Classification of Anovulation

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Classification of Anovulation

Evert J.P. van Santbrink


Oligo and anovulation represent a major cause of subfertility (LOE 3). It may either be clinically presented by a total absence of follicular development, resulting in amenorrhea, or in a disturbed development of a dominant follicle reflected by oligomenorrhea.

We consider the duration of the menstrual cycle to be normal if it is between 25 and 35 days with a median of 28 days (1). When the average duration of the menstrual cycle exceeds the 35-day limit, it is called oligomenorrhea; this is based on decreasing chances for ovulation and pregnancy when the duration of the menstrual cycle is prolonged (LOE 3; 2). We speak of amenorrhea when there is no menstrual cycle for a period of at least 6 months.


Classification of oligo or anovulation may be done in several ways: by the clinical appearance (primary or secondary), the organ of origin that causes the problem (hypothalamic, pituitary, or ovary), or the regulating system that causes the disturbance (hormonal, genetic, metabolic).

Most frequently, chronic anovulation is classified by World Health Organization (WHO) criteria, originally determined by Insler et al. (3,4). The criteria used are mean menstrual cycle duration (>35 days) and serum concentrations of follicle-stimulating hormone (FSH) and estradiol (E2). This classification can only be used after external influences on the hypothalamic–pituitary–ovarian system are excluded, such as hyperprolactinemia, adrenal hyperandrogenism, and thyroid dysfunction (LOE 4). For practical reasons, the etiology and treatment of primary amenorrhea are outside the scope of this book.

When the origin of menstrual cycle disturbance is situated in the hypothalamus or pituitary, resulting in both decreased serum FSH and estradiol concentrations, it is classified as WHO class 1 anovulation. Another etiology of anovulation may be ovarian failure: The ovaries are functioning insufficiently, and serum FSH is elevated whereas estradiol is low. This status, also known as premature ovarian insufficiency when occurrence is before the age of 40 years, can be classified as WHO3 anovulation. The largest part (about 80%) of anovulation patients exhibit normal FSH and estradiol serum concentrations and are classified as WHO class 2. Polycystic ovary syndrome (PCOS) encompasses a subgroup of these WHO2 patients (5). The criteria for establishing the diagnosis of PCOS have been under debate for an extensive period. Criteria set by the National Institute of Health in 1992 (6) combined androgen excess and ovarian dysfunction, while polycystic morphology of the ovaries was not included. Later on, the Rotterdam consensus meeting formulated strict PCOS criteria to facilitate comparison of clinical research from different institutes around the world and improve understanding of the etiology and treatment options (7,8). These criteria were also recently acknowledged by the Endocrine Society consensus meeting (9).

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