O-010 The One-and-Done Approach: does higher dosing of gonadotropins in predicted high and low responders increase the incidence of multiple live births from one ART-stimulation cycle?
Authors: Schouten N , De Vaan A , Eijkemans M , Broekmans F 
Published: June 2022

Abstract

Study question
Does higher gonadotropin dosing in predicted high and low responders lead to a higher reproductive potential from one ART-cycle?

Summary answer
Higher gonadotropin dosing may double the incidence of more than one child birth from one ART-stimulation cycle in predicted high responders.

What is known already
Several studies have been conducted to address individualization of the gonadotropin starting dose, one of them being the OPTIMIST-trial. This trial investigated whether an individualized gonadotropin starting dose improved cumulative live birth rates (cLBR) and treatment safety. There was no difference in cLBR between the standard and adjusted starting dose groups, yet a statistically significant decrease in the occurrence of ovarian hyper-stimulation syndrome (OHSS) in predicted high responders. The discussion arose if the higher dosed patients that achieved a live birth (LB) could have had supernumerary useable frozen embryos left, potentially resulting in multiple live births from one stimulation cycle.

Study design, size, duration
Predicted high and low responders (based on AFC) that achieved a LB in the OPTIMIST trial were included. Predicted high responders received either the standard (150 IU) or a reduced dosage gonadotropins (100 IU). Predicted low responders received a higher dose (225/450 IU) or the standard gonadotropin dose (150 IU). All known subsequent frozen embryo transfers after the 1st LB were analyzed for the chance of a second live birth from the same stimulation cycle.

Participants/materials, setting, methods
527 women had a LB in the OPTIMIST trial during the study period or thereafter from embryos obtained from the last stimulation cycle during the study period. Except for 23 women, data was collected regarding the return of these patients for a renewed child wish. Multiple imputation was performed (10 imputations, 20 iterations). Odds ratio (OR) with 95% confidence interval (CI) were calculated and adjusted for confounders if necessary.

Main results and the role of chance
Of the 504 women, 340 women had remaining frozen embryos. The incidence of at least two live births from one stimulation cycle was twice as high in the standard dosage arm (150 IU) of the predicted high responder group (21,5% versus 10,8%, OR 2.27 [95% CI, 1.19 – 4.31]. The incidence of at least two live births in the predicted low responder group did not differ (7,1% versus 6,2% for the higher versus the standard dosed group respectively, OR 1.04 [95% CI, 0.31 – 3.46]). After excluding 149 women with frozen embryos that did not return for their renewed child wish (resulting in a total of 355 women), the comparison showed that the incidence of at least two live births from one stimulation was 30.1% versus 15.0% for the 150 IU versus 100 IU high responder groups, OR 2.43 [95% CI, 1.25 - 4.74]. In the low responder group, 11,8% versus 9,0% had a second live birth in the 225/450 IU versus the 150 IU group (OR 1.60 [95% CI 0.43– 5.98]). More information on the number of embryos used for a second child and gonadotropin dose adjustments is currently obtained.

Limitations, reasons for caution
Not all women had returned for or used all their frozen embryos, which may lead to selection bias. The potential benefit of the one-and-done strategy needs to be balanced against higher safety risks and the clinical relevance should be interpreted with caution.

Wider implications of the findings
To date, no study investigated the total number of live births from one IVF/ICSI stimulation cycle in relation to the FSH dosage administered. These results stress the need for additional research to advice the clinician on choosing an appropriate starting dose which balances the reproductive potential and treatment safety risks.

Trial registration number
not applicable