Androlog of the Fertility and Sterility Dialog

Is the term ‘Non-Male Factor’ evidence-based?

Started 6 months ago

We read the recent systematic review in F and S Reviews by Bantel- Finet et al.1 with dismay.  This is the latest in twenty years of such reviews reinforcing the concept that among couples with non-male factor infertility; defined primarily based on routine semen analysis, ICSI is no more successful than IVF. We believe that this concept is fundamentally flawed.

Since IVF began in 1978, the standard male fertility workup has been a semen analysis alone. This has proved to be inadequate with up to a third of men being diagnosed with unexplained infertility2. In current practice, couples with ‘unexplained’ infertility are given IVF as the first option with no further investigation of the male partner. This is despite our knowledge that 25-30% of infertile men have palpable varicoceles; treatment of which improves their fertility3 and 20% of whom have asymptomatic but treatable infections4.

It is a matter of great disappointment that we, as a speciality, have made so little progress in 40 years, despite all the advanced andrological tests now at our disposal. Even the nomenclature of ‘male factor’ has a pejorative connotation.  According to this classification, all men have only ‘one factor’ causing their infertility.

In contrast, we are delighted to see the major learned societies are changing their views. Last year, when WHO published their laboratory manual for examination of human semen 2021:  Sperm DNA testing has been added as an extended test. In their words ‘The evaluation of sperm DNA testing could constitute an important addition of male infertility, becoming one of the most discussed promising biomarkers in basic and clinical andrology. Further, ASRM/AUA and EAU have revised their guidelines to include further investigations of both the man and his sperm for unexplained infertility, failed ART, and recurrent pregnancy loss (RPL).  ESHRE guidelines for RPL have also been updated to report its association with sperm DNA although none has been observed with semen analysis.

Finally, we need to consider the global cost of ignoring male reproductive health. Recent data indicate that infertile men have an increased risk of somatic disorders such as cancer and die younger than fertile men. Prof Chris Barratt has led a welcome global initiative, but government funding for such research has been pitiful, showing a lack of concern for men and their ongoing health.

 Prevarication until we have more evidence, more initiatives, more time in clinic is indefensible We must start now to provide adequate male fertility care and take to heart the immortal words ‘Perfection is the Enemy of Progress’.

Sheena E M Lewis1,2, Honorary Professor1, Queen’s University of Belfast, UK  CEO2 Examenlab Ltd, Unit 18A, Block K, Weavers Court Business Park, Linfield Road, Belfast BT12 5GH,


   Sandro C. Esteves

ANDROFERT, Andrology and Human Reproduction Clinic and Department of Surgery (Division of Urology), University of Campinas (UNICAMP), Campinas, SP, Brazil



  1. De Bantel-Finet A et al. Does intracytoplasmic sperm injection improve live birth rate when compared with conventional in vitro fertilization in non-male factor infertility? A systematic review and meta-analysis. Fertil Steril Rev Vol. 3, No. 1, January 2022
  2.  Hamada A, Esteves SC, Nizza M, Agarwal A. Unexplained male infertility: diagnosis and management. Int Braz J Urol. 2012 Sep-Oct;38(5):576-94. doi: 10.1590/s1677-55382012000500002. 

 3. Birowo et al. The benefits of varicocele repair for achieving pregnancy in male infertility: A systematic review and meta-analysis. Heliyon. 2020 Nov 5;6(11):e05439. doi: 10.1016/j.heliyon.2020.e05439. eCollection 2020 Nov.

 4. Boeri L, Salonia A et al. Semen infections in men with primary infertility in the real-life setting Fertility and Sterility Volume 113, Issue 6, June 2020, Pages 1174-1182