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Objective: To evaluate rates and reasons for treatment discontinuation in couples with male factor infertility and who failed to conceive. Design: Retrospective study. Setting: Male Sterility Center, University Hospital. Patient(s): A total of 407 couples consulting for male factor infertility and who discontinued treatment without conceiving. Intervention(s): None. Main Outcome Measure(s): Treatment, reasons for dropout, and reproductive outcomes after discontinuation. Result(s): Of the 407 patients, 218 (54%) had had fertility treatment (medical or surgical), and 189 (46%) underwent assisted reproductive techniques (ART) (intrauterine insemination [IUI], in vitro fertilization [IVF], or intracytoplasmic sperm injection [ICSI]). The main reasons for dropout were painfulness of treatment (15% for patients with non-ART treatment vs. 32% for patients who had undergone ART), its ineffectiveness (12% vs. 26%), and separation of the couple (18% vs. 7%). Of the 407 patients, 27% consulted in another fertility center, 8% succeeded in having a child by ART with male partner sperm, 1% by ART with donor sperm, and 11% through adoption. Conclusion(s): About half of the couples consulting for male factor infertility discontinued fertility treatment, and of those who discontinued only a fifth finally succeeded in having a child. Although support is available to couples during fertility care, ART is a physical and psychological burden. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Assisted reproduction techniques can minimize the risk of HIV female contamination when the male partner is HIV-infected. The aim of this study was to investigate the efficiency of sperm washing and intrauterine insemination (IUI) in these couples. Study design: Retrospective comparative study. Eighty-four HIV-1 serodicordant couples underwent 294 IUI. The control group was composed of 90 couples (320 IUI cycles) with donor sperm. Spermatozoa from HIV-1 infected male partner were prepared and tested for HIV-1 according to sperm washing method. Spermatozoa from HIV-1 and donor male were frozen before IUI. IUI were performed after ovarian stimulation. Main outcomes measures were pregnancy rate per cycle and baby take-home rate per couples. Results: Although the pregnancy rate and baby take-home rate were higher in IUI with sperm washing than in IUI using donor sperm (18.0 versus 14.7 and 52.4 versus 41.1, respectively), the differences were not statistically significant. In serodiscordant couples, blood estradiol levels under ovarian stimulation and total motile sperm inseminated were a determining factor in achieving pregnancy. No female HIV-1 contamination occurred. Conclusion: This study demonstrates that sperm washing and IUI are highly effective in enabling serodiscordant couples with an HIV-1 infected male partner to have a child. [Copyright &y& Elsevier]

To enable serodiscordant couples to reproduce while minimizing the risk of infecting the female partner and to demonstrate the feasibility of including these couples in an insemination program.Prospective follow-up study.Ambulatory IUIs.Fifty-six HIV-1–serodiscordant couples with a male infected partner.Sperm cell separation by the gradient density method followed by the swim-up method, virological detection, and IUI after ovarian stimulation.Pregnancy rate, HIV-1 test, and p24 antigenemia in women.Two hundred thirteen IUIs were performed, and 37 pregnancies occurred, resulting in 33 births and 2 ongoing pregnancies. Fifty percent of couples have a child. No women were infected.Our study demonstrates the efficiency of an IUI program with prepared and virologically tested spermatozoa in serodiscordant couples with an HIV-1–infected male partner, allowing the couples to have children without transmission of the virus to the female partner. [Copyright &y& Elsevier]

: ObjectiveTo study seminal excretion of human immunodeficiency virus type 1 (HIV-1) during 4 years of follow-up in an HIV-1–infected patient, the relationship between high viral excretion and inflammatory status of semen, and the efficiency of sperm processing methods in obtaining spermatozoa with undetectable RNA and proviral DNA levels.: DesignCase report.: SettingUniversity hospital and research group on human fertility.: Patient(s)One HIV-1–infected patient.: Intervention(s)Paired blood and semen samples were obtained during 4 years of follow-up.: Main outcome measure(s)CD4 cell count; blood and seminal plasma viral load; and HIV-1 RNA and proviral DNA in different cell fractions obtained during sperm processing, as measured by the density gradient method and the swim-up method; sperm parameters; and polymorphonuclear granulocyte count.: Result(s)Shedding of HIV-1 in semen was intermittent. The highest seminal viral loads were associated with a markedly increased polymorphonuclear granulocyte count, which reflects inflammation of the genital tract. Spermatozoa with undetectable levels of HIV-1 RNA or DNA were obtained regardless of the viral load in semen.: Conclusion(s)In an HIV-1–infected man with intermittent seminal viral excretion, sperm processing was effective in obtaining spermatozoa without detectable HIV-1 genomes. [Copyright &y& Elsevier]

Objective To determine consequences of lymphoma treatments on sperm characteristics and sperm DNA, and to evaluate predictors of sperm recovery. Design Multicenter prospective longitudinal study of patients analyzed before treatment and after 3, 6, 12, and 24 months. Setting University hospitals. Patient(s) Seventy-five Hodgkin lymphoma and non-Hodgkin lymphoma patients and a control group of 257 fertile men. Intervention(s) Semen analyses, and sperm DNA and chromatin assessments. Main Outcome Measure(s) Comparisons of sperm characteristics before and after treatment. Result(s) Patients already had altered sperm characteristics before lymphoma treatment, with no identified risk factor. Sperm count, total sperm count, motility, and vitality decreased after treatment, with lowest values at 3 and 6 months. Twelve months after treatment, mean sperm count recovered to pretreatment values after doxorubicin, bleomycin, vinblastine, darcarbacine (ABVD) or ABVD + radiotherapy, but not after doxorubicin, cyclophosphamide, vincristine, prednisone (CHOP) or mechlorethamine, oncovin, procarbazine, prednisone (MOPP) chemotherapies. It was noteworthy that 7% of patients remained azoospermic at 24 months. After 24 months, Kaplan-Meier estimates showed that more than 90% of patients will recover normal sperm count after ABVD or ABVD + radiotherapy vs. 61% for CHOP chemotherapies. In multivariate analyses including diagnosis and treatment protocol, only pretreatment total sperm count was related to recovery. Compared with a control group, lymphoma patients had higher sperm chromatin alterations and DNA fragmentation before any treatment. After treatment, DNA fragmentation assessed by TUNEL assay and sperm chromatin structure assay decreased from 3 and 6 months, respectively, while remaining higher than in the control group during follow-up. Conclusion(s) Lymphoma patients had altered sperm DNA and chromatin before treatment. Lymphoma treatment had damaging effects on spermatogenesis. These data on both the recovery period according to treatment modalities and the pre- and post-treatment chromatin status of sperm are useful tools for counseling patients wishing to conceive. [ABSTRACT FROM AUTHOR]

Objective: To determine the consequences of adjuvant testicular germ cell tumor treatment (TGCT) on sperm characteristics and sperm DNA, and to evaluate the predictors of sperm recovery. Design: Multicenter prospective longitudinal study of patients analyzed before treatment and after 3, 6, 12, and 24 months. Setting: University hospitals. Patient(s): One hundred twenty-nine volunteer TGCT patients and a control group of 257 fertile men. Intervention(s): Routine semen analyses, sperm DNA, and chromatin assessments. Main Outcome Measure(s): Comparisons of mean sperm characteristics before and after treatment, with sperm recovery analyzed by the Kaplan-Meier method. Result(s): The quantitative and qualitative sperm characteristics decreased after treatment, with lowest values at 3 and 6 months and with variations according to treatment type. The mean total sperm count recovered to pretreatment values at 12 months after treatment after two or fewer bleomycin, etoposide, and cisplatin (BEP) cycles, but not after radiotherapy or more than two BEP cycles. Only the treatment modalities and pretreatment sperm production were related to recovery of the World Health Organization reference sperm values. An increased proportion of patients had elevated high sperm DNA stainability at 6 months after radiotherapy. Conclusion(s): Adjuvant treatments for testicular germ cell tumor have drastic effects on spermatogenesis and sperm chromatin quality. These new data on both the recovery period according to treatment modalities and the post-treatment chromatin status of sperm are useful tools for counseling patients wishing to conceive. [ABSTRACT FROM AUTHOR]

To determine whether there is a risk of localized Zika virus (ZIKV) infection in the upper genital tract, specifically the oocytes, follicular fluids and endometrium, in exposed and/or recently infected reproductive-age women. ZIKV is an Aedes mosquito-borne Flavivirus that can lead to birth defects and to developmental anomalies when it infects pregnant women. Controlled observational clinical study following 179 female patients undergoing oocyte vitrification cycles in an academic fertility centre during the ZIKV epidemic in the French territories of the Americas. At the time, the French Ministry of Health issued a ban on medically-induced pregnancies. Oocyte vitrification cycles were the only means of preserving fertility options and ensuring Zika-free oocyte cryopreservation for currently exposed and/or recently infected patients. Samples of serum, urine, lower genital tract, endometrium, follicular fluid and immature oocytes were tested for ZIKV RNA (vRNA) by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Serological analysis for ZIKV antibodies was performed in succession for the duration of the study. The follow-up protocol was set up for more than 6 months post-exposure or post-onset. No vRNA was detected in the various samples from exposed patients. Furthermore, no vRNA was found in the upper genital tracts of women with a recent (3 months) history of acute infection. These findings represent evidence of a lack of vRNA persistence in the reproductive tract in ZIKV exposed and/or recently infected reproductive-age women and could help simplify current guidelines. [ABSTRACT FROM AUTHOR]

High performance assays are essential for the serological diagnosis of recent and past Zika virus (ZIKV) infections but few are presently available. We used two commercially available NS1 antigen-based enzyme-linked immunoassays to study the kinetics of anti-ZIKV IgM and IgG in 15 ZIKV-infected patients for up to 180 days after clinical onset. The Diapro assay detected anti-ZIKV IgM reactivity more frequently (100%) and for longer (median 53 days) than did the Euroimmun assay (60%; 13 days, P < 0.005). Both assays detected anti-ZIKV IgG reactivity 11 days after clinical onset in all subjects. ZIKV IgG reactivity decreased in 3 subjects, suggesting long-term false-negative results with the Euroimmun assay. Existing anti-Dengue antibodies seem to modify the detection of ZIKV IgG but the specificity of the immunoassays was not assessed. These enzyme-linked immunoassays were user-friendly and provided results rapidly in our hands but they need further assessment before being widely used for diagnosis or public health surveys. [ABSTRACT FROM AUTHOR]

Background: Evidence of human sexual transmission during Zika virus emergence is a matter of concern, particularly in procreation, but to date, kinetics of seminal shedding and the effects of infection on human reproductive function have not been described. To investigate the effects of Zika virus infection on semen and clearance of Zika virus from semen and body fluids, we aimed to study a cohort of Zika virus-infected men.Methods: This prospective observational study recruited men presenting with acute Zika virus infection at Pointe-à-Pitre University Hospital in Guadeloupe, French Caribbean, where a Zika virus outbreak occurred between April and November, 2016. Blood, urine, and semen were collected at days 7, 11, 20, 30, 60, 90, and 120 after symptom onset, and semen characteristics, such as total sperm count, sperm motility, vitality, and morphology, and reproductive hormone concentrations, such as testosterone, inhibin, follicle-stimulating hormone, and luteinising hormone, were assessed. At days 7, 11, and 20, semen was processed to isolate motile spermatozoa. Zika virus RNA was detected by RT-PCR using whole blood, serum, urine, seminal plasma, semen cells, and motile spermatozoa fractions. Zika virus was isolated from different sperm fractions on Vero E6 cultures.Findings: 15 male volunteers (mean age 35 years [SD 5; range 25-44) with acute Zika virus infection and positive Zika virus RNA detection in blood or urine were enrolled. Total sperm count was decreased from median 119 × 106 spermatozoa (IQR 22-234) at day 7 to 45·2 × 106 (16·5-89·6) at day 30 and 70 × 106 (28·5-81·4) at day 60, respectively, after Zika virus infection. Inhibin values increased from 93·5 pg/mL (IQR 55-162) at day 7 to 150 pg/mL (78-209) at day 120 when total sperm count recovered. In motile spermatozoa obtained after density gradient separation, Zika virus RNA was found in three of 14 patients at day 7, four of 15 at day 11, and four of 15 at day 20, and replication-competent virus was found in the tested patient. Seminal shedding kinetics seemed heterogeneous among patients. Whole blood was the fluid most frequently positive for Zika virus RNA (62 of 92 samples) and three patients remained positive at day 120.Interpretation: Semen alterations early after acute Zika virus infection might affect fertility and could be explained by virus effects on the testis and epididymis. Frequency of shedding and high viral load in semen, together with the presence of replicative virus in a motile spermatozoa fraction, can lead to Zika virus transmission during sexual contact and assisted reproduction procedures. Whole blood seems to be the best specimen for Zika virus RNA detection, diagnosis, and follow-up.Funding: Agence de la Biomédecine/Agence Régionale de Santé de la Guadeloupe/Inserm-REACTing. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of a mild induced testicular and epididymal hyperthermia (+2°C) on sperm chromatin integrity in men. Design: Experimental prospective study. Setting: University hospital. Patient(s): Five healthy fertile volunteers. Intervention(s): Testicular and epididymal hyperthermia was induced by maintaining the testes at inguinal position with the support of specially designed underwear 15 ± 1 hours daily for 120 consecutive days. Main Outcome Measure(s): Classic semen characteristics. Sperm DNA fragmentation index (DFI) and high DNA stainability (HDS) were analyzed by sperm chromatin structure assay. Result(s): Compared with baseline values, sperm DFI and HDS were significantly increased as early as day (D) 20 and D34, respectively, and remained elevated during the entire period of hyperthermia. Percentages of motile and viable spermatozoa decreased as early as D20 and D34, respectively, and total sperm count decreased at D34 during hyperthermia and remained low during the entire hyperthermia period. All studied parameters returned to respective baseline values at D73 after cessation of hyperthermia. Conclusion(s): Mild induced testicular and epididymal hyperthermia largely impaired sperm chromatin integrity, which appeared before any changes in sperm output. These findings may have clinical implications in male contraception, infertility, and assisted reproductive technology. [ABSTRACT FROM AUTHOR]

Objective: To study sperm parameters in patients infected with human immunodeficiency virus (HIV)-1 and to analyze mitochondrial DNA (mtDNA) in sperm according to the HIV treatment. Design: Observational study. Setting: University-affiliated teaching hospital. Patient(s): Thirty-two patients infected with HIV-1 and 31 noninfected healthy men provided semen samples. Intervention(s): None. Main Outcome Measure(s): After DNA extraction, mtDNA level was assessed using real-time polymerase chain reaction (PCR) (LightCycler) in whole semen and in selected spermatozoa from 90% density centrifugation gradients. For each sample, mtDNA and β-globin gene sequences were amplified and PCR products were quantified. The mtDNA-to-β-globin ratio expressed the number of mtDNA copies per cell. Result(s): Compared with the control group, several sperm parameters were altered in patients with HIV. The number of mtDNA copies per cell in whole semen was increased in HIV-infected patients (6.3 ± 6.3 vs. 3.5 ± 3.2). However, there was no statistically significant difference in mtDNA copy number in the spermatozoa obtained after density gradient centrifugation. The number of nucleoside analogue reverse transcriptase inhibitors (NRTI) taken by patients during treatment significantly influenced the mtDNA level in sperm (1 NRTI 7.6 ± 8.1, 2 NRTIs 7.0 ± 5.1, 3 NRTIs 3.2 ± 2.1). Conclusion(s): Using a specific method to measure sperm mtDNA, we demonstrated a decrease of mtDNA copies in spermatozoa after use of NRTIs with known mitochondrial toxicity. [ABSTRACT FROM AUTHOR]

Objective: To study sperm aneuploidy in a population of testicular cancer (TC) patients treated with the use of either bleomycin-etoposide-cisplatin (BEP) chemotherapy or radiotherapy.Design: Multicenter prospective longitudinal study of TC patients analyzed before treatment and after 3, 6, 12, and 24 months (T3-T24).Patient(s): Fifty-four TC patients and a control group of 10 fertile sperm donors.Setting: University hospital laboratories.Intervention(s): Routine semen analyses; sperm aneuploidy and diploidy.Main Outcome Measure(s): Comparison of sperm characteristics and sperm chromosome abnormalities during TC patient follow-up.Result(s): Semen characteristics recovered pretreatment values 12 months after radiotherapy and 24 months after more than two BEP cycles. A significant increase in sperm disomy YY and XX was observed in the TC group before treatment compared with the control group. After more than two BEP cycles, the mean sperm aneuploidy rate increased significantly at T12 and reached the pretreatment value at T24. After radiotherapy, the mean sperm aneuploidy returned to the pretreatment value at T12. At T24, nearly 40% of TC patients did not recover their pretreatment sperm aneuploidy rate.Conclusion(s): Genetic counseling of TC patients should include information on the potential elevated risk of aneuploid conceptus from sperm recovered after treatment and the necessity to postpone conception up to ≥12 months after radiotherapy and ≥24 months after more than two BEP chemotherapy cycles. However, few men receiving one or two BEP cycles and some dropouts are the main limitations of this study. [ABSTRACT FROM AUTHOR]

Objective: To assess sperm production and aneuploidy in Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) before and after treatments.Design: Multicenter, prospective, longitudinal study of lymphoma patients analyzed before treatment and after 3, 6, 12, and 24 months.Setting: University hospitals.Patient(s): Forty-five HL and 13 NHL patients were investigated before and after treatment. Treatment regimens were classified in two groups: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) with or without (±) radiotherapy, and CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)/MOPP-ABV (mechlorethamine, oncovin, procarbazine, prednisone-doxorubicin, bleomycin, vinblastine). A control group of 29 healthy men was also studied.Intervention(s): Semen analyses and aneuploidy study by FISH were performed at each time point.Main Outcome Measure(s): Comparison of mean sperm characteristics and percentage of sperm aneuploidy rates before and after treatment.Result(s): Before treatment, HL and NHL men had altered semen characteristics and higher sperm aneuploidy rates (median 0.76 [interquartile range 0.56-0.64]) than the control group (0.54 [0.46-0.74]). After treatment, sperm production was significantly lowered 3 and 6 months after ABVD ± radiotherapy or CHOP/MOPP-ABV. After ABVD ± radiotherapy, the aneuploidy rate increased significantly only at 3 months, and values obtained 1 or 2 years later were lower than pretreatment values. In contrast, in the CHOP/MOPP-ABV treatment group, semen characteristics and aneuploidy rate did not return to normal levels until 2 years after treatment.Conclusion(s): Lymphoma itself has consequences on sperm aneuploidy frequency before treatment. Moreover, lymphoma treatments have deleterious effects on sperm chromosomes related to treatment type and time since treatment. Patient counseling is essential concerning the transient but significant sperm aneuploidy induced by lymphoma and its treatments. [ABSTRACT FROM AUTHOR]

Objective: To report the effects of ribavirin plus pegylated interferon on semen parameters and sperm DNA integrity in a man given treatment for hepatitis C.Design: Case report.Setting: University-affiliated teaching hospital.Intervention(s): None.Patient(s): A 37-year-old man given treatment with ribavirin and pegylated interferon for hepatitis C.Main Outcome Measure(s): Semen parameters (sperm count, motility, round cells), sperm protamination state measured by sperm chromatin structure assay, and sperm DNA fragmentation measured by terminal uridine nick-end labeling assay.Result(s): The percentage of progressive spermatozoa and the number of motile sperm per ejaculate decreased during treatment. The round cell/spermatozoa ratio, which reflects spermatogenic abnormality, increased from 2.6% +/- 1.4% to 23.6% +/- 13.0% during treatment and returned to baseline value 4 months later. Moreover, the sperm DNA fragmentation index (as measured by sperm chromatin structure assay) increased very markedly during treatment (from 14.5% before to 69.2% at 7 months of treatment) and remained elevated 8 months later.Conclusion(s): This study reports for the first time not only quantitative but also qualitative alterations of spermatogenesis with DNA packaging abnormalities and emphasizes the need for prospective clinical studies. While the results of other studies are awaited, the alterations that persisted 8 months after treatment argue for a longer contraception period after treatment discontinuation in men. [ABSTRACT FROM AUTHOR]

Objective: To report parameters in semen samples and sperm DNA integrity in a healthy fertile volunteer over a 10-year period. Design: Case report. Setting: University-affiliated teaching hospital. Intervention(s): None. Patient(s): Semen samples from a nonsmoking healthy male volunteer of proven fertility aged from 40 to 50 years were collected and analyzed over a decade. Main Outcome Measure(s): Semen parameters (sperm count, total sperm count, percentage of progressive motility grades a+b, morphology, and percentage of living spermatozoa) and sperm DNA integrity, measured by sperm chromatin structure assay (SCSA) and terminal uridine nick-end labeling (TUNEL) assay. Result(s): Median (min–max) value of total sperm count was 330 (126–511) million. Motility and vitality presented a median of 50% (40%–75%) and 78% (53%–92%), respectively. Among semen parameters, morphology and vitality showed the lowest within-subject coefficient of variation (CVW) and the total sperm count the highest (8.1% and 12.0% vs. 34.9%). Median values of DNA fragmentation index (DFI) and high DNA stainability (HDS) were 12.7% (7.9%–16.5%) and 6.5% (5.5%–8.2%), respectively. Sperm DNA fragmentation presented a median value of 8.9%, a minimum value of 1.4% and maximum value of 18.6%. Compared with TUNEL data, SCSA parameters (DFI and HDS) showed less variation over the data collection period (47.4% vs. 22.4% and 13.0%, respectively). Conclusion(s): Our data show that in this healthy fertile volunteer, semen parameters and sperm DNA integrity remained normal, and no trend was observed over the study period. More interestingly, in this subject aged from 40 to 50 years old, sperm nucleus status presented less than 20% of sperm DNA fragmentation over a decade. [Copyright &y& Elsevier]