Table 1. Characteristics of the included study of PDE5is on sperm quality in this systematic review.
| Author | Publishment time | Country | Study design | Sample | Treatment course | Edition of WHO guidelines | Diagnostic criteria | Outcome indicators | Treatment group medicine & dosage | Mean±SD after treatment | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment | Control | Treatment | Control | p-value | |||||||||
| Aversa et al [13] | 2000 | Italy | Double-blind, randomized, placebo-controlled, cross-over | 20 | 20 | Once | 1992 | The inclusion criteria included normal erectile function, proven fertility, a stable relationship, normal electrocardiogram, no prior or concomitant serious illness or consumption of medications during the 3 months period prior to the study. | Sperm number (×106) Straight progressive motility (%) Grade a Straight progressive motility (%) Grade b Sperm abnormalities (%) |
100 mg Sildenafil (Viagra™; Pfizer, Sandwich, UK) | 98.8±14.7 | 94.8±17.2 | - |
| 36.4±2.9 | 31.9±2.4 | ||||||||||||
| 18.6±1.8 | 19.9±2.3 | ||||||||||||
| 52.4±3.1 | 50.4±3.5 | ||||||||||||
| Hellstrom et al [11] | 2003 | USA | Randomized, double-blind, placebo controlled, parallel group | 87 | 88 (10 mg group) | 6 months | 1999 | Healthy men or men with mild ED who were at least 45 years old were eligible. For subjects to be enrolled semen samples including a sperm concentration of 20 million/mL, 50% sperm motility, 50% normal sperm morphology, and 2 and 1.5 mL ejaculate volume in the 10 and 20 mg Tadalafil studies, respectively. | Mean sperm concentration (×106/mL) Mean ejaculate sperm count (×106) Mean % normal sperm morphology Mean % normal sperm motility |
10 and 20 mg Tadalafil | 10 mg study (baseline–change from baseline): 74.9–8.2; 217.5–41.7; 58.9+1.4; 61.5–2.5 | 10 mg study (baseline–change from baseline): 81.5+0.9; 232.6–22.0; 58.9+0.7; 61.8–2.8 | 10 mg study: 0.02; 0.089; 0.388; 0.643 |
| 89 (20 mg group) | 20 mg study (baseline–change from baseline): 76.8–4; 189–10; 62.4–1.1; 59.7–1.7 | 20 mg study (baseline–change from baseline): 78.6–4.2; 210.1–25.8; 63.2–2.3; 61.4–4.4 | 20 mg study: 0.913; 0.231; 0.138; 0.04 | ||||||||||
| Hellstrom et al [12] | 2008 | USA | Multicenter, randomized, double-blind, placebo-controlled | 95 | 96 | 9 months | 1999 | Healthy men or men with mild ED who were at least 45 years of age were eligible to enroll if their semen samples at baseline met the following criteria: sperm concentration of 20 million/mL (geometric mean of two samples), 50% motile sperm, 50% sperm with normal morphology, and semen volume 1.5 mL (arithmetic mean of two samples). | Sperm concentration (106/mL) Sperm count (million) Motile sperm (%) Normal sperm morphology (%) |
20 mg Tadalafil | Arithmetic mean 70.8; 191.9; 57.2; 58.0 | Arithmetic mean 73.8; 186.3; 59.4; 58.4 | Unadjusted p: 0.10; 0.95; 0.58; 0.63 |
| Jarvi et al [9] | 2008 | USA | Randomized, double-blind, placebo controlled, parallel group | 65 (Sildenafil 100 mg) | 65 | 6 months | 1992 | Subjects were included if they fulfilled the criteria of healthy male volunteers or males with ED, with the ability to produce semen samples without requiring ED therapy, 25 to 64 years old, baseline sperm concentration 20×106/mL or greater, sperm motility 50% or greater (A+B+C), 30% or more sperm with normal morphology and an ejaculate volume of 1 mL or more at each of 3 analyses during screening. | Sperm concentration Percentage normal sperm morphology |
Sildenafil 100 mg and Vardenafil 20 mg | - | - | - |
| 66 (Vardenafil 20 mg) | |||||||||||||
| Dimitriadis et al [14] | 2010 | Japan | Randomized, placebo controlled | 23 (Vardenafil 10 mg/d) | 22 | 3 months | 1999 | Vardenafil (10 mg/d, group A) or Sildenafil (50 mg/d, group B) or L-carnitine (1,000 mg/d, group C; positive controls) were administered to 23 (group A), 25 (group B), and 26 (group C) infertile men with oligoasthenospermia for 12 weeks. Another group of 22 infertile men with oligoasthenospermia (group D) served as a negative control group and receive no pharmacological treatment. | Semen volume (mL) Sperm concentration (×106/mL) Motion spermatozoa (%) Morphologically normal spermatozoa (%) |
Vardenafil 10 mg/d and Sildenafil 50 mg/d | Vardenafil 10 mg/d: 3.1±0.4; 22.6±8.2; 39.2±10.6; 40.6±9.0 | 2.3±0.5; 16.3±7.0; 24.7±10.8; 23.7±8.1 | - |
| 25 (Sildenafil 50 mg/d) | Sildenafil 50 mg/d: 2.8±0.4; 24.3±9.4; 47.1±12.2; 41.3±8.6 | ||||||||||||
| La Vignera et al [7] | 2013 | Italy | Randomized, placebo controlled | 20 (‘fibrosclerotic’ ultrasound forms [FSUF], male accessory gland infection [MAGI]) | 20 (FSUF MAGI) | 3 months | 2010 | A total of 80 infertile patients (31.0±7.0 years [range, 23–38 years]) with MAGI and erectile dysfunction were consecutively selected for this study. From an initial series of patients with MAGI, we selected the patients with ultrasound criteria suggestive of HCUF or FSUF vesiculitis. | Sperm concentration (×106/mL) Sperm count (million) Progressive motility (%) Morphology normal forms (%) Semen volume (mL) |
5 mg Tadalafil | HCUF MAGI: 14±6; 43.4±10.6; 18±8; 12±6; 3.1±1.6 | HCUF MAGI: 14±7; 33.6±5.6; 11±4; 9±5; 2.4±1.1 | - |
| 20 (‘hyper-trophic-congestive’ ultrasound forms [HCUF)] MAGI | 20 (HCUF MAGI) | FSUF MAGI: 9±3; 10.8±1.9; 10±3; 5±3; 1.2±0.6 | FSUF MAGI: 9.5±6.0; 11.4±3.6; 9±3; 4±4; 1.2±0.6 | ||||||||||
| Rago et al [6] | 2012 | Italy | Randomized, open label, parallel group | 73 (a single dose) | 65 | A single dose 15 days | 1999 | Males infertile for at least two years; no endocrine, andrological, organic or genetic disease; normal plasma levels of FSH (range 1–7 mIU/mL), LH (range 2–10 mIU/mL), and testosterone (range 3–9 ng/mL); no azoospermia and criptozoospermia; no antisperm antibodies. Additionally, patients with ED had to present symptoms for at least 6 months and should be treated with PDE5i for the first time. Two hundred and five subjects (mean age 38.0±4.8 year) with idiopathic and primary infertility were enrolled after signing in- formed consent. The patients were randomly assigned into three groups: group A (65 subjects), with non-pharmacological treatment; group B (73 subjects), treated with a single dose of Vardenafil 10 mg; group C (67 subjects), where patients received Vardenafil 10 mg every other day for 15 days. | Semen volume (mL) Sperm concentration (×106/mL) Sperm count (million) Motility spermatozoa (%) Sperm abnormalities (%) |
10 mg vardenafil | A single dose: 2.9±0; 13.1±0.7; 37.9±2.7; 28.3±1; 84.9±0.6 | 2.9±0.1; 13.3±1; 38.9±3.6; 19.7±1.2; 85.6±0.7 | - |
| 67 (15 days) | 15 days: 3.4±0.1; 23.2±2.1; 76.1±7.9; 28.6±1.3; 85.0±0.8 | ||||||||||||
| Yang et al [10] | 2014 | China | Randomized, placebo controlled | Normozoospermic group: 10 (Tadalafil 20 mg), 10 (Sildenafil 100 mg) | Normozoospermic group: 10 (Tadalafil 20 mg), 10 (Sildenafil 100 mg) | A single dose | 1999 | Ten normozoospermic patients and ten asthenozoospermic patients were randomly picked up from our andrological outpatient department respectively. Normozoospermic samples were defined according to the guidelines of WHO 1999). Enrolled patients (age ranged from 26 to 40 years) underwent detailed medical history and physical examination. Patients receiving PDE5i treatment, with chronic prostatitis, leucocytospermia or varicocele were excluded. | Semen volume (mL) Sperm concentration (×106/mL) Straight progressive motility (%) Grade a Motility spermatozoa (%) |
20 mg Tadalafil and 100 mg Sildenafil | Normozoospermic group: (Tadalafil 20 mg) 2.84±1.37; 37.45±10.96; 30.53±7.06; 72.50±6.25 (Sildenafil 100 mg) 2.75±1.32; 37.86±12.44; 30.24±6.95; 69.49±6.38 |
Normozoospermic group: 2.76±1.31; 36.36±13.59; 30.93±7.93; 70.35±7.38 | - |
| Asthenozoospermic group: 10 (Tadalafil 20 mg), 10 (Sildenafil 100 mg) | Asthenozoospermic group: 10 (Tadalafil 20 mg), 10 (Sildenafil 100 mg) | Asthenozoospermic group: (Tadalafil 20 mg) 2.18±0.95; 47.7±15.78; 15.58±11.75; 34.51±10.38 (Sildenafil 100 mg) 2.2±0.86; 45.64±13.35; 14.41±8.09; 33.23±10.94 |
Asthenozoospermic group: 2.38±1.41; 49.14±15.97; 13.93±7.74; 32.76±12.19 | ||||||||||
| Tsounapi et al [8] | 2018 | Japan | Randomized, placebo controlled | 43 | 42 | 3 months | 2010 | This study was initially scheduled to include infertile oligoasthenospermic men (according to the normal values for sperm concentration and sperm motility described in the 5th WHO manual for semen parameter reference values; WHO, 2010) with normal serum testosterone levels. | Semen volume (mL) Sperm concentration (×106/mL) Progressive motility (%) Morphology normal forms (%) |
25 mg Avanafil Bid | 3.2±0.7; 10.4±4.0; 20.0±10.0; 9.0±4.0 | 3.3±0.8; 5.8±2.9; 4.0±2.0; 8.0±4.0 | - |
PDE5is: Phosphodiesterase-5 inhibitors, WHO: World Health Organization, SD: standard deviation, ED: erectile dysfunction, FSH: follicle stimulating hormone, LH: luteinizing hormone, Bid: bis in die (twice a day).