Longitudinal profile of estrogen-related thrombotic biomarkers after cessation of combined hormonal contraceptives.

ABSTRACT: The persistence of risk of venous thromboembolism (VTE) due to combined hormonal contraceptives (CHCs), after their cessation, is unknown but important to guide clinical practice. The objective of this prospective cohort study was to define the time until normalization of estrogen-related thrombotic biomarkers after CHC cessation. We enrolled women aged 18 to 50 years who had decided to stop their CHC, excluding those with a personal history of VTE, anticoagulation, or pregnancy. The study started before cessation of CHC, with 6 visits afterwards (at 1, 2, 4, 6, and 12 weeks after cessation). Primary outcomes were normalized sensitivity ratios to activated protein C (nAPCsr) and to thrombomodulin (nTMsr), with sex hormone-binding globulin (SHBG) as a secondary end point. We also included control women without CHC. Among 66 CHC users, from baseline until 12 weeks, average levels of nAPCsr, nTMsr, and SHBG decreased from 4.11 (standard deviation [SD], 2.06), 2.53 (SD, 1.03), and 167 nmol/L (SD, 103) to 1.27 (SD, 0.82), 1.11 (SD, 0.58), and 55.4 nmol/L (SD, 26.7), respectively. On a relative scale, 85.8%, 81.3%, and 76.2% of the decrease from baseline until 12 weeks was achieved at 2 weeks and 86.7%, 85.5%, and 87.8% at 4 weeks after CHC cessation, respectively. Levels were not meaningfully modified throughout the study period among 28 control women. In conclusion, CHC cessation is followed by a rapid decrease in estrogen-related thrombotic biomarkers. Two to 4 weeks of cessation before planned major surgery or withdrawal of anticoagulants in patients with VTE appears sufficient for the majority of women. The trial is registered at www.clinicaltrials.gov as #NCT03949985.

Women's lived experience of endometriosis-related fertility issues.

OBJECTIVE: The aim of the present study is to conduct a qualitative investigation to provide a deeper understanding of women's views about endometriosis, fertility and their perception of reproductive options. METHODS: Semi-structured interviews were conducted by two female psychiatrists, specialized in gynecology and obstetrical consultation-liaison psychiatry, trained in qualitative procedures, with experience in qualitative studies and in psychological support of women attending infertility consultations. No prior relationship with respondents was established before data collection. Interviews were tape-recorded and transcribed. Interviews lasted 45-75 minutes. The transcripts were then analysed using thematic content analysis. RESULTS: Twenty-nine women were contacted. Twelve agreed to an interview at the hospital's infertility clinic. Eleven women with diverse sociodemographic characteristics were included. The key findings of thematic content analysis can be grouped into four topics: (1) Diagnostic announcement and initial delay; (2) Negative perceptions of initial care: pre-diagnosis phase; (3) Struggle with endometriosis and its treatment; (4) Issues related to health problems, fertility and reproductive options. CONCLUSION: Our analysis of the interviews corroborates the distressing impact of the trivialization of pain and the uncertainty of or the long quest for diagnosis. The findings also stress various associated issues, from the diagnostic delay to the low success rates of fertility treatments. This qualitative analysis contributes to better understand the accumulation of negative emotions within the illness trajectory and the poor dyadic adjustment within the couple.

Prothrombotic biomarkers during controlled ovarian stimulation for assisted reproductive technology.

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

[News on progestatives in gynaecology]. / Actualités sur les progestatifs en gynécologie.

Progesterone (P4), a steroid primarily secreted by the corpus luteum, placenta and adrenal glands, plays an essential role on female reproductive function. Progestins (PS) are synthetic analogues of P4 with specific steroid receptor affinities. A progestin-only-pill (POP) with an antimineralocorticoid effect was recently marketed with a tolerance and safety profile superior to existing POPs. In contrast, PS with antiandrogenic properties used at high doses for the treatment of hirsutism have been associated with an increased meningioma risk. New clinical and fundamental data open paths for research into the therapeutic use of P4 in cognition, neuroprotection and bone.

La progestérone (P4), stéroïde sécrété principalement par le corps jaune, le placenta et les glandes surrénales, joue un rôle essentiel dans le contrôle de la fonction reproductive de la femme. Les progestatifs de synthèse (PS) sont des analogues avec des affinités spécifiques sur les divers récepteurs stéroïdiens. Une pilule progestative (POP) aux effets antiminéralocorticoïdes a récemment été commercialisée avec un profil de tolérance et de sécurité supérieur aux POP existants. En revanche, des PS aux propriétés antiandrogènes utilisés en forte dose pour le traitement de l'hirsutisme ont été associés à un risque accru de méningiome. De nouvelles données cliniques et fondamentales ouvrent de nouvelles voies de recherche sur l'utilisation thérapeutique de la P4 dans les champs de la cognition, de la neuroprotection et de l'os.

Successful in vivo retrieval of oocytes after ovarian stimulation for fertility preservation before oophorectomy by laparotomy for a young patient with ovarian cancer: Case report and review of literature.

OBJECTIVE: To report a case of direct in vivo oocytes retrieval for fertility preservation before oophorectomy by open surgery in a young patient with ovarian cancer. DESIGN: case report and literature review. SETTING: University hospital. PATIENTS: A 29-year-old nulliparous patient, recently diagnosed with low grade serous ovarian carcinoma.The patient consented to the removal of her remaining ovary but wished to preserve oocytes and declined hysterectomy. Conventional trans-vaginal US-guided oocyte retrieval was contra-indicated because of the risk of malignant cell dissemination to the abdomen and the vaginal puncture sites. INTERVENTIONS: Controlled ovarian stimulation with gonadotrophins was realized. Comprehensive surgical staging was performed 35 h after ovulation triggering using rHCG. The oocytes retrieval was performed in vivo with ultrasound guidance at time of laparotomy before oophorectomy without any time of ischemia. RESULTS: Seven mature oocytes were obtained and vitrified. CONCLUSIONS: This case highlights the feasibility of in vivo oocytes retrieval of mature oocytes during open surgery for gynecologic cancers. By avoiding transvaginal follicular retrieval, the risk of malignant cell contamination to vaginal and parametrial tissues is reduced, limiting cancer upstaging.

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

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

[Uterine transplant: Clinical and ethical challenges in Switzerland]. / La greffe utérine en Suisse: les défis à venir.

Uterine transplant is a novel treatment option for women with absolute uterine infertility. Sixty uterine transplants have been performed worldwide to date. The first live birth happened in 2014 and since then 20 children have been born after this procedure. The procedure has several challenges: The donor is usually a woman alive. Surgery is long and complex for both the donor and the recipient, with a high risk of complications. Embryos have to be obtained through IVF. Pregnancies are at high risk for complications and require cesarean delivery, and transplant is temporary (the transplanted uterus is removed after pregnancy in order to allow discontinuation of immunosuppressive therapy). Uterine transplant is a new hope for women with absolute uterine infertility but a high-risk experimental procedure for the donor, the recipient and the newborns and raises major ethical questions.

La transplantation utérine est une possibilité nouvelle offerte aux femmes présentant une infertilité utérine absolue. Environ 60 greffes utérines ont été réalisées dans le monde. La première naissance a été obtenue en 2014 et depuis 20 enfants ont vu le jour. La «donneuse¼ est le plus souvent une donneuse vivante. Les étapes chirurgicales sont longues et le risque de complications élevé. L'entrée dans un tel programme nécessite l'obtention préalable d'embryons par fécondation in vitro. Les grossesses obtenues sont à haut risque et la naissance se fait par césarienne. La greffe est transitoire car le greffon sera retiré afin d'interrompre le traitement immunosuppresseur. Eût égard aux risques qu'elle fait courir aux «donneuses¼, aux «receveuses¼ et aux enfants obtenus, cette procédure expérimentale soulève de nombreuses questions éthiques.

The effect of mind-body interventions on psychological and pregnancy outcomes in infertile women: a systematic review.

Preliminary evidence suggests that mind-body interventions, including mindfulness-based interventions and yoga, may be effective in reducing mental health difficulties and psychological distress in infertile patients undergoing fertility treatments. We systematically reviewed and synthesized current medical literature of the effectiveness of mind-body interventions in reducing the severity of psychological distress and improving marital function and pregnancy outcomes in infertile women/couple. Databases including PsychINFO, PubMed, EMBASE, and the Cochrane Library were searched for relevant studies. Manual searches were conducted in relevant articles. We included 12 studies that met the inclusion criteria. Four studies were randomized controlled trials (RCT), 4 non-randomized controlled trial (NRCT), and 4 uncontrolled studies (UCT). Participation in a mind-body intervention was associated with reduced anxiety trait and depression scores. The reduction was of low or moderate amplitude in most studies. Our review offers evidence for the effectiveness of mind-body interventions in reducing anxiety state and depression in infertile women and a possible improvement in pregnancy rate. Further RCTs with a precise timing of intervention are needed.

Serum antimüllerian hormone concentration increases with ovarian endometrioma size.

OBJECTIVE: To examine whether serum antimüllerian hormone (AMH) levels correlate with the size of ovarian endometrioma (OMA). DESIGN: An observational cross-sectional study. SETTING: University hospital. PATIENT(S): Two hundred and sixty-seven nonpregnant women, aged 18-42 years, with no prior history of surgery for endometriosis and a histologically documented ovarian cyst. INTERVENTION(S): Surgical management for a benign ovarian cyst. MAIN OUTCOME MEASURE(S): Correlation between serum AMH concentration and cyst size according to OMA and non-OMA benign cyst. RESULT(S): Women with OMA were compared with a control group of women who had non-OMA benign ovarian cysts. The AMH assay samples were collected less than a month before the surgery. Between January 2004 and September 2016, 148 women were allocated to the OMA group and 119 to the non-OMA benign cyst group. The AMH concentrations were not statistically significantly different between the two groups (3.7 ± 2.8 ng/mL vs. 4.1 ± 3.3 ng/mL). A multiple linear regression model accounting for potential confounders revealed that the log10 of the serum AMH concentration positively correlated with the log10 of the OMA cyst volume (R2 = 0.23; coefficient = 0.05; 95% CI, 0.007-0.10). CONCLUSION(S): In women no prior history of surgery for endometriosis, serum AMH levels increased with cyst size in cases of OMA.

Understanding sexual pain in endometriosis.

Sexual dysfunctions, particularly sexual pain, are common in adult women of all ages. In patients with endometriosis, a chronic gynecological pain condition affecting women of reproductive age, sexual pain is the third most common symptom. Multiple biological factors are involved in endometriosis-related sexual pain including tissue damage, inflammation, hormonal changes, alterations within the peripheral and central nervous system and pelvic floor muscle dysfunctions. Conceptual models of sexual pain espouse a multifactorial view, with empirical evidence suggesting the implication of psychosexual and relationship difficulties in the development and persistence of sexual pain and associated distress. We review literature on the biological, psychological, sexual and interpersonal factors associated with development and persistence of sexual pain in women with endometriosis. In addition, we discuss chronic pain conditions frequently associated with endometriosis (vulvodynia, bladder pain syndrome and inflammatory bowel syndrome) and how they are linked with sexual pain. Finally we discuss the clinical implications and provided suggestions for future research and medical care, focusing on a multidisciplinary and biopsychosocial approach.

Endometrial Regeneration in Asherman's Syndrome: Clinical and Translational evidence of Stem Cell Therapies.

Asherman's Syndrome or Intrauterine adhesions is an acquired uterine condition where fibrous scarring forms within the uterine cavity, resulting in reduced menstrual flow, pelvic pain and infertility. Until recently, the molecular mechanisms leading to the formation of fibrosis were poorly understood, and the treatment of Asherman's syndrome has largely focused on hysteroscopic resection of adhesions, hormonal therapy, and physical barriers. Numerous studies have begun exploring the molecular mechanisms behind the fibrotic process underlying Asherman's Syndrome as well as the role of stem cells in the regeneration of the endometrium as a treatment modality. The present review offers a summary of available stem cell-based regeneration studies, as well as highlighting current gaps in research.

[Preimplantation genetic testing]. / Gynécologie-obstétrique: Tests préimplantatoires de l'embryonen médecine de reproduction.

Preimplantation genetic testing avoids the transmission of monogenic diseases or structural chromosome abnormality to the offspring in fertile couples. Furthermore, it allows screening for aneuploidies (PGT-A, Preimplantation genetic testing for aneuploidy), with the aim of selecting one euploid embryo before transfer in infertile couples undergoing in vitro fertilization (IVF). Indeed, aneuploidies are frequent and explain most IVF failures and early miscarriages. The indications for PGT-A remain controversial, due to the lack of clear evidence of improved outcomes after IVF. Cost-effectiveness studies and follow-up of neonatal outcomes are needed. Finally, each situation requires counseling taking into account ethical considerations.

Les tests préimplantatoires permettent à un couple fertile d'éviter la transmission d'une maladie monogénique ou d'une anomalie chromosomique structurelle à sa descendance. Mais ils peuvent également dépister des aneuploïdies (PGT-A, Preimplantation genetic testing for aneuploidy), avec pour but la sélection d'un embryon euploïde avant transfert in utero pour les couples infertiles réalisant une fécondation in vitro (FIV). En effet, les aneuploïdies, très fréquentes, sont à l'origine de la majorité des échecs d'implantation après FIV et des avortements spontanés précoces. Les indications du PGT-A restent néanmoins controversées en l'absence de preuve évidente d'une amélioration des résultats en FIV. Des études coût/efficacité et un suivi des issues néonatales sont nécessaires. Enfin, chaque situation nécessite un counseling en intégrant les aspects éthiques.

Shedding light on the fertility preservation debate in women with endometriosis: a swot analysis.

Endometriosis, a hormone-dependant condition affecting around 10% of women in their reproductive years, has frequent consequences on fertility. Indeed, a proportion of women will require assisted reproductive techniques or surgery in order to achieve pregnancy. Recent refining of stimulation protocols and vitrification techniques has created new possibilities in the field of fertility preservation. As a consequence, oocyte vitrification is now discussed not only in oncologic situations, but also in other conditions at risk of altered ovarian reserve and poor fertility outcome. In endometriosis, various mechanisms can impair ovarian function and diminish ovarian, particularly bilateral or repeated cystectomy. Fertility preservation could represent an option for women with endometriosis but still remains controversial. In order to shed some light on this complex subject and to outline different issues at stake we conducted a SWOT analysis highlighting strengths, weaknesses, opportunities and threats of oocyte vitrification in women with endometriosis.

Psychosocial impact of endometriosis: From co-morbidity to intervention.

Endometriosis-associated pelvic pain is a major health concern in women of childbearing age. Controlled studies have shown that endometriosis can adversely affect women and their partners' general psychological well-being, relationship adjustment and overall quality of life. Furthermore, women with endometriosis report significantly more sexual dysfunctions compared to healthy women. Empirical studies indicate that specific psychosocial factors may modulate pain experience, pain-related distress and treatment outcome. Research on psychosexual interventions in endometriosis treatment is limited but shows to be effective in reducing endometriosis-related pain and associated psychosexual outcomes. An individualized, couple-centered, multimodal approach to care, integrating psychosexual and medical management for endometriosis, is thought to be optimal.

[Hormonal treatments and venous thrombosis in women]. / Traitements hormonaux et risque de thrombose veineuse chez la femme.

Venous thromboembolism is frequently associated with hormonal factors in women. A thorough medical history taking of vascular risks and an individual evaluation of the risk-benefit ratio should precede any prescription of hormonal therapies. In contrary to progestin-only-pills, estroprogestative contraceptives increase 3-6 times the risk of venous thrombosis. In assisted reproductive techniques, venous thrombosis is frequently associated with the occurrence of a severe ovarian hyperstimulation syndrome. Antagonist ovarian stimulation protocols lower the risk of hyperstimulation and should therefore be preferred. Finally, at menopause, hormonal treatments combining transdermal estradiol and micronized progesterone do not seem to increment the risk of thrombosis.

La maladie veineuse thromboembolique est fréquemment associée aux facteurs hormonaux chez la femme. La prescription de toute thérapeutique hormonale sera précédée d'un interrogatoire minutieux à la recherche de facteurs de risque vasculaires et d'une évaluation individuelle de la balance bénéfice-risque. Contrairement à la contraception micro-progestative, la contraception œstroprogestative augmente le risque de thrombose veineuse de 3 à 6 fois. En procréation médicalement assistée, la thrombose veineuse est fréquemment associée à la survenue d'un syndrome d'hyperstimulation ovarienne sévère. Les protocoles de stimulation antagonistes minimisant le risque d'hyperstimulation ovarienne sont donc à privilégier. Enfin, après la ménopause, le traitement hormonal associant de l'œstradiol par voie percutanée et de la progestérone micronisée ne semble pas augmenter le risque de thrombose veineuse.

[Psychological distress and infertile couple : a global approach]. / Détresse psychologique des couples infertiles : une approche globale.

Infertility treatment doesn't stop in the technical and specific processing. The psychological distress may be very important and a frequent cause of drop-out during the medical procedure. Therefore the couple should be taken into account globally. Different level of counselling sessions should be offered to give the couple complete information about the procedure. The psychological counselling should be tailored to their need in term of coping strategies in the management of the stress or more specific psychotherapeutical approach. Indeed consultation-liaison psychiatric interventions should be offered when the couple is known for psychiatric comorbidities or is presenting anxio-depressive symptoms in reaction to medical procedure.

Le suivi du couple infertile ne se limite pas au diagnostic des causes et aux aspects techniques des traitements de procréation médicalement assistée. Les abandons de traitement sont une cause majeure d'absence de grossesse. Ainsi la prise en charge des aspects émotionnels et l'identification des couples à risque de détresse psychologique sont donc essentielles pour prévenir les abandons. Le counselling psychologique s'envisage à plusieurs niveaux. L'équipe gynécologique mettra l'accent sur l'information, la communication positive et l'identification des couples pouvant bénéficier de stratégies de gestion du stress. Enfin, le psychiatre de liaison prendra en charge les couples souffrant d'une pathologie psychiatrique préexistante ou qui développent des symptômes anxieux/dépressifs suite aux traitements.

Relationship between the magnetic resonance imaging appearance of adenomyosis and endometriosis phenotypes.

STUDY QUESTION: What is the relationship between endometriosis phenotypes superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA), deep infiltrating endometriosis (DIE) and the adenomyosis appearance by magnetic resonance imaging (MRI)? SUMMARY ANSWER: Focal adenomyosis located in the outer myometrium (FAOM) was observed more frequently in women with endometriosis, and was significantly associated with the DIE phenotype. WHAT IS KNOWN ALREADY: An association between endometriosis and adenomyosis has been reported previously, although data regarding the association between MRI appearance of adenomyosis and the endometriosis phenotype are currently still lacking. STUDY DESIGN, SIZE, DURATION: This was an observational, cross-sectional study using data prospectively collected from non-pregnant patients who were between 18 and 42 years of age, and who underwent surgery for symptomatic benign gynecological conditions between January 2011 and December 2014. For each patient, a standardized questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding the surgery. Only women with preoperative standardized uterine MRIs were retained for this study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Surgery was performed on 292 patients with signed consent and available preoperative MRIs. After a thorough surgical examination of the abdomino-pelvic cavity, 237 women with histologically proven endometriosis were allocated to the endometriosis group and 55 symptomatic women without evidence of endometriosis to the endometriosis free group. The existence of diffuse or FAOM was studied in both groups and according to surgical endometriosis phenotypes (SUP, OMA and DIE). MAIN RESULTS AND THE ROLE OF CHANCE: Adenomyosis was observed in 59.9% (n = 175) of the total sample population (n = 292). Based on MRI, the distribution of adenomyosis was as follows: isolated diffuse adenomyosis (53 patients; 18.2%), isolated FAOM (74 patients; 25.3%), associated diffuse and FAOM (48 patients; 16.4%). Diffuse adenomyosis (isolated and associated to FAOM) was observed in one-third of the patients regardless of whether they were endometriotic patients or endometriosis free women taken as controls (34.2% (81 cases) versus 36.4% (20 cases)); P = 0.764. Among endometriotic women, diffuse adenomyosis (isolated and associated to FAOM) failed to reach significant correlation with the endometriosis phenotypes (SUP, 20.0% (8 cases); OMA, 45.2% (14 cases) and DIE, 35.5% (59 cases); P = 0.068). In striking contrast, there was a significant increase in the frequency of FAOM in endometriosis-affected women than in controls (119 cases (50.2%) versus 5.4% (3 cases); P < 0.001). FAOM correlated with the endometriosis phenotypes, significantly with DIE (SUP, 7.5% (3 cases); OMA, 19.3% (6 cases) and DIE, 66.3% (110 cases); P < 0.001). LIMITATIONS, REASONS FOR CAUTION: There was a possible selection bias due to the specificity of the study design, as it only included surgical patients in a referral center that specializes in endometriosis surgery. Therefore, women referred to our center may have suffered from particularly severe forms of endometriosis. This could explain the high number of women with DIE (166/237-70%) in our study group. This referral bias for women with severe lesions may have amplified the difference in association of FAOM with the endometriosis-affected patients compared to women without endometriosis. Furthermore, according to inclusion criteria, women in the endometriosis free group were symptomatic women. This may introduce some bias as symptomatic women may be more prone to have associated adenomyosis that in turn could have been overrepresented in the endometriosis free group. Whether this selection could have introduced a bias in the relationship between endometriosis and adenomyosis remains unknown. WIDER IMPLICATIONS OF THE FINDINGS: This study opens the door to future epidemiological, clinical and mechanistic studies aimed at better characterizing diffuse and focal adenomyosis. Further studies are necessary to adequately determine if diffuse and focal adenomyosis are two separate entities that differ in terms of pathogenesis. STUDY FUNDING/COMPETING INTEREST(S): No funding supported this study. The authors have no conflict of interest to declare.

Interdisciplinary consensus on management of premenstrual disorders in Switzerland.

Premenstrual disorders (PMD) can affect women throughout their entire reproductive years. In 2016, an interdisciplinary expert meeting of general gynecologists, gynecological endocrinologists, psychiatrists and psychologists from Switzerland was held to provide an interdisciplinary algorithm on PMD management taking reproductive stages into account. The Swiss PMD algorithm differentiates between primary and secondary PMD care providers incorporating different levels of diagnostic and treatment. Treatment options include cognitive behavioral therapy, alternative therapy, antidepressants, ovulation suppression and diuretics. Treatment choice depends on prevalent PMD symptoms, (reproductive) age, family planning, cardiovascular risk factors, comorbidities, comedication and the woman's preference. Regular follow-ups are mandatory.