Ovulation occurs once each month and culminates when an egg is released from the ovarian follicle. Conception results when the egg is fertilized and the embryo successfully implants in the endometrium. If pregnancy does not occur, hormonal changes cause the endometrium to break down, which results in the monthly menstrual flow.
Ovulation must occur regularly, and the couple must have intercourse near the time of ovulation, for pregnancy to occur. There are numerous conditions that can lead to irregular (oligoovulation) or absent ovulation (anovulation). Before these conditions are discussed, it is necessary to have a basic understanding of how ovulation occurs and the major reproductive hormones that are involved. There are numerous additional hormonal processes that are beyond the scope of this discussion.
The hypothalamus is a small zone of nerve cells located at the base of the brain which regulates the output of various hormones by the pituitary gland, including
follicle stimulating hormone (FSH) and luteinizing hormone (LH). The hypothalamus senses hormone levels and signals the pituitary to increase or decrease its production of FSH and LH accordingly.
During the first few days of the menstrual cycle, the hypothalamus releases gonadotropin releasing hormone (GnRH), which travels to the pituitary and stimulates the production of FSH. FSH directly stimulates and supports the ovarian follicles each of which contains an egg.
Healthy follicles begin to secrete estrogen as they grow which stimulates the development of the lining of the uterus (endometrium). Estrogen levels are monitored by the hypothalamus and increasing levels signal a reduction in GnRH production with reduced FSH production by the pituitary gland. Injections of large amounts of FSH are given during ovulation induction cycles to cause the recruitment and development of several follicles.
Once the levels of estrogen peak, indicating follicular maturity, the pituitary releases a surge, or spike, of LH approximately 24-36 hours later, which causes ovulation. The remaining follicular structure on the ovary is termed the corpus luteum and it begins to produce progesterone to support endometrial development. Once the placenta develops in pregnancy, it also begins to produce progesterone.
There are numerous causes of ovulatory irregularities including thyroid dysfunction,
polycystic ovarian syndrome (PCOS),
hyperprolactinemia, adrenal dysfunction, excessive exercise, anorexia,
ovarian failure, and others.
PCOSis a common cause of ovulatory disorders and is discussed in detail on a separate Web page. PCOS patients usually have abnormally high levels of insulin, which leads to the overproduction of male hormones (androgens) and irregular ovulation.
Advancing age, or reduced ovarian reserve, is a common cause of ovulatory disorders. As eggs “age” they loose their capacity to develop and fertilize which results in low estrogen levels and anovulation. The
menopause occurs when there are few viable eggs left within the ovary; these women must use egg donors to conceive. Menopause can occur very early in some women.
Hyperprolactinemia is a condition characterized by abnormally elevated levels of the hormone prolactin. Prolactin is responsible for breast milk production in pregnant women. Abnormally elevated levels in women who are not pregnant leads to irregular or absent ovulation. Hyperprolactinemia is usually caused by a small benign tumor on the pituitary gland that can often be surgically removed. The drug Parlodel (bromocriptine) is effective in reducing prolactin levels.
Excessive exercise and reduced body fat can adversely effect ovulation by causing elevated androgen levels. Obesity can also lead to anovulation by increasing insulin levels, which also ultimately results in elevated androgen levels. Excessive exercise and reduced body fat can adversely affect ovulation by reducing the amount of FSH and LH made by the pituitary gland. Estrogen levels are also low in these women. Elevated body fat (obesity) may cause difficulty with ovulation because androgens are converted to estrogens in body fat. With more fat present, more estrogen is produced. This estrogen then reduces the amount of FSH and LH made by the pituitary gland, and thus can prevent normal ovulation.
Treatments for ovulatory disorders seek to correct the underlying cause and/or stimulate ovulation. For example,
metformin is used to treat
PCOS and its mode of action is to reduce insulin levels. Once insulin levels are normalized, androgen levels decrease, and ovulation can occur.
Clomid induces ovulation by competing with estrogen binding sites on the hypothalamus, and FSH directly stimulates the ovaries.