The metabolic syndrome and male infertility

The reproductive endocrinology and infertility subspecialist: definition, training, and scope of practice in the United States

Gracia C et al., 2025 · Fertility and Sterility

Updates to male infertility: AUA/ASRM guideline

Brannigan RE et al., 2024 · The Journal of Urology

Sperm Transport and Capacitation

Brannigan R et al., 2008 · GLOWM

It is well understood that a myriad of complex steps occur between the time of ejaculation and the union of the haploid number of chromosomes from each partner that results in the final process of fertilization. Consequently, it is easy to imagine the numerous potential problems that can occur at each step, and thus may prevent a successful pregnancy. Often overlooked are the complexities of sperm transport and the steps that must occur in the sperm, a process known as capacitation, before fertilization can occur. These processes of sperm delivery and potentiation are addressed in detail in this chapter.

Obesity leads to higher risk of sperm DNA damage in infertile patients

Dupont C et al., 2013 · Asian journal of andrology · Free full text on PubMed Central

There has been a growing interest over the past few years in the impact of male nutrition on fertility. Infertility has been linked to male overweight or obesity, and conventional semen parameter values seem to be altered in case of high body mass index (BMI). A few studies assessing the impact of BMI on sperm DNA integrity have been published, but they did not lead to a strong consensus. Our objective was to explore further the relationship between sperm DNA integrity and BMI, through a 3-year multicentre study. Three hundred and thirty male partners in subfertile couples were included. Using the terminal uridine nick-end labelling (TUNEL) assay, we observed an increased rate of sperm DNA damage in obese men (odds ratio (95% confidence interval): 2.5 (1.2-5.1)).

Reduced fertility among overweight and obese men

Sallmén M et al., 2006 · Epidemiology (Cambridge, Mass.)

Overweight and obese men have been reported to have lower sperm counts and hormonal changes, but data are lacking regarding effects on couple fertility. We examined the relationship between male body mass index (BMI) and infertility in couples enrolled in the Agricultural Health Study in the United States. The analysis sample was limited to couples (wife <40 years old) with an attempt at pregnancy in the last 4 years based on pregnancy and fertility data provided by wives. Infertility was defined as not conceiving a pregnancy after at least 12 months of unprotected intercourse regardless of whether or not a pregnancy ultimately occurred. Self-reported weight and height were used to calculate BMI (kg/m). Adjusted odds ratios (aORs) for infertility associated with increases in male BMI were calculated with logistic regression. Adjusting for potential confounders, a 3-unit increase in male BMI was associated with infertility (aOR = 1.12; 95% confidence interval = 1.01-1.25; n = 1329). There was a dose-response relationship, and the BMI effect was stronger when the data were limited to couples with the highest-quality infertility data. The association between BMI and infertility was similar for older and younger men, suggesting that erectile dysfunction in older men does not explain the association. This report of lower fertility in overweight and obese men needs replication. If the findings are robust, programs to prevent obesity may improve men's reproductive health and save medical costs for infertility treatment.

Insulin Sensitivity and Testicular Function in a Cohort of Adult Males Suspected of Being Insulin-Resistant

Contreras PH et al., 2018 · Front Med (Lausanne) · Free full text on PubMed Central

A cohort of 141 males (18-80 yo, 42.9 ± 12.9) strongly suspected of being Insulin Resistant (IR) was prospectively studied by determining their insulin sensitivity (Pancreatic Suppression Test, PST) and testicular function (total testosterone and SHBG). The subjects were labeled as IR when the Steady State Plasma Glucose (SSPG) was ≥150 mg/dL and Non-Insulin Resistant (NIR) when SSPG was <150 mg/dl; similarly, the subjects were labeled as Hypogonadal (HYPOG) when total testosterone was ≤3.0 ng/mL and Eugonadal (EUG) when total testosterone was >3.0 ng/mL. Two out of three subjects turned out to be IR, while around one in four subjects were HYPOG. Contingency analysis indicated a significant interdependence between insulin resistance and hypogonadism (chi-square was 4.69, p = 0.0303). Age (>43 yo) predicted hypogonadism (AUROC 0.606, p = 0.0308). Twice as many HYPOG subjects were IR as compared with EUG subjects. Also, HYPOG subjects exhibited higher SSPG values as compared with EUG subjects. Statistically, neither Weight nor BMI predicted hypogonadism, while Waist Circumference (>110 cm) was only a mediocre predictor (AUROC 0.640, p = 0.009). SSPG (>224 mg/dL) on the other hand, was the best predictor of hypogonadism (AUROC 0.709, p = 0.002), outperforming Waist Circumference (half of the subjects with an SSPG >224 mg/dL were HYPOG). Age did not predict insulin resistance, while Weight (>99 kg), BMI (>29), and especially, Waist Circumference (>99 cm, AUROC 0.812, p < 0.0001) were all predictors of insulin resistance. Almost 90% of the subjects with a waist circumference >99 cm was IR. As a logical consequence of the selection criteria (various clues suggesting insulin resistance), most subjects with normal weight in this cohort were IR (53.3%) while 20% were HYPOG. On the other hand, 13.6% of the obese subjects were NIR, and 2 out of 3 of them were both NIR and EUG. In conclusion, Waist Circumference predicted both insulin resistance (>99 cm) and hypogonadism (>110 cm), suggesting that the first hit of abdominal obesity is insulin resistance and the second hit is male hypogonadism. Normal weight did not protect from IR, while a relevant proportion of obese subjects were NIR (with 2/3 being also EUG).

Sperm Count and Hypogonadism as Markers of General Male Health

Ferlin A et al., 2021 · European urology focus

Some evidence suggests that infertile men, who are at increased risk for hypogonadism, metabolic derangements, and osteoporosis, have higher long-term morbidity and mortality than controls, but data are scarce and not conclusive. We tested whether semen quality and reproductive function could represent a marker of general male health. DESIGN, SETTING, A retrospective study of 5177 individuals from a prospectively collected database of 11516 males of infertile couples who had semen analysis in a tertiary university center. OUTCOME MEASUREMENTS Of them, 5177 had all data for reproductive hormones, testis ultrasound, and biochemical determinations for glucose and lipid metabolism. Hypogonadism was defined as testosterone <10.5nmol/l and/or luteinizing hormone >9.4 IU/l. Individuals with a total sperm count of <10 million had genetic testing (karyotype, Y chromosome microdeletions, and CFTR gene mutations) and those with hypogonadism underwent dual-energy x-ray absorptiometry for bone mineral density. Descriptive statistics and odds ratio (OR) calculation were used. Men with a low sperm count (<39 million/ejaculate) are at a high risk of hypogonadism (OR 12.2, 95% confidence interval [CI] 10.2-14.6) and have higher body mass index, waist circumference, systolic pressure, low-density lipoprotein cholesterol, triglycerides, and homeostatic model assessment (HOMA) index; lower high-density lipoprotein cholesterol; and a higher prevalence of metabolic syndrome (OR 1.246, 95 CI 1.005-1.545). All data are worse in men with hypogonadism, but a low sperm count per se is associated with a poor metabolic parameter. Men with hypogonadism have lower bone mineral density and 51% prevalence of osteoporosis/osteopenia. Longitudinal studies are necessary to support these data. This is the largest study with comprehensive evaluation of semen quality and reproductive function, etiology and risk factor determination, and metabolic, cardiovascular, and osteoporosis risk assessment, performed in men referred for fertility evaluation. A low sperm count is associated with poorer metabolic, cardiovascular, and bone health. Hypogonadism is mainly involved in this association, but a low sperm count in itself is a marker of general health. This large study evaluated semen quality, reproductive function, and metabolic risk in men referred for fertility evaluation, and showed that a man's semen count is a marker of his general health. Men with low sperm counts are more likely than those with normal sperm counts to have greater body fat, higher blood pressure, higher "bad" (low-density lipoprotein) cholesterol and triglycerides, and lower "good" (high-density lipoprotein) cholesterol. They also have a higher frequency of metabolic syndrome and insulin resistance, a condition that can lead to diabetes. Men with low sperm counts had a 12-fold increased risk of hypogonadism or low testosterone levels, and half of them had osteoporosis or low bone mass. Fertility evaluation gives men the unique opportunity for health assessment and disease prevention.