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A luteal estradiol stimulation protocol improves embryo number and quality for poor-responders undergoing ART
P-548 LOWER DOSES OF RECOMBINANT FOLLICLE STIMULATING HORMONE ARE REQUIRED PER LIVE BIRTH AS COMPARED TO MENOTROPINS IN INTRACYTOPLASMIC SPERM INJECTION CYCLES. S. C. Esteves, S. Verza, Jr, D. T. Schneider, S. F. Zabaglia. ANDROFERT - Centro de Refereˆncia Para Reproduc¸a˜o Masculina, Campinas, Sa˜o Paulo, Brazil. OBJECTIVE: To compare the clinical efficacy of three different gonadotropins for the ovarian stimulation after pituitary down-regulation in intracytoplasmic sperm injection (ICSI) cycles. DESIGN: Observational study. MATERIALS AND METHODS: We analyzed 865 consecutive ICSI cycles of controlled ovarian hyperstimulation (COH) after pituitary downregulation. COH procedure was done with either human menopausal gonadotropin (HMG: MenogonÒ, Ferring; n ¼ 299), highly-purified HMG (HPHMG: MenopurÒ, Ferring; n ¼ 330) or recombinant FSH (follitropin alfa [r-hFSH]: Gonal-FÒ, Serono; n ¼ 236). Laboratory and clinical protocols remained unchanged over time, except for the type of gonadotropin, which have been introduced sequentially, starting with HMG and followed by HP-HMG and r-hFSH. The primary endpoints were live birth rates and the total dose of gonadotropin per cycle, pregnancy and live births. Statistical analysis methods included ANOVA, Kruskal-Wallis and Chi-square tests, as appropriate. RESULTS: Live birth rates were not significantly different for HMG (26.4%), HMG-HP (34.6%) and r-hFSH (32.4%; P¼0.09) groups. The total dose of gonadotropin per cycle was significantly higher in HMG (2,685 720 IU) and HMG-HP (2,903 867 IU) groups, when compared to the r-hFSH-group (2,268 747 IU; P<0.001). Differences of 15.7% and 11.0% were respectively observed in favour of the r-hFSH group, when compared to HMG and HP-HMG, in terms of the total dose of gonadotropin required to achieve clinical pregnancies. Similar differences of 45.2% and 19.8% showed the superiority of the r-hFSH when compared to HMG and HP-HMG, respectively, in terms of the total dose of gonadotropin required to achieve live births. CONCLUSIONS: For each live birth, lower doses of r-hFSH were needed to achieve the ovarian stimulation in comparison to menotropins. Overall, respectively 42.5% and 19.8% more menotropin or highly-purified menotropin were required to achieve one live birth, compared to follitropin alfa, in a COH procedure using pituitary down-regulation for ICSI. Supported by: Institutional.
P-549 A LUTEAL ESTRADIOL STIMULATION PROTOCOL IMPROVES EMBRYO NUMBER AND QUALITY FOR POOR-RESPONDERS UNDERGOING ART. J. L. Frattarelli, M. J. Hill, G. D. E. McWilliams, K. A. Miller, R. T. Scott. Reproductive Medicine Associates of New Jersey, Morristown, NJ; Tripler Army Medical Center, Honolulu, HI. OBJECTIVE: Poor response to ovarian hyperstimulation is a complication in 5–18% of all IVF cycles. Through a search of the literature, we could find no published manuscript which evaluated a luteal estradiol protocol in poor responders. Two published manuscripts have evaluated the luteal estradiol protocol in normal responders. We therefore undertook a retrospective paired analysis evaluating patients at our center who had been treated with a luteal estradiol protocol and a standard poor-responder protocol. DESIGN: This is a two-phase retrospective cohort analysis: (1) a paired analysis of 60 couples undergoing 120 fresh IVF cycles and (2) a matched cohort analysis of 57 women less than 43 years of age who underwent a luteal estradiol protocol were compared to 228 matched control patients. MATERIALS AND METHODS: Controls were matched (4:1) for date of IVF procedure, patient age, basal antral follicle count, infertility diagnosis, ICSI or conventional insemination, embryos transferred, and stimulation protocol. The main outcome measures were (1) embryo quality for the paired analysis and (2) outcome rates for the matched cohort analysis. RESULTS: In both analyses, the luteal phase estrace protocol was noted to have require more total gonadotropins (P<0.01), more days of stimulation (P<0.01) and have higher peak estradiol levels (P<0.01). The luteal phase estradiol protocol resulted in significantly greater number and percentage of embryos R7 cells on day 3 (3.3 embryos vs. 1.9 embryos) (P<0.05). In the paired analysis, the luteal phase estradiol protocol had significantly more oocytes retrieved, mature oocytes, and embryos that did the standard protocol (P<0.05). In the matched cohort analysis, a trend towards improved delivery rates was seen in the luteal estradiol protocol (28.1% vs. 22.4%)
FERTILITY & STERILITYÒ
(P¼0.36) (RR ¼ 1.25; 95% CI: 0.78–2.03). A power analysis was performed that determined a need for 946 subjects to confirm a statistical difference in the live birth rates between the two protocols. CONCLUSIONS: The luteal estradiol protocol may represent a novel and more successful way to treat poor responders during IVF cycles.These data support an improvement in the quality and number of embryos in IVF poor responders when treated with a luteal phase estradiol protocol. Such a protocol could represent an important method for treating poor responding patients and may ultimately optimize outcome success for these patients. Supported by: None.
P-550 HUMAN CHORIONIC GONADOTROPIN INDUCED TRANSCRIPTIONAL PROFILING OF GRANULOSA CELLS FROM PATIENTS UNDERGOING IN VITRO FERTILIZATION. S. Coskun, M. S. Inan, L. A. Al-Alwan, R. Al-Rejjal, K. A. Awartani, S. Al-Hassan. Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. OBJECTIVE: Transcriptional profiling is an important tool to understand underlying molecular mechanism in various physiological and drug-induced biological processes. Human chorionic gonadotropin (hCG) has been used to induce ovulation and oocyte maturation. Although many genes that influence this process have been identified, we hypothesized that knowing the genes selectively expressed at the granulosa cells following hCG-induced ovulation would help us in understanding of the regulatory role of this hormone hoping to avoid disease process like ovarian hyperstimulation syndrome, and/or increasing the pregnancy rates by improving the quality of oocytes matured in response to hCG. Although the most common dose of hCG in IVF is 10,000 IU, there has been reports showing that 5,000 IU is also as effective. The objective of this study to evaluate the differential expression of whole genome after hCG treatment. DESIGN: Expression profilings of granulosa cells were performed in patients who received 0, 5,000 or 10,000 IU of hCG following human menopausal gonadotropin (hMG) treatment. MATERIALS AND METHODS: All patients with polycystic ovarian syndrome were included. They were stimulated with hMG. hCG injection was either withheld or administered according to the degree of response to hMG. None of the patients developed ovarian hyper stimulation syndrome. All granulosa cells from the follicular fluids have been collected. RNA was isolated and analyzed with Affymetrix genechip arrays. RESULTS: Hierarchical clustering based on whole gene expression revealed two distinct groups of patients in this experiment. All untreated patients were clustered into one group whereas hCG-treated patients classified into two subgroups based on the hCG doses. Comparison analysis revealed 15,051 transcripts differentially expressed between untreated and hCG treated patients. Among those, 2010 transcripts were only affected in 10,000 IU hCG group and 121 transcripts were modulated in a dose dependent manner. Several selectively expressed genes in hCG-induced granulosa cells compared to untreated granulosa cells were related to development or cell cycle. Pathway analysis also revealed activation of cell cycle pathway, insulin signaling pathway, WNT signaling pathway and TGF-Beta signaling pathway as a result of hCG treatment. CONCLUSIONS: These observations could help us in understanding the mechanisms of hCG action and finding the pathways possibly involved in healthy follicular maturation. Supported by: King Faisal Specialist Hospital and Research Center.
P-551 COMPARISON OF PREGNANCY OUTCOMES BETWEEN FOLLICLE STIMULATING HORMONE OR CLOMIPHENE CITRATE ADMINISTRATION COMBINED WITH INTRAUTERINE INSEMINATION FOR COUPLES WITH UNEXPLAINED INFERTILITY. J. Luk, D. Kuleta, J. C. Petrozza. Vincent Reproductive Medicine & IVF, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
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P-549 A LUTEAL ESTRADIOL STIMULATION PROTOCOL IMPROVES EMBRYO NUMBER AND QUALITY FOR POOR-RESPONDERS UNDERGOING ART. J. L. Frattarelli, M. J. Hill, G. D. E. McWilliams, K. A. Miller, R. T. Scott. Reproductive Medicine Associates of New Jersey, Morristown, NJ; Tripler Army Medical Center, Honolulu, HI. OBJECTIVE: Poor response to ovarian hyperstimulation is a complication in 5–18% of all IVF cycles. Through a search of the literature, we could find no published manuscript which evaluated a luteal estradiol protocol in poor responders. Two published manuscripts have evaluated the luteal estradiol protocol in normal responders. We therefore undertook a retrospective paired analysis evaluating patients at our center who had been treated with a luteal estradiol protocol and a standard poor-responder protocol. DESIGN: This is a two-phase retrospective cohort analysis: (1) a paired analysis of 60 couples undergoing 120 fresh IVF cycles and (2) a matched cohort analysis of 57 women less than 43 years of age who underwent a luteal estradiol protocol were compared to 228 matched control patients. MATERIALS AND METHODS: Controls were matched (4:1) for date of IVF procedure, patient age, basal antral follicle count, infertility diagnosis, ICSI or conventional insemination, embryos transferred, and stimulation protocol. The main outcome measures were (1) embryo quality for the paired analysis and (2) outcome rates for the matched cohort analysis. RESULTS: In both analyses, the luteal phase estrace protocol was noted to have require more total gonadotropins (P<0.01), more days of stimulation (P<0.01) and have higher peak estradiol levels (P<0.01). The luteal phase estradiol protocol resulted in significantly greater number and percentage of embryos R7 cells on day 3 (3.3 embryos vs. 1.9 embryos) (P<0.05). In the paired analysis, the luteal phase estradiol protocol had significantly more oocytes retrieved, mature oocytes, and embryos that did the standard protocol (P<0.05). In the matched cohort analysis, a trend towards improved delivery rates was seen in the luteal estradiol protocol (28.1% vs. 22.4%)
FERTILITY & STERILITYÒ
(P¼0.36) (RR ¼ 1.25; 95% CI: 0.78–2.03). A power analysis was performed that determined a need for 946 subjects to confirm a statistical difference in the live birth rates between the two protocols. CONCLUSIONS: The luteal estradiol protocol may represent a novel and more successful way to treat poor responders during IVF cycles.These data support an improvement in the quality and number of embryos in IVF poor responders when treated with a luteal phase estradiol protocol. Such a protocol could represent an important method for treating poor responding patients and may ultimately optimize outcome success for these patients. Supported by: None.
P-550 HUMAN CHORIONIC GONADOTROPIN INDUCED TRANSCRIPTIONAL PROFILING OF GRANULOSA CELLS FROM PATIENTS UNDERGOING IN VITRO FERTILIZATION. S. Coskun, M. S. Inan, L. A. Al-Alwan, R. Al-Rejjal, K. A. Awartani, S. Al-Hassan. Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. OBJECTIVE: Transcriptional profiling is an important tool to understand underlying molecular mechanism in various physiological and drug-induced biological processes. Human chorionic gonadotropin (hCG) has been used to induce ovulation and oocyte maturation. Although many genes that influence this process have been identified, we hypothesized that knowing the genes selectively expressed at the granulosa cells following hCG-induced ovulation would help us in understanding of the regulatory role of this hormone hoping to avoid disease process like ovarian hyperstimulation syndrome, and/or increasing the pregnancy rates by improving the quality of oocytes matured in response to hCG. Although the most common dose of hCG in IVF is 10,000 IU, there has been reports showing that 5,000 IU is also as effective. The objective of this study to evaluate the differential expression of whole genome after hCG treatment. DESIGN: Expression profilings of granulosa cells were performed in patients who received 0, 5,000 or 10,000 IU of hCG following human menopausal gonadotropin (hMG) treatment. MATERIALS AND METHODS: All patients with polycystic ovarian syndrome were included. They were stimulated with hMG. hCG injection was either withheld or administered according to the degree of response to hMG. None of the patients developed ovarian hyper stimulation syndrome. All granulosa cells from the follicular fluids have been collected. RNA was isolated and analyzed with Affymetrix genechip arrays. RESULTS: Hierarchical clustering based on whole gene expression revealed two distinct groups of patients in this experiment. All untreated patients were clustered into one group whereas hCG-treated patients classified into two subgroups based on the hCG doses. Comparison analysis revealed 15,051 transcripts differentially expressed between untreated and hCG treated patients. Among those, 2010 transcripts were only affected in 10,000 IU hCG group and 121 transcripts were modulated in a dose dependent manner. Several selectively expressed genes in hCG-induced granulosa cells compared to untreated granulosa cells were related to development or cell cycle. Pathway analysis also revealed activation of cell cycle pathway, insulin signaling pathway, WNT signaling pathway and TGF-Beta signaling pathway as a result of hCG treatment. CONCLUSIONS: These observations could help us in understanding the mechanisms of hCG action and finding the pathways possibly involved in healthy follicular maturation. Supported by: King Faisal Specialist Hospital and Research Center.
P-551 COMPARISON OF PREGNANCY OUTCOMES BETWEEN FOLLICLE STIMULATING HORMONE OR CLOMIPHENE CITRATE ADMINISTRATION COMBINED WITH INTRAUTERINE INSEMINATION FOR COUPLES WITH UNEXPLAINED INFERTILITY. J. Luk, D. Kuleta, J. C. Petrozza. Vincent Reproductive Medicine & IVF, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
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