[Continued from Remedies for Male Factor Infertility – Azoospermia]

The additional cost and unnatural nature of IVF has some benefits — both parents and embryos can be genetically tested in advance. If the parents have certain recessive genes, they can either use donor sperm or eggs to avoid offspring with significant defects, or roll the dice and check the resulting embryos for the issues they’d like to avoid. Most testing is motivated by a family history of genetic disease for one or both parents — it can be demonstrated that a certain inherited disease is not likely, or the opposite (in which case IVF

Our process involves both an egg donor and a separate gestational carrier (GC.) Both intended fathers and the egg donor were Counsyl tested; husband’s passed with no problems, while my genetic tests showed two fatal recessives and one “problematic” recessive (not fatal for years if ever, but weakening the adult.) Fortunately the egg donor’s test combined with ours showed no bad combinations.

The modern IVF process can freeze both sperm, eggs, and the embryos resulting from fertilization after 5-7 days; this reduces the difficulty of timing each element. Instead of rushing to inseminate fresh eggs with fresh sperm, the eggs and sperm can be frozen and thawed later for combination. The resulting embryos are typically cultured for 5-7 days and frozen as soon as they develop enough. In an echo of the quiet natural winnowing process, often only half or less of the eggs develop at all, and around a quarter look like good candidates for implantation.

The embryos are graded (letter grades!) A-D for development of the part of the cell mass that will be the child, and separately for the cells destined to form the placenta and accessories. This can be augmented by PGT-A (Preimplantation Genetic Testing for Aneuploidies) to determine which embryos are most likely to be viable. This is accomplished by taking out one or two cells from the less-critical part of the embryo and testing them. This is controversial because it is expensive, may possibly harm the embryo, and is not necessarily reliable because it’s not uncommon for cells in the embryo to have different genetic makeups (“mosaic.”) Nevertheless, choosing embryos that pass this test greatly improves the live birth rate for IVF. Desperate for offspring of their own, couples sometimes direct implantation of apparently unsound mosaic embryos, which can sometimes develop normally, but usually don’t.

Embryos that are missing entire chromosomes or major segments will either not make it to term or suffer serious defects that limit their lives. Since we are already intervening in the natural process and each attempt at pregnancy is very costly, using these tests to improve the odds is very much worth it.

While I was unable to produce viable spermatozoa, [husband’s] were fine and so we went forward with the egg donor and directed half the harvested eggs to be fertilized with his contribution.

Oct 18 2019

So they centrifuged my pathetic sample and found 4 live (if not terribly healthy) spermatozoa. Not really enough to work with!

Nov 21 2019

Egg donor at IVF doctor’ office in LA. Got an Amex charge notice, $16K, billed for the next few days until the extraction on the 23rd. 15 follicles ready, so harvest will likely be good (avg is around 10.) They will immediately fertilize half with Paul’s sample (frozen months ago) and freeze the rest of the eggs (waiting on my less-than-robust spermatozoa, which may have to be handled one-by-one.)

This first stage [husband’s] went well enough, though in hindsight we were both old enough to have benefitted from the Zymot sorting chip, which would have improved the health of the spermatozoa used for ICSI. Then we waited for reports from the culture lab to see how the little buggers did.

Nov 24 2019

Update: Got a report from the lab. Darwinian selection (which occurs silently in the normal process) underway. Of 9 oocytes, 2 rejected as immature. They thawed [husband’s] sample and selected sperm cells from a microscopic examination, then used ICSI to fertilize seven of the fresh eggs. Two of the remainder were discarded for not developing a healthy profile of pronuclei (PNs). Research has shown that the most healthy look is 2 normal-sized PNs, but other configurations (0, 1, 2.1 [one of the two is small]) have some chance of healthy development, so they are grown for more days in case they turn out fine (it turns out the male’s DNA can still be incorporated without the obvious signal of two PNs.) That leaves 5 growing. They weren’t specific about the 0N-1N-2N status of each. Kind of nerve-wracking.

Technology has improved a lot, but expect by a century from now that it will have progressed past “screening” to libraries of genetic material that can be recombined at will, and probably an artificial womb for gestation. Brave New Worldish. Costs will drop and it may eventually be seen as retrograde to have children the old-fashioned way. We’ve already seen lots of world-building where that cultural struggle is a theme.

BTW, any “super race” ideas (e..g., Star Trek’s Khan) will require a lot of arm-waving to explain how gene engineers can improve on the best/luckiest naturally born people. I don’t think (other than splicing out obviously damaging defects) anyone will be able to tailor the perfect combination of traits, and one thing we do know is that the natural diversity of talents contributes to the advantages of human teams….

Nov 28 2019

IVF update: the tech was rushed and so the report for Day 5 came in early. 3 embryos looked good enough for genetic testing (there was a differentiated clump of cells that will end up as the fetus and surrounding cells that end up as placenta, and it’s safe to remove one of those for the gene testing (shipped frozen to the lab.)) The 3 candidate embryos were then frozen. Testing comes back < 10 days. We haven’t heard from the surrogate wranglers about who might be available. I hope there’s more data to decide with. nov 30 2019 Day 7 report: the two zygotes not frozen didn’t develop and so were disposed of. 3 survivors were frozen Day 5, so that’s the choice for [husband's] kid. Kinda sad but as expected (the beyond-5-days embryos rarely develop enough). Was just reading about a PA bill that supposedly requires burial certificates for disposal of any fertilized egg. This is, of course, silly. Whether the bill actually says that is unclear, the usual amplification to get people outraged for clicks being in play. Dec 9 2019 Monday morning news: genetic tests done, 1 of the 3 embryos failed. Awww. I resent they don’t send us the report, but we can talk it over with the doctor if we schedule a Skype call. [later edit]: We got the genetic test results. Two euploid XYs (boys) and the aneuploid XY (female) who lacked the full complement of 16 chromosomes. Eek. The lottery odds favor us (only 16% chance neither XY will be carried to term) but still that worries me. [further note: I think they mean one Chromosome 16 is absent or incomplete, not 16 missing chromosomes.]

[Current state 2-1-2021: [husband’s] best embryo was implanted 7 months ago and is likely to be born to our surrogate in mid-April. We’re getting ready by buying all the equipment, clothes, diapers, etc.! We’ll get to mine later in the saga, which took much longer and had more issues with “Sperm DNA Fragmentation” (SDF) because I am older. Half of our first batch of eggs were fertilized with my sperm, and none survived culturing and screening.]