Adenomyosis: An Update Concerning Diagnosis, Treatment, and Fertility.

This review article aims to summarize current tools used in the diagnosis of adenomyosis with relative pharmacological and surgical treatment and to clarify the relative association between adenomyosis and infertility, considering the importance of an accurate diagnosis of this heterogeneous disease. Among different reported concepts, direction invagination of gland cells from the basalis endometrium deep into the myometrium is the most widely accepted opinion on the development of adenomyosis. Adenomyosis has been increasingly identified in young women with pain, AUB, infertility, or no symptoms by using imaging techniques such as transvaginal ultrasound and magnetic resonance. Furthermore, adenomyosis often coexists with other gynecological conditions, such as endometriosis and uterine fibroids, increasing the heterogeneity of available data. However, there is no agreement on the definition and classification of adenomyotic lesions from both the histopathology and the imaging points of view, and diagnosis remains difficult and unclear. A standard, universally accepted classification system needs to be implemented to improve our understanding and inform precise diagnosis of the type of adenomyosis. This could be the key to designing RCT studies and evaluating the impact of adenomyosis on quality of life in terms of menstrual symptoms, fertility, and pregnancy outcome, given the high risk of miscarriage and obstetric complications.

Intraovarian PRP injection improves oocyte quality and early embryo development in mouse models of chemotherapy-induced diminished ovarian reserve.

Intraovarian injection of platelet-rich plasma (PRP) has been recently proposed, with encouraging results to provide an alternative option to patients diagnosed with POR or POI. However, the broad spectrum of PRP effects on the reproductive function and the mechanisms of action in follicular activation, response to stimulation, and embryo quality have not yet been studied. In this study, we first induced poor ovarian reserve (POR) and premature ovarian insufficiency (POI) ovarian phenotypes in CD1 mice undergoing PRP or sham intraovarian injection. PRP administration reduced those alterations induced by chemotherapy in ovarian stroma and follicle morphology in both the POR and POI conditions. After ovarian stimulation, we found that PRP did not modify the MII-oocyte yield. Nevertheless, the amount of obtained 2-cell embryos and fertilization rate were increased, being especially relevant for the POI model. Further in vitro embryo culture led to improved blastocyst formation rates and higher numbers of good quality blastocysts in PRP vs. sham females in both the POR and POI conditions. These positive results of PRP injection were also validated in the C57Bl/6 stain. Altogether, our findings suggest a possible effect on oocyte and embryo quality. This effect is likely due to the increase of local paracrine signaling through the released growth factors in PRP-treated ovaries.

Psychological wellbeing of Italian students and clinical assessment tools at university counseling services during the COVID-19 pandemic: a systematic review.

Introduction: The COVID-19 pandemic brought about unprecedented problems for contemporary society. Among the numerous challenges faced following the spread of the virus, the need to provide assessment tools and remote psychological assistance certainly deserves particular attention. Indeed, this profound paradigm shift in psychological assessment and care occurred during a period of fragility for people already suffering from the restrictions imposed to stem the spread of the virus. One population particularly affected by the pandemic was students, including university students. The latter faced the pandemic in a particularly critical formative period. Methods: For these reasons, our systematic review has two main objectives: (i) identify the assessment tools and psychological dimensions most used/investigated during the pandemic in Italian university students; (ii) systematize and deepen our knowledge about the impact of the pandemic on the psychological wellbeing of Italian university students. Our search used PRISMA 2020 guidelines on Web of Science, Pubmed, Scopus, and EBSCOHost. Results: The results indicated that the psychological dimensions most investigated in university students during the pandemic were anxiety and depression. At the same time, the most used assessment instruments were the State-Trait Anxiety Inventory (STAI-Y) and the Beck Depression Inventory-II (BDI-II). Furthermore, it is clear from the results that the pandemic has harmed the psychological wellbeing of university students. Finally, we dedicated a section to discuss the interventions implemented by university counseling services during the pandemic. Discussion: This review could improve the work of university counseling services in this post-pandemic period and contribute to developing specific screening and assessment programs for future emergencies.

Subcutaneous G-CSF administration improves IVF outcomes in patients with recurrent implantation failure presenting a KIR/HLA-C mismatch.

RESEARCH QUESTION: Despite advances in assisted reproductive technologies, many blastocysts are lost unexpectedly during implantation. Alterations in maternal immune tolerance towards fetal antigens may contribute to adverse IVF outcomes. The purpose of this study is to evaluate whether administering Granulocyte Colony-Stimulating Factor (G-CSF) to couples with a Human Leukocyte Antigen/Killer-Cell Immunoglobulin-Like Receptor (HLA/KIR) mismatch could positively modulate the implantation process in patients with recurrent implantation failure (RIF). A KIR/HLA-C mismatch occurs when the interaction between KIRs and HLA-C causes an inhibition of NK cells, which may result in reduced G-CSF secretion leading to impaired placentation and increased risk of miscarriage, pre-eclampsia and fetal growth restriction. DESIGN: A retrospective monocentric cohort study conducted at the IVI Clinic in Rome, including women with a history of at least two failed blastocyst transfers. Couples underwent KIR and HLA-C testing. Couples with a KIR/HLA-C mismatch received G-CSF subcutaneously up to week nine of gestation. The mismatch included cases with inhibitory KIR genotypes and HLA-C2C2 females with HLA-C1C1, or C1C2 males or HLA-C1C2 females with male HLA-C2C2. The reproductive outcomes were assessed, and the logistic regression models controlled for potential confounders affecting IVF outcomes. RESULTS: 79 patients with RIF and a KIR/HLA-C mismatch were included in the study. 30 patients were administered G-CSF, and 49 received no treatment. In the univariate analysis, no statistically significant differences were reported in the reproductive outcomes after IVF between the women treated with G-CSF and the control group. However, the logistic regression analysis that controlled for confounding factors showed that patients treated with subcutaneous G-CSF had statistically significant higher ongoing-pregnancy (aOR=3.808) and live-birth (aOR=4.998) rates, and a lower miscarriage rate (aOR=0.057). No statistically significant differences were found in other reproductive outcomes. CONCLUSION: The use of subcutaneous G-CSF in patients with a KIR/HLA-C mismatch undergoing IVF may reduce miscarriage and improve live-birth rates. G-CSF may modulate NK-mediated immune mechanisms and improve trophoblast invasion and development. Randomized trials are warranted to validate these findings and enhance the chances of successful pregnancies in couples with an immunological mismatch.

Disentangling the role of gray matter volume and concentration in autism spectrum disorder: A meta-analytic investigation of 25 years of voxel-based morphometry research.

Despite over two decades of neuroimaging research, a unanimous definition of the pattern of structural variation associated with autism spectrum disorder (ASD) has yet to be found. One potential impeding issue could be the sometimes ambiguous use of measurements of variations in gray matter volume (GMV) or gray matter concentration (GMC). In fact, while both can be calculated using voxel-based morphometry analysis, these may reflect different underlying pathological mechanisms. We conducted a coordinate-based meta-analysis, keeping apart GMV and GMC studies of subjects with ASD. Results showed distinct and non-overlapping patterns for the two measures. GMV decreases were evident in the cerebellum, while GMC decreases were mainly found in the temporal and frontal regions. GMV increases were found in the parietal, temporal, and frontal brain regions, while GMC increases were observed in the anterior cingulate cortex and middle frontal gyrus. Age-stratified analyses suggested that such variations are dynamic across the ASD lifespan. The present findings emphasize the importance of considering GMV and GMC as distinct yet synergistic indices in autism research.

Female fertility preservation for family planning: a position statement of the Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR).

PURPOSE: This position statement by the Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR) aims to establish an optimal framework for fertility preservation outside the standard before oncological therapies. Key topics include the role of fertility units in comprehensive fertility assessment, factors impacting ovarian potential, available preservation methods, and appropriate criteria for offering such interventions. METHODS: The SIFES-MR writing group comprises Italian reproductive physicians, embryologists, and scientists. The consensus emerged after a six-month period of meetings, including extensive literature review, dialogue among authors and input from society members. Final approval was granted by the SIFES-MR governing council. RESULTS: Fertility counselling transitions from urgent to long-term care, emphasizing family planning. Age, along with ovarian reserve markers, is the primary predictor of female fertility. Various factors, including gynecological conditions, autoimmune disorders, and prior gonadotoxic therapies, may impact ovarian reserve. Oocyte cryopreservation should be the preferred method. Women 30-34 years old and 35-39 years old, without known pathologies impacting the ovarian reserve, should cryopreserve at least 12-13 and 15-20 oocytes to achieve the same chance of a spontaneous live birth they would have if they tried to conceive at the age of cryopreservation (63% and 52%, respectively in the two age groups). CONCLUSIONS: Optimal fertility counselling necessitates a long-term approach, that nurtures an understanding of fertility, facilitates timely evaluation of factors that may affect fertility, and explores fertility preservation choices at opportune intervals.

The ovarian stimulation regimen does not affect aneuploidy or blastocyst rate.

RESEARCH QUESTION: Could the total dose (<3000 IU or ≥3000 IU) and type of exogenous gonadotrophin (i.e. recombinant FSH and/or human menopausal gonadotrophin [HMG]) influence aneuploidy and blastulation rates and produce different reproductive outcomes? DESIGN: This retrospective, observational, multicentre cohort study included a total of 8466 patients undergoing IVF using autologous oocytes and preimplantation genetic testing for aneuploidies. Participants were divided according to the dosage of total gonadotrophins and stratified by maternal age. RESULTS: The aneuploidy rates, pregnancy outcomes and cumulative live birth rates (CLBR) were similar among women who received total gonadotrophin dosages of <3000 or ≥3000 IU. No statistical differences were reported in the blastulation rate with lower or higher gonadotrophin dosages. Women receiving a higher amount of HMG during ovarian stimulation had a lower aneuploidy rate (P = 0.02); when stratified according to age, younger women with a higher HMG dosage had lower aneuploidy rates (P< 0.001), while no statistical differences were observed in older women with higher or lower HMG dosages. No significant differences were observed in IVF outcomes or CLBR. CONCLUSIONS: High doses of gonadotrophins were not associated with rate of aneuploidy. However, an increased fraction of HMG in younger women was associated with a lower aneuploidy rate. The study demonstrated that the total gonadotrophin dosage did not influence aneuploidy, reproductive outcomes or CLBR. The increased gonadotrophin and HMG dosages used for ovarian stimulation did not precede aneuploidy, and the use of HMG should be evaluated on a case-by-case basis, according to the individual's characteristics and infertility type.

The effectiveness of Dragon Boat racing on body image and traumatic symptoms of breast cancer patients.

Objective: The present study investigated the effectiveness of a Dragon Boat training program in women with breast cancer body image and traumatic distress processing. Methods: 29 breast cancer patients (M(SD) age= 51 (7.41)) voluntarily participated in a physical activity program. Seventeen (Intervention Group) enrolled in a Dragon Boat racing program, while 12 (the Control Group) individually performed alternative physical activities. Before and after the intervention, patients completed the Body Image Scale (BIS) and the Impact of Event Scale - Revised (IES-R). Results: The Intervention Group reported a decrease in Body Image negative perception (Pillai's trace = .352, F(1,27) = 14.111, p = .001; partial η2 = .951) and in traumatic symptoms (Pillai's trace = .283, F(1,27) = 10.682, p = .003; partial η2 = .883). Conclusions: Authors discuss the role of Dragon Boat racing in improving positive body image after the experience of breast cancer.

In vitro fertilization and perinatal outcomes of patients with advanced maternal age after single frozen euploid embryo transfer: a propensity score-matched analysis of autologous and donor cycles.

OBJECTIVE: To evaluate in vitro fertilization (IVF) and perinatal outcomes of donor egg and autologous cycles in patients with advanced reproductive age after undergoing single frozen euploid embryo transfer. DESIGN: A multicenter, retrospective, cohort study. SETTING: University-affiliated and private IVF centers. PATIENT(S): Patients aged 39-46 years who underwent IVF with intracytoplasmic sperm injection and preimplantation genetic testing for aneuploidy using whole-chromosome sequencing with donor (n = 278) or autologous (n = 278) oocytes between October 2017 and October 2021. INTERVENTION(S): Single frozen euploid embryo transfer with donor or autologous euploid embryo. MAIN OUTCOME MEASURE(S): The main outcome measure was the live birth rate (LBR) after the first embryo transfer, calculated per embryo transfer. The secondary outcomes included the implantation rate, ectopic pregnancy rate, miscarriage rate, and gestational age and birth weight at the time of delivery. RESULT(S): Patients using donor or autologous oocytes had a similar likelihood of implantation (57.91% [51.87-63.78] vs. 57.19% [51.15-63.09]) and LBR (41.01% [95% confidence interval {CI}, 35.17-47.04] vs. 42.45% [95% CI, 36.56-48.49]). Furthermore, there were no significant differences in the ectopic pregnancy rate (0.72% [0.09-2.57] vs. 0.36% [0.01-1.99]), miscarriage rate (16.19% [12.06-21.05] vs. 14.39% [95% CI, 10.48-19.08]), gestational age (38.50 [38.08-38.92] vs. 39.16 [38.25-40.07] weeks), or birth weight of infants (2,982.25 [2,606.69-3,357.81] vs. 3,128.24 [2,962.30-3,294.17] kg). The univariate analysis showed no association between advanced maternal age and the LBR (relative risk, 1.03 [95% CI, 0.84-1.25]). Multivariate analysis using putative confounders for embryo competency found no associations with LBR (adjusted relative risk, 1.22 [95% CI, 0.75-1.98]). CONCLUSION(S): Patients with euploid blastocysts derived from donor or autologous oocytes did not reveal statistically significant differences in the LBR, implantation rate, ectopic pregnancy rate, miscarriage rate, duration of gestation, or infant birth weight. These findings suggest that age-related reproductive decline and/or poor IVF outcomes associated with women with advanced reproductive age undergoing IVF are heavily driven by embryonic aneuploidy.

Assessment of reproductive outcomes of fresh versus cryopreserved ejaculated sperm samples-a retrospective analysis of 44 423 oocyte donation ICSI cycles.

STUDY QUESTION: Does the use of frozen sperm affect live birth rate (LBR) and cumulative LBR (CLBR) compared to fresh sperm samples in oocyte donation ICSI cycles? SUMMARY ANSWER: Although there were slight decreases in pregnancy rates (PRs) and LBR, as well as CLBR per embryo replaced and per embryo transfer (ET), when frozen sperm samples were used compared to fresh ejaculates, their clinical impact was limited. WHAT IS KNOWN ALREADY: Sperm cryopreservation is part of the daily routine in reproduction clinics worldwide because of its many advantages in cycle planning. Nonetheless, there is a lack of agreement in terms of its impact on the outcomes of ICSI cycles. Previous studies showed conflicting conclusions and focused on different populations, which makes reaching consensus on the impact of sperm freezing-thawing complicated. Moreover, classical parameters are used to assess cycle success: pregnancy, live birth and miscarriage rates per ET. This study reports those measurements plus CLBR, which more accurately reflects the impact of the technique on the likelihood of achieving a newborn. STUDY DESIGN, SIZE, DURATION: A retrospective multicenter observational cohort study, including data from 37 041 couples and 44 423 ICSI procedures from January 2008 to June 2022, was carried out. The group using frozen sperm included 23 852 transferred embryos and 108 661 inseminated oocytes, whereas the fresh sample group comprised 73 953 embryos replaced and 381 509 injected oocytes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Outcomes measured per first ET and per ET were compared between groups using Fisher's exact test and Chi-squared test, as appropriate. Binary-logistics regression models were used to adjust the analyses according to clinically relevant co-variables. Kaplan-Meier curves plotted the CLBR per oocyte inseminated, per embryo replaced and per ET, and compared between groups using the Mantel-Cox test. Cox regressions were employed for the multivariate analyses of CLBR. MAIN RESULTS AND THE ROLE OF CHANCE: The frozen sperm group showed a slightly lower biochemical (3.55% and 2.56%), clinical (3.68% and 3.54%) and ongoing (3.63% and 3.15%) PR compared to the cycles using fresh sperm, respectively, both per first ET and per ET. LBR was 4.57% lower per first ET and 3.95% lower per ET in the frozen sperm group than the fresh sperm group. There was also a subtle increase of 2.66% in biochemical miscarriage rate per ET when using frozen versus fresh sperm. All these differences remained statistically significant after the multivariate analysis (adjusted P ≤ 0.001). There were statistically significant differences in CLBR per embryo replaced and per ET but not per oocyte used (adjusted P = 0.071). Despite the statistical significance of the differences between the groups, those using frozen sperm required only 0.54 more oocytes injected, 0.45 more embryos transferred and 0.41 more ET procedures, on average, to achieve a live birth compared to the fresh samples. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the study subjects the data to biases or potential errors during annotation on the source clinical and cycle records. This study uses multivariate analyses to control biases as much as possible. Using the oocyte donation model also contributes to reducing heterogeneity in the oocyte quality factor. WIDER IMPLICATIONS OF THE FINDINGS: The large sample sizes included in this study allowed for the detection of small changes in cycle success rates between groups. Although statistically significant, the decrease in PRs, LBR, and CLBR when using frozen sperm can be clinically overlooked in favor of the many benefits of sperm cryopreservation. STUDY FUNDING/COMPETING INTEREST(S): None declared. TRIAL REGISTRATION NUMBER: Not applicable.

A Study on the Sense of Parental Competence, Health Locus of Control and Levels of Anxiety, Depression and Somatization in Parents of Children with Type 1 Diabetes: Evidence on a Possible Relationship.

Background: Parents of children with chronic conditions face challenges that go beyond basic care and parenting responsibilities. Parents' experiences can be influenced by perceived stress, emotional experiences, feelings of helplessness, low sense of self-efficacy, anxiety and depression, reducing their quality of life. It is therefore not surprising that parents of children with chronic illnesses are more likely to experience stress, anxiety and depression than parents of healthy children. A prevalent chronic condition is type 1 diabetes. Methods: Parents (31 with children with type 1 diabetes diagnosis and 71 with children without chronic illness) were recruited to complete the measures of the Brief Symptom Inventory-18 (BSI-18), the Parent Health Locus of Control (PHLOC) and Parenting Sense of Competence (PSOC). Results: Significant differences in depression and internal locus of control were found; there was a positive correlation between internal LOC and efficacy in both samples; furthermore, there was a negative correlation between somatization and satisfaction in the experimental group. Conclusions: The ongoing experiences and challenges faced daily make parents perceive themselves as capable. Active involvement in supporting and managing the needs of child with type 1 diabetes could be a source of empowerment for the parent, contributing to the maintenance of their sense of competence. It is important, therefore, to consider the well-being and perception of the parent at a personal level, regardless of the child's situation.

Neuroprotective effects of niclosamide on disease progression via inflammatory pathways modulation in SOD1-G93A and FUS-associated amyotrophic lateral sclerosis models.

Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease influenced by genetic, epigenetic, and environmental factors, resulting in dysfunction in cellular and molecular pathways. The limited efficacy of current treatments highlights the need for combination therapies targeting multiple aspects of the disease. Niclosamide, an anthelminthic drug listed as an essential medicine, has been repurposed in clinical trials for different diseases due to its anti-inflammatory and anti-fibrotic properties. Niclosamide can inhibit various molecular pathways (e.g., STAT3, mTOR) that are dysregulated in ALS, suggesting its potential to disrupt these altered mechanisms associated with the pathology. We administered niclosamide intraperitoneally to two transgenic murine models, SOD1-G93A and FUS mice, mimicking key pathological processes of ALS. The treatment was initiated at the onset of symptoms, and we assessed disease progression by neurological scores, rotarod and wire tests, and monitored survival. Furthermore, we investigated cellular and molecular mechanisms affected by niclosamide in the spinal cord and muscle of ALS mice. In both models, the administration of niclosamide resulted in a slowdown of disease progression, an increase in survival rates, and an improvement in tissue pathology. This was characterised by reduced gliosis, motor neuron loss, muscle atrophy, and inflammatory pathways. Based on these results, our findings demonstrate that niclosamide can impact multiple pathways involved in ALS. This multi-targeted approach leads to a slowdown in the progression of the disease, positioning niclosamide as a promising candidate for repurposing in the treatment of ALS.

The adenomyosis/endometriosis IVF patient - call for clinical focus.

Endometriosis and adenomyosis are distinct clinical conditions that carry the same pathophysiological features. In recent years the clinical focus on assisted reproductive technology patients with either condition (E/A) has increased, in the recognition that this subgroup of patients might need special attention to obtain reproductive success. Endometriosis and adenomyosis are characterized by a disruption of progesterone and oestrogen signalling pathways, resulting in local oestrogen dominance and progesterone resistance at the receptor level. Recent scientific evidence suggests that the endometrial progesterone receptor resistance encountered in E/A patients can be overcome by a freeze-all policy, followed by down-regulating circulating oestradiol concentrations prior to frozen embryo transfer (FET), in combination with an increase in exogenous luteal phase progesterone supplementation in hormonal replacement therapy (HRT) FET cycles. Specifically, for adenomyosis patients who do not respond to gonadotrophin-releasing hormone agonist down-regulation in terms of a decrease in circulating oestradiol concentrations, a small case series has suggested that the addition of an aromatase inhibitor for 21 days prior to HRT-FET is a valid option. Endometriosis and adenomyosis are hormonally active diseases, which need to be treated by controlling local hyperoestrogenism and progesterone resistance. Based on physiology and recent preliminary clinical data, the authors of this opinion paper wish to stimulate discussion and spark interest in research in E/A patients.

Disruption of mitochondrial unfolded protein response results in telomere shortening in mouse oocytes and somatic cells.

Caseinolytic peptidase P (CLPP) plays a central role in mitochondrial unfolded protein response (mtUPR) by promoting the breakdown of misfolded proteins and setting in motion a cascade of reactions to re-establish protein homeostasis. Global germline deletion of Clpp in mice results in female infertility and accelerated follicular depletion. Telomeres are tandem repeats of 5'-TTAGGG-3' sequences found at the ends of the chromosomes. Telomeres are essential for maintaining chromosome stability during somatic cell division and their shortening is associated with cellular senescence and aging. In this study, we asked whether the infertility and ovarian aging phenotype caused by global germline deletion of Clpp is associated with somatic aging, and tested telomere length in tissues of young and aging mice. We found that impaired mtUPR caused by the lack of CLPP is associated with accelerated telomere shortening in both oocytes and somatic cells of aging mice. In addition, expression of several genes that maintain telomere integrity was decreased, and double-strand DNA breaks were increased in telomeric regions. Our results highlight how impaired mtUPR can affect telomere integrity and demonstrate a link between loss of mitochondrial protein hemostasis, infertility, and somatic aging.

Mitochondrial Unfolded Protein Response Gene Clpp Is Required for Oocyte Function and Female Fertility.

Mitochondrial unfolded protein stress response (mtUPR) plays a critical role in regulating cellular and metabolic stress response and helps maintain protein homeostasis. Caseinolytic peptidase P (CLPP) is one of the key regulators of mtUPR and promotes unfolded protein degradation. Previous studies demonstrated that global deletion of Clpp resulted in female infertility, whereas no impairment was found in the mouse model with targeted deletion of Clpp in cumulus/granulosa cells. These results suggest the need to delineate the function of Clpp in oocytes. In this study, we aimed to further explore the role of mtUPR in female reproductive competence and senescence using a mouse model. Oocyte-specific targeted deletion of Clpp in mice resulted in female subfertility associated with metabolic and functional abnormalities in oocytes, thus highlighting the importance of CLPP-mediated protein homeostasis in oocyte competence and reproductive function.

Impact of adenomyosis on in vitro fertilization outcomes in women undergoing donor oocyte transfers: a prospective observational study.

OBJECTIVE: To prospectively examine the association between adenomyosis type, location, and severity with reproductive outcomes in patients undergoing single embryo transfer (SET) with embryos derived from donor oocytes. DESIGN: A prospective observational cohort study. SETTING: University-affiliated in vitro fertilization center. PATIENTS: Patients with infertility with (n = 114) and without (n = 114) adenomyosis who received their first donor oocyte transfer between January 2019 and January 2023 were included in this study. INTERVENTIONS: Adenomyosis was confirmed with the presence of at least one direct feature visualized by 2- or 3-dimensional transvaginal ultrasound and classified according to type (diffuse or focal), localization (inner or outer myometrium and/or junctional zone [JZ]), and uterine extension (mild, moderate, or severe). After an artificial or natural endometrial preparation cycle, patients underwent SET in the blastocyst stage. MAIN OUTCOME MEASURES: The primary outcome was the implantation rate. The secondary outcomes were the clinical pregnancy, live birth, and miscarriage rates after SET. RESULTS: The presence of adenomyosis did not significantly affect the implantation, clinical pregnancy, or live birth rates. However, women with adenomyosis had a significantly higher miscarriage rate than those without adenomyosis (35.4% vs. 18.1%, respectively). The multivariate analysis assessed possible risk factors for each clinical outcome considered in the study and showed that adenomyosis affected the risk of miscarriage. Specifically, transvaginal sonography detection of adenomyosis in the JZ was associated with over threefold higher relative risk of miscarriage (relative risk [RR], 3.28; 95% confidence interval [CI], 1.38-7.78). Conversely, adenomyosis features detected exclusively in the outer myometrium were associated with a higher ongoing pregnancy rate (RR, 0.30; 95% CI, 0.13-0.72). Diffuse adenomyosis in the JZ and severe adenomyosis increased the relative risk of miscarriage two-fold (RR, 2.29; 95% CI, 1.22-4.30 and RR, 2.20; 95% CI, 1.19-4.04, respectively). CONCLUSIONS: This study demonstrated that although adenomyosis did not significantly reduce the odds of implantation, the direct signs of adenomyosis in the JZ and disease severity are significant risk factors for miscarriage in patients receiving donor oocyte transfers. This study highlights the importance of thorough ultrasound examination and detailed adenomyosis classification in the assessment and management of patients with infertility.

Oocyte Cryopreservation in Women with Ovarian Endometriosis.

Ovarian endometriosis is a gynecological condition that is closely associated with infertility-from its pathogenesis to treatment modalities, this condition presents a challenge both for patients and clinicians alike when seeking conception, due to low AMH levels, peritoneal inflammation, and the inadvertent removal of healthy ovarian parenchyma at surgery. In fact, around half of endometriosis patients seeking fertility require tertiary-level assisted reproduction techniques to achieve a live birth. Oocyte cryopreservation, a procedure initially designed for oncology patients, has emerged over recent years as a very promising treatment strategy for patients who have been diagnosed with ovarian endometriosis in order to preserve their fertility and obtain a live birth at a later stage in their lives. Counseling patients about oocyte preservation techniques at an early stage in the diagnosis, ideally before the age of 35 and especially prior to any surgical treatment, provides an excellent opportunity to discuss future fertility and the benefits associated with oocyte cryopreservation.

C9orf72 Toxic Species Affect ArfGAP-1 Function.

Compelling evidence indicates that defects in nucleocytoplasmic transport contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS). In particular, hexanucleotide (G4C2) repeat expansions in C9orf72, the most common cause of genetic ALS, have a widespread impact on the transport machinery that regulates the nucleocytoplasmic distribution of proteins and RNAs. We previously reported that the expression of G4C2 hexanucleotide repeats in cultured human and mouse cells caused a marked accumulation of poly(A) mRNAs in the cell nuclei. To further characterize the process, we set out to systematically identify the specific mRNAs that are altered in their nucleocytoplasmic distribution in the presence of C9orf72-ALS RNA repeats. Interestingly, pathway analysis showed that the mRNAs involved in membrane trafficking are particularly enriched among the identified mRNAs. Most importantly, functional studies in cultured cells and Drosophila indicated that C9orf72 toxic species affect the membrane trafficking route regulated by ADP-Ribosylation Factor 1 GTPase Activating Protein (ArfGAP-1), which exerts its GTPase-activating function on the small GTPase ADP-ribosylation factor 1 to dissociate coat proteins from Golgi-derived vesicles. We demonstrate that the function of ArfGAP-1 is specifically affected by expanded C9orf72 RNA repeats, as well as by C9orf72-related dipeptide repeat proteins (C9-DPRs), indicating the retrograde Golgi-to-ER vesicle-mediated transport as a target of C9orf72 toxicity.