A 37-year-old woman comes to the office for evaluation of infertility. She and her 39-year-old husband have not been able to conceive after 18 months of unprotected and frequent intercourse. Menstrual cycles occur every 28 days, last 5 days, and have heavy bleeding and cramping on the first day. The patient had a miscarriage at age 27 that required a dilation and curettage. The couple had another spontaneous pregnancy 6 years later that resulted in an uncomplicated term vaginal delivery. The patient feels well and has no medical conditions. She has never had a sexually transmitted infection. She does not use tobacco, alcohol, or illicit drugs. The patient is an aerobics instructor and teaches two 60-minute classes daily. Blood pressure is 120/80 mm Hg and pulse is 84/min. BMI is 23 kg/m². She has no thyromegaly. Breast examination shows no palpable masses, axillary lymphadenopathy, or expressed nipple discharge. Pelvic examination reveals normal external genitalia, a well-rugated vagina, a mobile uterus, and normal ovaries. Which of the following is the most likely underlying cause of this couple's failure to conceive?

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11ec25c8_d9c5_d2b4_bc81_b11e75303f30_MD0003_00 Spontaneous pregnancy rates decrease with increasing female age. Women are born with their lifetime supply of oocytes, and a sharp decline in conception rates is notable after age 35. Due to this decline, lack of conception after 6 months of unprotected intercourse in women age >35 is considered infertility. In women with regular menstrual cycles, infertility can occur due to diminished ovarian reserve, characterized by decreased oocyte number and quality. Regular menstrual periods still occur due to continuing ovulation, but fecundability (conception rate) decreases due to diminished oocyte quality. As ovarian reserve and function decline, estradiol and inhibin production decreases, and the normal negative feedback mechanism is suppressed. This causes FSH levels to become increasingly elevated as ovarian function decreases. Therefore, day 3 (eg, early follicular phase) FSH testing can be performed to assess ovarian function. Assisted reproductive techniques (eg, in vitro fertilization, oocyte/embryo donation) are available to couples with age-related infertility. (Choice B) Hypothalamic dysfunction (eg, hypogonadotropic hypogonadism) from intense exercise and relative caloric deficiency can cause anovulation and result in amenorrhea. This is unlikely to be the cause of infertility in the setting of normal menses. (Choice C) Hypothyroidism is associated with infertility but presents with irregular menses. (Choice D) Primary ovarian insufficiency refers to menopause before age 40. Patients with primary ovarian insufficiency present with amenorrhea, hot flashes, and vaginal atrophy (eg, minimal rugation). The condition is associated with concomitant autoimmune disorders or Turner syndrome. (Choices E and F) Uterine synechiae (eg, Asherman syndrome) and uterine leiomyomas are anatomic factors that may decrease conception rates. Uterine synechiae can occur after dilation and curettage, but this patient's subsequent normal pregnancy makes this condition unlikely. Leiomyomas typically cause abnormal uterine bleeding as well as pelvic pain or pressure with an irregularly enlarged uterus. Educational objective: Inability to conceive after 6 months of unprotected intercourse in women age >35 is considered infertility. This can occur due to diminished ovarian reserve, characterized by regular menstrual cycles and decreased oocyte number and quality. References: Poor ovarian reserve. (http://www.ncbi.nlm.nih.gov/pubmed/27382229)

A 37-Year-Old Woman Comes to the Office for Evaluation of Infertility