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What is male infertility?

Infertility, defined as the failure to achieve pregnancy after 12 months of regular, unprotected sexual intercourse, affects roughly 1 in 6 couples globally.¹Historically, this condition has been discussed as a female-related issue due to both ovarian and uterine factors; however, the importance of male factors is now considered highly relevant too.

Recent estimates are that male factors are involved in up to half of all infertility cases, with around 20–30% of infertility cases due to male factors alone and another 20–30% due to common causes in both sexual partners.²

Symptoms of male infertility

Infertile men may not experience any symptoms; however, in those that do, symptoms may be related to their sexual health and performance. It has been estimated that most infertile men could have low sexual desire and sexual satisfaction and that between 10–20% of infertile men have orgasmic dysfunction, erectile dysfunction, and/or premature ejaculation.³

Similarly, as low testosterone levels (hypogonadism) are present in up to 40% of infertile men, symptoms of low testosterone and infertility are often paired. In these cases, symptoms may include fatigue, irritability, depressed mood, gynecomastia, and reduced body and facial hair.

Diagnosis of male infertility

Couples should be evaluated for infertility when they fail to achieve a successful pregnancy after 12 months of regular, unprotected sexual intercourse. If the female partner is older than 35 years old, or the couple has a specific medical history that warrants earlier evaluation and treatment, then a health professional may evaluate a couple after 6 months of regular, unprotected sexual intercourse.

For the man, this should include a thorough evaluation of his reproductive history, involving questions about coital frequency and timing, duration of infertility, previous fertility, childhood illnesses and developmental history, medical illnesses, previous surgery, medications and allergies, sexual history (such as STIs), infections and exposures to gonadotoxins, and poor lifestyle.⁴

In most cases, a physical examination will be needed too. Depending on circumstances, hormone or genetic tests may be needed, as well as infection screens. Men may be required to have an ultrasound scan to check for testicular or prostate problems, blockages in the reproductive system, or poor blood flow in the testes (varicocele).

The diagnosis of infertility in men is mainly based on semen analysis, including the concentration, appearance, and motility of sperm.⁵In a large clinical study of 3,500 men from twelve countries over 5 continents whose partners achieved a pregnancy within 12 months of trying to conceive, 95% of them had a sperm concentration of 16 million/mL or above, sperm motility of 42% or above, progressive motility of 30% or above, and normal sperm morphology of 4% or above.⁶

As presented in the table below, the World Health Organisation has provided the lower limits of the accepted reference values for semen analysis to aid the diagnosis of male infertility.⁵ While these values are now accepted globally as the reference values for sperm parameters, not all men who fall below these values are infertile, and not all those with “normal” semen parameters are fertile.

‍

Parameter	Reference Value
Ejaculate volume	>1.4 ml
Sperm concentration	≥16 million/ml
Total sperm number	≥39× 10⁶ /ejaculate
Motility	≥42 %
Progressive motility	≥30 %
Vitality	≥54 %
Normal morphology	≥4%

‍

Indeed, infertility remains unexplained in up to 30% of couples when semen parameters are normal and no issues are found for the female partner.⁷ For these reasons, it is important to consider more advanced testing to determine whether sperm function or genetic integrity might be affected.

There is considerable evidence to show that both sperm DNA fragmentation and seminal oxidative stress are key players in male infertility.⁸ Tests for this can be offered when couples have had recurrent miscarriage in addition to cases of unexplained infertility.

Note: A couple may also have multiple factors contributing to infertility at the same time; therefore, an evaluation for male infertility should be performed concurrently with the female evaluation.

Male infertility is either due to a problem making and/or ejaculating good-quality sperm. A variety of factors may cause either one of these issues; however, in up to 40% of cases, there is no clear cause. When the cause is identifiable, it usually falls into one of the categories stated below.

Causes of male infertility

Sexual: Erectile dysfunction and premature ejaculation can cause male infertility, both of which have a strong psychological component.³ One of the largest causes of failure to conceive is insufficient sexual intercourse. It is important to have intercourse every other day if possible, during the two weeks in the middle of the partner’s cycle, provided she has a regular 28-day cycle.

Outside of that time, men should ejaculate every 3 days or so to keep the sperm healthy. Saving up sperm for the right time of the month only increases the buildup of dead and dying sperm. ‍

Physical: Undescended testes (cryptorchidism) is a major cause of infertility in adults, ⁴ particularly if surgery to correct this is not carried out within the first two years of life. Enlargement of the blood vessels in the testes (varicoceles) is present in 35–40% of infertile men. This can create excess heat in the scrotum and, in turn, reduce spermatogenesis and increase sperm DNA damage.¹⁰ Other physical causes of male infertility include rotation of the spermatic cord (testicular torsion) and semen entering the bladder rather than through the penis during orgasm (retrograde ejaculation).⁴‍

Hormone disorders: An imbalance in reproductive hormones, such as Kallman Syndrome, can lead to a significant impairment of sperm development and accounts for many of the cases of severe male factor infertility.¹¹

Genetic: Genetic causes account for approximately 5% in infertile men and increase to 15% for men with azoospermia.¹² Genetic abnormalities include chromosomal aberrations such as Klinefelter syndrome or Y-microdeletion and single gene mutations such as cystic fibrosis. These genetic abnormalities typically may cause a complete absence or very low number of sperm in the ejaculate.‍

Male accessory gland infections: recent evidence is coming to light indicating that infections of the urinary or genital tract can affect sperm parameters, particularly motility and vitality, and may be associated with male infertility.⁴‍

Medical illnesses: Semen parameters are often reflective of a man’s general health. There are many conditions that may increase the risk of male infertility, including cancer, diabetes, renal disease, liver failure, hemochromatosis, chronic obstructive pulmonary disease, prostatitis, cystic fibrosis, and multiple sclerosis.⁴^,¹⁴‍

Medications: Certain medications that can decrease fertility include chemotherapeutic agents, psychotropic medications, long-term cortico-steroid use, calcium-channel blockers, alpha-blockers, 5-alpha reductase inhibitors, and testosterone replacement therapy.⁴^,¹⁵‍

Obstructions: A blockage in the male reproductive tract occurs in up to 40% of men with azoospermia and usually occurs at the level of the epididymis.⁴‍

Lifestyle and environmental: Excess food intake and low exercise may lead to obesity, which has been shown to negatively affect testosterone levels, ejaculate volume, sperm concentration, and morphology.¹⁶ Smoking can also adversely affect fertility, ¹⁷as can recreational drugs, anabolic steroids, consumption of too much alcohol, and testicular heat exposure.¹⁸

Treatment of male infertility

Treatment for male infertility is highly dependent on the identified cause. It is absolutely crucial that couples struggling with infertility consult with a healthcare professional as soon as possible.

Speciﬁc interventions for male infertility include varicocele repair, correction of identiﬁable hormonal abnormalities (such as administration of follicle-stimulating hormone [FSH]), microsurgical reconstruction of obstructive conditions, and surgical relief of ejaculatory duct obstruction.¹⁶

The identification of male infertility may also inform whether the female partner requires specific treatment. For couples with mild male factor infertility, ovarian stimulation or intrauterine insemination (IUI) may be pursued by the female partner. In vitro fertilisation (IVF) is also indicated in cases of severe male factor infertility.¹²

Of course, there is the option for infertile couples to avoid treatment altogether. When left untreated, approximately 1 in 4 infertile couples will still conceive after 2 years, which goes down to 1 in 3 couples after 4 years. Even in men with severely low sperm count (<2 million sperm/mL), 7.6% pursuing fertility will have a successful pregnancy in their couple within 2 years.¹⁷

Prognosis of male infertility

As conceiving and raising a child is deeply important to many people, infertility is associated with significant mental stress. A review of the psychological consequences of male infertility reported that, irrespective of the cause, infertility increased the risk of depression, anxiety, and low self-esteem, all of which cumulated to reduce some aspects of quality of life.³

Many studies have also found male infertility is linked with poor health outcomes. For example, compared with fertile men, infertile men have a 26% higher risk of death.⁴ However, this association may be spurious and not necessarily indicative of a cause-and-effect relationship.

Infertile men are more likely to consume alcohol, smoke, eat poorly, and repeatedly use drugs such as cocaine and cannabinoids, all of which can negatively affect health. Moreover, up to 6% of men evaluated for male infertility will be found to have a more serious underlying pathology, such as cancer.⁵

‍It may therefore be the case that less healthy men are more likely to become infertile, as opposed to infertility itself causing health-related issues.

Fertility preservation

There are many situations where men are faced with the potential loss of their fertility, for example, if they are about to embark on chemotherapy or other medication or if they need surgery that may affect their fertility. Biological males who are considering gender reassignment are also faced with losing their fertility. For all these cases, freezing and storing sperm provides the best option for having a family in the future.⁴