Low estradiol responses in oocyte donors do not influence in vitro fertilization cycle outcomes

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

serum E2, which is reflected in follicular fluid, serum AMH of LE2 donors was non-signficantly higher than TE2 at HCG trigger. Despite suggested alterations in granulosa cell function in LE2, clinical results are excellent. P-310 Tuesday, October 31, 2017 OOCYTE MATURATION IN EGG FREEZE CYCLES IS SIGNIFICANTLY LOWER THAN IN FRESH ICSI CYCLES: CONTRIBUTING FACTORS IN OVER 5000 CASES. D. H. McCulloh,a D. C. Gonullu,b C. McCaffrey,a J. Grifo,c N. Noyes,d F. Licciardi.e aObstetrics and Gynecology, New York University Fertility Center, New York, NY; bTel Aviv University Sackler Faculty of Medicine, Ankara, Turkey; cNew York University Langone Medical Center, New York, NY; dNYU School of Medicine, New York, NY; eOBGYN, New York University Langone Medical Center, New York, NY. OBJECTIVE: One intermediate measure of success for egg freeze cycles is the number of mature eggs cryopreserved. Increasing the proportion of mature eggs per case could improve ultimate success: having a baby. The role of controlled ovarian hyperstimulation (COH) parameters in achieving maturation, while assumed, is not fully understood. We evaluated associations between Immaturity ((MI + GV oocytes)/total oocytes retrieved) and several COH parameters during OOF and ICSI cycles. DESIGN: Data for 2730 OOF and 2784 ICSI cycles were mined from our electronic medical records. Associations between COH parameters and immaturity were examined using stepwise multiple logistic regression (MLR). MATERIALS AND METHODS: MLR was performed with maximum log likelihood (LL) fitting. The Akaike Information Criterion was used to select significant parameters. COH parameters included: patient age (age), gonadotropin dose per day adjusted for age (dose/day), the fraction of gonadotropin provided by hMG (F(hMG)), the change in estradiol between trigger day and the next morning (E2), days of stimulation (days), and baseline FSH on day 2 or 3 of the cycle (FSH). RESULTS: The number of eggs retrieved was significantly greater for OOF (15.4 + 9.6) than for ICSI (12.9 + 7.8). The incidence of immaturity was significantly higher for OOF (26.6% + 19.2%) than for ICSI (21.2 + 18.4%). Age, Dose/day, F(hMG), E2, and days were significantly different for OOF vs ICSI. MLR of age and COH parameters was performed to see if differences in age and COH could account for the differences between OOF and ICSI cycles. Immaturity was related to trigger type (hCG vs leuprolide vs combination) and occurred more with fewer days, more dose/day, and lower F(hMG). After adjustment for these differences, Immaturity remained different between OOF (26.8%) and ICSI (21.0%) CONCLUSIONS: The higher Immaturity for OOF over ICSI cycles is partially explained by associations of immaturity with dose/day, F(hMG), days and the type of trigger. However, additional factors not examined (possibly fertility status and/or aggressiveness of retrievals) but associated with OOF and ICSI may also affect immaturity. Treating patients for more days, with less dose/day, with a higher F(hMG) and triggering with leuprolide may decrease the incidence of immature oocytes retrieved. Regression Equation

OR(Immaturity) ¼ -0.059 X days + 0.00083 X dose/day - 0.21 X F(hMG) + Offset Offsets: hCG trigger ¼ -0.436; Lupron trigger ¼ -0.639; Combo trigger ¼ -0.592

Eq. 1

P-311 Tuesday, October 31, 2017 THE EFFECT OF LEADING FOLLICLE SIZES ON PERCENTAGE OF USABLE GOOD-QUALITY BLASTOCYSTS FOR EMBRYO TRANSFER OR CRYOPRESERVATION. S. Anderson,a,b D. Brasile,a,b a a,b a,b T. Hartlein, B. Gocial, M. J. Glassner, J. J. Orris.a,b aMain Line b Fertility, Bryn Mawr, PA; Ob/gyn, Drexel University College of Medicine, Philadelphia, PA. OBJECTIVE: A goal of controlled ovarian stimulation is to obtain fertilizable oocytes that subsequently develop into competent embryos that result in pregnancies. The objective of this study was to determine if triggering when

FERTILITY & STERILITYÒ

the average size of the two leading follicles is greater than 20 mm affects percentage of usable good-quality blastocysts that develop from the cohort of fertilized oocytes. DESIGN: Retrospective study of 698 IVF cycles from 2016 and 2017 MATERIALS AND METHODS: The average size of the two leading follicles at the time of trigger was calculated for each cycle. The percentage of usable embryos was defined as the percentage of two-pronuclear (2pn) oocytes that developed into good-quality blastocysts that were transferred or cryopreserved. A multiple linear regression model that included age and anti-Mullerian hormone level as covariates was used. Follicle size (> or < 20 mm) was used as a binary variable. Data was weighted by the total number of 2pn oocytes. RESULTS: The multiple linear regression model estimated that the percentage of usable good-quality blastocysts that develop from the cohort of 2pn oocytes was significantly (p¼0.018) lower by 4.6% when the average size of the two leading follicles was greater than 20 mm on the day of trigger. There was no significant difference in age (35.7 vs 35.7 years old), total number of oocytes (13.8 vs 13.1), number of mature oocytes (9.4 vs 8.9), or percentage of mature oocytes (69.4% vs 68.4% ) between patients who were triggered when the two leading follicles averaged < 20 mm verses > 20 mm, respectively. CONCLUSIONS: The size of leading follicles at the time of trigger appears to affect the percentage of good-quality blastocysts that develop from a cohort of 2pn oocytes. Triggering when the leading follicles grow over 20 mm may have a negative impact on the oocyte cohort and resulting percentage of good-quality usable blastocysts. P-312 Tuesday, October 31, 2017 MULTI-CENTER EVALUATION OF THE ACCESS AMH ASSAY TO MEASURE AMH AS AN AID IN THE PREDICTION OF POOR OVARIAN RESPONSE TO CONTROLLED OVARIAN a C. Gracia,b M. J. Glassner,c STIMULATION. V. L. Baker, d e V. L. Schnell, K. Doody, C. Coddington,f L. A. Marshall,g A. J. Morales,h M. Pavone,i M. A. Behera,j E. A. Zbella,k M. M. Alper,l B. S. Shapiro,m J. Straseski,n D. Broyles.o aDivision of REI, Department of Obstetrics and Gyne, Stanford University, Stanford, CA; bUniversity of Pennsylvania, Philadelphia, PA; cMain Line Fertility Center, Bryn Mawr, PA; dCenter of Reproductive Medicine, Webster, TX; eCenter for Assisted Reproduction, Bedford, TX; fMayo Clinic, Rochester, MN; gPacific NW Fertility & IVF Specialists, Seattle, WA; hReproductive Endocrinologist, Fertility Specialists Medical Group, San Diego, CA; iNorthwestern University, Chicago, IL; jBloom Reproductive Institute, Scottsdale, AZ; kReproductive Endocrinology, Florida Fertility Institute, Clearwater, FL; lBoston IVF/ Harvard Medical School, Waltham, MA; mFertility Center of Las Vegas, Las Vegas, NV; nUniversity of Utah/ARUP Laboratories, Salt Lake City, UT; o Beckman Coulter, Inc, Carlsbad, CA. OBJECTIVE: Published literature suggests that Anti-M€ullerian Hormone (AMH) has potential for evaluating ovarian reserve and may be useful for prediction of poor ovarian response (POR) to controlled ovarian stimulation (COS), but cutpoints may vary depending on the AMH assay used. The objectives were to evaluate the automated Beckman Coulter Access 2 AMH assay for predicting POR to COS and to compare AMH with antral follicle count (AFC). DESIGN: Multi-center, prospective, cross-sectional study conducted at 13 US sites. Women (21 to 45 years old) of all racial backgrounds meeting eligibility criteria and undergoing COS were eligible. Inclusion criteria included first cycle of COS for IVF, regular menses, and both ovaries present. Women with PCOS, prior ovarian surgery, exposure to cytotoxic drugs or pelvic radiation therapy, or recent contraceptive use were excluded. Blood was collected and AFC was determined on day 2-4 of the menstrual cycle. The study was IRB approved and subjects provided informed consent. MATERIALS AND METHODS: 160 women were enrolled and underwent COS. Endpoint was oocytes retrieved with POR defined as %4 oocytes retrieved. Serum and plasma specimens were tested for AMH, FSH and estradiol using the Beckman Coulter Access 2 Immunoassay Analyzer. Receiver Operating Characteristics (ROC) analyses were used to determine sensitivity and specificity for AMH for predicting POR. SAS v. 9.4 was used for all analyses. RESULTS: The AMH cutoff at 90% specificity for predicting women with POR established using ROC analysis is 0.844 ng/mL with an associated sensitivity of 73.1%. ROC analysis showed AMH (AUC ¼ 0.927) was significantly better than AFC (AUC ¼ 0.843, p ¼ 0.0075) for predicting POR. CONCLUSIONS: This first report of AMH for predicting POR using the Access 2 Immunoassay is consistent with published data using earlier ELISA-based AMH assays, and supports that AMH may be a useful

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