Which isolated sperm abnormality is most related to sperm DNA damage in men presenting for infertility evaluation.

BACKGROUND: Sperm DNA damage is common in infertile men and is associated with poor semen parameters but the impact of an isolated sperm abnormality on sperm DNA damage has not been studied. OBJECTIVE: To evaluate sperm DNA damage in a large cohort of infertile men with isolated sperm defects. DESIGN, SETTING AND PARTICIPANTS: Retrospective study of 1084 consecutive, non-azoospermic infertile men with an isolated sperm defect: isolated oligozoospermia (iOligo), isolated asthenozoospermia (iAstheno) or isolated teratozoospermia (iTerato). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We examined and compared clinical parameters, conventional semen parameters and %sperm DNA fragmentation (%SDF, assessed by flow cytometry-based Terminal deoxynucleotidyl transferase-mediated dUTP Nick End-Labeling assay) in the three groups of men. RESULTS AND LIMITATIONS: The mean (±SD) %SDF was significantly higher in the iAstheno compared to the iOligo and iTerato groups (25.0 ± 14.0 vs. 19.2 ± 11.6 and 20.7 ± 12.1 %, respectively, P < 0.0001). Similarly, the proportion of men with high %SDF (>30 %) was significantly higher in the iAstheno compared to the iOligo and iTerato groups (31 % vs. 18 % and 19 %, respectively, P < 0.0001). In the group of 713 men with iAstheno, %SDF was positively correlated with paternal age (r = 0.20, P < 0.0001) and inversely correlated with %progressive motility (r = -0.18, P < 0.0001). In the subset of 218 men with iTerato, %SDF was also positively correlated with paternal age (r = 0.15, P = 0.018) and inversely correlated with %progressive motility (r = -0.26, P = 0.0001). CONCLUSIONS: In this large cohort of infertile men with isolated sperm abnormalities, we have found that the sperm DNA fragmentation level is highest in the men with sperm motility defects and that 31 % of these men have high levels of sperm DNA fragmentation. The data indicate that poor motility is the sperm parameter abnormality most closely related to sperm DNA damage.

Sperm vacuoles are linked to capacitation and acrosomal status.

STUDY QUESTION: Is the presence of nuclear vacuoles really a negative parameter? SUMMARY ANSWER: As sperm vacuoles are associated with acrosomal and capacitation status, they appear to be a reflection of normal sperm physiology. WHAT IS KNOWN ALREADY: The selection of sperm under a high magnification has been proposed as a strategy to increase the success rates of ICSI, through a better selection of sperm for injection. The presence of vacuoles on the sperm head is said to be a negative parameter. STUDY DESIGN, SIZE, DURATION: We incubated processed sperm for 90 min with two strong inducers of acrosome reaction (AR), i.e. hyaluronic acid (HA) and follicular fluid (FF) and studied the evolution of nuclear vacuoles, sperm morphology and chromatin compaction. PARTICIPANTS/MATERIALS, SETTING, METHODS: We tested the effect of incubating sperm samples with HA and FF for 90 min at 37°C on nuclear vacuoles. MAIN RESULTS AND THE ROLE OF CHANCE: Both HA and FF strongly induce AR after 90 min, without significantly modifying sperm nuclear condensation and morphology (Bartoov's criteria). We simultaneously observed a highly significant decrease in the presence of vacuoles. LIMITATIONS, REASONS FOR CAUTION: This is a descriptive study based on in vitro manipulations. WIDER IMPLICATIONS OF THE FINDINGS: Although intracytoplasmic morphologically selected sperm injection may be of benefit for couples with specific treatment indications, the results of this study make it difficult to justify its large-scale application. STUDY FUNDING/COMPETING INTEREST(S): Funding was granted by Laboratoire d'Eylau, Unilabs.

Zinc concentrations in serum and follicular fluid during ovarian stimulation and expression of Zn2+ transporters in human oocytes and cumulus cells.

Serum and follicular fluid zinc concentrations were investigated in patients undergoing assisted reproductive treatment. No correlation was found between zinc and oestradiol concentrations in serum. At the time of oocyte retrieval, zinc concentrations in follicular fluid were significantly lower than serum concentrations (P<0.0001). The expression of the two families of zinc transporters, ZnT and ZiP, as well as the metal regulatory transcription factors, MTF1 and 2, and metallothioneins, which are both involved in regulatory aspects of zinc transport, was assayed in cumulus cells and in germinal-vesicle oocytes. Most of the zinc transporters, metallothioneins and metal regulatory transcription factor are expressed in oocytes and not in cumulus cells. This may indicate an important role for zinc, in particular with potential linking to genome stability during early embryonic development. In contrast, cumulus cells seem to be at the end of their life's journey, with weak expression of transcriptional activity linked to cellular housekeeping.

High body mass index has a deleterious effect on semen parameters except morphology: results from a large cohort study.

OBJECTIVE: To evaluate the influence of body mass index (BMI) on semen characteristics. DESIGN: Cohort study. SETTING: Single private andrology laboratory. PATIENT(S): All patients (n=10,665) consulting for a semen analysis from October 9, 2010, to October 8, 2011. When analyses were repeated on the same patient, only the first was included. INTERVENTION(S): Recording of self-reported weight and height and of semen analysis. MAIN OUTCOME MEASURE(S): All parameters of standard semen analysis: pH, volume, sperm concentration per mL, total sperm count per ejaculate, motility (%) within 1 hour after ejaculation (overall and progressive), viability (%), and normal sperm morphology (%). Parametric and nonparametric statistical methods were applied, and results are given either with mean±SD, or 10th, 50th, and 90th percentiles. RESULT(S): Semen volume decreased from 3.3±1.6 to 2.7±1.6 mL when BMI increased from normal (20-25 kg/m2) to extreme obesity (>40 kg/m2). The same was true for semen concentration (56.4±54.9 to 39.4±51.0 million/mL), total sperm count (171±170 to 92±95 million), and progressive motility (36.9±16.8% to 34.7±17.1%). The percentage of cases with azoospermia and cryptozoospermia increased from 1.9% to 9.1% and from 4.7% to 15.2%, respectively. The other semen characteristics were not affected. Multivariate models including age and abstinence duration confirmed these results. CONCLUSION(S): In this study, on a large patient sample size, increased BMI was associated with decreased semen quality, affecting volume, concentration, and motility. The percentage of normal forms was not decreased.

Emerging molecular methods for male infertility investigation.

Male factors account for approximately 50% of reproductive pathology. Different disorders, including urogenital and endocrine system development abnormalities, lead to testicular and gametogenesis defects. Parallely, studies have reported that somatic and germ cell genome decay are a major cause of male infertility. It has been shown that in somatic karyotype, there is a higher incidence of chromosomal aberrations in infertile men than neonatal population and significant chromosome Y microdeletion or specific gene alterations in affected spermatogenesis. Karyotyping and FISH application at somatic and germ cell levels are no longer sufficient to investigate the potential contribution of genome disorders on male infertility. A wide range of molecular methods are required for better understanding of male infertility causes. Molecular omes and omics techniques have become a great tool to investigate male infertility from chromosome to protein. This review reports different molecular tests and methods that can be offered for male infertility investigation.

Sperm deoxyribonucleic acid damage in normozoospermic men is related to age and sperm progressive motility.

OBJECTIVE: To evaluate sperm DNA fragmentation in normozoospermic male partners of couples undergoing infertility evaluation. DESIGN: Retrospective cohort study. SETTING: Clinical andrology laboratory. PATIENT(S): A total of 1,974 consecutive normozoospermic men selected from a larger cohort of 4,345 consecutive, nonazoospermic men presenting for infertility evaluation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical parameters, conventional semen parameters, and sperm DNA fragmentation assessed by flow cytometry-based TUNEL assay and reported as percent sperm DNA fragmentation (%SDF). RESULT(S): The mean (± SD) %SDF and the proportion of men with high %SDF (>30%) were significantly lower in the normozoospermic compared with the entire cohort of 4,345 evaluable infertile men (17.6% ± 10.1% vs. 20.7% ± 12.4% and 11% vs. 20%, respectively). In the group of 1,974 normozoospermic men, %SDF was positively correlated with paternal age (r = 0.17) and inversely correlated with progressive motility (r = -0.26). In the subset of normozoospermic men with sperm parameters above the 50th percentile (≥ 73 × 10(6) sperm/mL, ≥ 55% progressive motility, and ≥ 14% normal forms, World Health Organization 2010 guidelines), 5% (4 of 83) had elevated %SDF (>30%). CONCLUSION(S): In this large cohort of normozoospermic men presenting for infertility evaluation, DNA fragmentation level is related to sperm motility and paternal age, and 11% of these men have high levels of sperm DNA fragmentation. Furthermore, the data indicate that a nonnegligible proportion (5%) of normozoospermic men with high-normal sperm parameters may also have significant sperm DNA fragmentation.

Management of infertility in women over 40.

Women's fertility potential is declining with age because of multiples intrinsic and extrinsic factors such as life style, oxidative stress and/or endocrine disruptors and is affecting the ability of these women to conceive naturally. This declining fertility potential and the late age of motherhood is increasing significantly the number of patients consulting infertility specialists. Different strategies of investigation and management are proposed to patients over 40 in order to overcome their infertility and improve the live birth rate in these patients. Intra Uterine Insemination (IUI) in women over 40 is associated with a low rate of ongoing pregnancy and IUI should not therefore be offered always as the first line of treatment. When the predictive factors are positive IVF/ICSI seem to be good alternatives until 43 years of age. Customized ovarian stimulation and flexible laboratory methods such as in vitro maturation (IVM), preimplantation genetic diagnosis (PGD), embryo vitrification and transfer after thawing in subsequent natural or artificial cycles can improve the success rate of ART in patients over 40. Meanwhile, oocyte and embryos donation remain good options for patient over 40 with a bad prognosis and can lead to successful ongoing pregnancies until 45 years of age. Ovarian tissue cryopreservation, oocyte vitrification at the germinal vesicle (GV) stage or metaphase II stage present a breakthrough for fertility preservation but the ideal age for starting fertility preservation is still debated as well as the minimum number of oocytes to be vitrified in order to optimize the chances of pregnancy when needed at an older age. This manuscript reports the results of our own experience from patients older than 40 in the light of the published data and discusses the different therapeutic alternatives which can be proposed to patients over 40 consulting ART centres.