Risks of adverse perinatal and infant outcomes by plurality and maternal fertility status

Risks of adverse perinatal and infant outcomes by plurality and maternal fertility status

Risks of Adverse Outcomes Compared to Fertile Women (AORs 95% CIs) Singletons Gestational Diabetes Pregnancy-Induced Hypertension Prenatal Uterine B...

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Risks of Adverse Outcomes Compared to Fertile Women (AORs 95% CIs)

Singletons

Gestational Diabetes Pregnancy-Induced Hypertension Prenatal Uterine Bleeding Placental Complications Prenatal Hospitalizations Primary Cesarean Delivery

Subfertile

ART

Subfertile

ART

1.33 (1.23, 1.45) 1.14 (1.05, 1.24) 1.66 (1.32, 2.07) 1.47 (1.28, 1.68) 1.30 (1.16, 1.46) 1.14 (1.08, 1.20)

1.22 (1.13, 1.32) 1.45 (1.36, 1.55) 4.10 (3.57, 4.70) 2.81 (2.55, 3.08) 1.88 (1.72, 2.06) 2.09 (2.00, 2.18)

1.44 (1.10, 1.87) 1.36 (1.12, 1.64) 1.89 (1.04, 3.43) 2.21 (1.54, 3.17) 1.36 (1.10, 1.68) 1.34 (1.14, 1.57)

1.25 (1.06, 1.48) 1.26 (1.12, 1.41) 2.58 (1.78, 3.72) 1.79 (1.40, 2.30) 1.31 (1.15, 1.49) 1.69 (1.54, 1.86)

P-167 Tuesday, October 18, 2016 TIME-LAPSE EMBRYO MORPHOKINETICS FOLLOWING GNRH AGONIST OR HCG TRIGGERING. G. Oron, O. Sapir, R. Garor, Y. Shufaro, H. Pinkas, B. Fisch, A. Ben-Haroush. IVF and infertility Unit, Beilinson Hospital, Rabin Medical Center, Petach Tikva, Israel. OBJECTIVE: GnRH agonist triggering is used instead of hCG in antagonist cycles, in order to diminish ovarian hyperstimulation in high risk patients. GnRH agonist triggering acts by eliciting an endogenous surge of LH and FSH, this effect on early embryonic development is still unknown. Our aim was to compare embryo morphokinetic parameters following GnRH agonist with hCG ovulation triggering, using the EmbryoScope time lapse monitoring system (TMS). DESIGN: A retrospective cohort study. MATERIALS AND METHODS: All TMS data of fresh ICSI cycles with antagonist protocol between 4/2013 - 1/2016 was analyzed. Embryo morphokinetic parameters1 and pregnancy rates were compared between the two groups. Timing of PB-extrusion, PN-fading, and cell cleavage from division to 2 cells (T2) up to the 5-cell stage (T5), second cell cycle duration (CC2¼ T3-T2) and synchrony in division from 2-cell to 4-cell blastomere embryos (S2¼T3-T2) were compared. Optimal CC2 was defined as R5 hours and optimal S2 was defined as < 1 hour. A separate analysis for the embryo culture medium: CSC (Irvine, USA), Global (Vitrolife, USA) and Sage (CooperSurgical, USA) was performed. RESULTS: 1954 embryos derived from cycles triggered with hCG (Group 1) and 606 embryos derived from cycles triggered with GnRHa (Group 2) were analyzed (274 and 60 patients, respectively). Oocyte maturation rates and fertilization rates were similar in both groups [84%and 72% in Group 1; 83% and 76% in Group 2]. Polar body (PB) extrusion occurred earlier in Group 1 than in Group 2 (3.8h  2.2 vs 4.2h  3.6, p¼0.015) and remained significant also in embryos cultured in CSC medium [Group 1 (n¼1358) 3.9 23 vs Group 2 (n¼379) 4.6  4.1, p< 0.001]. Embryos cultured in Global medium had a shorter PN fading in Group 1 (n¼352) than Group 2 (n¼204) (24.8  4.1 vs 26.0  3.6; p<0.0001). At the 2-cell stage, the percentage of embryos with no multinucleation and the proportion of symmetric- blastomere embryos was significantly higher in Group 1than in Group 2 [49.9% and 36.2% (p<0.001) and 87.1% and 82.9%; (p¼0.033); respectively]. There percentage of embryos that reached an optimal CC2 duration in Groups 1 and 2 was similar [79.1% (1543/1951) and 76.1% (461/606), p¼0.1]. The percentage of embryos with an optimal S2 was higher in Group 1 than in Group 2 [50.5% (985/1950) vs 43.2% (262/6060), p¼0.002]. Pregnancy rates in cycles with fresh embryo transfers were similar in Groups 1 and 2 (40.2% and 35.6%; p¼0.5). CONCLUSIONS: Morphokinetic parameters of embryos derived following hCG or GnRHa ovulation triggering were overall similar. It is yet to be determined whether the longer duration of several of the developmental kinetic parameters in embryos following GnRh agonist triggering is of any clinical significance. Reference: 1. Meseguer M, Herrero J, Tejera A, Hilligsøe KM, Ramsing NB, Remohı J.The use of morphokinetics as a predictor of embryo implantation. Hum Reprod 2011;26:2658-71. P-168 Tuesday, October 18, 2016 POSSIBLE PATIENTS CONCERNS REGARDING THE BLASTOCYST EUPLOIDY RATES OF DONOR OOCYTES. R. E. Anderson,a J. B. Whitney,b K. Waggoner,b M. C. Schiewe.b aSCCRM, Ovation Fertility, Newport Beach, CA; bART Lab, Ovation Fertility, Newport Beach, CA.

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ASRM Abstracts

Twins

OBJECTIVE: Is there a benefit to aneuploidy screening embryos derived from donor oocytes? What predictive value does knowing embryo ploidy statistics offer donor cycle recipients? DESIGN: A retrospective observational cohort analysis of 59 donor oocyte cycles, producing 564 PGS tested blastocysts (BL), was evaluated between 10/2013 to 01/2016. Aneuploidy rate and BL production were assessed and used to correlate predictive outcomes. MATERIALS AND METHODS: Patient embryos were cultured in Life Global media + LGPS, and biopsied at the BL stage. All biopsy samples were analyzed using NGS or aCGH. These cycles resulted in 667 BL and 79 transfers. In an effort to generate predictive values, cycles were analyzed to determine if the: (1) best quality embryo was euploid; (2) euploid embryo was on day 5; or (3) cycle produced R2 top quality day 5 euploid embryos. RESULTS: Euploidy at the BL stage was 67.7% with a mean of 6.5 euploid BL produced per cycle. 11 cycles failed to produce a euploidy rate above 50% and 6 cycles failed to attain a day 5 euploid BL (10%). With subjective morphology dictating standard transfer selection, we observed 17 cycles having their best quality embryo be aneuploid. At transfer, we achieved a 74.7% implantation rate, with a 4.7% spontaneous miscarriage rate. Using a theoretical model where morphology dictated transfer, the implantation rate would have been 50.8%, lower (p<0.01) than with PGS (74.7%). In contrast, 71.1% of cycles produced their two best quality embryos as euploid. In these cycles, using standard dual embryo transfers, we would have expected a twinning rate of at least 55%. Contrasting our 2010 data, we performed 23 dual, untested ET donor eggs cycles resulting in a 91% live birth rate and 67% twins. Applying morphology alone for single embryo transfer (SET), 29% of the cycles would have had an aneuploid transfer. CONCLUSIONS: Patient age is the leading factor contributing to aneuploidy. The international demand for routine SET for all cycles has placed increased pressure on improved embryo selection for transfer. While in the USA, SET of donor oocyte cycles is still not widely accepted, as dual embryo transfers offer increased success. Without knowing the ploidy status, many SET cycles would fail to result in a pregnancy, while >50% of the dual embryo transfers would produce twins. Embryo ploidy status is not the only factor contributing to implantation. When choosing to transfer on good prognosis cycles, unknown factors may negatively impact SET success. Thus, a conservative approach allowing multiple attempts for pregnancy is best. When embryo aneuploidy is unknown, risks for twins or failed implantation remain high. Although it is true that the aneuploidy rate of donated oocytes is relatively low, many cycles still produced sub-optimal euploidy and BL yields. Overall, single euploid ET is the best approach to optimize patient success and minimize multiple implantation risks. P-169 Tuesday, October 18, 2016 RISKS OF ADVERSE PERINATAL AND INFANT OUTCOMES BY PLURALITY AND MATERNAL FERTILITY STATUS. B. Luke,a D. Gopal,b H. Diop,c J. E. Stern.d aObstetrics, Gynecology, and Reproductive Biology, Michigan State University, East Lansing, MI; bCommunity Health Sciences, Boston University School of Public Health, Boston, MA; c Mass Department of Public Health, Mass Department of Public Health, Boston, MA; dObstetrics and Gynecology, Dartmouth-Hitchcock, Lebanon, NH. OBJECTIVE: To evaluate the effect of maternal fertility status on the risk of perinatal and infant outcomes by plurality. DESIGN: Longitudinal cohort study, linking cycles from the SART CORS, hospital discharge, and vital records from 2004-2010 in Massachusetts. MATERIALS AND METHODS: The study included three fertility groups: women without ART or other infertility treatment (fertile); women

Vol. 106, No. 3, Supplement, September 2016

Risks of Adverse Outcomes Compared to Fertile Women (AORs 95% CIs)

Singletons

Low Birthweight (<2,500g) Small-for-Gestation Birthweight Premature (<37 weeks) Infant Death*

Twins

Subfertile

ART

Subfertile

ART

1.35 (1.23, 1.49) 0.94 (0.86, 1.08) 1.37 (1.26, 1.49) 1.58 (1.03, 2.43)

1.90 (1.76, 2.05) 1.19 (1.11, 1.28) 1.90 (1.78, 2.04) 1.77 (1.20, 2.60)

1.16 (1.03, 1.30) 1.01 (0.88, 1.17) 1.23 (1.10, 1.37) 1.81 (1.18, 2.77)

1.14 (1.07, 1.22) 0.93 (0.85, 1.01) 1.20 (1.12, 1.28) 0.95 (0.69, 1.31)

*Limited to births 7/04-12/09 with indicators of subfertility but no ART treatment (subfertile), and women with ART treatment. The risks of perinatal and infant outcomes were modeled by plurality using logistic regression, adjusted for parental ages, race/ethnicity, education, payor status, and maternal pre-existing conditions (diabetes and chronic hypertension), and infant gender(s). Adjusted odds ratios (AORs) and 95% confidence intervals are reported. Fertile women were the reference group. RESULTS: The study population included 451,975 pregnancies: 447,510 fertile, 8,778 subfertile, and 13,687 ART; and 459,623 singleton and 10,352 twin pregnancies. The risks of adverse perinatal and infant outcomes by fertility status and plurality are shown below. The risks were significantly increased for singleton and twin infants born to both subfertile and ARTtreated women for low birthweight and prematurity, for singletons born to ART women for small-for-gestational age and infant death, and for singletons and twins born to subfertile women for infant death. CONCLUSIONS: The risks for adverse perinatal and infant outcomes are significantly increased for both subfertile and ART-treated women, even after stratifying by plurality and adjusting for confounding factors. Supported by: NIH grant R01 HD067270. P-170 Tuesday, October 18, 2016 FMR1 CGG REPEAT LENGTH AND OVARIAN FUNCTION IN A DONOR POPULATION. N. Banks,a G. Patounakis,a C. M. Owen,a M. W. Healy,a B. W. Whitcomb,b M. E. Hartman,c K. Devine,c K. S. Richter,c A. DeCherney,a E. Levens,c M. J. Hill.a aNICHD, Bethesda, MD; bUniversity of Massachusetts Amherst, Amherst, MA; cShady Grove Fertility Reproductive Science Center, Rockville, MD. OBJECTIVE: Previous studies have suggested that low FMR1 CGG repeat length (<26) may be a predictor of decreased functional ovarian reserve, but this has not been confirmed. Our objective is to study FMR1 CGG repeat length in a fertile donor population. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: From 2011-2015, a total of 326 egg donors had available FMR1 testing and underwent 514 stimulation cycles. The primary outcome was mature oocyte (MII) yield. Analysis was performed separately using patient maximum and minimum repeat length alleles. Generalized estimating equations (GEE) modeled the association of repeat length with MII yield while adjusting for female age and multiple cycles. A separate analysis with GEE modeling was performed grouping patients by FMR1 allele combinations using the definitions low repeats <26, normal 26-34 and high 34-55 and allele combinations designated by low-low, lownormal, et cetera. RESULTS: FMR1 CGG repeat length ranged from 19-44. Repeat length was not associated with MII yield for either the maximum or minimum allele. FMR1 groups included 31 low-low cycles, 115 low-normal, 11 low-high, 308 Repeat length by allele combinations

Allele Difference in number of Combination MIIs retrieved (unadjusted) Low-low Low-normal Low-high Normalnormal Normal-high

Difference in number of MIIs retrieved*

-0.05 (-2.13-2.03), p¼0.96 2.71 (-1.25-6.67), p¼0.18 -1.3 (-6.25-3.65), p¼0.6 Reference

0.22 (-2.07-2.52), p¼0.84 0.09 (-5.24-5.42), p¼0.97 -0.97 (-6.32-4.38), p¼0.72 Reference

-0.9 (-3.73-1.93), p¼0.53

-0.78 (-4.1-2.53), p¼0.64

*Adjusted for age and antral follicle count

FERTILITY & STERILITYÒ

normal-normal, 54 normal-high and 0 high-high. Comparison between the groups showed no difference in MII yield (table 1). Low-high repeat group was associated with 882 additional IUs total gonadotropin use (p¼0.038) and 116 additional IUs gonadotropin use per MII retrieved (p¼0.04) compared to reference. CONCLUSIONS: As more couples have access to FMR1 CGG repeat length through pre-conception genetic screening, data to guide patient counseling are increasingly important. We do not find a significant correlation between FMR1 repeat length and MII yield in a fertile donor population. Our data are reassuring that ovarian response is comparable in young fertile women with low repeat length alleles, but more studies are needed to follow these women as they age. Supported by: Work supported in part by the NICHD intramural research program. P-171 Tuesday, October 18, 2016 LACK OF PROGESTERONE RISE POST-TRIGGER CORRELATES WITH SUB-OPTIMAL CLINICAL OUTCOMES DESPITE NORMAL L. Sekhon,a,b FERTILIZATION RATE. J. Rodriguez-Purata,a J. A. Lee,a M. Luna,a T. Mukherjee,a,b A. B. Copperman,a,b B. Sandler.a,b aReproductive Medicine Associates of New York, New York, NY; bObstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, NY. OBJECTIVE: A rise in LH and P4 after an r-hCG trigger, which mimics an endogenous LH flare, indicates oocyte maturation initiation. P4 level posttrigger has been characterized as an independent predictor of number of total and mature oocytes retrieved. This study sought to analyze clinical outcomes in patients with differing levels luteinization. DESIGN: Retrospective. MATERIALS AND METHODS: Patients underwent an IVF cycle with a hCG trigger between 2002-2015. Patients post-trigger b-hCG<40 mIU/mL were excluded. P4 (ng/mL) rise post-trigger was considered absent (<1), low (1.0-1.5), intermediate (1.6-2.3) or normal rise (>2.3). Cohorts were segregated by fertilization rate (<25%, 25-50%, 51-75%, >75%) and P4 level was compared. Pearson correlations were used to analyze correlation between age, BMI, FSH, AMH and total GND dosage with post-trigger P4 levels. A binary logistic regression analysis was used to model the influence of P4 level on pregnancy rate (PR), clinical PR, loss rate and live birth rate (LBR). RESULTS: A total of 16087 cycles were studied. Patient’s demographic, stimulation, laboratory parameters and clinical outcomes are shown in Table 1. Normal (n¼10797; P4: 4.42.0), intermediate rise (n¼3535; P4: 2.00.3), low rise (n¼1321; P4: 1.30.1) and absent luteinization (n¼434; P4: 0.80.2) cycles were identified. Age (r¼ -0.17), BMI (r¼ -0.09), day 3 FSH (r¼ -0.19) and total GND dose (r¼ -0.23) had a negative correlation and AMH (r¼0.18) had a positive correlation with the level of P4. Fertilization rate was observed similar between <2.3 or >2.3 ng/mL: 51.7% vs. 53.6% vs. 54.2% vs. 55.8%, respectively (p<0.05). P4 level was similar when compared according to fertilization rate (<25, 25-50, 51-75 and >75): 2.9 vs. 3.4 vs. 3.6 vs. 3.2 ng/mL, respectively. Raw data analysis showed PR (34.4% vs. 41.6% vs. 49.6% vs. 56.5%, respectively; p<0.05), clinical PR (26.4% vs. 32.5% vs. 39.7% vs. 46.5%, respectively; p<0.05), loss rate (16.2% vs. 17.2% vs. 18.1% vs.18.2%, respectively; NS) and LBR (17.4% vs. 23.8% vs. 30.9% vs. 38.0%, respectively; p<0.05) increased with increasing P4 level. After adjusting for age, FSH, AMH, BMI and total GND dose in a logistic regression model, elevated P4 was still associated with increased odds of pregnancy (OR 1.074 (95% CI 1.056 - 1.092), p<0.05), clinical pregnancy (OR 1.068 (95% CI 1.051 - 1.086), p<0.05); and live birth (OR 1.074 (95% CI 1.057 - 1.093), p<0.05), with no influence on loss rate (OR 1.009 (95% CI 0.988 - 1.030), NS).

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