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Study question Is there a difference in oocyte competence among patients with different gonadotrophin polymorphisms, after ovarian stimulation with r-FSH? Summary Answer Higher DNA Fragmentation Index and cleaved caspase-3 related to lower level of pAKT has been observed in patients with specific gonadotrophin polymorphism (FSHR and LHB). What is known already • In our experience, the DFI, the percentage of cleaved caspase-3 and the pAKT on cumulus cells can be used as molecular markers of oocyte competence; • The polymorphic variant of LHB is characterized by an extra glycosylation signal into the β subunit. This molecular variation influences the pharmacokinetic properties of v-betaLH, showing an elevated bioactivity in vitro, but a significantly shorter half-life in circulation if compared with the wild type LH. These patients show sub-optimal ovarian response after pharmacological ovarian stimulation with r-FSH; We know that FSH receptor (FSHR) variants, Thr307/Asn680 and Ala307/Ser680, are involved in the response to ovarian stimulation. Study design, size, duration The aim of the study was to determine the apoptosis levels (in terms of percentage of DNA fragmentation and percentage of cleaved caspase-3) and the pAKT levels as potential markers of oocyte competence in the cumulus cells of individual patients with specific FSHR and LHB polymorphisms. It was a retrospective study. It was included 36 patients. The duration of the study was 12 months. Participants/materials, setting, methods Patients were normo-responder patients with a normal basic level of FSH (

Mitochondria of spermatozoa are different from the corresponding organelles of somatic cells, in both their morphology and biochemistry. The biochemical differences are essentially related to the existence of specific enzyme isoforms, which are characterized by peculiar kinetic and regulatory properties. As mitochondrial energy metabolism is a key factor supporting several sperm functions, these organelles host critical metabolic pathways during germ cell development and fertilization. Furthermore, spermatozoa can use different substrates, and therefore activate different metabolic pathways, depending on the available substrates and the physico-chemical conditions in which they operate. This versatility is critical to ensure fertilization success. However, the most valuable aspect of mitochondria function in all types of cells is the production of chemical energy in the form of ATP which can be used, in the case of spermatozoa, for sustaining sperm motility. The latter, on the other hand, represents one of the major determinants of male fertility. Accordingly, the presence of structural and functional alterations in mitochondria from asthenozoospermic subjects confirms the important role played by these organelles in energy maintenance of sperm motility. The present study gives an overview of the current knowledge on the energy-producing metabolic pathways operating inside human sperm mitochondria and critically analyse the differences with respect to somatic mitochondria. Such a comparison has also been carried out between the functional characteristics of human sperm mitochondria and those of other mammalian species. A deeper understanding of mitochondrial energy metabolism could open up new avenues of investigation in bioenergetics of human sperm mitochondria, both in physiological and pathological conditions.

The role of mitochondria in sperm motility was the subject of several investigations. However, different views on this topic emerged among scientists. In particular, very little is known on the mechanisms of energy production occurring during human sperm capacitation and related processes. In this study, we have investigated the mitochondrial respiratory efficiency in human sperm samples from normozoospermic subjects before and after swim-up selection and incubation under capacitating condition. Sperm cells, selected by swim-up treatment, were incubated up to 24 h and then demembranated by hypotonic swelling at selected times. The oxygen uptake rate was measured in both basal and swim-up selected samples by a polarographic assay. Mitochondria of swim-up selected cells showed an impressive oxygen consumption rate, which was about 20 times higher than that measured in basal samples. The high mitochondrial respiratory efficiency remained stable up to 24 h after the swim-up treatment. The respiration control ratio, the substrate specificity and the inhibitor sensitivity in the swim-up selected samples were similar to those of basal samples thereby suggesting that the physiology of mitochondria was preserved after the swim-up treatment. Furthermore, the remarkably high mitochondrial respiration in swim-up selected samples allowed the oxygraphic analysis of just 200,000 sperm cells. Sperm selection and incubation under capacitating condition are therefore associated with a high activity of the mitochondrial respiratory chain. The sperm oxygen consumption rate could be useful to exclude mitochondria malfunctioning in male infertility.