Psychosocial stress and ovarian function in adolescent and young adult cancer survivors.

STUDY QUESTION: Is psychosocial stress associated with ovarian function in reproductive-aged survivors of cancer diagnosed as adolescents and young adults (AYA survivors)? SUMMARY ANSWER: We observed no association between self-reported and biomarkers of psychosocial stress and ovarian function in AYA survivors. WHAT IS KNOWN ALREADY: Psychosocial stress suppresses hypothalamic-pituitary-ovarian axis, resulting in ovulatory dysfunction, decreased sex steroidogenesis and lower fertility in reproductive-aged women. Many cancer survivors experience high psychosocial stress and hypothalamic-pituitary-adrenal axis dysregulation. The menstrual pattern disturbances and infertility they experience have been attributed to ovarian follicle destruction, but the contribution of psychosocial stress to these phenotypes is unknown. STUDY DESIGN, SIZE, DURATION: A cross-sectional study was conducted estimating the association between perceived stress, measured by self-report and saliva cortisol, and ovarian function, measured by bleeding pattern, dried blood spot (DBS) FSH and LH, and saliva estradiol. We included 377 AYA survivor participants. PARTICIPANTS/MATERIALS, SETTING, METHODS: AYA survivor participants were ages 15-35 at cancer diagnosis and ages 18-40 at study enrollment, had completed primary cancer treatment, had a uterus and at least one ovary, did not have uncontrolled endocrinopathy and were not on hormone therapy. Recruited from cancer registries, physician referrals and cancer advocacy groups, participants provided self-reported information on psychosocial stress (Perceived Stress Scale-10 (PSS-10)) and on cancer and reproductive (fertility, contraception, menstrual pattern) characteristics. DBS samples were collected timed to the early follicular phase (cycle Days 3-7) for menstruating individuals and on a random day for amenorrheic individuals; saliva samples were collected three time points within 1 day. FSH and LH were measured by DBS ELISAs, cortisol was measured by ELISA and estradiol was measured by liquid chromatography tandem mass spectrometry. MAIN RESULTS AND THE ROLE OF CHANCE: The median age of participants was 34.0 years (range 19-41) at a median of 6.0 years since cancer diagnosis. The most common cancer was breast (32.1%). Median PSS-10 score was 15 (range 0-36), with 5.3% scoring ≥26, the cut point suggestive of severe stress. Cortisol levels followed a diurnal pattern and cortisol AUC was negatively correlated with PSS-10 scores (P = 0.03). Neither PSS-10 scores nor cortisol AUC were associated with FSH, LH, estradiol levels or menstrual pattern. Waking and evening cortisol and the cortisol awakening response also were not related to ovarian function measures. LIMITATIONS, REASONS FOR CAUTION: Our analysis is limited by its cross-sectional nature, heterogeneity of cancer diagnosis and treatments and low prevalence of severe stress. WIDER IMPLICATIONS OF THE FINDINGS: The lack of association between psychosocial stress and a variety of ovarian function measures in female AYA cancer survivors suggests that psychosocial stress does not have a significant impact on the reproductive axis of AYA survivors. This finding is important in counseling this population on their menstrual pattern and family building plans. STUDY FUNDING/COMPETING INTEREST(S): NIH HD080952, South Korea Health Industry Development Institute HI18C1837 (JK). Dr A.D. works for Bluebird Bio, Inc., Dr D.Z. works for ZRT Labs and Dr P.M.S. works for Ansh Labs, which did not sponsor, support or have oversight of this research. Other authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Lipidomic changes in mouse oocytes vitrified in PEG 8000-supplemented vitrification solutions.

Cryopreserved oocytes are inevitably exposed to cold stress, which negatively affects the cellular aspects of the oocytes. Lipidomic analysis of the oocytes reveals quantitative changes in lipid classes under conditions of cold stress, leading to potential freezing-vulnerability. We had previously shown that specific phospholipids are significantly downregulated in vitrified-warmed mouse oocytes compared to those in fresh oocytes. In this study, we examined whether supplementation of polyethylene glycol 8000 (PEG 8000) during vitrification influences the lipidome of the oocytes. We used liquid chromatography with tandem mass spectrometry (LC-MS/MS) to study the alteration in the lipidome in three groups of mouse oocytes: fresh, vitrified-warmed, and vitrified with PEG 8000-warmed during vitrification. In these groups, we targeted to analyze 21 lipid classes. We profiled 132 lipid species in the oocytes and statistical analyses revealed lipid classes that were up- or downregulated in these groups. Overall, our data revealed that several classes of lipids were affected during vitrification, and that oocytes vitrified with PEG 8000 to some extent alleviated the levels of changes in phospholipid and sphingolipid contents during vitrification. These results suggest that phospholipids and sphingolipids are influenced by PEG 8000 during vitrification and that PEG 8000 can be considered as a potential candidate for preserving membrane integrity during oocyte cryopreservation.

Relationship between fatty infiltration and gene expression in patients with medium rotator cuff tear.

BACKGROUND: Fatty infiltration (FI) is a key prognostic factor that affects outcomes after rotator cuff repair and is radiologically evaluated using the Goutallier classification. The purpose of this study was to assess alterations in gene and protein expression according to the Goutallier classification in the supraspinatus muscle and any relationships among various gene expression profiles. METHODS: Twenty-four samples of the supraspinatus muscle from 12 patients with a high FI grade (grade 3 or 4) and 12 patients with a low FI grade (grade 1 or 2) with medium-sized tears were acquired during arthroscopic surgery. Alterations in the expression of genes and proteins associated with adipogenesis, fibrosis, inflammation, and muscle atrophy were compared between the high- and low-FI groups using reverse-transcription quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. RESULTS: mRNA expression of not only the adipogenic genes (peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α; P < .001 and P = .020) but also the fibrosis-related gene (α-smooth muscle actin; P < .001), inflammation-related genes (interleukin [IL]-1ß and tumor necrosis factor α; P = .041 and P = .039), and muscle atrophy-related genes (atrogin 1 and myostatin; P = .006 and P < .001) was higher in the high-FI group compared with that in the low-FI group. In addition, adipogenic gene expression was significantly correlated with the expression of other categories of genes (all P < .05, except atrogin 1). A correlation of gene and protein expression was observed for IL-1ß (P = .027) and myostatin (P = .029). CONCLUSIONS: The radiologic grading of FI was associated with the expression of various genes, including adipogenic, fibrotic, inflammatory, and atrophy-related genes, and these genes were closely correlated with each other in terms of expression. This information could be helpful in patient counseling.

Molecular analysis of lipid uptake- and necroptosis-associated factor expression in vitrified-warmed mouse oocytes.

BACKGROUND: We had previously demonstrated that vitrification reduces the levels of certain phospholipid classes, and that oocytes from aged mice show a similar lipidome alteration, even without vitrification. In the current investigation, we examined if vitrification-warming of mouse oocytes from young and aged mice causes any changes in molecular aspects of lipid-associated features. METHODS: Metaphase II (MII) stage oocytes were harvested from young (10-14-week-old) and aged (45-54-week-old) mice by a superovulation regime with PMSG followed by hCG. We examined the status of the intracellular lipid pool and the integrity of the plasma membrane by staining oocytes with BODIPY 500/510 and CellMask live dyes. Expression of lipid uptake- and necroptosis-associated genes was assessed by quantitative PCR analyses, in oocytes from young and old mice, before and after vitrification. Localization patterns of two crucial necroptosis proteins, phosphorylated MLKL (pMLKL) and phosphorylated RIPK1 (pRIPK1) were examined in mouse oocytes by immunofluorescence staining. Necrostain-1 (Nec1), an inhibitor of RIPK1, was used to examine if RIPK1 activity is required to maintain oocyte quality during vitrification. RESULTS: We confirmed that vitrified-warmed oocytes from aged mice showed noticeable decrease in both CellMask and BODIPY 500/510 dyes. Among the lipid uptake-associated genes, Cd36 expression was higher in oocytes from aged mice. Necroptosis is a type of programmed cell death that involves damage to the plasma membrane, eventually resulting in cell rupture. The expression of necroptosis-associated genes did not significantly differ among groups. We observed that localization patterns of pMLKL and pRIPK1 were unique in mouse oocytes, showing association with microtubule organizing centers (MTOCs) and spindle poles. pMLKL was also localized on kinetochores of MII chromosomes. Oocytes treated with Nec1 during vitrification showed a decreased survival rate, indicating the importance of RIPK1 activity in oocyte vitrification. CONCLUSIONS: We report that oocytes from aged mice show differential expression of CD36, which suggests that CD36-mediated lipid uptake may be influenced by age. We also show for the first time that pMLKL and pRIPK1 exhibit unique localization pattern in mouse oocytes and this may suggest role(s) for these factors in non-necroptosis-associated cellular processes.

Improvement in Light Extraction Efficiency of InGaN/GaN Blue Light Emitting Diodes Using Sidewall Texturing.

Herein, we reported the effects of the geometric morphology of the sidewall on the extraction efficiency of GaN-based light-emitting diodes (LEDs). We performed numerical analysis based on the ray-tracing method. We found that the extraction efficiency of the LEDs increased with the texturing of the sidewall. The light output intensity of the LEDs (at an injection current of 100 mA) increased by 13.8% after sidewall texturing. These results confirmed that the geometric morphology of the sidewall plays an important role in improving the extraction efficiency of LEDs.

Influence of Smoking on the Expression of Genes and Proteins Related to Fat Infiltration, Inflammation, and Fibrosis in the Rotator Cuff Muscles of Patients With Chronic Rotator Cuff Tears: A Pilot Study.

PURPOSE: To evaluate the altered gene and protein expression patterns in the rotator cuff muscles of smokers and non-smokers with rotator cuff tears and to identify the smoking-associated key genetic factor(s) involved in rotator cuff muscle physiology. METHODS: Twenty-four samples of rotator cuff muscle from 12 current heavy smokers (mean age 61.8 ± 5.1 years) and age- and sex-matched 12 non-smokers (mean age 61.8 ± 6.9 years) with medium-sized tears were acquired during arthroscopic surgery. As a statistical method, the propensity score matching technique was used to select control group by 1:1 matching for age and sex. Inclusion criteria were patients who underwent arthroscopic repair for medium-sized full-thickness rotator cuff tears and those that were current smokers with a smoking history >20 packs/year. Patients lacking medium-sized tears, those with recent steroid injection history, isolated subscapularis tear, preoperative stiff shoulder, acute traumatic tear, or previous surgery on the same shoulder, or those that declined to participate were excluded. Alterations in the expression of genes and proteins associated with myogenesis, inflammation, adipogenesis, and muscle fibrosis were compared between smokers and non-smokers with reverse-transcription quantitative polymerase chain reaction, western blotting, and immunohistochemistry. RESULTS: Histologic analysis revealed increased inflammation and remarkable fat accumulation and fibrogenesis in the rotator cuff muscle from smokers compared with that from non-smokers. The mRNA expression levels of inflammatory high mobility group box 1 (HMGB1; P = .043), adipogenic CCAAT/enhancer-binding protein alpha (P = .046) and peroxisome proliferator-activated receptor gamma (PPARγ; P = .048), myogenic differentiation 1 (P = .032), fibrogenic alpha-smooth muscle actin (α-SMA; P = .033), and metalloproteinase 9 (P = .036) were significantly greater in samples from smokers than from non-smokers. A correlation was observed between gene and protein expression of HMGB1 (P = .034), PPARγ (P = .021), and α-SMA (P = .021). CONCLUSIONS: Smokers with rotator cuff tears showed high inflammation, large fat infiltration, and fibrosis in rotator cuff muscle that is associated with the increased expression of HMGB1, PPARγ, and α-SMA, respectively. LEVEL OF EVIDENCE: Case control study (Prognostic level III).

Correlation between Morphologic Grading and Euploidy Rates of Blastocysts, and Clinical Outcomes in In Vitro Fertilization Preimplantation Genetic Screening.

BACKGROUND: The standard morphological evaluation has been widely used for embryo selection, but it has limitations. This study aimed to investigate the correlation between morphologic grading and euploidy rate of in vitro fertilization (IVF) preimplantation genetic screening (PGS) and compare the pregnancy rates in young and old ages. METHODS: This is a retrospective study using the medical records of patients who underwent IVF procedures with PGS between January 2016 and February 2017 in a single center. The embryo grades were categorized into 4 groups: excellent, good, fair, and poor. Basic characteristics, euploidy rates, clinical pregnancy (CP) rates and ongoing pregnancy rates were analyzed. RESULTS: The excellent group had significantly higher rate of euploid embryos than fair group (47.82% vs. 29.33%; P = 0.023) and poor group (47.82% vs. 29.60%; P = 0.005). When the four groups were recategorized into two groups (excellent and good vs. fair and poor), they also showed significant difference in euploidy rates (44.52% vs. 29.53%; P = 0.002). When the patients were divided into two groups by age 35, the CP rates for those under and over 35 years old were 44.74% and 47.83%, respectively, which showed no significant difference. CONCLUSION: The significant differences among the euploidy rates of different morphologic embryo grades demonstrated the positive correlations between the morphologic grading of the embryo and the euploidy rate of PGS. Additionally, there was no significant difference between the younger and older patients' CP rates. These findings emphasize the fact that old age patients might benefit from PGS whatever the indication of PGS is.

Augmented Quantum Yield of a 2D Monolayer Photodetector by Surface Plasmon Coupling.

Monolayer (1L) transition metal dichalcogenides (TMDCs) are promising materials for nanoscale optoelectronic devices because of their direct band gap and wide absorption range (ultraviolet to infrared). However, 1L-TMDCs cannot be easily utilized for practical optoelectronic device applications (e.g., photodetectors, solar cells, and light-emitting diodes) because of their extremely low optical quantum yields (QYs). In this investigation, a high-gain 1L-MoS2 photodetector was successfully realized, based on the surface plasmon (SP) of the Ag nanowire (NW) network. Through systematic optical characterization of the hybrid structure consisting of a 1L-MoS2 and the Ag NW network, it was determined that a strong SP and strain relaxation effect influenced a greatly enhanced optical QY. The photoluminescence (PL) emission was drastically increased by a factor of 560, and the main peak was shifted to the neutral exciton of 1L-MoS2. Consequently, the overall photocurrent of the hybrid 1L-MoS2 photodetector was observed to be 250 times better than that of the pristine 1L-MoS2 photodetector. In addition, the photoresponsivity and photodetectivity of the hybrid photodetector were effectively improved by a factor of ∼1000. This study provides a new approach for realizing highly efficient optoelectronic devices based on TMDCs.

Oestrogen-induced expression of decay accelerating factor is spatiotemporally antagonised by progesterone-progesterone receptor signalling in mouse uterus.

Decay accelerating factor (DAF) is upregulated in the fetoplacental trophoblast, which protects the fetus from maternal complement injury. DAF was found to be downregulated in the endometrium of patients with repeated implantation failure. Thus, we examined the molecular mechanisms of DAF expression regulation by ovarian steroid hormones in the mouse uterus. Immunofluorescence staining demonstrated its exclusive localisation in the apical region of the epithelium in the uterus. Oestrogen (E2) significantly induced Daf mRNA in a time-dependent manner. Progesterone (P4) did not have any significant effect on Daf expression; however, it negatively modulated E2-induced DAF expression and RU486 effectively interfered with the inhibitory action of P4 in the uterus. During early pregnancy DAF was higher on Day 1 of pregnancy, but significantly decreased from Day 3, which is consistent with its E2-dependent regulation. Interestingly, DAF expression seemed to be influenced by the implanting blastocyst on Day 5 and it was gradually increased during preimplantation embryo development with peak levels at blastocyst stages. We demonstrated that E2-dependent DAF expression is antagonised by P4-progesterone receptor signalling in the uterine epithelium. Spatiotemporal regulation of DAF in the uterus and preimplantation embryos suggest that DAF functions as an immune modulator for embryo implantation and early pregnancy in mice.

Role of the Growth Temperature in MoS2 Growth by Chemical Vapor Deposition.

In this paper, we discuss the effect of synthesis temperature on the lateral growth of MoS2 thin films in chemical vapor deposition. With increasing temperature, surface coverage with MoS2 triangular islands is significantly improved due to an increase in the density of nuclei and fully continuous MoS2 thin film is grown when the growth temperature reached 800 °C. The MoS2 triangular islands grown at the temperature from 650 to 750 °C are monolayer and highly crystalline, whereas the large-area continuous film grown at the temperature of 800 °C is composed of double-layer or overlapping MoS2 nanosheets. Our research provides that synthesis temperature is the key to growth large area and high quality single crystal MoS2 films.

Decision making processes of women who seek elective oocyte cryopreservation.

PURPOSE: The aim of this study is to analyze women's opinions and their decision making processes regarding elective oocyte cryopreservation (OC). METHODS: One hundred twenty-four women who had elective OC counseling at the CHA Seoul Fertility Center were asked to complete a survey after their first visit. Data collection regarding age, marital status, monthly income, occupation, religion, reproductive history, questions about the participant's view on their own fecundity, and future parenthood were included. The modified Reproductive Concerns After Cancer scale and the Decisional Conflict Scale were used for analysis. RESULTS: The participants' mean age was 37.1 ± 4.8 years old. Eighty-six percent of the participants had regular periods. Ninety-two percent thought it was important to have their own biological offspring, and 86% were willing to pursue OC. Forty-nine percent appeared to have high DCS scores regarding making a decision of OC. Sixty-eight percent pursued OC, and the mean number of oocytes cryopreserved per patient was 10.5 ± 8.3. Multivariate analysis revealed that age was the only factor associated with high DCS scores (P = 0.002). Feeling less fertile than other women of same age and low DCS scores were the factors associated with pursuing OC (P = 0.02 and 0.004, respectively) after adjusting for possible confounding factors, including age. CONCLUSIONS: Older women had more difficulties in making decisions about OC. Adjusting for age, women who thought that they were less fertile than other women of same age and those with lower decisional conflict were more likely to pursue OC. Further studies should focus on the validation of older women's decisional conflicts regarding OC.

Increased proportion of mature oocytes with sustained-release growth hormone treatment in poor responders: a prospective randomized controlled study.

PURPOSE: Supplementation of growth hormone (GH) during controlled ovarian stimulation (COS) has been suggested to improve ovarian response. Despite potential benefits in poor responders, multiple injections of GH during COS are inconvenient. We conducted a randomized controlled study to evaluate the efficacy and safety of sustained-release human GH in poor responders undergoing in vitro fertilization (IVF). METHODS: This was a single-center, randomized, open-label, parallel study. Infertile women who satisfied the Bologna criteria for poor responders were randomized into GH treatment and control groups. The treatment group received a sustained-release GH (Eutropin Plus® 20 mg) three times before and during COS (mid-luteal, late luteal, and menstrual cycle day 2). The baseline characteristics and IVF outcomes were compared between the two groups. RESULTS: A total of 127 patients were included in the analysis. The mean age was 39.6 years and mean anti-Müllerian hormone level was 0.6 ng/ml. There was no significant difference in the baseline characteristics between GH treatment and control groups. The number of follicles on the human chorionic gonadotropin triggering day (3.1 ± 2.3 vs. 2.4 ± 1.6, P = 0.043) and the proportion of metaphase II oocytes (67.5 vs. 52.3%, P = 0.030) were higher in the GH group than in controls. The percentage of clinical and ongoing pregnancy and miscarriage was not different between the two groups. CONCLUSION: Supplementation of sustained-release GH before and during COS improved ovarian response, with an increase in mature oocytes in poor responders. Further studies are needed to ensure this benefit in general infertility patients.

Expression of aldo-keto reductase family 1, member C14 during ovulation in the rat.

The potent androgen 5α-dihydrotestosterone is metabolized to the weak androgen 5α-androstane-3α, 17ß-diol (3α-diol) by the enzyme aldo-keto reductase family 1, member C14 (Akr1c14) in rodents. The purpose of the present study was to investigate the regulation of Akr1c14 expression during the ovulatory process in rat ovaries. Northern blot analysis revealed that treatment of immature rats with equine chorionic gonadotropin resulted in lowered Akr1c14 expression, whereas subsequent treatment with human chorionic gonadotropin (hCG) increased ovarian Akr1c14 expression within 3 h. In situ hybridization analysis showed that Akr1c14 mRNA was localized in granulosa cells of growing follicles before hCG treatment, but it was also expressed in granulosa cells of preovulatory follicles after hCG treatment. Akr1c14 protein expression increased after 6 h of hCG treatment and was sustained at high levels until 12 h. The levels of 3α-diol in preovulatory follicles isolated from ovaries in vivo were fluctuated by hCG treatment; decreased at 6 h and increased at 9 h. Human CG-induced Akr1c14 expression was suppressed by treatment with the progesterone receptor antagonist RU486, but not with the cyclooxygenase inhibitor indomethacin. Taken together, these findings demonstrate the induction of Akr1c14 by hCG in granulosa cells of rat preovulatory follicles that was regulated by progesterone receptor antagonist.

Polycystic ovarian syndrome (PCOS), related symptoms/sequelae, and breast cancer risk in a population-based case-control study.

PURPOSE: Despite the overlap between the clinical symptoms/sequelae of polycystic ovarian syndrome (PCOS) and many known reproductive risk factors for breast cancer, the relationship between PCOS and breast cancer remains unclear, possibly because of the complex heterogeneity and challenges in diagnosing PCOS over time. We hypothesized that PCOS, specific PCOS-related symptoms/sequelae, or clusters of PCOS-related symptoms/sequelae may be differentially associated with pre- versus postmenopausal breast cancer risk. MATERIALS AND METHODS: Cases were 1,508 women newly diagnosed with a first primary in situ or invasive breast, and the 1,556 population-based controls were frequency-matched by age. RESULTS: History of physician-diagnosed PCOS was reported by 2.2 % (n = 67), among whom oral contraceptive (OC) use, irregular menstruation, and infertility due to ovulatory dysfunction were common. Using unconditional logistic regression, adjusted odds ratios (95 % CI) for PCOS were increased for premenopausal [2.74 (1.13, 6.63)], but not postmenopausal breast cancer [0.87 (0.44, 1.71)]. We used cluster analysis to investigate whether risk among all women varied by PCOS-related symptoms/sequelae, such as reproductive irregularities, OC use, and components of insulin resistance. In the cluster analysis, odds ratios were elevated among premenopausal women who had a history of OC use and no ovulatory dysfunction [1.39 (1.03, 1.88)], compared to those with fewer number of PCOS-related symptoms/sequelae. CONCLUSION: PCOS and associated PCOS-related symptoms/sequelae including OC use may play a role in the development of premenopausal breast cancer. Our findings require confirmation in studies with a larger number of premenopausal women with systematically applied diagnostic criteria for PCOS.

Young female cancer survivors' use of fertility care after completing cancer treatment.

PURPOSE: The purpose of the present study is to investigate factors associated with female young adult cancer survivors' (YCSs) use of fertility care (FC), including consultation or fertility treatment, after completing their cancer treatment. METHODS: In this cross-sectional study, females between that ages of 18 and 35 years who had been diagnosed with childhood, adolescent, or young adult cancers completed a 20-min web-based survey that included demographics, reproductive history, use of FC, fertility-related informational needs, and reproductive concerns. RESULTS: A total of 204 participants completed the survey. Participants' mean age was 28.3 ± 4.5 years. Thirty (15 %) participants reported using FC after cancer treatment. The majority of participants recalled not receiving enough information about fertility preservation options at the time of cancer diagnosis (73 %). In multivariable analysis, those with higher concerns about having children because of perceived risk to their personal health (P = 0.003) were less likely to report use of FC after cancer treatment. Those who had used FC before cancer treatment (P = 0.003) and who felt less fertile than age-matched women (P = 0.02) were more likely to use FC after their cancer treatment. CONCLUSIONS: While most YCSs in this cohort believed that they did not receive enough information about fertility and most wanted to have children, the vast majority did not seek FC. The findings of this study offer further evidence of the need for improved education and emotional support regarding reproductive options after cancer treatment is completed. Targeted discussions with YCSs about appropriate post-treatment FC options may improve providers' capacity to help YCSs meet their parenthood goals.

Early referral makes the decision-making about fertility preservation easier: a pilot survey study of young female cancer survivors.

PURPOSE: The purpose of the study was to investigate the association between patients' decision-making about fertility preservation (FP) and time between cancer diagnosis and FP consultation in young female cancer survivors. METHODS: This is a pilot survey study of women aged 18-43 years seen for FP consultation between April 2009 and December 2010. RESULTS: Among 52 women who completed the survey, 15 (29 %) had their FP consultation more than 2 weeks after their cancer diagnosis (late referral group) and 37 (71 %) were within 2 weeks of their cancer diagnosis (early referral group). In univariate analysis, the only difference between the late referral and early referral groups was a higher decisional conflict scale (DCS) in late referral group (p = 0.04). In multivariable analysis, late referral group was more likely to have high DCS (>35) compared to early referral group (odds ratio 4.8, 95 % confidence interval 1.5, 21.6) after adjusting for age, center, and type of cancer. CONCLUSION: Early referral to a fertility specialist can help patients make better decision about FP. This is the first study to suggest that early referral is important in patients' decision-making process about FP treatment. Our finding supports the benefit of early referral in patients who are interested in FP which is consistent with prior studies about FP referral patterns.

Fertility preservation in patients with haematological disorders: a retrospective cohort study.

This study investigated the factors associated with utilization of fertility preservation and the differences in treatments and outcomes by prior chemotherapy exposure in patients with haematological diseases. This study included all 67 women with haematological diseases seen for fertility preservation consultation at two university hospitals between 2006 and 2011. Of the total, 49% had lymphoma, 33% had leukaemia, 7% had myelodysplastic syndrome and 4% had aplastic anaemia; 46% had prior chemotherapy; and 33% were planning for bone marrow transplantation, 33% pursued ovarian stimulation and 7% used ovarian tissue banking; and 48% of patients did not pursue fertility preservation treatment. All five cycle cancellations were in the post-chemotherapy group: three patients with leukaemia and two with lymphoma. Patients with prior chemotherapy had lower baseline antral follicle count (10 versus 22) and received more gonadotrophins to achieve similar peak oestradiol concentrations, with no difference in oocyte yield (10.5 versus 10) after adjustment for age. Embryo yield was similar between those who had prior chemotherapy and those who had not. Half of the patients with haematological diseases who present for fertility preservation have been exposed to chemotherapy. While ovarian reserve is likely impaired in this group, oocyte yield may be acceptable.

Regioisomer-dependent endo- and exocyclic coordination of bis-dithiamacrocycles.

Syntheses of the regioisomers of bis-dithiamacrocycle and the regioisomer-controlled endo- and exocyclic coordination behaviors are reported. Direct bis-cyclization reaction of 1,2,4,5-tetra(bromomethyl)benzene with 3,6-dioxa-1,8-octanedithiol led to a mixture of two bis-dithiamacrocycle regioisomers (ortho-type; o-bis-L and meta-type; m-bis-L) which were separated by recrystallization and column chromatography. When the two isomers were reacted with AgPF6, o-bis-L gave an endocyclic one-dimensional (1-D) coordination polymer {[Ag3(o-bis-L)2(CH3CN)](PF6)3·2CH3CN}n (1) with a 3:2 (metal-to-ligand) stoichiometry, while m-bis-L afforded an exocoordination-based 1-D polymeric complex {[Ag(m-bis-L)](PF6)}n (2) with a 2:2 stoichiometry. The observed endo- and exocoordination modes depending on the isomers were discussed in terms of the S···S distances in the bis-dithiamacrocycle isomers. Due to the closer S···S distance in each macrocyclic ring, o-bis-L is suitable for the endocoordination. However, m-bis-L forms an exocyclic complex because the S···S distance between two macrocyclic rings is shorter than that in one macrocyclic ring. NMR experiments also revealed that o-bis-L and m-bis-L form the endo- and the exocyclic complexes, respectively, in solution.

Distortional supramolecular isomers of polyrotaxane coordination polymers: photoreactivity and sensing of nitro compounds.

Distortional isomers, or bond-stretch isomers, differ only in the length of one or more bonds, which is due to crystallographic disorder in most cases. The term distortional isomerism is introduced to describe the structures of polyrotaxane 2D coordination polymers (CPs) that differ only by the relative positions in the neighboring entangled axles. A large ring and a long spacer ligand in 2D CPs yielded four different supramolecular isomers, of which two have an entangled polyrotaxane structure. One pair of C=C bonds in the spacer ligand is well-aligned in one isomer and undergoes [2+2] cycloaddition reaction, whereas the other isomer is photoinert. They also have different sensing efficiency for several aromatic nitro compounds. However, both isomers show selective PL quenching for the Brady's reagent. Structurally similar supramolecular isomers with different photochemical reactivity and sensing abilities appear to be unprecedented.

Skin-Attached Arrayed Piezoelectric Sensors for Continuous and Safe Monitoring of Oculomotor Movements.

Abnormal oculomotor movements are known to be linked to various types of brain disorders, physical/mental shocks to the brain, and other neurological disorders, hence its monitoring can be developed into a simple but effective diagnostic tool. To overcome the limitations in the current eye-tracking system and electrooculography, a piezoelectric arrayed sensor system is developed using single-crystalline III-N thin-film transducers, which offers advantages of mechanical flexibility, biocompatibility, and high electromechanical conversion, for continuous monitoring of oculomotor movements by skin-attachable, safe, and highly sensitive sensors. The flexible piezoelectric eye movement sensor array (F-PEMSA), consisting of three transducers, is attached to the face temple area where it can be comfortably wearable and can detect the muscles' activity associated with the eye motions. Output voltages from upper, mid, and lower sensors (transducers) on different temple areas generate discernable patterns of output voltage signals with different combinations of positive/negative signs and their relative magnitudes for the various movements of eyeballs including 8 directional (lateral, vertical, and diagonal) and two rotational movements, which enable various types of saccade and pursuit tests. The F-PEMSA can be used in clinical studies on the brain-eye relationship to evaluate the functional integrity of multiple brain systems and cognitive processes.