ORIGINAL ARTICLE: ASSISTED REPRODUCTION
Utilization of the Bologna criteria: a promise unfulfilled? A review of published and unpublished/ongoing trials Aysen Boza, M.D.,a Sule Yildiz Oguz, M.D.,b Selim Misirlioglu, M.D.,b Kayhan Yakin, M.D.,a,b and Bulent Urman, M.D.a,b a Women's Health Center Assisted Reproduction Unit, American Hospital; and b Department of Obstetrics and Gynecology, Koc University School of Medicine, Istanbul, Turkey
Objective: To study the use of the Bologna criteria (BC) for the definition of poor ovarian responders (POR) in clinical practice and research. Design: Systematic review of published and unpublished/ongoing trials between January 2012 and August 2017 on POR. Setting: Not applicable. Patient(s): Not applicable. Intervention(s): The databases were searched using the relevant medical subject headings including all subheadings. The search was limited to humans and English language. The references of the included studies were cross-searched for possibly missed articles. Only clinical trials providing an evidence level R III were included. Case reports, review, letters, and hypothetical articles were excluded. Main Outcome Measure(s): Extracted studies were divided into two groups: studies in which the BC were used or not. Result(s): One hundred nine published clinical studies analyzing a total of 30,540 women and 112 unpublished/ongoing trials were identified. The BC were used to define POR in 56 (51%) of the published and 44 (39%) of the unpublished trials. The use of the BC gradually increased from 29% to 53% from 2012 to 2017. Asian researchers were more likely to use the BC compared with European and North American researchers (65%, 49%, and 23%, respectively). Neither the design of the study nor the impact factor of the publishing journal was correlated with the use of the BC. Conclusion(s): There is still reluctance to use the BC for the definition of POR, which makes it difficult to combine data from small studies and reach a meaningful conclusion. (Fertil SterilÒ 2017;-:-–-. Ó2017 by American Society for Reproductive Medicine.) Key Words: Poor ovarian response, Bologna criteria, definition Discuss: You can discuss this article with its authors and other readers at https://www.fertstertdialog.com/users/16110-fertilityand-sterility/posts/20408-24507
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efining poor ovarian response (POR) has been a longstanding challenge. Prompted by the call for a universally accepted definition, the European Society of Human Reproduction and Embryology organized a Campus Workshop in 2011 and published the ‘‘Bologna Criteria [BC] to Define Poor Responders’’ (1). POR was defined as the [1] collection of three or fewer oocytes in two prior ovarian stimulation cycles, [2] collection of three or fewer oocytes in a single
stimulation cycle from a woman who is over 40 years of age, [3] collection of three or fewer oocytes in a single stimulation cycle and an abnormal ovarian reserve test (ORT: antral follicle count less than five to seven follicles or antim€ ullerian hormone < 0.5–1.1 ng/mL), or [4] presence of an abnormal ORT in a woman over 40 years of age. A comprehensive review of the clinical trials on POR showed that until 2011, over 40 different definitions had been used (2). The introduction of a
Received June 13, 2017; revised September 19, 2017; accepted September 20, 2017. A.B. has nothing to disclose. S.Y.O. has nothing to disclose. S.M. has nothing to disclose. K.Y. has nothing to disclose. B.U. has nothing to disclose. Reprint requests: Aysen Boza, M.D., Amerikan Hastanesi, Guzelbahce sokak no. 20, Nisantasi 34065, Sisli, Istanbul, Turkey (E-mail:
[email protected]). Fertility and Sterility® Vol. -, No. -, - 2017 0015-0282/$36.00 Copyright ©2017 American Society for Reproductive Medicine, Published by Elsevier Inc. https://doi.org/10.1016/j.fertnstert.2017.09.024 VOL. - NO. - / - 2017
standardized definition would then be expected to overcome this confusion and undoubtedly lead to a more evidence-based prognostic approach. However, there are numerous studies published after the definition of the BC that still used somewhat arbitrary definitions of POR. Furthermore, ongoing trials and registered trials also declare the use of other criteria besides BC. The purpose of this study is to review the currently available literature to evaluate the level of incorporation of the BC into clinical practice and research.
MATERIALS AND METHODS The MEDLINE, PubMed, Ovid, Google Scholar, and Scopus electronic databases were searched by two authors (A.B., S.Y.) independently for relevant 1
ORIGINAL ARTICLE: ASSISTED REPRODUCTION
TABLE 1 The studies and their criteria to select the population of POR. Reference (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) (15) (16) (17) (18) (19) (20) (21) (22) (23) (24) (25) (26) (27) (28) (29) (30) (31) (32) (33) (34) (35) (36) (37) (38) (39) (40) (41) (42) (43) (44) (45) (46) (47)
Criteria Low oocyte yield (2,500 IU Basal FSH > 9 mIU/mL Women < 45 years old and with 10 mIU/mL, after day 5 FSH > 12 mIU/mL, AFC 10 mIU/mL and age > 35 years In previous IVF attempt,
