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.

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.

[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.

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.

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.

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.

Next Generation Sequencing Should Be Proposed to Every Woman With "Idiopathic" Primary Ovarian Insufficiency.

CONTEXT: Primary ovarian insufficiency (POI) affects 1% of women under 40 years of age. POI is idiopathic in more than 70% of cases. Though many candidate genes have been identified in recent years, the prevalence and pathogenicity of abnormalities are still difficult to establish. OBJECTIVE: Our primary objective was to evaluate the prevalence of gene variations in a large prospective multicentric POI cohort. Our secondary objective was to evaluate the correlation between phenotype and genotype. METHODS: Two hundred and sixty-nine well-phenotyped POI patients were screened for variants of 18 known POI genes (BMP15, DMC1, EIF2S2, FIGLA, FOXL2, FSHR, GDF9, GPR3, HFM1, LHX8, MSH5, NOBOX, NR5A1, PGRMC1, STAG3, XPNPEP2, BHLB, and FSHB) by next generation sequencing (NGS). Abnormalities were classified as "variant" or "variant of unknown signification" (VUS) according to available functional tests or algorithms (SIFT, Polyphen-2, MutationTaster). RESULTS: One hundred and two patients (38%) were identified as having at least 1 genetic abnormality. Sixty-seven patients (25%) presented at least 1 variant. Forty-eight patients presented at least 1 VUS (18%). Thirteen patients (5%) had combined abnormalities. NOBOX variants were the most common gene variants involved in POI (9%). Interestingly, we saw no significant differences in the previous family history of POI, ethnic origin, age at onset of POI, primary amenorrhea, or secondary menstrual disturbances between the different genotypes. CONCLUSION: In our study, a high percentage of patients presented gene variants detected by NGS analysis (38%). Every POI patient should undergo NGS analysis to improve medical cares of the patients.

Imaging for evaluation of endometriosis and adenomyosis.

Endometriosis and adenomyosis are two frequent diseases that impair women's quality of life by causing pain and infertility. Both endometriosis and adenomyosis are heterogeneous diseases that manifest as different forms. Adenomyosis may be described as diffuse adenomyosis, focal adenomyosis especially of the outer myometrium and cystic adenomyoma. Endometriosis has three phenotypes: superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA), and deep infiltrating endometriosis (DIE). These two diseases are closely linked, and it is now clear that adenomyosis can either arise on its own or coexist with endometriosis. There is a strong clinical relationship between endometriosis and adenomyosis according to their respective phenotypes. Various classifications are available to describe both diseases. Transvaginal ultrasonography (TVUS) and/or pelvic magnetic resonance imaging (MRI) are the first examination performed when endometriosis or adenomyosis are suspected. These two imaging techniques, used in a combination manner, allow accurate description of both endometriosis and adenomyosis, to assess the diagnosis and to improve clinical and surgical care. In this review, we described the different imaging aspects of endometriosis and adenomyosis to help the less experienced radiologist or gynecologist in the diagnosis and evaluation of those diseases.

Evolution of the neurosurgical management of progestin-associated meningiomas: a 23-year single-center experience.

PURPOSE: The improving knowledge of interactions between meningiomas and progestin refines the management of this specific condition. We assessed the changes over time of the management of progestin-associated meningiomas. METHODS: We retrospectively studied consecutive adult patients who had at least one meningioma in the context of progestin intake (October 1995-October 2018) in a tertiary adult Neurosurgical Center. RESULTS: 71 adult women with 125 progestin-associated meningiomas were included. The number of progestin-associated meningioma patients increased over time (0.5/year before 2008, 22.0/year after 2017). Progestin treatment was an approved indication in 27.0%. A mean of 1.7 ± 1.2 meningiomas were discovered per patient (median 1, range 1-6). Surgery was performed on 36 (28.8%) meningiomas and the histopathologic grading was WHO grade 1 in 61.1% and grade 2 in 38.9%. The conservative management of meningiomas increased over time (33.3% before 2008, 64.3% after 2017) and progestin treatment withdrawal increased over time (16.7% before 2008, 95.2% after 2017). Treatment withdrawal varied depending on the progestin derivative used (88.9% with cyproterone acetate, 84.6% with chlormadinone acetate, 28.6% with nomegestrol acetate, 66.7% with progestin derivative combination). The main reason for therapeutic management of meningiomas was the presence of clinical signs. Among the 54 meningiomas managed conservatively for which the progestin had been discontinued, MRI follow-up demonstrated a regression in 29.6%, a stability in 68.5%, and an ongoing growth in 1.9% of cases. CONCLUSIONS: Conservative management, including progestin treatment discontinuation, has grown over time with promising results in terms of efficacy and safety.

Hereditary Angioedema with and Without C1-Inhibitor Deficiency in Postmenopausal Women.

PURPOSE: Most types of hereditary angioedema (HAE) are worsened by endogenous or exogenous estrogens. Conversely, androgens can improve HAE with abnormal C1-Inhibitor (C1-INH) by increasing C1-INH concentrations. Menopause is associated with an extinction of ovarian estrogenic and androgenic secretion. There is currently insufficient information on postmenopausal women with HAE. The objective of this study was to describe the activity of HAE in postmenopausal women. METHODS: This was a French retrospective, multicenter study in postmenopausal women with HAE with or without C1-INH deficiency/dysfunction. The patients were classified before and after menopause with a previously validated HAE disease severity score. RESULTS: We included 65 women from 13 centers in France. The mean age was 62.7± 9.2 years, and the mean time between menopause and inclusion was 12.5± 9.1 years. HAE was associated with C1-INH deficiencyin 88% (n = 57) of the patients, a mutation of factor 12 in 8% (n = 5), a mutation in plasminogen gene in one, and unknown HAE for two. The HAE course was not different after menopause in 46.1% (n = 30), improved in 38.5% (n = 25), and worsened in 15.4% (n = 10). Improvement was correlated with estrogen sensitivity of angioedema before menopause (p = 0.06 for improvement vs no effect or worsening). In addition, we observed that only ten women received treatment (transdermal or oral estradiol+ progestogen) for their menopause symptoms. Among them, only 3 experienced worsening of symptoms (2 on transdermal and 1 on oral estradiol). CONCLUSION: Following menopause, most women with HAE remain stable but some worsen. Improvement was mainly observed in patients with previous estrogen sensitivity. More research is required in menopausal women with HAE to better understand how to manage climacteric symptoms.

Focal adenomyosis is associated with primary infertility.

OBJECTIVE: To study the association between adenomyosis and infertility, according to the adenomyosis phenotype as diagnosed by magnetic resonance imaging (MRI). DESIGN: A single-center, cross-sectional study. SETTING: University hospital-based research center. PATIENT(S): Patients between 18 and 42 years of age who were surgically explored for benign gynecological conditions at our institution between May 2005 and May 2018. Only women with uterine MRIs performed by a senior radiologist were retained for this study. INTERVENTION(S): Primary and secondary infertile women were compared with women without infertility. In addition, the women were diagnosed according to the MRI findings as having adenomyosis (focal adenomyosis of the outer myometrium [FAOM] and/or diffuse adenomyosis phenotypes) or no adenomyosis. MAIN OUTCOME MEASURE(S): Primary and secondary infertility-associated factors. RESULT(S): A total of 496 women were included in the study population. Three groups were compared: a no infertility group (n = 361), a primary infertility group (n = 84), and a secondary infertility group (n = 51). Among them, 248 women did not present adenomyosis lesions and 248 women had a radiological diagnosis of adenomyosis. The presence of FAOM was significantly associated with primary infertility. Diffuse adenomyosis was not found to be associated with infertility. The distribution of endometriosis or leiomyomas was not significantly different between the groups. After a multinomial regression model including the women's age and associated endometriosis or leiomyoma, the presence of FAOM was identified as an independent associated factor of primary infertility (adjusted odds ratio 1.9; 95% confidence interval 1.1-3.3). CONCLUSION(S): The presence of FAOM was associated with primary infertility. This study opens the door to future clinical and basic studies aimed at better characterization of FAOM and its infertility-related physiopathology.

Migraine in relation with endometriosis phenotypes: Results from a French case-control study.

BACKGROUND: Studies have shown a significant association between migraine and endometriosis, but no study has explored the relationship between migraine and endometriosis phenotypes: Superficial peritoneal endometriosis, ovarian endometrioma, and deep infiltrating endometriosis. METHODS: We conducted a case-control study using data collected from 314 women aged 18 to 42 years who had undergone surgery for benign gynecological conditions between January 2013 and December 2015. All women completed a self-administered headache questionnaire according to the IHS classification. Cases (n = 182) are women with histologically proven endometriosis and controls are women (n = 132) without endometriosis. Occurrence of migraine was studied according to endometriosis phenotypes. RESULTS: Migraine prevalence in cases was significantly higher compared with controls (35.2% vs. 17.4%, p = 0.003). The risk of endometriosis was significantly higher in migrainous women (OR = 2.62; 95% CI = 1.43-4.79). When we take into account endometriosis phenotypes, the risk of ovarian endometrioma and deep infiltrating endometriosis were significant (OR = 2.78; 95% CI = 1.11-6.98 and OR = 2.51; 95% CI = 1.25-5.07, respectively). In women with endometriosis, the intensity of chronic non-cyclical pelvic pain was significantly greater for those with migraine (visual analogic scale (VAS) = 3.6 ± 2.9) compared with the women without headache (VAS = 2.3 ± 2.8, p = 0.0065). CONCLUSION: Our study shows a significant association between migraine and endometriosis. In clinical practice, women of reproductive age who suffer from migraine should be screened for endometriosis criteria in order to optimise the medical and therapeutic care of this condition.

Spécificités du traitement médicamenteux antihypertenseur chez la femme.

The impact of antihypertensive drugs on blood pressure does not differ according to the sex. There are women-specific conditions or medical conditions encountered more frequently among womens that guide the selection of therapy such as a desire to become pregnant, a pregnancy, a polycystic ovarian syndrome, breast cancer, osteoporosis or migraine.

Clinical practice guidelines for contraception by the French National College of Gynecologists and Obstetricians (CNGOF).

The French College of Obstetrics and Gynecology (CNGOF) has released its first comprehensive recommendations for clinical practices in contraception, to provide physicians with an updated synthesis of the available data as a basis for their practice. The organizing committee and the working group adopted the objective methodological principles defined by the French Authority for Health (HAS) and selected 12 themes relevant to medical professionals' clinical practices concerning contraception. The available literature was screened through December 2017 and served as the basis of 12 texts, reviewed by experts and physicians from public and private practices, with experience in this field. These texts enabled us to develop evidence based, graded recommendations. Male and female sterilization, as well as the use of hormonal treatments not authorized for contraception ("off-label") were excluded from the scope of our review. Specific practical recommendations are provided for the management of contraception prescription, patient information concerning effectiveness, risks, and benefits of the different methods, patient follow-up, intrauterine contraception, emergency contraception, local and natural methods, contraception in teenagers, in women after 40, for women at high thromboembolism or cardiovascular risk, and for those at of primary cancer or relapse. The short- and mid-term future of contraception depends mainly on improving the use of currently available methods. This includes reinforced information for users and increased access to contraception for women, regardless of their social and clinical contexts. The objective of these guidelines is to aid in enabling this improvement.