Vitrified-warmed Blastocyst Transfer Cycles Research Articles

Maternal and perinatal outcomes in programmed versus natural vitrified-warmed blastocyst transfer cycles.

Do maternal and perinatal outcomes differ between natural and programmed frozen embryo transfer (FET) cycles? Retrospective cohort study at a university-affiliated fertility centre including 775 patients who underwent programmed or natural FET cycles resulting in a singleton live birth using blastocysts vitrified between 2013 and 2018. A total of 384 natural and 391 programmed FET singleton pregnancies were analysed. Programmed FET resulted in higher overall maternal complications (32.2% [126/391] versus 18.8% [72/384]; P < 0.01), including higher probability of hypertensive disorders of pregnancy (HDP) (15.3% [60/391] versus 6.3% [24/384]; P < 0.01), preterm premature rupture of membranes (2.6% [10/391] versus 0.3% [1/384]; P = 0.02) and caesarean delivery (53.2% [206/387] versus 42.8% [163/381]; P = 0.03) compared with natural FET. After controlling for potential confounders, including age, body mass index, parity, smoking status, history of diabetes or chronic hypertension, infertility diagnosis, number of embryos transferred and use of preimplantation genetic testing, the adjusted odds ratio for HDP was 2.39 (95% CI 1.37 to 4.17) and for overall maternal complications was 2.21 (95% CI 1.51 to 3.22) comparing programmed with natural FET groups. The groups did not significantly differ for any perinatal outcomes analysed, including birth weight (3357.9 ± 671.6 g versus 3318.4 ± 616.2 g; P = 0.40) or rate of birth defects (1.5% [6/391] versus 2.1% [8/384]; P = 0.57), respectively. Vitrified-warmed blastocyst transfer in a programmed cycle resulted in a twofold higher probability of HDP compared with transfer in a natural cycle. Natural FET cycle should, therefore, be recommended as first line for all eligible patients undergoing FET to reduce the risk of HDP.

Cell number considerations for blastocyst transfer in younger patients.

To investigate the role of the cell number at day 3 in blastocyst selection. Observational, retrospective, single-center clinical study. In part 1, 1211 single vitrified-warmed blastocyst transfer (SVBT) cycles were identified and reviewed. All the cycles were conventional in vitro fertilization (IVF) cycles and the first embryo transfer cycles. Most of patients had a risk of ovarian hyperstimulation syndrome and were young. In part 2, 864 IVF-derived blastocysts from 292 infertile couples underwent trophectoderm (TE) biopsy for preimplantation genetic testing for aneuploidies (PGT-A). No patient intervention. The first part was an analysis of the correlation between the cell number at day 3 and live birth rate (LBR) after SVBT, and the second part was an analysis of the correlation between the cell number at day 3 and euploid rate (ER) of blastocysts. In part 1, after correcting for the effects of other confounders, the cell number at day 3 had no significant effect on the LBR (OR 1.001, 95% CI 0.938-1.068). In part 2, after correcting for the effects of other confounders, the cell number at day 3 had no significant effect on the ER (OR 0.960, 95% CI 0.866-1.063). When the vitrified-warmed blastocysts obtained by conventional IVF are transferred into young patients, the cell number at day 3 is not a strong predictor of the LBR. In addition, the cell number at day 3 is not a strong predictor of ER of IVF-derived blastocysts too.

Strategies in the transfer of varying grades of vitrified-warmed blastocysts in women aged over 35 years: A propensity-matched analysis.

For in vitro fertilization, the optimal number of blastocysts to transfer according to blastocyst grade has not been well established, especially with respect to vitrified-warmed blastocyst transfer (VBT) in women aged over 35 years. This study aimed to compare the pregnancy and neonatal outcomes for three different VBT methods with variable numbers and qualities of blastocysts in women aged over 35 years. All VBT cycles were categorized into three groups according to blastocyst grade: GG (two good-quality blastocysts transferred), GP (one good-quality blastocyst transferred with one of poor quality) and GS (one good-quality blastocyst transferred). Blastocysts graded greater than or equal to 3BB were considered good quality. We conducted three 1:1 propensity score-matched analyses (GG vs GS, GP vs GS and GG vs GP) to compare the clinical pregnancy rate (CPR), live birth rate (LBR), multiple pregnancy rate (MPR), preterm birth rate and low birthweight rate. Compared to GS, GG had higher CPR and LBR; however, MPR was also higher with GG. There were no significant differences, except implantation rate and MPR between GP and GS. Although implantation rate and CPR with GG were higher than those with GP, there were no significant differences in LBR and MPR. To reduce high MPR after double blastocyst transfer methods, single good-quality blastocyst transfers are recommended in the VBT of women aged over 35 years. Transferring a good blastocyst with a poor one should be avoided because it confers no advantage.

Retrospective study of single vitrified-warmed blastocyst transfer cycles according to the presence of morphokinetic variables.

This study retrospectively assessed whether time-lapse data relating to developmental timing and morphology were associated with clinical outcomes, with the eventual goal of using morphokinetic variables to select embryos prospectively for cryopreservation. In this study, we examined the clinical outcomes of single vitrified-warmed blastocyst transfer cycles that were cultured in a time-lapse incubation system. The morphokinetic variables included uneven pronuclei, an uneven blastomere, multinucleation, and direct, rapid, and irregular division. A total of 164 single vitrified-warmed blastocyst transfer cycles were analyzed (102 cycles of regularly developed blastocysts and 62 cycles of blastocysts with morphokinetic variables). No significant differences in the age of females or the standard blastocyst morphology were found between these two groups. The regularly developed blastocysts showed significantly higher implantation and clinical pregnancy rates than the blastocysts exhibiting morphokinetic variables (30.4% vs. 9.7% and 37.3% vs. 14.5%, respectively; p<0.01). The blastocysts that exhibited morphokinetic variables showed different mean development times compared with the regularly developed blastocysts. Although morphokinetic variables are known to have fatal impacts on embryonic development, a considerable number of embryos developed to the blastocyst stage. Morphokinetic variables had negative effects on the implantation and clinical pregnancy rates in vitrified-warmed blastocyst transfer cycles. These findings suggest that blastocysts cultured in a time-lapse incubation system should be considered for selective cryopreservation according to morphokinetic variables.

Vitrified blastocyst transfer cycles with the use of only vaginal progesterone replacement with Endometrin have inferior ongoing pregnancy rates: results from the planned interim analysis of a three-arm randomized controlled noninferiority trial

To assess the noninferiority of vaginal P (Endometrin) compared with daily intramuscular P for replacement in programmed vitrified-warmed blastocyst transfer cycles and to assess the noninferiority of vaginal P in combination with intramuscular progesterone every third day compared with daily intramuscular P. Three-arm randomized controlled noninferiority study. To enable early recognition of inferiority if present, an a priori interim analysis was planned and completed once ongoing pregnancy data were available for 50% of the total enrollment goal. The results of this interim analysis are presented here. Assisted reproduction technology practice. Women undergoing transfer of nonbiopsied high quality vitrified-warmed blastocyst(s) in a programmed cycle. Vitrified-warmed blastocyst transfer with mode of P replacement determined by randomization to either: (1) 50mg daily intramuscular P only; (2) 200mg twice daily vaginal Endometrin; or (3) 200mg twice daily Endometrin plus 50mg intramuscular P every 3rd day. Live birth. The primary outcome of this interim analysis was ongoing pregnancy. A total of 645 cycles were randomly assigned to one of the three treatment arms, received at least one dose of P replacement therapy according to this assignment and underwent vitrified-warmed blastocyst transfer. These cycles were included in the intention-to-treat analysis. The study team, including the statistician, were blinded to the identity of the treatment arms, which were randomly labeled "A," "B," and "C" in the dataset. Ongoing pregnancy occurred in 50%, 47%, and 31% of cycles in arms A, B, and C respectively. Although arm C had an rate of positive hCG equivalent to the other two arms, the rate of pregnancy loss for arm C was significantly higher than for either of the two arms, resulting in a more than one-third lower rate of ongoing pregnancy. There were no statistically significant differences for any outcome tested between arms A and B. Results of a per-protocol analysis were nearly identical to those of the intention-to-treat analysis. On completion of these analyses, arm C was revealed to be the vaginal P only arm. Relative to regimens inclusive of intramuscular P, vaginal-only P replacement for vitrified-warmed blastocyst transfer results in decreased ongoing pregnancy, due to increased miscarriage, and should be avoided. Randomization to the vaginal-only arm was terminated with these findings. This trial is ongoing to assess the noninferiority of the vaginal plus every 3rd day intramuscular P arm compared with daily intramuscular P in terms of live birth. NLM identifier NCT02254577.

Effect of repeated cryopreservation on human embryo developmental potential

Repeated cryopreservation of surplus embryos from frozen-thawed cycles should occasionally be considered. The purpose of this retrospective cohort study was to evaluate the pregnancy and perinatal outcome of repeated cryopreservation by vitrification of human blastocysts derived from slowly frozen-thawed day 3 embryos. In total, 571 vitrified-warmed blastocyst transfer cycles were investigated. The vitrified-warmed blastocysts were derived from slowly frozen-thawed cleavage embryos (twice-cryopreserved group) or fresh embryos (control group) cultured to the blastocyst stage. Age, body mass index, endometrial thickness, blastocyst developmental rate and number of embryos transferred were not significantly different between twice-cryopreserved and control groups. Clinical pregnancy and implantation rates were also similar. Compared with controls, the miscarriage rate was significantly higher in the twice-cryopreserved group (33.93% versus 19.07%, P = 0.017). This resulted in a significantly lower live birth rate in the twice-cryopreserved group than in controls (29.13% versus 39.18, P = 0.038). No differences were observed in mean gestational age, birthweight and sex ratio of newborns between groups. In conclusion, acceptable clinical pregnancy outcomes may be expected from transfer of twice-cryopreserved human embryos. While the neonatal outcome is not affected, the correlation between the risk of higher pregnancy loss and repeated cryopreservation needs further investigation.

Clinical outcomes after IVF or ICSI using human blastocysts derived from oocytes containing aggregates of smooth endoplasmic reticulum

In this study the clinical and neo-natal outcomes after transfer of blastocysts derived from oocytes containing aggregates of smooth endoplasmic reticulum (SER) were compared between IVF and intracytoplasmic sperm injection (ICSI) cycles. Clinical and neo-natal outcomes of blastocysts in cycles with at least one SER metaphase II oocyte (SER + MII; SER + cycles) did not significantly differ between the two insemination methods. When SER + MII were cultured to day 5/6, fertilization, embryo cleavage and blastocyst rates were not significantly different between IVF and ICSI cycles. In vitrified-warmed blastocyst transfer cycles, the clinical pregnancy rates from SER + MII in IVF and ICSI did not significantly differ. In this study, 52 blastocysts (27 IVF and 25 ICSI) derived from SER + MII were transferred, yielding 15 newborns (5 IVF and 10 ICSI) and no malformations. Moreover, 300 blastocysts (175 IVF and 125 ICSI) derived from SER–MII were transferred, yielding 55 newborns (24 IVF and 31 ICSI cycles). Thus, blastocysts derived from SER + cycles exhibited an acceptable ongoing pregnancy rate after IVF (n = 125) or ICSI (n = 117) cycles. In conclusion, blastocysts from SER + MII in both IVF and ICSI cycles yield adequate ongoing pregnancy rates with neo-natal outcomes that do not differ from SER–MII.

Are perinatal outcomes affected by blastocyst vitrification and warming?

Transfer of cryopreserved-warmed embryos into an appropriately prepared uterus unaffected by controlled ovarian hyperstimulation is common in the practice of invitro fertilization. There is limited information on the effect of blastocyst vitrification and warming on perinatal outcomes. We sought to determine if perinatal outcomes are affected after the transfer of vitrified-warmed blastocysts compared to the transfer of fresh blastocysts, by comparing preeclampsia rate, birthweight, percentage of low birthweight, and preterm delivery rate between embryo transfer types. We performed a retrospective database cohort study of 289 fresh and 109 vitrified-warmed blastocyst transfer cycles at an academic medical center. Cycles were performed from July 2, 2009, through Dec. 8, 2014, and included infants born at ≥20 weeks gestational age, excluding donor egg cycles. We examined the association between transfer type (fresh or vitrified-warmed) and proportion of deliveries complicated by preeclampsia, preterm delivery(gestational age <37 weeks), and low birthweight (<2500 g). We assessed associations using generalized linear models, both unadjusted and adjusted, for maternal age, newborn sex, diabetes status, and parity. We observed more pregnancies complicated by preeclampsia following vitrified-warmed transfers (7.6%) compared to fresh embryo transfers (2.6%) (P= .023) (adjusted odds ratio, 3.1; 95% confidence interval, 1.2-8.4). Newborns resulting from vitrified-warmed embryo transfer cycles were similar to those resulting from fresh embryo transfer cycles with regard to low birthweight (7.4% vs 5.3%, P= .421), mean birthweight (3443 vs 3431 g, P= .865), and preterm delivery rate (9.2% vs 8.7%, P= .869). We conclude that embryo vitrification with warming may affect some perinatal outcomes since preeclampsia is increased compared to fresh blastocyst transfer. However, other perinatal outcomes such as low birthweight and preterm delivery rate are not affected. Fresh blastocyst transfers should be considered when possible as they may reduce the incidence of preeclampsia.

Trophectoderm morphology predicts outcomes of pregnancy in vitrified-warmed single-blastocyst transfer cycle in a Chinese population.

In this study, we estimated the effect of blastocoele expansion, ICM and TE quality after warming and culture on the rates of clinical pregnancy, live birth and miscarriage in vitrified-warmed single-blastocyst transfer cycle in a Chinese population. A retrospective analysis of 263 cycles of vitrified-warmed single-blastocyst transfers was performed. The blastocysts with higher TE grade significantly increased the rates of clinical pregnancy (OR = 0.59, 95 % CI, 0.35-0.99, P = 0.045, grade (A + B) vs grade C) and live birth (OR = 0.55, 95 % CI, 0.32-0.94, P = 0.029, grade (A + B) vs grade C). And the association between TE grade and the rate of live birth didn't change after the number of repeated cycles was adjusted (OR = 0.55, 95 % CI, 0.32-0.95, P = 0.033, grade (A + B) vs grade C). The number of repeated cycles was a confounding factor significantly different between the live birth and no live birth groups. By contrast, neither blastocoele expansion nor inner cell mass was statistically related to the rates of clinical pregnancy, live birth and miscarriage. Our data firstly provided the evidence that TE grading, but not ICM grading, was significantly associated with the clinical pregnancy rate and live birth rate in vitrified-warmed blastocyst transfer cycles in a Chinese population. TE morphology may help predict outcomes of pregnancy in single-blastocyst transfer.

Neonatal outcomes after the transfer of vitrified blastocysts: closed versus open vitrification system

BackgroundIncreasing evidence indicates that closed vitrification has been successfully used in the cryopreservation of human oocytes and embryos. Little information is available regarding the neonatal outcome of closed blastocysts vitrification. The aim of this study was to evaluate the effectiveness and safety of blastocyst vitrification using a high-security closed vitrification system compared with an open vitrification system.MethodsA total of 332 vitrified-warmed blastocyst transfer cycles between April 2010 and May 2012 were analyzed retrospectively. The post-thaw survival rate, implantation rate, clinical pregnancy rate, live birth rate, and neonatal outcome were recorded.ResultsThere were no significant differences between the open vitrification group and the close vitrification group regarding the post-thaw survival rate (98% versus 95.8%), clinical pregnancy rate (47.6% versus 42.2%), implantation rate (42.9% versus 35.6%), and live birth rate (39.8% versus 32.1%). In total, 332 warming cycles produced 131 healthy babies. There were no significant differences in the mean gestational age, the birth weight, and the birth length between the two groups. No adverse neonatal outcomes were observed in the children born after the transfer of closed vitrified blastocysts compared with the transfer of open vitrified blastocysts.ConclusionsThese data suggest that blastocyst vitrification using a closed vitrification device seems safe and effective with results comparable to those obtained through open vitrification.

Effect of the site of assisted hatching on vitrified-warmed blastocyst transfer cycles: a prospective randomized study

To assess the effect of assisted hatching (AH) site on the clinical outcomes in vitrified-warmed blastocyst transfer cycles. A total of 160 women who underwent vitrified-warmed blastocyst transfer cycles were randomized to either the ICM group (AH performing at the site near the inner cell mess, ICM), or the TE group (AH performing at the site opposite to the ICM). AH with laser zona drilling was performed 20 or 30 min after thawing once the ICM can be detected. Clinical pregnancy rate, implantation rate, live birth rate and the occurrence rate of monozygotic twins (MZT) pregnancy after transfer of these two groups were compared. No significant difference was found in the clinical pregnancy rate (63.8% vs. 67.5%), implantation rate (51.7% vs. 53.6%) and live birth rate (57.5% vs. 62.5%) between the ICM group and the TE group. The occurrence rate of MZT was comparable between the two groups (3.9% vs. 5.6%). The site of assisted hatching has no influence on the implantation, pregnancy and live birth rate in human vitrified-warmed blastocyst transfer cycles.

Clinical outcome of fresh and vitrified-warmed blastocyst and cleavage-stage embryo transfers in ethnic Chinese ART patients

ObjectivesThis study sought to evaluate the outcome of fresh and vitrified-warmed cleavage-stage and blastocyst-stage embryo transfers in patients undergoing ART treatment within an ethnic Chinese population.Study designWe compared the clinical results of embryo transfer on the 3rd (cleavage stage) or 5th (blastocyst stage) day after oocyte retrieval, including clinical pregnancy rates, implantation rates and multiple pregnancy rates.ResultsOur data showed that blastocyst transfer on day 5 did not significantly increase clinical pregnancy rate (41.07% vs 47.08%, p>0.05) and implantation rate (31.8% vs 31.2%, p>0.05) in patients under 35 years of age, in comparison with day 3 cleavage stage embryo transfer. In patients older than 35 years of age, the clinical pregnancy rate after blastocyst transfer was slightly decreased compared with cleavage stage embryo transfer (33.33% vs 42.31%, p>0.05). Unexpectedly, It was found that vitrified-warmed blastocyst transfer resulted in significantly higher clinical pregnancy rate (56.8%) and implantation rate (47%) compared with fresh blastocyst transfer in controlled stimulation cycles (41.07% and 31.8%, respectively). For patients under 35 years of age, the cumulative clinical pregnancy rate combining fresh and vitrified-warmed blastocyst transfer cycles were significantly higher compared to just cleavage-stage embryo transfer (70.1% versus 51.8%, p<0.05). However, the cumulative multiple pregnancy rates showed no significant difference between the two groups.ConclusionsIn an ethnic Chinese patient population, fresh blastocyst transfer does not significantly increase clinical pregnancy rate. However, subsequent vitrified-warmed blastocyst transfer in a non-controlled ovarian hyperstimulation cycle dramatically improves clinical outcomes. Therefore, blastocyst culture in tandem with vitrified-warmed blastocyst transfer is recommended as a favourable and promising protocol in human ART treatment, particularly for ethnic Chinese patients.

Vitrified-warmed blastocyst transfer cycles yield higher pregnancy and implantation rates compared with fresh blastocyst transfer cycles—time for a new embryo transfer strategy?

To compare the clinical outcome of fresh versus vitrified-warmed blastocyst transfer (BT) cycles. Retrospective study. Medical university affiliated hospital. Women aged less than 40 years undergoing BT cycles. Vitrification and warming of blastocyst with the Cryotop system. Clinical pregnancy rate (CPR), implantation rate (IR), and multiple pregnancy rate (MPR). In 110 fresh BT cycles versus 136 vitrified-warmed BT cycles performed from January 2007 to March 2010, the IR and CPR of vitrified-warmed BT cycles were 37.0% and 55.1%, respectively, which were statistically significantly higher than the corresponding values of 25.2% and 36.4% obtained for fresh BT cycles. Additionally, the MPR was not statistically significantly different between vitrified-warmed and fresh BT cycles when a similar number of blastocysts was transferred to patients. Vitrified-warmed BT cycles resulted in statistically significantly higher CPR and IR compared with fresh BT cycles. A new embryo transfer strategy is therefore proposed whereby fresh BT would be avoided in the initial ovarian stimulation cycle. Instead, all the patient's available blastocysts would be vitrified-warmed and transferred in subsequent cycles.

7 - Non-rhesus (D) Blood Group Isoimmunization in Obstetrics

In this study the clinical and neo-natal outcomes after transfer of blastocysts derived from oocytes containing aggregates of smooth endoplasmic reticulum (SER) were compared between IVF and intracytoplasmic sperm injection (ICSI) cycles. Clinical and neo-natal outcomes of blastocysts in cycles with at least one SER metaphase II oocyte (SER + MII; SER + cycles) did not significantly differ between the two insemination methods. When SER + MII were cultured to day 5/6, fertilization, embryo cleavage and blastocyst rates were not significantly different between IVF and ICSI cycles. In vitrified-warmed blastocyst transfer cycles, the clinical pregnancy rates from SER + MII in IVF and ICSI did not significantly differ. In this study, 52 blastocysts (27 IVF and 25 ICSI) derived from SER + MII were transferred, yielding 15 newborns (5 IVF and 10 ICSI) and no malformations. Moreover, 300 blastocysts (175 IVF and 125 ICSI) derived from SER–MII were transferred, yielding 55 newborns (24 IVF and 31 ICSI cycles). Thus, blastocysts derived from SER + cycles exhibited an acceptable ongoing pregnancy rate after IVF (n = 125) or ICSI (n = 117) cycles. In conclusion, blastocysts from SER + MII in both IVF and ICSI cycles yield adequate ongoing pregnancy rates with neo-natal outcomes that do not differ from SER–MII.