Last reviewed: May 12, 2026 Last updated: May 12, 2026

Written by: Jay Hastings , CEO of PlexusDx

Jay Hastings is the CEO of PlexusDx, a precision health company focused on genetic testing, blood biomarker insights, and personalized wellness recommendations. He has more than 20 years of experience across healthcare innovation, genomics, laboratory operations, healthcare investing, and strategic finance. His work has included scaling healthcare startups, leading CLIA lab integrations, and helping expand consumer access to precision health tools.

Medically reviewed by: Jayden Lee, PharmD, EMBA

Jayden Lee, PharmD, EMBA, is the PlexusDx Medical Science Liaison with a PharmD and MBA specializing in pharmacogenomics and clinical product development, with a proven ability to bridge the gap between genomic research and practical patient outcomes. Dr. Lee has more than 10 years of professional experience in clinical pharmacy, academia, and research.

This article is part of the PlexusDx Education Hub — your resource for evidence-based guidance on hormones & fertility. Browse all Hormones & Fertility education

Male-factor issues contribute to roughly half of the cases in which couples struggle to conceive, and genetics is one meaningful piece of that picture. Understanding the inherited factors that can affect sperm production or delivery helps frame a productive conversation with a fertility specialist.

How genetics contributes to male fertility

Sperm production is a complex process that requires hundreds of genes working across the testes, hormonal system, and DNA-repair machinery. When one of those steps is disrupted by an inherited variant, sperm count, motility, or shape can be affected. Genetics is only part of the story — hormones, lifestyle, and environment all matter — but for men with very low or absent sperm counts, a genetic cause is found often enough that specialists routinely test for it.

Y-chromosome microdeletions

The Y chromosome carries a region called AZF (azoospermia factor), split into segments AZFa, AZFb, and AZFc, that contains genes essential for sperm production. Small missing pieces — microdeletions — in these regions are among the most common genetic causes of severely low or absent sperm counts. Because these deletions sit on the Y chromosome, they can be passed to male offspring, which is one reason genetic counseling is part of the evaluation.

CFTR and obstructive causes

CFTR is best known as the cystic fibrosis gene, but certain CFTR variants cause a condition called congenital bilateral absence of the vas deferens (CBAVD) — the tubes that carry sperm never form properly. In these cases sperm may be produced normally but cannot be delivered. Men found to carry CFTR variants are typically referred for genetic counseling, since partner testing has implications for future children.

MTHFR, folate, and sperm quality

Folate metabolism supports the DNA synthesis and methylation that healthy sperm depend on. The MTHFR gene encodes an enzyme central to that pathway, and common variants such as C677T can reduce its efficiency. Research examining MTHFR and male fertility is mixed, but the broader point is well supported: adequate folate status and healthy methylation matter for sperm DNA integrity. This is why balanced nutrition is a standard part of fertility guidance.

Lifestyle, biology, and when to see a specialist

Not every factor is genetic. Sleep, heat exposure, smoking, alcohol, weight, and certain medications all influence sperm parameters, and many are modifiable with support from a provider. General, evidence-based habits — a nutrient-dense diet, regular activity, and avoiding known toxins — support reproductive health broadly. If you and a partner have been trying to conceive without success, a semen analysis and evaluation by a urologist or reproductive endocrinologist is the right next step. Genetics is a guide, not a diagnosis you can make at home.

Pathway-level genetic insight

Understanding your genetic baseline can add helpful context before a specialist visit. The Precision Peptide Genetic Test analyzes 14 pathways, 49 peptides, 150+ genetic insights — including variants in genes such as MTHFR that influence methylation and hormonal-pathway biology relevant to overall wellness. It is educational, not diagnostic: it tells you about your biology, not what to put in your body, and it does not diagnose infertility or predict fertility outcomes. Bringing that context to your provider is the "test before you invest" approach.

Frequently Asked Questions

Can genetics cause low sperm count?

Yes. Y-chromosome AZF microdeletions and certain CFTR variants are established genetic causes of very low or absent sperm counts, and other genes affect hormone signaling and sperm development. Genetic factors are common enough that fertility specialists routinely include genetic testing in the evaluation of male infertility.

Does the MTHFR gene affect male fertility?

Possibly. MTHFR influences folate metabolism and methylation, which support sperm DNA integrity. Research on MTHFR variants and fertility is mixed, but adequate folate status is broadly important for reproductive health. Any supplementation decisions should be guided by a healthcare provider rather than self-directed.

Can a genetic test tell me if I am fertile?

No. Fertility is assessed through semen analysis and clinical evaluation by a specialist, not a genetic test. Genetic insights describe inherited factors that can influence reproductive biology, adding educational context — they do not diagnose infertility, predict outcomes, or replace a medical workup.

What lifestyle factors affect sperm health?

Sleep, weight, smoking, alcohol, excessive heat, and some medications can all influence sperm count and quality, and many are modifiable. General habits like balanced nutrition and regular activity support reproductive health, but persistent concerns warrant evaluation by a urologist or reproductive endocrinologist.

Want genetic context before a fertility evaluation? The Precision Peptide Genetic Test offers pathway-level insight into your individual biology to inform an educated conversation with your specialist. Explore the Precision Peptide Genetic Test.

This article is part of the PlexusDx Education Hub. Browse all Hormones & Fertility education

Disclaimer: The Precision Peptide Genetic Test analyzes how your genes influence peptide-related biological pathways. It does not recommend, prescribe, or determine which peptides you should use. Consult a qualified healthcare provider before beginning any peptide protocol.

Medical and Editorial Standards

Medical review process: This article was reviewed for medical accuracy, scientific clarity, evidence alignment, and appropriate discussion of genetics, medications, supplements, biomarkers, and health-related claims.

Sources and evidence: PlexusDx educational content is developed using peer-reviewed research, clinical literature, reputable medical references, and, where applicable, public health or regulatory guidance. References are included at the end of the article when scientific, medical, or health-related claims are discussed.

Commercial transparency: PlexusDx offers genetic testing, blood biomarker testing, personalized supplement recommendations, and related precision wellness services. Product mentions are intended to help readers understand available options and should not be interpreted as medical advice.

Important disclaimer: PlexusDx educational content is for informational purposes only and should not be used as a substitute for professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before making decisions about medications, supplements, genetic testing, lab testing, or health-related care.