Assessing vaginal wall thickness by transvaginal ultrasound in breast cancer survivors: A pilot study

Aim: There is need for a straightforward objective measure to evaluate vaginal wall changes related to hypoestrogenism. The aim of this pilot study was to evaluate a transvaginal ultrasound procedure for the quantification of vaginal wall thickness in order to differentiate between healthy premenopausal women and postmenopausal women with genitourinary syndrome of menopause using ultra-low-level estrogen status as a model. Methods: We performed a prospective, two-arm, cross-sectional pilot study comparing vaginal wall thickness measured by transvaginal ultrasound in postmenopausal breast cancer survivors using aromatase inhibitors with genitourinary syndrome of menopause (GSM group) and healthy premenopausal women (control or C group) from October 2020 to March 2022. After intravaginal introduction of 20 cm3 of sonographic gel, vaginal wall thickness was measured by transvaginal ultrasound in the anterior, posterior, and right and left lateral walls (four quadrants). The study methods followed the STROBE checklist. Results: According to the results of a two-sided t-test, the mean vaginal wall thickness of the four quadrants in the GSM group was significantly less than that of the C group (2.25 mm vs 4.17 mm, respectively; p < 0.001). Likewise, the thickness of each of the vaginal walls (anterior, posterior, right and left lateral) statistically differed between the two groups (p < 0.001). Conclusion: Transvaginal ultrasound with intravaginal gel may be a feasible objective technique to assess genitourinary syndrome of menopause, showing clear differences in vaginal wall thickness between breast cancer survivors using aromatase inhibitors and premenopausal women. Possible correlations with symptoms or treatment response should be assessed in future studies

Correlació entre l’ecografia i l’endoscòpia en el diagnòstic de l’endometriosi

[cat] La present tesi doctoral titulada "CORRELACIÓ ENTRE L'ECOGRAFIA I L'ENDOSCÒPIA EN EL DIAGNÒSTIC DE L'ENDOMETRIOSI" neix amb la intenció d'avaluar la correlació existent entre l'ecografia transvaginal i l'endoscòpia en el diagnòstic de l'endometriosi. Està composta per la realització de 3 ESTUDIs que presenten uns objectius específics: 1. Avaluar la precisió de l'ecografia transvaginal en la predicció de la infiltració dels nòduls d'endometriosi a la bufeta i l'afectació del meat ureteral en pacients amb nòduls d'endometriosi vesical per tal de seleccionar quins procediments cistoscòpics es poden evitar en el procés diagnòstic. ESTUDI 1. 2. Descriure l'associació dels nòduls d'endometriosi vesical amb d’altres formes d'endometriosi i adenomiosi, així com la seva simptomatologia i la presència d'hidronefrosi. ESTUDI 1. 3. Avaluar la precisió diagnòstica de l'ecografia transvaginal en el diagnòstic prequirúrgic dels nòduls d'endometriosi profunda als lligaments uterosacres, al torus uterí i al fòrnix vaginal posterior en dones amb sospita d'endometriosi mitjançant la realització d'una maniobra ecogràfica protocol·litzada. ESTUDI 2. 4. Descriure l'associació dels nòduls d'endometriosi als lligaments uterosacres, al torus uterí i al fòrnix vaginal posterior amb la presència d'endometriosi en altres localitzacions, així com amb la seva simptomatologia. ESTUDI 2. 5. Avaluar si la presència d’adenomiosi, diagnosticada per ecografia transvaginal, incrementa el risc de complicacions quirúrgiques en pacients operades d'endometriosi profunda per laparoscòpia. ESTUDI 3. A l'ESTUDI 1, que avalua el compartiment anterior de la pelvis, s’ha demostrat una alta precisió diagnòstica de l'ecografia respecte a la cistoscòpia, tant en la predicció del grau d'infiltració del detrusor, com avaluant l'estat dels meats ureterals. Així doncs, l'ecografia és capaç de diagnosticar nòduls d'endometriosi amb infiltració parcial del detrusor, no visibles per cistoscòpia, que per tant, pot ser evitada. També permet identificar els meats ureterals i la distància dels meats al nòduls, fet amb repercussió quirúrgica. Finalment, l'ecografia, i no la cistoscòpia, permet realitzar un ESTUDI anatòmic complet de la pelvis, tenint en compte que els nòduls vesicals s'associen en pràcticament la totalitat dels casos a altres nòduls d'endometriosi profunda al compartiment posterior, amb adenomiosi i/o endometriomes. A l'ESTUDI 2, que avalua el compartiment posterior, l'ecografia transvaginal demostra de nou, comparada amb la laparoscòpia, una alta precisió diagnòstica en la detecció dels nòduls més freqüents a la pelvis: aquells als lligaments uterosacres. Amb una maniobra protocol·litzada, és possible la detecció de nòduls al torus uterí, lligaments uterosacres i fòrnix vaginal posterior. A causa de l'alta associació dels nòduls en aquestes localitzacions amb els nòduls rectals, la detecció dels primers hauria de ser un senyal d'alerta per a la cerca dels nòduls intestinals, amb un paper similar a l’sliding sign. Els nòduls intestinals, quan requereixen de cirurgia, són un dels factors de risc més importants per a patir complicacions postquirúrgiques. A l'ESTUDI 3, que avalua el compartiment mig de la pelvis, el diagnòstic de l’adenomiosi per ecografia transvaginal ha demostrat ser un factor de risc independent per a les complicacions de la cirurgia laparoscòpica de l'endometriosi. I sembla que la probabilitat de complicacions augmenta amb el nombre de criteris ecogràfics d’adenomiosi presents. De nou, l'ecografia és clau en el diagnòstic prequirúrgic de l'endometriosi, per a planificar la cirurgia i informar correctament a la pacient.[eng] This doctoral thesis entitled "CORRELACIÓ ENTRE L'ECOGRAFIA I L'ENDOSCÒPIA EN EL DIAGNÒSTIC DE L'ENDOMETRIOSI”- CORRELATIONSHIP BETWEEN ULTRASOUND AND ENDOSCOPY IN THE DIAGNOSIS OF ENDOMETRIOSIS is intended to evaluate the correlation between transvaginal ultrasound and endoscopy in the diagnosis of endometriosis. It is composed of three studies: In STUDY 1, which evaluates the anterior compartment of the pelvis, a high diagnostic accuracy of the ultrasound with respect to cystoscopic has been demonstrated, both in predicting the degree of infiltration of the detrusor, and in evaluating the state of ureteral meatus. Thus, ultrasound is able to diagnose endometriosis nodules with partial infiltration of the detrusor, not visible by cystoscopic, which can therefore be avoided. It also allows the identification of ureteral meatus and the distance of the meatus from the nodules, which have surgical impact. Finally, ultrasound, rather than cystoscope, allows a complete anatomical study of the pelvis, since vesical nodules are associated in almost all cases with other deep endometriosis nodules in the posterior compartment, with adenomyosis and/or endometriomas. In STUDY 2, which evaluates the posterior compartment, transvaginal ultrasound again demonstrates, compared to laparoscopic, high diagnostic accuracy in the detection of the most common nodules in the pelvis: those in uterosacral ligaments. With a protocolized technique, it is possible to detect nodules in uterine torus, uterosacral ligaments, and posterior vaginal fornix. Due to the high association of nodules in these locations with rectal nodules, the detection nodules in these three areas should be an alert signal for the search for intestinal nodules, with a role similar to the sliding sign. Intestinal nodules, when required for surgery, are one of the most important risk factors for post-surgical complications. In STUDY 3, which evaluates the mid compartment of the pelvis, the diagnosis of adenomyosis by transvaginal ultrasound has proven to be an independent risk factor for complications in endometriosis laparoscopic surgery. And it seems that the probability of complications increases with the number of ultrasound criteria of adenomyosis present. Again, ultrasound is key in the pre-surgical diagnosis of endometriosis, to plan surgery and correctly inform the patient

Oocytes maintain ROS-free mitochondrial metabolism by suppressing complex I

Oocytes form before birth and remain viable for several decades before fertilization1. Although poor oocyte quality accounts for most female fertility problems, little is known about how oocytes maintain cellular fitness, or why their quality eventually declines with age2. Reactive oxygen species (ROS) produced as by-products of mitochondrial activity are associated with lower rates of fertilization and embryo survival3-5. Yet, how healthy oocytes balance essential mitochondrial activity with the production of ROS is unknown. Here we show that oocytes evade ROS by remodelling the mitochondrial electron transport chain through elimination of complex I. Combining live-cell imaging and proteomics in human and Xenopus oocytes, we find that early oocytes exhibit greatly reduced levels of complex I. This is accompanied by a highly active mitochondrial unfolded protein response, which is indicative of an imbalanced electron transport chain. Biochemical and functional assays confirm that complex I is neither assembled nor active in early oocytes. Thus, we report a physiological cell type without complex I in animals. Our findings also clarify why patients with complex-I-related hereditary mitochondrial diseases do not experience subfertility. Complex I suppression represents an evolutionarily conserved strategy that allows longevity while maintaining biological activity in long-lived oocytes.The graphical representation in Extended Data Fig. 3a was adapted from the TMT Labeling Protocol, by BioRender.com (2022), retrieved from https://app.biorender.com/biorender-templates. E.B. acknowledges support from MINECO’s Proyectos de Excelencia (BFU2017-89373-P), and a European Research Council Starting Grant (DORMANTOOCYTE – 759107). We also acknowledge the support of the Spanish Ministry of Science and Innovation to the European Molecular Biology Laboratory partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme/Generalitat de Catalunya

Comparative analysis of vertebrates reveals that mouse primordial oocytes do not contain a Balbiani body

Oocytes spend the majority of their lifetime in a primordial state. The cellular and molecular biology of primordial oocytes is largely unexplored; yet, it is necessary to study them to understand the mechanisms through which oocytes maintain cellular fitness for decades, and why they eventually fail with age. Here, we develop enabling methods for live-imaging-based comparative characterization of Xenopus, mouse and human primordial oocytes. We show that primordial oocytes in all three vertebrate species contain active mitochondria, Golgi and lysosomes. We further demonstrate that human and Xenopus oocytes have a Balbiani body characterized by a dense accumulation of mitochondria in their cytoplasm. However, despite previous reports, we did not find a Balbiani body in mouse oocytes. Instead, we demonstrate that what was previously used as a marker for the Balbiani body in mouse primordial oocytes is in fact a ring-shaped Golgi that is not functionally associated with oocyte dormancy. This study provides the first insights into the organization of the cytoplasm in mammalian primordial oocytes, and clarifies the relative advantages and limitations of choosing different model organisms for studying oocyte dormancy.This study was supported by a European Research Council Starting Grant (ERC-StG-2017-759107) and the Ministerio de Ciencia e Innovación (MINECO - BFU2017-89373-P and PID2020-115127GB-I00 to E.B.). G.Z. acknowledges funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 754422. M.S. is supported by a Juan de la Cierva-Formación fellowship from the Ministerio de Ciencia e Innovación (FJC2019-041607-I; AEI; 10.13039/501100011033)

Factors Associated with a Post-Procedure Spontaneous Pregnancy after a Hysterosapingo-Foam-Sonography (HyFoSy): Results from a Multicenter Observational Study

Background: Tubal patency testing constitutes an essential part of infertility work-up. Hysterosalpingo-foam-sonography (HyFoSy) is currently one of the best tests for assessing tubal patency. The objective of our study was to evaluate the post-procedure rate of spontaneous pregnancy among infertile women submitted for an HyFoSy exam with ExEm® foam and the factors associated with this. Methods: Multicenter, prospective, observational study performed at six Spanish centers for gynecologic sonography and human reproduction. From December 2015 to June 2021, 799 infertile women underwent HyFoSy registration consecutively. The patients’ information was collected from their medical records. Multivariable regression analyses were performed, controlling for age, etiology, and time of sterility. The main outcome was to measure post-procedure spontaneous pregnancy rates and the factors associated with the achievement of pregnancy. Results: 201 (26.5%) women got spontaneous conception (SC group), whereas 557 (73.5%) women did not get pregnant (non-spontaneous conception group, NSC). The median time for reaching SC after HyFoSy was 4 months (CI 95% 3.1–4.9), 18.9% of them occurring the same month of the procedure. Couples with less than 18 months of infertility were 93% more likely to get pregnant after HyFoSy (OR 1.93, 95% CI 1.34–2.81; p < 0.001); SC were two times more frequent in women under 35 years with unexplained infertility (OR 2.22, 95% CI 1.07–4.65; P0.033). Conclusion: After HyFoSy, one in four patients got pregnant within the next twelve months. Couples with shorter infertility time, unexplained infertility, and women under 35 years are more likely to achieve SC after HyFoSy

Factors associated with a post-procedure spontaneous pregnancy after a hysterosapingo-foam-sonography (HyFoSy): results from a multicenter observational study

Background: Tubal patency testing constitutes an essential part of infertility work-up. Hysterosalpingo-foam-sonography (HyFoSy) is currently one of the best tests for assessing tubal patency. The objective of our study was to evaluate the post-procedure rate of spontaneous pregnancy among infertile women submitted for an HyFoSy exam with ExEm((R)) foam and the factors associated with this. Methods: Multicenter, prospective, observational study performed at six Spanish centers for gynecologic sonography and human reproduction. From December 2015 to June 2021, 799 infertile women underwent HyFoSy registration consecutively. The patients' information was collected from their medical records. Multivariable regression analyses were performed, controlling for age, etiology, and time of sterility. The main outcome was to measure post-procedure spontaneous pregnancy rates and the factors associated with the achievement of pregnancy. Results: 201 (26.5%) women got spontaneous conception (SC group), whereas 557 (73.5%) women did not get pregnant (non-spontaneous conception group, NSC). The median time for reaching SC after HyFoSy was 4 months (CI 95% 3.1-4.9), 18.9% of them occurring the same month of the procedure. Couples with less than 18 months of infertility were 93% more likely to get pregnant after HyFoSy (OR 1.93, 95% CI 1.34-2.81; p < 0.001); SC were two times more frequent in women under 35 years with unexplained infertility (OR 2.22, 95% CI 1.07-4.65; P0.033). Conclusion: After HyFoSy, one in four patients got pregnant within the next twelve months. Couples with shorter infertility time, unexplained infertility, and women under 35 years are more likely to achieve SC after HyFoSy