UZ Brussel-VUB - Ovulation problems

Ovulation problems

Hormonal profile during the menstrual cycle.

Incorrect hormonal interaction

in the brain
in the reproductive organs

We have already seen that ovulation problems account for 30% of infertility. This type of problem arises from 'mistakes' in the hormonal interaction within the woman. (See also menstrual cycle).

As a result, the egg ripening process isn't initiated, or is incomplete.

If no ovulation occurs, it is called 'anovulation'. In this case, no menstruation will take place either;
If there is a regularity problem with ovulation, then irregular periods will also be an issue. If however the menstruation remains regular, the condition is known as 'dysovulation'.
An absence of menstruation can also be caused by a premature exhaustion of the supply of egg cells in the ovaries. This is known as premature menopause.

Incorrect hormonal interaction

The normal process of egg cell ripening and ovulation is the result of a finely tuned hormonal interaction between the brain and the reproductive organs.

The hypothalamus excretes the hormone GnRH with clockwork regularity (every 60-90 minutes) depending on the stage of the menstrual cycle. This stimulates the hypofyse to produce FSH and LH. The latter of these two hormones further stimulates the ovaries to start the ripening process of follicles (tiny fluid filled sacs, each containing an egg cell). During this process, the follicles begin producing oestrogen through a transformation of testosterone in the surrounding cells.

In the brain

Disturbances in the Hypothalamus

If the hypothalamus fails to produce sufficient levels of GnRH hormone, the ripening process of the follicles will be compromised, resulting in anovulation. This rare condition can be treated by means of a GnRH-pump.
Stress and drastic or uncontrolled weight loss can also lead to disturbances in the production of GnRH, also resulting in irregular or incomplete ripening process. Relaxation methods or controlled, responsible weight loss can be initiated to rectify this, but if that is not effective, medication such as clomifeen citrate or gonadotrofines or a GnRH-pump may be required.

Disturbances in the Hypofyse

Sometimes, the hormonal disturbance is the result of too much prolactine in the blood. This 'stress hormone' is also produced in the hypofyse. High levels of it can lead to interference of the follicle ripening process and further to anovulation or dysovulation.
Quite often, an 'adenoma' or benign tumour in the tissue of the hypofyse is to blame. If it is a very small tumour (a micro-adenoma, sometimes visible on a brain scan), it can be treated with medication. In the rare case that it is a macro-adenoma (larger, visible also on an x-ray), surgery will be required to remove it.

Disturbances to the interaction between Hypothalamus and Hypofyse

Sometimes, blood tests reveal all hormonal levels to be normal, apart from progesterone, which would cause problems related to ovulation. This would indicate a disturbance in the interaction between the hypothalamus en hypofyse: something not right with the frequency and regularity of GnRH release, with unsynchronized production of FSH an LH as a result. This either leads to disturbances of follicle ripening, or in rarer cases, a failure of LH levels to peak, resulting in no ovulation.

In cases where the follicle ripening process is affected, (detectable with ultrasound scan) the treatment of choice is to administer clomifeen citrate or gonadotrofines, often combined with hCG injections at the end of the ripening process.

In the reproductive organs

A frequent cause of ovulation problems is the syndrome known as PCO or 'Polycystic Ovary Syndrome'.

PCO syndrome at laparoscopy

Due to a disturbance in the production of GnRH, FSH and LH, too little oestrogen is produced (by transforming testosterone) which thus leads to the follicles not ripening into complete, fertile egg cells. As a result, the outside walls of the ovaries contain too many small follicles, hence the name 'polycystic'. The ovaries become swollen and can reach the size of a snooker ball.
Symptoms: Excess testosterone can lead to acne, greasy hair and excess body hair. Often, the patient is overweight and prone to diabetes.

PCO syndrome probably has a genetic background. The condition can sometimes be treated laparoscopically, with lasers, but before commencing fertility treatment, preference is given to treatment with clomifeen citrate or gonadotrofines. It is also an indication for IVF treatment.

Premature menopause
The scientific term for this is 'Premature ovarian insufficiency' or POI, the term indicates precisely what is wrong, namely that the supply of primordial follicles (from which egg cellls ripen) in the ovaries is prematurely exhausted. The patient has no periods anymore and frequently suffers with hot flushes. The condition itself is not reversible. The only chance of pregnancy is with egg cell donation or embryo donation. Adoption is of course another possibility.