Myriam Daudin

Fertility after testicular cancer treatments: Results of a large multicenter study

Patients with testicular cancer have an excellent survival rate, and fertility is one of the main concerns of survivors. The authors investigated fertility status after treatment for testis cancer in long‐term survivors.

Congenital bilateral absence of the vas deferens: clinical characteristics, biological parameters, cystic fibrosis transmembrane conductance regulator gene mutations, and implications for genetic counseling.

OBJECTIVE To evaluate relationships between the phenotypic and genotypic characteristics of patients with congenital bilateral absence of the vas deferens (CBAVD). DESIGN Retrospective study. SETTING A university hospital urology-andrology department. PATIENT(S) Forty-one men with CBAVD. INTERVENTION(S) CBAVD was diagnosed during surgical and/or ultrasound exploration of the vasa deferentia (VD) (n = 39), or on the basis of impalpable scrotal VD (n = 2). MAIN OUTCOME MEASURE(S) History, clinical and seminal characteristics, and cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations including IVS-8 polyT analysis. RESULT(S) A palpable scrotal vas deferens was present as a fibrous cord or nonpermeable duct in 13% of patients undergoing surgical exploration. Seminal vesicles were bilaterally absent in 28% of patients. No CFTR gene mutation or 5T allele was detected in 24.5% of the patients. Two CBAVD patients with renal agenesis carried a CFTR gene mutation (DeltaF508/5T-9T and R117G/7T-9T). CBAVD patients who have both a semen volume of < or =1.0 mL and a semen pH of < 7.0 have a significantly higher risk of severe CFTR gene mutation (OR = 9.12 [95% CI = 1.81-49.50]). CONCLUSION(S) A palpable scrotal vas deferens was found in 13% of CBAVD patients. Semen volume of < or =1.0 mL and semen pH of < 7.0 in CBAVD patients were associated with a higher risk of severe CFTR gene mutations. Patients with CBAVD and renal agenesis should be screened for CFTR gene mutations before assisted reproductive techniques are used.

Factors of intermittent HIV-1 excretion in semen and efficiency of sperm processing in obtaining spermatozoa without HIV-1 genomes

Objective: To study the risk factors for HIV-1 in semen according to the localization of HIV-1 in sperm cell fractions and to assess the efficiency of sperm processing in obtaining spermatozoa without HIV-1 genomes. Methods: Ninety-four HIV-infected patients provided 281 paired blood and semen samples. Sperm cell separation was performed using two successive methods. HIV-1 RNA was quantified in blood and seminal plasma. HIV-1 RNA and DNA were detected in cell fractions. Results: HIV-1 RNA was found in 14% of seminal plasma samples and up to 8.7% of native semen cells were positive for HIV-1 RNA and DNA. Ten seminal plasma samples had detectable RNA although blood viral load was undetectable. Antiretroviral treatment reduced the likelihood of RNA detection in seminal plasma. For semen with polynuclear cells and HIV-1 RNA in seminal plasma, the likelihood of detecting HIV-1 genomes in semen cells was increased fourfold and sixfold, respectively. In 25% of patients, HIV-1 excretion was intermittent. In the group of patients with systematic negative seminal plasma, HIV-1 genomes were detected in up to 10% of sperm cell samples. Our method of sperm processing always enabled us to obtain spermatozoa without detectable HIV-1 genomes. Conclusions: Polynuclear cells in semen are a risk factor for seminal HIV-1 excretion. Blood viral load was the only predictive factor for the intermittence of HIV-1 excretion in semen over time. Sperm processing using two successive methods was effective in obtaining spermatozoa without detectable HIV-1 genomes regardless of the viral load level in native semen.

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

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.

Sperm cryopreservation in adolescents and young adults with cancer: results of the French national sperm banking network (CECOS)

OBJECTIVE To determine the feasibility of fertility preservation in adolescent males with cancer. DESIGN Large multicenter retrospective study of male patients ≤20 years from 23 centers of a national network of sperm banks over a 34-year period. SETTING Sperm banks. PATIENT(S) A total of 4,345 boys and young men aged 11 to 20 years. INTERVENTION(S) Age, cancer diagnosis, feasibility of sperm banking, and sperm parameters. MAIN OUTCOME MEASURE(S) Description of patients, and success of their fertility preservation. RESULT(S) We observed a mean yearly increase in referred patients of 9.5% (95% confidence interval, 9.1%-9.8%) between 1973 and 2007. Over the study period, the percentage of younger cancer patients who banked their sperm increased, especially in the 11-14 year age group, rising from 1% in 1986 to 9% in 2006. We found that 4,314 patients attempted to produce a semen sample, 4,004 succeeded, and sperm was banked for 3,616. The mean total sperm count was 61.75 × 10(6) for the 11-14 year age group, and 138.81 × 10(6) for the 18-20 year age group. It was noteworthy that intercenter variations in practices involving young patients seeking to preserve their fertility before cancer therapy were observed within this national network. CONCLUSION(S) Our results emphasize the need for decisive changes in public health policy to facilitate the access to reproductive health-care for young cancer patients.

Intermittent human immunodeficiency type 1 virus (HIV-1) shedding in semen and efficiency of sperm processing despite high seminal HIV-1 RNA levels

To 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. Case report. University hospital and research group on human fertility. One HIV-1-infected patient.Paired blood and semen samples were obtained during 4 years of follow-up.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. 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. In an HIV-1-infected man with intermittent seminal viral excretion, sperm processing was effective in obtaining spermatozoa without detectable HIV-1 genomes.

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

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.

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

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.