Pretreatment of polycystic ovarian syndrome (PCOS) patients with Metformin optimizes results from the clinical application of in vitro maturation, in vitro fertilization and embryo transfer (IVM-IVF)

Abstract

In vitro maturation of immature oocytes obtained from non-stimulated patients and in vitro fertilization and embryo transfer (IVM-IVF) is a relatively new assisted reproductive technology. IVM-IVF is a promising method to avoid the potential side effects of gonadotropins, such as ovarian hyperstimulation syndrome (OHSS), especially with polycystic ovarian syndrome (PCOS) patients, and can also reduces the cost. However, the pregnancy rates are much lower than those of IVF/ICSI in ovarian stimulation cycles. Metformin has been reported to improve ovarian function of PCOS patients due to the correction of their intrafollicular environment. Therefore, the present study was conducted to determine whether pretreatment of PCOS patients with Metformin improves the clinical outcomes of IVM-IVF. Retrospective analysis. IVM-IVF was performed on 70 PCOS patients (105 cycles), either with 1000 mg/day of Metformin pretreatment for 4 weeks before oocyte retrievals (Group A: 46 cycles) or without Metformin (Group B: 59 cycles). Follicular monitoring was started from cycle day 7. Follicles were aspirated when at least 2 follicles larger than 7 mm in diameter were identified before dominant follicle > 13 mm appeared. Human chorionic gonadotropin of 10,000 units was administrated 36 hrs before oocyte retrieval. Either fresh or frozen transfer was chosen depending on the thickness of endometrium (fresh ≥ 8 mm or frozen < 8 mm) at oocyte retrieval. There were 31 fresh cycles and 15 frozen cycles in group A and 36 fresh and 23 frozen cycles in group B. Immature oocytes were cultured in TCM 199 medium supplemented with 10 % patient’s serum for 24 hrs, and mature oocytes were selected for ICSI. Fertilization was assessed 19–21 hours after ICSI for the appearance of 2 distinct pronuclei and 2 polar bodies. Resulting day 3 embryos were transferred after exposure to protease solution for 24 hrs (biochemical assisted hatching). Number of immature oocytes retrieved in group A (16 ± 1.29) was significantly higher (p<0.01) than those in group B (9.0 ± 1.00). However, there were no significant differences in the rates of either maturation (52.5% vs. 55.6%) or fertilization (88.2% vs. 81.8%) between group A and B, respectively. Group A achieved significantly higher (p<0.05) transfer rate per retrieval than group B (80.7% vs. 47.2%, respectively) in fresh transfer cycles, but not in frozen-thawed transfer cycles (60.0% vs. 60.9%). There were no significant differences in pregnancy rates between group A and B either in fresh (19.1% vs. 13.3%) or frozen cycles (44.4% vs. 40.0%). However, the pregnancy rate of frozen cycles tended to be higher (p<0.1) than fresh cycles (44.4% vs. 16.0%) in group A. Metformin increased the number of immature oocytes retrieved. Reduced cancellation rate of embryo transfer and higher pregnancy rate in frozen cycle in group A indicated that Metformin pretreatment of PCOS patients might have improved thier resulting embryo quality in IVM-IVF through correction of the intrafollicular endocrinological environment. The present study suggests that Metformin pretreatment is an effective protocol for PCOS patients in IVM-IVF clinical application.