Fertility Preservation Ovarian Function and Regulation


Heidi Kühling-von Kaisenberg, Constantin Sylvius von Kaisenberg and Liselotte Mettler Department of Obstetrics, Gynaecology and Reproductive Medicine, Hannover Medical School


Abstract


Ovulation plays a major role in women’s lives. Extraction and synthesis of hormones has offered the possibility of interaction with ovarian function through either ovulation suppression or induction. The preservation of fertility at endoscopic surgery or in cancer treatment has become another important topic. Also, an increasing number of well trained and educated professional women are planning pregnancy at an advanced maternal age. Techniques such as cryopreservation are used to postpone pregnancy without increasing the genetic risks associated with advanced maternal age such as chromosomal abnormalities. The number of ovulations, which is modified through various interventions, may be involved in the complex process for cancer induction. This article provides a summary of the up-to-date literature on the anatomical and physiological basis of ovarian function and regulation, of conception and contraception, of fertility preservation in cancer cases with chemotherapy, radiation or extensive surgery and of the role of all of these elements in cancer induction.


Keywords Fertility preservation, cryopreservation, conception, contraception


Disclosure: The authors have no conflicts of interest to declare. Received: 3 September 2009 Accepted: 4 January 2010 Citation: European Obstetrics & Gynaecology, 2010;5:23–6 Correspondence: Liselotte Mettler, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Gynäkologie und Geburtshilfe, Arnold Heller Str 3, Haus 24, 24105 Kiel, Germany. E: lmettler@email.uni-kiel.de


Embryology, Physiology and Endocrinology When a girl is born her ovaries contain all the oocytes she will ever possess. The primordial germ cells reach the genital ridges from the yolk sac endoderm at five to six weeks post-fertilisation and form the basic reproductive unit of the ovary. There is evidence that all dominant pre-ovulatory follicles are selected from the pool of germ cells as early as at 24 weeks’ gestation. In each primordial follicle, an immature oocyte is surrounded by a single epithelial cell layer composed of granulosa cells. These are surrounded by a basal lamina, creating a microenvironment. As all primordial follicles are formed before birth, only a few survive until menopause (see Table 1).1,2


This is


completely different from the male, who starts producing spermatozoa only at puberty and then continues to do so until the end of his life.


Isolated oocytes do not grow in culture without their companion somatic cells, the granulosa cells, attached. Cutting-edge knowledge about oocyte maturation comes from trials of artificial oocyte production of pluripotent somatic or embryonic stem cells.3,4


Human


oocytes spontaneously complete nuclear maturation as they are released from follicles and cultured in vitro for up to 48 hours. Typical germinal vesicle breakdown (GVBD) occurs after 12 hours, but this does not happen simultaneously, and in some oocytes GVBD does not begin until 24 hours after the beginning of culture.1


After menarche, in every ovulatory cycle one recruited follicle usually grows during the follicular phase up to a diameter of approximately 22mm, ruptures, and, depending on the stimulus of follicle-stimulating hormone (FSH) and luteinising hormone (LH) at the time of ovulation,


© TOUCH BRIEFINGS 2010


releases the oocyte for fimbrial pick-up and fertilisation or for digestion by macrophages. The follicular defect is immediately closed by a healing mechanism of cytokines, which also form the corpus rubrum or, in the case of pregnancy, the corpus luteum graviditatis.


Hormone levels in the pre-ovulatory phase are characterised by a rise in oestrogen levels, low progesterone levels and an LH peak that directly triggers ovulation. Subsequently, progesterone rises until the end of the cycle.1


A normal cycle comprises various contributions from the central nervous system (CNS), the limbic system, the hypothalamus, the hypophysis and the ovaries, which have to work together. Disturbances in these interactions lead to ovarian dysfunction with follicular maturation disturbances, inadequate ovulation, inadequate functioning of the corpus luteum and resultant bleeding abnormalities. The 1973 World Health Organization (WHO) classification of ovarian dysfunction still gives the best general idea of diagnostic techniques and therapy.5


Women exhibit menstrual irregularity followed by menopause when the average number of primordial follicles per ovary decreases to approximately 100. Inhibin B is a major regulator of FSH secretion and a product of small antral follicles. Its levels respond to the early follicular phase increase and decrease in FSH. The age-related decrease in ovarian primordial follicle numbers, which is reflected in a decrease in the number of small antral follicles, leads to a decrease in inhibin B, which in turn leads to an increase in FSH. Concurrently, the concentrations of testosterone do not change significantly.


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