The Effect of Follicle-Stimulating Hormone Receptor (FSHR) Polymorphism on Outcomes of Controlled Ovarian Hyperstimulation (COH) and In-vitro Fertilization and Embryo Transfer (IVF-ET) / 대한불임학회지

OBJECTIVE: To investigate the association of FSH receptor (FSHR) polymorphism at position 680 with outcomes of controlled ovarian hyper-stimulation for IVF-ET in Korean women. Design: Genetic polymorphism analysis. MATERIALS AND METHODS: The FSHR polymorphism was analyzed by PCR-RFLP in 172 ovulatory women below the age of 40 year. Patients with polycystic ovary syndrome, endometriosis, or previous history of ovarian surgery were excluded. RESULTS: Genotype distribution was 41.9% for the Asn/Asn, 47.7% for the Asn/Ser, and 10.5% for the Ser/Ser FSHR genotype group. There was no difference in age of subjects and infertility diagnosis between genotype groups. When the patients were grouped according to their FSHR genotype, the basal levels of FSH (day 3) were significantly different among the three groups (6.0+/-0.3 IU/L (mean+/-SEM), 5.8+/-0.3 IU/L, and 8.6+/-1.2 IU/L for the Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively, p=0.002). The Ser/Ser group showed a higher total doses of gonadotropins required to achieve ovulation induction, and a lower serum estradiol levels at the time of hCG administration compared with other two groups, but the differences were of no statistical significance. The numbers of oocytes retrieved were significantly different among the three groups (8.6+/-0.8, 9.9+/-0.6, and 6.3+/-0.9, for the Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively, p=0.049). Clinical pregnancy rates were 42.4%, 25.9%, and 29.4% for the Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively. CONCLUSION: Homozygous Ser/Ser genotype of FSHR polymorphism at position 680 was associated with decreased ovarian response to gonadotropin stimulation for IVF-ET.

Clinical Efficacy of Reduced Dose GnRH Agonist Long Protocol for Controlled Ovarian Hyperstimulation in IVF-ET Patients with High Basal Serum FSH Level / 대한산부인과학회잡지

OBJECTIVE: To evaluate the clinical efficacy of half-dose and further reduced dose GnRH agonist long protocols for controlled ovarian hyperstimulation (COH) in in vitro fertilization and embryo transfer (IVF-ET) patients with high basal serum FSH level. METHODS: One hundred and two IVF-ET cycles performed in 84 infertile patients with high basal serum FSH level (FSH>10.0 mIU/mL) were included in this retrospective study. Study subjects were assigned in two groups: continuous half-dose GnRH agonist long protocol (Group A, n=63) vs. further reduced dose GnRH agonist long protocol (Group B, n=39) from half-dose at the start of GnRH agonist to 1/3 or 1/4 dose after pituitary suppression. Exogenous FSH or hMG was administered for COH in step-down mode, 4 or less embryos were transferred, and intramuscular progesterone or 8% progesterone gel was used for the luteal support. RESULTS: Serum estradiol (E2) level on hCG day was significantly higher in Group B (1,318.3 +/- 1,120.4 vs. 2,054.9 +/- 1,773.5 pg/mL, p=0.015). The number of transferable embryos was also significantly higher in Group B (2.9 +/- 1.7 vs. 3.7 +/- 2.0, p=0.027). There was no statistically significant difference in the outcomes such as the dose of gonadotropins administered, the number of oocytes retrieved, and the clinical pregnancy rate. CONCLUSION: GnRH agonist long protocol with the reduced dose from half-dose at the start to 1/3 or 1/4 of dose after pituitary suppression may be more beneficial for COH in IVF-ET patients with high basal serum FSH level. Further prospective randomized controlled study in a larger scale will be necessary to confirm this findings.

Clinical Efficacy of Reduced Dose GnRH Agonist Long Protocol for Controlled Ovarian Hyperstimulation in IVF-ET Patients with High Basal Serum FSH Level / 대한산부인과학회잡지

OBJECTIVE: To evaluate the clinical efficacy of half-dose and further reduced dose GnRH agonist long protocols for controlled ovarian hyperstimulation (COH) in in vitro fertilization and embryo transfer (IVF-ET) patients with high basal serum FSH level. METHODS: One hundred and two IVF-ET cycles performed in 84 infertile patients with high basal serum FSH level (FSH>10.0 mIU/mL) were included in this retrospective study. Study subjects were assigned in two groups: continuous half-dose GnRH agonist long protocol (Group A, n=63) vs. further reduced dose GnRH agonist long protocol (Group B, n=39) from half-dose at the start of GnRH agonist to 1/3 or 1/4 dose after pituitary suppression. Exogenous FSH or hMG was administered for COH in step-down mode, 4 or less embryos were transferred, and intramuscular progesterone or 8% progesterone gel was used for the luteal support. RESULTS: Serum estradiol (E2) level on hCG day was significantly higher in Group B (1,318.3 +/- 1,120.4 vs. 2,054.9 +/- 1,773.5 pg/mL, p=0.015). The number of transferable embryos was also significantly higher in Group B (2.9 +/- 1.7 vs. 3.7 +/- 2.0, p=0.027). There was no statistically significant difference in the outcomes such as the dose of gonadotropins administered, the number of oocytes retrieved, and the clinical pregnancy rate. CONCLUSION: GnRH agonist long protocol with the reduced dose from half-dose at the start to 1/3 or 1/4 of dose after pituitary suppression may be more beneficial for COH in IVF-ET patients with high basal serum FSH level. Further prospective randomized controlled study in a larger scale will be necessary to confirm this findings.

Clinical Efficacy and Hormonal Change of GnRH Antagonist in Controlled Ovarian Stimulation for IVF-ET / 대한불임학회지

OBJECTIVES: To evaluate the efficacy of GnRH antagonist cetrorelix in women undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) and to determine changes in serum hormone concentrations during cetrorelix administration. METHODS: We performed a clinical trial on 30 patients undergoing COH with highly purified follicular stimulating hormone (HP-FSH) and gonadotropin releasing hormone antagonist (GnRHant), cetrorelix. FSH was administrated from day 2 or 3 of cycle with fixed dose and adjusted according to individual response. 0.25 mg of cetrorelix was injected daily subcutaneously from stimulation day 5 until the day of hCG administration. Daily ultrasound monitoring was performed for growing follicles and serum levels of luteinizing hormone (LH), estradiol (E2) and progesterone were measured daily during cetrorelix administration. Up to 4 embryos were transferred. RESULTS: Mean age of enrolled patients was 32.0+/-3.4 years (mean +/-S.D.). All of 30 patients underwent oocyte pick-up, and embryo transfer was done in 28 patients. The total and mean numbers of received oocytes were 196 and 6.5+/-4.7, the number of fertilized eggs was 111, and the fertilization rate was 56.6%. Total duration of FSH administration was 9.2+/-2.2 days and mean of 24.3+/-7.7 ampules of HP-FSH was administered. Total duration of cetrorelix administration was 5.7+/-1.9 days. Serum LH and progesterone levels were maintained in the range of 1.4~2.9 mIU/mL and 0.3~0.6 ng/ mL, which respectively reflected effective prevention of premature LH surge. Clinical pregnancies were achieved in 9 patients, and overall clinical pregnancy rate was 30.0% per oocyte retrieval, and 32.1% per embryo transfer. CONCLUSION: GnRH antagonist is safe and convenient for COH for IVF-ET and effective with optimal pregnancy rate.

Clinical Efficacy of Serum Insulin-like Growth Factor- I (IGF-I), IGF-II, and IGF Binding Protein-3 (IGFBP-3) in Predicting the Prognosis of In Vitro Fertilization and Embryo Transfer / 대한산부인과학회잡지

OBJECTIVE: To evaluate the clinical efficacy of serum insulin-like growth factor-I (IGF-I), IGF-II, and IGF binding protein-3 (IGFBP-3) levels in predicting the prognosis of in vitro fertilization and embryo transfer (IVF-ET). MATERIALS AND METHODS: In 84 patients undergoing IVF-ET, serum levels of IGF-I , IGF-II, and IGFBP-3 were measured using immunoradiometric assay (IRMA) before the gonadotropin administration and on the hCG day of controlled ovarian hyperstimulation (COH). Serum levels of IGFs and IGFBP-3, and the outcomes of IVF-ET were retrospectively analyzed and compared between the pregnant (n=18) and nonpregnant (n=66) groups. RESULTS: There were no significant differences in the outcomes of COH such as total dosage of gonadotropins used, duration of COH, serum estradiol (E2) level on the hCG day, numbers of oocytes retrieved and fertilized, and number of embryos transferred between the pregnant and nonpregnant groups. No differences were found in serum levels of IGF- I , IGF-II, and IGFBP-3, and their ratios before the gonadotropin administration and on the hCG day of COH. Basal serum level of IGF-II was lower with the borderline significance in the pregnant group (796.9+/-159.6 vs. 908.9+/-338.9 ng/ml, p=0.056). The ratio of change in IGF-I to that of IGF-II was significantly higher in the pregnant group (0.066+/-0.489 vs. -0.582+/-2.091, p=0.045). CONCLUSION: Even though basal serum level of IGF-II was lower and the ratio of changes in IGF-I to IGF-II was higher in the pregnant group, serum levels of IGF-I , IGF-II, and IGFBP-3 do not seem to predict the prognosis of IVF-ET. Further investigations are necessary in a larger group of patients to elucidate the clinical efficacy of serum IGFs and IGFBPs levels in predicting the prognosis of IVF-ET.

Recombinant Human Follicle Stimulating Hormone (rFSH) versus Highly Purified Urinary FSH (uFSH): Oocyte and Embryo Quality / 대한산부인과학회잡지

OBJECTIVE: To estimate the efficacy of recombinant human follicle stimulating hormone (rFSH) versus highly purified urinary human FSH (uFSH) in women undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET). METHODS: From 1 January 2001 to 31 August 2001, A total of 254 cycles from 241 patients who attended infertility clinic at Samsung cheil hospital was enrolled in this study. With pituitary down regulation using GnRH agonist by short protocol, rFSH (Puregon(R), Organon, Netherlands) was administered in 131 cycles and uFSH (Metrodin-HP(R), Serono, Switzerland) was administered in 123 cycles. We analyzed ovarian response, pregnancy rate, live birth rate, oocyte quality and embryo quality. RESULTS: The clinical characteristics of two groups were not different. Total FSH dosages (1322.3+/-526.2 IU versus 2124.4+/-881.9 IU, p<0.001) and dosages per retrieved oocyte (90.6+/-36.0 IU versus 138.0+/-57.2 IU, p<0.001) were significantly lower in rFSH group than uFSH group. Clinical pregnancy rate and live birth rate of two groups were not significantly different. The rate of good quality oocyte (Grade I and II) from retrieved oocytes was higher in rFSH group (68.2% versus 64.8%, p=0.024), but after preincubating oocytes for 4 to 6 hours and removing cumulus cells in intracytoplasmic sperm injection (ICSI) cycles, nuclear maturity of oocytes were not significantly different. The quality of transferred embryos were not significantly different too. CONCLUSION: rFSH offered more effective ovarian response in COH and better quality of retrieved oocytes, compared with uFSH.

The Efficacy of Recombinant Human Follicle Stimulating Hormone (rhFSH) in Controlled Ovarian Hyperstimulation for In Vitro Fertilization and Embryo Transfer / 대한산부인과학회잡지

OBJECTIVE: To compare the efficacy and safety of recombinant human follicle stimulating hormone (rhFSH) versus highly purified urinary human FSH (uhFSH-HP) in women undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET). METHODS: Ninety-three women with tubal infertility, stage I/II endometriosis or unexplained infertility were admitted to this study. After pituitary desensitization using GnRH agonist, rhFSH (n=45) or uhFSH-HP (n=48) was administered with a step-down regimen in all patients. RESULTS: Patient's characteristics were comparable in both groups. Low responders were 20 in rhFSH group and 22 in uhFSH-HP group. The total dose of administered FSH was significantly lower in rhFSH group than that in uhFSH-HP grup (p<0.001). The days of stimulation were also significantly shorter in rhFSH group than those in uhFSH-HP group (p<0.05). However, there were no differences in IVF results such as the numbers of oocytes retrieved, oocytes fertilized, grade I/II embryos, embryos transferred between the two groups. There were also no differences in clinical pregnancy rate, miscarriage rate, and multiple pregnancy rate. Even in the low responder subgroup, COH using rhFSH was also associated with significant decreases in the total dose of FSH and the duration of stimulation required. IVF results and pregnancy outcomes were comparable in rhFSH and uhFSH-HP groups. CONCLUSION: These data suggest that the total dose of FSH and the duration of stimulation can be reduced by using rhFSH.

Pregnancy Rate Following Superovulation with Intrauterine Insemination in Infertile Patients / 대한산부인과학회잡지

OBJECTIVES: To investigate the efficiency of superovulation with intrauterine insemination (IUI) in infertile patients. MATERIALS AND METHODS: Seventy-two cycles of superovulation with IUI in 48 infertile couples in which gonadotrophins were used for hyperstimulation were analysed retrospectively. RESULTS: Overall clinical pregnancy rate was 33.3% per cycle and 45.8% per patient. By the infertility factor, patients with endometriosis showed the lowest pregnancy rate (10%). Cumulative pregnancy rate (CPR), obtained by life-table analysis, increased as the number of cycles increased: 25.0% for one cycle, 33.3% for two cycle, 40% for three cycle and 50% for more than four cycle. CONCLUSIONS: Superovulation with IUI is an effective treatment modality in patients with subfecundity, and is worth while trying prior to in vitro fertilization procedure in those patients.

Randomized Controlled Trial of Follicle-Stimulating Hormone Versus Human Menopausal Gonadotropin in Controlled Ovarian Hyperstimulation for in Vitro Fertilization and Embryo Transfer / 대한산부인과학회잡지

Recent evidence suggests that a high level of serum LH during follicular recruitment and development is associated with poor reproductive outcome. Consequently, exogenous LH administration for controlled ovarian hyperstimulation(COH) in in vitro fertilization and embryo transfer(IVF-ET) may be harmful to folliculogenesis. The purpose of this clinical study was to evaluate and compare the efficacy of human menopausal gonadotropin(hMG) and human follicle-stimulating hormone(hFSH) for COH with long protocol of gonadotropin-releasing hormone(GnRH) agonist in IVF-ET program. Randomized clinical trial was performed in 125 patiens undergoing IVF-ET at Seoul National University Hospital from May to Septebmer, 1995. The inclusion criteria of patients included age < 40 years and normal semen analysis, and the study population was also classified into two groups by the etiology of infertility : Group T - 95 patients with only tubal factor and Group O - 30 patients with endometriosis or anovulatory factor. There were no statistically significant differences in dosage(29.0+/-7.9 vs 26.0+/-6.8 ampoules) and duration(12.3+/-1.3 vs 12.2+/-1.5 days) of gonadotropin administration, serum E2 level on hCG day(1,943+/-1,255 vs 1,580+/-1,067 pg/mL), cancellation rate(7.5% vs 6.7%), number of oocytes retrieved(9.9+/-6.0 vs 11.3+/-6.0), fertilization rate(68.4% vs 64.5%), number of embryos transferred(4.7+/-2.0 vs 4.7+/-2.0), and preganancy rate per cycle(26.3% vs 24.4%) and per ET(28.4% vs 26.2%) between hMG(N=80) and hFSH(N=45) Groups. In Group T, no significant differnces in results of IVF-ET were also detected between hMG (N=61) and hFSH(N=34) Groups. In Group O, serum E2 level on hCG day was significantly higher in hMG Group (N=19) compared with hFSH Group(N=11), but other results of IVF-ET were similar in both Groups. As this study could not demonstrate any significant differences in results of IVF-ET between hMG and hFSH when used for COH in IVF-ET program, it could be concluded that hFSH is at least as efficacious as hMG for COH.

CONTROLLED OVARIAN HYPERRSTIMULATION SIGNIFICANTLY DECREASED THE EXPRESSION OF AQUAPORIN-3 IN MOUSE OOCYTES USING SEMI-QUANTITATIVE REAL-TIME PCR ANALYSIS / 解剖学报

Objective To study the effect of controlled ovarian Hyperstimulation(COH)on expression of AQP3 mRNA in mouse oocytes at metaphase Ⅱ. Methods Twenty female mice(6-7 weeks) were randomly allocated into 2 groups, mice in COH group were superovulated by intraperitoneal injection of 7.5 IU pregnant mare's serum gonadotropin(PMSG) followed by 5 IU human chorionic gonadotropin(HCG) after 46-48?h. Nothing was given to mice in control group and the estrus cycle was observed at 9?am everyday. 12-16?h following hCG injection (COH group) or at 8?am next day after the estrus (control group), mice were killed by cervical dislocation. The oviducts were excised.Cumulus masses were recovered from the dilated ampullae under a dissecting microscope,digested granulosa cells using hyaluronidase. Semi-quantitative real-time PCR of AQP3 mRNA in mouse MⅡoocytes was investigated with ?-actin as the internal control. Results Oocytes swelling assay showed that AQP3 mRNA expressed in mouse MⅡ oocytes. Using semi-quantitative real-time PCR, the expression of AQP3 mRNA was significantly decreased(P