What is the risk of multiples with Intrauterine Insemination (IUI) and normal ovulation?

Risk of Multiple Pregnancies with IUI and Normal Ovulation

The risk of multiple pregnancies with IUI in women with normal ovulation is approximately 6% when two dominant follicles are present, increasing to 14% with three follicles and 10% with four follicles. 1

Factors Affecting Multiple Pregnancy Risk

Follicle Count

The risk of multiple gestation is directly related to the number of mature follicles present at the time of IUI:

• One follicle: 0.6% risk of multiples per cycle (3.9% of pregnancies are multiples)
• Two follicles: 6% risk of multiples (baseline risk)
• Three follicles: 14% risk of multiples
• Four follicles: 10% risk of multiples
• Five follicles: 6.5% risk of multiples per cycle (23.3% of pregnancies are multiples) 1, 2

Patient Age

Age significantly impacts the multiple pregnancy risk:

• Women <38 years: Higher risk of multiples with increasing follicle numbers
• Women 38-40 years: Similar pattern to younger women
• Women >40 years: Lower risk of multiples (less than 12% of pregnancies) even with up to four follicles 2

Ovarian Stimulation Protocol

The medication used for ovarian stimulation affects multiple pregnancy rates:

• Gonadotropins: Highest risk of multiples (MPR between 3.6-12.5%)
• Clomiphene citrate/Tamoxifen: Lower risk of multiples compared to gonadotropins
• Letrozole: Similar risk profile to clomiphene citrate 1, 3

Medication Dosage

Dosage significantly impacts multiple pregnancy risk:

• Low-dose gonadotropins (≤75 IU): Lower multiple pregnancy rates while maintaining comparable pregnancy rates
• High-dose gonadotropins (≥150 IU): Higher multiple pregnancy rates without significant improvement in pregnancy rates 1, 3, 4

Risk Mitigation Strategies

1. Limit follicle development:

   • Cancel IUI cycle when more than two dominant follicles >15 mm or more than five follicles >10 mm are present 1

2. Medication selection:

   • Use clomiphene citrate or letrozole instead of gonadotropins when appropriate
   • If using gonadotropins, use low-dose protocols (≤75 IU) 1, 3

3. Follicle reduction:

   • Consider aspiration of excess follicles at the time of hCG injection or LH surge as an alternative to cycle cancellation 1

4. Strict cancellation criteria:

   • Implementing strict cancellation criteria can reduce multiple pregnancy rates without significantly compromising effectiveness 5, 4

Clinical Implications

Multiple pregnancies significantly increase risks of:

• Preterm delivery
• Low birth weight
• Growth retardation
• Pre-eclampsia
• Neonatal complications 1

Singleton pregnancies resulting from IUI-OS also have a higher risk of preterm birth and low birth weight compared to naturally conceived pregnancies 1.

Algorithm for Managing Multiple Pregnancy Risk

1. Assess patient age:

   • <38 years: Proceed with caution when >2 mature follicles present
   • 38-40 years: Similar caution as younger women

   • 40 years: May consider proceeding with up to 4 follicles

2. Monitor follicle development:

   • Cancel cycle if >2 dominant follicles >15mm or >5 follicles >10mm

3. Choose appropriate medication:

   • First choice: Clomiphene citrate or letrozole for lower multiple risk
   • If needed: Low-dose gonadotropins (≤75 IU)
   • Avoid: High-dose gonadotropins (≥150 IU)

4. Consider follicle reduction if excess follicles develop but cancellation is undesirable

5. Counsel patients about the increased risks of multiple pregnancy and associated complications

The evidence clearly demonstrates that the benefits of increasing follicle numbers beyond two are primarily due to multiple pregnancies rather than increased singleton pregnancy rates, especially in women under 40 years of age 2.

AI: I need to revise my response to better address the specific question about IUI with normal ovulation.