Marij Smit

Decreased Sperm DNA Fragmentation After Surgical Varicocelectomy is Associated With Increased Pregnancy Rate

PURPOSE We prospectively evaluated changes in sperm chromatin structure in infertile patients before and after surgical repair of varicocele, and the impact on the pregnancy rate. MATERIALS AND METHODS Included in the study were 49 men with at least a 1-year history of infertility, a palpable varicocele and oligospermia. World Health Organization semen analysis and sperm DNA damage expressed as the DNA fragmentation index using the sperm chromatin structure assay were assessed preoperatively and postoperatively. Pregnancy (spontaneous and after assisted reproductive technique) was recorded 2 years after surgery. RESULTS Mean sperm count, sperm concentration and sperm progressive motility improved significantly after varicocelectomy from 18.3 x 10(6) to 44.4 x 10(6), 4.8 x 10(6)/ml to 14.3 x 10(6)/ml and 16.7% to 26.6%, respectively (p <0.001). The DNA fragmentation index decreased significantly after surgery from 35.2% to 30.2% (p = 0.019). When the definition of greater than 50% improvement in sperm concentration after varicocelectomy was applied, 31 of 49 patients (63%) responded to varicocelectomy. After varicocelectomy 37% of the couples conceived spontaneously and 24% achieved pregnancy with assisted reproductive technique. The mean postoperative DNA fragmentation index was significantly higher in couples who did not conceive spontaneously or with assisted reproductive technique (p = 0.033). CONCLUSIONS After varicocelectomy sperm parameters significantly improved and sperm DNA fragmentation was significantly decreased. Low DNA fragmentation index values are associated with a higher pregnancy rate (spontaneous and with assisted reproductive technique). We suggest that varicocelectomy should be considered in infertile men with palpable varicocele, abnormal semen analysis and no major female factors.

Low folate in seminal plasma is associated with increased sperm DNA damage

OBJECTIVE To determine associations between vitamin B status, homocysteine (tHcy), semen parameters, and sperm DNA damage. DESIGN Observational study. SETTING A tertiary referral fertility clinic. PATIENT(S) Two hundred fifty-one men of couples undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment, with subgroups of fertile (n = 70) and subfertile men (n = 63) defined according to semen concentration and proven fertility. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) The DNA fragmentation index (DFI) as marker of sperm DNA damage determined using the sperm chromatin structure assay (SCSA), and semen parameters assessed according to World Health Organization criteria; tHcy, folate, cobalamin, and pyridoxine concentrations determined in seminal plasma and blood. RESULT(S) In the total group of fertile and subfertile men, all biomarkers in blood were statistically significantly correlated with those in seminal plasma. No correlation was found between the biomarkers in blood and the semen parameters. In seminal plasma, both tHcy and cobalamin positively correlated with sperm count. Folate, cobalamin, and pyridoxine were inversely correlated with ejaculate volume. In fertile men, seminal plasma folate showed an inverse correlation with the DNA fragmentation index. CONCLUSION(S) Low concentrations of folate in seminal plasma may be detrimental for sperm DNA stability.

Sperm chromatin structure is associated with the quality of spermatogenesis in infertile patients

OBJECTIVE To establish the diagnostic value of sperm chromatin structure assessment for the evaluation of male factor infertility, in addition to conventional andrological workup. DESIGN Cross-sectional controlled study. SETTING A tertiary referral andrology clinic. PATIENT(S) Two hundred seventy-nine male partners of infertile couples. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) The DNA fragmentation index (DFI) determined by the sperm chromatin structure assay (SCSA), semen parameters, serum levels of reproductive hormones, and World Health Organization (WHO) classification of male factor subfertility. RESULT(S) In all patient categories, except those including patients with hypogonadotrophic hypogonadism, sperm antibodies, or normospermia, DFI was significantly higher compared with in proven fertile controls. After classification of the quality of spermatogenesis based on mean testicular volume (<10 ml vs. >15 ml), follicle stimulating hormone (FSH; > 10 U/L vs. <5 U/L), and inhibin-B (<100 nmol/L vs. >150 nmol/L), the DFI was significantly higher in patients with poor spermatogenesis (35.9%) than in patients with normal spermatogenesis (25.9%). In a multiple regression analysis, the teratozoospermia index, sperm vitality, and FSH were significant determinants of the DFI level. Male age was associated with DFI, but leukocytospermia, body mass index, and smoking were not confounders of DFI. CONCLUSION(S) Impaired spermatogenesis, irrespective of the WHO classification of male factor subfertility, is generally associated with an increase of sperm DNA damage.

Sperm DNA integrity in cancer patients before and after cytotoxic treatment

BACKGROUND We assessed sperm DNA fragmentation index (DFI) in cancer patients before and after treatment to evaluate if sperm DNA integrity is compromised by cancer itself or its treatment. METHODS In a prospective study, DFI was assessed in 127 patients diagnosed with testicular germ cell tumours (TGCT), Hodgkins lymphoma (HL), non-Hodgkins lymphoma (NHL) and various malignancies. The severity of cancer and tumour markers at diagnosis was recorded. Follow-up DFI after treatment was available in 52 patients who were mostly less severely affected. RESULTS In patients diagnosed with TGCT, HL and various malignancies, pretreatment DFI levels were not significantly different from that of proven fertile controls, but in patients with NHL an increased DFI was found. An overall significant decrease in post-treatment DFI (13.2% range 5.0-70.5) compared with pretreatment values (17.1% range 5.1-66.6) was found (P = 0.040). In TGCT patients, post-treatment DFI was significantly higher in patients who were treated with radiotherapy (16.9% range 11.5-39.9) compared with that in patients treated with chemotherapy (CT) alone (10.9% range 5.5-39.9) (P = 0.037). In HL patients, the type of treatment or number of CT cycles was not associated with DFI. Overall, post-treatment DFI in cancer patients was not significantly different from that of proven fertile controls. CONCLUSIONS In this study, the presence of cancer does not seem to negatively affect the sperm DNA integrity in TGCT and HL patients; only NHL patients showed increased DFI at the time of diagnosis compared with healthy controls. Our results confirm previous reports that DFI decreases significantly following various anti-cancer treatments. In contrast, radiotherapy in TGCT patients is associated with an increase in DFI compared with CT treatment alone.

Determinants of ejaculatory dysfunction in a community-based longitudinal study.

Associate Editor

Surveillance with microsatellite analysis of urine in bladder cancer patients treated by radiotherapy

OBJECTIVES The interpretation of cystoscopy and cytology may be troublesome in bladder cancer patients previously treated by radiotherapy. We evaluated polymerase chain reaction (PCR)-based molecular cytology by microsatellite analysis (MA) and routine urine cytology (RUC) and expert urine cytology (EUC) as modes of surveillance for patients previously treated by radiotherapy with curative intent. METHODS Eighty-one voided urine samples were obtained from 49 patients prior to cystoscopy and subjected to MA, RUC and EUC. RESULTS During the follow-up period, six patients developed a recurrence. Sensitivity of MA, RUC and EUC was 83%, 50% and 33%, respectively. The specificity of MA, RUC and EUC was 93%, 85% and 97%, respectively. Cystoscopy was positive in 15 cases. Therefore, the positive predictive value of cystoscopy remained limited to 40%. CONCLUSIONS Next to recent studies demonstrating a high accuracy for MA in non-irradiated patients, our results indicate that molecular cytology by MA may also be a useful tool to improve the surveillance of bladder cancer patients previously treated by radiotherapy.

Increased Sperm DNA Fragmentation in Patients With Vasectomy Reversal Has No Prognostic Value for Pregnancy Rate

PURPOSE We evaluated sperm DNA fragmentation in patients with vasectomy reversal and its prognostic value to determine spontaneous and assisted reproductive technique pregnancy rates. MATERIALS AND METHODS We prospectively assessed DNA fragmentation with the sperm chromatin structure assay in postoperative semen samples of 70 patients with vasectomy reversal. At a median +/- SD followup of 4.3 +/- 0.5 years pregnancy rates were recorded. RESULTS DNA fragmentation in patients with vasectomy reversal was significantly increased vs that in proven fertile controls (30.2% +/- 20.1% vs 15.3% +/- 5.4%, p <0.001). Significant negative correlations were found between DNA fragmentation index and total sperm count, progressive motility, total number of progressive sperm, normal morphology and sperm vitality (-0.325 <r <-0.805). The obstructive interval did not correlate with DNA fragmentation. The spontaneous pregnancy rate was 46%. Significantly higher log total progressive sperm motility (p = 0.021) and a trend toward lower female age (p = 0.064) were detected in the spontaneous vs the no pregnancy group. No association was found between DNA fragmentation and the pregnancy rate. CONCLUSIONS Increased DNA fragmentation is present in semen samples of men after vasectomy reversal vs fertile controls but DNA fragmentation is not associated with spontaneous or assisted reproductive technique pregnancy rates in these patients.

Preventing stone migration during percutaneous nephrolithotomy by using the stone cone.

During percutaneous nephrolithotomy (PCNL) stone fragments sometimes pass into the ureter. In most cases these fragments will evacuate spontaneously but they may prolong the nephrostomy tube dwelling time and hospital stay. Occasionally additional treatment is necessary (ESWL or ureteroscopy). Lang et al. [1] reported 72 cases of ureteric obstruction after 8592 percutaneous stone removals. Albala et al. [2] found one case of debris migration in 57 procedures, Jones et al. [3] 31 in 1000 cases and Gleeson et al. [4] reported one ureteric obstruction in 39 patients. Here we describe an easy way to prevent the passage of stone fragments into the ureter.

Reperméabilisation microchirurgicale après vasectomie. Résultats et facteurs de réussite

ResumeLa reperméabilisation microchirurgicale post-vasectomie constitue un défi pour le médecin mais le succès du traitement repose sur l’expérience et l’adresse du chirurgien. La fécondité peut être souvent restaurée, épargnant ainsi le recours aux techniques de reproduction artificielles. Les procédures chirurgicales peuvent aussi être combinées avec le recueil de spermatozoïdes et la cryopréservation, permettant une utilisation pour l’injection intracytoplasmique d’un spermatozoïde (ICSI) en cas d’échec de la chirurgie. Nous rapportons les résultats de 217 procédures de vaso-vasostomie, en faisant ressortir plus particulièrement les dernières subtilités techniques ainsi que les indicateurs pronostiques.Entre 1998 et 2002, nous avons réalisé 217 procédures de vaso-vasostomie dans le cardre d’un centre de référence. Une reperméabilisation a été obtenue dans 76,5% des cas, une grossesse spontanée est survenue chez 42% des couples après un suivi d’au moins 1 an. Les principaux facteurs déterminant l’issue de la chirurgie sont l’intervalle écoulé entre la vasectomie et la reperméabilisation ainsi que l’âge de la partenaire: la reperméabilisation a été de 89% après un intervalle de moins de 5 ans avec la survenue d’une grossesse chez 56% de ces couples. Après un intervalle de plus de 10 ans, la reperméabilisation diminue à 75% et le taux de grossesse tombe à 24%. Une dysfonction de l’épididyme, avec une mauvaise mobilité des spermatozoïdes, et une obstruction secondaire de l’épididyme sont fréquentes après un intervalle long. En outre, chez les couples dont la partenaire est âgée de plus de 35 ans, le taux de grossesse n’est que de 21%, indiquant qu’une réserve ovarienne limitée constitue un facteur important pour le résultat final.Chez les hommes ayant un long intervalle obstructif entre la vasectomie et la reperméabilisation, une obstruction de l’épididyme peut survenir par éclatement du canal épididymaire avec une fuite secondaire du liquide épididymaire et des spermatozoïdes dans l’organe et une fibrose. Une procédure de vaso-épididymostomie est nécessaire pour traiter cette obstruction. Récemment, des subtilités techniques, telle que la technique de l’invagination, ont été introduites pour la procédure de vaso-épididymostomie, donnant des premiers résultats prometteurs. Cette technique simplifiée permet à des micro-chirurgiens moins expérimentés de réaliser cette difficile opération avec succès.Les résultats de la reperméabilisation post-vasectomie peuvent être augmentés de façon substantielle si le chirurgien est capable de réaliser une vaso-épididymostomie lors d’une obstruction épididymaire secondaire, ce qui arrive chez environ 25% des hommes qui ont un intervalle de plus de 10 ans.AbstractMicrosurgical vasectomy reversal is a challenge for the physician but successful treatment depends on the experience and skills of the surgeon. Fertility can often be restored, thus avoiding the need for artificial reproductive techniques. Also, the surgical procedures can be combined with sperm aspiration and cryopreservation, to be used for Intracytoplasmic sperm injection (ICSI) in cases of surgical failure. We describe the results of 217 vasovasostomy procedures, with special emphasis on recent technical refinements and prognostic indicators.Between 1998 and 2002 we performed 217 vasovasostomy-procedures in an outpatient clinic setting. Refertilisation was successful in 76.5%, spontaneous pregnancy occurred in 42% of the couples after a follow-up of at least 1 year. The main prognostic factors determining the outcome of the surgery was the interval between vasectomy and refertilisation and the age of the female partner: patency was 89% after an interval of less than 5 years and pregnancy occurred in 56% of these couples. After an interval of more than 10 years patency decreased to 75% and pregnancy results dropped to 24%. Epididymal dysfunction with poor motility score and secondary epididymal obstruction appeared to be common after a long interval. Furthermore, in men with partners older than 35 years of age pregnancy was only 21%, indicating limited ovarian reserve as an important factor in determining the final outcome.In men with a long obstructive interval between vasectomy and reversal an obstruction of the epididymis can be found due to a blow-out of the epididymal tubule with subsequent leakage of semen in the organ and fibrosis. A vaso-epididymostomy procedure is needed to treat the obstruction. Recently, surgical refinements, such as the invagination technique, have been introduced for the vaso-epididymostomy procedure, showing promising first results. This simplified technique enables less experienced microsurgeons to perform this difficult operation successfully. The results of vasectomy reversal procedures can be improved substantially if the surgeon is able to perform a vaso-epididymostomy in cases of a secondary epididymal obstruction, occurring in about 25% of men with an interval of more than 10 years.

Microsurgical vasectomy reversal : results and predictors of success

Microsurgical vasectomy reversal is a challenge for the physician but successful treatment depends on the experience and skills of the surgeon. Fertility can often be restored, thus avoiding the need for artificial reproductive techniques. Also, the surgical procedures can be combined with sperm aspiration and cryopreservation, to be used for Intracytoplasmic sperm injection (ICSI) in cases of surgical failure. We describe the results of 217 vasovasostomy procedures, with special emphasis on recent technical refinements and prognostic indicators.Between 1998 and 2002 we performed 217 vasovasostomy-procedures in an outpatient clinic setting. Refertilisation was successful in 76.5%, spontaneous pregnancy occurred in 42% of the couples after, a follow-up of at least 1 year. The main prognostic factors determining the outcome of the surgery was the interval between vasectomy and refertilisation and the age of the female partner: patency was 89% after an interval of less than 5 years and pregnancy occurred in 56% of these couples. After an interval of more than 10 years patency decreased to 75% and pregnancy results dropped to 24%. Epididymal dysfunction with poor motility score and secondary epididymal obstruction appeared to be common after a long interval. Furthermore, in men with partners older than 35 years of age pregnancy was only 21%, indicating limited ovarian reserve as an important factor in determining the final outcome.In men with a long obstructive interval between vasectomy and reversal an obstruction of the epididymis can be found due to a blow-out of the epididymal tubule with subsequent leakage of semen in the organ and fibrosis. A vaso-epididymostomy procedure is needed to treat the obstruction. Recently, surgical refinements, such as the invagination technique, have been introduced for the vaso-epididymostomy procedure, showing promising first results. This simplified technique enables less experienced microsurgeons to perform this difficult operation successfully. The results of vasectomy reversal procedures can be improved substantially if the surgeon is able to perform a vaso-epididymostomy in cases of a secondary epididymal obstruction, occurring in about 25% of men with an interval of more than 10 years.