Infertility in Women

Background

• Infertility is the inability to conceive after 1 year of unprotected sexual intercourse.
• Infertility occurs in about 15% of reproductive-aged couples worldwide and is more common in developing countries.
• Cause of infertility in couples may be multifactorial and may include:
  • combined male and female factors in about 40%
  • male factor infertility alone in about 26%-30%
  • ovulation disorders in about 21%-25%
  • tubal factors in about 14%-20%
  • cervical, uterine, or peritoneal disorders in about 10%-13%
  • idiopathic in about 25%-28%

Evaluation

• Evaluate couples for infertility:
  • after 1 year of frequent unprotected sexual intercourse for women < 35 years old without known risk factors for infertility (Strong recommendation)
  • after 6 months of unprotected intercourse in couples where woman aged > 35 years and/or in couples with known clinical cause or predisposing factors for infertility (Strong recommendation)
  • immediately in women > 40 years old and/or if there is an obvious cause for infertility or subfertility
• Evaluation includes:
  • history and physical exam, with evaluation of both partners together and individually
  • testing of ovulatory function via either of
    • midluteal serum progesterone level
    • urinary luteinizing hormone assessment via urinary ovulation kit
  • testing of tubal patency
    • Hysterosalpingography (HSG) and hysterosalpingo-contrast sonography (HyCoSy) may help detect suspected tubal abnormalities.
    • Laparoscopy and chromotubation (with dilute solution or methylene blue or indigo carmine inserted via the cervix) may help detect tubal patency or proximal/distal tubal occlusive disease.
• Evaluation may also include:
  • test of ovarian reserve using any of the following
    • FSH and estradiol levels on cycle day 2-4
    • clomiphene (Clomid) citrate challenge test
    • serum antimüllerian hormone levels
  • uterine evaluation
    • Hysteroscopy is the definitive method for diagnosis and treatment of intrauterine pathology, and is typically reserved for women with intracavitary abnormalities that may interfere with embryo implantation, such as submucous fibroids, endometrial polyps, uterine septum, adhesions, and chronic endometritis (Strong recommendation).
    • Hysterosalpingography (HSG) and hysterosalpingo-contrast sonography (HyCoSy) or saline infusion sonohistography (SIS) may help detect suspected uterine abnormalities.
  • assessment of serum thyroid stimulating hormone (TSH) in women with symptoms of ovulatory disorder
  • assessment of prolactin level in women with irregular cycles with or without galactorrhea and/or pituitary tumor
• Further testing is determined by the results of the initial evaluation and by the presence of any risk factors from the patient history.

Management

• Treatment of infertility is based on the underlying cause.
• The World Health Organization (WHO) has classified anovulation into groups according to its cause.
  • For patients with WHO Group I: hypogonadotropic hypogonadism (hypothalamic pituitary failure):
    • If body mass index (BMI) is < 19 kg/m², advise weight gain and/or exercise moderation.
    • First-line treatment includes ovulation induction with gonadotropins with luteinizing hormone activity or pulsatile administration of gonadotropin-releasing hormone (less common, not available in the United States) (Strong recommendation).
    • Second-line treatment is in vitro fertilization (IVF) (Strong recommendation).
  • For patients with WHO Group II: normogonadotropic normoestrogenic anovulation (polycystic ovary syndrome [PCOS]):
    • Weight loss may improve pregnancy outcomes if BMI is ≥ 30 kg/m².
    • First-line treatment includes ovulation induction with clomiphene, metformin, or a combination of both (Strong recommendation).
    • Second-line treatment may include laparoscopic ovarian drilling or ovulation induction with gonadotropins (with ovarian ultrasound monitoring) (Weak recommendation).
    • Third-line treatment is IVF (Strong recommendation).
  • For women with WHO Group III: hypergonadotropic hypoestrogenic anovulation (primary ovarian insufficiency), first-line therapy is IVF with donated oocytes.
  • For women with hyperprolactinemic amenorrhea, first-line therapy includes dopamine agonists (such as bromocriptine or cabergoline) (Strong recommendation).
• Treatment options for women with fallopian tube disorders:
  • Tubal microsurgery or laparoscopic tubal surgery may restore tubal patency in patients with mild tubal disease, but it may also increase the risk for subsequent ectopic pregnancy (Weak recommendation).
  • For patients with a hydrosalpinx, consider laparoscopic salpingectomy or occlusion prior to IVF.
• Women with amenorrhea and intrauterine adhesions should be offered hysteroscopic adhesiolysis to restore normal menstruation and increase the likelihood of conception (Strong recommendation).
• For women with endometriosis-associated infertility, options include surgery or assisted reproductive technology (ART) (which may include pretreatment with hormonal therapies such as gonadotropin-releasing hormone [GnRH] agonists) (Strong recommendation).
• For idiopathic infertility:
  • Advise patients to try to conceive naturally for 2 years (may include the year prior to fertility investigation) before considering an active intervention (Strong recommendation).
    • Regular unprotected intercourse (2-3 times/week) near the time of ovulation may increase the chance of conception.
    • Intercourse on multiple days during the fertile window (5 days preceding and the day of ovulation) should increase the likelihood of conception.
  • Consider IVF after 2 years of failed expectant management and regular unprotected intercourse.
  • Intrauterine insemination (IUI) (with or without ovarian stimulation) should not be routinely offered to patients with idiopathic infertility but may be considered for patients with social, cultural, or religious objections to IVF (Weak recommendation).
• Ovarian hyperstimulation syndrome (OHSS) is reported in about 1.4% of all IVF cycles and is considered the most serious complication resulting from controlled ovarian hyperstimulation in ART, with symptoms ranging from mild abdominal distension to organ failure or death.