Comparison of Clinical Outcomes Between IVM and Minimal Stimulation IVF in Patients With PCOS

Overview

Polycystic ovarian syndrome (PCOS) is most common endocrinologic disease in women of reproductive age with incidence of 6.6 \~ 8%. About fifty percent of the patients with PCOS manifest subfertility and significant proportion of these woman need assisted reproductive technology (ART). These patients are very sensitive to gonadotropins during conventional in vitro fertilization (IVF) and the risk of ovarian hyperstimulation syndrome (OHSS) is high. In vitro maturation (IVM) is an emerging alternative option to conventional IVF for minimizing the risk of OHSS in patients with PCOS. Until now, several studies has been reported the favorable outcomes of oocyte maturation rate, fertilization rate, clinical pregnancy rate, and live birth rate during IVM procedure. However, these results were from retrospective or observational study and there was no suitable randomized controlled trial (RCT). Therefore, this prospective RCT is aimed to compare and analyze the clinical outcomes between IVM and minimal stimulation IVF in women with PCOS, assessing if IVM is recommendable clinical practice or not.

Polycystic ovarian syndrome (PCOS) is most common endocrinologic disease in women of reproductive age with incidence of 6.6 \~ 8%. About fifty percent of the patients with PCOS manifest subfertility and significant proportion of these women need assisted reproductive technology (ART). These patients are very sensitive to gonadotropins during conventional in vitro fertilization (IVF) and the risk of ovarian hyperstimulation syndrome (OHSS), an iatrogenic complication, is very high. In vitro maturation (IVM) is has been suggested as an alternative option to conventional IVF for eliminating the risk of OHSS in patients with PCOS. In 1994, Trounson et al succeeded in fertilization of in vitro matured oocytes and transferring embryo during unstimulated IVF procedure in women with PCOS. Since then IVM was developed as one method of ART field. Previously it had been reported that maturation rate of oocytes retrieved from patients with PCOS were lower than oocytes from women without PCOS. However, in several observational studies, maturation rate of oocytes was up to 80.3%, fertilization was up to 21.9%\~50% per cycle, and live birth rated was 15.9% per retrieval and 33% per cycle. And in several retrospective case-control studies of comparing IVM and conventional IVF, the miscarriage rate and ectopic pregnancy rate were similar, whereas the maturation rate of oocyte was up to 84%, fertilization rate was 43\~70% and pregnancy rate was 22\~56%. Because ovarian stimulation is not utilized, OHSS risk is preventable and cost is effective in IVM procedure. Generally there are three types of IVM techniques; firstly, gonadotropin priming, in which technique small amount of gonadotropin is used for 3 to 5 days. Secondly, human chorionic gonadotropin (hCG) priming, in which hCG is used before oocyte retrieval. Thirdly, no gonadotropin and hCG priming is used. In gonadotropin-priming IVM technique, it had been reported that the number of retrieved oocytes were increased and pregnancy rate was improved from 0 to 29%, but there was no clear evidence of the efficacy. hCG priming technique, most commonly used technique, is for promoting meiotic resumption before full maturation of oocyte. The maturation rate of oocytes was 69\~84%, fertilization rate 45 \~ 80%, pregnancy rate 31 \~ 38.5% and live birth rate was 33% in the studies of investigating hCG priming IVM technique in women with PCOS. Summarizing these observational and retrospective studies, it is expectable that IVM is promising ART method in patients with PCOS, minimizing the risk of OHSS with improved clinical pregnancy rate. However, there was no suitable randomized controlled trial (RCT) to confirm whether IVM is recommendable primary clinical ART practice to women with PCOS. Therefore, this prospective RCT is aimed to compare and analyze the clinical outcomes between hCG-primed IVM protocol and minimal stimulation IVF with Gonadotropin-releasing hormone (GnRH) antagonist protocol in women with PCOS in fresh cycles.