Low Dose FSH Administration Over Metformin Pretreatment on Polycystic Ovarian Syndrome (PCOS) Patients Improves the Clinical Outcome of In Vitro Maturation and In Vitro Fertilization and Embryo Transfer (IVM-IVF) Treatment

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 option of assisted reproductive technologies (ART). Although IVM-IVF is not only a promising method to avoid the potential side effects of gonadotropins, ovarian hyperstimulation syndrome (OHSS), especially with polycystic ovarian syndrome (PCOS) patients, but also has so many advantages such as less medication, lower cost, and less stress, pregnancy rates are still inferior to conventional IVF-ET with ovarian stimulation. A beneficial effect of Metformin on IVM-IVF has been reported at last ASRM meeting (Fertil Steril 2004; 82, Suppl; O-123). The present study was conducted to determine whether administration of low dose FSH over Metformin pretreatment further improved the clinical outcomes of IVM-IVF treatment. Retrospective clinical study at private setting fertility clinic IVM-IVF was performed on 66 cycles, non pretreatment (Group A: 28 cycles), pretreatment with 1000-1500 mg/day Metformin at least for 4 weeks before oocyte retrievals (Group B: 26 cycles) or total dose of 450 units of FSH administration over Metformin pretreatment (Group C: 12 cycles). Follicular monitoring began from cycle day-7 and follicles were aspirated when at least 2 follicles reached more than 7mm in diameter before dominant follicle (>13.5mm) appeared. Human chorionic gonadotropin (hCG) of 10,000units was administered 36hours before retrieval. In group C, 150 units per day of FSH were administered for 3 days before hCG administration. Immature oocytes retrieved were cultured in TCM-199 medium supplemented with 20% of donor follicular fluid for 28hours and ICSI was performed on matured oocytes. Fertilization was confirmed by the presence of 2 pronuclei and 2 polar bodies 18hours after ICSI. Day-3 embryos were transferred after assisted hatching. Clinical pregnancy was identified by the appearance of gestational sac. Totally 855 (group A: 286, group B: 408, and group C: 161) immature oocytes were retrieved and used for analysis. Number of retrieved immature oocytes per cycle in group A (10.2 ± 7.2) was significantly lower (P<0.01) than either group B (15.7 ± 8.1) or group C (13.4 ± 10.0). However, there were no significant differences in either maturation rates (48.9%, 47.3% and 41.0%) or fertilization rates (81.4%, 87.6% and 83.3%) among group A, B and C, respectively. The rates of embryo transfer per retrieval were similar in group A (64.3%), B (80.8%) and C (66.7%). The pregnancy rates were highest in group C (50%), second in group B (26.7%) and lowest in group A (22.2%). Either Metformin alone or low dose FSH combined with Metformin pretreatment increased the number of immature oocyte retrieved. Combination of Metformin pretreatment with low dose FSH achieved highest pregnancy rate per transfer (50%) and second highest was Metformin pretreatment alone (26.7%). The pregnancy rate of IVM-IVF without any pretreatment was the lowest (22.2%). The present study suggests that pretreatment of PCOS patients with not only Metformin but also low dose FSH combined with Metformin enhances the clinical outcomes of IVM-IVF treatment.