Effect of small follicles on clinical pregnancy and multiple pregnancy rates in intrauterine insemination: a cohort study
Authors: Du Tong , Xie Qin , Qiu Jiaxin , Zhang Shiyi , Mol Ben W , Zhang Shaozhen , Kuang Yanping , Zhao Dong , Li Wentao 
Published: December 2023

Abstract

STUDY QUESTION
What is the effect of small follicles on clinical pregnancy and multiple pregnancy rates in women undergoing IUI with ovarian stimulation (IUI-OS)?

SUMMARY ANSWER
The presence of ≥2 small follicles with a diameter of 10–12 or 12–14 mm was associated with an increased chance of clinical pregnancy and the presence of any 12–14 mm or larger follicles, but not smaller follicles, was statistically significantly associated with an increased risk for multiple pregnancy.

WHAT IS KNOWN ALREADY
IUI-OS is widely used as the first-line treatment for unexplained or mild male factor infertility. However, IUI is associated with the risk of multiple pregnancy. While the positive association between the number of follicles ≥14 mm and the chance of pregnancy and the risk of multiple pregnancy is known, the impact of smaller follicles is uncertain.

STUDY DESIGN, SIZE, DURATION
This was a retrospective cohort study that included women undergoing IUI cycles from January 2007 to May 2021 in one assisted reproduction center.

PARTICIPANTS/MATERIALS, SETTING, METHODS
We studied the impact of the number and size of follicles on trigger day on clinical pregnancy and multiple pregnancy rates. Generalized estimation equation regression models were used to compute unadjusted and adjusted odds ratios and 95% CI in all women and only women who achieved clinical pregnancy separately. The chance of clinical pregnancy and multiple pregnancy for different numbers of small follicles in cycles with one &gt;18-mm follicle was calculated using marginal effects estimate.

MAIN RESULTS AND THE ROLE OF CHANCE
This cohort included 12 933 IUI cycles in 7504 women. The overall clinical pregnancy rate was 16.1% (2081/12 933), with a multiple pregnancy rate of 10.5% (218/2081). In the adjusted analysis, the chance of clinical pregnancy increased significantly with the increase in the number of follicles with the diameter of 14–16, 16–18, and 18–20 mm. As for 10–12 mm [adjusted odds ratio (aOR) 1.22, 95% CI 1.02–1.46] and 12–14 mm (aOR 1.29, 95% CI 1.07–1.56) follicles, only groups with ≥2 follicles of those sizes showed significantly increased chance of clinical pregnancy. In cycles that led to pregnancy, follicles with the diameter of 12–14 mm were associated with an increased risk of multiple pregnancy (aOR 1.73, 95% CI 1.19–2.53 for one such follicle; aOR 2.27, 95% CI 1.44–3.56 for ≥2 such follicles), while 10- to 12-mm follicles were not significantly associated with multiple pregnancy (aOR 1.18, 95% CI 0.72–1.95 for ≥2 such follicles). The associations of multiple pregnancy were similar when including all cycles.

LIMITATIONS, REASONS FOR CAUTION
This was a retrospective observational study from a single center. The records of follicle diameter in our center were of a 2-mm interval which limited our ability to analyze the size of follicle as a continuous variable. Also, the number of cycles with a high number of small follicles was still limited which impeded more detailed analysis on the ≥2 follicles subgroup. Similarly, the value of some parts of the marginal probability estimation for multiple pregnancy versus pregnancy according to size and number of follicles was also limited by the low sample size of certain combinations.

WIDER IMPLICATIONS OF THE FINDINGS
Follicles larger than 10 mm, especially those ≥12 mm, may need to be clearly recorded during transvaginal ultrasound surveillance and their potential effects on both pregnancy and multiple pregnancy can be discussed with couples undergoing IUI.

STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by the National Natural Science Foundation of China (Grant numbers 82201912, 82371651, and 82071615) and Shanghai Sailing Program (21YF1423200). B.W.M. is supported by an NHMRC Investigator grant (GNT1176437). B.W.M. reports consultancy for ObsEva and Merck and travel support from Merck. B.W.M. has received research funding from Ferring and Merck. The authors declare no other competing interests.

TRIAL REGISTRATION NUMBER
N/A.