The British Fertility Society defines infertility as ‘a disease of the reproductive system defined by the failure to achieve a pregnancy after 12 months or more of regular unprotected sex (without contraception) between a man and a woman”. 

In this article, we will review male factor infertility.

Causes of male factor infertility

1	Primary spermatogenic failure	This is defined by NICE as any spermatogenic abnormality caused by a condition other than hypothalamic pituitary disease.   Congenital: absence of testes, cryptorchidism, genetic abnormalities Acquired: testicular trauma/torsion, mumps orchitis, testicular tumour, systemic disease (e.g. liver cirrhosis), varicocele, cytotoxic agents Idiopathic
2	Genetics	Klinefelter’s syndrome: 47 XXY karyotype Kallmann syndrome leading to a hypogonadotropic hypogonadism Androgen insensitivity syndrome (karyotype of XY, phenotypically female)
3	Obstructive Azoospermia	Bilateral obstruction of the seminal ducts leading to a total absence of sperm in semen Causes include absent vas deferens, post-infection, post-surgery
4	Varicocele	Found in 25% men with abnormal semen analysis (Pathophysiology linking a varicocele with infertility is unclear, potentially due to increased scrotal temperature)
5	Hypogonadism	Primary: hypergonadotropic hypogonadism due to testicular failure Secondary: hypogonadotropic hypogonadism due to reduced gonadotrophin-releasing hormone (GnRH) and/or FSH/LH secretion Androgenic insensitivity: end organ resistance to gonadotrophins
6	Other	Medications: chemotherapy and cytotoxic agents, sulfasalazine, anabolic steroids Psychological factors leading to ejaculation disorders or erectile dysfunction Lifestyle factors: smoking, obesity, excessive alcohol, illicit drug use

 

History and Examination

History

Examination

Full medical, sexual and social history, including: Length of time trying to conceive Frequency and type of sexual intercourse Children born to the man Ejaculatory or erectile dysfunction Medications e.g. sulfasalazine, anabolic steroids, cytotoxic chemotherapy drugs Past medical history: mumps, STIs, testicular trauma, undescended testes, systemic disease (diabetes, liver cirrhosis), prior surgery e.g. orchidopexy Family history including genetic disorders such as cystic fibrosis Social and occupational history e.g. smoking, alcohol intake, exercise, diet

Physical examination may include: Calculation of BMI Genital examination: Position of urethral meatus, structural abnormalities of the peniis Testicular volume and consistency, varicocele, hernia, undescended testes Check for signs of hypogonadism: gynaecomastia, lack of body hair growth and a reduction in muscle mass Look for signs of anabolic steroid use

 

Primary Care Investigations

Semen analysis is the first line investigation for male factor infertility in primary care.

The results should be compared to the WHO reference values:

Semen volume	1.5ml or more
pH	7.2 or more
Sperm concentration	15 million spermatozoa per ml or more
Total sperm number	39 million spermatozoa per ejaculate or more
Total motility (percentage of progressive motility and non-progressive motility)	40% or more motile or 32% or more with progressive motility
Vitality	58% or more live spermatozoa
Sperm morphology (percentage of normal forms)	4% or more

 

• If the results of the first semen analysis are abnormal, then repeat testing is offered ideally 3 months after the initial test – this is to allow time for the spermatozoa cycle to be completed.
  • Repeat testing may be required sooner than 3 months if a severe deficiency is detected on the initial analysis e.g. azoospermia
• If initial semen analysis normal, there is no need for further testing.
• Referral to secondary care is required following 2 abnormal semen analysis results
• Chlamydia testing

Referral to Secondary Care 

Referral is required following two abnormal semen analysis results

According to NICE, an earlier referral may be warranted if the following are present:

• Previous genital pathology
• Previous urogenital surgery
• Previous STI
• Varicocele
• Significant systemic illness
• Abnormal genital examination
• Known reason for infertility e.g. previous cancer treatment

Secondary Care Investigations

Following a detailed review of the initial investigations undertaken in primary care, the following tests may also be considered in secondary care:

• Genetic testing
• Sperm culture
• Endocrine tests e.g. FSH and testosterone
• Imaging of the urogenital tract
• Testicular biopsy

Management of Male Factor Infertility

Lifestyle management

• Weight management
• Psychological stress management
• Lifestyle advice including smoking and alcohol cessation

 

Medical management

• Hypogonadotropic hypogonadism – gonadotrophin drugs should be offered
• NICE state that men with idiopathic semen abnormalities should not be offered medications such as anti-oestrogens or gonadotrophins as no benefit has been shown

 

Surgical management

• If obstructive azoospermia
  • Surgical correction can be offered

NICE state that surgery for varicoceles should not be offered as part of infertility treatment as it has not been shown to improve pregnancy rates

 

 

References

1. nice.org.uk. 2018.Scenario: Initial assessment | Management | Infertility | CKS | NICE. [online] Available at: <https://cks.nice.org.uk/topics/infertility/management/initial-assessment/> [Accessed 9 August 2022]
2. nice.org.uk. 2018.Causes of infertility | Background information | Infertility | CKS | NICE. [online] Available at: <https://cks.nice.org.uk/topics/infertility/background-information/causes-of-infertility/> [Accessed 9 August 2022].
3. nice.org.uk. 2018.Scenario: Management | Management | Infertility | CKS | NICE. [online] Available at: <https://cks.nice.org.uk/topics/infertility/management/management/> [Accessed 9 August 2022].
4. NICE Guideline CG156, 2013. Fertility problems: assessment and treatment. [online] Available at: <https://www.nice.org.uk/guidance/cg156/resources/fertility-problems-assessment-and-treatment-pdf-35109634660549> [Accessed 9 August 2022]
5. Harding, M., 2016. Infertility – Male. [online] Patient.info. Available at: <https://patient.info/doctor/infertility-male> [Accessed 9 August 2022].