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.

[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.

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.

[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.

[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.

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.

[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.

[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.

[The menopausal hormone therapy in 2016]. / Traitement hormonal de la ménopause en 2016.

The menopausal hormone therapy (MHT) is the first line treatment for climacteric symptoms related to estrogen deficiency. A personalized evaluation of the benefit-risk ratio should precede a MHT prescription, and take into consideration cardiovascular, thromboembolic, oncological and osteoporosis risks. MHT should be prescribed at the lowest effective dose and for the shortest duration, respecting the window of opportunity in the 10 years following menopause or before the age of 60 years. The choice of the MHT type depends on the patient's profile, her medical history and personal preferences, with the aim of improving quality of life from a physical, psychological and sexual point of view.

Le traitement hormonal de la ménopause (THM) est recommandé en première intention pour les symptômes climatériques liés à la carence œstrogénique. Une évaluation individuelle de la balance bénéfice/risque devrait être effectuée avant la prescription d'un THM, en prenant en compte des facteurs de risque cardiovasculaires, thromboemboliques, oncologiques et ostéoporotiques. Le THM devrait être prescrit à la dose minimale efficace pour une durée la plus courte possible, en respectant la « fenêtre d'opportunité thérapeutique ¼ de 10 ans après la ménopause ou avant l'âge de 60 ans. Le choix du type de THM se fait en fonction du profil, des antécédents et des préférences de la patiente, dans le but d'améliorer sa qualité de vie du point de vue physique, psychologique et sexuel.

Increased serum cancer antigen-125 is a marker for severity of deep endometriosis.

STUDY OBJECTIVE: To determine whether cancer antigen-125 (CA-125) levels are increased in women with endometriosis, especially in those with endometriomas (OMAs), deep infiltrating lesions (DIE), and superficial endometriosis (SUP) compared with controls without endometriosis in a large cohort of operated women. DESIGN: Cross-sectional study (Canadian Task Force classification II-2). SETTING: Tertiary-care university hospital. PATIENTS: Four hundred six women with histologically proven endometriosis and 279 women without endometriosis. INTERVENTIONS: Surgical examination of the abdomino-pelvic cavity. MEASUREMENTS AND MAIN RESULTS: Preoperative serum CA-125 antigen levels were evaluated by electrochemoluminescence immunoassay in women with endometriosis and controls. Correlations between serum CA-125 levels and clinical and anatomical characteristics of disease severity were examined. Women with endometriosis displayed higher mean serum CA-125 levels compared with disease-free controls (50.1 ± 62.4 U/mL vs 22.5 ± 25.2 U/mL; p ≤ .001). CA-125 levels were significantly increased in women with OMA (60.8 ± 63.5 U/mL) and DIE (55.2 ± 68.7 U/mL) compared with women with SUP (23.2 ± 24.5 U/mL) and controls (22.5 ± 25.2 U/mL). There was no difference in CA-125 levels between patients with SUP and controls and between patients with OMA and DIE. CA-125 serum levels were correlated with DIE severity: the mean number of DIE lesions and worst DIE lesion. CONCLUSION: Serum CA-125 levels were significantly increased in women with severe forms of endometriosis, OMA, and DIE lesions. In addition, elevated serum Ca-125 levels were associated with more severe and extended DIE lesions. In women with superficial peritoneal lesions, CA-125 levels were not different from women without endometriosis.

AMH concentration is not related to effective time to pregnancy in women who conceive naturally.

This study determined whether anti-Müllerian hormone (AMH) concentration influences the time necessary to conceive a live-born child--effective time to pregnancy (eTTP)--in a population of women who conceived naturally. This is an observational study of 87 women with a planned spontaneous pregnancy resulting in a live birth. eTTP was assessed retrospectively by a questionnaire and AMH was measured in a frozen serum sample from first trimester of pregnancy. eTTP was correlated with age (r=-0.24, P=0.02), but not with AMH (r=-0.10) or body mass index (r=0.05). With logistic regressions, the only variable that affected the probability of pregnancy within 3 or 6 months was age, irrespective of whether an AMH concentration limit of 1.0 ng/ml or 2.0 ng/ml was chosen. In conclusion, this study suggests that there is no relationship between AMH concentration and eTTP and therefore speaks against determining AMH in women who are not infertile for the purpose of predicting their chances of pregnancy. The findings are concordant with previous reports describing AMH as a quantitative but not a qualitative marker of ovarian reserve and therefore does not reflect a woman's ability to become pregnant. Anti-Müllerian hormone (AMH) is secreted by small growing ovarian follicles and reflects a woman's ovarian reserve - the number of primordial follicles at a given time. AMH concentrations has been extensively studied in infertile women but there are only scarce data on AMH in non-infertile women. Our objective was to determine whether AMH concentrations influence the time necessary to conceive a live-born child - also called effective time to pregnancy (eTTP) - in a population of women who conceived naturally. We conducted an observational study between 2007 and 2009 in which we assessed eTTP retrospectively in 87 women who had delivered a live-born child and measured AMH in a frozen blood sample collected during the first trimester of pregnancy. The results of our study show, as expected, a decrease of AMH concentrations as age increases but no relationship between AMH and eTTP. In conclusion, our study results suggest AMH concentrations do not influence the time necessary to conceive a live-born child spontaneously and therefore speak against determining AMH in women who are not infertile for the purpose of predicting their chances of pregnancy. Our findings are concordant with previous reports describing AMH as a quantitative but not a qualitative marker of ovarian function that does therefore not reflect a woman's ability to become pregnant.

Measurement of hs-CRP is irrelevant to diagnose and stage endometriosis: prospective study of 834 patients.

OBJECTIVE: The pathogenesis of endometriosis is associated with an inflammatory process. Here, we assessed if the levels of high-sensitivity C-reactive protein (hs-CRP) in serum could constitute an effective method for detecting systemic inflammation during endometriosis. STUDY DESIGN: This was a prospective, laboratory-based study, which was carried out in a tertiary care university hospital. Patients with histologically proven endometriosis (n = 370) and unaffected women (n = 464) were enrolled from January 2005 through December 2009. We performed complete surgical excision of endometriotic lesions with pathological analysis. In addition, hs-CRP levels were determined through a particle-enhanced immunoturbidimetric method. The hs-CRP levels were measured in both controls and women with endometriosis according to the established surgical classifications of endometriosis: superficial peritoneal endometriosis, endometrioma, and deep infiltration endometriosis. Also, hs-CRP levels were evaluated according to hormonal treatment and menstrual cycle. RESULTS: The hs-CRP serum levels did not statistically differ between women with endometriosis and controls (median in ng/mL [range]: 0.82 [0.04-42.89] vs 0.9 [0.03-43.73], respectively; P = .599). Moreover, subgroup analysis revealed no difference among superficial peritoneal endometriosis, endometrioma, deep infiltration endometriosis, and controls: 0.8 (0.15-13.35), 0.81 (0.04-38.82), 0.83 (0.09-42.89), and 0.9 (0.03-43.73), respectively; P = .872. Furthermore, no effect was observed regarding hormonal treatment or menstrual cycle. CONCLUSION: Although endometriosis is an inflammatory disease, we failed to identify any systemic changes in hs-CRP serum levels. Therefore, hs-CRP analysis appears to be irrelevant to the diagnosis and staging of endometriosis.

Randomized controlled trial comparing highly purified (HP-hCG) and recombinant hCG (r-hCG) for triggering ovulation in ART.

BACKGROUND: A randomized controlled trial (RCT) comparing highly purified human Choriogonadotrophin (HP-hCG) and recombinant hCG (r-hCG) both administered subcutaneously for triggering ovulation in controlled ovarian stimulation (COS) for Assisted Reproductive Technology (ART). METHODS: Multi-centre (n = 4), prospective, controlled, randomized, non-inferiority, parallel group, investigator blind design, including 147 patients. The trial was registered with www.clinicaltrials.gov, using the identifier: NCT00335569. The primary endpoint is the number of oocytes retrieved, while the secondary endpoints include embryo implantation, pregnancy and delivery rates as well as safety parameters. RESULTS: The number of retrieved oocytes was not inferior when HP-hCG was used as compared to r-hCG: the mean number was 13.3 (6.8) in HP-hCG and 12.5 (5.8) in the r-hCG group (p = 0.49) with a 95% CI (-1.34, 2.77). Regarding the secondary outcomes, there were also no differences in fertilization rate at 57.3% (467/815) vs. 61.3% (482/787) (p = 0.11), the number of embryos available for transfer and cryopreservation (2PN stage) and implantation, pregnancy and delivery rates. Furthermore, there were no differences in the number and type of adverse events reported. HP-hCG was therefore not inferior to r-hCG. CONCLUSIONS: HP-hCG and r-hCG are equally efficient and safe for triggering ovulation in ART and, both being administered subcutaneously, equally practical and well tolerated by patients.

[Measurement of serum AMH levels in gynecology: indications and limits]. / Dosage sérique de l'hormone antimüllérienne en gynécologie: indications et limites.

Antimüllerian hormone (AMH), a glycoprotein secreted by the granulosa cells of (pre)antral follicles, is a quantitative marker of the ovarian reserve. The dosage of AMH is predictive of the response to ovarian stimulation for in vitro fertilization and allows the detection of patients at risk of responding poorly to stimulation or of ovarian hyperstimulation syndrome (OHSS). AMH doesn't predict live-birth chances after IVF. Neither does AMH predict the chances of spontaneous pregnancy nor the success rates of ovarian stimulation with/without intra-uterine insemination. AMH is currently studied to predict the age at menopause, in the diagnosis of polycystic ovarian syndrome and in the context of surgical and medical treatments that can alter the ovarian reserve.

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.

In women with endometriosis anti-Müllerian hormone levels are decreased only in those with previous endometrioma surgery.

STUDY QUESTION: Are anti-Müllerian hormone (AMH) levels lower in women with endometriosis, notably those with endometriomas (OMAs) and deep infiltrating lesions, compared with controls without endometriosis? SUMMARY ANSWER: Endometriosis and OMAs per se do not result in lower AMH levels. AMH levels are decreased in women with previous OMA surgery independently of the presence of current OMAs. WHAT IS KNOWN ALREADY: The impact of endometriosis and OMAs per se on the ovarian reserve is controversial. Most previous studies have been conducted in infertile women. The strength of our study lies in the following points: (i) the selection of women undergoing surgery and not only according to the presence of infertility, (ii) the classification of women with endometriosis and controls based on strict surgical and histological criteria. STUDY DESIGN, SIZE, DURATION: Cross-sectional study using data prospectively collected in all non-pregnant <42-year-old patients, who were surgically explored for a benign gynaecological condition at a university tertiary referral centre between 2004 and 2008. For each patient, a structured questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding surgery. AMH levels were measured in serum samples drawn in the month preceding surgery, without regard to menstrual phase or hormonal therapy. PARTICIPANTS/MATERIALS, SETTING, METHODS: Operations were done on 1262 women between 2004 and 2008, of which 1133 signed the informed consent. Of the 566 women with a visual diagnosis of endometriosis, 411 had histologically proven endometriosis. Frozen serum samples for the AMH measurement were available in 313 of them. Out of the 554 women without visual endometriosis and without past endometriosis surgery, 413 had a frozen serum sample for the AMH measurement. Univariate analysis examined AMH levels according to baseline patient characteristics, the presence and type of endometriosis (superficial lesion, OMA, deep infiltrating lesion) and previous OMA surgery. Analysis of variance-covariance then examined the effects of co-variables on AMH levels. Finally, logistic regressions were conducted to examine the odds ratio (OR) of having AMH levels <1 ng/ml according to the same co-variables. MAIN RESULTS AND THE ROLE OF CHANCE: The difference in AMH levels between women with endometriosis and controls did not reach significance (3.6 ± 3.1 versus 4.1 ± 3.4 ng/ml, P = 0.06). Analysis of variance-covariance demonstrated that AMH levels significantly decreased with age (P < 0.001) and in women with prior OMA surgery irrespective of whether OMAs were present or not at the time of study (P < 0.05). Logistic regression revealed that two major factors were related to AMH levels <1 ng/ml: (i) age (compared with <29 years; 30-34 years OR = 3.1, 95% CI: 1.5-6.4, P = 0.01; 35-39 years OR = 7.0, 95% CI: 3.5-14.1, P = 0.001; ≥40 years OR = 20.8, 95% CI: 9.1-47.4, P = 0.001) and (ii) prior OMA surgery (OR = 3.0, 95% CI: 1.4-6.41, P = 0.01). LIMITATIONS, REASONS FOR CAUTION: The selection of our study population was based on a surgical diagnosis. Women with an asymptomatic form of endometriosis are therefore not included in our study. We cannot exclude that infertile women with OMAs associated with a diminished ovarian reserve, as assessed during their infertility work-up, were less likely to be referred for surgery and might therefore be underrepresented. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that OMAs per se do not diminish the ovarian reserve reflected by AMH levels but that alterations seen in women with endometriosis are a deleterious consequence of OMA surgery. These findings should be taken into account in the decision to operate OMAs in women with a desire for future pregnancy. STUDY FUNDING: none. Potential competing interests: none.