Diet and Exercise

IVF Journey: On SDF and Antioxidants, Sorting Chips

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

“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:

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.):

A “Spectrum Silver” equivalent

Kirkland 50+ Multivitamin

Antioxidant Vitamin C

Vitamin-D-3-2000iu

Vitamin-K-2-100mcg

Niacinamide-500mg

Methyl-Folate-1000mcg

Methyl Folate 1000mcg

Calcium-Magnesium-Zinc

Calcium Magnesium Zinc tablets

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. 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)

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

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

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

“selective estrogen receptor modulator (SERM)”

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

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

Nessun Dorma: Insomnia and Sleep Aids

Sleep deprivation side effects — Wikimedia

Most people experience less than satisfying sleep at least occasionally, but some sufferers go for years without relief. Not being able to fall asleep at the normal hour in a reasonable length of time is known as “sleep onset insomnia.” Older people especially may suffer from waking too soon or not getting enough deep sleep. Sleep is a complex neurochemical phenomenon, and a wide variety of different causes for poor sleep make it hard to diagnose and relieve.

What’s often called sleep hygiene is a collection of good practices and habits that tend to lead to better sleep. Harvard Medical School’s Division of Sleep Medicine has a good list.

If you’re getting exercise and avoiding caffeine or alcohol late in the evening, you might still have problems. Chemical sleep inducers in the form of drugs and supplements can help get you to sleep or keep you asleep, but prescription medications like Ambien and Lunesta can have side-effects, cost a lot, and can be addictive. Many people have been hooked on them (and the drugs of past eras like tranquilizers and sedatives) for years, unable to stop without going through far worse withdrawal symptoms.

If your problem is getting to sleep, your body and mind may be revved up and out of synch with your natural sleep hours. Not engaging in eating, drinking, or stimulating activities for a few hours before normal bedtime can help. Some natural supplements — chemicals already found in your body or food that promote sleep — work for many people. A list:

Melatonin, one of the body’s primary sleep signalling chemicals, is continuously produced by the pineal gland, but destroyed by light hitting the eyes, so it is a driver of the sleep-wake cycle that lags exposure to light; it’s partly because exposure to light synchronizes your sleep cycle that staying up late with bright lighting can disturb it. Taking natural melatonin a few hours before normal bedtime reinforces the natural cycle somewhat, although there’s little evidence of it crossing the blood-brain barrier after absorption by the digestive system. Try sprinkling a bit of melatonin in powdered form under your tongue, perhaps by opening a commercial capsule like these. Melatonin, like some other drugs and vitamins, can be absorbed somewhat by the blood-vessel-rich skin under the tongue — this is called sublingual administration. Melatonin successfully reduces time-to-sleep and insomnia for most people, though it is less effective at keeping you asleep. If you’re already getting up to go to the bathroom at 3 AM, though, you can do another sublingual dose of melatonin and sleep a few more hours successfully.

5-HTP or its precursor L-Tryptophan. Tryptophan is an amino acid component of the proteins in many meats, eggs, and dairy products, and is commonly believed to create the sleepiness after a big Thanksgiving turkey dinner — though turkey meat has no more L-Tryptophan than most other meats. It is also usually credited for the “glass of milk at bedtime” method for assisting sleep. After a Japanese manufacturer of L-Tryptophan produced contaminated batches in 1989, injuring thousands and killing as many as 37 people, L-Tryptophan was banned by the FDA in the US. These restrictions were loosened and finally lifted completely in 2005. As a result of that incident, though, more people still take 5-HTP, which is a metabolite of L-Tryptophan and his similar effects. A few hundred mg of either does tend to produce faster and deeper sleep in most people, and like melatonin thet are both safe and not habit-forming.

Valerian Root is somewhat less harmless. An old herbal standby, this herb in capsule form is used by millions as a sleep aid. While it does work, it can’t be recommended for any but the shortest-term use because it is a mild liver poison — long-term use damages liver function. Other herbal teas like chamomile also have some sedative effects without any obvious toxicities.

GABA is another amino acid and neurotransmitter which doesn’t seem to cross the blood-brain barrier, yet has some obvious effects, producing calm and deeper sleep and perhaps aiding production of growth hormone in older body builders who take it. I take a gram every night before bed and it seems to deepen sleep. It also has some side-effects reminiscent of the niacin flush for some, so be careful and experiment with small doses before trying more. A reliable low-cost provider of GABA powder which can be mixed into any drink is here. Capsules tend to provide less effective dosages.

Doxylamine succinate is an old standby which works fairly well and is cheap and safe as a sleep aid: as an antihistamine, it is obsolete because its side-effect of drowsiness is intolerable during the day. But while it’s unwise to take any drug regularly unless you really need to, it’s at least not addictive and is easy to buy OTC: as this Kirkland-label product from Costco, for example.

Everyone’s sleep problem is different, and with age staying asleep becomes the most common problem. Natural substances can help but good sleep hygiene should be tried first.

More reading on other topics:

Regulation Strangling Innovation: Planes, Trains, and Hyperloop
Public Schools in Poor Districts: For Control Not Education
Real-Life “Hunger Games”: Soft Oppression Destroys the Poor
The Social Decay of Black Neighborhoods (And Yours!)
Child Welfare Ideas: Every Child Gets a Government Guardian!
“Income Inequality” Propaganda is Just Disguised Materialism

The greatest hits from SubstrateWars.com (Science Fiction topics):

Fear is the Mindkiller
Mirror Neurons and Irene Gallo
YA Dystopias vs Heinlein et al: Social Justice Warriors Strike Again
Selective Outrage
Sons of Liberty vs. National Front
“Tomorrowland”: Tragic Misfire

Flossing: Absence of Proof is Not Proof of Absence

Flossing: Never Like the Photo

Dentists and media have been telling us for generations that brushing and daily flossing are absolutely critical for preservation of teeth and gums into old age. A flurry of publicity in the last few days has people wondering if this is another instance of authorities blindly asserting healthy living ideals that are not only wrong, but might actually be harmful, as the USDA’s Food Pyramid and advice to eat low-fat, high-carb diets were.

Let the New York Times story, which was typical, explain:

For decades, the federal government — not to mention your dentist — has insisted that daily flossing is necessary to prevent cavities and gums so diseased that your teeth fall out. Turns out, all that flossing may be overrated.

The latest dietary guidelines for Americans, issued by the Departments of Agriculture and Health and Human Services, quietly dropped any mention of flossing without notice. This week, The Associated Press reported that officials had never researched the effectiveness of regular flossing, as required, before cajoling Americans to do it.

In a statement issued on Tuesday, the American Academy of Periodontology acknowledged that most of the current evidence fell short because researchers had not been able to include enough participants or “examine gum health over a significant amount of time.”

The revelation has caused a stir among guilt-ridden citizens who strive to floss daily but fall short of that lofty goal. Among experts, however, it has been something of an open secret that flossing has not been shown to prevent cavities or severe periodontal disease.

A review of 12 randomized controlled trials published in The Cochrane Database of Systematic Reviews in 2011 found only “very unreliable” evidence that flossing might reduce plaque after one and three months. Researchers could not find any studies on the effectiveness of flossing combined with brushing for cavity prevention.

“It is very surprising that you have two habits, flossing and toothbrushing without fluoride, which are widely believed to prevent cavities and tooth loss, and yet we don’t have the randomized clinical trials to show they are effective,” said Dr. Philippe Hujoel, a professor of oral health sciences at the University of Washington in Seattle.

But this is not unusual. Double-blind scientific studies are very expensive, and impractical for long-term effects on large populations. Because flossing is a procedure done by the study subjects themselves, there is no way of telling whether self-reported flossing is done correctly or at all, and lying about having faithfully flossed to your dentist is one of the most common white lies. “I always floss daily” is right up there with “I never think lustful thoughts about [sexually-attractive person who is not my spouse]!” in the book of self-serving fibs.

“Absence of Proof is Not Proof of Absence” — the lack of evidence of an assertion (“flossing helps prevent gum disease and preserves teeth”) is not evidence that the assertion is false. That would be the fallacy of Argument from Ignorance, often seen in the argument that there is no God because there is no evidence that He/She/It exists. If we have no evidence, we can’t determine anything about truth or falsehood. So all of these clickbait stories hinting everyone has been wasting their time flossing and authorities are full of it are simply wrong.

No studies are really needed because long experience of millions of dentists shows that regular brushing and flossing do tend to prevent gum disease and loss of teeth. While the evidence is not proof as the FDA might require it if it were a newly-proposed drug, my own personal results from periods of less and more dental hygiene efforts demonstrated that flossing helps. My gums improved and I had far fewer problems once I found two excellent time-saving devices for brushing and flossing.

First, electric toothbrushes with high-speed oscillating brush heads make brushing your teeth thoroughly yet gently easy and quick. These are marketed as ultrasonic, though that’s exaggerating bit. Here’s the one I use:

Philips Sonicare Diamond Clean Toothbrush

Flossing is notoriously tedious, with some types of floss shredding between teeth, cutting into fingers trying to hold it, and being almost impossible to get between back molars without stretching your mouth uncomfortably. There are several flossing helpers that ease this by holding a short segment of floss at the end of a long handle you can reach back with, but this is still time-consuming.

I found a great appliance which uses puffs of water or mouthwash instead of floss, and easily reaches back to flush the spaces between back molars:

Philips Sonicare Airfloss Ultra

This does a decent job of flushing out food particles, but is far more practical than the dental irrigators (Waterpiks) which spray far more water and take much more time to use. With the Airfloss, you place the head at the lower end of the junction between two teeth, push the button, and *puff* a tiny amount of high-speed liquid flushes out the crack. The consensus is that while this is not as good as thorough flossing, it is much better than the haphazard and occasional flossing most people do, and by making it easy to add to your routine, far more likely to become a regular habit. My dentist started complimenting me on my gum health shortly after I started using it regularly, and it continues to be excellent. One note: because of the high-tech nature of the machine, it doesn’t last as long as one might like — I went through a warranty replacement, but the company was good about sending me a new one when it stopped working. If you have to buy one every two years, it’s still a great deal better than gum surgery. You also need to practice to avoid spraying your surroundings, but it’s still far less messy than Waterpiks.

Jeb Kinnison

Writing About Life and Love

Diet and Exercise

IVF Journey: On SDF and Antioxidants, Sorting Chips

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IVF Journey: Remedies for Male Factor Infertility – Azoospermia

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Nessun Dorma: Insomnia and Sleep Aids

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Flossing: Absence of Proof is Not Proof of Absence

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