Evolution of controlled stimulation protocols: selection factors and shifting paradigms

Mykola Gryshchenko moves the conversation from "how to stimulate" to "why" — proposing to view controlled ovarian stimulation not as an isolated tool but as part of an overall ART strategy.

The starting frame is a holistic approach. The programme's goal has evolved: from pregnancy rate to cumulative live births, and today to the birth of a healthy child — as many as the family wants, in reasonable time, without complications and at optimal cost. The two most troublesome ART complications are ovarian hyperstimulation syndrome and multiple pregnancy.

Stimulation, in Gryshchenko's view, does not exist in a vacuum: the choice is shaped by available technologies — freezing, oocyte vitrification, PGT, personalised transfer. Hence its evolution — from high-dose protocols with high OHSS rates to more restrained, antagonist-based and personalised regimens.

A key efficiency landmark is the plateau from about 18-20 oocytes per cycle: below it, more oocytes mean more prospects, both current and cumulative. By reserve, patients fall into three cohorts — normo-, hyper- and hypo-responders, each with its main task (for hyper, avoid OHSS; for hypo, do not lose time).

For hypo-responders the POSEIDON stratification is especially useful, dividing "poor-prospect" patients by age (before and after 35) and by whether a weak response was anticipated or met only during the cycle.

A separate thread is pharmacogenomics in real-world stimulation. Gryshchenko cites a 2025 study: genotyping the FSH receptor (FSHR N680S) and matching the drug to the receptor variant changes the live-birth rate — 40% with a personalised approach versus 29% without.

Protocol choice is shaped by many factors beyond the patient's profile: comorbidity (endometriosis, adenomyosis, oncological causes), the need for social fertility preservation, cultural and religious limits, the acceptability of donation and embryo storage, and the systemic resources of clinic and state.