Causes and Treatments of Ovulation Disorders

Ovulation disorders are commonly caused by a problem in the hypothalamic–pituitary axis or ovarian dysfunction, but they can also be secondarily caused by chronic diseases as below. In this case, elimination of the underlying cause can allow the resumption of normal menstruation.

  • Problems in the central nervous system: Pituitary tumors, severe stress, excessive exercise, anorexia
  • Problems in ovarian function: Ovarian aging (premature menopause), polycystic ovaries, ovarian lesions (ovarian tumors, ovarian inflammation)
  • Problems in metabolic functions: Thyroid disease, diabetes, abnormal hormonal secretions (hyperprolactinemia)
Types of Ovulation Disorders
Absent or rare menstruation

“Absent menstruation” refers to cases in which the woman does not have her period for more than 3 menstrual cycles.

Menstruation without ovulation (anovulation)

“Anovulation” refers to cases in which a follicular egg exhibits abnormal or suspended growth, or grows until ovulation but is not released by the ovary.

Short follicular phase

“Short follicular phase” refers to cases in which the time period between menstruation and ovulation is short (e.g., 8 to 10 days), whereas a healthy follicular phase would be 13-15 days.

Treatments for Ovulation Disorders

Ovulation induction with fertility drugs is also used in patients without ovulatory dysfunction. The goal is to stimulate the ovaries to produce more than one follicle per cycle leading to the release of multiple eggs in the hope that at least one egg will be fertilized and result in a pregnancy. The most commonly prescribed ovulation drugs are clomiphene citrate (CC), aromatase inhibitors (such as letrozole), and gonadotropins (FSH, LH, human menopausal gonadotropin (hMG), chorionic gonadotropin (hCG)).


Clomiphene citrate (CC)

50 to 150mg of clomiphene is taken per day for 5 days starting between the third and the fifth day of menstrual cycle. Ovulation must be confirmed by ultrasound, and once confirmed, the couple are advised to have timed-sexual intercourses to conceive a child. Common side effects include temporary thinning of endometrium, headaches, blurred vision and hot flashes.

Aromatase inhibitors

Aromatase inhibitors are medicines that temporarily decrease estrogen levels, which cause the pituitary gland to make more FSH. Treatment begins early in the cycle, usually starting on the second to fifth day after menstruation begins although it also can be started without a period if the woman is anovulatory. The typical dose is 2.5- 5 mg daily for five days.

Gonadotropins

Gonadotropins are fertility medications that contain FSH or LH alone or together. Unlike CC, aromatase inhibitors, and insulin-sensitizing agents which are taken by mouth, gonadotropins are delivered by injection. The gonadotropin treatment usually begins on day two or three of the menstrual cycle and the usual starting dose is 75 to 150 IU injected daily. Typically, seven to 12 days of stimulation is enough but this may be extended if the ovaries are slow to respond. The size of the follicles is monitored with ultrasound, and the blood estrogen level also may be measured frequently, both during the stimulation phase of treatment. If blood estrogen levels do not rise and ultrasound shows that the ovaries are not responding to gonadotropins, the dose may be increased, or, less commonly, the cycle may be cancelled. Side effects may include abdominal distention/discomfort, bloating sensation, mood swings, fatigue or restlessness. In most cases, the side effects are relieved by follicular aspiration.

Human Chorionic Gonadotropine (hCG)

Human chorionic gonadotropin (hCG) is similar in chemical structure and function to LH. An injection of hCG mimics the natural LH surge and causes the dominant follicle to release its egg and ovulate. Ovulation will usually occur about 36 hours after hCG is administered. hCG is typically used to trigger ovulation with gonadotropins, and may be used when CC or aromatase inhibitors are used to induce ovulation.

Combined method

Oral medications are sometimes used in combination with low dose gonadotropin injections, starting early in menstrual cycle. The dose of gonadotropin injections may increase according to the ovarian response.