The end is in sight

My heart pounded, rattling the jail bars I call my rib cage. I fought to keep my prisoner in line and continue supplying it with oxygen. The silence on the other end of the phone warped time itself as I sat on hold. I kept whispering over and over that we already had two. Finally, unable to locate my nurse, the patient coordinator returned to share the news herself:

four

We'd finally done it. For the first time, we finished an IVF cycle with an embryo loss rate from day 3 to day 6 within our clinic's standards of 40-60%. And now we have Four. Whole. Chances. Four more possibilities for euploid embryos when all's said and done in another two weeks' time. That's more pre-implantation genetic testing than I'd even budgeted for, and for once in this experience, that's an unexpected expense that I'm happy to absorb.

Decoding our journey:
- ICSI stands for intracytoplasmic sperm injection, the way our clinic fertilizes all the eggs, by individually selecting and directly injecting the best single sperm into each cell, as opposed to letting the sperm duke it out in a Petri dish.
- MII is metaphase 2, or fully mature. MI is metaphase 1, not fully mature but can potentially still mature in the lab after retrieval, and GV is germinal vesicle, a very immature egg.
- PN stands for pro-nuclei. About 16-18 hours after ICSI, you expect successfully fertilized eggs to have two: one pro-nucleus from the egg and one from the sperm. Zero pro-nuclei can either mean that fertilization failed or, if luck's on your side, that the two pro-nuclei have already fused and you're looking at a zygote: the very first cell unique to a potential future baby.
- On day 3, cleavage-stage embryos getted scored on their number of cells, their fragmentation (little portions of cells that break off during the divisions), and their cell symmetry (how evenly sized the collection of cells are). Generally, you want to see at least 6 cells. Fragmentation is scored from 1-6, but you've got a problem if you exceed 2 or 3. Symmetry is scored from 1-3, and 3 is a problem.
- Getting into blastocyst territory, Mor stands for morula, which is an indistinguishable ball of cells generally observed around day 4. EB1 is early blastocyst 1. The cavity inside the embryo is forming but it's around 25% of the ball of cells. EB2 is the next stage of early blastocyst, where that cavity has reached about 50-75% of the interior of the ball of cells.
- At last, we get to score those final survivors! The number indicates how much the embryo "expanded", with a 6 (maximum score) actually meaning that little one hatched, something I wrote about last month. I still can't get over the fact that humans hatch out of shells. The first letter is a score of the inner cell mass, what could become the baby itself. It's scored from A (many cells, excellent) to C (very few cells, poor). B is somewhere in between and is considered good.  The second letter is a score of the outer layer of cells, called the trophectoderm. Again, the scoring system is A (excellent) to C (poor).

This week has been such a rollercoaster. From a devastating fertilization report on Sunday in which it appeared a mere 7 of our original 14 eggs had fertilized to the high of Tuesday when in fact, not only had all 10 of the mature eggs from Saturday actually fertilized but, for the first time, not a single fertilized egg had failed to grow. Going into Friday, I wanted to hope but could hardly bare it after the heartache of the last two Day 6 reports.

The good news also leaves me a little salty because of how we got here: it took us three cycles to finally try (the painfully pricey) artificial oocyte activation via calcium ionophore. I know I just a dumped a word jumble on you but buckle up because a bit more's coming. As Zhang et al explain in Effect of calcium ionophore (A23187) on embryo development and its safety in PGT cycles (Frontiers in Endocrinology, 2023), 

Studies have shown that calcium oscillations are primarily initiated by sufficient amounts of phospholipase C zeta (PLCζ) released from the posterior region of the sperm acrosome. PLCζ hydrolyzes PIP2 into IP3 and DAG. IP3 then binds to receptors on the endoplasmic reticulum, causing calcium ions to flow from the calcium pool of the endoplasmic reticulum into the cytoplasm, leading to an increase in the intracellular calcium ion levels; this in turn stimulates calcium-dependent protein kinases, leading to a cascade response of cortical granule cytosolic and zona pellucida. DAG further stimulates and maintains these calcium oscillations through protein kinase C. Under normal conditions, the braking step during ICSI damages the plasma membrane of the sperm cell, leading to easier release of PLCζ, and thus, to calcium shock in the oocytes after ICSI fertilization. Nevertheless, oocyte activation fails in some patients. Some studies suggest that this may be due to the lack of PLCζ in sperm or mutations in the PLCζ gene. In addition, even sperm with normal PLCζ levels differ in their ability to activate oocytes. 

In layman's terms, if the sperm has an issue with one of its protein components, your eggs aren't waking up and they sure as heck aren't going to develop into healthy embryos. So how is there not a sperm test for this? Women are just expected to go through the pain, hassle, and emotional turmoil of several IVF cycles before shelling out thousands "just to see" if this might be the root cause of poor IVF outcomes. Do you realize how much easier it is to get a few extra sperm samples and test them for all their potential issues rather than repeatedly cycling me to figure this out?? Ugh, I can't even.

So yes, I'm thrilled that we appear to be nearing the end of our IVF journey and I am also salty AF. And tired. So tired. I can't wait to stop carefully managing a medical-appointment-riddled calendar, to get back the hours I spend each week fighting utterly incompetent health insurance reps, and to start reallocating our funds back to our depleted savings reserve rather than the endless pit of medical expenses. There's probably still a fourth cycle in the works, but probably not a fifth. The end is in sight.