Question 26. If I don’t have either PCOS or POF, then what is my problem and why am I not ovulating?

Some patients really do stick in your mind long after they have left the practice. A couple of years ago we had a patient who had absent periods and had failed to respond to clomid or gonadotropin injections. She had been told by another RE that she needed donor egg and there was no reason to think that she would ever respond to fertility drugs. Now it is pretty uncommon to find yourself in the position of talking a patient out of donor egg IVF...but that is exactly what Dr D had to do. The patient consented to a final go at fertility drugs. But as she had FHA (see below) the stimulation was long with slow increases in drug dose. Ultimately she did respond and ended up with a great pregnancy with her own eggs. The key was to realize that the patient had FHA and not PCOS and use the correct recipe. It is all about cooking those follicles/eggs correctly....bad recipe = bad eggs.

So here is today's Question of the Day from the new and improved 2nd Edition of 100 Questions and Answers about Infertility.


26. If I don’t have either PCOS or POF, then what is my problem and why am I not ovulating?


Hormone abnormalities other than PCOS can also lead to irregular menstrual cycles. Such abnormalities include problems with the thyroid gland (which produces a hormone that controls metabolism), abnormal levels of prolactin (a hormone that induces breast milk production), and a lack of hypothalamic/pituitary stimulation to the ovary known as functional hypothalamic amenorrhea (FHA). The pituitary gland has been called the master gland of the body; it secretes hormones that control a wide range of functions, including reproduction, metabolism, response to stress, water balance, and growth.

Women with irregular cycles should have both their thyroid hormone and prolactin levels measured, as problems with the thyroid gland can indirectly lead to elevations in prolactin. Low levels of thyroid hormone (hypothyroidism) and elevations in prolactin (hyperprolactinemia) can be readily treated with medication. In fact, treatment of hypothyroidism with oral thyroid hormone (levothyroxine) can promptly restore normal menstruation. Similarly, hyperprolactinemia usually responds quickly to bromocriptine therapy, often promptly restoring normal cycles.

An elevation of prolactin in the absence of any thyroid disease requires magnetic resonance imaging (MRI) of the brain to evaluate its cause. In such cases, hyperprolactinemia usually results from an increased growth of the prolactin-secreting cells in the pituitary gland forming a small tumor. If the prolactin-secreting tumor is less than 1 cm in diameter, then it is called a microadenoma, whereas a macroadenoma is greater than 1 cm in diameter.

Women without thyroid or prolactin issues who fail to have menstrual periods following treatment with progesterone are usually referred to as having functional hypothalamic amenorrhea (FHA). These women fail to produce normal levels of estrogen despite an appropriate complement of ovarian follicles. Women who are below ideal body weight and who exercise frequently and vigorously are particularly prone to developing this problem. Women with FHA are at risk for osteoporosis and should discuss with their physician the benefits of hormone therapy (such as oral contraceptives) when not attempting pregnancy. They should also undergo an MRI of the brain to rule out any structural etiology for their condition. Women who are below ideal body weight may resume normal menstrual cycles when they gain weight or decrease their exercise frequency and duration.

Infertility in women with FHA can be readily treated with injectible gonadotropins. In such women, the choice of medication is important as the drug should contain both FSH and L (Menopur) and not just FSH alone (Gonal-F, Follistim). Clomid rarely works in women with FHA, but nearly all women with FHA can undergo successful ovulation induction. As was discussed in the preceding question, an excessive response may lead to high order multiple pregnancy so care should be taken to cancel such a cycle or convert it to IVF or consider a follicle reduction procedure.