Shifting the landscape: Dominant C-terminal rare missense FOXL2 variants in non-syndromic primary ovarian failure etiology.

Pathogenic germline variants in the FOXL2 gene are associated with Blepharophimosis, Ptosis, and Epicanthus Inversus syndrome (BPES) in humans, an autosomal dominant condition. Two forms of BPES have emerged: (i) type I (BPES-I), characterized by ocular signs and primary ovarian failure (POI), and (ii) type II (BPES-II) with no systemic associations. This study aimed to compare the distribution of FOXL2 variants in idiopathic POI/DOR (diminished ovarian reserve) and both types of BPES, and to determine the involvement of FOXL2 in non-syndromic forms of POI/DOR. We studied the whole coding region of the FOXL2 gene using next-generation sequencing in 1282 patients with non-syndromic POI/DOR. Each identified FOXL2 variant was compared to its frequency in the general population, considering ethnicity. Screening of the entire coding region of the FOXL2 gene allowed us to identify 10 different variants, including nine missense variants. Of the patients with POI/DOR, 14 (1%) carried a FOXL2 variant. Significantly, six out of nine missense variants (67%) were overrepresented in our POI/DOR cohort compared to the general or specific ethnic subgroups. Our findings strongly suggest that five rare missense variants, mainly located in the C-terminal region of FOXL2 are high-risk factors for non-syndromic POI/DOR, though FOXL2 gene implication accounts for approximately 0.54% of non-syndromic POI/DOR cases. These results support the implementation of routine genetic screening for patients with POI/DOR in clinical settings.

Early Mortality, Cardiovascular, and Renal Diseases in Women's Lives Following Hypertensive Disorders of Pregnancy: The Prospective Nationwide Study CONCEPTION.

BACKGROUND: We aimed to evaluate the impact of hypertensive disorders of pregnancy occurrence, recurrence, onset time, and severity on mortality and on a wide range of cardiovascular outcomes in France. METHODS AND RESULTS: CONCEPTION (Cohort of Cardiovascular Diseases in Pregnancy) is a French nationwide prospective cohort using data from the National Health Data System. We included all women in CONCEPTION with no history of a cardiovascular event who delivered in France for the first time between 2010 and 2018 (N=2 819 655). Hypertensive disorders of pregnancy and cardiovascular outcomes during the study follow-up were identified using algorithms combining International Classification of Diseases, Tenth Revision (ICD-10) coded diagnoses during hospitalization and purchases of medication between 2010 and 2021. We fitted Cox models with time-varying exposure to assess the associations of hypertensive disorders of pregnancy with mortality and cardiovascular events. Women with gestational hypertension had a 1.25- to 2-fold higher risk of stroke, acute coronary syndrome, peripheral arterial disease, pulmonary embolism, and chronic kidney disease, and a 2- to 4-fold higher risk of rhythm and conduction disorder and heart failure. Women with preeclampsia had a 1.35- to 2-fold higher risk of rhythm or conduction disorder and pulmonary embolism during follow-up; a 2- to 4-fold higher risk of stroke, acute coronary syndrome, and peripheral arterial disease; and a 7- to 9-fold higher risk of heart failure and chronic kidney disease. They were 1.8 times more likely to die and 4.4 times more likely to die of cardiovascular causes. CONCLUSIONS: Hypertensive disorders of pregnancy drastically increase the risk of mortality, cardiovascular, and renal events early after pregnancy. Recurrent, severe, and early-onset preeclampsia further increases this risk.

NOBOX gene variants in premature ovarian insufficiency: ethnicity-dependent insights.

PURPOSE: Premature ovarian insufficiency (POI) affects approximately 1% of women before the age of 40. Genetic contribution is a significant component of POI. The NOBOX gene was considered one of the major genetic causes of POI. However, the pathogenicity and the penetrance of NOBOX variants remain unclear. METHODS: We studied the whole coding region of the NOBOX gene by next generation sequencing in a cohort of 810 patients with POI, and we compared the frequency of each identified NOBOX variant to the general population taking into account the ethnicity of each individual. RESULTS: Screening of the whole coding region of the NOBOX gene allowed us to identify 35 different variants, including 5 loss-of-function variants. In total, 171 patients with POI (25%) carried out at least one NOBOX variant. Regarding missense variants, we observed a significant overrepresentation of the most frequent ones in our 810 POI patients as compared to the general, except for p.(Arg117Trp). However, taking into account the ethnic origin of the individuals, we observed no significant OR difference for p.(Arg44Leu) and p.(Arg117Trp) in African subgroup and for p.(Asp452Asn) in European subgroup. CONCLUSION: This population study suggests that the p.(Arg44Leu) variant could be considered benign variant and that the p.(Asp452Asn) and p.(Arg117Trp) variants could be considered moderate risk pathogenic variants with probably partial and very low penetrance and/or expressivity. In contrast, p.(Gly91Trp) and p.(Gly152Arg) variants could be considered pathogenic variants with a moderate functional impact.

Stratification of the risk of ovarian dysfunction by studying the complexity of intermediate and premutation alleles of the FMR1 gene.

FMR1 premutation female carriers are at risk of developing premature/primary ovarian insufficiency (POI) with an incomplete penetrance. In this study, we determined the CGG repeat size among 1095 women with diminished ovarian reserve (DOR) / POI and characterized the CGG/AGG substructure in 44 women carrying an abnormal FMR1 repeat expansion number, compared to a group of 25 pregnant women carrying an abnormal FMR1 CGG repeat size. Allelic complexity scores of the FMR1 gene were calculated and compared between the two groups. In the DOR/POI cohort, 2.1% of women presented with an intermediate repeat size and 1.9% with a premutation. Our results suggest that the risk of POI is highest in the mid-range of CGG repeats. We observed that the allelic score is significantly higher in POI women compared to the pregnant women group (p-value = 0.02). We suggest that a high allelic score due to more than 2 AGG interspersions in the context of an intermediate number of repetitions could favor POI. Larger studies are still needed to evaluate the relevance of this new tool for the determination of the individual risk of developing POI in women with abnormal number of CGG repeats.

Aspirin for the Prevention of Early and Severe Pre-Eclampsia Recurrence: A Real-World Population-Based Study.

BACKGROUND: Many clinical trials have reported that low-dose aspirin decreases the risk of pre-eclampsia in women with prior pre-eclampsia. However, its impact in a real-world population has not been fully assessed. OBJECTIVES: To assess the rates of low-dose aspirin initiation during pregnancy in women with a history of pre-eclampsia, and to evaluate the impact of low-dose aspirin in prevention of pre-eclampsia recurrence in a real-world population. STUDY DESIGN: CONCEPTION is a French nationwide cohort study which uses data from the country's National Health Data System database. We included all women in France who gave birth at least twice between 2010-2018, and who had pre-eclampsia during their first pregnancy. Every dispensing of low-dose aspirin (75-300 mg) between the beginning of their second pregnancy and 36 weeks of gestation (WG) was identified. We used Poisson regression models to estimate the adjusted incidence rate ratios (aIRRs) of receiving aspirin at least once during their second pregnancy. In women who had early and/or severe pre-eclampsia during their first pregnancy, we estimated the IRRs of pre-eclampsia recurrence during their second pregnancy according to the aspirin therapy. RESULTS: In 28,467 women who were included in the study, the aspirin initiation rate during the second pregnancy ranged from 27.8% for women in whose first pregnancy the pre-eclampsia was mild and late, to 79.9% for those women whose pre-eclampsia was severe and early. Just over half (54.3%) of those treated with aspirin-initiated treatment before 16 WG and adhered to treatment. Compared with women with mild and late pre-eclampsia, the aIRRs (95% CI) for receiving aspirin at least once during the second pregnancy were 1.94 (1.86-2.03) for women with severe and late pre-eclampsia, 2.34 (2.17-2.52) for those with early and mild pre-eclampsia, and 2.87 [2.74-3.01] for those with early and severe pre-eclampsia E. Social deprivation was associated with a lower initiation of aspirin (IRR = 0.74 [0.70-0.78]). Aspirin was not associated with a lower risk of mild and late pre-eclampsia, severe and late pre-eclampsia, or mild and early pre-eclampsia during the second pregnancy. The aIRRs for severe and early pre-eclampsia during the second pregnancy were 0.77 (0.62-0.95) for women who received prescribed aspirin at least once, 0.71 (0.5-0.89) for those who initiated aspirin therapy before 16 WG, and 0.60 (0.47-0.77) for those who adhered to aspirin treatment throughout their second pregnancy. The risk of severe and early pre-eclampsia was lower only when the prescribed mean daily dose was ≥ 100 mg/day. CONCLUSION: In women with a history of pre-eclampsia, aspirin initiation during a second pregnancy and adherence to the prescribed dosage were largely insufficient, especially for women experiencing social deprivation. Aspirin initiated before 16 WG at a dose ≥ 100 mg/day was associated with a lower risk of severe and early pre-eclampsia.

Adverse Maternal and Infant Outcomes in Women With Chronic Hypertension in France (2010-2018): The Nationwide CONCEPTION Study.

Background It has been suggested that chronic hypertension is a risk factor for negative maternal and fetal outcomes during pregnancy and postpartum. We aimed to estimate the association of chronic hypertension on adverse maternal and infant outcomes and assess the impact of antihypertensive treatment and these outcomes. Methods and Results Using data from the French national health data system, we identified and included in the CONCEPTION cohort all women in France who delivered their first child between 2010 and 2018. Chronic hypertension before pregnancy was identified through antihypertensive medication purchases and by diagnosis during hospitalization. We assessed the incidence risk ratios (IRRs) of maternofetal outcomes using Poisson models. A total of 2 822 616 women were included, and 42 349 (1.5%) had chronic hypertension and 22 816 were treated during pregnancy. In Poisson models, the adjusted IRR (95% CI) of maternofetal outcomes for women with hypertension were as follows: 1.76 (1.54-2.01) for infant death, 1.73 (1.60-1.87) for small gestational age, 2.14 (1.89-2.43) for preterm birth, 4.58 (4.41-4.75) for preeclampsia, 1.33 (1.27-1.39) for cesarean delivery, 1.84 (1.47-2.31) for venous thromboembolism, 2.62 (1.71-4.01) for stroke or acute coronary syndrome, and 3.54 (2.11-5.93) for maternal death postpartum. In women with chronic hypertension, being treated with an antihypertensive drug during pregnancy was associated with a significantly lower risk of obstetric hemorrhage, stroke, and acute coronary syndrome during pregnancy and postpartum. Conclusions Chronic hypertension is a major risk factor of infant and maternal negative outcomes. In women with chronic hypertension, the risk of pregnancy and postpartum cardiovascular events may be decreased by antihypertensive treatment during pregnancy.

Contraception in breast cancer survivors from the FEERIC case-control study (performed on behalf of the Seintinelles research network).

OBJECTIVE: To compare the prevalence of contraception in breast cancer (BC) patients at risk of unintentional pregnancy (i.e. not currently pregnant or trying to get pregnant) and matched controls. STUDY DESIGN: The FEERIC study (Fertility, Pregnancy, Contraception after BC in France) is a prospective, multicenter case-control study, including localized BC patients aged 18-43 years, matched for age and parity to cancer-free volunteer controls in a 1:2 ratio. Data were collected through online questionnaires completed on the Seintinelles research platform. RESULTS: In a population of 1278 women at risk of unintentional pregnancy, the prevalence of contraception at study inclusion did not differ significantly between cases (340/431, 78.9%) and controls (666/847, 78.6%, p = 0.97). Contrarily, the contraceptive methods used were significantly different, with a higher proportion of copper IUD use in BC survivors (59.5% versus 25.0% in controls p < 0.001). For patients at risk of unintentional pregnancy, receiving information about chemotherapy-induced ovary damage at BC diagnosis (OR = 2.47 95%CI [ 1.39-4.37] and anti-HER2 treatment (OR = 2.46, 95% CI [ 1.14-6.16]) were significantly associated with the use of a contraception in multivariate analysis. CONCLUSION: In this large French study, BC survivors had a prevalence of contraception use similar to that for matched controls, though almost one in five women at risk of unintentional pregnancy did not use contraception. Dedicated consultations at cancer care centers could further improve access to information and contraception counseling.

Acute coronary syndrome during pregnancy and postpartum in France: the nationwide CONCEPTION study.

BACKGROUND: Cardiovascular diseases, including acute coronary syndromes, are the leading cause of maternal death in many developed countries. OBJECTIVE: We assessed acute coronary syndrome incidences during pregnancy, peripartum, and postpartum periods. We also compared overall pregnancy (ie, covering all 3 periods) incidence with that found in nonpregnant women of childbearing age. STUDY DESIGN: All women aged between 15 and 49 years without ischemic heart disease who delivered between 2010 and 2018 in France were included in the CONCEPTION cohort. Data were extracted from the French National Health Insurance Information System database. Acute coronary syndromes were defined according to the International Classification of Diseases, Tenth Revision codes recorded in the principal hospital diagnosis. We used Poisson regression to estimate crude acute coronary syndrome incidences, and tested age-adjusted Poisson models to compare the incidence risk ratio of acute coronary syndrome between pregnant and nonpregnant women, with 95% confidence intervals. RESULTS: Among 6,298,967 deliveries in France, we observed 225 first-time acute coronary syndrome diagnoses during overall pregnancy (overall pregnancy-related acute coronary syndrome incidence, 4.34/100,000 person-years; 1 case/23,000 pregnancies). In multivariate analysis, independent factors associated with acute coronary syndrome were age, social deprivation, obesity, tobacco use, chronic hypertension, and hypertensive disorders of pregnancy (all P<.05). Among the nonpregnant women aged 15 to 49 years in the general French population, 18,247 cases of acute coronary syndrome (incidence, 16.5/100,000 person-years) occurred throughout the whole study period (>100 million person-years). Compared with the acute coronary syndrome incidence in nonpregnant women, age-adjusted overall pregnancy-related acute coronary syndrome incidence was lower (incidence rate ratio, 0.76; 95% confidence interval, 0.57-0.98; P<.05). Although compared with nonpregnant women, age-adjusted incidence rates were lower during pregnancy, risk was increased during peripartum and postpartum periods. CONCLUSION: With an incidence of 4.34 per 100,000 person-years, acute coronary syndrome still accounts for a significant proportion of maternal mortality. The peripartum and postpartum periods remain high-risk periods, and greater efforts should be made in terms of acute coronary syndrome prevention, especially because several cardiovascular risk factors are treatable, such as tobacco use and hypertensive disorders of pregnancy.

Meningioma in patients exposed to progestin drugs: results from a real-life screening program.

PURPOSE: To report the results of systematic meningioma screening program implemented by French authorities in patients exposed to progestin therapies (cyproterone (CPA), nomegestrol (NA), and chlormadinone (CMA) acetate). METHODS: We conducted a prospective monocentric study on patients who, between September 2018 and April 2021, underwent standardized MRI (injection of gadolinium, then a T2 axial FLAIR and a 3D-T1 gradient-echo sequence) for meningioma screening. RESULTS: Of the 210 included patients, 15 (7.1%) had at least one meningioma; seven (7/15, 47%) had multiple meningiomas. Meningiomas were more frequent in older patients and after exposure to CPA (13/103, 13%) compared to NA (1/22, 4%) or CMA (1/85, 1%; P = 0.005). After CPA exposure, meningiomas were associated with longer treatment duration (median = 20 vs 7 years, P = 0.001) and higher cumulative dose (median = 91 g vs. 62 g, P = 0.014). Similarly, their multiplicity was associated with higher dose of CPA (median = 244 g vs 61 g, P = 0.027). Most meningiomas were ≤ 1 cm3 (44/58, 76%) and were convexity meningiomas (36/58, 62%). At diagnosis, patients were non-symptomatic, and all were managed conservatively. Among 14 patients with meningioma who stopped progestin exposure, meningioma burden decreased in 11 (79%) cases with no case of progression during MR follow-up. CONCLUSION: Systematic MR screening in progestin-exposed patients uncovers small and multiple meningiomas, which can be managed conservatively, decreasing in size after progestin discontinuation. The high rate of meningiomas after CPA exposure reinforces the need for systematic screening. For NA and CMA, further studies are needed to identify patients most likely to benefit from screening.

Incidence and Time Trends of Pregnancy-Related Stroke Between 2010 and 2018: The Nationwide CONCEPTION Study.

BACKGROUND AND OBJECTIVES: Despite the potentially devastating effects of pregnancy-related stroke, few studies have examined its incidence by type of stroke. We aimed to study the nationwide incidence rates and recent temporal trends for all types of pregnancy-related stroke and to compare these incidences with stroke incidence in nonpregnant women. METHODS: We conducted a study of 6,297,698 women aged 15-49 years who gave birth in France between 2010 and 2018 with no history of stroke before pregnancy by collecting data from the French National Health Insurance Information System database. Poisson regression was used to estimate the incidence by types of strokes for the different pregnancy periods and the incidence rate ratio of stroke in pregnant vs nonpregnant French women. RESULTS: Among the 6,297,698 women, 1,261 (24.0 per 100,000 person-years) experienced a first ever stroke during, antepartum peripartum, or the first 6 weeks of postpartum. Of the pregnancy-related strokes, 42.9% were ischemic (IS), 41.9% were hemorrhagic (with similar proportion of intracerebral and subarachnoid hemorrhage), and 17.4% were cerebral venous thrombosis (CVT). Compared with nonpregnant women, incidence rates of stroke were similar during pregnancy for IS (adjusted incidence risk ratio [IRR] 0.9 [0.8-1.1]), slightly higher for all hemorrhagic strokes (IRR 1.4 [1.2-1.8]), and considerably increased for CVT (IRR 8.1 [6.5-10.1]). Pregnancy-related stroke incidence rose between 2010 and 2018 for IS and HS but was stable for CVT. DISCUSSION: The risk of pregnancy-related CVT was more than 8-fold higher than that observed in nonpregnant women. The incidence of pregnancy-related IS and HS is increasing over time, and efforts should be made for prevention considering treatable cardiovascular risk factors and hypertensive disorders in pregnant women.

Long-term prophylaxis in hereditary angioedema management: Current practices in France and unmet needs.

Background: Hereditary angioedema (HAE) is characterized by unpredictable and potentially life-threatening attacks of cutaneous and submucosal swelling. Over the past decade, new agents, based on a better understanding of the underlying biologic mechanisms of HAE, have changed the face of long-term prophylaxis (LTP). Objective: The objective was to describe current practices and unmet needs with regard to LTP for HAE in expert centers in France. Methods: The study was conducted in France in 2020. Based on their experience with patients with HAE who had visited their center at least once in the past 3 years, physicians from 25 centers who are expert in the management of HAE were requested to fill in a questionnaire that encapsulated their active patient list, criteria for prescribing LTP, and medications used. They were asked about potential unmet needs with currently available therapies. They were asked to express their expectations with regard to the future of HAE management. Results: Analysis was restricted to 20 centers that had an active patient file and agreed to participate. There were 714 patients with C1 inhibitor (C1-INH) deficiency, of whom 423 (59.2%) were treated with LTP. Altered quality of life triggered the decision to start LTP, as did the frequency and severity of attacks. Ongoing LTP included androgens (28.4%), progestins (25.8%), lanadelumab (25.3%), tranexamic acid (14.2%), intravenous C1-INHs (5.6%), and recombinant C1-INH (0.7%). Twenty-nine percent of the patents with LTP were considered to still have unmet needs. Physicians' concerns varied among therapies: poor tolerability for androgens and progestins, a lack of efficacy for tranexamic acid and progestins, dosage form, and high costs for C1-INHs and lanadelumab. Physicians' expectations encompassed more-efficacious and better-tolerated medications, easier treatment administration for the sake of improved quality of life of patients, and less-expensive therapies. Conclusion: Despite the recent enrichment of the therapeutic armamentarium for LTP, physicians still expressed unmet needs with currently available therapies.

Pregnancy, fertility concerns and fertility preservation procedures in a national study of French breast cancer survivors.

RESEARCH QUESTION: What are the real-life oncofertility practices in young women diagnosed with breast cancer? DESIGN: The FEERIC (FErtility, prEgnancy, contRaceptIon after breast Cancer in France) study is a web-based cohort study launched with the French collaborative research platform Seintinelles. The current work is based on the enrolment self-administered questionnaire of 517 patients with prior breast cancer diagnosis, free from relapse and aged 18 to 43 years at inclusion (from 12 March 2018 to 27 June 2019). RESULTS: Median age at breast cancer diagnosis was 33.6 years and 424 patients (82.0%) received chemotherapy. Overall, 236 (45.6%) patients were offered specialized oncofertility counselling, 181 patients underwent at least one fertility preservation procedure (FPP); 125 (24.2%) underwent one or more FPP with material preservation (oocytes n = 108, 20.9%; embryos n = 31, 6.0%; ovarian cryopreservation n = 6, 1.2%) and 78 patients received gonadotrophin-releasing hormone agonists (15.1%). With a median follow-up of 26.9 months after the end of treatments, 133 pregnancies had occurred in 85 patients (16.4%), including 20 unplanned pregnancies (15.0%). Most of the pregnancies were natural conceptions (n = 113, 87.6%), while 16 (12.4%) required medical interventions. For the planned pregnancies, median time to the occurrence of an ongoing pregnancy was 3 months. Patients who had an unplanned pregnancy reported lower rates of information on the consequences of the treatments on fertility (P = 0.036) at diagnosis. CONCLUSIONS: Most of the patients were not offered proper specialized oncofertility counselling at the time of breast cancer diagnosis. Naturally conceived pregnancies after breast cancer were much more frequent than pregnancies resulting from the use of cryopreserved gametes. Adequate contraceptive counselling seems as important as information about fertility and might prevent unplanned pregnancies.

Low serum progesterone affects live birth rate in cryopreserved blastocyst transfer cycles using hormone replacement therapy.

RESEARCH QUESTION: Does serum progesterone concentration on the day of vitrified-warmed embryo transfer affect live birth rate (LBR) with hormonal replacement therapy (HRT) cycles? DESIGN: Observational cohort study of patients (n = 915) undergoing single autologous vitrified-warmed blastocyst transfer under HRT using vaginal micronized progesterone. Women were included once, between January 2019 and March 2020. Serum progesterone concentration was measured by a single laboratory on the morning of embryo transfer. The primary end point was LBR. Univariate and multivariate logistic regression models were used for statistical analyses. RESULTS: Median (25th-75th percentile) serum progesterone concentration on the day of embryo transfer was 12.5 ng/ml (9.8-15.3). The LBR was 31.5% (288/915) in the overall population. No significant differences were found in implantation rates (40.7% versus 44.9%); LBR was significantly lower in women with a progesterone concentration ≤25th percentile (≤9.8 ng/ml) (26.1% versus 33.2%, P = 0.045) versus women with a progesterone concentration >25th percentile. This correlated with a significantly higher early miscarriage rate (35.9% versus 21.6%, P = 0.005). After adjusting for potential confounding factors in multivariate analysis, low serum progesterone levels (≤9.8 ng/ml) remained significantly associated with lower LBR (OR 0.68 95% CI 0.48 to 0.97). CONCLUSION: A minimum serum progesterone concentration is needed to optimize reproductive outcomes in HRT cycles with single autologous vitrified-warmed blastocyst transfer. Whether modifications of progesterone administration routes, dosage, or both, can improve pregnancy rates needs further study so that treatment of patients undergoing HRT cycles can be further individualized.

[The risk-benefit balance of estrogen-progestogen hormonal contraception]. / La balance bénéfices-risques des contraceptions hormonales estroprogestatives.

Combined hormonal contraception (CHC) remains the most widely used contraceptive strategy, particularly in France. While the benefit-risk balance is very beneficial for the majority of women, its use must be cautious in some clinical situations and in particular in women at vascular risk. It is therefore essential to provide information on all the vascular risk factors before prescribing any CHC, regardless of their route of administration. From an oncological point of view, if the use of CHCs is associated with a slight increase in the risk of breast cancer, their potential benefits persist for many years after their discontinuation for the risk of ovarian and endometrial cancer. These benefits counteract largely the risk of breast cancer. Finally, CHCs provide non-contraceptive benefits, especially in clinical situations such as dysmenorrhea or severe endometriosis. Therefore, it is necessary to precisely assess the clinical context of each woman in order to adapt the best contraceptive strategy.

TITLE: La balance bénéfices-risques des contraceptions hormonales estroprogestatives. ABSTRACT: La contraception hormonale estroprogestative (COP) reste la stratégie contraceptive la plus utilisée, notamment en France. Si la balance bénéfices-risques est, pour la très grande majorité des femmes, très favorable, son utilisation doit être extrêmement prudente dans certaines situations cliniques et, en particulier, chez les femmes à risque vasculaire. Il est donc indispensable de renseigner l'ensemble des facteurs de risque vasculaire avant toute prescription de COP, quelle que soit sa voie d'administration. D'un point de vue carcinologique, si l'utilisation de la COP est associée à une discrète augmentation du risque de cancer du sein, les bénéfices méconnus, persistant de nombreuses années après son arrêt, vis-à-vis du risque de cancer de l'ovaire et de l'endomètre, contrebalancent largement ce risque mammaire. Enfin, la COP apporte des avantages non contraceptifs, notamment dans les situations cliniques telles que les dysménorrhées ou l'endométriose invalidante, améliorant profondément la qualité de vie des femmes. Il est donc nécessaire d'évaluer très précisément le contexte clinique de chaque femme afin d'adapter la meilleure stratégie contraceptive en minimisant les risques et pour bénéficier des avantages potentiels.

Hypertensive disorders of pregnancy and onset of chronic hypertension in France: the nationwide CONCEPTION study.

AIMS: Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal and foetal morbidity and mortality. We aimed to estimate the impact of HDP on the onset of chronic hypertension in primiparous women in the first years following childbirth. METHODS AND RESULTS: This nationwide cohort study used data from the French National Health Data System (SNDS). All eligible primiparous women without pre-existing chronic hypertension who delivered between 2010 and 2018 were included. Women were followed up from six weeks post-partum until onset of hypertension, a cardiovascular event, death, or the study end date (31 December 2018). The main outcome was a diagnosis of chronic hypertension. We used Cox models to estimate hazard ratios (HRs) of chronic hypertension for all types of HDP. Overall, 2 663 573 women were included with a mean follow-up time of 3.0 years. Among them, 180 063 (6.73%) had an HDP. Specifically 66 260 (2.16%) had pre-eclampsia (PE) and 113 803 (4.27%) had gestational hypertension (GH). Compared with women who had no HDP, the fully adjusted HRs of chronic hypertension were 6.03 [95% confidence interval (CI) 5.89-6.17] for GH, 8.10 (95% CI 7.88-8.33) for PE (all sorts), 12.95 (95% CI 12.29-13.65) for early PE, 9.90 (95% CI 9.53-10.28) for severe PE, and 13.17 (95% CI 12.74-13.60) for PE following GH. Hypertensive disorders of pregnancy exposure duration was an additional risk factor of chronic hypertension for all PE subgroups. Women with HDP consulted a general practitioner or cardiologist more frequently and earlier. CONCLUSION: Hypertensive disorders of pregnancy exposure greatly increased the risk of chronic hypertension in the first years following delivery.

Adenomyosis: An update regarding its diagnosis and clinical features.

Adenomyosis is a common gynecologic disease characterized by invasion of endometrial glands and stroma within the myometrium. Clinically, it can result in abnormal uterine bleeding, pelvic pain, and infertility. Adenomyosis has historically been diagnosed by histology of hysterectomy specimens. As a result of the development of imaging techniques, the diagnosis is nowadays possible by means of transvaginal pelvic ultrasound or pelvic magnetic resonance imaging. The use of pelvic imaging has demonstrated the existence of different forms of adenomyosis, notably allowing distinction between lesions of the external myometrium and those of the internal myometrium. The epidemiological and clinical characteristics may depend on the anatomical location of the adenomyosis lesions. In order to provide the best management for women with adenomyosis, the objective of this review is to provide an update regarding the diagnosis of adenomyosis and its clinical features according to the different adenomyosis phenotypes.

Position statement on the diagnosis and management of premature/primary ovarian insufficiency (except Turner Syndrome).

Premature ovarian insufficiency (POI) is a rare pathology affecting 1-2% of under-40 year-old women, 1 in 1000 under-30 year-olds and 1 in 10,000 under-20 year-olds. There are multiple etiologies, which can be classified as primary (chromosomal, genetic, auto-immune) and secondary or iatrogenic (surgical, or secondary to chemotherapy and/or radiotherapy). Despite important progress in genetics, more than 60% of cases of primary POI still have no identifiable etiology; these cases are known as idiopathic POI. POI is defined by the association of 1 clinical and 1 biological criterion: primary or secondary amenorrhea or spaniomenorrhea of>4 months with onset before 40 year of age, and elevated follicle-stimulating hormone (FSH)>25IU/L on 2 assays at>4 weeks' interval. Estradiol level is low, and anti-Müllerian hormone (AMH) levels have usually collapsed. Initial etiological work-up comprises auto-immune assessment, karyotype, FMR1 premutation screening and gene-panel study. If all of these are normal, the patient and parents may be offered genome-wide analysis under the "France Génomique" project. The term ovarian insufficiency suggests that the dysfunction is not necessarily definitive. In some cases, ovarian function may fluctuate, and spontaneous pregnancy is possible in around 6% of cases. In confirmed POI, hormone replacement therapy is to be recommended at least up to the physiological menopause age of 51 years. Management in a rare diseases center may be proposed.