Prospective randomized study on compliance with corifollitropin alfa treatment in oocyte donors

Prospective randomized study on compliance with corifollitropin alfa treatment in oocyte donors

MATERIALS AND METHODS: All SBTs in fresh, autologous ART cycles for 2010 at a large ART center were evaluated. To control for the quality of the trans...

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MATERIALS AND METHODS: All SBTs in fresh, autologous ART cycles for 2010 at a large ART center were evaluated. To control for the quality of the transferred embryo, only SBT of a SART grade ‘‘good’’ embryo were included in the analysis. Univariate logistic regression evaluated the impact of the number and the quality of the SVB cohort (embryo stage, inner cell mass grade, and trophectoderm grade) on implantation and live birth. Multiple logistic regression analysis included age, body mass index, the number of SVB, and the quality of the actual embryo transferred. RESULTS: 655 SBTs met inclusion criteria. The cohort implantation rate was 65% and the live birth rate was 54%. Univariate logistic regression demonstrated an increase in implantation (OR 1.09, 95%CI 1.03-1.15) and live birth (OR 1.06, 95%CI 1.02-1.09) with increasing number of SVBs. Multiple logistic regression analysis demonstrated patient age and the number of SVB to be significantly associated with implantation and live birth. The embryo stage, inner cell mass, and trophectoderm grades of SVB cohort were not predictive of implantation or live birth in the transferred embryo.

evidence of ascites within the initial 8 days after HCG administration was significantly reduced from 15.44% (21/136) in group2 to 2.21% (3/136) in Quinagolide group (P<0.0001). There was no significant statistical deference between two groups in the number of oocytes, fertilization rate, implantation rate, clinical pregnancy rate, and in frequency of moderate and sever late OHSS. CONCLUSION: The present study indicates that Quinagolide (Norprolac) is effectively reduced the development of OHSS in high risk ICSI patients without affecting the clinical pregnancy rate.

O-348 Wednesday, October 24, 2012 04:00 PM WITHDRAWN

Supernumerary Embryos and ART Clinical Outcomes. Supernumerary Embryos

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Number of Cycles 81 66 101 102 82 223 Implantation 51% 61% 63% 65% 70% 67% Live Birth 41% 45% 54% 58% 60% 56%

Multiple regression P value

<0.04 <0.02

CONCLUSION: The number of supernumerary vitrified blastocyst correlated positively with the odds of implantation and live birth in good quality single blastocyst transfers. Patients with supernumerary embryos are good candidates for single embryo transfer. Supported by: This research was supported, in part, by Intramural research program of the Program in Reproductive and Adult Endocrinology, NICHD, NIH.

OVARIAN STIMULATION: ART

O-347 Wednesday, October 24, 2012 03:45 PM ROLE OF QUINAGOLIDE (NORPROLAC) IN PREVENTING OVARIAN HYPERSTIMULATION SYNDROME (OHSS) IN HIGH RISK INTRACYTOPLASMIC SPERM INJECTION (ICSI) PATIENTS. M. Alhalabi,a,b S. Samawi,a N. Kafri,a J. Sharif,a A. Saker,b A. Othman.b aAssisted Reproduction Unit, Orient Hospital, Damascus, Syrian Arab Republic; bEmbryology & Reproductive Medicine, Faculty of Medicine, Damascus University, Damascus, Syrian Arab Republic. OBJECTIVE: OHSS appears to be induced by the ovarian release vascular endothelial growth factor (VEGF) and its receptor 2 (VEGFR2), causing increase vascular permeability (VP). Dopamine agonist (DA) inhibit VEGF/ VEGFR2 and thereby decrease VP. The aim of this study was to determine the efficacy of non-ergot derived Dopamine agonist Quinagolide (Norprolac: Ferring Pharmaceuticals) in preventing OHSS in high risk women undergoing ICSI, and how would it affect the outcome? DESIGN: Randomized control prospective study was performed in the period from June 2007 to June 2010. MATERIALS AND METHODS: A total of 272 women undergoing ICSI and at high risk of developing OHSS, were recruited for this study: - E2 level on day of HCG R 4000 pg/ml. - R 20 follicles R 10 mm. - Patients were similar as regards age, cause of infertility (male factor), BMI, long protocol, and luteal phase support. On day of HCG the patients were randomly divided into 2 groups: Group 1 (study group: 136 patients): were given Quinagolide (Norprolac) 150 mg daily from the day of HCG administration for 15 days. Group 2 (Control group: 136 patients): were not given Quinagolide. - OHSS symptoms were assessed according to Golan’s classification system 4, 8 and 12 days after HCG administration. Ascites was determined by transvaginal ultrasound. RESULTS: The incidence of OHSS in group 1 was 4.41%, while it was 19.12% in group 2 (P<0.0001). The incidence of patients with Ultrasound

FERTILITY & STERILITYÒ

O-349 Wednesday, October 24, 2012 04:15 PM PROSPECTIVE RANDOMIZED STUDY ON COMPLIANCE WITH CORIFOLLITROPIN ALFA TREATMENT IN OOCYTE DONORS. A. Requena,a D. Collado,a A. Izquierdo,b A. Ballesteros,b M. Mu~noz,c J. A. Garcıa-Velasco.a aIVI Madrid, Madrid, Spain; bIVI Barcelona, Barcelona, Spain; cIVI Alicante, Alicante, Spain. OBJECTIVE: The aim of our study was to evaluate the frequency of cancellations per initiated cycle as well as the level of satisfaction with treatment in donors using corifollitropin alfa during a controlled ovarian stimulation for IVF. DESIGN: Multicenter, randomized controlled trial.

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MATERIALS AND METHODS: We included 120 women participating in our oocyte donation program. Subjects were randomized to receive either a single 150 mg dose of corifollitropin alfa (ElonvaÒ) followed by daily administration of recombinant FSH from day 8 if deemed necessary, or daily injections of follitropin beta (PuregonÒ Pen) at a 200 IU/d starting dose. GnRH antagonist ganirelix (OrgalutranÒ) was introduced at 0.25 mg/day on day 5. Final oocyte maturation was induced by 0.1 mg of GnRH agonist triptorelin. Subjects were asked to fill out a questionnaire about their satisfaction with the stimulation treatment. RESULTS: One hundred and twenty donors were included in the study. There was no significant difference in age or weight between groups. The median duration of stimulation was 10 days in both groups, without any significant difference between them. In the group treated with ElonvaÒ, 26% (14/ 54) of women fulfilled criteria for triggering with GnRH agonist after 8 days of stimulation. The rest (40) of the donors needed another 54080 IU of recombinant FSH to reach the desired follicular development. In the group treated with PuregonÒ, the total gonadotropin dose was 1900280 IU. There were no significant differences in the number of retrieved oocytes (15.17.7 vs. 16.56.3) or percentage of metaphase II. No serious adverse effects were observed in subjects. Donors appreciated very positively the ease of drug administration in both groups. CONCLUSION: Although no significant differences were observed between the two medications, the use of corifollitropin alfa seems to offer some advantages in oocyte donors because of its safety, a trend for a lower cycle cancellation rate, and a high level of satisfaction among users.

tion and Genetics Center, Faculdade de Medicina do ABC, Santo Andre, SP, Brazil. OBJECTIVE: To investigate a possible influence of FSHR Ala307Thr and Asn680Ser variants on the controlled ovarian hyperstimulation outcomes. DESIGN: Cross-sectional study comprising 425 infertile women that undergone in vitro fertilization (IVF) [n¼100 Idiopathic infertility, n¼138 tube peritoneal, and n¼187 male factor]. All patients were younger than 38 years, had normal prolactin and TSH serum levels, presence of both ovaries without morphological abnormalities, ovulatory cycle, body mass index %30, no previous history of poor ovulatory response, and no evidence of endocrine disorders or endometriosis. MATERIALS AND METHODS: Detection of FSHR variants were performed using TaqMan methodology by real time PCR. The number of oocytes retrieved was considered in the controlled ovarian hyperstimulation outcomes. RESULTS: Statistical analysis revealed that women with FSHR Ala307Ala genotype had approximately three times less occurrence of ovarian hyperstimulation syndrome or low ovarian responses when compared to Ala307Thr and Thr307Thr genotypes (P¼0.017). CONCLUSION: FSHR Ala307Ala genotype could be associated with good predictor to controlled ovarian hyperstimulation in Brazilian women studied. Supported by: Grants from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo #2011/08681-1. FMABC/PIBIC for granting student Camila Martins Trevisan a Scientific Initiation scholarship.

O-350 Wednesday, October 24, 2012 04:30 PM DECLINE OF TRANSCRIPTIONAL ACTIVITY IN HUMAN CUMULUS CELLS UNDER IN VITRO COMPARED WITH IN VIVO MATURATION CONDITIONS IN PCOS PATIENTS. S. Hamamah,a,b S. Assou,a D. Haouzi,a L. Hesters,c N. Frydman,c R. Frydman.c aCHU Montpellier, Institute for Research in Biotherapy, Universite Montpellier1, INSERM U1040, Montpellier, Herault, France; bDepartement de Biologie de la Reproduction, UAM: AMP - DPI, Montpellier, Herault, France; cEmbryologie Cytogenetique, Service de Gynecologie Obstetrique, Clamart, Hauts de Seine, France. OBJECTIVE: To compare the transcriptional activity of human cumulus cells (CCs) between CCs isolated from metaphase II (MII) oocytes under in vitro maturation and these isolated from MII oocytes under in vivo conditions in PCOS patients. DESIGN: Patients with PCOS referred to our ART center either for in vitro (IVM) or for in vivo maturation conditions were included. MATERIALS AND METHODS: Total RNA was extracted from each CC sample and was hybridized on Affymetrix Human Genome U133 Plus 2.0 microarrays. Comparison between the two maturation conditions was performed by significance analysis of microarrays with 2-fold cut-off and false discovery rate (FDR <5%). RESULTS: Of the 4271 genes involved in the regulation of transcription explored via microarray, 1297 genes were differentially expressed (FC >2, FDR<0.05) between the CCs of oocytes matured under in vivo compared to those under IVM conditions. Interestingly, the vast majority of these genes are down-regulated in the CCs matured IVM conditions (714 genes). In CCs isolated from MII under IVM conditions, transcription regulating genes known to directly activate the aromatase expression such as RORA (x23, FDR¼0.003) and RORB (x14, FDR¼0.0004) and to co-activate different nuclear receptor like NCOA7 (x6.8, FDR¼0.0001) and NCOA3 (x6.6, FDR¼0.0001) were significantly down-regulated. A set of transcriptional genes involved in particular stress responses were preferentially expressed in CC-isolated under IVM conditions. Among these genes PSIP1 (x5.4, FDR¼0.0001) may play a protective role during stress-induced apoptosis and the TXNIP (x10, FDR¼0.0001) which is a mediator that protects cells against oxidative stress. CONCLUSION: The CCs surrounding oocytes isolated from MII under IVM were less transcriptionally active, compared with CCs isolated from MII oocytes under in vivo conditions. Consequently, there is a delay in the acquisition of CC competence under IVM conditions, opening a new perspective for the improvement of IVM conditions. Supported by: Ferring & Genevrier companies. O-351 Wednesday, October 24, 2012 04:45 PM FOLLICLE-STIMULATING HORMONE RECEPTOR GENE POLYMORPHISM AND OVARIAN RESPONSES TO CONTROLLED OVARIAN HYPERSTIMULATION. C. Peluso, D. M. Christofolini, C. M. Trevisan, E. B. Cordts, C. P. Barbosa, B. Bianco. Human Reproduc-

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ASRM Abstracts

O-352 Wednesday, October 24, 2012 05:00 PM VARIATION WITHIN THE NORMAL RANGE IN FRAGILE X MENTAL RETARDATION 1 (FMR1) GENE CGG REPEAT NUMBER IS NOT PREDICTIVE OF OVARIAN RESPONSIVENESS DURING IVF. M. D. Werner, K. Hong, L. Duffy, E. Forman, B. Devkota, R. Scott. Reproductive Medicine Associates of New Jersey, Morristown, NJ. OBJECTIVE: Expansions of the CGG repeat in FMR1 into the Fragile X premutation range have been associated with increased risk of primary ovarian insufficiency. Recently, some studies have suggested that variation within the normal range (<45) may be prognostic of an accelerated onset of reduced ovarian responsiveness. This study evaluates the relationship between CGG repeats in FMR1 and the number of mature oocytes retrieved during IVF. DESIGN: Retrospective. MATERIALS AND METHODS: All patients with FMR1 screening of CGG repeats were included. Ovarian responsiveness was assessed by the number of mature oocytes retrieved. Initially, the number of CGG repeats in the low copy, high copy, or combined values were examined for any relationship with number of mature oocytes and to determine if any threshold prognosticated response. Next, the CGG repeats for each copy of the FMR1 gene were classified as low, normal, or high using published thresholds and patients grouped accordingly (low-low, low-normal, etc) and compared for mature oocyte yield. Finally, patients were grouped by number of mature oocytes retrieved (low <4, normal 5-20, high >20) and the low, high, and combined counts for CGG repeats compared. Regression, ROC, ANOVA, and c2 were utilized. RESULTS: 689 women were studied in their 1st IVF cycle. No relationship between any CGG repeat level and mature oocytes was detectable. This was true when considering the gene with the lowest repeat number, the higher repeat number, or sum of the two (P¼.18). Similarly, grouping patients using established definitions demonstrated no relationship with mature oocytes retrieved (P¼.77). Finally, all ovarian response groups had equivalent mean CGG repeats in FMR1 (P¼.98). Controlling for age did not impact any finding. CONCLUSION: Variation in CGG repeats in the FMR1 gene are not related to ovarian responsiveness. Like most biologic parameters, variation within the normal range is not clinically significant.

O-353 Wednesday, October 24, 2012 05:15 PM GNRH ANTAGONIST (GNRHANT) DOES NOT HAVE A NEGATIVE EFFECT ON ENDOMETRIAL RECEPTIVITY: A COMPARISON OF OUTCOMES OF HIGH QUALITY EUPLOID BLASTOCYSTS IN FRESH ANTAGONIST VS. AGONIST CYCLES. K. H. Hong,a,b E. Forman,a K. Ferry,a R. Scott.a aReproductive Endocrinology, Reproductive Medicine Associates of New Jersey, Morristown, NJ; bObstetrics,

Vol. 98, No. 3, Supplement, September 2012