What is the recommended protocol for intrauterine insemination (IUI) with donated sperm?

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Last updated: November 12, 2025View editorial policy

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IUI Protocol with Donor Sperm

Women undergoing IUI with donor sperm should receive intrauterine insemination rather than intracervical insemination, combined with ovarian stimulation using low-dose gonadotropins (≤75 IU/day), clomiphene citrate, or tamoxifen, with single insemination performed 24-40 hours after hCG trigger or 1 day after spontaneous LH surge. 1

Route of Insemination

  • Intrauterine insemination (IUI) is superior to intracervical insemination (ICI) for donor sperm treatment, significantly improving both live birth rates (OR 1.98,95% CI 1.02-3.86) and pregnancy rates (OR 3.37,95% CI 1.90-5.96) after 6 cycles using cryopreserved sperm in stimulated cycles. 2

  • IUI results in higher clinical pregnancy rates than ICI in both natural cycles (OR 6.18,95% CI 1.91-20.03) and gonadotropin-stimulated cycles (OR 2.83,95% CI 1.38-5.78). 3

Ovarian Stimulation Protocol

  • Ovarian stimulation should be combined with IUI to improve live birth rates, particularly in women with good prognosis. 1

  • Use low-dose gonadotropins (≤75 IU/day starting dose), clomiphene citrate (100 mg/day from cycle days 5-10), or tamoxifen as acceptable first-line options. 1, 4

  • Gonadotropin stimulation (starting at 150 IU FSH) produces higher per-cycle pregnancy rates (14.4%) compared to clomiphene citrate fixed protocol (6.1%), though clomiphene has lower multiple pregnancy rates (12.5% vs 20%). 4

  • Do not add GnRH agonists to gonadotropins as they increase multiple pregnancy rates and costs without improving pregnancy rates. 1

Cycle Monitoring and Timing

  • Cancel the cycle if >2 follicles >15 mm OR >5 follicles >10 mm are present at time of hCG injection or LH surge to prevent high-order multiple pregnancies. 1

  • Aim for 2-4 preovulatory follicles, which significantly improves pregnancy rates (34.4% for two follicles, 31.5% for 3-4 follicles) compared to single follicle (20.9%). 5

  • Perform single IUI 24-40 hours after hCG trigger in stimulated cycles, or 1 day after spontaneous LH surge in natural cycles. 1

  • Double insemination per cycle does not improve pregnancy rates over single insemination and should not be performed. 1

Sperm Preparation

  • Use any standard preparation technique (swim-up, gradient centrifugation, or wash and centrifugation) as there is no evidence that one method is superior to another. 1

  • Ensure at least 0.75 million motile spermatozoa are inseminated, as this threshold significantly impacts both clinical pregnancy (25.9% vs 17.3%) and live birth rates (21.0% vs 13.0%). 6

Post-Insemination Care

  • Apply 10-15 minutes of bed rest immediately after insemination. 1

Number of Cycles

  • Perform at least 3 consecutive IUI cycles before considering transition to IVF/ICSI, as pregnancy rates continue to increase through multiple cycles. 1

  • After 3 failed IUI cycles with ovarian stimulation, transition to IVF/ICSI is the most cost-effective next step. 7

Age-Related Considerations

  • Success rates are significantly higher in women ≤35 years (30.5% per cycle) compared to women >35 years (18.1% per cycle). 5

  • Women's age is negatively associated with live birth rates and should be factored into counseling about expected success. 6

Infection Screening

  • Screen both partners for infectious agents (including HIV, hepatitis) based on local, regional, and national standards before initiating treatment. 1

Risk Counseling

  • Inform patients about increased risk of preterm birth and low birthweight in IUI-conceived pregnancies compared to spontaneous conception, even in singleton pregnancies. 1

  • Multiple pregnancy risk is 10-20% with gonadotropin stimulation but can be minimized through strict cycle cancellation criteria. 1, 3

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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