Euploid Embryo Transfer Cycles Research Articles

P-755 Effect of female age and specific cycle characteristics on success in modified natural frozen-thawed single euploid embryo transfer cycles (mNC/FET)

Abstract Study question Does the age of woman and specific cycle characteristics impact the success of modified natural frozen-thawed single euploid embryo transfer cycles (mNC/FET)? Summary answer The success rate of mNC/FET cycles is similar in all age groups. As the LH level increased ( above 23.5ng/dL) the success was significantly increased. What is known already The success of frozen embryo transfer can depend on various factors such as the patient’s age, the number of transferred embryos, the duration of embryo culture, and the method used to prepare the endometrium (Holschbach et al. 2023). However, there is currently insufficient evidence in the literature about the effect of age and cycle characteristics on the effectiveness of mNC/FET cycles in patients who have received single top and good quality euploid embryos. Study design, size, duration This study, conducted at Istanbul Memorial Hospital, ART and Reproductive Genetics Center, is a retrospective, single-centre analysis of 583 cycles of euploid mNC/FET in women aged 22-44 years. The study period was from July 2017 to January 2024. The cycles were divided into two groups based on the age of the women. Group A (n = 408) included women under the age of 38, while Group B (n = 175) included women aged 38 or above. Participants/materials, setting, methods The study investigated success predictors in mNC/FET with top and good-quality embryos. Excluded were women with recurrent pregnancy losses, recurrent implantation failure, high BMI (>35kg/m2), uterine/endometrial problems, severe male infertility, and autoimmune diseases. The mNC/FET success was a pregnancy lasting 12 weeks or more. The analysis included patient demographics and cycle outcomes. Chi-square, t-tests, and Mann-Whitney U tests assessed variables with a p-value < 0.005, indicating statistical significance. Main results and the role of chance No significant demographic differences were observed between the two groups, except for AMH levels. AMH levels were significantly higher in younger group than older group (3.02 ng/ml vs. 1.96 ng/ml, p = 0.000). The mNC/FET success rates were similar, with 76% in the younger group and 73% in the older group. Estradiol levels the day before trigger day were significantly higher in older group (278.02 pg/ml vs. 237.84pg/ml, p = 0.028). Both groups had similar mean LH levels (32.50 IU/L and 32.41 IU/L, respectively), estradiol levels and endometrial thickness on the trigger day. In the younger group, LH rise was observed later, follicular phase was longer, and embryo transfer day was later than the older group (p = 0.001). Univariate regression analysis revealed that increased LH level was an important independent variable in achieving mNC/FET success, with a 1.001-fold increase (p = 0.043). The LH levels of 23.5 IU/L or higher predicted high mNC/FET success with 60% sensitivity and 43% specificity based on the Receiver Operating Characteristic curve. (AUC: 0.606, %95 CI 0.540-0.671, p = 0.002). Prolonged infertility duration and previous ET failures reduced mNC/FET success by 0.889 and 0.544-fold, respectively (p = 0.002, p < 0.001). Higher β-hCG levels on days 14 and 16 increased mNC/FET success by 1.038-fold and 1.008-fold, respectively (p < 0.001). Limitations, reasons for caution Our study has limitations as it was retrospective. Prospective randomized studies are needed to evaluate the differences between the young (age <38) and old patient groups (age ≥38) based on mNC/FET success. The association between LH rise and mNC/FET success needs verification with a larger sample. Wider implications of the findings The mNC/FET success rates are similar in young (age <38) and old patient groups (age ≥38). However, prolonged infertility duration and previous failed ET cycles decreased the success of mNC/FET. Additionally, It is important to schedule trigger time after the optimum LH rise, which is 23.5 IU/L or higher. Trial registration number not applicable

P-407 Exploring the effectiveness of tailoring estradiol supplementation duration to mimic the natural cycle length in artificial endometrial preparation for frozen embryo transfer cycles

Abstract Study question Is an estrogen supplementation duration similar in length to the follicular phase of a natural cycle associated with a better clinical pregnancy rate? Summary answer An estradiol supplementation duration, which is proportional to the natural follicular phase length, results in significantly better outcomes compared to shorter exposure durations What is known already The last decade witnessed a major increase in the use of single euploid frozen embryos. Artificial endometrial preparation (AEP) has proven to be effective to prepare the endometrium for implantation. However, several features of AEP need to be clarified mainly the duration of estrogen supplementation and until now no study took into consideration the difference between exogenous estrogen supplementation and the actual length of the follicular phase of each patient during AEP. Furthermore, most of the studies focused on upper limit of estrogen exposure while few considered the lower limit. Unfortunately, the results on pregnancy rates were mixed. Study design, size, duration 663 single euploid frozen embryo transfer cycles were included. Patients underwent vaginal ultrasound and hormonal blood measurement (Estradiol, Progesterone) on day 2 of their cycle. Estradiol valerate (4 mg the first 2 days then 6 mg daily, Orally) was started on the same day and another control was done around day 10. When triple lining pattern of the endometrium was seen, vaginal progesterone was initiated (800 mg daily) and SET was done after 120 hours. Participants/materials, setting, methods Patients with reported regular menstrual cycle (25-35 days) were included and the difference between estrogen supplementation and the actual follicular phase was calculated for each patient. Patients were sorted into 2 groups as follows: 231 women with normal interval (±2 days of follicular phase length), and 432 women with short interval (-3 days or shorter). Only the first single euploid embryo transfer cycles were analyzed for these patients. Main results and the role of chance Whereas patients had similar characteristics in both groups, the corresponding clinical pregnancy rates in normal and short supplementation groups were 69.3% (160/231) and 64% (277/432), respectively. After balancing the groups for BMI, embryo quality and endometrial thickness with inverse treatment probability weighting, those who received estradiol supplementation proportional to their natural follicular phase length had significantly higher clinical pregnancy rates compared to those who received it for shorter durations (adjusted OR: 1.48, 95% CI: 1.16 – 1.89, P = 0.002). Serum estradiol levels were available for 523 cycles, the clinical pregnancy rate in those within the 1st quartile (<155pmol/L), 2nd to 3rd quartile (155 to 275pmol/L) and 4th quartile (>275pmol/L) were 70%, 64.7% and 63%. After adjusting for BMI and embryo quality, higher (>275pmol/L) (adjusted OR: 0.84, 95% CI: 0.53-1.32, P = 0.442) and lower(<155pmol/L) (adjusted OR: 1.37, 95% CI: 0.85-2.22, P = 0.202) estradiol levels were not significantly associated with clinical pregnancy. Limitations, reasons for caution The present study could not address the influence of very long estrogen supplementation on clinical pregnancy rate due to limited samples. Further prospective studies, including larger populations, are needed to confirm our findings Wider implications of the findings Our data indicate that mimicking individually the natural cycle regarding estrogen supplementation duration in AEP for single euploid embryo transfer cycles can produce significant improvement in clinical pregnancy rates. Trial registration number not applicable

A Comprehensive Review of the Endometrial Receptivity Array in Euploid Embryo Transfer Cycles.

The Endometrial Receptivity Array (ERA) is a revolutionary molecular diagnostic tool that determines the optimal timing for embryo transfer by analyzing the gene expression profile of endometrial tissue. This comprehensive review examines the significance and application of ERA in euploid embryo transfer cycles, where the implantation of embryos with the correct number of chromosomes is critical for achieving successful pregnancy outcomes. This review underscores its role in enhancing implantation rates and reducing pregnancy loss by assessing the evolution, methodology, clinical applications, efficacy, and challenges associated with ERA. Key findings highlight ERA's superior accuracy in identifying the window of implantation compared to traditional methods, resulting in improved clinical outcomes in assisted reproductive technology (ART) cycles. Despite its benefits, the review acknowledges challenges such as cost, accessibility, and the need for standardization. Recommendations for clinical practice emphasize the integration of ERA into routine ART protocols, comprehensive patient counseling, and the importance of multidisciplinary collaboration. The review outlines promising prospects, including technological advancements to make ERA more cost-effective, the development of refined gene expression profiles, and the potential integration with other emerging ART technologies. Further research directions include long-term studies on the outcomes of ERA-guided pregnancies and exploring its application in cases of recurrent implantation failure and unexplained infertility. Overall, ERA represents a significant advancement in reproductive medicine, offering a personalized approach to embryo transfer timing that can significantly improve the success rates of euploid embryo transfers.

Analysis of related factors influencing the detection rate of mosaic embryo and the pregnancy outcomes with mosaic embryo transfers

Objective: To explore the related factors influencing the detection rate of mosaic embryo and the pregnancy outcomes of mosaic embryo transfer in preimplantation genetic testing for aneuploidy (PGT-A) based on next generation sequencing (NGS) technology. Methods: A retrospective study was performed to analyze the clinical data of patients in 745 PGT-A cycles from January 2019 to May 2023 at Chongqing Health Center for Women and Children, including 2 850 blastocysts. The biopsy cells were tested using NGS technology, and the embryos were divided into three groups based on the test results, namely euploid embryos, aneuploid embryos and mosaic embryos. The influence of population characteristics and laboratory-related parameters on the detection rate of mosaic embryo were analyzed, and the pregnancy outcomes of 98 mosaic embryo transfer cycles and 486 euploid embryo transfer cycles were compared during the same period, including clinical pregnancy rate and live birth rate. Results: Among the embryos tested (n=2 850), the number and proportion of euploid embryos, aneuploid embryos and mosaic embryos were 1 489 (52.2%, 1 489/2 850), 917 (32.2%, 917/2 850) and 444 (15.6%, 444/2 850), respectively. Among mosaic embryos, 245 (55.2%, 245/444) were segmental mosaic embryos, 118 (26.6%, 118/444) were whole-chromosome mosaic embryos, and 81 (18.2%, 81/444) were complex mosaic embryos. NGS technology was performed in 4 genetic testing institutions and the detection rate of mosaic embryo fluctuated from 13.5% to 27.0%. The distributions of female age, level of anti-Müllerian hormone, PGT-A indications, ovulation-inducing treatments, gonadotropin (Gn) dosage, Gn days, inner cell mass grade, trophectoderm cell grade, genetic testing institutions and developmental stage of blastocyst were significantly different among the three groups (all P<0.05). Multi-factor analysis showed that the trophectoderm cell grade and genetic testing institutions were significantly related to the detection rate of mosaic embryo; compared with the trophectoderm cell graded as A, the detection rate of mosaic embryo was significantly increased in the trophectoderm cell graded as B-(OR=1.59, 95%CI: 1.04-2.44, P=0.033); compared with genetic testing institution a, the detection rate of mosaic embryo was significantly higher (OR=2.89, 95%CI: 2.10-3.98, P<0.001) in the testing institution c. The clinical pregnancy rate and live birth rate with mosaic embryos transfer were significantly lower than those of euploid embryos transfer (clinical pregnancy rate: 51.0% vs 65.2%, P=0.008; live birth rate: 39.4% vs 53.2%, P=0.017). After adjustment for age, PGT-A indications, trophectoderm cell grade and days of embryo culture in vitro, the clinical pregnancy rate and live birth rate with mosaic embryos transfer were significantly lower than those of euploid embryos transfer (clinical pregnancy rate: OR=0.52, 95%CI: 0.32-0.83, P=0.007; live birth rate: OR=0.50, 95%CI: 0.31-0.83, P=0.007). Conclusions: The trophectoderm cell grade and genetic testing institutions are related to the detection rate of mosaic embryo. Compared with euploid embryos transfer, the clinical pregnancy rate and live birth rate with mosaic embryos transfer are significantly reduced. For infertile couple without euploid embryos, transplantable mosaic embryos could be recommended according to the mosaic ratio and mosaic type in genetic counseling to obtain the optimal pregnancy outcome.

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.

The use of combined hormonal contraceptive for in-vitro fertilization cycle priming is not associated with decreased pregnancy rate in frozen embryo transfer cycles: a cohort study.

The objectives of this study are to evaluate the cycle outcomes from IVF treatment preceded by oral contraceptive pills (OCP) priming compared to estradiol pretreatment and to determine if there is a role for OCP priming for those undergoing frozen embryo transfers. The study took place at a university-affiliated fertility center in Canada. The study included in-vitro fertilization (IVF) antagonist cycles from Jan 2016 to Jun 2019. Those with protocol deviation or treatment cancellation were excluded. There were 2237 cycles by 1958 patients; 27% of cycles utilized OCP priming. The average age in the OCP group was 34 years old compared to 36.5 in the estradiol group (P<0.01). AMH was reported in 43% of patients and was 3.7ng/mL in the OCP group versus 2.2 ng/mL in the estradiol group (P<0.01). The number of oocytes (15.2 vs. 12.5) and number of blastocysts (4.6 vs. 3.3) were higher in the OCP group (P all <0.01). After adjusting for age and AMH with linear regression for the 978 cycles with recorded AMH (24% with OCP prime), a significantly higher number of oocytes (13.8 vs. 11.9, P=0.002) was still noted in the OCP group. There were 866 euploid embryo transfer cycles (28% with OCP prime). There were no significant differences in implantation (77% vs. 76%) or ongoing pregnancy rates (56% vs. 54%) between those who had a frozen embryo transfer after OCP primed compared to estradiol primed stimulation cycles (P all >0.6). There were no differences in pregnancy outcomes from euploid frozen blastocyst transfers after OCP primed antagonist cycles compared to estradiol pretreatment. In fact, the use of OCP pretreatment was associated with increased oocyte yield, keeping in mind demographic differences with the OCP pretreatment group being younger with higher anti-Müllerian hormone and a higher prevalence of PCOS. Thus, OCP priming should still be considered in specific populations, such as those with oligo-ovulation or adequate ovarian reserve.

Can endometrial compaction predict live birth rates in assisted reproductive technology cycles? A systematic review and meta-analysis.

Endometrial compaction (EC) is defined as the difference in endometrial thickness from the end of the follicular phase to the day of embryo transfer (ET). We aimed to determine the role of EC in predicting assisted reproductive technology (ART) success by conducting a meta-analysis of studies reporting the association between EC and clinical outcomes of ART. MEDLINE via PubMed, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from the date of inception to May 19, 2023. The primary outcome was live birth rate (LBR) per ET. Secondary outcomes were live birth or ongoing pregnancy per ET, ongoing pregnancy per ET, clinical pregnancy per ET, and miscarriage per clinical pregnancy. Fifteen studies were included. When data from all studies reporting live birth were pooled, overall LBR rates were comparable in cycles showing EC or not [RR = 0.97, 95%CI = 0.92 to 1.02; 10 studies, 11,710 transfer cycles]. In a subgroup of studies that included euploid ET cycles, a similar LBR for patients with and without EC was noted [RR = 0.99, 95%CI = 0.86 to 1.13, 4 studies, 1172 cycles]. The miscarriage rate did not seem to be affected by the presence or absence of EC [RR = 1.06, 95%CI = 0.90 to 1.24; 12 studies]. The predictive value of EC in determining LBR is limited, and assessment of EC may no longer be necessary, given these findings. PROSPERO CRD42023410389.

Effects of embryo characteristics in frozen-thawed single euploid blastocyst transfers on pregnancy outcomes: a retrospective cohort study

Objectives: Our study examined the effects of the trophectoderm biopsy (TB) day and the presence of necrotic foci (NF) or separate blastomeres (SB) within euploid embryos on in vitro fertilization (IVF) pregnancy outcomes. Methods: This retrospective cohort study was conducted from January 2017 to September 2021 at Memorial Sisli Hospital, Istanbul, Turkey. The study comprised a total of 2758 frozen-thawed euploid embryo transfer cycles. After thawing, blastocysts were graded using Gardner's classification Top-Quality (TQ), Good-Quality (GQ), Moderate-Quality (MQ), Poor-Quality (PQ) and further divided into groups according to the presence of NF and/or SB and evaluated for pregnancy outcomes. Results: There were significant correlations between pregnancy outcomes and the degree of blastocoele expansion, as well as the presence of NF or SB in the euploid embryo. Ongoing pregnancy rates were lower in the group with NF in the inner cell mass (ICM) or trophectoderm (TE) than in the group without NF. The presence of SB decreased the rates of ongoing pregnancy and increased the rates of miscarriage. Embryos with expansion grades ≤ 3 had lower rates of ongoing pregnancy and higher rates of miscarriage compared to embryos with expansion grades&amp;gt; 3. TQ and GQ embryos had a higher rate of ongoing pregnancy and a lower rate of miscarriage than MQ and PQ embryos. Conclusions: When selecting the embryo to be transferred to a patient, careful consideration should be given to the morphological grade of the embryo as well as whether or not it contains NF and SB.

P-729 Factors affecting live birth rates in frozen-thawed single euploid blastocyst transfer cycles

Abstract Study question What are the factors affecting the rates of live birth in frozen-thawed euploid embryo transfer cycles? Summary answer Some demographic characteristics, frozen embryo transfer (FET) cycle parameters, and embryo characteristics of patients affect live birth rates in euploid embryo transfer cycles. What is known already The aim of assisted reproductive techniques (ART) is to achieve live birth as soon as possible. Preimplantation genetic testing (PGT) is an embryo selection technique recommended to shorten the live birth time. In addition, PGT reduces the number of failed ART cycles by eliminating embryos with chromosomal abnormalities that will not implant or will cause miscarriage. Despite these, the live birth rate after euploid embryo transfer cycles is still not at the expected level. Study design, size, duration This retrospective cohort study was conducted between January 2011 and May 2021 at the IVF and Reproductive Genetics Centre, Memorial Sisli Hospital, Istanbul, Turkey. The study involved a total of 2783 frozen-thawed euploid embryo transfer cycles. Participants/materials, setting, methods 2873 euploid FET cycles were analysed in the study to determine factors affecting live birth rates. 30 parameters thought to affect live birth were identified and analysed by logistic regression analysis on the effects of live birth. These parameters include patients' demographics, fresh cycle and FET cycle characteristics, and embryo-related parameters on live birth effects in euploid embryo transfer cycles. Main results and the role of chance 53% of 2783 euploid embryo transfer cycles have resulted in a live birth. The birth rate was 0,5 times less in the group with a body mass index (BMI) of higher than 29 compared to the group with a BMI of less than 25 (p &amp;lt; 0.05). In cycles in which embryos of good-to-moderate-to-poor quality were transferred, the chance of live birth was lower than in cycles in which embryos of top quality were transferred (OR:0.837 OR:0.515 OR:0.528, respectively). The live birth rate was higher in cases where endometrial preparation was performed in natural cycles than in artificial cycles (OR:1.67, p &amp;lt; 0.05). Embryo transfers without separate blastomeres had a higher live birth rate than embryo transfers with separate blastomeres (OR:1.416, p &amp;lt; 0.006). The live birth rate was 0.7 times lower in the group that did not undergo embryo re-expansion 4 hours after thawing (p &amp;lt; 0.04). Embryo transfer on the sixth day was associated with a lower live birth rate than embryo transfer on the fifth day. (OR:0.6, p &amp;lt; 0.02). The group with a history of recurrent implantation failure (RIF) had a lower live birth rate than the group without a history of RIF (OR:0.5) Limitations, reasons for caution This study is a retrospective study. Wider implications of the findings In euploid embryo transfer cycles, clinicians and embryologists must know the parameters affecting live birth to guide treatment and select the embryo to be transferred first. In addition, the patient should be informed and guided about these factors. Trial registration number Not applicable

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.

ART outcome after euploid frozen embryo transfer is not affected by previous Cesarean section delivery in the absence of intracavitary fluid.

To evaluate the impact of a cesarean section (CS) on the chance of clinical pregnancy and live birth (LB) in frozen embryo transfer (FET) cycles in the setting of euploid embryos and the absence of intracavitary fluid (ICF) as causes of implantation failure were excluded. Retrospective study, including patients with at least one previous CS or at least one previous vaginal delivery, who underwent a euploid FET cycle. A total of 412 euploid embryo transfer cycles had been included. Patients' mean age was 34.5years and 42.48% of patients have had at least one previous CS. A clinical pregnancy was seen in 69.42% and 60.19% of the patients had a LB. Positive pregnancy test, clinical pregnancy, and LB rate were not significantly different between the groups without/with a history of a previous CS (p = 0.6/0.45/0.94, respectively). LB rate was significantly reduced by the presence of mucus on the ET catheter (OR: 0.413; p = 0.010), the BMI (OR: 0.946; p = 0.006), the combined embryo quality (embryo quality fair: OR: 0.444; p = 0.001; embryo quality low: OR: 0.062; p < 0.001), and by the HRT endometrial preparation approach (OR: 0.609; p = 0.023). The possible negative impact of a CS can be overcome when a euploid FET after exclusion of ICF is performed.

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.

P-195 Do the presence of necrotic foci and/or separate blastomeres, the blastocoele expansion degree affect pregnancy outcomes of frozen-thawed euploid blastocysts transfer cycles?

Abstract Study question Do the presence of necrotic foci and/or the presence of separate blastomeres and the blastocoele expansion degree affect pregnancy outcomes of frozen-thawed euploid embryo transfer cycles? Summary answer Significant correlations were observed between pregnancy outcomes and the degree of blastocoele expansion, the presence of necrotic foci or separate blastomeres in the euploid embryo. What is known already Implantation failure and pregnancy losses may occur despite the selection of a healthy euploid embryo for transfer and the elimination of other risk factors. Blastocyst morphology is known to affect pregnancy outcomes, but the effect of necrotic foci and/or separate blastomeres in the embryo on pregnancy outcomes needs further investigation. Study design, size, duration This is a retrospective cohort study and was conducted at ART and Reproductive Genetics Centre, Memorial, Sisli Hospital, Istanbul, Turkey between January 2017 and September 2021. A total of 2758 frozen-thawed euploid embryo transfer cycles were included in the study. Participants/materials, setting, methods After thawing, the embryos were divided into groups according to their morphological grades, whether there were necrotic foci and whether there were separate blastomeres, and were evaluated in terms of pregnancy outcomes. Blastocysts were graded by using Gardner and Schoolcraft’s grading system. Ongoing pregnancy was defined as a pregnancy that had reached 20 weeks. Miscarriage was defined as a pregnancy loss occurring before the 20th gestational week. Main results and the role of chance Our data showed that the presence of necrotic foci in the inner cell mass or trophectoderm reduced the ongoing pregnancy rates and increased the miscarriage rates. The ongoing pregnancy rate was lower (41.0%, vs 60.0%, p &amp;lt; 0.001) and the miscarriage rate was higher (27.3% vs 19.8%, p &amp;lt; 0.05) in the group with necrotic foci than in the group without necrotic foci. The presence of separate blastomeres decreased the ongoing pregnancy rates (50.3% in the group with separate blastomeres, 61.8% in the group without separate blastomeres) (p &amp;lt; 0.001) and increased the miscarriage rates (25.3% in the group with separate blastomeres, 18.8% in the group without separate blastomeres) (p &amp;gt; 0.004). The ongoing pregnancy rates for blastocoele expansion degrees of 2, 3, 4, 5, and 6 were 39.5%, 38.3%, 59.3%, 59.8%, and 61.4%, respectively and the miscarriage rates for blastocoele expansion degrees of 2, 3, 4, 5, and 6 were 35%, 33.3%, 21%, 21.2%, 18.4%, respectively. Embryos with degrees of expansion grade ≤ 3 had lower ongoing pregnancy rates and higher miscarriage rates than those with degrees of expansion &amp;gt; 3 (p &amp;lt; 0.01). Limitations, reasons for caution Retrospective study. Wider implications of the findings When choosing the embryo to be transferred in cases with more than one euploid embryo, the selection should be made by considering the blastocoele expansion degrees and the presence of necrotic foci and separate blastomeres in the embryo. Trial registration number not applicable

Similar implantation competence in euploid blastocysts developed on day 5 or day 6 in young women: a retrospective cohort study

The results from different studies are inconsistent regarding whether development potential correlated with embryo development speed after single euploid blastocyst transfer. The age-associated reproductive decline is not only because of the difference in aneuploidy rates but also because of metabolic and epigenetic changes of the embryos. Therefore, we aimed to assess the independent effect of embryo development speed on implantation potential in young women. A total of 326 young women who underwent preimplantation genetic testing for monogenic diseases with aneuploidy screening were analyzed. Day-5 and day-6 euploid blastocysts yielded similar implantation rates (65.20 vs. 61.22%). The odds ratio (OR) remained non-significant after adjusting for confounders (adjusted OR = 0.84, 95% confidence interval 0.52–1.36). There was a trend that day-6 euploid blastocysts had a higher miscarriage rate (13.33 vs. 9.20%). However, the live birth delivery rate of day-5 blastocysts was similar to that of day-6 blastocysts (59.20 vs. 53.06%). In the stratified analysis, live birth delivery rates were similar between day-5 and day-6 similarly graded euploid blastocysts (excellent and good, 62.04 vs. 64.71%; average, 58.73 vs. 53.70%; poor, 43.75 vs. 44.44%). Embryo development speed has no obvious impact on implantation competence in young women’s vitrified/warmed euploid embryo transfer cycles.

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.

Prospective analysis of progesterone exposure in programmed single thawed euploid embryo transfer cycles and outcomes.

In the era of personalized medicine and the increased use of frozen embryo transfer (FET), assay of the endometrium's receptivity prior to transfer has gained popularity, especially among patients. However, the optimal timing for single thawed euploid embryo transfers (STEET) in a programmed FET has yet to be determined Mackens et al. (Hum Reprod. 32(11):2234-42, 2017). We sought to examine the outcomes of euploid FETs by length of progesterone (P4) exposure. Prospective cohort study of programmed FETs of single euploid embryos between June 1, 2018, and December, 18, 2018, at our center. Subjects reported the exact start time for initiating progesterone. The transfer time was noted to calculate the primary independent variable, duration of progesterone exposure. Statistical analysis included ANOVA and Spearman's rho correlation, with p < 0.05 considered significant. Inclusion criteria were met for 253 programmed STEET cycles in the analysis. There was no significant difference in P4 duration when comparing outcome groups (112.8 ± 3.1 ongoing pregnancy (OP), 112.4 ± 4.4 spontaneous abortion (SAB), 111.6 ± 1.7 biochemical pregnancy (BP), 113.9 ± 5.7 no pregnancy (NP), F 1.76, df 3, p = 0.16). An ROC curve assessing the ability of P4 duration to predict ongoing pregnancy (OP) had an area under the curve of 0.467 (p = 0.38). Duration of P4 was not associated with outcome. Of the cycles, 65.6% resulted in ongoing pregnancy with our center's instructions resulting in an average progesterone exposure of 112.8h, with a range of 98.3-123.7h. With growing popularity for individualized testing, these results provide evidence for patient counseling of the high likelihood of ongoing pregnancy without personalized testing.

Prospective analysis of progesterone duration in programmed single thawed euploid embryo transfer cycles

Prospective analysis of progesterone duration in programmed single thawed euploid embryo transfer cycles