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STUDY QUESTION How do oocyte donors and recipients perceive the genetic link related to the transfer of nuclear DNA between donors and offspring? SUMMARY ANSWER Whether they are donors or recipients, individuals attach great importance to the transmission of their genetic heritage, since 94.5% would opt for the pronuclear transfer method to preserve this genetic link in the context of oocyte donation. WHAT IS KNOWN ALREADY Since 1983, the use of oocyte donation has increased worldwide. Performed in France since the late 1980s and initially offered to women with premature ovarian insufficiency, its indications have progressively expanded and now it is proposed in many indications to prevent the transmission of genetically inherited diseases. This has resulted in an increase in the waiting time for access to oocyte donation due to the difficulty in recruiting oocyte donors in French ART centres. Several articles have discussed how to fairly distribute donor oocytes to couples, but few have interviewed women in the general population to record their feelings about oocyte donation, as either the donor or recipient and the importance given to the genetic link between the oocyte donors and the children born. Mitochondrial replacement therapy (MRT) is a technique originally developed for women at risk of transmitting a mitochondrial DNA mutation. Recently, MRT has been considered for embryo arrest and oocyte rejuvenation as it could help females to reproduce with their own genetic material through the transfer of their oocyte nucleus into a healthy donor oocyte cytoplasm. STUDY DESIGN, SIZE, DURATION We conducted an opinion survey from January 2021 to December 2021, during which 1956 women completed the questionnaire. Thirteen participants were excluded from the analysis due to incomplete responses to all the questions. Consequently, 1943 women were included in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS We specifically developed a questionnaire for this study, which was created and distributed using the Drag'n Survey® software. The questionnaire consisted of 21 items presented alongside a video created with whiteboard animation software. The aim was to analyse whether certain factors, such as age, education level, marital status, number of children, use of ART for pregnancy, video viewing, and knowledge about oocyte donation, were associated with feelings towards oocyte donation, by using a univariate conditional logistic regression model. This statistical method was also used to assess whether women would be more inclined to consider oocyte donation with the pronuclear transfer technique rather than the whole oocyte donation. All parameters found to be statistically significant in the univariate analysis were subsequently tested in a multivariate model using logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE Most women were concerned about the biological genetic contribution of the donated oocyte (94.8%). The most common reason for a women's reluctance to donate their oocytes was their unwillingness to pass on their genetic material (33.3%). Nearly 70% of women who were initially hesitant to donate their oocytes indicated that they would reconsider their decision if the oocyte donation was conducted using donated cytoplasm and the pronuclear transfer technique. Concomitantly, >75% of the respondents mentioned that it would be easier to receive a cytoplasm donation. The largest proportion of the population surveyed (94.5%) expressed their support for its legalization. LIMITATIONS, REASONS FOR CAUTION In this study, a substantial portion of the responses came from individuals with medical or paramedical backgrounds, potentially introducing a recruitment bias among potential donors. The rate of missing responses to the question regarding the desire to become an oocyte donor was 13.6%, while the question about becoming an oocyte cytoplasm donor had a missing response rate of 23%. These missing responses may introduce a bias in the interpretation of the data. WIDER IMPLICATIONS OF THE FINDINGS This study was the first to demonstrate that, for the French population studied, the combination of oocyte cytoplasm donation with pronuclear transfer could offer a promising approach to enhance the acceptance of oocyte donation for both the donor and the recipient. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used for this study. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

The surge in online self-administered surveys has given rise to an extensive body of literature on respondent inattention, also known as careless or insufficient effort responding. This burgeoning literature has outlined the consequences of inattention and made important strides in developing effective methods to identify inattentive respondents. However, differences in terminology, as well as a multiplicity of different methods for measuring and correcting for inattention, have made this literature unwieldy. We present an overview of the current state of this literature, highlighting commonalities, emphasizing key debates, and outlining open questions deserving of future research. Additionally, we emphasize the key considerations that survey researchers should take into account when measuring attention. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does mitochondrial deficiency affect human embryonic preimplantation development? SUMMARY ANSWER The presence of a pathogenic mitochondrial variant triggers changes in the gene expression of preimplantation human embryos, compromising their development, cell differentiation, and survival. WHAT IS KNOWN ALREADY Quantitative and qualitative anomalies of mitochondrial DNA (mtDNA) are reportedly associated with impaired human embryonic development, but the underlying mechanisms remain unexplained. STUDY DESIGN, SIZE, DURATION Taking advantage of the preimplantation genetic testing for mitochondrial disorders in at-risk couples, we have compared gene expression of 9 human embryos carrying pathogenic variants in either mtDNA genes or nuclear genes encoding mitochondrial protein to 33 age-matched control embryos. PARTICIPANTS/MATERIALS, SETTING, METHODS Single-embryo transcriptomic analysis was performed on whole human blastocyst embryos donated to research. MAIN RESULTS AND THE ROLE OF CHANCE Specific pathogenic mitochondrial variants downregulate gene expression in preimplantation human embryos [566 genes in oxidative phosphorylation (OXPHOS)-deficient embryos], impacting transcriptional regulators, differentiation factors, and nuclear genes encoding mitochondrial proteins. These changes in gene expression primarily alter OXPHOS and cell survival pathways. LIMITATIONS, REASONS FOR CAUTION The number of OXPHOS-deficient embryos available for the study was limited owing to the rarity of this material. However, the molecular signature shared by all these embryos supports the relevance of the findings. WIDER IMPLICATIONS OF THE FINDINGS While identification of reliable markers of normal embryonic development is urgently needed in ART, our study prompts us to consider under-expression of the targeted genes reported here, as predictive biomarkers of mitochondrial dysfunction during preimplantation development. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the 'Association Française contre les Myopathies (AFM-Téléthon)' and the 'La Fondation Maladies Rares'. No competing interests to declare. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Can ovarian tissue cryopreservation (OTC) be performed after controlled ovarian hyperstimulation (COH)? SUMMARY ANSWER Unilateral oophorectomy after transvaginal oocyte retrieval is feasible on stimulated ovaries during one surgical step. WHAT IS KNOWN ALREADY In the fertility preservation (FP) field, the timeframe between patient referral and start of curative treatment is limited. Combining oocyte pick-up with ovarian tissue (OT) extraction has been reported to improve FP but COH applied before OT extraction is not currently recommended. STUDY DESIGN, SIZE, DURATION This retrospective cohort-controlled study involved 58 patients who underwent oocyte cryopreservation immediately followed by OTC between September 2009 and November 2021. The exclusion criteria were a delay between oocyte retrieval and OTC of >24 h (n = 5) and IVM of oocytes obtained ex vivo in the ovarian cortex (n = 2). This FP strategy was performed either after COH (stimulated group, n = 18) or after IVM (unstimulated group, n = 33). PARTICIPANTS/MATERIALS, SETTING, METHODS Oocyte retrieval followed by OT extraction on the same day was performed either without previous stimulation or after COH. Adverse effects of surgery and ovarian stimulation, mature oocyte yield and pathology findings of fresh OT were retrospectively analysed. Thawed OTs were analysed prospectively, for vascularization and apoptosis using immunohistochemistry, when patient consent was obtained. MAIN RESULTS AND THE ROLE OF CHANCE No surgical complication occurred after OTC surgery in either group. In particular, no severe bleeding was associated with COH. The number of mature oocytes obtained increased after COH (median = 8.5 (25% = 5.3–75% = 12.0)) compared to the unstimulated group (2.0 (1.0–5.3), P  <  0.001). Neither ovarian follicle density nor cell integrity was affected by COH. Fresh OT analysis showed congestion in half of the stimulated OT which was higher than in the unstimulated OT (3.1%, P  <  0.001). COH also increased haemorrhagic suffusion (COH + OTC: 66.7%; IVM + OTC: 18.8%, P  = 0.002) and oedema (COH + OTC: 55.6%; IVM + OTC: 9.4%, P  <  0.001). After thawing, the pathological findings were similar between both groups. No statistical difference in the number of blood vessels was observed between the groups. The oocyte apoptotic rate in thawed OT was not statistically different between the groups (ratio of positive cleaved caspase-3 staining oocytes/total number of oocytes equal to median 0.50 (0.33–0.85) and 0.45 (0.23–0.58) in unstimulated and stimulated groups respectively, P  =  0.720). LIMITATIONS, REASONS FOR CAUTION The study reports FP from a small number of women following OTC. Follicle density and other pathology findings are an estimate only. WIDER IMPLICATIONS OF THE FINDINGS Unilateral oophorectomy can be successfully performed after COH with limited bleeding risk and an absence of impact on thawed OT. This approach could be proposed to post pubertal patients when the number of mature oocytes expected is low or when the risk of residual pathology is high. The reduction of surgical steps for cancer patients also has positive implications for introducing this approach into clinical practice. STUDY FUNDING/COMPETING INTEREST(S) This work was made possible through the support of the reproductive department of Antoine-Béclère Hospital and of the pathological department of Bicêtre Hospital (Assistance Publique Hôpitaux de Paris, France). The authors have no conflict of interest to disclose in this study. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

When investors sell one asset and quickly buy another ("reinvestment days"), their trades suggest the original mental account is not closed, but is instead rolled into the new asset. Retail investors trading on their own accounts display a rolled disposition effect, selling the new position when its value exceeds the initial investment in the original position. On reinvestment days, these investors display no disposition effect (consistent with no disutility from realizing a loss) and make better selling decisions. Using a laboratory experiment, we show that reinvestment causally reduces the disposition effect and improves trading. [ABSTRACT FROM AUTHOR]

We experimentally test a theory of risky choice in which the perception of a lottery payoff is noisy due to information processing constraints in the brain. We model perception using the principle of efficient coding, which implies that perception is most accurate for those payoffs that occur most frequently. Across two preregistered laboratory experiments, we manipulate the distribution from which payoffs in the choice set are drawn. In our first experiment, we find that risk taking is more sensitive to payoffs that are presented more frequently. In a follow-up task, we incentivize subjects to classify which of two symbolic numbers is larger. Subjects exhibit higher accuracy and faster response times for numbers they have observed more frequently. In our second experiment, we manipulate the payoff distribution so that efficient coding modulates the strength of valuation biases. As we experimentally increase the frequency of large payoffs, we find that subjects perceive the upside of a risky lottery more accurately and take greater risk. Together, our experimental results suggest that risk taking depends systematically on the payoff distribution to which the decision maker's perceptual system has recently adapted. More broadly, our findings highlight the importance of imprecise and efficient coding in economic decision making. [ABSTRACT FROM AUTHOR]

We use neural data collected from an experimental asset market to measure regret preferences while subjects trade stocks. When subjects observe a positive return for a stock they chose not to purchase, a regret signal is observed in an area of the brain that is commonly active during reward processing. Subjects are unwilling to repurchase stocks that have recently increased in price, even though this is suboptimal in our experiment. The strength of stock repurchasing mistakes is correlated with the neural measures of regret. Subjects with high rates of repurchasing mistakes also exhibit large disposition effects. [ABSTRACT FROM AUTHOR]

Study Question: What are the chances of obtaining a healthy transferable cleavage-stage embryo according to the number of mature oocytes in fragile X mental retardation 1 (FMR1)-mutated or premutated females undergoing preimplantation genetic testing (PGT)?Summary Answer: In our population, a cycle with seven or more mature oocytes has an 83% chance of obtaining one or more healthy embryos.What Is Known Already: PGT may be an option to achieve a pregnancy with a healthy baby for FMR1 mutation carriers. In addition, FMR1 premutation is associated with a higher risk of diminished ovarian reserve and premature ovarian failure. The number of metaphase II (MII) oocytes needed to allow the transfer of a healthy embryo following PGT has never been investigated.Study Design, Size, Duration: The study is a monocentric retrospective observational study carried out from January 2006 to January 2020 that is associated with a case-control study and that analyzes 38 FMR1 mutation female carriers who are candidates for PGT; 16 carried the FMR1 premutation and 22 had the full FMR1 mutation.Participants/materials, Setting, Methods: A total of 95 controlled ovarian stimulation (COS) cycles for PGT for fragile X syndrome were analyzed, 49 in premutated patients and 46 in fully mutated women. Only patients aged ≤38 years with anti-Müllerian hormone (AMH) >1 ng/ml and antral follicle count (AFC) >10 follicles were eligible for the PGT procedure. Each COS cycle of the FMR1-PGT group was matched with the COS cycles of partners of males carrying any type of translocation (ratio 1:3). Conditional logistic regression was performed to compare the COS outcomes. We then estimated the number of mature oocytes needed to obtain at least one healthy embryo after PGT using receiver operating characteristic curve analysis.Main Results and the Role Of Chance: Overall, in the FMR1-PGT group, the median number of retrieved and mature oocytes per cycle was 11 (interquartile range 7-15) and 9 (6-12), respectively. The COS outcomes of FMR1 premutation or full mutation female carriers were not altered compared with the matched COS cycles in partners of males carrying a balanced translocation in their karyotype. Among the 6 (4-10) Day 3 embryos obtained in the FMR1-PGT group, a median number of 3 (1-6) embryos were morphologically eligible for biopsy, leading to 1 (1-3) healthy embryo. A cutoff value of seven MII oocytes yielded a sensitivity of 82% and a specificity of 61% of having at least one healthy embryo, whereas a cutoff value of 10 MII oocytes led to a specificity of 85% and improved positive predictive value.Limitations, Reasons For Caution: This study is retrospective, analyzing a limited number of cycles. Moreover, the patients who were included in a fresh PGT cycle were selected on ovarian reserve parameters and show high values in ovarian reserve tests. This information could influence our conclusion.Wider Implications Of the Findings: The results relate only to the target population of this study, with a correct ovarian reserve of AMH >1 and AFC >10. However, the information provided herein extends knowledge about the current state of COS for FMR1 mutation carriers in order to provide patients with proper counseling regarding the optimal number of oocytes needed to have a chance of transferring an unaffected embryo following PGT.Study Funding/competing Interest(s): None.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Interval-censored data analysis is important in biomedical statistics for any type of time-to-event response where the time of response is not known exactly, but rather only known to occur between two assessment times. Many clinical trials and longitudinal studies generate interval-censored data; one common example occurs in medical studies that entail periodic follow-up. In this article, we propose a survival forest method for interval-censored data based on the conditional inference framework. We describe how this framework can be adapted to the situation of interval-censored data. We show that the tuning parameters have a non-negligible effect on the survival forest performance and guidance is provided on how to tune the parameters in a data-dependent way to improve the overall performance of the method. Using Monte Carlo simulations, we find that the proposed survival forest is at least as effective as a survival tree method when the underlying model has a tree structure, performs similarly to an interval-censored Cox proportional hazards model fit when the true relationship is linear, and outperforms the survival tree method and Cox model when the true relationship is nonlinear. We illustrate the application of the method on a tooth emergence data set. [ABSTRACT FROM AUTHOR]

We analyze the long-run trends in executive compensation using a new dataset of top officers of large firms from 1936 to 2005. The median real value of compensation was remarkably flat from the late 1940s to the 1970s, revealing a weak relationship between pay and aggregate firm growth. By contrast, this correlation was much stronger in the past thirty years. This historical perspective also suggests that compensation arrangements have often helped to align managerial incentives with those of shareholders because executive wealth was sensitive to firm performance for most of our sample. These new facts pose a challenge to several common explanations for the rise in executive pay since the 1980s. [ABSTRACT FROM PUBLISHER]

Middle-school-age children are faced with a variety of developmental tasks, including the beginning phases of individuation from the family, building peer groups, social and emotional transitions, and cognitive shifts associated with the maturation process. This article summarizes how traumatic events impair and complicate these developmental tasks, which can lead to disruptive behaviors in the school setting. Following the call by Walkley and Cox for more attention to be given to trauma-informed schools, this article provides detailed information about the Animating Learning by Integrating and Validating Experience program: a school-based, trauma-informed intervention for middle school students. This public health model uses psychoeducation, cognitive differentiation, and brief stress reduction counseling sessions to facilitate socioemotional development and academic progress. Case examples from the authors' clinical work in the New Haven, Connecticut, urban public school system are provided. [ABSTRACT FROM AUTHOR]

Study Question: How can pre-meiotic germ cells persist in the human foetal ovary?Summary Answer: Numerous oogonia escaping meiotic entry were retrieved throughout human ovarian development simultaneously with the expression of signalling pathways preventing meiosis, typically described in the rodent embryonic testis.What Is Known Already: The transition from mitosis to meiosis is a key event in female germ cells that remains poorly documented in research on the human ovary. Previous reports described a strikingly asynchronous differentiation in the human female germ line during development, with the persistence of oogonia among oocytes and follicles during the second and third trimesters. The possible mechanisms allowing some cells to escape meiosis remain elusive.Study Design Size, Duration: In order to document the extent of this phenomenon, we detailed the expression profile of germ cell differentiation markers using 73 ovaries ranging from 6.4 to 35 weeks post-fertilization.Participants/materials Setting, Methods: Pre-meiotic markers were detected by immunohistochemistry or qRT-PCR. The expression of the main meiosis-preventing factors identified in mice was analysed, and their functionality assessed using organ cultures.Main Results and the Role Of Chance: Oogonia stained for AP2γ could be traced from the first trimester until the end of the third trimester. Female germ cell differentiation is organized both in time and space in a centripetal manner in the foetal human ovary. Unexpectedly, some features usually ascribed to rodent pre-spermatogonia could be observed in human foetal ovaries, such as NANOS2 expression and quiescence in some germ cells. The two main somatic signals known to inhibit meiosis in the mouse embryonic testis, CYP26B1 and FGF9, were detected in the human ovary and act simultaneously to repress STRA8 and meiosis in human foetal female germ cells.Large Scale Data: N/A.Limitations Reason For Caution: Our conclusions relied partly on in vitro experiments. Germ cells were not systematically identified with immunostaining and some may have thus escaped analysis.Wider Implications Of the Findings: We found evidence that a robust repression of meiotic entry is taking place in the human foetal ovary, possibly explaining the exceptional long-lasting presence of pre-meiotic germ cells until late gestational age. This result calls for a redefinition of the markers known as classical male markers, which may in fact characterize mammalian developing gonads irrespectively of their sex.Study Funding/competing Interest(s): This research was supported by the Université Paris Diderot-Paris 7 and Université Paris-Sud, CEA, INSERM, and Agence de la Biomédecine. The authors declare no conflict of interest. [ABSTRACT FROM AUTHOR]

BACKGROUND Oocyte maturation and competence to development depends on its close relationship with cumulus cells (CCs). However, the maturation conditions of human cumulus–oocyte complexes (COCs) might affect gene expression in both oocyte and CCs. We thus compared the transcriptome profiles of CCs isolated from in vivo and in vitro matured COCs at different nuclear maturation stages. METHODS Three groups of CCs from patients who underwent ICSI were included: CCs of patients with polycystic ovary syndrome (PCOS) referred for in vitro maturation (IVM), CCs from patients with PCOS for in vivo maturation (used as controls) and CCs from normal responders referred for in vivo maturation. CCs were isolated from COCs at the germinal vesicle, metaphase I and metaphase II stages. Microarray technology was used to analyse the global gene expression and significance analysis of microarray to compare the expression profiles of CCs from COCs at different nuclear maturation stages following IVM or in vivo maturation. Selected genes were validated by RT-qPCR. RESULTS In CCs isolated after IVM, genes related to cumulus expansion and oocyte maturation, such as EREG, AREG and PTX3, were down-regulated, while cell cycle-related genes were up-regulated in comparison with CCs from in vivo matured COCs from PCOS and normal responder patients. Moreover, irrespective of the stage of oocyte maturation, genes involved in DNA replication, recombination and repair were up-regulated in CCs after IVM. CONCLUSIONS The CC transcriptomic signature varies according to both the oocyte maturation stage and the maturation conditions. Our findings suggest a delay in the acquisition of the mature CC phenotype following IVM, opening a new perspective for the improvement in IVM conditions. [ABSTRACT FROM AUTHOR]

Background: The initiation of meiosis is crucial to fertility. While extensive studies in rodents have enhanced our understanding of this process, studies in human fetal ovary are lacking. Methods: We used RT-PCR and immunohistochemistry to investigate expression of meiotic factors in human fetal ovaries from 6 to 15 weeks post fertilization (wpf) and developed an organ culture model to study the initiation of human meiosis. Results: We observed the first meiotic cells at 11 wpf, when STRA8, SPO11 and DMC1 are first expressed. In culture, meiosis initiation is observed in 10 and 11 wpf ovaries and meiosis is maintained by addition of fetal calf serum. Meiosis is stimulated, compared with control, by retinoic acid (RA) (P < 0.05). No major change occurred in mRNA for CYP26B1, the RA-degrading enzyme proposed to control the timing of meiosis in mice. We did, however, observe increased mRNA levels for ALDH1A1 in human ovary when meiosis began, and evidence for a requirement to synthesize RA and thus sustain meiosis. Indeed, ALDH inhibition by citral prevented the appearance of meiotic cells. Finally, 8 wpf ovaries (and earlier stages) were unable to initiate meiosis whatever the length of culture, even in the presence of RA and serum. However, when human germ cells from 8 wpf ovaries were placed in a mouse ovarian environment, some did initiate meiosis. Conclusions: Our data indicate that meiosis initiation in the human ovary relies partially on RA, but that the progression and regulation of this process appears to differ in many aspects from that described in mice. [ABSTRACT FROM AUTHOR]

BACKGROUND: Myotonic dystrophy (MD) is characterized by myotonia, multisystemic lesions and hypogonadism. In women, the relationship between MD and infertility remains controversial. This study investigated the ovarian status and response to controlled ovarian stimulation (COS) in MD women entering our preimplantation genetic diagnosis programme. METHODS: We elected to compare MD patients with X-linked disorders (XLD) carriers, given that XLD have not been shown to affect ovarian status. On the one hand, we analysed all the cycles performed and, on the other hand, we conducted a subanalysis based on only first cycles. RESULTS: MD and XLD groups were similar with regard to women’s ages, day 3 parameters, number of oocytes retrieved, embryos obtained and prevalence of top quality embryos. The day of HCG was significantly delayed and the prevalence of poor quality embryos was higher in the MD group. The subanalysis on first cycles only also showed significantly fewer mature follicles on the day of HCG in MD population. Implantation and pregnancy rates were similar in both groups; however, no pregnancy occurred at the first cycle in MD (0 out of 4), whereas 77% of pregnancies (10/13) occurred at the first attempt in XLD carriers. CONCLUSIONS: These results indicate that the responsiveness to COS was moderately hindered in MD women as compared to controls. Reassuring data about implantation and pregnancy rates support the feasibility of PGD in selected mildly affected MD women. [ABSTRACT FROM AUTHOR]

BACKGROUND: To investigate the dynamics of serum anti-Mllerian hormone (AMH) levels during the luteal phase of controlled ovarian hyperstimulation (COH) and its possible association with follicle development. METHODS: We prospectively studied 34 women undergoing COH with GnRH agonist and FSH. On the day of hCG (dhCG), serum AMH, estradiol (E2), progesterone and hCG levels were measured, and ovarian follicles were sorted into three size classes: <12, 1215 and 1622?mm. Hormonal measurements were repeated 4 days (hCG+4) and 7 days (hCG+7) after hCG. RESULTS: From dhCG to hCG+4, we observed a decline in serum AMH levels (-643%; P<0.0001), which paralleled that of E2 levels. From hCG+4 to hCG+7, an increase in AMH levels occurred (8228%; P<0.02), whose magnitude was correlated with the number of

BACKGROUND: In vitro oocyte maturation (IVM) permits the use of immature oocytes in IVF. IVM does not require ovarian stimulation and so can be offered to patients at risk of ovarian hyperstimulation syndrome. METHODS: For this indication, we carried out 45 cycles of IVM in 33 women with polycystic ovarian syndrome (PCOS). RESULTS: A total of 509 cumulusoocyte complexes was obtained; 276 (54.2%) oocytes matured in 24?h and 45 (8.8%) in 48?h. The normal fertilization (2PN) rate of oocytes matured in 24 and 48?h was 69.5 and 73.3% respectively. Among the 214 embryos obtained, 103 were transferred and 30 were frozen. Forty transfers were performed (2.5 embryos/transfer). Eleven women had a positive -hCG test (26.2% of pregnancies/puncture, 27.5% of pregnancies/transfer) and nine women had a clinical pregnancy (20.0% of pregnancies/puncture, 22.5% of pregnancies/transfer). Five babies have been born and one pregnancy is ongoing. Results of the clinical examination carried out at birth were normal. CONCLUSIONS: Our results show that IVM may be offered as an alternative to conventional IVF and to ovarian drilling in women with PCOS. The role of IVM in the therapeutic armamentarium for this condition should be further clarified. [ABSTRACT FROM AUTHOR]

BACKGROUND: Most implantation failures after successful in vitro fertilization-embryo transfer (IVF-ET) result from inadequate uterine receptivity. There is currently no way to predict this receptivity. METHODS: We investigated whether the detection of interleukin-(IL)18 by ELISA in uterine luminal secretions might predict implantation failure. Secretions of 133 patients enrolled in our IVF-ET program were sampled by uterine flushing immediately before oocyte retrieval. We assessed the following outcomes: pregnancy rate, multiple pregnancy rate, and implantation rate per embryo transferred. RESULTS: Interleukin-18 was detected in the flushing fluid of 38 patients (28.6%). Although the two groups were comparable for all other characteristics (age, etiology, ovarian reserve, number of embryos transferred, quality of embryos), all outcome variables differed significantly. The pregnancy rate was 37.9% in the IL-18 −ve group and 15% in the IL-18 + ve group, the multiple pregnancy rate 27.7% and 0%, and the implantation rate per embryo transferred 19.4% and 6.7% (all comparisons, P=0.02). Only embryos meeting good quality criteria were transferred to 65 patients: 50 IL-18 −ve and 15 IL-18 +ve. The pregnancy rate was 51% for the IL-18 −ve group and 20% for the IL-18 +ve group, the multiple pregnancy rate 36% and 0.0%, respectively, and the implantation rate 29% and 8.3% (P=0.02). CONCLUSION: This non-invasive and simple method predicted inadequate uterine receptivity, independent of embryo quality. [ABSTRACT FROM AUTHOR]

BACKGROUND: The purpose of this study was to investigate whether luteal estradiol (E2) administration reduces follicular size discrepancies and enhances ovarian response in recombinant FSH (r-FSH)/GnRH antagonist protocols. METHODS: We studied prospectively 90 IVF-embryo transfer (ET) candidates who were randomly pre-treated with 17β-E2 (4 mg/day) from day 20 until next cycle day 2 (E2 group, n = 47) or served as controls (control group, n = 43). On day 3, all women started r-FSH treatment. A single 3 mg dose of GnRH antagonist was administered eventually according to follicular maturation. Outcome measures were magnitude of size discrepancy of growing follicles on day 8 of r-FSH treatment and number of follicles ≥16 mm in diameter on the day of HCG. RESULTS: On day 8, follicles were smaller (9.9 ± 2.5 versus 10.9 ± 3.4 mm, P < 0.001) and their size discrepancies attenuated (P < 0.001) in the E2 group compared with the control group. This was associated with more ≥16 mm follicles, mature oocytes and embryos in the E2 group. CONCLUSIONS: Luteal E2 administration reduces the pace of growth, improves size homogeneity of antral follicles on day 8 of r-FSH treatment and increases the number of follicles reaching maturation at once. Coordination of follicular development optimizes ovarian response to r-FSH/GnRH antagonist protocols and may constitute an attractive approach to improving their outcome. [ABSTRACT FROM AUTHOR]

With an incidence of approximately 1 in 500 male newborns, the 47,XXY genotype is one the most common sex chromosome anomalies. It is also the most frequent genetic cause of human infertility. Some non-mosaic 47,XXY patients have sperm production which allows infertility treatment to be offered by ICSI. Therefore, the risk of transmitting a chromosome anomaly to the next generation is an important problem in reproductive genetic counselling of these patients. Here, we report on a twin pregnancy where two karyotypically normal neonates 46,XX and 46,XY were born after the use of ICSI in assisted reproduction of a patient with a non-mosaic 47,XXY syndrome. To date, only 38 evolving pregnancies including the present cases, have been reported after ICSI using sperm from non-mosaic 47,XXY patients. Although these data are scarce, they suggest that the risk of chromosome anomaly in the offspring of these patients is low; hence, their reproductive genetic counselling can be reassuring, and management of the pregnancy can proceed with caution. [ABSTRACT FROM AUTHOR]

Background: Twin birth weight discordance is associated with a poor perinatal outcome. The aim of this study was to analyse the risk factors of growth discordance among dichorionic twin pregnancies.Methods: A cohort of 346 dichorionic twin pregnancies delivered at one perinatal centre between January 1996 and December 1999 was analysed. Two groups were created, according to the presence or absence of intra-pair birth weight discordance (n = 75 and 271 respectively). Birth weight discordance was defined as a difference of >/=20% of the weight of the heavier twin. The two groups were compared by uni- and multivariate analysis, with regard to the woman's characteristics, risk factors for growth restriction or discordance, and outcome of pregnancy.Results: Pregnancies with birth weight discordance had a poor outcome compared with pregnancies without discordance, with a 4-fold increase in neonatal mortality. The rate of iatrogenic embryo reduction was significantly higher in discordant pregnancies (14.7 versus 6.6%, P = 0.03). The risk of birth weight discordance was increased with a larger starting number of embryos before reduction [20.2% (64/317), 28.6% (6/21), 57.1% (4/7) and 100% (1/1) respectively, for an initial number of two (no reduction), three, four, and five embryos, P = 0.02]. In multivariate analysis, embryo reduction was the only significant risk factor for the occurrence of birth weight discordance [adjusted odds ratio (OR) = 2.3 (1.0-5.2)].Conclusions: Birth weight discordance carries a poor perinatal outcome. Embryo reduction is an independent risk factor for birth weight discordance in dichorionic twins. This finding emphasises the need for better control of assisted reproductive technology in order to avoid high-order multiple pregnancies. [ABSTRACT FROM AUTHOR]

Background: The study aim was to investigate possible changes in serum anti-Müllerian hormone (AMH) levels during controlled ovarian hyperstimulation (COH), and their possible relationship with follicular development and other ovarian hormones.Methods: A total of 93 women undergoing COH with GnRH agonist and FSH was studied prospectively. Serum levels of AMH, inhibin B, estradiol (E(2)), progesterone, testosterone and Delta(4)-androstenedione were measured when pituitary suppression was achieved (baseline), on days 6 and 8 of FSH treatment, and on the day of hCG. The number of small (<12 mm) and large (>/=12 mm) antral follicles were estimated using ultrasound.Results: Serum AMH levels declined progressively (baseline, 1.21 +/- 0.11 ng/ml; day 6, 0.91 +/- 0.09 ng/ml; day 8, 0.77 +/- 0.08 ng/ml; and day of hCG, 0.53 +/- 0.06 ng/ml), whereas-as expected-the other hormone levels increased during FSH treatment. Throughout COH, serum AMH levels correlated positively with the number of small but not large antral follicles, and with inhibin B serum levels. No correlation between AMH and the other hormones was observed.Conclusions: Serum AMH levels decline gradually during multiple follicular maturation, probably reflecting the dramatic reduction in the number of small antral follicles due to COH, and confirming the scarce AMH expression by larger follicles. [ABSTRACT FROM AUTHOR]

Background: The study aim was to compare the relationship between serum anti-Müllerian hormone (AMH) levels and other markers of ovarian function with early antral follicle count on day 3.Methods: A total of 75 infertile women was studied prospectively. On cycle day 3, serum levels of AMH, inhibin B, estradiol (E(2)), FSH and LH levels were measured, and the number of early antral follicles (2-10 mm in diameter) estimated at ultrasound scanning to compare the strengths of hormonal-follicular correlations.Results: Median (range) serum levels of AMH, inhibin B, E(2), FSH and LH were 1.39 ng/ml (0.24-6.40), 90 (16-182) pg/ml, 31 (15-111) pg/ml, 7.0 (2.9-19.3) mIU/ml and 4.7 (1.2-11.7) mIU/ml respectively, and follicular count was 12 (1-35). Serum AMH levels were more strongly correlated (P < 0.001) with follicular count (r = 0.74, P < 0.0001) than were serum levels of inhibin B (r = 0.29, P < 0.001), E(2) (r = -0.08, P = NS), FSH (r = -0.29, P < 0.001) and LH (r = 0.05, P = NS).Conclusions: Serum AMH levels were more robustly correlated with the number of early antral follicles than inhibin B, E(2), FSH and LH on cycle day 3. This suggests that AMH may reflect ovarian follicular status better than the usual hormone markers. [ABSTRACT FROM AUTHOR]

Study Question: Are in vitro maturation (IVM) rates of cumulus-oocyte complexes (COCs), retrieved from breast cancer patients seeking urgent fertility preservation (FP) before neoadjuvant chemotherapy, different between those recovered in the follicular or in the luteal phase of the cycle?Summary Answer: The present investigation reveals no major difference in the number of COCs recovered or their IVM rates whatever the phase of the cycle at which egg retrieval is performed, suggesting that IVM is a promising tool for breast cancer patients seeking urgent oocyte cryopreservation.What Is Known Already: FP now represents a standard of care for young cancer patients having to undergo gonadotoxic treatment. Mature oocyte cryopreservation after IVM of COCs has been proposed for urgent FP, especially in women, who have no time to undergo ovarian stimulation, or when it is contraindicated.Study Design, Size, Duration: From January 2011 to December 2014, we prospectively studied 248 breast cancer patients awaiting neoadjuvant chemotherapy, aged 18-40 years, candidates for oocyte vitrification following IVM, either at the follicular or the luteal phase of the cycle.Participants/materials, Setting, Methods: Serum anti-Müllerian hormone and progesterone levels and antral follicle count (AFC) were measured prior to oocyte retrieval. Patients were sorted into two groups according to the phase of the cycle during which eggs were harvested (Follicular phase group, n = 127 and Luteal phase group, n = 121). Number of COCs recovered, maturation rates after 48 h of culture and total number of oocytes cryopreserved were assessed. Moreover, the oocyte retrieval rate (ORR) was calculated by the number of COCs recovered ×100/AFC.Main Results and the Role Of Chance: In the Follicular and the Luteal phase groups, women were comparable in terms of age, BMI and markers of follicular ovarian status. There was no significant difference in the number of COCs recovered (mean ± SEM), 9.3 ± 0.7 versus 11.1 ± 0.8, and ORR (median (range)) 43.1 (1-100) versus 47.8 (7.7-100)%. Moreover, maturation rates after 48 h of culture (median (range)) were comparable in the follicular and luteal phase groups, 66.7 (20-100) versus 64.5 (0-100)%. Finally, the total number of oocytes cryopreserved (mean ± SEM) was similar in both groups (6.2 ± 0.4 versus 6.8 ± 0.5).Limitations, Reasons For Caution: Despite the intact meiotic competence of immature oocytes recovered during the follicular or the luteal phase, there is a dramatic lack of data regarding the outcome of IVM oocytes cryopreserved in cancer patients.Wider Implications Of the Findings: IVM of oocytes may be an interesting method of FP in urgent situations. Improving the culture conditions will be needed to increase the maturation rates and the overall potential of in vitro matured oocytes.Study Funding/competing Interests: None.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: Couples with a risk of transmitting X-linked diseases who are included in a preimplantation genetic diagnosis (PGD) programme need early and rapid fetal sex determination in two situations. The first situation is for the control of embryo sexing after PGD and the second situation is for those couples having a spontaneous pregnancy before the start of their PGD cycle. Among invasive techniques, chorionic villus sampling is the earliest procedure for fetal sex determination and molecular analysis of X-linked genetic disorders during the first trimester but it is associated with a risk of fetal loss. Non-invasive procedures such as ultrasound examination allow reliable fetal sex determination only during the second trimester. Reliable fetal sex determination can now be realised by using SRY gene amplification in maternal blood.Methods and Results: We report the use of fetal sex determination from maternal serum as a diagnostic tool for the control of embryo sexing (two cases) and to manage spontaneous pregnancies in couples included in a PGD programme for X-linked diseases (five cases). Fetal sex determination using SRY gene amplification in maternal serum were in complete concordance with fetal sex observed by cytogenetic analysis or ultrasound examination and at birth. This novel strategy allowed the PGD results to be controlled precociously and avoided the performance of invasive procedures in four cases of female fetus.Conclusions: This rapid fetal sex determination during the first trimester provides advantages to both clinicians and patients in a PGD centre. [ABSTRACT FROM AUTHOR]

Background: In order to provide better genetic counselling for Robertsonian translocation carriers, the meiotic segregation of chromosomes 13, 14 and 21 from six infertile (13;14) and (14;21) Robertsonian translocation carriers was examined.Methods: Dual-colour fluorescence in-situ hybridization analysis using locus-specific probes was carried out on spermatozoa of translocation carriers. Spermatozoa from six proven fertile subjects were analysed using the same probes as controls.Results: We observed that the frequencies of unbalanced spermatozoa were similar in the (13;14) translocation carriers (9.0, 10.0 and 12.9%) and in the (14;21) translocation carriers (8.7, 7.2 and 7.0%). These frequencies were significantly increased compared with the control population (P < 0.05).Conclusions: This high frequency might justify the use of preimplantation genetic diagnosis in these patients where the translocation is usually associated with infertility, requiring intracytoplasmic sperm injection, as it might improve the outcome of the assisted reproduction technique. [ABSTRACT FROM AUTHOR]

High-frequency uterine contractions at the time of non-cavitating embryo transfer influence adversely IVF–embryo transfer outcome. This prompted us to quantify prospectively the possible decline in uterine contraction frequency occurring during later stages of the luteal phase of ovarian stimulation, up to the time of blastocyst transfers, in 43 IVF–embryo transfer candidates. Contractility was assessed on the day of human chorionic gonadotrophin (HCG) administration, 4 days after HCG (non-cavitating embryo transfer; HCG + 4), and 7 days after HCG (blastocyst transfers; HCG + 7). For this, 2 min sagittal uterine scans were obtained by ultrasound and digitized with a computerized system for the assessment of uterine contraction frequency. Our results indicated that a slight, yet significant, decrease in uterine contraction frequency, observed from the day of HCG (4.4 ± 0.2 contractions/min) to HCG + 4 (3.5 + 0.2 contractions/min), was followed by a more pronounced, additional decrease between HCG + 4 and HCG + 7 (1.5 ± 0.2 contractions/min; P < 0.001). In conclusion, during the luteal phase of ovarian stimulation, uterine contractility decreases progressively, and reaches a nearly quiescent status 7 days after HCG administration, at the time of blastocyst transfers. It is possible that such a uterine relaxation assists blastocyst implantation. [ABSTRACT FROM PUBLISHER]

We studied 98 in-vitro fertilization (IVF) patients with a high basal follicle stimulating hormone (FSH;>6.5 IU/I) concentration on day 3 who were treated with a low dose gonadotrophin-releasing hormone agonist (GnRHa) protocol and who had received in the previous 6 months a long protocol with GnRHa in a depot formula. The evaluation was made using the previous IVF cycle of the same patient as a control. The mean ± SD age of the patients was 34.1 ± 4.2 years. The use of a low dose agonist protocol ended with significantly less ampoules (37.5 versus 46.1), a shorter duration of stimulation (10.7 versus 12.3 days), a higher oestradiol concentration on day 8 (1068 versus 495 pg/ml), a higher number of mature oocytes (5.9 versus 4.4) and a higher number of good quality embryos (3.3 versus 2.3). The cancellation rate was lower (11 versus 24%). A GnRHa low dose protocol may be the protocol of choice for patients with high FSH concentrations on day 3. Larger randomized studies are needed to confirm these data. [ABSTRACT FROM PUBLISHER]

Sperm–zona binding, sperm–oocyte penetration and pronucleus formation in oocytes obtained after in-vitro fertilization (IVF) failure were studied by analysing DNA fluorescence. Oocytes were classified according to their maturational status, sperm–zona pellucida binding and sperm–oocyte penetration. Spermatozoa were classified as normal or abnormal according to conventional parameters. Sperm–zona binding and sperm–oocyte penetration into uncleaved oocytes were positively related to fertilization: 6.2% of those oocytes from cohorts where none of the oocytes fertilized had >10 spermatozoa bound to the zona, and 7.7% of them were penetrated. When at least one oocyte per cohort fertilized, these rates were 37.1 and 41.1% respectively. Sperm–zona binding is related more strongly to sperm-oocyte penetration, even without pronucleus formation, than to the maturational status of the oocyte: 26.9% of the oocytes were penetrated by spermatozoa, of which 20.7% had reached the pronuclear stage. For 25 out of 78 couples with a total IVF failure, whatever the spermiogram, defective sperm–zona binding, sperm–oocyte penetration or pronucleus formation was observed. Sperm–zona binding and penetration were positively related, especially when oocytes came from patients with partial IVF failure. Clinical information concerning the fertilizing capacity of oocytes and spermatozoa after IVF failure can be obtained by the simultaneous analysis of sperm–zona binding and sperm–oocyte penetration, and whether or not the latter results in pronucleus formation. [ABSTRACT FROM PUBLISHER]

Six patients with interstitial pregnancies were treated with systemic or local injections of methotrexate, 15 mg i.m. daily for 5 days, or 1 mg/kg for 1 day. One dose of folinic acid rescue (50 mg) was administered on the first day of the treatment course. Diagnosis of interstitial pregnancy was established either by laparoscopy or transvaginal ultrasound. Out of six patients, five had serial measurements of serum human chorionic gonadotrophin (HCG), progesterone (P) and 17β-oestradiol (E) until either the ectopic pregnancy resolved or surgery was performed. For one patient operated on day 1 after medical treatment, no serial serum measurements were performed. Serum HCG became undetectable under medical treatment in only four of the six patients. Out of these four patients, three had an initial level of HCG <1000 mIU/ml. Two patients underwent surgery (salpingectomy) because either the level of serum HCG did not decrease after the course of methotrexate therapy or it was required the next day to stop haemorrhage. In these patients, the initial level of HCG at the time of diagnosis, was 5300 and 43 000 mJU/ml, respectively. In the four patients who received conservative medical treatment only, the next menstrual period occurred 20–46 days after the onset of methotrexate and was preceded by luteal activity. A control hysterosalpingography performed 2 months later showed that in the four patients who received medical treatment only, the Fallopian tube was patent, and three became pregnant within 1 year of the methotrexate therapy. One of two patients who failed to respond to medical treatment and required surgical treatment, became pregnant 6 months later. Our results suggest that methotrexate is a viable alternative to surgery for interstitial pregnancies. When the initial level of serum HCG is <1000 mIU/ml, the chances that medical treatment will succeed are increased. This suggests therefore that conservative management of interstitial pregnancies with methotrexate can be considered in selected cases, as is currently the position for the more common tubal pregnancies. [ABSTRACT FROM PUBLISHER]

The gonadotrophic regulation of folliculogenesis has been extensively investigated but little attention has been paid to the influence of early follicular phase levels of endogenous FSH and the FSH/LH ratio when planning ovulation stimulation therapy for IVF. The influence of these factors was investigated in the three studies reported in this paper. A fixed schedule of ovulation stimulation therapy which employed standard treatment regimens, irrespective of the ovarian response, was used to eliminate variation due to treatment factors. Cycles were pretreated with an oestrogen-progestogen contraceptive pill or a progestogen (norethister one). It was found that both oestrogen-progestogen and progestogen alone decreased the plasma FSH level, although the FSH/LH ratio was significantly reduced only by oestrogen-progestogens. In clinical IYF studies, oestrogen-progestogen pretreatment was associated with a significant reduction in the preovulatory concentration of oestradiol in plasma and the number of aspirated follicles, compared to norethisterone. The administration of FSH for 2 days following oestrogen-progestogen pretreatment and prior to the fixed schedule of ovulation stimulation normalized ovarian steroidogenesis and follicular development. Early follicular phase supplementation with FSH had no influence on progestogen pretreated cycles. The final experiment investigated the influence of FSH/LH levels in the early folticular phase on the outcome of ovarian stimulation. The preovulatory oestradiol concentration was reduced when baseline FSH/LH levels were low compared with when these values were high. Administration of FSH for 2 days in the early follicular phase improved the preovulatory level of oestradiol when baseline FSH/LH was low but had no effect when baseline FSH/LH levels were high. It is concluded that the response to administered ovarian stimulants is governed by the FSH/LH ratio prior to stimulation and that when this value is low, it can be augmented, and the ovarian response subsequently improved, by administering FSH prior to ovulation stimulation therapy. These results may have implications for clinical IVF programmes. [ABSTRACT FROM PUBLISHER]

Two theoretical literatures, one using Bayesian Nash equilibrium (BNE), and the other using noisy rational expectations equilibrium (NREE), both provide a foundation for understanding how private information is impounded into asset prices, yet some of their predictions are conflicting. Here, we compare for the first time, the two theories using data from carefully controlled laboratory asset markets. In the dynamics, we find strong evidence for BNE theory, although final prices support predictions of the NREE theory. Finally, we document that price volatility increases when information is being impounded in prices. [ABSTRACT FROM PUBLISHER]

Background: Since in rodents anti-Müllerian hormone (AMH) has been shown to inhibit antral follicle responsiveness to FSH, we aimed at verifying whether a relationship exists between serum AMH levels and antral follicle responsiveness to exogenous FSH in normo-cycling women. Methods: Serum AMH, estradiol (E(2)) and FSH levels were prospectively measured on cycle day 3 in patients undergoing controlled ovarian hyperstimulation (COH) with a time-release GnRH agonist and standardized FSH doses. In 162 patients, follicles were counted after pituitary suppression and before FSH administration (baseline; small antral follicles; 3-8 mm), and on the day of hCG (dhCG; pre-ovulatory follicles; 16-22 mm). Antral follicle responsiveness to FSH was estimated by the Follicular Output RaTe (FORT), determined by the ratio pre-ovulatory follicle count on dhCG × 100/small antral follicle count at baseline. Results: Serum AMH levels were positively correlated with the number of small antral follicles at baseline (r = 0.59; P < 0.0001) and pre-ovulatory follicles on dhCG (r = 0.17; P < 0.04). Overall, FORT was 47.5 ± 1.4% and failed to be influenced by the woman's age, BMI or basal E(2) and FSH level. Conversely, multiple regression analysis showed that FORT was negatively correlated with AMH levels (r = -0.30; P < 0.001), irrespective of duration of COH and total FSH dose. Conclusions: The percentage of follicles that effectively respond to FSH by reaching pre-ovulatory maturation is negatively and independently related to serum AMH levels. Although the mechanisms underlying this finding remain unclear, it is in keeping with the hypothesis that AMH inhibits follicle sensitivity to FSH. [ABSTRACT FROM AUTHOR]

This essay examines the portrayal of African diasporic culture in the Southern U.S. through an exploration of oral tradition by anthropologist Zora Neale Hurston. Relations between black and white, northerners and southerners, and educated and uneducated African Americans are discussed. The role of literacy and of the textualization of African American oral traditions in Hurston's life and work are also explored.

In recent years, a large academic debate has tried to explain the rapid rise in CEO pay experienced over the past three decades. In this article, I review the main proposed theories, which span views of compensation as the result of a competitive labor market for executives to theories based on excess of managerial power. Some of these hypotheses have found support in cross-sectional evidence, but it has proven more difficult to determine which factors have caused the observed changes in pay over time. An alternative strategy is to evaluate the fit of plausible explanations out of sample by contrasting them with the evolution in executive pay and the market for managers during earlier time periods. A case study of General Electric suggests that evidence for earlier decades can speak of the recent trends and reveals the limitations of current explanations to address the long-run data. (JEL codes: G30, J33, M52, N82) [ABSTRACT FROM PUBLISHER]

In many clinical trials patients are intermittently assessed for the transition to an intermediate state, such as occurrence of a disease-related nonfatal event, and death. Estimation of the distribution of nonfatal event free survival time, that is, the time to the first occurrence of the nonfatal event or death, is the primary focus of the data analysis. The difficulty with this estimation is that the intermittent assessment of patients results in two forms of incompleteness: the times of occurrence of nonfatal events are interval censored and, when a nonfatal event does not occur by the time of the last assessment, a patient's nonfatal event status is not known from the time of the last assessment until the end of follow-up for death. We consider both forms of incompleteness within the framework of an “illness–death” model. We develop nonparametric maximum likelihood (ML) estimation in an “illness–death” model from interval-censored observations with missing status of intermediate transition. We show that the ML estimators are self-consistent and propose an algorithm for obtaining them. This work thus provides new methodology for the analysis of incomplete data that arise from clinical trials. We apply this methodology to the data from a recently reported cancer clinical trial ( Bonner et al., 2006 , New England Journal of Medicine 354, 567–578) and compare our estimation results with those obtained using a Food and Drug Administration recommended convention. [ABSTRACT FROM AUTHOR]

Background: We have previously shown that male human fetal germ cells are highly radiosensitive and that their death depends on p53 activation. Male germ cell apoptosis was initiated with doses as low as 0.1 Gy and was prevented by pifithrin alpha, a p53 inhibitor. In this study, we investigated the radiosensitivity of early female and male fetal proliferating germ cells.Methods and Results: Both male and female fetal germ cells displayed a similar number of gamma H2AX foci in response to ionizing radiation (IR). In organ culture of human fetal ovaries, the germ cells underwent apoptosis only when exposed to high doses of IR (1.5 Gy and above). Accumulation of p53 was detected in irradiated male human fetal germ cells but not in female ones. Inhibition of p53 with pifithrin alpha did not affect oogonia apoptosis following irradiation. IR induced apoptosis similarly in mouse fetal ovaries in organ culture and in vivo during oogonial proliferation. Germ cell survival in testes from p53 knockout or p63 knockout mice exposed to IR was better than wild-type, whereas female germ cell survival was unaffected by p53 or p63 knockout.Conclusions: These findings show that pre-meiotic male and female fetal germ cells behave differently in response to a genotoxic stress--irradiation--with oogonia being less sensitive and undergoing p53-independent apoptosis. [ABSTRACT FROM AUTHOR]

Background: The accurate assessment of FSH concentration is important for evaluating ovarian function prior to IVF. However, a number of different assay techniques are currently in use, leading to inconsistencies in the hormone data being reported. To address this problem, we measured FSH concentration using a number of commercially available systems.Methods: Day 3 serum FSH levels were measured in 215 healthy fertile women using six different immunoassays: Coatria (125)I (Bio-Mérieux), ACS-180 (Bayer Diagnostics), Advia-Centaur (Bayer Diagnostics), Vitros ECi (Ortho-Clinical Diagnostics), Architect i2000 (Abbott) and Elecsys 2010 (Roche Diagnostics).Results: According to the immunoassay, means +/- SD of FSH concentrations were: 6.5 +/- 2.2 mIU/ml for Coatria (125)I, 6.8 +/- 2.7 mIU/ml for Advia-Centaur, 6.7 +/- 3.0 mIU/ml for Vitros ECi, 7.6 +/- 3.0 mIU/ml for ACS-180, 8.2 +/- 3.3 mIU/ml for Architect i2000 and 8.8 +/- 3.0 mIU/ml for Elecsys 2010.Conclusion: Day 3 FSH values determined by six different immunoassays were significantly different (P < 0.01, paired t-test). Physicians must take care when interpreting results from different clinical laboratories. [ABSTRACT FROM AUTHOR]