Women are born with a lifetime’s supply of eggs within their ovaries. Each month FSH stimulates the recruitment and development of ovarian follicles each of which contains an egg.
Irregular (oligoovulation) or no (anovulation) ovulation can have many causes which are often endocrine in nature. The reproductive hormone system is governed by a complex series of interactions in a system known as the “hypothalamic-pituitary-adrenal axis”. The hypothalamus, located at the base of the brain, serves as the master gland “regulator” of the various hormones involved in reproduction.
During the first days of the ovulatory cycle, the hypothalamus produces gonadotropin releasing hormone (GnRH) which travels to the pituitary where it stimulates the production of follicle stimulating hormone (FSH). FSH directly stimulates the recruitment of eggs within the ovarian follicles and supports their development. When additional FSH is given by injection in an IVF cycle, it stimulates the development of multiple follicles because the fertility specialist and embryologist need numerous eggs for the IVF processes.
As healthy follicles develop, they produce estrogen which is monitored by the hypothalamus. As estrogen levels increase, the hypothalamus signals the pituitary to adjust FSH output accordingly.
Once the hormone levels signal that the follicles are mature, the hypothalamus releases GnRH which travels to the pituitary and signals a surge of luteinizing hormone (LH). This surge in LH signals the final stages of follicular development and causes ovulation 34-36 hours later.
After the eggs are ovulated, the remaining follicular structure is known as the corpus luteum. The corpus luteum produces progesterone which is needed for proper thickening and vascularization of the endometrium. The endometrium must be sufficiently developed to support an embryo and fetus. Progesterone is also produced by the placenta. Insufficient progesterone may cause a “luteal phase defect” wherein the endometrium does not properly develop. This condition is effectively treated with progesterone medications.
Disruption of any of these processes can lead to ovulatory disorders. Advanced female age is a major cause of infertility and is diagnosed by an elevated day 3 FSH level and possibly the Clomid Challenge Test. FSH levels above 10 signal that there are few “healthy follicles” and indicates reduced ovarian reserve. After the menopause, the condition is known as ovarian failure since no viable eggs remain. Premature or perimenopause can occur in much younger women.
PCOS causes irregular ovulation because there is an abnormal elevation of male hormones (androgens) which causes overproduction of estrogen. Elevated or depressed levels of thyroid hormones can also cause ovulatory disorders as can stress and excessive exercise.
Hyperprolactinemia is another condition that can cause ovulatory irregularities. Prolactin is the hormone responsible for breast milk production in pregnant women. Elevated levels in non pregnant women (hyperprolactinemia) can lead to irregular, or no, ovulation.
The drugs used to treat ovulatory disorders fall into three classes: 1) Clomid® competes for estrogen receptors at the hypothalamus. This causes the hypothalamus to release GnRH which stimulates FSH production by the pituitary. 2) FSH directly stimulates the ovarian follicles. 3) Metformin® reverses hyperinsulinemia in PCOS patients and allows normal ovulation to resume.
In most cases, except notably in women with ovarian failure, ovulation can be established using one of these medications. Women with ovarian failure must use an egg donor if they wish to experience pregnancy and delivery. Fortunately, success rates are high in women who utilize an egg donor.