Ovulatory Disorders- Diagnosis and Treatment

One of the most common causes of female infertility is ovulatory disorders, which include irregular ovulation (oligoovulation) or no ovulation (anovulation). Anovulation is usually associated with complete lack of menses (amenorrhea) unless progestational agents such as Provera® or Prometrium® are given. The ovulatory cycle begins with egg recruitment followed by follicular development, thickening and vascularization of the endometrium, various hormonal interactions, and a spike in luteinizing hormone (LH) which stimulates ovulation once the eggs mature. This is followed by fertilization and implantation of the embryo into the endometrium.

There are many hormonal “abnormalities” that can lead to ovulatory disorders. The hypothalamus can be thought of as the “reproductive hormone regulator gland”. It measures the levels of FSH, LH, estrogen, progesterone, and other hormones and adjusts output accordingly.

The processes involved in ovulation include the initial production of FSH to stimulate follicular development. The hypothalamus releases gonadotropin-releasing hormone (GnRH) which travels to the pituitary where it stimulates the release of FSH. FSH stimulates and supports egg development within the ovarian follicles.  As the eggs mature, they produce estrogen which helps stimulate endometrial development. Estrogen levels are monitored by the hypothalamus and FSH production is adjusted accordingly.  During this time, progesterone is produced to help support endometrial development.

Once the follicles mature, the hypothalamus releases GnRH which signals the pituitary to release a “spike” of luteinizing hormone thus precipitating ovulation.  After ovulation, progesterone is initially produced by the remaining follicular structure (the corpus luteum) and later by the placenta.

Disruptions of any of these processes can lead to ovulatory disorders. For example, patients with polycystic ovarian syndrome (PCOS) often have chronically elevated levels of androgens that prevent successful ovulation. Also, women of advancing age may experience reduced ovarian reserve (fewer viable eggs that can fertilize and develop normally) leading to anovulation.

Chronically elevated levels of prolactin (hyperprolactinemia), which is the hormone responsible for breast milk production in pregnant women, can precipitate ovulatory disorders.  Excessive exercise, stress, and being severely underweight or obese are common causes of anovulation or oligoovulation.  Additionally, abnormal levels of thyroid hormones can lead to ovulatory irregularities. Ovulatory disorders can result for unexplained reasons.

Fortunately, ovulation inducing/regulating products are available for most of these conditions. A full description of each can be viewed in the “Fertility Drugs” section of the Web site.  Clomid® is usually the “first line” ovulation induction agent that works by “competing” with estrogen receptors at the hypothalamus.  The hypothalamus “perceives” lower estrogen levels due to this “blockade” and FSH production increases.

Injectable follicle stimulating hormone (FSH) stimulates the follicles directly to cause their recruitment and support their development. Other specific treatments include Parlodel® and Dostinex® for hyperprolactinemia and metformin for hyperinsulinemic PCOS patients.

In most cases, ovulation can be induced, or regulated, except in women who have very low ovarian reserve, congenital abnormalities of the ovaries, where the ovaries were damaged with chemotherapy or radiation for cancer treatment, premature menopause, or other specific conditions. Donor egg IVF may be the only option for some of these women.