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Clinical Trial
. 2017 Nov;5(6):1115-1123.
doi: 10.1111/andr.12420. Epub 2017 Oct 5.

Isotretinoin administration improves sperm production in men with infertility from oligoasthenozoospermia: a pilot study

J K Amory  1 , K A Ostrowski  2 , J R Gannon  3 , K Berkseth  1 , F Stevison  4 , N Isoherranen  4 , C H Muller  2 , T Walsh  2
Affiliations
Clinical Trial

Isotretinoin administration improves sperm production in men with infertility from oligoasthenozoospermia: a pilot study

J K Amory et al. Andrology. 2017 Nov.

Abstract

There is currently no effective medical therapy for men with infertility due to oligoasthenozoospermia. As men with abnormal sperm production have lower concentrations of 13-cis-retinoic acid in their testes, we hypothesized that men with infertility from oligoasthenozoospermia might have improved sperm counts when treated with isotretinoin (13-cis-retinoic acid). We conducted a single-site, single-arm, pilot study to determine the effect of therapy with isotretinoin on sperm indices in 19 infertile men with oligoasthenozoospermia. Subjects were men between 21 and 60 years of age with infertility for longer than 12 months associated with sperm concentrations below 15 million sperm/mL. All men received isotretinoin 20 mg by mouth twice daily for 20 weeks. Subjects had semen analyses, physical examinations, and laboratory tests every 4 weeks during treatment. Nineteen men enrolled in the study. Median (25th, 75th) sperm concentration increased from 2.5 (0.1, 5.9) million/mL at baseline to 3.8 (2.1, 13.0) million/mL at the end of treatment (p = 0.006). No significant changes in sperm motility were observed. There was a trend toward improved sperm morphology (p = 0.056). Six pregnancies (three spontaneous and three from intracytoplasmic sperm injection) and five births occurred during the study. Four of the births, including all three of the spontaneous pregnancies, were observed in men with improvements in sperm counts with isotretinoin therapy. Treatment was well tolerated. Isotretinoin therapy improves sperm production in some men with oligoasthenozoospermia. Additional studies of isotretinoin in men with infertility from oligoasthenozoospermia are warranted.

Keywords: 13-cis-retinoic acid; male infertility; semen analysis; spermatogenesis; spermatogonial differentiation.

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Figures

Figure 1
Figure 1
Sperm concentation (medians, interquartile ranges) before, during and after treatment with isotretinoin for twenty weeks. Panel A depicts the twelve men with a baseline total motile sperm count of greater than one million, and panel B depicts the seven men with fewer than 1 million total, motile sperm at baseline. Note the log scale of the y-Axis of panel B. *p<0.05 compared with baseline.
Figure 1
Figure 1
Sperm concentation (medians, interquartile ranges) before, during and after treatment with isotretinoin for twenty weeks. Panel A depicts the twelve men with a baseline total motile sperm count of greater than one million, and panel B depicts the seven men with fewer than 1 million total, motile sperm at baseline. Note the log scale of the y-Axis of panel B. *p<0.05 compared with baseline.
Figure 2
Figure 2
Total motile sperm counts for each subject. The baseline and treatment values are an average of three semen samples prior to or during treament. The follow-up values are an average of the two semen samples obtained 12 and 24 weeks following treatment. Panel A depicts the twelve men with a baseline total motile sperm count of greater than one million, and panel B depicts the seven men with fewer than 1 million total, motile sperm at baseline (B). Panel C shows the percent change in total motile sperm between baseline and the end of treatment. Note the log scale of the y-axis of panel B. * no follow-up sample; ** follow-up sample with total, motile sperm count of zero.
Figure 2
Figure 2
Total motile sperm counts for each subject. The baseline and treatment values are an average of three semen samples prior to or during treament. The follow-up values are an average of the two semen samples obtained 12 and 24 weeks following treatment. Panel A depicts the twelve men with a baseline total motile sperm count of greater than one million, and panel B depicts the seven men with fewer than 1 million total, motile sperm at baseline (B). Panel C shows the percent change in total motile sperm between baseline and the end of treatment. Note the log scale of the y-axis of panel B. * no follow-up sample; ** follow-up sample with total, motile sperm count of zero.
Figure 2
Figure 2
Total motile sperm counts for each subject. The baseline and treatment values are an average of three semen samples prior to or during treament. The follow-up values are an average of the two semen samples obtained 12 and 24 weeks following treatment. Panel A depicts the twelve men with a baseline total motile sperm count of greater than one million, and panel B depicts the seven men with fewer than 1 million total, motile sperm at baseline (B). Panel C shows the percent change in total motile sperm between baseline and the end of treatment. Note the log scale of the y-axis of panel B. * no follow-up sample; ** follow-up sample with total, motile sperm count of zero.
Figure 3
Figure 3
Serum 13-cis-retinoic acid (A) and all-trans-retinoic acid (B) concentrations before, during and after treatment. All values are means ± SD. *p<0.05, **p<0.01 compared with baseline.
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