Assessment of the Pelvic Pain Experienced by Infertile Women is of Prime Importance for Diagnosing Endometriosis.

OBJECTIVE: To provide evidence regarding the significance of painful symptoms among women suffering from infertility. DESIGN: An observational retrospective cross-sectional study. SETTINGS: University hospital-based research center. PATIENTS: Infertile patients aged between 18 and 42 years surgically explored for benign gynecological conditions between 01-2004 and 12-2020. INTERVENTIONS: For each patient, a standardized questionnaire was completed during a face-to-face interview conducted by the surgeon in the month preceding the surgery. Preoperative assessment the pain symptoms was recorded. Pain intensity was assessed with a 10cm visual analog scale (VAS). The pain was considered to be severe when the VAS score was ≥ 7. MEASUREMENTS AND MAIN RESULTS: Surgery was performed in 839 infertile women. 451 women had severe pelvic pain. Infertile patients with severe pain significantly more often had endometriosis (67.4% versus 30.7% respectively; p <.001) than infertile women without severe pelvic pain, and especially deep infiltrating lesions (43.2% versus 8.5% respectively; p <.001). Moreover, these women more often had intestinal endometriosis lesions (28.4% vs 1.8%; p <.001). After multivariable regression analysis, the presence of endometriosis, irrespective of the phenotype (superficial lesions (OR1.84 [1.19-2.86] and/or ovarian endometrioma OR 2.79 [1.70-4.59] and/or deep infiltrating endometriosis OR 4.49 [2.69-7.51]), and the presence of at least one intestine endometriosis lesion (OR6.49 [2.69-7.51] were significantly associated with severe pelvic pain. CONCLUSION: Severe pelvic pain is significantly associated with endometriosis and especially deep infiltrating lesions in a population of infertile women. These results demonstrate the importance of thorough questioning regarding pelvic pain symptoms during the initial management of infertile patients.

Questionnaire-based screening of adolescents and young adult women can identify markers associated with endometriosis.

STUDY QUESTION: Do adolescents and young adult women (YAW) with histologically proven endometriosis present a specific clinical history? SUMMARY ANSWER: Questionnaire screening of adolescents and YAW can identify clinical markers associated with histologically proven endometriosis. WHAT IS KNOWN ALREADY: Some validated questionaries can contribute to an earlier endometriosis diagnosis in adults. None of these scores, however, have been validated for adolescents or YAW. STUDY DESIGN, SIZE, DURATION: This was an observational cross-sectional study using prospectively recorded data performed between January 2005 and January 2020 in a single university tertiary referral centre for endometriosis diagnosis and management. After a thorough surgical examination of the abdomino-pelvic cavity, women with histologically proven endometriosis were allocated to the endometriosis group, and symptomatic women without evidence of endometriosis were allocated to the endometriosis-free control group. The endometriotic patients were allocated into two sub-groups according to their age: adolescent (≤20 years) and YAW (21-24 years). PARTICIPANTS/MATERIALS, SETTING, METHODS: Adolescents and YAW ≤24 years of age were operated for a symptomatic benign gynaecological condition with signed informed consent. A standardized questionnaire was prospectively completed in the month before the surgery and included epidemiological data, pelvic pain scores, family history of endometriosis, and symptoms experienced during adolescence. The study searched for correlations by univariate analysis to determine clinical markers of endometriosis in adolescents and YAW compared with endometriosis-free control patients. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 262 study participants, 77 women were adolescents (≤20 years of age) and 185 patients (70.6%) were YAW. The endometriosis group included 118 patients (45.0%) and 144 (55.0%) were assigned to the control group. A family history of endometriosis, absenteeism from school during menstruation, history of fainting spells during menstruation, and prescription of oral contraceptive pills for intense dysmenorrhea were significantly more frequently observed in the endometriotic patients. The prevalence and mean pain scores for dysmenorrhea, deep dyspareunia, non-cyclic chronic pelvic pain and gastrointestinal and lower urinary tract symptoms were significantly greater in the endometriosis group, as was experienced rectal bleeding. LIMITATIONS, REASONS FOR CAUTION: The study was performed in a single referral centre that treats patients with potentially more severe disease. This questionnaire was evaluated on a population of patients with an indication for endometriosis surgery, which can also select patients with more severe disease. Women with asymptomatic endometriosis were not considered in this study. These factors can affect the external validity of this study. WIDER IMPLICATIONS OF THE FINDINGS: Patient interviews are relevant to the diagnosis of endometriosis in adolescents and YAW. Combined with imaging and clinical examination, this approach will enable earlier diagnosis and treatment, while remaining non-invasive and rapid. STUDY FUNDING/COMPETING INTEREST(S): The study received no funding from external sources. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

An integrated multi-tissue approach for endometriosis candidate biomarkers: a systematic review.

Biomarker identification could help in deciphering endometriosis pathophysiology in addition to their use in the development of non invasive diagnostic and prognostic approaches, that are essential to greatly improve patient care. Despite extensive efforts, no single potential biomarker or combination has been clinically validated for endometriosis.Many studies have investigated endometriosis-associated biological markers in specific tissues, but an integrative approach across tissues is lacking. The aim of this review is to propose a comprehensive overview of identified biomarkers based on tissue or biological compartment, while taking into account endometriosis phenotypes (superficial, ovarian or deep, or rASRM stages), menstrual cycle phases, treatments and symptoms.We searched PubMed and Embase databases for articles matching the following criteria: 'endometriosis' present in the title and the associated term 'biomarkers' found as Medical Subject Headings (MeSH) terms or in all fields. We restricted to publications in English and on human populations. Relevant articles published between 01 January 2005 (when endometriosis phenotypes start to be described in papers) and 01 September 2022 were critically analysed and discussed.Four hundred forty seven articles on endometriosis biomarkers that included a control group without endometriosis and provided specific information on endometriosis phenotypes are included in this review. Presence of information or adjustment controlling for menstrual cycle phase, symptoms and treatments is highlighted, and the results are further summarized by biological compartment. The 9 biological compartments studied for endometriosis biomarker research are in order of frequency: peripheral blood, eutopic endometrium, peritoneal fluid, ovaries, urine, menstrual blood, saliva, feces and cervical mucus. Adjustments of results on disease phenotypes, cycle phases, treatments and symptoms are present in 70%, 29%, 3% and 6% of selected articles, respectively. A total of 1107 biomarkers were identified in these biological compartments. Of these, 74 were found in several biological compartments by at least two independent research teams and only 4 (TNF-a, MMP-9, TIMP-1 and miR-451) are detected in at least 3 tissues with cohorts of 30 women or more.Integrative analysis is a crucial step to highlight potential pitfalls behind the lack of success in the search for clinically relevant endometriosis biomarkers, and to illuminate the physiopathology of this disease.

Effects of Ulipristal Acetate on Reactive Oxygen Species and Proinflammatory Cytokine Release by Epithelial and Stromal Cells from Human Endometrium and Endometriosis.

Endometriosis is a condition characterized by increased oxidative stress and chronic inflammation, which can be treated with progestins and other progesterone receptor ligands. However, some patients are refractory to this treatment and the reason is uncertain. Here we investigated the effects of the selective progesterone receptor modulator ulipristal acetate (UPA) on proliferation, reactive oxygen species (ROS), and proinflammatory cytokine production by endometriotic cells and endometrial cells from women with histologically proven endometriosis (n = 22) and endometriosis-free controls (n = 6). Epithelial and stromal cells were isolated and treated in triplicate for 24 h with 1 µM, 10 µM, or 100 µM UPA. Cells were tested for proliferation and ROS production, while cell supernatants were assayed for interleukin (IL)-6, C-C motif chemokine ligand 2 (CCL2), and tumor necrosis factor (TNF)-α concentrations. Proliferation, ROS production, and IL-6 and CCL2 secretion were increased in non-stimulated epithelial and stromal cells from endometriotic lesions compared to endometrial cells from endometriosis patients and controls. UPA induced a dose-dependent increase of cell proliferation only in endometriosis, while enhancing ROS production by all cell types evaluated. UPA reduced CCL2 production in controls but failed to do that in endometriosis, whereas TNF-α was undetectable. We conclude that treatment of endometriotic cells with UPA stimulated in vitro proliferation and ROS production and failed to revert the proinflammatory cytokine excess that characterized these cells, unravelling possible mechanisms of drug resistance in the treatment of endometriosis.

The "freeze-all" strategy seems to improve the chances of birth in adenomyosis-affected women.

OBJECTIVE: To compare assisted reproductive technologies (ARTs) outcomes between fresh vs. freeze-all strategies in infertile women affected by adenomyosis. DESIGN: A single-center observational study. SETTINGS: University hospital-based research center. PATIENTS: Adenomyosis-affected women undergoing blastocyst embryo transfer after in vitro fertilization and intracytoplasmic sperm injection between January 1, 2018, and November 31, 2021. The diagnosis of adenomyosis was based on imaging criteria (i.e., transvaginal ultrasound and/or magnetic resonance imaging). INTERVENTION(S): Women who underwent a freeze-all strategy were compared with those who underwent a fresh embryo transfer (ET) strategy. MAIN OUTCOME MEASURE(S): Cumulative live birth rate (LBR). RESULTS: A total of 306 women were included in the analysis: 111 in the fresh ET group and 195 in the freeze-all group. The adenomyosis phenotype (internal diffuse adenomyosis, external focal adenomyosis, and adenomyoma) was not significantly different between the two groups. The cumulative LBR (86 [44.1%] vs. 34 [30.6%], respectively), and the cumulative ongoing pregnancy rate (88 [45.1%] vs. 36 [32.4%], respectively) were significantly higher in the freeze-all group compared with the fresh ET group. After multivariate logistic regression analysis, the freeze-all strategy in women with adenomyosis was associated with significantly higher odds of live birth compared with fresh ET (odds ratio = 1.80; 95% confidence interval = 1.02-3.16). CONCLUSION: The freeze-all strategy in women afflicted with adenomyosis undergoing ART was associated with significantly higher cumulative LBRs. Our preliminary results suggest that the freeze-all strategy is an attractive option that increases ART success rates. Additional studies, with a randomized design, should be conducted to further test whether the freeze-all strategy enhances the pregnancy rate in adenomyosis-affected women.

Oocyte donation outcomes in endometriosis patients with multiple IVF failures.

RESEARCH QUESTION: What are the reproductive outcomes and the prognostic factors of live birth rates in patients with endometriosis referred to oocyte donation after multiple IVF failures? DESIGN: Observational cohort study including all women with endometriosis-related infertility and two or more failed IVF/intracytoplasmic sperm injection (ICSI) cycles referred to oocyte donation between January 2013 and June 2022. Endometriosis was diagnosed based on published imaging criteria, and was confirmed histologically in women who had a history of surgery for endometriosis. The main outcome measured was the cumulative live birth rate (CLBR). The characteristics of women who had a live birth were compared with those who did not using univariate and multivariate analysis to identify determinant factors of fertility outcome. RESULTS: Fifty-seven patients underwent 90 oocyte donation cycles after 244 failed autologous IVF cycles. The mean ± SD age of the population was 36.8 ± 3.3 years, with a mean duration of infertility of 3.6 ± 2.2 years, and a mean number of autologous IVF/ICSI cycles of 4.4 ± 2.3 cycles per patient. Three patients (5.3%) had superficial peritoneal endometriosis, two patients (3.5%) had ovarian endometriomas, and 52 patients (91.2%) had deep infiltrating endometriosis, among which 30 patients (57.7%) had bowel lesions. Thirty patients (52.6%) had associated adenomyosis. Overall, CLBR per patient was 36/57 (63.2%). After multivariate analysis, only being nulligravida (P=0.002) remained an independent negative predictive factor of the live birth rate. Previous surgery did not impact reproductive outcomes. CONCLUSION: This study suggests that oocyte donation appears to be a viable option to optimize the live birth rate in women with endometriosis-related infertility and recurrent IVF failures.

Fertility preservation in women with benign gynaecological conditions.

Although a wealth of data has been published regarding fertility preservation (FP) in women with malignant diseases who receive gonadotoxic treatment, the role of FP in non-malignant conditions has been studied to a much lesser extent. These include benign haematological, autoimmune, and genetic disorders, as well as a multitude of benign gynaecological conditions (BGCs) that may compromise ovarian reserve and/or reproductive potential due to pathogenic mechanisms or as a result of medical or surgical treatments. Alongside accumulating data that document the reproductive potential of cryopreserved oocytes and ovarian tissue, there is potential interest in FP for women with BGCs at risk of infertility; however, there are currently insufficient data about FP in women with BGCs to develop guidelines for clinical practice. The purpose of this article is to appraise the available evidence regarding FP for BGC and discuss potential strategies for FP based on estimated ovarian impairment and on short-term and long-term reproductive goals of patients. Cost-effectiveness considerations and patients' perspectives will also be discussed.

Magnetic resonance imaging presentation of diffuse and focal adenomyosis before and after pregnancy.

RESEARCH QUESTION: Is there a change in magnetic resonance imaging (MRI) criteria of diffuse and focal phenotypes of adenomyosis before and after pregnancy? DESIGN: A retrospective, monocentric, observational study in a single academic tertiary referral centre for endometriosis diagnosis and management. Women were followed for symptomatic adenomyosis, and without a prior history of surgery who give birth after 24+0 weeks. For each patient, pelvic MRI pre- and post-pregnancy was performed by two experienced radiologists with the same image acquisition protocol. Diffuse and focal adenomyosis MRI presentation were analysed before and after pregnancy. RESULTS: Between January 2010 and September 2020, of the 139 patients analysed, 96 (69.1%) had adenomyosis at MRI distributed as follow: 22 (15.8%) presented diffuse adenomyosis, 55 (39.6%) focal adenomyosis and 19 (13.7%) both phenotypes. The frequency of isolated diffuse adenomyosis on MRI was significantly lower before versus after pregnancy (n = 22 [15.8%] versus n = 41 [29.5%], P = 0.01). The frequency of isolated focal adenomyosis was significantly higher before pregnancy than after pregnancy (n = 55 [39.6%] versus n = 34 [24.5%], P = 0.01). The mean volume of all focal adenomyosis lesions on MRI decreased significantly after pregnancy, from 6.7 ± 2.5 mm3 to 6.4 ± 2.3 mm3, P = 0.01. CONCLUSION: The current data indicate that, based on MRI, there is an increase in diffuse adenomyosis and a decrease in focal adenomyosis after pregnancy.

Testicular impairment in Primary Adrenal Insufficiency caused by Nicotinamide Nucleotide Transhydrogenase (NNT) deficiency - a case report: implication of oxidative stress and importance of fertility preservation.

INTRODUCTION: Nicotinamide nucleotide transhydrogenase (NNT) gene deficiency has recently been shown to be involved in Primary Adrenal Insufficiency (PAI). NNT encodes an inner mitochondrial membrane protein that produces large amounts of NADPH. NADPH is used in several biosynthesis pathways and the oxidoreduction of free radicals by the glutathione and thioredoxin systems in mitochondria. Patients with PAI due to NNT deficiency may also exhibit extra-adrenal manifestations, usually including gonadal impairment. CASE REPORT: We present the case of a 35-year-old patient referred to our center for primary infertility with non-obstructive azoospermia, in a context of PAI and obesity. PAI genetic exploration carried out at the age of thirty revealed NNT deficiency due to the presence of two deleterious mutations (one on each allele) in the NNT gene. Scrotal ultrasound revealed a right Testicular Adrenal Rest Tumor (TART). Intensification of glucocorticoid therapy over the course of 8 months failed to reduce the TART volume or improve sperm production and endocrine function. No spermatozoa were found after surgical exploration of both testes, and subsequent histopathological analysis revealed bilateral Sertoli cell-only syndrome. A retrospective review of the hypothalamic-pituitary-gonadic axis hormonal assessment over 20 years showed progressive impairment of testicular function, accelerated during adulthood, leading to hypergonadotropic hypogonadism and non-obstructive azoospermia when the patient reached his thirties, while the PAI remained controlled over the same period. CONCLUSION: This case report provides, for the first time, direct evidence of complete germ line loss in an azoospermic man with NNT deficiency. Additional data further support the hypothesis of a determinant role of oxidative cellular damage due to reactive oxygen species (ROS) imbalance in the severe gonadal impairment observed in this NNT-deficient patient. Early and regular evaluation of gonadal function should be performed in patients with PAI, especially with NNT deficiency, as soon as the patients reach puberty. Fertility preservation options should then be provided in early adulthood for these patients.

RéSUMé: INTRODUCTION: Le gène Nicotinamide Nucleotide Transhydrogenase (NNT) a été récemment impliqué dans l'Insuffisance Surrénalienne Primaire (ISP). Il code pour une protéine de la membrane mitochondriale interne qui produit de fortes quantités de NADPH. Le NADPH est utilisé par plusieurs voies de biosynthèse et dans l'oxydo-réduction de radicaux libres par les voies de signalisation impliquant le glutathion et la thioredoxine dans la mitochondrie. Les patients avec une ISP, en lien avec un déficit du gène NNT, peuvent également présenter des manifestations extra-surrénaliennes, dont une altération gonadique. CAS CLINIQUE: Nous présentons le cas clinique d'un homme de 35 ans adressé à notre centre d'Assistance Médicale à la Procréation pour infertilité primaire avec azoospermie non obstructive, dans un contexte d'ISP et d'obésité. L'exploration génétique effectuée à l'âge de 30 ans a identifié un déficit complet de la protéine NNT dû à la présence de deux mutations hétérozygotes (une sur chaque allèle), délétères. L'échographie scrotale a montré une tumeur testiculaire d'origine surrénalienne à droite. L'intensification du traitement par glucocorticoides pendant 8 mois n'a pas réduit le volume de la tumeur ni amélioré la production spermatique ou la fonction testiculaire endocrine. Aucun spermatozoïde n'a été retrouvé après exploration chirurgicale testiculaire bilatérale, en lien avec un syndrome de Cellules de Sertoli Seules. L'étude rétrospective de l'axe hypothalamo-hypophysaire-gonadique monte une altération progressive de la fonction testiculaire, accélérée à l'âge adulte, aboutissant à un hypogonadisme hypergonadotrope et une azoospermie non-obstructive à 30 ans, alors que l'ISP était contrôlée pendant cette période. CONCLUSION: Ce cas clinique met en évidence pour la première fois une disparition complète de la lignée germinale chez un patient avec un déficit en NNT. Il avance des arguments en faveur de l'hypothèse d'un rôle déterminant des dommages cellulaires, dus à un excès de radicaux oxygénés dans cette atteinte régulière de la fonction gonadique. Cette dernière devrait être suivie à partir de la puberté chez les patients ISP et plus particulièrement ceux ayant un déficit en NNT. Une préservation de la fertilité pourrait leur être proposée lorsqu'ils deviennent adultes.

Decrease of dysmenorrhoea with hormonal treatment is a marker of endometriosis severity.

RESEARCH QUESTION: Is a decrease in dysmenorrhoea after suppressive hormonal therapy a marker of the endometriosis phenotype and of greater disease severity? DESIGN: Retrospective observational cohort study conducted in a French university hospital, between January 2004 and December 2019. Non-pregnant women aged younger than 42 years, who tested for dysmenorrhoea relief after suppressive hormonal therapy before surgery, and who had histological confirmation of endometriosis, were included. The comparisons were carried out according to the results of the suppressive hormonal test. RESULTS: Of the 578 histologically proven endometriosis patients with preoperative pain symptoms, the rate of dysmenorrhoea decrease after suppressive hormonal therapy was 88.2% (n = 510). These patients had a higher incidence of deep infiltrating endometriosis (DIE) intestinal lesions (45.7% [233/510] versus 30.8% [21/68], P = 0.01) and an increased rate of multiple DIE lesions (two or more) (72.8% [287/394] versus 56.4% [22/39], P = 0.02). After multivariate analysis, decrease of dysmenorrhoea after suppressive hormonal therapy remained significantly associated with the severe DIE phenotype (adjusted OR 3.9, 95% CI 2.0 to 7.6, P < 0.001). CONCLUSION: In women with endometriosis, a decrease of dysmenorrhoea after suppressive hormonal therapy is associated with the DIE phenotype and is a marker of greater severity.

IVF/ICSI Outcomes After a Freeze-All Strategy: an Observational Cohort Study.

In order to inform patients undergoing ART regarding their chances for motherhood, it seems useful to describe "freeze all" outcomes according to the different potential indications. The goal of this study was to examine the impact of a "freeze-all approach" on the cumulative live birth rate (cLBR) according to the indication. It is a cohort study including women who had undergone ovarian stimulation (OS) using an antagonist protocol with GnRH agonist triggering between 09.2016 and 09.2018 followed by a freeze-all cycle of blastocyst embryos. The ART outcomes were compared between the two main indications of the freeze-all strategy which were in our cohort: risk of ovarian hyperstimulation syndrome (OHSS) and endometriosis. The ART outcomes were also described for the others indications (inadequate endometrium and/or premature progesterone elevation at trigger day, two or more previous ART failures, and autoimmune disease and/or a high risk of thromboembolic disease (AI and/or TE risk)). In total, 658 women were included. The cLBR in the total population was 37.7% (248/658). The cLBR was significantly higher in the "OHSS risk" group (133/281, 47.3%) than in the "endometriosis" group (69/190, 36.3%) (p = 0.017). No significant differences were noted regarding perinatal outcomes, except a significantly higher risk of placenta praevia (PP) observed in the "endometriosis" group (10.1%) (p = 0.002). The "freeze-all approach" yielded good results in terms of the cLBR and especially in case of OHSS risk. These data should be taken into account when informing patients about the ART strategy and their chances of motherhood.

Influence of endometrioma size on ART outcomes.

RESEARCH QUESTION: Does endometrioma size affect the number of oocytes retrieved after ovarian stimulation in women with endometriosis-related infertility undergoing IVF/intracytoplasmic sperm injection (ICSI)? DESIGN: Cohort study of infertile women with unilateral or bilateral endometrioma(s) associated with deep infiltrating endometriosis, undergoing their first IVF/ICSI cycle between January 2014 and November 2021. A total of 326 women with an adequate imaging work-up with transvaginal ultrasound and/or magnetic resonance imaging performed by senior radiologists before the start of ovarian stimulation was included. Prognostic factors associated with the number of oocytes retrieved were analysed. IVF/ICSI outcomes were compared between five groups defined according to the largest endometrioma diameter (<2, 2 to <4, 4 to <6, 6 to <8 and ≥8 cm). RESULTS: Factors that significantly reduced the number of oocytes retrieved after adjustment by multiple linear regression were women's age (regression coefficient -0.18; 95% confidence interval [95% CI] -0.31 to-0.06; P = 0.005), smoking habit (-2.02; 95% CI -3.42 to -0.62; P = 0.005), day 3 FSH concentration (-0.20; 95% CI -0.39 to -0.02; P = 0.031) and a previous history of surgery for ovarian endometriosis (-1.32; 95% CI -2.63 to -0.02; P = 0.047). Antral follicle count and oestradiol concentration on the trigger day were positively correlated with the number of oocytes retrieved (0.14; 95% CI 0.08 to 0.19; P < 0.001 and 0.003; 95% CI 0.002 to 0.004; P < 0.001, respectively). The mean number of oocytes retrieved was not significantly different between the five groups (P = 0.413), nor were the cumulative live birth rate, the number of cancelled cycles and perinatal outcomes. CONCLUSIONS: No significant difference in the number of oocytes retrieved was observed according to endometrioma size. This study suggests that ovarian stimulation can be of benefit to women irrespective of the endometrioma size.

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

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

Endometriosis increases the rate of spontaneous early miscarriage in women who have adenomyosis lesions.

RESEARCH QUESTION: In women with radiologically diagnosed adenomyosis, is the presence of endometriosis associated with a higher rate of miscarriage? DESIGN: An observational cohort study of women who received medical care for benign gynaecological conditions between May 2005 and May 2018. Women who had adenomyosis lesions visualized by uterine magnetic resonance imaging (MRI) were included. Women who had never been pregnant were excluded. Women with adenomyosis identified by MRI but who did not have endometriosis lesions (control group) were compared with women with adenomyosis and endometriosis lesions (study group). Primary outcome was rate of a previous history of early miscarriage. RESULTS: A total of 214 pregnancies in the study group and 53 pregnancies in the control group were analysed. The rate of a previous miscarriage was significantly higher among women with adenomyosis and endometriosis lesions compared with women in the control group (61/214 [28.5%] versus 6/53 [11.3%], respectively, P = 0.009). A multivariable generalized estimating equation logistic regression model, adjusted for adenomyosis and endometriosis phenotypes, found that the association between endometriosis and adenomyosis significantly increased the risk of miscarriage (OR 3.2, 95% CI 1.1 to 9.65). The risk was significantly higher with deep infiltrating endometriosis (OR 4.37, 95% CI 1.32 to 14.53). CONCLUSIONS: Women affected by endometriosis had a significantly higher rate of previous spontaneous miscarriage than women without endometriosis with adenomyosis lesions identified by MRI. Mechanistic studies are needed to establish the complex link between the presence of endometriosis and adenomyosis and the rate of spontaneous miscarriage.

ART Outcomes After Hysteroscopic Proximal Tubal Occlusion Versus Laparoscopic Salpingectomy for Hydrosalpinx Management in Endometriosis Patients.

The objective of this paper is to compare assisted reproductive technology (ART) cumulative live birth rates after hysteroscopic proximal tubal occlusion and laparoscopic salpingectomy in endometriosis patients, for management of hydrosalpinx. This is an observational cohort study at a university hospital, including all endometriosis patients with hydrosalpinges undergoing ART, between January 2013 and December 2018. The patients underwent either laparoscopic salpingectomy or hysteroscopic proximal tubal occlusion with Essure® when laparoscopy was not an option (extensive pelvic adhesions at exploratory laparoscopy or a history of multiple abdominal surgeries with frozen pelvis). The diagnosis of endometriosis was based on published imaging criteria using transvaginal sonography (TVUS) and magnetic resonance imaging (MRI). Endometriosis patients with hydrosalpinges diagnosed by hysterosalpingography and/or TVUS and/or MRI were included. The primary outcome was the cumulative live birth rate. A total of 104 patients were included in the study; 74 underwent laparoscopic salpingectomy and 30 underwent proximal tubal occlusion with Essure®. The Essure® group had longer infertility durations (58.9 ± 30.0 months vs. 39.5 ± 19.1 months, p = 0.002) and a higher incidence of associated adenomyosis (76.7% vs. 39.1%, p < 0.001) than the salpingectomy group. The cumulative live birth rate was 56.6% after 44 ART cycles in the Essure® group and 40.5% after 99 ART cycles in the salpingectomy group (p = 0.13). In a population of endometriosis patients undergoing ART, women treated by Essure® for management of hydrosalpinx have similar cumulative live birth rates as women treated by laparoscopic salpingectomy.

Fertility preservation for patients affected by endometriosis should ideally be carried out before surgery.

RESEARCH QUESTION: What prognostic factors relate to a high oocyte yield in fertility preservation for women affected by endometriosis? DESIGN: Observational cohort study conducted in a tertiary care university hospital between April 2015 and January 2019. Women who had undergone fertility preservation with ovarian stimulation for oocytes and embryo vitrification for endometriosis were included. Prognostic factors associated with the number of oocytes retrieved after the first ovarian stimulation were analysed. RESULTS: A total of 146 women who had undergone 258 ovarian stimulation cycles were included; 82 (56.2%) had undergone more than one ovarian stimulation cycle; 72.6% had at least one endometrioma lesion; and 36.3% had previously undergone surgery for endometriosis. After adjustment by multiple linear regression, the factors that significantly reduced the number of oocytes retrieved were previous history of surgery for ovarian endometriosis (coefficient -1.08; 95% CI -2.02 to -0.15; P = 0.024); women's age (-0.21; 95% CI -0.41 to -0.01; P = 0.039); and total dose of gonadotrophin used (-0.01; 95% CI -0.01 to -0.00; P = 0.047). Anti-Müllerian hormone serum level and gravidity positively correlated with an increase in the number of oocytes retrieved (1.65; 95% CI 1.13 to 2.17; P < 0.001 and 3.30; 95% CI 0.91 to 5.68; P = 0.007, respectively) after the first ovarian stimulation cycle. CONCLUSION: A history of surgery for ovarian endometriosis was associated with significantly lower oocyte yields. Fertility preservation should be integrated into endometriosis management. Fertility preservation should ideally be made available to the patient before surgery.

Adenomyosis: An update regarding its diagnosis and clinical features.

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

Imaging for evaluation of endometriosis and adenomyosis.

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

Adenomyosis is associated with specific proton nuclear magnetic resonance (1H-NMR) serum metabolic profiles.

OBJECTIVE: To determine whether the adenomyosis phenotype affects the proton nuclear magnetic resonance (1H-NMR)-based serum metabolic profile of patients. DESIGN: Cohort study. SETTING: University hospital-based research center. PATIENTS: Seventy-seven patients who underwent laparoscopy for a benign gynecologic condition. INTERVENTIONS: Pelvic magnetic resonance imaging and collection of a venous peripheral blood sample were performed during the preoperative workup. The women were allocated to the adenomyosis group (n = 32), or the control group (n = 45). The adenomyosis group was further subdivided into two groups: diffuse adenomyosis of the inner myometrium (n = 14) and focal adenomyosis of the outer myometrium (n = 18). Other adenomyosis phenotypes were excluded. MAIN OUTCOME MEASURES: Metabolomic profiling based on 1H-NMR spectroscopy in combination with statistical approaches. RESULTS: The serum metabolic profiles of the patients with adenomyosis indicated lower concentrations of 3-hydroxybutyrate, glutamate, and serine compared with controls. Conversely, the concentrations of proline, choline, citrate, 2-hydroxybutyrate, and creatinine were higher in the adenomyosis group. The focal adenomyosis of the outer myometrium and the diffuse adenomyosis phenotypes also each exhibited a specific metabolic profile. CONCLUSION: Serum metabolic changes were detected in women with features of adenomyosis compared with their disease-free counterparts, and a number of specific metabolic pathways appear to be engaged according to the adenomyosis phenotype. The metabolites with altered levels are particularly involved in immune activation as well as cell proliferation and cell migration. Nevertheless, this study did find evidence of a correlation between metabolite levels and symptoms thought to be related to adenomyosis. Further studies are required to determine the clinical significance of these differences in metabolic profiles.