A 28-year-old woman, gravida 0 para 0, comes to the office with her husband, age 38, for evaluation of infertility. The couple has not conceived despite frequent intercourse without contraception for over a year. Menarche was at age 13. The patient's menstrual cycles are irregular, and her last period was 8 weeks ago. She has no nipple discharge. She had trichomoniasis as a teenager. Sexually transmitted infection testing at her most recent annual examination was negative. Her husband had a normal semen analysis. The patient takes a daily prenatal vitamin and does not use tobacco, alcohol, or illicit drugs. BMI is 28 kg/m². Blood pressure is 130/80 mm Hg and pulse is 84/min. Heart and lung examination is normal. The abdomen is soft and nontender, with no palpable masses. Pelvic examination shows normal external genitalia and a mobile uterus without adnexal masses. Urine pregnancy test is negative. Serum TSH and prolactin levels are normal. Free testosterone levels are elevated. Which of the following is the most likely cause of this couple's infertility?

Question

Quizplus · Accepted Answer

11ec25c8_d9e0_5fbd_bc81_57fd745705cd_MD0003_00 This patient has infertility, irregular menses, and hyperandrogenism, features concerning for polycystic ovary syndrome (PCOS). Hyperandrogenism, resulting from ovarian steroid overproduction, can be diagnosed clinically (eg, hirsutism, acne, alopecia) or biochemically with elevated serum testosterone levels. In addition to hyperandrogenism, many patients with PCOS have persistently elevated estrone levels due to peripheral androgen conversion in adipose tissue and decreased levels of sex-hormone-binding globulin. Such high estrone levels affect gonadotropin-releasing hormone (GnRH) pulses at the level of the hypothalamus, resulting in high frequency, short interval GnRH pulses. The high frequency GnRH pulses preferentially produce LH, resulting in an imbalance in LH and FSH release from the anterior pituitary. The LH/FSH imbalance results in a lack of LH surge. In the ovary, this results in the failure of follicle maturation and oocyte release (eg, anovulation). In patients with PCOS who are pursuing pregnancy, weight loss is the first-line treatment as it restores ovulatory cycles; if unsuccessful, ovulation induction agents (eg, letrozole, clomiphene citrate) may be used. (Choice B) Failure of müllerian duct fusion (eg, müllerian agenesis) is an anatomic cause of infertility. Patients typically present with primary amenorrhea, a foreshortened vagina with no palpable uterus, and normal hormone levels. (Choices C and D) Impaired oocyte transport through the fallopian tube may be caused by pelvic fibrosis and adhesions from pelvic inflammatory disease or endometriosis. Patients have regular menses, chronic pelvic pain, and normal testosterone levels. (Choice E) Although primary ovarian insufficiency may present with infertility and oligomenorrhea, patients typically have a concomitant autoimmune disorder and normal testosterone levels. (Choice F) Turner syndrome is a sex chromosome monosomy (45,XO), and these patients may have primary ovarian insufficiency characterized by an elevated FSH level. Other typical features of Turner syndrome include short stature, "shield" chest, and webbed neck. Educational objective: Polycystic ovarian syndrome (PCOS) is characterized by irregular menses and clinical or biochemical evidence of hyperandrogenism. Patients with PCOS may have infertility due to anovulation from failed follicular maturation. References: Genetic, hormonal and metabolic aspects of PCOS: an update. (http://www.ncbi.nlm.nih.gov/pubmed/27423183)

A 28-Year-Old Woman, Gravida 0 Para 0, Comes to the Office