Context:

Spinal cord injury (SCI) is most often the result of a trauma to the spinal cord, but can also be associated with congenital or degenerative disease. In the United States alone, there are currently approximately a quarter million people with SCI. Sexual dysfunction in people with SCI may have both physiological and psychological (e.g., body image, self esteem) elements that can be distressing regardless of the persons' gender, age or culture. Although some men with SCI are unable to have erections, many still maintain the ability to have some erectile function, albeit of insufficient quality and duration for intercourse. Many techniques currently exist to remediate erectile dysfunction in men with SCI. These include devices such as the vacuum erection device as well as the injection of vasoactive drugs into the penis. A recent innovation to improve erectile function in men with SCI has been the approval of the drugs such as sildenafil (Viagra®). Remediation of sexual dysfunction in women with SCI has until recently been largely ignored in the literature.

Objectives:

This report focuses on two questions: (1) issues related to fertility, pregnancy rates, and live births in persons with SCI, and (2) issues related to male impotence post-SCI.

Reproductive health: What is the current fertility rate for men and women after SCI? Are fertility rates changed by freezing a new patient's sperm? Are there better fertility rates using electroejaculation or vibration? Does order of method influence outcome? To improve fertility rates, when should invasive techniques such as testicular biopsy or aspiration or ICSI be pursued? Are there pregnancy complications and prospective obstetric management issues for SCI females?

Male sexuality: How has the availability of Viagra® and other remediation affected sexual function, frequency of activity, and adjustment after SCI? Is Viagra® really more benign than intracavernous injections? How does the morbidity of prostaglandin injections compare to the older (less expensive) papaverine? What is the morbidity of vacuum tumescence devices? What indications, if any, remain for implantable penile prosthetic devices?

Data Sources:

The databases searched were Medline (1966-June Week 1 2003), Premedline (June 13 2003) and CINAHL (1975-June Week 1 2003), the Cochrane Central Register of Controlled Trials, (1st Quarter, 2003), SocioFile (1974-June 2003) and PsycInfo (1887-June Week 1 2003). The annual proceedings (1997-2002, inclusive) of several groups were searched: the American Urological Association, International Society of Sexual and Impotence Research, International Society for the Study of Woman's Sexual Health, American Paraplegia Society, American Association of Spinal Cord Injury Nurses, American Association of Spinal Cord Injury Psychologists and Social Workers, American Association of Sex Educators, Counselors and Therapists, American Spinal Injury Association, American Academy of Physical Medicine and Rehabilitation, and American Congress of Rehabilitation Medicine. Several manufacturers were also approached for potential data including: Eli Lilly Canada Inc., Bayer Group, Unimed Pharmaceuticals Inc., Mentor Corporation, Vivus Inc., Timm Medical Technologies, Schering-Plough Corporation, Pfizer, Sabex 2002 Inc., and Novartis Pharmaceuticals.

Study Selection:

All results of searches for evidence were screened against the eligibility criteria. As an extension of the phase I feasibility study, two reviewers were employed at the relevance assessment phase of the evidence review. Two levels of screening for relevance were used, with the first level directed at bibliographic records during phase I, the feasibility study (i.e., title, authors, key words, abstract), and the second level focused on those “full report” articles retrieved based on the results of the first level of screening. Following a calibration exercise, two reviewers independently broad screened the title, abstract, and key words from each bibliographic record for relevance by liberally applying the eligibility criteria. The record was retained if it appeared to contain pertinent study information. If the reviewers did not agree in finding at least one unequivocal reason for excluding a report, it was entered into the next phase of the review. The screening process also identified which of the two questions the record addressed. Excluded studies were noted, as was the reason for their ineligibility.

Data Extraction:

Data abstracted included the characteristics of the report (e.g., publication status, language of publication, year of publication), study (e.g., sample size; research design; number of arms), population (e.g., age; percent males; diagnosis description), intervention/exposure (e.g., Viagra® for sexual function; testicular biopsy for fertility rates) and participant dropouts and withdrawals. A qualitative synthesis was completed for all studies included in the evidence report. This was performed on a question-specific basis, with studies grouped according to research design. Each synthesis includes a narrative summary of the key defining features of the study report, if stated, population, intervention/exposure, outcomes, study quality, applicability, and individual study results. Meta-analytical techniques for single proportions were used, when appropriate.

Data Synthesis:

A total of 2,420 bibliographic records were retrieved. After duplicate records were removed, 2,082 unique items remained. An additional 46 potentially relevant studies were identified through conference abstracts or were nominated by manufacturers. A total of 2,128 reports were evaluated against the eligibility criteria. In total, 122 reports were included in the systematic review: 66 of the reports examined fertility and 56 reports examined sexual dysfunction in individuals with SCI.

The 122 studies included 6,668 individuals, ranging in age from 16 years to 81 years, of which 78% of the studies reported 100% male participation, with 6% reporting all female participation. The complete spectrum of SCI severity was included across the studies. The majority of studies included in this review used a non-comparative study design (61%) to address the question under consideration. The quality of reporting of the 122 studies included was less than optimal. For example, of the 75 non-comparative studies, none of them reported on all the quality items we used to evaluate their reports.

No studies were found that investigated fertility in females after SCI. For male fertility, ejaculation interventions in the last decade resulted in an overall ejaculation response rate of 95% (random effects pooled estimate: 0.95 [95% C.I. 0.91, 0.99]). Data from 13 studies over the past 10 years documenting pregnancy rates indicate rates of 51% (random effects pooled estimate: 0.51 [95% C.I. 0.42, 0.60]). Data from the 11 studies over the past 10 years documenting live-birth rates indicate live birth rates of 41% (random effects pooled estimate: 0.41 [95% C.I. 0.33, 0.49]).

We found eight reports that examined the phenomena of sexual arousal in response to physical and cognitive stimulation in women. These papers describe the separate roles of physical reflex and cognitive pathways in the sexual response in SCI females, but did not test treatment methods for dysfunction. Several interventions (i.e., behavioral, topical agents, intraurethral Alprosatadil, intracavernous injections, vacuum tumescence devices, penile implants, sacral stimulators, and pharmacological) have been used to evaluate male sexual dysfunction. We identified one study that demonstrated improvement in penile rigidity in 10 SCI males before and after biofeedback, followed by home perineal muscle training exercises. Three non-comparative case-series studies and one controlled trial examined the use of topical vasodilators for erectile dysfunction in 53 SCI males, all demonstrating low efficacy or tolerability. Two case-series studies involving 30 SCI males describe the use of intraurethral Alproatadil for SCI male erectile dysfunction with high tolerability but low efficacy. Eight non-comparative case series involving 263 SCI males using intracavernous penile injections of vasodilating agents described poolable efficacy data along with side-effect profiles. The injection technique was highly efficacious, with a 90% satisfactory erection response rate (random effects pooled estimate: 0.90 [95% C.I. 0.83, 0.97]) and was well tolerated when appropriate precautions were taken. Only two case series involving 50 males examined vacuum tumescence devices. Although well tolerated, only a select group chose to use these devices; those that did choose to use them reported a high level of satisfaction. Nine studies, of which two were RCTs and seven were case-series studies, evaluated Viagra® in 627 SCI males. Although less efficacious than injections, Viagra® resulted in a 79% successful erectile function (random effects pooled estimate: 0.79 [95% C.I. 0.68, 0.90]). In addition, Viagra® was well tolerated and often preferred by SCI males. Finally, five case-series studies examined the efficacy and morbidity of penile implants in 363 male SCI subjects, and demonstrated a high satisfaction rate but also had a much higher complication rate than the other treatment options.

Conclusions:

Apart from case reports and opinion pieces, there is a paucity of literature regarding fertility and pregnancy in SCI females. There is a relatively large body of evidence regarding males with SCI. Using vibration and electroejaculation, most SCI males can produce semen for fertility purposes. The level of invasiveness is likely more of a factor than either the choice or the order of these two interventions. Vibration should be tried at least on all upper motor neuron injuries first, with electroejaculation reserved for those individuals in whom vibration failed and those with lower motor neuron injuries. Advanced fertility techniques can increase pregnancy rates for an SCI male to above 50% per couple. Freezing of sperm, unless done in the first one or two weeks after SCI, and even if done earlier, is unlikely to make a significant improvement in SCI fertility rates and therefore is not widely practiced. Penile injection, Viagra®, and vacuum devices can help most erectile function problems in SCI males, making the need for penile implants less common. These interventions positively affect sexual activity at least in the short-term. Long-term sexual adjustment has not been examined.