Retrieval of larger oocyte cohorts maximizes in vitro fertilization (IVF) birth rates per cycle

chromosomal status of embryos and, therefore, oocyte-embryo health. Hence, we decided to investigate whether serum AMH levels are independently related to IVF-ET ouctome, in particular, miscarriage rates. DESIGN: Prospective study. MATERIALS AND METHODS: We studied 2,365 infertile women undergoing 2,688 IVF-ET cycles. All of them had a reference, centralized, serum AMH measurement using AMH Gen II ELISA and started COH within the 12 subsequent months. Each AMH determination was paired to a single cycle. Patients had a normal karyotype, no history of genetic disorders, congenital malformation or recurrent pregnancy loss, and no uterine abnormalities. Cycles were sorted into 3 different age groups: %33 years (n¼1,033), 34-36 years (n¼690) and R37 years (n¼965) and into 3 different AMH groups: Low AMH (0.04-1.60 ng/mL; n¼540), Intermediate AMH (1.61-5.59 ng/mL; n¼1,608), and High AMH (5.60-35.00 ng/mL; n¼540). Binary logistic regression was conducted to verify whether AMH was related to miscarriage rates independently of age and ovarian response to COH. RESULTS: Our data showed that clinical pregnancy and live birth rates increased from the Low to the High AMH groups, independently from age and oocyte yield. It is remarkable that, in the Low AMH group, miscarriage rates were higher than those in the Intermediate or High AMH groups. Differences reached statistical significance in 34-36 years (33%, 15%, and 17.0%, respectively; P<0.02), and R37 years (35%, 26%, and 18%, respectively; P<0.04), but not in %33 years groups. Yet, binary logistic regression run over the whole population confirmed the association between serum AMH and miscarriage rates, independently of patient’s age and oocyte yield. CONCLUSIONS: This extensive investigation showed that, irrespective of age and ovarian response to COH, patients aged >34 years with low AMH levels displayed poorer IVF-ET outcome, in particular, higher miscarriage rates. This supports the hypothesis that AMH is not only a biomarker of oocyte quantity but may be also related to oocyte reproductive potential. Further ageand oocyte yield- controlled studies, possibly including preimplantation genetic screening of embryos, will be contributive to challenge these results. O-86 Monday, October 17, 2016 11:30 AM ARE ALL TWINS FOLLOWING ELECTIVE SINGLE EMBRYO TRANSFER (ESET) MONOZYGOTIC? ANALYSIS OF 32,600 ESET CYCLES REPORTED TO SART. S. Zaghi,a M. G. Vega,b E. Buyuk,c R. Fritz,a S. K. Jindal.d aAlbert Einstein College of Medicine, Bronx, NY; b Department of Obstetrics & Gynecology & Women’s Health, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY; cAlbert Einstein College of Medicine / Montefiore M, Bronx, NY; dObGyn and Women’s Health, Montefiore’s Institute for Reproductive Medicine and Health, Hartsdale, NY. OBJECTIVE: Elective Single Embryo Transfer (eSET) has recently become standard of care for younger patients and has decreased the incidence of twins and multiple births. Despite transferring a single embryo, twin and multiple pregnancies with different gender neonates have been reported. We seek to determine the incidence and risk factors of dizygotic twinning in eSET cycles. DESIGN: Population-based retrospective cohort study of cycles from the SART CORS database. MATERIALS AND METHODS: 32,600 fresh and frozen autologous IVF cycles in women 35 years or younger undergoing eSET between 2010 and 2013 were assessed. Gender difference in live births was used to assess dizygosity. To establish the number of same gender twins, Weinberg’s differential rule was used. Weinberg’s differential rule states that the rate of dizygotic twinning is twice the rate of twins that have discordant gender. The primary outcome measure was the rate of dizygotic twinning in fresh and frozen IVF cycles undergoing eSET. Student t-test, Mann-Whitney U, Fisher’s exact test and ChiSquare were used for statistical analysis, p 0.05 was considered significant. RESULTS: A total of 14,986 births were reported with 14,737 (98.3%) singletons, 244 (1.6%) twins and 5 (0.3%) triplets. Out of 249 multiple births, 239 had fetal genders recorded. Twenty deliveries with discordant gender neonates were recorded (8.3%) in fresh and frozen cycles. When applying Weinberg’s differential rule, the rate of dizygotic twinning increased to 40/239 (16.7%) in eSET. Fresh embryo transfers resulted in 15/183 (8.2%) discordant gender neonates versus 5/56 (8.9%) in frozen embryo transfers, p 0.86. Patients with dizygotic twinning had a higher BMI than patients with monozygotic twinning (27.5  1.5 vs. 24.4  0.4, p 0.02). No significant difference was observed in age, race, smoking, etiology, embryo stage at transfer, ICSI, unstimulated or stimulated cycles or history of tubal disease or surgery. CONCLUSIONS: eSET in young and good prognosis patients is an effective way to decrease the chances of multiple pregnancies. If eSET results in twin or multiple pregnancy, there is a 1 in 6 chance of dizygotic pregnancy.

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ASRM Abstracts

Patient with higher BMI may be at risk for dizygotic twinning. Further research is needed to identify those at greater risk. O-87 Monday, October 17, 2016 11:45 AM MATERNAL AND NEONATAL OUTCOMES IN WOMEN OF ADVANCED MATERNAL AGE (AMA) UNDERGOING TWO IN VITRO FERTILIZATION (IVF) SINGLETON PREGNANCIES, AS COMPARED TO ONE IVF TWIN PREGNANCY. S. Amrane,a P. Ghosh,a D. E. Reichman,b Z. Rosenwaks,b S. E. Gelber.a aObstetrics and Gynecology, New York Presbyterian- Weill Cornell Medicine, New York, NY; bCenter for Reproductive Medicine and Infertility, Weill Cornell Medical College, New York, NY. OBJECTIVE: This study seeks to compare maternal and neonatal outcomes for women of AMA undergoing two IVF pregnancies resulting in singleton gestations versus women with one IVF pregnancy resulting in a twin gestation. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Patients 37 years old and greater at the time of oocyte retrieval, who had either two consecutive singleton gestations from IVF (n ¼ 45) or one twin gestation from IVF (n ¼ 175), were included. Both IVF and delivery at our center were required. Maternal and neonatal outcomes were obtained by chart review. Primary maternal outcomes included antepartum admission, length of hospital stay, preeclampsia, PPROM, and cesarean section. Primary neonatal outcomes included low birth weight (LBW), very low birth weight (VLBW), intrauterine growth restriction (IUGR), neonatal intensive care unit (NICU) admission, length of NICU/neonatal stay, and markers of severe neonatal morbidity including retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), sepsis, and bronchopulmonary dysplasia (BPD). For singleton pregnancies, outcomes were counted as having occurred if present in one or both pregnancies. Continuous outcomes were log-transformed. Bivariate tests were performed using t-tests for continuous variables, and chi-square test or Fisher’s exact test for categorical variables. Outcomes with p-values<0.10 were tested in regression framework to obtain odds ratios. RESULTS: There were significantly increased rates of antepartum admission (OR 5.22, 95% CI 1.54-17.66), PPROM (OR 8.92, 95% CI 1.18-67.39), cesarean section (OR 10.08, 95% CI 4.58-22.47), LBW (OR 24.52, 95% CI 8.35-72.02), and NICU admission (OR 5.12, 95% CI 2.17-12.10) in the twin group as compared to the singleton group. Length of neonatal hospital stay and length of NICU stay were also longer in the twin group (OR 1.14, 95% CI 1.04-1.24), and OR 1.28, 95% CI 1.09-1.49). The twin group demonstrated a tendency towards an increased rate of preeclampsia (OR 3.98, 95% CI 0.9117.40) and IUGR (OR 6.41, 95% CI 0.84-48.49). All cases of VLBW occurred in the twin group (n ¼ 20). The only cases of ROP (n¼6), sepsis (n¼3), BPD (n¼3), and IVH (n¼1) occurred in the twin group. There were three neonatal deaths in the IVF twin group, and none in the singleton group. CONCLUSIONS: In women of AMA, undergoing two subsequent IVF singleton pregnancies is less morbid than undergoing one IVF twin pregnancy. However, severe morbidity and neonatal mortality were relatively rare in the twin group. Patients with the goal of having two children should be counseled about the neonatal and maternal risks associated with twin pregnancies as compared to two consecutive singleton pregnancies, prior to making decisions about how many embryos to transfer.

O-88 Monday, October 17, 2016 12:00 PM RETRIEVAL OF LARGER OOCYTE COHORTS MAXIMIZES IN VITRO FERTILIZATION (IVF) BIRTH RATES PER CYCLE. M. T. Connell,a K. S. Richter,b M. J. Tucker,b J. Graham,b A. DeCherney,a M. J. Hill,a M. Levy.b aNIH, Bethesda, MD; bShady Grove Fertility Reproductive Science Center, Rockville, MD. OBJECTIVE: To determine if retrieval of larger cohorts of oocytes adversely affects IVF treatment outcomes. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: A retrospective cohort study of all autologous IVF cycles among patients under 35 years from 2009-2014 was performed. Excluded from the analysis were patients with a diagnosis of diminished ovarian reserve, uterine factor, chromosomal abnormalities, or cancer, patients being treated for fertility preservation, use of preimplantation genetic screening, oocyte or embryo cryopreservation prior to the blastocyst stage, or incomplete insemination of the retrieved cohort. All embryo

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

Number of Oocytes Retrieved Outcome Number of cycles Percentage of cycles with no viable embryos available for transfer or cryopreservation Live birth per fresh embryo transfer cycle Live born child per freshly transferred embryo Surplus blastocysts vitrified per cycle with fresh transfer Estimated total live born children per retrieval cycle

1-4 338 11.8% P<0.0001 vs 5-9 oocytes

5-9 1631 2.5% P<0.0001 vs 10-19 oocytes

10-19 4374 0.7%

20-29 1673 0.6%

R30 557 0.5%

31.8% P<0.0001 vs 5-9 oocytes 24.6% P<0.0001 vs 5-9 oocytes 0.1 P¼0.001 vs 5-9 oocytes 0.37 P<0.0001 vs 5-9 oocytes

45.7% P<0.0001 vs 10-19 oocytes 36.5% P<0.0001 vs 10-19 oocytes 0.6 P<0.0001 vs 10-19 oocytes 0.76 P<0.0001 vs 10-19 oocytes

51.2%

51.5%

49.7%

43.1%

44.6%

44.8%

cryopreservation was performed using vitrification protocols at the expanded blastocyst stage (minimum ICM and trophectoderm grades of BB) on day 5 or 6 after oocyte retrieval. Potential births from the transfer of all vitrified blastocyst were estimated based on our observed birth rate (35%) per vitrified/warmed blastocyst among autologous patients in this age range. RESULTS: At total of 8,573 cycles were evaluated. Cycles with retrieval of 1-4 oocytes or 5-9 oocytes were much less likely to have viable embryos available for transfer or cryopreservation, had much lower live birth rates per fresh embryo transfer cycle, and had many fewer children per freshly transferred embryo compared to larger retrieved oocyte cohorts. The numbers of surplus blastocysts that were cryopreserved per fresh embryo transfer cycle, and the estimated total number of live born children resulting from the transfer of all fresh and cryopreserved embryos per oocyte retrieval cycle, both increased substantially with each incremental increase in the size of the retrieved oocyte cohort. CONCLUSIONS: Previous data has suggested there may be lower live birth rates with higher number of oocytes retrieved (1). The current data among this good prognosis population of patients show that live birth per fresh transfer is not adversely affected by higher oocyte retrieval numbers. Furthermore, more oocytes lead to higher numbers of vitrified embryos and ultimately higher live births per retrieval event. References: 1. Sunkara SK, Rittenberg V, Raine-Fenning N, Bhattacharya S, Zamora J, Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod 2011;26:1768-74. Supported by: This research was supported, in part, by Intramural research program of the Program in Reproductive and Adult Endocrinology, NICHD, NIH. O-89 Monday, October 17, 2016 12:15 PM IVF IN WOMEN OF 45 YEARS AND OLDER: THE LARGEST SINGLE CENTER COHORT TO DATE. V. Gunnala, M. Irani, Z. Rosenwaks, S. D. Spandorfer. The Ronald O. Perelman and Claudia Cohen CRM, Weill Cornell Medicine, New York, NY.

1.8 P<0.0001 vs 20-29 oocytes 1.26 P<0.0001 vs 20-29 oocytes

3.5 P<0.0001 vs R30 oocytes 1.84 P<0.0001 vs R30 oocytes

5.4 2.58

OBJECTIVE: To determine IVF outcomes in women 45 years and older using autologous oocytes. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: 1,077 fresh IVF cycles in women 45 years and older were reviewed from 1/1995-6/2015. PGD/S, natural IVF, and donor egg cycles were excluded. Patient demographics, IVF cycle characteristics, total pregnancy loss, clinical pregnancy and live birth rates were analyzed for the different age groups (age 45 n ¼773, age 46 n ¼221, age 47 n¼57, age 48 n¼22, age 49 n¼5). Fisher exact t test, Kruskal-Walis, and Chi-square were used to evaluate the data and p < 0.05 was considered significant. RESULTS: Mean age of patients in the study cohort was 45.4  0.72. 11.7% of patients did not start due to an elevated FSH or cyst and 28.5% of patients were canceled prior to oocyte retrieval. There was no difference in demographic characteristics between age groups as well as no difference in mean # of oocytes harvested (7.2  4.8) or number of embryo transferred (3.4  1.9). The overall pregnancy rate per retrieval was 17.2% (117/680), of which 82.1% (96/117) ended in a pregnancy loss. Although there was no difference in IVF outcomes between age groups, an overall clinical pregnancy rate of 8.8% (60/680) and delivery rate of 3.1% (21/680) were found. 20/21 live births were in the 45 year old group and one live birth was found in women age 46. There was no live births in any patient with % 4 oocytes retrieved. CONCLUSIONS: IVF may be a reasonable option for women age 45 with an acceptable ovarian reserve, however with very low prognosis. Patients with % 4 follicles should be counseled appropriately that based on these results positive pregnancy seems highly unlikely. O-90 Monday, October 17, 2016 12:30 PM DOES A WORSENING IN ENDOMETRIAL STRIPE PATTERN CORRELATE WITH INCREASING PROGESTERONE LEVELS IN IVF CYCLES? M. W. Healy,a H. Wolfe,b B. Yauger,b R. Chason,b N. Banks,a C. M. Owen,a A. DeCherney,a J. Csokmay,b M. J. Hill.a aNational Institutes of Health- NICHD, Bethesda, MD; bDepartment of OB/ GYN, Walter Reed National Military Medical Center, Bethesda, MD.

IVF Cycle Characteristics

age

45 (n ¼733)

46 (n¼221)

47 (n¼57)

48 (n¼22)

49 (n¼5)

p value

Parity (Median) # oocytes harvested # mature oocytes # 2PN # embryos transferred % cycle starts with no ET

0 (0-1) 7.1  4.8 5.7  4.1 4.0  3.3 3.4  1.8 32.8%

0 (0-1) 7.4  4.8 5.9  3.9 4.2  3.2 3.5  2.1 32.8%

0 (0-1) 6.3  5.0 4.7  3.6 3.1  3.0 2.9  1.7 45.1%

1 (0-2) 6.1  5.2 5.0  4.0 2.9  2.4 2.9  2.1 63.2%

0 (0-1) 16  2.8 10.5  0.7 6.5  0.7 5.0  0.0 60.0%

0.17 0.08 0.28 0.29 0.29 0.53

age

45 (n¼5/08)

Positive pregnancy/retrieval clinical pregnancy/ retrieval live birth/retrieval Total pregnancy loss (BC + SAB/total pregnancy)

FERTILITY & STERILITYÒ

21.0% 9.8% 3.9% 79.2%

46 (n¼140)

47 (n¼34)

48 (n¼8)

49 (n¼2)

p value

12.1% 6.4% 0.7% 94.1%

8.8% 2.9% 0% 100%

0% 0% 0% N/A

50% 0% 0% 100%

0.07 0.52 0.23 0.44

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