Infertility

  1. When a patient consults you with concerns about difficulties becoming pregnant:
    1. Take an appropriate history (e.g., ask how long they have been trying, assess menstrual history, determine coital frequency and timing) before providing reassurance or investigating further.
    2. Ensure follow-up at an appropriate time (e.g., after one to two years of trying; in general, do not investigate infertility too early).
  2. In patients with fertility concerns, provide advice that accurately describes the likelihood of fertility.
  3. With older couples who have fertility concerns, refer earlier for investigation and treatment, as their likelihood of infertility is higher.
  4. When choosing to investigate primary or secondary infertility, ensure that both partners are assessed.
  5. In couples who are likely infertile, discuss adoption when the time is right. (Remember that adoption often takes a long time.)
  6. In evaluating female patients with fertility concerns and menstrual abnormalities, look for specific signs and symptoms of certain conditions (e.g., polycystic ovarian syndrome, hyperprolactinemia, thyroid disease) to direct further investigations (e.g., prolactin, thyroid-stimulating hormone, and luteal phase progesterone testing).

See Pregnancy.

General Overview

  • No conception after 12 months of unprotected and frequent intercourse
    • Primary (no previous pregnancy)
    • Secondary (after previous conception)
      • Always ask about pregnancy with other partners!
  • When to investigate and refer
    • >1 year of trying to conceive (85% will conceive after one year)
    • >35yo at 6mo
    • >40yo immediately
      • Sooner if history of infertility, PID, pelvic surgery/CT/RT (in either partner), recurrent pregnancy loss, moderate-severe endometriosis

History (both patient and partner)

  • Length of infertility
  • Frequency and timing of intercourse
  • Difficulties with intercourse
  • Previous infertility investigations/treatments
  • OBGYN history (Menstrual cycle, STI, previous pregnancies)
  • PMH, Fam Hx
  • Medications, smoking, alcohol, drugs
  • Exposures (Radiation, toxins, surgery)

Differential Diagnosis

  • Female
    • Ovulatory dysfunction - 20%
      • PCOS
      • Premature ovarian failure
      • Hypothalamic suppression (exercise, eating disorder, stress, hyperprolactinemia)
      • Thyroid disease
      • Advanced maternal age
      • Turner syndrome
      • Medications (contraceptives, corticosteroids, antidepressants, antipsychotics, chemotherapy)
    • Uterine/tubal factors - 20%
      • PID
      • Prior ectopic pregnancies
      • Endometriosis
      • Adhesions
      • Fibroids
      • Asherman syndrome
    • Cervical factors (eg. cervical stenosis)
    • Peritoneal factors
  • Male- 30%
    • Testicular (sperm disorders - eg. azoospermia)
      • Cryptorchidism
      • Irradiation
      • Varicocele
      • Androgen insensitivity
      • Klinefelter syndrome
      • Infection (Mumps orchitis)
      • Drugs (Marijuana, spirinolactone, ketoconazole, alcohol)
    • Pre-Testicular
      • Hypogonadotropic hypogonadism
      • Hypothyroidism
      • Hyperprolactinemia
      • Pituitary tumor
      • Drugs, alcohol, smoking
      • Medications (chemotherapy, steroids, spironolactone, phenytoin)
    • Post-Testicular
      • Hypospadias
      • Vas deferens obstruction
      • Congenital absence of Vas deferens in Cystic Fibrosis
      • Infection (prostatitis)
      • Retrograde ejaculation
      • Erectile dysfunction
      • Iatrogenic (vasectomy)

Investigations

  • Prolactin, TSH
  • Ovarian reserve testing
    • Day 3 FSH, LH, estradiol
      • Ovarian aging if FSH >14IU/L and high estradiol
      • Clomiphene challenge has poor predictive value
    • Mid-Luteal Day 21 (or LMP -7d) progesterone
      • Progesterone >5ng/mL (15.9 nmol/L) r/o anovulatory
        • Consider repeating progesterone weekly if irregular until menses
  • Consider
    • Clomiphene citrate challenge test (CCCT)
    • AMH (anti-mullerian hormone)
    • DHEA
    • r/o STI (HIV, Hep B, Hep C, G+C)
  • Preconception
    • Rubella, Varicella titres
    • Pap
    • Genetic testing if indicated
  • Imaging
    • Hysterosalpingography
    • Pelvic U/S (antral follicle count, r/o fibroids, cysts)
    • Hysteroscopy
    • Laparoscopy (endometriosis)
  • Semen analysis: Count (>20mill), motility (>50%), volume (2-5mL), morphology (>30%), pH, WBC (<1mil/mL)
    • 3-6 days abstinence
    • Repeat if abnormal in one month

Management

  • Encourage weight loss if BMI >30
  • Stop smoking, drugs, alcohol
  • Anovulatory
    • Consider Clomiphene Citrate 50mg PO daily x 5 days on day 3-5
      • Counsel on risks of multiple pregnancy, hyperstimulation syndorme, thrombosis, ovarian cancer
      • If no pregnancy after 3-6 cycles, refer to specialist
  • Referral to fertility specialist
    • Ovulation induction
      • Clomiphene citrate
      • Metformin (PCOS)
      • Gonadotropin
      • Bromocriptine (to lower prolactin)
    • Surgical
      • Tuboplasty
      • Lysis of adhesions
    • Assisted reproductive technology (IVF, ICSI)
    • Sperm/ovarian donation
  • Consider adoption