The ejaculate is produced by combining the secretions of the prostate with the contents of the ampullary parts of the vasa deferentia, followed by their expulsion from the urethra washed out by fluid from the seminal vesicles [ 1]. There are many causes of difficulty with ejaculation, which may lead to partial or complete loss of the process. Total absence of production of semen at the time of orgasm is termed aspermia, and this must be distinguished from azoospermia, which indicates absence of spermatozoa from the ejaculate. When there is no ejaculate at all, it is important to establish whether there is total failure of ejaculation or retrograde ejaculation. As the management is different, although the causes may be similar, it is important to recognize the true nature of ejaculatory dysfunction early in the diagnostic evaluation.
The normal ejaculate can be divided into four to six fractions [ 2] and serial biochemical analysis of their component parts confirms that the order of contraction of the various organs normally follows the sequence outlined above. Thus, the first part contains the most spermatozoa and subsequent fractions contain sequentially less. Acid phosphatase, citric acid and zinc, emanating from the prostate, are in highest concentration in the first part of the ejaculate, whereas fructose, coming from the seminal vesicles, increases in concentration towards the end of the ejaculatory process. Alteration of the pH values in successive parts of the ejaculate indicates how the acid component provided by the prostate is serially mixed with the more alkaline contribution of the fructose-rich fluid from the seminal vesicles. The prostate contributes 15–30% of the entire ejaculate and the seminal vesicular secretion 50–80%; there is also a small contribution to the first part of the ejaculate from the bulbourethral (Cowper’s) glands, which is rich in enzymes and plasminogen activator [ 3].
Ejaculation is under sympathetic nervous control [ 4]. The efferent sympathetic nerves emerge from the spinal column at T10-L2 to form the lumbar sympathetic ganglia, from which the descending nerves encircle the aorta on each side, before coming together in the midline to form the hypogastric plexus just below the bifurcation of the aorta ( Fig. 1). From there, the hypogastric nerves pass through the pelvis to terminate as postganglionic fibres on the bladder neck, prostate, vasa deferentia and seminal vesicles [ 5]. Sympathetic nervous stimulation leads to contraction of the prostate, vesicles and vasa deferentia with partial bladder neck closure which produces ejaculation: division of these nerve fibres therefore causes loss of ejaculation. Parasympathetic innervation of the corpora cavernosa, prostate, base of bladder and bladder neck is from the S2 to S4 roots via the pelvic nerves; injury to these nerves (e.g. during radical prostatectomy) leads to loss of erection. Expulsion of the contents of the urethra, the final act of ejaculation, is by contraction of the somatic muscles surrounding the urethra, which are innervated via the pudendal nerve.
The organic causes of ejaculatory duct obstruction have been well defined, and can be broadly classified into congenital and acquired [ 6]. Functional abnormalities may be behavioural, may follow neurological damage or be induced by drugs. The cause of the malfunction should be defined as accurately as possible before treatment is instituted.
Haemospermia requires a full investigation [ 7]. Culture of expressed prostatic secretion and urine will define the nature of an infective process, e.g. prostatitis [ 8], and urine cytology and serum PSA should be assayed to exclude bladder or prostatic cancer. Ultrasonography of the testicles and epididymes should define any local disease. TRUS will detect structural abnormality in the prostate or seminal vesicles, or may show a stone in the ejaculatory duct or even a Müllerian duct cyst; cystoscopy is seldom helpful.
If a man has difficulty with ejaculation, or has a small volume or absent ejaculate, it must first be established whether the problem is congenital or acquired. A careful clinical history should be taken, and physical examination will establish whether the testicles and epididymes are normal, and whether the vasa are present or absent, on each side. Next, it is essential to establish whether there is retrograde or completely absent ejaculation, by examination of a deposit of urine after centrifugation. The presence of spermatozoa indicates retrograde ejaculation. These facts will allow the patient to be placed into one of several broad categories, after which a more detailed evaluation can take place.
Patients with ejaculatory duct obstruction usually present with infertility. Seminal analysis shows absence of part or the entire component of the ejaculate that comes from the vasa and seminal vesicles via the ejaculatory ducts. The volume is low (usually <1.5 mL), the pH is low (<7) and the fructose content is either low (<1.2 g/L) or absent. If both vasa are palpable, a diagnosis of ejaculatory duct obstruction is very likely. The diagnosis should be confirmed by TRUS and the exact cause defined by percutaneous perineal puncture of the distended seminal vesicles (or other cystic structures) to define the anatomy as clearly as possible ( Fig. 2). Exploration of the scrotum and vasography ( Fig. 3) should be delayed until arrangements have been made for definitive treatment of the obstructing lesion.
When there are no vasa, it is important to establish whether the condition is unilateral or bilateral. With unilateral absence of the vas deferens, the urinary system must also be checked by ultrasonography, as coexisting renal anomalies may be present [ 9]. Cystic malformation may occur, which can impede normal ejaculation from the contralateral side. Zinner’s syndrome [ 10] associates this abnormality with ipsilateral absence of the kidney. Unilateral testicular obstruction can lead to production of antisperm antibodies in individuals who are immunologically responsive; this can cause infertility even though the contralateral testis is unobstructed, and may complicate restoration of fertility after reconstruction [ 11].
With bilateral absence or malformation of the vasa, it is essential to consider whether the anomaly may be part of a genetic defect associated with carriage of the potentially harmful cystic fibrosis (CF) chromosome anomaly [ 12]. Treatment by assisted reproduction could lead to the birth of an affected child if the female partner also carries the CF gene. Genetic counselling should always precede definitive treatment in such cases.
As the male fetus develops, the Müllerian ducts normally disappear from above downwards ( Fig. 4) under the influence of Müllerian inhibitory factor (MIF), which is produced by the Sertoli cells in the primitive testis. Failure of complete absorption may leave a small Müllerian duct remnant at the lower end that lies between the ejaculatory ducts.
The Wolffian (mesonephric) ducts are composed of three distinct areas ( Fig. 5). The upper part forms the epididymis and distal vas deferens, while the proximal vas deferens, seminal vesicle and ejaculatory duct are derived from the middle area. The most caudal part is the common mesonephric duct, from which the ureteric bud springs at ≈4 weeks of development; this becomes the ureter, and will induce the metanephric blastema to form the kidney. The urogenital sinus reabsorbs the lower end of this structure, and the ureteric orifices are thus separated from the vasa deferentia, seminal vesicles and ejaculatory ducts. Several complex anomalies may occur in this area leading to ectopic opening of the vas deferens and sometimes associated with anorectal anomalies [ 13]. If too much of the proximal vas precursor is absorbed, a variable amount of the proximal vas, seminal vesicle and/or ejaculatory duct may be absent. There may also be coexisting abnormalities in the ipsilateral kidney or ureter.
Müllerian duct cyst
Persistence of a small remnant of the Müllerian duct may lead to a cyst forming between the ejaculatory ducts which can become obstructed and cause diminution of the volume of the ejaculate and infertility. Haemospermia is not uncommon in these patients. Seminal analysis shows the changes characteristic of obstruction (see above), and both vasa are palpable; the epididymes usually feel distended. The diagnosis is made by TRUS and the lesion can be delineated by percutaneous puncture of the cyst with instillation of radio-opaque medium (see Fig. 2). The cyst can be incised or de-roofed endoscopically after delineating its extent by injecting blue dye (see below). The ejaculate volume and seminal quality then improves in most cases [ 14].
Wolffian duct abnormalities
Congenital anomalies may be either sporadic, with a localized defect in the proximal part of the vas deferens, or there may be a generalized maldevelopment due to a systemic genetic abnormality [ 9]. The latter is usually bilateral and is often associated with carriage of the CF gene [ 12]. Unilateral absence of the vas deferens was observed in 5%, and bilateral absence in 18% of 370 azoospermic males with normal serum FSH levels investigated by the author [ 15].
Local Wolffian duct abnormality involves loss of a variable amount of one vas deferens, seminal vesicle and/or ejaculatory duct, and sometimes part of the ipsilateral urinary system as well. The loss appears to commence at the proximal juxta-urethral end and extend laterally (Pryor and Hendry, unpublished observations; ( Fig. 6a,b). Unilateral absence of the vas deferens with the kidney and ureter may also be associated with maldevelopment of the ipsilateral part of the bladder neck and trigone, which can fail to close effectively thus allowing retrograde ejaculation to occur (see below).
Hypospadias, epispadias, bladder exstrophy
Congenital malformation of the penis can deflect the ejaculate and prevent it from emerging at the tip of the penis. Correction of the defect using modern reconstructive techniques can ensure that the semen is deposited high in the vagina at intercourse. After correction of severe epispadias or bladder exstrophy, sexual activity can be good despite a short penis, and pregnancies may be produced even after cystectomy and urinary diversion [ 16], but artificial insemination may be necessary.
Open bladder neck
Congenital incompetence of bladder neck closure is sometimes associated with unilateral absence of the genito-urinary tract, and this can lead to retrograde ejaculation. The man may report that he has never seen a normal emission. The condition is recognized by TRUS or cystoscopy and may be corrected by bladder neck reconstruction. Alternatively, spermatozoa can be retrieved from the urine by centrifugation and used for insemination [ 17].
Ejaculatory duct obstruction or ejaculatory failure due to pelvic nerve damage may follow correction of imperforate anus. The ‘pull-through’ procedure passes close to the posterior aspect of the prostate and damage to the ejaculatory mechanism is most likely if there has been a recto-urethral fistula that required closure. Analysis of 20 subfertile men who had repair of imperforate anus in infancy indicated that seven had no ejaculate, 11 were azoospermic, one was severely oligozoospermic and only one had a normal sperm concentration in a very small volume of ejaculate [ 18]. Investigation revealed that both vasa were blocked in five men and one vas in a further eight patients, apparently as a result of the original operative procedure.
Bladder neck incision, prostatectomy, excision of rectum and para-aortic lymphadenectomy are all examples of operative procedures that carry a risk of damage to the ejaculatory mechanism or its nervous control. In a recent survey, informed consent to TURP included written reference to these facts in only one-third of patients, irrespective of whether the men were married, single or widowed [ 19].
Retrograde ejaculation occurs in ≈25% of men after TURP and to a lesser extent after bladder neck incision, due to failure of bladder neck closure [ 19]. After radical prostatectomy, ejaculation is inevitably lost, as the seminal vesicles are removed with the prostate gland, and erectile impotence was the rule until detailed anatomical studies showed where the parasympathetic nerves ran behind the prostate gland [ 20], and a nerve-sparing operative technique was developed [ 21].
Genital infection such as gonorrhoea or nonspecific urethritis can produce cicatrization and obstruction anywhere in the male reproductive tract, especially if treatment is delayed. Urinary infection, especially if complicated by epididymitis, can also produce obstruction that may be situated at ejaculatory duct level. Ejaculatory duct obstruction after infection may also be occur following prolonged catheterization, e.g. after a road traffic accident or an episode of intensive care. A history of such an episode should alert the urologist to such a possibility. Routine vasography in subfertile men with azoospermia and normal serum FSH levels revealed post-infective vasal blocks in 8% and acquired ejaculatory duct obstruction in 4% [ 15]. Such blocks are often asymmetric, so that epididymal obstruction on one side may coexist with a more proximal block on the other. They are often associated with high titres of antisperm antibodies, initially provoked by the infective process [ 22] and perpetuated by the obstruction [ 23]. Recognition of this immunological response to the obstruction is important, as corrective surgery is significantly less successful in the presence of such antibodies [ 24].
Schistosomiasis is endemic in large parts of Africa and is seen with increasing frequency in tourists returning from Africa who have contracted the disease whilst enjoying water sports; Lake Malawi has acquired an evil reputation in this respect. The disease may present with haemospermia [ 25], and fibrosis and calcification may lead to genital obstruction. Genito-urinary tuberculosis can cause great damage to the male reproductive tracts, and as healing occurs with calcification, the lesions may be irreparable, in the author’s experience. A plain X-ray will often show the extent of the disease.
Haemospermia is seldom as ominous a symptom as haematuria, but this complaint should not be ignored. Analysis of the findings in 81 patients revealed that an inflammatory cause could be defined in most men under 30 years of age; however, there were a few (8%) with more serious disease, including carcinoma of prostate and bladder [ 26]. It should also be remembered that schistosomiasis and tuberculosis can present in this way.
Routine investigation of haemospermia by TRUS not uncommonly reveals the presence of small stones in the ejaculatory ducts, which may be associated with obstruction and dilatation of the seminal vesicles. Such stones usually pass spontaneously, although resection of the distal parts of the ducts may occasionally be required if the symptoms are pressing or pain is persistent.
A period of spinal shock occurs for some weeks after such an injury, during which erection and ejaculation may be impossible. Once the initial phase is over, damage to the spinal cord at the level of T10 to L2 may affect central reflex pathways and lead to permanent loss of ejaculation. Injury above T11 may allow reflex erection and ejaculation, although this may provoke autonomic dysreflexia with marked rise in blood pressure [ 27]. Many of couples so affected are keen to produce a family, and investigation and treatment may help them to achieve this aim [ 28].
This operation is usually performed to clear lymph node metastases from testicular tumours, when the sympathetic nerves and ganglia may also be removed, leading to loss of ejaculation. Early studies showed that up to three-quarters of patients lost antegrade ejaculation after full bilateral retroperitoneal lymph node dissection (RPLND) [ 29]. As a result of careful anatomical studies, the technique of RPLND has been modified with ‘nerve-sparing’ so that antegrade ejaculation is now maintained in 70–90% of patients [ 30, 31]. Some temporary loss of ejaculation is not uncommon but generally recovers over the months following the procedure.
A quarter of the patients who complete chemotherapy for advanced testicular tumour have residual masses in the para-aortic region; when resected, this tissue is found to contain residual cancer (malignant teratoma undifferentiated, MTU) in 20% [ 32]. Amongst 231 consecutive patients undergoing para-aortic lymphadenectomy after chemotherapy at the Royal Marsden Hospital, there was MTU in 21% [ 33]. In 186 patients, a nerve-sparing operative technique introduced in 1984 lead to a significant reduction in ejaculatory dysfunction, from 37% to 19% [ 34]. Loss of ejaculation occurred significantly more often after bilateral (46%) than after unilateral (14%) dissection, and was related to the size of the excised mass (4 cm 4%; 4–8 cm 19%; >8 cm 60%). The chemotherapy combination used for the treatment of metastatic testicular tumours, e.g. bleomycin-etoposide-cisplatinum (BEP), provides a good chance of recovery of spermatogenesis after 1–2 years [ 35]. It is therefore particularly important that patients at high risk of loss of ejaculation should be recognized early in the course of their treatment, so that seminal analysis and cryopreservation of semen can be arranged in suitable cases [ 36]. Excellent results have been reported with artificial insemination using cryopreserved semen [ 37].
Congenital anorgasmia is a rare but well-defined cause of total absence of ejaculation [ 38]. Usually ascribed to an over-strict upbringing, the individual is unable to achieve orgasm and hence never ejaculates. Nocturnal emission may occur, but repression of the normal sexual responses to stimulation prevents the individual from achieving climax and ejaculation. Psychotherapy may help, but orgasm can usually be provoked by vibration.
This common complaint is generally ascribed to anxiety. However, recent careful observational studies have indicated that there is hypersensitivity of the penile skin, as evidenced by perception of minute vibratory stimuli in those suffering from this condition compared with controls. Interestingly, the hypersensitivity appeared to be confined to penile skin, and there was no significant difference in skin sensitivity elsewhere, e.g. on the index finger [ 39]. Many drugs delay orgasm and ejaculation and this effect can be used in the treatment of premature ejaculation.
Side-effects of drug therapy
Many commonly used drugs cause delay or absence of orgasm and ejaculation (see Table 1) [ 40]. The prevalence of both impotence and failure of ejaculation is higher in treated hypertensive patients than in matched controls. Methyldopa, for example, leads to loss of libido and delayed ejaculation, as well as erectile difficulty [ 41]. While psychotropic drugs are also associated with sexual dysfunction in a high proportion of patients, it is not always clear whether this is due to the drugs or to the underlying illness. Nevertheless, it is known that up to 40% of patients taking monoamine oxidase inhibitors experience sexual dysfunction, and the tricyclic antidepressants can cause reduced libido, erectile impotence and delayed ejaculation in up to 20% of patients. Selective serotonin re-uptake inhibitors are less often associated with adverse side-effects; however, fluoxetine (Prozac) does cause delay in ejaculation and absence of orgasm in up to 40% of patients. A new drug, mirtazapine (Istrin), which is a noradrenergic and specific serotonergic antidepressant, is claimed not to have this undesirable side-effect, but does produce drowsiness when first taken, which may diminish interest in sexual activity. These adverse side-effects are important, as they may lead to noncompliance in taking the required dose of the drug. On the other hand, these effects can be used therapeutically to treat premature ejaculation.
Table 1. Drugs known to be associated with impairment of ejaculation and drugs used to achieve seminal emission. From 
Other drugs with adrenergic or anticholinergic effects can enhance ejaculation by sensitizing the nerve endings in the seminal vesicles and vasa deferentia, and by encouraging closure of the bladder neck ( Table 1) [ 40]. These have been used with limited success to treat retrograde ejaculation, or loss of ejaculation after para-aortic lymphadenectomy (see below).
Adult polycystic kidney disease has been found in association with pathological dilatation of the seminal vesicles in six patients [ 42]. TRUS and percutaneous puncture of the seminal vesicles before and after resection of the ejaculatory ducts revealed that the gross dilatation of the seminal vesicles was not caused by obstruction, but appeared to be due to atonicity (megavesicles). These ultrasonographic appearances, when described previously, were incorrectly thought to be due to seminal vesicle cysts. Pathological dilatation of the seminal vesicles in the absence of obstruction has been described previously, although the aetiology remains obscure [ 43].
Premature ejaculation can be treated by the application of local anaesthetic gel, which reduces penile skin sensitivity. The cream is kept in contact with the skin with a condom for 30 min, after which a significant improvement has been reported [ 44]. However, it is important to wash off the local anaesthetic before intercourse, if the diminution of vaginal sensitivity in the female partner is to be avoided [ 45]. Clomipramine, a tricyclic antidepressant, has been shown to produce significant delay in time to orgasm, with increased satisfaction with sex life, in a prospective controlled trial, given in a dose of 25 mg 12–24 h before intercourse [ 46]. Fluoxetine (Prozac) given in a dose of 20 mg daily for 1 week and 40 mg daily thereafter has also been used, and produced significant benefit after 4 weeks of treatment [ 47]. The female partners involved in the latter study subjected the effects to careful scrutiny, including verification of intravaginal latency time.
Retrograde ejaculation can be treated with adrenergic drugs such as ephedrine, 30–60 mg, or a tricyclic antidepressant with noradrenaline re-uptake blocking action, such as desipramine, 50 mg, taken 1–2 h before sexual activity. One patient with azoospermia and small-volume ejaculate associated with an open bladder neck and unilateral absence of the vas deferens responded well to ephedrine, the seminal analysis becoming normal, and subsequently a pregnancy was produced. Alternatively, spermatozoa can be retrieved from postorgasmic urine by centrifugation after retrograde ejaculation, resuspended and used successfully for artificial insemination; a cumulative pregnancy rate as high as 72% at 6 months has been achieved [ 17].
In some paraplegic patients, application of a vibrator to the penis will lead to ejaculation [ 48]; in others, electroejaculation may be necessary to produce spermatozoa that can be used for insemination. If the spinal reflex arc is intact, a hypogastric plexus stimulator ( Fig. 7) will provoke ejaculation [ 49]. This method has the advantage that it can be used in the security and privacy of the patients’ home, and repeated ejaculation can improve the quality of the semen. Alternatively, direct electroejaculation by rectal probe may be effective, but this generally requires a general anaesthetic and is carried out in hospital [ 50]. In a recent analysis of 40 paraplegic patients, 22 successfully produced pregnancies by natural insemination or assisted reproductive techniques [ 28].
Drug treatment for loss of ejaculation after para-aortic lymphadenectomy is not very successful [ 51] but direct electroejaculation can produce spermatozoa for insemination [ 52]. It is important to anticipate this complication in young men with testicular tumours who may need chemotherapy or node dissection, and arrangements should be made for sperm storage at the earliest opportunity before treatment commences. Excellent results can be obtained with artificial insemination using cryopreserved spermatozoa [ 37].
Ejaculatory duct obstruction can be treated endoscopically. It is very helpful if the lesion is accurately defined preoperatively by TRUS, so that operative arrangements can be made in advance. The obstruction should be defined radiologically by vasography or percutaneous puncture, and 5–10 mL of 1% methylene blue dye instilled to indicate when the ejaculatory system has been entered. The patient should be placed in the lithotomy position and suitable drapes applied to allow access to rectal examination during the procedure. After preliminary cystoscopy, the resectoscope or optical urethrotome is inserted. A Müllerian duct cyst may simply be incised, releasing a gush of fluid, but there is a tendency for the incision to heal over and it may be preferable to resect the edges or make a cruciate incision. If the ejaculatory ducts are blocked at their lower ends, it may be simpler to resect the verumontanum, commencing just above it in the prostatic urethra and drawing the loop carefully downward ( Fig. 8). The appearance of the dilated ejaculatory ducts is characteristic and easily recognized, resembling a horse’s nostrils. Pressure on the seminal vesicles will produce abundant efflux once the obstruction has been relieved.
An analysis of the results obtained from 87 patients with ejaculatory duct obstruction is summarized in Table 2; incision of the Müllerian duct cyst was the most successful procedure, but satisfactory results have been obtained in other patients, and have continued to be seen since this study was completed. If reconstruction is not possible, sperm can be withdrawn by microscopic epididymal sperm aspiration or percutaneously and used for in vitro fertilization [ 53]. Attempts to insert a permanent sperm reservoir gave only limited success and this treatment has now been abandoned [ 54].
Table 2. The number of patients with ejaculatory duct obstruction by group, the number successfully treated/number with adequate follow-up in each group (from )
I express my appreciation to the late Mr Keith Yeates, not only for his constant help and encouragement in my andrology work, but also for all that he did for British urology. The legacy of his foresight and hard work has much to do with the success of our speciality today. I am also most grateful to my colleague Mr John Pryor, for kindly reading this manuscript and advising me on the treatment and interpretation of the often complex malformations that occur in this area. I am also grateful to Dr David Rickards for help with interpretation of the radiological images.