Effect of double cleavage stage versus sequential cleavage and blastocyst stage embryo transfer on clinical pregnancy rates

Objective:To compare clinical pregnancy rates following sequential day-3 and day-5 embryo transfer with double or sequential cleavage-stage transfers.Methods:This study enrolled 242 patients undergoing gonadotropin-releasing hormone antagonist protocol and fresh embryo transfer.Basal follicle stimulating hormone,luteinizing hormone,serum estradiol and anti-Müllerian hormone levels and controlled ovarian stimulation outcomes were noted.Of 242 women,135 underwent double embryo transfer on day 2 or day 3(the double group),54 women underwent sequential embryo transfer on day 2 and day 3(the D2/D3 group),and 53 underwent sequential embryo transfer on day 3 and day 5(the D3/D5 group).Clinical pregnancy rates were compared among the groups.Results:Female age,body mass index,basal follicle stimulating hormone,luteinizing hormone and estradiol levels were similar among the groups(P>0.05).The D3/D5 group had a significantly higher number of metaphaseⅡoocytes,fertilized oocytes and good quality embryos on day 3 compared with the double group and the D2/D3 group(P<0.001).Clinical pregnancy rates in the double,D2/D3 and D3/D5 groups were 26.6%(36/135),16.6%(9/54)and 37.7%(20/53),respectively.There was no significant difference in clinical pregnancy rates between the double group and the D2/D3 group(P=0.204)or the D3/D5 group(P=0.188).The D3/D5 group had significantly higher clinical pregnancy rates compared with the D2/D3 group(P=0.025).Conclusions:Sequential cleavage-stage transfer(D2/D3)or cleavage stage and blastocyst transfer(D3/D5)does not improve clinical pregnancy rates compared with double cleavage-stage embryo transfer.Although sequential transfer seems to be an effective option in certain patient populations,routine application of this technique might not be a suitable approach in an unselected population to improve assisted reproductive technology outcomes.

Perinatal outcomes of frozen-thawed embryo transfer following blastocyst-stage embryo transfer compared to those of cleavage-stage embryo transfer:analysis of 9408 singleton newborns using propensity score analysis

Objective:Regarding frozen-thawed embryo transfer(FET),there is limited consensus on whether extending embryo culture from the cleavage stage to the blastocyst stage affects perinatal outcomes.This study aimed to compare perinatal outcomes of singletons between blastocyst-stage embryo transfer(BT)and cleavage-stage embryo transfer(CT)in FET.Methods:A total of 9408 FET cycles that met the inclusion criteria were included in this retrospective cohort study between 2019 and 2022.Blastocyst-stage embryo transfers were performed in the BT group,and cleavage-stage embryo transfers were performed in the CT group.Multivariate logistic regression analyses were performed,as well as propensity score matching(PSM)to adjust for confounders.Results:After PSM,a higher risk of pre-term birth(PTB;odds ratio[OR]:1.23,95%confidence interval[CI]:1.00-1.50,P=0.048)and being large for gestational age(LGA;OR:1.16,95%CI:1.00-1.35,P=0.050)was observed in the BT group compared to that in the CT group.After stratified PSM,in the subgroup under 35 years of age,only an increased risk of LGA was observed in the BT group compared to the CT group.Perinatal outcomes in the double-embryo transfer subgroup were similar to those in the unstratified group.However,in the subgroup beyond 35 years of age and the single embryo transfer subgroup,perinatal outcomes were not statistically different between the BT and CT groups(P>0.05).Conclusions:In FET,prolonged embryo culture to the blastocyst stage increased the risk of PTB and LGA in single fetuses.However,stratified analysis based on age and the number of transferred embryos yielded different results,necessitating further mechanistic studies.

Pregnancy outcomes following supplementation of single dose GnRH agonist to sustain the luteal phase in antagonist fresh embryo transfer cycles:A multicentric prospective cohort study

Objective:To determine whether a single dose of gonadotropin-releasing hormone(GnRH)agonist administered subcutaneously in addition to the regular progesterone supplementation could provide a better luteal support in antagonist protocol fresh embryo transfer cycles.Methods:This prospective,multicentric,cohort study included total 140 women,70 in each group.Controlled ovarian stimulation was carried out as per fixed GnRH antagonist protocol.The trigger was given with hCG.In vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)was performed and day-3 embryos were transferred.Patients were divided into groups 1 and 2 based on computer generated randomization sheet.Six days following oocyte retrieval,group 1 received 0.2 mg decapeptyl subcutaneously in addition to regular progesterone support while group 2 received progesterone only.Luteal support was given for 14 days to both groups;if pregnancy was confirmed luteal support was continued till 12 weeks of gestation.The clinical pregnancy rate was the primary outcome.The implantation rate,miscarriage rate,live birth delivery rate,and multiple pregnancy rates were the secondary outcomes.Results:A total of 140 patients were analysed,70 in each group.Clinical pregnancy rates(47.1%vs.35.7%;P=0.17),implantation rates(23.4%vs.18.1%,P=0.24),live birth delivery rates(41.4%vs.27.1%,P=0.08),and multiple pregnancy rates(21.2%vs.16.0%,P=0.74)were higher in group 1 than in group 2.Group 1 had a lower miscarriage rate than group 2(5.7%vs.8.6%;P=0.75).However,these differences were not statistically significant between the two groups.Conclusions:Administration of a single dose of GnRH agonist in addition to regular natural micronized vaginal progesterone as luteal support in GnRH antagonist protocol cycles marginally improves implantation rates,clinical pregnancy rates,and live birth delivery rates.However,more studies with higher sample sizes are needed before any conclusive statements about GnRH agonist as luteal phase support can be made.

Effect of vitrification on clinical outcomes of cleavage-stage embryos with poor quality in human embryo cryopreservation

Objective: To evaluate the effect of morphologic factors on survival rate (SR), pregnancy rate (PR), and implantation rate (IR) of human embryo vitrification following frozen embryo transfer (FET) on day 3 post-ovulation.Methods: Women undergoing FET (n = 921) with embryos cryopreserved by vitrification between 2012 and 2013 were enrolled in this retrospective cohort study.Results: Embryos with >9 blastomeres yielded the highest SR of 100%. Lower SR was observed in embryos with 5 to 6 (57.5%) and 4 blastomeres (41.4%). In terms of blastomere symmetry, the SR of embryos with equally sized blastomeres was significantly higher than that of embryos with unequally sized cells (82.5%vs. 64.6%,P < 0.05). As fragmentation increased, SR decreased from 92.1% to 20.6% (P < 0.05). Significant differences were observed among groups when analyzing PR and IR according to the 3 embryonic parameters before vitrification. Embryos with 13 to 16 blastomeres yielded the highest PR (39.5%) and IR (24.1 %). The PR and IR of embryos with blastomeres of equal size were significantly higher than those with unequally sized blastomeres (36.5%vs. 21.7%, 23.7%vs. 12.4%,P < 0.05). After warming, embryos with 13 to 16 blastomeres yielded the highest PR and IR (40.9% and 24.2%, respectively). The PR and IR were observed to grow with an increase in the percentage of intact blastomeres (23.2%-38.2%, 14.2%-23.2%).Conclusions: These results show that vitrification methods do not effectively improve survival outcomes for embryos of poor quality and it is needed to develop a comprehensive vitrification protocol that considers all the practical aspects, including the current limitation regarding cleavage-stage embryos of poor quality.