P-763 Intrauterine insemination following controlled ovarian stimulation with gonadotropins: how to lower the multiple pregnancy rate without decreasing the live birth rate ?
Authors: El Hachem H , Berdin A , Bellaïche K , May-Panloup P , Prevost S , Bouet P E 
Published: June 2023

Abstract

Study question
What cancelation policy in controlled ovarian stimulation-intrauterine insemination (COS-IUI) cycles allows to lower the multiple pregnancy rate (MPR) without decreasing the live birth rate (LBR)?

Summary answer
An algorithm based on the woman’s age, serum Estradiol level and number of follicles ≥14 mm on trigger day reduces the MPR without impacting LBR.

What is known already
While the MPR in IVF cycles has significantly decreased in the past decades, it has remained stable and relatively high in COS-IUI cycles, at around 10-15%. The main reason behind this continuously high MPR in COS-IUI cycles has been the relative inability to lower it without significantly decreasing the overall pregnancy rates. Several risk factors are associated with MP in COS-IUI cycles, and recommendations have varied between the different scientific societies, but to date, there is no consensus on the best strategy to decrease the risk of MP in COS-IUI cycles without compromising the pregnancy and live birth rates.

Study design, size, duration
A bicentric observational cohort study at the Angers University Hospital (group A) and the Besançon University Hospital (group B) between January 2011 to December 2019. Approximately 350-400 IUI cycles are performed yearly in each center. All patients who had a clinical pregnancy following COS-IUI during the study period were included. Our main outcome measure was the MPR and our secondary outcome measures were the clinical pregnancy (CP), miscarriage and LBR.

Participants/materials, setting, methods
In group A, the starting gonadotropin dose was 50-100 IU/day, and the algorithm for cycle cancelation was based on the woman’s age, serum Estradiol (E2) level, and number of follicles ≥14 mm on trigger day. In group B, the starting gonadotropin dose was 100-150 IU/day and the cancelation policy was case-by-case and physician dependent, based on the woman’s age, number of follicles ≥15 mm, and number of previous failed COS-IUI cycles, without predefined cut-offs.

Main results and the role of chance
We included 6582 COS-IUI cycles (3387 in group A and 3195 in group B) that resulted in 884 clinical pregnancies (790 singletons, 86 twins and 8 triplets). The MPR was significantly lower in group A compared to group B (8.1% vs 13.3%, p = 0.01). The CPR (13.4% vs 13.4%, p = 0.99), the miscarriage rate (14.5% vs 15.6%, p = 0.64) and the LBR (10.8% vs 11.9%, p = 0.16) were comparable between groups A and B. Univariate analysis showed the following factors to be predictive of the risk of MP: the treatment center (OR = 1.73 [1.12-2.68]), the number of follicles ≥10 mm (OR = 1.22 [1.11-1.36]) and ≥14 mm on trigger day (OR = 1.43[1.20-1.70]). Multivariate analysis also showed the following factors to be predictive of the MP risk: the treatment center (aOR=1.63 [1.02-2.60]), the number of follicles ≥ 10 mm (aOR=1.20 [1.07-1.34]) and ≥14 mm on trigger day (aOR=1.39 [1.16-1.66]). The cycle cancelation rate was comparable between groups A and B (7.2% vs 7.2%, p = 0.93), while cycle cancelation rate for excessive response to COS was significantly lower in group A compared to group B (19.3% vs 35.9%, p &lt; 0.001). The rate of divergence from cancelation protocol was significantly lower in group A compared to group B (0.09% vs 1.1% p &lt; 0.001)

Limitations, reasons for caution
The main limitation of our study is the retrospective design. The algorithm needs to be tested in other populations for further validation.

Wider implications of the findings
The use of low starting doses of gonadotropins (50-100 IU/day), and the application of a strict algorithm that takes into account the woman’s age, serum E2 level and number of follicles ≥14 mm on trigger day allows to optimize the success rates of COS-IUI cycles

Trial registration number
Not applicable