| Objective : The objective of the present study is to compare the obstetric outcomes of long-acting gonadotropin-releasing hormone agonist protocle with flexible Gn RH antagonist protocol and the influences of the protocols on BMP15 and GDF9 in follicle fluid of polycystic ovary syndrome patients undergoing in vitro fertilization cycle.Materials and Methods:This study includes two parts:the retrospective study and the prospective cohort study.In the retrospective study, we indexed our database from January 2011 to Octomber 2015 to find patients.Inclusion citeria were as follows:(1)diagnosed as PCOS with ESHR/EASRM citeria;(2)age were no more than 35 years old;(3)without diseases as endocrinopathies, hypercholesterolemia, neoplasm,uterine malformation;211 patients were divided into two groups:long agonist group(n=156) and antagonist group(n=55). Descriptive statistics were recorded for the patients’ age, body mass index(BMI),infertility duration, number of IVF attempts, basal FSH level, basal LH level, basal T level, infertility factors, number of days of stimulation, the total gonadotropin dose administered, serum hormone(LH, E2, P) level and endometrial thickness and morphology on the day of h CG administration, number of oocytes collected, fertilization rate, cleavage rate, number of available embryos,implantation rate,clinical pregnancy rate, cycle cancellation rate and OHSS rate,ectopic pregnancy rate and live birth rate. The prospective cohort study was performed from December 2015 to January 2016 in the Second Hospital of Hebei Medical University. Objects were patients who meet the citeria mentioned before. There were 42 patients involved in the study. They were divided into two groups according to the COH protocol randomly,including long agonist group(n=22) and antagonist group(n=20). On the HCG administration day,3ml blood was collected from the ulnar vein.On the OPU day,the follicle fluid was collected from mature follicles without stain. After centrifugating, serum and supernatant was collected. All of these samples were preserved in-80℃ ultra low temperature freezer to tset the level of BMP15 and GDF9. Moreover, number of oocytes collected,fertilization rate, cleavage rate, number of available embryos, implantation rate,clinical pregnancy rate, cycle cancellation rate and OHSS rate were compared between two groups. All data were analyzed with SPSS 13.0 software. Statistical significance was set at P < 0.05.Result: In the retrospective study, the basic characteristics such as age, body mass index, duration of infertility and basic level of serum FSH in both groups were matched. The constituent ratios of etiology were almost similar in the two groups. However,the basal serum LH level(8.6±5.2m IU/ml vs6.6±5.0 m IU/ml)and basal serum T level(1.0±0.8 ng/ml vs 0.69±0.4 ng/ml) in long agonist group were significantly higher than that in the antagonist group(P<0.05). Duration of stimulation(12.45±3.67 vs 10.69±3.50) and total gonadotrophin required(2824.63±1067.81 IUvs 2139.81±1242.62IU) were higher in the long agonist protocol compared with the antagonist protocol(P<0.05).Within the long agonist protocol group, the LH level(0.93±0.66 m IU/ml vs4.32±4.67 m IU/ml), the P level(1.17±0.69 ng/ml vs 1.91±3.09 ng/ml) and P/E2(P(ng/ml) x 1,000/E2(pg/ml)) ratio(0.30±0.19 vs 0.46±0.62) on the day of h CG administration were significantly lower, as compared with that of the antagonist protocol group(P<0.05).And the endometrium on HCG day was significantly thicker in long agonist protocol group than the antagonist protocol group(11.03±1.96 mm vs9.87±1.95 mm, P<0.05). Furthermore, the fertility rate(84.4%vs78.6%), cleavage rate(99.00%vs97.9%),cycle cancellation rate(50.6%vs30.9%), implantation(55.3%vs32.2%)and clinical pregnancy rates(72.7%vs50.0%)of the long agonist protocol group were significantly higher, as compared with those of the antagonist protocol group(P<0.05). Other parameters included: levels of E2 on the day of h CG administration, the mean number of oocytes retrieved, the number of available embryos, the number of transferred embryos, severe OHSS incidences and the incidence of ectopic pregnancies,abortion rate, living birth rate,all of which exhibited no significant differences.In the prospective cohort study, the basic characteristics such as age, body mass index, duration of infertility, basic level of serum FSH,basic level of serum LH,basic level of serum T and the constituent ratios of etiology in both groups were matched. Duration of stimulation(13.09±2.49 vs 12.00±4.68) and total gonadotrophin required(2470.45±839.22 IUvs 1853.00±690.26IU) were lower in the antagonist compared with long agonist protocol(P<0.05). The serum P level on the day of HCG administration was lower than that in the antagonist protocol,which was unsignificantly.Endometrium thickness on the day of HCG administration in the long agonist protocol group had a trend of greater than that observed in the antagonist protocol group; however significance was not reached. Within the long agonist protocol group, the LH level(1.26±0.35 m IU/ml vs3.08±2.13 m IU/ml) and P/E2(P(ng/ml) x 1,000/E2(pg/ml)) ratio(0.30±0.13 vs 0.39±0.12) on the day of h CG administration were significantly lower, as compared with that of the antagonist protocol group(P<0.05). Furthermore, the fertility rate(84.4%vs78.6%) of the long agonist protocol group were significantly higher, as compared with those of the antagonist protocol group(P<0.05). Other parameters included: levels of E2 on the day of h CG administration, the mean number of oocytes retrieved, the number of available embryos, the number of transferred embryos, severe OHSS incidences,cleavage rate, cycle cancellation rate,implantation rate, clinical pregnancy rate,all of which exhibited no significant differences,this phenomenon maybe relate with small sample size. The BMP15 level in serum and follicle fluid was 3.87±5.61ng/ml and 6.27±5.58ng/ml, respectively; thus greater than that observed in the antagonist protocol group(0.93±0.22 ng/ml and 1.05±0.32ng/ml, respectively);it was significantly(P<0.05).However,the difference of the GDF9 level in serum and follicle fluid wasn’t significantly.Conclusion: The long agonist protocol had higher implantation rate and clinical pregnancy rate which might be caused by the better endometrium and higher quality embros. The antagonist protocol had a lower gonadotrophin requirement and shorter duration of stimulation, which means more financial than long agonist protocol. PCOS patients using antagonist protocol lean to have less OHSS occurring.Thus both of the long agonist protocol and the antagonist protocol are effective for PCOS patients.The level of BMP-15、GDF-9 is related with occyte qulity and fertilization rate closely. |
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