HoldsUp

DavidPerlmutterMD · 2026-02-03 · David Perlmutter (host), Rachel Swanson

Optimizing Fertility: What Actually Moves the Needle | Rachel Swanson

28 research-tied claims examined: 3 overstated 25 supported

25

Supported by research

0:00:00Rachel Swansonsupportedmoderate

Mitochondrial dysfunction driven by oxidative stress is a major reason why egg quality declines with unhealthy habits, and infertility is often an early sign of mitochondrial performance issues.

"Remember, mitochondrial dysfunction driven by oxidative stress is a major reason why egg quality can decline with unhealthy habits, and infertility is often the earliest sign that our mitochondria might be having some performance issues." (said at 0:00:00)

Published reviews and mechanistic studies in reproductive biology support the claim. Oocytes possess the highest mitochondrial density of any human cell and rely heavily on mitochondrial ATP production, calcium regulation, and redox balance during maturation and fertilization. Lifestyle factors, obesity, metabolic stress, and environmental exposures promote reactive oxygen species (ROS) accumulation, which causes oxidative stress, damages mitochondrial DNA, disrupts mitochondrial dynamics, and impairs ATP synthesis, directly driving reductions in oocyte competence. Because oocytes and ovarian tissue are exceptionally sensitive to bioenergetic deficits and oxidative burden, reproductive dysfunction and infertility frequently serve as prominent early indicators of cellular and mitochondrial performance impairment.

0:00:55David Perlmutter (host)supportedmoderate

Infertility rates have steadily climbed over the past several decades, with estimates suggesting nearly one in five couples struggle to conceive.

"In fact, rates are actually steadily climbing over the past several decades, with estimates suggesting that nearly one in five couples struggle to conceive." (said at 0:00:55)

Global epidemiological analyses confirm that infertility rates have been steadily climbing over recent decades. Data from the Global Burden of Disease (GBD) Study spanning 1990 to 2021 show that both the total number of cases and age-standardized prevalence rates for male and female infertility have consistently increased worldwide, with female age-standardized prevalence increasing by approximately 0.59% to 0.70% annually and seeing the fastest growth in high-sociodemographic regions. In addition, global and national surveillance data (such as WHO estimates of ~17.5% or 1 in 6 lifetime prevalence, and CDC estimates identifying ~19% or nearly 1 in 5 married women with no prior births struggling with infertility) align with the estimate that roughly one in five couples face difficulty conceiving.

0:11:00Rachel Swansonsupportedmoderate

Metabolic function influences the quality of eggs, sperm, and embryos, as well as hormone signaling, conception rates, and IVF success rates.

"But the data is extremely clear that metabolic function influences the quality of our eggs, sperm, embryos. It influences hormones, hormone signaling. It influences the chances of conceiving, IVF success rates." (said at 0:11:00)

Extensive clinical and mechanistic research supports the claim that metabolic health and function significantly impact gamete quality (oocytes and sperm), embryo competence, reproductive hormone signaling, natural conception rates, and assisted reproductive technology (IVF) outcomes. Systematic reviews and large cohort studies show that metabolic disorders—such as metabolic syndrome, insulin resistance, and obesity—negatively affect semen parameters, sperm DNA integrity, oocyte developmental competence, endometrial receptivity, and IVF live birth rates while increasing miscarriage risk.

0:11:30Rachel Swansonsupportedmoderate

A father's metabolic health before pregnancy influences pregnancy complications for the woman, such as miscarriage, recurrent pregnancy loss, and preeclampsia.

"And yes, to touch on the father's point, the father's metabolic health before pregnancy influences pregnancy complications for the woman, such as miscarriage, recurrent pregnancy loss, and preeclampsia." (said at 0:11:30)

Large retrospective cohort studies analyzing insurance claims data show that preconception paternal metabolic health—measured by metabolic syndrome components and chronic disease burden—is significantly associated with adverse maternal and pregnancy outcomes. Specific findings include higher odds of preeclampsia and eclampsia in healthy women whose partners had metabolic syndrome components (PMID 33895399), as well as increased risk of pregnancy loss, including miscarriage (PMID 33336240). Narrative and systematic reviews further confirm that paternal metabolic health contributes to pregnancy loss and maternal hypertensive complications (PMID 38334037, PMID 34599616).

0:14:40Rachel Swansonsupportedmoderate

Only about 1 in 8 to 1 in 10 people in the United States are considered metabolically healthy based on five basic clinical biomarkers.

"I think about how either, you know, 1 in 8 to 1 in 10 people are considered metabolically healthy in this country based off of, I mean, five basic clinical markers that are arguably not even the best biomarkers." (said at 0:14:40)

Nationally representative data from the National Health and Nutrition Examination Survey (NHANES) support the statement. In a landmark 2019 analysis evaluating five standard clinical components of cardiometabolic health (waist circumference, fasting glucose/HbA1c, blood pressure, triglycerides, and HDL cholesterol without medication use), only 12.2% (approximately 1 in 8) of U.S. adults met optimal criteria for all five markers. Subsequent NHANES analyses assessing trends through 2018 found that optimal cardiometabolic health declined even further to approximately 6.8% (around 1 in 15) of American adults.

0:15:20Rachel Swansonsupportedlow

Nearly half of women experiencing infertility or recurrent pregnancy loss have undiagnosed pre-diabetes.

"I mean, one study even found that nearly half of women experiencing infertility or recurrent pregnancy loss had undiagnosed pre-diabetes." (said at 0:15:20)

A 2019 retrospective cohort study of women presenting with infertility or recurrent pregnancy loss (RPL) to a reproductive endocrinology clinic evaluated screening for pre-diabetes using both HbA1c and 2-hour oral glucose tolerance testing (2h GTT). Among 188 women who underwent both tests, 47.3% (89/188) tested positive for pre-diabetes by one or both methods (44.1% by HbA1c and 10.6% by 2h GTT). The speaker's statement accurately summarizes the specific finding of this single retrospective study.

0:15:44Rachel Swansonsupportedmoderate

A father's metabolic dysfunction prior to conception can increase the mother's risk for pregnancy loss and preeclampsia by about 20%.

"So what I found just so fascinating with dad's metabolic health is when I was looking into the data and found that he can increase mom's risk for pregnancy loss and preeclampsia by about 20% depending on how severe his metabolic dysfunction is prior to that couple getting pregnant." (said at 0:15:44)

Large retrospective cohort studies analyzing US insurance claims data directly support this claim. In a study of 669,256 births to healthy mothers, paternal preconception metabolic syndrome was associated with a dose-dependent increase in the mother's odds of preeclampsia (21% higher odds for preeclampsia without severe features and 19% higher odds for preeclampsia with severe features among men with ≥2 metabolic syndrome components compared to men with none). Similarly, an analysis of 958,804 pregnancies found that the risk of pregnancy loss increased in a dose-dependent manner by up to 19% (relative risk 1.19) for fathers with three or more metabolic syndrome components.

0:25:42Rachel Swansonsupportedmoderate

Repeated antibiotic use in early infancy increases a child's risk for obesity.

"One is I think about how uh early in life in infancy, you know, repeated antibiotic use um unfortunately, it does kind of carpet bomb the gut microbiome. And the data the data is very clear that that um, you know, those then children are at greater risk for obesity." (said at 0:25:42)

Multiple systematic reviews and meta-analyses of observational cohort studies confirm that antibiotic exposure during infancy—particularly repeated courses and exposure during the first six months of life—is associated with a modestly increased risk of childhood overweight and obesity. A meta-analysis of over 527,000 children found that receiving more than one antibiotic treatment during infancy was associated with a 24% increased odds of childhood overweight or obesity (OR 1.24, 95% CI 1.09–1.43), whereas a single course was not significantly associated with elevated risk.

0:26:40Rachel Swansonsupportedmoderate

Repeated exposure to antibiotics early in life increases the likelihood of developing allergies and autoimmunity.

"in terms of the immune system, again, those that repeated exposure of antibiotics early in life, they are at a higher, you know, likelihood of developing allergies and autoimmunity." (said at 0:26:40)

Large-scale population-based cohort studies and systematic reviews consistently demonstrate that early-life exposure to antibiotics—particularly repeated courses exhibiting a dose-response relationship—is associated with an increased risk of developing allergic conditions (such as asthma, atopic dermatitis, allergic rhinitis, and food allergies) as well as immune-mediated and autoimmune conditions (such as celiac disease, juvenile arthritis, and type 1 diabetes). Because the primary evidence comes from observational registries and cohort studies, potential residual confounding (such as underlying infections or familial predisposition) cannot be completely ruled out, but the observed associations and dose-response patterns support the claim.

0:26:58Rachel Swansonsupportedvery low

Lipopolysaccharide produced by gut dysbiosis can leak into circulation and trigger inflammation at the epididymis where sperm mature.

"So if we have dysbiosis, chronic dysbiosis in the gut, so let's call that an overgrowth of gram-negative bacteria producing lipopolysaccharide. You've discussed this so many times before, that can leak out of the gut and into circulation. And guess what? That can trigger inflammation at also the site where sperm mature, called the epididymis." (said at 0:26:58)

Published preclinical and translational studies support the claim that gut dysbiosis can increase circulating lipopolysaccharide (metabolic endotoxemia) and trigger localized inflammation in the epididymis, impairing sperm motility and maturation. For instance, a 2020 study published in Gut demonstrated that transplanting gut microbiota from high-fat diet-fed mice into normal-diet mice increased Gram-negative bacterial abundance (such as Bacteroides and Prevotella), elevated blood endotoxin levels, and significantly increased pro-inflammatory cytokine expression in the epididymis. Observational data in human subjects from the same study showed that blood endotoxin levels correlated with gut bacterial shifts and negatively correlated with sperm motility. Because direct causal evidence for this specific axis is derived primarily from rodent fecal microbiota transplantation models alongside observational human associations, the GRADE certainty is very low.

0:28:14Rachel Swansonsupportedhigh

PCOS is the number one cause of anovulatory infertility globally.

"So yes, this is the number one cause of anovulatory uh infertility globally." (said at 0:28:14)

Polycystic ovary syndrome (PCOS) is widely recognized in reproductive medicine and global epidemiological analyses as the leading cause of anovulatory infertility worldwide, accounting for an estimated 70% to 80% of all cases of anovulatory subfertility.

0:18:48David Perlmutter (host)supportedmoderate

Exposure to 40 Hz sensory stimulation increases brain gamma activity and has been reported in early clinical research to be associated with slower cognitive decline in some participants.

"We know that when you're exposed to 40 Hz stimulation, this is linked to what we call increasing gamma activity in the brain. In other words, balance in the brain, which is really a fundamental for brain health and brain functionality. In fact, in early clinical research using what's called 40 Hz stimulation, researchers have reported signals that are consistent with a slower decline in cognitive function in some participants." (said at 0:18:48)

Early clinical trials, systematic reviews, and meta-analyses support the claim. Sensory stimulation at 40 Hz (using visual, auditory, or combined audiovisual modalities) reliably drives neural entrainment, increasing gamma-band electroencephalographic activity in the brain. Early-phase clinical studies and meta-analyses in patients with mild cognitive impairment and Alzheimer's disease have reported signals of therapeutic benefit, including reduced rates of cognitive decline and improvements on standardized cognitive assessments (such as the MMSE and ADAS-cog) among treated participants compared to controls, though researchers emphasize that larger randomized trials are needed to establish long-term clinical efficacy.

0:23:34Rachel Swansonsupportedmoderate

Certain classes of antibiotics can induce stress in human mitochondria because mitochondria retain bacterial-derived enzymes due to their bacterial evolutionary origin.

"That's why, you know, some antibiotic classes that target bacteria in the gut can ultimately like stress out the mitochondria because they still have those bacterial-derived enzymes." (said at 0:23:34)

Because mitochondria originated through endosymbiosis of an ancestral alpha-proteobacterium, they retain structural and functional homologies with bacterial machinery—including mitochondrial ribosomes, RNA polymerases, topoisomerases, and respiratory chain components. Multiple classes of antibiotics (such as aminoglycosides, tetracyclines, oxazolidinones, macrolides, chloramphenicol, and fluoroquinolones) can inhibit mitochondrial protein translation or function, inducing mitochondrial dysfunction, reactive oxygen species (ROS) overproduction, and cellular oxidative stress.

0:31:44Rachel Swansonsupportedmoderate

Vaginal microbiome community state type IV (CST IV) is associated with worse pregnancy outcomes and lower IVF success.

"community state type IV is associated with worse uh pregnancy outcomes and IVF success." (said at 0:31:44)

The claim is supported by published literature. Vaginal microbiome community state type IV (CST IV) is characterized by a low relative abundance of *Lactobacillus* species and a high diversity of anaerobic bacteria (associated with bacterial vaginosis and vaginal dysbiosis). High-diversity CST IV communities are significantly associated with adverse pregnancy outcomes, including preterm birth and miscarriage/early pregnancy loss. Furthermore, systematic review and meta-analytic evidence links CST IV and vaginal dysbiosis to lower clinical pregnancy rates and increased early pregnancy loss in patients undergoing IVF.

0:34:34Rachel Swansonsupportedmoderate

Certain stain-resistant and absorbent period products contain per- and polyfluoroalkyl substances (PFAS).

"I think about all of these innovative period products that, you know, absorb blood, and how how they can do this and how they can resist stains is by, you know, these um by basically putting on these very harmful chemicals called PFAS" (said at 0:34:34)

Published analytical studies confirm that per- and polyfluoroalkyl substances (PFAS) are utilized in textiles and personal hygiene products (including sanitary pads, menstrual cups, and stain- or water-resistant apparel) due to their water-, oil-, and stain-repellent characteristics. Chemical testing of personal care and consumer textile products demonstrates detectable concentrations of targeted PFAS and total fluorine in items designed with stain- and liquid-resistant properties.

0:39:43Rachel Swansonsupportedmoderate

Periodontal disease is associated with impaired sperm quality, reduced fertility potential in women, and an increased risk of pregnancy complications such as preeclampsia and preterm birth.

"dysbiosis in this area coupled with inflammation really sets the stage for periodontal disease. That is a systemic issue that's associated with issues with sperm quality, reduced fertility potential in women, um a higher risk of pregnancy complications like preeclampsia and preterm birth." (said at 0:39:43)

Published systematic reviews and observational studies support the claim that periodontal disease is associated with impaired sperm quality (decreased motility, abnormal morphology, and increased DNA fragmentation), reduced fertility potential in women (decreased fecundability and higher prevalence of periodontitis in women with infertility), and an increased risk of pregnancy complications including preeclampsia and preterm birth. However, while observational evidence consistently demonstrates these epidemiological associations, evidence from interventional trials (e.g., Cochrane systematic review of periodontal treatment) indicates that treating periodontitis during pregnancy does not significantly lower the risk of preterm birth or preeclampsia, suggesting the relationship may not be directly causal or that preconception treatment is required.

0:40:20Rachel Swansonsupportedmoderate

Porphyromonas gingivalis has been detected in amyloid-beta plaques in the brain and in arterial plaque in the heart.

"they've also spoken about the association with, you know, P. gingivalis, for example, in terms of being associated with um Alzheimer's, because they found this in amyloid beta plaque. But they've also found this, by the way, in um the P. gingivalis in artery plaque in the in the heart" (said at 0:40:20)

Published molecular and postmortem studies have detected Porphyromonas gingivalis (and its virulence factors, such as gingipains) in the brains of patients with Alzheimer's disease, where it is associated with amyloid-beta and tau pathology. Similarly, systematic reviews and tissue analyses demonstrate that P. gingivalis DNA and antigens are frequently identified in coronary atherosclerotic plaques and atheroma samples from patients with cardiovascular disease.

0:43:36Rachel Swansonsupportedmoderate

Mitochondrial dysfunction driven by oxidative stress is a major mechanism contributing to the decline in egg quality.

"Remember, mitochondrial dysfunction driven by oxidative stress is a major reason why egg quality can decline with unhealthy habits" (said at 0:43:36)

Extensive literature in reproductive biology establishes that oxidative stress and subsequent mitochondrial dysfunction are central mechanisms underlying the decline in oocyte (egg) quality. Accumulation of reactive oxygen species (ROS)—exacerbated by aging, environmental toxins, and adverse lifestyle factors—damages mitochondrial DNA and membrane integrity, impairs ATP production, disrupts spindle assembly and chromosome segregation during meiosis, and compromises overall developmental competence.

0:45:30Rachel Swansonsupportedlow

Women with the highest levels of exposure to endocrine-disrupting chemicals enter menopause nearly 4 years earlier than those with the lowest exposure.

"coupled with women with the highest exposure of endocrine-disrupting chemicals, they it's they tend to enter menopause significantly earlier, like the data I reviewed, nearly 4 years earlier than those with the lowest exposure." (said at 0:45:30)

A 2015 cross-sectional analysis of NHANES data (1999–2008) evaluating 111 endocrine-disrupting chemicals (EDCs) found that women with the highest exposure levels (highest decile or >90th percentile) to specific EDCs—including certain PCBs, pesticides, furans, and phthalates—experienced menopause between 1.9 and 3.8 years earlier (up to nearly 4 years earlier) compared to women with lower exposure levels. Because these findings are derived from observational, cross-sectional survey data, the overall certainty of evidence is low due to the potential for confounding and reverse causation.

0:46:05Rachel Swansonsupportedmoderate

BPA, phthalates, PFAS, and pesticides/herbicides have published human outcome data linking exposure to adverse fertility outcomes including eggs retrieved, time to conception, and sperm quality.

"So I see for fertility, the only players that I included in the book, Dr. Perlmutter, is the ones that I can have human outcome data for, which are four main ones. Um, we have BPA, phthalates, PFAS, which is per- and polyfluoroalkyl substances, and um pesticides and herbicides. Those are kind of the four categories. There are many, many others by all means, but those are the ones that we have um human outcome data in in relation to, you know, the eggs being retrieved, and um time to conception, and sperm quality, and odds of getting pregnant, for example." (said at 0:46:05)

Published human epidemiological literature, including multiple systematic reviews and meta-analyses, documents associations between exposure to bisphenol A (BPA), phthalates, per- and polyfluoroalkyl substances (PFAS), and pesticides/herbicides and various human fertility endpoints. Specifically, observational cohort studies in both general and clinical populations have examined and linked these chemical classes to altered sperm quality (concentration, motility, DNA integrity), delayed time to pregnancy (TTP/fecundability), and assisted reproduction outcomes such as oocyte retrieval yields and fertilization success.

0:48:13Rachel Swansonsupportedhigh

A landmark orthopedic trial demonstrated that patients undergoing sham surgery achieved the same outcomes as those undergoing real surgery.

"think about, you know, the placebo effect, for example, how you can, you know, studies have shown that you can undergo a sham surgery and have the same outcomes as undergoing um a real surgery. I mean, I'm at least referring to, you know, a study in orthopedics that was done that was really a landmark trial." (said at 0:48:13)

Landmark double-blind, randomized controlled trials in orthopedics have demonstrated that patients undergoing sham surgery (placebo surgical procedures) experienced equivalent symptomatic and functional outcomes compared to those receiving real arthroscopic surgery. Specifically, Moseley et al. (2002) showed that arthroscopic lavage or débridement for osteoarthritis of the knee resulted in no better pain relief or functional improvement over 24 months than a placebo procedure with simulated incisions. Similarly, Sihvonen et al. (2013) demonstrated that arthroscopic partial meniscectomy for degenerative meniscus tears was no more effective than sham surgery at 12 months.

0:55:45Rachel Swansonsupportedlow

A study published in a major medical journal found an association between higher levels of micro- and nanoplastics in carotid artery plaque and increased risk of cardiovascular disease.

"That's why we see these associations with higher micro-nanoplastics and like, you know, carotid artery plaque and heart disease. This was in, you know, JAMA or New England, um, Journal of Medicine or one of those." (said at 0:55:45)

A prospective observational study published in The New England Journal of Medicine (Marfella et al., 2024) analyzed excised carotid plaque from 257 patients undergoing carotid endarterectomy. Microplastics and nanoplastics (primarily polyethylene and polyvinyl chloride) were detected in 58.4% of patients. Over a mean follow-up of 34 months, patients with detectable plastics in their carotid plaques had a significantly higher risk of a composite cardiovascular endpoint (myocardial infarction, stroke, or death from any cause) compared to those without detectable plastics (HR 4.53; 95% CI, 2.00 to 10.27). Because this is an observational cohort prone to potential residual confounding, the certainty of evidence is low.

0:45:02Rachel Swansonsupportedmoderate

Endocrine-disrupting chemicals (EDCs) are associated with an increased risk of premature ovarian insufficiency.

"These endocrine-disrupting chemicals, here's what's so wild: you know, I see them as like almost um accelerants of reproductive aging, because they're associated with increased risk for premature ovarian insufficiency." (said at 0:45:02)

Epidemiological and mechanistic evidence supports the association between exposure to endocrine-disrupting chemicals (EDCs)—including bisphenols, phthalates, and per- and polyfluoroalkyl substances (PFAS)—and an increased risk of premature ovarian insufficiency (POI) and accelerated ovarian aging. Observational and case-control studies consistently observe that higher exposures to these environmental toxicants correlate with elevated POI risk, decreased anti-Müllerian hormone (AMH) levels, reduced antral follicle count, and earlier onset of menopause.

0:40:35Rachel Swansonsupportedmoderate

Porphyromonas gingivalis infection is associated with inflammatory bowel disease and certain types of cancer.

"But they've also found this, by the way, in um the P. gingivalis in artery plaque in the in the heart, um associated with inflammatory bowel disease, a few cancer types." (said at 0:40:35)

Published observational and mechanistic evidence supports the link between Porphyromonas gingivalis infection/periodontal dysbiosis and extra-oral diseases, specifically inflammatory bowel disease (IBD) and certain gastrointestinal malignancies such as colorectal cancer.

1:00:40David Perlmutter (host)supportedmoderate

Microorganisms residing in the gut, vaginal microbiome, and mouth shape human reproductive health.

"So from the trillions of microbial—we call them allies—that shape our reproductive health in, uh, the gut and vaginal microbiome and even in the mouth" (said at 1:00:40)

Published literature confirms that microbial communities across multiple body sites—including the gut, vaginal tract, and oral cavity—play critical roles in human reproductive physiology, endocrine signaling, fertility, and pregnancy outcomes. Meta-analyses and cohort studies have linked distinct taxonomic and functional shifts in the vaginal, gastrointestinal, and oral microbiomes to reproductive conditions such as polycystic ovary syndrome, endometriosis, gestational diabetes, and preterm birth.

Unverified means no publication matching the claim was located; it does not prove the claim false. Spotted an error? See the corrections policy - disputes from the people quoted are prioritized.