IVF Journey: Remedies for Male Factor Infertility – Azoospermia

[continued from Donor Eggs.]

Update: in real time, offspring #1 is at 32 weeks, with two months to do. He is reportedly very active during the day, but sleeps at night, which is very helpful so his gestational carrier (GC) can sleep. #2 is frozen in pre-launch until his GC is ready, probably next month.

Now for my part of the tale: my sperm tests came back stamped “azoospermia,” which is the condition of having no spermatozoa in your semen sample. This is rare for older men (who usually have at least a few feeble wrigglers), but is common for any man of any age who has been on testosterone replacement therapy for a length of time.

July 30 2019

The saga continues. World-class LA IVF doc refers me to either a Beverly Hills or Century City urologist-fertility specialist. They turn out to require an office visit starting with a $400 phone consult to come up with a treatment plan (and there are no promises you’ll get one.) Meanwhile, I find sources online, especially a comparative study of treatments. (These were funded in an effort to test use of testosterone itself as a male contraceptive; it does quite reliably induce temporary sterility, but they were doing baseline studies to see what (patentable, easier, more targeted) molecules they might find.)

So the treatment is: 1) Stop T, wait. Most men restart sperm production in a year. 2) Accelerate recovery using the same kind of hormonal manipulation used on egg donors. Notably, clomiphene citrate (cheap, easy to get) and injections of hCG (expensive, hard to get, subject of a silly diet craze as well.) I can find bootleg sources of both but it would sure be nice if our legitimate system wasn’t such a clusterfuck. Something like 80% of the men in studies recover in 2-3 months (but they were on average much younger.)

So I called the most prominent of three Eisenhower medical group urologists. No appt until Feb (7 months.) Not useful.

It’s amusing that all healthcare types think the patient is central and should have informed consent, but then make it an exercise in paying gatekeepers and wasting time no matter how informed the patient might be. I’ve had a few doctors with enough experience and intuition that they can quickly judge and decide matters. But much more commonly I can research the narrow subject of my rare condition and know as much or more about it than they do in a day or two. But thousands of dollars and hours of wasted time are the price of lost freedom. The rest of us must pay in time and $ so that stupid people can be protected from their mistakes.

BTW, there are websites where you can order up lab tests from Labcorp and Quest for cash prices. The full battery of STD and other blood tests the IVF doc wants costs about $450 cash there. Given only a few of these would be covered under our grossly expensive ACA-monopoly insurance policy, may just pay cash. I can’t get my primary care doc’s staff to do anything. Tomorrow I see my doctor and four tests that were supposed to be done for a 1/18 appt I had to cancel have never been set up so we won’t be able to discuss results as is their plan; Eisenhower is a nonprofit run by doctors and they are trying to make all patients over 40 come in three times a year and constantly undergo screening for bp and cholesterol, pushing everyone onto medications and keeping those office visits (and revenue) coming in. “Nonprofit” doesn’t mean no one is making money.

In hindsight, it was a mistake not to go to the Beverly Hills fertility specialist. My primary care doctor helpfully prescribed the hCG (available from a local compounding pharmacy — a few months later, the FDA forbid such compounding, and after that I had to use GoodRx coupons to get it from a regular pharmacy: both products start from encapsulated powder which has to be mixed with distilled water, so what the compounding pharmacist used to do, the patient now has to do. The injections are simple — subcutaneous (just under the skin, into a fat layer) and water-based so small-needle insulin syringes can be used. My doctor had me on 25 ml every other day, which seemed to be enough.

The full regimen I went on included more drugs (oral):

    Clomiphene, 50 mg / every other day – inhibits the feedback loop that suppresses natural testosterone. It’s a “selective estrogen receptor modulator (SERM)”

    Anastrazole, 1 mg /day – suppresses estrogen production via aromatase inhibition.

    hCG, .25 ml / every other day – chemically similar to luteinizing hormone, so shields testosterone and sperm production from negative feedback loops. Restored my levels of FSH (follicle-stimulating hormone) to normal in six months.

To cut to the chase, I ceased t-supplementation in early August and after failing to fertilize a single egg from the first batch, went to the Beverly Hills fertility guy (via Zoom, since the pandemic caused him to waive his usual requirement of examining new patients in person.) That world-renowned expert recommended what I was already taking, plus use of a Zymot sperm-sorting chip to select the best spermatozoa for ICSI (more about that in a later post.) We had to wait months for our egg donor’s second donation before trying again, but this time it worked — more than a year since I started rehab, we had four new frozen embryos (my children-to-be) that passed all screenings.

The graph showing my hormonal recovery:

FSH and T graph 5-13-20 showing recovery to normal levels

FSH and T recovery graph

How our IVF Journey Began

I’ll try to use my personal journal to proceed in chronological order — we began knowing little about IVF, and research took some time.

I haven’t made much of it here, but my husband of 15 years is a guy, which I think, unless the PC terminology has changed recently, makes us a gay couple having children. Our new neighborhood of 60 or so houses has two other gay couples with children already in residence, so we’re not unusual. This street has many children already and more on the way since the schools are considered top-notch and we’re within easy commuting distance of San Diego’s high-tech employers.

The first reason we started to think about kids was the experience of raising two puppies. I haven’t had a pet since I was five, and the sense of taking care of and training a young animal is similar enough to raising children that I realized we would enjoy it (after the initial unpleasantness!). We had both had some desire for kids earlier in our lives, but the hurdles then seemed insurmountable and of course we were busy with work.

First entry from my personal journal, June 5, 2019:

I checked again to see if it’s too late for us to have a kid of our own. No *outright* reason not to, except the $150-200K to order up a donor egg, IVF, and surrogate mother, *and* I’d be feeble long before the child left for college. Not that upper class families shrunk from sending their kids to boarding school at 12. If you’re not independent enough by then, you soon will be. 🙂 Kid would get a nice trust fund and of course lots of attention. I can’t get anything done anyway, might as well nurture, no?

As of two years ago, we were both retired from normal full-time work, so it now seemed practical to handle the baby years. Half the stamina, but two people home most of the time!

I found some online sources, and a surrogacy agency supportive of gay couples (and run by two gay dads.) Near enough, in LA, so I talked to them and they referred us to a West LA IVF doctor to get started.

July 2 2019:

I was going to write something about our Skype meeting with the LA baby consultants coming up later, but running out of time. We’re far from designer babies, but the current crude technology and regulation does let you 1) seek out and pay a premium for the egg donor with rare characteristics (it’s a hoot that Ivy League Asian women are the gold standard for certain seekers and so get the highest payments), and 2) you can’t do gene tests of the eggs yet without damaging them, but you can test embryos by removing a few pre-placental cells early, seemingly doing no harm at that stage. By choosing those without gross abnormalities you can reduce miscarriages and select for sex. We might try for twins, actually, for that 1.5x the costs for 1 and the sibling experience….

[Husband] is onboard. Which suddenly changes our plans for later life. Sort of like a Hail Mary pass on your last down, I’m starting to downgrade my expectations for my own work to put effort into the fresh new entrants in the race. They, at least, won’t be crippled by a lack of early support.

We found out later that multi-embryo surrogacy (hoping to improve chances of having one, but often ending up with twins) is no longer considered wise; this is partly because the technology has improved so 50-60% of screened and well-timed implantations result in a healthy birth, just as high as for multi-embryo attempts which risk twins and complications. Our meticulous IVF doctor won’t do multis anymore. This became the consensus in the last five years or so. Other changes in the technology made it just as safe to freeze embryos after 5-7 days of development, which allows the implantation at the perfect time for success. So our process was 1) freeze sperm, 2) have the egg donor provide eggs, and 3) fertilize eggs with sperm via ICSI (which is now standard for late-in-life IVF — ICSI is “intracytoplasmic sperm injection,” where the lucky sperm is injected into the egg by a very fine needle.) The resulting zygotes are cultured and observed for 5-7 days, graded on an A-F scale for viability, and genetically tested to improve likelihood of a successful birth.

micorphoto of needle injecting egg with a spermatozoa]

Needle injecting a single spermatozoa into an egg.

In hindsight, the natural process for prime-aged young people is error-prone and hit-or-miss, resulting in early miscarriages and other bad things. Nature’s Way includes Nature’s Punishments. Typically the natural way is to try many times and succeed enough to keep the species going, and the winnowing process sifts out most”tries” — either the egg doesn’t get fertilized, or if fertilized doesn’t implant, or if implanted doesn’t develop properly, and is expelled via silent miscarriage before the mother is even aware of being pregnant, or develops long enough for underlying defects to cause a later miscarriage. The latter feel like tragic losses, but it’s part of the natural process and no one’s fault.

We had both done sperm tests. [Husband] did fine, I did not — my test report was stamped “azoospermia,” which means zero spermatozoa in the sample. Turns out my decade of testosterone supplementation (“exogenous testosterone”) was the cause; complex feedback loops shut down both endogenous production of T and sperm production, which made drug companies run studies of such sufferers hoping to find the male Pill. No such drugs were found, but the cause and recovery are thoroughly documented in medical journals.

So I was hoping I could catch up with time and treatment — younger men in the same boat can have fertility restored in 3-6 months, but as the doctor warned me, that doesn’t mean an old man can recover as quickly, or at all.

[Husband] went ahead and started the process by driving to LA to deposit his contribution.

Aug 8 2019:

Project stall: [Husband] drove all the way to West LA (2+ hours) to make a 10:30 AM appointment to give a sperm sample for freezing. Two hours later, he’s told “we need more than that, could you come back next week?” The legally-required FDA paperwork only lasts 7 days so you can’t wait longer or you have to pay for it again (several hundred dollars?) So he goes back Tuesday leaving here at 6 AM. At least the doc complimented him on his youthful motility.

Meanwhile, I’m just working on producing a gamete or two. Tap tap tap.

[to be continued: “How We Did It,” in installments.]