What factors can increase Intrauterine Insemination (IUI) success?

From the Guidelines

To increase IUI success rates, it is recommended to use gonadotrophins at doses of 75 IU or lower, as higher doses have similar pregnancy rates but increase multiple pregnancy rates, as shown in a systematic review and meta-analysis by Cohlen et al. 1. Several factors can increase IUI (intrauterine insemination) success rates. The most significant include:

• Female age under 35
• Good sperm quality with counts above 10 million motile sperm
• Proper timing of the procedure relative to ovulation Medication protocols can substantially improve outcomes, particularly ovulation induction with medications like Clomid (clomiphene citrate) at 50-100mg daily for days 3-7 of the menstrual cycle, or injectable gonadotropins like Follistim or Gonal-F at individualized doses (typically 75-150 IU daily) 1. Triggering ovulation with hCG (Ovidrel 250mcg or Pregnyl 10,000 units) approximately 36 hours before IUI optimizes timing, as shown in a review by Cohlen et al. 1. Multiple IUI attempts improve cumulative success rates, with most pregnancies occurring within the first three to four cycles. Addressing underlying fertility issues such as treating endometriosis, managing thyroid disorders, or controlling insulin resistance in PCOS patients can enhance outcomes. Lifestyle modifications including maintaining a healthy BMI, avoiding smoking and excessive alcohol, reducing caffeine intake, and taking prenatal vitamins with folic acid (400mcg daily) for at least three months before treatment can further improve success rates. The biological rationale for IUI is bypassing potential cervical barriers and placing a concentrated sample of motile sperm closer to the fallopian tubes, thereby increasing the chances of successful fertilization. Additionally, a well-controlled mild OS with gonadotrophins aiming for two dominant follicles is the most effective strategy when performing IUI for unexplained infertility, minimal to mild endometriosis and moderate to mild male factor infertility, as shown in a review by Cohlen et al. 2. It is also recommended to perform a single insemination per cycle, as there is insufficient evidence for a beneficial effect of double insemination in couples with unexplained infertility, as shown in a systematic review by Polyzos et al. 3. Pre-washing the catheter with culture medium prior to IUI seems to increase the success rate per cycle and could be recommended in Good Laboratory Practice Guidelines, as shown in a study by Pont et al. 2. The time interval from the end of sperm preparation to IUI in the range of 40–80 min has a potential positive effect on pregnancy rate, as shown in a prospective multi-centre cohort study by Fauque et al. 2. Sperm DNA fragmentation and age of the man were the only two parameters that were able to predict IUI outcome, as shown in a prospective cohort study by Duran et al. 2. In the delivery of fertility care interventions and treatments, the prevention of multiple pregnancies should be as important as optimizing live birth rates, as shown in a review by Cohlen et al. 1. Overall, a combination of these factors can increase IUI success rates and improve outcomes for couples undergoing fertility treatment.

From the FDA Drug Label

During clinical investigations, 7578 patients received clomiphene citrate, some of whom had impediments to ovulation other than ovulatory dysfunction In those clinical trials, successful therapy characterized by pregnancy occurred in approximately 30% of these patients.

The factors that can increase IUI success are not directly mentioned in the provided drug label. However, it can be inferred that ovulation induction therapy with clomiphene citrate may be a factor, as it resulted in a pregnancy rate of approximately 30% in clinical trials 4.

• Successful therapy was characterized by pregnancy in the clinical trials.
• The label does not provide explicit information on the factors that increase IUI success.

From the Research

Factors Affecting IUI Success

The success of Intrauterine Insemination (IUI) can be influenced by several factors, including:

• Infertility diagnosis: IUI is most effective for women with ovulatory dysfunction and unexplained infertility, and least effective for women with tubal factor and stage III-IV endometriosis 5
• Semen parameters: Most data support IUI for men with a total motile count > 5 million and post-wash sperm count > 1 million 5
• Stimulation regimens: Letrozole and clomiphene citrate result in similar pregnancy outcomes and are recommended over gonadotropins given increased risk for multiple pregnancies with gonadotropins 5, 6, 7
• Maternal and paternal age: Advancing maternal and paternal age negatively impact pregnancy rates 5
• Maternal BMI: Elevated maternal BMI increases medication requirements without impacting pregnancy outcomes 5
• Timing of IUI: IUI performed at either 24 hours or 36 hours after ovulation triggered by hCG injection does not change clinical pregnancy rates for PCOS patients, but patients with unexplained infertility seem to benefit from earlier IUI procedures 8

Stimulation Protocols

Different stimulation protocols can affect IUI outcomes, including:

• Clomiphene citrate versus letrozole: Letrozole appears to be a good alternative to clomiphene citrate with fewer side effects 7
• Gonadotropins: Controlled ovarian stimulation, particularly with low-dose gonadotropins, with IUI offers significant benefit in terms of pregnancy outcomes compared with natural cycle or timed intercourse 9
• Minimal stimulation: Minimal stimulation using discretely administered gonadotropin combined with clomiphene citrate or letrozole for IUI cycles can decrease the development of OHSS and multiple pregnancies, while maintaining comparable pregnancy rates 6

Prognostic Indicators

Important prognostic indicators of success with IUI include:

• Age of patient: Advanced maternal age negatively impacts pregnancy rates 5, 9
• Duration of infertility: Longer duration of infertility can negatively impact pregnancy rates 9
• Stimulation protocol: Different stimulation protocols can affect IUI outcomes 5, 6, 7, 9
• Infertility etiology: IUI is most effective for women with ovulatory dysfunction and unexplained infertility, and least effective for women with tubal factor and stage III-IV endometriosis 5, 9
• Number of cycles: Most pregnancies occur within the first four IUI cycles, after which in vitro fertilization should be considered 5
• Timing of insemination: IUI performed at either 24 hours or 36 hours after ovulation triggered by hCG injection does not change clinical pregnancy rates for PCOS patients, but patients with unexplained infertility seem to benefit from earlier IUI procedures 8
• Number of preovulatory follicles: The number of preovulatory follicles on the day of hCG can affect pregnancy outcomes 9
• Processed total motile sperm: Processed total motile sperm > 10 million can affect pregnancy outcomes 9
• Insemination count: Insemination count > 1 × 10^6 with > 4% normal spermatozoa can affect pregnancy outcomes 9