Study question: Are there any advantages to "mild stimulation" protocols before conventional stimulation?Summary answer: Wide usage of "mild stimulation" in clinical practice seems inappropriate, due to large percentage of women with inadequate (poor and suboptimal) response to stimulation with traditional doses of gonadotropins among patients with IVF programs.What is known already: Conventional stimulation is a kind of "gold standard" in the modern practice of Assisted Reproductive Technologies (ART). In recent years, many different so-called "mild stimulation" protocols were designed to reduce physical, emotional and financial risks associated with conventional schemes.Study design, size, and duration: The study included 4445 infertile women from 20 to 43years old.
Participants/materials, setting, and methods:We analyzed results of IVF programs in terms of pregnancy rate in stimulated cycles and embryo transfers (pregnancy rate index per embryo transfer and per cycle). Ovarian stimulation in the IVF cycles was carried out according to the long protocol of down-regulation with the appointment of a GnRH agonist or a short protocol with GnRH antagonist.Main results and the role of chance: In case of standard stimulation, the highest pregnancy rate indexes per embryo transfer and per cycle were mentioned in patient's groups with 8-22 rather than 4-7oocytes. With hyperergic response in most cases of embryo transfers cancels patients save chances of high enough cumulative pregnancy rate index by using the freeze-all strategy, which provides possibility for subsequent use of obtained embryos in un stimulated cycles.
Limitations, reasons for caution:This study is based on retrospective analysis of data of all patients who were involved in the IVF programs in a specific period of time without considering the factor of patients' infertility.
Wider implications of the findings:Our study shows that proponents of "mild stimulation" do not take into account the fact that quite a significant proportion of women may be resistant to standard (and even high) doses of gonadotropins due to a possible polymorphism of the FSH-receptor, associated with genes mutations encoding them. As a result, the appointment of lower doses of gonadotropins may lead to a deterioration of clinical outcomes of IVF compared to cycles where the conventional scheme is used. In case of hyperergic response, using of freeze-all strategy may be effective in preventing the progression of ovarian hyperstimulation syndrome.