1 Department of Obstetrics and Gynecology, Medical University of Lübeck, 2 Fertility Center Hamburg and 3 Krankenhaus RosenhöheBielefeld, Germany
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Abstract |
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Key words: ICSI/infertility/retrograde ejaculation
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Introduction |
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The most common urological surgical procedure leading to retrograde ejaculation is prostatectomy (Yavetz et al., 1994). Other causes of retrograde ejaculation are diabetic neuropathy, bladder neck resection or incision due to outflow obstruction, surgical injury to the sympathetic nerves after bilateral radical lymph node dissection performed because of testicular tumour, sympathectomy, and abdominalperineal resection. Adrenoreceptor blocking agents may also cause retrograde ejaculation, while multiple sclerosis and tumours are infrequent causes.
In a small group of patients, no clear cause for the condition can be found. These cases of idiopathic retrograde ejaculation are thought to be due to a progressive widening of the bladder neck which allows the passage of spermatozoa, especially when the bladder is empty (Gerris et al., 1994).
Retrograde ejaculation should be suspected in any case of azoospermia and the diagnosis is confirmed by finding spermatozoa in post-ejaculatory urine. Any spermatozoa found in the pellet after urinary centrifugation will almost invariably be dead due to the combined effects of osmotic stress, low pH and urea toxicity (Mortimer, 1994). Because surgical and medical therapies have not been successful in the restoration of antegrade ejaculation, the most common technique used to treat couples with male infertility resulting from retrograde ejaculation has been to obtain spermatozoa after masturbation or intercourse either directly from the bladder or from the urine. Recovered sperm have been subjected to several of the standard assisted reproductive techniques, including intracytoplasmic sperm injection (ICSI) (Gerris et al., 1994
).
The objective of this retrospective clinical study was to further assess the benefits of ICSI treatment in cases of anejaculatory infertility due to retrograde ejaculation.
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Materials and methods |
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The mean male age was 35.5 years (range 2948 years) and the mean female age was 33.1 years (range 2742 years). Mean duration of infertility was 5.5 years.
The women were found to be healthy at a routine gynaecological examination and all had regular menstruations. No extensive infertility investigation had been carried out because of the presence of the obviously severe male factor.
Among these couples, nine men were suffering from idiopathic retrograde ejaculation (patients no. 1, 2, 6, 7, 11, 13, 14, 15, 16), two men had previously undergone treatment for testicular tumour (patients no. 8, 12), two men had a spinal cord injury (patients no. 3, 9), one had a history of bladder reconstruction for bladder exstrophy (patient no. 4), one had undergone epididymo-vasostomy because of obstruction in the epididymis (patient no. 5) and one had a history of outflow obstruction (patient no. 10). Thus there was generally poor sperm morphology in this group of 16 men. Three of the men had been previously treated with artificial insemination and two with IVF, with negative results. Because infertility was long-standing, no medical treatment of the study patients was attempted.
Recovery of spermatozoa from the urine
Because the normally acidic urine is considered to be spermicidal the patients were instructed to alkalinize their urine by ingesting 1 g of sodium bicarbonate the night before and a further 1 g on the morning of the procedure. They were asked to empty their bladder before masturbation, to obtain the post-ejaculatory urine as quickly as possible after ejaculation, and then to deliver the sample immediately to the laboratory. The urine samples were divided into 10 ml aliquots and centrifuged for 5 min at 300 g at room temperature.
Sperm parameters were assessed according to World Health Organization guidelines (WHO, 1992). Different methods of sperm preparation were employed, i.e. swim-up, glass wool filtration and Percoll gradient centrifugation. The choice of the method for sperm preparation depended upon which protocol was in common use in each of the three centres in our study. For the swim-up method, the sperm pellets were resuspended in 1 ml Ham's F-10 medium with 15% umbilical cord serum and centrifuged again at 300 g for 5 min. The pellets were pooled together and washed once with Ham's F-10 medium with 15% umbilical cord serum. The supernatant was removed and finally the pellet was resuspended in 0.5 ml medium and incubated at 37°C for 1 h. For glass wool filtration the spermatozoa were washed, resuspended in 0.5 ml Ham's F-10 medium, layered over the wet glass wool column and allowed to filter by gravity. After the sperm suspension had filtered through, the filter was rinsed with 0.2 ml Ham's F-10 medium to flush out any remaining viable spermatozoa trapped in the glass wool column. The whole procedure was performed at room temperature.
The semen of seven patients was subjected to Percoll gradient centrifugation. An aliquot of 1 ml suspended spermatozoa was placed on a discontinuous Percoll gradient (usually 45/90%) and centrifuged at 300 g for 20 min. The pellet was resuspended in 3 ml HEPES-buffered Earle's medium and the Percoll was removed by centrifugation at 300 g for 10 min. The sperm suspension was transferred to an Eppendorf container with a small amount of medium.
Ovarian stimulation
Ovarian stimulation was achieved by the administration of human menopausal gonadotrophins (HMG) (Humegon; Organon, Oss, The Netherlands; or Menogon; Ferring, Kiel, Germany) or purified urinary follicle stimulating hormone (FSH,Fertinorm HP; Ares Serono, Freiburg, Germany) or recombinant FSH (Gonal-F; Serono) after pituitary suppression with a gonadotrophin releasing hormone agonist (GnRHa, Decapeptyl Depot; Ferring) according to the long protocol. Ovulation was induced by the administration of 10000 IU human chorionic gonadotrophin (HCG) when the leading follicle measured >20 mm in diameter on ultrasound and an adequate serum concentration of oestradiol was detected. At 36 h after ovulation induction, oocyte retrieval was carried out by vaginal ultrasound-guided puncture of the follicles under general anaesthesia, if required.
Oocyte preparation and ICSI procedure
Oocytes were treated with 0.5% hyaluronidase (Sigma Co., Hamburg, Germany) for 1015 s to induce lysis of the cumulus oophorus cells. Cells of the corona radiata were removed mechanically with a Pasteur pipette under stereomicroscopic guidance at a magnification of x50. Subsequently, the maturity of the oocytes was determined. Only oocytes in the metaphase II were used for the ICSI procedure. The microinjection procedure has been described previously (Van Steirteghem et al., 1993). Immediately prior to the ICSI procedure, 5 µl of 10% polyvinylpyrrolidone solution was added to the sperm-containing droplet to reduce sperm motility (Al Hasani et al., 1995
). Injected oocytes were examined at 1618 h after injection to determine whether or not they were fertilized. Embryos were categorized according to the relative proportion of anucleate fragments present in the perivitelline space: excellent, with no anucleate fragments; good, where <20% of the embryo was fragmented; fair, where the proportion of fragmentation was between 20 and 50%. A maximum of three cleaving embryos were replaced (according to German Embryo Protection Law) in the uterus ~48 h after oocyte retrieval. Luteal phase support was performed with the administration of natural micronized progesterone (vaginal tablets Utrogestan 200 mg x3; BesinsIscovesco, Paris, France).
Clinical pregnancy was defined as the presence of a gestational sac as well as at least one fetal heartbeat on ultrasonographic screening. Abortion was defined as pregnancy loss before 20 weeks of gestational age.
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Results |
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Discussion |
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There are two categories of retrograde ejaculation: one consists of men who have been evaluated for infertility, and the other comprises patients with urological complaints who reported retrograde ejaculation as a consequence of surgical treatment. Among infertile patients the distribution of the aetiologies varies because of differences in the ages of the patients (Yavetz et al., 1994). Medical treatment of retrograde ejaculation with
-adrenergic agents, anticholinergics and imipramine may restore antegrade ejaculation, but the overall success rates with these drugs is low (Andaloro and Dube 1975
; Sandler, 1979
; Brooks et al., 1980
).
The results of surgical treatment (e.g. surgical correction of bladder neck incompetence, endoscopic injection of polytetrafluorethylene) are considered to be uncertain with occasional recurrence of the symptoms (Abrahams et al., 1975; O'Donnel and Puri, 1986
).
Because urine has a detrimental effect on sperm quality various methods have been used to retrieve spermatozoa from post-ejaculation urine samples. Appropriate medium can be injected into the bladder by catheterization before masturbation, but this invasive method is not acceptable to the majority of patients (Hotchkiss et al., 1955). Successful recovery of spermatozoa from the urine has been achieved after alkalinization of the urine by oral intake of sodium bicarbonate and water (Check et al., 1990
). Although pregnancies have been obtained following intrauterine insemination (IUI) (Milingos et al., 1993
), IVF (Bosman et al., 1990
), gamete intra-Fallopian transfer GIFT (Vernon et al., 1988
), pronuclear stage tubal transfer (PROST) (Hulme et al., 1991
) and ICSI (Gerris et al., 1994
) most reports have concerned only one or a few cases.
A case of retrograde ejaculation was reported (Jimenez et al., 1997) in which pregnancy was achieved by ICSI using spermatozoa collected from the urine and cryopreserved. The authors suggested that, in infertile men with retrograde ejaculation, postcoital or postmasturbation spermatozoa recovered in voided urine may be cryopreserved so as to ensure its availability for ICSI.
A heterogeneous group of 17 couples with infertility following treatment for testicular cancer was also evaluated (Rosenlund et al., 1998). Seven of these men had retrograde ejaculation. In this study, 15 couples underwent a total of 21 treatment cycles resulting in 18 embryo transfers. Spermatozoa were obtained by transrectal electroejaculation in 16 cycles, by masturbation in three cycles, and by TESE in one. In one cycle, no spermatozoa were found using TESE. Fertilization and cleavage were achieved by IVF in seven cycles and by ICSI in 11 cycles; average fertilization rates of 57% and 55% respectively were achieved. In all, 12 clinical pregnancies occurred, of which one aborted in the first trimester. For the seven men who had retrograde ejaculation, transrectal electroejaculation resulted in a sufficient number of spermatozoa for IVF or ICSI in all cases.
With the increasing success of ICSI in all types of severe male factor infertility, use of this technique has become more widespread. Because the number and motility of the spermatozoa retrieved from urine is very difficult to predict and may, in some cases, be very poor, we have chosen to use only ICSI in these patients rather than IUI or IVF.
The group of patients described in this study is heterogeneous and illustrates the complex nature of infertility due to retrograde ejaculation. Some of them had been managed in the past with artificial insemination and surgical treatment, unsuccessfully. As expected, sperm count was highly variable between subjects. The urinary environment resulted in a marked reduction in sperm motility and in some samples total abolition of sperm movements was found. The motility ranged from 0 to 34%, while the total count of spermatozoa ranged from 0.01 to 75x106/ml before preparation. In almost all patients the spermatozoa had abnormal morphology. In some patients the quality of spermatozoa was extremely poor, eliminating the possibility of performing conventional IVF. For these couples, ICSI offered the last possibility of conceiving a child using assisted fertilization. With ICSI the fertilization rate averaged 51.2% and seven clinical pregnancies were achieved. Three spontaneous first trimester abortions occurred, but the other pregnancies were delivered or are ongoing.
In our opinion, infertility resulting from retrograde ejaculation that is resistant to medical treatment and of long duration can be managed by using assisted reproductive techniques and especially ICSI. Our results show that the aetiology of retrograde ejaculation appears to have no impact on the outcome with regard to fertilization rate and pregnancy rate when ICSI is utilized. In our study, there was a definite decrease in the sperm concentrations of men suffering from retrograde ejaculation.
In conclusion, in patients with retrograde ejaculation the use of ICSI may be feasible for couples in whom the men are resistant to medical treatment and have sperm quality which is so low or unpredictable that IUI or conventional methods of IVF are not possible.
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Notes |
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References |
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Submitted on February 5, 1999; accepted on May 25, 1999.