Although single aetiologies may occur, some of these categories (e.g. anovulation and male factor) may coexist, and this will need to be taken into account when planning investigations or treatment.
Table 45.3 Classification of disorders of ovulation '
Site of lesion
Hypogonadotrophic Hypo-oestrogenic Normoprolactinaemic WHO type I Normogonadotrophic
Normo-oestrogenic Normoprolactinaemic WHO type II Hypergonadotrophic Hyper-oestrogenic Normoprolactinaemic WHO type III Hyperprolactinaemic
Hypothalamic pituitary Ovarian axis
Low FSH* Normal prolactin Low oestradiol
Normal oestradiol Normal prolactin
High FSH Low oestradiol Normal prolactin
Low FSH Low oestradiol High prolactin
* FSH, follicle stimulating hormone.
Adapted from: Templeton et al. (2000) Management of infertility for the MRCOG and beyond. RCOG, Press London ISBN 1-900364-29-8.
Absence of ovulation (anovulation) or infrequent ovulation (oligo-ovulation) is seen in a fifth of all women presenting with infertility. Types of anovulatory infertility can be further classified as shown in Table 45.3.
Table 45.4 PCOS - the revised 2003 diagnostic criteria
Diagnosis of PCOS includes the presence of two out of the three listed below:
1. Oligo- and/or anovulation
2. Clinical and/or biochemical signs of hyperandrogenism*
And the absence of other endocrine causes: Congenital adrenal hyperplasia Androgen secreting tumours Cushings syndrome Hyperprolactinaemia Thyroid dysfunction
* Clinical indicators of hyperandrogenism are hirsutism, acne and androgenic alopecia. The elevation of free testosterone and/or free testosterone (free androgen) index (FAI) are the biochemical indicators of PCOS. Some women with PCOS may have isolated elevations in dehydroepiandrosteronesulphate (DHEAS). " The definition of polycystic appearing ovaries on scan includes the presence of 12 or more follicles in each ovary measuring 2-9 mm in diameter, and increased ovarian volume (>10 ml). The ovarian volume is calculated using the formula (0.5 x length x width x thickness). The distribution of follicles is not included in the definition and only one ovary fitting the description is sufficient for the diagnosis.
Adapted from: The Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group, 2004.
serum testosterone, dehydroepiandrostenedione sulphate (DHEAS) and 17 hydroxy progesterone.
HYPOTHALAMUS AND PITUITARY (HYPOGONADOTROPHIC HYPOGONADISM) (WHO TYPE I)
Abnormalities of gonadotrophin releasing hormone (GnRH) agonist secretion are associated with very low levels of oestradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Kallman's Syndrome is a congenital cause of anovulation characterized by isolated gonadotrophin deficiency and anosmia. Acquired causes include pituitary tumours, pituitary necrosis (Sheehan's syndrome), stress and excessive weight loss or exercise. Clinical examination of the visual fields and imaging of the pituitary fossa are indicated when a space occupying pituitary lesion is suspected.
The majority of women with normogodatotrophic anovulation have polycystic ovary syndrome (PCOS). Other causes include congenital adrenal hyperplasia, adrenal tumours and androgen producing ovarian tumours. The last three conditions present with coexistent hir-sutism and require more detailed investigations including
Polycystic ovary syndrome (PCOS) accounts for over 75% of all women with anovulation (Adams et al. 1986). Clinical features are heterogeneous and can vary in the same individual over time. Women with PCOS may present with anovulatory infertility, menstrual irregularities (usually oligoamenorrhoea/amenorrhoea), hirsutism and obesity. The currently accepted criteria for the diagnosis of PCOS are shown in Table 45.4 (see Chapter 39).
HYPERGONADOTROPHIC HYPOGONADISM (WHO TYPE III)
Amenorrhoea with elevated serum FSH and low or unde-tectable oestrogen levels signify ovarian failure. Known causes include Turners Syndrome (XO), Turner mosaic (XO, XX, XX) gonadal dysgenesis, autoimmune disorders, irradiation or chemotherapy. In many cases the cause is unknown. Turner's syndrome is characterized by a kary-otype of 45 (XO) and phenotypic abnormalities including short stature, webbing of the neck, shield chest and cubitus valgus. By puberty the gonads can be identified as 'streak' ovaries with no functioning follicles by the age of puberty. In Turner mosaics, (45X/46XX) spontaneous ovulation and menstruation may occur.
Increased levels of prolactin interfere with normal pulsatile secretion of GnRH, resulting in anovulation, amen-orrhoea and occasionally galactorrhoea associated with low FSH and oestradiol levels. Hyperprolactinaemia is a feature of prolactin producing pituitary adenomas or tumours blocking inhibitory control of the hypothalamus. Other causes include primary hypothyroidism, chronic renal failure, and drugs such as the combined oral pill, dopamine depleting agents (reserpine, methyldopa) and dopamine receptor inhibiting agents (metoclopramide and phenothiazines).
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