Day-3 vs. Day-5 fresh embryo transfer.

OBJECTIVE: Embryo transfer on day-5 has been associated with higher success rates, therefore our IVF clinics started to extend embryo culture until blastocyst stage. This study aimed to compare the success rates of day-3 vs. day-5 embryo transfers. METHODS: We had 266 patients included, all having undergone ICSI, with 221 patients having undergone day-3 embryo transfers, and 45 patients having undergone day-5 embryo transfers. Patients with more than five good quality embryos on day-3 were chosen to prolong the culture of embryos into day-5. RESULTS: There were no significant differences in patient characteristics, including baseline LH, FSH, Prolactin and Estradiol hormone levels. In addition, there were also no significant differences in rFSH total dosage and duration of stimulation day. Final estradiol levels, number of follicles, retrieved oocytes, matured oocytes, fertilized oocytes and number of embryos were significantly higher in day-5 compared to day-3 embryo transfer groups. Number of embryos transferred on day-3, were significantly higher compared to day-5. Neither group showed any significant differences in clinical pregnancy, implantation, multiple pregnancy or living birth rates. There were no differences in birth weights and lengths, head circumstances and Apgar Scores between both groups either in singleton or twin group. CONCLUSIONS: Transferring embryos at day-3 may provide the same benefits as day-5 embryo transfers to patients. However, more embryos were required to be transferred to achieve these comparable results.

The influence of oxygen concentration during embryo culture on obstetric and neonatal outcomes: a secondary analysis of a randomized controlled trial.

STUDY QUESTION: Does oxygen concentration during 3-day embryo culture affect obstetric and neonatal outcomes? SUMMARY ANSWER: Oxygen concentration during 3-day embryo culture does not seem to affect the obstetric and neonatal outcomes measured. WHAT IS KNOWN ALREADY: Atmospheric oxygen appears to be harmful during extended embryo culture. Embryo culture conditions might therefore be a potential risk factor for subsequent fetal development and the health of future children. No data are available concerning the obstetrics and neonatal outcomes after Day 3 transfer of embryos cultured under reduced and atmospheric oxygen tensions. STUDY DESIGN, SIZE, DURATION: A secondary analysis of a previous randomized controlled trial assessing clinical pregnancy outcomes was carried out. This analysis included 1125 consecutive oocyte donation cycles utilizing ICSI or IVF and Day 3 embryo transfers between November 2009 and April 2012. The whole cohort of donated oocytes from patients who agreed to participate in the study were randomly allocated (1:1 ratio) to a reduced O2 tension group (6% O2) or an air-exposed group (20% O2) based on a computer-generated randomization list. Fresh and vitrified oocytes were used for oocyte donation. Only those pregnancies with a live birth at or beyond 24 weeks of gestation were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: Day 3 embryos were cultured in an atmosphere of 5.5% CO2, 6% O2, 88.5% N2 versus a dual gas system in air. MAIN RESULTS AND THE ROLE OF CHANCE: From the eligible 1125 cycles, 564 were allocated to the 6% O2 group and 561 cycles to the 20% O2 group. However, 50 and 62 cycles did not reach embryo transfer in the 6% and 20% O2 groups, respectively. No differences were found between 6% O2 and atmospheric O2 tension in the number of livebirths per embryo transfer (mean ± SD, 0.5 ± 0.7 versus 0.5 ± 0.7), pregnancy complications or neonatal outcomes. Both groups (6% and atmospheric O2) had similar single and twin delivery rates (40.8% versus 38.1% and 10.7% versus 12.3%, respectively). Preterm delivery rates and very preterm delivery rates (10.80% versus 13.24% and 1.25% versus 2.94%, respectively), birthweight (3229 ± 561 g versus 3154 ± 731 g), low birthweight (2.92% versus 2.45%), birth height (50.18 ± 2.41 cm versus 49.7 ± 3.59 cm), head circumference (34.16 ± 1.87 cm versus 33.09 ± 1.85 cm) and 1 min Apgar scores (8.96 ± 0.87 versus 8.89 ± 0.96) were also similar between 6% and atmospheric O2 groups, respectively. LIMITATIONS, REASONS FOR CAUTION: The number of liveborns finally analyzed is still small and not all obstetric and neonatal variables could be evaluated. Furthermore, a small proportion of the obstetric and neonatal data was obtained through a questionnaire filled out by the patients themselves. One reason for the lack of effect of oxygen concentration on pregnancy outcome could be the absence of trophectoderm cells at cleavage stage, which may make Day 3 embryos less susceptible to hypoxic conditions. WIDER IMPLICATIONS OF THE FINDINGS: Nowadays many IVF laboratories use a more physiological oxygen concentration for embryo culture. However, the benefits of using low oxygen concentration on both laboratory and clinical outcomes during embryo culture are still under debate. Furthermore, long-term studies investigating the effect of using atmospheric O2 are also needed. Gathering these type of clinical data is indeed, quite relevant from the safety perspective. The present data show that, at least in egg donation cycles undergoing Day 3 embryo transfers, culturing embryos under atmospheric oxygen concentration seems not to affect perinatal outcomes. STUDY FUNDING/COMPETING INTEREST(S): The present project was supported by the R + D program of the Regional Valencian Government, Spain (IMPIVA IMDTF/2011/214). The authors declare that they have no conflict of interest with respect to the content of this manuscript. TRIAL REGISTRATION NUMBER: NCT01532193.

The sequential embryo transfer compared to blastocyst embryo transfer in in vitro fertilization (IVF) cycle in patients with the three repeated consecutive IVF. A randomized controlled trial.

The purpose of this study was to determine the pregnancy rate in the double sequential transfer of embryos on both day 3 and day 5 compared to day 5 alone, in in vitro fertilization-embryo transfer (IVF/ET) in patients with the three repeated consecutive IVF failures. In this controlled trial, women scheduled for IVF/ET with the three repeated consecutive IVF failures were randomized to either sequential transfer of embryos on day 2 and on day 5 after ovum pick-up (group 1, n = 60) or blastocyst ET on day 5 (group 2, n = 60) as a control group. The primary outcome measures were the chemical and clinical pregnancy rate. Baseline and cycle characteristics were comparable in both groups. Chemical and clinical pregnancy rate was similar in the sequential ET group (40%) compared to the day 5 of ET group (38.3%) (p value = .85). It seems that the double ET does not increase the chance of pregnancy rate compared to blastocyst ET on day 5 in the patients with the three repeated IVF-ET failures.

Over Ten-Cell Good Embryo Transfers on Day Three have Equivalent Clinical Outcomes with Those of Eight-Cell Embryos in Female Patients Aged ≤35 Years: A Retrospective Cohort Study.

BACKGROUND/AIM: To compare the clinical outcomes between > 10- and 8-cell good quality embryos on day 3. METHODS: A retrospective study of a cohort of 459 patients was included in the fresh embryo transfer (ET) cycle group from January 2009 to April 2016. In this group, 2 good quality embryos on day 3, were transferred on corresponding dates, in 75 patients (> 10-cell embryos), and in 384 patients (8-cell embryos). Seven hundred and forty four patients, with 1 blastocyst transferred derived from > 10-cell (n = 183) or 8-cell (n = 561) good quality embryos on day 3, were assigned in the frozen ET (FET) group. RESULTS: In the ET group, the clinical pregnancy and live birth rates of the > 10-cell transfer patients were comparable with those of the 8-cell transfer group (62.67 vs. 69.27%, 60.00 vs. 59.90%, respectively); however, the miscarriage rate of > 10-cell transfers was significantly lower than that of 8-cell transfers (4.26 vs. 13.53%, p < 0.05). In the FET group, there were no statistically significant differences found in the clinical pregnancy, live birth, and miscarriage rates between one > 10-cell-derived and one 8-cell-derived blastocyst transfers (71.04 vs. 65.78%, 59.02 vs. 54.19%, and 16.92 vs. 17.62%, respectively). CONCLUSIONS: The results suggested that > 10- and 8-cell, good quality embryos on day 3, had comparable viability and clinical outcomes.

Risk of ectopic pregnancy following day-5 embryo transfer compared with day-3 transfer.

The incidence of ectopic pregnancy after IVF is increased approximately 2.5-5-fold compared with natural conceptions; however, the aetiology for this increased risk remains unclear. One proposed practice change to decrease the incidence of ectopic pregnancy is blastocyst embryo transfer on day 5 rather than cleavage-stage embryo transfer on day 3. A retrospective cohort study was conducted to compare the risk of ectopic pregnancy following fresh day-5 embryo transfer with day-3 embryo transfer among women who underwent IVF and achieved pregnancy from 1998 to 2011. There were 13,654 eligible pregnancies; 277 were ectopic. The incidence of ectopic pregnancy was 2.1% among day-3 pregnancies and 1.6% among day-5 pregnancies. The adjusted risk ratio for ectopic pregnancy from day-5 compared with day-3 transfer was 0.71 (95% confidence interval 0.46-1.10). Although this analysis included 13,654 cycles, with a two-sided significance level of 0.05, it had only 21.9% power to detect a difference between the low incidence of ectopic pregnancy among both day-3 and day-5 transfers. In conclusion, this study was not able to demonstrate a difference in the risk of ectopic pregnancy among day-3 compared with day-5 transfers.

Comparative study of pregnancy outcomes between day 3 embryo transfer and day 5 blastocyst transfer in patients with progesterone elevation.

OBJECTIVE: To explore the effects of progesterone (P) elevation on pregnancy outcomes of day 3 embryo and day 5 blastocyst transfer. METHODS: Clinical outcomes (pregnancy and ectopic pregnancy rates) following day 3 embryo and day 5 blastocyst transfer cycles were retrospectively analysed. Day 3 embryo and day 5 blastocyst transfer cycles were divided into normal P level (P ≤ 1.5 ng/ml) and P elevation group (P > 1.5 ng/ml), based on the serum P level on the day of human chorionic gonadotropin (hCG) administration. RESULTS: A total of 2868 cycles were analysed. In day 3 embryo transfer cycles (n = 2345), the clinical pregnancy rate was significantly higher in the normal P level group compared with the P elevation group (55.4% versus 46.7%, respectively) and the ectopic pregnancy rate was significantly lower in the normal P level group compared with the P elevation group (2.8% versus 7.9%, respectively). In day 5 blastocyst transfer cycles (n = 523), there were no significant differences in the clinical pregnancy and ectopic pregnancy rates between the two groups, based on the P level. CONCLUSION: These preliminary findings suggest that day 5 blastocyst transfer should be adopted for patients with P elevation on the day of hCG administration.

Application of two different synthetic sequential media for the human IVF-ET program: a prospective, randomized, and comparative study.

OBJECTIVE: Since IVF program was first established, various types of media and culture systems have been developed either in-house or commercially. The aim of this study was to compare the efficacy of in-house Maria Research Center (MRC) media to that of commercially available Sydney IVF media in human day 3 embryo transfer cycles. METHODS: Three hundred sixty nine couples were included in this prospective, randomized, and comparative study. All couples undergoing IVF treatment at the Maria Fertility Hospital were randomly assigned to either Sydney IVF (n=178) or MRC (n=191) media. RESULTS: No difference was observed between the MRC media and Sydney IVF media groups with respect to fertilization rate (74.4% vs. 75.5%). The clinical pregnancy and implantation rates of MRC media (47.1% and 20.0%, respectively) were also similar to those of Sydney IVF media (44.4% and 19.4%, respectively). However, the proportion of embryos with good quality on day 3 was significantly higher in the MRC media group than the Sydney IVF media group (50.2% vs. 43.2%) (p<0.05). CONCLUSION: MRC media were as effective as Sydney IVF media for sustaining embryo development and pregnancy rates. The present study implies that MRC media can be a suitable alternative to commercially available media for human IVF-ET program.

Application of two different synthetic sequential media for the human IVF-ET program: a prospective, randomized, and comparative study / 대한생식의학회지

OBJECTIVE: Since IVF program was first established, various types of media and culture systems have been developed either in-house or commercially. The aim of this study was to compare the efficacy of in-house Maria Research Center (MRC) media to that of commercially available Sydney IVF media in human day 3 embryo transfer cycles. METHODS: Three hundred sixty nine couples were included in this prospective, randomized, and comparative study. All couples undergoing IVF treatment at the Maria Fertility Hospital were randomly assigned to either Sydney IVF (n=178) or MRC (n=191) media. RESULTS: No difference was observed between the MRC media and Sydney IVF media groups with respect to fertilization rate (74.4% vs. 75.5%). The clinical pregnancy and implantation rates of MRC media (47.1% and 20.0%, respectively) were also similar to those of Sydney IVF media (44.4% and 19.4%, respectively). However, the proportion of embryos with good quality on day 3 was significantly higher in the MRC media group than the Sydney IVF media group (50.2% vs. 43.2%) (p<0.05). CONCLUSION: MRC media were as effective as Sydney IVF media for sustaining embryo development and pregnancy rates. The present study implies that MRC media can be a suitable alternative to commercially available media for human IVF-ET program.

A Study Comparing In Vitro Fertilization Results After Day 2 and Day 3 Embryo Transfer / 대한산부인과학회잡지

OBJECTIVE: To compare the clinical outcomes of day 2 embryo tranfer with those of day 3 embryo transfer after In Vitro Fertilization (IVF). METHODS: Medical records of 192 patients (217 cases) undergoing IVF-ET at Chonnam National University Hospital from February 1995 to July 2001 were reviewed. The number of cases of the day 2 transfer (D-2) group and the day 3 transfer (D-3) group was 152 and 65, respectively. Clinical characteristics, mean number of fertilized oocytes, frequency of embyo qualities, mean number of embyo transferred, cumulative embryo score (CES) per transfer, pregnancy rate per cycle, clinical pregnancy rate per cycle and implantation rate per transferred embyo were compared between the two groups. RESULTS: In embyo quality, grade I in D-2 group (69.5%) was much more than in D-3 group (52.3%) in number, and grade III and IV in D-3 group (9.7% and 6.2%) was much more than in D-2 group (1.0% and 0.2%). CES was significantly higher in D-3 group than in D-2 group (62.4+/-40.0 versus 49.1+/-34.2). However, there were no statistically significant differences between the two groups in number of fertilized oocytes, number of embryo transferred, pregnancy rate, implantation rate and pregnancy outcome. There were also no significant differences between the two groups in implantation and pregnancy rates according to age, under 35 vs over 35 and the presence or absence of previous IVF-ET failure. CONCLUSION: There were no difference in the pregnancy rate and implantation rate between the two groups. The CES which indicates the quality of embryo was higer in D-3 group than in D-2 group. Since this study did not show the direct effect of better quality of D-3 embryo on implantation rate and pregnancy rate, further investigation should be needed. In addition, further studies about improving culture media for embryonic development and selecting better quality embryos for delayed embryo transfer should be continued.

Cumulative Pregnancy Rate of In Vitro Fertilization and Embryo Transfer With Intracytoplasmic Sperm Injection / 대한산부인과학회잡지

OBJECTIVE: To compare the clinical outcomes between Day 2 and Day 3 embryo transfer(ET) groups in in vitro fertilization and embryo transfer(IVF-ET) with intracytoplasmic sperm injection(ICSI). METHODS: From May, 1997 to December, 1998, 174 cycles of IVF-ET with ICSI were performed and classified into two groups: Day 2 ET group(n=134) and Day 3 ET group (n=40). In Day 3 ET group, embryos fertilized after ICSI were cultured in vitro for further 24 hours in M3 media. RESULTS: There were no significant differences in the age and BMI of patients, basal serum FSH level, protocol of controlled ovarian hyperstimulation(COH), indication of ICSI, and source of sperm for ICSI between two groups. Only the number of the previous failed IVF-ET cycles was significantly higher in Day 3 ET group(p<0.05). Serum E2 level on hCG day, the numbers of oocytes retrieved after COH, oocytes fertilized after ICSI, and embryos transferred, and the rates of fertilization, cleavage, and implantation showed no significant differences. However, cumulative embryo score(CES) was significantly higher in Day 3 ET group(p<0.05). Although there were no significant differences in the rates of pregnancy per ET, spontaneous abortion, and live birth, the rates of biochemical and multiple pregnancy were significantly higher in Day 3 ET group(p<0.05). CONCLUSIONS: In IVF-ET with ICSI, the relatively higher CES may contribute to the higher risk of multiple pregnancy in Day 3 ET group, compared with the conventional Day 2 ET group.