Tsung-Jui Chen, Wei-Lin Zheng, Chun-Hsin Liu, I-Hang Huang, H. Lai, Mark Liu
{"title":"Using Deep Learning with Large Dataset of Microscope Images to Develop an Automated Embryo Grading System","authors":"Tsung-Jui Chen, Wei-Lin Zheng, Chun-Hsin Liu, I-Hang Huang, H. Lai, Mark Liu","doi":"10.1142/S2661318219500051","DOIUrl":"https://doi.org/10.1142/S2661318219500051","url":null,"abstract":"The assessment of embryo viability for in vitro fertilization (IVF) is mainly based on subjective visual analysis, with the limitation of intra- and inter-observer variation and a time-consuming task. In this study, we used deep learning with large dataset of microscopic embryo images to develop an automated grading system for embryo assessment. This study included a total of 171,239 images from 16,201 embryos of 4,146 IVF cycles at Stork Fertility Center (https://www.e-stork.com.tw) from March 6, 2014 to April 13, 2018. The images were captured by inverted microscope (Zeiss Axio Observer Z1) at 112 to 116 hours (Day 5) or 136 to 140 hours (Day 6) after fertilization. Using a pre-trained network trained on the ImageNet dataset as convolution base, we applied Convolutional Neural Network (CNN) on embryo images, using ResNet50 architecture to fine-tune ImageNet parameters. The predicted grading results was compared with the grading results from trained embryologists to evaluate the model performance. The images were labeled by trained embryologists, based on Gardner’s grading system: blastocyst development ranking from 3–6, ICM quality as A, B, or C; and TE quality as a, b, or c. After pre-processing, the images were divided into training, validation, and test groups, in which 60% were allocated to the training group, 20% to the validation group, and 20% to the test group. The ResNet50 algorithm was trained on the 60% images allocated to the training group, and the algorithm’s performance was evaluated using the 20% images allocated to the test group. The results showed an average predictive accuracy of 75.36% for the all three grading categories: 96.24% for blastocyst development, 91.07% for ICM quality, and 84.42% for TE quality. To the best of our knowledge, this is the first study of an automatic embryo grading system using large dataset from Asian population. Combing the promising results obtained in this study with time-lapse microscope system integrated with IVF Electronic Medical Record platform, a fully automated and non-invasive pipeline for embryo assessment will be achieved.","PeriodicalId":34382,"journal":{"name":"Fertility Reproduction","volume":"104 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85036619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Vitamin D and Infertility: The Evidence","authors":"M. Hornstein","doi":"10.1142/S266131821950004X","DOIUrl":"https://doi.org/10.1142/S266131821950004X","url":null,"abstract":"Vitamin D is a lipid soluble vitamin synthesized by the skin upon exposure to UV light. Approximately 10–20% of vitamin D comes from dietary sources and 25OH-D is its circulating form. Vitamin D receptors are found in reproductive tissues including ovary, uterus, and endometrium permitting investigators to hypothesize a role for vitamin D in reproduction. Indeed, a number of animal studies provide evidence of vitamin D’s importance in fertility. Studies in humans, however, generally have not supported an effect of vitamin D on fertility outcomes. Several retrospective cohort studies did not demonstrate an association between vitamin D levels and pregnancy. Similarly, one study did not find correlation between anovulatory infertility and vitamin D intake. Very low levels of vitamin D, however, were associated with miscarriage in another study. A large meta-analysis of 11 studies and 2700 women did show an improvement in IVF success rates in those with higher levels of vitamin D. Finally, two small studies on vitamin D supplementation and pregnancy did not show a benefit of increasing vitamin D intake. In conclusion, the literature at best shows a minimal impact of vitamin D on infertility and IVF outcomes.","PeriodicalId":34382,"journal":{"name":"Fertility Reproduction","volume":"113 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79201260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Place of In Vitro Maturation in Assisted Reproductive Technology","authors":"L. Vuong, T. Ho, R. Gilchrist, J. Smitz","doi":"10.1142/S2661318219300022","DOIUrl":"https://doi.org/10.1142/S2661318219300022","url":null,"abstract":"In vitro maturation (IVM) is an assisted reproductive technology (ART) whereby immature cumulus-oocyte complexes are collected and matured in vitro, without need for controlled ovarian stimulation and ovulation triggering. Advantages of IVM over in vitro fertilization (IVF) include mild or no stimulation, lower medication costs and less patient burden. However, early clinical outcomes with IVM were suboptimal. More recently, clinical studies reported live birth rates after IVM of about 40%. New IVM culture systems are being used to improve the efficacy of IVM. These have been in widespread use for animals for many years and are now showing promise in the clinical setting. Patients more likely to benefit from IVM over IVF include those at risk of OHSS (e.g. women with polycystic ovary syndrome), when the time for ovarian stimulation is limited, or where sustained elevations of estradiol are contraindicated (e.g. oncofertility indications). The main barrier to use of IVM to date was its relative efficacy compared with IVF, and there have also been concerns over the health of infants born following IVM. However, no differences in congenital abnormalities between IVM and other ARTs have been identified. In addition, there is a lack of both experience and standardized protocols. Strategies to overcome barriers to the use of IVM include better training for clinicians, more and better funded research in the field, and improved recognition of IVM by fertility specialists. Overall, IVM offers a valuable alternative for ART in select patient populations. New approaches to IVM appear to have the potential to achieve pregnancy outcomes equivalent to those after IVF. Increasing the use of IVM in the future can be achieved with improved training and education for fertility specialists, and increased funding for IVM research, with the ultimate goal of improving fertility outcomes.","PeriodicalId":34382,"journal":{"name":"Fertility Reproduction","volume":"74 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S2661318219300022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72453639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Message from Professor P. C. Wong","authors":"P. Wong","doi":"10.1142/S2661318219710026","DOIUrl":"https://doi.org/10.1142/S2661318219710026","url":null,"abstract":"","PeriodicalId":34382,"journal":{"name":"Fertility Reproduction","volume":"236 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74757136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Johnson, N. Johnson, S. Baidya, S. Jessup, C. Print, A. Muthukaruppan, L. Chamley, W. Hadden, M. L. Hull, Sunali Y Mehta, A. Shelling
{"title":"Randomised Trial of Lipiodol Uterine Bathing Effect (LUBE) in Women with Endometriosis-Related Infertility","authors":"N. Johnson, N. Johnson, S. Baidya, S. Jessup, C. Print, A. Muthukaruppan, L. Chamley, W. Hadden, M. L. Hull, Sunali Y Mehta, A. Shelling","doi":"10.1142/S2661318219500063","DOIUrl":"https://doi.org/10.1142/S2661318219500063","url":null,"abstract":"BACKGROUND: We aimed to assess whether lipiodol alters endometrial gene expression through a uterine bathing effect that might enhance receptivity to embryo implantation. METHODS: An open-label randomised controlled trial design in a single-centre tertiary infertility service. Twelve women with endometriosis (n [Formula: see text] 11) or previous successful lipiodol procedure (n [Formula: see text] 1) were randomised to receive immediate or delayed lipiodol hysterosalpingography, followed by endometrial biopsy. Endometrial samples were assessed for gene expression, using Affymetrix microarrays and validation studies using reverse transcriptase quantitative polymerase chain reaction analysis. Subsequent endometrial gene expression responses to treatment and clinical fertility outcomes were assessed. RESULTS: Eleven of 12 women had successful endometrial sampling procedures. Nine women had successful pregnancies within the 9-month follow-up phase. Following lipiodol bathing we identified 20 down-regulated and 13 up-regulated genes with p [Formula: see text] 0.05 and with magnitude of change [Formula: see text]1.5-fold in at least three of the four women, with osteopontin being the only gene down-regulated in all four women. CONCLUSIONS: This study supports the concept of a uterine bathing effect of lipiodol altering endometrial biology and gene expression. Whether regulation of inflammation and immune response pathways by lipiodol might contribute to an increase in endometrial receptivity to embryo implantation merits further investigation.","PeriodicalId":34382,"journal":{"name":"Fertility Reproduction","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78039628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Zika Virus Infection and Implications for Reproduction","authors":"M. Giles, S. Cole","doi":"10.1142/S2661318219300010","DOIUrl":"https://doi.org/10.1142/S2661318219300010","url":null,"abstract":"Zika virus infection during pregnancy can have devastating effects on the foetus leading to congenital Zika syndrome. It is relevant therefore for couples living in countries with endemic Zika virus to understand the strategies they can utilise to reduce the chance of infection. In addition, couples planning pregnancy, or who are already pregnant, travelling to countries with Zika virus need to be informed of the potential risk and implications for future reproductive planning.","PeriodicalId":34382,"journal":{"name":"Fertility Reproduction","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86585267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Mubarak, S. Acharyya, V. Viardot-Foucault, H. Tan, J. Phoon
{"title":"A Comparison of the Miscarriage and Live Birth Rate for Frozen Embryo Transfer According to Two Endometrial Preparations: Natural or Primed with Estrogens","authors":"S. Mubarak, S. Acharyya, V. Viardot-Foucault, H. Tan, J. Phoon","doi":"10.1142/S2661318219500038","DOIUrl":"https://doi.org/10.1142/S2661318219500038","url":null,"abstract":"Objective The primary objective is to compare miscarriage rates in frozen-thawed embryo transfer (FET) cycles, according to the endometrial preparation used either artificial through the administration of exogenous estrogen and progesterone or natural without any treatment, during a spontaneous ovulatory cycle. The secondary objective is to compare the live birth rates between the two endometrial preparations. Study design This is a retrospective study done at KK Women’s and Children’s Hospital Singapore. We included women who underwent FET cycles either with hormone replacement treatment (HRT) or no treatment (natural) for the endometrial preparation, regardless of their cycle number, from 1 January 2011 till 31 December 2015. Results A total of 2,752 FET cycles were included in our analysis. The natural cycle followed by vaginal progesterone support was used in 1,221 cycles and the HRT cycle with estrogen and vaginal progesterone was used in 1,531 cycles. There is a significantly higher miscarriage rate in the HRT group (38.4%) compared with the natural group (22.3%). The live birth rate is significantly higher in the natural group (22.8%) compared with the HRT group (17.3%). The multivariate analysis further shows that the HRT therapy is independently associated with an increased risk of miscarriage (adjusted odds ratio 2.05; 95% confidence interval 1.45–2.90; [Formula: see text] <0.001) and hence lower odds of live birth (adjusted odds ratio 0.69; 95% confidence interval 0.56–0.84; [Formula: see text] <0.001) after adjusting for the patient’s age at which the embryo was cryopreserved, race, body mass index, main indications for in vitro fertilization, number of embryos transferred and type of embryo transferred. Conclusion We have shown in this study that the miscarriage rate is higher in the HRT FET group and that this increased miscarriage rate translates into a lower live birth rate in the HRT group. Thus, we conclude that patients with regular menstrual cycles should be offered a natural FET cycle to achieve better outcomes in terms of live birth rate and reducing the miscarriage rate.","PeriodicalId":34382,"journal":{"name":"Fertility Reproduction","volume":"97 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80735164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Foreword by Professor Gab Kovacs","authors":"Amanda Kovacs","doi":"10.1142/S2661318219010011","DOIUrl":"https://doi.org/10.1142/S2661318219010011","url":null,"abstract":"","PeriodicalId":34382,"journal":{"name":"Fertility Reproduction","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81079664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Tale of Two Hormones","authors":"T. Foran","doi":"10.1142/S2661318219500026","DOIUrl":"https://doi.org/10.1142/S2661318219500026","url":null,"abstract":"The development of the steroid hormones currently used in contraception and menopausal hormone replacement provides an interesting story in terms of brilliant research, international rivalry, major advances and sheer serendipity. This paper provides a historical perspective on the use of oestrogens and progestogens in clinical practice from the 1920s until the present day.","PeriodicalId":34382,"journal":{"name":"Fertility Reproduction","volume":"10 2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73338475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Message from Editor-in-Chief","authors":"","doi":"10.1142/s2661318221010015","DOIUrl":"https://doi.org/10.1142/s2661318221010015","url":null,"abstract":"This article discusses the development of premedical and preclinical education in the Netherlands between 1865, when the ‘unity of licensure’ was achieved, and 1965, a year which marked the beginning of a series of innovations which resulted in a complete overhaul of the classical medical curriculum. It will be argued that Dutch premedical and preclinical education during the century between 1865 and 1965 was featured by a comprehensive treatment of the natural and preclinical sciences in order to provide students with a ‘solid foundation’ upon which their clinical knowledge and, eventually, their clinical competence should be built. However, the curriculum suffered from several major shortcomings: it was educationally insufficient, it lacked internal dynamics, it was extremely compartmentalized, and it became increasingly overloaded. As a consequence of both rigid legislation and an obsolete educational philosophy, these curricular shortcomings could not adequately be dealt with. Consequently, in the early 1960s, when the number of medical students exploded, the curriculum more or less imploded under its own weight. New legislation and the foundation of two new medical schools in the 1960s and 1970s, which could design their curriculum almost ‘from scratch,’ finally paved the way for implementing the major curricular innovations at the time already long overdue. Development and organization of medical education in the Netherlands Nineteenth-century academic medical education in the Netherlands closely resembled that in Germany, the Nordic countries, Austria-Hungary and Switzerland, where it had developed from the work of lecturing university professors in the Middle Ages. In the second half of the 17 century and the first decades of the 18 century, Dutch medical schools ranked at the top of contemporary medical education; for example, Herman Boerhaave (1668-1738) was not only an excellent clinical teacher, but also developed the direct precursor of the ‘discipline-based curriculum,’ later adopted by many American medical schools as well, which dominated medical education until the 1970s. Boerhaave’s ideal curriculum consisted of a premedical phase (dedicated to mathematics and natural sciences), a preclinical phase (which featured animal and human dissection, post-mortem examinations, artificially produced diseases in animals, and knowledge of medicines) and finally a clinical phase, in which the student would be allowed at the bedside. After Boerhaave’s death, his system of clinical education gradually passed into disuse, and by the early 19th century, the French and English medical faculties had widely surpassed the Dutch. Like elsewhere, there was at the time in the Netherlands an extensive ‘second class’ of medical practitioners, predominantly trained by apprenticeship or at so-called ‘Clinical Schools’: rural and urban surgeons, rural and urban general practitioners, physicians who were only allowed to practice on board of ships or in the a","PeriodicalId":34382,"journal":{"name":"Fertility Reproduction","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88149404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}