Single Euploid Embryo Transfer Cycles Research Articles

Effect of postthaw change in embryo score on single euploid embryo transfer success rates

ObjectiveTo assess whether the change in embryo morphology from pre-cryopreservation to post-thaw is associated with embryo transfer success rates in single euploid embryo transfer cycles. DesignRetrospective cohort study SubjectsPatients who underwent a single euploid embryo transfer cycle from September 2016 – April 2022 were included. A decision support tool was used to assign each embryo a reproductive potential score based on the day of biopsy, expansion, and grade of trophectoderm and inner cell mass (ICM) at the time of cryopreservation and post-thaw.(1) Embryos were divided into 4 groups: Group 1 included embryos with the same score post-thaw (reference), Group 2 higher score, Group 3 lower score, and Group 4 embryos that did not re-expand post-thaw. Intervention(s)No interventions administered. Main Outcome MeasuresPrimary outcome was live birth rates per embryo transfer (LBR). Secondary outcomes included chemical pregnancy, clinical pregnancy, and clinical pregnancy loss rate. Comparative statistics and univariate analyses were performed using Kruskal-Wallis and chi-square tests. Multivariate logistic regression fitted with generalized estimating equation was performed to compare the odds of live birth between groups. ResultsA total of 7750 embryo transfers performed for 4613 patients met inclusion criteria: 5331 in Group 1, 486 in Group 2, 1726 in Group 3, and 207 in group 4. On univariate analysis, there was a statistically significant difference in LBR between groups 1, 2, 3, and 4 (55.8% vs 51.4%, 47.5%, 26.6%, p<0.0001). Logistic regression controlling for oocyte age, AMH, BMI, endometrial thickness, year of embryo transfer, time from thaw to final grading, and embryo score prior to cryopreservation showed significantly lower odds of LBR when the embryo was downgraded (OR 0.70, CI 0.62-0.79, p=<.0001) or did not re-expand (OR 0.36, CI 0.26-0.51 p=<.0001) compared with no change in score. When controlling for all variables, there was a significant increase in odds of live birth between embryos that had higher score post-thaw versus those without a change (OR 1.42, CI 1.14-1.76, p=0.002). There was no significant difference in clinical pregnancy loss rate among the 4 groups. ConclusionsThe change in quality of the embryo post-thaw is an important factor in embryo transfer success. In an adjusted analysis, the chemical pregnancy, clinical pregnancy, and LBR per embryo transfer are all significantly decreased in embryos that were downgraded or did not expand on the day of single euploid embryo transfer. Embryos that re-expand and improve their quality post-thaw have the highest odds of live birth.

Single Euploid Embryo Transfer Outcomes After Uterine Septum Resection

ObjectiveTo study pregnancy outcomes after single euploid embryo transfer (SEET) in patients who underwent prior uterine septum resection to those with uteri of normal contour, without Müllerian anomalies or uterine abnormalities including polyps or fibroids, and without a history of prior uterine surgeries. DesignRetrospective cohort study SettingSingle academic affiliated center Patients60 cycles of patients with prior hysteroscopic uterine septum resection who underwent an autologous SEET between 2012-2020 were used as the investigational cohort. A 3:1 ratio propensity score matched control cohort of 180 single euploid embryo transfer cycles from patients without a history of uterine septa were used as the control group. Intervention(s)No interventions administered. Measurements and Main ResultsPregnancy, clinical pregnancy loss, ongoing clinical pregnancy, and live birth rates in patients with history of uterine septum resection compared to matched patients without Müllerian anomalies or uterine surgeries. Patients with a prior uterine septum had significantly lower rates of chemical pregnancy (58.33% vs 77.2%, p=0.004), implantation (41.67% vs 65.6%, p=0.001), and live birth (33.33% vs 57.8%, p=0.001) per transfer. No statistical difference in clinical pregnancy loss rates was found when comparing septum patients with controls (8.33% vs 7.8%, p=0.89). ConclusionPatients with history of hysteroscopic resection who undergo in vitro fertilization are more susceptible to suboptimal clinical outcomes compared to patients with normal uteri. Early pregnancy loss rates in patients with a uterine septum are higher than in those without, however, after resection, the rates are comparable. Patients born with septate uteri require assessment of surgical intervention prior to SEET and to optimize their reproductive outcomes.

Beyond appearance: Can morphologically low-grade euploid blastocysts yield successful pregnancies?

The primary objective of this investigation is to evaluate how morphological quality affects the pregnancy outcomes in euploid embryos determined by preimplantation genetic testing for aneuploidies (PGT-A). Concurrently, as a secondary objective, we aim to identify which specific aspects of morphological evaluation exert the most significant impact on these outcomes. A retrospective analysis of 451 single euploid embryo transfer cycles at our clinic was conducted. Embryos were evaluated based on the degree of blastocyst expansion, inner cell mass (ICM), trophectoderm (TE) morphology, and the day of blastocyst vitrification. Outcomes between morphologically low-grade and high-grade embryos were compared. Additionally, the study analyzed which morphological factors most influenced pregnancy outcomes. Pregnancy outcomes were significantly lower in morphologically low-grade blastocysts compared to high-grade ones. Among the morphological evaluations, the ICM assessment was significantly associated with the live birth rate. Our study indicates that the morphological quality of euploid embryos, particularly the evaluation of the ICM, plays a crucial role in IVF-ET success.

P-542 How should we prepare the endometrium in euploid embryo transfer cycles? Modified natural or artificial endometrial preparation?

Abstract Study question Does modified natural endometrial preparation in single euploid frozen-thawed embryo transfer (FET) cycles affect chance of pregnancy and risk of miscarriage compared to artificial? Summary answer The rate of clinical pregnancy and live birth increases while the rate of miscarriage decreases in modified natural FET cycles compared to artificial FET cycles. What is known already Corpus luteum produces growth factors, angiogenic factors and vasoactive substances as well as hormones. These substances play role for initial placentation. Early maternal endocrine milieu resulting exogenous estrogen and progesterone could damage placentation, which may in turn cause miscarriage. High estradiol levels might also be responsible for decreased pregnancy rates (Wu et al 2021). Study design, size, duration This retrospective, single center study evaluated 1890 frozen single euploid embryo transfer cycles in women between 20-43 years old from January 2017 to September 2021. The study is based on data obtained from Istanbul Memorial Hospital, ART and Reproductive Genetics Center. FET cycles were analyzed in two groups according to different endometrial preparation protocol. Group A (n = 1335): modified natural FET cycles (mNat/FET) and Group B (n = 555): artificial FET cycles (AC-FET). Participants/materials, setting, methods Only good prognosis patients with ages between 20-43 years old were included. Exclusion criterias were women age 44 and above, recurrent abortion history, BMI&amp;gt;35 kg/m 2, endometrial factor, uterin factor (adenomyosis, mullerian anomaly) history. NGS was used to study trophoectoderm biopsy material in all cases. Patients demographics, cycle characteristics and pregnancy outcomes were analyzed. Main results and the role of chance We analyzed the effect of endometrial preparation methods on pregnancy outcomes between the two groups after excluding confounding factors in single euploid embryo transfer cycles. There were no significant differences in patient demographics and cycle characteristics such as age, body-mass index, infertility duration, previous IVF attempts, AMH level, daily gonadotropin dosage used, number of oocytes obtained, mature oocytes and fertilized oocytes between the two groups. There was no significant difference between the morphologic grading of the transferred embryos in both groups. However, all pregnancy outcomes were statistically significantly different in two groups. In group A, biochemical pregnancy rate (76.9% vs. 73.9%, p:0.04), clinical pregnancy rate (71% vs. 65.7%, p &amp;lt; 0.01), live birth rate (65.4% vs. 50.5%, p &amp;lt; 0.01) were significantly higher than in group B. Also, biochemical pregnancy loss rate (7.7% vs. 11%, p:0.01), clinical pregnancy loss rate (6.7% vs. 21%, p &amp;lt; 0.01), second trimester pregnancy loss rate (0.8% vs. 1.5%, p:0.04) were significantly lower compared to group B. Limitations, reasons for caution The limitation of our study include the fact that this was a retrospective analysis. Prospective randomised studies are necessary to evaluate the differences between the two groups according to pregnancy outcomes. Wider implications of the findings This study shows that pregnancy outcomes are better in patients undergoing mNat/FET even after controlling for confounding factors when comparing mNat/FET and AC-FET in single euploid FET cycles. As a result, in appropriate patients, mNat/FET with higher pregnancy rate and live birth rate should be preferred as much as feasible. Trial registration number Not applicable

Polycystic ovary syndrome increases the rate of early spontaneous miscarriage in women who have undergone single vitrified euploid blastocyst transfer

Research questionDoes polycystic ovary syndrome (PCOS) independently influence the risk of early spontaneous miscarriage in patients undergoing single euploid vitrified blastocyst transfer? DesignThis observational cohort study retrospectively analysed 1498 patients undergoing their first single euploid blastocyst frozen transfer cycles between October 2016 and December 2021. Patients were divided into PCOS and non-PCOS groups according to the Rotterdam criteria. Logistic regression analysis was conducted to study the independent effect of maternal PCOS status on early spontaneous miscarriage after single euploid embryo transfer after adjusting for confounding factors. ResultsNo statistically significant differences were identified in the rates of positive pregnancy test (68.95% versus 64.86%, P = 0.196) or clinical pregnancy (59.93% versus 57.33%, P = 0.429) between the PCOS and non-PCOS groups after single euploid embryo transfer. Early spontaneous miscarriage occurred more frequently in women with PCOS compared with controls (18.67% versus 12.00%, P = 0.023). In single euploid embryo transfer cycles, PCOS significantly increased the incidence of early spontaneous miscarriage after adjusting for some potential confounders (adjusted odds ratio 1.649, 95% CI 1.032 to 2.635, P = 0.036). ConclusionsAlthough no significant difference was observed in clinical pregnancy rates, PCOS status increased the risk of early spontaneous miscarriage after single vitrified euploid blastocyst transfer, suggesting an additional role of endometrial dysfunction affected by endocrine disorders. Further studies are needed to investigate the specific mechanisms and effective intervention strategies.

What to advise to patients with only one good quality blastocyst, PGT-A or not? Outcomes of 2064 cycles

PurposeTo evaluate whether preimplantation genetic testing for aneuploidy (PGT-A) is beneficial for patients who have only one blastocyst available for biopsy or transfer.MethodsThis retrospective study was based on 1126 single blastocyst PGT-A and 938 non-PGT-A cycles, a total of 2064 ART cycles which resulted in a single good quality blastocyst in women between 20 and 45 years old. The PGT-A group had 225 single euploid embryo transfer cycles and the non-PGT-A group had 938 single blastocyst embryo transfer cycles.ResultsIn the generalized linear mixed model (GLMM), female age and PGT-A variables were found to be significant variables on pregnancy outcomes. In the PGT-A cases, regardless of the effect of other variables, the probabilities of clinical pregnancy and live birth were found to be 3.907 and 3.448 fold higher respectively than in the non-PGT-A cases (p < 0.001). In non PGT-A cases, the probability of a total pregnancy loss was found to be 1.943 fold higher (p = 0.013).ConclusionPGT-A in the presence of a single blastocyst significantly increases clinical pregnancy and live birth rates and decreases total pregnancy losses regardless of age. In addition, aneuploid embryo transfer cancelations prevent ineffective and potentially risky transfers.

DOES THE MOSAIC EMBRYO RATIO OF PGT-A CYCLES IMPACT THE LIVE BIRTH CHANCE EVEN WHEN AN EUPLOID EMBRYO IS TRANSFERRED?

Preimplantation genetic testing for aneuploidy (PGT-A) has the potential to detect mosaicism in trophectoderm biopsies with Next-Generation Sequencing (NGS). Many couples who opted for PGT-A have both euploid and mosaic embryos in their cohort of tested embryos. However, little is known about how live birth outcomes are affected by mosaic embryo ratios of PGT-A tested embryos even though euploid embryos are transferred. This retrospective study was based on 636 PGT-A tested frozen-thawed single euploid embryo transfer cycles of which live birth outcome is known. The inclusion criteria were having at least one euploid and one mosaic embryos. Mosaicism was reported for PGT-A outcomes deviated for 20-80% from 2 chromosome copy number. Mosaic embryo ratio was defined as the number of mosaic embryos divided by the total number of blastocysts tested. This data included embryo transfers between January 2017 and March 2020 in a single ART clinic. PGT-A was done by NGS ReproSeq on IonTorrent S5 (Thermo Fisher) following trophectoderm biopsy. For the categorical data Chi-Square test was used. For continuous variables, Mann-Whitney Test was applied. Pearson correlation coefficient was used for testing how two variables are related to each other. The live birth rate of the study group was 55.8%. When data was evaluated according to the live birth status (+(n=355) or -(n=281)), no significant differences were observed for the number of oocytes collected, mature oocytes, blastocysts, biopsied blastocysts, number of euploid and mosaic embryos per cycle. Female age at the time of transfer and mosaic embryo ratio were statistically significant (p=0.015 and p=0.040, respectively). Female age for women who had reached live-birth was 0.9 years less and mosaic embryo ratio was 2.3% less when compared to women who did not reach live-birth. As only female age and mosaic embryo ratio were found to be statistically significant between the groups, their relationship with each other was tested and found to be inversely correlated, eg. with increasing female age, the mosaic embryo ratio was decreasing (r= -0.07, -0.14 to -0.01 95% CI, p=0.021). The median value for mosaic embryo ratio was 28.6%. When the study group was divided into two with 28.6% as a cut-off, the live birth rate was 10.1% higher for cycles with lower mosaic embryo ratio (62.4% vs 52.3%) (p=0.160). The live-birth rate for euploid FET with at least 1 mosaic embryo was not statistically different when compared to 1193 euploid FET of PGT-A cycles with no mosaic embryo (55.8% vs 55.3%, respectively) (p=0.839). Diverse molecular mechanisms including altered cell cycle checkpoints, aberrations of the centrosome and failed chromatid cohesion are known to contribute to mitotic errors (McCoy, 2017). Although euploid, some embryos from the same PGT-A tested cohort may be affected by the molecular pathways contributing to embryonic mosaicism.

Direct correlation between Β-HCG levels and trophectoderm morphology quality in single euploid embryo transfer cycles

Embryonic trophectoderm (TE) cells play a key role in apposition, adhesion, and invasion of the maternal endometrium during early implantation. Blastocysts are morphologically graded (expansion stage (EXP); inner cell mass (ICM); trophectoderm (TE) cells) to better understand embryonic competence and improve selection at transfer. Data is scarce regarding the relationship of embryo TE quality and early levels of β-hCG, a biochemical marker of early embryo implantation and placentation. Previously, we demonstrated that embryo TE quality does not correlate with major adverse perinatal outcomes or placental weight at delivery.

Pregnancy outcomes with frozen-thawed single euploid blastocyst transfer following IVF cycles using HCG versus GNRH agonist trigger for final oocyte maturation

It is now well known that GnRH agonist (GnRHa) when used to trigger final oocyte maturation results in early luteolysis and consequently luteal phase dysfunction in fresh autologous IVF cycles. However, with the use of adjuvant low dose hCG, pregnancy outcomes are favorable and comparable to after hCG trigger(1). This suggests that GnRHa trigger does not impact oocyte or embryo quality. Furthermore, previous studies have shown comparable live birth rates after frozen-thawed embryo transfer (FET) cycles utilizing embryos obtained from cycles triggered previously with GnRHa versus hCG (2). Previous studies have also shown comparable euploid rates after GnRHa and hCG trigger (3). However, there are no studies evaluating pregnancy rates after transfer of euploid frozen embryos derived from cycles triggered with either GnRHa or hCG trigger. To compare pregnancy outcomes for frozen-thawed single euploid embryo transfer cycles that were generated from cycles triggered with either GnRHa or hCG. Retrospective cohort study done at a single academic IVF center evaluating frozen-thawed embryo transfer (FET) cycles in which single euploid blastocysts were transferred over a four year period. All embryos were generated in preceding fresh autologous IVF cycle in which hCG or GnRHa was used for final oocyte maturation. Embryos were subsequently transferred in a medicated or natural frozen cycle (44.3% medicated cycles in hCG group v. 37.0% in GnRHa group, p>0.05.) Patients were excluded if they had >1 embryo transferred, day 3 embryo biopsies, donor oocyte cycles or dual trigger with both hCG and GnRHa. Primary outcome was ongoing pregnancy rate or live birth rate (OPR/LBR) Secondary outcomes were clinical pregnancy rate (CPR), clinical loss rate (CLR) and multiple pregnancy rate (MPR.) Student’s t-test was used to analyze continuous variables and Chi Square test was used for categorical variables. Multivariate logistical regression was performed to control for potential confounding variables. A p-value of <0.05 was considered statistically significant. A total of 215 FET cycles were included for analysis (hCG trigger, n=115 subjects; GnRHa trigger, n=100 subjects.) The GnRHa group was significantly younger (34.8 years old v. 37.2 years old) and had higher baseline AMH values (4.55 ng/ml versus 2.1 ng/ml) than the hCG group, respectively (p<0.05.) There was no significant difference in OPR/LBR (60.9% v. 62.0%), CPR (68.7% v. 69.0%), CLR (8.9% v. 10.1%) or MPR (1.3% v. 2.9%) in the GnRHa v. hCG groups, respectively. Using logistic regression to control for the significant confounding variables of age and AMH value, the adjusted odds ratio for live birth was 1.09 (95% CI 0.60-1.99, p=0.77) when GnRHa trigger was compared to hCG trigger.Table 1Pregnancy Outcomes After Single Euploid Embryo Transfer in FET cycles Triggered by hCG or GnRHa Stratified by AgeAge Group<35 YO>35 YOAll PatientsPregnancy OutcomehCG (n=29)GnRHa (n=55)hCG (n=86)GnRHa (n=45)hCG (n=115)GnRHa (n=100)IR20/29 (69.0%)41/55 (74.5%)60/86 (69.8%)29/45 (64.4%)80/115 (69.6%)70/100 (70.0%)CPR19/29 (65.5%)41/55 (74.5%)60/86 (69.8%)28/45 (62.2%)79/115 (68.7%)69/100 (69.0%)OPR/LBR16/19 (55.2%)36/55 (65.5%)54/86 (62.8%)26/45 (57.8%)70/115 (60.9%)62/100 (62.0%)CLR3/19 (15.8%)5/41 (12.2%)6/60 (10.0%)2/28 (7.1%)9/79 (8.9%)7/69 (10.1%)MPR1/19 (5.3%)1/41 (2.4%)0/60 (0.0%)1/28 (3.6%)1/79 (1.3%)2/69 (2.9%)∗ There were no significant differences in any of the variables listed above (p>0.05) Open table in a new tab ∗ There were no significant differences in any of the variables listed above (p>0.05) Our findings confirm that euploid embryos created after hCG or GnRHa trigger have the same potential for pregnancy.

Behind the bleed: analysis of the formation of subchorionic hematomas (SCH) in single euploid embryo transfer cycles by protocol

Subchorionic hematomas (SCH) are a known risk factor for poor obstetric outcomes such as spontaneous abortion and preterm delivery. We sought to determine if there is a difference in the prevalence of SCH formation in pregnancies after frozen embryo transfer (FET) between natural and programmed preparation. Retrospective cohort study of single euploid FET cycles resulting in clinical pregnancy performed between 1/2016 and 12/2017 at our center. All single euploid FET cycles utilizing Next Generation Sequencing were reviewed. Exclusion criteria included FET cycles with ploidy determined by aCGH, or cycles in which untested, mosaic, or multiple embryos were transferred. All transfer cycles that resulted in clinical pregnancy (defined as presence of gestational sac) were included. These cycles were analyzed by protocol; natural versus programmed. Patients undergoing programmed cycles took oral estradiol daily followed by either 50-75mg intramuscular progesterone (P4) in oil or vaginal P4 suppository. Patients undergoing natural cycles (or supplemented with letrozole for 5 days) were monitored until a dominant follicle reached >18mm and ovulation was confirmed followed by the initiation of vaginal P4 suppository. SCH were documented at the time of luteal ultrasound as a measurable clot behind the gestational sac. Primary outcome was the rate of SCH noted on luteal ultrasound. Statistical analyses included students T-test, chi-squared and Fischer’s Exact test where appropriate (mean +/- SD, p < 0.05). A total of 719 cycles were included; 86 natural and 633 programmed (Table 1). SCH formation was diagnosed in 12.9% (n = 93) of clinical pregnancies. The formation of SCH was significantly lower in natural cycles compared to programmed cycles (RR 0.4, 95% CI 0.17 - 0.98, p < 0.04). Relevant cycle parameters were similar between groups (Table 1); cycle day 28 estrogen was higher in programmed cycles reflecting exogenous estrogen exposure. When programmed cycles utilizing vaginal P4 only were excluded (n=36), the formation of SCH is still statistically lower in natural compared to programmed cycles (5.8% v 14.2%, RR 0.4 (0.17-0.97, p <0.03). SCH occurred less frequently in single euploid embryo transfers using a “natural” endometrial preparation. Further analyses of long term outcomes could help provide insight into estimates of obstetrical risk.Tabled 1SCH Formation in Clinical Pregnancies by FET Protocol: Patient and Cycle CharacteristicsNatural Cycles (n=86)Programmed Cycles (n=633)p - valueDeveloped SCH5.8% (5/86)14.0% (88/633)p < 0.04 RR 0.4 (0.17-0.98)Average CD SCH diagnosed44.8±3.547.7±7.3p < 0.40Age37.45±4.336.81±4.4p < 0.20CD 28 hCG202.3±147.4189.3±176.5p < 0.52CD 28 E2284.9±234.5477.4±395.2p < 0.0001CD 28 P426.4±11.326.7±17.9p < 0.89Transfer Difficulty Marked “Easy” by Provider91.9% (79/86)95.6% (605/633)p < 0.13 RR 1.84 (0.83-4.1)Endometrial Thickness (mm)8.8±1.510.4±2.4p < 0.54 Open table in a new tab

Serum progesterone levels greater than 20ng/dl on day of embryo transfer are associated with lower live birth and higher pregnancy loss rates.

Progesterone (P4) is essential for support of the endometrium and implantation of an embryo in the normal menstrual cycle. In programed frozen embryo transfer cycles using exogenous P4 is necessary, as the endogenous production of P4 requires a functioning corpus luteum that is not present in programed cycles. To date, there is continuing debate about ideal serum estradiol and P4 values in frozen embryo transfer cycles. Patients underwent single euploid embryo frozen transfer cycles from 2010 to 2013 at a single large academic center. Patients using donor oocytes and patients with changes in progesterone dose during the cycles in question were excluded. All cycles were programed and intramuscular P4 was used exclusively. Only patients administering the same daily dose of P4 throughout the cycle were included (N = 213 patients). Main outcomes were ongoing pregnancy/live birth rates (OPR/LBR), clinical pregnancy rates (CPR), and spontaneous abortions/biochemical pregnancies. CPR was defined by the presence of a sac on 1st trimester ultrasound. Missed abortions were calculated per pregnancy with a sac. Receiver operator characteristic curves (ROC curves) and chi-squared tests were performed for statistical analysis. Two groups based on day 19 P4 levels were compared (group A, P4 < 20ng/ml; group B, P4 > 20ng/ml). OPR/LBRs were 65 vs. 49%, group A vs. B, p value = 0.02, RR = 1.33 (1.1-1.7). Missed abortion and biochemical rates were higher in group B as opposed to group A, 27 vs. 12%, p = 0.01, RR = 0.45(0.24-0.86). When P4 was stratified into five groups based on nanogram per milliliter of progesterone on day 19 (10-15, 15-20, 20-30, 30-40, and >40), there was a trend downward in OPR/LBR (70, 62, 52, 50, and 33%, respectively). There was also an increase in missed abortion/biochemical rates (7, 15, 27, 32, and 20%, respectively). Multiple logistic regression showed an increase in OPR/LBR when accounting for age, day 2 FSH, weight, number of embryos biopsied, and number of euploid embryos. P4 levels >20ng/ml on the day of transfer (during frozen single euploid embryo transfer cycles) were associated with decreased OPR/LBR.