Evaluation of Infertility

Content Review: July 2023 Last Update:

Infertility is a condition that affects millions of individuals and couples. Although the timing and scope of testing for infertility depend on many factors, when possible, an integrated analysis of both female and male reproductive partners is recommended. The evaluation of infertility may include a medical history, laboratory testing, imaging, and other procedures to identify the underlying cause.    Laboratory testing may involve semen analysis for males and bloodwork to assess hormone concentrations and/or to detect possible genetic causes of infertility for both females and males.

Quick Answers for Clinicians

What are some common causes of infertility, and how is laboratory testing used in their assessment?

Many conditions are associated with infertility. In female reproductive partners, ovulatory dysfunction, which may be associated with amenorrhea, is a common cause of infertility.  Ovulatory dysfunction may itself be caused by polycystic ovary syndrome (PCOS).  Decreased ovarian reserve is another common cause of infertility in female reproductive partners.  Refer to the Laboratory Tests to Evaluate Female Infertility table for additional information. In male reproductive partners, semen abnormalities, which may be caused by conditions such as hypogonadism, are often associated with infertility.  Refer to the Laboratory Tests to Evaluate Male Infertility table for additional information. Other causes of infertility that may affect either the female or male reproductive partner include thyroid disease, sexually transmitted infections, structural abnormalities, and some genetic conditions.  

Indications for Testing

An evaluation of infertility is appropriate for reproductive partners who are unable to achieve pregnancy within 1 year of regular unprotected intercourse.    The same evaluation may also be appropriate after 6 months if the female reproductive partner is 35 to 40 years of age, or sooner if the female partner is >40 years of age. 

The same evaluation that would be performed for infertility may also be appropriate for individuals who may be at increased risk of infertility or have a condition associated with infertility (eg, amenorrhea, PCOS, sexual dysfunction). 

Finally, an evaluation adapted to specific circumstances may also be appropriate for individuals or couples who are using donor sperm, pursuing reciprocal in vitro fertilization, using preimplantation genetic testing, pursuing other fertility treatments, or using assisted reproductive technology (ART) for reasons other than infertility (eg, recurrent pregnancy loss). 

Laboratory Testing

For female reproductive partners, laboratory testing plays an important role in the evaluation of infertility, which also includes a thorough history, targeted physical examination, and imaging.   For male reproductive partners, laboratory testing should be performed (beginning with semen analysis) and a medical history should be obtained concurrently with the evaluation of the female partner.   

Female Infertility Evaluation

Refer to the ARUP Consult Infertility Testing for the Female Reproductive Partner algorithm for a visual overview of the recommended testing strategy.

Laboratory Tests to Evaluate Female Infertility
Test Recommendations
Endocrine Tests

TSH

May be appropriate because untreated thyroid disease can have an adverse effect on fertility 

AMH

Use to assess ovarian reserve  

Low concentrations are associated with poor ovarian reserve and response to stimulation 

Serum can be collected on any day of the menstrual cycle  

FSH

Can be used to predict response to ovarian stimulation  

High concentrations are consistent with poor response to ovarian stimulation 

Measurements should be made on day 2-4  or 2-5  of the menstrual cycle

Should be measured with estradiol  

Evaluation for PCOS is suggested if FSH and estradiol are normal in the presence of anovulation or oligomenorrhea 

Estradiol

May assist with the interpretation of FSH test results  

Elevated basal concentrations are consistent with decreased ovarian reserve 

Evaluation for PCOS is suggested if FSH and estradiol are normal in the presence of anovulation or oligomenorrhea 

Should not be ordered as a standalone test 

LH

Use to assess ovulation 

Positive test provides evidence of ovulation 

Can be measured in urine using a commercially available test kit 

Urine (especially evening or midday urine) results generally correspond to serum measurements 

High basal concentrations may occur in individuals with PCOS 

Progesterone

Use to detect ovulation 

A high result implies ovulation  

Collect serum approximately 1 week before the start of menses (eg, day 21 of a 28-day cycle) 

A single measurement is insufficient to determine luteal phase quality because concentrations fluctuate over the course of a day 

Prolactin

Testing is recommended if there is amenorrhea, galactorrhea, or oligomenorrhea 

Not recommended in the routine evaluation of infertility if menses are regular and galactorrhea is absent 

Genetic Tests

FMR1 testing

Recommended in individuals <40 yrs of age with high FSH concentrations or ovarian insufficiency or failure without apparent cause 

Fragile X premutations confer a risk of primary ovarian insufficiency

CFTR testing

Recommended if ≥1 causative variants for cystic fibrosis are detected in the male reproductive partner 

Expanded carrier screening, or gene sequencing including 5T analysis, may be useful

AMH, anti-Müllerian hormone; FSH, follicle-stimulating hormone; LH, luteinizing hormone; TSH, thyroid-stimulating hormone

Chromosome analysis, immunologic testing, the postcoital test, and thrombophilia testing are not generally recommended in the evaluation of infertility in the female reproductive partner. 

Male Infertility Evaluation

Refer to the Infertility Testing for the Male Reproductive Partner algorithm for an overview of the recommended testing strategy.

Laboratory Tests to Evaluate Male Infertility
Test Recommendations
Semen Tests

Semen analysis

Recommended concurrently with the evaluation of the female partner   

Semen fructose

Low semen fructose suggests obstruction 

Not a commonly used test

Endocrine Tests

TSH

May be appropriate because untreated thyroid disease can have an adverse effect on fertility 

FSH

May be used in the diagnosis of abnormalities of spermatogenesis, obstructive azoospermia, or hypogonadism 

High or high normal concentrations suggest abnormalities of spermatogenesis 

Low concentrations with azoospermia suggest obstructive azoospermia 

Low concentrations with low LH and testosterone are consistent with hypogonadotropic hypogonadism 

A single measurement is usually adequate despite potentially varying concentrations throughout the day 

LH

May be used to assess spermatogenesis 

High LH is consistent with severely impaired spermatogenesis 

Low concentrations with low FSH and testosterone are consistent with hypogonadotropic hypogonadism 

A single measurement is usually adequate despite potentially varying concentrations throughout the day 

Testosterone

Recommended for individuals with azoospermia, erectile dysfunction, low libido, suspected hormone abnormalities, or testicular atrophy 

Serum total testosterone using an immunoassay is the initial recommended test

Repeat testing that includes total testosterone and free or bioavailable testosterone is recommended if the initial results are low 

Because concentrations decrease over the course of the day, fasting specimens should be collected in the morning 

Low concentrations are consistent with hypogonadotropic hypogonadism or severely impaired spermatogenesis 

Prolactin

Recommended if there is low or low-normal LH in the presence of erectile dysfunction, low libido, and/or low testosterone 

Concentrations outside the reference interval (high or low) may be associated with sexual dysfunction 

Repeat fasting measurement is recommended if initial results are high but ≤1.5 times the upper limit of the reference interval 

If results are repeatedly high, an evaluation for hyperprolactinemia is recommended 

Genetic Tests

Karyotyping

Recommended if there is azoospermia or severe oligospermia with an elevated FSH concentration, testicular atrophy, or suspected impaired sperm production 

Recommended if there is repeat pregnancy loss 

May identify abnormalities such as Klinefelter syndrome or Robertsonian translocations 

Y chromosome microdeletion analysis

Recommended if there is azoospermia or severe oligospermia with an elevated FSH concentration, testicular atrophy, or suspected impaired sperm production 

Fertility options may be informed by test results

CFTR testing

Testing for cystic fibrosis is recommended if there is vasal agenesis or idiopathic obstructive azoospermia, including CBAVD 

Expanded carrier screening, or gene sequencing including 5T analysis, may be useful 

CBAVD, congenital bilateral absence of the vas deferens

Advanced sperm function tests (eg, hemizona assays, sperm penetration tests), antisperm antibody tests, immunologic testing, sperm aneuploidy testing, sperm DNA fragmentation analysis, the postcoital test, and thrombophilia testing are not generally recommended in the evaluation of infertility in the male reproductive partner.  However, some of these tests may be useful in the appropriate clinical context (eg, to follow up on suggestive results of other tests).

ARUP Laboratory Tests

Female Infertility Evaluation

Ovarian Reserve
Ovulatory Function
Genetic Testing

Male Infertility Evaluation

Hormone Testing

Free testosterone concentrations are estimated from measurements of total testosterone and sex hormone-binding globulin concentrations.

The concentration of free testosterone is derived from a mathematical expression based on the constant for the binding of testosterone to sex hormone-binding globulin.

The concentrations of free and bioavailable testosterone are derived from mathematical expressions based on constants for the binding of testosterone to albumin and/or sex hormone-binding globulin.

Genetic Testing

References

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