Blastocyst-stage Transfer Research Articles

Transdermal versus oral estrogen: clinical outcomes in patients undergoing frozen-thawed single blastocyst transfer cycles without GnRHa suppression, a prospective randomized clinical trial

PurposeTo conduct a non-inferiority study to compare the clinical outcomes of transdermal estrogen patch and oral estrogen in patients undergoing frozen-thawed single blastocyst transfer non-donor cycles without GnRHagonist (GnRHa) suppression.MethodsA total of 317 women with irregular menses or anovulatory cycle undergoing frozen-thawed embryo transfer (FET) non-donor cycles without GnRHa suppression were involved in a prospective randomized clinical trial between May 2017 and October 2017. The trial was conducted in an ART and Reproductive Genetics Centre within a private hospital. The unit is designated as a teaching center by the Turkish Ministry of Health. Oral or transdermal estrogen was administered in patients undergoing frozen-thawed single blastocyst transfer. The outcomes of the study were the following: endometrial thickness on the day of progesterone administration, implantation rate, and clinical and viable ongoing pregnancy rates.ResultsEndometrial thickness and clinical outcomes of oral and transdermal estrogen administration were equally successful (p > 0.05).ConclusionNo significant difference was found in endometrial thickness on the day of progesterone administration nor in clinical outcomes between transdermal estrogen and oral estrogen in patients undergoing frozen-thawed single blastocyst stage transfer cycles without GnRHa suppression.

Single instead of double day-five blastocyst transfer maintains the same clinical pregnancy rate and decreases multiple pregnancy and abortion rates in fresh IVF cycles

The main objective of this study is to reduce multiple pregnancies and abortions without modifying the clinical pregnancy rate in fresh IVF cycles by transferring single day-five blastocysts A retrospective analysis of three embryo transfer strategies for all patients enrolled in a fresh IVF cycle between October 2015 and December 2017. We compared Group 1 (G1) 93 double cleavage stage embryo transfers, Group 2 (G2) 39 double blastocyst stage embryo transfers and Group 3 (G3) 259 single blastocyst stage embryo transfers. The variables analysed were clinical pregnancy, multiple pregnancy, abortion and implantation rates All fresh IVF cycles included in this study were incubated in K-System® G-185 or ThermoFisher Scientic® Heracell 150i incubators with Sage® or Global Total® Mediums. Chi square independence test and Fisher's exact test were used to compare clinical pregnancy, implantation, multiple pregnancies and abortions rates between the three groups. When independence tests were significant, parametric and non-parametric comparison tests were used in pairs. Additionally, the odds ratio obtained for each variable was reported Results showed that there is no statistical difference in clinical pregnancy rates when transferring embryos in the cleavage or blastocyst stage (p-value=0.8352). However, there is an important reduction in the multiple pregnancies achieved when transferring only one blastocyst (1%) compared with double embryo cleavage stage transfer (33%) and double blastocyst stage transfer (33%). The independence between groups and multiple pregnancies was rejected (p-value<0.0001). The comparison of proportions were significant between G1 and G3 (p-value<0.0001), and between G2 and G3 (p-value<0.0001). In addition, as we expected the implantation rate was highly improved when only one embryo in the blastocyst stage was transferred (41%) in comparison to two blastocysts (26%) or two cleavage embryos (24%) transfers. The independence was rejected (p-value<0.0001). The comparison of proportions were significant between G1 and G3 (p-value=0.0007), and between G2 and G3 (p-value=0.0375). The odds ratio for implantation rates obtained, with G1 as reference, were 1.1129 for G2 and 2.0967 for G3. Finally, the decrease in the abortion rate was striking, 20% for G1, 5% for G2 and 10% for G3. There is not a statistical significance among the groups (p-value=0.1352), however, these proportions show a tendency, transferring in blastocyst stage suffers fewer abortions than in cleavage stage. The main limitation of this study is the difference in the number of patients in each group We conclude that single day-five transfer in fresh IVF cycles decreases multiple pregnancy and abortion rates and increases implantation rates without affecting the number of clinical pregnancies achieved

The risk of birth defects among children born after vitrified blastocyst transfers and those born after fresh and vitrified cleavage-stage embryo transfers.

To explore the risk of birth defects among children born after vitrified blastocyst transfers and those born after fresh and vitrified cleavage-stage embryo transfers. A retrospective cohort study was conducted including infants born after fresh and vitrified day 3 embryo transfers and those born after vitrified day 5 or 6 blastocyst transfers from January 2005 through December 2016. The outcome measures included any birth defect, multiple birth defects and 13 individual categories of birth defects. Any birth defect occurred in 1.15% of infants born after fresh day 3 embryo transfers, 1.75% of infants born after vitrified day 3 embryo transfers, 1.60% of infants born after vitrified day 5 blastocyst transfers and 1.10% of infants born after vitrified day 6 blastocyst transfers. There was no difference in the risk of birth defects between vitrified blastocyst-stage transfers and vitrified cleavage-stage transfers (including day 5 vs. day 3 and day 6 vs. day 3) among all births or in only singletons or twins. For infants born after cleavage-stage embryo transfers at day 3, there was no difference in the risk of birth defects between fresh embryo transfers and vitrified embryo transfers among all births or in only singletons or twins. Transfer of vitrified day 5 or 6 blastocysts does not increase the risk of birth defects compared with vitrified day 3 embryos. However, randomized control trials and follow-up studies of the long-term outcome of children born after blastocyst-stage transfers are needed to confirm the clinical safety of extending embryo culture to the blastocyst stage.

Improved outcomes after blastocyst-stage frozen-thawed embryo transfers compared with cleavage stage: a Society for Assisted Reproductive Technologies Clinical Outcomes Reporting System study

To investigate whether there is a difference in obstetrical and perinatal outcomes in blastocyst frozen-thawed embryo transfers (FETs) compared with cleavage-stage FET. A retrospective cohort study. Not applicable. Women undergoing autologous FETs at either the blastocyst stage (n = 118,572) or the cleavage stage (n = 117,619) reported to the Society for Assisted Reproductive Technology in the years 2004-2013. None. Live birth, gestational age, birth weight, miscarriage. After controlling for confounders, there were a 49% increased odds of live birth after blastocyst-stage FET compared with cleavage-stage FET (odds ratio [OR] = 1.49; 95% confidence interval [CI], 1.44, 1.54). Additionally, blastocyst FET was associated with a 68% (OR = 1.68; 95% CI, 1.63, 1.74) increased odds of clinical pregnancy and an 7% (OR = 0.93; 95% CI, 0.88, 0.92) decreased odds of miscarriage. There was also a 16% increased odds of preterm delivery (OR = 1.16; 95% CI, 1.06, 1.27) after blastocyst FET but no difference in birth weights. In patients undergoing FET, blastocyst-stage transfer is associated with higher live-birth rates when compared with cleavage-stage transfers. Furthermore, perinatal outcomes are similar between the groups.

No advantage of fresh blastocyst versus cleavage stage embryo transfer in women under the age of 39: a randomized controlled study.

Is there a difference in implantation and pregnancy rates between embryos transferred electively at cleavage or blastocyst stage in infertile women ≤ 38years with at least four zygotes on day 1 post retrieval? A randomized clinical trial was conducted in a single tertiary care hospital with a sample size of 194 patients in each arm for a total population of 388 women. Patients less than 39years of age with more than three fertilized oocytes and less than four previous assisted reproductive technology (ART) attempts were inclusion criteria. The two groups were similar for age, years of infertility, indication to treatment, basal antimüllerian hormone and FSH, number of previous ART cycles, primary or secondary infertility, type of induction protocol, days of stimulation, total gonadotrophin dose, and estradiol (E2) and progesterone (P) levels at trigger. No statistically significant differences were found in terms of number of retrieved oocytes, inseminated oocytes, fertilization rate, canceled transfers (7.73% in blastocyst and 3.61% in cleavage stage group), and cycles with frozen embryos and/or oocytes. Although a higher number of fertilized oocytes were in the blastocyst stage group (6.18 ± 1.46 vs 5.89 ± 1.54, p = 0.052), a statistically greater number of embryos/randomized cycle were transferred at cleavage stage (1.93 ± 0.371) compared with the number of transferred blastocysts (1.80 ± 0.56), probably due to the number of embryos not reaching blastocyst stage (3.09%). The implantation rate (28.37 vs 25.67%), pregnancy rate per cycle (36.06 vs38.66%), transfer (39.66 vs 40.11%), spontaneous abortions (19.72% vs 12.00%), delivery rate per cycle (27.84 vs 32.99%), and transfer (30.17 vs 34.22%) were not significantly different between the blastocyst and cleavage stage groups. The twin delivery rate was higher in the blastocyst stage group, although not significant (42.59 vs 28.12%). The mean numbers of frozen blastocyst (2.30 ± 1.40 vs 2.02 ± 1.00) and frozen oocytes (7.09 ± 3.55vs 6.79 ± 3.26) were not significantly different between the two groups. Fresh blastocyst-stage transfer versus cleavage-stage transfer did not show any significant difference in terms of implantation and pregnancy rate in this selected group of patients. A high twin delivery rate in both groups (35.59%) was registered, and although not significant, they were higher in the blastocyst transfer group (42.59 vs 28.12%). Our conclusion supports considering single embryo transfer (SET) policy, even in cleavage stage in patients younger than 39years with at least four zygotes. ClinicalTrials.gov registration number NCT02639000.

What is the optimal timing of embryo transfer when there are only up to two embryos at cleavage stage?

Not only has there been a debate whether embryo transfer should be performed at the cleavage stage or at the blastocyst stage but there is also uncertainty regarding when to transfer if there are only one or two embryos at the cleavage stage. The aim of this study was to compare the pregnancy rate of day 3 transfers vs. blastocyst stage transfers in patients who had only one or two embryos at the cleavage stage on day 3.

The slow growing embryo and premature progesterone elevation: compounding factors for embryo-endometrial asynchrony

Is there an association of progesterone (P4) on the day of trigger with live birth in autologous ART transfer cycles on day 5 versus day 6? P4 had a greater negative effect on live birth in day 6 fresh transfers compared to day 5 fresh transfers. Premature P4 elevation is associated with lower live birth rates in fresh autologous ART cycles, likely due to worsened endometrial-embryo asynchrony. Few studies have evaluated whether the effect of an elevated P4 on the day of trigger is different on live birth rates with a day 5 compared to a day 6 embryo transfer. This was a retrospective cohort study with autologous IVF cycles with fresh embryo transfers on day 5 and day 6 from 2011 to 2014. A total of 4120 day 5 and 230 day 6 fresh autologous embryo transfers were included. The primary outcome was live birth, defined as a live born baby at 24 weeks gestation or later. Patients from a large private ART practice were included. Analysis was performed with generalized estimating equations (GEE) modeling and receiver operating characteristic (ROC) curves. Day 6 transfers were less likely to have good quality embryos (73% versus 83%, P < 0.001) but the cohorts had similar rates of blastocyst stage transfer (92% versus 91%, P = 0.92). Live birth was less likely in fresh day 6 versus day 5 embryo transfers (34% versus 46%, P = 0.01) even when controlling for embryo confounders. In adjusted GEE models, the effect of P4 as a continuous variable on live birth was more pronounced on day 6 (P < 0.001). Similarly, the effect of P4 > 1.5 ng/ml on day of trigger was more pronounced on day 6 than day 5 (P < 0.001). Day 6 live birth rates were 8% lower than day 5 when P4 was in the normal range (P = 0.04), but became 17% lower when P4 was > 1.5 ng/ml (P < 0.01). ROC curves for P4 predicting live birth demonstrated a greater AUC in day 6 transfers (AUC 0.59, 95% CI 0.51-0.66) than day 5 (AUC 0.54, 95% CI 0.52-0.55). Interaction testing of P4 × day of embryo transfer was highly significant (P < 0.001), further suggesting that the effect of P4 was more pronounced on day 6 embryo transfer. In fresh oocyte retrieval cycles with elevated P4, a subsequent 760 frozen-thaw transfers did not demonstrate a difference between embryos that were frozen after blastulation on day 5 versus 6. Limitations include the retrospective design and the inability to control for certain confounding variables, such as thaw survival rates between day 5 and day 6 blastocysts. Also, the data set lacks the known ploidy status of the embryos and the progesterone assay is not currently optimized to discriminate between patients with a P4 of 1.5 versus 1.8 ng/ml. This study suggests further endometrial-embryo asynchrony when a slow growing embryo is combined with an advanced endometrium, ultimately leading to decreased live births. This suggests that premature elevated P4 may be a factor in the lower live birth rates in day 6 fresh embryo transfers. Further studies are needed to evaluate if a frozen embryo transfer cycle can ameliorate the effect of elevated P4 on the day of trigger among these slower growing embryos that reach blastocyst staging on day 6. No external funding was received for this study. There are no conflicts of interest to declare. Not applicable.

Obstetrical and perinatal outcomes following blastocyst transfer compared to cleavage transfer: a systematic review and meta-analysis.

Is blastocyst transfer safe when compared to cleavage stage embryo transfer regarding obstetric and perinatal outcomes? The clinical equipoise between blastocyst and cleavage stage embryo transfer remains as the evidence associating blastocyst transfer with some adverse perinatal outcomes is of low/very low quality. Extended embryo culture to the blastocyst stage provides some theoretical advantages and disadvantages. While it permits embryo self-selection, it also exposes those embryos to possible harm due to the in vitro environment. Both effectiveness and safety should be weighed to permit evidence-based decisions in clinical practice. This is a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies reporting perinatal outcomes for singletons comparing the deliveries resulting from blastocyst and cleavage stage embryo transfer. Observational studies were included because the primary outcomes, perinatal mortality and birth defects, are rare and require a large number of participants (>50 000) to be properly assessed. The last electronic searches were last run on 11 March2016. There were 12 observational studies encompassing 195 325 singleton pregnancies included in the study. No RCT reported the studied outcomes. The quality of the included studies was evaluated according to the Newcastle-Ottawa Scale and the quality of the evidence was evaluated according to GRADE criteria. Blastocyst stage transfer was associated with increased risks of preterm birth (<37 weeks), verypreterm birth (<32 weeks), large for gestational age and perinatal mortality, although the latter was only identified from one study. Conversely, blastocyst stage transfer was associated with a decrease in the risks of small for gestational age and vanishing twins, although the latter was reported by only one study. The observational nature of the included studies and some inconsistency and imprecision in the analysis contributed to decreasing our confidence in the estimates. Due to the overall low quality of available evidence, the clinical equipoise between cleavage stage and blastocyst transfer remains. More large well-conducted studies are needed to clarify the potential risks and benefits of blastocyst transfer. As this review was initiated to support global recommendations on best practice, and in light of the challenges in lower resource settings to offer extended culture to blastocyst stage, it is critical to take into consideration these obstetric and neonatal outcomes in order to ensure any recommendation will not result in the overburdening of existing maternal and child health care systems and services. No external funding was either sought or obtained for this study. The authors have no competing interests to declare. CRD42015023910.

Cumulative live birth rates after fresh and vitrified cleavage-stage versus blastocyst-stage embryo transfer in the first treatment cycle.

Do cumulative live birth rates differ between single cleavage-stage Day 3 transfer and single blastocyst-stage Day 5 transfer? Cumulative live birth rates after Day 3 and 5 transfers were similar in young patients when the vitrified embryo transfers were also taken into account. Previous evidence has shown that the probability of live birth following IVF with a fresh embryo transfer is significantly higher after blastocyst-stage Day 5 transfer. However, because the introduction of vitrification has enhanced the survival of cryopreserved embryos and improved pregnancy rates, the optimal outcome measure for this comparison should now be cumulative live birth rates, as these include the eventual contribution of vitrified-warmed embryos. Our retrospective study included first IVF/ICSI cycles performed between January 2010 and December 2013 at a tertiary care centre. All patients were scheduled for fresh single embryo transfer, either on Day 3 (n=377) or on Day 5 (n=623). Both IVF and ICSI cycles were included and the sperm used were either fresh or frozen partner ejaculates, or frozen donor ejaculates. The primary outcome was cumulative live birth (after 24 weeks) rate per started cycle, including the eventual contribution of vitrification until the birth of a first child. Live birth rates per started cycle were significantly lower after transferring the fresh single cleavage-stage embryo, compared to a blastocyst (31.3% and 37.8%, respectively, P =0.041). Furthermore, the number of embryo transfers necessary until the first live birth was significantly lower for blastocyst-stage embryos (P <0.001). However, the cumulative live birth rates were 52.6% for cleavage-stage and 52.5% for blastocyst-stage transfers (P =0.989). The extrapolation of the results is limited by the retrospective nature of the study. Furthermore, the analysis was restricted to patients under 36 years of age undergoing their first treatment cycle. These results deserve further clinical consideration in terms of time and cost efficiency. A subsequent analysis of the neonatal outcomes is necessary to confirm the safety of treatment cycles using extended culture. No external funding was received and there are no conflicts of interest to declare.

Are we transferring too many embryos in the most favorable group of fresh autologous ivf cycles: a 2013 update

Our group has reported a high rate of non-compliance with the American Society for Reproductive Medicine/Society for Assisted Reproductive Technologies (ASRM/SART) embryo transfer (ET) guidelines in first fresh autologous cycles from 2011-2012, especially for blastocyst stage transfers. This led to an unacceptable multiple pregnancy rate (MPR) in patients <35 years. The objective of this study was to determine the noncompliance rate for first fresh IVF cycles with excess cryopreserved embryos, using the 2013 SART data and assess the impact of this on MPR in this most favorable group of patients.

Pregnancy outcome after blastocyst stage transfer comparing to early cleavage stage embryo transfer

Blastocyst transfer has been introduced as an alternative for improving the chance for in vitro fertilizations (IVF) implantation. The present study was to evaluate pregnancy rates when embryo transfer was performed either on day 2–3 (cleavage stage) or on day 4–5 (blastocyst stage). This randomized clinical trial included 118 infertile women. All the study subjects underwent controlled ovarian stimulation using a long protocol and randomized into two groups. BS group (n = 57), the culture was extended to day 5 (blastocyst stage) and in the CS-group (n = 61), embryo culture was continued to day 3 (cleavage stage). Ongoing pregnancies, abortion, implantation rate were evaluated. No significant differences were seen in the pregnancy rate between the two groups (33.3% in the BS group versus 27.9% in the CS group; p = 0.519). Abortion, implantation rate in two groups are not significant. Despite the lack of statistical difference between the two study groups, our data suggest that blastocyst transfer may be associated with a higher pregnancy and an overall better implantation rates. However, further studies with larger sample size are mandatory to confirm these findings.

How compliant are member clinics in following ASRM/SART blastocyst stage transfer guidelines?: an analysis of 34,140 fresh first autologous cycles from the SART registry

ASRM and SART regularly update guidelines on the maximum number of embryos to transfer per cycle in various age groups. Providers/patients, however, often elect to transfer more than the recommended number of embryos, which can lead to an unnecessary increase in the number of multiple pregnancies. The objective of this study was to determine the prevalence of blastocyst transfer cycles that do not conform to current recommended embryo transfer (ET) limits and assess the impact of noncompliance on multiple pregnancy rate (MPR) in first IVF cycles with a favorable prognosis. Retrospective cohort study. 34,140 first fresh autologous IVF cycles in women under 43 undergoing blastocyst stage (day 5 and 6) ET from the 2011-2012 SART registry were stratified into cohorts based on ASRM defined age bins. Cycles were classified as compliant (C) or noncompliant (NC) based on their adherence to published 2009/2013 guidelines based on first IVF cycles with a favorable prognosis. Main outcomes were the percentage of C and NC cycles in each age group as well as the MPR (≥2 fetal heart beats on ultrasound) in each of these groups. Secondary outcomes included clinical pregnancy rate (CPR), live birth rate (LBR), and singletons. Data were analyzed using two-sided Welch's t-test for each age category and the Benjamini-Hochberg procedure was used to control the false discovery rate. The vast majority of cycles performed in women <35 were NC (71%) and resulted in significantly higher CPR, LBR and MPR compared to C cycles. When women under 35 underwent a NC ET cycle, MPR was significantly higher compared to C cycles. Far fewer cycles were NC in the older age groups. In women >35, NC cycles demonstrated lower LBR but significantly higher MPR (Table). In a sub-analysis of C cycles among patients 35-37 and 38-40 years, transferring two embryos resulted in a higher LBR than transferring one embryo (50.4% vs. 40.9%, p<0.001 and 42.1% vs. 30%, p<0.001, respectively). However, the MPR was also significantly higher in each of these age groups for two versus one embryo transfer (40.5% vs. 1.7%, p<0.001 and 34% vs. 2%, p<0.001, respectively).Tabled 1Pregnancy Outcomes and Multiple Pregnancy Rate based on Age and Number of Embryos Transferred<35yo35-37yo38-40yoCompliant (1 ET)Noncompliant (≥2 ET)Compliant (1-2 ET)Noncompliant (≥ 3 ET)Compliant (1-2 ET)Noncompliant (≥ 3 ET)n61211500868644043524897Compliance (%)297194.45.679.720.3ET (mean)121.73.11.83.1ET (range)12-51-23-51-23-7CPR (%)57.664.8 **5846 **51.645.7 *LBR (%)4956.4 **47.938.4 **39.833.3 **Singletons (%)97.251.7 **68.252 **70.964.3 *MPR (%)2.848.3 **31.848 **29.135.7 **=p Open table in a new tab *=p Among all age groups, women <35 are at highest risk of undergoing a NC cycle resulting in a significantly higher MPR. Adherence to ET guidelines in women under 35 would result in an immediate and significant reduction in national MPR. Furthermore, if the optimal measure of success of IVF is a singleton delivery, guidelines in women over 35 need to be modified to recommend single blastocyst transfer in first cycles.

Zygote intrafallopian tube transfer versus intrauterine cleavage or blastocyst stage transfer after intracytoplasmic sperm injection cycles in patients with repeated implantation failure: A prospective follow-up study.

This study aimed to compare the outcomes between zygote intrafallopian transfer (ZIFT) with intrauterine day-3 (cleavage stage) embryo transfer and intrauterine day-5 (blastocyst stage) embryo transfer in patients undergoing intracytoplasmic sperm injection. This prospective study was performed at Royan Institute, Tehran, Iran, between January 2012 and January 2014. Two hundred fifty women with more than three unexplained implantation failures were divided non-randomly into three groups according to embryonic age and methods used as follows: (i) intrauterine cleavage-stage embryo transfer (n = 100); (ii) intrauterine blastocyst-stage embryo transfer (n = 50); and (iii) ZIFT (n = 100). Implantation, clinical pregnancy, miscarriage and live birth rates were our main outcomes. Patients' characteristics and ovarian response were comparable among the three groups. Implantation rate (56.1% vs 27.9%) was significantly higher in the blastocyst group as compared to the ZIFT group; however, clinical pregnancy rate (38% vs 23%) was not statistically significantly different between the two groups, but due to the significantly higher miscarriage rate (34.7% vs 5.3%) in the ZIFT group, the live birth rate was significantly higher in the blastocyst group (P = 0.04). No significant differences were found between the cleavage-stage and blastocyst-stage groups in terms of implantation, clinical pregnancy, miscarriage and live birth rates. We do not recommend the use of the ZIFT procedure for patients with repeated implantation failures. It seems that replication of cleavage- or blastocyst-stage embryo transfer is more efficient and affordable.

Early maternal serum ß-human chorionic gonadotropin (ß-hCG) levels and sex-related growth difference of IVF embryos.

Maternal serum ß-human chorionic gonadotropin (ß-hCG) represents the trophoblastic cell mass and is an indirect measurement of embryo development at early implantation stage. Studies in animals and human embryos detected sex-related growth differences (SRGD) in favour of male embryos during the pre-implantation period. The purpose of our study was to correlate SRGD and maternal serum ß-hCG at 16 days after embryo transfer. We retrospectively analysed all (fresh and frozen) non-donor, single embryo transfers (SET), elective and not elective, that were performed between December 2008 and December 2013. We included ß-hCG values from day 16 after oocyte collection of pregnancies resulting in live birth. Neonatal gender was retrieved from patient files. Male and female embryos were further grouped to cleavage and blastocyst stage transfers. Regression analysis for confounding variables included maternal age, maternal body mass index (BMI), use of micromanipulation (ICSI), embryo quality (grade), assisted hatching, day of transfer and fresh or frozen embryo transfer. Seven hundred eighty-six non-donor SETs resulted in live birth. After including only day 16 serum ß-hCG results, 525 SETs were analysed. Neonatal gender was available for 522 cases. Mean maternal serum ß-hCG levels were similar, 347 ± 191 IU/L in the male newborn group and 371 ± 200 IU/L in the female group. The difference between ß-hCG levels remained insignificant after adjusting for confounding variables. Early maternal ß-hCG levels after embryo transfers did not represent SRGD in our study.

A prospective trial comparing sequential day 3/day 5 transfer with cleavage stage transfer and blastocyst stage transfer

The purpose of this study was to critically evaluate the effect of sequential embryo transfer in randomized patients undergoing assisted in vitro conception. A randomized prospective study was conducted and the outcomes of 505 patients were analyzed, of which 107 women underwent sequential embryo transfer on day 3 and day 5 (D3/D5 group), 283 women underwent day-3 embryo transfer only (D3 control group) and 115 women underwent day-5 embryo transfer only (D5 control group) in the assisted reproduction center of Lilavati Hospital, Mumbai from March 2012 to March 2013. The results showed that the clinical pregnancy rate of the D3/D5 group was significantly higher than that of the D3 group (48.5% versus 29.3%), whereas the clinical pregnancy rates of the D3/D5 and D5 groups were not significantly different (48.5% vs. 53.0%). Day-3/day-5 sequential embryo transfer yields satisfactory clinical pregnancy rates in a subset of patients with repeated implantation failures (35.2%), while avoiding cycle cancellation that happened with about 11% patients that were meant for blastocyst only transfer.

Blastocyst transfer is not associated with increased rates of monozygotic twins when controlling for embryo cohort quality

To compare monozygotic twinning (MZT) rates in patients undergoing blastocyst or cleavage-stage ET. Retrospective cohort. Academic research center. Autologous, fresh IVF cycles resulting in a clinical pregnancy from 1999 to 2014. None. Monozygotic twin pregnancy in blastocyst-stage transfer vs. cleavage-stage transfer when controlling for patient prognosis and embryo cohort quality factors. There were a total of 9,969 fresh transfer cycles resulting in a pregnancy during the study period. Of these pregnancies, 234 monozygotic twin pregnancies were identified (2.4%). Of all transfers, 5,191 were cleavage-stage and 4,778 were blastocyst-stage transfers. There were a total of 99 MZT identified in the cleavage-stage group (1.9%) and 135 MZT in the blastocyst ET group (2.4%), which was significant. Multivariable logistic regression revealed that increasing age was associated with a significant reduction in MZT, regardless of transfer order. Embryo cohort quality factors, including the number and proportion of six- to eight-cell embryos and availability of supernumerary embryos, were also significant. When controlling for patient age, time period during which the cycle took place, the number and proportion of six- to eight-cell embryos, and availability of supernumerary embryos, there was no longer a difference in MZT rate between blastocyst and cleavage transfer. Patient prognosis and embryo cohort quality seem to be major factors in MZT rate in women undergoing blastocyst transfer. Although technology-based effects cannot be excluded, patient and embryo characteristics play an important role.

A comparative study between cleavage stage embryo transfer at day 3 and blastocyst stage transfer at day 5 in in-vitro fertilization/intra-cytoplasmic sperm injection on clinical pregnancy rates.

OBJECTIVE:To evaluate the efficacy of blastocyst transfer in comparison with cleavage stage transfer.STUDY DESIGN:A randomized, prospective study was conducted in Infertility clinic, Department of Obstetrics and Gynecology, Mahatma Gandhi Hospital, Jaipur on 300 patients aged 25-40 years undergoing in-vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) cycle from May 2010-April 2011. When three or more Grade-I embryos were observed on day 2 of culture, patients were divided randomly into two study groups, cleavage stage transfer and blastocyst transfer group having 150 patients each. Primary outcomes evaluated were, Clinical pregnancy rate and Implantation rate. The results were analyzed using proportions, standard deviation and Chi-square test.RESULTS:Both the groups were similar for age, indication and number of embryos transferred. Clinical pregnancies after blastocyst transfer were significantly higher 66 (44.0%) compared to cleavage stage embryo transfer 44 (29.33%) (P < 0.01). Implantation rate for blastocyst transfer group was also significantly higher (P < 0.001).CONCLUSION:Blastocyst transfer having higher implantation rate and clinical pregnancy rate lead to reduction in multiple pregnancies.

Comparison of embryo developmental competence derived from letrozole and clomiphene citrate for ovarian stimulation in elderly infertile women

There are infertile women, or poor responders, from whom oocytes cannot be retrieved because of a low response to hormonal ovarian stimulation. Most of these patients are over 40 years old. Clomiphene citrate (CC) treatment or natural cycle may be prescribed for these women during assisted reproductive technology (ART). Recently aromatase inhibitors (AIs) have been used for ovarian stimulation instead of CC or natural cycle. Letrozole (LZ) is one of the most popular AIs, but there are few comparative studies of the LZ and CC cycles. In particular, there are few analyses of developmental competence up to blastocyst stage and blastocyst transfer. The aim of this study was to compare the CC cycle to the LZ cycle for embryo developmental ability in infertile patients over 40 years old. We screened 2310 IVF cycles between 2009 and 2012 at our clinic. All patients were over 40 years old. The patients were supplemented with either LZ (n=1137) or CC (n=1173). Mature oocytes (LZ, n=658; CC, n=996) were used for IVF on oocyte retrieval (Day 0). At Day 1, embryos were cultured and vitrified when they progressed to the expanded blastocyst stage. Vitrificated blastocysts were warmed and transferred to patients. We compared outcomes of CC cycle and LZ cycle treated patients. In the LZ cycle, cancellation rates were significantly lower than those of the CC cycle (5.4% vs. 10.6%). The rates of cycle retrieved MII oocytes were not significantly different between the two groups. The blastocyst cryopreservation rate in the LZ cycle was significantly higher than that of the CC cycle (34.7% vs. 28.8%). There was no significant difference in the pregnancy rates between the two groups (CC, 35.1%; LZ, 30.7%). LZ treatment improves IVF outcomes in elderly patients because of lower cancelation rates and higher blastocyst cryopreservation rates. LZ may be the regimen of first choice to ovarian stimulation for patients over 40 years old.

Number of embryos for transfer following in vitro fertilisation or intra-cytoplasmic sperm injection.

Multiple embryo transfer during in vitro fertilisation (IVF) increases multiple pregnancy rates causing maternal and perinatal morbidity. Single embryo transfer is now being seriously considered as a means of minimising the risk of multiple pregnancy. However, this needs to be balanced against the risk of jeopardising the overall live birth rate. To evaluate the effectiveness and safety of different policies for the number of embryos transferred in couples who undergo assisted reproductive technology (ART). We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, from inception to July 2013. We handsearched reference lists of articles, trial registers and relevant conference proceedings and contacted researchers in the field. We included randomised controlled trials (RCTs) comparing different policies for the number of embryos transferred following IVF or intra-cytoplasmic sperm injection (ICSI) in subfertile women. Studies of fresh or frozen and thawed transfer of one, two, three or four embryos at cleavage or blastocyst stage were eligible. Two review authors independently assessed trial eligibility and risk of bias and extracted the data. The overall quality of the evidence was graded in a summary of findings table. Fourteen RCTs were included in the review (2165 women). Thirteen compared cleavage-stage transfers (2017 women) and two compared blastocyst transfers (148 women): one study compared both. No studies compared repeated multiple versus repeated single embryo transfer (SET). DET versus repeated SETDET was compared with repeated SET in three studies of cleavage-stage transfer. In these studies the SET group received either two cycles of fresh SET (one study) or one cycle of fresh SET followed by one frozen SET in a natural or hormone-stimulated cycle (two studies). When these three studies were pooled, the cumulative live birth rate after one cycle of DET was not significantly different from the rate after repeated SET (OR 1.22, 95% CI 0.92 to 1.62, three studies, n=811, I(2)=0%, low quality evidence). This suggests that for a woman with a 40% chance of live birth following a single cycle of DET, the chance following repeated SET would be between 30% and 42%. The multiple pregnancy rate was significantly higher in the DET group (OR 30.54, 95% CI 7.46 to 124.95, three RCTs, n = 811, I(2) = 23%, low quality evidence), suggesting that for a woman with a 15% risk of multiple pregnancy following a single cycle of DET, the risk following repeated SET would be between 0% and 2%. Single-cycle DET versus single-cycle SETA single cycle of DET was compared with a single cycle of SET in 10 studies, nine comparing cleavage-stage transfers and two comparing blastocyst-stage transfers. When all studies were pooled the live birth rate was significantly higher in the DET group (OR 2.07, 95% CI 1.68 to 2.57, nine studies, n = 1564, I(2) = 0%, high quality evidence). This suggests that for a woman with a 40% chance of live birth following a single cycle of DET, the chance following a single cycle of SET would be between 22% and 30%. The multiple pregnancy rate was also significantly higher in the DET group (OR 8.47, 95% CI 4.97 to 14.43, 10 studies, n = 1612, I(2) = 45%, high quality evidence), suggesting that for a woman with a 15% risk of multiple pregnancy following a single cycle of DET, the risk following a single cycle of SET would be between 1% and 4%. The heterogeneity for this analysis was attributable to a study with a high rate of cross-over between treatment arms. Other comparisons Other fresh cycle comparisons were evaluated in three studies which compared DET versus transfer of three or four embryos. Live birth rates did not differ significantly between the groups for any comparison, but there was a significantly lower multiple pregnancy rate in the DET group than in the three embryo transfer (TET) group (OR 0.36, 95% CI 0.13 to 0.99, two studies, n = 343, I(2) = 0%). In a single fresh IVF cycle, single embryo transfer is associated with a lower live birth rate than double embryo transfer. However, there is no evidence of a significant difference in the cumulative live birth rate when a single cycle of double embryo transfer is compared with repeated SET (either two cycles of fresh SET or one cycle of fresh SET followed by one frozen SET in a natural or hormone-stimulated cycle). Single embryo transfer is associated with much lower rates of multiple pregnancy than other embryo transfer policies. A policy of repeated SET may minimise the risk of multiple pregnancy in couples undergoing ART without substantially reducing the likelihood of achieving a live birth. Most of the evidence currently available concerns younger women with a good prognosis.

Extended culture and the risk of preterm delivery in singletons: confounding by indication?

Sir,Wereadwithinteresttherecentarticle(Daretal.,2013)suggestingthatsingletonsbornafterextendedculturemayhaveahigherriskofpretermdelivery than those born after Day 3 transfer. While the importance ofoptimizing embryo culture and improving obstetrical outcomes after invitro fertilization should not be underestimated, we believe this studysuffersfromaseriousmethodologicalflaw,namely‘confoundingbyindi-cation’. Due to this bias, blastocyst-stage transfer—the most effectivemeansofimprovingselectionandreducingmultiplegestation(Papaniko-laouetal.,2006)—maybeincorrectlyblamedforthissmalldifferenceinpreterm delivery risk (17.2 versus 14.1%).Theauthorshypothesizethat‘extendedculturemaycausedifferencesinimplantationandplacentation’thatpresumablypredisposetopretermdelivery. However, the differences that they attribute to extendedculture presuppose that the two populations (Day 3 transfer and Day5/6 transfer recipients) have the same a priori risk of preterm delivery.In fact,this is unlikely to be the case.Itiswellknownthatelectivesingleembryotransfer(eSET)isunderu-tilized.WhileeSETaccountedforonly4.0%ofcyclesinCanadain2006(Gunbyet al.,2011), 20.2%of theDay5/6deliveriesin this study wereafter SET, compared with only 5.8% in the Day 3 group. Patients whohaveacontraindicationtomultiplegestationduetoapriorpretermde-livery, cervical incompetence, uterine anomalyor medical complicationalmost universally receive eSET and prior research has demonstratedthat, likely due to these underlying factors, SET recipients may be atincreased risk for preterm delivery (Grady et al., 2012). Even adjustingfor the number of embryos transferred, as was performed by Daret al., maynot correct for this sourceof bias.Furthermore, by not including any data on the number of embryostransferred or implantation rates, it is not possible to determine theprobabilityofatermdeliverypercycleinitiated.Patientsengageininfer-tility treatment with the goal of achieving a healthy term delivery. Sincethere are significantly more deliveries per blastocyst transfer than perDay3 transfer, patients have a higher likelihood of aterm deliveryafterblastocyst transfer. Though the authors of this study and a recentstudy looking at IVF singleton deliveries in the USA (Kalra et al., 2012)take the ‘glass half-empty’ interpretation, an optimist could look atblastocyst transfer as a way to increase term deliveries, especiallywhen single blastocyst transferis employed.In order to properly assess the potential impact of extended cultureon gestational age, future studies must control for the underlying riskof preterm delivery. Otherwise we fear that the concern raised by thisstudy may have the unintended consequence of shifting more patientsto cleavage-stage, multiple embryo transfers with resulting increasedriskof preterm delivery due to multiple gestation.