Ovulation disorder: causes, symptoms, diagnosis, treatment

Ovulation disorder is abnormal, irregular, or absent ovulation. Menstrual periods are often irregular or absent. Diagnosis is based on history or can be confirmed by measuring hormone levels or pelvic ultrasonography. Treatment for ovulation disorder is ovulation induction with clomiphene or other drugs.

Chronic ovulation disorder in premenopausal women is most often associated with polycystic ovary syndrome (PCOS), but also has many other causes, such as hyperprolactinemia and hypothalamic dysfunction (hypothalamic amenorrhea).

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Symptoms of ovulation disorders

You may suspect ovulation disorders in cases where menstruation is irregular or absent, there is no previous swelling of the mammary glands, no abdominal enlargement or irritability.

Taking daily morning basal body temperature measurements can help determine the timing of ovulation. However, this method is imprecise and may be off by as much as 2 days. More accurate methods include home tests to detect an increase in urinary LH excretion 24–36 h before ovulation, pelvic ultrasonography to monitor ovarian follicle diameter growth and rupture, and serum progesterone levels of 3 ng/mL (9.75 nmol/L) or elevated urinary levels of the metabolite pregnanediol glucuronide (measured, if possible, 1 week before the onset of the next menstrual period); these values indicate the onset of ovulation.

In case of irregular ovulation, disorders of the pituitary gland, hypothalamus or ovaries (for example, PCOS) are identified.

Treatment of ovulation disorders

Ovulation can be induced with medications. Typically, in the presence of chronic anovulation due to hyperprolactinemia, the initial treatment is the antiestrogen clomiphene citrate. In the absence of menstruation, uterine bleeding is induced by medroxyprogesterone acetate 5-10 mg orally once a day for 5-10 days. Clomiphene is prescribed at 50 mg from the fifth day of the menstrual cycle for 5 days. Ovulation is usually noted on the 5th-10th day (usually the 7th day) after the last day of clomiphene intake; if ovulation occurs, the next menstruation is noted 35 days after the previous menstrual bleeding. The daily dose of clomiphene citrate can be increased by 50 mg every 2 cycles with a maximum dosage of 200 mg/dose to induce ovulation. Treatment can be continued as needed for 4 ovulatory cycles.

Adverse effects of clomiphene include vasomotor flushes (10%), bloating (6%), breast tenderness (2%), nausea (3%), visual symptoms (1-2%), and headaches (1-2%). Multiple pregnancy (twins) and ovarian hyperstimulation syndrome occur in 5% of cases. Ovarian cysts are the most common. A preliminary suggestion of a link between clomiphene use for more than 12 cycles and ovarian cancer has not been confirmed.

For patients with PCOS, most of whom have insulin resistance, insulin-sensitizing drugs are prescribed before ovulation induction. These include metformin 750-1000 mg orally once a day (or 500-750 mg orally twice a day), less commonly thiazolidinediones (eg, rosiglitazone, pioglitazone). If insulin sensitivity is ineffective, clomiphene may be added.

In patients with ovulatory dysfunction who do not respond to clomiphene, human gonadotropin preparations (eg, containing purified or recombinant FSH and variable amounts of LH) may be given. These preparations are given intramuscularly or subcutaneously; they typically contain 75 IU FSH, with or without active LH. These preparations are usually given once daily, beginning 3–5 days after induced or spontaneous bleeding; ideally they stimulate the maturation of 1–3 follicles, detectable ultrasonographically, over 7–14 days. Ovulation is also induced by hCG 5000–10,000 IU intramuscularly after follicle maturation; criteria for ovulation induction may vary, but the most typical criterion is the enlargement of at least one follicle to a diameter greater than 16 mm. However, ovulation induction is not performed in patients with a high risk of multiple pregnancy or ovarian hyperstimulation syndrome. Risk factors include the presence of more than 3 follicles with a diameter greater than 16 mm and preovulatory serum estradiol levels greater than 1500 pg/mL (possibly greater than 1000 pg/mL in women with several small ovarian follicles).

Following gonadotropin therapy, 10-30% of successful pregnancies are multiple. Ovarian hyperstimulation syndrome occurs in 10-20% of patients; the ovaries become significantly enlarged with fluid in the peritoneal cavity, causing potentially life-threatening ascites and hypovolemia.

Underlying disorders require treatment (e.g. hyperprolactinemia). In the presence of hypothalamic amenorrhea, gonadorelin acetate (synthetic GnRH) is administered as intravenous infusions to induce ovulation. Bolus doses of 2.5-5.0 mcg (pulse doses) administered regularly every 60-90 min are most effective. Gonadorelin acetate rarely causes multiple pregnancies.