hcg

IVF Journey: On SDF and Antioxidants, Sorting Chips

Zymot sperm sorting chip (photo credit: Zymot)

Zymot sperm sorting chip

I offer up my own experience here since it may help older/infertile men seeking to be fathers. It’s anecdotal, not statistical, but I did go from zero sperm to 4 to millions in a year. And my first try turned out badly with the eight eggs assigned to me — only two developed, and they were genetically abnormal, which meant more cost and delay to have our egg donor back again. By then more time had passed and presumably the Zymot sorting chip picked out better sperm for ICSI, so it was successful — four good embryos from 20 eggs, which is more than usual.

Disclaimer: this is not medical advice, just what happened to me, so if you are persuaded to follow a similar regimen, there is no guarantee it will work. If you are infertile in middle age and are seeing the clock run out, you would be wise to consult a fertility specialist.

My first try at IVF didn’t result in any viable embryos, presumably because there was SDF (Sperm DNA Fragmentation) — damage to the DNA of the sperm, thought to be the result of oxidative stress on the way from production to delivery and rustiness of the sperm production process in older males. The IVF doctor warned me that such cases can be permanent or take over a year to remedy with medical assistance.

Sperm DNA Fragmentation (SDF):

Men with sperm motility defects often have high levels of sperm DNA fragmentation. The degree of DNA fragmentation in sperm cells can predict outcomes for in vitro fertilization (IVF) and its expansion intracytoplasmic sperm injection (ICSI). The sperm chromatin dispersion test (SCD) and TUNEL assay are both effective in detecting sperm DNA damage. Using bright-field microscopy, the SCD test appears to be more sensitive than the TUNEL assay.

Its main units of measurement is the DNA Fragmentation Index (DFI). A DFI of 20% or more significantly reduces the success rates after ICSI. (more)

I never had an actual test for SDF, but the failure of 8 eggs to produce one viable embryo with my sperm strongly suggested SDF. One of the many causes of SDF is oxidative stress, so it can help (and do little harm) to up your intake of antioxidants.

March 27 2020

We had a great Zoom teleconference with Dr. [Redacted], who’s quite knowledgable (world expert and of course not cheap.) He commended me on my self-help recovery treatment. He also badmouthed compounding pharmacy rHCG and offered to prescribe the regular pharma variety (high-priced, no doubt.)

He’s plugging use of a “Darwinian selection” chip which selects the best by making them compete to swim down a microfluidic channel. This is the culmination of similar ideas in a Petri dish. I may be a good candidate for such since the last test showed 300K sperm, half motile. The more drastic collection from the testicles may not be necessary. The doctor consults for the chip company [Zymot], and he also suggested a line of antioxidant supplements he developed. I checked the ingredients of his branded supplement, and I had already been taking all of them with one exception, so it was less costly to just buy the missing ingredient and add that to my usual vitamins.

Dr. [Redacted] name-dropped [gay Silicon Valley billionaire], who he said “is in the same boat,” not wanting to have his sperm selected by a community-college-educated technician. I appreciate *justified* elitism… but people do come from around the world to our IVF doctor. It costs little extra to use the Zymot or similar sorting chips, so it would be wise for all older men to consider it.

I rarely meet anyone who knows more about much of anything than I do, so that was refreshing. And no one knows when the ASRM will relax the “no procedures unless ongoing” restriction. There’s more data on pregnancy effects (limited) and transfer of the virus to the baby (doesn’t seem to happen), so it’d be nice if they allowed the plans of millions to proceed. Which reminds me of the “no cataract surgery because it’s not critical” ruling. Postponing trans surgery (medically unnecessary, should be discouraged for minors) is no loss, but this is a taste of M4A: some high council will decide on political grounds whether your treatment is necessary or not.

As it turns out, implantation of the first boy was delayed over six months by the ASRM guidelines, which were in turn guidelines of the CMS (Centers for Medicare and Medicaid Services) which decided hospitals and clinics should postpone all non-emergency procedures to keep beds and staffing free for COVID-19 patients. This emptied hospitals and laid off staff, postponing important surgery (cancer biopsies, for one) and causing worse outcomes for millions of people. And how many tens or hundreds of thousands of IVF babies will now never be born?

Repeating the drug regimen from the previous post:

    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.

Antioxidant Supplements: One commercial supplement (FH Pro for Men) has this ingredient list:

Vitamin A (as beta-carotene) 1500 mcg, Vitamin C (as ascorbic acid) 120 mg, Vitamin D (as cholecalciferol) 30 mcg, Vitamin E (as d-alpha tocopheryl succinate and mixed tocopherols) 134 mg, Vitamin K1 (phytonadione) 40 mcg, Vitamin K2 (menaquinone-4) 40 mcg , Thiamin (as thiamine HCl) 3 mg, Riboflavin (as riboflavin 5 phosphate) 3.4 mg, Niacin (as niacinamide) 20 mg, Vitamin B6 (as pyridoxal 5 phosphate) 25 mg, Folate (from L-5-Methyltetrahydrofolate, calcium) 1360 mcg DFE, Vitamin B12 (as methylcobalamin) 1000 mcg, Biotin (as d-biotin) 600 mcg, Pantothenic acid (as d-calcium pantothenate) 20 mg, Iodine (as potassium iodide) 150 mcg, Zinc (as zinc citrate) 30 mg, Selenium (as selenomethionine) 140 mcg, Copper (as copper sulfate) 1 mg, Manganese (as manganese bisglycinate chelate) 2 mg, Chromium (as chromium picolinate) 120 mcg, Molybdenum (as molybdenum glycinate chelate) 75 mcg, L-carnitine L-tartrate 2000 mg, L-arginine HCl 350 mg, CoQ10 (as ubiquinone) 200 mg, N-acetyl cysteine 200 mg, Grape seed extract 20 mg, Lycopene 10 mg, Benfotiamine 1 mg, Vegetable capsule (hypromellose), Microcrystalline cellulose, Magnesium stearate, Silicon dioxide.

See this study for results with this commercial supplement. Some of these ingredients are questionable. Taking an array of antioxidants is normally not especially beneficial (results of studies are mixed — no effects or even deleterious effects), but in case of SDF, six months of these will probably help.

You can buy this high-priced premixed formula as capsules here (FH Pro for Men) or do it yourself at lower cost (but less convenience.) If you don’t mind taking lots of pills twice a day in hopes it will help with SDF, here’s what I took:

    Daily multivitamin for older people (“Spectrum Silver” equivalent)
    Vitamin C (500 mg)
    Vitamin D (2000 IU)
    Vitamin K2
    Niacinamide
    Methyl Folate
    Cal-Mag-Zinc
    Acetyl-L-Carnitine
    L-Arginine HCl
    coQ10 (ubiquinone)
    NAC (N-Acetyl-Cysteine)

Amazon links for these (note that if you buy through these Amazon affiliate links, a tiny percentage of your purchase costs comes back to me; it’s always appreciated.):

Typical multivitamin for older people

A “Spectrum Silver” equivalent

Kirkland 50+ Multivitamin

Vitamin-C-1000mg

Antioxidant Vitamin C

Vitamin C 1000mg

Vitamin-D-3-2000iu

Vitamin-D-3-2000iu

Vitamin D-3 2000IU

Vitamin-K-2-100mcg

Vitamin-K-2-100mcg

Vitamin K-2 100 mcg

Niacinamide-500mg

Niacinamide-500mg

Niacinamide 500mg

Methyl-Folate-1000mcg

Methyl-Folate-1000mcg

Methyl Folate 1000mcg

Calcium Magnesium Zinc

Calcium-Magnesium-Zinc

Calcium Magnesium Zinc tablets

Acetyl-L-Carnitine bulk powder

Acetyl-L-Carnitine bulk powder

Acetyl-L-Carnitine bulk powder. This is more cost-effective; add to a protein shake or other strongly-flavored liquid to cover the taste.

L-Arginine-Powder

L-Arginine Powder

L-Arginine Powder. This tastes so foul it spoils anything liquid. I found it best to dissolve it in warm water to drink quickly, then immediately rinse.

Coenzyme Q10 (Ubiquinol)-100mg

Coenzyme Q10 (Ubiquinol)-100mg

CoEnzyme Q10 (Ubiquinol)

N Acetyl Cysteine

N Acetyl Cysteine (NAC)

N Acetyl Cysteine (NAC)

The drugs in the list previously mentioned all require prescriptions. The HCG in particular is used not only by men restoring fertility, but by women doing an IVF cycle; a diet fad (which is now fading) had people injecting themselves with large bootleg quantities to lose weight.

Here’s what a packaged pharmacy bottle looks like — inside the box is a vial of lyophilized (dried and preserved particulate) HCG and a vial of sterile water. Since the FDA no longer allows compounding pharmacies to do this for you, you have to mix it yourself by using a syringe to move water from the water vial to the hCG vial. The result is a water-based, injectable HCG that begins to spoil immediately, so use it in 30-60 days at most.

Packaged HCG

Packaged HCG

The syringes for these subcutaneous (just beneath the skin) injections are readily available because they are used in the billions for self-administered insulin shots. The procedure is to find an area underlain by fat (often around the naval) and pinch the skin to insert the very fine and short needle before injecting. This is usually nearly painless. The syringes look like this:

B-D .3 ml syringe

B-D .3 ml syringe

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