Does undetectable serum anti-mullerian hormone (AMH) level preclude live birth in women undergoing in vitro fertilization?

OBJECTIVE: To model morphologic assessments of embryo quality predictive of live birth. DESIGN: Longitudinal cohort using cycles as reported in the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System between 2007 and 2010. MATERIALS AND METHODS: Live birth rates were modeled by morphological assessments using backward-stepping logistic regression, separately for each day of transfer (2-6) and number of embryos transferred (1 or 2). With two embryos, the better morphologic measure was used for modeling. Additional models were also developed adding number of oocytes retrieved and embryos cryopreserved (results not shown). Model results are presented as odds ratios (<1 signifies poorer outcome) and 95% confidence intervals. RESULTS: Morphologic assessments of grade, stage, fragmentation, and symmetry were significant for the day 2 and 3 models, and grade, stage, and inner cell mass for the day 5 model. The models for days 3 and 5 with two embryos transferred are shown below. Day of Transfer Day 3 Sample size (cycles) 57,743 AOR GRADE Good 1.00 Fair 0.79 Poor 0.53 STAGE 1-3 cells 0.41 4-6 cells 0.36 7-8+ cells 1.00 Morula 1.01 FRAGMENTATION 0% 1.00 1-10% 1.00 11-25% 0.84 >25% 0.73 SYMMETRY Perfect 1.00 Moderate 0.87 Severe 0.62

95% CI GRADE Reference Good 0.74, 0.83 Fair 0.45, 0.62 Poor STAGE 0.31, 0.53 Morula 0.33, 0.39 Early Blastocyst Reference Expanded Blastocyst 0.87, 1.17 Hatched Blastocyst INNER CELL MASS Reference Good 0.95, 1.04 Fair 0.77, 0.92 Poor 0.58, 0.92 TROPHECTODERM Reference Good 0.82, 0.91 Fair 0.49, 0.79 Poor

Day 5 58,796 AOR 95% CI 1.00 0.85 0.62

Reference 0.80, 0.90 0.52, 0.75

0.42 0.62 1.00 1.06

0.36, 0.49 0.59, 0.66 Reference 1.01, 1.12

1.00 0.84 0.67

Reference 0.79, 0.89 0.56, 0.80

1.00 0.96 0.92

Reference 0.91, 1.02 0.84, 1.02

CONCLUSION: These findings confirm the significant association between embryo quality collected using national embryo morphology fields and live birth following ART. Supported by: SART. P-1225 Thursday, October 17, 2013 CONTRACTION OF BLASTOCYST IS STRONGLY RELATED WITH LOWER IMPLANTATION SUCCESS; A TIME-LAPSE STUDY. J. Marcos Alises,a S. Perez,b D. Gumbao,a M. Molla Silva,a M. Meseguer,b J. Landeras Gutierrez.a aIVF Laboratory, Instituto Valenciano de Infertilidad (IVI Murcia), Murcia, Spain; bIVF Laboratory, Instituto Valenciano de Infertilidad (IVI Valencia), Valencia, Spain. OBJECTIVE: Identify the contraction of Blastocysts as a new predictive marker for implantation. DESIGN: The Natural Hatching (NH) is a phenomenon necessary for the implantation of the Human Blastocyst.By Time-lapse system,we have observed in the laboratory a pattern of contraction in the Blastocyst,before this phenomenon.We have defined contraction,as a phenomenon in which the trophoectoderm is detached from the zona pellucida in more than 50% of its surface.According to the literature,this kind of blastocyst contraction influences negatively in the process of Blastocysts NH. MATERIALS AND METHODS: We performed a retrospective study,between 09/09/2009 and 01/07/2012 in IVI clinics in Murcia and Valencia .A total of 716 blastocysts transferred were analysed,from those 139 presented contraction (19.4%),85 of them one,8 presented two and 2 three contractions.We analysed those embryos with known implantation and were divided into two groups;A)Embryos without contraction (408) and,B) Embryos with at least one contraction (94).We have demonstrated statistically that all embryos studied are morphologically comparable in both groups,for D+2,D+3 and D+5 of embryonic development. RESULTS: GroupA:438 blastocysts transferred,who had not any contraction, had an implantation rate of 48.52% (CI95% 46.65-53.39). GroupB:64

FERTILITY & STERILITYÒ

blastocysts transferred who had at least one contraction, had an implantation rate of 35.11% (CI95% 25.27-44.93). The percentage of embryos that presented hatching were comparable in group A and B 28.7% vs 31.4% respectively. CONCLUSION: From these results, we can conclude that, in embryos cultured in vitro,contractions plays some important roles in embryo implantation,affecting negatively the embryo quality and reducing implantation chances.We must study the contraction pattern of the blastocyst,being detrimental for embryo implantation to improve our reproductive success. Supported by: S.Niimura.Time-Lapse Videomigraphic Analyses of Contractions in mouse Blastocysts (J.Reprod.Dev.49:413-423,2003). P-1226 Thursday, October 17, 2013 CLEAVAGE STAGE EMBRYO QUALITY: A GOOD PRGNOSTIC INDICATOR FOR PATIENTS WITH POOR QUALITY BLASTOCYSTS ON THE DAY OF EMBRYO TRANSFER. C. A. Guerrero,a T. Ferguson,b R. Chilvers,a D. Noorhasan,a J. S. Goldstein.a aFertility Specialists of Texas, Frisco, TX; bTexas Health Presbyterian Hospital Dallas, Dallas, TX. OBJECTIVE: The objective of this study was to determine the effect of cleavage stage embryo quality on clinical outcomes for patients with poor blastocyst development on the day of embryo transfer. DESIGN: Review of data retrospectively collected over a period of 5 years. Patients with poor blastocyst development were divided into two treatment (Trt) groups based on the quality of the cleavage stage embryos the blastocysts developed from. Trt 1) Derived from high quality cleavage embryos. Trt 2) Derived from low quality cleavage embryos. Severe male factor patients and donor oocytes were excluded. MATERIALS AND METHODS: Patients %37 years old (n¼101) undergoing IVF with poor blastocyst development on the day of embryo transfer were used in this study. Embryos were cultured in sequential media under 6% CO2, 5% O2 and 89% Nitrogen. Cleavage embryos were classified as of high or low quality based on the number of blastomeres, cell symmetry and percentage of fragmentation. Clinical end points and laboratory parameters were analyzed using Fisher’s exact test and t-test as appropriate. RESULTS: There was a higher implantation and clinical pregnancy rate after transferring poor quality blastocysts when they were derived from high quality as compared to low quality cleavage stage embryos. The biochemical pregnancy rate was higher when transferring poor quality blastocysts produced from low quality day 3 embryos. No difference was noted between treatment groups for number of oocytes retrieved, number of embryos transferred and patient age. Clinical outcomes for patients transferring poor quality blastocysts Trt

n

Biochemical Pregnancy (%)

Implantation Rate (%)

Clinical Pregnancy (%)

1 2

46 55

1 (2)a 8 (15)b

34 (35)a 21 (19)b

27 (59)a 20 (36)b

a,b Different superscripts within columns indicate significant differences (P<0.05).

CONCLUSION: Patients with poor blastocyst quality on the day of embryo transfer have superior clinical outcomes when the blastocysts are derived from high quality as compared to low quality day 3 embryos. P-1227 Thursday, October 17, 2013 DOES UNDETECTABLE SERUM ANTI-MULLERIAN HORMONE (AMH) LEVEL PRECLUDE LIVE BIRTH IN WOMEN UNDERGOK. McKnight,b ING IN VITRO FERTILIZATION? B. Zhou,a L. McKenzie,b T. Hickman.b aObstetrics and Gynecology, The Methodist Hospital, Houston, TX; bReproductive Endocrinology and Infertility, Houston IVF, Houston, TX. OBJECTIVE: To determine if an undetectable (< 0.16 ng/mL) serum AMH level precludes successful live birth among women undergoing in vitro fertilization in a clinical setting. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: The study included women aged 21-45 years undergoing IVF from 1/2010 through 12/2011 at our institution.

S501

Exclusion criteria included no available AMH level and patients utilizing donor oocytes. Patient medical records were analyzed for AMH level, age, oocytes retrieved, number of fertilized oocytes, implantation rate, cycle cancellation, and cycle outcomes. Women were grouped according to AMH level, < 0.16 ng/mL (n ¼ 35) and compared with those > 1.0 ng/ mL (n ¼ 203). Serum AMH samples were drawn prior to initiating IVF treatment, and subsequent completed IVF cycles were analyzed. The primary outcome measured was live birth rate. Secondary outcomes included cycle cancellation rate, number of oocytes retrieved, number of fertilized oocytes, implantation rate, and pregnancy rate. Mann U Whitney and Fisher’s exact tests were used in data analysis, with P<0.05 considered statistically significant. RESULTS:

AMH < 0.16 ng/mL (n ¼ 35)

AMH > 1.0 ng/mL (n ¼ 203)

37.7  2.6 < 0.16 5.7 4.9  2.6 2.9  2.4 2.0  0.8

34.3  3.7 3.0  0.6 0.5 17.0  6.0 9.4  4.4 2.4  0.6

21.7  27.0 48.6

36.0  35.8 66

0.116 0.038

34.3

53.7

0.026

28.6

46.3

0.037

P < 0.001 < 0.001 0.057 < 0.001 < 0.001 0.02

CONCLUSION: Patients with an undetectable AMH were more likely to be older, have fewer oocytes retrieved, have fewer fertilized oocytes, and have lower pregnancy and live birth rates. Interestingly, this group still exhibited a respectable live birth rate (28.6%). Patients with undetectable AMH should be counseled regarding their lower prognosis for pregnancy, but not necessarily be discouraged from autologous IVF treatment. P-1228 Thursday, October 17, 2013 EMBRYO SELECTION MODEL DEFINED USING MORPHOKINETIC DATA FROM HUMAN EMBRYOS TO PREDICT IMPLANS. B. Fishel,a TATION AND LIVE BIRTH. A. J. Campbell,a S. Duffy,b S. Montgomery.b aCARE Fertility, Nottingham, Notts, United Kingdom; bCARE Fertility, Manchester, Greater Manchester, United Kingdom. OBJECTIVE: To develop a selection model by comparing morphokinetic variables between embryos that resulted in a clinical pregnancy (FHB) or live birth (LB) and those that did not. DESIGN: Retrospective data analysis of morphokinetic variables of embryo development according to outcome. MATERIALS AND METHODS: Using EmbryoScopeÔ, time in hours(h) post ICSI to reach 2 (t2), 3, 4, 5 and 8 cells, duration of second (cc2) and third (cc3) cell cycles and incidence of multinucleation at two(MN2) and four cells (MN4), were recorded.For 310 day 3 transferred embryos, known Implantation Data value (KID) was defined as 1, if FHB was seen at 7+/- 1 week or LB reported (+ve), and 0 for no FHB/LB (-ve). KID rate (KID-R) ¼ number of KID +ve embryos/KID +ve + KID -ve x 100%. For LB, KID-R was calculated from transfers >10 months ago. KID-R were compared by morphokinetic variables using Fishers test within and outside the groups to identify exclusion criteria. A split model was estimated using these criteria and regressive partitioning. RESULTS: Significant differences were only seen between embryos where t2>30h and t2<¼30h (p¼0.004) or cc2<2h and cc2>¼2h (p¼0.003). Excluding t2>30h or cc2<2h (now referred to as EX) increased KID-R FHB from 12-16% (n¼243) and KID-R LB from 8-12% (n¼99). The strongest splitting variable was EX; KID-R ¼0% for FHB and LB. For embryos not excluded by EX, t4 was the strongest splitting variable.

S502

All EX (t2>30h or cc2<2h) Not EX and t4>¼39.12h(FHB) or t4>¼38.46h(LB) Not EX and t4<39.12h(FHB) or t4<38.46h(LB)

KID-R FHB(%)

n

KID-R LB(%)

n

12 0 6

310 73 72

8 0 3

143 44 37

20

165

18

32

exclude exclude select

FHB - AICc¼566, AUC¼0.72; LB - AICc¼306, AUC¼0.77.

TABLE 1.

Age AMH Cycle cancellation (%) Oocytes retrieved 2PN Embryos per embryo transfer Implantation rate (%) Pregnancy rate (% per cycle) Clinical pregnancy rate (% per cycle) Live birth rate (% per cycle)

Day 3 Selection model

ASRM Abstracts

Sensitivity of the models with two outcomes; selected/excluded was 0.89 (FHB) and 0.92 (LB); Specificity was 0.52 and 0.63 respectively. CONCLUSION: The prospective use of highly sensitive models based on live birth data promises to enhance clinical outcome. Specificity will be confounded by patient factors and the models may be centre specific.

P-1229 Thursday, October 17, 2013 A NEW OOCYTE SCORING SYSTEM WITH BETTER PREDICTABILITY FOR CLINICAL PREGNANCY THAN DAY 3 EMBRYO QUALITY. E. Lazzaroni,a N. Gleicher,a,b Y. Yu,a V. A. Kushnir,a A. Shohat-Tal,a D. H. Barad.a,b aCenter for Human Reproduction, New York, NY; bFoundation for Reproductive Medicine, New York, NY. OBJECTIVE: To assess a new oocyte grading system in comparison to embryo quality in predicting clinical pregnancy rates with IVF. DESIGN: Prospective cohort study. MATERIALS AND METHODS: This data includes observations from 94 patients undergoing IVF. Egg quality is described by 6 characteristics: morphology, cytoplasm, perivitelline space, zona pellucida, polar body and size, with each scored as -1 (below average), 0 (average) or 1 (above average). Embryo grade, and cell number describe embryo quality on day 3 after retrieval. Pregnancy was indicated by intrauterine gestational sac with evidence of a fetal heartbeat. We used Generalized Estimating Equations (GEE) models adjusted for age to correct for multiple observations from each patient. All analyses are conducted using SAS 9.2. RESULTS: Average age of patients was 37.3  7.03 years; mean oocyte yield was 7.97  5.76; and average total oocyte score was -1.05  2.24. Day-3 embryos were as follows: Cell number 135 (26% > 8-cell)/ 343(66%) ¼ 8-cell/ 41(7.9%) < 8-cell; Grade (low grade to high grade in 5 levels) ¼ 6(1.2%)/7(1.4%)/18(3.6%)/109(22%)/231(45.7%)/136(26.8%). Total oocyte score (adjusted for patient age) was directly related to odds of increased embryo cell numbers (OR 1.12, P¼ 0.025), embryo grade (OR 1.19, P < 0.001) and clinical pregnancy [OR 1.58 (95% CI 1.23 to 2.02, p < 0.001)]. Restricting the analysis to day three embryos of high quality (8-cell/ good grade) total oocyte score was still predictive of clinical pregnancy [OR 2.078 (95% CI 1.26 to 3.44, P < 0.001)]. CONCLUSION: The here newly described oocyte scoring system is highly predictive of day-3 embryo score and of clinical pregnancy, and is a better predictor of clinical pregnancy than the day-3 embryo score. Supported by: Foundation for Reproductive Medicine, Center for Human Reproduction. P-1230 Thursday, October 17, 2013 WHAT IS THE OPTIMAL NUMBER OF OOCYTES NEEDED TO OPTIMIZE PREGNANCY WITH OOCYTE DONATION CYCLES? S. H. Purcell,a B. Tilley,a M. Meintjes,b M. R. Thomas,a a aa K. L. Lee, S. J. Chantilis. Dallas-Fort Worth Fertility Associates, Dallas, TX; bDallas Fertility Center, Dallas, TX. OBJECTIVE: Presently, the majority of egg donation is conducted with fresh oocytes. In October 2012 the ASRM removed the experimental designation for oocyte cryopreservation, and there are efforts underway to create or expand egg banks for recipients. Typically, egg banks sell 6-9 oocytes for use by the recipient, which is usually less than the number of eggs available for a fresh recipient cycle. We reviewed recipient outcomes in an effort to

Vol. 100, No. 3, Supplement, September 2013