Leaked BlackBerry Radio, App World, Podcasts, & News App For OS 6

The guys over at BBH-Plus got their hands on a 6.1 OS and have been busy all afternoon leaking the applications found in the OS including: BlackBerry Radio, Visual Voicemail, App World, Podcasts, and  News. UPDATE: Added Facebook for BlackBerry

NOTE: The applications are only for OS 6.0,  they will not work on other devices as far as we know.

If you get errors about BBID .cods missing, Install this OTA:
http://www.bbh-plus.net/downloads.php?do=file&id=2044

If you get errors about BBID .cods missing, Install this OTA:
http://www.bbh-plus.net/downloads.php?do=file&id=2044

Thanks to Tashana and Fubaz for sending this in.

Source: BBH PLUS

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Do polymorphic variants of chromosomes affect the outcome of in vitro fertilization and embryo transfer treatment?

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Y. Hong1, Y.-W. Zhou1, J. Tao2, S.-X. Wang2 and X.-M. Zhao1,*

1Department of Reproductive Medicine, Renji Hospital of Shanghai Jiaotong University, Shanghai 200001, China

2Pediatric Medicine Research Institute, Xinhua Hospital of Shanghai Jiaotong University, Shanghai 200092, China *Correspondence address. E-mail: zhao_xiao_ming{at}hotmail.comReceived November 15, 2009. Revision received October 7, 2010. Accepted November 8, 2010. BACKGROUND The aim of this study was to investigate the effect of chromosomal polymorphic variations on the outcome of IVF and embryo transfer (IVF–embryo transfer) treatment for infertile couples.

METHODS During the period from October 2006 to December 2009, 1978 infertile couples who had received their first IVF–embryo transfer treatment cycle in our hospital were selected for this retrospective study, and the frequency of chromosomal polymorphic variations was calculated. From these, 1671 couples were selected and divided into three groups: 1402 couples with normal chromosomes (Group 1/control group), 82 couples with chromosomal polymorphic variations in only females (Group 2) and 187 couples with chromosomal polymorphic variations in only males (Group 3). The clinical pregnancy rates (CPR), early miscarriage rates and ongoing pregnancy rates after IVF–embryo transfer treatment were compared.

RESULTS There were no statistically significant differences among the three groups in implantation rates (29.37% in the control group, 29.70% in Group 2 and 31.41% in Group 3, P > 0.05) and CPR (45.86, 46.34 and 51.87%, respectively, P > 0.05). Although there was a trend toward higher first trimester pregnancy loss rates in Group 3 (male chromosomal polymorphic variations), but not in Group 2, compared with normal karyotype couples (10.31 versus 6.84%), the difference did not reach significance (P > 0.05).

CONCLUSIONS Chromosomal polymorphic variations appear to have no adverse effects on the outcome of IVF–embryo transfer treatment.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

This ArticleHum. Reprod. (2011) 26 (4): 933-940. doi: 10.1093/humrep/deq333 First published online: January 25, 2011

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PGD for a complex chromosomal rearrangement by array comparative genomic hybridization

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E. Vanneste1,2, C. Melotte1, T. Voet1, C. Robberecht1, S. Debrock2, A. Pexsters3, C. Staessen4, C. Tomassetti2, E. Legius1, T. D'Hooghe2 and J.R. Vermeesch1,*

1Center for Human Genetics, UZ Gasthuisberg, 3000 Leuven, Belgium

2Leuven University Fertility Center, UZ Gasthuisberg, 3000 Leuven, Belgium

3Department of Obstetrics and Gynaecology, UZ Gasthuisberg 3000 Leuven, Belgium

4Center for Medical Genetics, University Hospital Brussels, 1090 Brussels, Belgium *Correspondence address. E-mail: joris.vermeesch{at}uzleuven.beReceived July 16, 2010. Revision received December 20, 2010. Accepted January 7, 2011. Patients carrying a chromosomal rearrangement (CR) have an increased risk for chromosomally unbalanced conceptions. Preimplantation genetic diagnosis (PGD) may avoid the transfer of embryos carrying unbalanced rearrangements, therefore increasing the chance of pregnancy. Only 7–12 loci can be screened by fluorescence in situ hybridization whereas microarray technology can detect genome-wide imbalances at the single cell level. We performed PGD for a CR carrier with karyotype 46,XY,ins(3;2)(p23;q23q14.2),t(6;14)(p12.2;q13) using array comparative genomic hybridization. Selection of embryos for transfer was only based on copy number status of the chromosomes involved in both rearrangements. In two ICSI–PGD cycles, nine and seven embryos were analysed by array, leaving three and one embryo(s) suitable for transfer, respectively. The sensitivity and specificity of single cell arrays was 100 and 88.8%, respectively. In both cycles a single embryo was transferred, resulting in pregnancy following the second cycle. The embryo giving rise to the pregnancy was normal/balanced for the insertion and translocation but carried a trisomy 8 and nullisomy 9 in one of the two biopsied blastomeres. After 7 weeks of pregnancy the couple miscarried. Genetic analysis following hystero-embryoscopy showed a diploid (90%)/tetraploid (10%) mosaic chorion, while the gestational sac was empty. No chromosome 8 aneuploidy was detected in the chorion, while 8% of the cells carried a monosomy for chromosome 9. In summary, we demonstrate the feasibility and determine the accuracy of single cell array technology to test against transmission of the unbalanced meiotic products that can derive from CRs. Our findings also demonstrate that the genomic constitution of extra-embryonic tissue cannot necessarily be predicted from the copy number status of a single blastomere.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 941-949. doi: 10.1093/humrep/der004 First published online: February 2, 2011

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Reply: In situ identification of follicles in ovarian cortex as a tool for quantifying follicle density, viability and developmental potential in strategies to preserve female fertility

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Haplotype analysis of chemokine CXCL12 polymorphisms and susceptibility to premature ovarian failure in Chinese women

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Binbin Wang1,2,†, Peisu Suo1,2,†, Beili Chen3, Zhaolian Wei2, Lu Yang3, Sirui Zhou1,2, Jing Wang1,2, Yunxia Cao3 and Xu Ma1,2,4,*

1Center for Genetics, National Research Institute for Family Planning, 12, Dahuisi Road, Haidian, Beijing 100081, China

2Peking Union Medical College, Beijing, China

3Reproductive Medicine Center, First Affiliated Hospital, Anhui Medical University, Hefei, China

4World Health Organization Collaborating Centre for Research in Human Reproduction, Beijing, China *Correspondence address. Tel: +86-10-62176870; Fax: +86-10-62179151; E-mail: genetic{at}263.net.cn?† These authors contributed equally to the work.

Received June 5, 2010. Revision received December 19, 2010. Accepted January 5, 2011. BACKGROUND Chemokine (C-X-C motif) ligand 12 (CXCL12/stromal cell-derived factor 1) has been suggested to play an essential role in primordial germ cell migration, colonization and survival, and in the primordial to primary follicle transition. This study was performed to investigate an association of polymorphisms in CXCL12 with the risk of premature ovarian failure (POF) in Chinese patients.

METHODS Tagging single nucleotide polymorphisms (SNPs) were selected using the Chinese HapMap database. Five SNPs (rs4948878, rs1801157, rs266087, rs266093 and rs1029153) were genotyped by direct sequencing in 111 patients with POF and 183 healthy controls recruited from the First Affiliated Hospital, Anhui Medical University, China.

RESULTS Compared with controls, there were significantly higher frequencies of the rs1801157 A allele and haplotype C-T-A-T-T in cases with POF [P = 6.38E-07, odds ratio (OR) = 3.10, 95% confidence interval (CI) 1.955–4.890 by allele; P = 7.0E-04, OR = 2.39, 95% CI 1.43–3.97 by haplotype]. No differences were observed for the other four SNPs between POF cases and controls.

CONCLUSIONS A strong association between a CXCL12 polymorphism and POF was established in Chinese patients, suggesting that CXCL12 might be a new candidate gene involved in POF. The A allele of CXCL12 polymorphism rs1801157 is a possible risk factor for developing POF. However, further independent studies are necessary to confirm our findings.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 950-954. doi: 10.1093/humrep/der001 First published online: February 4, 2011

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The association of maternal factors with delayed implantation and the initial rise of urinary human chorionic gonadotrophin

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A.M.Z. Jukic1,*, C.R. Weinberg2, D.D. Baird1 and A.J. Wilcox1

1Epidemiology Branch, National Institute of Environmental Health Sciences, PO Box 12233, MD A3-05, Durham, NC 27709, USA

2Biostatistics Branch, National Institute of Environmental Health Sciences, PO Box 12233, MD A3-05, Durham, NC 27709, USA *Correspondence address. E-mail: jukica{at}niehs.nih.govReceived August 4, 2010. Revision received January 5, 2011. Accepted January 11, 2011. BACKGROUND Late implantation and the pattern of early rise in hCG have been associated with early pregnancy loss. We explored factors that might be predictive of these markers of poor embryonic health in spontaneously conceived pregnancies.

METHODS Participants in the North Carolina Early Pregnancy Study collected daily first-morning urine specimens while attempting to conceive. Samples were assayed for estrogen and progesterone metabolites (to identify day of ovulation) and hCG (to detect conception). Data were available for 190 pregnancies, 48 of which ended in early loss (within 6 weeks of the last menstrual period). We used logistic regression to identify characteristics associated with late implantation (=10 days post-ovulation). For pregnancies surviving at least 6 weeks (n= 142), we used linear mixed models to identify factors associated with variations in hCG rise in the first 7 days from detection.

RESULTS Later implantation was associated with current maternal smoking [odds ratio (OR): 5.7; 95% confidence interval (CI): 1.1–30] and with oocytes that were likely to have been fertilized late in their post-ovulatory lifespan (OR: 5.1; CI: 1.9–16). Older women had a faster rise in hCG (P= 0.01), as did women who had relatively late menarche (P for trend = 0.02). Women exposed in utero to diethylstilbestrol showed an unusual pattern of slow initial hCG rise followed by a fast increase, a pattern significantly different from that of unexposed women (P= 0.002).

CONCLUSIONS Although limited by small numbers and infrequent exposures, our analyses suggest that a woman's exposures both early in life and at the time of pregnancy may influence early development of the conceptus.

Published by Oxford University Press 2011This ArticleHum. Reprod. (2011) 26 (4): 920-926. doi: 10.1093/humrep/der009 First published online: February 2, 2011

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Constitutional change of Italian legislation on assisted reproduction technology improves pregnancy rate especially in older patients

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Paola Scaruffi1, Maria Rita Primavera1, Luiza Helena Abbamonte1, Shanti Levi1, Caterina De Leo2, Annamaria Nicoletti1 and Paola Anserini1,*

1Center of Physiopathology of Human Reproduction, Department of Obstetrics and Gynecology, ‘San Martino’ Hospital, L.go R. Benzi, 10, 16132 Genova, Italy

2Department of Obstetrics and Gynecology, University of Genova, Genova, Italy *Correspondence address. Tel: +39-010-5555843; Fax: +39-010-5556909; E-mail: paola.anserini{at}hsanmartino.itSir,

In February 2004, the Italian Parliament approved a law (namely 40/2004) regulating assisted reproduction technology ( Benagiano and Gianaroli, 2004). This law imposed many limitations on Italian reproductive specialists. The most important of these restrictions was the provision that no more than three oocytes could be fertilized at one time during an IVF treatment, since all embryos obtained had to be transferred simultaneously. On May 2009, the Italian Constitutional Court outlawed some restrictions set out in the 40/2004 law ( Benagiano and Gianaroli, 2010). The most important point of the ruling is that embryo protection is limited by the imperative to ensure a concrete possibility to achieve a successful pregnancy. The Court also strongly reaffirmed the supremacy of the physician's judgment in carrying out a full evaluation and a personalized treatment plan for each woman and couple. Therefore, Italian reproductive specialists can now define an individualized optimal number of embryos to give the best chance of achieving a pregnancy while limiting the number of cryopreserved embryos.

The recently published article by Levi Setti et al. (2010) reported a retrospective analysis of 3274 IVF cycles, comparing fresh cycles before and after the 40/2004 law was modified. No significant difference was found between the two groups in terms of patients’ age, basal FSH levels, …

This ArticleHum. Reprod. (2011) 26 (4): 959-961. doi: 10.1093/humrep/der014 First published online: February 11, 2011

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Dietary iron intake during early pregnancy and birth outcomes in a cohort of British women

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Nisreen A. Alwan1,*, Darren C. Greenwood2, Nigel A.B. Simpson3, Harry J. McArdle4, Keith M. Godfrey5,6 and Janet E. Cade1

1Nutritional Epidemiology Group, Centre for Epidemiology and Biostatistics, School of Food Science and Nutrition, University of Leeds, Leeds, LS2 9JT, UK

2Division of Biostatistics, Centre for Epidemiology and Biostatistics, University of Leeds, Leeds, UK

3Department of Obstetrics and Gynaecology, University of Leeds, Leeds, UK

4Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK

5MRC Lifecourse Epidemiology Unit, Southampton, UK

6NIHR Nutrition, Diet & Lifestyle Biomedical Research Unit, Southampton, UK *Correspondence address. Tel: +44-113-343-6990; Fax: +44-113-343-4877; E-mail: n.alwan{at}leeds.ac.ukReceived October 10, 2010. Revision received November 13, 2010. Accepted December 20, 2010. BACKGROUND Iron deficiency during pregnancy is associated with adverse birth outcomes, particularly, if present during early gestation. Iron supplements are widely recommended during pregnancy, but evidence of their benefit in relation to infant outcomes is not established. This study was performed in the UK, where iron supplements are not routinely recommended during pregnancy, to investigate the association between iron intake in pregnancy and size at birth.

METHODS From a prospective cohort of 1274 pregnant women aged 18–45 years, dietary intake was reported in a 24-h recall administered by a research midwife at 12-week gestation. Dietary supplement intake was ascertained using dietary recall and three questionnaires in the first, second and third trimesters.

RESULTS Of the cohort of pregnant women, 80% reported dietary iron intake below the UK Reference Nutrient Intake of 14.8 mg/day. Those reported taking iron-containing supplements in the first, second and third trimesters were 24, 15 and 8%, respectively. Women with dietary iron intake >14.8 mg/day were more likely to be older, have a higher socioeconomic profile and take supplements during the first trimester. Vegetarians were less likely to have low dietary iron intake [odds ratio = 0.5, 95% confidence interval (CI): 0.4, 0.8] and more likely to take supplements during the first and second trimesters. Total iron intake, but not iron intake from food only, was associated with birthweight centile (adjusted change = 2.5 centiles/10 mg increase in iron, 95% CI: 0.4, 4.6). This association was stronger in the high vitamin C intake group, but effect modification was not significant.

CONCLUSION There was a positive relationship between total iron intake, from food and supplements, in early pregnancy and birthweight. Iron intake, both from diet and supplements, during the first trimester of pregnancy was higher in vegetarians and women with a better socioeconomic profile.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

This ArticleHum. Reprod. (2011) 26 (4): 911-919. doi: 10.1093/humrep/der005 First published online: February 7, 2011

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Anti-Mullerian hormone in short girls born small for gestational age and the effect of growth hormone treatment

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A.J. Lem1,2,*, V.H. Boonstra2, J.S. Renes2, P.E. Breukhoven2, F.H. de Jong3, J.S.E. Laven4 and A.C.S. Hokken-Koelega1,2

1Dutch Growth Research Foundation, P.O. Box 23068, 3001 KB Rotterdam, The Netherlands

2Division of Endocrinology, Department of Paediatrics, Sophia Children's Hospital, Erasmus MC, 3000 CA Rotterdam, The Netherlands

3Division of Endocrinology, Department of Internal Medicine, Erasmus MC, 3000 CA Rotterdam, The Netherlands

4Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Erasmus MC, 3000 CA Rotterdam, The Netherlands *Correspondence address. Tel: +31-10-22-515-33; Fax: +31-10-22-501-33; E-mail: a.lem{at}kindengroei.nlReceived October 8, 2010. Revision received November 18, 2010. Accepted December 14, 2010. Background Fetal growth restriction is thought to negatively influence reproductive function in later life. Serum anti-Müllerian hormone (AMH) is a marker of the primordial follicle pool. The objectives of this study were to evaluate the effect of being born small for gestational age (SGA) on serum AMH levels and to investigate the effect of growth hormone (GH) treatment on serum AMH levels in short SGA girls.

METHODS Serum AMH levels were investigated in 246 prepubertal girls aged 3–10 years: 119 untreated short SGA and 127 healthy controls. Associations between AMH levels and clinical characteristics were analysed using multiple regression analyses. In addition, we investigated the effect of GH treatment on serum AMH levels in short SGA girls.

RESULTS Serum AMH levels were similar in short SGA and healthy control girls (P= 0.95). In short SGA girls, AMH levels were not significantly influenced by birth weight standard deviation score (SDS), birth length SDS and gestational age, even after adjustment for age, height SDS and body mass index (BMI) SDS at sampling, socio-economic status and maternal smoking during gestation. Serum AMH levels did not change during 4 years of GH treatment in short SGA girls (P= 0.43).

ConclusionS Serum AMH levels in prepubertal short SGA girls are similar to healthy controls, indicating that the follicle pool is not compromised due to SGA birth. GH treatment has no effect on AMH levels in short SGA girls.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 898-903. doi: 10.1093/humrep/deq391 First published online: January 12, 2011

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Fibroids not encroaching the endometrial cavity and IVF success rate: a prospective study

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Edgardo Somigliana1,*, Silvia De Benedictis1,2, Paolo Vercellini1,2, Anna Elisa Nicolosi1, Laura Benaglia1,2, Claudia Scarduelli1, Guido Ragni1 and Luigi Fedele1,2

1Department of Obset/Gynecol-Fondazione Cà Granda, Ospedale Maggiore Policlinico, Via Commenda 12, 20122 Milano, Italy

2Università degli Studi di Milano, Milan, Italy *Correspondence address. Tel: +39-349-2267868; E-mail: dadosomigliana{at}yahoo.itReceived August 17, 2010. Revision received December 28, 2010. Accepted January 13, 2011. BACKGROUND The impact of fibroids, not encroaching the endometrial cavity, have on the rate of success of IVF is still controversial. Recent meta-analyses suggest a detrimental effect of intramural lesions but not subserosal lesions. However, they also emphasize the need for further evidence. In order to elucidate this, we designed a prospective cohort study to compare the rate of success of IVF in women with and without fibroids.

METHODS Exposed women were those with asymptomatic intramural or subserosal fibroids with a diameter below 50 mm and who were selected for IVF. Unexposed women were those free of fibroids, who were matched to cases by age and number of previous IVF cycles. All recruited patients underwent hystero-sonography to rule out intra-cavitary lesions.

RESULTS There were 119 cases and 119 controls recruited. The number of clinical pregnancies in women with and without fibroids was 28 (24%) and 22 (19%), respectively (P= 0.43). The adjusted odds ratio (OR) for pregnancy in affected women was 1.38 [95% confidence interval (CI): 0.73–2.60]. The number of deliveries was 22 (18%) and 16 (13%), respectively (P= 0.38). The adjusted OR was 1.45 (95% CI: 0.71–2.94). Similar results emerged when focusing exclusively on women carrying intramural lesions (n= 80 couples). There was no significant relationship between clinical outcome and either the number or size of the fibroids.

CONCLUSIONS In asymptomatic patients selected for IVF, small fibroids not encroaching the endometrial cavity did not impact on the rate of success of the procedure.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 834-839. doi: 10.1093/humrep/der015 First published online: February 11, 2011

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Increased zona pellucida thickness and meiotic spindle disruption in oocytes from cigarette smoking mice

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Phoebe C. Jennings1, Julie A. Merriman1, Emma L. Beckett1,2, Philip M. Hansbro1,2 and Keith T. Jones1,*

1School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW 2308, Australia

2Centre for Asthma and Respiratory Disease and Hunter Medical Research Institute, The University of Newcastle, Callaghan, NSW 2308, Australia *Correspondence address. Tel: +61-2-49-21-66-82; Fax: +61-2-49-21-79-03; E-mail: keith.jones{at}newcastle.edu.auReceived October 5, 2010. Revision received December 13, 2010. Accepted December 17, 2010. BACKGROUND The precise effects of cigarette smoking on female fertility have not yet been clearly defined. We have used a mouse model that mimics human smoking and is able to control for variables that may confound clinical studies to assess the impact of chronic smoking on the quality of mouse oocytes.

METHODS Mice received cigarette smoke directly to their lungs for 12 weeks. Lung tissue was analyzed for emphysematous changes and cumulus enclosed oocytes (CEOs) were recovered to study their quality. CEOs were in vitro matured, fixed and stained for chromatin and tubulin. Meiotic spindles, chromatin and the zona pellucida were all examined using confocal microscopy.

RESULTS After 12 weeks of cigarette smoking, mice developed alveolar tissue damage that was determined by an increase in destructive index of the lung parenchyma. The numbers of oocytes recovered and the rates of oocyte maturation were not significantly different from non-smoking mice. However, oocytes from smoking mice had a significantly thicker zona pellucida along with shorter and wider meiotic spindles. Furthermore in total, almost a quarter of oocytes from smoking mice were abnormal as assessed by either errors in chromosomal congression or spindle shape.

CONCLUSIONS We have used a novel model of inhalational cigarette smoking to show that chronic smoking has a detrimental effect on oocyte quality, and this can be observed even though oocytes are removed from the ovary and cultured in vitro.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 878-884. doi: 10.1093/humrep/deq393 First published online: January 12, 2011

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Abnormal activation of Ras/Raf/MAPK and RhoA/ROCKII signalling pathways in eutopic endometrial stromal cells of patients with endometriosis

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I.Y. Yotova, P. Quan, N. Leditznig, U. Beer, R. Wenzl and W. Tschugguel*

Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria *Correspondence address. E-mail: walter.tschugguel{at}meduniwien.ac.atReceived August 30, 2010. Revision received December 29, 2010. Accepted January 10, 2011. BACKGROUND Enhanced proliferation and survival of eutopic endometrial cells from patients with endometriosis compared with healthy women is associated with abnormal activation of extra-cellular signal-regulated kinases 1 and 2 (ERK1/2). Given the role of Ras/Raf/mitogen-activated protein kinase (MAPK) and RhoA/ROCKII signalling pathways in the regulation of cell proliferation and migration, we analysed their possible roles in endometriosis.

METHODS Primary eutopic endometrial stromal cells of patients with endometriosis (Eu-hESC, n= 16) and endometriosis-free controls (Co-hESC, n= 14) were harvested and subjected to proliferation and migration assays as well as kinase activity assays and immunoblot analysis of proteins from the Ras/Raf/MAPK and RhoA/ROCKII signalling pathways. Effects of ROCKII (Y-27632) and MAPK (U0126) inhibitors or siRNA knockdown of ROCKII, Raf-1 and B-Raf were analysed.

RESULTS The proliferation rate of Eu-hESC was 54% higher than Co-hESC. Eu-hESC also displayed a 75% higher migration rate than Co-hESC. Eu-hESC displayed higher levels of ERK phosphorylation (83%) and p27 expression (61%) and lower levels of Raf-1 protein (47%) compared with controls. In addition to an inhibitory effect on cell proliferation, ROCKII knockdown led to significant down-regulation of cyclinD1 and p27 but did not affect ERK phosphorylation. Down-regulation of Raf-1 by siRNA was dispensable for cell proliferation control but led to an increase in ROCKII activity and a decrease in cell migration. B-Raf was shown to act as a regulator of hESC proliferation by modulating cellular ERK1/2 activity and cyclinD1 levels. Eu-hESC displayed 2.4-fold higher B-Raf activity compared with Co-hESC and therefore exhibit abnormally activated Ras/Raf/MAPK signalling.

CONCLUSIONS We show that the same molecular mechanisms operate in Co- and Eu-hESC. The differences in cell proliferation and migration between both cell types are likely due to increased activation of Ras/Raf/MAPK and RhoA/ROCKII signalling pathways in cells from endometriosis patients.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 885-897. doi: 10.1093/humrep/der010 First published online: February 7, 2011

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The post-operative decline in serum anti-Mullerian hormone correlates with the bilaterality and severity of endometriosis

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Wakana Hirokawa1,2, Akira Iwase1,2,*, Maki Goto1,2, Sachiko Takikawa1, Yoshinari Nagatomo1, Tatsuo Nakahara1, Bayasula Bayasula1, Tomoko Nakamura1, Shuichi Manabe1 and Fumitaka Kikkawa1

1Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan

2Department of Maternal and Perinatal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan *Correspondence address. Tel: +81-52-744-2261; Fax: +81-52-744-2268; E-mail: akiwase{at}med.nagoya-u.ac.jpReceived October 31, 2010. Revision received December 22, 2010. Accepted January 7, 2011. BACKGROUND To assess the impact of ovarian cystectomy for endometriomas on the ovarian reserve, we evaluated the pre- and post-operative levels of serum anti-Müllerian hormone (AMH). We also analyzed the correlations between factors related to endometriosis and surgery for endometriomas and the serum AMH levels to investigate which factors affect ovarian reserve.

METHODS Thirty-eight patients who were undergoing ovarian cystectomy for unilateral endometrioma (n = 20) and bilateral endometriomas (n = 18) participated. Preoperative and post-operative serum samples were collected and assayed for AMH levels, and changes between the two samples were analyzed in association with parameters of endometriosis and surgery for endometriomas.

RESULTS The mean AMH level was 3.9 ng/ml prior to surgery, and was reduced to 2.1 ng/ml at 1 month post-surgery. The rate of decline of the serum AMH level was significantly higher in the bilateral group than the unilateral group (62.8 ± 29.6 versus 24.7 ± 32.5%, P < 0.001). The rate of decline in the serum AMH levels showed a significant correlation to the revised American Society for Reproductive Medicine (rASRM) score (P = 0.003), but not age, cyst diameter, blood loss during the operation or the number of follicles removed in the specimens.

CONCLUSIONS Our results suggest that the decrease in ovarian reserve should be taken into account in patients indicated for cystectomy for bilateral endometriomas or unilateral endometrioma with high rASRM scores.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 904-910. doi: 10.1093/humrep/der006 First published online: February 2, 2011

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Supportive care for women with unexplained recurrent miscarriage: patients' perspectives

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A.M. Musters1,*, E.F. Taminiau-Bloem2, E. van den Boogaard1, F. van der Veen1 and M. Goddijn1

1Centre for Reproductive Medicine, Department of Obstetrics and Gynaecology (H4-240), Academic Medical Centre, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands

2Department of Medical Psychology, Academic Medical Centre, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands *Correspondence address. Tel: +31-20-5669111; Fax: +31-20-6971651/31-20-5669104; E-mail: a.m.musters{at}amc.uva.nl/a.m.musters{at}amc.nlReceived November 29, 2010. Revision received January 4, 2011. Accepted January 12, 2011. BACKGROUND Supportive care is currently the only ‘therapy’ that can be offered to women with unexplained recurrent miscarriage (RM). What these women themselves prefer as supportive care in their next pregnancy has never been substantiated. Therefore the aim of this study was to explore what women with unexplained RM prefer as supportive care during their next pregnancy.

METHODS We performed explorative, semi-structured, in-depth interviews. The interviews were performed with 15 women with unexplained RM who were actively seeking conception. All interviews were conducted by telephone. The interviews were fully transcribed and two researchers independently identified text segments from the transcribed interviews and categorized them in the appropriate domain.

RESULTS Women identified 20 different supportive care options; 16 of these options were preferred for their next pregnancy. Examples of the preferred supportive care were early and frequently repeated ultrasounds, ßHCG monitoring, practical advice concerning life style and diet, emotional support in the form of counselling, a clear policy for the upcoming 12 weeks and medication. The four supportive care options that were not preferred by the women were admittance to a hospital ward at the same gestational age as previous miscarriages, Complementary Alternative Medicine, ultrasound every other day and receiving supportive care from their general practitioner.

CONCLUSIONS Our study identified several relevant preferences for supportive care in women with unexplained RM. Many of these can be offered by the gynaecologist and will help in guaranteeing high-quality patient-centred care.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 873-877. doi: 10.1093/humrep/der021 First published online: February 11, 2011

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To continue or discontinue storage of cryopreserved embryos? Patients' decisions in view of their child wish

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V. Provoost1,*, G. Pennings1, P. De Sutter2, J. Gerris2, A. Van de Velde2 and M. Dhont2

1Bioethics Institute Ghent, Ghent University, Blandijnberg 2, B-9000 Ghent, Belgium

2Department of Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium *Correspondence address. E-mail: veerle.provoost{at}ugent.beReceived August 19, 2010. Revision received November 23, 2010. Accepted December 3, 2010. OBJECTIVE Cryopreservation of supernumerary embryos resulting from IVF treatment offers extra chances to conceive. The objective of this study is to describe patients’ decisions to continue or discontinue storage of their embryos after a minimum storage period of 2 years.

METHODS Female patients who had embryos stored at the Infertility Centre of the Ghent University Hospital (Belgium) were sent a mail questionnaire to be completed anonymously.

RESULTS The questionnaire had a response rate of 79% (326/412). After an embryo storage period of at least 2 years, 40% of the couples who were still together wished to continue storage of their embryos. Half of these had no concrete plans for a transfer and wanted to postpone the decision or keep all options open. For those who decided to discontinue storage (60%), the main reason was the completion of their families. Despite the fact that the patients’ child wish was the main factor in their storage decision, two groups of patients with distinct profiles made decisions that were inconsistent with their child wish: those who wanted to continue storage while not wanting a(nother) child (7% of those with no child wish), and those who wanted a(nother) child but decided to discontinue storage (25% of those with a child wish). Overall, these patients more often expressed emotional difficulties regarding this decision.

CONCLUSIONS This study demonstrates the importance of gaining more insight into patients’ embryo storage decisions (along with their embryo disposition decisions) and into the emotional factors playing a role in patients’ decision-making.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 861-872. doi: 10.1093/humrep/deq392 First published online: January 18, 2011

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Mood disorders in oocyte donor candidates: brief report and implications for future research

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Katherine E. Williams1,*, Pascale G. Stemmle2, Lynn M. Westphal3 and Natalie L. Rasgon1

1Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Room 2358, Stanford, CA 94305-5723, USA

2PGSP-Stanford Psy.D. Consortium, Palo Alto, CA, USA

3Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA, USA *Correspondence address. Fax: +650 724-3144; E-mail: elliew{at}stanford.eduReceived October 17, 2010. Revision received December 2, 2010. Accepted December 14, 2010. BACKGROUND IVF, using donor oocytes, has become increasingly common. The donation procedure carries psychiatric risks, including depression, anxiety and rarely, psychosis, and this risk increases when there is a past history of psychiatric illness. We report on the psychiatric status, at intake assessment, of a group of candidate oocyte donors.

METHODS The authors reviewed clinical records of 63 women continuously presenting to a University medical center for psychiatric evaluation as part of the screening process for oocyte donation. A board certified psychiatrist administered a structured clinical interview to candidate donors, and self-report measures were obtained from 28 women.

RESULTS There was a significant discrepancy between psychiatric history of depression and current mood status, as measured by both clinical interview and psychometric self-report data. Nearly one-quarter of candidate donors (22%) reported a history of major depressive disorder; however, all candidate donors denied current mood disturbance on clinical interview, and mean Beck depression inventory and profile of mood states scores were lower than expected compared with psychometric norms (P < 0.0005), epidemiological data and the recurrent nature of depressive disorders.

CONCLUSIONS Candidate donors may minimize psychiatric symptoms. Given the potential for ovarian stimulation protocols to induce or exacerbate mood symptoms, and the moderate heritability of mood disorders, careful evaluation of candidate donor affective disorder history is recommended. This evaluation should focus on sensitivity to mood destabilization during times of hormonal change. Measures that examine whether a candidate donor may have a tendency to present herself in an overly favorable manner, and/or a tendency to minimize symptoms, are recommended.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 847-852. doi: 10.1093/humrep/deq394 First published online: January 17, 2011

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Two decades after legislation on identifiable donors in Sweden: are recipient couples ready to be open about using gamete donation?

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S. Isaksson1, A. Skoog Svanberg2, G. Sydsjö3, A. Thurin-Kjellberg4, P.-O. Karlström2,5, N.-G. Solensten6 and C. Lampic7,*

1Department of Public Health and Caring Sciences, Uppsala University, S-751 22 Uppsala, Sweden

2Department of Women's and Children's Health, Uppsala University, S-751 85 Uppsala, Sweden

3Division of Obstetrics and Gynaecology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, S-581 85 Linköping, Sweden

4Institute of Clinical Sciences, Sahlgrenska Academy, S-416 85 Gothenburg, Sweden

5Department of Clinical Science, Intervention, and Technology, Karolinska Institute, S-141 86 Huddinge, Sweden

6IVF-clinic Umeå in Collaboration with Umeå University Hospital, S-901 85 Umeå, Sweden

7Department of Neurobiology, Care Sciences and Society, Karolinska Institute, S-141 83 Huddinge, Sweden *Correspondence address. Email: claudia.lampic{at}ki.seReceived June 24, 2010. Revision received November 23, 2010. Accepted November 30, 2010. BACKGROUND Two decades after the introduction of Swedish legislation that allows children born as a result of gamete donation access to identifying information about the donor, a nationwide multicentre study on the psychosocial consequences of this legislation for recipients and donors of gametes was initiated in 2005. The aim of the present study was to investigate recipient couples’ attitudes and behaviour regarding disclosure to offspring and others, attitudes towards genetic parenthood and perceptions of information regarding parenthood after donation.

METHODS The present study is part of the prospective longitudinal ‘Swedish study on gamete donation', including all fertility clinics performing donation treatment in Sweden. A consecutive cohort of 152 heterosexual recipient couples of donated oocytes (72% response) and 127 heterosexual recipient couples of donated sperm (81% response) accepted participation in the study. In connection with the donation treatment, male and female participants individually completed two questionnaires with study-specific instruments concerning disclosure, genetic parenthood and informational aspects.

RESULTS About 90% of participants (in couples receiving anonymous donated gametes) supported disclosure and openness to the offspring concerning his/her genetic origin. Only 6% of all participants had not told other people about their donation treatment. Between 26 and 40% of participants wanted additional information/support about parenthood following donation treatment.

CONCLUSIONS Two decades after the Swedish legislation of identifiable gamete donors, recipient couples of anonymously donated sperm and oocytes are relatively open about their treatment and support disclosure to offspring. Recipient couples may benefit from more information and support regarding parenthood after gamete donation. Further studies are required to follow-up on the future parents’ actual disclosure behaviour directed to offspring.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 853-860. doi: 10.1093/humrep/deq365 First published online: January 5, 2011

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PC6 levels in uterine lavage are closely associated with uterine receptivity and significantly lower in a subgroup of women with unexplained infertility

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Sophea Heng1, Natalie J. Hannan1, Luk J.F. Rombauts2, Lois A. Salamonsen1 and Guiying Nie1,*

1Prince Henry's Institute of Medical Research, PO Box 5152, 246 Clayton Rd, Clayton, VIC 3168, Australia

2Department of Obstetrics and Gynecology, Monash University, Clayton, VIC 3168, Australia *Correspondence address. Tel: +61-3-9594-4380; Fax: +61-3-9594-6125; E-mail: guiying.nie{at}princehenrys.orgReceived November 15, 2010. Revision received December 19, 2010. Accepted December 29, 2010. BACKGROUND Embryo implantation requires a healthy embryo and a receptive uterus. Uterine incompetence contributes significantly to implantation failure and infertility. To date, there are no reliable biochemical methods that can determine whether the uterus is receptive. Proprotein convertase 5/6 (PC6) is tightly regulated in the uterus and critical for receptivity and implantation; its secretory nature predicts PC6 to be secreted into the uterine cavity. The present study examines whether PC6 is detectable in uterine lavage and whether there is any correlation between secreted PC6 levels and uterine receptivity.

METHODS Western blotting determined the presence of PC6 protein in uterine lavage. A sensitive and high-throughput activity assay was established and validated. This assay was applied to 103 lavages collected from different phases of the menstrual cycle from women with proven fertility or unexplained infertility.

RESULTS Uterine lavage contained PC6 protein with levels paralleling enzymatic activity. PC6 levels were significantly higher in the receptive than in the non-receptive phase in fertile women, and the putative receptive phase levels in a subgroup of women with unexplained infertility were significantly lower than in the fertile counterparts.

CONCLUSIONS PC6 levels in uterine lavage are significantly elevated in the luteal phase of fertile women and markedly reduced in a subgroup of women with unexplained infertility. Uterine fluid is a valuable source of material to evaluate uterine function. Detection of PC6 in uterine fluid may lead to the development of a rapid and relatively non-surgical assessment of uterine receptivity.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 840-846. doi: 10.1093/humrep/der002 First published online: January 27, 2011

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Aberrant spindle structures responsible for recurrent human metaphase I oocyte arrest with attempts to induce meiosis artificially

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B. Heindryckx1,*, S. Lierman1, C.M. Combelles2, C.A. Cuvelier3, J. Gerris1 and P. De Sutter1

1Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium

2Biology Department, Middlebury College, Middlebury, VT, USA

3Department of Pathology, Ghent University Hospital, Ghent, Belgium *Correspondence address. Tel: +32-9-332-4748; Fax: +32-9-332-4972; E-mail: bjorn.heindryckx{at}ugent.beReceived September 7, 2010. Revision received November 22, 2010. Accepted December 20, 2010. BACKGROUND In some couples, not all retrieved oocytes mature, even after prolonged in vitro culture. The underlying mechanisms are not known, although ionophore treatment may alleviate metaphase I (MI) arrest in some mouse strains. We attempted to induce first polar body (PB) extrusion and fertilization using assisted oocyte activation (AOA) after ICSI in maturation-resistant human MI oocytes.

METHODS Four ICSI patients are described in this retrospective study. A pilot study tested the calcium ionophore ionomycin (10 µM) on donated MI oocytes from patients with a normal number of metaphase II (MII) oocytes. Subsequently, ionomycin was used to induce first PB extrusion in two patients showing maturation-resistant MI oocytes. AOA, by calcium injection and ionomycin exposure, was applied when mature oocytes were available. Oocytes were analysed by polarized microscopy and immunostaining.

RESULTS Ionomycin induced the first PB extrusion in MI oocytes from patients with a normal number of retrieved MII oocytes, while extended in vitro culture failed to achieve the MII stage. Similarly, ionomycin induced first PB extrusion in one of two patients with recurrent maturation-resistant MI oocytes. Use of ICSI combined with AOA on MII oocytes matured in vitro or in vivo resulted in failed or abnormal fertilization with no further embryo cleavage potential. Highly abnormal spindle and chromosome configurations were observed in MI maturation-resistant oocytes, in contrast to control MI oocytes.

CONCLUSIONS Ionophore induced first PB extrusion in MI oocytes from patients without maturation arrest but to a lower extent in maturation-resistant MI oocytes. Immunofluorescence staining and confocal analysis revealed, for the first time, highly abnormal spindle/chromosomal structures that may be responsible for this maturation arrest.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 791-800. doi: 10.1093/humrep/deq400 First published online: January 17, 2011

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Novel alleles of HLA-DQ and -DR loci show association with recurrent miscarriages among South Indian women

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Meka Aruna1, Theeya Nagaraja1, Sadaranga Andal Bhaskar2, Surapaneni Tarakeswari3, Alla Govardhan Reddy4, Kumarasamy Thangaraj4, Lalji Singh4 and B. Mohan Reddy1,*

1Molecular Anthropology Group, Biological Anthropology Unit, Indian Statistical Institute, Street No. 8, Habsiguda, Hyderabad 500007, India

2Lakshmi Fertility Clinic, Pogathota, Nellore 524001, India

3Fernandez Hospital, Bogulkunta, Hyderabad 500001, India

4Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India *Correspondence address. E-mail: bmr{at}isi.ac.in; bmrisi{at}gmail.comReceived March 24, 2010. Revision received January 9, 2011. Accepted January 17, 2011. BACKGROUND In this study, recurrent miscarriages (RMs) are defined as loss of two or more clinically detectable pregnancies before 20 weeks of gestation. HLA has been thought to play a role in RM. However, the results of earlier studies on the role of different human leucocyte antigen (HLA) genes were conflicting and inconclusive. In the present study, we investigate HLA genes (HLA-DRA, HLA-DRB1, HLA-DQA1 and HLA-DQB1) in RM couples with unknown etiology and normal couples.

METHODS Blood samples from 143 RM couples and 150 control couples were analyzed, firstly to validate previously reported association studies and secondly to explore whether any novel alleles or haplotypes specific to Indian populations can be observed to be associated with RM. HLA typing was carried out by DNA sequencing.

RESULTS Results suggest an association of the DQB1*03:03:02 allele with RM (odd ratio = 2.66; pc = 0.02; confidence interval = 1.47–4.84). Haplotypes of the DQA1 and DQB1 risk alleles also showed a significant association with RM, albeit not after Bonferroni correction for multiple comparisons.

CONCLUSIONS HLA-DQB1 appears to have a strong involvement in the manifestation of RM in this population from South India. The current genetic analysis of RM and control couples not only highlights the genes exhibiting a strong etiological role but also reflects the protective nature of some HLA genes against RM. Nevertheless, most of these alleles/haplotypes were not those that are implicated in RM in other ethnic backgrounds, and hence require further validation in other populations of India, from different ethnic and/or geographic backgrounds.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 765-774. doi: 10.1093/humrep/der024 First published online: February 15, 2011

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Observer agreement in the evaluation of the uterine cavity by hysteroscopy prior to in vitro fertilization

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J.C. Kasius1,*, F.J.M. Broekmans1, S. Veersema2, M.J.C. Eijkemans3, E.J.P. van Santbrink4, P. Devroey5, B.C.J.M. Fauser1 and H.M. Fatemi5

1Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands

2Department of Reproductive Medicine and Gynecology, St Antonius hospital, Nieuwegein, The Netherlands

3Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands

4Department of Reproductive Medicine and Gynecology, Erasmus University Medical Center, Rotterdam, The Netherlands

5Department of Reproductive Medicine, Academic Hospital at the Dutch-speaking Brussels Free University, 1090 Brussels, Belgium *Correspondence address. Fax: +31-887555433; E-mail: j.c.kasius{at}umcutrecht.nlReceived July 14, 2010. Revision received December 15, 2010. Accepted January 5, 2011. BACKGROUND Hysteroscopy is known as the most accurate test for diagnosing intrauterine pathology. To optimize fertility treatment, it is increasingly common to perform hysteroscopy as a routine procedure prior to IVF. However, literature on the reproducibility of screening hysteroscopy is lacking. Therefore, the aim of the study was to assess the intra- and inter-observer agreement in the individual evaluation of the uterine cavity using video recordings of hysteroscopy procedures in asymptomatic patients prior to IVF.

METHODS Screening hysteroscopies of 123 unselected, asymptomatic, infertile women with an indication for IVF/ICSI treatment were recorded on DVD. After editing, the hysteroscopy performer and three other experienced gynecologists independently assessed all recordings, focusing on the appearance of predefined intrauterine abnormalities (i.e. endometrial polyps, myomas, adhesions or septa). The intra- and inter-observer agreement was calculated and expressed as perfect agreement and ? coefficient or intraclass correlation coefficient.

RESULTS In total, 123 hysteroscopy procedures were recorded. After editing and selection, based on the record quality, 107 remained for assessment and analysis. The intraobserver agreement on the appearance of any of the predefined intrauterine abnormalities was substantial (? = 0.707), whereas the interobserver agreement was moderate (? = 0.491). Perfect agreement occurred only in 77.6% of the cases.

CONCLUSIONS Interobserver agreement among experienced gynecologists appeared to be rather disappointing. The latter may have implications for the diagnostic accuracy of screening hysteroscopy prior to IVF, as well as for its clinical significance in IVF programs.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 801-807. doi: 10.1093/humrep/der003 First published online: February 9, 2011

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Fertility determinants after conservative surgery for mucinous borderline tumours of the ovary (excluding peritoneal pseudomyxoma)

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Martin Koskas1, Catherine Uzan1, Sebastien Gouy1, Patricia Pautier2, Catherine Lhommé2, Christine Haie-Meder3, Pierre Duvillard4 and Philippe Morice1,5,*

1Department of Gynecologic Surgery, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France

2Department of Oncology, Institut Gustave Roussy, Villejuif, France

3Department of Radiotherapy, Institut Gustave Roussy, Villejuif, France

4Department of Pathology, Institut Gustave Roussy, Villejuif, France

5University Paris Sud, Institut Gustave Roussy, Villejuif, France *Correspondence address. Tel: +33-1-42-11-44-39; Fax: +33-1-42-11-52-13; E-mail: morice{at}igr.frReceived August 18, 2010. Revision received November 8, 2010. Accepted December 17, 2010. BACKGROUND The aim of this study was to define determinants of fertility in patients treated conservatively for mucinous borderline ovarian tumours (MBOTs), and to compare outcomes after salpingo-oophorectomy or cystectomy.

METHODS This was a retrospective cohort study of fertility results in a series of patients treated conservatively for MBOTs and desiring pregnancy. Conservative surgery was defined as preservation of the uterus and ovarian tissue in one or both adnexa(e). Fertility results were compared with patients who had undergone a cystectomy or a (salpingo-)oophorectomy. Only patients with a minimum of 1 year of follow-up were included. Epidemiological, surgical, histological parameters and other prognostic factors for fertility results were investigated.

RESULTS A group of 31 patients who had been treated conservatively between 1997 and 2004 and who desired pregnancy were investigated. Patients were treated by unilateral salpingo-oophorectomy (USO) (n = 19) or cystectomy (n = 12). The 5-year recurrence-free survival rate was higher in the USO group compared with the cystectomy group (94.7 versus 49.1%, P = 0.041). Among the 31 women, 12 had become pregnant. The 5-year probabilities of pregnancy were comparable between the cystectomy and salpingo-oophorectomy groups (41.8 and 45.9%, respectively, P= 0.66). None of the other factors studied (epidemiological, surgical and histological parameters) were associated with fertility results.

CONCLUSIONS The use of salpingo-oophorectomy rather than cystectomy should be preferred during conservative surgery for patients with MBOTs because it decreases the risk of recurrence and does not impair fertility.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 808-814. doi: 10.1093/humrep/deq399 First published online: January 24, 2011

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Efficacy of oocyte vitrification combined with blastocyst stage transfer in an egg donation program

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Javier I. García*, Luis Noriega-Portella and Luis Noriega-Hoces

Laboratory of Assisted Reproduction, PRANOR Group of Assisted Reproduction, Concebir Clinic, Los Olivos 364, San Isidro, Lima, Peru *Correspondence address. Tel: +51-1-422-5246; E-mail: jgarciaf{at}hotmail.comReceived May 18, 2010. Revision received November 29, 2010. Accepted January 7, 2011. BACKGROUND A successful oocyte vitrification program is important for women with various indications for assisted reproduction technology. The objective of this study was to report the outcome of vitrification of oocytes, obtained through an oocyte donation program, by evaluating the embryo development, pregnancy and implantation rates (IRs) after blastocyst transfer.

METHODS A total of 1098 oocytes were obtained from 78 donors. There were 312 oocytes used in the study group (vitrified oocytes) and 786 used in the control group (fresh oocytes). There were 34 recipients who received blastocysts obtained from vitrified oocytes and 58 recipients who received blastocysts from fresh oocytes. The fertilization rate, cleavage rate, embryo quality, pregnancy rate (PR) and IR were compared between groups.

RESULTS Vitrified oocytes showed a survival rate of 89.4%. There was no difference in the fertilization rate (76.1 and 87.5%), Day 2 cleavage rate (96.3 and 98.0%) or blastocyst formation rate (41.3 and 45.3%) for the study and control groups, respectively. PRs, IRs and miscarriages rates (MRs) were similar for the study group compared with the control group (PR: 61.8 versus 60.0%; IR: 43.9 versus 42.9%; MR: 9.5 versus 5.9%).

CONCLUSIONS The developmental competence of embryos obtained from vitrified oocytes is not affected by the vitrification procedure, since they preserve the potential to be fertilized and to develop into high-quality blastocysts, similar to embryos from fresh oocytes. The successful clinical outcome indicates the use of this procedure for oocyte donation programs and for oocyte storage in general.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 782-790. doi: 10.1093/humrep/der008 First published online: February 7, 2011

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Decidual HtrA3 negatively regulates trophoblast invasion during human placentation

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Harmeet Singh1,*, Yaeta Endo2 and Guiying Nie1

1Prince Henry's Institute of Medical Research, PO Box 5152, 246 Clayton Road, Clayton, VIC 3168, Australia

2Cell-Free Science and Technology Research Center, Ehime University, Matsuyama, Japan *Correspondence address. Fax: +61-3-9594-6125; E-mail: harmeet.singh{at}princehenrys.orgReceived November 17, 2010. Revision received December 23, 2010. Accepted January 12, 2011. BACKGROUND Controlled trophoblast invasion into the maternal decidua (interstitial invasion) is important for placental development. Factors secreted by the maternal decidual cells and the extravillous trophoblast can influence trophoblast invasion and abnormalities in the invasion process may lead to pregnancy complications. Serine protease HtrA3 is highly expressed in the decidual cells in the late secretory phase of the menstrual cycle and throughout pregnancy, and in most trophoblast cell types, apart from the invading interstitial trophoblast during the first trimester. HtrA3 and its family members are down-regulated in a number of cancers and are proposed as tumour suppressors. The current study aimed to investigate whether HtrA3 is secreted by decidual cells, and whether inhibiting such secretion alters trophoblast invasion.

METHODS AND RESULTS Human endometrial stromal cells (HESCs) were decidualized with estradiol, medroxyprogesterone acetate and cyclic adenosine monophosphate. Real-time RT–PCR, western blotting and immunocytochemistry confirmed that HtrA3 mRNA and protein expression increased during decidualization. HtrA3 was also detected in the conditioned media (CM) of the decidualized HESCs, confirming its secretion. For functional studies, a protease-inactive mutant form of HtrA3 which was previously confirmed to be a dominant-negative inhibitor was produced using wheat germ cell-free technology. CM from decidualized HESCs significantly suppressed invasion of trophoblast HTR-8 cells (P < 0.01), whereas inhibition of HtrA3 in this CM by exogenous HtrA3 mutant resulted in increased trophoblast HTR-8 cell invasion (P < 0.001).

CONCLUSIONS These results strongly support the hypothesis that decidual HtrA3 negatively regulates trophoblast invasion.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 748-757. doi: 10.1093/humrep/der019 First published online: February 14, 2011

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Editorial: Two cheers for clinical practice guidelines: the hopes and headaches of quality improvement in reproductive healthcare

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Ed Hughes*

Professor of Obstetrics and Gynecology, McMaster University, 1200 Main Street West, Hamilton, ON, Canada L8N 3Z5*Correspondence address. E-mail: hughese{at}mcmaster.caReceived January 12, 2011. Revision received January 12, 2011. Accepted January 14, 2011. Effective and timely knowledge transfer is the engine of evidence-based medicine. ESHRE and other professional societies are key players in the process of knowledge transfer. They facilitate scientific dialogue in many different ways and provide frameworks for the generation of clinical practice guidelines (CPGs). While enormous thought and effort goes into the execution of clinical trials and the subsequent development of CPGs based on them, little is known about the effectiveness of guideline uptake in the field of reproductive medicine. How successful are guidelines in improving quality of care? What strategies beyond simple guideline publication, most effectively lead to change in practice? The study by Mourad et al. ( 2010) takes a bold and pragmatic look at these questions, on behalf of fertility care-givers and patients.

Based in Holland, this group used a relatively new and increasingly common design platform: cluster randomization. This means that the unit of allocation was not, as is usual, the individual patient, but instead a group of patients, in this case those attending a particular fertility clinic. The main reason for using cluster randomization is to avoid the risk of contamination: to keep separate the influences of the two strategies under study. Here, it would have been impossible to provide two types of CPG reinforcement strategy to the same physicians and expect them to apply them separately to individual patients within their practices. Important limitations of cluster randomization stem from the correlation that exists between patients within …

This ArticleHum. Reprod. (2011) 26 (4): 815-816. doi: 10.1093/humrep/der023 First published online: February 2, 2011

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Treating women under 36 years old without top-quality embryos on day 2: a prospective study comparing double embryo transfer with single blastocyst transfer

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F. Guerif1,2,3,4,*, C. Frapsauce1,2,3,4, C. Chavez1, V. Cadoret1,2,3,4 and D. Royere1,2,3,4

1Service de Médecine et Biologie de la Reproduction, CHRU de Tours, F-37044 Tours, France

2Université François Rabelais de Tours, F-37041 Tours, France

3INRA, UMR85 PRC, F-37380 Nouzilly, France

4CNRS, UMR6175 PRC, F-37380 Nouzilly, France *Correspondence address. Service de Medecine et Biologie de la Reproduction, 2 boulevard Tonnelle, 37000 Tours, France. E-mail: guerif{at}med.univ-tours.frReceived November 17, 2010. Revision received January 4, 2011. Accepted January 11, 2011. BACKGROUND Embryologists currently face a challenge when counselling patients regarding the stage and the number of embryos to transfer when no top-quality embryos (TQE) are available.

METHODS The aim of this study was to evaluate the efficacy of single blastocyst transfer (SBT) in comparison with the transfer of two cleavage-stage embryos in women under 36 years old. A total of 450 women under 36 years undergoing their first or second IVF treatment who had no TQE on Day 2 were included in this prospective study. Couples were assigned to either a SBT or a double cleavage-stage embryo transfer (DET). The clinical end-points monitored were rates of implantation, delivery and multiple deliveries.

RESULTS The rate of transfer was significantly lower for couples assigned to the SBT group compared with the DET group (88 versus 100%, respectively, P < 0.001) while the delivery rate per oocyte retrieval was similar in both groups (26.7%). By contrast, the rate of multiple deliveries was significantly lower in the SBT group compared with the DET group (3.3 versus 23.3%, respectively, P < 0.01). Blastocyst cryopreservation was twice as high in the SBT group compared with the DET group (39 versus 18%, respectively, P < 0.001).

CONCLUSIONS These findings show the value of extended embryo culture for couples without TQE. In such situations, delaying embryo transfer in order to select a single blastocyst with the highest potential for implantation can reduce the number of multiple pregnancies. Furthermore, our results demonstrate that extended culture allows blastocyst cryopreservation from embryos not available for Day 2 cryopreservation.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 775-781. doi: 10.1093/humrep/der020 First published online: February 9, 2011

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Patient-centred infertility care: a qualitative study to listen to the patient's voice

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E.A.F. Dancet1,2,*†, I.W.H. Van Empel2,†, P. Rober3, W.L.D.M. Nelen2, J.A.M. Kremer2 and T.M. D'Hooghe1

1Leuven University Fertility Centre, Leuven University Hospital, Herestraat 49, Leuven, Belgium

2Department Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, The Netherlands

3Centre for Family and Sexual Sciences, Leuven University, Leuven, Belgium *Correspondence address. E-mail: eline.dancet{at}uz.kuleuven.be?† Both first authors contributed equally.

Received September 10, 2010. Revision received January 4, 2011. Accepted January 14, 2011. BACKGROUND High-quality care for patients faced with infertility should be patient-centred. Few studies have provided in-depth insights into the patient's perspective on care and, to the best of our knowledge, no study has provided a model of the complex concept ‘patient-centred infertility care’. Therefore, a qualitative study aimed at understanding ‘patient-centred infertility care’ from the patient's perspective was conducted.

METHODS Fourteen focus group discussions were organized with patients (n = 103) from two European countries to find out about patients’ positive and negative experiences with infertility care. Content analysis of the transcripts and analysis of patients’ priority lists were conducted.

RESULTS The patient-centredness of infertility care depends on 10 detailed dimensions, which can be divided into system and human factors, and there is a two-way interaction between both kinds of factors. System factors, in order of patient's priority, are: provision of information, competence of clinic and staff, coordination and integration, accessibility, continuity and transition and physical comfort. Human factors, in order of patient’s priority, are: attitude of and relationship with staff, communication, patient involvement and privacy and emotional support.

CONCLUSIONS This study provides a detailed patient's description of the concept ‘patient-centred infertility care’ and an interaction model that aids understanding of the concept. Fertility clinics are encouraged to improve the patient-centredness of their care by taking into account the detailed description of the dimensions of patient-centred infertility care, and by paying attention to both system and human factors and their interaction when setting up ‘patient-centred improvement projects’.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 827-833. doi: 10.1093/humrep/der022 First published online: February 11, 2011

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A multi-faceted strategy to improve the use of national fertility guidelines; a cluster-randomized controlled trial

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Selma M. Mourad1,2, Rosella P.M.G. Hermens2, Janine Liefers2, Reinier P. Akkermans2, G.A. Zielhuis3, E. Adang3, Richard P.T.M. Grol2, Willianne L.D.M. Nelen1 and Jan A.M. Kremer1,*

1Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands

2Scientific Institute for Quality of Healthcare (IQ Healthcare), Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands

3Department of Epidemiology, Biostatistics and Health Technology Assessment, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands *Correspondence address. E-mail: j.kremer{at}obgyn.umcn.nlReceived February 2, 2010. Revision received August 9, 2010. Accepted September 30, 2010. BACKGROUND Proper use of clinical practice guidelines can decrease variation in care between settings. However, actual use of fertility guidelines is suboptimal and in need of improvement. Hence, a cluster-randomized controlled trial was designed to study the effects of two strategies to implement national Dutch guidelines on comprehensive fertility care.

METHODS Sixteen fertility clinics participated in the trial. A minimal, professional-oriented implementation strategy of audit and feedback was tested versus a maximal multi-faceted strategy that was both professional and patient oriented. The extent of adherence to guideline recommendations, reflected in quality indicator scores, was the primary outcome measure. To gain an insight into unwanted side effects, patient anxiety and depression scores were gathered as secondary outcomes. Data collection encompassed medical record search, patient and professional questionnaires.

RESULTS A total of 1499 couples were included at baseline and 1396 at the after-measurement. No overall significant improvement in indicator scores was found for either strategy [odds ratios ranging from 0.23 (95% confidence interval (CI): 0.06–0.95) to 6.66 (95% CI: 0.33–132.8]. Secondary outcomes did not differ significantly for both groups, although selected anxiety scores appeared lower in the maximal intervention group. Process evaluation of the trial revealed positive patient experiences with the intervention material [e.g. an increased understanding of their doctor's treatment policy (61%), an increased ability to ask questions about the treatment (61%)]. Professionals’ appreciation of intervention elements varied, and execution of the multi-faceted strategy appeared incomplete.

DISCUSSION Absence of an intervention effect may be due to the nature of the strategies, incomplete execution or flaws in study design. Process evaluation data raise the question of whether professionals should be the only stakeholder responsible for guideline implementation. This study therefore contributes to an increased understanding of fertility guideline implementation in general, and the role of patients in particular.

Clinical Trials.gov: NCT00119925.

© The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org This ArticleHum. Reprod. (2011) 26 (4): 817-826. doi: 10.1093/humrep/deq299 First published online: December 6, 2010

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Association of polymorphisms/haplotypes of the genes encoding vascular endothelial growth factor and its KDR receptor with recurrent pregnancy loss

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Mei-Tsz Su1,2, Sheng-Hsiang Lin2, I-Wen Lee1, Yi-Chi Chen3 and Pao-Lin Kuo1,*

1Division of Genetics, Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, 138 Sheng-Li Road, Tainan 704, Taiwan

2Graduate Institute of Clinical Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan

3Department of Economics, National Cheng Kung University, Tainan, Taiwan *Correspondence address. Fax: +886-6-276-6185; E-mail: paolink{at}mail.ncku.edu.twReceived October 17, 2010. Revision received November 22, 2010. Accepted December 17, 2010. BACKGROUND Vascular endothelial growth factor (VEGF) and its kinase insert domain receptor (KDR) play an important role in angiogenesis, and their gene expression patterns also suggest a close relationship with early pregnancy. However, limited information is available regarding the role of the VEGF system, especially its KDR receptor, in recurrent pregnancy loss (RPL). This study was conducted to investigate a genetic association between VEGF and its receptor gene (KDR) with idiopathic RPL.

METHODS In this case–control study, 115 women who had experienced at least two consecutive spontaneous miscarriages (n= 62 women with two miscarriages, n= 53 with three or more) and 170 controls were included. A total of 14 tag single-nucleotide polymorphisms (SNPs) of VEGF and KDR were selected from the HapMap Web site and three functional SNPs [rs1570360 (-1154G/A) of VEGF; rs2305948 (V297I) and rs1870377 (Q472H) of the KDR gene] were genotyped using primer extension analysis. We further used multifactor dimensionality reduction analysis to evaluate gene–gene interactions.

RESULTS One tag SNP (rs6838752) and the functional SNP (Q472H) of the KDR gene were in complete linkage and showed significant differences between patients and controls (P< 0.05). The frequencies of haplotypes of VEGF (A-T-G haplotype) and KDR (A-C-A-T-G haplotype) showed significant differences in patients versus controls (P< 0.05). All comparisons with controls remained significant when the subgroup of women with three or more miscarriages was analyzed.

CONCLUSIONS VEGF and its receptor gene (KDR) are associated with idiopathic RPL. The VEGF/KDR system jointly contributes to recurrent miscarriage in Taiwanese Han women.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 758-764. doi: 10.1093/humrep/deq401 First published online: January 20, 2011

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