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Written By THT Editorial Team

Dr. Asmita Pandey

Reviewed by Dr. Asmita Pandey, Fertility Expert , M.D. (OB/GYN) 

Infertility is a prevalent issue with an estimated 9% of couples worldwide experiencing fertility challenges, half of which are attributed to male factors 1 Revolutionary genetic studies like exploring the Y chromosomes sequencing (2)DNA fragmentation techniques as well as recent technological advances like ICSI procedures shed light on various causes and potential treatments for male infertility, offering hope for effected couples.

Challenges & Causes of Male Infertility 1,3,4

Male infertility can stem from a range of factors, including genetic mutations, lifestyle factors, medical illnesses, environmental exposures, and medications. Genetic variations have been identified as a leading cause of male infertility, with recent studies focused on deciphering these genetic markers to develop targeted therapies 1,3 4 . Additionally, oxidative stress has been recognized as a significant contributor to sperm DNA damage and impaired function, emphasizing the potential role of antioxidant supplementation in mitigating these effects 1, 3

Dr Hagai Levine, an epidemiologist at the Hebrew University of Jerusalem, and his colleagues published an analysis in 2017 and an update in 2022 , these two papers found about a 50 percent decrease in sperm concentration since 1970s. 5, 6. 

Furthermore, the decline in sperm count is paralleled by declines in testosterone and increases in testicular cancer and male genital anomalies.

Treatment Approaches 1,3,4,7

Oxidative damage of sperm DNA is positively linked with oligoasthenoteratozoospermia (OAT), and male infertility. The antioxidants are being explored worldwide to combat OAT, sperm DNA fragmentation and reactive oxygen species. Recent prospective, double-blind, randomized, placebo-controlled multi centre trial by Patki et al was conducted in 300 sub-fertile males (25-45 years) has explored the use of antioxidants with a proprietary formula of micronutrients, essential amino acids, antioxidants, and vitamins such as coenzyme Q10, L-carnitine, L-arginine, L-glutathione, vitamins like C, E, B6, B12, B1, A, D, ginseng extract, lycopene, folic acid along with elemental zinc, iron, copper selenium, manganese. Subjects were randomised in either the antioxidant blend treatment group or placebo group, assessed changes in sperm count, motility, normal morphology, semen volume, and percent DFI before and after treatment (90 days). Study results confirmed the well-researched fact of antioxidants being effective to reduce oxidative stress and thus improve sperm DNA integrity and also improved semen parameters in males aged 40 and above.

Furthermore, advancements in reproductive technologies, including intra cytoplasmic sperm injection (ICSI), have significantly enhanced fertilization rates, especially in cases where traditional IVF methods may not be successful 1, 3

Role of Varicocelectomy and Testicular Sperm Extraction 1,3

Conventional male reproductive surgeries, such as varicocelectomy and testicular sperm extraction (TESE), have been studied to broaden their indications for addressing male factor infertility. Varicocelectomy, in particular, has shown improvements in semen parameters, including sperm concentration and motility, following repair 12

Infertility Evaluation & counselling. 3

The American Urological Association (AUA) and American Society for Reproductive Medicine (ASRM) have provided guidelines for the diagnosis and treatment of male infertility, emphasizing the importance of a thorough evaluation to identify potentially treatable causes 3. Moreover, male infertility risk factors, reproductive history, and medical interventions that may impact fertility should be carefully assessed during the evaluation process 3. ASRM/AUA guidelines recommend Clinicians should advise couples with advanced paternal age (≥40) that there is an increased risk of adverse health outcomes for their offsprings. 8

Future Directions and Considerations

Efforts to understand the molecular and genetic factors responsible for spermatogenesis and fertilization are ongoing, offering the potential for improved outcomes in male factor infertility 1,3 . Additionally, the use of assisted reproductive technologies, such as intrauterine insemination (IUI) and in vitro fertilization (IVF), remains crucial in overcoming various causes of idiopathic infertility 3, 4

In conclusion, recent advances in male infertility research have provided valuable insights into the causes and potential treatments for this prevalent condition. By focusing on genetic variations, oxidative stress, and innovative treatment approaches, researchers aim to improve fertility outcomes for affected individuals. 


  1. Boivin J, et al. “International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care.” Hum Reprod. 2007.
  2. Nature ,Vol 621 14 September 2023.
  3. Smits RM, et al. “Antioxidants for male subfertility.” Cochrane Database Syst Rev. 2019.
  4. Schlegel PN, et al. “Diagnosis and treatment of infertility in men: AUA/ASRM guideline part II.” Fertil Steril. 2021.
  5. Human Reproduction Update, Volume 23, Issue 6, November-December 2017,
  6. Human Reproduction Update, Volume 29, Issue 2, March-April 2023
  7. Transl Clin Pharmacol. 2023 Mar;31(1):28-39
  8. https://www.auanet.org/documents/Guidelines/PDF/Male-Infertility-Guideline.pdf