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. 2024 Jul 29;24(1):158.
doi: 10.1186/s12894-024-01545-1.

Pharmacological non-hormonal treatment options for male infertility: a systematic review and network meta-analysis

Bassel H Al Wattar  1   2   3 , Michael P Rimmer  4 , Jhia J Teh  5 , Scott C Mackenzie  4 , Omar F Ammar  6 , Carolyn Croucher  7 , Eleni Anastasiadis  8 , Patrick Gordon  9 , Allan Pacey  10 , Kevin McEleny  11 , Phillipa Sangster  12
Affiliations

Pharmacological non-hormonal treatment options for male infertility: a systematic review and network meta-analysis

Bassel H Al Wattar et al. BMC Urol. .

Erratum in

Abstract

Background: Male factor infertility affect up to 50% of couples unable to conceive spontaneously. Several non-hormonal pharmacological treatments have been proposed to boost spermatogenesis and increase chances of conception in men with infertility. Still, no clear evidence exists on the most effective treatment strategy.

Objective: We aimed to compare the effectiveness of non-hormonal pharmacological treatment options for men with infertility using a systematic review and network meta-analysis.

Methods: We searched MEDLINE, EMBASE, and CENTRAL until October 2023 for randomised/quasi-randomised trials that evaluated any non-hormonal pharmacological treatment options for men with idiopathic semen abnormalities or those with hypogonadism. We performed pairwise and network meta-analyses using a random effect model. We assessed risk of bias, heterogeneity, and network inconsistency. We calculated the mean rank and the surface under the cumulative ranking curve (SUCRA) for each intervention the maximum likelihood to achieve each of reported outcomes. We reported primarily on sperm concentration and other important semen and biochemical outcomes using standardised mean difference (SMD) and 95% confidence-intervals(CI).

Results: We included 14 randomised trials evaluating four treatments (Clomiphene citrate, Tamoxifen, Aromatase inhibitors, anti-oxidants) and their combinations in 1342 men. The overall quality of included trials was low. Sperm concentration improved with clomiphene compared to anti-oxidants (SMD 2.15, 95%CI 0.78-3.52), aromatase inhibitor (SMD 2.93, 95%CI 1.23-4.62), tamoxifen (SMD - 1.96, 95%CI -3.57; -0.36) but not compared to placebo (SMD - 1.53, 95%CI -3.52- 0.47). Clomiphene had the highest likelihood to achieve the maximum change in sperm concentration (SUCRA 97.4). All treatments showed similar effect for sperm motility, semen volume, and normal sperm morphology. FSH levels showed significant improvement with clomiphene vs.anti-oxidant (SMD 1.48, 95%CI 0.44-2.51) but not compared to placebo. The evidence networks for LH and testosterone suffered from significant inconsistency (p = 0.01) with similar trend of improvement with clomiphene compared to other treatments but not compared to placebo.

Conclusion: There is insufficient evidence to support the routine use of Clomiphene, tamoxifen, and aromatase inhibitors to optimise semen parameters in men with infertility. Future randomised trials are needed to confirm the efficacy of clomiphene in improving fertility outcomes in men.

Prospero: CRD42023430179.

Keywords: Anastrozole; Clomiphene; Letrozole; Male infertility; Network meta-analysis; Oligospermia; Randomised trials; Systematic review; Tamoxifen.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Study selection and inclusion process of randomised trials evaluating non-hormonal pharmacological treatment options for male infertility
Fig. 2
Fig. 2
Network of randomised trials comparing non-hormonal pharmacological treatment options for male infertility. The dots’ size represents the number of participants in each comparison arm and the lines’ thickness represent the number of randomised trials comparing each two treatments directly
Fig. 3
Fig. 3
Forest plots of network meta-analysis of changes in sperm concentration and motility across non-hormonal pharmacological treatment options for male infertility
Fig. 4
Fig. 4
Surface under the cumulative ranking curve of changes in semen parameters following the use of non-hormonal pharmacological treatment options for male infertility. Surface under the cumulative ranking curve expressed in percentage. Higher values suggest higher likelihood of the treatment achieving the outcome of interest
See this image and copyright information in PMC

References

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