What Does Unexpected Suboptimal Response During Ovarian Stimulation Suggest, an Overlooked Group?

Unlike poor ovarian response, despite being predicted to be normal responders based on their ovarian reserve markers, many patients respond suboptimally to ovarian stimulation. Although we can improve the number of retrieved oocytes by increasing the recombinant FSH dose and adding LH, the effect of suboptimal ovarian response on cumulative live birth rate (CLBR) and offspring safety is unclear. This study focuses on the unexpected suboptimal response during ovulation induction, and its causes and outcomes are analysed for the first time with a large amount of data used to compare the cumulative pregnancy rate (CPR), CLBR and offspring safety of patients with one complete ART cycle with all embryos used. Our analysis included 5218 patients treated with the GnRH agonist long protocol for their first IVF-embryo transfer (ET) cycles. Patients were divided into two groups according to whether the ovarian response was suboptimal. Propensity score matching (PSM) was utilized for sampling at up to 1:1 nearest-neighbour matching with caliper 0.05 to balance the baseline and improve comparability between the groups. Results showed that age, BMI and basal FSH were independent risk factors for slow response; the initial dosage of Gn, FSH on the first day of Gn, and LH on the first day of Gn were independent protective factors for suboptimal response. Suboptimal responders were also more likely to have irregular menses. Regarding the clinical pregnancy rate of the fresh IVF/ICSI-ET cycles, the adjusted results of the two groups were not significantly different. There was no difference in the CPR, CLBR, or offspring safety-related data, such as gestational age, preterm delivery rate, birthweight, birth-height and Apgar Scores between the two groups after PSM. Age-related changes in the number of oocytes retrieved from women aged 20-40 years old between the two groups were different, indicating that suboptimal response in elderly patients suggests a decline in ovarian reserve. Although we can now improve the outcomes of suboptimal responders, it increases the cost to the patients and the time to live birth, which requires further attention.

Automated summary

This study analyzed the impact of unexpected suboptimal response during ovulation induction on pregnancy rate and offspring safety, comparing patients with normal ovarian response and suboptimal ovarian response with a large amount of data. Results showed that factors such as age, BMI, and baseline FSH were associated with slow ovarian response, while initial dosage of Gn, FSH, and LH levels were protective factors against suboptimal response. Age-related differences in the number of retrieved oocytes suggest a decline in ovarian reserve in elderly patients with suboptimal response.