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Davina Tribbick,1 Michael Salzberg,2,3 Maria Ftanou,2,4 William R Connell,5 Finlay Macrae,6,7 Michael A Kamm,5,6,8 Glen W Bates,1 Georgina Cunningham,5 David W Austin,9 Simon R Knowles1–3,6,7 1Faculty of Life and Social Sciences, Swinburne University of Technology, Melbourne, VIC, Australia; 2Department of Psychiatry, St Vincent's Hospital, Melbourne, VIC, Australia; 3Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia; 4Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia; 5Department of Gastroenterology, St Vincent's Hospital, Melbourne, VIC, Australia; 6Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, VIC, Australia; 7Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; 8Imperial College, London, UK; 9Department of Psychology, Deakin University, Melbourne, VIC, Australia Background: This study aimed to characterize prevalence of anxiety and depressive conditions and uptake of mental health services in an Australian inflammatory bowel disease (IBD) outpatient setting. Methods: Eighty-one IBD patients (39 males, mean age 35 years) attending a tertiary hospital IBD outpatient clinic participated in this study. Disease severity was evaluated according to the Manitoba Index. Diagnosis of an anxiety or depressive condition was based upon the Mini-International Neuropsychiatric Interview and the Hospital Anxiety and Depression Scale. Results: Based on Hospital Anxiety and Depression Scale subscale scores >8 and meeting Mini-International Neuropsychiatric Interview criteria, 16 (19.8%) participants had at least one anxiety condition, while nine (11.1%) had a depressive disorder present. Active IBD status was associated with higher prevalence rates across all anxiety and depressive conditions. Generalized anxiety was the most common (12 participants, 14.8%) anxiety condition, and major depressive disorder (recurrent) was the most common depressive condition reported (five participants, 6.2%). Seventeen participants (21%) reported currently seeking help for mental health issues while 12.4% were identified has having at least one psychological condition but not seeking treatment. Conclusion: We conclude that rates of anxiety and depression are high in this cohort, and that IBD-focused psychological services should be a key component of any holistic IBD service, especially for those identified as having active IBD. Keywords: inflammatory bowel disease, psychological conditions, disease activity

In the roundtable that follows, clinicians discuss a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research. Article discussed: Hurst BS, Hickman JM, Matthews ML, Usadi RS, Marshburn PB. Novel clomiphene 'stair-step' protocol reduces time to ovulation in women with polycystic ovarian syndrome. Am J Obstet Gynecol 2009;200:510.e1-510.e4. [ABSTRACT FROM AUTHOR]

Elevated follicle-stimulating hormone (FSH) levels during the early follicular phase or in response to the clomiphene citrate challenge test indicate diminished ovarian reserve and poor reproductive potential. We performed a retrospective analysis of 413 infertile women, 23 to 40 years of age, who underwent 523 cycles of in vitro fertilization (IVF) to identify the critical FSH values that would predict a poor likelihood of success in our military IVF program. Each woman underwent a clomiphene citrate challenge test within 1 year of each IVF cycle. The overall live birth and implantation rates were 43% and 24%, respectively. The critical values for day 3 and day 10 FSH levels were 14.1 and 16.9 mIU/mL, respectively, with a 0% live birth rate and a 5% implantation rate above these levels. There were no differences in the live birth/implantation rates when stratified for FSH levels below the critical values. Medical centers offering IVF should determine their critical FSH values, to help identify patients unlikely to benefit from IVF and to ensure appropriate allocation of resources and realistic expectations for infertile couples. [ABSTRACT FROM AUTHOR]

Fears of negative evaluation (FNEs) and fears of positive evaluation (FPEs) comprise a bivalent model of evaluation that can explain the aetiology and maintenance of Social Anxiety Disorder (SAD). In this study, we examined an extended version of this model which incorporates two related cognitive processes (concerns about reprisal and discounting of positive outcomes) as partial mediators of the effects of FNEs and FPEs. We built on earlier work by including a broader measure of social anxiety across different social situations and comparing models for groups of participants with and without probable SAD. Structural equation modelling was utilised to test the model in a sample of 890 university students (74.8% female, mean age 29.49). We replicated the findings of Cook et al. in the overall sample and in the group with probable SAD. FNEs and FPEs predicted social anxiety directly and were serially mediated by concerns about reprisal and discounting positive outcomes. The model was also a good fit for those without SAD; however, in the model, FNEs were no longer a direct predictor of social anxiety. The findings confirm the utility of the extended bivalent model and have implications for psychoevolutionary accounts of social anxiety.

Introduction: HIV-positive gay men continue to experience stigma related to sexual orientation and HIV status. Although resilience toward such stressors can be achieved, limited Australian research exists that examines how resilience is strengthened toward these dual stigmas., Methods: A total of 20 men from Melbourne, Australia, participated in semi-structured interviews between March and October 2019 to explore ways in which they manage such stigmas., Results: Reflexive thematic analysis identified two primary themes: (1) "intrapersonal control," which relates to individual mind set and lifestyle changes that participants utilized to strengthen resilience; (2) "systemic change," which includes participants' needs for better public health messaging. Findings show resilience was enhanced when proactive approaches to sexual orientation, HIV health appraisal, lifestyle changes, and social support were made. Further, outdated HIV awareness campaigns and a lack of current messaging regarding HIV transmission in the wider community were identified as inhibiting resilience development and promoting stigma among gay men., Conclusion: The results from this study show ways that Australian gay men strengthen their resilience through both intrapersonal (e.g., self-awareness, reappraisal, and self-efficacy) and external resources (e.g., education and public awareness) and how health care providers and social policy makers could better support the men to achieve this., Social-Policy Implications: Findings suggest that targeted public health responses are required to compliment the advances made in biomedicine and viral suppression., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The Author(s) 2023.)

The COVID-19 pandemic has resulted in negative mental health outcomes throughout the world, and its impact on social interactions and relationships is likely to be evident in problematic social anxiety. This systematic review qualitatively synthesized data from studies that have reported on the effects of the pandemic on social anxiety. A systematic search of Web of Science Core Collection, Embase, PsychINFO, Scopus, EBSCOhost, Cochrane Central Register of Controlled Trials, and Proquest Central-Dissertations and Theses was conducted, with thirty-three studies meeting the inclusion criteria. The results suggest that social anxiety has been heightened in the general population due to the pandemic, with women and low-income earners being especially vulnerable. Other contributing factors include impaired coping strategies, lower socio-emotional well-being, limited support networks, and contraction of the SARS-CoV-2 virus. Individuals with a Social Anxiety Disorder diagnosis may be at risk of a deterioration of mental health in general. Limitations of the literature reviewed include the predominance of cross-sectional study designs, which limit causal inferences are limited. Additionally, associations may be inflated as many studies have not accounted for mediating variables. Taken together, the research suggests that social anxiety, either pre-pandemic or arising due to the pandemic environment, has contributed to a variety of negative mental health outcomes related to social anxiety.

Cognitive Behavioural Therapy (CBT) is effective in treating Social Anxiety Disorder (SAD). However, less is known about whether gains achieved in disorder-specific and secondary outcomes (e.g., depression, general anxiety, quality of life, and self-esteem) are maintained 12 months or longer. A systematic literature search yielded 25 relevant studies that administered CBT to participants with SAD. Multivariate meta-analyses of post-treatment assessments, found that CBT was superior to control conditions in reducing social anxiety (g =.74), depression (g =.52), general anxiety (g =.69) and improving quality of life (g =.39). The within-groups effect sizes revealed that 12 months or more after CBT treatment, symptoms continued to improve for social anxiety (g av =.23) and quality of life (g av =.17), and gains were maintained for depressive (g av =.06) and general anxiety symptoms (g av =.03). However, meta-analyses of long-term outcomes lack comparison groups. Moderation was non-significant for the treatment model, format, number of sessions, treatment duration, or inclusion of booster sessions. Future research may investigate what drives improvement after treatment cessation and how CBT affects other co-occurring symptomatology. Taken together, CBT produces many benefits for SAD and individuals with co-occurring symptoms can benefit from extant SAD-focused treatments., Competing Interests: Declarations of interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: Self-compassion constitutes a positive way of relating towards the self that enables emotional regulation and reduces emotional distress. This research first explored differences among a sample of persons with social anxiety disorder (SAD) and groups of high socially anxious (HSA) and low socially anxious (LSA) students on self-compassion, emotion regulation, and social anxiety. We then investigated emotional regulation as a mediator of the prediction of social anxiety by self-compassion and the influence of depressed mood on those relationships., Design: Study 1 compared a SAD group to matched groups of HSA and LSA students. Study 2 utilized the total sample (n = 330 students and n = 33 SAD) to test mediation. Self-compassion and emotion regulation were predictors of social anxiety and depression a covariate., Results: In Study 1, the SAD group did not differ from the HSA group on most aspects of self-compassion and emotional regulation but was higher on depression. Both were lower on most measures and higher on depression than the LSA group. In Study 2, higher self-compassion predicted lower social interaction anxiety, and emotional regulation strategies mediated this effect, regardless of depression. However, for social performance anxiety, controlling for depression removed mediation. Refraining from uncompassionate responses was directly connected to social anxiety, whereas compassionate responses influenced social anxiety via emotional regulation., Conclusions: Results affirm the ameliorative role of self-compassion on social anxiety and emotion regulation strategies as mechanisms of that influence. However, self-compassion's influence was affected by depression and type of social anxiety. Also, refraining from uncompassionate self-responding appears to be of prime importance in predicting social anxiety, whereas compassionate self-responding influences social anxiety via emotion regulation., (© 2022 The Authors. Psychology and Psychotherapy: Theory, Research and Practice published by John Wiley & Sons Ltd on behalf of The British Psychological Society.)

Objectives: Self-compassion and emotional regulation have been identified as constructive attitudes towards the self which can reduce emotional distress. This study is the first to examine the role of a self-compassionate attitude towards the self in reducing symptoms of social anxiety. The study also explored the role of emotional regulation strategies of cognitive reappraisal (CR) and expressive suppression (ES) as mechanisms that mediate the impact of self-compassion on social anxiety., Design: Structural equation modelling (SEM) was conducted on cross-sectional correlational data with MPlus version 6., Methods: A sample of 750 undergraduate students (378 men and 372 women) completed an online survey comprised of well validated self-report measures of social anxiety, emotional regulation and self-compassion., Results: Structural equation modelling showed that self-compassion predicted lower social anxiety directly and indirectly through lower ES. Higher self-compassion also predicted higher CR. Contrary to expectation, CR did not predict lower social anxiety. Exploratory analyses of self-compassion divided into Compassionate Self-responding (CSR) and Refraining from Non-compassionate Responding (RUSR) identified RUSR as a predictor of lower social anxiety directly and indirectly via ES and CR. CSR had no direct effect on social anxiety but did so indirectly via CR., Conclusions: The findings provide preliminary evidence that self-compassion can play an important role in alleviating social anxiety and that emotion regulation through ES and CR are important mechanisms of that influence., Practitioner Points: Adopting a more compassionate attitude towards the self can reduce the symptoms of social anxiety Emotional regulation through reducing emotional suppression may be a mechanism whereby higher levels of self-compassion reduce symptoms of social anxiety. Although higher levels of self-compassion predict greater use of emotional regulation through cognitive appraisal, cognitive appraisal does not predict levels of symptoms of social anxiety The capacity to refrain from non-compassionate self-responding may reduce symptoms of social anxiety directly and indirectly through lower levels of emotional suppression and greater cognitive reappraisal (CR). However, compassionate self-responding only influences symptoms of social anxiety through CR., (© 2020 British Psychological Society.)

Study Question: Among infertile women undergoing ovarian stimulation, is allostatic load (AL), a measure of chronic physiological stress, associated with subsequent fertility and pregnancy outcomes?, Summary Answer: AL at baseline was not associated with conception, spontaneous abortion or live birth, however, it was significantly associated with increased odds of pre-eclampsia and preterm birth among women who had a live birth in the study., What Is Known Already: Several studies have linked AL during pregnancy to adverse outcomes including preterm birth and pre-eclampsia, hypothesizing that it may contribute to well-documented disparities in pregnancy and birth outcomes. However, AL biomarkers change over the course of pregnancy, raising questions as to whether gestational AL assessment is a valid measure of cumulative physiologic stress starting long before pregnancy. To better understand how AL may impact reproductive outcomes, AL measurement in the non-pregnant state (i.e. prior to conception) is needed., Study Design, Size, Duration: A secondary data analysis based on data from 836 women who participated in Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS), a multi-center, randomized clinical trial of ovarian stimulation conducted from 2011 to 2014., Participants/materials, Setting, Methods: Ovulatory women with unexplained infertility (ages 18-40) were enrolled and at baseline, biological and anthropometric measures were collected. AL scores were calculated as a composite of the following baseline variables determined a priori: BMI, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, dehydroepiandrosterone sulfate, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, C-reactive protein and HOMA score. Participants received ovarian stimulation for up to four cycles and if they conceived, were followed throughout pregnancy. We fit multi-variable logistic regression models examining AL (one-tailed and two-tailed) in relation to the following reproductive outcomes: conception, spontaneous abortion, live birth, pre-eclampsia, preterm birth and low birthweight., Main Results and the Role of Chance: Adjusting for covariates, a unit increase in two-tailed AL score was associated with 62% increased odds of pre-eclampsia (OR: 1.62, 95% CI: 1.14, 2.38) 44% increased odds of preterm birth (OR: 1.44, 95% CI: 1.02, 2.08), and 39% increased odds of low birthweight (OR: 1.39, 95% CI: 0.99, 1.97). The relationship between AL and preterm birth was mediated by pre-eclampsia (P = 0.0003). In one-tailed AL analyses, associations were similar, but slightly attenuated. AL was not associated with fertility outcomes (conception, spontaneous abortion, live birth)., Limitations, Reasons for Caution: Results may not be generalizable to fertile women who conceive naturally or women with other types of infertility. Comparisons to previous, related work are difficult because variables included in AL composite measures vary across studies. AL may be indicative of overall poor health, rather than being specific to chronic physiological stress., Wider Implications of the Findings: Our results suggest that chronic physiological stress may not impact success of ovarian stimulation, however, they confirm and extend previous work suggesting that AL is associated with adverse pregnancy outcomes. Physiological dysregulation due to chronic stress has been proposed as a possible mechanism underlying disparities in birth outcomes, which are currently poorly understood. Assessing biomarkers of physiological dysregulation pre-conception or in early pregnancy, may help to identify women at risk of adverse pregnancy outcomes, particularly pre-eclampsia., Study Funding/competing Interest(s): Support for AMIGOS was provided by: U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936 and U10HD055925. Support for the current analysis was provided by T32ES007271, R25HD075737, P30ES001247 and P30ES005022. This research was made possible by funding by American Recovery and Reinvestment Act. The content is solely the responsibility of the authors and does not necessarily represent the official views of NICHD, NIEHS or NIH. E.B., W.V., O.M., R.A., M.R., V.B., G.W.B., C.C., E.E., S.K., R.U., P.C, H.Z., N.S. and S.T. have nothing to disclose. R.L. reported serving as a consultant to Abbvie, Bayer, Kindex, Odega, Millendo and Fractyl and serving as a site investigator and receiving grants from Ferring. K.H. reported receiving grants from Roche Diagnostics and Ferring. R.R. reported a grant from AbbVie. M.D. reported being on the Board of Directors of and a stockholder in Advanced Reproductive Care., Trial Registration Number: Clinical Trials.gov number: NCT01044862.

Introduction and Hypothesis: The objective was to prospectively characterize dynamic pelvic 3-Tesla magnetic resonance imaging (dp3T MRI) findings in nulligravida women and characterize changes 6 months after delivery in the same woman., Methods: In this prospective study, nulligravida women seeking assisted reproductive technology for pregnancy were recruited. After physical examination by Pelvic Organ Prolapse Quantification (POP-Q), Brink assessment and measures including the Pelvic Floor Distress Inventory-20 and Pelvic Floor Impact Questionnaire-7, pre-pregnancy dp3T MRI at rest, with strain, and evacuation were performed. Assessments were repeated ≥6 months postpartum. Analysis included Welch and paired t tests for continuous variables, Fisher's exact test for differences in categorical outcomes, and paired t tests for postpartum symptoms., Results: Nineteen subjects (mean ± SD age, 31 ± 5 years) completed baseline clinical and dp3T MRI studies, 15 delivered and 10 (30.5 ± 3 years) completed pre-pregnancy and post-delivery clinical and dp3T MRI assessments. There were no significant changes in scores of validated questionnaires (all p > 0.05) or on POP-Q measures post-delivery. Two (20%) subjects without pre-pregnancy levator tears had tears on MRI post-delivery. MRI measures of pelvic organ descent were increased post-delivery. Seventeen pelvic soft-tissue parameters increased by greater than 10% post-delivery, including 5 out of 70 (7.1%), 17 out of 110 (15.5%), and 50 out of 110 (45.5%) values exceeding thresholds at rest, strain, and evacuation respectively., Conclusions: Dynamic pelvic 3T MRI detected levator tears and increased pelvic organ descent, which can be directly attributed to pregnancy and delivery.

Problem: Psychiatric disorders and stress in women have been associated with poor IVF outcome. We hypothesized that both partners in the infertile couples are emotionally affected, and cytokines in both may link psychological to reproductive outcome., Method of Study: Forty-five IVF couples completed questionnaires and visual analog scales for stress and psychiatric disorders and had cytokines measured in serum, semen, cervicovaginal, and follicular fluids. Multivariable analyses, t tests, maximum likelihood estimates, Spearman correlation, and data mining were applied., Results: Psychopathology was found in 72% of the couples. Female and male stress were associated with stress, anxiety, and depression in the respective partner, and with a lower likelihood of clinical pregnancy and live birth. Lower serum TGF-β and higher cervicovaginal IL-6 and IL-1β were associated with stress. In data decision trees, cytokines in relation to stress and depression in both partners were found indicative of IVF failure., Conclusion: Infertile couples may benefit from psychiatric evaluation and treatment of both partners., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Prostaglandins are formed by enzymatic and non-enzymatic mechanisms. They have been detected in human ovarian follicular fluid (HFF), a medium rich in growth factors and nutrients important for oocyte growth and fertility. However, the comprehensive identification of HFF prostaglandins has not been addressed. Here we use hybrid triple quadrupole time-of-flight and triple quadrupole mass spectrometers to comprehensively analyze prostaglandins in HFF. We identified PGE1, PGE2, PGF2α, and other prostaglandins synthesized via prostaglandin-endoperoxide synthase (i.e. Cox) cascades. We also identified specific PGF2α isomers (F2-isoprostanes) and PGF3α analogs whose structures are inconsistent with Cox-dependent formation. A prospective cohort pilot study of infertility patient subtypes revealed two potential associations. F2-isoprostanes are decreased in the diminished ovarian reserve subtype and elevated PGF2α may be associated with decreased live birth. Other than PGF2α, only body mass index >25kg/m 2 correlated with poor in vitro fertilization outcome. Our studies suggest that HFF contains prostaglandins formed from at least two mechanisms, which may correlate with distinct clinical parameters., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: While female sexual dysfunction is a frequent occurrence, characteristics in infertile women are not well delineated. Furthermore, the impact of infertility etiology on the characteristics in women with differing androgen levels observed in women with polycystic ovary syndrome and unexplained infertility has not been assessed., Objective: The objective of the study was to determine the characteristics of sexual dysfunction in women with polycystic ovary syndrome and unexplained infertility., Study Design: A secondary data analysis was performed on 2 of Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Networks clinical trials: Pregnancy in Polycystic Ovary Syndrome Study II and Assessment of Multiple Intrauterine Gestations From Ovarian Stimulation. Both protocols assessed female sexual function using the Female Sexual Function Inventory and the Female Sexual Distress Scale., Results: Women with polycystic ovary syndrome had higher weight and body mass index than women with unexplained infertility (each P < .001), greater phenotypic (Ferriman-Gallwey hirsutism score, sebum score, and acne score; each P < .001), and hormonal (testosterone, free testosterone, and dehydroepiandrosterone; each P < .001) evidence of androgen excess. Sexual function scores, as assessed by the Female Sexual Function Inventory, were nearly identical. The Female Sexual Distress Scale total score was higher in women with polycystic ovary syndrome. The mean Female Sexual Function Inventory total score increased slightly as the free androgen index increased, mainly as a result of the desire subscore. This association was more pronounced in the women with unexplained infertility., Conclusion: Reproductive-age women with infertility associated with polycystic ovary syndrome and unexplained infertility, despite phenotypic and biochemical differences in androgenic manifestations, do not manifest clinically significant differences in sexual function., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Context: In overweight/obese women with polycystic ovary syndrome (PCOS), the relative benefit of delaying infertility treatment to lose weight vs seeking immediate treatment is unknown., Objective: We compared the results of two, multicenter, concurrent clinical trials treating infertility in women with PCOS., Design, Setting, and Participants: This was a secondary analysis of two randomized trials conducted at academic health centers studying women 18-40 years of age who were overweight/obese and infertile with PCOS., Intervention: We compared immediate treatment with clomiphene from the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial (N = 187) to delayed treatment with clomiphene after preconception treatment with continuous oral contraceptives, lifestyle modification (Lifestyle: including caloric restriction, antiobesity medication, behavioral modification, and exercise) or the combination of both (combined) from the Treatment of Hyperandrogenism Versus Insulin Resistance in Infertile Polycystic Ovary Syndrome (OWL PCOS) trial (N = 142)., Main Outcome Measures: Live birth, pregnancy loss, and ovulation were measured., Results: In PPCOS II, after four cycles of clomiphene, the cumulative per-cycle ovulation rate was 44.7% (277/619) and the cumulative live birth rate was 10.2% (19/187), nearly identical to that after oral contraceptive pretreatment in the OWL PCOS trial (ovulation 45% [67/149] and live birth: 8.5% [4/47]). In comparison, deferred clomiphene treatment preceded by lifestyle and combined treatment in OWL PCOS offered a significantly better cumulative ovulation rate compared to immediate treatment with clomiphene. (Lifestyle: 62.0% [80/129]; risk ratio compared to PPCOS II = 1.4; 95% confidence interval [CI], 1.1-1.7; P = .003; combined: 64.3% [83/129]; risk ratio compared to PPCOS II = 1.4; 95% CI, 1.2-1.8; P < .001 and a significantly better live birth rate lifestyle: 25.0% [12/48]; risk ratio compared to PPCOS II = 2.5; 95% CI, 1.3-4.7; P = .01 and combined: 25.5% [12/47]; risk ratio compared to PPCOS II = 2.5; 95% CI, 1.3-4.8; P = .01)., Conclusions: These data show the benefit of improved ovulation and live birth with delayed infertility treatment with clomiphene citrate when preceded by lifestyle modification with weight loss compared with immediate treatment. Pretreatment with oral contraceptives likely has little effect on the ovulation and live birth rate compared with immediate treatment.

Objective: To summarize the available evidence for the efficacy of various treatments for unexplained infertility., Design: Systematic review., Setting: Not applicable., Patient(s): Patients aged 18-40 years with unexplained infertility., Intervention(s): Clomiphene citrate, letrozole, timed intercourse, IUI, gonadotropins, IVF, and IVF-intracytoplasmic sperm injection., Main Outcome Measure(s): Clinical pregnancy rate, ongoing pregnancy rate, and live birth rate., Result(s): Thirteen studies with a total of 3,081 patients were identified by systematic search and met inclusion criteria. The available literature demonstrates that expectant management may be comparable to treatment with clomiphene and timed intercourse or IUI. Clomiphene may be more effective than letrozole, and treatment with gonadotropins seems more effective, albeit with significantly higher risk of multiple gestations than either oral agent. On the basis of current data, IVF, with or without intracytoplasmic sperm injection, is no more effective than gonadotropins with IUI for unexplained infertility., Conclusion(s): Adequately powered, randomized controlled trials that compare all of the available treatments for unexplained infertility are needed. Until such data are available, clinicians should individualize the management of unexplained infertility with appropriate counseling regarding the empiric nature of current treatment options including IVF., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The standard therapy for women with unexplained infertility is gonadotropin or clomiphene citrate. Ovarian stimulation with letrozole has been proposed to reduce multiple gestations while maintaining live birth rates., Methods: We enrolled couples with unexplained infertility in a multicenter, randomized trial. Ovulatory women 18 to 40 years of age with at least one patent fallopian tube were randomly assigned to ovarian stimulation (up to four cycles) with gonadotropin (301 women), clomiphene (300), or letrozole (299). The primary outcome was the rate of multiple gestations among women with clinical pregnancies., Results: After treatment with gonadotropin, clomiphene, or letrozole, clinical pregnancies occurred in 35.5%, 28.3%, and 22.4% of cycles, and live birth in 32.2%, 23.3%, and 18.7%, respectively; pregnancy rates with letrozole were significantly lower than the rates with standard therapy (gonadotropin or clomiphene) (P=0.003) or gonadotropin alone (P<0.001) but not with clomiphene alone (P=0.10). Among ongoing pregnancies with fetal heart activity, the multiple gestation rate with letrozole (9 of 67 pregnancies, 13%) did not differ significantly from the rate with gonadotropin or clomiphene (42 of 192, 22%; P=0.15) or clomiphene alone (8 of 85, 9%; P=0.44) but was lower than the rate with gonadotropin alone (34 of 107, 32%; P=0.006). All multiple gestations in the clomiphene and letrozole groups were twins, whereas gonadotropin treatment resulted in 24 twin and 10 triplet gestations. There were no significant differences among groups in the frequencies of congenital anomalies or major fetal and neonatal complications., Conclusions: In women with unexplained infertility, ovarian stimulation with letrozole resulted in a significantly lower frequency of multiple gestation but also a lower frequency of live birth, as compared with gonadotropin but not as compared with clomiphene. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01044862.).

Study Question: Can we build and validate predictive models for ovulation and pregnancy outcomes in infertile women with polycystic ovary syndrome (PCOS)?, Summary Answer: We were able to develop and validate a predictive model for pregnancy outcomes in women with PCOS using simple clinical and biochemical criteria particularly duration of attempting conception, which was the most consistent predictor among all considered factors for pregnancy outcomes., What Is Known Already: Predictive models for ovulation and pregnancy outcomes in infertile women with polycystic ovary syndrome have been reported, but such models require validation., Study Design, Size, and Duration: This is a secondary analysis of the data from the Pregnancy in Polycystic Ovary Syndrome I and II (PPCOS-I and -II) trials. Both trials were double-blind, randomized clinical trials that included 626 and 750 infertile women with PCOS, respectively. PPCOS-I participants were randomized to either clomiphene citrate (CC), metformin, or their combination, and PPCOS-II participants to either letrozole or CC for up to five treatment cycles., Participants/materials, Setting, and Methods: Linear logistic regression models were fitted using treatment, BMI, and other published variables as predictors of ovulation, conception, clinical pregnancy, and live birth as the outcome one at a time. We first evaluated previously reported significant predictors, and then constructed new prediction models. Receiver operating characteristic (ROC) curves were constructed and the area under the curves (AUCs) was calculated to compare performance using different models and data. Chi-square tests were used to examine the goodness-of-fit and prediction power of logistic regression model., Main Results and the Role of Chance: Predictive factors were similar between PPCOS-I and II, but the two participant samples differed statistically significantly but the differences were clinically minor on key baseline characteristics and hormone levels. Women in PPCOS-II had an overall more severe PCOS phenotype than women in PPCOS-I. The clinically minor but statistically significant differences may be due to the large sample sizes. Younger age, lower baseline free androgen index and insulin, shorter duration of attempting conception, and higher baseline sex hormone-binding globulin significantly predicted at least one pregnancy outcome. The ROC curves (with AUCs of 0.66-0.76) and calibration plots and chi-square tests indicated stable predictive power of the identified variables (P-values ≥0.07 for all goodness-of-fit and validation tests)., Limitations, Reasons for Caution: This is a secondary analysis. Although our primary objective was to confirm previously reported results and identify new predictors of ovulation and pregnancy outcomes among PPCOS-II participants, our approach is exploratory and warrants further replication., Wider Implications of the Findings: We have largely confirmed the predictors that were identified in the PPCOS-I trial. However, we have also revealed new predictors, particularly the role of smoking. While a history of ever smoking was not a significant predictor for live birth, a closer look at current, quit, and never smoking revealed that current smoking was a significant risk factor., Study Funding/competing Interests: The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Grants U10 HD27049, U10 HD38992, U10HD055925, U10 HD39005, U10 HD33172, U10 HD38998, U10 HD055936, U10 HD055942, and U10 HD055944; and U54-HD29834. Heilongjiang University of Chinese Medicine Grants 051277 and B201005. R.S.L. reports receiving consulting fees from Euroscreen, AstraZeneca, Clarus Therapeutics, and Takeda, and grant support from Ferring, Astra Zeneca, and Toba. K.R.H. reports receiving grant support from Roche Diagnostics and Ferring Pharmascience. G.C. reports receiving Honorarium and grant support from Abbvie Pharmaceuticals and Bayer Pharmaceuticals. M.P.D. holds equity from Advanced Reproductive Care Inc. and DS Biotech, receives fees from Advanced Reproductive Care Inc., Actamax, Auxogyn, ZSX Medical, Halt Medical, and Neomed, and receives grant support from Boehringer-Ingelheim, Abbott, and BioSante, Ferring Pharmaceuticals, and EMD Serono. H.Z. receives research support from the Chinese 1000-scholar plan. Others report no disclosures other than NIH grant support., Trial Registration Number: PPCOS-I and -II were respectively registered at Clinicaltrials.gov: NCT00719186 and NCT00719186., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Intramural leiomyomas have been long debated as a potential cause of infertility and pregnancy loss., Findings: Previous research has linked intramural fibroids to defective implantation, as well as to abnormal peristaltic events of the uterine smooth muscle. Previous reports describe the effects of intramural fibroids on normal human fertility and early pregnancy loss, specifically in regards to implantation failure., Conclusion: A thorough understanding of prior research may direct new research focus, leading to better understanding of leiomyoma-associated infertility.

Aim: This study examined the distress of first-episode psychosis (FEP) beyond the acute episode. It focused on how people understand the experience of FEP and its negative impact and how this relates to the traumagenic phenomena., Methods: This research was a longitudinal qualitative study including interpretative phenomenological analysis of interview data. Ten people who had experienced FEP were interviewed 3-6 months following their psychotic episode (time one) and again 3 months after their initial interview (time two). Clinicians and significant others were interviewed at time two., Results: Interpretative phenomenological analysis of the interview data supported a conceptualization of recovery from FEP within a broad trauma framework. The traumatic nature of FEP was found to be extended beyond the acute episode and was not linked to symptoms of post-traumatic stress disorder (PTSD) but included impact on identity, relationships and worldview., Conclusions: The diagnosis of PTSD does not appear to capture all aspects of the distress of FEP. Traumagenic distress appears explained by incorporating a range of negative emotions, viewing the impact of FEP as ongoing rather than contained to the acute episode, and recognizes disruption of the individual's views of the self, others and the world., (© 2013 Wiley Publishing Asia Pty Ltd.)

Objective: To identify baseline characteristics of women with unexplained infertility to determine whether treatment with an aromatase inhibitor will result in a lower rate of multiple gestations than current standard ovulation induction medications., Design: Randomized, prospective clinical trial., Setting: Multicenter university-based clinical practices., Patient(s): A total of 900 couples with unexplained infertility., Intervention(s): Collection of baseline demographics, blood samples, and ultrasonographic assessments., Main Outcome Measure(s): Demographic, laboratory, imaging, and survey characteristics., Result(s): Demographic characteristics of women receiving clomiphene citrate (CC), letrozole, or gonadotropins for ovarian stimulation were very consistent. Their mean age was 32.2 ± 4.4 years and infertility duration was 34.7 ± 25.7 months, with 59% primary infertility. More than one-third of the women were current or past smokers. The mean body mass index (BMI) was 27 and mean antimüllerian hormone level was 2.6; only 11 women (1.3%) had antral follicle counts of <5. Similar observations were identified for hormonal profiles, ultrasound characterization of the ovaries, semen parameters, and quality of life assessments in both male and female partners., Conclusion(s): The cause of infertility in the couples recruited to this treatment trial is elusive, as the women were regularly ovulating and had evidence of good ovarian reserve both by basal FSH, antimüllerian hormone levels, and antral follicle counts; the male partners had normal semen parameters. The three treatment groups have common baseline characteristics, thereby providing comparable patient populations for testing the hypothesis that use of letrozole for ovarian stimulation can reduce the rates of multiples from that observed with gonadotropin and CC treatment., Clinical Trial Registration Number: NCT 01044862., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Before initiating ovulation induction, it is important to evaluate the underlying cause of a patient's anovulation and to make lifestyle modifications or treat underlying medical conditions, as appropriate. Here, ovulation induction agents are discussed with attention to their pharmacology, indications for use, therapy regimens, and efficacy. Adjuvant therapies and appropriate monitoring are also reviewed., (Copyright © 2015 Elsevier Inc. All rights reserved.)