Mature Follicle Count and Multiple Gestation Risk Based on Patient Age in Intrauterine Insemination Cycles With Ovarian Stimulation

Abstract

Objective: To estimate the risk of a multiple gestation pregnancy in ovarian stimulation intrauterine insemination (IUI) cycles when stratified by patient age and mature follicle number.

Methods: We conducted a retrospective cohort study at a single private practice fertility center of IUI cycles performed from 2004 to 2017. Intervention(s) were ovarian stimulation and IUI if postwash total motile sperm count was more than 8 million. Mature follicles were defined as 14 mm or more as measured on the day of ovulation trigger. Main outcomes and measures were rates of clinical pregnancy and multiple gestation.

Results: We identified 24,649 women who underwent a total of 50,473 IUI cycles. Increasing the number of mature follicles from one to five at the time of IUI in women younger than age 38 years increased the clinical pregnancy rate from 14.6% to 21.9% (adjusted odds ratio [aOR] 1.6, 95% CI 1.4-1.9), almost entirely from a marked increase in multiple gestations per cycle from 0.6% to 6.5% (aOR 9.9, 95% CI 6.9-14.2). There was little increase in singleton pregnancies per IUI (14.1-16.4%) regardless of mature follicle number. The per-pregnancy twin and higher-order multiple gestation risk significantly increased (3.9-23.3%, P<.01 and 0.2-10.6%, P<.01, respectively) when comparing one with five mature follicles present at the time of IUI (P<.01). In women younger than age 38 years with more than three follicles present, more than one quarter of all pregnancies were multiples. Similar findings occurred in women aged 38-40 years. In women older than age 40 years, up to four follicles tripled the odds of pregnancy (aOR 3.1, 95% CI 2.1-4.5) while maintaining a less than 12% risk of multiple gestation per pregnancy and a 1.0% absolute risk of multiples.

Conclusion: Caution should be used in proceeding with IUI after ovarian stimulation when there are more than two mature follicles in women younger than age 40 years owing to the substantially increased risk of multiple gestation without an improved chance of singleton clinical pregnancy.

Figure 1:

Clinical pregnancy, singleton, and multiple pregnancy rates per intrauterine insemination (IUI) in patients of all ages (A), patients <38 years of age (B), 38–40 years of age (C), and 41–44 years of age (D). The total height of each column represents the total clinical pregnancy rate per IUI based on follicle number and further divided into singleton (blue) and multiples (yellow) per IUI. The yellow columns are also the absolute risk of a multiple gestation per IUI, further categorized by number of follicles (1–5) that are ≥14 mm on the day of ovulation trigger. Generalized estimating equations were used to adjust for multiple cycles per patient.

Figure 2:

Relative risk of multiples: multiples per pregnancy by follicle number at ovulation trigger in patients of all ages (A), patients <38 years of age (B), 38–40 years of age (C), and 41–44 years of age (D). There were no quadruplets in women 38 years of age and older. Generalized estimating equations were used to adjust for multiple cycles per patient.

Figure 3:

Heat maps to guide clinical decisions and counseling patients on the risks versus benefits of their pregnancy outcome. Clinical pregnancy rate (A), absolute multiple risk: multiples/intrauterine insemination (IUI) (B), and relative multiple risk: multiples/clinical pregnancy (C). The red region indicates low pregnancy success or high multiples risk, yellow indicates moderate pregnancy success or multiples risk, and green indicates highest success in acquiring a pregnancy or lowest multiples risk. Follicle number across the bottom of the graphs are ≥14 mm in size. This tool can counsel the patient, based on her age and number of follicles present, what her overall clinical pregnancy rate is, absolute multiple risk (multiples/IUI), and if she became pregnant, what her risk of multiples would be (relative risk). *Percentages are rounded to the closest whole number and represent mean outcomes from the study. 95% CI of the actual risk are not shown.