• Infertility is defined as lack of pregnancy after 1 year of unprotected regular intercourse
• It is also the period of time wherein the couple has been trying to conceive but without success after which investigation is performed and possible therapy applied 
• Infertility can be primary (no pregnancy has ever occurred) or secondary (pregnancy has occurred irrespective of the outcome)
• The prevalence rates of infertility are difficult to establish because of male and female factors that complicate any estimate which may only focus on the woman and the pregnancy outcome 
  • The difficulty of determining the prevalence of infertility is also associated with the lack of consistent definition use and tools for diagnosing, managing or reporting infertile couples

Ovulatory Disorders

• Account for about 30% of infertility and manifest clinically with irregular menstruation or absence of periods

• Characterized by low gonadotropins [follicle-stimulating hormone (FSH), luteinizing hormone (LH)], normal prolactin, low estradiol; hypothalamic amenorrhea
• Common causes include excessive exercise and low body mass index (BMI); infiltrative diseases and tumors of the hypothalamus and pituitary may also cause hypogonadotropic hypogonadism due to decreased GnRH release or gonadotropin deficiency
• Causes approximately 10% of ovulatory problems

• Most common cause of anovulatory infertility (70%); normogonadotropic normoestrogenic anovulation
• Diagnosis is based on 2003 Rotterdam criteria:
  • 2 out of 3 of the following: Oligo-ovulation or anovulation, clinical or biochemical signs of hyperandrogenism, polycystic ovaries
  • Exclusion of other causes (congenital adrenal hyperplasia, androgen-secreting tumors, Cushing’s syndrome, thyroid disease, prolactinoma)

• Characterized by hypergonadotropic hypoestrogenism
• Premature ovarian failure is irreversible and unsuitable for ovulation induction
• Accounts for 4-5% of ovulation disorders

• LH and FSH are usually at the lower end of the normal range and estradiol is low
• Diagnosis is confirmed with a single measurement of serum prolactin level above 25 mcg/L
• Many women present with secondary amenorrhea and occasionally, galactorrhea
• Imaging of the pituitary fossa, eg MRI, may be needed to evaluate the cause of hyperprolactinemia
• Prolactinomas or lactotroph adenomas are benign pituitary gland tumors that produce prolactin that causes higher than normal concentrations of prolactin in the blood

Other Causes of Infertility

Cervical Factors

• Refer to abnormalities of the mucus-sperm interaction

Endometriosis

• Associated with reduced fertility, with most large series studies suggesting that young women with mild endometriosis spontaneously conceive at a rate of only 2-3% per month, far below the healthy monthly rate of 20%
• Possible mechanisms for endometriosis-associated infertility include abnormalities in oocyte and embryo quality and utero-tubal transport, altered peritoneal, hormonal and cell-mediated function, distorted pelvic anatomy and impaired implantation 

Tubal Factors

• 14% of female infertility is attributed to tubal factors
• Most common cause of tubal infertility is proximal tubal obstruction
• Semen analysis and ovulation assessment should be performed prior to testing for tubal patency
• It is recommended that women be screened first for C trachomatis infection and treated accordingly prior to any uterine instrumentation
• Chlamydial infection, a major cause of PID, can lead to tubal infertility
  • Elevated Chlamydia antibody titer (>1:256) is associated with high likelihood of tubal damage

• Blocked tubal structures are diagnosed by HSG, sonohysterography and/or laparoscopy, and dye

Uterine Abnormalities

• Polyps, adhesions, fibroids may be associated with infertility but exact role is unknown