[Clinical outcome after transfer of vitrified blastocysts in relation to freezing indication]. / Devenir clinique après transfert de blastocystes vitrifiés selon l'indication de congélation.

OBJECTIVES: In France, embryo thawing concern 45.8% of attempts at assisted reproductive technologies excluding artificial inseminations. This proportion is constantly increasing for various reasons. The main objective of this study is to compare the live birth rate following frozen blastocyst transfer (FBT) according to the initial indication for freezing. METHODS: This is a retrospective study including patients who underwent FBT between 01/01/2020 and 06/30/2022 at the Regional University Hospital Center of Tours. The results were compared (univariate and multivariate analyses) between the three main indications for freezing: freezing of the complete cohort of blastocysts for risk of ovarian hyperstimulation (=OHS), freezing of supernumerary blastocysts after fresh blastocyst transfer (BT) with pregnancy (=second request) or without pregnancy (=BT failure). Results have also been described for other indications. RESULTS: Among the 963 FBT cycles selected, 28% of live births by thawing were obtained, all indications of freezing combined. A significantly lower rate was identified in the FBT failure group compared to the OHS group. However, after adjustment, the results remained significant for the age of the patient on the freezing cycle but not for the indication for freezing. CONCLUSIONS: The outcome of a FBT does not seem significantly impacted by the indication of freezing considering the confounding factors. The prospective analysis of more data from a multicenter study would be necessary to confirm these results.

Fresh or frozen day 6 blastocyst transfer: is there still a question?

BACKGROUND: The Live Birth Rate (LBR) after day 5 (D5) blastocyst transfer is significantly higher than that with D6 embryos in both fresh and frozen-vitrified embryo transfer cycles, according to the most recently published meta-analyses. Therefore, for women obtaining only D6 blastocysts, the chances of pregnancy may be lower but nonetheless sufficient to warrant transferring such embryos. The best strategy for transfer (i.e., in fresh versus frozen cycles) remains unclear and there is a paucity of data on this subject. METHODS: A total of 896 couples with D6 single blastocyst transfers were retrospectively analyzed: patients receiving a fresh D6 embryo transfer (Fresh D6 transfer group, n = 109) versus those receiving a frozen-thawed D6 embryo transfer (Frozen D6 transfer group, n = 787). A subgroup comprising a freeze-all cycle without any previous fresh or frozen D5 embryo transfers (Elective frozen D6, n = 77) was considered and also compared with the Fresh D6 transfer group. We compared LBR between these two groups. Correlation between D6 blastocyst morphology according to Gardner's classification and live birth occurrence was also evaluated. Statistical analysis was carried out using univariate and multivariate logistic regression models. RESULTS: The LBR was significantly lower after a fresh D6 blastocyst transfer compared to the LBR with a frozen-thawed D6 blastocyst transfer [5.5% (6/109) vs. 12.5% (98/787), p = 0.034]. Comparison between LBR after Elective frozen D6 group to the Fresh D6 blastocyst transfers confirmed the superiority of frozen D6 blastocyst transfers. Statistical analysis of the blastocyst morphology parameters showed that both trophectoderm (TE) and inner cell mass (ICM) grades were significantly associated with the LBR after D6 embryo transfer (p < 0.001, p = 0.037). Multiple logistic regression revealed that frozen D6 thawed transfer was independently associated with a higher LBR compared with fresh D6 transfer (OR = 2.54; 95% CI: [1.05-6.17]; p = 0.038). Our results also show that transferring a good or top-quality D6 blastocyst increased the chances of a live birth by more than threefold. CONCLUSIONS: Our results indicate that transferring D6 blastocysts in frozen cycles improves the LBR, making it the best embryo transfer strategy for these slow-growing embryos. CLINICAL TRIAL NUMBER: Not applicable.

Assessing the clinical viability of micro 3 pronuclei zygotes.

PURPOSE: What is the rate of euploidy and clinical viability of embryos resulting from micro 3 pronuclei zygotes? METHODS: Retrospective cohort analysis in a single, academic in vitro fertilization (IVF) center from March 2018 to June 2021. Cohorts were separated by fertilization as either a 2 pronuclear zygote (2PN) or micro 3 pronuclear zygote (micro 3PN). PGT-A was performed to identify embryonic ploidy rates in embryos created from micro 3PN zygotes. The clinical outcomes of all transferred euploid micro 3PN zygotes were evaluated from frozen embryo transfer (FET) cycles. RESULTS: During the designated study period, 75,903 mature oocytes were retrieved and underwent ICSI. Of these, 60,161 were fertilized as 2PN zygotes (79.3%) and 183 fertilized as micro 3PN zygotes (0.24%). Of the micro 3PN-derived embryos that underwent biopsy, 27.5% (n=11/42) were deemed euploid by PGT-A, compared to 51.4% (n=12,301/23,923) of 2PN-derived embryos, p=0.06. Four micro 3PN-derived embryos were transferred in subsequent single euploid FET cycles, which includes one live birth and one ongoing pregnancy. CONCLUSION: Micro 3PN zygotes that develop to the blastocyst stage and meet the criteria for embryo biopsy have the potential to be euploid by preimplantation genetic testing for aneuploidy (PGT-A) and if selected for transfer can achieve a live birth. Although there are a significantly lower number of micro 3PN embryos that make it to blastocyst biopsy, the potential to continue to culture abnormally fertilized oocytes may give these patients a chance at pregnancy that they previously did not have.

Day after rescue ICSI: eliminating total fertilization failure after conventional IVF with high live birth rates following cryopreserved blastocyst transfer.

STUDY QUESTION: What is the impact of day after rescue ICSI (r-ICSI) on success of fresh and frozen embryo transfers? SUMMARY ANSWER: The use of r-ICSI can virtually allay fears of total fertilization failure (TFF) after conventional IVF (C-IVF) and achieve high live birth rates after frozen blastocyst transfer. WHAT IS KNOWN ALREADY: More infertility clinics have resorted to the use of ICSI in place of C-IVF in IVF treatment owing to fear of TFF or a low fertilization rate. r-ICSI has been attempted either on the day of IVF or the day after. Day after r-ICSI has proved unsuccessful in the past. STUDY DESIGN, SIZE, DURATION: A retrospective data analysis was performed of 16 608 qualifying cases between April 2010 and July 2021 conducted at a single private academically affiliated fertility clinic. PARTICIPANTS/MATERIALS, SETTING, METHODS: r-ICSI was performed principally on patients with >4 metaphase II oocytes, showing no signs of fertilization 18 h after C-IVF. C-IVF was performed on patients who had >4 million total motile sperm after preparation. r-ICSI was then performed 18-24 h after insemination, using the sperm sample from the previous day. r-ICSI fertilization rates, cryopreservation of cleavage and blastocysts embryos, and pregnancy rates after fresh or frozen transfer were then assessed. MAIN RESULTS AND THE ROLE OF CHANCE: r-ICSI was performed on 377 patients (2.3% of eligible retrieval cycles) who had a mean (±SD) female and male age of 35.9 ± 4.5 and 38.1 ± 9.1 years, respectively. A total of 5459 oocytes were initially retrieved. Of the oocytes undergoing r-ICSI, 2389 (49.5%) fertilized normally, and 205 (54.4%) patients underwent a fresh embryo transfer. The live birth rates were 23/186 (12.3%) for fresh cleavage and 5/19 (26.3%) for fresh blastocyst stage transfers. In 145 cycles a blastocyst was frozen, and 137 transfers were performed with a 64/137 (46.7%) live birth rate. Of the 377 cycles receiving r-ICSI only, 25 of the qualifying cases failed to have any fertilization, reducing TFF to 25/16 608 (0.15%). LIMITATIONS, REASONS FOR CAUTION: This was a single-center retrospective study on a specific subset of patients, which may limit its generalizability to other clinics. WIDER IMPLICATIONS OF THE FINDINGS: r-ICSI allows a second opportunity to fertilize oocytes despite poor initial outcomes. Patients who had a frozen blastocyst transfer achieved high live birth rates, indicating that a resynchronization of the embryo with the endometrium can optimize r-ICSI cases. r-ICSI allays fears of TFF when using C-IVF, providing evidence that the overuse of ICSI in patients without male factor may not be warranted. STUDY FUNDING/COMPETING INTEREST(S): The study was internally funded by Boston IVF. The authors declare that they have no conflict of interest in relation to the data published in the article. TRIAL REGISTRATION NUMBER: N/A.

PGT-A improved singleton live birth rate among all age groups of women who underwent elective single blastocyst transfer: a single-centre retrospective study.

PURPOSE: This study assessed the difference in singleton live birth rate (SLBR) between preimplantation genetic testing for aneuploidy (PGT-A) and non-PGT in patients undergoing elective single frozen blastocyst transfer (eSFBT). METHODS: This retrospective cohort study evaluated 10,701 cycles of eSFBT, including PGT-A (n = 3125) and non-PGT (n = 7576). Cycles were further stratified according to age at retrieval. The main outcome was SLBR; secondary outcomes were clinical pregnancy, conception rates, and multiple live birth rate. Confounders were adjusted using multivariable logistic regression models, and the trend test was performed using the general linear model. RESULTS: SLBR was negatively correlated with age in the non-PGT group (p-trend < 0.001) but not in PGT-A group (p-trend = 0.974). Stratified by the age, SLBR were significantly different between two groups except for the 20-24-year-old group: PGT-A vs non-PGT group in 20-24, 25-29, 30-34, 35-39 and ≥ 40-year-old subgroups were, 53.5% vs 53.2%, 53.5% vs 48.0%, 53.5% vs 43.1%, 53.3% vs 32.5%, and 42.9% vs 17.6%, respectively. In addition, after adjusting for potential confounders, SLBR still remained significantly different in all age groups except in the youngest quartile (PGT-A vs non-PGT group, 20-24: adjusted odds ratio (aOR), 1.33, 95% CI, 0.92-1.92, p = 0.129; 25-29: aOR, 1.32, 95% CI, 1.14-1.52, p < 0.001; 30-34: aOR, 1.91, 95% CI, 1.65-2.20, p < 0.001; 35-39: aOR, 2.50, 95% CI, 1.97-3.17, p < 0.001; ≥ 40: aOR, 3.54, 95% CI, 1.66-7.55, p = 0.001). CONCLUSION: PGT-A might improve SLBR among all age groups and play an increasingly important role in SLBR in older patients who underwent eSFBT.

Influence of post-thaw culture duration on pregnancy outcomes in frozen blastocyst transfer cycles.

In this study, we aimed to evaluate whether post-thaw culture duration affected the clinical outcomes of frozen blastocyst transfer. This retrospective cohort study included 3,901 frozen-thawed blastocyst transfer cycles. The cohorts were divided into two groups based on the developmental stage (day 5 [D5] and day 6 [D6]) and culture duration after thawing (short culture, 2-6 h; long culture, 18-20 h). Women in the short culture group following D6 blastocyst transfer were further divided into three subgroups depending on the post-thaw culture period (2, 4, and 6 h). The main outcomes, namely live birth rate (LBR), implantation rate (IR), clinical pregnancy rate (CPR), and abortion rate (AR), showed no statistical differences within the groups following D5 blastocyst transfer. Patients in the long culture group had significantly lower IR (35.5 vs. 45.8%, p < 0.001), CPR (45.3 vs. 56.6%, p = 0.001), and LBR (35.5 vs. 48.5%, p < 0.001) but a significantly higher AR (21.6 vs. 14.3%, p = 0.049) following D6 blastocyst transfer than those in the short culture group. However, the data failed to present the superiority of any short culture duration over another on the live birth outcome for embryos vitrified on D6 (adjusted odds ratio [aOR]: 0.96, 95% confidence interval [95% CI]: 0.53-1.73, p = 0.881, for the 4-h vs. 2-h subgroup; aOR: 1.01, 95% CI: 0.68-1.49, p = 0.974, for the 6-h vs. 2-h subgroup). Both post-thaw protocols can be applied to patients with D5 blastocysts. To optimize the pregnancy outcomes following D6 blastocyst transfer, a short culture period is recommended. Any of the three short culture durations (2, 4, and 6 h) can be applied, depending on the workflow of the laboratory.

Endometrial preparation and maternal and obstetrical outcomes after frozen blastocyst transfer.

BACKGROUND: Two types of endometrial preparation protocols are used for frozen embryo transfers in current practice: hormone replacement and the natural cycle. Endometrial preparation in the natural cycle reportedly increases the chances of live birth and decreases early pregnancy loss compared with that in the hormone replacement cycle. However, the influence of endometrial preparation on maternal and neonatal health remains unclear. OBJECTIVE: This study aimed to investigate whether the differences between hormone replacement cycle and natural cycle influence perinatal outcomes and risk of congenital anomalies in frozen-thawed blastocyst transfer fetuses or births. STUDY DESIGN: Perinatal outcomes and congenital abnormalities were compared between the natural and hormone replacement cycles. According to the timing of ovulation, frozen-thawed blastocyst transfers in the natural cycle were classified into 2 patterns: on day 4.5 (ovulation 4.5) or day 5 (ovulation 5.0) after ovulation. When the serum luteinizing hormone level was not increased on the day of the trigger, a single vitrified-warmed blastocyst transfer was performed on day 7 after the trigger (ovulation 5.0). When the luteinizing hormone level was slightly increased on the day of trigger, single vitrified-warmed blastocyst transfer was performed on day 6 after the trigger (ovulation 5.0). In total, 67,018 cycles (ovulation 4.5, 29,705 cycles; ovulation 5.0, 31,995 cycles; hormone replacement, 5318 cycles) of frozen-thawed blastocyst transfer between January 2008 and December 2017 at Kato Ladies Clinic were retrospectively analyzed. During the study period, embryo cryopreservation was performed using a vitrification method in all cycles. RESULTS: Hormone replacement cycles were associated with a higher occurrence of hypertensive disorders of pregnancy (adjusted odds ratio, 2.16; 95% confidence interval, 1.66-2.81) and placenta accreta (adjusted odds ratio, 4.14; 95% confidence interval, 1.64-10.44) compared with the natural cycle. The risks of cesarean delivery (adjusted odds ratio, 1.93; 95% confidence interval, 1.78-2.18), preterm birth (adjusted odds ratio, 1.55; 95% confidence interval, 1.25-1.93), and low birthweight (adjusted odds ratio, 1.42; 95% confidence interval, 1.18-1.73) were also higher for hormone replacement cycles. No significant difference in the risk of congenital anomalies was observed between the 2 cycles. CONCLUSION: The risk of hypertensive disorders of pregnancy, placenta accreta, cesarean delivery, preterm delivery, and low birthweight was higher in hormone replacement cycles than in natural cycles, whereas the risk of congenital anomalies was similar between both cycles. Further follow-up is needed to investigate these risks and to explore alternative endometrial preparation methods.

Blastocyst development rate influences singleton gestational age of similarly graded blastocysts after vitrified-warmed single embryo transfer cycles.

RESEARCH QUESTION: Does the development rate of blastocysts influence neonatal outcomes after blastocyst transfer cycles when the morphological score of the transferred blastocysts is similar? DESIGN: A retrospective study involving singleton live births born to 1280 women undergoing single frozen blastocyst transfers (FBTs) between January 2016 and December 2018 at a tertiary care centre. Patients were grouped into day-5 or day-6 groups depending on the development rate of blastocysts. These were further grouped into four groups based on the blastocyst inner cell mass and trophectoderm scoring: excellent (AA); good (AB or BA); average (AC, CA or BB); and poor (BC or CB). The primary outcomes were gestational age and singleton birth weight. RESULTS: Singletons resulting from day-5 single FBT were at a lower risk of preterm birth than those resulting from day-6 single FBT (adjusted OR 0.63, 95% CI 0.41 to 0.97, P = 0.035). In the day-5 good-quality blastocyst group and day-5 average-quality blastocyst group, singletons were at a lower risk of preterm birth than those resulting from day-6 groups, respectively (adjusted OR 0.22, 95% CI 0.08 to 0.63, P = 0.005 and adjusted OR 0.52, 95% CI 0.29 to 0.94, P = 0.03). CONCLUSIONS: Day-6 single FBT was associated with a higher risk of preterm birth compared with day-5 single FBT in good and average morphological scoring blastocysts. Our analysis was restricted to women with singleton births from single FBTs. Future prospective studies are required to confirm the findings.

Live birth rate following frozen-thawed blastocyst transfer is higher in high-grade day 6 blastocysts than in low-grade day 5 blastocysts.

Background: Day 5 (D5) blastocysts are generally given priority to transfer than day 6 (D6) blastocysts; however, which one should be prioritized to transfer when only low-grade D5 and high-grade D6 blastocysts are available? Methods: A large retrospective cohort study was carried out to evaluate the live birth rate (LBR) following D5 and D6 blastocysts in single frozen-thawed blastocyst transfer (FBT) during January 2014 and December 2018. A multivariate logistic regression was conducted to evaluate the combined impact of expansion day (D5 and D6) and blastocyst quality (high grade/low grade) on LBR, accounting for the potential confounding factors. The biopsied blastocysts from a consecutive PGT-A case series during February 2013 to December 2021 were analyzed in a supplementary study. Results: The LBR achieved in high-grade D6 blastocyst transfer was significantly higher than that in low-grade D5 blastocyst transfer (50.43% vs. 40.70%, aOR 1.54, 95% CI 1.05-2.26, p = 0.027). There were no significant differences in preterm birth rate, very preterm birth rate, mean live birth weight, and birth weight <1,500 g and >4,000 g between the two cohorts. As for aneuploidy analysis in PGT, there were 54.55% of euploid blastocysts (30/55) among high-grade D6 blastocysts, significantly higher than the 41.39% of euploid blastocysts (565/1,365) among low-grade D5 blastocysts (p < 0.001). Conclusions: Our data suggest that D6 blastocysts with high morphology grading are preferred than D5 blastocysts with low morphology grading when selecting blastocyst transfer to shorten the time of conception.

The perinatal outcomes of frozen-thawed blastocyst transfer are better than fresh blastocyst transfer: a systematic review and meta-analysis.

OBJECTIVES: Transfer of cryopreserved-warmed blastocysts is common in the practice of in vitro fertilization. The purpose of the study is to examine the available evidence and determine whether cryopreservation of blastocysts and subsequent frozen blastocyst transfer (BT) result in better outcomes than fresh BT. MATERIAL AND METHODS: Related studies comparing outcomes of in vitro fertilization (IVF) cycles between fresh and frozen BTs were retrieved from Medline, Cochrane Central Register of Clinical Trials, EMBASE, DARE, and CINAHL through March 2020. The outcomes of interest were preterm birth, extremely preterm birth, small for gestational age, large for gestational age, low birth weight, extremely low birth weight, caesarean section, perinatal mortality and preeclampsia. The analysis was performed using Rev Man 5.1 software. Risk ratios (RRs) and risk differences were calculated with 95% confidence intervals, to evaluate the results of each outcome. The quality of the referenced studies was assessed using the Newcastle-Ottawa scale (NOS) checklists. RESULTS: Nine studies with 42,342 women incorporated in this meta-analysis. The incidence of preterm birth (RR = 0.89, 95% CI: 0.82, 0.97) and small for gestational age (RR = 0.55, 95% CI 0.41-0.74) was low in frozen BT group. There was no significant difference in the risk of low birth weight (RR = 0.89, 95% CI: 0.67, 1.19) and perinatal mortality (RR = 1.47, 95% CI: 0.85, 2.55) between frozen-thawed and fresh BT. Singleton pregnancy after frozen BT was associated with higher large for gestational age (RR = 1.47, 95% CI: 1.37, 1.57), caesarean section rates (RR = 1.24, 95% CI: 1.13, 1.36) and preeclampsia compared with fresh BT (RR = 1.85, 95% CI: 1.22, 2.82). CONCLUSIONS: The frozen BT results in better perinatal outcomes compared with that of fresh BT. Furthermore, comprehensive randomized clinical trials comparing freeze-all with fresh BT cycles are needed to draw sound conclusions.

Which factors affect the likelihood of miscarriage after single euploid blastocyst transfer?

RESEARCH QUESTION: Which parameters affect the likelihood of miscarriage after single euploid frozen-thawed blastocyst transfer (FBT)? DESIGN: In this retrospective study, clinical and laboratory data from 1051 single euploid FBTs were evaluated. Exclusion criteria were endocrine or systemic pathologies, uterine anomalies or pathologies, unilateral or bilateral hydrosalpinx, karyotypic abnormalities (either maternal or paternal) or thrombophilia. Patients were divided into two groups according to pregnancy outcome: live birth and miscarriage. RESULTS: Body mass index (BMI) (25.98 ± 0.5 versus 24.36 ± 0.21, P = 0.019), duration of infertility (6.62 ± 0.54 versus 4.92 ± 0.18, P = 0.006) and number of previous miscarriages (1.36 ± 0.13 versus 0.79 ± 0.05, P < 0.001) were significantly higher in the miscarriage group (n = 100) than in the live birth group (n = 589). Although the trophectoderm and inner cell mass (ICM) percentage scores were not statistically different among the miscarriage and live birth groups, the percentage of day-6 biopsied embryos was significantly higher in the miscarriage group. Binary logistic regression analysis revealed that BMI (OR 1.083, 95% CI 1.013 to 1.158, P = 0.02) and number of previous miscarriages (OR 1.279, 95% CI 1.013 to 1.158, P = 0.038) were independent factors for miscarriage. Patients with elevated BMI and a higher number of miscarriages were at increased risk of miscarriage. CONCLUSION: After a single euploid FBT, BMI and number of previous miscarriages are predictors of miscarriage. Lifestyle interventions before FBT may decrease miscarriage rates.

Lower chromosomal abnormality frequencies in miscarried conceptuses from frozen blastocyst transfers in ART.

STUDY QUESTION: Are blastocyst culture and cryopreservation in ART associated with chromosomal abnormalities in miscarried products of conception (POC)? SUMMARY ANSWER: Frozen blastocyst transfer in women aged 35 years or older and frozen embryo transfer (ET) (including both cleavage-stage embryo and blastocyst) in women aged <35 years are associated with decreased frequencies of embryonic chromosomal abnormalities in miscarried POC. WHAT IS KNOWN ALREADY: Blastocyst culture and embryo cryopreservation have been previously associated with favorable ART treatment outcomes and widely applied in clinical practice. However, the association between these embryo manipulation procedures and embryonic chromosomal abnormalities has not been evaluated to the best of our knowledge. STUDY DESIGN, SIZE, DURATION: This retrospective study included a total of 720 patients who underwent IVF/ICSI, and the retained POC were obtained. A single-nucleotide polymorphism (SNP)-based chromosomal microarray analysis (CMA) of all miscarried conceptuses was performed. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was based on the Clinical Reproductive Medicine Management System/Electronic Medical Record Cohort Database (CCRM/EMRCD) at our center. In total, 720 miscarried POCs were collected from patients undergoing ART (including fresh cleavage-stage ET, fresh blastocyst transfer, frozen cleavage-stage ET and frozen blastocyst transfer), and the incidences and profiles of cytogenetic abnormalities in the miscarried conceptuses were measured via SNP-based CMA. MAIN RESULTS AND THE ROLE OF CHANCE: The chromosomal abnormality rate in POC varied from 33.7% to 66.7% among the different ET strategies. In the patients aged ≥35 years, frozen blastocyst transfer was significantly associated with a lower incidence of chromosomal aberrations in the POCs (adjusted odds ratio (aOR): 0.171 (95% CI: 0.040-0.738); P = 0.018) than fresh blastocyst transfer. In the patients aged <35 years, frozen ET was significantly associated with a lower incidence of chromosomal aberrations than fresh ET in both cleavage-stage ET cycles and blastocyst transfers cycles (aOR: 0.545 (0.338-0.879), P = 0.013; and aOR: 0.357 (0.175-0.730), P = 0.005, respectively). Trisomy was the most frequent abnormal embryonic karyotype in the different ET strategies, and its frequency significantly differed among strategies (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: This study was retrospectively designed, and we cannot draw any definite conclusions from our results regarding the adequate safety of embryo cryopreservation in ongoing pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: To our knowledge, this is the first study assessing the associations of ET strategies with the probability of miscarriage associated with embryonic chromosomal abnormalities. However, the underlying mechanism of these associations is unknown; this study may promote research concerning ET strategies and promote comprehensive consultations and recommendations for patients. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Natural Science Foundation of China (Grant No.81571409), Science and Technology Research Project of Henan (Grant No. 172102310009) and Medical Science and Technology Research Project of Henan (Grant No. 201701005). The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Clinical outcomes following frozen-thawed blastocyst transfers with blastocysts derived from different cell numbers on day 3: a retrospective cohort study.

PURPOSE: To evaluate clinical outcomes after frozen-thawed blastocyst transfer (TBT) with blastocysts which were derived from different cell numbers on day 3. METHODS: The study included 1444 patients undergoing single autologous frozen-thawed blastocyst transfer cycles, which were allocated to five groups according to the cell numbers on day 3 of the transferred blastocysts: ≤ 6-cell (n = 109), 7-cell (n = 169), 8-cell (n = 811), 9-cell (n = 136), and ≥ 10-cell (n = 219). RESULTS: The LBR of the ≤ 6-cell group was found to be statistically lower than that of the 8-cell group in single TBT cycles which had been transferred with fair quality blastocysts (defined as 4BB according to Gardner's grading scale) (41.28% vs 55.73%, P = 0.004), while the miscarriage rate was significantly higher for the ≤ 6-cell group compared with the 8-cell group (25.00% vs 13.74%, P = 0.02). No differences were found between the two groups in terms of cPR (P = 0.06). However, for blastocysts categorized as high quality according to Gardner's classification (defined as 4AA/4AB/4BA), cPR, LBR, and early miscarriage rates did not differ between the two groups (P = 0.76, P = 0.44, P = 0.40, respectively). CONCLUSIONS: When transferring blastocysts, an evaluation of the cleavage stage should be performed along with blastocyst morphology to shorten the time of conceiving.

Uterine artery Doppler in singleton pregnancies conceived after in-vitro fertilization or intracytoplasmic sperm injection with fresh vs frozen blastocyst transfer: longitudinal cohort study.

OBJECTIVE: Pregnancies conceived by frozen blastocyst transfer (FBT) have higher gestational age and weight at birth as compared to those derived by fresh blastocyst transfer. The aim of this study was to evaluate uterine artery pulsatility index (UtA-PI) in pregnancies conceived by in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) techniques using fresh vs cryopreserved blastocysts. METHODS: This was a prospective longitudinal study of viable singleton IVF/ICSI pregnancies conceived after FBT or fresh blastocyst transfer, that underwent serial ultrasound assessment at San Raffaele Hospital, Milan, Italy at 7-37 gestational weeks. We excluded pregnancies conceived using other assisted reproductive techniques such as egg donation, twin gestation, pregnancy with abnormality and those resulting in miscarriage. Pregnant women underwent ultrasound assessment at 7-10, 11-14, 18-25 and 26-37 weeks' gestation. Mean UtA-PI was measured using Doppler ultrasound according to The Fetal Medicine Foundation criteria. Pregnancy outcomes were recorded. The primary outcome was mean UtA-PI measurement and secondary outcomes were gestational age at birth, birth weight and fetal and maternal complications, including small-for-gestational age (SGA), pre-eclampsia and large-for-gestational age. UtA-PI values were made Gaussian after log10 transformation. Analysis of repeated measures using a multilevel linear mixed model (fixed effects and random effects) was performed. The possible effect of other covariates on UtA-PI Doppler values, including body mass index, SGA and pre-eclampsia, was also evaluated. RESULTS: A total of 367 IVF/ICSI cycles, comprising 164 with fresh blastocyst transfer and 203 with FBT, were included and a total of 625 observations (median, 2.5 (range, 1-4)) were collected and analyzed. The FBT group had on average 14% lower UtA-PI compared with the fresh-blastocyst-transfer group. In pregnancies with SGA fetuses, UtA-PI was 18% higher compared to pregnancies without, irrespective of the study group. Pregnancies that underwent fresh blastocyst transfer had significantly lower birth-weight centile (43.4 ± 23.3 vs 50.0 ± 23.1; P = 0.007) and a higher rate of SGA (7.9% vs 2.0%; P = 0.008) compared to those that underwent FBT. No significant differences were found between the two groups with respect to gestational age at birth and rates of preterm birth, pre-eclampsia, gestational diabetes mellitus and large-for-gestational age. CONCLUSION: UtA-PI and the proportion of SGA are lower in IVF/ICSI pregnancies conceived after FBT as compared to fresh blastocyst transfer. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Endometrial thickness on the day of the LH surge: an effective predictor of pregnancy outcomes after modified natural cycle-frozen blastocyst transfer.

STUDY QUESTION: Can the endometrial thickness (EMT) on the day of the LH surge predict pregnancy outcomes after single vitrified-warmed blastocyst transfers (SVBTs) in modified natural cycles? SUMMARY ANSWER: Decreased EMT on the day of the LH surge is associated with older female age and a shortened proliferation phase and may be associated with low live birth and high chemical pregnancy rates. WHAT IS KNOWN ALREADY: The relation between EMT on the day of embryo transfer (ET) and pregnancy outcomes remains controversial; although numerous studies reported an association between decreased EMT on the day of ET and a reduced likelihood of pregnancy, recent studies demonstrated that the EMT on the day of ET had limited independent prognostic value for pregnancy outcomes after IVF. The relation between EMT on the day of the LH surge and pregnancy outcomes after SVBT in modified natural cycles is currently unknown. STUDY DESIGN SIZE DURATION: In total, 808 SVBTs in modified natural cycles, performed from November 2018 to October 2019, were analysed in this retrospective cohort study. Associations of EMT on the days of the LH surge with SVBT and clinical and ongoing pregnancy rates were statistically evaluated. Clinical and ongoing pregnancy rates were defined as the ultrasonographic observation of a gestational sac 3 weeks after SVBTs and the observation of a foetal heartbeat 5 weeks after SVBTs, respectively. Similarly, factors potentially associated with the EMT on day of the LH surge, such as patient and cycle characteristics, were investigated. PARTICIPANTS/MATERIALS SETTING METHODS: The study includes IVF/ICSI patients aged 24-47 years, who underwent their first SVBT in the study period. After monitoring follicular development and serum hormone levels, ovulation was triggered via a nasal spray containing a GnRH agonist. After ovulation was confirmed, SVBTs were performed on Day 5. The EMT was evaluated by transvaginal ultrasonography on the day of the LH surge and immediately before the SVBT procedure. MAIN RESULTS AND THE ROLE OF CHANCE: Of the original 901 patients, 93 who were outliers for FSH or proliferative phase duration data were excluded from the analysis. Patients were classified according to quartiles of EMT on day of the LH surge, as follows: EMT < 8.1 mm, 8.1 mm ≤ EMT < 9.1 mm, 9.1 mm ≤ EMT < 10.6 mm and EMT ≥ 10.6 mm. Decreased EMT on day of the LH surge was associated with lower live birth (P = 0.0016) and higher chemical pregnancy (P = 0.0011) rates. Similarly, patients were classified according to quartiles of EMT on day of the SVBT, as follows: EMT < 9.1 mm, 9.1 mm ≤ EMT < 10.1 mm, 10.1 mm ≤ EMT < 12.1 mm and EMT ≥ 12.1 mm. A decreased EMT on the day of SVBT was associated with a lower live birth rate (P = 0.0095) but not chemical pregnancy rate (P = 0.1640). Additionally, multivariate logistic regression analysis revealed a significant correlation between EMT on day of the LH surge and ongoing pregnancy; however, no correlation was observed between EMT on the day of SVBT and ongoing pregnancy (adjusted odds ratio 0.952; 95% CI, 0.850-1.066; P = 0.3981). A decreased EMT on day of the LH surge was significantly associated with greater female age (P = 0.0003) and a shortened follicular/proliferation phase (P < 0.0001). LIMITATIONS REASONS FOR CAUTION: The data used in this study were obtained from a single-centre cohort; therefore, multi-centre studies are required to ascertain the generalisability of these findings to other clinics with different protocols and/or patient demographics. WIDER IMPLICATIONS OF THE FINDINGS: This is the first report demonstrating a significant correlation between EMT on day of the LH surge and pregnancy outcomes after frozen blastocyst transfer in modified natural cycles. Our results suggest that EMT on day of the LH surge may be an effective predictor of the live birth rate. STUDY FUNDING/COMPETING INTERESTS: This study was supported by resources from the Kato Ladies Clinic. The authors have no conflicts of interest to declare.

Fresh transfer outcome predicts the success of a subsequent frozen transfer utilizing blastocysts of the same cohort.

The objective of this retrospective analysis was to assess whether the outcomes of fresh blastocyst transfer cycles are predictive of the chances for pregnancy and live birth in subsequent frozen blastocyst transfer cycles using sibling embryos from the same retrieval. Clinical pregnancy rate (CPR) and live birth rate (LBR) per fresh and frozen blastocyst transfer were assessed. All subgroups had similar patient and cycle characteristics. Overall, CPR and LBR in fresh cycles were 44% and 29%, and in frozen were 34% and 30%, respectively. However, the CPR and LBR in frozen cycles were significantly higher in patients who were not pregnant with their fresh cycles (CPR 43% versus 22%, P=0.01; and LBR 36% versus 17%, P=0.03, respectively). When fresh cycles are unsuccessful, the remaining frozen blastocysts of the same cohort have the same chance of success in producing a clinical pregnancy as the fresh cycle (43% versus 44%). Frozen cycles following successful fresh cycles have significantly lower CPR and LBR. These data reinforce the concept that only a few embryos per cohort are competent for a live birth. During IVF cycles, many patients are fortunate enough to have excess high-quality embryos remaining after their embryo transfer. These embryos can be frozen, or cryopreserved, for later transfer. The transfer of cryopreserved embryos increases the cumulative success rates after a single IVF stimulation. Many studies have examined success rates such as clinical pregnancy rate and live birth rate in frozen embryo transfer cycles. While these frozen embryo transfer cycles have excellent success rates, they are significantly lower than success rates in cycles where a "fresh", non-frozen, embryo is transferred. Few studies have carefully examined the impact of the result of the fresh embryo transfer (whether the patient became pregnant or not) on subsequent frozen embryo transfer success. Here we show that women who are not pregnant after a fresh embryo transfer have higher success rates in subsequent frozen embryo transfer cycles that use frozen embryos generated during a single IVF cycle. In these women (not pregnant after a fresh embryo transfer), frozen embryo transfer pregnancy rates are the same as rates using fresh embryos.