Infertility is a common and often distressing problem
affecting approximately 1 in 6 couples. Statistics confirm that
the incidence of infertility is not actually increasing. More couples
are, however, seeking help and advice as treatments become more
readily available and effective. Having worked in the specialist
area of infertility for fifteen years, I appreciate that many couples
find a diagnosis of polycystic ovarian syndrome (PCOS) confusing
and difficult to understand. I have therefore chosen to reflect
on this particular cause of infertility in order to increase my
own knowledge, thus enabling me to readily supply information and
advice to women and their partners.
PCOS is a highly variable and individual disorder
which was first described by Drs. Stein and Leventhal in 1935. They
identified a group of infertile women who had menstrual abnormalities
and enlarged ovaries (now known as polycystic ovaries). They also
described hirsutism and obesity amongst this group. Not all women
with polycystic ovaries however, will exhibit these features. Goldzieher
J. W. and Green J. A. (1962) reported that in women with surgically
proven polycystic ovaries, 20% had no menstrual irregularities,
50% were not obese and 31% were not hirsute. Polson et. al. (1988)
confirmed these findings and reported that polycystic ovaries are
found in 22% of the normal population i.e. women who had not sought
treatment for menstrual disturbances, infertility or hirsutism.
PCOS may be classified using three main criteria:
1. Clinical presentation, 2. Biochemical characterisation
and 3. Characterisation of ovarian abnormalities.
It is these three criteria which are important for
the diagnosis and classification of PCOS.
Most women with PCOS have a history of normal menstrual
age but develop irregular cycles after the menarche. It is clear
therefore that some women presenting with infertility may have had
physiological difficulties in their teenage years, and may have
foreseen the impact that this would have on their reproductive health
in the future. Women with PCOS often have excessive hair growth
and may be overweight. Yen (1980) noted that more than 80% of women
with PCOS were obese prior to the onset of puberty. Although obesity
is frequently associated with this condition it is unclear whether
it is an intrinsic component or a predisposing state as weight loss
is frequently associated with the correction of hormonal abnormalities
and the re-establishment of regular ovulation.
As there is a high prevalence of PCOS in families
of affected individuals, the syndrome may have a genetic component
(Hauge et. al., 1988). Hypertension, diabetes, insulin resistance
and obesity occur more often in families of PCOS women, whilst endocrine
abnormalities and disturbed testicular function have been described
in male family members. A recent study of familial PCOS has identified
premature balding in male relatives as the male phenotye of PCOS
(Carey et. al., 1993).
Biochemical assessment of women with PCOS will now
be discussed and involves assessing hormonal levels in the blood
stream. At the time of birth a woman has between 200,000 and 400,000
primordial follicles within each ovary. As a consequence of a cyclic
release of hormones the menstrual cycle occurs, a primordial follicle
will mature during each cycle and a mature oocyte will be released.
Follicle stimulating hormone (FSH) and Leutenising hormone (LH)
are Gonadotrophic hormones released by the anterior pituitary gland
which act directly on the ovary. These hormones convert pre-antral
follicles to antral or Graafian follicles and each one appears to
exert its effects at different locations within the follicle. The
granulosa cells of the follicles bind FSH whereas only the cells
of the theca interna bind LH. Proliferation of the granulosa and
thecal cells cause an increase in follicular size. During this phase
of growth the follicle will increase its synthesis of androgens
from acetate and cholesterol and this conversion is greatly stimulated
by LH As the follicle continues to increase In size the synthesis
of oestrogen's increases and the largest more advanced follicle
releases steroids into the circulation. These steroids feedback
negatively to the pituitary and this leads to a progressive reduction
in circulating FSH and therefore limits development of further follicles.
Oestrogen, in conjunction with FSH plays a crucial role within the
follicle towards the second phase of growth. Together they stimulate
the appearance of LH binding sites on the outer layer of the granlosa
cells which previously lacked them. The Graafian follicle will die
unless a brief surge of high levels of gonadotrophin coincides with
the appearance of these LH receptors. The surge of LH has two effects.
Firstly, ovulation occurs and the oocyte is expelled from the follicle
and secondly, it changes the whole endocrinology of the follicle,
forming a corpus luteum after ovulation. The corpus luteum then
secretes progesterone and some oestrogens which will support a developing
embryo.
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