Varicocelectomy improves the fertility of males with normal semen

Varicocelectomy improves the fertility of males with normal semen

The impact of varicocelectomy on sperm DNA fragmentation and pregnancy rate in subfertile men with normal semen parameters: A pilot study

doi.org/10.1080/2090598X.2021.1889746

Background

Several studies in the past investigated the effect of varicocele surgery (varicocelectomy) on fertility outcomes in men with noticeable varicoceles and abnormal semen parameters, according to WHO reference limits.

In this regard varicocelectomy is considered the ‘gold standard’ treatment option for subfertile men with varicoceles and abnormal semen results, however WHO reference limits are not a guarantee of male fertility.

Sperm DNA fragmentation (SDF) is an important parameter which describes the loss of DNA integrity among the sperm within the semen sample. Excess SDF can abruptly stop embryo development, cause implantation failure and early pregnancy loss.

To date studies exploring the effect of varicocelectomy on SDF has only consisted of males with abnormal semen parameters and excluded males with varicoceles, high SDF and normal semen parameters. 

Aim

To evaluate the outcome of microsurgical subinguinal varicocelectomy on the DNA fragmentation index (DFI) and spontaneous pregnancy rate of men with noticeable varicoceles and normal semen parameters.

Methodology

Males were recruited from the Department of Urology at the Qena Faculty of Medicine (Eygpt) for this study. Only males with at least 1 year history of male factor subfertility, a noticeable varicocele, normal semen parameters, high DFI (>25%) and ‘normal’ female partners were accepted for this study. Females were considered normal following a negative hysterosalpingography (HSG) with normal menstruation and ovarian reserve.

Any patient featuring discreet or recurrent varicoceles, cryptorchidism, pyospermia, genital infection, obesity, smoking, alcohol or drug abuse, exposed to gonadotoxins, cancer or female infertility factor were automatically excluded from the study.

In total 95 males qualified for this study of which 45 (Surgery group) proceeded with varicocelectomy and 50 (Control group) choose to monitor without further intervention. Males in both groups were advised to maintain a good lifestyle, avoid hot baths and tight clothes for the duration of the study.

All semen samples were collected following 3-5 days of sexual abstinence and analysed within the hour according to WHO guidelines for quality assurance. Sperm DNA fragmentation was measured using the Halo test which detects the percentage of sperm with an abnormal chromatin structure.

In the study group, microsurgical subinguinal varicocelectomy was carried out by a single surgeon using an operating microscope (x10-20) and standard surgical technique. 

All patients, post surgery or non-surgery, had a follow up assessment at 6 and 12 months.

Results

A total of 10 patients were lost to follow-up over the 1 year period resulting in 45 surgery patients and 40 controls. Mean age of males was 33.4 and 33.1 years, among the surgery and control groups respectively, with mean female age of 25.8 and 25.9 years likewise.

Comparision of baseline characteristics between the 2 groups showed no statistically significant differences in BMI, duration or type of infertility, varicoceles laterality and grade. Over 80% of males in both groups were diagnosed with primary infertility. 

Baseline WHO sperm parameters of the study group prior to surgery was;

  • 26.2 million/mL sperm concentration
  • 33.4% progressive motility
  • 4.3% normal morphology

Baseline DFI test results also showed no significant difference (34.9% vs. 35.33%) between the surgery and control groups respectively at the beginning of the study.

At the 6-month follow-up, DFI had significantly reduced in both the surgery group (25.8% vs. 34.9%) and control group (31.3% vs. 35.3%). Interestingly at 6 months follow-up, 60% (27/45) of males who had surgery had reduced their DFI below the 25% cut-off value, while in the control group no male was able to reduce their DFI below the 25% cut-off value.

Similarly sperm concentration was significantly increased (32.5 vs. 26.1 million/mL) post varicocele surgery at the 6-month mark with a moderate increase in normal morphology (5.2 vs 4.3 %) also seen.

Overall this resulted in 14/45 (31.1%) spontaneous pregnancies at the 6-month mark and 28/45 (62.2%) spontaneous pregnancies within 12 months for the surgery group.

In contrast the control group only had a total of 4/40 (13.3%) spontaneous pregnancies at the 6-month mark and 9/40 (30%) spontaneous pregnancies within 12 months.

Interestingly spontaneous pregnancies occurred in 85% of males with a DFI < 25% within the surgery group, supporting previous studies that DFI > 25% is associated with male infertility.


SUMMARY: Does removing varicocele improve fertility

Surgical removal of varicoceles in males with normal sperm results & high DNA fragmentation index (DFI) increased sperm concentration (32.5 vs. 26.1 million/mL), decreased DFI (25.8% vs. 34.9%) & doubled the rate of spontaneous pregnancy (62.2% vs. 30%) 12 months post surgery compared to controls.


Limitations

  1. Small study size.
  2. Non-randomised study groups

Funding

No external funding was declared for this study.

Glossary

Chromatin
A highly organised complex of DNA and proteins.

Cryptorchidism
Undescended Testicles.

Gonadotoxins
Any substance or drug that can cause temporary or permanent damage to the ovaries or testicles.

Laterality
Left or right side.

Pyospermia
High number of white blood cells in the semen also known as leukocytospermia.

Subinguinal
Below Poupart’s ligament.

Similar studies

Roque M and Esteves S C, (2018). Effect of varicocele repair on sperm DNA fragmentation: a review. https://doi.org/10.1007/s11255-018-1839-4

Abdelbaki S A, et al. (2017). The impact of coexisting sperm DNA fragmentation and seminal oxidative stress on the outcome of varicocelectomy in infertile patients: A prospective controlled study. https://doi.org/10.1016/j.aju.2017.03.002

Alhathal N, et al. (2016). Beneficial effects of microsurgical varicocoelectomy on sperm maturation, DNA fragmentation, and nuclear sulfhydryl groups: a prospective trial. https://doi.org/10.1111/andr.12256

Peluso G, et al. (2013). The study of spermatic DNA fragmentation and sperm motility in infertile subjects. https://doi.org/10.4081/aiua.2013.1.8

Smit M, et al. (2009). Decreased Sperm DNA Fragmentation After Surgical Varicocelectomy is Associated With Increased Pregnancy Rate. https://doi.org/10.1016/j.juro.2009.08.161

Smith R, et al. (2005). Increased sperm DNA damage in patients with varicocele: relationship with seminal oxidative stress. https://doi.org/10.1093/humrep/dei429


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