Low Sperm Count Overview

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Low Sperm Count Overview

Updated: 19-July-2024

Introduction

Low sperm count, also known as oligospermia or oligozoospermia, happens when a man has 15 million or less sperm per millilitre (mL) of semen.

There are 3 forms of oligospermia:

  • Mild oligospermia (10-15 million sperm/mL)
  • Moderate oligospermia (5-10 million sperm/mL)
  • Severe oligospermia (< 5 million sperm/mL)

According to the World Health Organization reference values, only 5% of males with mild oligospermia achieve a ‘time to pregnancy’ of less than 12 months with their partner.

Source: Cooper T G, et al. (2009)

The exact prevalence of low sperm count among the general population is unknown due to a lack of high quality studies. However among couples seeking fertility treatment, where male factors is the sole cause of infertility, low sperm count accounts for 8 out of 10 cases.

Although adult sperm count is by and large pre-set during early infancy (3 months of age), semen volume and sperm motility, along with the quantity and quality of sperm declines gradually post-puberty as men get older and oxidative stress levels increase.1,2,3

In fact, the male body continues to produce sperm, well past the age of 80.4 At this point in life though testicular volume and NAD+ levels begin to decrease leading to a rapid decline in spermatogenesis and overall fertility.5

In infertile males this rapid decline seems to occur much sooner.

With a significant drop in progressive sperm motility, morphology and vitality beginning around 35 years of age.6 This is also true for men diagnosed with oligospermia, with Stalker et al. reporting sperm (epigenetic) age to be significantly older than normal for these men.7 These results suggest age is a critical factor for infertile men who want to start a family one day.

A semen analysis is the first test for male infertility. Any sperm parameter in the 5th percentile (5% of males to conceive within 12 months of intercourse), is considered abnormal and the male infertile, if no female factors exist after 12 months of trying to conceive.

Initial semen analysis of low sperm count is then confirmed by repeating the test 3 months later. This allows spermatogenesis, the biological process where sperm develop from germ cells in the testis, to repeat one full cycle.

However semen analysis fails to pinpoint the cause of low sperm count.

The male reproductive system itself is regulated by a complex network of positive and negative feedback loops, beginning at the hypothalamus in the brain which releases gonadotrophin-releasing hormone (GnRH) in a pulsatile manner.

GnRH causes the secretion of gonadotrophins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), from the anterior pituitary gland which stimulate the (Leydig, Sertoli) cells in the testis, to produce sex steroids and inhibin, and in turn apply negative feedback to GnRH, LH and FSH secretion.

Any disruption to this network directly impairs the function of the testis, which is to synthesize testosterone and produce sperm.

In fact, the loss of one or both of these functions, known as male hypogonadism, is commonly found in 4 out of 10 men with oligospermia.8 Interestingly, FSH levels can possibly predict the onset of oligospermia in the majority of cases. A recent study reported males with elevated FSH levels (FSH ≥ 7.6 IU/mL) were highly likely to develop oligospermia within 2 years of initial hormone tests.9

Hypogonadism itself can be further diagnosed as primary hypogonadism or secondary hypogonadism.

Primary hypogonadism indicates a problem with the testicles, causing impaired spermatogenesis, low testosterone and an increase in gonadotrophins.

Secondary hypogonadism (also called hypogonadotropic hypogonadism) indicates a problem in the brain (i.e. pituitary gland or hypothalamus) causing low levels of gonadotrophins, reduced spermatogenesis and low testosterone.

Although low levels of testosterone (TT < 264ng/dL) was not significantly linked to impaired semen parameters, in a recent study of males with total sperm count > 5 million requiring further study.10

Primary hypogonadism and secondary hypogonadism can both be caused by congenital disorders or acquired after birth.

Even in acquired cases of secondary hypogonadism, such as obesity, subsequent high levels of exercise may also cause an increase in inflammation, leading to no improvement in either gonadotrophin or testosterone levels and sperm quality.11

Overall the hypothalamic-pituitary-testis (HPT) axis in males is finely balanced with changes in energy balance, between exercise and inflammation, regulating the expression of kisspeptin, which controls the levels of GnRH (gonadotropin-releasing hormones), LH, FSH and testosterone.

Spermatogenesis

Sperm cell production, also known as spermatogenesis, is a complex process involving several organs, mainly the testicles and two glands (hypothalamus and pituitary) in the brain.

This process occurs in 3 distinct phases after puberty, in which mature sperms cells are produced from primordial germ cells.

Phase 1 (Spermatocytogenesis)

During this phase, also known as the mitotic or proliferative phase, dark spermatogonia which are undifferentiated stem cells, go through mitosis to produce more stem cells, among those dark spermatogonia, some differentiate into pale spermatogonia that further differentiate into B spermatogonia.

Phase 2 (Spermatidogenesis)

In this (meiosis) phase, B spermatogonia leave the basement membrane of the seminiferous tubule, pass through the blood-testis barrier and divide into 2 primary spermatocytes each.

Two sequential meiotic divisions then follows:

  • Each primary spermatocytes divides into 2 secondary spermatocytes
  • Each secondary spermatocytes divide into 2 spermatids.

Phase 3 (Spermiogenesis)

Each spermatid then differentiate into a mature spermatozoon. The body produces around 100 million mature sperm cells each day.

The whole process of spermatogenesis takes around 74 days to be completed and a further 12 to 21 days is needed for the sperm to travel from the epididymis to the ejaculatory ducts.

Therefore, it takes approximately 3 months for any changes to be reflected in the ejaculated sperm.

Symptoms of Low Sperm Count

The main sign of low sperm count in a male is the inability to conceive a child despite 1 year of frequent and unprotected intercourse.

The inability to conceive despite 1 year of frequent and unprotected intercourse is defined as infertility in a couple.

Other symptoms may include:

  • Low sex drive or erectile dysfunction
  • Swelling, lump and pain in the testicular area
  • Low facial or body hair
  • Less opaque (translucent) semen after liquefication

Risks Associated with Low Sperm Count

Men suffering from low sperm count are susceptible to further issues such as:

  • Stress, loss of self-esteem and relationship issues due to difficulties trying to conceive.
  • Increased risk of cancer.

CANCER

Several studies undertaken have linked low sperm count to a higher risk of cancer.12,13,14,15 Although, no cause-and-effect relationship was directly established, infertile men should consult their Doctor to discuss long-term monitoring strategies.

Causes of Low Sperm Count

The causes of low sperm count fall into 3 main categories:

  • Medical
  • Environmental
  • Lifestyle

Diagnosis of Low Sperm Count

The inability to conceive despite 1 year of frequent and unprotected intercourse is defined as infertility in a couple. At this stage, it is advised that both partners consult a doctor since the inability to conceive frequently occurs due to a combination of male and female issues.

For males partners at this initial consultation, the European Academy of Andrology recommends Doctors perform the following:

  • General physical examination to assess for signs of hypogonadism.
  • Physical examination of the scrotum to assess: the volume and consistency of the testicles and epididymis, the total or partial absence of deferent ducts, and the presence of varicoceles.
  • Two semen analyses (3 months apart) according to the WHO guidelines.

Semen analysis evaluates both the quantity and quality of sperm.

Semen samples can be collected in the clinic or at home following 2 to 7 days of sexual abstinence. However, if collected at home, the sample should be kept at room temperature and delivered to the laboratory immediately.

Men are diagnosed with oligospermia only if total sperm count is less than 39 million and all other parameters are normal.

The test should then be repeated after 3 months at the same laboratory to minimise variables and confirm any abnormal values. Importantly, males with borderline results should request a third semen analysis to potentially avoid unnecessary treatment.16,17

On the other hand, men diagnosed with severe oligospermia may be advised to immediately bank their sperm in lieu of treatment due to the high risk of developing secondary azoospermia.18

HOME SPERM COUNT TESTING KITS

Some at-home testing kits to detect low sperm count are available over the counter. Unfortunately these kits can not duplicate the accuracy or range of semen parameters, measured in an accredited laboratory. As such results should always be interpreted with caution.

After diagnosis the doctor might request additional tests to determine the cause of low sperm count.

These additional tests may include:

  • Scrotal ultrasound to check the testicles and surrounding tissue.
  • Transrectal ultrasound to check for any blockages in the ejaculatory ducts and seminal vesicles.
  • Post-ejaculation urinalysis to check for retrograde ejaculation. This happens when the sperm cells travel backwards into the bladder during ejaculation.
  • Blood tests to check the level of hormones secreted by the testicles and pituitary gland or signs of genetic abnormality.
  • Other less common tests:
    i) Biopsy of the testicles to evaluate if there is normal production of sperm.
    ii) Anti-sperm antibody tests to check if the immune system is attacking the sperm cells.
    iii) Specialized sperm function tests to determine the penetration strength or attaching potential of the sperm cells.

Multiple blood samples across the day may be required for accurate results and diagnosis.

Source: Abbara A, et al. (2023)

Treatment of Low Sperm Count

The initial advice of physicians for males diagnosed with low sperm count is to keep trying, by having intercourse every 1-2 days during the woman’s fertile window, as a significant proportion of couples manage to conceive naturally in the preceding 12 months.

In fact, studies consistently show that ejaculatory abstinence beyond 24 hours significantly decreases sperm count in males diagnosed with oligospermia.19,20,21

However, depending on the physicians initial findings, they may also recommend you begin one of several treatment options.

Treatment options for men with low sperm count include: lifestyle, supplements, environment, surgery, medication and Assisted Reproductive Technology.

Low sperm count can be reversed in some acquired cases of the condition, such as those caused by obesity, smoking, recreational drugs & steroid use. On the other hand, cases of low sperm count caused by congenital disorders or cancer treatments (chemotherapy, gonadotoxins) cannot be cured.

References

  1. Henriksen L S, et al. (2022). Serum Testosterone Levels in 3-Month-Old Boys Predict Their Semen Quality as Young Adults. https://academic.oup.com/jcem/article/107/7/1965/6552307 ↩︎
  2. Nago M, et al. (2021). Aging increases oxidative stress in semen. https://icurology.org/DOIx.php?id=10.4111/icu.20200066 ↩︎
  3. Collodel G, et al. (2021). Influence of age on sperm characteristics evaluated by light and electron microscopies. https://www.nature.com/articles/s41598-021-84051-w ↩︎
  4. Handelsman D J and Staraj S, (1985). Testicular Size: The Effects of Aging, Malnutrition, and Illness. https://onlinelibrary.wiley.com/doi/10.1002/j.1939-4640.1985.tb00830.x ↩︎
  5. Meyer-Ficca M L, et al. (2022). Low NAD+ Levels Are Associated With a Decline of Spermatogenesis in Transgenic ANDY and Aging Mice. https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.896356/full ↩︎
  6. Demirkol M K, et al. (2021). At What Age Threshold does the Decline in Semen Parameters Begin? https://jcpsp.pk/article-detail/at-what-age-threshold-does-the-decline-in-semen-parameters-begin ↩︎
  7. Stalker K, eat al. (2022). Tissue specific age acceleration patterns in the sperm of oligozoospermic men. https://www.frontiersin.org/journals/reproductive-health/articles/10.3389/frph.2022.1043904/full ↩︎
  8. Sussman E M, et al. (2008). Hormonal Evaluation of the Infertile Male: Has It Evolved? https://www.sciencedirect.com/science/article/abs/pii/S0094014308000086 ↩︎
  9. Fantus R J, et al. (2023). Compensated Hypospermatogenesis: Elevated Follicle-stimulating Hormone Predicts Decline in Semen Parameters Among Men With Normal Index Semen Analysis. https://www.goldjournal.net/article/S0090-4295(23)00063-8/abstract ↩︎
  10. Di Guardo F, et al. (2020). Low Testosterone and Semen Parameters in Male Partners of Infertile Couples Undergoing IVF with a Total Sperm Count Greater than 5 Million. https://www.mdpi.com/2077-0383/9/12/3824 ↩︎
  11. Chang B, et al. (2021). Leptin and inflammatory factors play a synergistic role in the regulation of reproduction in male mice through hypothalamic kisspeptin-mediated energy balance. https://rbej.biomedcentral.com/articles/10.1186/s12958-021-00698-0 ↩︎
  12. Hanson H A, et al. (2016), Subfertility increases risk of testicular cancer: evidence from population-based semen samples. https://www.fertstert.org/article/S0015-0282(15)02038-5/fulltext ↩︎
  13. Eisenberg M L, et al. (2015). Increased Risk of Cancer in Infertile Men: Analysis of U.S. Claims Data. https://www.auajournals.org/doi/10.1016/j.juro.2014.11.080 ↩︎
  14. Eisenberg M L, et al. (2013). Increased risk of cancer among azoospermic men. https://www.fertstert.org/article/S0015-0282(13)00631-6/fulltext ↩︎
  15. Jacobsen R, et al. (2000). Risk of testicular cancer in men with abnormal semen characteristics: cohort study. https://www.bmj.com/content/321/7264/789.long ↩︎
  16. Zuvela E and Matson P, (2023). Effect of the technical variability of counting chambers upon the interpretation of sperm concentration results. https://www.rbmojournal.com/article/S1472-6483(23)00876-3/abstract ↩︎
  17. Aznavour Y, et al. (2022). Semen parameter variability among users of at-home sperm testing kits. https://bmcurol.biomedcentral.com/articles/10.1186/s12894-022-01134-0 ↩︎
  18. Karavani G, et al. (2024). Idiopathic secondary azoospermia occurrence in men with oligospermia over time. https://link.springer.com/article/10.1007/s10815-024-03179-6 ↩︎
  19. Xie M, et al. (2024). The Association between Abstinence Period and Semen Parameters in Humans: Results in Normal Samples and Different Sperm Pathology. https://www.mdpi.com/2075-1729/14/2/188 ↩︎
  20. Akhigbe R E, et al. (2022). Influence of ejaculatory abstinence period on semen quality of 5165 normozoospermic and oligozoospermic Nigerian men: A retrospective study. https://onlinelibrary.wiley.com/doi/10.1002/hsr2.722 ↩︎
  21. Levitas E, et al. (2005). Relationship between the duration of sexual abstinence and semen quality: analysis of 9,489 semen samples. https://www.fertstert.org/article/S0015-0282(05)00540-6/fulltext ↩︎

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Causes of Low Sperm Count

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