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Biomedical subjects

G R Dohle

Publications and source records attributed to G R Dohle.

At least 19 recordsLinked to original sources

Clinical correlates of the biological variation of sperm DNA fragmentation in infertile men attending an andrology outpatient clinic.

Determination of sperm DNA fragmentation, as assessed by the sperm chromatin structure assay (SCSA), has become an important tool for the evaluation of semen quality. The aim of the present study was to describe the biological variation of sperm DNA fragmentation in men attending an andrology clinic and to identify clinical correlates of the biological variation of sperm DNA fragmentation. For this study, two consecutive semen samples from 100 patients attending our andrology outpatient clinic were subjected to semen analysis, performed in parallel according to WHO guidelines and by SCSA. A good agreement between pairs of samples was found for SCSA-derived variables, as indicated by a significantly lower median coefficient of variation (CV) of the DNA Fragmentation Index (DFI) and the high DNA stainability (HDS) compared with WHO semen parameters. In half of the men attending our andrology clinic, however, the individual biological variation of DFI and HDS, expressed as CV of two samples, exceeded 10%. Dysregulation of spermatogenesis, as seen as testicular insufficiency or varicocele, was not associated with increased variability of DFI or HDS. A backward multiple linear regression analysis, however, indicated that the biological variation of DFI may be more profound in men with characteristics of normal spermatogenesis. In conclusion, we confirm previous reports that sperm DNA fragmentation has a lower biological variability than classical semen parameters. We hypothesize that the sperm chromatin structure may be more influenced in patients with normal spermatogenesis, whereas in men with disturbed spermatogenesis, the chromatin structure may be already so impaired that the effect of unidentified factors leading to variability of sperm DNA fragmentation in time may not be as profound.

Chromatin↗

[Revised guideline 'Vasectomy' from the Dutch Urological Association].

Vasectomy is a simple and reliable method of contraception. Problems associated with vasectomy include inadequate patient information, complications of the procedure e.g. infection and scrotal bleeding (4-22%), chronic scrotal pain after the procedure (2-5%) and spontaneous recanalisation with return of fertility (0.03-I12%). Later in life a substantial number of men come to regret having a vasectomy, notably those who underwent it at a young age and those without children of their own. After 10 years 2.4% of vasectomised Dutch men have a refertilisation procedure (usually a vasovasostomy) because of the wish for children in a new relationship. Since vasectomy is an elective procedure and not done on medical indication, it requires an extensive informed-consent procedure for the patient. Insufficient information may result in inadequate follow-up, omission of semen analysis, and consequent legal procedures should complications or pregnancy ensue. Clearance after the first semen analysis at 3 months can be given if azoospermia is seen or if less than 100,000 non-motile spermatozoa are present in the ejaculate.

Humans↗

[Microsurgical vasovasostomy at the Erasmus MC, 1998-2002: results and predictive factors].

OBJECTIVE: To determine the results ofmicrosurgical vasovasostomy procedures with special emphasis on the technical aspects and predictive factors for successful procedures. DESIGN: Descriptive. METHOD: In 1998-2002, 217 vasovasostomy procedures were performed in an outpatients' clinic setting at the Erasmus MC, Rotterdam, The Netherlands. RESULTS: Refertilisation was successful in 77% of men and 42% of couples reported a spontaneous pregnancy within one year. The most important predictive factors for a successful outcome were the interval between vasectomy and reversal and the age of the partner. Patency rates were 89% and 62% when the interval was < 5 years and > 15 years, respectively. Rates of spontaneous pregnancy were 56% and 21%, respectively. These reductions in rates of patency and pregnancy were attributed primarily to epididymal dysfunction and an increasing interval between vasectomy and reversal. Only 20% of men with a partner aged > 35 years reported spontaneous pregnancies. The risk of secondary epididymal obstruction was 25% after an interval of > 10 years. For these cases, a vasoepididymostomy is needed to achieve patency.

Adult↗

Clinical laboratory evaluation of male subfertility.

Male subfertility is a common problem with a complex etiology, requiring a complete andrological work-up for proper diagnosis. The male reproductive tract is controlled by a well-balanced hormonal system, in which hypothalamic (GnRH), pituitary (LH, FSH) and testicular hormones (androgens, inhibin B) participate. Any disturbance of this hormonal system may therefore lead to testicular dysfunction and interfere with the spermatogenesis process. In addition, also other components along the ductal system, such as epididymis, prostate and seminal vesicles, that improve sperm fertility by contributing their secretions to the semen, might function inadequately and thus fail to enhance the fertilizing capacity of the sperm cells. External factors (heat, chemicals, life style) and anatomical abnormalities (varicocele) were shown to have a negative influence on male fertility. In a number of patients genetic defects can be identified as the cause of their infertility. Laboratory tests are available to assess hormone concentrations, semen composition, accessory gland function and sperm cell function. Conventional semen analysis includes the determination of sperm concentration, semen volume, sperm motility (qualitative and quantitative), sperm morphology, sperm cell vitality, pH, leucocytes and antibodies. The usefulness of the determination of these parameters as predictor of fertility appears to be rather limited, however. Therefore, alternative tests, some based on more functional aspects (sperm penetration, capacitation, acrosome reaction), have been developed. Furthermore, there is an increasing attention for the assessment of DNA integrity, for instance by the flowcytometer-based Sperm Chromation Structure Assay (SCSA), as an additional or alternative parameter of sperm quality. It is likely and desirable that further assays with better predictive value are being developed in the near future.

Fertilization↗

Bilateral testicular microlithiasis predicts the presence of the precursor of testicular germ cell tumors in subfertile men.

PURPOSE: A high prevalence of testicular microlithiasis has been described in adolescent and adult clinical cases of invasive testicular germ cell tumor (TGCT), that is seminomas and nonseminomas. However, to our knowledge it remains to be established whether testicular microlithiasis also indicates the presence of the pre-invasive lesion of this cancer, known as carcinoma in situ (CIS). We determined the predictive value of unilateral and bilateral testicular microlithiasis for CIS in subfertile men, a known risk population for TGCTs (approximately 1%). MATERIALS AND METHODS: In a retrospective cross-sectional study the association between testicular microlithiasis and CIS was studied in a group of 263 men referred for subfertility. Testicular microlithiasis and CIS were diagnosed in all men by scrotal ultrasound and in testicular histology specimens as part of the routine evaluation of all patients. RESULTS: Of the 263 subfertile men 53 (20%) had testicular microlithiasis. No CIS or TGCT was identified in the 23 men with unilateral testicular microlithiasis. In contrast, 6 of the 30 men (20%) with bilateral testicular microlithiasis were diagnosed with CIS. Therefore, the prevalence of CIS in subfertile men with bilateral testicular microlithiasis is significantly higher than in patients without testicular microlithiasis (1 of 210, 0.5%) and with unilateral testicular microlithiasis (0 of 23, 0%) (p <0.0001). CONCLUSIONS: Bilateral testicular microlithiasis is indicative for CIS in subfertile men. Since these men are at particular risk for invasive TGCT, an assessment of testicular microlithiasis is a valuable tool for the early diagnosis of this disease.

Adult↗

[Post mortem semen acquisition: not without 'informed consent'].

Recently, two requests for post-mortem semen acquisition were evaluated and rejected. The first request was from the wife of a man who died after the wedding night. In the second case, the wife requested that electroejaculation be done on a man who was brain dead because of a gunshot wound in the head. In both cases, the fact that there was no written consent from the men involved before they died was the deciding reason not to grant the requests. Written consent is legally and ethically seen as the final episode of a period in which persons have considered the consequences of the acquisition, storage and use of semen after the death of the husband.

Adult↗

Male contraception: mechanical, hormonal and non-hormonal methods.

There is a definite need for an effective and reversible form of male contraception, both for maintaining a stable population in industrial countries and for diminishing population growth in developing countries. It has been agreed upon that contraception is an essential component of reproductive health for men and women (the Weimar Manifesto on Male Contraception). The development of new, effective methods of male contraception has been identified as a high priority by the WHO Task Force on methods of regulation of male fertility. Hormonal male contraception is based on suppression of gondotrophins and substitution of testosterone in order to maintain male sexual function and bone mineralisation and to prevent muscle waist. For complete interruption of spermatogenesis, an adequate suppression of intratesticular testosterone production is needed. Various contraceptive regimens have been developed and tested, including testosterone monotherapy, androgen/progestin combinations, testosterone with GnRH analogs, and selective androgen and progestin receptor modulators. The combination of testosterone with progestogen is currently the most promising approach to hormonal male contraception. Also, several non-hormonal approaches to male contraception are promising and may offer the foundation for developing new male contraceptives.

Condoms↗

Androgens and male fertility.

Androgens play a crucial role in the development of male reproductive organs such as the epididymis, vas deferens, seminal vesicle, prostate and the penis. Furthermore, androgens are needed for puberty, male fertility and male sexual function. High levels of intratesticular testosterone, secreted by the leydig cells, are necessary for spermatogenesis. Intratesticular testosterone is mainly bound to androgen binding protein and secreted into the seminiferous tubules. Inside the sertoli cells, testosterone is selectively bound to the androgen receptor and activation of the receptor will result in initiation and maintenance of the spermatogenic process and inhibition of germ cell apoptosis. The androgen receptor is found in all male reproductive organs and can be stimulated by either testosterone or its more potential metabolite dihydrotestosterone. Severe defects of the androgen receptor may result in abnormal male sexual development. More subtle modulations can be a potential cause of male infertility. Treatment of an infertile man with testosterone does improve spermatogenesis, since exogenous administrated testosterone and its metabolite estrogen will suppress both GnRH production by the hypothalamus and Luteinising hormone production by the pituitary gland and subsequently suppress testicular testosterone production. Also, high levels of testosterone are needed inside the testis and this can never be accomplished by oral or parenteral administration of androgens. Suppression of testosterone production by the leydig cells will result in a deficient spermatogenesis, as can be seen in men taking anabolic-androgenic steroids. Suppression of spermatogenesis by testosterone administration is also the basis for the development of a male contraceptive. During cytotoxic treatment or irradiation suppression of intratesticular testosterone production cells may prevent irreversible damage to the spermotogonial stem cells.

Androgens↗

Subtotal obstruction of the male reproductive tract.

Bilateral obstruction of the male reproductive tract is suspected in men with azoospermia, normal testicular volume and normal FSH. A testicular biopsy is required to differentiate between an obstruction and a testicular insufficiency. Unilateral or subtotal bilateral obstructions and epididymal dysfunction may cause severe oligozoospermia in men with a normal spermatogenesis. However, information on spermatogenesis in oligozoospermic men is lacking, since testicular biopsy is not routinely performed. Men with a sperm concentration of <1 x 10(6) spermatozoa/ml were investigated for possible partial obstruction by performing a testicular biopsy under local anaesthesia. Spermatogenesis was determined by the Johnsen scoring method. A testicular biopsy was performed in 78 men with severe oligozoospermia. The medical history showed male accessory gland infection in 12.8%, previous hernia repair in 14.1% and a history of cryptorchidism in 12.8%. A normal or slightly disturbed spermatogenesis (Johnsen score >8) was present in 39/78 (50%) of the men. Hernia repair occurred more often in men with normal spermatogenesis. A varicocele was predominantly seen in men with a disturbed spermatogenesis. FSH was significantly lower ( P<0.0001) in men with normal spermatogenesis. Subtotal obstruction of the male reproductive tract is a frequent cause of severe oligozoospermia in men with a normal testicular volume and a normal FSH. In other cases, an epididymal dysfunction might explain the oligozoospermia in men with a normal testicular biopsy score.

Biopsy↗

The effect of cryptorchidism on inhibin B in a subfertile population.

OBJECTIVE: Prepubertal cryptorchidism may cause fertility problems in adulthood, due to impaired spermatogenesis. Serum inhibin B has emerged as an accurate marker of spermatogenesis. The aim of this study was to evaluate the impact of a history of cryptorchidism on serum inhibin B levels and other markers of spermatogenesis in subfertile men. PATIENTS AND MEASUREMENTS: In a retrospective study, the effect of cryptorchidism on inhibin B, FSH, LH, free testosterone, testicular volume and semen parameters was assessed in a case-control study within a population of 2613 subfertile men. Of these, 161 and 102 subjects had a history of, respectively, unilateral and bilateral cryptorchidism that was treated by orchiopexy in childhood. Hormone data were complete for 64 cryptorchid patients (32 unilateral and 32 bilateral). A group of 128 patients was randomly selected out of the remaining group of 2350 men with idiopathic subfertility. An additional control group consisted of 32 fertile men from the general population. RESULTS: In cryptorchid subfertile men, inhibin B concentrations were significantly lower than in noncryptorchid subfertile men and fertile men (103 ng/l, 143 ng/l and 148 ng/l, respectively; P < 0.01). The FSH concentration was significantly higher in cryptorchid men vs. noncryptorchid men and controls (6.1 IU/l vs. 3.3 and 2.9 IU/l, respectively; P < 0.01). Testicular volumes and sperm concentration of cryptorchid men were significantly lower than in noncryptorchid subfertile men (12 vs. 15 ml, P < 0.01 and 3.8 x 10(6) sperm/ml vs. 17.4 x 10(6) sperm/ml; P < 0.05). A significantly higher inhibin B level and sperm concentration was observed in men undergoing orchiopexy at an early age (1-4 years) compared with men treated between 5 and 9 years or later (P < 0.05). CONCLUSION: Spermatogenesis is more impaired in cryptorchid subfertile men compared to men with idiopathic subfertility, as reflected by a lower inhibin B concentration.

Adult↗

Inflammatory-associated obstructions of the male reproductive tract.

A history of urogenital inflammation occurs in 5-12% of men attending infertility clinics. Usually, infection has a detrimental effect on sperm quality by reducing concentration and motility, and possibly affecting the number of morphological normal spermatozoa. In addition, infection may be the source of auto-antibodies against spermatozoa, found in about 8% of the infertile male population. In contrast to the situation in women, there is no clear evidence that male accessory gland infections can result in epididymal blockage or vassal obstruction, with the exception of genital tuberculosis. Although Chlamydia trachomatis is a well-documented source of chronic prostatitis, the infection does not seem to cause obstruction of the reproductive tract, as it does in women. If male urogenital infection causes obstruction it is most likely located at the level of the ejaculatory ducts. Chronic prostatitis has been proved to cause scarring of the prostatic and ejaculatory ducts, resulting in low seminal volume with low fructose and alpha-glucosidase. Many of these men present with severe oligozoospermia or azoospermia, normal size testis and normal gonadotrophins. We performed an excisional testicular biopsy in all men presenting with <1 million spermatozoa per millilitre and found that 39 of 78 (50%) had a normal spermatogenesis. A history of male accessory genital infection was found in 12% of the men and 10% had abnormalities found on transrectal ultrasound of the prostate (like oedema, dilatation of the seminal vesicles and ejaculatory ducts) intraprostatic calcifications and dilatation of the periprostatic venous plexus. Ejaculatory duct obstruction is a common cause of male infertility and infections are present in at least 22-50% of these men. Transurethral resection of the ejaculatory ducts may result in a significant improvement of the sperm quality and in spontaneous pregnancies in up to 25% of the couples. In case of failure sperm aspiration from the epididymis and intracytoplasmic sperm injection is the treatment of choice.

Adult↗

The limited practical value of color Doppler sonography in the differential diagnosis of men with erectile dysfunction.

From the files of the outpatient urology department 44 men with ED had undergone both psychophysiological diagnostic screening (PDS, VSS, VSS+VIB, ICI+VSS+VIB) and color Doppler sonography testing (CDS, including VSS). PDS was carried out by one medical physiologist, CDS by one urologist. The diagnoses reached could be compared. This study revealed that CDS in ED-patients often resulted in an incorrect diagnosis, that is a presumed vascular abnormality while many such patients demonstrated firm erections under PDS-laboratory test conditions. Thus, it was concluded that CDS as a (first) screening test in ED-patients is of limited value. It was further emphasized that PDS, although giving quite relevant information about possible etiology and therapeutic treatment, is not a necessary first screen. Good history taking, preferably of the man and his partner, is still the basic first screen and quite often offers enough information to make a treatment plan with reasonable likelihood of success.

Adult↗

Intracavernosal injection therapy with and without sexological counselling in men with erectile dysfunction.

OBJECTIVE: To compare the acceptance of and satisfaction with intracavernosal injection (ICI) therapy with and without sexological counselling in men with erectile dysfunction (ED). PATIENTS AND METHODS: In a prospective randomized study, men were alternately assigned to ICI without sexological counselling (-SC) or with sexological counselling (+SC). In all, 70 patients were included, i.e. 35 in each group; 57 (28 -SC, 29 +SC) were interviewed by telephone after a mean follow-up of 11.3 months to determine their use of ICI and reasons for discontinuing. RESULTS: There were no differences between the groups in discontinuation of ICI (overall 30%), in reasons for discontinuing ICI (24% did so because of the return of spontaneous erections) or in sexual functioning. CONCLUSION: There was no positive contribution from additional sexological counselling but extensive information and support by the urologist seems to be sufficient, resulting in a high acceptance rate of ICI. The discontinuation rate (30%) is one of the lowest reported.

Adult↗

Genetic risk factors in infertile men with severe oligozoospermia and azoospermia.

BACKGROUND: Male infertility due to severe oligozoospermia and azoospermia has been associated with a number of genetic risk factors. METHODS: In this study 150 men from couples requesting ICSI were investigated for genetic abnormalities, such as constitutive chromosome abnormalities, microdeletions of the Y chromosome (AZF region) and mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. RESULTS: Genetic analysis identified 16/150 (10.6%) abnormal karyotypes, 8/150 (5.3%) AZFc deletions and 14/150 (9.3%) CFTR gene mutations. An abnormal karyotype was found both in men with oligozoospermia and azoospermia: 9 men had a sex-chromosomal aneuploidy, 6 translocations were identified and one marker chromosome was found. Y chromosomal microdeletions were mainly associated with male infertility, due to testicular insufficiency. All deletions identified comprised the AZFc region, containing the Deleted in Azoospermia (DAZ) gene. CFTR gene mutations were commonly seen in men with congenital absence of the vas deferens, but also in 16% of men with azoospermia without any apparent abnormality of the vas deferens. CONCLUSIONS: A genetic abnormality was identified in 36/150 (24%) men with extreme oligozoospermia and azoospermia. Application of ICSI in these couples can result in offspring with an enhanced risk of unbalanced chromosome complement, male infertility due to the transmission of a Y-chromosomal microdeletion, and cystic fibrosis if both partners are CFTR gene mutation carriers. Genetic testing and counselling is clearly indicated for these couples before ICSI is considered.

Chromosome Aberrations↗

Increased serum inhibin B levels after varicocele treatment.

OBJECTIVE: Inhibin B is secreted by Sertoli cells in response to FSH and is the major feedback regulator of FSH secretion in man. The serum inhibin B level has emerged as a good marker of spermatogenesis and Sertoli cell function. Varicocele has been associated with infertility and disturbed spermatogenesis. We have studied the effect of varicocele treatment on serum inhibin B levels, with the aim of investigating the effect on spermatogenesis and the involvement of the Sertoli cell in varicocele pathophysiology. DESIGN AND PATIENTS: In a pre-post test design, the effect of varicocele surgery on inhibin B levels was studied in 30 infertile men. MEASUREMENTS: Endocrinology (inhibin B, FSH, LH, SHBG and testosterone) and semen analysis (sperm concentration, motility and morphology). RESULTS: In men receiving varicocele treatment, a significant increase in serum inhibin B levels was observed from 133.9 +/- 13.4 pretreatment to 167.8 +/- 16.1 ng/l after treatment (mean +/- SEM, P < 0.0001). No significant changes were observed in serum levels of FSH, LH and testosterone. The serum SHBG level decreased from 32.9 +/- 3.5 to 28.6 +/- 3.4 nmol/l (mean +/- SEM, P = 0.04) and the free androgen index was significantly increased from 66 +/- 5.9 pretreatment to 85 +/- 6.8 after treatment (P = 0.02, mean +/- SEM). Semen analysis showed a significant improvement in sperm concentration, from 6.5 +/- 1.9 pretreatment to 19.3 +/- 4.9 x 106/ml after treatment (P = 0.003, mean +/- SEM), and in sperm motility from the baseline level of 17 +/- 3 to 32 +/- 4% after treatment (P = 0.001, mean +/- SEM). CONCLUSIONS: Varicocele treatment can increase serum inhibin B levels, indicating improvement of spermatogenesis and Sertoli cell function. This finding suggests that the pathophysiology of varicocele involves impairment of Sertoli cell function or a different distribution of germ cell stages.

Adult↗