because I knew how much my heart broke last time around. I probably took 10 tests that day. All. Were. Positive. I was pregnant. It worked.

My beta blood work was scheduled for day 9, but I couldn’t wait so I went on day 8. It was within the minimum levels they had hoped for (they look for 50 on day 9, I was 46 on day 8). I went back two days after that and it had more than doubled to 108. Heck yessss!

I continued testing a couple of times a day, eventually upgrading from my crappy Amazon pee sticks to the fancy first response tests. I tracked my progression day to day to make sure my levels were getting darker, and they did continually.

I was so cautious. Could this really be happening? My brain and heart couldn’t believe it but my eyes were seeing it. I got a “dye stealer” on day 12 after transfer (when the test line is darker than the control line). This eased my mind substantially.

Now, the hardest wait of all – the 7 week ultrasound. 3 weeks of torture were ahead of us. I repeated cheesy mantras such as “my body accepts this pregnancy”, kept my feet warm and stopped eating foods I wasn’t allowed in pregnancy. I reminded myself every hour of every day that I was still pregnant and we were so very lucky. I stocked up on pregnancy books, just in case. I ordered a pregnancy pillow and welcomed my first small bouts of nausea. I also got to continue those wonderful suppositories and PIO injections.

This was finally happening.

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On day 6 the clinic called to tell us that they had biopsied and frozen 6 embryos, in addition to the one 4AA they inserted into my uterus. I jumped for frigging joy. 6 embryos out of 13 eggs retrieved is unheard of. There were others, too, but they didn’t meat the grading requirements to freeze. Every lab is a bit different on how they grade and what they believe it’s worth keeping. 6 was amazing. They biopsied them and mailed the samples off to Igenomix, a genetics lab that tests for chromosomal abnormalities.

PGT-A Chromosomal testing is helpful in some ways. The unfortunate thing is that most clinics make you decide whether to PGTA test before you even begin your cycle. There’s an increased cost to set this up, so if you don’t get embryos you’re out that money. In addition to this, for each embryo you send out, you pay a testing fee per embryo. At the time, ours was $550 per embryo, so an addition $3300 after our cycle. It’s not chump change.

PGT-A testing doesn’t find everything though. It tests for the most common genetic abnormalities, such as common trisomies. There other types of PGT tests too, but this is the most common. Skip the next section if you don’t care to read about the specifics…

– Preimplantation genetic testing for aneuploidy (PGT-A): This type of PGT screens embryos for certain chromosome abnormalities. Human embryos typically have 23 pairs of chromosomes (46 total) in each cell.  One chromosome in each pair is contributed by the egg, and the other is contributed by the sperm.  It is common for embryos to have random chromosome abnormalities such as a missing or extra chromosome, which is called aneuploidy.  In the majority of cases, these chromosome abnormalities happen by chance and are not inherited from a parent or donor.  Embryos with aneuploidy are more likely to result in miscarriage or a failed transfer.  Some types of aneuploidy may result in the birth of a baby with a chromosome condition such as Down syndrome or Turner syndrome.
– Preimplantation genetic testing for monogenic disorders (PGT-M): This type of PGT is performed when a patient has an increased risk for a specific genetic condition to occur in their embryos.  PGT-M is appropriate when an individual is affected with a genetic condition that could be passed on to their children, for individuals who are carriers for an X-linked condition, or when an individual and their partner or donor are both carriers for the same autosomal recessive condition.
– Preimplantation genetic testing for structural rearrangements (PGT-SR): This type of PGT is performed when a patient or their partner has a rearrangement of their own chromosomes such as a translocation or inversion.  A person with a translocation or inversion is at increased risk to produce embryos with missing or extra pieces of chromosomes.  Embryos with missing or extra pieces of chromosomes are more likely to result in miscarriage, stillbirth, or a child with serious health issues.
(Source)

If you have suspected monogenic disorders, sometimes they will send you for IVF not because of infertility, but so they can test for these disorders. For PGT-A, its for people who have a need to do IVF otherwise, and it gives them peace of mind. The results can come back either Euploid, Aneuploid, Mosaic, or No Data.

I’ll also note, when testing for chromosomal abnormalities in blastocysts, it is done by taking a miniscule sample from the embryo. This sample will ideally contain all the data needed to say whether the inner and outer portions of the embyro are chromosomally normal, however the data is taken from the outer portions which will eventually form the placenta (not the fetus). The inside portion will form the fetus and is usually left untouched.

Euploid Embryos are embryos with normal chromosomes. People often say your fertility shits the bed at 35 and it drops off a cliff. For some it does, but Euploidy and Aneuploidy are the reason they state this. You may be able to make lots of eggs and fertilize those eggs, and they may make it to blasts, but they might all be aneuploid.

Here’s a chart showing the probability of Euploidy at different ages:

Aneuploidy is when an embryo comes back with one or more extra or missing chromosomes. This can result in either a nonviable pregnancy, babies that may not survive after birth, or a surviving newborn with congenital birth defects and functional abnormalities. Most aneuploid embryos won’t implant, but at times they do, and it can be the main cause of early miscarriage. When getting pregnant ‘the old fashioned way’, we have know way of knowing whether our embryos are euploid or aneuploid, and this can sometimes be why a cycle isn’t working.

Mosaic results are a different beast. No tests are perfect. A mosaic outcome *could* result in a live birth – it’s heavily debated in the fertility community, so some clinics will implant Mosaics while others will not. In PGT-A, mosaicism is defined as a mixture of 20% to 80% aneuploid and euploid DNA content, with some euploid content.

No Data embryos occur when there is not enough genetic material in the biopsied sample to provide a picture of the genetic makeup of the embryo. These are often given the option to retest, or to transfer blindly. Re-testing requires thawing the embryo, re-biopsying it, refreezing it and sending it off again. This can damage the embryo so some people choose to forgo additional testing.

PGT-A testing can help you select the embryo that is most likely to end in a successful pregnancy/live birth. However, having a PGT-A normal embryo does not guarantee a successful transfer cycle.

The 3 embryo rule
Many doctors will say it takes 3 Euploid tested embryos to achieve a 95% chance of pregnancy in most individuals. Many first transfers of PGTA-Normal embryos will result in a pregnancy. Those who take more than 3 transfers likely have other underlying issues at play which may or may not be evident.

Now that you’ve had a science lesson!

We sent out embryos off for testing and waited a painful two weeks over Christmas 2022 for our results.

In the meantime, I was still PUPO. They encourage you not to test at home during IVF due to a variety of factors. You go in for your beta bloodwork usually 9-14 days after your transfer, depending on the clinic. I went on day 9. I was feeling good until a few days before. We had a bunch of embryos and so much hope. I caved and tested at home.

Stark White.

I went for my betas on December 19, and the result came back as <1, which means you are not pregnant. Our first perfect little embryo (pictured in the last post) didn’t make it. I was sad. But I was still hopeful.

On December 26 I got a call and voicemail with my PGT-A results. Then logged into my portal – the portal is where they keep all of your communications, docs, med schedule and results. It’s like a beast of a database from the year 2000. I logged in and the embryologist had sent me SOMEONE ELSES RESULTS. I was super confused. Not to mention the concern I had that someone also got my results, and all of my personal information to boot.

I tried to reach the embryologist but as the clinic wasn’t open officially until Jan 3, I was left in the dark. The results in the voicemail differed from the results in my portal for the other couple. So I went with what was in the voicemail (which turned out to be correct).

13 Eggs Collected
13 Eggs Mature
13 Eggs Fertilized
7 Blasts (6 tested, 1 failed transfer)
We found out 2/6 were Euploid, 2 were Aneuploid and 2 were No Data.

I was pretty happy, considering we had been lucky with attrition at that time. 2 Euploids meant two more shots at this thing. and 2 No Data could be more hope!

I’ll fast forward to February, when we decided we’d retest the No Data embryos. We thought for sure one would be Euploid. Tragically, neither embryo survived the thaw. We lost 5/7 embryos in two months due to attrition, aneuploidy and failed implantation.

Our goal was one child, and we felt pretty damn positive about our two normal embryos and got to work on preparing for another embryo transfer.

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