Classification of Anovulation

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Classification of Anovulation

Evert J.P. van Santbrink

Introduction

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

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).

Relevant criteria used for the definition of PCOS should not only be able to create a strictly defined group of patients (diagnosis based on a dysfunction of a specific organ system), but may also have predictive value on the treatment possibilities and treatment outcome (prognosis, severity of the illness). As we are increasingly aware that initial patient characteristics rather than the chosen treatment modality determine treatment success or failure, this clinical tool may enable us to apply an individually tailored treatment approach.

The Rotterdam criteria for PCOS diagnosis encompass the presence of two of the following criteria: androgen excess (biochemical or clinical), ovulatory dysfunction, or polycystic ovaries on ultrasound. Establishing the diagnosis may be complicated in adolescents and menopausal women (LOE 4). Although hyperandrogenism has a central role to the presentation in adolescents, the phenotype in postmenopausal women is less consistent. It may be concluded that using the Rotterdam criteria instead of the NIH criteria for PCOS, patients with less severe metabolic derangement will be added to the PCOS group (10).

Conclusion

The most common classification system of chronic oligo or anovulation is proposed by the WHO and based on hormonal serum concentrations of FSH and estradiol (Table 2.3). Before using this, hyperprolactinemia, adrenal hyperandrogenism and thyroid dysfunction have to be excluded. The majority of patients are classified as WHO class 2 anovulation, and a substantial number of these patients fulfill PCOS criteria. The most widely accepted criteria for PCOS diagnosis are the Rotterdam criteria.

TABLE 2.3

Endocrine Classification of Oligo and Anovulation (WHO)

TABLE 2.1

Level of Evidence of Statements

TABLE 2.2

Grade of Strength for Recommendations

REFERENCES

1. van Santbrink EJ, Hop WC, van Dessel HJ, de Jong FH, Fauser BC. Decremental FSH and dominant follicle development during the normal menstrual cycle. Fertil Steril 1995; 64:37–43.

2. Wise LA, Mikkelsen EM, Rothman KJ, Riis AH, Sørensen HT, Huybrechts KF, Hatch EE. A prospective cohort study of menstrual characteristics and time to pregnancy. Am J Epidemiol 2011; 174(6):701–9.

3. Insler V, Melmed H, Mashiah S, Monselise M, Lunenfeld B, Rabau E. Functional classification of patients selected for gonadotropic therapy. Obstet Gynecol 1968; 32:620–6.

4. Rowe PJ, Comhaire FA, Hargreave TB, Mellow HJ. WHO manual for the standardized investigation and diagnosis of the infertile couple. Cambridge University Press, Cambridge, England. 1997; 1–80.

5. Van Santbrink EJ, Hop WC, Fauser BC. Classification of normogonadotropic infertility: Polycystic ovaries diagnosed by ultrasound versus endocrine characteristics of polycystic ovary syndrome. Fertil Steril 1997; 67:452–8.

6. Zawadzki JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: Towards a rationale approach. In: Dunaif A, Givens JR, Haseltine FP, Merriam GR. Polycystic ovary syndrome. Blackwell Scientific Publications, Boston. 1992; 377–84.

7. PCOS consensus. The Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19:41–7.

8. PCOS consensus. The Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Fertil Steril 2004; 81:19–25.

9. Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R et al. Diagnosis and treatment of polycystic ovary syndrome: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2013 Dec; 98(12):4565–92.

10. Broekmans FJ, Knauff EA, Valkenburg O et al. PCOS according to the Rotterdam consensus criteria: Change in prevalence among WHO-II anovulation and association with metabolic factors. BJOG 2006; 1210–7.

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