Is Fertility Genetic? A Closer Look at Inherited Factors

Fertility is shaped by genetic, environmental, and lifestyle factors. While health and age are commonly emphasized, inherited traits also play a role. Understanding genetics in reproductive potential helps explain fertility challenges and informs possible interventions.

Scientific advancements have identified genetic components linked to hormone regulation, ovarian reserve, and sperm production. However, genes do not act alone—external influences and epigenetic modifications also affect fertility outcomes.

Genetic Variations And Reproductive Hormones

Reproductive hormone regulation is influenced by genetic variations affecting hormone synthesis, receptor sensitivity, and signaling pathways. The follicle-stimulating hormone receptor (FSHR) gene, for example, plays a role in ovarian follicle development and spermatogenesis. Variants in this gene can alter receptor responsiveness to follicle-stimulating hormone (FSH), impacting ovarian reserve and sperm production. A study in The Journal of Clinical Endocrinology & Metabolism found that certain FSHR polymorphisms are linked to lower ovarian response to stimulation during assisted reproductive treatments.

Luteinizing hormone (LH) and its receptor (LHCGR) also exhibit genetic variability affecting reproductive function. Mutations in LHCGR have been associated with Leydig cell hypoplasia, impacting testosterone production and male fertility. In women, variations in this gene contribute to polycystic ovary syndrome (PCOS), a condition that disrupts ovulation. Research in Human Reproduction has shown that specific LHCGR polymorphisms are more common in individuals with PCOS, highlighting the genetic basis of hormone-related fertility disorders.

Estrogen metabolism is another area influenced by genetics. The CYP19A1 gene encodes aromatase, the enzyme responsible for converting androgens into estrogens. Variants in this gene can alter estrogen levels, affecting endometrial receptivity and ovarian function. A Fertility and Sterility meta-analysis reported that certain CYP19A1 polymorphisms influence estradiol levels, which may impact implantation success in women undergoing in vitro fertilization (IVF). In men, disruptions in estrogen balance due to genetic mutations can impair sperm maturation and motility.

Chromosomal Factors In Fertility

Chromosomal integrity is crucial for reproductive health, influencing gamete formation and embryo viability. Chromosomal abnormalities, including numerical aberrations, structural rearrangements, and mosaicism, can impair conception or increase miscarriage risk. Advances in genetic screening have revealed the extent of chromosomal contributions to infertility.

Aneuploidy, an abnormal number of chromosomes, is one of the most common chromosomal disruptions affecting fertility. In women, age-related aneuploidy in oocytes significantly contributes to declining fertility and recurrent pregnancy loss. Research in The New England Journal of Medicine has shown that aneuploidy incidence rises sharply after the mid-30s, leading to conditions such as trisomy 21 (Down syndrome) or monosomy X (Turner syndrome). In men, sperm aneuploidy can compromise embryo development, with studies in Fertility and Sterility finding that elevated sperm aneuploidy rates reduce fertilization success in assisted reproductive technologies (ART).

Structural chromosomal rearrangements, such as translocations, inversions, and deletions, can disrupt fertility by interfering with gene expression and meiosis. Reciprocal translocations, where chromosome segments exchange places, often go unnoticed but can result in unbalanced gametes, leading to implantation failure or miscarriage. A study in Human Reproduction Update found that 2–5% of couples experiencing recurrent pregnancy loss carry balanced translocations, underscoring the importance of karyotype analysis in fertility evaluations. Similarly, Y chromosome microdeletions, particularly in the azoospermia factor (AZF) regions, have been linked to severe male infertility.

Mosaicism, where an individual has genetically distinct cell lines, further complicates reproductive outcomes. Somatic mosaicism affecting sex chromosomes can result in conditions such as Turner syndrome mosaicism (45,X/46,XX) or Klinefelter syndrome mosaicism (46,XY/47,XXY), impacting gonadal function and fertility. Research in The American Journal of Medical Genetics indicates that some individuals with mosaic Klinefelter syndrome retain partial spermatogenesis, allowing for sperm retrieval via testicular sperm extraction (TESE) in select cases.

Hereditary Conditions Affecting Ovarian Reserve

Ovarian reserve—the number of eggs a woman is born with—is largely determined during fetal development, but genetic factors influence how quickly this supply depletes. Some women experience diminished ovarian reserve (DOR) earlier than expected, a condition often linked to hereditary factors. Studies show that women with a family history of early menopause or infertility frequently face similar reproductive challenges.

One of the most well-documented genetic influences on ovarian reserve involves mutations in the FOXL2 gene, which regulates follicular development and ovarian maintenance. Mutations in this gene are associated with premature ovarian insufficiency (POI), leading to menopause before age 40. Variations in the FSHR gene can also impair ovarian responsiveness to hormonal signals, reducing follicular recruitment and egg yield in assisted reproductive treatments.

Beyond single-gene mutations, polygenic factors contribute to ovarian reserve variability. Genome-wide association studies (GWAS) have identified multiple loci linked to reproductive lifespan, including MCM8 and MCM9, which are involved in DNA repair and meiotic stability. Deficiencies in these pathways can accelerate follicular atresia. Additionally, Fragile X premutation carriers (55–200 CGG repeats in the FMR1 gene) face an increased risk of POI, with up to 20% experiencing ovarian failure before the expected age of menopause.

Gene-Environment Interplay

While genetics lay the foundation for reproductive potential, environmental factors influence how these traits manifest. Endocrine-disrupting chemicals (EDCs), such as bisphenol A (BPA) and phthalates, have been shown to interfere with hormone signaling, potentially accelerating ovarian aging in genetically predisposed individuals. Research in Environmental Health Perspectives suggests that women with specific estrogen receptor gene polymorphisms may be more vulnerable to the ovarian-damaging effects of these chemicals.

Nutritional status also modulates genetic influences on fertility. Variants in genes involved in folate metabolism, such as MTHFR, affect homocysteine levels and have been linked to impaired ovarian function. However, sufficient folic acid intake can mitigate some of these effects, demonstrating how dietary interventions can counteract genetic predispositions. Studies on caloric restriction suggest that nutrient availability influences ovarian reserve, with epigenetic modifications altering gene expression related to follicular development.

Epigenetic Patterns In Reproductive Potential

Epigenetic modifications influence gene expression without altering DNA sequences. These include DNA methylation, histone modifications, and non-coding RNA activity, which regulate reproductive gene expression. While epigenetic programming establishes reproductive function early in life, environmental factors such as diet, stress, and EDCs can reshape these patterns over time.

DNA methylation plays a key role in ovarian function and spermatogenesis. Disruptions in this process have been linked to conditions such as PCOS and diminished ovarian reserve. Studies have found that aberrant methylation of folliculogenesis-related genes, such as GDF9 and BMP15, can impair ovarian function. In men, altered methylation of spermatogenesis-related genes, including H19 and MEST, has been associated with lower sperm counts and reduced motility.

Histone modifications further refine reproductive gene expression. Acetylation and methylation of histones regulate ovarian aging and sperm quality. Research has shown that histone modifications affect follicle activation, with changes in histone acetylation linked to POI. In sperm cells, disrupted histone retention has been observed in cases of unexplained male infertility. Unlike genetic mutations, epigenetic changes are potentially reversible, offering a promising avenue for therapeutic interventions.

Genetic Testing For Fertility-Related Traits

Genetic testing is increasingly used to assess reproductive potential and identify infertility causes. These tests analyze genetic markers linked to ovarian reserve, hormone sensitivity, and sperm quality, providing insights into potential reproductive challenges. While genetic testing cannot guarantee predictive certainty, it helps guide fertility treatment decisions.

Carrier screening identifies individuals who carry mutations linked to inherited reproductive disorders. Conditions such as Fragile X-associated POI and Y chromosome microdeletions can be detected through genetic testing, allowing for early intervention. Additionally, polygenic risk scores for reproductive traits are being developed to assess the likelihood of early menopause, recurrent pregnancy loss, or reduced sperm production.

Genetic testing is also integrated into assisted reproductive technologies. Preimplantation genetic testing (PGT) enables the selection of embryos with normal chromosomal and genetic profiles, improving pregnancy success rates. This is particularly beneficial for individuals with known chromosomal translocations or hereditary conditions affecting embryo viability. As research progresses, genetic testing is expected to play a growing role in personalized fertility care.