Collaborative digital platform France - Cuba: oncorehabilitation in reproductive and sexual health.

BACKGROUND: In the French West-Indies, few studies have been performed on fertility and sexual problems in cancer survivors, which are frequent and recurring issues reported by surveys on unmet needs. Additionally, mutualizing human and material resources and promoting cooperation through a collaborative platform are the most appropriate response to complex health pathways in the Caribbean territories. Implementation of such a collaborative platform will help to launch a strategic Caribbean partnership to transfer theoretical and technical skills and care standards in oncofertility and oncosexuality. METHODS: We propose to set up a collaborative digital platform to strengthen, from the French expertise, Cuban health professionals' knowledge, know-how, and skills in oncofertility and oncosexuality. The project will be coordinated by a coordinating, scientific, and supervisory committee, and the main activities will include: 1. Theoretical training in e-learning adapted to low-speed Internet. 2. Practical training in fertility preservation and sexual rehabilitation. 3. Digital multidisciplinary consultation meetings for medical decisions to be taken for complex clinical cases. The platform will benefit from a recurrent evaluation, by the two cancer registries of Martinique and Cuba, with the following performance indicators: number of Cuban professionals trained, number of professionals sensitized, hourly volumes (or number of training courses provided), satisfaction of trained professionals, number of e-RCPs carried out online and number of missionaries supported. These indicators will be set up and analyzed by the registers. This project meets the Cuban and French health policies (cancer plans and national sexual health strategies) and will be implemented in liaison with the Health Agencies of both countries and the Embassy of France in Cuba. DISCUSSION: This project aims to provide support through bilateral exchanges to improve reproductive and sexual health in Cuba's cancer patients. This collaboration will be based on a long-lasting French expertise and a solid Cuban health system. Consequently, this collaborative digital platform will contribute to data collection for cancer surveillance, and the two participating countries will ultimately be identified in the Caribbean as having centers of competence and excellence in oncofertility and oncosexuality with care standards.

Triglycerides as a Metabolic Target in Afrocaribbean Infertile Women with Polycystic Ovary Syndrome.

Background: Polycystic ovary syndrome (PCOS) is classically associated with insulin resistance, metabolic syndrome, or type 2 diabetes. Infertile Afrocaribbean (AC) women with PCOS may have metabolic features that could help to better target their management. Objective: To evaluate the characteristics of PCOS in this population and their metabolic profile to target the worst metabolic parameter. Methods: A retrospective study including infertile AC women for 4 years. PCOS was diagnosed using Rotterdam criteria and compared with non-PCOS women referred consecutively for infertility during the same period. Results: Among 981 AC women evaluated for infertility, PCOS was found in 17%. PCOS women were younger than non-PCOS women. After age and body mass index (BMI) matching, only fasting blood glucose and triglyceride levels were higher in PCOS women compared with non-PCOS women. PCOS was positively correlated with triglyceride levels and negatively with vitamin D levels. PCOS women with obesity had low high-density lipoprotein-cholesterol and increased triglyceride levels compared with those without obesity. No correlation was found between lipids or glucose levels and androgen levels. Multivariate analysis showed that only triglycerides were independently related to PCOS after adjustment for age and BMI. Conclusions: In the AC population where the prevalence of obesity and diabetes is increased, the metabolic profile of infertile women with PCOS is mainly characterized by hypertriglyceridemia, with a higher risk of visceral obesity and nonalcoholic fatty liver disease. Interventional studies would be useful to evaluate the predictive value of hypertriglyceridemia on diabetes and cardiovascular diseases in this population.

Upper and lower genital tract Zika virus screening in a large cohort of reproductive-age women during the Americas epidemic.

RESEARCH QUESTION: 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. DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Zika virus infects human testicular tissue and germ cells.

Zika virus (ZIKV) is a teratogenic mosquito-borne flavivirus that can be sexually transmitted from man to woman. The finding of high viral loads and prolonged viral shedding in semen suggests that ZIKV replicates within the human male genital tract, but its target organs are unknown. Using ex vivo infection of organotypic cultures, we demonstrated here that ZIKV replicates in human testicular tissue and infects a broad range of cell types, including germ cells, which we also identified as infected in semen from ZIKV-infected donors. ZIKV had no major deleterious effect on the morphology and hormonal production of the human testis explants. Infection induced a broad antiviral response but no IFN upregulation and minimal proinflammatory response in testis explants, with no cytopathic effect. Finally, we studied ZIKV infection in mouse testis and compared it to human infection. This study provides key insights into how ZIKV may persist in semen and alter semen parameters, as well as a valuable tool for testing antiviral agents.

Kinetics of anti-ZIKV antibodies after Zika infection using two commercial enzyme-linked immunoassays.

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 180days after clinical onset. The Diapro assay detected anti-ZIKV IgM reactivity more frequently (100%) and for longer (median 53days) than did the Euroimmun assay (60%; 13days, P<0.005). Both assays detected anti-ZIKV IgG reactivity 11days 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.

Effect of acute Zika virus infection on sperm and virus clearance in body fluids: a prospective observational study.

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.