The Clinical Study Of Low Ovarian Response In In Vitro Fertilization And Embryo Transfer

[Background]Ovarian response refers to the ovarian sensitivity to exogenous gonadotropins, which is closely related to ovarian reserve. As we all know, ovarian response is critical for getting a sufficient number of oocytes and embryos in controlled ovarian stimulation treatment. According to predicted correctly of ovarian reserve and ovarian response, making a suitable controlled ovarian stimulation and gonadotropin dose could reduce the risk of ART complications and improve the success rate of IVF-ET. Low responders have a fewer retrieved oocytes and serum estradiol levels. Thus, they have lower pregnancy rates and higher cancellation rates. Low ovarian response mainly divided into two categories. Low responders was the most common, presenting the number of oocytes≤3or Gn high dose (daily dose≥375IU/d), which mainly due to the decline of ovarian reserve. The other was follicle development retardation or stagnation, presenting the duration of gonadotropins more than15days, which often had normal ovarian reserve.Although several protocols have been proposed for clinical management of low ovarian response in IVF, the ideal stimulation for low responders still remain a challenge. In addition, there were few studies on this issue of the patients with normal ovarian reserve but low response (presenting follicle development retardation or stagnation, called as ’unexpected low responders’), So it is worthy for further study. Therefore, the purpose of this study is to explore the use of controlled ovarian stimulation in different low responders in IVF-ET, in order to obtain a better IVF-ET treatment outcome.Part1The clinic study of controlled ovarian stimulation for lowresponders with diminished ovarian reserve in in vitro fertilization and embryo transferOBJECTIVETo investigate the efficacy of natural cycle and controlled ovarian stimulation in low responders with diminished ovarian reserve undergoing IVF-ET treatment. MATERIALS AND METHODS1. A total of170low responders with diminished ovarian reserve treated with249in vitro fertilization cycles were analyzed retrospectively since June2007to December2010in reproductive medicine center of Nan Fang Hospital. According to the different protocle, the patients were divided into group Al (NC-IVF, n=87), group B1(GnRH-a short protocol, n=43) and group C1(GnRH-antagonist regimen, n=119). The features and outcome of patients between the three groups were analyzed by SPSS13.0statistic software using One-way ANOVA and Chi-Square test. P<0.05was considered statistically significant difference.2. A total of24poor responders with diminished ovarian reserve treated with66in vitro fertilization cycles were analyzed retrospectively since June2007to December2010in reproductive medicine center of Nan Fang Hospital. They all had previous failure IVF-ET treatment. Also according to the different protocle, the patients were divided into group A2(NC-IVF, n=36),group B2(GnRH-a short protocol, n=6) and group C2(GnRH-antagonist regimen, n=24). The features and outcome of patients between the two groups were analyzed by SPSS13.0statistic software using One-way ANOVA and Chi-Square test. P<0.05was considered statistically significant difference.RESULTS1. The comparison of different protocols in low responders with diminished ovarian reserve.1.1According to One-way ANOVA analysis, Group B1and Group C1had a higher age (F=5.532, P=0.004) and AFC (F=4.715, P=0.010) than group A1, but a lower basal FSH level (F=4.715, P=0.010). The infertility duration showed no significant differences between the three groups (P>0.05).1.2The gonadotropin dose (F=283.254, P=0.000), peak estradiol (F=79.234, P=0.000),≥14mm follicle number (F=40.014, P=0.000) and≥10mm follicle number (F=57.292, P=0.000) of group B1and C1were higher than group A1. There was no statistical significance difference in the number of≥17mm follicle and thicknesses of endometrial (P>0.05).1.3According to One-way ANOVA analysis and Chi-Square test, group B1and C1had a higher follicle number (F=60.049, P=0.000), oocytes retrieved number (F=77.429, P=0.000) and oocytes retrieved rate (x2=12.110, P=0.002) than group A1, but a lower cancellation rate (χ2=42.046, P=0.000). Group B1had a lower cleavage rate than other groups (χ2=6.082, P=0.048). there were no significant differences showed in fertility rate, good quality embryo rate, implantation rate, pregnancy rate and early abortion rate between the three groups (P>0.05).2. The comparison of different protocols in low responders with diminished ovarian reserve in repetition period.2.1There were no significant differences showed in the age, infertility duration, base-FSH level, and AFC between the three groups (P>0.05).2.2According to One-way ANOVA analysis, the total gonadotropin dose, peak estradiol, thicknesses of endometrial, different radial line of follicles of group B2and C2were higher than group A2(P<0.05).2.3According to One-way ANOVA analysis and Chi-Square test, group B2and C2had a higher follicle number (F=12.741, P=0.001) and oocytes retrieved number (F=19.924, P=0.000) than group A2, but a lower cancellation rate (χ2=6.797, P=0.033). there were no significant differences showed in fertility rate, oocytes retrieved rate, cleavage rate, good quality embryo rate, implantation rate, and pregnancy rate between the three groups (P>0.05).CONCLUSIONS1. Low responders with diminished ovarian reserve had a dissatisfactory clinic outcome and a decreased pregnancy rate in in vitro fertilization and embryo transfer treatment.2. For the low responders with diminished ovarian reserve, the controlled ovarian stimulation (GnRH-a short protocol and GnRH-antagonist regimen) and the natural cycle can obtain similar clinical outcomes. But the natural cycle have a significant increased cancellation rate. Clinicians could choose the two protocols or convert the use of two regimens according to the condition of patients.Part2The clinic study of prolonged duration of gonadotropin administration for unexpected low responders in in vitro fertilization and embryo transferOBJECTIVE To investigate the impact of prolonged duration of gonadotropin administration on unexpected low responders for in vitro fertilization.MATERIALS AND METHODSA total of123oocyte retrieved cycles in patients conducted in our center between Jan,2007and Apr,2011were analyzed as a observation group retrospectively in this study, which the duration of gonadotropin more than15days. A total of173oocyte retrieved cycles in patients conducted in our center between Jan,2007and Apr,2011were analyzed as a control group, which the duration of gonadotropin between8～14days. Based on the difference of the duration of gonadotropin administration, the patients of observation group were divided into three groups: Group A(16-20d)(n=74), Group B(21-25d)(n=31), Group C(>26d)(n=18). The clinical characteristics and outcomes between three groups were analyzed by SPSS13.0software. Compare the baseline characteristic and the treatment of the patients from different groups using One-way ANOVA and Chi-Square test. P<0.05was considered statistically significant difference.RESULTS1. The age, infertility duration, base-LH and base-FSH/LH showed no significant differences between the four groups (P>0.05). Group observation have more AFC than group-control (F=28.101, P=0.000). As the increasing of the duration of gonadotropin administration, the BMI increased gradually (F=11.342, P=0.000)2. As the increasing of the duration of gonadotropin administration, the starting gonadotropin dose (F=104.387, P=0.000), peak estradiol (F=6.975, P=0.000), LH level(F=2.976,P=0.039),P level(F=10.468, P=0.000)an the number of≥17mm follicles (F=11.481, P=0.000) decreased gradually, but the total gonadotropin dose (F=4.927, P=0.004), duration of gonadotropin administration (F=834.618, P=0.000), the number of≥14mm (F=2.959, P=0.041) and≥10mm follicles (F=21.035, P=0.000) increased. There were no significant differences showed in thicknesses of endometrial on the day of HCG administration and oocytes retried (P>0.05).3. According to One-way ANOVA test, as the increasing of duration of gonadotropin administration, the number of follicles (F=16.285, P=0.000) and mature oocytes (F=2.812, P=0.049) increased. There were no significant differences showed in the number of oocytes retrieved, MI eggs, GV eggs, atresia eggs,2PN, total embryos and good quality embryo (P>0.05).Compared with group control, observation group had a higher2PN cleave rate (χ2=8.100, P=0.044), good quality embryo rate (x2=28.251, P=0.000) and implantation rate(χ2=13.214,P=0.004), but a lower oocytes retrieved rate(χ2=69.510, P=0.000) and fertility rate (χ2=8.908, P=0.031). There were no significant differences showed in the early abortion rate, clinic pregnancy rate, ongoing pregnancy rate, live birth rate and cancellation rate(P>0.05).CONCLUSIONS1. A part of the unexpected responders may be due to the low Gn start, resulting in follicles in a quiescent state or part of the latch, which lead to the the prolonged duration of gonadotropins.2. Prolonging the duration of gonadotropin had no adverse effect on the quality of oocytes and embryos and the cycle cancellation rate, which lead to a satisfying treatment outcome.