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Published by American Society for Reproductive Medicine · ASRM Quality of Evidence and Strength of Recommendations
Up to 30% of couples experiencing infertility are diagnosed with unexplained infertility after a standard evaluation. Since no treatable cause is identified, treatment is by necessity empiric. Commonly used treatments include ovarian stimulation with oral medications or injectable gonadotropins with intrauterine insemination, and in vitro fertilization.
Key Takeaways
It is not recommended to perform IUI in natural cycles for the treatment of unexplained infertility. It is less effective than OS with IUI and likely no more effective than expectant management.
It is not recommended to use clomiphene citrate with timed intercourse as a treatment for unexplained infertility, as it is no more effective than expectant management.
It is not recommended to use letrozole with timed intercourse as a treatment for unexplained infertility, as it is no more effective than expectant management.
It is not recommended to use gonadotropins with timed intercourse in the treatment of unexplained infertility. Studies report either no difference in pregnancy outcomes compared to OS with oral agents or higher pregnancy rates associated with a higher risk of multiple-gestation pregnancy.
It is recommended to use clomiphene citrate with IUI in the treatment of couples with unexplained infertility.
It is recommended that letrozole with IUI treatments be considered as an alternative regimen for couples with unexplained infertility, as studies to date suggest similar efficacy. Of note, letrozole is not FDA approved for treatment of unexplained infertility, but is considered an effective and well tolerated option.
It is not recommended to use letrozole or clomiphene citrate plus conventional-dose gonadotropins with IUI, as most studies associated with improved pregnancy rate over OS-IUI with oral medications are also associated with an increased risk of multiple-gestation pregnancy.
It is not recommended to use low-dose gonadotropins with IUI in the treatment of unexplained infertility, as it is more complex and expensive, and likely no more effective than OS with oral medications with IUI.
It is not recommended to use conventional-dose gonadotropins with IUI, as most studies associated with improved pregnancy rate over OS-IUI with oral medications are also associated with a high multiple-gestation pregnancy rate.
It is recommended that a single IUI be performed between 0 and 36 hours relative to hCG injection in OS with IUI treatments.
It is recommended that couples with unexplained infertility initially undergo a course (typically 3 or 4 cycles) of OS and IUI with oral agents. For those unsuccessful with OS and IUI treatments with oral agents, IVF is recommended rather than OS and IUI with gonadotropins.
Clinical Topic
Unexplained Infertility
Objectives
To provide evidence-based recommendations to practicing physicians and others regarding the effectiveness and safety of therapies for unexplained infertility.
Target Patient Population
Couples with unexplained infertility
Diagnostic Criteria
Demonstration of at least one patent fallopian tube, documentation of ovulation of the female partner, and a semen analysis with an adequate number of motile sperm for the male partner.
Target Providers
Therapeutic Area
Reproductive MedicineGuideline Scope
Inclusion Criteria
Exclusion Criteria
Special Populations
System: ASRM Quality of Evidence and Strength of Recommendations
Evidence Levels
Recommendation Strength
Monitoring Guidance
Ultrasound monitoring for timing of IUI does not improve pregnancy outcomes compared to urinary LH monitoring in clomiphene citrate-IUI treatments.
Difficulty
advanced
Learning Paths