Spinal Cord Injury Related Infertility


Type of injury

Ejaculation rate (%)

Complete upper motor neuron

Incomplete upper motor neuron

Complete lower motor neuron

Incomplete lower motor neuron

4–11

32

18

70



Disruption of the reflex arc causes anejaculation: an absolute lack of ejaculate despite normal sexual stimulation due to failure of the emission phase of ejaculation [33]. Spinal cord injury is the commonest cause of neurogenic anejaculation [33].




Sperm Retrieval in Men with SCI


After the initial period of spinal shock, 85% of men will have some degree of erectile function, and 2 years after their injury only 10% of SCI men are able to ejaculate successfully during intercourse [34].

Historically, anticholinesterases were the first class of drugs used to assist with ejaculation. Guttman, in the early seventies, originally used intrathecal prostigmin to induce ejaculation in SCI men with some success, but the use of the drug was discontinued due to significant side effects including autonomic dysreflexia [35]. Subcutaneous physostigmine with concomitant administration of N–butylhyoscine was described by Chapelle et al. [36], but again discontinued due to parasympathetic side effects. Despite its undesirable side effect profile, there are reports of successful pregnancies in paraplegic men following intrathecal neostigmine administration [37]. Prostatic massage is also another simple, inexpensive, noninvasive method for obtaining ejaculatory fluid from neurogenic anejaculatory patients, and successful pregnancies have been reported [38, 39].

The non-pharmacologic methods used for anejaculation consist of (1) assisted ejaculatory techniques—penile vibratory stimulation (PVS) and electro-ejaculation (EEJ); and (2) methods where the sperm are directly collected from the testis—surgical sperm retrieval techniques, e.g., percutaneous epididymal sperm aspiration (PESA), testicular sperm aspiration (TESA), testicular sperm extraction (TESE), and others.


Penile Vibratory Stimulation


PVS was first described by Sobrero in 1965 [40] and is one of the simplest methods used for collection of sperm in SCI men.


Technique


A special vibrator (Ferticare Personal) is placed on the penile base or glans and vibration applied until ejaculation occurs. Typically, the procedure is stopped every 5 min to assess for any penile skin changes. It works best in men with lesions above T10 or incomplete lesions and requires intact dorsal penile nerves and a reflex arc. It is contraindicated in cardiac disease or untreated hypertension as autonomic dysreflexia may occur. Severe irritation of the glans penis is a relative contraindication, and extreme care should be taken if the patient has a penile prosthesis [41]. (In our center, we do not recommend this for patients with a penile prosthesis.) Proper positioning of the patient (usually at 45°) and bladder preparation are required with prompt drainage of the bladder and instillation of a buffering agent prior to initiation of PVS. Suprapubic catheters should be clamped, the urethral catheter should be removed, and an appropriate sterile device held at the external meatus to facilitate collection of ejaculate. As a technique, it has practical advantages over electro-ejaculation as it can be administered at home with partner involvement and cooperation, enhancing the sexual experience, is relatively inexpensive, and does not require an anesthetic [30]. With time, it can be patient administered and instead of special vibrators, many patients report success with generic vibratory sex devices.


Prognostic Factors


The most important factor that can predict success with PVS is the presence of an intact T10–S4 spinal segment and an intact dorsal nerve of penis. Presence of hip flexion reflex (L2–S1) and presence of bulbocavernosus reflex are also good predictors of success. Lesions below T10 and men with absence of hip flexion and bulbocavernosus response are associated with poor response. PVS is less successful in men within 6–18 months post injury [30].


Success


In optimal patients (injuries above T10), PVS is successful in up to 85% patients. In patients with an injury below T10, the success rate falls to 15%. In patients who have a favorable response, two-thirds are likely to have antegrade ejaculation and one-third have retrograde ejaculation [30]. PVS is a suitable technique for sperm retrieval for any SCI patient, and the best results are obtained with higher amplitude vibrators [40] and in injuries above spinal level T10. Use of a higher amplitude vibrator has been shown to yield semen samples in up to 95% of patients with an intact lumbosacral cord [42]. Sperm quality however, is variable (Table 14.2).


Table 14.2
Ejaculatory rates with penile vibro-stimulation






























 
Specimen

Method

No. of procedures

Antegrade alone

Retrograde alone

Combined

No specimen

Success rate

Penile vibratory stimulation

14

9

0

2

3

78.5%


Electro-Ejaculation


EEJ is an alternative method for sperm collection and can be used for similar indications as PVS. EEJ is, however, much more invasive, as it requires medical intervention and the patient may require general or spinal anesthesia [30].

Electro-ejaculation as a technique was originally designed to assist in animal husbandry and was first described in the 1930s [43]. In humans, the technique was first described by Horne in 1948 [23] and became an established technique for assisted reproduction in the SCI patients in the late 1980s [44]. The first reported pregnancy as a result of electro-ejaculation was reported by an Australian group in 1975 [45], and later in Japan in 1992 [46].


Technique


A trained physician in a theatre environment, usually using general anesthesia, must perform electro-ejaculation. A spinal anesthetic may also be used with lesions above T10. The patient is placed in the lateral decubitus position, and the bladder is temporarily catheterized to allow emptying and permit insertion of buffering solution into the bladder [30].

A rectal probe is inserted and voltage progressively increased in 1–5 v increments, which eventually stimulates the peri-prostatic and peri-rectal sympathetic nerves until ejaculation occurs [32]. The probe temperature is monitored throughout the procedure and the procedure suspended if the temperature rises above 40 °C. During emission, the sympathetic nerves cause closure of the internal sphincter, preventing retrograde ejaculation and concomitant peristalsis of the ductus deferens. Stimulation with EEJ also leads to parasympathetic peristalsis of the urethral musculature, and contraction of the bulbospongiosus allowing emission of semen [47].

Seminal emission depends on the level and completeness of the lesion, and a significant amount of sperm may be expressed into the bladder. Urethral milking may be required (with an assistant) as penile erection may not always occur with electro-ejaculation [48]. The antegrade fraction is collected in a sterile container held by an assistant at the meatus. Postoperatively, the bladder is again catheterized to obtain the retrograde fraction, which can be centrifuged. Rectal pathology is a contraindication, and patients with lesions above T6 are prone to dysreflexic episodes and may require calcium channel blockage at induction, or a spinal anaesthetic.


Prognostic Factors


The indications for EEJ are similar to PVS. However, EEJ is successful in injuries below T10, and the technique can be used successfully in the absence of hip flexion and bulbocavernosus reflexes. EEJ can also be used within six months of the injury, and the level and completeness of the injury are not predictors of success. The overall success is similar at all levels [30], but when compared to PVS, electro-ejaculation is a more expensive procedure and must be done in a clinical environment.


Success


Results from one of the earliest large studies demonstrated that 93% of patients with upper motor neuron lesions achieved antegrade ejaculation via this method with 63% of lower motor neuron patients also achieving it [46]. Aside from SCI, it can be successfully used in other forms of iatrogenic anejaculatory dysfunction, such as following retroperitoneal surgery for disseminated testicular cancer [49]. The quality of sperm is often suboptimal and in our experience improves with control of infection and frequent ejaculations. The data for our centre has been summarized in Table 14.3.


Table 14.3
Ejaculatory rates with electro-ejaculation






























 
Specimen

Method

No. of procedures

Antegrade alone

Retrograde alone

Combined

No specimen

Success rate

Electro-ejaculation

96

3

30

55

8

91.6%


Surgical Sperm Retrieval


Prior to the introduction of sperm retrieval techniques, donor semen was the only method of achieving pregnancy available to azoospermic men. The introduction of surgical sperm retrieval techniques revolutionized the management of sub-fertility in men with SCI. Men in whom no ejaculate can be obtained or whose ejaculate contains no viable sperm require more invasive forms of intervention: surgical sperm retrieval. Sperm can be obtained through various techniques from either the epididymis or testis by percutaneous aspiration, biopsy, or formal surgical exploration [33]. In SCI men, both testicular sperm aspiration (TESA) and testicular sperm extraction (TESE) are used for sperm extraction.


Technique


Testicular sperm aspiration (TESA) can be done under local anesthesia. A needle is inserted into the testicular parenchyma directly through the scrotal skin. The upper, interpolar and lower poles of the testis are sampled with a 19-gauge needle. Single or multiple punctures can be used. Side effects include hematoma formation.

TESE is another method of sperm retrieval. Testicular sperm extraction involves incising the tunica albuginea, applying pressure to the testis and retrieving the extruded tissue. Single site TESE, multiple site TESE, and micro-TESE have all been described [50]. Like TESA, it is a blind technique and cannot identify the active sperm-producing areas of the excised tissue until tissue has been extracted from the patient [51]. Micro-TESE is a microsurgical technique that aims to identify seminiferous tubules more likely to contain viable spermatozoa. Under a microscope, tubules containing developing germ cells rather than Sertoli cells in isolation will appear larger and more opaque than tubules without [51].

In our center, we now exclusively use TESE as a method of surgical sperm retrieval and dependent on testicular volume, we may explore one or both testes. This has superseded TESA, as sperm quality and quantity in spite of multiple punctures was very variable with TESA.


Prognostic Factors


Surgical sperm extraction techniques are suitable for all SCI patients. The techniques can be used irrespective of their level or completeness of the injury. These techniques can also be used in the first six months post injury, as well as (a) in patients with low volume testes, (b) in all forms of bladder management and (c) in patients with frequent recurrent infections.

The main disadvantage of surgical sperm retrieval techniques is that the amount of sperm obtained is very small; hence, the female partner eventually requires in vitro fertilization (IVF) followed by intracytoplasmic sperm injection (ICSI). As sperm retrieval is done independent of the female partner the sperm specimen is cryopreserved.


Success


The success of these techniques is comparable to the success rates in the able-bodied patients. The data from our centre is summarized in Table 14.4.


Table 14.4
Retrieval and fertilization rates according to etiology
























Etiology

Retrieval rate

Fertilization rate (%)

Obstructive azoospermia

141/141 = 100%

79.1

Non-obstructive azoospermia

27/60 = 45%

54.2

Spinal cord injury

11/11 = 100%

100


Sperm Transport and Storage


Our centre is based in Southport and Ormskirk National Health Service (NHS) Trust, Southport, Merseyside, United Kingdom. It is a district general hospital that provides secondary level care for the local population. The North West Regional Spinal Injury Unit is also based in the hospital. Assisted conception units with facilities for IVF, ICSI, and other advanced fertility techniques are located in regional tertiary centres. Our regional centre is based in Liverpool Women’s Hospital, 30 miles away.

This model, with a spinal injury unit and separate assisted conception unit being located in two different hospitals, is not unusual in the UK. However, it creates unique problems for the management of infertility in spinal cord injury patients. The challenge arises because the sperm retrieval is performed in the spinal unit and then the sperm specimen is transported to the assisted conception unit for analysis, cryopreservation and eventual treatment.

The management protocols for our patients have been established over the last 25 years and consist of an integrated pathway that includes referral, assessment, sperm collection and assisted conception for spinal patients undergoing fertility treatment. In the UK, assisted conception treatment of infertility is done under the guidance of the Human Fertilization and Embryology Authority (HFEA). The treatment protocols in our center fulfill the HFEA criteria [52].

Following surgical sperm retrieval, the specimen is immediately transported by car in G-Mops™ Plus (Vitrolife, Göteborg, Sweden) [52] culture medium to the assisted conception unit where the specimen is then assessed for sperm parameters and then cryopreserved. Post-thaw analysis is performed a few days later to confirm viability.

In our center, we only use cryopreserved sperm for the subsequent treatment, which is IVF/ICSI. We have not found any deterioration in the fertilization rates in the SCI patients compared to the sperm from the able-bodied men (Table 14.4).

The advantages of the model described include the following: (1) collection of sperm is done according to the suitability and convenience of the spinal injury patient, and (2) the outcome is not affected by either the level or type of injury. In addition, the assisted conception can be scheduled to suit the couple. Sperm collection and cryopreservation can also be done for single men for future use as well.


Semen Analysis


There are well-defined and significant differences in the seminal quality and the seminogram of the men with SCI, when compared to able-bodied, ambulant men, and this is proposed to be multifactorial. Typically, volume may be normal but frequently discolored—a condition known as “rusty pipe syndrome of unknown etiology.” [20]. Specimens of ejaculate from spinal patients typically have an increased count but have poor quality, specifically for motility and viability [25, 53]. Changes in seminal parameters occur as soon as two weeks after acute injury [54]. Early work in the field of SCI related fertility identified various factors thought to contribute to poor semen quality in SCI men, namely urinary tract infections, method of bladder management, static prostatic fluid, testicular hyperthermia and histological changes, hormonal alterations, presence of antibodies, and use of chronic medications [55]. Hirsch et al. [56] proposed that testicular failure and accessory sexual gland dysfunction may also be responsible for poor semen quality in spinal cord injury patients. Method of bladder drainage has been shown to influence the amount of motile spermatozoa with intermittent self-catheterization being the optimum method that is “sperm friendly.” [57]. Additionally, level of neurological insult is also important and demonstrates a linear relationship with caudal injuries demonstrating the most deleterious effects on motility [22].

The World Health Organization (WHO) criteria for assessment of semen are considered the gold standard for the assessment of semen analysis (Table 14.5) [58].


Table 14.5
World Health Organization (WHO) reference limits for semen analysis (WHO—5th edition [58])

























Criteria

Reference limits for semen analysis

Volume (ml)

1.5 ml

Total sperm (millions in ejaculate)

39 million

Sperm concentration (millions per ml)

15 millions per ml

Total motility

40

% normal morphology

4%

However, the same criteria cannot always be applied to the semen specimen obtained from a spinal injury patient because of the unique circumstances that apply to this patient cohort. These include the following: infrequent ejaculations, the need to keep the specimen from entering the bladder and the requirement to instill culture medium intravesically. The results from our center are described in Table 14.6, and when compared to the WHO reference limits (Table 14.5), it is obvious that all the parameters do not conform.


Table 14.6
Quantitative semen parameters in the ejaculates of the spinal injury patients
















































 
Volume (mls) (May include culture media)

Concentration/ml

Motility (%)

Cells (HPF)

Range

Average

Range

Average

Range

Average

Range

Average

Antegrade

0.4–20

7

0.2–350

111

1–89

15

1–11

4

Retrograde

1–80

25

0.4–450

44

1–15

4

13–26

15


Case Discussion and Presentation


Spinal cord injury typically occurs in men at the peak of their reproductive potential (with the average age at injury being 33.4 years) and remains the commonest cause of neurogenic ejaculatory dysfunction [29, 33]. Additionally, altered seminal quality and erectile dysfunction contribute to fertility concerns in the SCI man. The natural ability to conceive is altered due to sacral autonomic disruption [47], and, therefore, neurogenic ejaculatory failure is of paramount importance when dealing with fertility concerns in a spinal cord injury patient. Infertility affects more than 90% of men with SCI [20]. As most men are anejaculatory, they commonly present to a urologist for fertility advice, treatment of erectile dysfunction, or sperm retrieval [28].

Although reflex erections still occur in spinal cord patients, they are usually not of a sufficient duration to permit intercourse. However, because the vascular mechanisms are intact, treatment of erectile dysfunction in the spinal cord-injured men is similar to the treatment strategies used in the ambulant male with phosphodiesterase type 5 (PDE5) inhibitors, intracavernosal injections, vacuum devices, and penile implants (see Chap. 13) [59]. Due to altered sensation in the spinal patient, the use of inflatable implants over rigid implants is favored as it reduces the risk of implant erosion. Therefore, erectile dysfunction alone does not pose difficulties for sperm retrieval [59].

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Sep 23, 2017 | Posted by in UROLOGY | Comments Off on Spinal Cord Injury Related Infertility

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