Sperm Quality and Fertility in Men with SCI

Semen quality has been observed to decline after SCI (Deforge et al. 2005). In the first 2-3 days after injury semen obtained by EEJ was limited but had returned to normal quality by 6-10 days post-injury (Mallidis et al. 1994). After approximately 2 weeks post-injury 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. 1997b; Ibrahim 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 non-SCI 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.

Discussion

Spinal cord injury (SCI) significantly impairs semen quality, resulting in lower sperm motility (i.e., sperm’s ability to swim/move) and viability (lifespan); often starting within two weeks of injury, sperm may move slowly or not at all, defined as ‘asthenozoospermia’ (Patki et al. 2008; Anderson et al 2018; Momen et al. 2007). Though actual sperm count often remains unaffected, the percentage of moving sperm is severely reduced (approximately 10-20%) compared to men without SCI (approximately 50%; motility normally required for pregnancy to occur is approximately +40%; Ibrahim et al. 2009; Salsabili et al. 2006; Vargas-Baquero et al. 2020). Generally, neither level of injury nor time since injury affects semen quality, though people with incomplete injuries tend to have higher sperm motility than people with complete injuries (Chalas et al. 2022; Vargas-Baquero et al. 2020).

Sperm motility seems to be primarily affected by changes to the seminal plasma; Brackett et al. (1996) demonstrated that SCI sperm motility was improved when prepared with seminal plasma from men without SCI. Researchers have postulated these findings are due to the high number of leukocytes (activated T-cells) which can secrete cytotoxic substances and cytokines (IL1-beta, TNFalpha, IL-6) (Basu et al. 2004). Two studies (Brackett et al. 2007a; Cohen et al. 2004) 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. Additionally, poor sperm motility may be attributed to seminal plasma secondary to disturbed nervous systems and anejaculation (Brackett et al. 2000; 2007a), and alterations in testicular function or morphological anomalies in the sperm (Chapelle et al. 1988; Elliott et al. 2000; Monga et al. 2001).

Sperm DNA fragmentation (SDF), DNA damage, and breakage are higher among people with SCI. Gosálvez et al. (2022)found that double strand DNA breakage (DSB) was higher in men with SCI (57.5%) than non-SCI controls (4.6%) (p=0.000). Other non-favorable ejaculate parameters of high levels of SDF, pro-oxidant capacity and leukocyte concentration, were also observed at a much higher frequency in people with SCI patients (88.3%, 177.0, 2.6) versus non-SCI controls (15.5%, 116.0, 0.4) (all p<0.01) (Vargas-Baquero et al. 2020). However, Ibrahim et al. (2009) found that monoclonal antibodies and receptor interference agents do not change the degree of DNA fragmentation in sperm from participants with SCI.

Types of bladder management can also affect sperm quality. There are a few studies documenting that low pressure emptying by clean intermittent catheterization improves semen quality when compared to indwelling catheterization, reflex voiding, or straining (Patki et al. 2008; Ohl et al. 1989; Rutkowski et al. 1995). Botox treatment for detrusor 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. Probenecid, a medication used to reduce uric acid levels in the body, has also shown promising results to improve sperm motility (Ibrahim et al. 2017). Ibrahim et al. (2014, 2015) found that 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%).

Retrieval Methods and Effects on Sperm Motility

There are multiple studies documenting that the type of sperm retrieval method is related to sperm quality and motility. There is also some evidence to suggest that vibratory stimuli seems to produce better semen quality samples than electroejaculation in terms of motility (Ohl et al. 1997; Le Chapelain et al. 1998). One larger case-control study found that 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%; Kathiresan et al. 2012). One larger case-control study found that sperm retrieved via PVS had significant higher sperm concentration and higher sperm motility, even though mean sperm motility was significantly lower in men with SCI (5% vs. 35%; p<0.01; Cito et al. (2020). Sperm aspirated from the vas deferens (i.e., sperm duct) 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).

Semen quality appeared to improve with repeated ejaculations in some (Matthews et al. 1996; Giulini et al. 2004; Hamid et al. 2006), and not in others (Sarkarati et al. 1987; Das et al. 2006), though, it has been suggested that semen parameters improve with consecutive days of EEJ (Mallidis et al. 2000). In contrast, other studies 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 period. One study found improved sperm motility after 3 months of weekly PVS performed by patients at home (Beretta et al. 1989), however, most studies found no statistically significant improvement in sperm motility after regular ejaculation by PVS or EEJ (Siosteen et al. 1990; Sønksen et al. 1999; Das et al. 2006; Hamid et al. 2006).

Once ejaculated, sperm motility in men with SCI declines rapidly, and storing at body temperature (in a 37°C incubator) may exacerbate this process (Brackett et al. 1997b). However, results are mixed as to whether cryopreservation has a positive or negative effect on sperm motility. Padron et al. (1994) showed a reduction in sperm motility (65%) in men with SCI to normal with thawing after cryopreservation, preferring the vapor only method. However, Reignier et al. (2018) found that there were no statistically significant declines in sperm parameters over time (0 to >15 years) with delayed cryopreservation. 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).

Conclusion

There is level 2 evidence (Chalas et al. 2022) that semen parameters are not correlated to time post-SCI or AIS score.

There is level 2 evidence (Brackett et al. 1997a; Ohl 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 2 evidence that aspirated sperm from the vas deferens has significant better motility and viability than ejaculated sperm in men with SCI (Brackett et al. 2000).

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 participants with SCI.

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 2 evidence (Reignier et al. 2018) and 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.

There are 3 studies with level 3 evidence (Cito et al. 2020; Gosálvez et al. 2022; Vargas-Baquero et al. 2020) that there is greater DNA damage and lower favorable semen characteristics in men with SCI when compared to non-SCI controls.

There is level 3 evidence (Cito et al. 2020) that PVS resulted in greater sperm concentration and higher sperm motility, though sperm motility was significantly lower in men with SCI (5% vs. 35%).

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