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Sexual and Reproductive Health

Sperm Quality

Unfortunately, semen quality is also noted to decline after SCI (Deforge et al. 2005). Semen obtained by EEP in the first 2-3 days after injury was scant, but had normal quality by 6-10 days post-injury (Mallidis et al. 1994). After approximately 2 weeks semen quality deteriorates to levels approaching those observed in males with chronic SCI. After 6 months to 1 year, there is no relationship between duration of injury and sperm quality (Sarkarati et al. 1987). Semen quality in men with chronic SCI is reported to have decreased motility and viability, although total numbers of sperm tend to remain high (Brackett et al. 1997bIbrahim et al. 2009). Sperm DNA damage, which is another method of assessing semen quality, has also been shown to be higher among men with SCI when compared to able-bodied controls (Brackett et al. 2008). The following studies investigate the effects of various factors on sperm quality, including: repeated ejaculations, different methods of bladder management, antegrade versus retrograde ejaculation, vibratory stimulation versus electroejaculation, surgical extraction, heat and alterations to seminal plasma. In their chapter on fertility after SCI in the book Spinal Cord Injury Rehabilitation, Brackett and Ibrahim (2009) also provide a review of other areas related to sperm quality.

Author Year; Country
Score
Research Design
Total Sample Size
Methods Outcome
Hamid et al. 2006; UK
PEDro=6
RCT
Level 1
N=32
Population: Men with SCI; Age: mean
40.3-37.1 yrs, range 23-48; Level of injury:
above T10; Time since injury: mean 4.8-7.0
yrs, range 0.7-19.
Treatment: Weekly penile vibratory
ejaculation (PVE) for 3 months vs PVE at
baseline and at 3 months.
Outcome Measures: Sperm morphology,
forward progression, and motility.
  1. Morphology and forward progression improved in the group with weekly PVE.
  2. Motility improved in the group with weekly PVE but did not reach statistical significance.
Brackett et al. 2002; USA
PEDro=5
RCT
Level 2
N=12
Population: Mean age=36.2 yrs, > 2 yrs post-injury, C4-T11.
Treatment: Electroejaculation was
performed with the Seager Model 14
electroejaculation unit. A total of 99
electroejaculation trials were administered
4-8 weeks apart according to a random
schedule. Each trial consisted of
continuous or interrupted current delivery.
Outcome Measures: Semen quality.
  1. For anterograde ejaculation, interrupted current produced greater semen volume (2 vs .9 ml), total sperm count (130 vs 79 million) and number of motile sperm (34 vs 25 million) compared to continuous current delivery.
  2. In retrograde fractions, total sperm count was higher for continuous (113.6 million) than for interrupted delivery (29 million).
  3. Retrograde sperm motility was lower than anterograde sperm motility regardless of the method used.
Giulini et al. 2004; Italy
PEDro=5
RCT
Level 2
N=34
Population: 34 couples (males with SCI), 21-37 yrs (females), 28-46 yrs (males), paraplegia, tetraplegia, C6-L1.
Treatment: The male partner was randomly assigned to single transrectal
electroejaculation or multiple (baseline, 1-
month, 3- month) transrectal
electroejaculation before intracytoplasmic
sperm injection (ICSI).
Outcome Measures: Sperm concentration, morphology, and motility.
  1. Electroejaculation was successful in 32 of 34 cases. The rate of normal sperm morphology was not different between groups.
  2. The mean sperm concentration and rate of total sperm motility increased at 1- and 3-month in multitransrectal electroejaculation group.
  3. A fertilization rate of 63.6% was observed and the pregnancy rate per patient was significantly higher in multi-transrectal electroejaculation group.
Kathiresan et al. 2012; USA
Case series
Level 4
N SCI=444
N controls=61
Population: 444 men with SCI with no
known causes of infertility other than SCI;
level of injury: 176 cervical, 193 T1-T10, 70
T11-caudal; 115 complete, 126 incomplete.
Controls: 61 able-bodied (AB) men, healthy
with no history of infertility.
Treatment: Retrospective chart review of
Male Fertility Research Program participants from 1991 to 2011. Sperm retrieval methods
included masturbation, penile vibratory
stimulation (PVS), and electroejaculation
(EEJ).
Outcome measures: sperm retrieval
method (masturbation, PVS, EEJ), semen
volume, sperm concentration, sperm motility, total sperm count.
  1. Sperm retrieval method in SCI participants: masturbation (n=43), PVS (n=243), EEJ (n=158). Sperm retrieval method in AB control group: masturbation (n=61).
  2. Sperm motility was significantly higher in the SCI-masturbation group (36.9%) than the PVS group (25.9%) or EEJ group (15.0%), but lower compared with a control group of 61 non-SCI healthy men who collected their semen by masturbation (58.0%).
  3. The SCI-masturbation group had similar antegrade sperm concentration as the PVS group, and control group, but significantly higher than the EEJ group
Qiu et al. 2012;
China
Pre-post
Level 4
N SCI=26
N controls=16
Population: 26 infertile men with SCI
(primary infertility present in 9), mean(SD)
age 33.8(2.9) yrs, mean(SD) DOI 8.6(3.0)
yrs (range 1-11 yrs), level of injury: C5-C6
(n=4), T2-T12 (n=22), mean(SD) yrs of
infertility 6.8(4.2) yrs; Controls: 16 non-SCI
fertile donors (all had previously fathered at
least one child), mean(SD) age 32.9(2.1) yrs.
Treatment: Collection of semen samples in SCI men using penile vibratory stimulation
(PVS) (n=14), percutaneous vasal sperm
aspiration (PVSA) (n=12); collection of
semen samples in non-SCI donors all by
masturbation (n=16).
Outcome measures: sperm vitality and
DNA integrity, sperm chromosomal
aneuploidy.
  1. The number of round cells per millilitre of semen obtained from the penile vibratory stimulation (PVS) group was between 1 million and 12 million.
  2. The rate of sperm DNA fragmentation was higher in the PVS group than in the percutaneous vassal sperm aspiration (PVSA) group.
Caremel et al. 2011; Canada
Case series
Level 4
N=11
Population: 11 men with SCI; mean age 29 yrs (range 21-40); 11 complete C5-T6; mean DOI 74 mos, (range 18-163 mos).
Treatment: cystoscopic intradetrusor
botulinum neurotoxin A injections were
performed with 300 units of Botox (n=10) or 1000 units of Dysport (n=3) for overactive
bladder. Two patients received two BT
injections at 7 months interval using different dosages, were therefore treated as
independent tests. Ejaculation tests were
done pre- and post-BT injections using
penile vibrator stimulation or electroejaculation combined as needed with oral midodrine and/or intracavernous
injection or phosphodiesterase inhibitors.
Outcome Measures: Ejaculation type and volume, sperm count, mobility, vitality.
  1. Anterograde ejaculations dropped from 77% pre-BT to 54% post-BT.
  2. The proportion of retrograde ejaculation or anejaculation increased from 23% pre-BT to 46% post-BT. There was a statistically significant drop in average volume of semen from 1.8 mL pre-BT to 1 mL post-BT.
  3. Sperm mobility, sperm count and vitality were unaffected by Botox treatment, though vitality showed trend for improvement.
  4. Semen culture improved following Botox treatment with 72% of semen samples infected pre-BT compared with 29% post-BT.
McGuire et al. 2011; Ireland
Case series
Level 4
N=31
Population: 31 men, 29 with acquired spinal cord injury (complete lesion (n=18),
incomplete lesion (n=11). Injury levels: C3-C7; T1-T5; T11-L3), 2 with congenital spinal abnormality.
Treatment: Electroejaculatory stimulation
(EES) done with Seager model rectal probe;
n= 27 (87%) underwent EES once, n=4
(13%) underwent EES several times.
Outcome measures: The Mann-Whitney U
test, semen analysis (volume, density,
motility, normal morphology and live sperm); pregnancy rate.
  1. Of the 25 patients whose partners underwent insemination with the EES semen, 9 (36%) became pregnant. All pregnancies resulted in live births.
  2. 1 patient developed autonomic dysreflexia necessitating stopping EES before obtaining any ejaculate. No other side effects or complications were reported.
  3. Semen analysis findings in 15 patients showed that mean semen volume and mean density were within the normal World Health organization reference ranges.
  4. 30 patients produced antegrade, retrograde, or both types of ejaculate.
  5. Only 1 patient failed to produce any ejaculate.
Ibrahim et al. 2009; USA
Prospective controlled trial
Level 2
N=24
Population: 12 men with traumatic SCI and 12 able-bodied men as controls.
Treatment: Sperm sample from each
subject was divided into 4 groups: Group 1:
no treatment; Group 2: added phosphate
buffered saline (PBS); Group 3: monoclonal
antibodies (MAB) against target cytokines IL6, IL-1β, and TNF-α; Group 4: receptor
interference agents (RI) against the same
cytokines.
Outcome Measures: Sperm concentration; sperm motility; sperm viability; Sperm DNA damage (DFI).
  1. The mean sperm motility and viability was significantly lower in the SCI group compared to the controls.
  2. The sperm from the SCI group had a significantly higher DFI than the controls.
  3. After treatment with MAD or RI, the DFI decreased slightly in 70% of samples (difference not significant).
  4. No difference in viability between treatment groups was found.
  5. Sperm motility of treatment groups was not compared.
Hibi et al. 2008;
Japan
Post-test
Level 4
N=8
Population: 8 participants with cervical SCI and neurogenic anejaculation (age 26 – 46, mean 35.6).
Treatment: Retrograde vasal sperm
aspiration (ReVSA).
Outcome Measures: Presence of motile
sperm.
  1. Motile sperm was recovered in all participants who underwent ReVSA (11 procedures total).
  2. The retrieved sperm concentration was 109.4(64.7) × 106/mL (range 31.2-156.3 × 106 /mL).
  3. The retrieved motility of sperm was 69.8(16.8)% (range 50-91%).
  4. Clinical pregnancies were achieved in 8 cases.
Kanto et al. 2008; Japan
Case control
Level 3
N=56
Population: 22 men with SCI (age 21-41);
data on 34 men with obstructive
azoospermia was obtained retrospectively
for control.
Treatment: Testicular sperm extraction
(TESE); if unsuccessful, microdissection
TESE was performed, followed by
intracytoplasmic injection (ICSI)
Outcome Measures: Fertilization;
pregnancy.
  1. TESE successfully retrieved sperm in 19 participants with SCI.
  2. ICSI resulted in a fertilization rate of 236 of 364 (64.8%) in SCI couples and 14/19 achieved pregnancy.
  3. In couples with obstructive azoospermia, ICSI resulted in a fertilization rate of 435 of 567 (77%) and 29/34 achieved pregnancy.
  4. Pregnancy rate was significantly higher in couples with SCI using fresh testicular sperm-ICSI compared to frozen-thawed sperm-ICSI.
Brackett et al. 2007; USA
Pre-post
Level 4
N SCI=11
N controls=5
Population: 11 men with SCI and 5 ablebodied men; Age: mean(SD) range
31.9(2.3)-30.7(3.6) yrs; Level of injury: C4 to
T11; mean(SD) time since injury 9(2.0) yrs.
Treatment: Agents added to sperm to
neutralize cytokines (IL-1beta, IL-6, and
TNF-alpha) at the receptor level.
Outcome Measures: Percentage sperm
motility.
  1. Significantly improved sperm motility in men with SCI when there was interference with receptors to all 3 cytokines. No significant improvement when only 1 or 2 cytokines neutralized.
  2. Neutralizing agents had no effect in able-bodied men.
Das et al. 2006;
UK
Case series
Level 4
N=16
Population: 16 men with SCI; Age: median
37 yrs, range 24-46; Level of injury: C4-L1;
Impairment: complete (n=9), incomplete
(n=7); Time since injury: median 12.5 yrs,
range 5-43.
Treatment: Repeated electro-ejaculation (3
successive EE at 2-4 week intervals).
Outcome measures: Semen volume,
sperm concentration, sperm motility, sperm
variability, and total motile sperm
concentration.
  1. No improvement in sperm volume, motility, or total motile count in
    successive samples.
Salsabili et al. 2006; Iran
Case series
Level 4
N SCI=89
N controls=49
Population: 89 men with SCI and 49 ablebodied men; mean(SD) age: (SCI) 34(3.7)
yrs, (AB controls) 36(4.76) yrs; Injury levels
C4-L2, all complete; Time since injury range
11-18 yrs.
Treatment: 1) Semen collection by electroejaculation (EE), masturbation penile
vibratory stimulation (PVS) or percutaneous
epididymal sperm aspiration (PESA); 2)
Intracytoplasmic sperm injection (ICSI).
Outcome measures: Quality and quantity of
sperm, including sperm count, volume, PH,
density, motility, viscosity, and white blood
cells.
  1. EE was the most commonly used method of semen retrieval in men with SCI (78.7%).
  2. Normal form, motility, and viability were significantly lower in men with SCI than neurologically intact men.
  3. In men with SCI, there was no difference in sperm parameters produced by EE and other methods of sperm collection.
  4. Rate of oocytes fertilization in SCI group by EE/ICSI was 60%.
Cohen et al. 2004; USA
Pre-Post
Level 4
N = 17
Population: 17 men with SCI, mean age
35.2 yrs.
Treatment: Antegrade semen specimens
from all participants split into 8 groups.
Group 1: no treatment. Group 2 to 8: semen
treated with different combinations of
monoclonal antibodies to IL1-β, IL6, and
TNF-α.
Outcome Measures: mean sperm motility.
  1. Sperm motility increased in all groups 2-8 but increase attained significance only in group 8 (group receiving antibodies against all 3 cytokines).
  2. Groups with pretreatment sperm motility between 11-30% showed greatest improvement after treatment.
Monga et al. 2001; USA
Prospective controlled trial
Level 2
N=12
Population: 7 participants with SCI, 5 fertile
age matched donors, age range=27-54 yrs,
5 to 31 yrs post-injury, C4-C7, 5 incomplete,
2 complete.
Treatment: Electrovibratory stimulation.
Outcome Measures: semen quality.
  1. The majority of sperm (65%) exhibited degenerative changes and significant axonemal defects.
  2. A significant percentage of sperm (65%) demonstrated disappearance of fiber doublets.
  3. Incubation of normal sperm with seminal fluid of participants with SCI induced a significant 43% decrease in motility within 15 min.
Brackett et al. 2000; USA
Prospective controlled trial
Level 2
N=26
Population: 12 men with SCI, 14 ablebodied controls; Age (men with SCI): range
29-40 yrs; Injury level: C4-L1; Mean time
since injury: 14.6 yrs; Able-bodied controls
all had vasectomy and biological children.
Treatment: 1) sperm retrieved by electrical
stimulator or vibratory stimulation for
participants with SCI, 2) sperm retrieval
before exposure to the seminal and
prostatic fluids during vasectomy surgery in
controls and vas aspiration surgery in
participants with SCI.
Outcome Measures: Sperm quality.
  1. Sperm was obtained from 9/12 patients with SCI and 12/14 nonSCI patients having a vasectomy.
  2. Aspirated sperm had greater motility (54.4%) and viability (74.1%) compared to ejaculated sperm (14.1%) motility and viability (26.1%) among patients with SCI.
  3. Controls showed no difference between aspirated and ejaculated sperm.
  4. The seminal plasma in men with SCI is likely abnormal and toxic to sperm.
Mallidis et al. 2000; Australia
Post-test
Level 4
N=9
Population: 9 men; Age: mean 28 yrs,
range 22-36 yrs.
Treatment: Electroejaculation using CGS
Electroejaculator with progressively
increasing sine wave current at 20 Hz over
4 consecutive days.
Outcome Measures: Semen quality.
  1. Mean sperm motility increased 23% on days 2 and 3; however, sperm concentration and volume decreased.
  2. In 3 of 7 patients sperm motility still remained low.
  3. Major gains in sperm motility and viability were achieved by day 2 with some improvements in day 3 for three patients.
Chen et al. 1999;
USA
Post-test
Level 4
N=14
Population: 14 men; Age: range 25-41 yrs,
Injury level: 8 cervical, 6 thoracic;
Impairment grade: Frankel A (n=8), B (n=4),
and C (n=2); Hip flexion reflex in 13 (93%)
and spasticity in 12 (86%).
Treatment: Antegrade sample obtained
using Ling vibrator. Bladder catheterized for
collection of any retrograde ejaculate.
Vibratory stimulation at clinic every 2-4 wks.
Outcome Measures: Sperm quality.
  1. Antegrade specimens collected in 51 trials (84%) and retrograde specimens obtained in all 61 trials (100%).
  2. Non-statistically significant trend toward higher sperm counts in the antegrade samples (mean=74.1 million) than in retrograde (40 million).
  3. No difference in sperm motility and morphology between antegrade and retrograde specimens.
  4. Fructose and zinc were present in all antegrade and retrograde specimens.
Brackett et al. 1997a; USA
Prospective controlled trial
Level 2
N=77
Population: 77 males, 45% cervical, 51%
thoracic, 4% lumbar.
Treatment: 1) vibration (n=23), 2)
electroejaculation (n=44) or 3) underwent
both procedures (n=10).
Outcome Measures: Sperm quality.
  1. Increased motile sperm with vibratory stimulation compared to electroejaculation.
  2. No difference in total sperm count.
Brackett et al. 1997b; USA
Prospective controlled trial
Level 2
N=19
Population: 10 men with SCI, 9 agematched men without SCI; Age: mean 33.1
yrs; Injury level: C4-C5 (n=5), T5-T6 (n=4),
T12 (n=1); Time since injury 11.4 yrs.
Treatment: Electroejaculator (Seager
model 14, 1-10 Volts) or laboratory
stimulation. Specimens stored at room
temperature (23°C) or body temperature
(37°C).
Outcome Measures: Semen quality, fertility
rates.
  1. Heat did not affect rate of degradation in motility in control specimens, but body temperature reduced sperm motility in SCI specimens compared to room temperature.
Ohl et al. 1997;
USA
Prospective controlled trial
Level 2
N=11
Population: All males.
Treatment: n=5 FertiCare Clinic Vibrator
(2.5 mm, 100Hz, for 3 min) or
electroejaculation (Seager model 11).
Outcome Measures: Sperm quality.
  1. No difference in antegrade sperm count, but penile vibratory stimulation specimens had greater motility, viability and motile sperm count compared to EE.
  2. No difference in sperm functional assessment (mucus or sperm penetration assay).
  3. Electroejaculation was more painful and less preferred than penile vibratory stimulation.
Brackett et al. 1996; USA
Prospective controlled trial
Level 2
N=26
Population: 12 men with SCI; Age: range
18-42 yrs; Injury level: thoracic; Time since
injury: range 3-28 yrs; Age matched controls
(n=14).
Treatment: Vibratory stimulation (SCI) or
masturbation (controls). Effect of SCI
seminal plasma was tested on control
sperm and vice versa.
Outcomes Measures: Seminal parameters.
  1. At 5 minutes, seminal plasma from men with SCI reduced motility of sperm from control.
  2. Seminal plasma from controls improved motility of sperm from men with SCI.
  3. At 60 minutes the values were not different from each other.
Matthews et al. 1996; USA
Case-control
Level 3
N=40
Population: 18 men with SCI and 22 men
without SCI; Injury level: 2 cervical, 15
thoracic, 1 lumbar, 33 of 40 men were in a
relationship with a female.
Treatment: Retrospective review of
electrical stimulator with rectal stimulation
followed by intrauterine insemination (126
cycles in n=33) or in vitro fertilization (n=7
total 14 cycles).
Outcome Measures: Fertility rates, seminal
parameters, ejaculatory rates, cycle
function, pregnancy rates.
  1. Motile sperm were obtained in 95% of men. Semen quality improved with subsequent rectal probe ejaculation in 23/35 men.
  2. Antegrade ejaculations produced greater percentage sperm motility in 59% of procedures in which both types of ejaculation were obtained in a patient.
  3. However, total motile sperm in retrograde samples exceeded antegrade in 57% of the cases.
  4. Pregnancy rate: 15/33 couples achieved pregnancy (45%), of which, 10/15 were achieved through intrauterine insemination.
  5. Pregnancies leading to live birth were recorded in 5/7 couples undergoing IVF.
Rutkowski et al. 1995; Australia
Case series
Level 4
N=70
Population: 70 men with SCI, Age: mean
30 yrs, range 19-59 yrs; Injury level: C1-C8
(n=36), T1-T9 (n=19), T1-T9 (n=15), T10-L2
(n=15); Mean time since injury: 6 yrs.
Treatment: Vibroejaculation at 10-50Hz, 3
cycles for 45seconds (n=36) or
electroejaculation (n=34).
Outcome Measures: Seminal parameters,
type of catheterization, method of
ejaculation.
  1. Neurological level and method of bladder management were found to be significant variables that influenced 70% of the patients’ sperm sample quality.
  2. As neurological level became more caudal, motile sperm decreased. Use of a catheter greatly increased the number of motile sperm.
  3. Intermittent self-catheterization was superior to suprapubic catheter or no catheter (reflex voiding).
Padron et al. 1994; USA
Pre-post
Level 4
N SCI=9
N controls=10
Population: 9 men with SCI and 10 ablebodied men; Age: (SCI) mean 30.2 yrs,
SEM=1.2, (controls) mean 24.3 yrs,
SEM=3.6; Injury level: cervical 33%,
thoracic 55%, lumbar 11%; Time since
injury >1yr.
Treatment: Cryopreservation of sperm by
liquid nitrogen vapor only (V) vs vapor for 12
minutes followed by submersion into liquid
nitrogen (V+N2) vs direct submersion into
liquid nitrogen (N2).
Outcome measures: Mean percent motility
in fresh sperm samples, post-thaw percent
and grade of motility.
  1. Mean percent motility of fresh sperm samples for participants with SCI (21.0%) was lower than for control participants (55.7%).
  2. After thawing, the mean percent drop in motility for men with SCI was 64.7% (V), 74.5% (V+N2), and 81.6% (N2) respectively, with no difference between control and men with SCI by method of freezing.
  3. Vapor only as a freezing method was superior to V+N2 and N2 for retention of sperm motility in both control and men with SCI.
Wang et al. 1992; Taiwan
Post-test
Level 4
N=25
Population: 32 men; Age: range 18-40 yrs;
Injury level: C4-L1, 23 tetraplegia, 9
paraplegia, 5 incomplete, 27 complete
Treatment: Vibrator stimulation (29/32
participants with hip flexion reflex) or
electrostimulation (3 participants), 4-6
months of ‘at-home’ treatment, 1x/week
stimulation.
Outcome Measures: Semen quality.
  1. Initial stimulation yielded semen in 29 men (91%; 22 had antegrade and 7 retrograde ejaculation).
  2. 16 with antegrade ejaculation started 4-6 months of home stimulation which resulted in a rise of semen volume and fructose and acid phosphatase levels in seminal plasma (improved function of the seminal vesicles and prostate).
  3. % motile sperm was low (before and after treatment period).
  4. 11 men (69%) showed normal or nearly normal penetration tests after the period of regular stimulation.
Chapelle et al. 1988; France
Prospective controlled trial
Level 2
N=148
Population: 135 men with SCI and 13 age
matched controls; Age (men with SCI):
range 18-47 yrs; Impairment grade:
complete.
Treatment: 0.2mg physostigmine.
Outcome Measures: Ejaculation rates and
procreation, level of injured metamers,
testicular volume.
  1. 75/135 patients ejaculated after pharmacologic intervention.
  2. Only 3/75 who could ejaculate had lesions T12-L2 lesions and testicle volume was significantly lower in patients with injured T12 segments.
Halstead et al. 1987; USA
Post-test
Level 4
N=12
Population: 12 men with SCI; Age: range
23-38 yrs; Injury level: C5-C6 (n=4), T3-T12
(n=7), L1 (n=1), paraplegia (n=8),
tetraplegia (n=4); Impairment grade: AIS A
(n=7), B (n=1), C (n=3), D (n=1); Time since
injury: range 0.5-18 yrs.
Treatment: Rectal probe electroejaculation
on 38 occasions.
Outcome Measures: Ejaculation response
and sperm quality.
  1. Anterograde ejaculation occurred in 9 patients with improvement in % motility and total live sperm count on repeated stimulations in 5 patients.
  2. Significant retrograde ejaculation occurred in 1 patient.
  3. Sperm acceptable for artificial insemination from 4 patients.
Sarkarati et al. 1987; USA
Post-test
Level 4
N=34
Population: 34 men with SCI; Age: range
16-36 yrs; Injury level: 14 cervical (3
complete, 11 incomplete), 13 thoracic T1-T9
(all complete), 7 T10-L3 (3 complete, 4
incomplete).
Treatment: Vibratory stimulation and/or
electrostimulation.
Outcome Measures: Ejaculation response,
semen quality.
  1. Semen obtained during first 6 months after injury was not of a quality consistent with successful fertilization, owing to poor motility.
  2. Semen quality and motility were better in patients who had been injured for more than 6 months.
  3. Repeated electro-ejaculation did not improve the quality of semen
da Silva et al. 2016; Brazil
Case Control
Level 3
N=23
Population: 23 individuals; 12 SCI patients
(mean age=38±10 years) and 11 controls;
level of injury ranged from C4 –T6.
Treatment: Antegrade semen specimens
were collected using penile vibratory
stimulation (PVS). Controls collected semen
by masturbation in specific sterile containers
after at least 3 days, but not longer than 7
days, of ejaculatory abstinence.
Outcome Measures: Sperm concentration
(millions of sperm/ml ejaculate), total sperm
count, sperm motility (% with forward
progression), seminal white blood cell
(WBC) concentration (millions of WBC/ml
ejaculate).
  1. Alpha-2-macroglobulin (A2M) is three times more abundant in the seminal plasma (SP) of SCI patients but no direct correlation between motility and A2M levels were observed.
  2. Approximately 41% of all characterized protease inhibitors elevated in SCI are members of the largest family – the serpin family – 12 serpins were quantified and it was observed that SERPINB9 and SERPINB13 were exclusively identified in the SP of SCI patients.
  3. SERPINA5, the main serpin in human SP (seminal concentrations ranging between 150–200g/ml)
  4. (35–37) is three times more abundant in SCI.
  5. Results indicate no relationship between sperm motility and the concentration of leukocytes in the semen of men with SCI.
  6. Antibiotics used to treat UTIs resulted in little or no change to the semen parameters of SCI patients suggesting that noninfectious causes of an inflammatory response in the semen may be of more importance than previously thought.
Krebs et al. 2015;
Switzerland
Cross-Sectional
Level 5
N=16
Population: 16 men with SCI and suffering
from anejaculation. 28 semen samples
underwent long term cryopreservation of
more than 3 years and total sperm motility
of >5% or viability of >10%.
Treatment: None. Semen quality analysis
both prior to and after a median of 11 years
of cryopreservation.
Outcome Measures: Semen quality,
motility, and viability.
  1. Cryopreservation resulted in a decrease in total sperm motility (median=2.5%, 95% CI 0-4%) and viability (median=7%, 95% CI 6- 13%). Long-term cryopreservation of semen from SCI men results in essentially immotile sperm with minimal viability.
  2. Complete SCI had a negative effect on sperm viability (ρ<0.0001) and tetraplegia had a negative effect on pre-cryopreservation sperm viability and post-cryopreservation motility (ρ<0.035).
  3. There were no differences between the semen parameters of samples collected early (up to 3 weeks) after SCI, those collected later, or those collected using assisted ejaculation techniques.
Ibrahim et al. 2014; USA
Prospective Controlled Trial
Level 2
N=32
Population: Semen samples from 32 men
with SCI (mean age=38 years; level of injury
C3 to L1; mean time post-injury=14 years)
were collected. All participants were past the
period of spinal shock (≥ 12 months) and
were in general good health with no active
urinary tract infections.
Treatment: Semen was obtained using the
standard methods of penile vibratory
stimulation (PVS) or electroejaculation (EEJ),
where each subject served as their own
control. Each sample was divided and
treated with a vehicle control, normal goat
IgG-control, or with a polyclonal antibody
against ASC.
Outcome Measures: Sperm concentration,
total motile sperm count (TMSC), and four
grades of sperm motility using the World
Health Organization (WHO) method.
  1. After treatment with anti-ASC polyclonal antibody, mean sperm motility signiticantly increased from 11.5% (95% CI, 6.3-16.7) to 18.3% (95% CI, 11.8-24.8).
  2. 30 patients showed improvement in sperm motility, one patient showed no change in sperm motility, and one had a small decrease in sperm motility.
  3. Samples treated with the IgG control did not show significant changes in sperm motility.
  4. Improvements were most pronounced in the subgroup whose starting sperm motility ranged from 6-40% and whose mean motility improved from 13.3% (95% CI, 9.3- 17.3) to 23.9% (95% CI, 14.7-23.0).
Ibrahim et al. 2015; USA
Prospective Controlled Trial
Level 2
N=45
Population: 30 men with spinal cord injury
and 15 age-matched control participants.
Treatment: None.
Outcome Measures: the present study
measured serum concentrations of inhibin B
and anti-Mullerian hormone (AMH).
  1. Serum concentrations of inhibin B and testosterone were significantly lower in the spinal cord injury group compared to the control group. (22.6±3.2% vs. 63.6±2.8%)
  2. A statistically significant negative relationship was observed between serum concentrations of inhibin B and follicle stimulating hormone in both the spinal cord injury group and the control group, and between inhibin B and luteinizing hormone in the spinal cord injury group only.
  3. A significant positive relationship was also observed between inhibin B and sperm concentration in the spinal cord injury group.
  4. Although serum concentrations of inhibin B were significantly lower in the spinal cord injury group than in controls, inhibin B and anti-Mullerian hormone serum concentrations did not provide an additional diagnostic tool for male infertility in this population.
Ibrahim et al. 2015; USA
Pre-Post
Level 4
N=18
Population: 18 men with SCI who ejaculated
regularly by penile vibratory stimulation
(PVS) or ejaculation.
Treatment: Probenecid was administered in
phases. Phase 1 had participants receive
250 mg orally twice a day for 1 week. Phase
2 had participants who completed phase 1
with no complications were given 500 mg
orally twice a day for 3 weeks. Semen was
analyzed at three time points: Pre-treatment
(Pre-Rx), 1-2 days before Phase 1; Posttreatment (Post-Rx), 1-2 days after
completion of Phase 2; Follow-up (F/U), 4
weeks after completion of Phase 2.
Outcome Measures: sperm motility
  1. Probenecid treatment resulted in improved sperm motility in 17 of 18 men, where sperm motility increased from 18% to 25%
  2. Linear sperm motility increased rapidly significantly after 4 weeks of treatment (5% vs 16%) and continued after the end of treatment (5% vs. 15%).
  3. The improvement in motility continued 4 weeks after end of probenecid treatment but did not reach statistical significance (18% vs. 22%).
Ibrahim et al. 2017; USA
Pre-post
Level 4
N=20
Population: 20 men with SCI who ejaculated
regularly by penile vibratory stimulation
(PVS) or ejaculation.
Treatment: Probenecid was administered for
4 weeks (250 mg twice a day for 1 week,
followed by 500 mg twice a day for 3 weeks).
Semen quality was assessed at three time
points: pre-treatment, post-treatment
(immediately after the 4-week treatment),
and follow-up (4 weeks after the last pill was
ingested).
Outcome Measures: Sperm motility
  1. Sperm motility improved in each subject after 4 weeks of oral probenecid. The mean percent of sperm with progressive motility increased from 19% to 26% (P < 0.05) and the mean percent of sperm with rapid linear motility went from 5% to 17%, (P<0.001). (the improvement continued into the four week follow up period).
  2. Similar improvements were seen in the total motile sperm count (15 million, 28 million, and 27 million at pre-treatment, post-treatment, and follow-up, respectively), but sperm concentration was not significantly different at pre-treatment, post-treatment, and follow-up, (52 million, 53 million and 53 million).

Discussion

Results from studies vary, however, in general they show similar reductions in sperm parameters in antegrade and retrograde samples, except for decreased motility in non-alkalinized retrograde samples and one study which showed antegrade samples were better in motility and viability than retrograde samples (Ohl et al. 1997). There is also some evidence to suggest that vibratory stimulus seems to produce more viable samples than electroejaculation in terms of motility (Ohl et al. 1997Le Chapelain et al. 1998). Semen quality appeared to improve with repeated ejaculations in some series (Matthews et al. 1996Giulini et al. 2004Hamid et al. 2006), and not in others (Sarkarati et al. 1987Das et al. 2006). It has been suggested that parameters improve with consecutive days of electroejaculation (Mallidis et al. 2000). Once-weekly vibrator stimulation resulted in an increase of semen volume and of fructose and acid phosphatase levels in the seminal plasma (suggesting improved function of the seminal vesicles and prostate) (Siösteen et al. 1990), whereas other investigators reported that too frequent ejaculation caused semen quality to deteriorate (Wang et al. 1992). The possibility of improvement in semen parameters appears to be related to consistency of ejaculations over a regulated time period. One study found improved sperm motility after 3 months of weekly PVS performed by patients at home (Beretta et al. 1989). The majority of studies, however, found no statistically significant improvement in sperm motility after regular ejaculation by PVS or EEJ (Siosteen et al. 1990; Sonksen et al. 1999; Das et al. 2006; Hamid et al. 2006).

Poor sperm motility may be due in part to the seminal plasma secondary to disturbed nervous systems and anejaculation (Brackett et al. 20002007a), and there may also be alterations in testicular function or morphological anomalies in the sperm (Chapelle et al. 1988Elliott et al. 2000Monga et al. 2001). Sperm aspirated from the vas prior to exposure to seminal fluid in men with SCI had significantly better motility (54% vs 14%) and greater viability (74% vs 26%) in comparison to sperm retrieved from same group by VS or EE (Brackett et al. 2000). These researchers had previously demonstrated an inhibitory effect of SCI seminal plasma on normal sperm motility, as well as improvement of SCI sperm motility when prepared with normal seminal plasma (Brackett et al. 1996). In addition, the same group (Brackett et al. 2007aCohen et al. 2004) have recently shown that cytokines in the semen of men with SCI may play a key role in inhibiting sperm motility, with inactivation of the relevant receptors leading to improved sperm motility. Both studies (Cohen et al. 2004Brackett et al. 2007a) examined the effect of treating semen with different combinations of antibodies on motility and both found that sperm motility significantly increased with the combination of antibodies that acted against all 3 relevant cytokines. In a prospective controlled trial, Ibrahim et al. (2008) found no damage to sperm treated with cytokine inhibitors and suggested that further studies investigating cytokine inhibitors as a therapy for low sperm mobility are warranted. Probenecid has shown promising results to improve sperm motility (Ibrahim et al. 2017).

Once ejaculated, sperm motility in men with SCI declines rapidly, and storing at body temperature (in a 37°C incubator) may exacerbate this (Brackett et al. 1997b). Bladder management also seems to affect sperm quality, with low pressure emptying by clean intermittent catheterization improving semen quality over indwelling catheterization, reflex voiding or straining (Ohl et al. 1989Rutkowski et al. 1995). Ibrahim et al. (2014, 2015) found that slight improvement in sperm motility were achieved after treatment with anti-ASC polyclonal antibody (mean sperm motility increased from 11.5% to 18.3%) and after probenecid treatment (sperm motility increased from 18% to 25%).

Padron et al. (1994) showed a similar reduction in sperm motility (65%) in men with SCI to normal with thawing after cryopreservation, preferring the vapor only method. Krebs et al. (2015) found that complete tetraplegia has a negative effect on pre-cryopreservation sperm viability and post-cryopreservation motility, and that there were no differences between the semen parameters of samples collected early (up to 3 weeks) after SCI, those collected later, or those collected using assisted ejaculation techniques. Given this and reported reliability of retrieval methods, there seems no point in cryopreserving semen for later insemination unless collected acutely within the first 1-2 week window while sperm quality is still normal (Mallidis et al. 1994).

Botox treatment for detreusor dyssynergia has beneficial and detrimental effects on ejaculation function (Caremel et al. 2011). The detrimental effects involve retrograde ejaculation and reduced semen volume, which result from reduce contraction of the smooth muscle sexual accessory due to the toxin. A beneficial effect is improved semen quality due to the reduced contamination of the semen by urinary infection.

Conclusion

There is level 2 evidence (Brackett et al. 1997aOhl et al. 1997) that using a penile vibratory stimulus produces samples with better sperm motility than from electrostimulation.

There is level 2 evidence (from 1 weak RCT: Brackett et al. 2002) that sperm obtained by antegrade samples has better motility than retrograde samples and that interrupted current produces higher sperm motility than continuous current.

There is level 4 evidence (Rutkowski et al. 1995) that bladder management by clean intermittent catheterization (with low pressure filling and emptying) may improve semen quality over indwelling catheterization, reflex voiding or straining.

There is level 4 evidence (Caremel et al. 2011) that botox injections to the overactive bladder may reduce semen volume, but increase semen quality.

There is level 4 evidence (Hibi et al. 2008) that retrograde vasal sperm aspiration can retrieve sperm of sufficient motility to afford pregnancy.

There is level 2 evidence that SCI sperm quality can be improved by placing sperm from SCI in able-bodied seminal plasma (Brackett et al. 1996), and that aspirated sperm from the vas deferens has better motility than that ejaculated (Brackett et al. 2000), demonstrating the etiology of poor semen quality may lie within the seminal plasma in men with SCI. These techniques have not been studied clinically with respect to pregnancy rates.

There is level 4 evidence (Cohen et al. 2004Brackett et al. 2007a) that interference with receptors to all 3 cytokines in semen can improve sperm motility.

There is level 2 evidence (Ibrahim et al. 2009) that monoclonal antibodies and receptor interference agents do not change the degree of DNA fragmentation in sperm from subjects with SCI.

There is level 3 evidence (Kanto et al. 2008) that testicular sperm extraction followed by intracytoplasmic injection is an effective way to induce pregnancy, with fresh sperm giving better results than frozen-thawed sperm.

There is Level 2 evidence (Ibrahim et al. 2014, 2015) that found slight improvements in sperm motility were achieved after treatment with anti-ASC polyclonal antibody (mean sperm motility increased from 11.5% to 18.3%) and after Probenecid treatment (sperm motility increased from 18% to 25%).

There is Level 5 evidence (Krebs et al. 2015) that found complete tetraplegia has a negative effect on pre-cryopreservation sperm viability and post-cryopreservation motility, and that there were no differences between the semen parameters of samples collected early (up to 3 weeks) after SCI, those collected later, or those collected using assisted ejaculation techniques.

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