A 32-year-old woman comes to the office due to difficulty conceiving despite frequent, unprotected intercourse with her husband over the last 3 years. She has had multiple sexual partners in the past and never became pregnant despite inconsistent condom use. Menses started at age 12 and are irregular. The patient has had recurrent vaginal candidiasis for which she uses an over-the-counter vaginal suppository. Vital signs are normal. The thyroid is not enlarged. She has thick, dark, velvety plaques under her axillae. Breast examination is normal. Abdominal examination shows no masses. Pelvic examination reveals normal external genitalia; a small, mobile uterus with no cervical motion tenderness; and bilaterally enlarged ovaries. TSH, LH, and prolactin levels are normal. Which of the following is the most appropriate therapy for this patient's infertility?

Question

A 32-year-old woman comes to the office due to difficulty conceiving despite frequent, unprotected intercourse with her husband over the last 3 years.  She has had multiple sexual partners in the past and never became pregnant despite inconsistent condom use.  Menses started at age 12 and are irregular.  The patient has had recurrent vaginal candidiasis for which she uses an over-the-counter vaginal suppository.  Vital signs are normal.  The thyroid is not enlarged.  She has thick, dark, velvety plaques under her axillae.  Breast examination is normal.  Abdominal examination shows no masses.  Pelvic examination reveals normal external genitalia; a small, mobile uterus with no cervical motion tenderness; and bilaterally enlarged ovaries.  TSH, LH, and prolactin levels are normal.  Which of the following is the most appropriate therapy for this patient's infertility?

Quizplus · Accepted Answer

11ec25c8_d9df_c37c_bc81_bf57b798c019_MD0003_00 This patient has menstrual irregularities (suggesting anovulation), infertility, and enlarged ovaries. In addition, the presence of acanthosis nigricans indicates insulin resistance. These are clinical manifestations of polycystic ovary syndrome (PCOS). Although patients with PCOS can have elevated serum testosterone or LH levels, serum concentrations can also be normal with symptoms due to a relative imbalance in hormone levels (ie, LH/FSH ratio) rather than absolute values. Most patients with PCOS are obese and have persistently high estrogen levels due to the peripheral conversion of androgens to estrogens in adipose tissue. These high estrogen levels suppress the hypothalamic-pituitary-ovarian axis by creating constant negative feedback. Therefore, weight loss is the first-line treatment to reestablish ovulation by decreasing the peripheral estrogen conversion. If weight loss is unsuccessful, ovulation can be induced with letrozole, an aromatase inhibitor, which inhibits the conversion of androgens to estrogens. The resultant decreased estradiol secretion causes a positive feedback mechanism to the pituitary gland, thereby increasing and normalizing LH and FSH levels. This creates an LH surge that results in ovulation. Letrozole is the first-line ovulation induction agent in patients with PCOS due to higher live birth rates compared with clomiphene citrate. (Choice A) Dopamine agonists (eg, bromocriptine) are used to treat hyperprolactinemia, a condition that can cause anovulation and irregular menses; however, prolactin levels are normal in this patient. (Choice B) Cyclic progesterone may be administered for endometrial protection against uncontrolled endometrial proliferation due to elevated estrogen levels in patients with PCOS. However, progesterone does not facilitate ovulation and is not used to treat infertility. (Choice C) Laparoscopic fulguration of lesions improves fertility in patients with endometriosis, a condition characterized by regular, painful menses (ie, dysmenorrhea) or chronic pelvic pain, which are not present in this patient. (Choice E) Levothyroxine is used to treat hypothyroidism, which can cause menstrual irregularities. This diagnosis is unlikely in this patient with a normal thyroid examination and normal TSH level. Educational objective: Polycystic ovary syndrome (PCOS) causes infertility due to anovulation and may present with irregular menses, enlarged ovaries, and signs of insulin resistance. Ovulation can be induced with letrozole (an aromatase inhibitor) in patients with PCOS. References: Genetic, hormonal and metabolic aspects of PCOS: an update. (http://www.ncbi.nlm.nih.gov/pubmed/27423183) Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/29797697) Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/25006718)

A 32-Year-Old Woman Comes to the Office Due to Difficulty