Can Intrauterine Insemination (IUI) be done with frozen sperm?

Can IUI Be Done with Frozen Sperm?

Yes, intrauterine insemination (IUI) can absolutely be performed with frozen sperm and has been successfully used for decades, with the first successful human pregnancy from frozen sperm reported in 1953. 1

Historical Foundation and Current Practice

Frozen sperm has been a cornerstone of assisted reproduction since Dr. Jerome K. Sherman introduced glycerol-based sperm preservation methods in 1953. 1 The technique is now one of the most widely used methods globally for donor insemination (DI), particularly for:

• Single women desiring pregnancy 1
• Azoospermia or severe male factor infertility 1
• Y-chromosome linked genetic diseases 1
• Fertility preservation before gonadotoxic therapy 1

Sperm Preparation and Processing

Frozen sperm must be thawed and prepared using standard sperm washing techniques before IUI. 1 The 2018 Human Reproduction Update guidelines specify that preparation should follow WHO manual protocols using simple wash, swim-up, or gradient techniques. 1

Multiple preparation methods have been studied:

• Simple washing achieved 19.1% pregnancy rate per cycle 2
• Sephadex columns achieved 16.9% pregnancy rate per cycle 2
• Percoll density gradient achieved 11.4% pregnancy rate per cycle 2

Importantly, while Percoll gradient produced sperm with superior motility and morphology parameters, this did not translate to improved pregnancy rates, suggesting that averaged motility values have limited predictive value for frozen-thawed sperm fertility potential. 2

Clinical Outcomes: Frozen vs. Fresh Sperm

The evidence shows that frozen sperm can achieve comparable pregnancy outcomes to fresh sperm in IUI cycles, though some nuances exist:

Overall Effectiveness

• IUI with frozen donor sperm achieved 9.7% pregnancy rate per cycle compared to 3.9% with intracervical insemination in a prospective randomized trial 3
• A large 2023 study of 5,335 IUI cycles found overall clinical pregnancy rates of 9.4% with frozen versus 13.0% with fresh sperm (p<0.001), though this difference disappeared after adjusting for confounders in most subgroups 4

Stimulation Protocol Matters

The type of ovarian stimulation significantly impacts whether frozen versus fresh sperm makes a difference:

• Oral medication cycles (clomiphene/letrozole): Fresh sperm showed advantage with adjusted odds ratio 0.49 for clinical pregnancy favoring fresh (p=0.041) 4
• Gonadotropin cycles: No significant difference between frozen and fresh 4
• Natural/unstimulated cycles: Frozen sperm actually showed higher live birth odds (adjOR 1.08) and cumulative pregnancy rate (34% vs 15%, p=0.002) 4

Time to Pregnancy

Time to conception was slightly longer with frozen sperm (3.84 vs 2.58 cycles, p<0.001), though cumulative pregnancy rates and live birth rates ultimately showed no significant differences. 4

Critical Success Factors

Post-thaw sperm parameters that predict IUI success:

• Total motile percentage >17% best predicted pregnancy 5
• Motile concentration >0.9 × 10⁶/mL was the optimal threshold 5
• Progressive and total motile sperm concentration were significantly higher in pregnancy groups 5

Interestingly, CASA-measured velocity parameters (VAP, VCL, VSL, LIN, STR, ALH) did not predict pregnancy outcomes. 5

Important Clinical Considerations

Patient factors influencing success with frozen sperm IUI:

• Age: Treatment outcome significantly influenced by patient age 3
• Ovulatory status: Regular ovulation improves outcomes 3
• Endometriosis: Negatively impacts success rates 3
• Donor variability: Despite normal semen parameters, some donors have markedly reduced sperm fecundity after freezing 3

Practical Algorithm

For IUI with frozen sperm:

1. Thaw sperm using standard protocols 1
2. Prepare using simple wash, swim-up, or gradient technique per WHO manual 1
3. Verify post-preparation total motility >17% and concentration >0.9 × 10⁶/mL 5
4. Perform single insemination 24-40 hours after hCG trigger or 1 day after spontaneous LH surge 1
5. Apply 10-15 minutes bed rest post-procedure 1

IUI-Ready Cryopreservation

Specialized IUI-ready freezing protocols exist that eliminate the need for post-thaw processing. A prospective randomized trial showed IUI-ready preparations achieved 36% pregnancy rate per cycle versus 19.6% with conventional freezing, though retrospective data showed equivalent results (11.3% vs 13.9%). 6 The majority of pregnancies (13 of 23) occurred in the first cycle, with only 2 pregnancies after 4+ cycles. 6

Common Pitfalls to Avoid

• Do not rely solely on CASA velocity parameters to predict frozen sperm success—total motility percentage and concentration are superior predictors 5
• Do not assume all donors freeze equally well—some have markedly reduced post-thaw fecundity despite normal pre-freeze parameters 3
• Consider fresh sperm preferentially for oral medication stimulation cycles if available, as this subgroup showed reduced success with frozen sperm 4
• Do not continue IUI beyond 3-4 cycles without success—most pregnancies occur early, and IVF/ICSI should be considered 6