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      Types of ovarian activity in women and their significance: the continuum (a reinterpretation of early findings)

      review-article
      Human Reproduction Update
      Oxford University Press

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          Abstract

          BACKGROUND

          There are many types of ovarian activity that occur in women. This review provides information on the relationship between the hormone values and the degree of biological response to the hormones including the frequency and degree of uterine bleeding. The continuous process is termed the ‘Continuum’ and is thus similar to other processes in the body.

          METHODS

          This review draws on information already published from monitoring ovarian activity by urinary oestrogen and pregnanediol measurements using timed 24-h specimens of urine. Much of the rationalization was derived from 5 to 6 year studies of girls progressing from childhood to adulthood, women progressing through menopause, and the return of fertility post-partum. During these times, all the reported types of ovarian activity were encountered.

          RESULTS

          All cycle types can be understood in terms of steps in the normal maturation of fertility at the beginning of reproductive life, its return post-partum and its demise at menopause. Each step merges into the next and therefore the sequence is termed the ‘Continuum’. Unpredictable movement from fertile to infertile types and back can occur at any time during reproductive life. Stress is a major causative factor. Hormonal definitions for each step, the relevance of the various cycle types in determining fertility and in the initiation of uterine bleeding and the roles of the pituitary hormones in causing them, are presented.

          CONCLUSIONS

          The findings explain the erratic fertility of women and why ovulation is not always associated with fertility. They provide an understanding of the various types of ovarian activity and their relation to pituitary function, fertility and uterine bleeding.

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          Most cited references45

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          A new model for ovarian follicular development during the human menstrual cycle.

          To evaluate changes in ovarian follicle dynamics during the human menstrual cycle to test the hypothesis that folliculogenesis occurs in a wave-like fashion. Prospective longitudinal study. Healthy volunteers in an academic research environment. Fifty healthy women of reproductive age (range 19-43 years) with a history of regular menstrual cycles not taking medications known to interfere with reproductive function were evaluated. Transvaginal ultrasonography was performed daily for one interovulatory interval (IOI). Changes in the diameter and number of follicles > or =5 mm were evaluated. Sixty-eight percent of women exhibited two waves of follicle development during the IOI and 32% exhibited three waves. Waves were characterized by an increase and subsequent decrease in the number of follicles > or =5 mm occurring in association with the growth of > or =2 follicles to > or =6 mm. A day effect and day by wave interaction were detected in the mean diameter of the largest three follicles and the number of follicles > or =5 mm. The follicular wave phenomenon in women provides a new model for ovarian function during the menstrual cycle and will improve our understanding of the ovarian response to fertility and hormonal contraceptive regimens.
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            Pituitary control of ovarian function--concepts derived from gonadotrophin therapy.

            From experience gained in the monitoring of ovarian responses to gonadotropin therapy, it has been possible to develop concepts concerning the mechanisms which operate during the normal menstrual cycle. It is shown that the ovarian requirement for FSH operates in a very narrow range, involving changes in concentration of only 10%; this range operates from a threshold level, through an intermediate level to a maximum level. After adequate stimulation, the follicle goes through a costing phase during which it is independent of further FSH stimulation and it acquires sensitivity to LH. Methods for determining optimum requirements for FSH and HCG for the induction of singleton pregnancies are presented. The relevance of the findings in providing hypotheses explaining some aspects of ovulatory and anovulatory cycles are discussed.
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              Urinary estrogen and progesterone metabolite concentrations in menstrual cycles of fertile women with non-conception, early pregnancy loss or clinical pregnancy.

              Knowledge is limited of how estrogen and progesterone variability in fertile women are associated with achieving pregnancy. From 1996 to 1998, we enrolled 347 textile workers without hormone treatment in Anhui, China, who provided daily urine and data upon stopping contraception for up to 1 year until clinical pregnancy. Urinary hCG was assayed to detect conception and early pregnancy losses. We compared urinary concentrations of estrone conjugates (E(1)C) and pregnanediol-3-glucuronide (PdG) in 266 clinical pregnancies, 63 early pregnancy losses and 272 non-conception cycles from 347 women and also in 94 clinical pregnancy and 94 non-conception cycles from the same women. Using generalized estimating equations and relative to 266 clinical pregnancy cycles, log(E(1)C) was lower in 272 non-conception cycles [beta = -0.3 ng/mg creatinine (Cr); SE = 0.1; P < 0.0001]. On average, daily E(1)C was 18 ng/mg Cr lower in non-conception cycles than in clinical pregnancy cycles. Relative to 94 clinical pregnancy cycles, log(E(1)C) was lower in 94 non-conception cycles (beta = -0.4 ng/mg Cr; SE = 0.1; P < 0.0001) from the same women (average difference in daily E(1)C was 20 ng/mg Cr). The odds of E(1)C less than the 10th percentile (<30 ng/mg Cr) were higher in early pregnancy loss cycles [odds ratio (OR) = 4.8; P = 0.0027] than in clinical pregnancy cycles in the early luteal phase. Compared with clinical pregnancy cycles, log(PdG) concentrations were lower in non-conception cycles during the follicular phase, but this analysis lacked power for multiple testing. Estrogen concentrations varied from cycle to cycle, and higher estrogen was associated with achieving clinical pregnancy.
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                Author and article information

                Journal
                Hum Reprod Update
                humupd
                humupd
                Human Reproduction Update
                Oxford University Press
                1355-4786
                1460-2369
                Mar-Apr 2011
                5 October 2010
                5 October 2010
                : 17
                : 2
                : 141-158
                Affiliations
                Emeritus Professor of Obstetrics and Gynaecology, simpleUniversity of Melbourne , Melbourne, Victoria 3010, Australia
                Author notes
                [* ]Correspondence address. Adrian Thomas, 206 Albert Street, East Melbourne, Victoria, Australia. 3002; Tel: +61-3-94197918; Fax: +61-3-94194407; E-mail: athomas@ 123456melbpc.org.au
                [†]

                Professor James Boyer Brown passed away on 31st October 2009.

                Article
                dmq040
                10.1093/humupd/dmq040
                3039221
                20923873
                61b76fdd-c2fe-4833-848f-8dd58e866191
                © The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. For Permissions, please email: journals.permissions@oxfordjournals.org

                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

                History
                : 16 May 2010
                : 21 July 2010
                : 2 August 2010
                Categories
                Reviews

                Human biology
                Human biology

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