Blood samples from women with Polycystic Ovarian Syndrome show that gonadotrophin secretion is disordered resulting in increased plasma LH relative to FSH levels. FSH peaks, which characterise ovulatory cycles, are absent and therefore pro-ovulatory follicular development ceases. Thus the granulosa cells do not acquire a fully activated aromatase system and remain unresponsive to LH. Because of this, healthy follicles in polycystic ovaries rarely develop beyond 5mm. Oestrogens are normally converted from androgens in the presence of aromatase which is decreased when high levels of: H exists. In women with Polycystic Ovarian Syndrome therefore, oestrogen synthesis and production of oestradiol from granulosa cells is decreased and atresia of the follicle occurs. This atresia causes a build up of secondary interstitial tissue and ovarian stroma. This disorder of gonadotrophin secretion causes anovulation.
Women with Polycystic Ovarian Syndrome have elevated plasma androgen levels i.e. raised serum concentration of testosterone, and this may represent the most sensitive single biochemical marker of Polycystic Ovarian Syndrome. These increased androgens are secondary to pulsatile release of LH by the pituitary and cause hirsutism and can be associated with acne and oily skin.
Assessment of serum levels of progesterone on day 21 of the menstrual cycle will deternine whether ovulation has occurred by detecting high levels of progesterone which is secreted by the corpus luteum. Other blood tests may be performed to exclude other causes of hyperandrogenism, such as Cushing’s Disease, hyperprolactinaemia or thyroid dysfunction.
The third criteria used to classify and diagnose Polycystic Ovarian Syndrome are the characterisation of ovarian abnormalities, with ultrasonography representing a recent and non-invasive technique to identify any ovarian changes. Hughesdon (1982) describes the polycystic ovary histologically as being typically increased in size and although an average number of primordial follicles are apparent, the number of ripening and atretic follicles present is usually doubled. There is a tendency for the tunica to be increased and it contains many collagen fibres. There is also an increase in sub-cortical stroma and this is derived primarily from the atretic follicles.
During atresia there is a striking hypertrophy of the theca cells which then disperse into the interstitial tissue. The increased number of follicles measuring 2-10mm in diameter can be easily visualised with ultrasound. These follicles are usually seen around the edge of the ovary and give it a classical pearl-necklace appearance. Ultrasonography will also demonstrate the increased stroma which typifies the polycystic ovary. An excellent correlation has been shown between morphological appearance, as observed on ultrasound, and that shown on histology , thus ensuring ultrasound can be reliably used for the diagnosis of Polycystic Ovarian Syndrome.
As already noted Polycystic Ovarian Syndrome is a complicated and unpredictable disorder which generally causes anovulation and therefore infertility. The treatment that will be offered will be aimed at resolving this anovulation. One of the earliest forms of treatment performed by Stein and Leventhal (1935), known as ovarian wedge resection has now been largely abandoned due to the need for laparotomy and the potential for development of adhesions. This surgical procedure was found to achieve successful ovulation in approximately 80% of women and ovarian diathermy has been used recently as an effective alternative with similar results.
The exact mechanism by which either procedure induces ovulation is unclear. As H J van Gelderp (1991) points out, most studies using these techniques have demonstrated that serum androgens and oestrogen levels fall in the post-operative period and this may eliminate the positive feedback effect of these steroids on the pituitary. The LH levels will return to normal and the normalisation of the FSH and LH ratio allows follicular maturation to occur. This return to a normal ovulatory cycle is thought to be only temporary but may enable women to achieve a pregnancy.
Anti-oestrogens such as Clomiphene Citrate and Tamoxifen may be used to induce ovulation in women with Polycystic Ovarian Syndrome. They act by binding hypothalmic oestogen receptors and therefore release the hypothalamus from the negative feedback effects of endogenous oestrogens. This leads to an increase in FSH and LH production, which then stimulates follicular growth. Ovulation rates of 80% are usually achieved with clomiphene and the cumulative pregnancy rate is 40-50% (Hammond et. al., 1983). This medication should not be continued for more than six months as with prolonged use the risk of developing invasive ovarian tumours is increased.
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