Nathalie Moinard

Zika virus in semen of a patient returning from a non-epidemic area.

894 www.thelancet.com/infection Vol 16 August 2016 one or more other microorganisms (Staphylococcus aureus, Enterococcus faecalis, Staphylococcus hominis, Corynebacterium pseudodiphtericum, and Aeromonas spp). We treated one of our cases with only antituberculosis therapy without surgery, and treated four with surgery followed by antituberculosis therapy, including debridement, antibiotics, and implant retention in one case, and two-stage prosthesis exchange in the three other cases. The mean length of antituberculosis therapy was 11 months. Remission was observed in four cases with an average follow-up of 24 months. One patient died of systemic tuberculosis after 2 months of treatment. Despite the high volume of arthroplasty, tuberculosis prosthetic joint infection is rare. Early prosthetic joint infection might be explained by pre-existing tuberculous coxitis. In other cases, tuberculosis prosthetic joint infection is likely to be a haematogenous infection following systemic tuberculosis. Diagnosis of tuberculosis prosthetic joint infection is mainly reached through positive cultures of deep samples. Nevertheless, percutaneous biopsy has been shown to be an alternative diagnostic method, as used in two of our cases. On the basis of our data, we believe that tuberculosis prosthetic joint infection is certainly under-reported and should be considered in culture-negative prosthetic joint infections, and not only in patients with a past medical history of osteoarticular tuberculosis. Previous or concomitant infection with another pathogen should not exclude diagnosis. Careful histological analysis, systematic mycobacterial cultures, and the contribution of specific PCR detection could help physicians to diagnose tuberculosis prosthetic joint infection.

Impact of chemotherapy and radiotherapy for testicular germ cell tumors on spermatogenesis and sperm DNA: a multicenter prospective study from the CECOS network

OBJECTIVEnTo 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.nnnDESIGNnMulticenter prospective longitudinal study of patients analyzed before treatment and after 3, 6, 12, and 24 months.nnnSETTINGnUniversity hospitals.nnnPATIENT(S)nOne hundred twenty-nine volunteer TGCT patients and a control group of 257 fertile men.nnnINTERVENTION(S)nRoutine semen analyses, sperm DNA, and chromatin assessments.nnnMAIN OUTCOME MEASURE(S)nComparisons of mean sperm characteristics before and after treatment, with sperm recovery analyzed by the Kaplan-Meier method.nnnRESULT(S)nThe 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.nnnCONCLUSION(S)nAdjuvant 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.

Mild induced testicular and epididymal hyperthermia alters sperm chromatin integrity in men

OBJECTIVEnTo investigate the effects of a mild induced testicular and epididymal hyperthermia (+2°C) on sperm chromatin integrity in men.nnnDESIGNnExperimental prospective study.nnnSETTINGnUniversity hospital.nnnPATIENT(S)nFive healthy fertile volunteers.nnnINTERVENTION(S)nTesticular 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.nnnMAIN OUTCOME MEASURE(S)nClassic semen characteristics. Sperm DNA fragmentation index (DFI) and high DNA stainability (HDS) were analyzed by sperm chromatin structure assay.nnnRESULT(S)nCompared 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.nnnCONCLUSION(S)nMild 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.

Impact of lymphoma treatments on spermatogenesis and sperm deoxyribonucleic acid: a multicenter prospective study from the CECOS network

OBJECTIVEnTo determine consequences of lymphoma treatments on sperm characteristics and sperm DNA, and to evaluate predictors of sperm recovery.nnnDESIGNnMulticenter prospective longitudinal study of patients analyzed before treatment and after 3, 6, 12, and 24 months.nnnSETTINGnUniversity hospitals.nnnPATIENT(S)nSeventy-five Hodgkin lymphoma and non-Hodgkin lymphoma patients and a control group of 257 fertile men.nnnINTERVENTION(S)nSemen analyses, and sperm DNA and chromatin assessments.nnnMAIN OUTCOME MEASURE(S)nComparisons of sperm characteristics before and after treatment.nnnRESULT(S)nPatients 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.nnnCONCLUSION(S)nLymphoma 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.

Determining Seminal Plasma Human Immunodeficiency Virus Type 1 Load in the Context of Efficient Highly Active Antiretroviral Therapy

ABSTRACT The semen plasma virus load is measured to ensure the safety of sperm processing during medically assisted procreation (MAP) for couples with a human immunodeficiency virus type 1 (HIV-1)-infected man. A practical, automated protocol using the COBAS Ampliprep CAP/CTM kit in the COBAS TaqMan96 system was developed to measure the HIV-1 load in semen plasma samples. HIV-1 was detected in 13.4% of the semen samples processed at our MAP center. Of the eight patients having a detectable semen HIV-1 load, five had no detectable virus in their blood plasma. This highlights the residual risk of HIV-1 transmission during unprotected intercourse and raises the question of the possible consequences of ineffective highly active antiretroviral therapy in the genital tract.

Decrease of mitochondrial DNA level in sperm from patients infected with human immunodeficiency virus-1 linked to nucleoside analogue reverse transcriptase inhibitors

OBJECTIVEnTo 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.nnnDESIGNnObservational study.nnnSETTINGnUniversity-affiliated teaching hospital.nnnPATIENT(S)nThirty-two patients infected with HIV-1 and 31 noninfected healthy men provided semen samples.nnnINTERVENTION(S)nNone.nnnMAIN OUTCOME MEASURE(S)nAfter 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.nnnRESULT(S)nCompared 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).nnnCONCLUSION(S)nUsing a specific method to measure sperm mtDNA, we demonstrated a decrease of mtDNA copies in spermatozoa after use of NRTIs with known mitochondrial toxicity.

Ribavirin and pegylated interferon treatment for hepatitis C was associated not only with semen alterations but also with sperm deoxyribonucleic acid fragmentation in humans

OBJECTIVEnTo report the effects of ribavirin plus pegylated interferon on semen parameters and sperm DNA integrity in a man given treatment for hepatitis C.nnnDESIGNnCase report.nnnSETTINGnUniversity-affiliated teaching hospital.nnnINTERVENTION(S)nNone.nnnPATIENT(S)nA 37-year-old man given treatment with ribavirin and pegylated interferon for hepatitis C.nnnMAIN OUTCOME MEASURE(S)nSemen 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.nnnRESULT(S)nThe 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.nnnCONCLUSION(S)nThis 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.

In vitro assessment of the adverse effects of antiretroviral drugs on the human male gamete.

This study was designed to investigate the in vitro effects of didanosine, zidovudine, saquinavir and indinavir, commonly used in highly active antiretroviral therapy, on human sperm fertility parameters. Thirty semen samples from healthy men were collected and prepared by gradient density method. Aliquots of 90% fractions with >80% motile spermatozoa were incubated for 1, 3, and 6h with different concentrations of the antiretroviral drugs (20, 40, and 80 μg/ml). Sperm motility was evaluated by computer assisted sperm analysis system. Sperm mitochondrial potential was evaluated using 3,3-dihexyloxacarbocyanine iodide (DIOC(6)) and the acrosome reaction was examined using pisum sativum agglutinin method. A dose-dependent decrease in sperm motility was observed with saquinavir. Saquinavir also induced a significant time and dose-dependent decrease in mitochondrial potential and an increase in spontaneous acrosome reaction. These findings indicate that, in vitro, higher doses of saquinavir have adverse effects on sperm motility, mitochondrial potential and acrosome reaction.

Antiviral effect of maraviroc in semen: a case report.

We describe the antiviral effect of maraviroc in a patient who had been shedding high levels of HIV-1 in seminal fluid for three years despite an undetectable blood plasma viral load. Adding maraviroc to HAART stopped the seminal shedding. We discuss the mechanisms involved and the effect on sexual transmission.

Impact of Hodgkin or non-Hodgkin lymphoma and their treatments on sperm aneuploidy: a prospective study by the French CECOS network.

OBJECTIVEnTo assess sperm production and aneuploidy in Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) before and after treatments.nnnDESIGNnMulticenter, prospective, longitudinal study of lymphoma patients analyzed before treatment and after 3, 6, 12, and 24xa0months.nnnSETTINGnUniversity hospitals.nnnPATIENT(S)nForty-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.nnnINTERVENTION(S)nSemen analyses and aneuploidy study by FISH were performed at each time point.nnnMAIN OUTCOME MEASURE(S)nComparison of mean sperm characteristics and percentage of sperm aneuploidy rates before and after treatment.nnnRESULT(S)nBefore 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 6xa0months after ABVD ± radiotherapy or CHOP/MOPP-ABV. After ABVD ± radiotherapy, the aneuploidy rate increased significantly only at 3xa0months, and values obtained 1 or 2xa0years 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 2xa0years after treatment.nnnCONCLUSION(S)nLymphoma 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.