Infertility means not being able to become pregnant after a year of trying with unprotected and frequent sex. Infertility is fairly common, occurring in about 15% of couples. There are treatments specific to men or to women, and ones used for both partners. About 50% of couples treated for infertility go on to have babies.^[1]

An evaluation for an infertility diagnosis is usually started after inability to achieve pregnancy after 12 months of unprotected and frequent intercourse. People with a past medical history of infertility and women older than 35 years may also choose to be evaluated for a diagnosis. An evaluation usually involves recording the patient’s history (e.g., sexual practices, exposure to toxins or certain medications, surgeries), physical examination and imaging of reproduction organs, and certain laboratory tests (e.g., semen analysis, ovulation hormone levels).^[2]

Medical treatment for “unexplained” infertility can include induction of ovulation with medications, intrauterine insemination (IUI), or the two treatments together. IUI involves removing chemicals from semen that may slow the movement of the sperm and physically placing the sperm into the uterus with a catheter. Other infertility treatments include injectable ovulation hormones, in vitro fertilization (sperm and egg fertilization is done in a test tube and then delivered into the uterus for implantation), surgery to fix anatomical blockages and irregularities, and other methods. Treatments for individuals are usually specific to the factors causing infertility and vary from person to person.^[2]

Supplements have been usually studied in combination with medical infertility treatments. Small studies suggest that males with infertility that take dietary supplements like zinc, vitamin E, or L-carnitine may have improved sperm motility and/or increased success with assisted reproductive technologies.^[2] Many other dietary supplements have been studied for infertility with no good evidence of benefit. Some of these supplements include black seed oil, ginger, coenzyme Q10, and vitamin D.^[3]

In the case that the infertility is “unexplained” by anatomical or other causes, couples may benefit from altering their lifestyle and behaviors. For example, couples may engage in timed-intercourse during the period of the highest fertility for the woman. This usually involves using kits that detect the increase of hormones to signify ovulation (luteinizing hormone surge) and helps to predict the days that the woman has the highest fertility.^[2]

Lifestyle factors that can help with infertility include stopping smoking and alcohol and substance use, as well as maintaining a healthy weight, since obesity is correlated with a higher risk of infertility.^[2]

Causes of infertility include male factors, female factors, and “unexplained” factors. Common causes of infertility usually involve abnormalities within the female or male reproductive organs.

In males, 40%–50% of infertility cases have an unknown cause; 30%–40% are caused by primary hypogonadism (where the testes produce little-to-no testosterone); the remaining 10%–20% are caused by things such as impaired sperm transport due to obstruction, erectile dysfunction, and retrograde ejaculation. For female infertility, 40% of cases are caused by ovulation disorders attributed to aging, low ovarian reserve, endocrine disorders, polycystic ovary syndrome (PCOS), etc.; 30% are caused by obstruction of the fallopian tubes due to pelvic inflammatory disease, surgery, etc.; the remaining cases are caused by endometriosis and other conditions.^[2]

At its core, ED is caused by a deficit in NO release, cyclic GMP (cGMP) and calcium signaling, or smooth muscle relaxation. However, many overlapping mechanisms can interrupt this signaling cascade.

Psychogenic or sympathetic-mediated ED is caused by stress, depression, or anxiety about sexual performance. Neurogenic ED is caused by a deficit in nerve signaling to the penis, which may be secondary to spinal cord injury, traumatic brain injury, or surgery. Vasculogenic ED — the most common form of ED — is caused by underlying vascular disease, endothelial dysfunction, and structural changes to the arterial walls. Iatrogenic ED is most often the result of pelvic surgery or the use of medications. Finally, endocrine causes of ED include low levels of androgens (e.g., testosterone) and other hormones.

A number of medications have been linked to ED, including antihypertensives (blood pressure medications); 5𝛼-reductase inhibitors, anti-androgens, luteinizing hormone-releasing agonists and antagonists (used to treat prostate cancer), antidepressant medications, and opiates.^[4]