Building a family at advanced parental age: a systematic review on the risks and opportunities for parents and their offspring.

STUDY QUESTION: What is the existing empirical literature on the psychosocial health and wellbeing of the parents and offspring born at an advanced parental age (APA), defined as 40 years onwards? SUMMARY ANSWER: Although the studies show discrepancies in defining who is an APA parent and an imbalance in the empirical evidence for offspring, mothers, and fathers, there is a drive towards finding psychotic disorders and (neuro-)developmental disorders among the offspring; overall, the observed advantages and disadvantages are difficult to compare. WHAT IS KNOWN ALREADY: In many societies, children are born to parents at advanced ages and there is rising attention in the literature towards the consequences of this trend. STUDY DESIGN SIZE DURATION: The systematic search was conducted in six electronic databases (PubMed including Medline, Embase, Scopus, PsycInfo, CINAHL, and SocINDEX) and was limited to papers published between 2000 and 2021 and to English-language articles. Search terms used across all six electronic databases were: ('advanced parental age' OR 'advanced maternal age' OR 'advanced paternal age' OR 'advanced reproductive age' OR 'late parent*' OR 'late motherhood' OR 'late fatherhood') AND ('IVF' OR 'in vitro fertilization' OR 'in-vitro-fertilization' OR 'fertilization in vitro' OR 'ICSI' OR 'intracytoplasmic sperm injection' OR 'reproductive techn*' OR 'assisted reproductive technolog*' OR 'assisted reproduction' OR 'assisted conception' OR 'reproduction' OR 'conception' OR 'birth*' OR 'pregnan*') AND ('wellbeing' OR 'well-being' OR 'psycho-social' OR 'social' OR 'ethical' OR 'right to reproduce' OR 'justice' OR 'family functioning' OR 'parental competenc*' OR 'ageism' OR 'reproductive autonomy' OR 'outcome' OR 'risk*' OR 'benefit*'). PARTICIPANTS/MATERIALS SETTING METHODS: The included papers were empirical studies in English published between 2000 and 2021, where the study either examined the wellbeing and psychosocial health of parents and/or their children, or focused on parental competences of APA parents or on the functioning of families with APA parents. A quality assessment of the identified studies was performed with the QATSDD tool. Additionally, 20% of studies were double-checked at the data extraction and quality assessment stage to avoid bias. The variables sought were: the geographical location, the year of publication, the methodological approach, the definitions of APA used, what study group was at the centre of the research, what research topic was studied, and what advantages and disadvantages of APA were found. MAIN RESULTS AND THE ROLE OF CHANCE: A total number of 5403 articles were identified, leading to 2543 articles being included for title and abstract screening after removal of duplicates. This resulted in 98 articles included for a full-text reading by four researchers. Ultimately, 69 studies were included in the final sample. The key results concerned four aspects relevant to the research goals. (i) The studies showed discrepancies in defining who is an APA parent. (ii) There was an imbalance in the empirical evidence produced for different participant groups (mothers, fathers, and offspring), with offspring being the most studied study subjects. (iii) The research topics studied underlined the increased risks of neuro-developmental and psychotic disorders among offspring. (iv) The observed advantages and disadvantages were varied and could not be compared, especially for the offspring of APA parents. LIMITATIONS REASONS FOR CAUTION: Only English-language studies, published between 2000 and 2021, found in the above-mentioned databases were considered for this review. WIDER IMPLICATIONS OF THE FINDINGS: More research is necessary to understand the risks and benefits of building a family at an APA for the offspring when they reach adulthood. Furthermore, studies that explore the perspective of older fathers and older parents from non-Western societies would be highly informative. STUDY FUNDING/COMPETING INTERESTS: The writing of this manuscript was permitted by financial support provided by the Swiss National Science Foundation (Weave/Lead Agency funding program, grant number 10001AL_197415/1, project title 'Family Building at Advanced Parental Age: An Interdisciplinary Approach'). The funder had no role in the drafting of this manuscript and the views expressed therein are those of the authors. The authors have no conflicts of interest. REGISTRATION NUMBER: This systematic review is registered in Prospero: CRD42022304564.

[Sperm donation in Switzerland]. / Don de sperme en Suisse.

The acceptance of "marriage for all" in Switzerland has enabled married couples to have access to medically assisted reproduction (MAR) through sperm donation from July 2022. We present the Swiss legal context of sperm donation, the different techniques, the selection of donors and the method of attribution to recipient couples. This article also describes the complexities of managing a sperm bank in Switzerland, presents some of the figures associated and address the fundamental question of access to origins and the secrecy that may be linked to sperm donation.

L'acceptation du « mariage pour tous ¼ en Suisse a permis aux couples de femmes mariées d'avoir accès à la procréation médicalement assistée (PMA) par don de sperme dès juillet 2022. Nous présentons le contexte légal de la pratique du don de sperme en Suisse, les différentes techniques, la sélection des donneurs et le mode d'attribution aux couples receveurs. Cet article décrit également la complexité de la gestion d'une banque de sperme en Suisse, présente quelques chiffres liés à cette activité et aborde également la question fondamentale de l'accès aux origines et du secret qui peut être lié au don de sperme.

Rethinking advanced motherhood: a new ethical narrative.

The aim of the study is to rethink the ethics of advanced motherhood. In the literature, delayed childbearing is usually discussed in the context of reproductive justice, and in relationship to ethical issues associated with the use and risk of assisted reproductive technologies. We aim to go beyond these more "traditional" ways in which reproductive ethics is framed by revisiting ethics itself through the lens of the figure of the so-called "older" mother. For this purpose, we start by exploring some of the deep seated socio-cultural discourses in the context of procreation: ageism, ableism and the widespread bias towards geneticism and pronatalism. Afterwards, we provide a critical overview of the key arguments against or in support of advanced motherhood. We then briefly discuss how entrenchment by both sides has produced an impasse in the debate on the ethics of advanced motherhood and proceed by arguing that it is fundamental to bring about a change in this narrative. For this purpose, we will revisit the feminist usage of the concept of vulnerability which will allow us both to criticize culturally prescribed norms about motherhood and to address the painful reality of age-related fertility decline. In the last section, we argue that instead of defining "older" motherhood as an ethical problem, we should problematize the fact that female reproductive ageing is an understudied and ill-sourced topic. We believe that allocating resources to research to better understand female reproductive ageing is not only ethically permissible, but might even be ethically desirable.

Turner syndrome: skin, liver, eyes, dental and ENT evaluation should be improved.

Introduction: Turner syndrome association with multi-organ system comorbidities highlights the need for effective implementation of follow-up guidelines. We aimed to assess the adequacy of care with international guidelines published in 2007 and 2017 and to describe the phenotype of patients. Methods: In this multicenter retrospective descriptive cohort study, we collected growth and pubertal parameters, associated comorbidities, treatment, and karyotype in patients diagnosed at age <18 years between 1993 and 2022. We assessed age-appropriate recommendation follow-up (children, adolescents and adults) according to the 2007 guidelines if the last visit was before 2017 (18 recommendations) and the 2017 guidelines if the last visit was after 2017 (19 recommendations). Results: We included 68 patients followed at Lausanne University Hospital (n=64) and at Neuchatel Regional Hospital (RHNe) (n=4). 2.9% of patients underwent all recommended investigations.Overall, 68.9 ± 22.5% and 78.5 ± 20.6% of the recommendations were followed, before and after 2017 respectively. High implementation rates were found for height, weight and BMI (100%), cardiac (80 to 100%) and renal (90 to 100%) imaging. Low implementation rates were found for Ear, Nose and Throat (ENT) (56.5%), skin (38.5%), dental (23.1%), ophthalmological (10%) and cholestasis (0 to 29%) assessments, depending on age and time of visit. In adults (n=33), the mean proportion of followed recommendations was lower before than after 2017: 63.5 ± 25.8% vs. 78.7 ± 23.4%, p=0.039. Conclusion: Growth parameters, cardiac and renal imaging are well followed. However, efforts should be made for dental, ENT, ophthalmological, skin and cholestasis assessments. Adequacy of follow-up improved with the quality of transition to adult care.

Prothrombotic biomarkers during controlled ovarian stimulation for assisted reproductive technology.

OBJECTIVE: To assess the impact of 3 different ovarian stimulation protocols on surrogate biomarkers of coagulation. DESIGN: Observational multicenter cohort study. SETTING: The study was conducted in assisted reproductive technology (ART) units. PATIENTS: Infertile women undergoing ART in 2017-2019 were included. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Our primary outcome was the endogenous thrombin potential (ETP) assessed by the calibrated automated thrombogram. The ETP was measured at baseline (T1), on the day of ovulation triggering (T2), and 7 days after triggering (T3). Three protocols were prescribed according to the standards used and without hormonal before treatment: agonist protocol with human chorionic gonadotropin (hCG) trigger (ag-hCG), antagonist protocol with hCG trigger (atg-hCG), or GnRH agonist trigger. The evolution of ETP was compared among groups using a mixed-effects linear regression model. RESULT(S): Sixty-four women with a mean age of 37.8 years participated in the study: of which 24, 16, 24 received ag-hCG, atg-hCG, and GnRH agonist triggers, respectively. As expected, the mean serum estradiol levels in GnRH agonist trigger were statistically higher at T2 and lower at T3 than that for both ag-hCG and atg-hCG. Overall, the ETP evolution over time was statistically different between the groups. Values were similar between groups at T1 and increased at T2 in each group. The greatest difference occurred between T2 and T3 in each group. The ETP continued to increase at T3 in ag-hCG (+110 nM/L × min) and atg-hCG (+171 nM/L × min), but it remained stable in GnRH agonist trigger (-2 nM/L × min). Sex hormone-binding globulin showed persistent increase at T3 despite the fall in estradiol levels, particularly in the GnRH agonist trigger group. CONCLUSION(S): The ag-hCG and atg-hCG groups were associated with a higher hypercoagulable state at T3 than the GnRH agonist trigger group. However, our results show the persistence of a hypercoagulable state after the GnRH agonist triggering despite a sharp drop in estradiol levels. These findings may support the use of GnRH agonist trigger protocol in patients with high thrombotic risk and gives new insight into the fact that coagulation parameters could be disturbed for long time periods. CLINICAL TRIAL REGISTRATION NUMBER: NCT04188444.

Testicular tissue cryopreservation for fertility preservation in prepubertal and adolescent boys: A 6 year experience from a Swiss multi-center network.

Testicular tissue cryopreservation is the only option of fertility preservation in prepubertal boys. While it is considered experimental, since procedures to obtain mature spermatozoa from prepubertal testicular tissue are still under development, testicular tissue cryopreservation programs have emerged worldwide. Our aim was to study the feasibility and safety of a program of testicular tissue cryopreservation in prepubertal and adolescent boys facing gonadotoxic treatment in three University hospitals in Switzerland. Testicular tissue cryopreservation was accepted by 90% of families, with a total of 35 patients included. The average patient age was 8.5 years (range 7 months to 18.5 years). Malignancies were the most common diagnosis (31 patients, 88.6%) with 16 (45.7%) solid tumors and 15 (42.9%) hematological malignancies. Four (11.4%) patients had a benign condition. The main indication for testicular tissue cryopreservation was conditioning for hematologic stem cell transplantation (25 patients, 71.4%). Testicular tissue was cryopreserved according to the freezing protocol of Louvain Catholic University (Belgium), which includes either only immature testicular tissue freezing, or mature and immature testicular tissue freezing depending on the age of the patient and the presence or absence of haploid cells. The median number of spermatogonia per tubule cross-section was 2 (range 0-6) and spermatozoa were found in only one patient. Tumoral cells were found in one testicular biopsy of a leukemic patient. There were two minor adverse events and none of them required medical treatment or surgical revision. Five patients died during follow-up. Our data demonstrate the feasibility and safety of a program of testicular tissue cryopreservation coordinated by a multidisciplinary team of fertility preservation. Despite the experimental aspect of the procedure, the acceptation rate was high, which highlights the willingness of families and patients to participate in testicular tissue cryopreservation.

Infertility workup: identifying endometriosis.

Endometriosis was classically diagnosed during diagnostic laparoscopies, which used to be routinely performed up until a decade ago or so. This practice fitted with the long-held belief that surgery was the gold standard for diagnosing endometriosis. Today, the abandon of routine diagnostic laparoscopies-in favor of assisted reproductive technology-first therapeutic approaches-has created a void for diagnosing endometriosis. Modern-day imaging techniques-ultrasound and magnetic resonance imaging-when used with a systematic approach have offered a reliable replacement option for diagnosing endometriosis. In infertility, endometriosis should be identified or excluded on the basis of past history or confirmation or exclusion suspicion on the basis of history and/or physical examination.

ESHRE guideline: endometriosis.

STUDY QUESTION: How should endometriosis be diagnosed and managed based on the best available evidence from published literature? SUMMARY ANSWER: The current guideline provides 109 recommendations on diagnosis, treatments for pain and infertility, management of disease recurrence, asymptomatic or extrapelvic disease, endometriosis in adolescents and postmenopausal women, prevention and the association with cancer. WHAT IS KNOWN ALREADY: Endometriosis is a chronic condition with a plethora of presentations in terms of not only the occurrence of lesions, but also the presence of signs and symptoms. The most important symptoms include pain and infertility. STUDY DESIGN SIZE DURATION: The guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 1 December 2020 and written in English were included in the literature review. PARTICIPANTS/MATERIALS SETTING METHODS: Based on the collected evidence, recommendations were formulated and discussed within specialist subgroups and then presented to the core guideline development group (GDG) until consensus was reached. A stakeholder review was organized after finalization of the draft. The final version was approved by the GDG and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE: This guideline aims to help clinicians to apply best care for women with endometriosis. Although studies mostly focus on women of reproductive age, the guideline also addresses endometriosis in adolescents and postmenopausal women. The guideline outlines the diagnostic process for endometriosis, which challenges laparoscopy and histology as gold standard diagnostic tests. The options for treatment of endometriosis-associated pain symptoms include analgesics, medical treatments and surgery. Non-pharmacological treatments are also discussed. For management of endometriosis-associated infertility, surgical treatment and/or medically assisted reproduction are feasible. While most of the more recent studies confirm previous ESHRE recommendations, there are five topics in which significant changes to recommendations were required and changes in clinical practice are to be expected. LIMITATIONS REASONS FOR CAUTION: The guideline describes different management options but, based on existing evidence, no firm recommendations could be formulated on the most appropriate treatments. Also, for specific clinical issues, such as asymptomatic endometriosis or extrapelvic endometriosis, the evidence is too scarce to make evidence-based recommendations. WIDER IMPLICATIONS OF THE FINDINGS: The guideline provides clinicians with clear advice on best practice in endometriosis care, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in endometriosis. STUDY FUNDING/COMPETING INTERESTS: The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payments. C.M.B. reports grants from Bayer Healthcare and the European Commission; Participation on a Data Safety Monitoring Board or Advisory Board with ObsEva (Data Safety Monitoring Group) and Myovant (Scientific Advisory Group). A.B. reports grants from FEMaLE executive board member and European Commission Horizon 2020 grant; consulting fees from Ethicon Endo Surgery, Medtronic; honoraria for lectures from Ethicon; and support for meeting attendance from Gedeon Richter; A.H. reports grants from MRC, NIHR, CSO, Roche Diagnostics, Astra Zeneca, Ferring; Consulting fees from Roche Diagnostics, Nordic Pharma, Chugai and Benevolent Al Bio Limited all paid to the institution; a pending patent on Serum endometriosis biomarker; he is also Chair of TSC for STOP-OHSS and CERM trials. O.H. reports consulting fees and speaker's fees from Gedeon Richter and Bayer AG; support for attending meetings from Gedeon-Richter, and leadership roles at the Finnish Society for Obstetrics and Gynecology and the Nordic federation of the societies of obstetrics and gynecology. L.K. reports consulting fees from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; honoraria for lectures from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; support for attending meetings from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; he also has a leadership role in the German Society of Gynecological Endocrinology (DGGEF). M.K. reports grants from French Foundation for Medical Research (FRM), Australian Ministry of Health, Medical Research Future Fund and French National Cancer Institute; support for meeting attendance from European Society for Gynaecological Endoscopy (ESGE), European Congress on Endometriosis (EEC) and ESHRE; She is an advisory Board Member, FEMaLe Project (Finding Endometriosis Using Machine Learning), Scientific Committee Chair for the French Foundation for Research on Endometriosis and Scientific Committee Chair for the ComPaRe-Endometriosis cohort. A.N. reports grants from Merck SA and Ferring; speaker fees from Merck SA and Ferring; support for meeting attendance from Merck SA; Participation on a Data Safety Monitoring Board or Advisory Board with Nordic Pharma and Merck SA; she also is a board member of medical advisory board, Endometriosis Society, the Netherlands (patients advocacy group) and an executive board member of the World Endometriosis Society. E.S. reports grants from National Institute for Health Research UK, Rosetrees Trust, Barts and the London Charity; Royalties from De Gruyter (book editor); consulting fees from Hologic; speakers fees from Hologic, Johnson & Johnson, Medtronic, Intuitive, Olympus and Karl Storz; Participation in the Medicines for Women's Health Expert Advisory Group with Medicines and Healthcare Products Regulatory Agency (MHRA); he is also Ambassador for the World Endometriosis Society. C.T. reports grants from Merck SA; Consulting fees from Gedeon Richter, Nordic Pharma and Merck SA; speaker fees from Merck SA, all paid to the institution; and support for meeting attendance from Ferring, Gedeon Richter and Merck SA. The other authors have no conflicts of interest to declare. DISCLAIMER: This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose (Full disclaimer available at www.eshre.eu/guidelines.).

Use and Effectiveness of Sperm Cryopreservation for Adolescents and Young Adults: A 37-Year Bicentric Experience.

Aim: Sperm cryopreservation (SCP) should be offered to every adolescent before gonadotoxic treatment, but experience in this age range is still relatively limited. The goal of this study is to assess how to optimize this procedure. Methods and Patients: One hundred thirty-three patients between 12 and 20 years old, who underwent SCP between 1980 and 2017, were included. Baseline data (age, indication for SCP, and semen parameters at freezing) and follow-up data (outcome of sperm straws and follow-up of sperm quality) were collected and analyzed. Results: SCP is feasible from the age of 12. Semen assessment parameters at this age were close to parameters of adults. However, we observed quantitative impairments in testicular tumors and qualitative impairments in leukemia and bone marrow failure. Four patients (3%) used their cryopreserved semen for medically assisted reproduction, 15 patients died (11.3%), 18 asked for destruction of their straws (13.5%), and nine samples were destroyed because of lack of news (6.8%). Very few patients underwent a sperm analysis after treatment. Conclusions: SCP is an efficient, still underused, procedure for adolescents and young adults. Cryopreserved sperm is rarely used and rarely destroyed, but studies with a longer follow-up are needed to better assess these observations. Follow-up with a specialist of reproductive medicine is valuable for better information of the patient.

Hypergonadotropic hypogonadism after ovarian tissue cryopreservation on a 13-year-old female: A case report and review of the literature.

Ovarian failure is a major long-term adverse event following gonadotoxic treatment of malignant diseases. Ovarian tissue cryopreservation can be offered in some conditions to preserve fertility. We report the case of a 13-year-old female with a diagnosis of acute myeloid leukemia, who presented with hypergonadotropic hypogonadism after unilateral ovariectomy for fertility preservation and before highly gonadotoxic treatment. Even though damage seemed only partial, this case suggests that the remaining contralateral ovarian function may be compromised after ovarian tissue cryopreservation, leading per se to a hypergonadotropic hypogonadism. Although indication of ovarian cryopreservation is not called into question in situations of highly gonadotoxic therapy, this procedure should only be performed after evaluation by a specialized multidisciplinary team and provided a solid indication.

Waddlia chondrophila and Male Infertility.

Waddlia chondrophila, a Chlamydia-like bacterium, has been previously associated with adverse pregnancy outcomes. Analogously to Chlamydia trachomatis, W. chondrophila also negatively impacts human semen and may be a source of impaired male fertility. In this study, we analyzed W. chondrophila seroprevalence in a population of male patients of infertile couples and the impact of past exposition to this bacterium on semen parameters. Our results show a surprisingly high seroprevalence of W. chondrophila, which contrasts with a previous study focusing on a population of healthy men. Nevertheless, we did not observe any significant association between positive serology and abnormal sperm parameters. This may suggest that a negative impact on semen is observed only during an ongoing infection. Alternatively, W. chondrophila may have an immune impact on male fertility, as previously postulated for women with adverse pregnancy outcomes.

[Preimplantation genetic testing: legal and ethical aspects in clinical practice]. / Tests génétiques préimplantatoires†: enjeux légaux et éthiques dans la pratique clinique.

In Switzerland, since modifications of the law regulating reproductive medicine introduced the 1rst of September 2017, preimplantation genetic testing (PGT) has been legalised. Infertile couples undergoing in vitro fertilization (IVF) can benefit from this technology by detecting which embryos are aneuploid (ie abnormal number of chromosomes, PGT-A). This is performed in order to transfer euploid embryos (normal number of chromosomes) and to optimise success, though data are limited. Couples at risk of transmitting a severe monogenic disease or unbalanced translocation can undergo PGT for monogenic disease or chromosomal structural rearrangements (PGT-M/SR). These tests are subject to strict legal criteria. Their clinical application needs to be approved through a multidisciplinary approach taking into account legal and ethical issues while respecting the autonomy of the couples.

Depuis le 1er septembre 2017, les tests génétiques préimplantatoires (PGT) sont autorisés en Suisse suite aux modifications de la loi sur la procréation médicalement assistée (LPMA). Les couples infertiles qui effectuent une fécondation in vitro (FIV) peuvent bénéficier d'un PGT des aneuploïdies (PGT-A) dans le but de transférer des embryons euploïdes (nombre normal de chromosomes) et ainsi optimiser leurs chances de succès, sous réserve de données encore limitées. Les couples à risque de transmettre une maladie monogénique grave ou une translocation déséquilibrée peuvent avoir recours au PGT d'une anomalie d'un gène unique ou d'une anomalie de structure de chromosome (PGT-M/SR), dans les limites d'un cadre légal strict. Leur mise en pratique doit être décidée de manière pluridisciplinaire en tenant compte des enjeux légaux et éthiques dans le respect de l'autonomie des couples.

Bacterial Colonization of the Female Upper Genital Tract.

Bacteria colonize most of the human body, and the female genital tract is not an exception. While the existence of a vaginal microbiota has been well established, the upper genital tract has been considered a sterile environment, with a general assumption that bacterial presence is associated with adverse clinical manifestation. However, recent metagenomic studies identified specific patterns of microbiota colonizing the uterus, fallopian tubes, ovaries, and placenta. These results need confirmation and further investigations since the data are only scarce. Bacterial colonization of these sites appears different from the vaginal one, despite evidence that vaginal bacteria could ascend to the upper genital tract through the cervix. Are these bacteria only commensal or do they play a role in the physiology of the female upper genital tract? Which are the genera that may have a negative and a positive impact on the female reproductive function? The aim of this review is to critically present all available data on upper genital tract microbiota and discuss its role in human reproduction, ranging from the technical aspects of these types of analyses to the description of specific bacterial genera. Although still very limited, research focusing on genital colonization of bacteria other than the vaginal milieu might bring novel insights into physiopathology of human reproduction.

Sperm Microbiota and Its Impact on Semen Parameters.

Compared to its female counterpart, the microbiota of the male genital tract has not been studied extensively. With this study, we aimed to evaluate the bacterial composition of seminal fluid and its impact on sperm parameters. We hypothesized that a dysbiotic microbiota composition may have an influence on sperm quality. Semen samples of 26 men with normal spermiogram and 68 men with at least one abnormal spermiogram parameter were included in the study. Samples were stratified based on total sperm count, spermatozoa concentration, progressive motility, total motility and spermatozoa morphology. Microbiota profiling was performed using 16S rRNA gene amplicons sequencing and total bacterial load was determined using a panbacterial quantitative PCR. Semen samples broadly clustered into three microbiota profiles: Prevotella-enriched, Lactobacillus-enriched, and polymicrobial. Prevotella-enriched samples had the highest bacterial load (p < 0.05). Network analysis identified three main co-occurrence modules, among which two contained bacteria commonly found in the vaginal flora. Genera from the same module displayed similar oxygen requirements, arguing for the presence of different ecological niches for bacteria that colonize semen through the passage. Contrary to our hypothesis, shifts in overall microbiota composition (beta-diversity) did not correlate with spermiogram parameters. Similarly, we did not find any difference in microbial richness or diversity (alpha-diversity). Differential abundance testing, however, revealed three specific genera that were significantly enriched or depleted in some of the sperm quality groups (p < 0.05). Prevotella relative abundance was increased in samples with defective sperm motility while Staphylococcus was increased in the corresponding control group. In addition, we observed an increased relative abundance of Lactobacillus in samples with normal sperm morphology. Our study indicates that overall bacterial content of sperm might not play a major role in male infertility. Although no major shifts in microbiota composition or diversity were found, the differential abundance of specific bacterial genera in the sperm suggests that a small subset of microbes might impact the spermatozoal physiology during sperm transition, more specifically motility and morphology. Further studies are required to challenge this finding and develop potential strategies to induce the formation of a healthy seminal microbiota.

Successful Ovarian Stimulation for Fertility Preservation in a Patient with Chronic Myeloid Leukemia: Switch from Nilotinib to Interferon-α.

The development of tyrosine-kinase inhibitors (TKIs) has improved survival of patients with chronic myeloid leukemia (CML). Some patients may become resistant to TKIs and require hematopoietic stem cell transplant (HSCT) that is highly gonadotoxic. Fertility preservation with ovarian stimulation might be indicated but is challenging if patients need to remain on TKIs until HSCT because TKIs may compromise follicular development and response to ovarian stimulation. We report the case of a patient with CML resistant to TKI and planned for an HSCT, in which treatment by TKI was replaced by interferon-α before and during ovarian stimulation for fertility preservation. Successful ovarian stimulation was performed, allowing cryopreservation of nine zygotes. Hematopoietic stem cell transplantation was performed, and at present, 3 years later, the patient presents a sustained major molecular response.

[Assisted reproductive technology : strategies of elective single embryo transfer]. / Procréation médicalement assistée : stratégies de transfert électif d'un seul embryon.

The development of assisted reproductive technology (ART) has led to the birth of nearly 6 million children since the first IVF baby in 1978. For many years, it was routine practice to transfer multiple embryos in order to obtain the highest pregnancy rates. This strategy has induced a dramatic increase in multiple pregnancies and the associated complications for the mother and the child. Following better awareness of these issues, ART specialists have tried to reduce multiple pregnancy rates with the goal of producing a single, healthy full term baby. Improvement in embryo culture and cryopreservation are the key factors leading to the strategy of elective single embryo transfer (eSET) which represents the best option to achieving this goal. However eSET strategy needs to be implemented in good prognosis patient with good quality embryos.

Le développement des techniques de procréation médicalement assistée (PMA) a permis la naissance de presque 6 millions d'enfants depuis le premier bébé né par FIV en 1978. Pendant de nombreuses années, le transfert de plusieurs embryons était réalisé de routine afin d'obtenir les meilleurs taux de grossesses. Cette pratique a abouti à une augmentation inquiétante des grossesses multiples et des complications associées pour la mère et l'enfant. Les acteurs de la PMA ont alors eu comme but la naissance à terme d'un enfant en bonne santé. Les techniques de culture et de cryoconservation d'embryons ont permis de développer des stratégies de transfert électif d'un seul embryon (eSET). Toutefois, pour ne pas diminuer les chances de grossesses, l'eSET doit être utilisé chez des patientes à bon pronostic et avec des embryons de bonne qualité.

Zika virus: A new threat to human reproduction.

Zika virus (ZIKV) was first isolated in 1947 in a rhesus monkey from the Zika forest of Uganda. Until 2007, only 14 human cases were reported. The first large human outbreak occurred in 2007 (Yap Island, Federated States of Micronesia, Pacific) followed by French Polynesia in 2013 and Brazil in 2015. The virus is mainly transmitted through Aedes mosquito bites, but sexual and post-transfusion transmissions have been reported. Symptoms include low-grade fever, maculopapular rash, conjunctivitis, myalgia, arthralgia, and asthenia. During the recent outbreaks in French Polynesia and Brazil, ZIKV infection has been associated with two major complications: microcephaly and Guillain-Barré syndrome. Since fetal infection includes other birth defects, congenital Zika syndrome has been used to define in utero infection. The majority of sexual transmission occurred from a symptomatic male to a female, but female-to-male and male-to-male transmission have been reported. Asymptomatic male-to-female transmission has also been described. Importantly, ZIKV RNA can persist at least 6 months in semen. The male urogenital tract may therefore act as a reservoir for the virus. ZIKV RNA was detected in a cervical swab of a patient 3 days after presenting the classic symptoms suggesting a potential tropism for the female genital tract. Long-lasting presence of ZIKV RNA might not indicate that the individual is infectious but makes recommendation for couples potentially exposed to the virus and willing to conceive difficult. It will also be important to determine whether genital ZIKV infection might have a deleterious effect on male and female fertility.

[Osteoporosis in menopausal women between 40 and 65 years old : an algorithm for the gynaecologist]. / Ostéoporose chez les femmes ménopausées entre 40 et 65 ans : algorithme pour le gynécologue.

Osteoporosis is a bone disease that promotes the development of fragility fractures. An algorithm is proposed for the gynaecologists'use to diagnose and treat osteoporosis in young menopausal women. The fracture risk can be calculated with the FRAX tool. If the 10-year fracture risk is ≥ 10 %, a bone densitometry is recommended, and the result is integrated in the FRAX tool. If the risk is between 10 and 20 %, a treatment should be discussed individually and, in some cases, a pharmacologic preventive treatment, by menopause hormonal treatment or SERMs, can be initiated. A pharmacologic treatment (bisphosphonates or dénosumab) is recommended in case of previous fragility fracture or risk ≥ 20 %, independently of a T-score < -2.5 DS. Patients have to be referred in case of treatment failure or intolerance, and at the end of any denosumab therapy.

L'ostéoporose est une maladie de l'os favorisant des fractures de fragilité. L'algorithme proposé est destiné aux gynécologues pour le diagnostic et le traitement de l'ostéoporose chez la jeune femme ménopausée. L'outil FRAX permet de calculer le risque fracturaire ; si le risque est ≥ 10 % sur dix ans, une densitométrie osseuse est recommandée et le résultat sera intégré dans l'outil FRAX. Si le risque est entre 10­20 %, un traitement peut être discuté et, dans certains cas, on proposera une prévention par traitement hormonal de la ménopause ou par un SERM. Un traitement pharmacologique (bisphosphonates ou dénosumab) est recommandé en présence d'antécédent de fracture de fragilité, ou de risque ≥ 20 %, indépendamment d'un T-score < ­2,5 DS. Il faut référer les patientes en cas d'échec ou intolérance au traitement, et à la fin de tout traitement par dénosumab.

Astressin B, a nonselective corticotropin-releasing hormone receptor antagonist, prevents the inhibitory effect of ghrelin on luteinizing hormone pulse frequency in the ovariectomized rhesus monkey.

Administration of ghrelin, a key peptide in the regulation of energy homeostasis, has been shown to decrease LH pulse frequency while concomitantly elevating cortisol levels. Because increased endogenous CRH release in stress is associated with an inhibition of reproductive function, we have tested here whether the pulsatile LH decrease after ghrelin may reflect an activated hypothalamic-pituitary-adrenal axis and be prevented by a CRH antagonist. After a 3-h baseline LH pulse frequency monitoring, five adult ovariectomized rhesus monkeys received a 5-h saline (protocol 1) or ghrelin (100-microg bolus followed by 100 microg/h, protocol 2) infusion. In protocols 3 and 4, animals were given astressin B, a nonspecific CRH receptor antagonist (0.45 mg/kg im) 90 min before ghrelin or saline infusion. Blood samples were taken every 15 min for LH measurements, whereas cortisol and GH were measured every 45 min. Mean LH pulse frequency during the 5-h ghrelin infusion was significantly lower than in all other treatments (P < 0.05) and when compared with the baseline period (P < 0.05). Pretreatment with astressin B prevented the decrease. Ghrelin stimulated cortisol and GH secretion, whereas astressin B pretreatment prevented the cortisol, but not the GH, release. Our data indicate that CRH release mediates the inhibitory effect of ghrelin on LH pulse frequency and suggest that the inhibitory impact of an insufficient energy balance on reproductive function may in part be mediated by the hypothalamic-pituitary-adrenal axis.