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      Age, anti-müllerian hormone, antral follicles count to predict amenorrhea or oligomenorrhea after chemotherapy with cyclophosphamide

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          Abstract

          Background

          A cohort study was performed to identify ovarian reserve markers (ORM) that predicts amenorrhea or oligomenorrhea 6 months after cyclophosphamide CTX in women with breast cancer.

          Methods

          52 eumenorrheic patients with breast cancer were enrolled. FSH, anti-Müllerian hormone (AMH), antral follicles count (AFC) were measured before and 6 months after CTX. A logistic regression for independent samples and determination of the ROC curve were performed.

          Results

          The age of 32 years presented 96 % of sensitivity and 39 % of specificity to predict amenorrhea or oligomenorrhea with ROC area under the curve (AUC) of 0.77. ovarian reserve marker (ORM) with power to predict amenorrhea or oligomenorrhea in women after CTX were AMH <3.32 ng/mL (sensitivity of 85 %, specificity of 75 % and AUC 0.87), AFC <13 follicles (sensitivity 81 %, specificity 62 %, AUC 0.81). AMH cutoff to predict amenorrhea was 1.87 ng/mL (sensitivity 82 %, specificity 83 %, AUC 0.84) and AFC cutoff was 9 follicles (sensitivity 71 %, specificity 78 %, AUC 0.73).

          Conclusions

          ≥32-years-old women, AMH <3.32 ng/mL and AFC <13 follicles determined significantly higher risk of amenorrhea or oligomenorrhea after CTX with cyclophosphamide. The ORM age (≥32 years) analyzed together with AMH or AFC increases sensitivity and specificity in predicting amenorrhea or oligomenorrhea.

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          Most cited references20

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          The antral follicle count: practical recommendations for better standardization.

          To provide recommendations for the standardized use of the Antral follicle count (AFC) which is used to predict ovarian response to gonadotrophin stimulation during assisted reproductive technology treatment. However, the nature of the follicles that are visualized by ultrasound and the competence of the oocytes held within are largely unknown. In addition, there is considerable variability in the clinical definitions and technical methods used to count and measure antral follicles in both published studies and clinical practice. In December 2007, specialist reproductive medicine clinicians and scientists attended a workshop in an effort to address these issues. Literature concerning the physiology and measurement of ovarian antral follicles was reviewed, clinical and technical considerations regarding antral follicle measurement were discussed, and an operational definition of AFC was developed. None. None. Simple recommendations were established for the standardization of AFC assessment in routine clinical practice. The basic clinical and technical requirements required for AFC evaluation were agreed upon, and a systematic method of measuring and counting antral follicles in routine practice was proposed. The use of a standardized approach according to the practical recommendations for antral follicle counting as presented is encouraged in future clinical trials and routine practice. The authors also advocate a systematic evaluation of these recommendations as standardized study data become available. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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            Incidence, time course, and determinants of menstrual bleeding after breast cancer treatment: a prospective study.

            To assess ovarian function using the surrogate of monthly bleeding after breast cancer treatment in premenopausal women. Five hundred ninety-five US women age 20 to 45 years were accrued from January 1998 to July 2002 within 8 months of diagnosis with stages I to III breast cancer (median follow-up 45 months). Daily bleeding records were obtained prospectively, as well as extensive clinical, demographic, quality of life, and treatment data. Repeated measures logistic regression was used to assess which variables were predictive of monthly bleeding. Significantly different proportions of women had monthly bleeding depending on their age (P < .001), chemotherapy program (P < .001), and time since treatment regimen. In the month after the standard course of doxorubicin and cyclophosphamide (AC), whether or not followed by paclitaxel or docetaxel, approximately 16% had monthly bleeding compared with the cyclophosphamide, methotrexate, fluorouracil (CMF) group, in which 48% bled (P < .001). Following any AC regimen, there was a slow recovery phase of about 9 months followed by a plateau, during which almost half continued monthly bleeding for the remainder of the follow-up period compared with after CMF in which there was no recovery phase and a continual decline in monthly bleeding to approximately 18% of women at study end (P < .001). Tamoxifen use decreased bleeding between months 12 and 24 after chemotherapy with 15% fewer women having bleeding. Using daily menstrual bleeding records, it is demonstrated that age, the specific chemotherapy regimen received, and tamoxifen use impact ovarian function.
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              Impact of cancer therapies on ovarian reserve.

              To determine whether measures of ovarian reserve differ between females exposed to cancer therapies in a dose-dependent manner as compared with healthy controls of similar age and late reproductive age. Cross-sectional analysis of data from a prospective cohort study. University medical center. Seventy-one cancer survivors aged 15-39 years; 67 healthy, similarly aged unexposed subjects; and 69 regularly menstruating women of late reproductive age (40-52 years). None. Early follicular-phase hormones (FSH, E(2), inhibin B, antimüllerian hormone [AMH]) and ovarian ultrasound measurements (ovarian volume and antral follicle counts [AFC]) were compared using multivariable linear regression. In adjusted models, FSH, AMH, and AFC differed between exposed vs. unexposed subjects (FSH 11.12 mIU/mL vs. 7.25 mIU/mL; AMH 0.81 ng/mL vs. 2.85 ng/mL; AFC 14.55 vs. 27.20). In participants with an FSH <10 mIU/mL, survivors had lower levels of AMH and AFC compared with controls. Alkylating agent dose score was associated with increased levels of FSH and decreased levels of AMH. Exposure to pelvic radiation was associated with impairment in FSH, AMH, AFC, and ovarian volume. Antimüllerian hormone was similar in women previously exposed to high-dose cancer therapy and 40-42-year-old controls. Measures of ovarian reserve are impaired in a dose-dependent manner among cancer survivors compared with unexposed females of similar age. Reproductive hormone levels in menstruating survivors exposed to high-dose therapy are similar to those in late-reproductive-age women. The predictive value of measures for pregnancy and menopause must be studied. CLINICALTRIALS.GOV IDENTIFIER: NCT01143844. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                angelamdavila@yahoo.com.br
                vbiolchi@gmail.com
                0055 51 33598117 , edcapp@ufrgs.br
                hcorleta@gmail.com
                Journal
                J Ovarian Res
                J Ovarian Res
                Journal of Ovarian Research
                BioMed Central (London )
                1757-2215
                14 December 2015
                14 December 2015
                2015
                : 8
                : 82
                Affiliations
                [ ]Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul School of Medicine, Bento Gonçalves, RS Brazil
                [ ]Graduate Program in Biological Sciences: Physiology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Lajeado, RS Brazil
                [ ]Department of Obstetrics and Gynecology, Hospital de Clínicas de Porto Alegre, Sul School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS Brazil
                [ ]Department of Gynecological Endocrinology and Reproductive Medicine, University Hospital Heidelberg, Heidelberg, Germany
                [ ]GENERAR, Porto Alegre, RS Brazil
                [ ]Serviço de Ginecologia e Obstetrícia - Hospital de Clínicas de Porto Alegre Rua Ramiro Barcelos, 2350/11° andar, Porto Alegre, CEP 90035-903 RS Brazil
                Author information
                http://orcid.org/0000-0002-1039-7940
                Article
                209
                10.1186/s13048-015-0209-4
                4678664
                26667243
                fbd862a3-7893-4812-9518-1b68b8d1ca58
                © D’Avila et al. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 22 October 2015
                : 9 December 2015
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                Obstetrics & Gynecology
                anti-müllerian hormone,antral follicles count,ovarian reserve,amenorrhea related chemotherapy,anovulation related chemotherapy

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