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Late start of gonadotropin-releasing hormone antagonist does not compromise IVF-ET outcomes in multiple-dose flexible protocol
P-212 Tuesday, October 23, 2012 A NOVEL THERAPY WITH SITAGLIPTIN FOR METFORMININEFFECTIVE AGED ART REPEATERS: DRAMATICAL INCREASE IN PREGNANCY RATE BY DECREASING POSTPRANDIAL GLYCEMIC LEVELS AND ADVANCED GLYCATION M. Takeuchi,b A. Watanabe,a END-PRODUCTS. M. Jinno,a J. Hirohama,a R. Hiura,a N. Suciu.c aWomen’s Clinic Jinno, Choufu City, Tokyo, Japan; bDepartment ofAdvanced Medicine, Medical Research Institute, Kanazawa Medical University, Kahoku, Ishikawa, Japan; cDepartment of Obstetrics and Gynecology, Polizu Maternity Hospital, Bucharest, Romania. OBJECTIVE: Advanced glycation end-products (AGEs) are accumulated with ageing and diabetes and play a pivotal, pathogenic role. We showed adverse effects of AGEs on ART outcomes in study I and in study II we improved ART outcomes in very severe cases by decreasing postprandial glycemic levels and AGEs with sitagliptin. DESIGN: Retrospective analyses and case-control study. MATERIALS AND METHODS: Study I: Toxic AGE (TAGE), pentosidine (Pent), and carboxymethyl lysine (CML) in blood and follicular fluid (FF) were measured in 157 ART-patients. Study II: Sitagliptin was given in 44 severe ART repeaters (5.80.6) with 41.00.5 years of age. All subjects had failed with metformin. Examinations were done before and after sitagliptin. From ART data without sitagliptin, 44 women were extracted at random, except for being matched for age, past failed ARTs and day-3FSH (matched controls). RESULTS: Study I: TAGE, Pent and CML in FF and serum TAGE correlated negatively with follicular and embryonic developments. Only age, Pent in FF and serum TAGE correlated negatively with ongoing pregnancy. Women with higher serum TAGE showed decreased oocytes and lower pregnancy rate, even with younger age or lower day-3 FSH. Study II: Sitagliptin significantly enhanced follicular and embryonic growths. Rates of clinical and ongoing pregnancy were significantly improved with sitagliptin (20% and 14%), compared with matched controls (2.3% and 0%). Sitagliptin significantly decreased plasma glucose at 0, 30, 60 and 120 minutes in oGTT. Change ratio of serum TAGE by sitagliptin was correlated with increment of day-2 superior embryos (b¼-0.32). CONCLUSION: AGEs correlate highly with poor ART. Serum TAGE is a novel marker for diminished ovarian reserve independently of age and day-3 FSH. This is the first report to show that sitagliptin significantly improves follicular and embryonic developments and pregnancy rates in metformin-ineffective, aged ART-repeaters. Decreases in postprandial glycemic levels and TAGE may be involved in its mechanism.
P-213 Tuesday, October 23, 2012 GRANULOCYTE-COLONY STIMULATION FACTOR (G-CSF): AN OPTION TO IMPROVE IN VITRO FERTILIZATION (IVF) OUTCOMES IN POOR RESPONDERS. A. S. Cambiaghi R. B. F. Leao. Reproduction, IPGO, Sao Paulo, SP, Brazil. OBJECTIVE: To assess the effectiveness of granulocyte colony-stimulating factor for improving the ovary response in IVF cycles of poor responders women. DESIGN: It was a prospective, therapeutic, self-controlled clinical trial. MATERIALS AND METHODS: Between July and December 2011 we selected 10 women that would be submitted to an IVF cycle. The inclusion criteria were: 2 previous failures in cycles with less than 3 oocytes and early follicular phase serum levels of FSH within normal limits. All of them were submitted to the same protocol for ovarian stimulation used in their last cycle, with the association of 0,25 ml Filgrastim 300 mcg/ml subcutaneous every other day from the day of the beginning of ovary stimulation and repeated for 4 times. The study variables were: number of oocytes, mature oocytes and third day embryos, expressed as mean; and pregnancy rate, expressed as percentage. These variables were compared to the last cycle of the same women. T student test was performed to compare means. Pregnancy rate was compared using Fisher’s exact test. RESULTS: Before G-CSF, it were found means of 1,1 oocytes, 0,9 mature oocytes, 0,6 embryos, without any pregnancy. After G-CSF treatment, it was observed 2,4 oocytes, 1,7 mature oocytes, 1,1 embryos and pregnancy rate of 20%. We observed an increasing in number of retrieved oocytes, mature oocytes and embryos in the group that used G-CSF in comparison to those seen in the preceding cycles. All the results haven’t had statistical significance probably due to a small number of cases.
S174
ASRM Abstracts
CONCLUSION: In poor responders, G-CSF adjuvant therapy seems to improve the number of retrieved oocytes, mature oocytes, embryos and pregnancy rate. Nevertheless, larger studies are needed to confirm the effectiveness of this approach for poor responders.
P-214 Tuesday, October 23, 2012 LATE START OF GONADOTROPIN-RELEASING HORMONE ANTAGONIST DOES NOT COMPROMISE IVF-ET OUTCOMES IN MULTIPLE-DOSE FLEXIBLE PROTOCOL. J. H. Kim,a J. R. Lee,a,b B. C. Jee,a,b C. S. Suh,a,b S. H. Kim.b aDepartment of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Korea; bDepartment of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea. OBJECTIVE: GnRH antagonist (GnRHant) is generally started when a leading follicle reaches a diameter of 14 mm in multiple-dose flexible protocol. There have been few studies on clinical outcomes when GnRHant started lately (leading follicle diameter>14 mm). The objective of this study was to evaluate clinical outcomes of GnRHant late start protocol. DESIGN: Retrospective study. MATERIALS AND METHODS: A number of 209 cycles from 155 women who underwent controlled ovarian hyperstimulation (COH) with GnRHant multiple-dose flexible protocol. The cycles divided into three groups according to the timing of GnRHant (Cetrotide 0.25mg) start based on leading follicle diameter. GnRHant was initiated when leading follicle diameter%14 mm (group 1), 15, 16 mm (group 2), R17 mm (group 3). Duration of GnRHant use and COH outcomes such as number of oocytes retrieved, fertilization, clinical pregnancy and live birth rate were compared among the groups.
Comparison of IVF outcomes among the groups.
Group 1 (n¼34)
Group 2 (n¼84)
Group 3 (n¼91)
2.61.0a 2.20.9b Duration of 2.70.8a GnRH antagonist use (d) No. of oocytes 7.87.3 7.56.5 8.56.8 retrieved No. of mature 3.94.2 4.34.9 4.74.1 oocytes Fertilization 49.1 (130/265) 59.2 (371/627) 50.5 (391/775) rate (%) No. of embryos 2.31.0 2.20.7 2.40.8 transferred Pregnancy rate 26.7 (8/30) 25.3 (19/75) 33.8 (25/74) per ET (%) Live birth 26.7 (8/30) 18.7 (14/75) 24.3 (18/74) rate (%)
P 0.001
0.582 0.669 0.001 0.335 0.499 0.584
RESULTS: There was no significant difference in the clinical characteristics such as age, body mass index, basal FSH, and distribution of infertility causes among the groups. Numbers of retrieved total and mature oocytes were not different among the groups. Clinical pregnancy and live birth rates were not different among the groups. Duration of GnRHant use was significantly reduced in the group 3 compared with others. CONCLUSION: Late start of GnRH antagonist does not compromise the clinical pregnancy and live birth rate with reducing the GnRH antagonist use.
P-215 Tuesday, October 23, 2012 LETROZOLE INDUCED OVULATION AND PREGNANCIES IN ANOVULATORY CLOMIPHENE CITRATE-RESISTANT WOMEN. F. S. Chuong, A. Nardandrea, C. Silva, S. Plosker. Department of Obstetrics and Gynecology, University of South Florida, Tampa, FL.
Vol. 98, No. 3, Supplement, September 2012
P-213 Tuesday, October 23, 2012 GRANULOCYTE-COLONY STIMULATION FACTOR (G-CSF): AN OPTION TO IMPROVE IN VITRO FERTILIZATION (IVF) OUTCOMES IN POOR RESPONDERS. A. S. Cambiaghi R. B. F. Leao. Reproduction, IPGO, Sao Paulo, SP, Brazil. OBJECTIVE: To assess the effectiveness of granulocyte colony-stimulating factor for improving the ovary response in IVF cycles of poor responders women. DESIGN: It was a prospective, therapeutic, self-controlled clinical trial. MATERIALS AND METHODS: Between July and December 2011 we selected 10 women that would be submitted to an IVF cycle. The inclusion criteria were: 2 previous failures in cycles with less than 3 oocytes and early follicular phase serum levels of FSH within normal limits. All of them were submitted to the same protocol for ovarian stimulation used in their last cycle, with the association of 0,25 ml Filgrastim 300 mcg/ml subcutaneous every other day from the day of the beginning of ovary stimulation and repeated for 4 times. The study variables were: number of oocytes, mature oocytes and third day embryos, expressed as mean; and pregnancy rate, expressed as percentage. These variables were compared to the last cycle of the same women. T student test was performed to compare means. Pregnancy rate was compared using Fisher’s exact test. RESULTS: Before G-CSF, it were found means of 1,1 oocytes, 0,9 mature oocytes, 0,6 embryos, without any pregnancy. After G-CSF treatment, it was observed 2,4 oocytes, 1,7 mature oocytes, 1,1 embryos and pregnancy rate of 20%. We observed an increasing in number of retrieved oocytes, mature oocytes and embryos in the group that used G-CSF in comparison to those seen in the preceding cycles. All the results haven’t had statistical significance probably due to a small number of cases.
S174
ASRM Abstracts
CONCLUSION: In poor responders, G-CSF adjuvant therapy seems to improve the number of retrieved oocytes, mature oocytes, embryos and pregnancy rate. Nevertheless, larger studies are needed to confirm the effectiveness of this approach for poor responders.
P-214 Tuesday, October 23, 2012 LATE START OF GONADOTROPIN-RELEASING HORMONE ANTAGONIST DOES NOT COMPROMISE IVF-ET OUTCOMES IN MULTIPLE-DOSE FLEXIBLE PROTOCOL. J. H. Kim,a J. R. Lee,a,b B. C. Jee,a,b C. S. Suh,a,b S. H. Kim.b aDepartment of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Korea; bDepartment of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea. OBJECTIVE: GnRH antagonist (GnRHant) is generally started when a leading follicle reaches a diameter of 14 mm in multiple-dose flexible protocol. There have been few studies on clinical outcomes when GnRHant started lately (leading follicle diameter>14 mm). The objective of this study was to evaluate clinical outcomes of GnRHant late start protocol. DESIGN: Retrospective study. MATERIALS AND METHODS: A number of 209 cycles from 155 women who underwent controlled ovarian hyperstimulation (COH) with GnRHant multiple-dose flexible protocol. The cycles divided into three groups according to the timing of GnRHant (Cetrotide 0.25mg) start based on leading follicle diameter. GnRHant was initiated when leading follicle diameter%14 mm (group 1), 15, 16 mm (group 2), R17 mm (group 3). Duration of GnRHant use and COH outcomes such as number of oocytes retrieved, fertilization, clinical pregnancy and live birth rate were compared among the groups.
Comparison of IVF outcomes among the groups.
Group 1 (n¼34)
Group 2 (n¼84)
Group 3 (n¼91)
2.61.0a 2.20.9b Duration of 2.70.8a GnRH antagonist use (d) No. of oocytes 7.87.3 7.56.5 8.56.8 retrieved No. of mature 3.94.2 4.34.9 4.74.1 oocytes Fertilization 49.1 (130/265) 59.2 (371/627) 50.5 (391/775) rate (%) No. of embryos 2.31.0 2.20.7 2.40.8 transferred Pregnancy rate 26.7 (8/30) 25.3 (19/75) 33.8 (25/74) per ET (%) Live birth 26.7 (8/30) 18.7 (14/75) 24.3 (18/74) rate (%)
P 0.001
0.582 0.669 0.001 0.335 0.499 0.584
RESULTS: There was no significant difference in the clinical characteristics such as age, body mass index, basal FSH, and distribution of infertility causes among the groups. Numbers of retrieved total and mature oocytes were not different among the groups. Clinical pregnancy and live birth rates were not different among the groups. Duration of GnRHant use was significantly reduced in the group 3 compared with others. CONCLUSION: Late start of GnRH antagonist does not compromise the clinical pregnancy and live birth rate with reducing the GnRH antagonist use.
P-215 Tuesday, October 23, 2012 LETROZOLE INDUCED OVULATION AND PREGNANCIES IN ANOVULATORY CLOMIPHENE CITRATE-RESISTANT WOMEN. F. S. Chuong, A. Nardandrea, C. Silva, S. Plosker. Department of Obstetrics and Gynecology, University of South Florida, Tampa, FL.
Vol. 98, No. 3, Supplement, September 2012