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Anovulation (not ovulating) is one of the common reasons of infertility. Normally, one of the ovaries releases a single mature egg every month, and this is called ovulation. Egg maturation and ovulation is stimulated by two hormones secreted by the pituitary - follicle stimulating hormone (FSH) and luteinizing hormone (LH) . These two hormones must be produced in appropriate amounts throughout the monthly cycle for normal ovulation to occur. Every month, at the start of the menstrual cycle, in response to the FSH produced by the pituitary gland, about 30-40 primordial follicles start to grow. Of these, only one matures to form a large fluid-filled structure, called a Graafian follicle which contains a mature egg, while the others die ( a process called atresia). The mature egg is released from the follicle when the follicle ruptures in response to a surge of LH produced by the pituitary.After ovulation has occured, the follicle from which the egg has been released forms a cystic structure called the corpus luteum. This is responsible for progesterone production in the second half of the cycle.

Most women who have regular periods have ovulatory cycles. Women who fail to ovulate or who have abnormal ovulation usually have a disturbance of their menstrual pattern. This may take the form of complete lack of periods (amenorrhoea), irregular or delayed periods (oligomenorrhoea) or occasionally a shortened cycle due to a defect in the second part (luteal phase) of the cycle.

Abnormal ovulation

Abnormalities of ovulation ( anovulation) may appear in several ways. Menstrual cycles shorter than 21 days or longer than 35 days are often associated with anovulation. In addition, patients may skip menstrual periods for time intervals of three months or more and this is called oligomenorrhea (infrequent periods) . If the periods stop entirely, this is called amenorrhea.

Many hormonal systems work together to produce regular menstrual periods, and the blood levels of the hormones that make up these systems need to be tested in order to determine the reason for the ovulatory disorders.

The hormone blood tests, which are usually done on the third day of your cycle, test for the levels of the following key reproductive hormones :

The FSH level: The FSH level gives a good idea of the number of eggs remaining in the ovaries. A high FSH level suggests that the ovary has either failed or has started to fail. If the FSH level is very high (in the menopausal range) then the diagnosis is ovarian failure. If the level is borderline, then some doctors will do a clomiphene stimulated FSH level, which allows for an earlier diagnosis of failing ovaries. On the other hand, a low FSH level suggests hypogonadotropic hypogonadism. This seemingly verbose term simply means that the ovary in these patients is not working properly because of inadequate production of FSH by the pituitary gland. However, in most anovulatory patients, the FSH level will be in the normal range, and this can be reassuring.

The LH level: This is the other gonadotropin hormone produced by the pituitary; and provides much the same information the FSH level does. Another useful test is the LH:FSH ratio which is normally 1:1.

If, however, the LH level is much higher than the FSH level,this suggests a diagnosis of polycystic ovarian disease.

Thyroxine and TSH: These tests for thyroid function. The thyroxine level is high in patients with overactive thyroid glands (hyperthyroidism). In patients with decreased thyroid function (hypothyroidism), the TSH level is increased.

Prolactin: Prolactin is a hormone produced by the pituitary gland that induces lactation or milk formation.. High prolactin levels (hyperprolactinemia) can interfere with ovulation . A milky discharge from the breast nipple , not related to pregnancy or nursing , is called galactorrhea, and this is a telltale symptom of high prolactin levels and needs to be investigated. If the prolactin level is elevated, the doctor will need to recheck it to confirm it is persistently high. There are many reasons for an elevated prolactin level, including certain drugs as well as stress. In some women, the reason for a high prolactin level can be a small tumour in the pituitary gland. This is called a prolactinoma or microadenoma, and the doctor may advise you have an X-ray of the skull ( or even a CT scan or MRI scan) to rule out this possibility. However, most infertile women with hyperprolactinemia can be easily treated with a medicine called bromocryptine, which is a dopamine agonist medication . Another medication which can be used to treat hyperprolactinemia is oral cabergoline, which is usually taken twice a week. Only if the pituitary tumour is very large ( microadenoma) is surgical removal needed, and this is very uncommon.

Ovarian failure

Ovarian failure is a disease in which the ovaries fail to produce eggs. This disease is uncommon, occurring in only about 10% of women whose periods do not occur at all, a condition called amenorrhea (absence of periods). Ovarian failure may be genetic (for example, in girls with Turner's syndrome, a chromosomal disorder) or may be acquired (for example, following radiation or chemotherapy for cancers; surgery to remove the ovaries for treating ovarian cancer or severe endometriosis; autoimmune ovarian failure; or for unexplained reasons.) Ovarian failure is diagnosed by finding a high FSH level. In such patients it is usually not possible to stimulate ovulation and they have any eggs, and they suffer a premature menopause. The only effective medical treatment for these patients is the use of egg donation for IVF or GIFT. However, in a very small proportion of these patients, ovulation can resume spontaneously.

Induction of ovulation

What forms of treatments are available for inducing ovulation?

The most commonly prescribed medicines for induction of ovulation include the following: clomiphene citrate, human menopausal gonadotrophin (HMG) and follicle stimulating hormone (FSH), HCG (human chorionic gonadotropin), bromocriptine, GnRH (gonadotropin releasing hormone) and GnRH analogue.

For women with hypogonadotropic hypogonadism (low FSH and LH levels), the treatment of first choice is HMG. This is effective replacement therapy; and excellent pregnancy rates can be achieved in these women.

For women affected by hyperprolactinemia, the drug of first choice is bromocriptine.

For most other women, the drug of first choice is clomiphene - the "workhorse" of ovulation induction. If this does not work, then HMG is resorted to.

Poor responders to HMG can be treated with GnRH analogues in conjunction with the HMG; or by adding a hormone called the human growth hormone.(HGH).

HCG (human chorionic gonadotropin) is given to trigger off the release of the egg.

In patients with high androgen levels (high blood levels of male hormones), dexamethasone can be used as an adjunct, since this suppresses androgen production.

Often ovulation induction requires an investment of time, money, energy and emotion before a satisfactory response is achieved. After all, every woman is different and there can be no standard "formulae". Careful monitoring of the response to ovulation induction is the key to therapy - and this usually involves daily ultrasound scans and/or blood tests. It is often a tedious process - which may involve "trial and error" to tailor the therapy to the individual patient's ovulatory response. With the treatments available today, however, correcting ovulatory dysfunction is one of the most rewarding and successful of infertility treatments.

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