Domestic use of pesticides during early periods of development and risk of testicular germ cell tumors in adulthood: a French nationwide case-control study.

BACKGROUND: Testicular germ cell tumours (TGCT) are the most frequent cancers in young men in developed countries and their incidence rate has doubled worldwide over the past 40 years. Early life exposures to pesticides are suspected to increase TGCT risk. Our research aimed at estimating adult TGCT risk associated with parental domestic use of pesticides during early periods of child development. METHODS: We conducted a case-control study of 304 TGCT cases, aged 18-45 years old, recruited in 20 French university hospitals, and 274 controls frequency-matched on hospital and birth year. Participants' mothers provided information on their domestic use of pesticides from 1 year before start of pregnancy to 1 year after their son's birth, for gardening activities, treatment of indoor plants, pets, wood and mold, and pest control. Odds ratios (OR) for TGCT (overall and by histological subtype) and 95% confidence intervals (CI) were estimated using conditional logistic regression. RESULTS: Prevalence of reported domestic use of pesticides was 77.3% for insecticides, 15.9% for fungicides and 12.1% for herbicides. While no association was found for any use of insecticides (OR = 1.27, CI = 0.80-2.01) or herbicides (OR = 1.15, CI = 0.67-2.00), elevated risks of TGCT overall (OR = 1.73, CI = 1.04-2.87) and non-seminoma subtype (OR = 2.44, CI = 1.26-4.74) were observed for any use of fungicides. When specific purposes were examined, using fungicides and/or insecticides for woodwork (OR = 2.35, CI = 1.06-5.20) and using insecticides on cats and dogs (OR = 1.95, CI = 1.12-3.40) were associated with increased risk of non-seminoma subtype. We found no association for seminoma subtype. CONCLUSIONS: Although recall bias may partially explain the elevated ORs, our study provides some evidence of a positive association between domestic use of pesticides during early periods of development, particularly fungicides and risk of adult TGCT and non-seminoma. Given the common domestic use of pesticides in France, further research on TGCT risk is warranted.

Women utilizing oocyte donation have a decreased live birth rate if they displayed a low progesterone level in a previous hormonal replacement mock cycle.

PURPOSE: Is serum progesterone(P) level on day 2 of vaginal P administration in a hormonally substituted mock cycle predictive of live birth in oocyte donation(OD)? METHODS: Retrospective analysis of 110 mock cycles from 2008 to 2016 of OD recipients having at least one subsequent embryo transfer (ET). Endometrial preparation consisted of sequential administration of vaginal estradiol, followed by transdermal estradiol and 600 mg/day vaginal micronized P. In mock cycles, serum P was measured 2 days after vaginal P introduction. OD was performed 1 to 3 years later, without P measurement. RESULTS: In mock cycles, mean serum P level on day 2 was 12.8 ± 4.5 ng/mL (range: 4-28 ng/mL). A total of 32% patients had P < 10 ng/mL. At the time of first OD, age of recipients and donors, number of retrieved and attributed oocytes, and number of transferred embryos were comparable between patients with P < 10 ng/mL in their mock cycles compared with P ≥ 10 ng/mL. Pregnancy and live birth rate after first ET were significantly lower for patients with P < 10ng/mL (9% vs. 35 %; P = 0.002 and 9% vs. 32%; P = 0.008, respectively). Considering both fresh and subsequent frozen-thawed ET, cumulative live birth rate per-patient and per-transfer were significantly lower in patients with P < 10 ng/mL in their mock cycle (14% vs. 35%; P = 0.02 and 11% vs. 27%; P = 0.03). CONCLUSION: A low P level in hormonally substituted cycles several years before ET performed with the same endometrial preparation is associated with a significantly lower chance of live birth. This suggests that altered vaginal P absorption is a permanent phenomenon. Monitoring serum P in hormonally substituted cycles appears mandatory to adjust luteal P substitution.

[AFU and SALF recommendations for the evaluation of male infertility]. / Recommandations de l'AFU et de la SALF concernant l'évaluation de l'homme infertile.

BACKGROUND: The aim of these Association Française d'Urologie (AFU) and Société d'Andrologie de Langue Française (SALF) common recommendations are to provide practice guidelines for the French Urological and Andrological community regarding the evaluation of infertile men. MATERIAL AND METHODS: Literature search in PubMed using the keywords "male infertility", "diagnosis", "management" and "evaluation" limited to clinical articles in English and French prior to 1/01/2020. To inform the level of evidence, the HAS grading system (2013) was applied. RESULTS: Concerning the evaluation of infertile men, the AFU and the SALF recommend : (1) a systematic interview exploring the family history, the fertility history of the man outside the couple, the patient's personal history that may have an impact on his fertility, lifestyle habits, treatments, symptoms and possible sexual difficulties of the couple; (2) a general physical examination to assess signs of hypogonadism and secondary sexual characters; (3) a scrotal physical examination performed by an urologist or andrologist to assess (i) the testes for volume and consistency, (ii) vas deferens and epididymes for total or partial absence or nodules, and (iii) presence of varicoceles; (4) Performing two semen analyses, according to World Health Organization guidelines, if the first one has at least one abnormaly; (5) a scrotal ultrasound as part of routine investigation, that can be completed with an endorectal pelvic ultrasound according to the clinic; (6) an endocrine evaluation with at least a Testosterone and FSH serum determination; (7) Karyotype analysis in infertile men with a sperm concentration ≤10 106/mL; (8) assessment of Yq microdeletions in infertile men with a sperm concentration ≤1 106/mL; (9) Cystic fibrosis transmembrane conductance regulator gene evaluation in case of suspicion for bilateral or unilateral congenital agenesis of vas deferens and seminal vesicles. The interest of tests analyzing DNA fragmentation (TUNEL, SCSA) is still under investigation. CONCLUSION: These guidelines can be applied in routine clinical practice in all infertile men.

In vitro maturation is a viable option for urgent fertility preservation in young women with hematological conditions.

Fertility preservation embraces different techniques developed to improve young women chances of becoming mothers after healing. Among them, in vitro maturation (IVM) procedure is based on oocyte retrieval without any gonadotropin treatment, feasible under locoregional or local anesthesia, with very low operative complications. The present retrospective analysis of a preliminary case series of 25 women diagnosed with Hodgkin or non-Hodgkin lymphoma aims to evaluate the feasibility of IVM for urgent fertility preservation purposes in hematological context. A median of five mature oocytes was cryopreserved after one cycle of IVM, performed without delaying the start of the chemotherapy (median delay from histological diagnosis to start of the chemotherapy 17.5 days). No association was found between lymphomas' characteristics and the number of recovered or frozen oocytes. Although experimental, this technique could be relevant when fertility preservation has to be performed within a short time frame and without additional surgery nor any risk of malignant cells reintroduction.

Different exposure windows to low doses of genistein and/or vinclozolin result in contrasted disorders of testis function and gene expression of exposed rats and their unexposed progeny.

Living species including humans are continuously exposed to low levels of a myriad of endocrine active compounds that may affect their reproductive function. In contrast, experimental designs scrutinizing this question mostly consider the gestational/lactational period, select high unrealistic doses and, have rarely investigated the possible reproductive consequences in the progeny. The present study aimed at assessing comparatively a set of male reproductive endpoints according to exposure windows, gestational/lactational versus pre-pubertal to adulthood, using low doses of endocrine active substances in male rats as well as their unexposed male progeny. Animals were orally exposed to 1 mg/kg bw/d of genistein and/or vinclozolin, from conception to weaning or from prepuberty to young adulthood. A number of reproductive endpoints were assessed as well as testicular mRNA expression profiles, in the exposed rats and their unexposed progeny. Overall, the low dosage used only affected weakly most of classical reproductive endpoints. However, the gestational/lactational exposure to vinclozolin alone or combined to genistein significantly delayed the puberty onset. Contrasting with the gestational/lactational exposure, a decreased sperm production was found in the animals exposed to genistein and vinclozolin from the pre-pubertal period but also in their progeny for vinclozolin and the mixture. The expression level of several genes involved in meiosis, apoptosis and steroidogenesis was also affected differentially as a function of the exposure window in both exposed rats and unexposed offspring. We also provide further evidence that doses of endocrine active substances relevant with human exposure may affect the male reproductive phenotype and testicular transcriptome in the exposed generation as well as in the indirectly exposed offspring.

[Missions and organization of the CECOS]. / Organisation et missions des CECOS.

Missions and organization of the CECOS. The 26 centers for study and conservation of human sperm and eggs (CECOS) are distributed on the French territory and have two mainly missions: to assure the sperm, oocytes and embryo donations, and the fertility preservation before a gonad toxic treatment such as for example cancer treatments. To assure their missions the CECOS includes a multidisciplinary team and a cryobiology platform and are associated with units of assisted reproductive technologies in university hospitals. They are included in network within the French Federation of the CECOS. The objective is to facilitate an equal access to the reproduction with donor gametes and to the fertility preservation. The CECOS federation, thanks to its commissions and its annual seminar, is also an authority of reference, of ethical reflection and scientific research.

Organisation et missions des CECOS. Les 26 centres d'étude et de conservation des oeufs et du sperme humains (CECOS) recouvrent le territoire français et ont principalement pour mission d'assurer le don de spermatozoïdes, d'ovocytes et d'embryons ainsi que la préservation de la fertilité de l'homme, de la femme et de l'enfant, lorsque celle-ci risque d'être prématurément altérée ou avant un traitement gonadotoxique, comme par exemple certains traitements du cancer. Pour assurer leurs missions, les CECOS incluent une équipe pluridisciplinaire et un plateau de cryobiologie et sont associés aux centres d'assistance médicale à la procréation (AMP) dans les centres hospitaliers universitaires. Ils sont regroupés en réseau au sein de la Fédération française des CECOS. L'objectif est de faciliter un accès équitable à la procréation avec gamètes de donneur ou donneuse et à la préservation de la fertilité. La Fédération française des CECOS, grâce à ses commissions et son séminaire, est une instance de référence, de réflexion éthique et de recherche scientifique.

[Extension of the Use of Gametes in Intra-couple (EUGIC): How to use trans woman' spermatozoa?] / Extension de l'Utilisation de Gamètes en IntraConjugal (EUGIC) : quel usage des spermatozoïdes d'une femme trans ?

OBJECTIVE: The French Law relating to Bioethics allows access to medically assisted reproduction for lesbian couples and single women and has expanded the possibilities for self-preservation of gametes. The question now arises of new uses of gametes of the couple, within couples of two cis women, one cis woman and one transgender woman, or two transgender individuals. The acronym EUGIC (Extension of the Use of Gametes in IntraCouple) allows these new situations to be grouped together, particularly if gametes have already been previously cryopreserved, thus avoiding the need for gamete donation. METHODS: Analysis of the different situations of sperm use from a trans woman using gametes available within the couple rather than gamete donation. RESULTS: The inconsistency in the use of sperm from a trans woman, the situations already encountered by professionals, the prospects for filiation for a trans woman as well as the issues related to the interest of the unborn child are discussed. CONCLUSION: French law does not fully address the use of a trans woman's spermatozoa to meet the new EUGIC requirements and leads to complex situations for healthcare professionals.

Fertility outcomes several years after urgent fertility preservation for patients with breast cancer.

OBJECTIVE: To study the fertility outcomes of women who tried to conceive after breast cancer (BC) treatment and fertility preservation. DESIGN: Retrospective observational, bicentric cohort study. SETTING: University hospital. PATIENTS: Patients with BC. INTERVENTION: All patients who had undergone fertility preservation before BC treatment between January 2013 and July 2019 were included (n = 844). The endpoint date was March 1, 2022. Patients with missing data on pregnancy attempts after a cancer diagnosis (n = 195) were excluded from the pregnancy analysis. MAIN OUTCOME MEASURES: Cumulative incidences of pregnancy and live birth (LB) were calculated. For women who became pregnant, the time to conception was calculated between the first fertility preservation consultation and the estimated day of conception. For those who did not conceive, we considered the time between the first fertility preservation consultation and the endpoint date, or the date of patient death. A Cox regression model was used to study the predictive factors for pregnancy and LB. RESULTS: Among the 649 patients with available data on pregnancy attempts after BC diagnosis, 255 (39.3% [35.5-43.2]) tried to conceive (median follow-up of 6.5 years). Overall, 135 (52.9% [46.6-59.2]) of these patients achieved a pregnancy, mainly through unassisted conception (79.3% [72.8-84.8]), and 99 reported an LB (representing 38.8% of patients who attempted conception). In our cohort, 48 months after the first fertility preservation consultation, the cumulative incidence of pregnancy was 33.1% ([27.6-37.9]). After adjustment for age, parity, type of chemotherapy administration, and endocrine therapy, only multiparity at diagnosis and absence of chemotherapy were positive predictive factors of pregnancy after cancer. Of the 793 patients who had vitrified oocytes and embryos, 68 used them (27% [21.3-32.5] of the patients who tried to conceive), resulting in 8 LBs (11.8% [5.2-21.9]). Women who used their cryopreserved oocytes and embryos were older at the first consultation of fertility preservation (hazard ratio 1.71 [1.42-2.21]), and chose more often to vitrify embryos (hazard ratio 1.76 [1.28-2.23]). CONCLUSION: Although pregnancy rates after fertility preservation for patients with BC are low, most conceptions are achieved without medical assistance. Our findings provide useful information to advise women on the different techniques of fertility preservation, their efficacy, and safety, as well as the relatively high chances of unassisted conception.

Chromosomal abnormalities in oocyte donor candidates: a French survey of over 8200 karyotypes.

OBJECTIVE: To study karyotypes of more than 8,200 oocyte donor candidates in nulliparous or multiparous women compared to a reference population. DESIGN: A retrospective observational multicentric study. SUBJECTS: The study included two cohorts of oocyte donor candidates recruited between January 2005 and October 2021: multiparous women with at least one child at the time of recruitment, and nulliparous women. Both were compared to a reference population composed of female newborns from literature. EXPOSURE: Not applicable. MAIN OUTCOME MEASURES: Blood lymphocyte karyotype. RESULTS: A total of 8229 oocyte donor candidates from 22 fertility centers were included in this study. Nulliparous women (n=1890) and multiparous ones (n=6339) were compared to 8102 female newborns. Overall, 65 candidates were carriers of chromosomal abnormalities and were therefore excluded from the donation process (0.79%, 95% CI: 0.60-0.98). The occurrence of balanced structural chromosomal rearrangements was globally increased in the study population (0.49%, 95% CI: 0.34-0.64) compared to female newborns (0.24%, 95% CI: 0.34-0.64, p=0.0086). The number of reciprocal translocations was increased 5-fold in nulliparous oocyte donor candidates (0.37%, 95% CI: 0.10-0.64, p=0.013). The incidence of sex chromosome mosaicism was notably increased in multiparous oocyte donor candidates, with 17 cases (0.27%, 95% CI: 0.14-0.40, p=0.0052). Among chromosomal aberration carriers only two nulliparous women (one reciprocal translocation and one sex chromosome mosaicism) had fertility issues with a diagnosis of premature ovarian failure. CONCLUSION: In this comprehensive 16-years French experience of karyotyping in oocyte donor candidates, we confirmed an increased incidence of balanced structural chromosomal rearrangements, especially among those without children at the time of recruitment. Karyotyping could be considered to identify any chromosomal abnormalities that may not be easily detectable through medical questioning. These abnormalities pose an inherent genetic risk for gamete recipients if left undetected.

Environmental levels of oestrogenic and antiandrogenic compounds feminize digit ratios in male rats and their unexposed male progeny.

Digit length ratios, especially the second-to-fourth digit ratio (2D : 4D), are associated with various pathological and behavioural conditions in many species including humans and are dependent upon prenatal androgen to oestrogen balance. It is unknown whether digit ratios are modified by environmental exposure to ubiquitous endocrine disruptors. We studied the effect on adult male Wistar rat digit ratios of a gestational exposure to the oestrogenic and antiandrogenic compounds bisphenol A (BPA), genistein and vinclozolin, in low doses, and in combination with investigating in parallel a possible sexual dimorphism of this trait. We also investigated the effects on the male progeny not exposed during gestation. X-rays were taken of the left and right forepaws, and 2D-5D proximal to distal phalanx distances were measured by a standardized procedure based on semi-automatic image analysis. We provide evidence that there is a sexual dimorphism of digit ratios in the Wistar rat, and we found that BPA alone or in combination with genistein and vinclozolin significantly feminized digit ratios in male rats. Intriguingly, significant feminization of digit ratios was also found in the unexposed male progeny of males that had been exposed to compound mixtures. In conclusion, prenatal environmental levels of endocrine-active substances permanently disrupt digit ratios. Digit ratio measurement in adults is thus a promising biomarker of prenatal exposure to low-dose endocrine disruptors in rodents, with potential implications for future studies in humans.

[Ethical implications of supporting trans or questioning children and adolescents: Articulation with reproductive health]. / Enjeux éthiques de l'accompagnement des enfants et des adolescents et adolescentes trans ou en questionnement : articulation à la santé reproductive.

Supporting children and adolescents who are trans or who are questioning cannot be done without an ethical reflection on one's own practice as a health professional. It is important to consider the young person as a whole, including reproductive health issues. This article proposes, through the principles of Beauchamps and Childress, an ethical reflection on the issues of beneficence - not maleficence, and of autonomy and justice for adolescents, young adults, and future trans or questioning parents. For adolescents, concerning the possibilities of medical treatment of gender affirmation, we need to propose information in terms of impact on fertility and, if necessary, proposals for the possibilities of preserving their reproductive capacities. These issues require to question the state of scientific knowledge in terms of parenthood of trans people and questioning. We propose here a state of knowledge of these realities, put in perspectives of the axes of ethical reflections inherent to guidance. In fine, it appears that the major ethical stake concerns the child to be born. Finally, it is necessary to consider the quality of life of the future parents and the impact of their medical follow-up.

Title: Enjeux éthiques de l'accompagnement des enfants et des adolescents et adolescentes trans ou en questionnement : articulation à la santé reproductive. Abstract: L'accompagnement des enfants et des adolescents et adolescentes trans ou en questionnement ne peut faire l'économie d'une pensée éthique réflexive de sa propre pratique en tant que professionnel de santé. Il est important de considérer le jeune dans sa globalité, et cela également en ce qui concerne les enjeux en santé reproductive. Cet article propose, au travers des principes de Tom Beauchamps et James Childress1, une réflexion éthique des enjeux de bienfaisance/non nuisance, d'autonomie et de justice, pour les adolescents, jeunes adultes, et futurs parents trans ou en questionnement. Pour les adolescents et les adolescentes, autour des possibilités de traitement médical d'affirmation de genre, il est nécessaire de proposer des informations, en termes d'impact sur la fertilité et, le cas échéant, des propositions de possibilités de conservation de ses capacités reproductives. Ces enjeux nécessitent d'interroger l'état des connaissances scientifiques en termes de parentalité des personnes trans et en questionnement. Nous proposons ici un état des lieux des connaissances de ces réalités, mises en perspective des axes de réflexions éthiques inhérentes aux accompagnements. In fine, il apparaît que l'enjeu éthique majeur porte sur l'enfant à naître. À cela, il est nécessaire de considérer la qualité de vie des futurs parents et l'impact des accompagnements médicaux des personnes.

Disease-free survival does not differ according to fertility preservation technique for young women with breast cancer.

OBJECTIVE: To study whether fertility preservation strategies using ovarian stimulation or without using it impact long-term disease-free survival of patients with breast cancer. DESIGN: Retrospective bicentric cohort study. SETTING: Two university hospitals. PATIENT(S): In this study, 740 women with breast cancer, aged 18-43 years, who received primary fertility preservation between 2013 and 2019 after a diagnosis of localized breast cancer were included. INTERVENTION(S): Overall, 328 patients underwent at least 1 ovarian stimulation cycle (STIM group) and 412 had a technique without hormonal administration (no STIM group). MAIN OUTCOME MEASURE(S): Disease-free survival and overall survival up to May 2021 were compared between the 2 groups by log-rank test. Cox proportional-hazard regression model was used for multivariable analyses. RESULT(S): Out of the 740 women who underwent fertility preservation, follow-up data were available for 269 women in the STIM group (82%) and 330 (80%) in the no STIM group. Kaplan-Meier estimates of disease-free survival at 4 years were 87.9% (82.8%-92.2%) and 83.1% (78.4%-87.3%) in the STIM and no STIM groups, respectively. After adjustment on prognostic parameters, no significant difference in breast cancer recurrence rate was observed between the STIM and no STIM groups (hazard ratios, 0.83 [0.64-1.08]). Kaplan-Meier estimate of overall survival at 4 years was 97.6% (95.3%-99.2%) and 93.6% (90.9%-95.9%) in the STIM and no STIM groups, respectively. Overall survival was higher in the STIM group than no STIM group (log-rank test). After adjustment on prognostic parameters, the risk of death remained significantly lower in the STIM group (Hazard Ratio, 0.55 [0.35-0.85]). CONCLUSION(S): In our cohort, STIM for fertility preservation in breast cancer did not significantly impact disease-free survival but was associated with higher overall survival. The disease-free survival and overall survival of young patients with breast cancer were not impacted by fertility preservation techniques irrespective of the timing of chemotherapy (neoadjuvant or adjuvant) and the use of ovarian stimulation. Nevertheless, because death and recurrence were rare events, these results should be taken with caution.

Efficient pathway for men fertility preservation in testicular cancer or lymphoma: a cross-sectional study of national 2018 data.

BACKGROUND: In 15-49 years-old men, the main cancers are testicular cancer (TC) and lymphomas (L): freezing of ejaculated sperm is primarily used for male fertility preservation (FP) before cancer treatment. Our objective was to analyze the French FP rate in 15-49 years-old men diagnosed with TC or L in 2018. We designed a national descriptive cross-sectional study of sperm banking rate in men with a diagnosis of TC, Hodgkin L (HL) or non-Hodgkin L (NHL). From the French National Cancer Institute (INCa) 2018 data, we extracted the estimated incidence of TC and L in metropolitan France. From the 2018 activity report of CECOS network (Centers for Study and Banking of Eggs and Sperm), we extracted the number of men with TC or L who banked ejaculated sperm. We estimated the proportion of 15-49 years-old men diagnosed with TC or L who banked sperm. RESULTS: Among 15-49 years-old men, INCa estimated 38,048 new cancer diagnoses in metropolitan France in 2018: 2,630 TC and 3,913 L (943 HL and 2,970 NHL). The CECOS network provided data from 26/27 metropolitan centers (96% response rate): 1,079 sperm banking for men with TC, 375 for HL and 211 for NHL. We estimated that the 2018 sperm banking rate in France was 41% for TC, 40% for HL, and 7% for NHL. CONCLUSIONS: To our knowledge, our paper is the first cross-sectional study with multicenter and national data analyzing FP rate in cancer men: it suggests an efficient pathway for men to FP before cancer treatment, compared to previously published studies. Although sperm banking rate in 15-49 years-old men could definitely be improved, further studies should evaluate the information given to patients before gonadotoxic treatments, the factors associated with the absence of sperm banking and whether this lack of referral induces a loss of chance for these men.

RéSUMé: CONTEXTE: Chez les hommes de 15 à 49 ans, les principaux cancers sont le cancer du testicule (CT) et les lymhomes (L): la congélation de spermatozoïdes éjaculés est utilisée en première intention pour leur préservation de fertilité (PF) avant traitement du cancer. Notre objectif était d'analyser le taux de PF chez les hommes de 15 à 49 ans diagnostiqués avec un CT ou un L en 2018 en France. Nous avons réalisé une étude nationale transversale descriptive du taux de congelation de spermatozoïdes chez les hommes âgés de 15 à 49 ans diagnostiqués avec un CT, un L de Hodgkin (LH) ou un L non-Hodgkinien (LNH). A partir des données de l'Institut National du Cancer (INCa) de 2018, nous avons extrait l'incidence estimée de CT et de L en France métropolitaine. A partir des données du bilan d'activité 2018 de la Federation Française des CECOS (Centre d'Etude et de Conservation des Oeufs et du Sperme), nous avons extrait le nombre d'hommes avec un CT ou un L qui ont congelé leurs spermatozoïdes. Nous avons enfin estimé la proportion d'hommes de 15 à 49 ans diagnostiqués avec un CT ou un L qui ont congelé leurs spermatozoïdes. RéSULTATS: Chez les hommes de 15 à 49 ans, l'INCa a estimé en 2018 38 048 nouveaux cas de cancers diagnostiqués en France métropolitaine en 2018: 2 630 CT et 3 913 L (943 LH et 2 970 LNH). Le réseau des CECOS a produit les résultats issus de 26/27 centres métropolitains (taux de réponse de 96%): 1 079 congélations de sperme pour des hommes atteints de CT, 375 pour LH et 211 pour LNH. Nous avons estimé que le taux de congelation de spermatozoïdes de 2018 en France était de 41% pour le CT, 40% pour le LH et 7% pour le LNH. CONCLUSIONS: A notre connaissance, notre travail est la première étude transversale multicentrique de données nationales analysant le taux de PF chez les hommes atteints de cancer: il suggère un parcours patient efficace pour la PF des hommes avant traitement d'un cancer, par rapport aux études précédemment publiées. Bien que le taux de PF chez les hommes puisse certainemen être amélioré, des études futures devraient évaluer l'information donnée aux patients avant traitement gonadotoxique, les facteurs associés à l'absence de PF et si le défaut d'adressage au CECOS induit un perte de chance pour ces hommes. MOTS-CLéS: Chimiothérapie, Radiothérapie, Oncofertiité, Azoospermia, Paternité.

Sperm parameters and male fertility after bariatric surgery: three case series.

Recent studies have underlined the impact of obesity on sperm parameters, but very few data are available on the effect of weight loss on male fertility. This article reports the case series of three male patients who underwent rapid and major weight loss following bariatric surgery and the consequences of this surgery on semen parameters and fertility. A severe worsening of semen parameters was observed during the months after bariatric surgery, including extreme oligoasthenoteratozoospermia, but azoospermia was not observed. This effect may hypothetically be the result of two opposite mechanisms: (i) the suppression of the deleterious effects of obesity; and (ii) the negative impact of both nutritional deficiencies and the release of toxic substances. Information about potential reproductive consequences of bariatric surgery should be given to patients and sperm cryopreservation before surgery proposed. However, for one case, the alterations of spermatogenesis were reversible 2 years after the surgical procedure. Finally, intracytoplasmic sperm injection with fresh spermatozoa after male bariatric surgery can be successful, as demonstrated here, where clinical pregnancies were obtained for two out of the three couples.

Spatiotemporal trends in human semen quality.

Over the past four decades, studies of various designs have reported spatial and temporal trends in human semen quality. Several standardized-methodology studies in homogeneous populations that compare specific cities within a country or a continent provide clear evidence of geographical differences in sperm production, even over short distances within the same country. Human sperm production is widely believed to be declining over time, but evidence from the scientific literature is less clear. Studies based on repeated cross-sectional data from a single centre have shown mixed results. Among the numerous retrospective studies conducted in a single centre, only some included homogeneous groups of men and appropriate methods, and most of them suggest a temporal decrease in human sperm production in the geographical areas considered. Conclusions reporting temporal trends in sperm production that came from existing retrospective multicentre studies based on individual semen data and those using means, medians or estimates of sperm production are questionable, owing to intrinsic limitations in the studies performed. Regardless of study design, studies on the percentage of motile or morphologically normal spermatozoa are still limited by the inherent variability in assessment. Overall, available data do not enable us to conclude that human semen quality is deteriorating worldwide or in the Western world, but that a trend is observed in some specific areas. To understand these trends and contrasts in sperm and semen quality, prospective studies should be encouraged and combined with assessment of the male exposome.

[Fertility preservation in transgender people]. / Préservation de la fertilité chez les personnes transgenres.

Most of transgender people plan to have a family but their fertility may be affected by gender affirmation. Hormone therapy can permanently affect gamete production, especially in trans women. Sex reassignment surgery leads to permanent sterility. In France, networks of health professionals have been organized and recommend access to fertility preservation for trans people. However, gamete collection is often difficult due to hormonal incongruence for trans women or to the invasive nature of the procedure for trans men. Future studies are required to assess the use of self-preserved gametes by trans people.

Title: Préservation de la fertilité chez les personnes transgenres. Abstract: La majorité des personnes transgenres envisage de fonder une famille, mais leur fertilité peut être altérée par l'affirmation du genre. L'hormonothérapie peut affecter durablement la production de gamètes, notamment chez les femmes trans. La chirurgie de réassignation sexuelle entraîne une stérilité définitive. En France, des réseaux de professionnels de santé se sont organisés. Ils recommandent l'accès à la préservation de la fertilité dans le cadre de la transidentité. Cependant, le recueil de gamètes reste souvent difficile en raison de l'incongruence hormonale pour les femmes trans, ou du caractère invasif de la procédure pour les hommes trans. De futures études permettront de statuer sur l'utilisation des gamètes autoconservés.

Turner syndrome: French National Diagnosis and Care Protocol (NDCP; National Diagnosis and Care Protocol).

Turner syndrome (TS; ORPHA 881) is a rare condition in which all or part of one X chromosome is absent from some or all cells. It affects approximately one in every 1/2500 liveborn girls. The most frequently observed karyotypes are 45,X (40-50%) and the 45,X/46,XX mosaic karyotype (15-25%). Karyotypes with an X isochromosome (45,X/46,isoXq or 45,X/46,isoXp), a Y chromosome, X ring chromosome or deletions of the X chromosome are less frequent. The objective of the French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins) is to provide health professionals with information about the optimal management and care for patients, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Growth and Developmental Endocrine disorders, is available from the French Health Authority website. Turner Syndrome is associated with several phenotypic conditions and a higher risk of comorbidity. The most frequently reported features are growth retardation with short adult stature and gonadal dysgenesis. TS may be associated with various congenital (heart and kidney) or acquired diseases (autoimmune thyroid disease, celiac disease, hearing loss, overweight/obesity, glucose intolerance/type 2 diabetes, dyslipidemia, cardiovascular complications and liver dysfunction). Most of the clinical traits of TS are due to the haploinsufficiency of various genes on the X chromosome, particularly those in the pseudoautosomal regions (PAR 1 and PAR 2), which normally escape the physiological process of X inactivation, although other regions may also be implicated. The management of patients with TS requires collaboration between several healthcare providers. The attending physician, in collaboration with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. The various elements of this PNDS are designed to provide such support.

Exploiting differences in caspase-2 and -3 S2 subsites for selectivity: structure-based design, solid-phase synthesis and in vitro activity of novel substrate-based caspase-2 inhibitors.

Several caspases have been implicated in the pathogenesis of Huntington's disease (HD); however, existing caspase inhibitors lack the selectivity required to investigate the specific involvement of individual caspases in the neuronal cell death associated with HD. In order to explore the potential role played by caspase-2, the potent but non-selective canonical Ac-VDVAD-CHO caspase-2 inhibitor 1 was rationally modified at the P(2) residue in an attempt to decrease its activity against caspase-3. With the aid of structural information on the caspase-2, and -3 active sites and molecular modeling, a 3-(S)-substituted-l-proline along with four additional scaffold variants were selected as P(2) elements for their predicted ability to clash sterically with a residue of the caspase-3 S(2) pocket. These elements were then incorporated by solid-phase synthesis into pentapeptide aldehydes 33a-v. Proline-based compound 33h bearing a bulky 3-(S)-substituent displayed advantageous characteristics in biochemical and cellular assays with 20- to 60-fold increased selectivity for caspase-2 and ∼200-fold decreased caspase-3 potency compared to the reference inhibitor 1. Further optimization of this prototype compound may lead to the discovery of valuable pharmacological tools for the study of caspase-2 mediated cell death, particularly as it relates to HD.

Fertility preservation and sperm donation in transgender individuals: The current situation within the French CECOS network.

BACKGROUND: Many studies reported that reproductive desire could be high among transgender individuals. In France, fertility preservation and sperm donation were very little proposed to transgender individuals until recently, mainly because the Bioethics Law allows the use of assisted reproductive technologies only in infertile couples and prohibits surrogacy. OBJECTIVES: To evaluate the distribution of care on the French territory concerning fertility preservation and sperm donation in transgender individuals. MATERIALS AND METHODS: A multicentric national survey was carried out between January 2019 and October 2020 in 28 assisted reproductive technology centres of the French CECOS (Centres d'Etudes et de Conservation des Oeufs et du Sperme) network. Each centre was questioned to find out how many transgender individuals came, were informed and cared for fertility preservation and sperm donation. RESULTS: Concerning fertility preservation, 71.4% of centres received transgender individuals and performed gamete cryopreservation; 581 transgender individuals consulted for fertility preservation. Transgender women were more likely to desire (p < 0.0001) and achieve (p < 0.0001) fertility preservation than transgender men. Concerning sperm donation in couples including a transgender man, 68% of centres offer the complete course from the first consultation to the completion of the assisted reproductive technology cycles; 122 offsprings have been conceived with sperm donation in couples including a transgender man since 1999. DISCUSSION: Our results showed that even if all centres do not propose fertility preservation or sperm donation in transgender individuals, these assisted reproductive technologies are present throughout the French territory. The major point is that both fertility preservation and sperm donation in transgender individuals have grown significantly and that the care of these patients is improving year after year. CONCLUSION: In France, most of CECOS centres can take care of transgender individuals for fertility preservation and sperm donation. The French Bioethics Law allows these latter, and transgender individuals can benefit from a financial support of the national health care insurance for fertility preservation and sperm donation.