Aneuploidy rates are unaffected by choice of trigger medication in human IVF-ET cycles

OVARIAN STIMULATION P-305 Tuesday, October 31, 2017 CHOICE OF TRIGGER MEDICATION DOES NOT AFFECT OOCYTE MATURITY AT RETRIEVAL. C. A. Hernandez-Nieto,a T. G. Nazem,b J. A. Lee,b D. Gounko,b E. Cervantes,b A. B. Copperman,c B. Sandler.d aReproductive Endocrinology and Infertility, RMA of NY, New York, NY; bReproductive Medicine Associates of New York, New York, NY; cObstetrics and Gynecology, RMANY-Mount Sinai, New York, NY; dReproductive Medicine Associates of New York, New York City, NY. OBJECTIVE: Traditionally, final oocyte maturation with Human Chorionic Gonadotropin (hCG) was a used as a standard component of IVF stimulation protocols. Currently, GnRH agonist and dual triggers have become the treatment of choice, as they have nearly eliminated the incidence of Ovarian Hyperstimulation Syndrome (OHSS). This study sought to compare whether choice of trigger medication had an effect on oocyte maturation rates DESIGN: Retrospective cohort analysis MATERIALS AND METHODS: The study included patients undergoing IVF who were stimulated using the GnRH antagonist protocol between January 2002 and February 2017. Only patients classified as normal responders (AMH R1pmol/L, basal antral follicular count R10 and basal FSH %10IU/mL) were included. Cycles were segregated into 4 groups (Group A: GnRh agonist (leuprolide acetate 2mg); Group B: Dual trigger (leuprolide acetate 40IU + 1000IU p-hCH) ; Group C: Recombinant hCG (250 mg R-hCG); and Group D: purified hCG (10,000IU P-hCG)). Data was analyzed by ANOVA with Tukey’s studentized range test, with significance at p <0.05. Multivariate logistic regression analysis was performed to distinguish possible influence of clinical factors on the rate of oocyte maturation. RESULTS: Of the 2,049 IVF cycles included, dual trigger was most commonly used (1172 cycles (57.3%)) followed by R-hCG:498 cycles (24.3%), (P-hCG: 201 cycles (9.8%)), GnRH agonist was administered least (178 cycles (8.6%))(Table 1). Overall, 62.9% of oocytes reached the MII stage of development. When using P-hCG as a control group, significant differences between the MII rates per group were observed. (p <0.0001). When adjusted for age, body mass index and the total number of eggs retrieved; no difference was observed between trigger method and the rate of MII oocyte formation. (Table 1). CONCLUSIONS: The GnRH agonist and dual triggers has proven to be a valuable option when treating patients who are at risk of OHSS and offers a greater margin of safety compared with the hCG trigger protocol. The study demonstrates no significant differences in the number of mature oocytes at retrieval when comparing different trigger strategies. Trigger medication choice can be based on patient-specific clinical characteristics that can reassure a decreased risk of OHSS without compromising oocyte maturity rates. Reference: 1. Youssef MA, Van der Veen F, Al-Inany HG, Mochtar MH, Griesinger G, Nagi Mohesen M, Aboulfoutouh I, van Wely M. Gonadotropinreleasing hormone agonist versus HCG for oocyte triggering in antagonist-assisted reproductive technology. Cochrane Database Syst Rev. 2014 Oct 31;(10):CD008046

ANEUPLOIDY RATES ARE UNAFFECTED BY CHOICE OF TRIGGER MEDICATION IN HUMAN IVF-ET T. G. Nazem,b CYCLES. C. A. Hernandez-Nieto,a J. A. Lee,b M. Luna,b A. B. Copperman,c B. Sandler.d aReproductive Endocrinology and Infertility, RMA of NY, New York, NY; bReproductive Medicine Associates of New York, New York, NY; cObstetrics and Gynecology, RMANY-Mount Sinai, New York, NY; dReproductive Medicine Associates of New York, New York City, NY. OBJECTIVE: Clinicians have a variety of medications available for triggering final oocyte maturation prior to egg retrieval. GnRH agonists with or without low doses of hCG has been increasingly popular due to its advantage of minimizing the risk of ovarian hyperstimulation syndrome (OHSS). A study using GnRH agonist demonstrated an increased incidence of meiotic aberrations in non-fertilized oocytes, although the rate of aneuploidy was not significantly enhanced. This study sought to explore the relationship between varying trigger strategies and ploidy outcomes in assisted reproduction technology treatment cycles. DESIGN: Retrospective cohort analysis MATERIALS AND METHODS: Patients who underwent an IVF cycle(s) with preimplantation genetic screening (PGS) between January 2012 and February 2017 were included. Only GnRH antagonist stimulation protocol cycles and patients categorized as normal responders (AMH R1pmol/L; basal antral follicular count R10; basal FSH %10IU/mL) were included. Oocyte donation cycles were excluded. Cycles were segregated into 4 groups (GroupA: GnRh agonist (leuprolide acetate 2mg); GroupB: Dual trigger (leuprolide acetate 2mg + 1000 IU R-hCG); GroupC: R-hCG (250 mg); and GroupD: P-hCG (10000 IU)) Data was analyzed by ANOVA and Brown Forsythe’s tests, significance set at p <0.05. Multivariate logistic regression was performed to observe variability in clinical factors and ploidy outcomes. RESULTS: A total of 704 cycles were included in the study: Group A: 62 cycles (8.8%) Group B: 463 cycles (65.7%) Group C: 108 cycles (15.34%) and Group D: 71 cycles (10.1%) Overall 53% of screened embryos were found to be euploid: Group A: 58.9% Group B: 53.48% Group C: 44.59% and Group D: 49.2%. Significant differences in age, eggs retrieved, MII oocytes and embryos biopsied between the groups (p <0.0001) were observed, albeit ploidy outcomes were similar. After adjusting for age, BMI, number of MII oocytes and blasts biopsied per cycle, no association between the trigger type and ploidy outcome was observed. (Table1). CONCLUSIONS: The type of trigger medication used during an IVF GnRH antagonist protocol cycles does not appear to influence ploidy Table 1. Odds ratio estimates and profile - likelihood confidence intervals

Odds ratio estimates

Variable Age BMI MII oocyte count Biopsied blastocysts Dual trigger vs P-hCG GnRH agonist vs P-hCG R-hCG vs P-hCG

0.791 0.984 1.02 0.61 0.83 1.04 0.82

95% confidence limits

P value

0.75 - 0.82 0.95 - 1.01 1.02 - 1.05 0.5 - 0.65 0.49 - 1.39 0.52 - 2.08 0.45 - 1.52

<0.0001 NS <0.0001 <0.0001 NS NS NS

P-306 Tuesday, October 31, 2017 Table 1. Cycle demographics, post retrieval metrics and Odds ratio estimates.

Variable

GnRH agonist N¼178

Dual trigger N¼1172

Mean Age 34.9 (4.1) 35.8 (3.8) Mean BMI 23.4 (4.4) 23.6 (4.2) # Eggs retrieved 4254 22485 Mean Eggs retrieved 24.1 (11.3) 19.4 (8.8) # MII oocytes 2548 14302 Mean MII oocytes 14.4 (12) 12.3 (9.2) % Maturity 59.8 63.6 Odds ratio estimates and profile - likelihood 95% Wald confidence intervals Dual trigger vs P-hCG 0.968 GnRH agonist vs P-hCG 1.19 R-hCG vs P-hCG 0.967

FERTILITY & STERILITYÒ

R-hCG N¼498

P-hCG N¼201

P value

37.1 (4.0) 23.1 (3.8) 7210 14.9 (6.7) 4542 9.4 (6.4) 62.9

36.9 (4.1) 25.2 (5.6) 2575 13.2 (6.1) 1613 8.2 (5.8) 62.4

<0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001

0.74 - 1.24 0.82 - 1.74 0.733 - 1.27

NS NS NS

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outcome regardless of patient age, oocyte retrieval count, or embryos available for biopsy. The opportunity to choose triggers allows clinicians to offer patients personalized treatment approach and minimize risks of treatment including OHSS. References: 1. Hodes-Wertz B, McCulloh DH, Berkeley AS, Grifo JA. Changing ovarian stimulation parameters in a subsequent cycle does not increase the number of euploid embryos. Fertil Steril. 2015 Apr;103(4):947-53.2. 2. Nogueira D, Friedler S, Schachter M, Raziel A, Ron-El R, Smitz J.Oocyte maturity and preimplantation development in relation to follicle diameter in gonadotropin-releasing hormone agonist or antagonist treatments. Fertil Steril. 2006 Mar;85(3):578-83. 3. Schachter M, Friedler S, Ron-El R, Zimmerman AL, Strassburger D, Bern O, Raziel A. Can pregnancy rate be improved in gonadotropinreleasing hormone (GnRH) antagonist cycles by administering GnRH agonist before oocyte retrieval? A prospective, randomized study. Fertil Steril. 2008 Oct;90(4):1087-93.

P-307 Tuesday, October 31, 2017 CORIFOLLITROPIN ALFA WAS NOT DETRIMENTAL TO FOLLICULAR OVARIAN RESPONSIVENESS MEASURED BY FOLLICULAR OUTPUT RATE (FORT). R. C. Donato,a C. K. Bessow,a V. K. Genro,b,c R. B. Chapon,a,c T. O. de Souza,a J. S. Cunha-Filho.d,c aUniversidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; bHospital de Cl
ınicas de Porto Alegre, Porto Alegre, Brazil; cInsemine Human Reproduction Center, Porto Alegre, Brazil; dOB/GYN, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. OBJECTIVE: To assess whether an administration of corifollitropin alfa (long acting FSH) modifies the follicular cohort, measured by the Follicular Output Rate (FORT), compared to human menopausal gonadotropin (hMG) in controlled ovarian stimulation (COS) for in vitro fertilization (IVF). DESIGN: It was performed a prospective cohort study. MATERIALS AND METHODS: It was recruited 94 infertile patients submitted to COS for IVF from January, 2015 to January, 2017. Patients were divided into two groups: 47 received corifollitropin alfa and 47 received hMG. The following variables were analyzed in each group: FORT, age, antral follicular count (AFC), number of oocyte retrieved, metaphase II oocytes (MII), embryo quality (Mean Graduated Embryo Score) and fertilization rate. FORT was calculated as the ratio of pre-ovulatory follicle (16-22 mm in diameter) count on day of human chorionic gonadotrophin  100/ small antral follicle (3 -8 mm in diameter) count at baseline. RESULTS: When we compared ovarian stimulation between corifollitropin alfa and hMG, there were no differences in terms of FORT (mean SD) (4231 vs. 4126, P¼0.854), age (332 years in both groups, P¼0.501), AFC (104.4 vs. 124.9, P¼0.207), retrieved oocyte (8.35 vs. 8.24.3, P¼0.417), embryo score (7318 vs. 7423, P¼0.734) and fertilization rate (69% vs. 66%, P¼0.659), for corifollitropin and hMG groups, respectively. Moreover, pregnancy rates were not different between both groups (44.7% and 42.5%, P¼0.825). CONCLUSIONS: Corifollitropin alfa administration during controlled ovarian stimulation for IVF was not detrimental to follicular ovarian responsiveness measured by FORT. This is the first report evaluating ovarian follicular response after corifollitropin alfa measured by FORT; demonstrating that the bolus effect of this drug is a great alternative for COS. References: Supported by: CNPq, HCPA-FIPE, CAPES P-308 Tuesday, October 31, 2017 THE EFFECT OF CLOMIPHENE CITRATE (CC) DOSE AND INITIATION DAY ON ENDOMETRIAL THICKNESS (ET) IN WOMEN UNDERGOING CLOMIPHENE CITRATE/INTRAUTERINE INSEMINATION (CC/IUI) CYCLES. P. Bortoletto,a I. Dimitriadis,a G. Christou,a E. Hariton,a J. J. Locascio,b J. C. Petrozza,a I. Souter.a aMassachusetts General Hospital Fertility Center, Boston, MA; bMassachusetts General Hospital, Boston, MA. OBJECTIVE: To evaluate whether CC dose and initiation day affects ET in patients undergoing CC/IUI cycles. DESIGN: Retrospective cohort study at a large academic fertility center.

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ASRM Abstracts

MATERIALS AND METHODS: Data from 2453 CC/IUI cycles (1051 women) that took place between 12/2003 to 12/2015 were reviewed. Patients underwent CC/IUI ultrasound monitored and hCG-triggered cycles with an individualized 5-day course of CC at doses ranging from 25, 50, 100 or 150 mg starting on either cycle days 2, 3, 4, 5, or 6. A mixed random and fixed effects general linear model was conducted with a backward elimination algorithm (p<0.01 cutoff) where ET was the dependent variable and both CC dose and initiation day were the primary fixed effect predictors. Age, body mass index (BMI) and day-3 FSH were included as covariates. RESULTS: Mean (SD) age, BMI, day-3 FSH, and ET at first cycle were: 33.5 (4.3) years, 24.5 (4.7) Kg/m2, 7.1 (2.8) IU/L, and 7.0 (2.1) mm, respectively. Both BMI and treatment attempt number (1st vs. repeat attempt after prior conception cycle) correlated positively with ET (p<0.0001). Significant interactions between i) CC dose and initiation day (p¼0.003), and ii) CC dose and day-3 FSH (p¼0.01) were noted. Overall, higher CC doses initiated at later cycle days were associated with a thinner ET. Similarly, higher CC doses in patients with higher day-3 FSH levels (FSH: 10 IU/L) were also associated with a thinner ET. Specifically, in all patients with later CC cycle starts (day-4 or day-5), the endometrium became thinner as the CC dose increased, irrespective of the patient’s day-3 FSH level. However, in patients with lower FSH levels (FSH: 5 or 7 IU/L), if CC was started earlier (day-2 or day-3) then the increase in the dose did not negatively affect the ET. CONCLUSIONS: Our results suggest that effects of CC on ET vary depending on dose, initiation day and day-3 FSH levels. When using higher doses of CC (100 or 150 mg), earlier cycle start (day-2 or day-3) might attenuate CC negative’s effect on ET irrespective of day-FSH levels. P-309 Tuesday, October 31, 2017 LOW ESTRADIOL RESPONSES IN OOCYTE DONORS DO NOT INFLUENCE IN VITRO FERTILIZATION CYCLE OUTCOMES. K. L. Palmerola, B. J. Rudick, R. Lobo. Obstetrics & Gynecology, NYP Columbia University, New York, NY. OBJECTIVE: In vitro fertilization (IVF) success correlates with higher estradiol (E2) responses. We have identified a cohort of oocyte donors whose E2 levels defy this observation. We aimed to define the incidence of low E2 (LE2) responses in oocyte donors, and to compare number of oocytes retrieved, fertilization rate, embryo development and IVF outcomes in donors with typical E2 (TE2) versus LE2 responses. We also considered possible mechanisms responsible for LE2. DESIGN: Retrospective Cohort Study MATERIALS AND METHODS: A review of donor oocyte cycles performed at a single center from January 2010 to December 2016 was conducted. Donor demographics, ovarian reserve testing, ovarian stimulation characteristics, and IVF cycle outcomes were collected. Only FSH/antagonist cycles were included. TE2 responses were defined as E2 greater than 200 pg/mL per follicle. LE2 responses were defined as E2 less than 100pg/mL per follicle. Low E2 serum levels were confirmed with a different assay system. Antim€ullerian hormone (AMH) levels were obtained on the day of peak E2 in LE2 and TE2 groups, and a portion of follicular fluid samples were analysed. Characteristics and outcomes of donor groups with TE2 versus LE2 were compared. RESULTS: 366 donor cycles were identified. 184 (50.2%) cycles had LE2, including 74 (20.2%) with values of E2 less than 50 pg/mL per follicle. LE2 donors were younger (25.6 vs. 27.4 years, LE2 vs. TE2, p¼0.0004) with higher percentage Caucasian versus TE2 donors (80.4 vs. 57%, p¼0.0024). LE2 donors received higher total doses of gonadotropins (2097.5 vs. 1764.6 IU, p¼0.0004), longer stimulation (10.8 vs. 9.8 days, p<0.0001), and demonstrated higher gonadotropin to E2 ratios versus TE2 donors (2.30 vs. 0.55, p<0.0001). Nevertheless, LE2 cycles resulted in a greater number of mature oocytes (22.1 vs. 13.6, p<0.0001), fertilizations (17.5 vs. 10.7, p<0.0001), and transferred or cryopreserved blastocysts (8.0 vs. 4.8, p¼0.0002) versus TE2 cycles. The percentage of chromosomally normal embryos after PGS was similar between LE2 and TE2 cycles (68.1 vs. 63.1%, p¼0.86). Pregnancy outcomes were also similar. Sixty-two donors with LE2 underwent multiple cycles and 14 (22.6%) had LE2 with all cycles. Mean serum AMH obtained on the day of peak E2 was non-significantly higher in LE2 patients versus TE2 donors (3.21 vs. 1.72, p¼0.72). Preliminary data of LE2 follicular fluid E2 showed lower E2 from mature follicles (117.6 ng/mL vs. established values of greater than 300 ng/mL). CONCLUSIONS: The prevalence of LE2 responses in donors appears to be high (50.2%), with 20.2% of cycles having extremely low E2 responses. LE2 does not portend poor outcome in oocyte donors. Despite a suboptimal rise in

Vol. 108, No. 3, Supplement, September 2017