USE OF A MILD SUPEROVULATION INDUCTION PROTOCOL IN ASSISTED REPRODUCTIVE TECHNOLOGY PROGRAMS: EFFICIENCY AND SAFETY

Objective. To optimize an in vitro fertilization and embryo transfer (IVF and ET) program for patients at high risk for ovarian hyperstimulation syndrome (OHSS), by using a modified mild superovulation induction protocol. Subjects and methods. One hundred and forty-six married couples of reproductive age, who needed an IVF program, were examined. Group 1 (a study group) consisted of 75 patients who had a mild superovulation induction regimen on day 5 of their menstrual cycle (MC). Group 2 (a comparison group) comprised 71 patients whose superovulation induction was carried out according to the standard protocol using gonadotropin-releasing hormone antagonists on days 2-3 of MC. ET in the induction cycle was done in 46 patients from the comparison group; embryo cryopreservation and transfer in the following MC were performed in 25 patients due to the high risk of OHSS. Results. The patients at high risk for OHSS who were treated by a mild superovulation induction protocol were found to have a significant increase in the average count of mature oocytes by 1.3 times and that of good-quality embryos by 1.4 times despite a 1.6-fold reduction in the total number of obtained oocytes as compared to those who received the standard protocol. With the use of the mild induction protocol as compared to the protocol, the significant (3.4 and 2.5-fold) increases in HLA-G1 and HLA-G5 mRNA expressions, respectively, in the follicular fluid cells were associated with the good outcome of the IVF and PE program. The patients with endometrial implantation failures in the implantation window after VF and PE program were noted to have an increase in gene mRNA expressions in the proinflammatory cytokines: tumor necrosis factor-α by 5 times, IL-18 by 3.2 times, and IL-1β by 6.2 times in the cycle preceding induction, which is a poor prognostic sign for pregnancy occurrence. The application of the mild superovulation induction versus standard protocol could reduce the incidence of OHSS by 1.8-fold. After the use of the standard protocol versus the mild one, the elevation of vascular endothelial growth factor (VEGF) receptors type 1 and 2 by 1.3 times on the day of administration of an ovulation trigger and that of VEGF by 1.2 times on the ET day are prognostically significant in the development of OHSS. With the mild and standard protocols, the pregnancy rate per ET has no statistically significant differences (36.5 and 32.7%, respectively). The efficiency of the mild protocol is 1.4 times higher than that of transfer of the cryopreserved embryos obtained due to ET withdrawal because of a high risk for OHSS in the patients receiving the standard protocol. Conclusion. It is reasonable to use the mild superovulation induction protocol in patients with a high ovarian reserve due to the fact that the protocol shows a higher efficiency and has low drug, psychological, and economic loads than the standard protocol involving the transfer of the cryopreserved embryos due to transfer withdrawal because of a high risk for OHSS.

infertility, mild induction protocol, ovarian hyperstimulation syndrome, follicular fluid, biological markers