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Biomedical subjects

Daniel R Franken

Publications and source records attributed to Daniel R Franken.

6 recordsLinked to original sources

The clinical significance of sperm-zona pellucida binding: 17 years later.

The development of homologous functional bio-assays for sperm quality assessment has been a focal point of reproductive biologists in order to provide a scientifically- based diagnosis in cases of fertilization failure. The availability of viable oocytes still remains an important limiting factor for laboratories to embark on the methodology of assays that examine sperm-oocyte interaction. The use of zonae pellucidae obtained from oocytes derived from post mortem tissue and failed in vitro fertilization cycles, enhanced the availability of zona material. Sperm-zona pellucida binding has been illustrated to be an essential requisite during human fertilization. This fundamental biological step can be measured under hemizona assay as well intact-oocyte test conditions. The sensitivity and specificity of sperm-zona binding results indicated the assay to be positively and significantly correlated with in vitro fertilization outcome. Furthermore, highly significant correlations were demonstrated between normal sperm morphology, hyperactivated motility, sperm creatine kinase activity and the zona binding capacity of a given sperm sample. It was concluded that andrology testing remains an ever-growing component in the work-up of the infertile couple. We enter the next millennium with many questions that remain to be answered by the hand of efficacious screening techniques and a new formidable therapy in intracytoplasmic sperm injection.

Animals↗

Effect of acute in vivo sildenafil citrate and in vitro 8-bromo-cGMP treatments on semen parameters and sperm function.

OBJECTIVE: To determine the effect of acute in vivo sildenafil citrate (VIAGRA) and in vitro 8-Bromo-cGMP treatments on semen parameters and sperm function. DESIGN: Prospective double-blind, placebo-controlled, crossover, two-period clinical investigation. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Twenty male volunteers with normal erectile function and normal electrocardiogram were recruited. INTERVENTION(S): In vivo: 50 mg of sildenafil citrate (VIAGRA) or placebo was administered p.o., and semen samples were collected 1 hour after administration of the test drug. In vitro: 8-Bromo-cGMP (20 microM; 60 minutes) was added to semen samples. MAIN OUTCOME MEASURE(S): Macroscopic and microscopic seminal parameters were measured and motility studies performed. Various acrosome reaction studies and sperm-zona pellucida binding studies were also done. RESULT(S): Either sildenafil citrate (VIAGRA) or 8-Bromo-cGMP treatments had no effect on both macroscopic and microscopic seminal parameters as well as the acrosome reaction. Sperm-zona pellucida binding results were however increased to 148.75% and 134%, respectively, by these treatments. Various kinematical parameters increased after treatment with the most significant increase detected in the population of rapid cells. CONCLUSION(S): VIAGRA can be used successfully to enhance sperm motility and binding to the oocyte especially during fertility treatments.

Acrosome Reaction↗

Relationship between zona pellucida-induced acrosome reaction, sperm morphology, sperm-zona pellucida binding, and in vitro fertilization.

OBJECTIVE: To evaluate the possible relationships between sperm morphology, acrosome responsiveness to solubilized human zona pellucida, and sperm-zona binding potential among [1] consecutive andrology referrals and [2] randomly selected in vitro fertilization (IVF) cases. DESIGN: Prospective analytical study. SETTING: Academic training hospital.Randomly selected couples consulting for infertility. INTERVENTION(S): Acrosome reaction response to solubilized human zona pellucida was recorded. MAIN OUTCOME MEASURE(S): We determined the difference in the percentage of sperm that acrosome reacted after exposure to solubilized zona pellucida and spontaneous acrosome reaction. The results were expressed as percentage zona induced acrosome reaction (ZIAR). RESULT(S): Data were analyzed using correlation coefficients (r) and receiver operator characteristics (ROC curve analyses). The ROC curve analyses indicated ZIAR to be a sensitive indicator for fertilization failure during IVF therapy, with sensitivity and specificity of 81% and 75%, respectively. For andrology referrals, a positive and statistically significant correlation existed between ZIAR data and sperm morphology (r = 0.65) and sperm-zona binding (r = 0.57). CONCLUSION(S): ZIAR results provide further information regarding dysfunctional sperm and can be used as an additional diagnostic test. Our results predicted fertilization failure during IVF treatment.

Acrosome Reaction↗

Monitoring technologist reading skills in a sperm morphology quality control program.

OBJECTIVE: The value of sperm morphology as a predictor of a man's fertilizing potential has often been challenged because of different classification systems used to distinguish between normal and abnormal spermatozoa. The study aimed to monitor the reading skills of 53 laboratory technologists who are enrolled in a continuous quality control program for sperm morphology assessment. DESIGN: Prospective analytical study. SETTINGS: Academic hospital and academic institution setting. PATIENT(S): Sperm samples from the sperm donor program and andrology technicians from sub-Saharan Africa. INTERVENTION(S): Papanicolaou-stained sperm slides were prepared and shipped on a quarterly basis to participating laboratories. Papanicolaou-prestained sperm morphology slides were used as test material for 21 months. MAIN OUTCOME MEASURE(S): Percentage normal spermatozoa.A new statistical model was developed to record reading skills of the participating technicians. Reading skills were classified as marginal (5.7% of cases), good (11.3% of cases), and excellent (83% of cases). RESULT(S): Participants maintained their morphological reading skills and agreed with the reference laboratory by not exceeding a SD limit of 0.2 to set stringent standards for the program. CONCLUSION(S): Technician proficiency can be monitored using the results of a quality control program. A continuous quality control program can be initiated only after intensive training, because baseline values at the onset of the quality control program serves as an internal reference value.

Clinical Competence↗

Zona pellucida-induced acrosome reaction in human sperm: dependency on activation of pertussis toxin-sensitive G(i) protein and extracellular calcium, and priming effect of progesterone and follicular fluid.

In these studies, we aimed to characterize the effects of the physiological, homologous agonists of the acrosome reaction, i.e. the zona pellucida (ZP) and progesterone/follicular fluid, on human sperm. The specific aims of our studies were: (i) to examine the dependency of the solubilized ZP-induced acrosome reaction on G(i) protein activation and presence of extracellular calcium; and (ii) to determine whether progesterone/follicular fluid exert a priming or synergist effect on the solubilized ZP-induced acrosome reaction. Highly motile sperm from fertile donors were exposed to the agonists in a microassay and the acrosomal status of live sperm was determined by indirect immunofluorescence using PSA-FITC/Hoechst double-staining. Pretreatment with pertussis-toxin (100 ng/ml) and EGTA (2.5 mmol/l) significantly inhibited the ZP-induced acrosome reaction without affecting the spontaneous rate of exocytosis. Progesterone (1.25 microg/ml) and human follicular fluid (10%) exerted a priming, time-dependent effect on the ZP-induced acrosome reaction. These studies demonstrated that: (i) acrosomal exocytosis of capacitated human sperm triggered by the homologous ZP is dependent on the activation of G(i) proteins (pertussis toxin-sensitive) and the presence of extracellular calcium; and (ii) progesterone and follicular fluid exert a priming effect on the ZP-induced acrosome reaction.

Acrosome Reaction↗

African experience with sperm morphology training courses.

This paper reports on the results of a 6-year ongoing training and quality control programme for sperm morphology. The programme consists of a 5-day semenology workshop, during which participants receive intensive training on issues such as sperm concentration, motility, vitality and morphology. Following the workshop, all the participants are enrolled in a continuous quality control (CQC) programme for sperm morphology. These workshops and quality control programmes are presented by the Department of Obstetrics and Gynaecology at Tygerberg Hospital (South Africa) in conjunction with the World Health Organization's (WHO) Special Programme for Research Development and Research Training. Seventy individuals from 11 countries in sub-Saharan Africa have been trained since 1997; 58 of these are still participating in the quality control programme. Using the results from the quality control programme, participants were classified according to their sperm morphology reading skills recorded over an extended period. It is concluded that an external quality control programme can be highly successful, on condition that it is presented continuously with a 3-4 month interval between tests.

Africa↗