Frozen Embryo Transfer Group Research Articles

Anthropometric measurements of term singletons at 6 years of age born from fresh and frozen embryo transfer: A multicenter prospective study in Japan.

The purpose of this study is to compare anthropometric measurements between term singletons conceived via fresh embryo transfer (FreET) and frozen embryo transfer (FET) and those born via natural conception (NC) or fertility treatments milder than assisted reproductive technology (non-ART) at 6 years of age. A total of 8149 children were enrolled, and questionnaires about anthropometric measures (weight, height, BMI) were addressed to parents, when the children were 1.5, 3, and 6 years of age. A total of 3299 term singletons were enrolled at birth: 533, 476, 916, and 1374 in the NC, non-ART, FreET, and FET groups, respectively. A total of 1635 term singletons (290, 176, 467, and 702 in the NC, non-ART, FreET, and FET groups respectively) were enrolled until 6 years of age (follow-up rate, approximately 50%). When non-ART group was used as control, the FreET children were 1.0cm taller than the non-ART children at 6 years of age, after adjusting for confounding factors. However, no differences were observed in the anthropometric data among the non-ART, ART, and NC children at 6 years of age. At 6 years of age, term singletons were taller in the FreET group than in the non-ART group, after adjusting for confounders.

High birth weight and greater gestational age at birth in singletons born after frozen compared to fresh embryo transfer

ObjectiveWhile many studies agree that the fetal birth weight is higher after frozen embryo transfer (FET), few studies have explored the difference in fetal weight change during such pregnancies. This cohort study was to identify the difference in fetal birth weight and gestational age at birth between singletons born following fresh ET and those born following FET. Materials and methodsThis was a hospital-based cohort study using clinical data from the Kaohsiung Chang Gung Memorial Hospital Obstetric and Neonatal Database from January 1, 2007, to December 1, 2018. A sample of 784 eligible women who had singleton pregnancies and live-born deliveries after 428 fresh ET or 356 FET between January 2007 and December 2018. ResultsCompared with those in the fresh ET group, singletons in the FET group had higher birth weight (3137 g [2880–3441 g] vs. 3060 g [2710–3340 g], p < 0.05), were born later (39.0 weeks of gestation [38.0–40.0 weeks] vs. 38.0 weeks of gestation [37.0–39.0 weeks], p < 0.05), and had a lower incidence of preterm birth (10.4% vs. 15.2%, p < 0.05). The difference in birth weight was not associated with maternal body weight (BW) or body mass index, increase in maternal BW in the third trimester, but related to the total increase in maternal BW during pregnancy. ConclusionsThe birthweight of singletons born following FET and fresh ET became significant in the late third trimester. The main reason is that singletons conceived from FET were at a lower relative risk of preterm delivery and had a higher gestational age at birth.

Chromosomal analysis of 262 miscarried conceptuses: a retrospective study

BackgroundEmbryonic chromosomal abnormality is one of the significant causative factors of pregnancy loss. Our goal was to investigate the differences of chromosomal abnormality between different conception modes in miscarried products of conception (POCs).MethodsA retrospective study included 262 miscarried POCs from 167 women undergoing assisted reproductive treatment (ART) and 95 spontaneous pregnant (SP) women during March 2019 to March 2022 in Renmin Hospital of Wuhan University. Subgroups were divided according to age, fertilization method, types and stages of embryo transfer. The profiles of cytogenetic abnormalities in the miscarried POCs were measured via next-generation sequencing.ResultsThe rate of chromosomal abnormality in the fresh embryo transfer group and the cleavage embryo transfer group was significantly higher than that in the frozen embryo transfer group (79.2% vs. 36%, P = 0.0001) and the blastocyst transfer group (66.7% vs. 32.1%, P = 0.0001) respectively. There was no significant difference in the rate of chromosomal abnormalities when compared by maternal age (49.2% vs. 62%, P = 0.066), types of conception (49.7% vs. 57.9%, P = 0.202), fertilization method (49.6% vs. 48.7%, P = 0.927) and frequency of abortion (56% vs. 47.6%, P = 0.183). However, the women aged ≥ 35 years had more frequent numerical abnormality (P = 0.002); patients using assisted reproductive technology had more rate of chromosomal structural abnormalities (26.5% vs. 7.3%, P = 0.005); the ICSI fertilization group has more frequency of deletion/microdeletion than the IVF fertilization group (80% vs. 31.3%, P = 0.019).ConclusionBlastocyst transfer might help to reduce the incidence of miscarriage. In addition, “freezing all” should be considered if encountered hyper ovarian stimulation, to avoid the negative effect of high estrogen environment on embryo development. The higher incidence of structural abnormalities in miscarried POCs from assisted reproductive patients reminds us to pay attention to the safety of the technology for offspring.

Pregnancy Outcomes after Frozen Embryo Transfer and Fresh Embryo Transfer in Women of Advanced Maternal Age: Single-Center Experience.

Delayed childbearing leads to increased assisted reproductive technology use by women of advanced maternal age (AMA). It is unclear whether fresh or frozen embryo transfer (FET) is the better option. We aimed to assess maternal and neonatal outcomes in patients having their first FET after a freeze-all cycle versus those having their first fresh embryo transfer (ET). We reviewed 720 women of AMA undergoing a first fresh ET (n = 375) or FET (n = 345) between January 2016 and April 2021. No significant difference in the live birth rate was found between FET and fresh ET (19.7% vs. 24.3%, p = 0.141). The clinical pregnancy rate was significantly lower in the FET group than in the fresh ET group (26.4 % (91/345) vs. 33.6% (126/375), p = 0.035), but FET resulted in higher birthweights (3217.16 ± 734.44 vs. 3003.37 ± 635.00, p = 0.037) and was associated with a lower incidence of preterm births (2.6% vs. 5.6%, p = 0.046). The risks of other maternal and neonatal outcomes did not differ significantly between the groups. Among women of AMA, the transfer of frozen embryos did not result in significantly higher rates of live birth than fresh embryos did; however, a freeze-all strategy may not be beneficial for the women of AMA.

Fetal neurosonography and infant neurobehavior following conception by assisted reproductive technology with fresh or frozen embryo transfer.

We aimed to explore fetal cortical brain development by neurosonography in fetuses conceived by assisted reproductive technology (ART), including frozen and fresh embryo transfer (ET), compared with those conceived spontaneously (SC), and to investigate its association with infant neurobehavior at 12 months of age. This was a prospective cohort study of 210 singleton pregnancies, including 70 SC pregnancies, 70 conceived by in-vitro fertilization (IVF) following frozen ET and 70 conceived by IVF after fresh ET. Fetal neurosonography was performed at 32 ± 2 gestational weeks to assess cortical development. Sulci depths were measured offline and normalized by biparietal diameter (BPD). Ages and Stages Questionnaires (ASQ) were completed postnatally, at 12 ± 1 months of corrected age. Neurosonographic findings were adjusted by regression analysis for maternal age, ethnicity, parity, fetal sex and fetal-weight centile and gestational age at scan, and ASQ scores were adjusted for maternal age, ethnicity, parity, educational level and employment status, gestational age at birth, breastfeeding, infant sex and infant age at the ASQ evaluation. Overall, in comparison to the SC fetuses, fetuses conceived by ART showed statistically significant differences in cortical development, with reduced parieto-occipital sulci depth adjusted for BPD (mean ± SD: fresh ET, 12.5 ± 2.5 vs frozen ET, 13.4 ± 2.6 vs SC, 13.4 ± 2.6, P < 0.001), cingulate sulci depth adjusted for BPD (median (interquartile range (IQR)): fresh ET, 5.8 (4.2-7.4) vs frozen ET, 5.8 (4.1-7.5) vs SC, 6.5 (4.8-7.8), P = 0.001) and calcarine sulci depth adjusted for BPD (median (IQR): fresh ET, 13.5 (10.1-16.1) vs frozen ET, 14.5 (12.1-15.8) vs SC, 16.4 (14.3-17.9), P < 0.001), together with lower Sylvian fissure grading score. Changes in cortical development were more pronounced in the fresh ET than in the frozen ET group. ART infants showed lower ASQ scores as compared to SC infants, particularly in the fresh ET group (mean ± SD global ASQ Z-score: fresh ET, -0.3 ± 0.4 vs frozen ET, -0.2 ± 0.4 vs SC, 0 ± 0.4, P < 0.001). Fetuses conceived by ART show a distinctive pattern of cortical development and suboptimal infant neurodevelopment, with more pronounced changes in those conceived following fresh ET. These findings support the existence of in-utero brain reorganization associated with ART and warrant follow-up studies to assess its long-term persistence. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Comparison of Clinical Pregnancy Outcomes after Fresh and Frozen Embryo Transfer.

Objectives To analyze the clinical outcomes of the patients who underwent fresh or frozen embryo transfer, as well as the neonatal outcomes. Methods We conducted a retrospective analysis of women who underwent in vitro fertilization with fresh and frozen embryo transfer from January 2019 to January 2021. All of the included embryo transfers resulted in live births at ≥28 weeks of gestation. All of the patients were divided into two groups according to the assisted reproductive technique that was used (fresh embryo transfer group (n = 101) and frozen embryo transfer group (n = 125)). Both groups were divided into subgroups based on a maternal age of ≥35 years. Result(s). Between the two groups, only the cesarean section rate was higher in the frozen transfer group, while no differences were shown for other outcomes. There were significant differences in the gestational hypertension and postpartum hemorrhage rates based on the subgroup comparison. No significant differences were detected in the offspring. Conclusions Comparing fresh and frozen embryo transfers did not reveal any significant superiority. Venerable age exerts an apparent influence on pregnancy complications. Frozen embryo transfer is not always the best choice.

Health of singletons born after frozen embryo transfer until early adulthood: a Finnish register study.

Is the health of singletons born after frozen embryo transfer (FET) comparable to that of singletons born after fresh embryo transfer (ET) until early adulthood? The health of singletons born after FET does not differ from that of singletons born after fresh ET. The differences in perinatal outcomes of children born after FET and fresh ET are well known. FET is associated with an increased risk of large-for-gestational-age but diminished risks of preterm birth (PTB), small-for-gestational-age and decreased perinatal mortality compared to fresh ET. However, knowledge on the long-term health after FET is scarce. This retrospective register-based cohort study compares singletons born after FET (n = 1825) between the years 1995 and 2006 to those born after fresh ET (n = 2933) and natural conception (NC, n = 31 136) with a mean follow-up time of 18-20 years. Singletons born after FET were compared to those born after fresh ET and NC regarding the frequencies of diagnoses in the main ICD-10 chapters (International Statistical Classification of Diseases and Related Health Problems, 10th revision), the number of outpatient visits and hospital admissions, and mortality. Adjustments were made for PTB, maternal age, parity, socioeconomic status based on mother's occupation and offspring sex. The study combines data from the Finnish Medical Birth Register, the Finnish Care Register for Health Care (CRHC) and the Cause-of-Death Register at Statistics Finland. The Student's T-test was used for continuous variables, and the Chi-square test was used for categorical variables. Cox regression was used to estimate crude and adjusted hazard ratios (HRs and aHRs, respectively). A general linear model was used to compare the means of outpatient visits, hospital admissions and lengths of hospital stays per person. No significant differences between the FET and fresh ET groups were found in the frequency of diagnoses in any of the ICD-10 chapters or in the parameters describing the need for hospital care. However, compared to the NC group, higher proportions in the FET group had outpatient visits in the hospital (93.5% vs 92.2%, aHR 1.23, 95% CI 1.17, 1.30) or hospital admissions (48% vs 46.5%, aHR 1.28, 95% CI 1.19, 1.37). Compared to the NC group, the FET group had elevated adjusted risks of diagnoses of infectious and parasitic diseases (aHR 1.24; 95% CI 1.11, 1.38), neoplasms (aHR 1.68; 95% CI 1.48, 1.91), diseases of the eye and adnexa, the ear or mastoid process (aHR 1.11; 95% CI 1.01, 1.21), the respiratory system (aHR 1.15; 95% CI 1.06, 1.23), the digestive system (aHR 1.17; 95% CI 1.05, 1.32), the skin or subcutaneous tissue (aHR 1.28; 95% CI 1.14, 1.43) and the genitourinary system (aHR 1.27; 95% CI 1.11, 1.45), as well as congenital malformations or chromosomal abnormalities (aHR 1.31; 95% CI 1.14, 1.50) and symptoms, signs or abnormal clinical or laboratory findings (aHR 1.25, 95% CI 1.16, 1.34). Only hospital-based inpatient and outpatient care is covered by the CRHC register, excluding milder cases diagnosed elsewhere. We were not able to study the effect of ART treatments and subfertility separately in our setting. In addition, although our cohort is reasonably sized, even larger cohorts would be needed to reliably study rare outcomes, such as cancer. For many ICD-10 chapters, we present the first published data on the long-term outcome of singletons born after FET. The results on FET versus fresh ET are reassuring, whereas the results on FET versus NC warrant further investigation. Finnish government research funding was obtained for this study. Funding was also obtained from the Finnish Medical Society Duodecim, the Päivikki and Sakari Sohlberg Foundation, Orion Research Foundation, Finnish Society of Obstetrics and Gynaecology (research grants to A.M.T.) and Finnish government research funding. The funding sources were not involved in the planning or execution of the study. The authors have no competing interests to declare. N/A.

"Double Frozen Transfer" Could Influence the Perinatal and Children's Growth: A Nested Case-Control Study of 6705 Live Birth Cycles.

ObjectiveThis study aims to evaluate neonatal and children growth outcomes of cryotransfer of embryos developed from frozen gametes [double frozen transfer (DFT)].MethodsThis nested case-control study included 6,705 women who had a singleton live birth after embryo transfer at the Center for Reproductive Medicine, Shandong University, from 2008 to 2020. Of these, 745 women underwent frozen embryo transfer (FET) using embryos developed from frozen gametes (DFT). Propensity score methodology was used to balance the two groups by maternal age and body mass index (BMI) before evaluating outcomes. After age and BMI were matched using the propensity score methodology in a ratio of 1:4, the control groups enrolled 2,980 women who underwent fresh embryo transfer (ET) and 2,980 women underwent FET from fresh gametes. The children born were followed to at least 5 years of age, and some were followed up to 10 years. Neonatal outcomes and childhood growth measurements were compared among the three groups.ResultsThe average birth weight of the DFT group (3,462 g) was significantly higher than the FET group (3,458 g) and ET group (3,412 g). The rate of large for gestational age (LGA) babies in the DFT and FET group was higher than that for the ET group (30.9% vs. 24.8%; 29.4% vs. 24.8%, respectively). After adjusting for different confounder combinations in the three models, the birth weight and risk of LGA in the DFT and FET groups were still higher than in the ET group, and the values group of P for trend in the models were significant. In multiple linear regression analysis of the children’s development, the height Z-score of children born from the DFT and FET group was higher than that for children from the ET group (β = 0.21, 95% CI 0.07–0.35; b = 0.17, 95% CI 0.05–0.28, respectively). However, childhood growth measurements including body weight Z-score and BMI Z-score were not significantly different among the three groups. In addition, the proportion of male children born from DET was higher than that from ET.ConclusionsThere is an increased risk of LGA babies associated with pregnancies conceived from DFT. Children are inclined to be taller in the future in this group than after FET. The related etiology and pathophysiology mechanisms still need to be revealed. In the future, well-designed, observational studies with in-depth collection of patients’ characteristics may shed more light on this issue.

Early Spontaneous Abortion in Fresh- and Frozen-Embryo Transfers: An Analysis of Over 35,000 Transfer Cycles.

BackgroundThe aim of this study was to explore the risk factors for early spontaneous abortion (ESA) in fresh- and frozen-embryo transfers.MethodsThis retrospective cohort study comprised a total of 35,076 patients, including 15,557 women in the fresh-embryo transfer group and 19,519 women in the frozen-embryo transfer group from January 2016 to December 2020. The primary outcome of this study was ESA, which we defined as the termination of embryonic development before 12 weeks of pregnancy (i.e., an early abortion after artificial multi-fetal pregnancy reduction was excluded).ResultsIn the 35,076 ART transfer cycles, the incidence of ESA was 5.77% (2023/35,076), and the incidence rates for ESA in fresh and frozen cycles were 4.93% (767 of 15,557) and 6.43% (1,256 of 19,519), respectively. Using a multivariate logistic regression analysis model, maternal age, body mass index (BMI), and number of embryos transferred were independent predictors for ESA. In addition, frozen-thawed transfer was a risk factor for ESA as compared with fresh transfer (OR = 1.207; 95% CI, 1.094–1.331; P = 0.000), blastocyst transfer was risk factor for ESA as compared with cleavage transfer (OR =1.373; 95% CI, 1.186–1.591; P = 0.000 in the total group; OR = 1.291; 95% CI, 1.111–1.499; P = 0.001 in the frozen-transfer group), and unexplained infertility was a protective factor for ESA only in the frozen group (OR = 0.746; 95% CI, 0.565–0.984; P = 0.038).ConclusionsMaternal age, BMI, number of embryos transferred, and frozen-thawed transfer were independent risk factors for ESA in assisted reproductive technology treatment cycles.

Perinatal outcome of babies born after using a simplified IVF culture system versus ICSI with sibling oocytes: a prospective cohort study

Research questionIs there a difference in perinatal outcome in the same patient cohort for babies conceived following randomization of sibling oocytes allocated to a simplified IVF culture system (SCS) or intracytoplasmic sperm injection (ICSI) followed by conventional culturing? DesignThe study compared the perinatal outcomes of 367 babies born from 1 January 2013 until 31 December 2020 after using split SCS and ICSI insemination of sibling oocytes in a selected group of normo-responsive women, excluding cases of severe male infertility. Primary outcome measures were preterm birth (PTB; <37 weeks’ gestation), low birthweight (LBW; <2.5 kg) and small for gestational age (SGA) as a primary outcome parameter while secondary outcome measures included mean birthweight, mean gestational age, extreme prematurity (<32 weeks), very low birthweight (<1.5 kg), perinatal mortality, multiple pregnancy and Caesarean section rate. ResultsA total of 105 and 103 singleton babies were born after fresh embryo transfer (FRET) and 71 and 50 singletons after frozen embryo transfer (FET) in the SCS and ICSI groups, respectively. For babies born after FRET, the LBW rate was 2.9% (3/105) for SCS and 7.8% (8/103) for ICSI (P = 0.10). LBW occurred in 4.2% (3/71) and 0% (0/50) of babies born after the transfer of cryopreserved-thawed SCS and ICSI embryos, respectively (P = 0.14). The rate of PTB was 3.8% and 6.8% for SCS and ICSI in FRET cycles (P = 0.33), and 8.5% and 6.0% for SCS and ICSI in FET cycles (P = 0.62). One congenital malformation was found in the SCS FET group. ConclusionThere was no difference in perinatal outcome for singleton and twin babies born after SCS and ICSI.

Differences in Ectopic Pregnancy Rates between Fresh and Frozen Embryo Transfer after In Vitro Fertilization: A Large Retrospective Study.

Ectopic pregnancy (EP) is increasingly found in women treated with in vitro fertilization and embryo transfer (IVF–ET). With the development of the freeze-all policy in reproductive medicine, it is controversial whether frozen embryo transfer (FET) could reduce the rate of EP. In this single-center, large-sample retrospective study, we analyzed 16,048 human chorionic gonadotrophin (hCG)-positive patients who underwent fresh embryo transfer (ET) or FET cycles between January 2013 and March 2022. Throughout the study, the total EP rate was 2.09% (336/16,048), 2.16% (82/3803) in the ET group, and 2.07% (254/12,245) in the FET group. After adjustment for age, infertility causes, and other confounding factors, logistic regression results showed no statistical difference in EP rates between FET and ET groups (odds ratio (OR) 0.93 (0.71–1.22), p > 0.05). However, among the 3808 patients who underwent fresh ET cycles, the OR for EP was significantly lower in the long agonist protocol group than in the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol group (OR 0.45 (0.22–0.93), p < 0.05). Through a large retrospective study, we demonstrated a slightly lower EP rate in FET cycles than in fresh ET cycles, but there was no significant difference. The long agonist protocol in ET cycles had a significantly lower risk of EP than the GnRH-ant protocol.

Alteration of LncRNA expression in mice placentae after frozen embryo transfer is associated with increased fetal weight

The birthweight after frozen embryo transfer (FET) was significantly higher compared with fresh embryo transfer (fresh ET), while the mechanism remains unclear. In this study, we transferred vitrified-warmed or fresh mice blastocysts into pseudopregnant recipients (n=11 each group) produced by natural mating to avoid the influence of superovulation. The fetal weight, placental weight, placental efficiency and placental architecture were studied at E18.5. Placental RNA-Seq analysis was used to identify candidate different lncRNAs and mRNAs between the FET group and the fresh ET group. We found that the fetal weight was increased in the FET group, with increased placental efficiency and the proportion of placental function related labyrinth zone area. 554 lncRNAs and 1012 mRNAs were differentially expressed. KEGG and GO enrichment analyses showed these differentially expressed lncRNAs and their targeted mRNAs might be related to placental morphogenesis. Furthermore, the most differentially expressed 15 lncRNAs and 15 mRNAs were validated by qRT-PCR, we found the LncRNA embryonic stem cells expressed 1 (Lncenc1) was significantly decreased, and Gjb5, which played an important role in labyrinth zone development, was increased. Gjb5 protein increase was further confirmed by Western blot. Lncenc1 and Gjb5 had 48 predicted co-targeted miRNAs, while the correlation analysis of Lncenc1 and Gjb5 mRNA showed a significant inverse correlation. The results showed that FET treatment might enhance the placental function to increase mouse fetal weight via the network diagram of Lncenc1-miRNA-Gjb5.

Adverse obstetric and perinatal outcomes in 2333 singleton pregnancies conceived after different endometrial preparation protocols: a retrospective study in China

BackgroupFrozen-thawed embryo transfer is rising worldwide. One adverse effect of programmed frozen embryo transfer (FET) reported in some studies is an increased risk of adverse obstetric and perinatal outcomes. Meanwhile, body mass index (BMI) also has adverse effect on obstetric and perinatal outcomes. In this study, we investigated that the influence of different endometrial preparation protocols on obstetric and perinatal outcomes and the role of BMI in it.MethodThis retrospective cohort study included 2333 singleton deliveries after frozen-thaw embryo transfer at our centre between 2014 and 2021, including 550 cycles with programmed FET, 1783 cycles with true natural cycle FET (tNC-FET). In further analysis according to BMI grouped by Asian criterion, group A (18.5 kg/m2 ≤ BMI < 24.00 kg/m2) included 1257 subjects, group B (24 kg/m2 ≤ BMI < 28.00 kg/m2) included 503 subjects and group C (BMI ≥ 28 kg/m2) included 573 subjects. Baseline characteristics of the two groups were compared and analyzed. Binary logistic regression analyses were performed to explore the association between obstetric and perinatal outcomes and endometrial preparation protocols.ResultsThere were no significant differences in the placenta previa, gestational diabetes mellitus(GDM), preterm premature rupture of membranes (PPROM), cesarean section (CS) and macrosomia between the tNC-FET and programmed FET groups (P > 0.05). The programmed FET cycles were associated to a higher risk of pregnancy-induced hypertension (PIH) compared with the tNC-FET cycles (7.3% vs 4.4%, crude OR 1.71[1.16–2.54]; adjusted OR 1.845[1.03–3.30]). After dividing the patients into three groups according to the BMI, The programmed FET cycles were associated to a higher risk of PIH in group C (14.4% vs 6.2%, crude OR 2.55 [1.42–4.55]; adjusted OR 4.71 [1.77–12.55]) compared with the tNC-FET cycles. But there was no statistically significant difference in group A and group B. Programmed FET group compared with the tNC-FET group, the risk of PIH increase as the body mass index increase.ConclusionThis study showed a tendency toward increasing risk of PIH in programmed FET cycle compared with the tNC-FET cycle, and the risk of PIH increases as BMI increases. Increased risk of preterm birth and low birth weight is linked to increased risk of PIH.

Comparison of the Effectiveness of Endometrial Receptivity Analysis (ERA) to Guide Personalized Embryo Transfer with Conventional Frozen Embryo Transfer in 281 Chinese Women with Recurrent Implantation Failure.

BackgroundThis study aimed to compare the effectiveness of endometrial receptivity analysis (ERA)-guided personalized embryo transfer (pET) with conventional frozen embryo transfer (FET) in 281 Chinese women with recurrent implantation failure (RIF).Material/MethodsA total of 281 eligible patients with RIF were recruited and assigned to ERA (ERA followed by pET) and FET groups. The clinical pregnancy outcomes were compared between the 2 groups.ResultsThere were no significant differences between the ERA and FET groups in terms of endometrial thickness on the day of embryo transfer, mean attempts of assisted reproductive technology (ART) treatment, anti-Mullerian hormone, follicle-stimulating hormone, or antral follicle count in the fresh cycle (P>0.05). The ERA test identified 35% of samples as receptive and 65% as nonreceptive, and comparable pregnancy outcomes were observed between receptive and nonreceptive patients (P>0.05). Higher pregnancy and implantation rates were found in the ERA group than in the FET group (P<0.01), while no significant differences were detected between the 2 groups in terms of miscarriage rates (P>0.05).ConclusionsIn this study of Chinese women with RIF undergoing in vitro fertilization and embryo transfer, ERA-guided pET resulted in a significant improvement in pregnancy and implantation rates when compared with FET.

Do frozen embryo transfers modify the epigenetic control of imprinted genes and transposable elements in newborns compared with fresh embryo transfers and natural conceptions?

To determine whether the epigenetic control of imprinted genes (IGs) and transposable elements (TEs) differs at birth between fresh or frozen embryo transfers and natural conceptions. Prospective study. University hospital. A total of 202 singleton births were divided into three groups: 84 natural pregnancies (controls), 66 invitro fertilization/intracytoplasmic sperm injection with fresh embryo transfers, and 52 vitro fertilization/intracytoplasmic sperm injection with frozen embryo transfers. None. Pyrosequencing was used to assess the DNA methylation profiles of three IGs (H19/IGF2:IG-DMR [two sequences], KCNQ1OT1:TSS-DMR, and SNURF:TSS-DMR) and two TEs (LINE-1 and HERV-FRD) in cord blood and placenta. The quantitative reverse transcriptase polymerase chain reaction was used to study the transcription of three IGs (H19, KCNQ1, and SNRPN) and two TEs (LINE-1 and ORF2). After adjustment, the placental DNA methylation levels of H19/IGF2 were lower in the fresh embryo transfer group than in the control (H19/IGF2-seq1) and frozen embryo transfer (H19/IGF2-seq2) groups. The DNA methylation rate for LINE-1 was lower in placentas from the fresh embryo transfer group than in placentas from the control and frozen embryo transfer groups and for HERV-FRD compared with controls. In cord blood, DNA methylation levels were not significantly associated with the mode of conception. The relative expression of LINE-1 and ORF2 was decreased in both cord blood and placental tissues from fresh embryo transfer conceptions compared with natural conceptions and frozen embryo transfer conceptions. Compared with natural conceptions and frozen embryo transfers, fresh embryo transfers were associated with methylation and/or transcription changes in some TEs and IGs, mostly in placental samples, which could indicate altered placental epigenetic regulation resulting from ovarian stimulation protocols.

Age-specific effect of fresh versus frozen embryo transfer on fetal anomalies or intrauterine growth restriction rate

ObjectiveTo compare the prevalence of congenital fetal anomalies or intrauterine fetal growth restriction (IUGR) diagnosed prenatally between two in-vitro fertilization (IVF) methods—fresh embryo transfer (ET) and frozen embryo transfer (FET). Materials and methodsWe retrospectively reviewed medical records of patients that had conceived via IVF, and had a fetal anatomical scan performed at Taiji Clinic between 2015 and 2019. The prevalence of fetal anomalies or IUGR between both IVF methods were compared. Prevalence of congenital anomalies or IUGR by maternal age and embryo transfer type were compared by means of Chi-square analysis. Using multivariate logistic regression, we investigated factors that might be associated with higher rates of fetal anomalies or IUGR, such as parity and number of embryos transferred. ResultsA total of 2441 cases were selected (ET: n = 627 and FET: n = 1814). There was non-significant difference in the prevalence of fetal anomalies or IUGR between ET and FET groups (6.4% vs. 5.5%, p = 0.39). However, among women younger than 34 years of age, prevalence of fetal anomalies or IUGR was significantly higher in ET group (4.6% vs. 9.9%, p = 0.03). ConclusionsOur findings suggest an age-specific effect of IVF method on the rate of fetal anomalies or IUGR and may provide useful information for physicians and infertile couples to optimize their IVF treatment plans and improve birth outcomes.

P–395 Obstetric and perinatal outcomes of pregnancies resulting from fresh versus frozen embryo transfer – a sibling cohort

Abstract Study question We aimed to compare obstetric and perinatal outcomes between pregnancies conceived by in vitro fertilization (IVF) with fresh embryo transfer and frozen embryo transfer (FET) in the same women. Summary answer IVF pregnancies following fresh and FET entailed the same obstetric and perinatal outcomes, when compared in the same women. What is known already: There seems to be a difference in adverse outcomes between pregnancies following fresh and FET, as fresh transfer has repeatedly been associated with a higher risk of preterm birth and small for gestational age neonates, and the FET with preeclampsia and large for gestational age neonates. The overall lower incidence of adverse obstetric outcomes in FET may relate to the transfer of an embryo to a uterine environment in the setting of more physiological estradiol level but may also relate to patient characteristics which allow for freezing and subsequent transfer. Study design, size, duration This was a retrospective cohort of 214 deliveries during a 13-year period. Participants/materials, setting, methods The study was performed in a tertiary hospital. The cohort included live singleton deliveries (&amp;gt;24 weeks of gestation) and excluded pregnancies following egg donation. Each fresh transfer IVF pregnancy was matched to a FET pregnancy by the same woman (1:1 ratio). Main results and the role of chance A total of 107 fresh transfer pregnancies were matched to 107 FET pregnancies, in the same women. Mean maternal age was lower in the fresh transfer group compared to the FET group (30.4 vs. 32.5 years, p &amp;lt; 0.001), as was body mass index (BMI) (p = 0.001). A higher rate of nulliparity was noted in fresh transfer pregnancies (64.5% vs. 12.1%, p &amp;lt; 0.001). Mean birthweight was higher in the FET group (3160 vs. 3081 grams, respectively, p &amp;lt; 0.001), although the rates of low birth weight and small for gestational age neonates did not differ between the groups. Preterm deliveries occurred in 10.3% and 9.3% of fresh transfer and FET pregnancies respectively, p = 0.79. On multivariate linear regression analysis, the type of embryo transfer - FET or fresh - was not independently associated with birthweight, after adjustment for women’s age, nulliparity and BMI. Limitations, reasons for caution The study relied on coding in patient files, and thus certain data were missing for analysis, such as paternal identity. In addition, women included had at least two successful IVF pregnancies, and at least one cycle in which embryo freezing was performed. This may confer a selection bias. Wider implications of the findings: Our study of sibling deliveries after fresh and FET, points to a similar prognosis for the main obstetric and perinatal outcomes. This adds to current research which points to similar development of children following fresh and FET and is reassuring for clinicians consulting patients who are eligible for both options. Trial registration number Not applicable

P–406 Placental histopathology is different in specific subsets of ICSI singleton pregnancies with programmed cycles : a prospective study

Abstract Study question Does embryo vitrification or donor oocytes (DO) alter the histopathology of the placenta in ICSI singleton pregnancies with similar endometrial preparation? Summary answer Placentas from programmed cycles had significantly more immune/idiopathic-inflammation with vitrified-thawed embryos versus fresh transfer and significantly more maternal vascular-malperfusion(MVM) in DO versus autologous oocyte(AO) pregnancies. What is known already DO pregnancies and frozen embryo transfer(FET) pregnancies with programmed cycles are associated with hypertensive complications. As these complications are linked with abnormal placentation, comparing the placental histopathology in these pregnancies may point to a causative association. Studies of placental histopathology in DO in comparison to AO pregnancies show a dysregulated immune process and vasculopathy. The hormonal milieu during implantation remains an important confounder. Placental histopathology in fresh/ frozen cycles has recently shown variable results. To isolate the effect of embryo vitrification on placental histopathology, the donor oocyte model can provide valuable data, which till now is scarcely available. Study design, size, duration A prospective cohort study conducted in a tertiary center from 2018–2020. Placental histopathology, pregnancy-outcomes were studied in 116 ICSI singleton pregnancies≥28 weeks. Group1-Pregnancies with DO, by FET(n = 32) and freshET(n = 34) were compared to study the effect of embryo-vitrification. Group2-Pregnancies by DO FET(n = 32) were compared to AO FET(n = 50) to study the effect of DO. All patients had ICSI, cleavage embryo-transfer, programmed cycles and delivered at the same institute. The placentas were examined by pathologists (blinded to the ET type). Participants/materials, setting, methods 116 singleton pregnancies were followed for hypertensive disorders of pregnancy (HDP), preterm delivery(PTD&amp;lt;37weeks) and low birth-weight (LBW&amp;lt;2.5kg). Placentas were examined for cord mal-insertions Placental histopathology lesions were classified into 4 groups according to ‘Amsterdam criteria’ infectious-inflammatory, immune/ idiopathic-inflammatory, MVM, fetal vascular malperfusion (FVM). Chi-square and t-tests were used to compare outcomes across groups. Adjusted odds ratio were calculated using logistic regression. Statistical significance set at P &amp;lt;.05, two-tailed. Main results and the role of chance No patient had a history of chronic hypertension/smoking. Group 1 Patients conceived by DO, with FET and freshET were comparable with regards to age (34.1 vs 36.4years, P=.07),BMI(26.7 vs 27.1 kg/m2,P=.6),nulliparity(81%vs82%,P=.9) HDP(25%vs29.4%,P=0.69),birth-weight(2.48 vs 2.47kg,P=.93) LBW(31.3%vs41.2%,P=.41)respectively PTD was significantly less in donor FET versus donor freshET (6.3%vs47.1%P=.0002) Placental weight and cord mal-insertions were comparable for FET vs freshET (466 vs 486gms P=.03 12.5%vs23.5% P=.25)respectively. Amongst the placental histopathology lesions, immune/ idiopathic-inflammatory lesions were significantly more in the FET vs freshET group (37.5% vs 11.8%,P=.02)The other lesions were comparable infectious-inflammatory(6.3%vs17.6%,P=.16), MVM(75%vs58.8%, P=.16),FVM(18.8%vs17.6%,P=.9) Group 2 Patients conceived by DO compared to AO by FET were significantly older and had a higher BMI (34.1vs31.7years,P=.02 ,26.7vs25.5 kg/m2,P=.002) respectively. Nulliparity was comparable(81%vs92%,P=.15) Birth weight was significantly less in DO vs AO(2.4vs2.7kg,P=.02) HDP and LBW were significantly more in DO vs AO(25%vs8% ,P=.03, 31.3%vs 8%,P=.007),respectively. PTD was comparable(6.3%vs8.0%,P=.77). Placental weight was significantly less in DO vs AO (466 vs 513gms,P=.03) cord mal-insertions were comparable(12.5% vs 24%,P=.2) The MVM lesions were significantly more in the DO group compared to AO(75% vs 40%,P=.002) The difference remained after adjusting for age/BMI/HDP (AOR 4.31;95% CI 1.24–14.8;P=.02). The rest of placental lesions were comparable in DO vs AO, infectious-inflammatory lesions(6.3%vs16%,P=.19) immune/idiopathic-inflammatory lesions(37.5%vs28%,P=.37) FVM(18.8% vs 12%,P=.4)respectively. Limitations, reasons for caution These findings are based on a small number of patients. The results observed need to be confirmed using a larger study sample. Wider implications of the findings: Placentas in pregnancies by embryo-vitrification, in a DO-model, had significantly more immune/idiopathic-inflammation, the cause/significance of this needs to be explored. Placentas in DO-pregnancies had significantly more MVM-lesions and increased risk of HDP, emphasizing the clinical/histopathological link of DO with HDP and the need for counselling/preventive strategies for HDP in DO-pregnancie. Trial registration number Not applicable

Euploid Day-5 Blastocysts Versus Euploid Day-6 Blastocysts — Will the Reproductive Outcomes Differ? An Observational Study

Background and objective: Day-5 blastocyst embryos are usually chosen for assisted reproductive therapy. We compared the reproductive outcomes of the euploid blastocysts developed on Day 5 versus Day 6. Methods: This single-center, retrospective observational study analyzed patients aged 25–45 years, who underwent intracytoplasmic sperm injection from December 2014 to November 2018. Depending on the day of trophectoderm biopsy, patients were categorized into Day-5 and Day-6 groups. Percentages of euploid embryos were calculated for both groups, and elective single euploid blastocysts were transferred in a frozen embryo transfer (FET) cycles. The study endpoints were the comparisons of the reproductive outcomes including clinical pregnancy rate (CPR), implantation rate (IR), miscarriage rate (MR), and live birth rate (LBR) between Day-5 and Day-6 euploid FET groups. Results: A total of 801 embryos from 184 patients were evaluated [Day 5 ([Formula: see text]); Day 6 ([Formula: see text]); 42.45% were euploid] with the rate of euploidy in Day-5 and Day-6 groups at 42.52% and 40.62%, respectively. A total of 126 patients underwent FET with 126 elective single euploid embryos (Day 5: 117; Day 6: 9). For Day-5 versus Day-6 groups, a significantly higher IR (61.54% vs. 44.44%; [Formula: see text]), CPR (61.54% vs. 44.44%; [Formula: see text]), and LBR (61.54% vs. 33.33%; [Formula: see text]) were reported. Multivariate analysis on ANOVA suggested, comparable pregnancy rates at Day 5 and Day 6 ([Formula: see text]). Conclusions: Day-5 euploid blastocysts seem to offer better reproductive outcomes than Day-6 euploid blastocysts. Further research is recommended to evaluate the reproductive outcomes of Day-6 blastocysts.

Fertility outcomes in women after controlled ovarian stimulation with gonadotropin releasing hormone agonist long protocol: fresh versus frozen embryo transfer

BackgroundAlong with progress in embryo cryopreservation, especially the vitrification, freeze all strategy has become more acceptable than ever. Some studies have found comparable or higher live birth rate with frozen embryo transfer (FET) than with fresh embryo transfer(ET)in gonadotropin releasing hormone antagonist (GnRH-ant) protocol. However from our literature research, there have been no reports about live birth rate comparison between fresh ET and FET with gonadotropin releasing hormone agonist (GnRH-a) long protocol. The aim of this study is to retrospectively investigate whether patients benefit from freeze all strategy in GnRH-a protocol using real-world data.MethodsThis is a retrospective cohort study, in which women undergoing fresh ET or FET with GnRH-a long protocol at Chongqing Reproductive and Genetics Institute from January 2016 to December 2018 were evaluated. The primary outcome was live birth rate. The secondary outcomes were implantation rate, clinical pregnancy rate, pregnancy loss and ectopic pregnancy rate.ResultsA total of 7,814 patients met inclusion criteria, implementing 5,216 fresh ET cycles and 2,598 FET cycles, respectively. The demographic characteristics of the patients were significantly different between fresh ET and FET groups, except BMI. After controlling for a broad range of potential confounders including age, infertility duration, BMI, AMH, number of oocytes retrieved and of available embryos, multivariate logistic regression analysis demonstrated that there was no significant difference in clinical pregnancy rate, ectopic pregnancy rate and pregnancy loss rate between two groups (all P > 0.05). However, the implantation rate and live birth rate in fresh ET group were significantly higher than FET group (P < 0.001 and P = 0.012, respectively).ConclusionsUnder GnRH-a long protocol, compared to FET, fresh ET was associated with higher implantation rate and live birth rate in infertile patients that underwent in vitro fertilization (IVF). The freeze all strategy should be individualized and made with caution especially with GnRH-a long protocol.