A 34-year-old woman comes to the office for treatment of infertility. The patient has been trying to become pregnant with her current partner for the past year but has not yet conceived. Since menarche, she has had irregular menses, occurring every 3-6 months, with 7-14 days of bleeding. The patient's last menstrual period was 2 months ago. Over the last 6 months, she has tried to lose weight with exercise and diet but has been unsuccessful. The patient has no chronic medical conditions or prior surgeries. She takes a daily prenatal vitamin and has no medication allergies. The patient does not use tobacco, alcohol, or illicit drugs. BMI is 33 kg/m². On skin examination, there is moderate acne on the chest and back and terminal hairs on the upper lip. Pelvic examination shows a nulliparous cervix, a normal uterus, and bilateral enlarged ovaries. The remainder of the physical examination is unremarkable. Hysterosalpingography reveals a normal uterine cavity with bilateral tubal patency, and her partner's semen analysis is normal. A urine pregnancy test is negative. Which of the following is the best treatment option for this patient's infertility?

Question

Quizplus · Accepted Answer

Explanation: 11ec2b69_c147_ef41_8f63_d9adb820d289_MD0005_00 This patient with irregular menses and signs of hyperandrogenism (eg, acne, hirsutism) likely has polycystic ovary syndrome (PCOS), a common cause of infertility due to chronic anovulation. Ovulation induction agents (eg, letrozole, clomiphene) can treat anovulatory fertility by increasing gonadotropin levels (ie, FSH, LH), which stimulates ovulation. Letrozole and clomiphene stimulate gonadotropin release via the manipulation of different targets on the hypothalamic-pituitary-ovarian (HPO) axis: Letrozole acts on the ovaries. Ovarian theca cells produce androgens, which are converted to estrogen by the enzyme aromatase within ovarian granulosa cells. Patients with PCOS typically have increased ovarian androgen production, which leads to increased ovarian estrogen production and the inhibition of GnRH, FSH, and LH release due to negative feedback on the HPO axis. Letrozole inhibits aromatase, thereby inhibiting conversion of androgen to estrogen at the ovary. This decrease in estrogen provides feedback to the hypothalamus to increase GnRH secretion, which increases pituitary FSH release and stimulates ovulation. Clomiphene acts on the hypothalamus. It depletes hypothalamic estrogen receptors, leading the hypothalamus to perceive low estrogen levels. Without negative feedback from estrogen, the hypothalamus increases GnRH release, which increases FSH and LH levels and induces ovulation. (Choice B) Leuprolide is a GnRH agonist that causes decreased pulsatile GnRH release. The result is decreased FSH, LH, and estrogen levels (ie, hypogonadotropic hypogonadal state), which would worsen rather than improve infertility. (Choice C) Metformin can be used in patients with PCOS who have insulin resistance (eg, impaired glucose tolerance); however, it is not used for anovulatory infertility due to lower pregnancy and live-birth rates compared to letrozole and clomiphene. (Choice D) Progesterone is secreted by the corpus luteum during the luteal phase of the menstrual cycle (ie, following ovulation) to prepare the endometrium for possible pregnancy implantation. Although cyclic progesterone withdrawal can be used in anovulatory patients for endometrial protection (ie, prevention of hyperplasia/cancer), it does not treat infertility. (Choice E) Spironolactone blocks peripheral androgen receptors and can be used to treat hyperandrogenic symptoms (eg, acne, hirsutism) associated with PCOS. However, spironolactone does not enhance fertility and is not recommended in patients desiring pregnancy because of the risk for fetal abnormalities. Educational objective: Polycystic ovary syndrome (PCOS) causes infertility due to chronic anovulation. Affected patients can be treated with letrozole, an aromatase inhibitor that inhibits ovarian estrogen production to stimulate gonadotropin release and induce ovulation.

A 34-Year-Old Woman Comes to the Office for Treatment of Infertility