Male Infertility

TOG 2020 update

Introduction

Lifestyle factors and male infertility

Obesity and weight loss

Statistically significant relationship between obesity & semen analysis parameters
Obese men → more likely to be oligospermic or azoospermic
Paternal obesity negatively affects ART outcome
Conflicting results regarding effect of significant weight loss on semen analysis parameters

Diet

Vegetables, fruits, fish, poultry, cereals & low-fat dairy products→ positively associated with sperm quality
Processed meat, full-fat dairy products, alcohol, coffee & sugar-sweetened beverages→ poor semen quality & lower fecundity rates
Favourable effects of Selenium, Zinc, Omega-3 fatty acids, Coenzyme Q10 & Carnitines on semen parameters

Vitamins and antioxidants

Oxidative stress (OS) can impair sperm motility, reduce fertilising ability & cause sperm DNA damage
Antioxidants can protect cells from OS
Many antioxidant supplements commercially available, but none has high-quality clinical data
Antioxidant use: ↑ live birth rats (OR1.79) ↑ clinical pregnancy rate (OR 2.9)
Overall low quality evidence

Cigarette smoking and vaping

Smoking negatively affects semen quality but underlying mechanism not yet clear
No definite relationship between smoking & ♂ infertility but current available evidence supports smoking cessation & ↓sing tobacco exposure for couple trying to conceive
Smoking associated with ↓ sperm count, motility & abnormal morphology → leads to ↓ in sperm quality in both fertile & infertile men (higher effect in infertile)
Worsened semen quality in moderate & heavy smokers
Oligospermia more prevalent in smokers (RR 1.29)
Paternal smoking adversely affects ART outcomes
Risk of treatment failure (specially miscarriage) reduces by 4% in former smokers with each additional year following smoking cessation
Vaping refers to e-cigarettes which contain propylene glycol, vegetable glycerine, nicotine, food-grade flavouring & water. Generally viewed as less harmful but does have negative effect on spermatogenesis & OS

Alcohol

>50% men drink alcohol yet effect on ♂ fertility not well understood
Overall→ lower semen quality but variable & dose-dependent effect on semen parameters
Habitual alcohol intake→ ↓ semen quality & changes in reproductive hormones
Semen volume, sperm count, motility & number of morphological normal sperm ALL decreased significantly

Caffeine

Apparently unaffected semen characteristics but ♂ coffee drinking associated with prolonged time to pregnancy
May be associated with sperm aneuploidy & DNA breaks but no other DNA damage

Stress

Psychological stress→ ↓ sperm concentration, progressive motility & ↑ fraction of sperm with abnormal morphology
Primarily caused by suppression of testosterone by ↑ corticosteroid levels
Antidepressants drugs→ negatively affect sexual function & semen quality
Manage stress non-pharmacologically→ CBT, psychotherapy, fertility counselling & support

Sleep

Sleep duration associated with testis size in healthy young men
Sleep disturbance may contribute to ♂ infertility
Testosterone has diurnal pattern & ↑ coinciding with REM sleep (rather than malatonin)
Prolactin ↑ during sleep & levels are sleep-dependent
Co-effects of stress/depression & poor sleep on fertility
Log-term use of hypnotics → not recommended

Sperm assessment and selection

Semen Analysis (SA)

Essential in evaluation & initial lab test
Single SA usually sufficient to decide the most appropriate management pathway
If initial SA ≥1 abnormal parameters→ Consider Repeat
Men with risk factors or abnormal semen parameters→ Refer to male reproductive specialist for full evaluation

Sperm DNA Fragmentation

SA has limited diagnostic accuracy & cannot predict ART outcomes
Main function of Spermatozoa: DNA delivery to oocyte at fertilisation and sperm DNA integrity is key for its competence
Tests to evaluate sperm DNA fragmentation (SDF): SCSA, SCD, TUNEL, COMET
Percentage of spermatozoa with DNA fragmentation higher in infertile men
Association between high SDF & poor reproductive outcomes in natural conception/ IUI but unable to predict with ART outcomes
No treatment for high SDF proven yet

New developments in sperm selection in ART

Sperm Selection → key step in ART which affects both treatment success rate & offspring health
Standard methods are density gradient centrifugation or swim-up both with similar ART outcomes
Live birth after ICSI → 25-30% per (fresh) treatment cycle
(Only names of latest techniques of sperm selection are mentioned here. Please refer to original article for details in this section)

Genetic testing in male infertility

Normal sperm production → result of aggregated action of up to 2300 genes
Many genetic cause remain unknown
Genetic Testing
- Recommended→ specifically in severely oligospermic or azoospermic male
- Goals→ identify genetic conditions which could pass to offspring & to identify men who would benefit from surgical sperm retrieval procedures
Routinely recommended for evaluation of severe male factor infertility including
Karyotype, Y chromosome micro-deletion analysis & CFTR mutation analysis for men with CABVD (only offer diagnosis for 20% of men with infertility)

Karyotyping→ can only detect DNA abnormalities that are ≥4 million base pairs
Most common aneuploidy→ Klinfelter Syndrome (47,XXY) identified in 11% of azoospermic males
Less common→ testicular disorder of sex development (46,XX), translocations (balanced or unbalanced), inversions, insertions or deletions
AZF region (on Y-chromosome) deleted in 7% azoospermic & 2.9% of oligospermic
Prognosis of sperm retrieval predicted by specific location of AZF micro-deletion
- AZFc region→ good prognosis
- AZFb & AZFa regions→ very poor prognosis
Approximately 1% of spermatozoa in an ejaculate of fertile male are aneuploid if evaluated for chromosome 13, 18, 21, X and Y
Sperm chromosome aneuploidy testing→ not recommended as a screening tool