Women who fail to achieve a successful pregnancy after 12 months of regular, unprotected intercourse should be evaluated with the diagnosis of infertility. Evaluation should be initiated after 6 months for women >35 years. If over 40 years of age, an even more rapid evaluation “is warranted”.

Indications for Immediate Evaluation Include 

• History of oligo / amenorrhea | Known/ suspected uterine, tubal,  peritoneal disease | Endometriosis (stage III/IV) | Known/ suspected male factor subfertility

Definition of Unexplained Infertility (30% of infertile couples) 

• Above definition of infertility is met
• Infertility evaluation is normal
• Minimum evaluation: Confirm ovulatory function | Tubal patency | Semen analysis

CLINICAL ACTIONS:

Relevant History

• Infertility related
  • Menstrual history
  • Pregnancy history
  • Previous contraception
  • Frequency of intercourse
  • Previous evaluations and treatments
  • Family history of reproductive problems and birth defects
• Surgical history
• History of endocrine abnormalities such as
  • Hypothyroidism
  • Hyperprolactinemia
• Abnormal cervical cancer screening and treatments
• Medications and allergies including
  • Occupational exposures
  • Tobacco, alcohol, drugs

Physical Exam

• Vital signs including BMI
• Thyroid exam
• Breast exam
• Evaluation of androgen excess
  • Acne
  • Hirsutism
  • Male pattern balding
  • Clitoromegaly
  • Pelvic examination including evaluation of cul de sac masses / nodularity

Ovulatory Dysfunction Evaluation

• Menstrual history of abnormal bleeding / oligo or amenorrhea
  • Regular menses likely to be ovulating
  • Cycles can be from 25 to 35 days, but if regular and especially if menstrual molimina is present, ovulatory function is likely to be normal
• Serial basal body temperature
• Serum progesterone approx. 1 week prior to menses
  • >3 ng/mL (15.9 nmol per L) indicates ovulation
• Urinary LH (ovulation predictor kits)
• Cervical mucous changes (clear, stretchy)

Note: Test TSH (thyroid function) and prolactin (hyperprolactinemia) in women with ovulatory dysfunction

Ovarian Reserve Assessment

• Ovarian reserve testing may be of help in the following scenarios (higher risk for diminished ovarian reserve)
  • > 35 years
  • Unexplained infertility
  • Planning ART
  • Poor response to GnRH stimulation
  • Have family history of early menopause
  • At higher risk of diminished ovarian reserve (e.g., chemotherapy and/or pelvic irradiation; ovarian surgery for endometriomas)
• Ovarian reserve can be measured by the following
  • Basal FSH and estradiol (E2) levels on days 2-5
    • FSH > 10 IU/L: Lesser response to ovarian stimulation
  • Serum anti-Mullerian hormone (AMH) levels (independent of day): <1 ng/mL
  • Antral follicle count on cycle day 2-5 (early follicular phase)
    • Low count: Fewer than 5 to 7 follicles
• The best surrogate marker for oocyte quality is age
• Note: Unexplained diminished ovarian reserve or elevated FSH <40 years: Offer Fragile X carrier screening for FMR1 premutation (associated with premature ovarian failure)

SYNOPSIS:

Evaluation of women for infertility should be timely, cost effective, and initially focused on the most common causes of infertility such as ovulatory dysfunction. If ovulatory function is normal, uterine anatomy and tubal patency should be investigated.  Tests for ovarian reserve can not predict failure to conceive and therefore should not be used to deny fertility treatment. Ovarian reserve testing should not be used to predict the likelihood of spontaneous conception or menopause.

KEY POINTS:

• Cervical factors are rarely the primary cause of infertility
  • Treat cervicitis if noted
  • Post coital tests are no longer recommended
• Uterine abnormalities can be evaluated with
  • Sonohysterography: Can detect abnormal intrauterine structures
  • Hysteroscopy: Definitive diagnosis under direct visualization
  • HSG: While lower sensitivity (e.g., only 50% sensitivity of polyps, can detect Müllerian anomalies
  • Ultrasound (3-D) & Pelvic MRI: Confirmation and diagnosis of Müllerian anomalies
• Tubal Patency
  • Evaluate with with hysterosalpingogram (HSG)
  • Contrast sonohysterography
    • No FDA approved contrast agents available in the US | “Role of tubal patency is evolving as more data on its use are available”
• Peritoneal factors (endometriosis / pelvic adhesions) requires laparoscopy for diagnosis
  • If assisted reproductive technology is warranted based on severe male factor infertility or known tubal occlusion, laparoscopy may not be necessary and it is not recommended for routine evaluation of the infertile woman without pelvic pathology
• Male Factor
  • ACOG/ ASRM recommends evaluating both partners at the same time due to high percentage of infertility caused by male factor (40 to 50%)
  • Minimal evaluation: Reproductive history and semen analysis
• Diagnostic code:
  • Female infertility associated with anovulation N97.0
  • Female infertility of tubal origin N97.1
  • Female infertilty of uterine origin N97.2
  • Female infertility of other origin N97.8
  • Female infertility, unspecified N97.9

Learn More – Primary Sources:

ACOG and ASRM Committee Opinion 781: Infertility Workup for the Women’s Health Specialist

ACOG Committee Opinion 773: The Use of Antimüllerian Hormone in Women Not Seeking Fertility Care

Locate a Reproductive Endocrinologist:

REI Locator – ASRM

Related ObG Topics:

Managing Abnormal Uterine Bleeding with Ovulatory Dysfunction

Secondary Amenorrhea: Workup and Diagnosis  

Prolactinoma: Early Detection, Evaluation and Management

Do AMH Levels Truly Predict Ovarian Reserve in Women Over 30?