New doors are opening for couples with idiopathic fertility

By: Dr. Robyn Murphy, ND

The global rates of infertility have steadily climbed over the past few decades to affect up to 15% of all couples. (Sun 2019) While the causes of infertility are multifactorial, 50% of cases of infertility are estimated to be due to genetic factors. (Zorrilla & Yatsenko, 2013) Numerous couples experience ‘idiopathic infertility’, meaning the reasons are unknown after investigative result come back normal. Up to 75% of male infertility cases are reported as idiopathic. (Filipponi, 2009) Unfortunately for these individuals there is little offered in regard to treatment.

Preimplantation genetic testing (PGT) of an embryo is a common genetic test that looks for specific genetic alterations related to the chromosomal number and structure and specific genetic diseases; however, these tests are only available for patients’ undergoing ART and does not prevent the occurrence of genetic abnormalities. What about preconception testing and optimizing the gametes to increase the likelihood of a healthy embryo from the start?

Lifestyle fertility genetics is a novel area of development that uncovers genetic predispositions that impact lifestyle factors known to affect the processes and diseases responsible for reproduction. This is a shift in perspective to look upstream at the DNA of mom and dad prior to conception to optimize sperm and egg quality and address underlying conditions that affect fertility. This is particularly helpful in idiopathic cases. The panel contains genetic markers that influence risk for nutrient deficiencies, oxidative stress, metabolic changes, response to dietary interventions, and sensitivity to environmental toxins.


Genes influence nutrient absorption, transportation and bioavailability, which impact both male and female fertility, such as spermatogenesis, sperm quality, aneuploidy and DNA fragmentation and egg quality, hormone balance, ovulatory disturbances, pregnancy rate, fetal and maternal health, respectively.

Variations in genes related to vitamin D transportation and receptor binding increase the risk of vitamin D deficiency by up to 40%. At-risk alleles in the VDR gene are associated with early pregnancy loss. (Djurovic 2020) In these individuals, standard recommended dose of 800-2000IU may be insufficient to replenish vitamin D stores.


TCF7L2 and CRY1 genes influence carbohydrate sensitivity and development of insulin resistance, which can delay pregnancy and lead to gestational diabetes. Women who consume less than 40% of their total caloric intake from carbohydrates reduce the effects of these genes and show an improved glucose response compared to those with the ‘wild type’ or normal versions of these genes.


Those who inherit the FUT2 ‘non-secretor’ mutation have an increased risk of dysbiosis, including the development of oral and vaginal candidiasis and recurrent urinary tract infections. Recent studies reveal how recurrent infections alter the uterine microbiome and may be an underlying factor to recurrent pregnancy loss.

Oxidative Stress and DNA Damage

Variations in CYP1A1 and CYP1A2 gene alter enzyme activity and susceptibility to environmental toxins. At-risk alleles may lead to a 7-fold increase in risk of polyaromatic hydrocarbon (PAH) induced oxidative DNA damage with exposure. PAHs create reactive oxygen species (ROS) and bind directly to and damage DNA, reducing meiotic division during spermatogenesis leading to low sperm count and mobility. (Madeen, 2017)


While preconception genetic testing is a novel concept, it offers couples additional insights to individualize dietary, nutritional and lifestyle interventions that have the potential to have a big impact on reproduction.



  1. Djurovic J, et al. Polymorphisms and haplotypes in VDR gene are associated with female idiopathic infertility. Human Fertility. 2020 Apr 2;23(2):101–10.
  2. Filipponi D, Feil R. Perturbation of genomic imprinting in oligozoospermia. Epigenetics. 2009 Jan;4(1):27–30.
  3. Madeen EP, Williams DE. Environmental PAH Exposure and Male Idiopathic Infertility: A Review on Early Life Exposures and Adult Diagnosis. Rev Environ Health. 2017 Mar 1;32(1–2):73–81.
  4. Sun H, Gong T-T, Jiang Y-T, Zhang S, Zhao Y-H, Wu Q-J. Global, regional, and national prevalence and disability-adjusted life-years for infertility in 195 countries and territories, 1990–2017: results from a global burden of disease study, 2017. Aging (Albany NY). 2019 Dec 2;11(23):10952–91.
  5. Zorrilla M, Yatsenko AN. The Genetics of Infertility: Current Status of the Field. Curr Genet Med Rep [Internet]. 2013 Dec 1 [cited 2019 Sep 9];1(4). 1.