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In men, inhibin B is the circulating isoform involved in the regulation of follicle stimulating hormone (FSH) secretion. Within the testis, inhibin B may have a role in Sertoli and germ cell interactions, thus secretion into seminal plasma may reflect seminiferous tubule function. Using specific immunoassays, inhibin B was present in seminal plasma in fertile men (n = 105) and in unselected men attending an infertility clinic (n = 174) with a wide range in concentration from undetectable (<15 pg/ml) up to 54,100 pg/ml (geometric mean 280 pg/ml). There was a highly significant correlation between seminal plasma inhibin B concentration and sperm concentration (r = 0.46, P < 0.001), but no correlation with percentages of spermatozoa with progressive motility or normal morphology. Inhibin A and isoforms containing pro and alphaC immunoreactivity were not detectable. In post-vasectomy seminal plasma samples (18 of 20) inhibin B was undetectable, indicating that the testis is the predominant source. In unselected men attending an infertility clinic, inhibin B was undetectable in 17% (present in remainder; maximum concentration 26,200 pg/ml; mean 263 pg/ml), with a highly significant correlation between seminal plasma inhibin B and sperm concentration (r = 0.55, P < 0.0001). In men with oligo/ azoospermia (sperm concentration <20 x 10(6)/ml), seminal plasma inhibin B concentrations were lower in those with elevated plasma FSH concentrations (mean values 42 and 205 pg/ml, P < 0.05). Inhibin alpha and betaB subunits were localized predominantly in Sertoli and Leydig cells, using immunohistochemistry. We conclude that inhibin B of testicular origin is present in normal human seminal plasma, but with a very wide range in concentration, and may reflect the functional state of the seminiferous epithelium. [ABSTRACT FROM AUTHOR]

Background: Endometrial cancer is the most common gynaecological malignancy; risk factors include exposure to oestrogens and high body mass index. Expression of enzymes involved in biosynthesis of oestrogens and prostaglandins (PG) is often higher in endometrial cancers when compared with levels detected in normal endometrium. Oestrogens bind one of two receptors (ERalpha and ERbeta) encoded by separate genes. The full-length receptors function as ligand-activated transcription factors; splice variant isoforms of ERbeta lacking a ligand-binding domain have also been described. PGs act in an autocrine or paracrine manner by binding to specific G-protein coupled receptors.Methods: We compared expression of ERs, progesterone receptor (PR) and cyclooxygenase-2 (COX-2) in stage 1 endometrial adenocarcinomas graded as well (G1), moderately (G2) or poorly (G3) differentiated (n >or= 10 each group) using qRTPCR, single and double immunohistochemistry. We used endometrial adenocarcinoma cell lines to investigate the impact of PGF2alpha on expression of ERs and PR.Results: Full length ERbeta (ERbeta1) and two ERbeta variants (ERbeta2, ERbeta5) were expressed in endometrial cancers regardless of grade and the proteins were immunolocalised to the nuclei of cells in both epithelial and stromal compartments. Immunoexpression of COX-2 was most intense in cells that were ERalphaneg/low. Expression of PR in endometrial adenocarcinoma (Ishikawa) cell lines and tissues broadly paralleled that of ERalpha. Treatment of adenocarcinoma cells with PGF2alpha reduced expression of ERalpha but had no impact on ERbeta1. Cells incubated with PGF2alpha were unable to increase expression of PR mRNA when they were incubated with E2.Conclusion: We have demonstrated that ERbeta5 protein is expressed in stage 1 endometrial adenocarcinomas. Expression of three ERbeta variants, including the full-length protein is not grade-dependent and most cells in poorly differentiated cancers are ERbetapos/ERalphaneg. We found evidence of a link between COX-2, its product PGF2alpha, and expression of ERalpha and PR that sheds new light on the cross talk between steroid and PG signalling pathways in this disease. [ABSTRACT FROM AUTHOR]

Screens for estrogen receptor (ER) alpha and ERbeta messenger RNA in primary ovarian surface epithelial cell (OSE) cultures by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Reverse transcription of total RNA into single-stranded complementary DNA for PCR; Detectability of ERalpha and ERbeta products by Southern analysis in cultured OSE cells.

Objective: To evaluate whether serum antimüllerian hormone (AMH) levels are affected in early maturing girls, and whether pituitary suppression by long-acting GnRH agonist (GnRH-a) affects AMH.Design: Secondary analyses of a prospective clinical study.Setting: Tertiary pediatric center.Patient(s): Fifteen girls followed during GnRH-a treatment. Evaluations before, 3 and 12 months after initiation, as well as 6 months after discontinuation of treatment. To evaluate whether AMH levels were affected in early maturing girls, baseline levels were compared with levels in healthy girls (matched for age, n = 129; matched for pubertal Tanner stage, n = 119).Intervention(s): Patients were treated with SC injections of leuprolide acetate (LA; Procren 3.75 mg every 28th day).Main Outcome Measure(s): Basal serum levels of AMH, E(2), inhibin B, FSH, and LH, as well as GnRH-stimulated levels of FSH and LH.Result(s): At baseline, the median (range) of AMH levels in the patients was 20.3 pmol/L (2.0-30.0 pmol/L). After 3 months of GnRH-a treatment, AMH declined to 10.4 pmol/L (range, <2.0-27.0 pmol/L). The AMH suppression was maintained after 12 months of treatment (14.4 pmol/L [range, <2.0-29.6 pmol/L]). Six months after discontinuation of GnRH-a treatment, AMH levels were similar to pretreatment levels (18.8 pmol/L (range, 5.8-46.9 pmol/L)). Before treatment, AMH levels in early maturing girls did not differ significantly from AMH levels in healthy age-matched girls (median, 20 vs. 23 pmol/L) or Tanner-matched girls (median, 20 vs. 19 pmol/L).Conclusion(s): The partial suppression of AMH by GnRH-a treatment is consistent with previous studies suggesting partial gonadotropin-dependence of AMH. [ABSTRACT FROM AUTHOR]

CONTEXT: Despite the widespread popularity of alternative medical approaches to respiratory and allergic disorders, there is a lack of scientific substantiation of their benefits. OBJECTIVE: Assessment of the therapeutic benefit of an integrative holistic approach to the treatment of chronic sinusitis. DESIGN: Patients began a 5-month program consisting of 5 evening sessions of 2 hours each in October of 1999. SETTING: The program was held in the offices of one of the authors (WSS). PATIENTS: Ten patients of an allergist-immunologist specialist (WSS), symptomatic despite aggressive conventional treatment for their chronic sinusitis, were recruited to participate in an integrative holistic medical education and treatment program consisting of 5 sessions and evaluated at a 1-year follow-up. Sessions consisted of education in lifestyle and indoor-air modification, nasal hygiene, and treatment with fluconazole. Eight of 9 subjects were located and provided feedback 7 years and 6 months later, in June 2007. MAIN OUTCOME MEASURES: Health-related quality of life (QOL) was assessed using the short-form QOL survey (SF-12) and rhinitis QOL by the Rhinitis Quality of Life Questionnaire (RQLQ). RESULTS: No significant differences emerged in the SF-12 or mini-RQLQ scores comparing visit 2 with visit 1. Statistically significant improvement for physical and mental subscales of the SF-12 emerged comparing the results of visit 4 with visit 2 after the addition offluconazole treatment to the regimen, persisting through an additional year of follow-up. Feedback at 7.5 years confirmed marked long-term improvement in chronic sinusitis symptoms compared to their pre-study condition. [ABSTRACT FROM AUTHOR]

The supremacy of combined oral contraceptives (OCs) is being challenged. For too long combined OCs have been seen as synonymous with contraception, helping to maintain ignorance of alternative methods. Further, the efficacy of these OCs and condoms is often compromised by incorrect or inconsistent use. We particularly welcome developments in male systemic methods, that allow men to share not only in conception but also in contraception, and methods that are completely forgettable once instituted, especially if usable by adolescents. [ABSTRACT FROM AUTHOR]

Chelation therapy is thought to not only remove contaminating metals but also to decrease free radical production. However, in standard ethylene diamine tetracetic acid (EDTA) chelation therapy, high doses of vitamin C with potential pro-oxidant effects are often added to the chelation solution. The authors demonstrated previously that the intravenous administration of the standard chelation cocktail, containing high amounts of vitamin C, resulted in an acute transitory pro-oxidant burst that should be avoided in the treatment of pathologies at risk of increased oxidative stress such as diabetes and cardiovascular disease. The current study was designed to determine the acute and chronic biochemical effects of chelation therapy on accepted clinical, antioxidant variables. An EDTA chelation cocktail not containing ascorbic acid was administered to six adult patients for five weeks (10 sessions of chelation therapy); antioxidant indicators were monitored. Immediately after the initial chelation session, in contrast with the data previously reported with the standard cocktail containing high doses of vitamin C, none of the oxidative stress markers were adversely modified. After five weeks, plasma peroxide levels, monitored by malondialdehyde, decreased by 20 percent, and DNA damage, monitored by formamidopyrimidine-DNA glycosylase (Fpg) sensitive sites, decreased by 22 percent. Remaining antioxidant-related variables did not change. In summary, this study demonstrates that multiple sessions of EDTA chelation therapy in combination with vitamins and minerals, but without added ascorbic acid, decreases oxidative stress. These results should be beneficial in the treatment of diseases associated with increased oxidative stress such as diabetes and cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The value of anti-mullerian hormone (AMH) as a marker of the ovarian reserve is becoming clear in a range of clinical contexts. This study reports the external validation of a quadratic model-based AMH--age nomogram using a cohort of 15,834 US women. All models previously investigated for the decline in ovarian reserve (i.e. linear, bi-linear, decay curve, power and quadratic models) tended to overestimate AMH by approximately 11% versus the published nomogram, indicating some between-population heterogeneity. Bootstrapping of 1000 datasets indicated that the quadratic model provided the best fit, confirming the choice of this model in the AMH-age nomogram. This nomogram can therefore be used with confidence for the interpretation of AMH in clinical populations. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether circulating levels of antimüllerian hormone (AMH) predict fecundability in young healthy women.Design: Prospective cohort study.Setting: General community.Patient(s): A total of 186 couples who intended to discontinue contraception to become pregnant were followed until pregnancy or for six menstrual cycles.Intervention(s): None.Main Outcome Measure(s): Fecundability was evaluated by the monthly probability of conceiving (i.e., fecundability ratio [FR]). In addition, circulating levels of LH, FSH, T, and sex hormone-binding globulin (SHBG) were evaluated in 158 of 186 women.Result(s): Fifty-nine percent of couples conceived during the study period. Compared to the reference group of women with medium AMH (AMH quintiles 2-4), fecundability did not differ significantly in women with low AMH (AMH quintile 1) (FR 0.81; 95% confidence interval [CI] 0.44-1.40). In contrast, women with high AMH (AMH quintile 5) had reduced fecundability (FR 0.62; 95% CI 0.39-0.99) after adjustment for covariates (woman's age, body mass index [BMI], smoking, diseases affecting fecundability, and oligozoospermia). Irregular menstrual cycles were more prevalent in women with high AMH compared with women with low or medium AMH levels, and they had higher levels of LH (geometric mean: 8.4 vs. 5.3 IU/L) and LH:FSH ratio (2.4 vs. 1.8). After exclusion of women with irregular cycles, women with high AMH still had reduced fecundability (FR 0.48; 95% CI 0.27-0.85) and elevated LH:FSH ratio (2.4 vs. 1.7).Conclusion(s): Low AMH in healthy women in their mid-20s did not predict reduced fecundability. Even after exclusion of women with irregular cycles, the probability of conceiving was reduced in women with high AMH. [ABSTRACT FROM AUTHOR]

Methods: This systematic review was prospectively registered with PROSPERO (CRD42023426005) and the data collected in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The quality of reporting of included studies was evaluated in accordance with the CONSORT statement., Results: Eleven randomized controlled trials were identified. Evaluation of the reviewed studies revealed low levels of overall compliance with the CONSORT statement highlighting the need for improved reporting. Key areas included insufficient information about - the intervention (for replicability), participant flow, recruitment, and treatment effect sizes. Study discussions did not fully consider limitations and generalizability, and the discussion/interpretation of the findings were often incongruent with the results and therefore misleading. Only two studies reported a significant difference between sham and active tDCS for OCD outcomes, with small effect sizes noted., Conclusions: The variability in protocols, lack of consistency in procedures, combined with limited significant findings, makes it difficult to draw any meaningful conclusions about the effectiveness of tDCS for OCD. Future studies need to be appropriately powered, empirically driven, randomized sham-controlled clinical trials.

Background: Survival from childhood and adolescent cancer has increased, but the chance of a livebirth in female survivors under 18 years at diagnosis may be reduced., Methods: We performed a national population-based analysis, including all female cancer survivors diagnosed in Scotland before the age of 18 years between 1981 and 2012. Scottish Cancer Registry records were linked to Scottish maternity records. Females from the exposed group with no pregnancies before cancer diagnosis (n = 2118) were compared with three general population controls matched for age and year of diagnosis., Findings: The cumulative incidence of a livebirth for all diagnoses was reduced to 37% (95% CI 33-40%) for cancer survivors at 30 years of age vs 58% (57-60%) for controls. The deficit varying by diagnosis: for lymphoid leukaemia, the cumulative incidence at 30 years was 29% (23-36%) vs 57% (52-61%) for controls with similar deficits in CNS tumours and retinoblastoma. There was a steady improvement in the chance of livebirth in those diagnosed more recently., Interpretation: We have shown a reduced chance of livebirth in female survivors of cancer diagnosed before age 18. The deficit is present for all diagnoses., (© 2024. The Author(s).)

Female hypogonadism (FH) is a relatively common endocrine disorder in women of premenopausal age, but there are significant uncertainties and wide variation in its management. Most current guidelines are monospecialty and only address premature ovarian insufficiency (POI); some allude to management in very brief and general terms, and most rely upon the extrapolation of evidence from the studies relating to physiological estrogen deficiency in postmenopausal women. The Society for Endocrinology commissioned new guidance to provide all care providers with a multidisciplinary perspective on managing patients with all forms of FH. It has been compiled using expertise from Endocrinology, Primary Care, Gynaecology and Reproductive Health practices, with contributions from expert patients and a patient support group, to help clinicians best manage FH resulting from both POI and hypothalamo-pituitary disorders, whether organic or functional., (© 2024 The Author(s). Clinical Endocrinology published by John Wiley & Sons Ltd.)

Reactive oxygen species (ROS) are generated by aerobic metabolism, and their deleterious effects are buffered by the cellular antioxidant response, which prevents oxidative stress. The nuclear factor erythroid 2-related factor 2 (NRF2) is a master transcriptional regulator of the antioxidant response. Basal levels of NRF2 are kept low by ubiquitin-dependent degradation of NRF2 by E3 ligases, including the Kelch-like ECH-associated protein 1 (KEAP1). Here, we show that the stability and function of NRF2 is regulated by the type I phosphatidylinositol phosphate kinase γ (PIPKIγ), which binds NRF2 and transfers its product phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P 2 ) to NRF2. PtdIns(4,5)P 2 binding recruits the small heat shock protein HSP27 to the complex. Silencing PIPKIγ or HSP27 destabilizes NRF2, reduces expression of its target gene HO-1, and sensitizes cells to oxidative stress. These data demonstrate an unexpected role of phosphoinositides and HSP27 in regulating NRF2 and point to PIPKIγ and HSP27 as drug targets to destabilize NRF2 in cancer., In Brief: Phosphoinositides are coupled to NRF2 by PIPKIγ, and HSP27 is recruited and stabilizes NRF2, promoting stress-resistance.

In six studies, we examined two foundational questions about moral praise. First, what makes an action praiseworthy? In Study 1, participants reported that actions that exceed duties (compared with dutiful actions) deserve greater praise and are perceived as less likely to happen. Second, what do observers infer from praise? Praise may communicate information about local norms. In Study 2, we found that-in general-participants expect praise to increase the likelihood of a behavior. However, in Studies 3-6, participants inferred that moral behavior that receives praise is less common and is less required and expected of people. These inferences led individuals to judge that someone would be less likely to perform a behavior that was praised. These studies provide insight into the lay beliefs and communicative function of moral praise., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The roles of initially kisspeptin and subsequently neurokinin B pathways in the regulation of human reproduction through the control of GnRH secretion were first identified 20 years ago, as essential for the onset of puberty in both boys and girls. Within that short time we already now have the first licence for clinical use for a neurokinin antagonist in a related indication, for menopausal vasomotor symptoms. Between these two markers of the start and end of the reproductive lifespan, it is clear that these pathways underlie many of the aspects of the hypothalamic regulation of reproduction which had hitherto been enigmatic. In this review, we describe the data currently available from studies designed to elucidate the roles of kisspeptin and neurokinin B in human ovarian function, specifically the regulation of follicle development leading up to ovulation, and in the control of the mid-cycle GnRH/LH surge that triggers ovulation. These studies, undertaken with only very limited pharmacological tools, provide evidence that the neurokinin B pathway is important in controlling the hypothalamic contribution to the precise gonadotropic drive to the ovary that is necessary for mono-ovulation, whereas the switch from negative to positive estrogenic feedback results in kisspeptin-mediated increased GnRH secretion. Potential therapeutic opportunities in conditions characterised by disordered hypothalamic/pituitary function, polycystic ovary syndrome, and functional hypothalamic amenorrhoea, and in the induced LH surge that is a necessary part of IVF treatment are discussed., (© 2024 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.)

Ovarian tissue cryopreservation (OTC) is increasingly offered globally as a fertility preservation strategy for both postpubertal women and prepubertal girls, with subsequent reimplantation of cryopreserved ovarian cortex resulting in a rapidly growing number of live births. There remains very limited evidence of efficacy from tissue stored when the patient was prepubertal or from conditions affecting the ovary directly, e.g., Turner syndrome. Although OTC is becoming a more established practice, several clinical dilemmas remain from a practical and ethical standpoint. This review discusses the challenges regarding optimal patient selection for the procedure, the use of OTC in patients with a poor prognosis, the potential of reimplantation of tissue contaminated with malignant cells, and the role of OTC in those with an intrinsic ovarian disorder., Competing Interests: Declaration of Interests C.E.D. has nothing to disclose. R.A.A. has received consulting fees from Roche Diagnostics outside the submitted work., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

The concept of a hormonal approach that sufficiently and reversibly suppresses spermatogenesis to the level required for effective contraception has been developed and tested over several decades. The reality of achieving this has been confirmed using both testosterone alone and combination methods using a progestogen with a physiological dose of testosterone, necessary to replace the lack of endogenous testosterone production by the suppressed testes. A range of both long-acting and self-administered combination methods are effective, including injection, implant and gel methods of administration, with up to 95% of men achieving sufficient spermatogenic suppression. New steroids are also being trialled. Surveys show the widespread willingness of men and their female partners to use novel male methods, suggesting the potential of this approach to contribute to global family planning and sustainable development goals. This approach to contraception can clearly be effective, and needs to move from relatively small scale testing to large scale pre-marketing trials: only then can information about long-term safety and real-world acceptability be obtained., Competing Interests: Declaration of competing interest RAA and JRW are investigators in the current NICHD NES-T male contraceptive trial. JRW is an Associate Editor for BMJ Sexual and Reproductive Health and has received an educational grant from Gedeon Richter., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Breast cancer is the most common malignancy in women of reproductive age and chemotherapy protocols impair fertility, frequently necessitating fertility preservation (FP) referral. Embryo, oocyte, or ovarian tissue cryopreservation are established FP modalities in women with breast cancer but there are few data on their uptake over time. In this study our aim was to determine the regional time trends and utility differences for fertility preservation methods of reproductive tissue cryopreservation., Methods: This multicenter study included 1623 women diagnosed with breast cancer from 7 tertiary centers in 6 countries (Brazil, Italy, Scotland, South Korea, Turkey, USA). Participant centers provided the details of FP cryopreservation approaches broken down annually from 2012 to 2021. Women with newly diagnosed breast cancer, aged 18-45 years who were referred for FP at participating centers and had normal ovarian function at the time were included., Results: We found a mean increase of 7% per year (P = .002, adjusting for centers) in the number of women referred for FP. Of those who were referred (n = 1623), a mean 38.7% underwent FP (n = 629), with a range of 12% in South Korea) to 95% in Brazil. The number of women undergoing ovarian stimulation for FP continually increased until 2021, with oocyte cryopreservation being the most common procedure throughout the study period (P = .014 for time trend). The proportion of random start ovarian stimulation cycles increased each year from 58.3% in 2012 to 86.8% in 2021, (P = .005 for time trend, and P = .04 for 2012 vs. 2021)., Conclusions: The utility of FP has steadily increased for young women with breast cancer over the last decade, although regional differences significantly influence FP practices. The findings of our study could have value for policy making in FP care for young women with breast cancer at the local, regional, or global level., Competing Interests: Disclosure Dr. Lambertini reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD, and Exact Sciences; speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Takeda, Knight, Ipsen, and AstraZeneca; travel Grants from Gilead, Daiichi Sankyo, Roche and a research grant (to his Institution) from Gilead, all outside the submitted work. All other authors state that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To undertake a one-stage meta-analysis of individual patient data from randomized trials comparing individualized dosing of follitropin delta vs. other forms of follitropin (alpha and beta) for live birth (LB) rates (LBR) and safety parameters in women undergoing ovarian stimulation for in vitro fertilization treatment., Design: Systematic review with individual patient data meta-analysis., Setting: Not applicable., Patients: Women undergoing ovarian stimulation for in vitro fertilization treatment., Interventions: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Web of Science to identify eligible phase 3 trials between January 1, 2000, and February 1, 2023., Main Outcome Measures: All analyses were based on individual participant data. We used a general linear mixed effects logistic regression model using fixed effects for treatment drugs interacting with log (AMH) level, age, and random effects for country and trial to compare the primary efficacy and safety outcomes of LB and early ovarian hyperstimulation syndrome (OHSS) and/or the need for OHSS preventative measures, with ovarian stimulation parameters and neonatal outcomes also assessed. PROSPERO registration: CRD42023399711., Results: Three trials met inclusion criteria and included 2,685 women undertaking 2,682 cycles between October 2013 and May 2020, with LB follow-up through to February 1, 2023. For women with an elevated AMH level (≥15 pmol/L), there was high-quality evidence that the use of individualized dosing of follitropin delta was associated with an increased LB rate (adjusted odds ratio [adj OR] 1.64, 95% confidence interval [CI] 1.14, 2.36). Safety outcomes were also improved with a reduced risk of both early OHSS and/or the need for preventative interventions (adj OR 0.27, 95% CI 0.15, 0.49) and early moderate or severe OHSS (adj OR 0.30, 95% CI 0.16, 0.58). These improvements in outcomes were obtained with a lower total dose of gonadotropin (-48.7 μg, 95% CI -53.7, -43.8) and no adjustments in the daily dose. In contrast, similar LB rates (adj OR 0.86, 95% CI 0.63, 1.17) and safety outcomes (adj OR 1.92, 95% CI 0.76, 4.87) were observed for women with an AMH level of <15 pmol/L. There were no clinically meaningful differences in neonatal outcomes., Conclusion: Using follitropin delta in an AMH level and weight-based algorithm rather than conventional licensed dosing of follitropin alpha or beta for ovarian stimulation in women is associated with improved LB rates and safety outcomes for women with elevated AMH levels., Competing Interests: Declaration of Interests S.M.N reports funding from Modern Health Inc. for the submitted work; funding from Wellbeing of Women, Chief Scientist Office, NIHR, MRC, and OA; Consulting fees from Access Fertility, Modern Health Inc., Ferring Pharmaceuticals, Merck Serone, IBSA, Roche, and TFP; honoraria from Ferring Pharmaceuticals, Merck Serono, IBSA, and Roche; Payment for expert testimony from various legal companies; travel support from Ferring Pharmaceuticals and Merch Serono; NIHR Trials chair outside the submitted work; and has participated in Advisory Boards and received consultancy or speakers’ fees from Access Fertility, Beckman Coulter, Ferring, Finox, Merck, Modern Fertility, MSD, Roche Diagnostics, and The Fertility Partnership. M.S. has nothing to disclose. K.A. has nothing to disclose. R.A.A. has participated in Advisory Boards and received consultancy or speakers’ fees from IBSA, Ferring, Merck, and Roche Diagnostics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There are limited data on the risks of obstetric complications among survivors of adolescent and young adult cancer with most previous studies only reporting risks for all types of cancers combined. The aim of this study was to quantify deficits in birth rates and risks of obstetric complications for female survivors of 17 specific types of adolescent and young adult cancer., Methods: The Teenage and Young Adult Cancer Survivor Study (TYACSS)-a retrospective, population-based cohort of 200 945 5-year survivors of cancer diagnosed at age 15-39 years from England and Wales-was linked to the English Hospital Episode Statistics (HES) database from April 1, 1997, to March 31, 2022. The cohort included 17 different types of adolescent and young adult cancers. We ascertained 27 specific obstetric complications through HES among 96 947 women in the TYACSS cohort. Observed and expected numbers for births and obstetric complications were compared between the study cohort and the general population of England to identify survivors of adolescent and young adult cancer at a heighted risk of birth deficits and obstetric complications relative to the general population., Findings: Between April 1, 1997, and March 31, 2022, 21 437 births were observed among 13 886 female survivors of adolescent and young adult cancer from England, which was lower than expected (observed-to-expected ratio: 0·68, 95% CI 0·67-0·69). Other survivors of genitourinary, cervical, and breast cancer had under 50% of expected births. Focusing on more common (observed ≥100) obstetric complications that were at least moderately in excess (observed-to-expected ratio ≥1·25), survivors of cervical cancer were at risk of malpresentation of fetus, obstructed labour, amniotic fluid and membranes disorders, premature rupture of membranes, preterm birth, placental disorders including placenta praevia, and antepartum haemorrhage. Survivors of leukaemia were at risk of preterm delivery, obstructed labour, postpartum haemorrhage, and retained placenta. Survivors of all other specific cancers had no more than two obstetric complications that exceeded an observed-to-expected ratio of 1·25 or greater., Interpretation: Survivors of cervical cancer and leukaemia are at risk of several serious obstetric complications; therefore, any pregnancy should be considered high-risk and would benefit from obstetrician-led antenatal care. Despite observing deficits in birth rates across all 17 different types of adolescent and young adult cancer, we provide reassurance for almost all survivors of adolescent and young adult cancer concerning their risk of almost all obstetric complications. Our results provide evidence for the development of clinical guidelines relating to counselling and surveillance of obstetrical risk for female survivors of adolescent and young adult cancer., Funding: Children with Cancer UK, The Brain Tumour Charity, and Academy of Medical Sciences., Competing Interests: Declaration of interests RAA reports grants from Ferring Pharmaceuticals, UK Research and Innovation, and Children with Cancer UK, outside the submitted work. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Study Question: Does a purpose-designed Decision Aid for women considering elective egg freezing (EEF) impact decisional conflict and other decision-related outcomes?, Summary Answer: The Decision Aid reduces decisional conflict, prepares women for decision-making, and does not cause distress., What Is Already Known: Elective egg-freezing decisions are complex, with 78% of women reporting high decisional conflict. Decision Aids are used to support complex health decisions. We developed an online Decision Aid for women considering EEF and demonstrated that it was acceptable and useful in Phase 1 testing., Study Design, Size, Duration: A single-blind, two-arm parallel group randomized controlled trial was carried out. Target sample size was 286 participants. Randomization was 1:1 to the control (existing website information) or intervention (Decision Aid plus existing website information) group and stratified by Australian state/territory and prior IVF specialist consultation. Participants were recruited between September 2020 and March 2021 with outcomes recorded over 12 months. Data were collected using online surveys and data collection was completed in March 2022., Participants/materials, Setting, Methods: Females aged ≥18 years, living in Australia, considering EEF, proficient in English, and with internet access were recruited using multiple methods including social media posts, Google advertising, newsletter/noticeboard posts, and fertility clinic promotion. After completing the baseline survey, participants were emailed their allocated website link(s). Follow-up surveys were sent at 6 and 12 months. Primary outcome was decisional conflict (Decisional Conflict Scale). Other outcomes included distress (Depression Anxiety and Stress Scale), knowledge about egg freezing and female age-related infertility (study-specific measure), whether a decision was made, preparedness to decide about egg freezing (Preparation for Decision-Making Scale), informed choice (Multi-Dimensional Measure of Informed Choice), and decision regret (Decision Regret Scale)., Main Results and the Role of Chance: Overall, 306 participants (mean age 30 years; SD: 5.2) were randomized (intervention n = 150, control n = 156). Decisional Conflict Scale scores were significantly lower at 12 months (mean score difference: -6.99 [95% CI: -12.96, -1.02], P = 0.022) for the intervention versus control group after adjusting for baseline decisional conflict. At 6 months, the intervention group felt significantly more prepared to decide about EEF than the control (mean score difference: 9.22 [95% CI: 2.35, 16.08], P = 0.009). At 12 months, no group differences were observed in distress (mean score difference: 0.61 [95% CI: -3.72, 4.93], P = 0.783), knowledge (mean score difference: 0.23 [95% CI: -0.21, 0.66], P = 0.309), or whether a decision was made (relative risk: 1.21 [95% CI: 0.90, 1.64], P = 0.212). No group differences were found in informed choice (relative risk: 1.00 [95% CI: 0.81, 1.25], P = 0.983) or decision regret (median score difference: -5.00 [95% CI: -15.30, 5.30], P = 0.337) amongst participants who had decided about EEF by 12 months (intervention n = 48, control n = 45)., Limitations, Reasons for Caution: Unknown participant uptake and potential sampling bias due to the recruitment methods used and restrictions caused by the coronavirus disease 2019 pandemic. Some outcomes had small sample sizes limiting the inferences made. The use of study-specific or adapted validated measures may impact the reliability of some results., Wider Implications of the Findings: This is the first randomized controlled trial to evaluate a Decision Aid for EEF. The Decision Aid reduced decisional conflict and improved women's preparation for decision making. The tool will be made publicly available and can be tailored for international use., Study Funding/competing Interest(s): The Decision Aid was developed with funding from the Royal Women's Hospital Foundation and McBain Family Trust. The study was funded by a National Health and Medical Research Council (NHMRC) Project Grant APP1163202, awarded to M. Hickey, M. Peate, R.J. Norman, and R. Hart (2019-2021). S.S., M.P., D.K., and S.B. were supported by the NHMRC Project Grant APP1163202 to perform this work. R.H. is Medical Director of Fertility Specialists of Western Australia and National Medical Director of City Fertility. He has received grants from MSD, Merck-Serono, and Ferring Pharmaceuticals unrelated to this study and is a shareholder of CHA-SMG. R.L. is Director of Women's Health Melbourne (Medical Practice), ANZSREI Executive Secretary (Honorary), RANZCOG CREI Subspecialty Committee Member (Honorary), and a Fertility Specialist at Life Fertility Clinic Melbourne and Royal Women's Hospital Public Fertility Service. R.A.A. has received grants from Ferring Pharmaceuticals unrelated to this study. M.H., K.H., and R.J.N. have no conflicts to declare., Trial Registration Number: ACTRN12620001032943., Trial Registration Date: 11 August 2020., Date of First Patient’s Enrolment: 29 September 2020., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Purpose: To explore cancer-related cognitive impairment (CRCI) in older adults with acute myeloid leukemia (AML) receiving venetoclax in combination with hypomethylating agents or low-dose cytarabine chemotherapy., Methods: This study is a longitudinal, qualitative descriptive study. Participants were recruited using purposive sampling. Semi-structured interviews were conducted among 11 older adults with AML at cycle 2, cycle 4, and cycle 7 of chemotherapy. An early end-of-study interview was conducted for those who changed treatment plans during the study follow-up., Results: A total of 22 transcripts were included for thematic analysis. Four themes emerged: (1) CRCI experiences, (2) impact of CRCI, (3) CRCI coping strategies, and (4) perceived CRCI-related factors. Older adults with AML experienced challenges in memory, language, and attention both intermittently and daily. These cognitive changes impacted their emotion, daily activities, social connection, and their caregivers' responsibilities. Hence, these older adults with AML developed problem-solving and emotional coping strategies to cope with CRCI. Older adults with AML also identified demographic, physiology/clinical, psychological, and other factors that might contribute to CRCI., Conclusion: This study offers important insight for clinicians to understand how older adults with AML experience CRCI and how it impacts their daily routines. It indicates that clinicians should ask patients about their experience with cognitive changes at each encounter to provide support or coping strategies as needed to prevent CRCI from further hindering their quality of life., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)