Franco Dondero

Bio: Franco Dondero is an academic researcher from Sapienza University of Rome. The author has contributed to research in topics: Sperm & Sperm motility. The author has an hindex of 28, co-authored 82 publications receiving 3448 citations.

Study of apoptotic DNA fragmentation in human spermatozoa

Abstract: The aim of our work was to define and better understand apoptosis in the spermatozoa of normal subjects, infertile patients and patients affected by specific tumoral diseases employing the method of the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling and confirming the results by electron microscopy. We studied 23 healthy, normozoospermic subjects (group A), 29 oligoasthenoteratozoospermic patients, affected by various andrological pathologies (group B), 28 patients with Hodgkin's disease (C1) and 30 patients with testicular cancer (C2). Our data demonstrate that the percentage of apoptosis in normozoospermic subjects (group A) is significantly lower than in all the other groups (B, C1, C2) (P < 0.001). This confirms that high DNA fragmentation is one of the characteristics of spermatogenetic failure. The induction of apoptosis, which can also be a basic response to neoplastic disease, can even act right up to the mature male gamete. Our results suggest that apoptosis could be the final result of various pathologies and of a deregulation of spermatogenesis control systems.

Full‐term pregnancies achieved with ICSI despite high levels of sperm chromatin damage

Abstract: Background Sperm DNA integrity is essential for the accurate transmission of genetic information. The clinical significance of this assessment lies in its association with not only natural conception rates, but also the success of assisted reproduction technology (ART). It has been reported that sperm chromatin structure assay (SCSA) identified thresholds for negative pregnancy outcome after ART when the DNA fragmentation index (DFI), previously known as COMPalphat, was >30%. Methods In a prospective clinical study, we examined 34 male infertile patients, the husbands of women undergoing conventional IVF or ICSI. SCSA and ART were carried out on semen aliquots taken from the same ejaculate. Fertilization rate, embryo quality and pregnancy rates were correlated to SCSA parameters, DFI and highly DNA stainable (HDS) cells. Results No differences were seen in SCSA parameter values between patients initiating pregnancies and not doing so in either ICSI or conventional IVF. Pregnancies and normal delivery were obtained even with high levels of DFI. Conclusions There is still controversy over whether analytical techniques currently in use are able to identify the level of damage to spermatozoa. Large-scale studies should be conducted in different clinical settings to determine the effects of sperm DNA damage on the outcome of ART.

Lipids of the sperm plasma membrane: from polyunsaturated fatty acids considered as markers of sperm function to possible scavenger therapy

Abstract: This article is, in part, a review of present knowledge regarding the lipid metabolism of the sperm cell and the lipid composition of the sperm plasma membrane. It is also a summary of our research on this topic, reporting published and unpublished data. The article tries to cover both basic and clinical research. Sperm cells use lipid metabolic pathways for the production of part of their energy. The double leaflets of the membrane are not simply a passive, bilayer, lipidic film in which the receptors receive their molecular specific signals, but are a very specialized structure. Complete maturation of the lipids of the sperm cell membrane is reached after passage of the spermatozoon through the epididymis. A specific composition of phospholipids and a significant concentration of polyunsaturated fatty acids (PUFA) have been shown to be present in sperm membranes. Plasmalogen is a special kind of phospholipid found exclusively in spermatozoa and other cells with the capacity to react promptly to stimuli. In addition, we have found a high concentration of the n-3 PUFA family in the sperm membrane. Seminal plasma has a highly specialized scavenger system that defends the sperm membrane against lipoperoxidation. Various pathologies and systemic predisposition can lead to an antioxidant/pro-oxidant disequilibrium. Clinical trials with natural scavengers could be a useful research area in which to seek a treatment for these pathologies. Of the natural scavengers, glutathione has been shown to restore the physiological constitution of PUFA in the cell membrane under certain conditions.

Placebo-controlled, double-blind, cross-over trial of glutathione therapy in male infertility.

Abstract: Glutathione therapy was used for 2 months in a placebo-controlled double-blind cross-over trial of 20 infertile patients with dyspermia associated with unilateral varicocele (VAR) or germ-free genital tract inflammation (INF). The patients received either glutathione (group 1) or placebo (group 2) for 2 months, then they crossed over to the alternative treatment for a further 2 months. The patients were randomly and blindly assigned to treatment (one i.m. injection every other day of either 600 mg glutathione or an equal volume of a placebo preparation). The standard semen analysis and the computer-assisted sperm motility analyses were carried out before treatment and during the trial. Statistical cross-over analysis, case-control study and treatment efficacy test were carried out on groups 1 and 2 and differences in the effects of therapy between VAR and INF patients with varicocele or inflammation were tested. Glutathione therapy demonstrated a statistically significant positive effect on sperm motility, in particular on the percentage of forward motility, the kinetic parameters of the computerized analysis and on sperm morphology. The findings of this study indicate that glutathione therapy could represent a possible therapeutical tool for both of the selected andrological pathologies.

American Society of Clinical Oncology Recommendations on Fertility Preservation in Cancer Patients

Abstract: Purpose To develop guidance to practicing oncologists about available fertility preservation methods and related issues in people treated for cancer. Methods An expert panel and a writing committee were formed. The questions to be addressed by the guideline were determined, and a systematic review of the literature from 1987 to 2005 was performed, and included a search of online databases and consultation with content experts. Results The literature review found many cohort studies, case series, and case reports, but relatively few randomized or definitive trials examining the success and impact of fertility preservation methods in people with cancer. Fertility preservation methods are used infrequently in people with cancer. Recommendations As part of education and informed consent before cancer therapy, oncologists should address the possibility of infertility with patients treated during their reproductive years and be prepared to discuss possible fertility preservation options or refer appropriate and interested patients to reproductive specialists. Clinician judgment should be employed in the timing of raising this issue, but discussion at the earliest possible opportunity is encouraged. Sperm and embryo cryopreservation are considered standard practice and are widely available; other available fertility preservation methods should be considered investigational and be performed in centers with the necessary expertise.

Oxidative stress and male infertility—a clinical perspective

Abstract: Oxidative stress occurs when the production of potentially destructive reactive oxygen species (ROS) exceeds the bodies own natural antioxidant defenses, resulting in cellular damage. Oxidative stress is a common pathology seen in approximately half of all infertile men. ROS, defined as including oxygen ions, free radicals and peroxides are generated by sperm and seminal leukocytes within semen and produce infertility by two key mechanisms. First, they damage the sperm membrane, decreasing sperm motility and its ability to fuse with the oocyte. Second, ROS can alter the sperm DNA, resulting in the passage of defective paternal DNA on to the conceptus. This review will provide an overview of oxidative biochemistry related to sperm health and will identify which men are most at risk of oxidative infertility. Finally, the review will outline methods available for diagnosing oxidative stress and the various treatments available.