Frozen versus fresh embryo transfer in ovulatory women

Comparison of outcomes of e between R-ICSI embryos and C-ICSI embryosmbryo transfers

group

R-ICSI cleavage fresh (N¼700)

C-ICSI cleavage fresh (N¼700)

R-ICSI cleavage frozen (N¼108)

C-ICSI cleavage frozen (N¼108)

R-ICSI blast frozen (N¼216)

C-ICSI blast frozen (N¼216)

IR p-value

3.81% < .001

27.74%

12.69% < .001

31.05%

42.38% >.05

45.13%

OBJECTIVE: To determine the value of transferring blastocyst embryos just from rescue ICSI(R-ICSI)of 1-day-old oocytes in frozen-thawed cycles. DESIGN: A case-control study. MATERIALS AND METHODS: The current study was a retrospective analysis of embryo transfers of just R-ICSI embryos using fresh cleavagestage embryos (R-ICSI cleavage fresh) , frozen-thawed cleavage-stage RICSI embryos (R-ICSI cleavage frozen) , and frozen blastocyst-stage RICSI embryos (R-ICSI blast frozen) between January 2009 and June 2016. To study the effect of R-ICSI transfer, comparison groups were used: fresh cycles of conventional ICSI (C-ICSI cleavage fresh), and frozen-thawed cycles cleavage-stage (C-ICSI cleavage frozen) and blastocyst-stage (C-ICSI blast frozen). Comparison groups were matched for cycle and patient characteristics to the R-ICSI group. The inclusion criteria for comparison groups were [1] matched one-to-one on participant age and number of oocytes retrieved between the R-ICSI groups and comparison groups and [2] transfer of just conventional ICSI (C-ICSI) embryos during the same period as in the R-ICSI group. A better synchronization of embryo development with the endometrium is adjusted in R-ICSI cleavage frozen and R-ICSI blast frozen. RESULTS: For fresh cycles, the Implantation rate (IR) in the R-ICSI cleavage fresh was lower than that in the C-ICSI cleavage fresh . For frozen-thawed cycles, the IR in the R-ICSI cleavage frozen was lower than that in the C-ICSI cleavage frozen , but the IR in R-ICSI blast frozen was comparable to that of C-ICSI blast frozen. CONCLUSIONS: Blastocyst culture facilitates the selection of R-ICSI embryos with developmental potential for transfer and transfer in frozethawed cycles can achieve a better synchronization of the embryo developmental stage and the endometrial secretory pattern. So it is recommended that embryos from R- ICSI cycles are cultured to blastocyst, cryopreserved and subsequently used in frozen-thawed cycles.

P-155 Tuesday, October 31, 2017 ARE PREGNANCY RATES AFFECTED BY DAY OF BLASTOCYST CRYOPRESERVATION IN SINGLE EUPLOID FROZEN EMBRYO TRANSFER CYCLES? J. Thorne, L. A. Kaye, A. Bartolucci, C. A. Benadiva, J. Nulsen, L. Engmann. Dept. of Reproductive Endocrinology & Infertility, University of Connecticut Health Center, Farmington, CT. OBJECTIVE: There is inconclusive evidence whether day of cryopreservation of euploid embryos affects pregnancy rates. We sought to compare pregnancy outcomes between euploid blastocyst embryos cryopreserved on either day 5 or 6. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: 126 cycles performed at a large university-based center during a period of January 2013 through December 2016 were evaluated. Euploid embryos cryopreserved on either day 5 (n¼77) or day 6 (n¼51) and utilized in a single frozen embryo transfer (FET) cycle were included for analysis. Preimplantation genetic screening was performed by either array Comparative Genomic Hybridization or Next-Generation Sequencing. Only high quality blastocyst embryos were biopsied and frozen. The primary outcome was ongoing pregnancy rate (OPR). Secondary outPregnancy Outcomes

IR, n (%) CPR, n (%) OPR, n (%) CLR, n (%) MGR, n (%)

Day 5

Day 6

55/77 (71.4) 53/77 (68.8) 45/77 (58.4) 8/53 (15.1) 1/53 (1.9)

36/51 (70.6) 35/51 (68.6) 32/51 (62.7) 3/35 (8.6) 2/35 (5.7)

ns¼not significant

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ASRM Abstracts

p-value ns ns ns ns ns

comes included implantation rate (IR), clinical pregnancy rate (CPR), clinical loss rate (CLR) and multiple gestation rate (MGR). Student’s t-test and MannWhitney test were used to assess continuous variables depending on how the data was distributed. Chi-square was used to assess categorical variables. Multivariate logistical regression was performed to control for potential confounding variables. A p-value <0.05 was considered statistically significant. RESULTS: No significant differences were noted between the groups for age (35.54.3 vs. 35.54.0), BMI (25.85.8 vs. 25.24.6), AMH level (3.12.3 vs. 3.64.4), previous live birth (37.7% vs. 49.0%), diagnosis of recurrent pregnancy loss (RPL) (23% vs. 14%) and number of prior FET cycles (0.30.7 vs. 0.60.9). There were no differences in pregnancy outcomes between the two groups (Table). Using bivariate analysis there was no difference in OPR between the two groups (OR: 0.84, 95% CI 0.40 - 1.73, p¼0.63). A multivariate regression analysis was performed to control for the potential confounding variables of age, BMI, previous live birth, diagnosis of RPL, or prior FET resulting in an adjusted odds ratio for OPR of 0.78 (95% CI 0.37 1.65, p¼0.51). CONCLUSIONS: Day of cryopreservation does not affect pregnancy outcomes in single euploid blastocyst transfers. Rate of multiples remains low in single embryo transfer cycles. P-156 Tuesday, October 31, 2017 FROZEN VERSUS FRESH EMBRYO TRANSFER IN OVULATORY WOMEN. Z. Chen,a Y. Shi,b D. Wei,b H. Zhang,c Z. Wang,b J. Li,b R. S. Legro.d aShandong University, Jinan, China; bCenter for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; c Yale School of Public Health, New Haven, CT; dPenn State University College of Medicine. OBJECTIVE: Elective frozen embryo transfer in anovulatory women with polycystic ovary syndrome has improved live birth but higher pre-eclampsia rates than a fresh transfer, but the risk/benefit ratio in ovulatory women is uncertain. This study was designed to compare the live birth rate as well as obstetric and neonatal complications between frozen and fresh embryo transfer in women with ovulations. DESIGN: This was a multicenter randomized controlled study participated by 20 study sites in China. Patients with regular menstrual cycle who were undergoing their first cycle of IVF with or without ICSI were enrolled. On day of oocyte retrieval, eligible patients were randomized to undergoing fresh embryo transfer or freeze-all and frozen embryo transfer. MATERIALS AND METHODS: A total of 2157 women were enrolled. Gonadotropin releasing hormone antagonist protocol was used for ovarian stimulation in all patients. Up to two cleavage-stage embryos were transferred in both groups. The primary outcome was a live birth after the first transfer, which was defined as delivery of any neonate R28 week’s gestation with signs of life. The secondary outcomes included moderate and severe ovarian hyperstimulation syndrome rate, clinical pregnancy rate, implantation rate, ongoing pregnancy rate, pregnancy loss rate, incidence of obstetric and perinatal complications. RESULTS: The live birth rate in the frozen vs the fresh group (48.8% vs. 50.2%, relative risk (RR): 0.97, 95% confidence interval (CI): 0.89-1.06, P¼0.50) as well as the rates of implantation, clinical pregnancy, overall pregnancy loss, and ongoing pregnancy were comparable. However, the rate of second-trimester pregnancy loss was lower in the frozen embryo transfer group (1.5% vs. 4.7%, RR: 0.33, 95% CI: 0.16-0.68, P¼0.002). Frozen embryo transfer significantly reduced the risk of ovarian hyperstimulation syndrome compared with fresh embryo transfer (0.7% vs. 2.0%, RR: 0.32, 95% CI: 0.14-0.74, P¼0.005). The risks of obstetric and neonatal complications were comparable between the two groups. There was no significant difference in birth weight between the two groups. CONCLUSIONS: Compared with fresh embryo transfer, frozen embryo transfer offered a similar rate of live birth with reduced risks of ovarian hyperstimulation syndrome and second-trimester pregnancy loss. The benefit-

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

risk ratio of freeze-all versus fresh embryo transfer in ovulatory women varied from anovulatory women. P-157 Tuesday, October 31, 2017 ELEVATED ESTRADIOL IN FROZEN-THAWED EMBRYO TRANSFERS CYCLES AND PERINATAL RISK. A. Sokalska, M. A. Mainigi, J. Vresilovic, S. Senapati. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA. OBJECTIVE: While most pregnancies after assisted reproductive technologies are healthy, IVF has been associated with a greater risk of adverse perinatal outcomes. Recent data suggest that frozen embryo transfer cycles in some subpopulations are associated with increased risk of preeclampsia, however the mechanism is unclear. The aim of this study was to determine factors influencing pregnancy and perinatal outcomes in frozen embryo transfer cycles. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Autologous vitrified-thawed embryo transfer (FET) cycles 2012 -February 2017 resulting in positive pregnancy test were reviewed (n¼619; 562 programmed FET, 57 natural cycle FET). Cycles were analyzed based on estradiol level at the time of initiation of the progesterone supplementation in the programmed cycles or before follicle collapse in the natural cycles. Cycles with an estradiol level above the 95th percentile (E2 R1500 pg/mL) were compared to those with an estradiol level <1500pg/mL. Multivariable logistic and linear regression modeling were used to compare pregnancy and perinatal outcomes adjusted for maternal age, diagnosis, embryo stage at transfer, number of embryos transferred, endometrial thickness, frozen embryo transfer protocol, number of delivered infants, neonatal sex, and year of transfer as appropriate. RESULTS: Baseline characteristics including age, race, ethnicity, diagnosis, embryo stage at transfer, number of embryos transferred were comparable for both estradiol exposure groups. There was no difference in the rate of miscarriages, biochemical pregnancies, ectopic pregnancies and ongoing pregnancies by estradiol level prior to progesterone initiation in unadjusted and adjusted models (p>0.05). Amongst singleton pregnancies, an incidence of pre-eclampsia was significantly higher in the group with estradiol level R1500 pg/mL compared to the group with estradiol level <1500 pg/mL (38% vs. 11%, p¼0.011, AOR 4.7, 95% CI [1.4,15.4]), while the geometric mean birth weight was 452 g lower in those with estradiol level R1500 pg/mL compared to those with estradiol <1500pg/mL (p¼0.01, ARR -452, 95% CI [-794 , -110]). CONCLUSIONS: Present data demonstrates that elevated estradiol level in frozen embryo transfer cycles is associated with the increased risk of preeclampsia and low birth weight in singleton pregnancies. These findings suggest that hormonal milieu of the uterine environment, even in frozen embryo transfer cycles, may affect placentation leading to adverse perinatal outcomes. Supported by: K12HD001265 (SS) P-158 Tuesday, October 31, 2017 OUTCOMES OF NEONATES BORN FOLLOWING TRANSFER OF FROZEN-THAWED CLEAVAGE EMBRYOS WITH BLASTOMERE LOSS: A MULTICENTER PROSPECTIVE STUDY IN CHINA. Y. Wu, C. Li, H. Huang. The International Peace Maternity & Child Health Hospital, Shanghai, China. OBJECTIVE: To evaluate the pregnancy outcomes and the safety of neonates born following frozen-thawed cleavage embryos with blastomere loss.

Frozen Embryo Transfer Age < 35 35-37 38-40 41-42 43-44 > 44

DESIGN: Multicenter prospective study including all frozen-thawed cleavage embryo transfer (FET) cycles was conducted in China. MATERIALS AND METHODS: A total of 9,846 transfer cycles with only intact embryos and 2,259 transfer cycles with only blastomere-lost embryos were included. FET pregnancy outcomes including implantation rate, clinical pregnancy rate, pregnancy loss rate, pregnancy termination due to fetal defects, stillbirth and live birth rate were assessed. The outcomes of neonates born following the transfer of blastomere-lost embryos were compared to those born following the transfer of intact embryos using multilevel logistic regression. RESULTS: A total of 12,105 FET cycles were included in analysis (2,259 cycles in blastomere loss group and 9,846 cycles in intact embryo group). Compared with FET cycles of intact embryo, embryo with blastomere loss transfers showed significantly poorer outcomes with respect to implantation rate, pregnancy rate and live birth rate. However, following embryo implantation, the two groups were similar with respect to live birth rate per clinical pregnancy. Among the 4229 neonates, multiples neonates born from embryos with blastomere loss were at an increased risk of SGA (aOR¼1.50, 95%CI, 1.00-2.25). Similar results were observed among singletons (aOR¼1.84, 95%CI, 0.99-3.37), however, the confidence interval did not exclude the null effect. No association were found between blastomere loss and subsequent occurrence of congenital anomalies or neonatal mortality. However, neonates born from blastomere-lost embryos showed an increased risk of transient tachypnea of the newborn (TTN, aOR¼5.21, 95%CI, 2.42-11.22). CONCLUSIONS: Transfer of embryos with blastomere loss was associated with a reduced rates of conception. Once embryos with blastomere loss are implanted, pregnancies appear to have the same probability of progressing to live birth, but with an increased risk of SGA and TTN. Supported by: Medical Crossover Foundation of Shanghai Jiao Tong University (No. YG2015MS42)

P-159 Tuesday, October 31, 2017 WOMEN OVER 37 HAVE SUPERIOR PREGNANCY RATES WITH FROZEN COMPARED WITH FRESH EMBRYO TRANSFERS - AN ANALYSIS OF 43,5765 CYCLES FROM THE NATIONAL ART SURVEILLANCE SYSTEM (NASS). J. Keenan,a E. Marshall,b E. Heidel.c aObstetrics and Gynecology, Division of Reproductive Endocrinology, University of Tennessee Graduate School of Medicine, Knoxville, TN; bWest Virginia University School of Medicine, Morgantown, WV; cSurgery, University of Tennessee Graduate School of Medicine, Knoxville, TN. OBJECTIVE: Fresh vs. Frozen embryo transfer is a topic of much debate. However, despite much research, no one has to date evaluated whether age plays a role in live birth rates following frozen ET. The objective of this study was to evaluate the US data on LBR following fresh vs frozen ET as it relates to the age of the patient. DESIGN: Observational retrospective cohort study. MATERIALS AND METHODS: The CDC provided data on live birth rates following fresh and frozen ET grouped by age from the 2013 NASS. This data for frozen cycles is not routinely reported by the CDC. IRB approval was not required according to the design of the analysis. Frequency statistics were used to describe categorical variables. For between-subjects comparisons of categorical outcomes at each age grouping, Chi-square analysis was performed to yield unadjusted odds ratios (OR) with 95% confidence intervals (95% CI). Cochran-Mantel-Haenszel tests were done to establish trends in live births across age groupings between frozen ET and fresh ET. Bonferroni correction used to account for experiment-wise error rates when testing multiple hypotheses concurrently. All analyses were conducted using SPSS Version 21 (Armonk, NY: IBM Corp).

Fresh Embryo Transfer

Total ET

Live Births

% Live Birth

Total ET

Live Births

% Live Birth

Odds Ratio (95% CI)

P-value

20423 10374 7713 3005 1329 732

9002 4160 771 910 312 104

44.1 40.1 35.7 30.3 23.5 14.2

33750 15941 13456 6588 3086 750

15992 6269 3822 1066 252 22

47.4 39.3 28.4 16.2 8.2 2.9

0.88 (0.85-0.91) 1.03 (0.98-1.09) 1.40 (1.32-1.49) 2.25 (2.03-2.49) 3.45 (2.88-4.13) 5.48 (3.42-8.79)

< 0.001 ¼ 0.21 < 0.001 <0.001 <0.001 <0.001

Data are LBR after frozen and fresh embryo transfers grouped according to age with associated OR, 95% CI, and p-value

FERTILITY & STERILITYÒ

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