#351 ‒ Male fertility: optimizing reproductive health, diagnosing and treating infertility, and navigating testosterone replacement therapy | Paul Turek, M.D.

The complex nature of male fertility is discussed, highlighting the sophisticated processes of sperm production, maturation, and the daunting journey sperm must undertake to fertilize an egg.

Sperm Production and Maturation Process

Paul Turek delves into the intricate process of spermatogenesis, beginning with a spermatogonial stem cell. Categorized as a remarkable cell and the adult counterpart of an embryonic stem cell, Turek sheds light on its multipotent capability to generate diverse body structures when placed in a suitable environment. This process encompasses a profound cellular transformation over approximately six to seven weeks to create a sperm. Vitamin A notably influences this maturation, which from the stage of a round cell with half the number of chromosomes to one with a tail and motor assembly, encompasses about three weeks. It was revealed through deuterium-labeled water that it takes an average of 74 days to produce a sperm.

Sperm Navigate Cervix, Uterus, and Fallopian Tubes to Reach Egg

The formidable journey sperm partake in after ejaculation is akin to a 20-mile swim for a human, traversing through the cervix and uterus to reach the egg. Some sperm manage to bind to the oviduct and bide their time there. Moreover, Turek elucidates on conditions like globospermia, where sperm cannot naturally fertilize an egg due to the absence of the acrosome. He also sheds light on the sperm's role beyond binding, highlighting its contribution to calcium activation that prevents polyspermy in an egg.

Sperm's Adaptations For Detecting and Responding To Egg Signals Assist Their Journey

Sperm ingeniously mature in the epididymis, learning to detect follicular fluid, akin to an olfactory sense, aiding them in navigating towards the egg. From an initial inefficient motion, sperm build progressive motility, allowing for a straighter pathway forward.

Rarity of Conception Despite Evolutionary Pressure

Despite the evolutionary importance of conception, only a fraction of sperm overcome the numerous obstacles to reach the egg.

Only a Fraction of Sperm Reach the Egg

Of the approximately 100 million sperm that start the journey, a staggering reduction in numbers is evident, with only around 5 million breaching the first barrier and a mere one or handful succeeding at the fallopian tube level.

Immune and Biological Defenses Hin ...

Factors such as heat exposure, environmental toxins, stress, and medical treatments contribute to male fertility issues. Paul Turek, a fertility expert, highlights the multitude of elements that can affect sperm quality and male reproductive health.

Impact of Heat on Sperm Production and Quality

Testes Are Outside Body for Cooler Temperature

The testes are situated outside the body to maintain a cooler temperature, which is crucial for sperm production. The optimal temperature for testicular enzymes is about three degrees cooler than the body's core, at 95 degrees Fahrenheit. The testes are immunologically walled off, with structures like the Sertoli cells providing a barrier akin to the blood-brain barrier. This separation helps with temperature regulation as the testes can raise or lower to adjust temperature.

Heat From Hot Tubs, Saunas, and Excessive Exercise Can Damage Sperm and Reduce Fertility

Excessive heat can cause male infertility due to overheating which leads to oxidative stress, damaging sperm. Turek notes the detrimental effects of hot tubs and saunas on fertility, as submersion in these hot environments can quickly raise the temperature of the testes. This impact is significant since even a change in testicle temperature can have a substantial effect on sperm production and quality. A study cited by Turek showed that men who ceased hot bath habits saw increases in semen quality by up to 600 percent in six months, primarily driven by motility improvement.

Turek also discusses the adverse effects of excessive exercise, indicating that strenuous activity beyond 80% of VO2 max can negatively impact fertility. He specifically connects motility issues in a semen analysis to heat exposure and stresses the importance of avoiding excessively warm environments like hot tubs to protect sperm health.

Men Should Avoid Excessive Heat to Protect Fertility

Turek recommends avoiding a "lethal dose" of excessive heat exposure, for instance, using a hot tub at 104 degrees for 20 minutes, three times a week, as it could result in a zero sperm count. He emphasizes the importance of avoiding environments like saunas or steam rooms that may elevate the temperature of the testes for sustained fertility.

Toxins, Stress, and Environment's Impact on Sperm

Environmental Toxins Affect Sperm Quality and Function

Turek raises awareness about the tens of thousands of chemicals in common use that have not been adequately tested for their reproductive effects. These include industrial solvents, fuels, and other toxic substances that can negatively affect sperm quality.

Stress Disrupts Hormones Regulating Sperm Production, Reducing Fertility

Stress is a significant factor impacting fertility by activating the sympathetic nervous system, which disrupts the hormone regulation of sperm production. Attia reveals that during his time in residency, the stress and sleep deprivation he experienced led to low levels of [restricted term]. Moreover, exercise taken to extreme levels can also significantly diminish sperm counts and [restricted term] levels, showcasing that physical stress can have a profound negative impact.

Lifestyle Factors Affecting Male Infertility

Lifestyle choices such as alcohol consumption, drug use, including marijuana and nicotine, are mentioned to alter sperm epigenetics and negatively affect fertility. Turek also points to obesity and diet as contributing factors towards male infertility.

[restricted term] Therapy and Fertility Interplay

Exogenous [restricted term] can suppress natural [restricted term] production and sperm manufacturing, often leading to infertility. Turek notes that various formulations have differing impacts, with some being less inhibitory than others. The suppression of LH and FSH also plays a role, with exogenous [restricted term] ceasing all natural production, which is evident when blood tests show low [restricted term] levels after an extended period without the drug.

Exogenous [restricted term] Can Suppress Natural [restricted term], Sperm Production, and Lead To Infertility

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Advanced technologies and impactful research are leading the transformations in male reproductive health, with a focus on infertility treatment and the impact of paternal age on offspring.

Advanced Sperm Sorting and Genetic Testing Techniques

Both the quality and selection of sperm are crucial in assisted reproduction. The hosts discuss advanced sperm sorting techniques and genetic testing that are improving the odds of conception.

Microfluidic and Genetic Assays Enhance Selection of Healthiest Sperm for Assisted Reproduction

Paul Turek talks about using microfluidics in challenging infertility cases, such as globospermia, where sperm fail to penetrate the egg. This technology helps select the healthiest sperm for assisted reproduction. He notes that cases of testicular sperm show a higher rate of chromosomal abnormalities compared to ejaculated sperm, which suggests a post-production filtering that favours healthier sperm.

Technologies Enhance Conception Chances in Abnormal Sperm or Genetic Issues

AI is being looked at for sperm selection and to standardize sperm morphology evaluation. Turek points out that AI's image recognition capabilities could improve the standardization of semen analysis. He also elaborates on a bespoke approach for semen analysis which provides more detailed information than computer-assisted semen analysis (CASA).

Innovative Treatments for Male Infertility

Sperm extraction and anatomical repairs are key areas of advancement in treating male infertility, with varicocele repair being a common modifiable factor affecting fertility.

Sperm Extraction and Varicocele Repair Can Enhance Sperm Quality

Turek discusses a study on varicocele repair, the most common treatable condition affecting male fertility. He explains that varicoceles, similar to varicose veins, occur in the scrotum and create a heat issue detrimental to sperm production. Physical symptoms can include a 'bag of worms' feeling or a discrepancy in testicular size. The varicocele repair surgery is an hour-long outpatient procedure utilizing microsurgery for a quicker recovery. Post-repair, sperm counts can improve, and the chance of natural conception increases.

Impact of Paternal Age ...

The episode explores the disparities in fertility that occur with age between men and women and the varying physiological effects aging has on reproductive health and genetic integrity in male versus female bodies.

Women's Fertility Declines Faster With Age Than Men's

Women Have a Limited Egg Supply, Decreasing In Quality and Quantity Over Time

Women are born with a finite number of eggs—about one million at conception, one million at birth, and only about a thousand ovulated over a lifetime. This reserve of eggs sharply declines by the age of 45, often leaving women without remaining viable eggs. Unlike sperm, eggs do not mature until they are called upon and age without evolving.

Men Produce Sperm Throughout Life, but Quality and Genetic Integrity Decline With Age

Sperm, on the other hand, are continuously produced throughout a man's life. This constant renewal leads to constant division, environmental influence, and the accrual of mutations and epigenetic changes that can be transferred to offspring. As men age, the number of mutations in sperm increases, raising the probability of neurodevelopmental and neurodegenerative issues in their offspring. Paternal age is suggested to contribute to an increased rate of chromosomal abnormalities.

Challenges and Considerations for Male Fertility and Aging

Klinefelter Syndrome and Vas Deferens Absence Affect Male Fertility

Men with Klinefelter syndrome have an extra X chromosome and experience fertility issues, as only about 10% of their sperm will carry this additional chromosome. Klinefelter syndrome is cited as the most common genetic cause for the complete absence of sperm in semen. Additionally, Paul Turek discusses physical examinations for diagnosing male infertility, including the congenital absence of the vas deferens found in 1 in 500 men. These men may appear healthy and have normal testicles, but the absence of the vas deferens leads to natural sterility or infertility.

Men with cystic fibrosis typically have no vas deferens, making natural conception impossible. Interestingly, some healthy men without cystic fibrosis also lack the vas deferens, indicating they could be carriers for the genetic markers of the disease.

Paternal Age Effects on Offspring Health and Genetic Risks

The conversation underscores the potential risks involved with older paternal age. Turek advises sperm banking, especially before treatments like chemotherapy. He outlines a "hockey stick curve" in risk for offspring of older fathers, denoting a slow linear increase in risk up to age 50 or 60, followed ...