Freshet Research Articles

Is frozen embryo transfer better than fresh embryo transfer in women undergoing intracytoplasmic sperm injection over the age of thirty-five? A single referral centre experience

Developments in embryo freezing techniques in recent years have increased the chance of pregnancy after frozen embryo transfers. In this study we aimed to compare the pregnancy outcomes between fresh (ET) and frozen-thawed embryo transfer (FET) and to evaluate the benefits of embryo freezing strategy for a woman of advanced age. A total of 513 ET cycles in women over the age of 35 years, including 397 fresh ET cycles and 116 FET cycles were reviewed. Mean age was 37.7 ± 2.91 years in FET cycles and 38 ± 2.8 in fresh cycles (p = .327). The patients undergoing FET cycles had higher oestradiol levels and progesterone levels on the day of trigger in their previous fresh cycles compared to that of fresh ET cycles (1675 pmol/L versus 991 pmol/L; 1.43 pmol/L versus 0.96 pmol/L; p < .005, respectively). Biochemical pregnancy rates (43% versus 32%; p = .048), clinical pregnancy rates (38% versus 29%; p = .030) and live birth rates (30% versus 19.6%; p = .013) were significantly higher in the FET than in the fresh ET over 35 years of age. IMPACT STATEMENT What is alreday known on this subject? Ovarian stimulation commonly results in the generation of more embryos than are necessary for the fresh embryo transfer. Therefore, cryopreservation and subsequent replacement of frozen–thawed embryos is an integral part of assisted reproductive technique (ART) programs. As IVF technology improved, embryo freezing was performed to allow subsequent transfer if the fresh cycle was unsuccessful. What do the results of this study add? Clinical pregnancy rates and live birth rates were found to be higher in frozen thawed embryo transfer group compared to fresh embryo transfer group over the age of 35. What are the implications of these findings for clinical practice and/or further research? Frozen thawed embryo transfer seems to be a reasonable and favourable method compared to fresh embryo transfer in patients over 35 years.

Do Strategies Favoring Frozen-thawed Embryo Transfer Have an Impact on Differences in IVF Success Rate, Multiple Pregnancy Rate, and Cost per Live Birth Between Fertility Clinics?

The aim of this retrospective cohort study is to establish whether strategies favoring frozen-thawed embryo transfer (FET) have an impact on differences in cumulative live birth rate (CLBR), weighted mean cost per live birth, and multiple pregnancy rate (MPR) between fertility clinics. Data were extracted from the Assisted Reproductive Technology (ART) Italian National Registry and refer to classical IVF or intracytoplasmic sperm injection (ICSI) cycles performed in 2018 in public funded Lombardy region fertility clinics. Propensity to FET cycles was expressed with the so-called freezing tendency index (FTI): [(No. of FETs + No. of transfers of embryos obtained from frozen-thawed oocytes) / (No. of fresh ETs + No. of canceled IVF cycles + Numerator)] × 100. Fertility clinics were divided according to their FTI: group A (FTI: 0-20%); group B (FTI: 20-40%); and group C (FTI: 40-60%). Groups A, B, and C included 6, 8, and 8 fertility clinics, respectively. The CLBR (95% CI) per started COH cycle was 13.1% (11.8-14.5%) in group A, 19.6% (18.6-20.7%) in group B, and 27.8% (26.8-28.9%) in group C (p < 0.0001). The weighted mean live birth cost was 32,770 ± 10,662 € in group A, 25,863 ± 11,510 € in group B, and 20,426 ± 3788 € in group C (p < 0.0001). The MPR (95% CI) was 15.4% (12.1-19.4%) in group A, 10.2% (8.7-12.1%) in group B (p = 0.0065), and 6.3% (5.2-7.6%) in group C (p = 0.0001). In conclusion, our results suggest that strategies favoring FET cycles are associated with an increased CLBR, a decreased weighted mean cost per live birth, and a decreased MPR.

Impact of preimplantation genetic testing for aneuploidies (PGT-A) on first trimester biochemical markers – PAPP-A (placenta-associated plasma protein) and free β-hCG (human chorionic gonadotropin)

Objective The objective of the study was to study the effect of preimplantation genetic testing for aneuploidies (PGT-A) performed at blastocyst stage on the levels of first trimester biomarkers. Methods This is an observational, collaborative, retrospective study. Seven hundred and twenty-eight patients were included in the study. Patients were with singleton pregnancies resulting from either natural conception (NC), or assisted reproductive techniques (ARTs) with PGT-A and frozen embryo transfer (FET) (ART/PGT-A/FET) or after ART without PGT-A and fresh ET (ART/no PGT-A/fresh ET) or FET (ART/no PGT-A/FET), who had first trimester combined screening test between 11 and 14 gestational weeks. They were stratified into four groups: group A (ART/PGT-A/FET) – 143 patients; group B (ART/no PGT-A/FET) – 100 patients; group C (ART/no PGT-A/fresh ET) – 346 patients, and group D (NC) – 139 patients. Results Statistically significant differences among the examined groups were observed for maternal age, BMI, ethnicity, and parity. The median placenta-associated plasma protein (PAPP-A) was lowest in the group with ART/PGT-A/FET and the highest result was obtained in the group with ART/no PGT-A/FET. Statistically significant difference in the median PAPP-A levels was identified among the examined groups (p = .0186). When a subgroup analysis was performed, a statistically significant difference was observed in the median PAPP-A between ART/PGT-A/FET group versus ART/no PGT-A/FET group (p = .01) and NC versus ART/no PGT-A/FET (p = .01). A similar trend toward statistical significance was noted when comparing NC versus ART/no PGT-A/fresh ET (p = .06). Multivariate analysis elucidated that when age is present in the model, the effect of any method of conception or testing for aneuploidy disappears. The other factors (BMI, ethnicity, and parity) do not influence the levels of PAPP-A. The lowest median free human chorionic gonadotropin (β-HCG) was recorded in the NC group and the highest result was identified in the group with IVF/PGT-A/FET. No statistically significant difference was observed in the median concentration levels of free β-hCG among the compared groups (p = .5789) and when subgroup analysis was performed (p>.05). The normality of the distribution of variables was analyzed by the Kolmogorov–Smirnov test and the median PAPP-A and free βhCG concentration difference by the Wilcoxon rank-sum test with nonparametric ANOVA. Conclusions Testing for aneuploidy (PGT-A) and the decision to transfer either fresh or cryopreserved embryos (ET) appear not to affect the levels of first trimester biochemical markers. The findings of the present study should be a baseline for future studies and could be used to improve the antenatal screening counseling for women with ART pregnancies and PGT-A.

Embryo blastulation and quality between days 5 and 6 of extended embryo culture.

This study aims to know what proportion of culture day 5 pre-blastocyst-stage embryos develop into blastocysts by culture day 6 and what patient and cycle characteristics are associated with delayed blastocyst formation. A retrospective observational cohort analysis was performed including a total of 9886 embryos from 1008 IVF cycles in 835 patients, who underwent treatment between January 1, 2016, and December 31, 2018. Autologous fresh in vitro fertilization (IVF) cycles at a single academic center were included in the analysis. Embryos were group-cultured using single-step culture media. Blastulation was defined as the presence of a new blastocyst. Usable blastulation was defined as the presence of a new good or excellent quality, expanded, hatching, or hatched blastocysts. The mean blastulation rate between days 5 and 6 of extended embryo culture was 30.9%. The mean percentage of embryos developing into usable blastocyst-stage embryos was 19.8%. The factors associated with blastulation on day 6 included the total number of embryos and the number of pre-blastocysts on day 5, as well as the use of ICSI. Age, the number of total embryos, those remained in culture and pre-blastocysts, as well as the blastulation rate on day 5 were associated with usable blastulation. It is important to know the usable blastocyst development rate between culture days 5 and 6 in order to adequately counsel patients debating whether to proceed with fresh ET on day 5 or forego ET with the expectation that embryos will be biopsied for PGT and/or cryopreserved on culture day 6. Our findings provide evidence to help guide patients in this difficult decision.

Factors Influencing the Live Birth Rate Following Fresh Embryo Transfer Cycles in Infertile Women After Endometrioma Cystectomy.

Background: Reproductive outcomes after fresh in vitro fertilization/intracytoplasmic sperm injection–embryo transfer (IVF/ICSI–ET) cycles are diverse in infertile women with a history of ovarian cystectomy for endometriomas. We aimed to develop a logistic regression model based on patients' characteristics including number of embryos transferred and stimulation protocols to predict the live birth rate in fresh IVF/ICSI–ET cycles for such patients.Methods: We recruited 513 infertile women with a history of ovarian cystectomy for endometriomas who underwent their first fresh ET with different stimulation protocols following IVF/ICSI cycles in our unit from January 2014 to December 2018. One or two embryo are implanted. Clinical and laboratory parameters potentially affecting the live birth rate following fresh ET cycles were analyzed. Univariable and multivariable analyses were performed to assess the relationship between predictive factors and live birth rate.Results: The overall live birth rate was 240/513 (46.8%). Multivariable modified Poisson regression models showed that two factors were significantly lowers the probability of live birth: female age ≥ 5 years (aOR 0.603; 95% CI 0.389–0.933; P = 0.023); BMI range 21–24.99 kg/m2 compared with BMI <21 kg/m2 (aOR 0.572; 95% CI 0.372–0.881, P = 0.011). And two factors significantly increased the probability of live birth: AFC >7 (aOR 1.591; 95% CI 1.075–2.353; P = 0.020); two embryos transferred (aOR 1.607; 95% CI 1.089–2.372; P = 0.017).Conclusions: For these infertile women who had undergone ovarian cystectomy for endometriosis, female age <35 years, AFC > 7, and two embryos transferred might achieve better clinical fresh IVF/ICSI–ET outcomes. BMI <21 kg/m2 or ≥25 kg/m2 might also have positive effects on the live birth rate, but different ovarian stimulation protocols had no significant effects. However, a larger sample size may be needed for further study.

Does fresh or frozen embryo transfer affect imprinted gene expressions in human term placenta?

Our research aimed to compare the epigenetic alterations between placentae of in vitro fertilization (IVF) patients and spontaneous pregnancies. Additionally, the expression levels of proliferation markers (PCNA, Ki67) and glucose transporter proteins (GLUT1, GLUT3) were assessed in control and IVF placentae to examine the possible consequences of epigenetic alterations on placental development. Control group placentae were obtained from spontaneous pregnancies of healthy women (n = 16). IVF placentae were obtained from fresh (n = 16) and frozen (n = 16) embryo transfer pregnancies. A group of maternal and paternal imprint genes H19, IGF2, IGF2, IGF2R, PHLDA2, PLAGL1, MASH2, GRB10, PEG1, PEG3, and PEG10 were detected by Real-Time PCR. Additionally, PCNA, Ki67, GLUT1, and GLUT3 protein levels were assessed by immunohistochemistry and western blot. In the fresh embryo transfer placenta group (fETP), gene expression of paternal PEG1 and PEG10 was upregulated compared with the control group. Increased gene expression in paternal PEG1 and maternal IGFR2 genes was detected in the frozen embryo transfer placenta group (FET) compared with the control group. Conversely, expression levels of H19 and IGF2 genes were downregulated in the FET group. On the other hand, GLUT3 and PCNA expression was increased in FET group placentae. IVF techniques affect placental imprinted gene expressions which are important for proper placental development. Imprinted genes are differently expressed in fresh ET placentae and frozen ET placentae. In conclusion, these data indicate that altered imprinted gene expression may affect glucose transport and cell proliferation, therefore play an important role in placental development.

High birth weight and large-for-gestational-age in singletons born after frozen compared to fresh embryo transfer, by gestational week: a Nordic register study from the CoNARTaS group.

When do the differences in birth weights become apparent between singletons born after frozen embryo transfer (FET) and fresh embryo transfer (fresh ET)? Mean birth weights after FET become significantly higher starting from gestational week (GW) 33 among boys and from GW 34 among girls. In recent years, there has been a steep rise in recorded FET treatments, enabling widespread use of elective single embryo transfer, thus reducing the risks associated with multiple gestations. However, singletons born after FET are heavier and there is a higher risk of large-for-gestational-age (LGA) (birth weight > 90 percentiles) compared to fresh ET. In contrast, risk of small-for-gestational-age (SGA, birth weight < 10 percentiles) is lower in singletons born after FET compared to fresh ET. The reasons, timing and consequences of these differences remain largely unclear. There is limited evidence about whether this difference in growth develops before the last trimester of pregnancy. This retrospective Nordic register-based cohort study compared singletons born after FET (n = 17500) to singletons born after fresh ET (n = 69510) and natural conception (NC, n = 3311588). All live born singletons born between the years 2000 and 2015 in Denmark, Norway and Sweden at gestational age ≥22 weeks were included from the population-based Committee of Nordic ART and Safety (CoNARTaS) study population. Children born after FET were compared to those born after fresh ET and NC for mean birth weight and proportion of LGA and SGA for each GW at birth. Chi-square test and tests for relative proportions were used to compare categorical variables and Student's t-test was used to compare continuous variables. Adjusted odds ratios (aORs) for LGA and SGA were calculated using logistic regressions, adjusting for year of birth, maternal age, parity, BMI, chronic hypertension, diabetes, smoking and offspring sex. Mean birth weights were significantly higher after FET compared to fresh ET starting from GW 33 (range from 75 g to 228 g by week) for boys and starting from GW 34 (range from 90 g to 236 g by week) for girls. Boys born after FET had a significantly higher proportion of LGA (11.0-15.1%) at birth between GW 36 and 42, compared to those born after fresh ET (7.1-9.4%) (range from P < 0.001 to P = 0.048 by week). For girls born after FET, the difference was seen between GW 37 and 42 (10.6-13.4%) compared to those born after fresh ET (6.6-8.0%) (range from P < 0.001 to P = 0.009 by week).The proportion of SGA was significantly lower among boys born after FET (7.6-8.7%) compared to fresh ET (11.9-13.6%) between GW 36 and 42 (range from P < 0.001 to P = 0.016 by week). For girls born after FET, the difference was seen between GW 38 and 42 (7.0-9.3%) compared to those born after fresh ET (13.0-14.6%) (P < 0.001). The proportion of LGA (12.3-15.1%) was significantly higher for boys born after FET between GW 38 and 41 (P < 0.001) and for girls born after FET (12.6-13.4%) between GW 37 and 40 (range from P < 0.001 to P = 0.018 by week), compared to naturally conceived boys (9.7-9.9%) and girls (9.0-10.0%). All singletons born after FET had a higher risk of LGA compared to singletons born after fresh ET (aOR 1.87, 95% CI 1.76-1.98) and singletons born after NC (aOR 1.28, 95% CI 1.22-1.35). There may be residual confounding factors that we were not able to control for, most importantly the causes of preterm birth, which may also influence foetal growth. A further limitation is that we have no knowledge on growth patterns between implantation and GW 22. Finally, the number of children born extremely preterm or post-term was limited even in this large study population. This is, to date, the largest study on birth weights among preterm and term ART singletons with a population-based design and NC control group. The results suggest that the freeze-thaw process is associated with higher birthweights and greater risk of LGA at least in the last trimester of pregnancy. This is an important aspect of the safety profile of ART. More research is needed on the long-term outcome of these children. The CoNARTaS collaboration has received the following funding: the Nordic Trial Alliance: a pilot project jointly funded by the Nordic Council of Ministers and NordForsk [71450], the Central Norway Regional Health Authorities [46045000], the Norwegian Cancer Society [182356-2016], the Nordic Federation of Obstetrics and Gynaecology [NF13041, NF15058, NF16026 and NF17043], the Interreg Öresund-Kattegat-Skagerrak European Regional Development Fund (ReproUnion project) and the Research Council of Norway's Centre of Excellence funding scheme [262700]. None of the authors have any competing interests to declare. ISRCTN11780826.

Pregnancy outcomes following in vitro fertilization using fresh or frozen embryo transfer.

ObjectiveThe aim of this study was to investigate the pregnancy outcomes in women undergoing IVF using fresh and/or frozen embryo transfer.MethodsIn this retrospective patient record study, we reviewed 2,872 infertile women’s files, who were candidates for IVF. The patients were classified into two groups, including those who underwent fresh embryo transfer (n=1628) and/or frozen embryo transfer (FET) (n=1244).ResultsFertility was achieved in 313 (19.23%) and 356 (28.62%) patients, who underwent fresh ET and FET, respectively. The rates of clinical pregnancy, ongoing pregnancy, and live births were significantly higher in the FET group than the fresh ET group. The incidence of multiple pregnancies, perinatal mortality, abortion in the first trimester, preterm delivery, and low birth weight were significantly higher among fresh ET group [38 (35.51%), 15 (14.50%), 72 (23.01%), 26 (8.30%), and 33 (10.54%), respectively] than in the FET group [25 (15.33%), 6 (6.87%), 63 (17.69%), 14 (3.93%), and 20 (5.61%); p<0.05]. In addition, the incidence of ectopic pregnancies, abortion in the second trimester, gestational diabetes, preeclampsia, and placenta previa were higher in the fresh ET group, but not significantly so (p>0.05).ConclusionsWomen who underwent IVF via FET showed more successful fertility and pregnancy outcomes compared to those who underwent IVF by fresh ET.

Cost-effectiveness of freeze-all policy – A retrospective study based upon the outcome of cumulative live births

ObjectWe have previously reported that cumulative live birth rates (CLBRs) are higher in the freeze-all group compared with controls (64.3% vs. 45.8%, p = 0.001). Here, we aim to determine if the freeze-all policy is more cost-effective than fresh embryo transfer followed by frozen-thawed embryo transfer (FET). Materials and methodsThe analysis consisted of 704 ART (Assisted reproductive technology) cycles, which included in IVF (In vitro fertilisation) and ICSI (Intra Cytoplasmic Sperm Injection) cycles performed in Taichung Veterans General Hospital, Taiwan between January 2012 and June 2014. The freeze-all group involved 84 patients and the fresh Group 625 patients. Patients were followed up until all embryos obtained from a single controlled ovarian hyper-stimulation cycle were used up, or a live birth had been achieved. The total cost related to treatment of each patient was recorded. The incremental cost-effectiveness ratio (ICER) was based on the incremental cost per couple and the incremental live birth rate of the freeze-all strategy compared with the fresh ET strategy. Probabilistic sensitivity analysis (PSA) and a cost-effectiveness acceptability curve (CEAC) were performed. ResultsThe total treatment cost per patient was significantly higher for the freeze-all group than in the fresh group (USD 3419.93 ± 638.13 vs. $2920.59 ± 711.08 p < 0.001). However, the total treatment cost per live birth in the freeze-all group was US $5319.89, vs. US $6382.42 in the fresh group. CEAC show that the freeze-all policy was a cost-effective treatment at a threshold of US $2703.57 for one additional live birth. Considering the Willingness-to-pay threshold per live birth, the probability was 60.1% at the threshold of US $2896.5, with the freeze-all group being more cost-effective than the fresh-ET group; or 90.1% at the threshold of $4183.8. ConclusionThe freeze-all policy is a cost-effective treatment, as long as the additional cost of US $2703.57 per additional live birth is financially acceptable for the subjects.

Is conception by in vitro fertilization associated with altered antenatal and postnatal growth trajectories?

To study whether the growth trajectory of the first, second, and third trimester, birth, and 5 years of age differs between children born following fresh embryo transfer (fresh ET), frozen-thawed embryo transfer (FET), and children born after natural conception (NC). Historical cohort study of children. The analysis compared cross-sectional and longitudinal differences in measurement between individuals stratified by method of conception. Not applicable. Participants were born between 1997 and 2012 by NC (n = 65,683), fresh ET (n = 576), and FET (n = 179). Data were available for method of conception and fetal, maternal, and neonatal characteristics and measurements at 5 years. None MAIN OUTCOME MEASURE(S): Size at first, second, and third trimester, birth, and 5 years. In the longitudinal model, first trimester crown-rump length was significantly longer after fresh ET compared to NC. Second trimester head size was larger after fresh ET and after FET compared to NC. Birth weight was lower after fresh ET conception compared to FET. At 5 years of age, children conceived by fresh ET and FET were no heavier than peers conceived by NC. Individuals conceived by invitro fertilization have significantly different antenatal growth trajectories during the first and second trimester compared to those conceived by NC, and differences persist at birth for weight and head size. The relevance of these different growth trajectories remains uncertain, and larger prospective studies are required.

A freeze-all strategy does not increase live birth rates in women of advanced reproductive age.

Does a freeze-all strategy improve live birth rates in women of different age groups? Retrospective cohort study of 1882 first embryo transfer cycles, performed between January 2013 and December 2015. Reproductive outcomes between fresh (FRESH) or frozen (FROZEN) embryo transfers were compared in patients stratified by age: < 35, between 35 and 38, or > 38years. Student's t test for independent samples and χ2analyses were used as needed. A multivariable logistic regression analysis was performed adjusting for age, triggering drug, number of retrieved oocytes, number of transferred embryos, and percentage of top-quality embryos. Live birth rates (LBR) were significantly higher for FROZEN in the < 35years group (43.7% vs 24%; p< 0.001). In both the 35-38 and > 38years groups, LBR for FROZEN vs FRESH were not statistically different (30.9% in the FROZEN group vs 29.3% in the FRESH group, p= 0.70, and 19.8% in the FROZEN group vs 12.7% in the FRESH group, p= 0.07, respectively). The multivariate analysis found a significantly positive effect of performing FROZEN on LBR in the younger group (OR 2.46, 95% CI 1.31-4.62; p = 0.005) but had no impact in women between 35 and 38years (OR 1.01, 95% CI 0.55-1.83; p = 0.98) or older (OR 0.96, 95% CI 0.43-2.13; p = 0.92). Performing a freeze-all strategy seems to result in better reproductive outcomes when compared with a fresh ET in women under 35years, with no significant impact on older women.

FRESH EMBRYO TRANSFER IMPROVES LIVE BIRTH RATE OVER FROZEN EMBRYO TRANSFER IN FRESHLY RETRIEVED DONOR EGG CYCLES

To test the hypothesis that in cycles using embryos derived from freshly retrieved donor eggs, a fresh embryo transfer (fresh ET) is more likely to result in a clinical pregnancy and live birth compared to a cryopreserved-thawed embryo transfer (CET). Retrospective cohort study using national data from the Society for Assisted Reproductive Technology (SART). Donor egg cycles in the SART database from 2014-2017 were collected. Only cycles using freshly retrieved eggs from anonymous donors were included. Cycles in which eggs were previously frozen, a known donor was used, or recipient age at time of transfer was over 55 years were excluded. All included cycles had at least one embryo available to transfer at either the cleavage or blastocyst stage. Using log binomial regression, relative risks and 95% confidence intervals were calculated for clinical pregnancy rate (CPR), live birth rate (LBR) and miscarriage rate. Crude and adjusted analyses were performed, controlling for donor age. Of a total of 51,942 donor egg cycles, 15,308 (29.5%) were fresh ET cycles and 36,634 (70.5%) were CET cycles. Both groups were similar in terms of age, gravidity, parity, BMI, infertility diagnosis, and race/ethnicity. A majority of recipients had blastocyst(s) transferred (92.4% of fresh ETs and 96.5% of CETS), with a similar mean number of embryos transferred: 1.52 ± 0.52 in the fresh and 1.39 ± 0.53 in the CET groups. Both CPR and LBR were lower after CET compared to fresh ET (CPR 54.2% vs 66.7%, aRR 0.78 [95% CI 0.76-0.79]; LBR 44.0% vs 56.6%, aRR 0.74 [95% CI 0.72-0.75]), controlled for donor age. Miscarriage rate was similar for both (9.4% following CET vs 9.3% following fresh ET, aRR 1.02 [95% CI 0.96-1.10]). CPR and LBR following transfer of fresh non-PGT-A embryos were statistically significantly higher than following transfer of PGT-A embryos (either fresh or frozen) with no difference in miscarriage rates (Table).Tabled 1Fresh non-PGT-AN = 15044Fresh and frozen PGT-AN = 2327Frozen PGT-AN = 2063RR (95% CI)aRR (95% CI)*RR (95% CI) ‡aRR (95% CI) * ‡Clinical pregnancy10026 (66.6%)1420 (61.0%)1237 (60.0%)0.92 (0.88-0.95)0.89 (0.85-0.94)0.90 (0.87-0.93)0.84 (0.79-0.90)Live birth8505 (56.5%)1191 (51.2%)1031 (50.0%)0.91 (0.87-0.94)0.89 (0.83-0.95)0.88 (0.84-0.93)0.82 (0.75-0.89)Miscarriage1396 (9.3%)203 (8.7%)183 (8.9%)0.94 (0.82-1.08)0.94 (0.76-1.17)0.96 (0.83-1.11)1.01 (0.80-1.29)* adjusted for donor age. ‡ relative risk for only frozen PGT-A compared to fresh non-PGT-A Open table in a new tab * adjusted for donor age. ‡ relative risk for only frozen PGT-A compared to fresh non-PGT-A Both CPR and LBR following the use of fresh donor eggs are over 10% higher after a fresh rather than frozen embryo transfer. This study suggests that recipients should be encouraged to undergo fresh donor egg embryo transfer without PGT-A.

Author

We analyzed some parameters, affecting the success rates of in vitro procedures taken from the national registers of Japan, China, and the USA. We compare birth rates for frozen embryo transfer (FET) and fresh ET after IVF / ICSI procedures, and we believe one of the reasons for the higher FET success rate is the “therapeutic” effect on embryos following the freezing / thawing procedure. This phenomenon has been described in our “Theory about the Embryo Cryo-Treatment”. We believe that cryopreservation helps to partially eliminate the negative impact of air pollution caused by the pollution of the environment on the development and implantation of embryos.

Endometrial thickness is associated with incidence of small-for-gestational-age infants in fresh in vitro fertilization–intracytoplasmic sperm injection and embryo transfer cycles

To investigate whether endometrial thickness (EMT) is associated with adverse obstetric and neonatal outcomes in fresh invitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycles. Retrospective cohort study. University-based reproductive medical center. Women under the age of 42 years who underwent IVF/ICSI treatment and received fresh ET in our unit from January 2017 to December 2018, resulting in a live singleton birth. Controlled ovarian hyperstimulation and IVF/ICSI; fresh ET. Birth weight, gestational age, small for gestational age (SGA), large for gestational age (LGA), placenta previa, placental abruption, hypertensive disorders, and gestational diabetes mellitus. The risk of being born SGA was statistically significantly increased in the EMT ≤7.5 mm group compared with those from the EMT >12 mm group (adjusted odds ratio [aOR] 2.391; 95% confidence interval [CI], 1.155-4.950). Moreover, maternal body mass index, secondary infertility, preterm delivery, and hypertensive disorders were all independent predictors for SGA. The mean birth weights of singletons in women with EMT ≤7.5 mm were lower than in the groups with EMT >7.5-12 mm and EMT >12 mm (3.25 ± 0.56 kg vs. 3.38 ± 0.51 kg and 3.39 ± 0.53 kg, respectively). After fresh IVF/ICSI-ET, the risk of SGA was increased twofold in women with EMT ≤7.5 mm compared with women with EMT >12 mm. We suggest that women with a thin EMT after obtaining a pregnancy by IVF should receive improved prenatal care to reduce the risk of delivering a SGA infant.

Clinical outcomes of fresh versus frozen embryo transfers and its influence on mid-trimester miscarriage and fetal birth weight: A retrospective study

Aim: The aim of the study was to compare the clinical outcomes of fresh and frozen embryo transfer (FET) in women undergoing assisted reproductive technology and its influence on mid-trimester miscarriage and fetal birth weight.Materials and Methods: The study was conducted between June 2016 and June 2019. The study group comprised 778 cycles, of women, who were undertaken in this retrospective analysis of in vitro fertilization cycles who underwent fresh and FET. These women were randomly divided into two groups, fresh embryo transfers (n = 410) and FETs (n = 368). Both groups were compared with their respective outcome measures such as the clinical pregnancy rates (CPRs), miscarriage rates, multiple pregnancy rates as well as live births and birth weights.Results: The mean age of the participants in fresh and FET groups was 31.13 ± 4.39 and 31.45 ± 4.25, respectively. There were statistically significant differences with respect to clinical pregnancy (P = 0.002) between the groups. Fetal miscarriage rates (30.14% vs. 23.53%) as well as birth weights were not statistically significant (P = 0.164) between fresh versus FET. The results clinically signified that the FET gives a lower miscarriage rate and higher CPRs while not affecting the average fetal birth weight.Conclusion: Adjusting the baseline characteristics and exclusion criteria of participants, women undergoing FET were associated with better clinical outcomes than women undergoing fresh ET cycles Contrary to existing literature, our incidence of neonatal morbidities, or large birth weights were not increased and fetal macrosomia did not occur. Gaining debates on the advantage of frozen over fresh transfers and its effects on obstetric and neonatal outcomes may require a large multicenter pooling of data and analyses.

Factors associated with embryo splitting and clinical outcome of monozygotic twins in pregnancies after IVF and ICSI.

What factors are associated with monozygotic twins (MZT) after autologous IVF/ICSI with fresh and frozen/thawed single embryo transfer (SET) and what is the outcome of MZT?Factors associated with increased MZT were blastocyst transfer and elective single embryo transfer (eSET), with MZT showing a lower gestational age at birth and neonatal weight but higher perinatal mortality only after fresh transfer.ART is associated with an increased incidence of MZT, which carries higher perinatal mortality. However, risk factors associated with MZT are still controversial.A population-based retrospective analysis of data extracted from ART cycles reported to the Latin American Registry of ART between January 2012 and December 2016 was used in order to study the frequency and outcome of MZT after SET.In total, 2925 clinical pregnancies obtained after autologous IVF/ICSI with fresh SET were used to study biomedical factors possibly associated with MZT, such as maternal age, type of insemination, use of assisted hatching, stage of embryo development at transfer, elective or non-elective SET and preimplantation genetic testing. Another group of 3085 clinical pregnancies obtained after SET of frozen-thawed embryo transfer (FET) was also used to study the possible association between embryo freezing and MZT. Only pregnancies with complete follow-up until birth were included in this analysis. The diagnosis of MZT was established by transvaginal ultrasound performed at 6–8 weeks of amenorrhea. The rate of MZT for each potential risk factor was obtained and a multivariable logistic regression was performed in order to account for the above-mentioned factors. Pregnancies were followed until birth and the early neonatal period in order to assess the rate of miscarriage and stillbirths, gestational age at birth, neonatal weight and early neonatal mortality.There were 76 MZT out of 2925 clinical pregnancies with fresh SET (2.6%) and 69 MZT out of 3085 clinical pregnancies after FET (2.2%) (odds ratio (OR) = 0.85, 95% CI 0.61–1.19). A statistically significantly increase in MZT rate was observed with blastocyst compared with cleavage stage ET (3.4 versus 2.0%, respectively; OR = 1.70, 95% CI 1.05–2.76). When confounding variables were considered, eSET was also significantly associated with an increase in the odds of MZT (OR = 1.74, 95% CI 1.04–2.92). Overall perinatal mortality was higher in MZT compared with singletons, but this rise was only significant after fresh ET.Limitations of the current study result from the fact that MZT were diagnosed with ultrasound performed at 6–8 weeks of amenorrhea; therefore, spontaneous embryo reductions taking place earlier were missed.Reproductive health providers must inform their patients that blastocyst transfer and eSET of fresh embryos are associated with a statistically significantly increase in the odds of MZT and that perinatal mortality after fresh ET is significantly higher in MZT than in singletons.The Latin American Registry of ART receives direct funding from Ferring Pharmaceuticals, but no specific funding was received to undertake this study. None of the authors declare conflict of interest.

2776 Uterine Volume Assessment as a Predictor of in vitro Fertilization Pregnancy Outcomes

Study Objective To investigate the association between uterine size and pregnancy outcomes in IVF cycles. Design Retrospective cohort study. Setting University-affiliated fertility center. Patients or Participants Women with primary infertility Interventions Fresh ET. Measurements and Main Results Uterine volume was used as a surrogate for uterine size. Uterine measurements (length, width, thickness) were obtained in each woman. Uterine volume was calculated using the prolate ellipsoid volume formula (V=0.52 x L x W x T). Baseline demographics, IVF cycle characteristics and perinatal outcomes were measured. Term birth, defined by live birth >37 weeks of gestation was considered the primary outcome of interest. The odds of pre-term and term birth were estimated in each uterine volume quartile. A receiving-operator-characteristic (ROC) curve with a corresponding area-under-the-curve (AUC) was generated to assess the performance of uterine volume as predictor of term birth. The study included 261 patients with live singleton births. The median (IQR) age, height, weight, body mass index (BMI) and uterine volume for the study cohort was 34 (31-39) years, 163 (160-167) cm, 137 (122-155) lbs, 22.1 (20.3-24.9) kg/m2 and 55.5 (43.2-67.9) mL, respectively. The rates of term birth and pre-term birth were 224/261(85.8%) and 37/261 (14.2%). There was no difference in the baseline demographics or IVF cycle characteristics of women with term birth or pre-term births. The overall odds of term birth increased with uterine volume. Specifically, the odds of term birth in 4th quartile (highest uterine volume) were 3.4 (95% CI 2.1-7.4; P=0.01) times higher than the 1st quartile. Uterine volume was found to be a strong predictor of term birth (AUC=0.87). Conclusion Our findings suggest that baseline uterine volume is a strong predictor of term birth after fresh ET. These findings require prospective validation in larger sample sizes given the multifactorial nature of term birth.

The Deferred Embryo Transfer Strategy Seems Not to be a Good Option After Repeated IVF/ICSI Cycle Failures

The aim of this study was to assess whether a deferred frozen-thawed embryo transfer (Def-ET) offers any benefits compared to a fresh ET strategy in women who have had 2 or more consecutive in vitro fertilization (IVF)/intracytoplasmic injection (ICSI) cycle failures. An observational cohort study in a tertiary referral care center including 416 cycles from women with a previous history of 2 or more consecutive IVF/ICSI failures cycles. Both Def-ET and fresh ET strategies were compared using univariate and multivariate logistic regression models. The main outcome measured was the cumulative live birth rate (CLBR). A total of 416 cycles were included in the analysis: 197 in the fresh ET group and 219 in the Def-ET group. The CLBR was not significantly different between the fresh and Def-ET groups (58/197 [29.4%] and 57/219 [26.0%], respectively, P = .437). In addition, after the first ET, there was no significant difference in the live birth rate between the fresh ET and Def-ET groups (50/197 [25.4%] vs 44/219 [20.1%], respectively). Multivariate logistic regression analysis indicated that compared to the fresh strategy, the Def-ET strategy was not associated with a higher probability of live birth. In cases with 2 or more consecutive prior IVF/ICSI cycle failures, a Def-ET strategy did not result in better ART outcomes than a fresh ET strategy.

South asian women have poorer IVF outcomes despite being younger and having better ovarian reserve compared to caucasians

IVF outcomes in ethnic minorities have been reported previously to be worse compared to Caucasians (C), including those of South Asian (SA) descent (India, Pakistan, Bangladesh, Nepal). Little has been published on ovarian stimulation parameters in SA as compared to C. Retrospective. A total of 557 cycles were reviewed (176 in SA and 401 in C). Markers of ovarian reserve (AMH, AFC, FSH, E) and cycle outcomes were compared between the two groups. The clinical outcome of those who had a fresh embryo transfer were also compared. SA women were significantly younger (34.3 vs 35.7 yrs, P< 0.001), had lower basal E2 (37.8 vs 42.1 pg/ml, P=0.042), higher AMH (3.54 vs 2.84 ng/ml, P=0.018), lower basal Vit D (31.9 vs 36.6 ng/ml, P=0.001), required less gonadotropins (3374.6 vs 3567 IU, P=0.045), had lower peak Vit D (40.8 vs 45.4, P=0.008), and had lower total blastocyst number (2.64 vs 3.1, P=0.036). For those who had a fresh ET (43 SA and 75 C), the live birth rate was lower in SA (52.7% vs 67.4%, P=0.014). For those undergoing PGT-A, there was a lower incidence of euploid embryos in C (150 cycles in C and 87 in SA) (45.6% in SA vs 35.6% in C, P=0.042).Tabled 1SA (N=176)C (N=401)P-valueAge34.3 ± 4.235.7 ± 4.1< 0.0001AMH3.5 ± 6.502.84 ± 2.910.018AFC15.1 ± 9.714.2 ± 8.80.29Basal E237.8 ± 21.542.1± 23.90.042Basal Vit D31.9 ± 14.0336.6 ± 13.13< 0.0001Gonadotropins (IU)3375 ± 10683567 ± 10540.045Peak Vit D40.8 ± 14.345.4 ± 13.50.008#Blastocysts2.64 ± 2.23.1 ± 2.50.036 Open table in a new tab Despite being significantly younger and having better ovarian reserve, SA women had significant differences in stimulation parameters. For those who had a fresh ET, SA women had a significantly lower live birth rate compared to Caucasians.

Improved embryology outcome and morphokinetic characteristics of embryos derived from frozen/thawed oocytes injected 3 versus 2 hours post-warming

To assess whether the duration of recovery following the warming of cryopreserved oocytes affects the morphological and morphokinetic properties of the developing embryo. This is a retrospective data analysis examining the effect of the post-warming recovery duration of vitrified oocytes prior to ICSI. Frozen oocytes from 36 patients (July 2018 to March 2019), either autologous or donor, were included in the study. The study examined cycles in which the oocytes were injected within a 2-hour recovery period and compared them to those in which the oocytes were injected within 3 hours or more within the same patient oocyte cohort. All injected oocytes were cultured individually in time-lapse incubators (TLM; EmbryoScope, Vitrolife, Sweden). Embryo transfers occurred on D3 or D5 regardless of the study groups. Standard oocyte freezing protocol included vitrification 2 hours after retrieval using a Kitazato-based (Japan) vitrification media. Oocyte warming was performed using Kitazato thaw media. ICSI was performed in the standard fashion, and embryos were annotated daily for their developmental hallmarks. Embryo selection for ET or freezing was performed by standard laboratory protocols. No significant differences were observed in 2PN and/or abnormal fertilization rates between the groups. Similarly, on day 3, no significant differences were found in the average cell numbers or in the average number of good (≥8 cells, <20% frag.), fair (5-7 cells, any abnormal cleavages), and poor (≤4 cells) embryos. Equally, the incidence of abnormal cleavage patterns was similar among the cohort. More embryos were selected for transfer from the 3-hour group than from the 2-hour group (51.1% vs. 48.9%; p=0.78). There were no significant differences in the utilization rate (the number of embryos transferred fresh plus blastocysts frozen) between the 3- and 2-hour groups (49.6% vs. 49.6%, respectively). The time-lapse morphokinetic data indicated faster-growing embryos in the 3- versus 2-hour group. This difference is apparent in late-stage morphokinetic parameters (t9 to tsB). The 3-hour group produced significantly better quality blastocysts in cycles that were either frozen upfront, fresh D5 ET, or PGT (p=0.03). The duration of the recovery time post-warming showed no significant differences in overall embryology outcomes prior to blastocyst formation. However, at the BL stage, the 3-hour group demonstrated improvement in morphokinetic parameters and in overall BL quality.