Ovulation is the result of a maturation process that occurs within the hypothalamic-pituitary-ovarian (HPO) axis and is orchestrated by a neuroendocrine cascade terminating in the ovaries. Any alteration in this results in a failure to release a mature ovum, leading to anovulatory cycles. Anovulatory disorders may manifest in a variety of clinical presentations, ranging from luteal insufficiency to amenorrhea. Anovulatory disorders account for about 30 to 40 percent of all cases of female infertility. These disorders are generally amongst the most easily diagnosed and most treatable cause of infertility.1 Most of these women have oligomenorrhea, arbitrarily defined as menstruation that occurs at intervals of 35 days to 6 months. While ovulation may occasionally occur, spontaneous conception is unlikely. Therapeutic options have expanded significantly in recent years from clomiphene to gonadotropins. Induction of ovulation in these women is aimed at inducing monofollicular development and subsequent ovulation. Induction of ovulation should be differentiated from stimulation of multiple follicle development in ovulatory women, as is done in association with assisted reproductive technologies. The method of ovulation induction (OI) selected by the clinician should be based upon the underlying cause of anovulation and the efficacy, costs, risks and potential complications associated with each method as they apply to the individual woman. This chapter reviews the common types of anovulation including their pathogenesis, diagnosis and efficacy of the different treatment regimens that are used and our approach to the management of such woman. Some of these disorders are reviewed in greater detail elsewhere in this book.
WORLD HEALTH ORGANIZATION CLASSIFICATION OF ANOVULATION
The clinical approach in management of patients with ovarian dysfunction requires an understanding of its causes. Classification of ovulatory dysfunction based on their cause was originally described by Lunenfeld and lnsler and then by European Society for Human Reproduction and Embryology (ESHRE) and again modified by World Health Organization (WHO). According to WHO, ovulatory dysfunction is classified into three main categories on the basis of menstrual cycle length; oligomenorrhea (menstrual cycles > 35 days) or amenorrhea (menstrual cycle > 6 months) in combination with serum hormonal levels of prolactin (PRL), follicle stimulating hormone (FSH) and estradiol (E2) (Box 1).
WHO CLASS 1
Hypogonadotropic Hypogonadism This group accounts for 5 to 10 percent of anovulation. Women in this group, frequently present with amenorrhea.
Etiology Hypogonadotropic hypogonadism (HH) can be congenital or acquired. Congenital HH is further divided into anosmic HH (Kallmann’s syndrome) and normosmic isolated HH (idiopathic HH). Kallmann’s syndrome itself is a heterogeneous disorder with an X-linked form due to mutations in Kal1 gene (the gene encoding for anosmin-1 protein) and other forms with autosomal transmission. Pathology of idiopathic HH is failure of gonadotropinreleasing hormone (GnRH) neurons in the hypothalamus to differentiate or develop resulting in either lack of or apulsatile GnRH secretion.