Does polycystic ovarian morphology influence the response to treatment with pulsatile GnRH in functional hypothalamic amenorrhea?

BACKGROUND: Pulsatile GnRH therapy is the gold standard treatment for ovulation induction in women having functional hypothalamic amenorrhea (FHA). The use of pulsatile GnRH therapy in FHA patients with polycystic ovarian morphology (PCOM), called “FHA-PCOM”, has been little studied in the literature and results remain contradictory. The aim of this study was to compare the outcomes of pulsatile GnRH therapy for ovulation induction between FHA and “FHA-PCOM” patients in order to search for an eventual impact of PCOM. METHODS: Retrospective study from August 2002 to June 2015, including 27 patients with FHA and 40 “FHA-PCOM” patients (85 and 104 initiated cycles, respectively) treated by pulsatile GnRH therapy for induction ovulation. RESULTS: The two groups were similar except for markers of PCOM (follicle number per ovary, serum Anti-Müllerian Hormone level and ovarian area), which were significantly higher in patients with “FHA-PCOM”. There was no significant difference between the groups concerning the ovarian response: with equivalent doses of GnRH, both groups had similar ovulation (80.8 vs 77.7 %, NS) and excessive response rates (12.5 vs 10.6 %, NS). There was no significant difference in on-going pregnancy rates (26.9 vs 20 % per initiated cycle, NS), as well as in miscarriage, multiple pregnancy or biochemical pregnancy rates. CONCLUSION: Pulsatile GnRH seems to be a successful and safe method for ovulation induction in “FHA-PCOM” patients. If results were confirmed by prospective studies, GnRH therapy could therefore become a first-line treatment for this specific population, just as it is for women with FHA without PCOM

Long-COVID cognitive impairments and reproductive hormone deficits in men may stem from GnRH neuronal death

BACKGROUND: We have recently demonstrated a causal link between loss of gonadotropin-releasing hormone (GnRH), the master molecule regulating reproduction, and cognitive deficits during pathological aging, including Down syndrome and Alzheimer's disease. Olfactory and cognitive alterations, which persist in some COVID-19 patients, and long-term hypotestosteronaemia in SARS-CoV-2-infected men are also reminiscent of the consequences of deficient GnRH, suggesting that GnRH system neuroinvasion could underlie certain post-COVID symptoms and thus lead to accelerated or exacerbated cognitive decline. METHODS: We explored the hormonal profile of COVID-19 patients and targets of SARS-CoV-2 infection in post-mortem patient brains and human fetal tissue. FINDINGS: We found that persistent hypotestosteronaemia in some men could indeed be of hypothalamic origin, favouring post-COVID cognitive or neurological symptoms, and that changes in testosterone levels and body weight over time were inversely correlated. Infection of olfactory sensory neurons and multifunctional hypothalamic glia called tanycytes highlighted at least two viable neuroinvasion routes. Furthermore, GnRH neurons themselves were dying in all patient brains studied, dramatically reducing GnRH expression. Human fetal olfactory and vomeronasal epithelia, from which GnRH neurons arise, and fetal GnRH neurons also appeared susceptible to infection. INTERPRETATION: Putative GnRH neuron and tanycyte dysfunction following SARS-CoV-2 neuroinvasion could be responsible for serious reproductive, metabolic, and mental health consequences in long-COVID and lead to an increased risk of neurodevelopmental and neurodegenerative pathologies over time in all age groups. FUNDING: European Research Council (ERC) grant agreements No 810331, No 725149, No 804236, the European Union Horizon 2020 research and innovation program No 847941, the Fondation pour la Recherche Médicale (FRM) and the Agence Nationale de la Recherche en Santé (ANRS) No ECTZ200878 Long Covid 2021 ANRS0167 SIGNAL, Agence Nationale de la recherche (ANR) grant agreements No ANR-19-CE16-0021-02, No ANR-11-LABEX-0009, No. ANR-10-LABEX-0046, No. ANR-16-IDEX-0004, Inserm Cross-Cutting Scientific Program HuDeCA, the CHU Lille Bonus H, the UK Medical Research Council (MRC) and National Institute of Health and care Research (NIHR)

Polycystic ovary syndrome

The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.Polycystic ovary syndrome (PCOS) affects 5-20% of women of reproductive age worldwide. The condition is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology (PCOM) - with excessive androgen production by the ovaries being a key feature of PCOS. Metabolic dysfunction characterized by insulin resistance and compensatory hyperinsulinaemia is evident in the vast majority of affected individuals. PCOS increases the risk for type 2 diabetes mellitus, gestational diabetes and other pregnancy-related complications, venous thromboembolism, cerebrovascular and cardiovascular events and endometrial cancer. PCOS is a diagnosis of exclusion, based primarily on the presence of hyperandrogenism, ovulatory dysfunction and PCOM. Treatment should be tailored to the complaints and needs of the patient and involves targeting metabolic abnormalities through lifestyle changes, medication and potentially surgery for the prevention and management of excess weight, androgen suppression and/or blockade, endometrial protection, reproductive therapy and the detection and treatment of psychological features. This Primer summarizes the current state of knowledge regarding the epidemiology, mechanisms and pathophysiology, diagnosis, screening and prevention, management and future investigational directions of the disorder.Robert J Norman, Ruijin Wu and Marcin T Stankiewic

Approach to sexuality and sexual dysfunction by reproductive doctors in France

International audienceNumerous studies have examined the negative impact of medically assisted reproduction (MAR) on patients’ sex lives. It appears necessary to question patients and sometimes to counsel them about management for their sexual and reproductive health. In this study prospective, quantitative, multicenter trial conducted from December 2018 through February 2019, we contacted the offices of all clinical MAR centers registered with the Agence de la Biomedecine (Biomedical Agency) to obtain a list of email addresses of the doctors working there and sent them questionnaires. We received 171 responses. The respondents were very predominantly women (89%), and their median age was 34 years (range: 28–64). Overall, 56% always discussed sexual function during their first consultation, 30% often, and 14% sometimes. We compared two groups: the “regular discussion” (RD) group, which included the doctors (n = 147) who responded “always” and “often”. The “occasional discussion” (OD) group included those (n = 24) who responded “sometimes”. The RD group discussed scheduling sexual relations less often than the OD group (P = 0.029). The RD and OD groups differed significantly in their rates of questions about the frequency of sexual relations (P = 0.04) and about problems of penetration (P = 0.025) and desire (P = 0.041); the RD group asked more often about all of these topics. In the RD group, 37% of the respondents had a sex therapist working at their center, and in the OD group, 21%, while respectively 9% and 17% did not know to whom or where to refer these patients, and 93% and 75% thought a sex therapist with expertise in MAR would be useful at their center. This study shows deficiencies in the management of sexual dysfunctions in MAR patients. Some actions that might improve the situation include: the creation of a directory of sex therapists, the creation of job lines at MAR centers for sex therapists specialized in this field, and the development of patient brochures and questionnaires

Abord de la sexualité et des dysfonctions sexuelles par les médecins de la reproduction en France

International audienceDe nombreuses études ont étudié l’impact négatif de l’aide médicale à la procréation (AMP) sur la vie sexuelle des patients. Il apparaît nécessaire d’interroger les patients et de les orienter pour leur apporter une prise en charge de leur santé sexuelle et reproductive. Dans cette étude quantitative, prospective, multicentrique de décembre 2018 à février 2019, nous avons contacté tous les secrétariats des centres d’AMP cliniques recensés par l’Agence de biomédecine (ABM) afin de diffuser un questionnaire aux médecins par mail. Nous avons recueilli 171 réponses. Les médecins ayant répondu étaient pour 89 % des femmes, l’âge médian était de 34 ans [28–64]. Cinquante-six pour cent abordent toujours la sexualité au cours de leur première consultation, 30 % souvent, 14 % parfois. Nous avons établi deux groupes : le groupe « Abord régulier » (AR) qui comprend les médecins (n=147) ayant répondu oui, toujours et souvent. Et le groupe « Abord occasionnel » (AO) pour ceux (n=24) ayant répondu parfois. Le groupe AR aborde moins souvent la programmation des rapports sexuels que le groupe AO (p=0,029). On trouve des différences significatives entre les deux groupes AR et AO pour la recherche de la fréquence des rapports sexuels (p=0,04), les troubles de la pénétration (p=0,025) et les troubles du désir (p=0,041), ces derniers sont plus recherchés par le groupe AR. Trente-sept pour cent et 21 % ont un sexologue dans leur centre. Et 9 % et 17 % ne savent ni à qui ni où les adresser. Quatre-vingt-treize pour cent et 75 % des groupes AR et AO pensent qu’un sexologue en AMP serait utile dans leur centre. Cette étude montre une carence de prise en charge sexologique des patients en AMP, certaines actions pourraient y palier : la création d’un annuaire de sexologues, la création de postes de sexologues référents en AMP, la mise à disposition de brochures et questionnaires pour les patients

[Migraine and contraception].

International audienceMigraine is a common pathology in women. Migraine disease is well defined by the International Headache Society and has to be distinguished from others types of headaches. The occurrence of migraine attacks is frequently linked to the menstrual cycle. Many studies have related a connexion with hormonal fluctuations and migraine event. Migraine with aura is currently identified as a stroke risk factor and this risk dramatically increases in case of oestroprogestative pill intake and smoking. The World Health Organization established guidelines about oestroprogestative intake in case of migraine while strictly contraindicating oestroprogestative intake in patients with migraine with aura. This review explains the influence of different contraceptive intake, oral contraceptive regimens, and type of oestrogen in oestroprogestative contraceptive on migraine occurrence

Contraception et obésité

International audienceThe prevalence of obesity is increasing massively over several decades in industrialized countries. Obese women are sexually active but they use fewer contraceptive methods and are at high risk of unintended pregnancy. In addition, obesity is an important risk factor for venous thromboembolism events and arterial thrombosis (myocardial infarction and ischemic stroke). All of these data are to be considered in choosing a contraceptive method for obese women. Except depot medroxyprogesterone acetate injection, the progestin-only contraceptives (progestin only pills and etonogestrel subdermal implant) and the intra-uterine devices are the preferred contraceptive methods in obese women. The combined estrogen-progestin contraceptives (pill, patch and vaginal ring) may be proposed in very strict conditions (no other associated vascular risk factor). Obesity does not increase the risk of failure of most contraceptive methods. Bariatric surgery is a complex situation. It requires to program a possible pregnancy and contraception is needed for several months. Some bariatric surgical techniques such as by-pass can induce gastrointestinal malabsorption. In this situation, all oral contraceptives are not recommended because of a higher risk of failure

Recurrent maternal virilization during pregnancy in patients with PCOS: two clinical cases

Abstract Background Maternal virilization during pregnancy is a rare phenomenon. Polycystic ovary syndrome (PCOS), luteoma and luteinic cysts are the most frequent and benign etiologies. This article presents two cases of recurrent maternal virilization during pregnancy. Clinical cases Our reported cases were young women with Afro-Caribbean and Nigerian origins. Data were collected by history-taking, clinical examination, laboratory investigations, transabdominal ultrasonographic examination and Magnetic Resonance Imaging. Both patients were diagnosed with PCOS according to the Rotterdam criteria. During each of their pregnancies they both developed an explosive hirsutism, a deepening in the voice, a clitoromegaly. Gestational diabetes occurred during pregnancies. There was no fetal virilization, despite raising androgen levels, more than tenfold to normal. Improvement of hirsutism and normalization of androgens were described in postpartum. Conclusion Only few cases of maternal virilization during pregnancy were reported in literature and even fewer concern recurrent and bilateral ovarian etiology. Hyperplasia of ovarian theca cells seems to be the most likely explanation, which would suggest that PCOS belongs to a spectrum of abnormal reactivity of the ovary to human Chorionic Gonadotrophin (hCG) stimulation along with luteoma and luteinic cyst of pregnancy.  Insulin resistance could worsen hyperandrogenism but is not enough to explain virilization. Treatment should focus on protecting the fetus of possible virilization as well as its mother, but also on preserving the subsequent fertility in both