Management of women with abnormal uterine bleeding: Clinical practice guidelines of the French National College of Gynaecologists and Obstetricians (CNGOF).

OBJECTIVE: To provide French guidelines for the management of women with abnormal uterine bleeding (AUB). DESIGN: A consensus committee of 26 experts was formed. A formal conflict-of-interest policy was developed at the beginning of the process and enforced throughout. The entire guidelines process was conducted independently of any industry funding (i.e. pharmaceutical or medical device companies). The authors were advised to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. METHODS: The last guidelines from the Collège National des Gynécologues et Obstétriciens Français on the management of women with AUB were published in 2008. The literature seems now sufficient for an update. The committee studied questions within 7 fields (diagnosis; adolescents; idiopathic AUB; endometrial hyperplasia and polyps; type 0-2 fibroids; type 3 or higher fibroids; and adenomyosis). Each question was formulated in a PICO (Patients, Intervention, Comparison, Outcome) format and evidence profiles were compiled. The GRADE® methodology was applied to the literature review and the formulation of recommendations. RESULTS: The experts' synthesis work and the application of the GRADE method resulted in 36 recommendations. Among the formalized recommendations, 19 are strong and 17 weak. No response was found in the literature for 14 questions. We chose to abstain from recommendations rather than providing advice based solely on expert clinical experience. CONCLUSIONS: The 36 recommendations make it possible to specify the diagnostic and therapeutic strategies for various clinical situations practitioners encounter, from the simplest to the most complex.

Recurrence of hypertensive disorders of pregnancy: results from a nationwide prospective cohort study (CONCEPTION).

OBJECTIVE: To assess the risk of gestational hypertension (GH) and pre-eclampsia (PE) during a second pregnancy after occurrence during a first pregnancy. DESIGN: Prospective cohort study. SETTING: CONCEPTION is a French nationwide cohort study that used data from the National Health Data System (SNDS) database. METHODS: We included all women who gave birth for the first time in France in 2010-2018 and who subsequently gave birth. We identified GH and PE through hospital diagnoses and the dispensing of anti-hypertensive drugs. The incidence rate ratios (IRR) of all hypertensive disorder of pregnancy (HDP) during the second pregnancy were estimated using Poisson models adjusted for confounding. MAIN OUTCOME MEASURES: Incidence rate ratios of HDP during the second pregnancy. RESULTS: Of the 2 829 274 women included, 238 506 (8.4%) were diagnosed with HDP during their first pregnancy. In women with GH during their first pregnancy, 11.3% (IRR 4.5, 95% confidence interval [CI] 4.4-4.7) and 3.4% (IRR 5.0, 95% CI 4.8-5.3) developed GH and PE during their second pregnancy, respectively. In women with PE during their first pregnancy, 7.4% (IRR 2.6, 95% CI 2.5-2.7) and 14.7% (IRR 14.3, 95% CI 13.6-15.0) developed GH and PE during their second pregnancy, respectively. The more severe and earlier the PE during the first pregnancy, the stronger the likelihood of having PE during the second pregnancy. Maternal age, social deprivation, obesity, diabetes and chronic hypertension were all associated with PE recurrence. CONCLUSION: These results can guide policymaking that focuses on improving counselling for women who wish to become pregnant more than once, by identifying those who would benefit more from tailored management of modifiable risk factors, and heightened surveillance during post-first pregnancies.

Clinical factors associated with low serum progesterone levels on the day of frozen blastocyst transfer in hormonal replacement therapy cycles.

STUDY QUESTION: Which factors are associated with low serum progesterone (P) levels on the day of frozen embryo transfer (FET), in HRT cycles? SUMMARY ANSWER: BMI, parity and non-European geographic origin are factors associated with low serum P levels on the day of FET in HRT cycles. WHAT IS KNOWN ALREADY: The detrimental impact of low serum P concentrations on HRT-FET outcomes is commonly recognized. However, the factors accounting for P level disparities among patients receiving the same luteal phase support treatment remain to be elucidated, to help clinicians predicting which subgroups of patients would benefit from a tailored P supplementation. STUDY DESIGN, SIZE, DURATION: Observational cohort study with 915 patients undergoing HRT-FET at a tertiary care university hospital, between January 2019 and March 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients undergoing single autologous blastocyst FET under HRT using exogenous estradiol and vaginal micronized progesterone for endometrial preparation. Women were only included once during the study period. The serum progesterone level was measured in the morning of the FET, in a single laboratory. Independent factors associated with low serum P levels (defined as ≤9.8 ng/ml, according to a previous published study) were analyzed using univariate and multivariate logistic regression models. MAIN RESULTS AND THE ROLE OF CHANCE: Two hundred and twenty-six patients (24.7%) had a low serum P level, on the day of the FET. Patients with a serum P level ≤9.8 ng/ml had a lower live birth rate (26.1% vs 33.2%, P = 0.045) and a higher rate of early miscarriage (35.2% vs 21.5%, P = 0.008). Univariate analysis showed that BMI (P < 0.001), parity (P = 0.001), non-European geographic origin (P = 0.001), the duration of infertility (P = 0.018) and the use of oral estradiol for endometrial preparation (P = 0.009) were significantly associated with low serum P levels. Moreover, the proportion of active smokers was significantly lower in the 'low P concentrations' group (P = 0.002). After multivariate analysis, BMI (odds ratio (OR) 1.06 95% CI (1.02-1.11), P = 0.002), parity (OR 1.32 95% CI (1.04-1.66), P = 0.022), non-European geographic origin (OR 1.70 95% CI (1.21-2.39), P = 0.002) and active smoking (OR 0.43 95% CI (0.22-0.87), P = 0.018) remained independent factors associated with serum P levels ≤9.8 ng/ml. LIMITATIONS, REASONS FOR CAUTION: The main limitation of this study is its observational design, leading to a risk of selection and confusion bias that cannot be ruled out, although a multivariable analysis was performed to minimize this. WIDER IMPLICATIONS OF THE FINDINGS: Extrapolation of our results to other laboratories, or other routes and/or doses of administering progesterone also needs to be validated. There is urgent need for future research on clinical factors affecting P concentrations and the underlying pathophysiological mechanisms, to help clinicians in predicting which subgroups of patients would benefit from individualized luteal phase support. STUDY FUNDING/COMPETING INTEREST(S): No funding/no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Management of postmenopausal women: Collège National des Gynécologues et Obstétriciens Français (CNGOF) and Groupe d'Etude sur la Ménopause et le Vieillissement (GEMVi) Clinical Practice Guidelines.

AIM: The aim of these recommendations is to set forth an individualized approach to the management of early postmenopausal women (i.e., within the first 10 years after natural menopause) covering all aspects of lifestyle and therapeutic management, with or without menopause hormone therapy (MHT). MATERIALS AND METHODS: Literature review and consensus of French expert opinion. Recommendations were graded according to the HAS methodology and levels of evidence derived from the international literature, except when there was no good-quality evidence. SUMMARY RECOMMENDATIONS: The beginning of menopause is an ideal time for each woman to evaluate her health status by assessing her bone, cardiovascular, and cancer-related risk factors that may be amplified by postmenopausal estrogen deficiency and by reviewing her lifestyle habits. Improving lifestyle, including nutrition and physical activity, and avoiding risk factors (notably smoking), should be recommended to all women. MHT remains the most effective treatment for vasomotor symptoms but it could be also recommended as first-line treatment for the prevention of osteoporosis in early postmenopausal women at low to moderate risk for fracture. The risks of MHT differ depending on its type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used. There is reasonable evidence that using transdermal estradiol in association with micronized progesterone or dydrogesterone may limit both the venous thromboembolic risk associated with oral estrogens and the risk of breast cancer associated with synthetic progestins. Treatment should be individualized to each woman, by using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of its benefit-risk balance. For bothersome genitourinary syndrome of menopause (GSM) symptoms, vaginal treatment with lubricants and moisturizers is recommended as first-line treatment together with low-dose vaginal estrogen therapy, depending on the clinical course. No recommendation of an optimal duration of MHT can be made, but it must take into consideration the initial indication for MHT as well as each woman's benefit-risk balance. Management of gynecological side-effects of MHT is also examined. These recommendations are endorsed by the Groupe d'Etude sur la Ménopause et le Vieillissement hormonal (GEMVI) and the Collège National des Gynécologues-Obstétriciens Français (CNGOF).

[Management of women with abnormal uterine bleeding: Clinical practice guidelines of the French National College of Gynecologists and Obstetricians (CNGOF)]. / Prise en charge des ménorragies : recommandations pour la pratique clinique du Collège national des gynécologues et obstétriciens français (CNGOF).

OBJECTIVE: To provide French guidelines for the management of women with abnormal uterine bleeding (AUB). DESIGN: A consensus committee of 26 experts was formed. A formal conflict-of-interest (COI) policy was developed at the beginning of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding (i.e. pharmaceutical, or medical devices). The authors were advised to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. METHODS: The last guidelines from the Collège national des gynécologues et obstétriciens français (CNGOF) on the management of women with AUB was published in 2008. The literature seems now sufficient for an update. The committee studied questions within 7 fields (diagnosis; adolescent; idiopathic AUB; endometrial hyperplasia and polyps; fibroids type 0 to 2; fibroids type 3 and more; adenomyosis). Each question was formulated in a PICO (Patients, Intervention, Comparison, Outcome) format and the evidence profiles were produced. The literature review and recommendations were made according to the GRADE® methodology. RESULTS: The experts' synthesis work and the application of the GRADE method resulted in 36 recommendations. Among the formalized recommendations, 19 present a strong agreement and 17 a weak agreement. Fourteen questions did not find any response in the literature. We preferred to abstain from recommending instead of providing expert advice. CONCLUSIONS: The 36 recommendations made it possible to specify the diagnostic and therapeutic strategies of various clinical situations managed by the practitioner, from the simplest to the most complex.

Prise en charge des ménorragies : recommandations pour la pratique clinique du Collège National des Gynécologues et Obstétriciens Français (CNGOF) [Pré-print] / Management of women with abnormal uterine bleeding: clinical practice guidelines of the French National College of Gynecologists and Obstetricians (CNGOF) [Pré-print]

Émettre des recommandations pour la prise en charge des femmes ayant des ménorragies. Un comité de 26 experts a été constitué. Une politique de déclaration et de suivi des liens d'intérêts a été appliquée et respectée durant tout le processus de réalisation du référentiel. De même, celui-ci n'a bénéficié d'aucun financement provenant d'une entreprise commercialisant un produit de santé (médicament ou dispositif médical). Le comité devait respecter et suivre la méthode GRADE® (Grading of Recommendations Assessment, Development and Evaluation) pour évaluer la qualité des données factuelles sur lesquelles étaient fondées les recommandations. Les dernières recommandations du Collège National des Gynécologues et Obstétriciens Français (CNGOF) sur la prise en charge des femmes ayant des ménorragies ont été publiées en 2008. Nous avons souhaité réactualiser ces recommandations selon la méthodologie GRADE® en identifiant 7 champs différents (diagnostic ; adolescente ; ménorragies idiopathiques ; hyperplasie et polype de l'endomètre ; myomes de type 0 à 2 ; myomes de type 3 et plus ; adénomyose). Chaque question a été formulée selon le format PICO (Patients, Intervention, Comparison, Outcome). L'analyse de la littérature et les recommandations ont été formulées selon la méthodologie GRADE. Le travail de synthèse des experts et l'application de la méthode GRADE ont abouti à 36 recommandations. Parmi les recommandations, 19 ont été établies avec un accord fort et 17 avec un accord faible. Il n'a pas été possible de statuer pour 14 questions pour lesquelles nous avons préféré nous abstenir plutôt que de fournir des avis d'experts.Les 36 recommandations ont permis de préciser les stratégies diagnostiques et thérapeutiques des différentes situations cliniques des plus simples au plus complexes rencontrées par le praticien.

To provide French guidelines for the management of women with abnormal uterine bleeding (AUB). A consensus committee of 26 experts was formed. A formal conflict-of-interest (COI) policy was developed at the beginning of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding (i.e. pharmaceutical, or medical devices). The authors were advised to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. The last guidelines from the Collège National des Gynécologues et Obstétriciens Français (CNGOF) on the management of women with AUB was published in 2008. The literature seems now sufficient for an update. The committee studied questions within 7 fields (diagnosis; adolescent; idiopathic AUB; endometrial hyperplasia and polyps; fibroids type 0 to 2; fibroids type 3 and more; adenomyosis). Each question was formulated in a PICO (Patients, Intervention, Comparison, Outcome) format and the evidence profiles were produced. The literature review and recommendations were made according to the GRADE® methodology. The experts' synthesis work and the application of the GRADE method resulted in 36 recommendations. Among the formalized recommendations, 19 present a strong agreement and 17 a weak agreement. Fourteen questions did not find any response in the literature. We preferred to abstain from recommending instead of providing expert advice. The 36 recommendations made it possible to specify the diagnostic and therapeutic strategies of various clinical situations managed by the practitioner, from the simplest to the most complex.

[Differential diagnosis of vasomotor symptoms. Postmenopausal women management: CNGOF and GEMVi clinical practice guidelines]. / Diagnostics différentiels des bouffées vasomotrices post-ménopausiques. RPC Les femmes ménopausées de CNGOF et du GEMVi.

Hormone replacement therapy (HRT) significantly decreases the frequency and intensity of vasomotor symptoms (VMS). It is recommended to evaluate clinical efficacy of HRT on VMS. The absence of reduction in VMS after adaptation of the modalities of the HRT suggests the possibility of atypical VMS. They should be evoked in the following clinical circumstances: when they do not give way with an adapted HRT (compliance and good use); when they appear or reappear long after menopause; when there are changes to the usual VMS; when they are associated with other functional signs. A first and second-line assessment is offered, after an interview and a detailed clinical examination, which will guide further explorations. The treatment is above all etiological when the results are positive. When the results are negative, an adaptation of the HRT can be proposed.

[Menopause and risk of thromboembolic events. Postmenopausal women management: CNGOF and GEMVi clinical practice guidelines]. / Ménopause et risque thromboembolique veineux. RPC Les femmes ménopausées du CNGOF et du GEMVi.

The incidence of venous thromboembolism (VTE) increases with age with an annual incidence of 1.25/1000 women in the 40-59 age group. Menopausal hormone therapy (MHT) may also increase the risk of VTE. This risk must be assessed during the first consultation before initiating MHT and assess each renewal of the MHT. MHT with oral estrogen combined (or not) with progestin increases the risk of VTE by about 70%. Using transdermal estrogen does not appear to increase the risk of VTE in women. VTE risk appears to be modulated by the type of progestin combined in MHT. The risk of VTE associated with MHT with transdermal estradiol appears to be safe in women using micronised progesterone and pregnane derivatives and higher in women using norpregnane derivatives . To limit the risk of VTE associated with MHT, transdermal estradiol use is recommended. In women at risk of VTE, MHT with oral estrogen is contraindicated. MHT with transdermal estradiol associated (or not) with micronised progesterone or dydrogesterone may be used in women with low or moderate risk of VTE.

[Menopausal hormone therapy an cardiovascular risk. Postmenopausal women management: CNGOF and GEMVi clinical practice guidelines]. / Traitement hormonal de ménopause et risque cardiovasculaire. RPC Les femmes ménopausées du CNGOF et du GEMVi.

Cardiovascular risk is one of the major challenges of menopausal hormone therapy (MHT). Thus, during a consultation of menopause, it is essential to considering the classic cardiovascular risk factors but also those more specific to women in order to evaluate the level of cardiovascular risk: high risk, intermediate risk or low risk. Cardiovascular disease (myocardial infarction or ischemic stroke) are rare disease in women compared to men. However, they represent the leading cause of death in women after menopause in France. Publications of randomized trials have widely questioned the expected benefit of MHT on arterial risk. It should be noted that almost all of these trials concerned the combination of orally conjugated equine estrogens (ECE) associated or not with medroxyprogesterone acetate. Meta-analyses of all randomized trials show an increased risk of ischemic stroke associated with the use of oral MHT while the use of transdermal estrogen therapy combined with progesterone will be safe. The risk of coronary heart disease is not increased and appears to be significantly reduced when the MHT is started less than 10 years after menopause or before the age of 60. These results suggest that the timing of initiation of the MHT, the type of MHT and all of the risk factors should be carefully considered before starting MHT.

[Non-hormonal alternatives for the management of menopausal hot flushes. Postmenopausal women management: CNGOF and GEMVi clinical practice guidelines]. / Alternatives non hormonales de prise en charge des bouffées vasomotrices post-ménopausiques. RPC Les femmes ménopausées du CNGOF et du GEMVi.

One of the major symptoms of climacteric syndrome is hot flushes (HF). They are most often experienced as very disabling. Estrogen therapy is the most effective treatment. However, it may be contraindicated in some women. The aim of this article is to provide a review of the scientific literature on pharmacological and non-pharmacological alternatives in this context. Only randomized trials and meta-analyses of randomized trials were considered. This review shows that some treatments usually used in non-gynecological or endocrinological disease have significant effect in reducing the frequency and/or severity of HF. Hence, some selective serotonin reuptake inhibitors (paroxetine, citalopram and escitalopram), serotonin and norepinephrine reuptake inhibitors (venlafaxine, desvenlafaxine) gabapentin, pregabalin and clonidine have a statistically effect as compared with placebo in reducing, the frequency and/or severity of HF. Some phytoestrogens, such as genistein, may also reduce the frequency of HF. Regarding non-pharmacological interventions, hypnosis, acupuncture or yoga have been analyzed with significant beneficial results, even if their evaluation is difficult by the absence of a good placebo group in most trials. By contrast, other approaches, both pharmacological or non-pharmacological, appear to be ineffective in the management of HT. These include homeopathy, vitamin E, alanine, omega 3, numerous phytoestrogens (red clover, black cohosh…), primrose oil, physical activity. In women suffering from breast cancer, several additional problems are added. On the one hand because all phytoestrogens are contraindicated and on the other hand, in patients using tamoxifen, because the molecules, that interact with CYP2D6, are to be formally avoided because of potential interaction with this anti-estrogen treatment. In conclusion, several pharmacological and non-pharmacological alternatives have significant efficacy in the management of severe HF.

Adenomyosis of the inner and outer myometrium are associated with different clinical profiles.

STUDY QUESTION: Do adenomyosis phenotypes such as external or internal adenomyosis, as diagnosed by MRI, have the same clinical characteristics? SUMMARY ANSWER: External adenomyosis was found more often in young and nulliparous women and was associated with deep infiltrating endometriosis, whereas, in contrast, internal adenomyosis was more often associated with heavy menstrual bleeding (HMB) but no differences were noted in terms of pain symptoms. WHAT IS KNOWN ALREADY: Adenomyosis is characterized by the presence of endometrial glands and stroma deep within the myometrium, giving rise to dysmenorrhea, pelvic pain and menorrhagia. Various forms have been described, including adenomyosis of the outer myometrium (external adenomyosis), which corresponds to lesions separated from the junctional zone (JZ), and adenomyosis of the inner myometrium (internal adenomyosis), which is mostly characterized by endometrial implants scattered throughout the myometrium and enlargement of the JZ. Although the pathogenesis of adenomyosis is not clearly understood, several lines of evidence suggest that these two phenotypes could have distinct origins. The clinical presentation of different forms of adenomyosis in patients warrants further investigation. STUDY DESIGN, SIZE, DURATION: This was an observational study that used data collected prospectively in non-pregnant patients aged between 18 and 42 years who had undergone surgical exploration for benign gynecological conditions at our institution between May 2005 and May 2018. Only women with a pelvic MRI performed by a senior radiologist during the preoperative work-up were retained for this study. For each patient, a standardized questionnaire was completed during a face-to-face interview conducted by the surgeon in the month preceding the surgery. The women's histories (notably their age, gravidity, history of surgery and associated endometriosis), as well as clinical symptoms such as the pain intensity, presence of menorrhagia and infertility, were noted. PARTICIPANTS/MATERIALS, SETTING, METHODS: A pelvic MRI was performed in 496 women operated at our center for a benign gynecological disease who had provided signed informed consent. Of these, 248 women had a radiological diagnosis of adenomyosis. Based on the MRI findings, the women were diagnosed as having external and/or internal adenomyosis. The women were allocated to two groups according to the adenomyosis phenotype (only external adenomyosis vs only internal adenomyosis). Women exhibiting an association of both adenomyosis forms were analyzed separately. MAIN RESULTS AND THE ROLE OF CHANCE: In all, following the MRI findings, 109 women (44.0%) exhibited only external adenomyosis, while 78 (31.5%) had only internal adenomyosis. The women with external adenomyosis were significantly younger (mean ± SD; 31.9 ± 4.6 vs 33.8 ± 5.2 years; P = 0.006), more often nulligravid (P ≤ 0.001) and more likely to exhibit an associated endometriosis (P < 0.001) compared to the women in the internal adenomyosis group. Moreover, the women exhibiting internal adenomyosis significantly more often had a history of previous uterine surgery (P = 0.002) and HMB (62 (80%) vs 58 (53.2%), P < 0.001) compared to the women with external adenomyosis. No differences in the pain scores (i.e. dysmenorrhea, non-cyclic pelvic pain and dyspareunia) were observed between the two groups. LIMITATIONS, REASONS FOR CAUTION: The exclusive inclusion of surgical patients could constitute a possible selection bias, as the women referred to our center may have suffered from particularly severe clinical symptoms. WIDER IMPLICATIONS OF THE FINDINGS: Further studies are needed to explore the pathogenesis by which these types of adenomyosis occur. This could help with the development of new treatment strategies specific for each entity. STUDY FUNDING/COMPETING INTEREST(S): none. TRIAL REGISTRATION NUMBER: N/A.

Symptomatic progestin-associated atypical grade II meningioma. A first case report.

BACKGROUND: Long-term use of high-dose progestin is known to promote the development of meningioma. Atypical meningioma in a patient under progestin has not previously been reported. CASE REPORT: A 53-year-old right-handed woman presented with focal onset seizures, without impaired consciousness. Medical history featured endometriosis, treated successively by cyproterone acetate 25mg/day for 2 months then 50mg/day for 101 months, and chlormadinone acetate 5mg/day for 68 months then 10mg/day for 83 months. Brain MRI revealed multiple extra-axial lesions suggestive of left central meningioma associated with anterior skull base meningiomatosis. Surgical resection of the left central meningioma was achieved and progestin was withdrawn. Neuropathology diagnosed grade II atypical meningioma. Close clinical and imaging monitoring was implemented without adjuvant oncological treatment. At 25 months, imaging follow-up showed no recurrence of the left central meningioma and a significant regression of all other lesions, except for the right frontal lesion. CONCLUSIONS: Neurosurgeons should be aware of the possible aggressiveness of meningioma in patients under progestin, and particularly those treated by different types of progestin over a long period of time without interruption. This may require systematic close monitoring, to adapt neurosurgical management.

[Hypertension and menopausal hormone therapy]. / HTA et traitement hormonal de la menopause.

Can menopausal hormone therapy (HT) be used in hypertensive women? The group of experts of the French Society of Hypertension has carried out a review of the recent literature in order to answer this question, based on the most recent scientific publications. If use of oral HT is associated with a discreet increase in blood pressure, the transdermal route seems to be safer. The first results of major randomized trials of HT had alerted to an increase in cardiovascular events and breast cancer with the use of oral HT, generally, tipping the benefit-risk balance of the deleterious side. Complementary analyzes have shown the importance of the window of intervention (less than 10 years after the menopause) and the age of the woman to start the HT. On the contrary, they have shown a significant decrease of the coronary events. For woman suffering from hypertension and important climacteric symptoms, it is important to evaluate the whole cardiovascular risk in order to decide the possibility of prescribing a HT. Thus, the group of experts proposes a prescription assistance algorithm based on the stratification of cardiovascular risk, always favoring, when it is authorized, HT by transdermal route of administration.

Arterial and venous complications after fertility treatment: A French nationwide cohort study.

OBJECTIVES: To determine whether the risk of thromboembolic complications is higher in women following unsuccessful fertility treatment (FT) and in pregnant women following successful FT, and whether the risk differs according to FT type. STUDY DESIGN: This is an observational prospective cohort study. All French women aged 18-45 years who received FT between 2013 and 2015 were selected from the French health insurance claim database which registers healthcare consumption for the entire French population. All FT reimbursed over a 28-day period from the date of the first FT were considered to constitute one FT cycle. Each FT cycle was classified according to type: either simple ovulation induction (OI) or ovulation stimulation (OS). All hospitalisations with a diagnosis of venous thromboembolism (VTE), arterial thrombosis (AT) or ovarian hyperstimulation syndrome (OHSS) were identified for the selected women in the French hospital discharge database. Poisson regressions were used to estimate incidence rate ratios (IRR) by comparing i) the incidence of thromboembolic complications (i.e., VTE and AT) and OHSS following unsuccessful FT cycles with the incidence of these two diseases in all non-pregnant women of the same age range (i.e. non-pregnant control group), and ii) incidence of thromboembolic complications and OHSS in women who became pregnant following successful FT with the incidence in women of the same age range with spontaneous (i.e., no FT) pregnancies (i.e., pregnant control group (spontaneous pregnancy)). RESULTS: During the study period, 277,913 women underwent FT, for a total of 788,007 FT cycles, with 82,821 FT-related pregnancies. Among unsuccessful FT cycles, 75 VTE and 43 AT were observed. OS treatment cycles but not OI were associated with a higher risk of VTE than in reference group (age-adjusted IRR 1.74, 95%CI [1.30-2.34]). Among FT-related pregnancies, 207 VTE and 35 AT were reported. VTE and AT incidence rates during the first trimester were higher after OS treatment cycles than in the pregnant control group (spontaneous pregnancy) after adjusting for age and twin/multiple pregnancies (IRRVTE = 3.29, 95%CI [2.24-4.81]; IRRAT = 2.63, 95%CI [1.06-6.51]). CONCLUSION: Monitoring women undergoing FT, especially OS, irrespective of pregnancy status is crucial. The risk of thromboembolic complications in the first trimester for FT-related pregnancies seems to be higher than that for spontaneous pregnancies.

[Contraception: CNGOF Guidelines for Clinical Practice (Short Version)]. / Contraception : Recommandations pour la Pratique Clinique du CNGOF (texte court).

The French College of Obstetrics and Gynecology (CNGOF) releases its first global recommendations for clinical practice in contraception, to provide physicians with an updated synthesis of available data as a basis for their practice. The French Health Authority (HAS) methodology was used. Twelve practical issues were selected by the organizing committee and the task force members. The available literature was screened until December 2017, and allowed the release of evidence-based, graded recommendations. This synthesis is issued from 12 developed texts, previously reviewed by experts and physicians from public and private practices, with an experience in the contraceptive field. Male and female sterilization, as well as the use of hormonal treatments without contraceptive label were excluded from the field of this analysis. Specific practical recommendations on the management of contraception prescription, patient information including efficacy, risks, and benefits of the different contraception methods, follow up, intrauterine contraception, emergency contraception, local and natural methods, contraception in teenagers and after 40, contraception in vascular high-risk situations, and in case of cancer risk are provided. The short/mid-term future of contraception mostly relies on improving the use of currently available methods. This includes reinforced information for users and increased access to contraception for women, whatever the social and clinical context. That is the goal of these recommendations.

[Hormonal contraception and vascular risk: CNGOF Contraception Guidelines]. / Contraception hormonale et risque vasculaire. RPC Contraception CNGOF.

Venous thromboembolism and arterial ischemic events are the main deleterious diseases associated with the use of combined hormonal contraceptives (CHC). Even though their composition has been substantially improved, the vascular risk persists with the most recent CHCs use. If the vascular risk associated with CHCs containing 50µg EE is significantly higher than with those containing less than 50µg, there is no evidence that the CHCs containing either 30 or 20µg of EE induce different venous risks. CHC containing gestodene, desogestrel, drospirenone or cyproterone acetate are associated with a higher risk of venous thrombosis compared with levonorgestrel-containing CHCs. CHC containing norgestimate are associated with similar venous thrombosis risk than CHC containing levonorgestrel. Venous thrombosis risk of non-oral routes of administration of CHC appears to be equivalent to the risk of CHC containing gestodene or desogestrel, but this result is based on a small number of epidemiological studies. Before prescribing a CHC, it is important to determine all vascular risk factors. Family history of ischemic arterial event or venous thromboembolism disease should be routinely sought before any CHC prescription. All CHCs are contraindicated in women with biological thrombophilia, in women with combined vascular risk factors, in women with first-degree family history of arterial or venous event (under age 50) as well as in women suffering of migraine with aura. Progestin-only contraceptives are not associated with vascular risk (arterial or venous) outside of medroxyprogesterone acetate. In women with higher vascular risk, progestin-only contraceptives (administered by oral, sous-cutaneous or intra-uterine routes) can be prescribed.

Progesterone, progestins and the breast in menopause treatment.

Breast cancer is the main risk associated with menopause hormone therapy (MHT). It is a hormone-dependent cancer. In postmenopausal women, about 80% of cases are estradiol receptor-positive. In cohort studies only estradiol receptor-positive breast cancers are promoted by MHT. Different levels of risk with estrogen-only treatment and combined treatment with estrogen + progestin are shown in randomized trials and observational studies. Several non-randomized studies show a lower risk with progesterone and retroprogesterone than with synthetic progestins. Progesterone and progestin are non-selective ligands for the progesterone receptor and bind also with other steroid receptors, with agonistic or antagonistic effects according to the structure of the molecule. Their half-life and metabolism are also different, progesterone being rapidly degraded with a short half-life. These aspects will be discussed in this review.

Migraine, hormones and the menopausal transition.

Migraine is a common, disabling and incapacitating headache disorder that may be triggered by many factors, such as hormones especially during the perimenopausal period, where large alterations in estradiol levels can occur. The evidence implies that hormonal fluctuations are one of the important triggers of migraine. During reproductive life and during hormonal contraception, the course of migraine can be impacted. Different types of migraine with and without aura can be variously influenced by hormones. Migraine can constitute a risk factor for stroke and this must be taken in account for menopause hormone therapy. Hormone therapy is a possible approach to prevent migraine that happens during the menopause transition. Scarce data on the various regimens and types of hormone therapy are available. Transdermal estradiol displays a more favorable profile on migraine than oral estrogens because it may provide more constant levels of estrogens.