Abstract

ObjectiveIn vitro maturation of immature oocytes and in vitro fertilization and transfer of resulting embryo (IVM-IVF) is a relatively new option of assisted reproductive technologies (ART). IVM-IVF is not only a promising method to avoid the potential side effects of gonadotropins, such as ovarian hyperstimulation syndrome (OHSS), especially with polycystic ovarian syndrome (PCOS) patients, but it also has many advantages such as less medication, lower cost, and less stress. Nevertheless, pregnancy rates are still inferior to conventional IVF-ET with ovarian stimulation. The beneficial effect of Metformin (Fertil Steril 2004; 82, Sup.2; O-123), low dose FSH plus Metformin (Fertil Steril 2005; 84, Sup.1; O-203), and frozen-thawed cycles (Fertil Steril 2002; 76, 3S; P-353) on IVM-IVF has been reported at previous ASRM meetings. This present study was conducted to determine whether combination of all three regimens above could achieve comparable clinical outcomes to conventional IVF-ET treatment with ovarian stimulation.DesignRetrospective clinical study at private setting fertility clinic.Materials and methodsIVM-IVF with low dose FSH over Metformin pretreatment was performed in 43 cycles of PCOS patients, either with fresh transfer (15 cycles), or frozen-thawed transfer (28 cycles). All patients were pretreated with 1000-1500 mg/day of Metformin at least for 4 weeks before oocyte retrievals. Follicular monitoring began from cycle day 7, and 150units per day of FSH were administered for 3 days on average until follicles reached 8mm in diameter. When endometrial thickness was <8mm at this point, fertilized oocytes were chosen to be vitrified for subsequent frozen-thawed transfer. Human chorionic gonadotropin (hCG) of 10,000 units was administered 36hours before retrieval. Immature oocytes retrieved were cultured in TCM-199 medium supplemented with 20% patient’s serum 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 a gestational sac.ResultsA total of 644 immature oocytes (mean=15/patient) were retrieved, and 48% of them matured in vitro; 87% of the matured oocytes became normally fertilized. The rate of embryo transfer per retrieval in fresh cycles was 60.0% (9/15), which was higher than that of frozen-thawed cycles (46.4%: 13/28). The pregnancy rates of fresh transfer cycles and frozen-thawed transfer cycles were 55.6% (5/9) and 38.5% (5/13), respectively. Combined pregnancy rate of fresh and frozen-thawed cycles was 45.5% (10/22).ConclusionThe present study suggests that IVM-IVF combined with low dose FSH plus Metformin pre-treatment, and frozen-thawed transfer cycles for PCOS patients achieves an acceptable pregnancy rate as a routine option of ART procedures. Moreover, IVM-IVF is a much more patient-friendly ART treatment when compared to conventional IVF with ovarian stimulation. Given these enhancements, IVM-IVF should be considered more often as a routine choice of ART, especially in PCOS patients. ObjectiveIn vitro maturation of immature oocytes and in vitro fertilization and transfer of resulting embryo (IVM-IVF) is a relatively new option of assisted reproductive technologies (ART). IVM-IVF is not only a promising method to avoid the potential side effects of gonadotropins, such as ovarian hyperstimulation syndrome (OHSS), especially with polycystic ovarian syndrome (PCOS) patients, but it also has many advantages such as less medication, lower cost, and less stress. Nevertheless, pregnancy rates are still inferior to conventional IVF-ET with ovarian stimulation. The beneficial effect of Metformin (Fertil Steril 2004; 82, Sup.2; O-123), low dose FSH plus Metformin (Fertil Steril 2005; 84, Sup.1; O-203), and frozen-thawed cycles (Fertil Steril 2002; 76, 3S; P-353) on IVM-IVF has been reported at previous ASRM meetings. This present study was conducted to determine whether combination of all three regimens above could achieve comparable clinical outcomes to conventional IVF-ET treatment with ovarian stimulation. In vitro maturation of immature oocytes and in vitro fertilization and transfer of resulting embryo (IVM-IVF) is a relatively new option of assisted reproductive technologies (ART). IVM-IVF is not only a promising method to avoid the potential side effects of gonadotropins, such as ovarian hyperstimulation syndrome (OHSS), especially with polycystic ovarian syndrome (PCOS) patients, but it also has many advantages such as less medication, lower cost, and less stress. Nevertheless, pregnancy rates are still inferior to conventional IVF-ET with ovarian stimulation. The beneficial effect of Metformin (Fertil Steril 2004; 82, Sup.2; O-123), low dose FSH plus Metformin (Fertil Steril 2005; 84, Sup.1; O-203), and frozen-thawed cycles (Fertil Steril 2002; 76, 3S; P-353) on IVM-IVF has been reported at previous ASRM meetings. This present study was conducted to determine whether combination of all three regimens above could achieve comparable clinical outcomes to conventional IVF-ET treatment with ovarian stimulation. DesignRetrospective clinical study at private setting fertility clinic. Retrospective clinical study at private setting fertility clinic. Materials and methodsIVM-IVF with low dose FSH over Metformin pretreatment was performed in 43 cycles of PCOS patients, either with fresh transfer (15 cycles), or frozen-thawed transfer (28 cycles). All patients were pretreated with 1000-1500 mg/day of Metformin at least for 4 weeks before oocyte retrievals. Follicular monitoring began from cycle day 7, and 150units per day of FSH were administered for 3 days on average until follicles reached 8mm in diameter. When endometrial thickness was <8mm at this point, fertilized oocytes were chosen to be vitrified for subsequent frozen-thawed transfer. Human chorionic gonadotropin (hCG) of 10,000 units was administered 36hours before retrieval. Immature oocytes retrieved were cultured in TCM-199 medium supplemented with 20% patient’s serum 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 a gestational sac. IVM-IVF with low dose FSH over Metformin pretreatment was performed in 43 cycles of PCOS patients, either with fresh transfer (15 cycles), or frozen-thawed transfer (28 cycles). All patients were pretreated with 1000-1500 mg/day of Metformin at least for 4 weeks before oocyte retrievals. Follicular monitoring began from cycle day 7, and 150units per day of FSH were administered for 3 days on average until follicles reached 8mm in diameter. When endometrial thickness was <8mm at this point, fertilized oocytes were chosen to be vitrified for subsequent frozen-thawed transfer. Human chorionic gonadotropin (hCG) of 10,000 units was administered 36hours before retrieval. Immature oocytes retrieved were cultured in TCM-199 medium supplemented with 20% patient’s serum 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 a gestational sac. ResultsA total of 644 immature oocytes (mean=15/patient) were retrieved, and 48% of them matured in vitro; 87% of the matured oocytes became normally fertilized. The rate of embryo transfer per retrieval in fresh cycles was 60.0% (9/15), which was higher than that of frozen-thawed cycles (46.4%: 13/28). The pregnancy rates of fresh transfer cycles and frozen-thawed transfer cycles were 55.6% (5/9) and 38.5% (5/13), respectively. Combined pregnancy rate of fresh and frozen-thawed cycles was 45.5% (10/22). A total of 644 immature oocytes (mean=15/patient) were retrieved, and 48% of them matured in vitro; 87% of the matured oocytes became normally fertilized. The rate of embryo transfer per retrieval in fresh cycles was 60.0% (9/15), which was higher than that of frozen-thawed cycles (46.4%: 13/28). The pregnancy rates of fresh transfer cycles and frozen-thawed transfer cycles were 55.6% (5/9) and 38.5% (5/13), respectively. Combined pregnancy rate of fresh and frozen-thawed cycles was 45.5% (10/22). ConclusionThe present study suggests that IVM-IVF combined with low dose FSH plus Metformin pre-treatment, and frozen-thawed transfer cycles for PCOS patients achieves an acceptable pregnancy rate as a routine option of ART procedures. Moreover, IVM-IVF is a much more patient-friendly ART treatment when compared to conventional IVF with ovarian stimulation. Given these enhancements, IVM-IVF should be considered more often as a routine choice of ART, especially in PCOS patients. The present study suggests that IVM-IVF combined with low dose FSH plus Metformin pre-treatment, and frozen-thawed transfer cycles for PCOS patients achieves an acceptable pregnancy rate as a routine option of ART procedures. Moreover, IVM-IVF is a much more patient-friendly ART treatment when compared to conventional IVF with ovarian stimulation. Given these enhancements, IVM-IVF should be considered more often as a routine choice of ART, especially in PCOS patients.

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