Advanced glycation end-products accumulation compromises embryonic development and achievement of pregnancy by assisted reproductive technology

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Masao Jinno1,*, Masayoshi Takeuchi2, Aiko Watanabe1, Koji Teruya3, Jun Hirohama1, Noriko Eguchi1 and Aiko Miyazaki4

1Women's Clinic Jinno, 3-1-39-201 Kokuryou-chou, Choufu City, Tokyo 182-0022, Japan

2Department of Life Pharmacy, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa City, Ishikawa, Japan

3Department of Public Health, School of Health Sciences, Kyorin University, Hachioji City, Tokyo, Japan

4HUSHIMI Pharmatheuticals, Kagawa, Japan *Correspondence address. Tel: +81-424-80-3105; Fax: +81-424-80-3105; E-mail: mjinno{at}s9.dion.ne.jpReceived August 20, 2010. Revision received December 2, 2010. Accepted December 10, 2010. BACKGROUND Advanced glycation end-products (AGE) are pivotal in aging and diabetes. Aging and polycystic ovary syndrome, a diabetes-associated disease, often cause infertility. We examined how AGE accumulation affects assisted reproductive technology (ART) outcomes.

METHODS In this retrospective analysis, toxic AGE (TAGE), pentosidine (Pent) and carboxymethyl lysine (CML) in blood and follicular fluid (FF) were measured in 157 ART-patients. We analyzed associations of AGE with ART outcomes and pre-ART clinical factors.

RESULTS TAGE, Pent and CML in FF and TAGE in serum, showed significant negative correlations with estradiol and numbers of follicles larger than 12 mm in diameter, retrieved oocytes, fertilized oocytes and embryos. AGE, Pent in FF and TAGE in serum showed significant negative correlations with ongoing pregnancy. Areas under receiver-operating characteristic curves for AGE (0.709), Pent in FF (0.686) and TAGE in serum (0.667) were significantly larger than for the reference (0.5). Women with serum TAGE above 7.24 U/ml showed decreased oocyte numbers and ongoing pregnancy rates, even with younger age or lower Day-3 FSH. Serum TAGE correlated positively with leptin (R = 0.51), BMI, low-density lipoprotein, triglyceride, glucose, homeostasis model assessment-insulin resistance and insulin.

CONCLUSIONS Serum TAGE and FF Pent accumulations correlated highly with poor follicular and embryonic development and with a lower likelihood of ongoing pregnancy. Serum TAGE predicts poor ART outcomes independent of age and Day-3 FSH.

© 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 (3): 604-610. doi: 10.1093/humrep/deq388 First published online: January 12, 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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