Male Fertility and Resulting Pregnancy

Unfortunately, after SCI semen quality declines necessitating assistive reproductive technologies to compensate for the alterations (Elliott 2003). Pregnancy rates are lower than the general population but have been much improved since the advent of in vitro fertilization (IVF) and intracytoplasmic injection (ICSI).

Author Year; Country
Score
Research Design
Total Sample Size
Methods Outcome
Bechoua et al. 2013;
France
Case Series
Level 5
N=19
Population: 19 men with SCI (6
quadriplegics, 13 paraplegics, mean
age=25.2±5.6 years) who underwent sperm
cryopreservation from 1995 to 2011.
Treatment: Two groups were outlined based
on sperm retrieval method: antegrade
ejaculation group (n=10) and surgical sperm
retrieval (SSR) group (n=9).
Outcome Measures: Samples was analyzed
according to the guidelines of the World
Health Organization. Pregnancy outcomes in
the 8 couples who chose to undergo Intra
Cytoplasmic Sperm Injection (ICSI) were
assessed.
1. Fertilization rates were 57 and 55% in
the antegrade ejaculation and SSR
groups respectively.
2. The embryo’s cleavage rates were 90
and 93% in the antegrade ejaculation
and SSR groups respectively.
3. Within the 8 couples that received ICSI,
5 couples achieved pregnancy.
4. Pregnancy rates per couple were 50%
and 75% in the antegrade ejaculation
and SSR groups respectively.
Leduc 2012;
Canada
Case series
Level 5
N=31 (couples)
Population: 31 couples with male partners
with SCI and fertility disorder as result from
SCI; mean(SD) age: SCI men 29.7(4.8) yrs,
range 23-48, female partners 29.3(4.8) yrs,
range 25-41; mean(SD) DOI: 7.6(6) yrs,
range 1-29; 10 cervical, 20 thoracic, 1
lumbar.
Treatment: Semen samples obtained by
manual stimulation (n=10, including 6 treated
by sc physostigmine), penile vibratory
stimulation (PVS) (n=4), electroejaculation
(EEJ) (n=5), and testicular sperm extraction
(n=12). Assisted reproductive technique
(ART) selected according to sperm
parameters (IVI, IUI, IVF).
Outcome measures: Sperm parameters
(count, motility), number of pregnancies,
births, and paternities, pregnancy rate/cycle.
1. Among the 10 couples treated with
intravaginal insemination, 9 pregnancies
occurred among 7 couples.
2. No pregnancies resulted from
intrauterine insemination (2 cases).
3. Among the 18 couples treated with IVF,
12 pregnancies were reported among 10
couples.
4. The pregnancy rate/cycle was 43%.
5. Following these assisted reproductive
techniques (ARTs) the pregnancy rate
reached 55%.
6. Overall 20 men with SCI (64% of the
group) became fathers to at least one
child.
Kathiresan et al. 2011;
USA
Retrospective analysis
Level 5
N=82
Population: 82 male patients with SCI and
their female partners; mean(SD) age
36.1(0.7) yrs, mean time after injury 0.8 yrs
(range 0.7-34.0 yrs).
Treatment: 45 couples performed
intravaginal insemination (IVI); intrauterine
insemination (IUI) was performed in 57
couples.
Outcome Measures: Method of sperm
retrieval, sperm quality, occurrence of
pregnancy, live birth, pregnancy rate (PR),
pregnancy losses, multiple gestations, total
motile sperm count (TMSC).
1. Of the 45 couples with IVI, 17 couples
had 20 pregnancies with 3 couples
achieving pregnancy twice (16 through
penile vibratory stimulation; 1 through
electroejaculation; and 3 through
masturbation). Eighteen live births
occurred.
2. Average time from male partner’s first
semen analysis to time of pregnancy
was 6.9(1.25) mos. The mean antegrade
TMSC in men achieving vs. not
achieving pregnancy was not statistically
significant: 90.1(30.8) million (range 2.6-
425.7 million) vs. 76.5(21.0) million
(range 0.3-544.5 million).
3. 57 couples underwent IUI, where 14
couples had 19 pregnancies and 21 live
births (1 twin and 1 triplet pregnancy
occurred, both by IUI cycles stimulated
by gonadotropins). Cycle fecundity was
7.9% (19 pregnancies of 241 cycles).
Semen collected by PVS (6
pregnancies) and EEJ (13).
McGuire et al. 2011;
Ireland
Retrospective review (case
series)
Level 5
N=31
Population: 31 men (mean age 35 yrs,
range 24-49), 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: EES done with Seager model
rectal probe. Electroejaculatory stimulation
(EES) – 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. One patient developed autonomic
dysreflexia necessitating stopping EES
before obtaining any ejaculate. No other
side effects or complications were
reported.
3. 30 patients produced antegrade,
retrograde, or both types of ejaculate
Hibi et al. 2008;
Japan
Post-test
Level 4
N=8
Population: 8 participants with cervical SCI
and neurogenic anejaculation (age 26-46 yrs,
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.
Engin-Üstün et al. 2006;
Turkey
Case series
Level 4
N=44
Population: Men with SCI and partner;
median age 26.0-29.5 yrs, range 20-31; 4
cervical, 38 thoracic, 2 lumbar.
Treatment: Retrieval by electro-ejaculation
(EE), testicular sperm extraction (TESE) or
prostatic massage (PM).
Outcome Measures: Fertilization
rate,pregnancy rate, live birth rate, sperm
counts, sperm motility.
1. Fertilization, pregnancy and live birth
rates were same between 3 methods.
2. Sperm count and sperm motility were
the same between EE and PM method.
Shieh et al. 2003; Taiwan
Post-test
Level 4
N=10
Population: 10 men with SCI and partner;
Age: range 27-37 yrs; Injury level: C6-T12, 9
incomplete and 1 complete, 9 paraplegia &
1 tetraplegia; Time since injury: range 4-20
yrs.
Treatment: If semen sample from
electroejaculation (EE) was of fair quality,
then 3 cycles of intrauterine insemination
prior to intracytoplasmic sperm injection
treatment (ICSI). If semen samples were
poor, ICSI was suggested. If no sperm from
EE, surgical retrieval of sperm was
performed.
Outcome Measures: Pregnancy rates.
1. 7 clinical pregnancies achieved, 2 of
which ended with spontaneous
abortion. 1 couple accomplished
pregnancy by ICSI with cryopreserved
sperm from vasal aspiration.
2. The fertilization and pregnancy rates of
ICSI cycles using sperm from men with
SCI were comparable to men without
SCI.
3. One couple attained pregnancy by
using donor sperm.
4. The cumulative successful pregnancy
rate per couple was 80%.
Heruti et al. 2001;
Israel
Post-test
Level 4
N=84
Population: 84 men with SCI, 49 couples;
Age: range 19-45 yrs; Injury level: cervical
(34.5%), thoracic (59.5%), lumbar (5.9%);
Impairment grade: AIS A (n=63), B (n=15),
C (n=5), D (n=1); Time since injury: range 4
months-34 yrs.
Treatment: Electroejaculation followed by
intrauterine insemination for 3 trials
(10million sperm/cc). If this did not result in
fertilization, intracytoplasmic sperm injection
and IVF.
Outcome Measures: Volume, sperm count,
motility, morphology, total motile sperm
count, conception.
1. Ejaculation occurred in 98.6% of
patients, with sperm in 88% of patients
and enough viable sperm in 54.8%.
2. Antegrade semen parameters had
significantly better sperm count,
morphology and motility than retrograde
samples.
3. No significant improvements were seen
in seminal parameters after repeated
ejaculations.
4. 69.2% overall pregnancy rate/couple.
33% (5/15) after intrauterine
insemination, 70% (14/20) after IVF.
5. 26 live births (n=12 singletons, n=5
twins, n=1 triplets) and 4 abortions.
Ohl et al. 2001;
USA
Post-test
Level 4
N=121
Population: 121 couples (87 men with SCI
and partner).
Treatment: Electroejaculation followed by
intrauterine insemination (IUI) was the route
of sperm delivery. If not successful after 3-6
cycles of IUI, GIFT (gamete intrafallopian
transfer) or IVF procedures were
recommended.
Outcome Measures: Pregnancy success
and pregnancy outcomes.
1. 52/121 became pregnant, 39 by IUI
alone.
2. All patients undergoing IVF had
significantly higher cycle fecundity than
did those undergoing IUI.
3. The rates of spontaneous abortion and
multiple gestations were 23% and 12%,
respectively.
Pryor et al. 2001;
USA
Prospective controlled trial
Level 2
N=11
Population: 11 men with SCI and their
partner; Injury level: tetraplegia.
Treatment: Electrical stimulation or
vibratory stimulation followed by 1)
intrauterine insemination of partner 24 hour
after Luteinizing Hormone surge (n=5), 2) 50
mg clomiphene citrate & hCG, followed by
insemination after 32-34 hours (n=5), or 3)
same as #2, except 38-40 hour delay
(n=10).
Outcome Measures: Fertility rates, seminal
parameters.
1. No pregnancies with protocol 1 or 2.
6/10 patients became pregnant with
protocol 3, which has the longest delay
between drug administration and
insemination.
Schatte et al. 2000;
USA
Post-test
Level 4
N=17
Population: 10 men with SCI (7 non-SCI
related anejaculation); mean age 38.9 yrs.
Treatment: Electroejaculation and
intracytoplasmic sperm injection (ICSCI) and
results compared to 620 ICSI cycles for nonSCI male infertility with normal ejaculation.
Outcome Measures: Pregnancy rate.
1. ICSI resulted in a median fertilization of
60%, 15% pregnancies per cycle and
29% pregnancies per couple.
2. Pregnancy rates were lower for the
anejaculation group compared to the
severe male factor group.
Taylor et al. 1999;
Australia
Post-test
Level 4
N=19
Population: 19 men with SCI; Age: range
24-44 yrs; Injury level: C4-C9 (n=9), T4-
T12/L1 (n=10), 12 complete and 7
incomplete; Time since injury: range 1-24
yrs.
Treatment: Sperm was extracted through
vibrator application or electroejaculation
followed by assisted reproductive treatments
(intrauterine insemination, gamete
intrafallopian transfer, in vitro fertilization
and embryo transfer, intracytoplasmic sperm
injection).
Outcome Measures: Seminal parameters,
pregnancy rates (intrauterine insemination,
gamete intrafallopian transfer,
intracytoplasmic sperm injection).
1. 14/19 achieved at least 1 pregnancy.
2. Methods used: Intrauterine
insemination 12% (11/92), gamete
Intrafallopian transfer 38.9% (8/18),
intracytoplasmic sperm injection 19.2%
(5/21).
3. In patients with incomplete lesions
vibratory stimulation was more
frequently successful (4/7) 53%.
4. Complete lesions required more
advanced procedures to achieve
pregnancy, (7/12) 58% required
electroejaculation.
Brinsden et al. 1997;
UK
Post-test
Level 4
N=35
Population: 35 men with SCI and their
female partners; Age: (men) range 24-47
yrs, (female) range 21-43 yrs; Injury level:
C5-L1; Time since injury: range 1-27 yrs.
Treatment: Trans-rectal electroejaculation
with in-vitro fertilization. 71 IVF cycles were
used.
Outcome Measures: Pregnancies,
fertilization rate, motile sperm count.
1. Pregnancy rates: 18 total (14 were
fresh embryo transfers, 4 were frozen
embryo transfers).
2. Pregnancy rate per treatment cycle was
21.2% (18/35).
3. Overall clinical pregnancy rate per
stimulated IVF treatment was 25.4%
(18/71).
Chung et al. 1997;
USA
Post-test
Level 4
N=27
Population: 24 men with SCI, 3 men with
retroperitoneal dissection; Age: range 4-48
yrs; Time since injury: range 3-25 yrs.
Treatment: Electrostimulation and
nifidepine (10mg) for prophylaxis of
autonomic dysreflexia.
Outcome Measures: Ejaculation rates,
pregnancy rates, seminal parameters.
1. 7 pregnancies in 13 couples with a total
of 56 intrauterine insemination, 2
spontaneous abortions, 4 live births, 1
ongoing twin pregnancy.
Hultling et al. 1997;
Sweden
Post-test
Level 4
N=25
Population: 22 men with SCI and female
partner; Age (men): range 25-51 yrs,
(female): range 21-38 yrs; Injury level: C2-
L3; Time since injury: range 3-33 yrs.
Treatment: Vibratory or electrical
stimulation followed by IVF.
Outcome Measures: Conception.
1. Pregnancy rate: 16/25 pregnancies
occurred leading to 11 deliveries.
2. n=9 singletons, n=2 sets of twins; n=4
miscarriages during the first or second
trimester (1 case of intrauterine death in
week 31 of gestation).
3. Pregnancy occurred in all groups of
patients in the AIS scale A-D from
injuries from C2-L2.
4. Clinical pregnancy rate was 31% and
the cumulative pregnancy rates up to
four cycles were 56%.
Sonksen et al. 1997;
Denmark
Case series
Level 5
N=28
Population: 28 men with SCI and female
partner; Age (men): range 24-43 yrs,
(female): mean 29 yrs, range 19-39 yrs;
Injury level: C2-L4; Time since injury: range
1-22 yrs.
Treatment: Males with SCI: vibratory
stimulation or electroejaculation. Female
partners: assisted reproductive techniques
(vaginal self-insemination at home,
intrauterine insemination, in vitro fertilization
with or without intracytoplasmic sperm
injection).
Outcome Measures: Ejaculation rates,
seminal parameters, pregnancy rates.
1. All men were able to ejaculate, 22 by
vibratory stimulation (all with lesion
above T10), 6 by electroejaculation.
2. 4/16 achieved pregnancy and had
healthy babies. This was achieved by
home vibratory stimulation and selfinsemination within 2 years.
3. All couples that had children had
significantly higher median motile
sperm per ejaculate (105 million vs. 10
million).
4. Overall 9/28 couples (32%) achieved 10
pregnancies with a delivery of 9 healthy
babies.
Nehra et al. 1996;
USA
Case Series
Level 4
N=78
Population: 78 men with SCI (33 couples);
Age: range 23-44 yrs; Injury level: 37
cervical, 41 thoracic.
Treatment: Retrospective review of
electrical stimulation followed by cervical
self-insemination, intrauterine insemination,
in vitro fertilization, or gamete intrafallopian
transfer.
Outcome Measures: Sperm quality,
pregnancy rates.
1. Vibratory stimulation achieved
ejaculation in 20/37 cervical patients,
14/26 at or above T10 and 0/15 below
T10.
2. Pregnancy rates: 17/27 achieved
pregnancy (10 with vibratory stim, 7
with electroejaculation).
3. 5/8 achieved self-home insemination
with PVS.
4. 17/27 couples were successful at
conception (5 self-insemination, 5
intrauterine insemination and 7 assisted
reproductive techniques).
5. 20 live births in 14 couples.
Brackett et al. 1995;
USA
Case series
Level 4
N=23
Population: 23 (21 with SCI) men and
partner; Age: range 26-42 yrs; Injury level:
cervical (n=7), thoracic (n=12), lumbar
(n=2); Time since injury: range 2-28 yrs.
Treatment: Vibrostimulation or electroejaculation with ovulation induction by
clomiphene citrate or gonadotropins and
intrauterine insemination (IUI).
Outcome measures: Pregnancy and live
births.
1. Six pregnancies (7 live births) occurred
in 60 cycles of IUI (cumulative
pregnancy rate 26%).
2. Six couples who failed after a total of 33
IUI cycles, and 1 couple with no
previous IUI cycles initiated 10 cycles of
in vitro fertilization, resulting in 5
pregnancies (pregnancy rate 71%): 1
live birth, 1 ongoing pregnancy, 1
ectopic pregnancy, 2 spontaneous
abortions.
Dahlberg et al. 1995;
Finland
Post-test
Level 4
N=63
Population: Men with SCI and 35 female
partners; Age: range 21-42 yrs; Level of
injury: C1-C5 to L1-L2.
Treatment: Sperm was extracted through
vibrator application, drug application
(Nifidepine 10-30mg), and electroejaculation
or sperm aspiration from the vas deferens.
Sperm was then introduced by insemination
or IVF.
Outcome Measures: Live births.
1. Fertility rates: of 35 males seeking
pregnancy, 29 could produce viable
sperm.
2. Live births: n=24 children from 18/35
couples). Miscarriages: n=4.
Pryor et al. 1995;
USA
Post-test
Level 4
N=6
Population: 6 men with SCI; Age: range 30-
35 yrs: Injury level: C4-C7; Time since
injury: 6-18 yrs.
Treatment: Vibratory stimulation (using
4,200rpm for 5-45min, with 5 min breaks
every 5 min) followed by intrauterine
inseminations.
Outcome Measures: Pregnancy rates.
1. Pregnancies occurred in 5/6 of the
partners. 2 partners delivered healthy
boys, 1 partner miscarried at 9 wks.
2. One couple has completed second
vibratory stimulation without conception
and will try again.
Hultling et al. 1994;
Sweden
Post-test
Level 4
N=12
Population: 12 men with SCI and female
partner; Age: range 27-38 yrs; Injury level:
C4-L3; Time since injury: range 4-33 yrs.
Treatment: Vibratory stimulation and, if
necessary, physostigmine and/or
electroejaculation followed by IVF.
Outcome Measures: Seminal parameters,
pregnancy rates.
1. Pregnancy rates: 7 pregnancies in 6
couples, 3 spontaneous abortions, 2
live births, 2 ongoing pregnancies.
Buch & Zorn 1993;
USA
Post-test
Level 4
N=18
Population: 18 men with SCI; Age range
22-43 yrs; Injury level: C5-T12; Impairment
grade: AIS A (n=12), B-D (n=6); Time since
injury: range 2-22 yrs.
Treatment: Rectal probe electroejaculation
(RPE).
Outcome Measures: Sperm retrieval,
sperm quality, live births.
1. After fertility testing, 6/18 men
proceeded to use RPE in effort to
conceive. Sperm obtained in 16/18
cases.
2. Ejaculate total sperm count=306 million
(good), but motility (22%) was poor.
3. Adequate sperm retrieval after
processing yielded normal sperm
penetration assay in 4/16 (25%) cases
in which sperm was obtained.
4. Live births in 2/6 couples attempting
conception.
Lucas et al. 1991;
UK
Post-test
Level 4
N=14
Population: 12 men with SCI, 2 men
without SCI (diabetes); mean age 34.6 yrs,
range 25-46; Injury level: C5-T10.
Treatment: Electrical stimulator (up to 35V,
900mA, 50Hz).
Outcome Measures: Fertility rates, seminal
parameters, pregnancy rates.
1. Seminal parameters: volume obtained:
a few drops to 5.5ml, % of progressive
motility: 0-60%, and sperm
concentration: 0-260 million/ml.
2. 1 pregnancy recorded (father: T10
paraplegia, 8 yrs post-injury,
54million/ml, 30% motility) resulted in a
singleton with no genetic abnormalities.

Discussion

Pregnancy rates of partners of men with SCI, although somewhat dependent on sperm motility, are improved consistently with higher levels of reproductive assisted technology. Fertility rates improve progressively with the use of assisted reproductive technology (ART) and more advanced techniques, as follows:

  • At home (intercourse or vaginal insemination)
  • Intrauterine insemination
  • In vitro fertilization (IVF)
  • IVF + intracytoplasmic sperm injection (ICSI)

Reports have varied in their description of pregnancy rates, using either pregnancy rate per couple or pregnancy rate per insemination method. In general, reported as per couple, there has been considerable improvement in rates over the last 20 years due to better technology (Brinsden et al. 1997Schatte et al. 2000). In collation of reports by many authors, there appears to be an average 30-50% pregnancy rate and a 40% live birth rate (Beretta et al. 1989Hultling et al. 1994Dahlberg et al. 1995Chung et al. 1997Hultling et al. 1997Heruti et al. 2001Sheih et al. 2003Giulini et al. 2004). Cumulative pregnancy rates could go as high as 80% (Sheih et al. 2003). The number of attempts varied greatly, with pregnancy unlikely to occur after 5 attempts of any method (recognizing that some couples advanced on the continuum of increasing ART). Cycle fecundity rate (chance of pregnancy per cycle) for intrauterine insemination is <15%, whereas for IVF/ICSI it is between 25-40%. In one study, it was felt that delayed timing of intrauterine insemination resulted in significantly improved pregnancy rates in female partners of men with tetraplegia (Pryor et al. 2001). While fresh semen samples were preferred, cryopreserved semen samples were used successfully for IVF technology. Cryopreservation of embryos to be replaced at a later date is also useful (Buch & Zorn 1993). Multiple gestations were more frequent with IVF/ICSI. Testicular aspiration has been used less commonly, since it commits the man and his partner to IVF/ICSI procedures. One case control study however, found that pregnancy rates among couples using testicular aspirated sperm from males with SCI, were comparable to the rates among couples using the same procedure from able-bodied controls with obstructive azoospermia (Kanto et al. 2008). The use of retrograde vasal sperm aspiration has also shown to be a reliable method for consistent sperm recovery such that a high pregnancy rate and cryopreservation of excess sperm for future use was possible (Hibi 2008).

Estimates of the feasibility of and effort required to pursue biological fatherhood after SCI are emerging. This cumulative evidence and substantial clinical experience suggest starting with an appropriate clinical assessment of neurological impairment, physical health, bladder management and risk factors for the man (i.e. autonomic dysreflexia), as well as fertility history and blood work for the female partner. Assessment of sperm retrieval methods follows with evaluation of the resultant semen samples retrieved. Female intervention is determined by her fertility factors and by the quality of semen available. The least invasive and least expensive insemination options are pursued after weighing invasiveness and risk of sperm retrieval and semen quality. Men with SCI stand a good chance (>50%) of becoming biological fathers when they have access to specialized clinics and care. Recently, Bechoua et al. (2013) found fertilization rates of 55-57%, embryo cleavage rates of 90-93%, and pregnancy rates of 50-75% when using antegrade ejaculation or surgical sperm retrieval (SSR).

Conclusion

There is level 3 (Kanto et al. 2008) and level 4 evidence (Buch and Zorn 1993Hultling et al. 1994Brackett et al. 1995Dahlberg et al. 1995Pryor et al. 1995Nehra et al. 1996Brinsden et al. 1997Chung et al. 1997Hultling et al. 1997Sønksen et al. 1997Taylor et al. 1999Schatte et al. 2000Heruti et al. 2001Ohl et al. 2001Shieh et al. 2003Hibi 2008McGuire et al. 2011Kathiresan et al. 2011Leduc 2012) that men with SCI have a good chance of becoming biological fathers with access to specialized care utilizing reproductive assisted technology.