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. 1997; Schatte 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. 1989; Hultling et al. 1994; Dahlberg et al. 1995; Chung et al. 1997; Hultling et al. 1997; Heruti et al. 2001; Sheih et al. 2003; Giulini 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 1993; Hultling et al. 1994; Brackett et al. 1995; Dahlberg et al. 1995; Pryor et al. 1995; Nehra et al. 1996; Brinsden et al. 1997; Chung et al. 1997; Hultling et al. 1997; Sønksen et al. 1997; Taylor et al. 1999; Schatte et al. 2000; Heruti et al. 2001; Ohl et al. 2001; Shieh et al. 2003; Hibi 2008, McGuire et al. 2011; Kathiresan et al. 2011; Leduc 2012) that men with SCI have a good chance of becoming biological fathers with access to specialized care utilizing reproductive assisted technology.
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