Female Infertility

Aka: Female Infertility, Infertility, Subfertility, Assisted Reproductive Technology, Assisted Reproductive Techniques

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II. Definition

  1. No conception in 6 months in women over age 35 years
  2. No conception in 1 year without Contraception
    1. Primary Infertility: Nulligravida
    2. Secondary Infertility: Prior pregnancies

III. Epidemiology

  1. Affects up to 15% of couples in the United States

IV. History

  1. History taken with both partners present
  2. Prior Pregnancy and outcomes
  3. General Factors
    1. Age
    2. Previous pregnancies
    3. Number of contiguous months attempting conception
  4. Symptoms of Sexually Transmitted Disease
    1. Vaginal Discharge
    2. Dysuria
    3. Abdominal Pain
    4. Fever
  5. Medications and substances
  6. Toxin exposures
  7. Menstrual History
  8. Sexual History
    1. Timing of intercourse in Menstrual Cycle
    2. Frequency of intercourse
      1. Optimally every day or every other day in Ovulation
    3. Lubricant use (spermatotoxic)
    4. History of Impotence
    5. Dyspareunia
    6. Technique

V. Exam

  1. Breast Exam
    1. Breast formation
    2. Galactorrhea
  2. Genitourinary Exam
    1. Uterine masses
    2. Vaginal Discharge
  3. Endocrine (Hyperandrogenism)
    1. Hirsutism
    2. Acne Vulgaris
    3. Clitoromegaly

VI. Causes

  1. General
    1. Infertility is multifactorial in 40% of cases
    2. In at least 25% of cases, no Infertility cause is identified
  2. Female Infertility Causes
    1. See Female Infertility Causes
    2. Ovulatory Dysfunction accounts for 21-25% of cases
    3. Tubal factors account for 14-20% of cases
  3. Male Infertility Causes
    1. See Male Infertility
    2. Male factors account for 26-30% of cases

VII. Evaluation: Male Factor

  1. See Male Infertility
  2. History
    1. Prior conceived children
    2. History of testicular or scrotal surgery
    3. History of testicular infection (Mumps)
  3. Labs
    1. Semen Analysis
    2. Test for Sexually Transmitted Disease
      1. Mandatory for in vitro fertilization

VIII. Evaluation: Female factor

  1. History related to Infertility Causes
  2. Confirm Ovulation
    1. Serum Progesterone (preferred)
      1. See Mid-Luteal Serum Progesterone for protocol
      2. Obtain Serum Progesterone on Day 21 of cycle (or 7 days before anticipated Menses onset)
      3. Serum Progesterone > 5 ng/ml (15.8 nmol/L) suggests Ovulation
    2. Other measures to confirm Ovulation
      1. Basal Body Temperature (not recommended, unreliable)
      2. Urine Luteinizing Hormone
  3. Aproach
    1. See below for evaluations of non-ovulating and ovulating women

IX. Evaluation: Female Factor - Not ovulating

  1. Evaluate for Anovulation causes
    1. Follicle Stimulating Hormone
    2. Serum Prolactin
    3. Thyroid Stimulating Hormone
  2. Evaluate for Premature Ovarian Failure (age >35 years)
    1. Serum Follicle Stimulating Hormone (FSH) on Day 3 of cycle
      1. Increased FSH >15-29 IU/L on day 3 suggests decreased likelihood of conception
      2. Increased FSH >30-40 IU/L (at any time) and low Serum Estradiol suggests Premature Ovarian Failure
    2. Serum Estradiol (on Day 3 of cycle if menstruating)
      1. Decreased Serum Estradiol
        1. FSH increased: Premature Ovarian Failure
        2. FSH decreased: Hypothalamic-Pituitary failure
      2. Increased Serum Estradiol > 60-80 pg/ml and normal FSH predicts lower conception rate
        1. Associated with ovarian insufficiency (or decreased ovarian reserve)
    3. Other tests (low efficacy)
      1. Clomiphene Citrate (Clomid) challenge
      2. Transvaginal Ultrasound (assess antral follicle count)
  3. Consider Hyperandrogenism
    1. Serum 17a-Hydroxyprogesterone
    2. Serum Testosterone

X. Evaluation: Female Factor - Ovulating

  1. Assess tubal patency
    1. No tubal obstruction risk factors
      1. Hysterosalpinography
    2. Tubal obstruction risk factors (Ectopic Pregnancy, pelvic infections, Endometriosis)
      1. Hysteroscopy
      2. Laparoscopy (with dye)
    3. Other measures
      1. Transvaginal Ultrasound
  2. Other measures that are not recommended (do not affect management)
    1. Avoid post-coital Cervical Mucus testing
    2. Endometrial Biopsy for histologic dating
      1. Endometrial Biopsy is only indicated for suspected pathology (e.g. Endometrial Cancer Risk Factors)

XI. Management

  1. General measures
    1. Tobacco Cessation
    2. Limit Alcohol
    3. Target health weight
      1. Goal Body Mass Index (BMI) >20 kg/m2 and <30 kg/m2
  2. Treat specific conditions if present
    1. Hyperprolactinemia
    2. Hypothalamic-Pituitary Failure
      1. Underweight women or over Exercisers with Amenorrhea, low Serum FSH and low Estradiol
      2. Encourage normalization of weight and moderation of Exercise
    3. Polycystic Ovary Syndrome (PCOS)
      1. Encourage weight loss, Exercise and lifestyle modification
      2. Clomiphene (Clomid)
      3. Metformin (Glucophage) 1500 mg daily
        1. Initial studies were promising and did increase Ovulation rates
        2. However does not increase the live birth rate
        3. Lord (2003) BMJ 327: 951 [PubMed]
        4. Sun (2013) Arch Gynecol Obstet 288(2): 423-30 [PubMed]
      4. Laparoscopic Ovarian Drilling
    4. Tubal disease
      1. Tubal repair surgery
    5. Endometriosis
      1. Laparoscopic ablation
    6. Male Infertility
      1. Treat cause (e.g. Varicocele Repair)
      2. Artificial Insemmination, Intrauterine insemination
  3. Ovulatory Dysfunction management
    1. Clomiphene Citrate (Clomid)
    2. Gonadotropins (for central Hypogonadism)
  4. Unexplained or refractory Infertility
    1. Precaution in unexplained Infertility
      1. Intrauterine insemination and Ovulation induction do not increase pregnancy rates
    2. Referral to Assisted Reproductive Technology (ART) as indicated
    3. Ovulatory Dysfunction management (as above)
    4. Intrauterine insemination
    5. In-Vitro Fertilization

XII. Prognosis

  1. Overall fertility rate with treatment: 50%
  2. Even without treatment, 50% will conceive in the second year of attempting pregnancy
  3. Predictors of lower success rate
    1. Tubal causes of Infertility (20% fertility rate)
    2. Severe Endometriosis (17% fertility rate)
    3. Longer duration of Infertility
    4. No prior fertility history
    5. Women over age 30-35 years
  4. Reference
    1. Collins (2004) Hum Reprod Update 10:309-16 [PubMed]

XIII. Complications: Assisted Reproductive Technology (ART)

  1. Ovarian Hyperstimulation Syndrome (OHSS)
  2. Heterotopic Pregnancy
  3. Ovarian Torsion
    1. Increased risk with Assisted Reproductive Technology (ART), especially with Ovulation induction (e.g. Clomid)
    2. Multiple cysts that form on the stimulated ovary can act as a lead point for torsion

XIV. References

  1. (2012) Fertil Steril 98(2): 302-7 [PubMed]
  2. (2004) Fertil Steril 82(suppl 1):S169-72 [PubMed]
  3. Jose-Miller (2007) Am Fam Physician 75(6):849-58 [PubMed]
  4. Lindsay (2014) Am Fam Physician 91(5): 308-14 [PubMed]

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