Intrauterine Insemination (IUI) is a common, less invasive fertility treatment that places washed and concentrated sperm directly into the uterus, aiming to increase the chance of fertilization. This procedure is frequently paired with controlled ovarian stimulation (COS) using fertility medications to encourage the ovaries to develop more than one egg. While the goal is a healthy pregnancy, the most desirable outcome is typically a singleton pregnancy. The risk of conceiving multiples, especially twins, is a significant consideration, and managing this risk revolves entirely around the number of mature follicles that develop.
Understanding Ovarian Stimulation and Follicle Development
Controlled ovarian stimulation is the process of using hormonal medications to encourage the ovaries to produce eggs, which are housed inside fluid-filled sacs called follicles. Medications such as Clomiphene Citrate, Letrozole, or injectable gonadotropins are utilized to stimulate this growth, moving beyond the single follicle that typically matures in a natural menstrual cycle. The number of mature follicles is directly related to the number of eggs that may be released during ovulation, which dictates the potential for a multiple pregnancy.
A follicle is considered mature and ready to release a viable egg when it reaches a specific size, typically between 18 to 24 millimeters in diameter. Monitoring this development is accomplished through regular transvaginal ultrasound scans during the IUI cycle. This monitoring is essential because it provides the data needed to determine the optimal timing for the insemination procedure and to assess the risk of twins or higher-order multiples. The final step is often the administration of a “trigger shot,” such as human chorionic gonadotropin (hCG), which induces the release of the egg(s) approximately 36 hours later.
The Twin Risk Threshold: Follicle Count and Multiples Probability
The use of ovarian stimulation in IUI cycles inherently increases the risk of a multiple pregnancy compared to natural conception, where the chance of twins is roughly 1–2%. The probability of conceiving twins or higher-order multiples rises with each additional mature follicle present at the time of insemination. This risk assessment guides the decision to proceed with or cancel the IUI cycle.
When only one mature follicle is present, the risk of a multiple pregnancy is low, remaining close to the natural conception rate. However, even with a single follicle, there is still a small chance of identical twins, which occurs if the single fertilized egg splits into two embryos.
The target for many fertility specialists is to achieve two mature follicles, as this range maximizes the chance of a successful pregnancy while maintaining an acceptable risk profile for multiples. With two mature follicles, the chance of twins increases significantly compared to one. For women under 38, the risk of twins when two follicles are present is estimated to be around 8% per pregnancy.
The risk escalates notably when three or more mature follicles are present. For women under 40, caution is strongly advised in proceeding with IUI if more than two mature follicles are observed. The increased chance of pregnancy is mostly due to the increased rate of multiples, not an improved chance of a singleton birth.
When four or more mature follicles are present, the probability of twins, triplets, or even higher-order multiples becomes substantially elevated, often prompting physicians to consider cycle cancellation. For women under 38, proceeding with five mature follicles can increase the risk of a multiple gestation to as high as 23.3% per pregnancy. This cumulative risk is why the number of mature follicles is the most important factor in determining safety and suitability for proceeding with IUI.
Medical Decisions: Cycle Cancellation and Risk Mitigation
When monitoring reveals that the follicle count has crossed the safety threshold, typically when three or more mature follicles are present, the fertility clinic may recommend cycle cancellation. Cycle cancellation means the patient does not proceed with the insemination procedure and is instructed to abstain from intercourse. The rationale is patient safety, as multiple gestations carry significant health risks for both the pregnant person and the babies, including a higher incidence of preterm birth, low birth weight, and preeclampsia.
The specific threshold for cancellation varies based on a patient’s age and medical history. For women under 40, exceeding two mature follicles often causes concern. For patients over 40, the risk of multiples remains lower even with a higher follicle count, likely due to decreased egg quality with age, meaning an IUI may proceed with up to four follicles.
In cases where cancellation is necessary, the fertility team may offer alternatives. Options include converting the cycle to an In Vitro Fertilization (IVF) cycle, which allows for eggs to be retrieved and fertilized outside the body, with only a single embryo transferred to control the risk of multiples. Alternatively, the patient may wait for the next cycle, during which the medication dosage will be adjusted downward to encourage a more controlled ovarian response and limit the number of mature follicles.