A 37-year-old woman comes to the office for evaluation of infertility. The patient and her 39-year-old husband have been unable to conceive after 18 months of unprotected and frequent intercourse. Menstrual cycles occur every 28 days and last 5 days; she has 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 is an aerobics instructor and teaches 2 hour-long 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 inability to conceive?
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Spontaneous pregnancy rates decrease with increasing female age. Women are born with a lifetime supply of oocytes, and a sharp decline in conception rates is notable at 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 (ie, 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 (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) due to 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 have 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; however, this patient has normal menses (as opposed to light menses/amenorrhea from endometrial scarring) and had a subsequent normal pregnancy following surgery, which makes this condition unlikely. Leiomyomas typically cause heavy menstrual bleeding throughout the entirety of menses (as opposed to heavy bleeding on day 1). In addition, physical examination may show an enlarged, irregularly contoured uterus (not seen in this patient), which makes this diagnosis less likely.
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.