P–359 Blastocyst quality, transfer difficulty and endometrial thickness affect clinical pregnancy after frozen embryo transfer (FET) of euploid blastocysts in the upper uterine cavity

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Bayram ◽  
N D Munck ◽  
A Abdala ◽  
I Elkhatib ◽  
A El-Damen ◽  
...  

Abstract Study question Which factors affect the clinical pregnancy rate (CPR) after single euploid frozen embryo transfers (FET), when the blastocyst is transferred in the upper uterine cavity area? Summary answer Blastocyst quality, embryo transfer difficulty and endometrial thickness affect the CPR in FET. What is known already There is a limited understanding of the factors affecting success rates after FET. The most important factors influencing implantation rates are patient characteristics, type of endometrial preparation, embryo quality and transfer difficulty. It has been shown that the position of the euploid blastocyst, measured as distance from the fundus (DFF) of the uterine cavity (mm), affects the implantation potential. Although the ideal location within the uterine cavity is still being debated in very heterogeneous patient populations, most studies have found that the highest pregnancy rates are obtained when the embryo is placed in the upper area of the uterine cavity. Study design, size, duration This single center retrospective cohort study included a total of 603 single euploid FET cycles, in the upper half of the uterine cavity, between January 2019 and November 2020 in ART Fertility Clinic Abu Dhabi, UAE. Participants/materials, setting, methods Trophectoderm biopsy samples were subjected to Next Generation Sequencing to screen the ploidy state. Vitrification and warming were performed using the Cryotop method (Kitazato, Biopharma). The full length of the uterine cavity and the longitudinal distance between the fundal endometrial surface and the air bubble after transfer were measured. Main results and the role of chance The patients were on average 33.9 (19–46) years old. The FET was performed in a natural cycle (NC) (n = 278) or hormone replacement therapy (HRT) (n = 325). Of the 603 transfers which had been performed in the upper half of the uterus, 412 (68.3%) resulted in a pregnancy and 311 (51.5%) in a clinical pregnancy. After bivariate analysis, the clinical pregnancy rate was significantly higher for high quality blastocysts (grade 1–2 versus 3–4) (p < 0.001), after easy embryo transfers (p = 0.001) and for higher endometrial thickness (p = 0.027). After performing a multivariate logistic regression analysis to consider the effect of all explanatory variables (age, Anti Müllerian hormone, body mass index, endometrial thickness, quality of the blastocyst, difficulty of the transfer [requirement of additional instrumentation], presence of mucus or blood on the transfer catheter, day 5 or day 6 biopsy, FET endometrial preparation), the clinical pregnancy was affected by the endometrial thickness: OR 1.20 [1.05–1.37], p = 0.007; transfer difficulty: OR 0.44 [0.25–0.79], p = 0.006; blastocyst quality 3: OR 0.38 [0.18–0.79], p = 0.01 and blastocyst quality 4: OR 0.15 [0.06–0.37], p < 0.0001. Age did not affect the clinical pregnancy after transferring a single euploid blastocyst: OR 1.03 [1.00–1.06], p = 0.052. Limitations, reasons for caution The limitation of this study was its retrospective nature and the small sample size. Other parameters may be important in live birth outcomes. Wider implications of the findings: Optimization of clinical pregnancy outcomes after FET depends on multiple factors. Even after transfer of euploid blastocysts in the upper uterine cavity, the endometrial thickness, transfer difficulty and blastocyst quality will still affect the clinical pregnancy outcomes. Trial registration number NA

2020 ◽  
Vol 35 (12) ◽  
pp. 2746-2754
Author(s):  
Peter Movilla ◽  
Jennifer Wang ◽  
Tammy Chen ◽  
Blanca Morales ◽  
Joyce Wang ◽  
...  

Abstract STUDY QUESTION Is there an association between endometrial thickness (EMT) measurement and clinical pregnancy rate among Asherman syndrome (AS) patients utilizing IVF and embryo transfer (ET)? SUMMARY ANSWER EMT measurements may not be associated with successful clinical pregnancy among AS patients undergoing IVF. WHAT IS KNOWN ALREADY Clinical pregnancy rate after IVF is significantly lower in patients with a thin endometrium, defined as a maximum EMT of <7 mm. However, AS patients often have a thin EMT measurement due to intrauterine scarring, with a paucity of data and no guidance on what EMT cutoff is appropriate when planning an ET among these patients. STUDY DESIGN, SIZE, DURATION This is a retrospective cohort study of 45 AS patients treated at a specialized advanced hysteroscopic clinic from 1 January 2015, to 1 March 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS Review of EMT measurements prior to a total of 90 ETs, among 45 AS patients. The impact of the maximum EMT measurement prior to ET on clinical pregnancy rate was analyzed. MAIN RESULTS AND THE ROLE OF CHANCE A total of 25/45 (55.6%) AS patients ultimately went on to have ≥1 clinical pregnancy following a mean ± SD of 2.00 ± 1.26 ET attempts. There was a total of 90 ETs among the 45 AS patients, with 29/90 (32.2%) ETs resulting in a clinical pregnancy. Younger patient age (P = 0.05) and oocyte donation (P = 0.01) were the only variables identified to be significant predictors for a positive clinical pregnancy outcome on bivariate analysis. The mean EMT measurement prior to all ETs among AS patients was 7.5 ± 1.6 mm. EMT measurement prior to ET did not predict a positive clinical pregnancy on either bivariate (P = 0.84) or multivariable analysis (odds ratio 0.91, P = 0.60). 31.8% of EMT measurements measured <7.0 mm. In this small cohort, no difference in the clinical pregnancy rate was detected when comparing ETs with EMT measurements of <7.0 mm versus ≥7.0 mm (P = 0.83). The mean EMT measurement decreased with increasing AS disease severity; 8.0 ± 1.6 mm for mild disease, 7.0 ± 1.4 mm for moderate disease and 5.4 ± 0.1 mm for severe disease. LIMITATIONS, REASONS FOR CAUTION Our small sample size limits our ability to draw any definitive conclusions. In addition, patients utilized various infertility clinics. This limits our ability to evaluate the consistency of EMT measurements and the IVF care that was received. WIDER IMPLICATIONS OF THE FINDINGS EMT measurement cutoff values should be used with caution if canceling a scheduled ET in AS patients. STUDY FUNDING/COMPETING INTEREST(S) This study was not funded. K.I. reports personal fees from Karl Stroz and personal fees from Medtronics outside the submitted work. The other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
P C Jindal ◽  
M Singh

Abstract Study question Does GCSF by intrauterine route leads to better result in the treatment of thin endometrium as compared to GCSF by the subcutaneous route, in IVF-ICSI Cycles? Summary answer Yes, GCSF by intrauterine route leads to better result in the treatment of thin endometrium as compared to subcutaneous-GCSF, in ART Cycles? What is known already GCSF, is a member of the colony stimulating factor family of cytokines and growth factors. GCSF receptors are expressed in high concentration on dominant follicle, particularly at preovulatory stage.The endometrium also shows an increased expression of these receptors. GCSF concentration rises in the follicular fluid at the same time. Serum levels of GCSF are found to be in direct correlation with levels of GCSF in follicular fluid. Serum levels increase progressively from the day the embryo-transfer to the day of implantation. GCSF has been found to be beneficial in patients with thin endometrium and recurrent implantation failure. Study design, size, duration This was a RCT conducted between 2018–2019. 30 patients with thin endometrium were enrolled in each group. In either group, GCSF was given if endometrium was less than 7mm on day 14, maximum of two doses were administered. Patients undergoing frozen embryo transfer were recruited in the study, after meeting the inclusion and exclusion criteria. Primary outcome measured was increase in endometrium thickness and the secondary outcome was the clinical pregnancy rate and abortion-rate. Participants/materials, setting, methods 60 patients with thin endometrium were randomly divided into two groups. Group A: Inj. GCSF (300 mcg/1 ml) subcutaneously on Day 14 onwards alternate days for two doses. Group B: Inj. GCSF (300 mcg/1 ml) instilled slowly into the uterine cavity using an intrauterine insemination (IUI) catheter under USG guidance. Endometrial thickness was assessed after 48 h. If endometrial thickness was found to be < 7 mm, a second infusion of GCSF was carried out. Main results and the role of chance In the subcutaneous group (group-A) the mean endometrial thickness before GCSF injection was 5.8 ± 0.6 mm and, after injection it increased to 6.9 ± 0.4 mm. Similarly, in the intrauterine group (group-B) the mean endometrial thickness before GCSF was 5.9 ± 0.7 which increased to a mean of 7.9 ± 0.5 after GCSF instillation. The difference between endometrial thickness before and after intrauterine infusion of GCSF was more than that in the subcutaneous group. In group-A, 08 patients conceived out of 30 patients ( clinical pregnancy rate 26.6%) and in group B 11 conceived out of 30 patients in whom GCSF was instilled intrauterine (pregnancy rate 36.6%). Thus, there was a difference in the clinical pregnancy rate in the two groups, the intrauterine group yielding a higher clinical pregnancy rate, but it was not statistically significant. Because of the thin endometrium, we found an abortion rate of 25% (2/8) in the subcutaneous-GCSF group, and an abortion rate of 18% (2/11) in the intrauterine GCSF group. Limitations, reasons for caution There are few potential limitations because of the small sample size. Confounders such as obesity, smoking and alcohol intake, presence of adenomyosis and endometriosis, were not taken into consideration. Though prevalence of obesity is usually low in Indian women. Habits of smoking and alcohol are exceedingly uncommon in Indian women. Wider implications of the findings: Use of GCSF plays an important role in management of patients of thin endometrium undergoing embryo transfer. It is an easily available and economical preparation in developing countries and the intrauterine instillation of GCSF can be easily practiced in an ART unit with good results in resistant thin endometrium patients. Trial registration number Not applicable


2021 ◽  
Vol 12 ◽  
Author(s):  
Danjun Li ◽  
Shuzin Khor ◽  
Jialyu Huang ◽  
Qiuju Chen ◽  
Qifeng Lyu ◽  
...  

ObjectiveTo evaluate the clinical effect of mild stimulation with letrozole on pregnancy outcomes in ovulatory women undergoing frozen embryo transfer (FET) compared to natural cycle.DesignRetrospective observational study.SettingTertiary care academic medical center.PopulationA total of 6,874 infertile women with regular menstrual cycles (21-35 days) met the criteria for this study in the period from 2013 to 2020.MethodsAll patients who were prepared for and underwent FET were divided into two groups: a modified natural cycle (NC) group (n=3,958) and a letrozole cycle group (n=2,916).Main Outcome MeasuresThe primary outcome of the study was clinical pregnancy rate. Secondary outcome measures were endometrial thickness, rates of implantation, positive HCG test, live birth, early miscarriage and ectopic pregnancy.ResultsThe clinical pregnancy rate was not statistically different between the modified NC-FET group and the letrozole-FFT group before (crude OR 0.99, 95% CI 0.90-1.09, P=0.902>0.05) and after propensity score matching (PSM) (crude OR 1.01, 95% CI 0.91-1.12, P=0.870>0.05). After multivariable logistic regression analysis, the clinical pregnancy rate remained insignificant before (adjusted OR 1.00, 95% CI 0.91-1.10, P=0.979>0.05) and after matching (adjusted OR 1.00, 95% CI 0.89-1.11, P=0.936>0.05), respectively. Similarly, in the crude and adjusted analysis, the positive HCG test, implantation, live birth and early miscarriage rates were also comparable in the letrozole-FFT group and modified NC-FET group before and after matching. Furthermore, the endometrial thickness of letrozole-FFT group was similar to that of modified NC-FET group with adjusted analysis.ConclusionOur observation suggests that mild stimulation with letrozole could produce similar pregnancy outcomes in ovulatory patients who undergo FET when compared with a natural cycle.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
R Abalı ◽  
F K Boynukalın ◽  
M Gültomruk ◽  
Z Yarkiner ◽  
M Bahçeci

Abstract Study question Does the outcome of the first euploid frozen-thawed blastocyst embryo transfer affect the subsequent euploid FBT originating from the same cohort of oocytes? Summary answer The clinical pregnancy rate and ongoing pregnancy rate of the subsequent FBT are higher if a clinical pregnancy was attained in the first euploid FBT. What is known already Numerous factors including patient, cycle and embryological characteristics affect the outcome of an IVF treatment cycle. There is no data available whether the outcome of euploid FBT has an impact on the outcome of the subsequent euploid FBT of embryos originating from the same cohort of retrieved oocytes. Study design, size, duration The study enrolled cycles preimplantation genetic test for aneuploidy (PGT-A) performed between January 2016 and July 2019 at the Bahceci Fulya IVF Center. A total of 1051 patients with single euploid FBT were evaluated and resulted live birth (n = 589, live birth rate (LBR): 56%(589/1051)), miscarriage (n = 100, miscarriage rate (MR): 14.5% (100/689)) and no clinical pregnancy (n = 362, 34,4%, (362/1051)). 159 FBT after the first single euploid FBT originating from the same cohort of oocytes were analyzed. Participants/materials, setting, methods Second euploid FBT cycle after first FBT with a clinical pregnancy were compared to frozen-thawed cycles after a without a pregnancy. Logistic regression analysis was utilized to adjust for potential confounders including female age, body mass index, embryo quality, day of embryo frozen, number previous failed attempt, number of previous miscarriage, endometrial thickness, outcome of the first euploid FBT. Main results and the role of chance The pregnancy outcome from the first euploid FBT in the study group was resulted live birth (25.1%, (40/159)), miscarriage (15.7%, (25/159)) and no clinical pregnancy (59.1%, (94/159). The pregnancy outcome of the subsequent euploid embryo transfer from the same oocyte cohort was clinical pregnancy rate (CPR): (67.3%, (107/159) ongoing pregnancy rate (OPR) (52.2% (83/159) and MR (22.4%, (24/107)). The CPR in the subsequent euploid FBT was 80% (52/65) among patients who achieved a clinical pregnancy in the first euploid FBT and 58.5% (55/94) of those who did not (p = 0.0045). The OPR in the subsequent euploid FBT was 64.6% (42/65) among patients who achieved a clinical pregnancy in first euploid FBT and 43.6% (41/94) of those who did not (p = 0.009). On a multivariate regression analysis, clinical pregnancy in the first euploid FBT was a significant independent predictor for a pregnancy in the subsequent FBT transfer (p = 0.003). Limitations, reasons for caution The limitation of the study is in the retrospective nature of the study. As the PGT-A strategy significantly decreases number of transferable embryos, the sample size of the study is limited. Wider implications of the findings: Identifying predictive factors for the success of euploid FBT is important. These can help physicians while counseling patients regarding the outcome of the previous euploid FBT. Trial registration number NA


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lifang Yuan ◽  
Hongbo Wu ◽  
Weiyu Huang ◽  
Yin Bi ◽  
Aiping Qin ◽  
...  

Abstract Background This meta-analysis summarizes evidence from studies using metformin (Met) to improve endometrial receptivity (ER) in women with PCOS. Methods Following the PRISMA protocol, we conducted a comprehensive search of academic literature from various databases, including PubMed, EMbase and Cochrane libraries. Studies published in English before Jan 27, 2021, were recruited for primary screening. Data on endometrial thickness (EMT), endometrial artery resistance index (RI), clinical pregnancy rate (CPR) and miscarriage rate (MR) were extracted and analyzed. Results Sixty-two eligible studies that included 6571 patients were evaluated in this meta-analysis. Primary indicators are EMT and endometrial aetery RI; secondary indicators include the clinical pregnancy rate and miscarriage rate. Metformin significantly increased EMT (SMD = 2.04, 95% CI (0.96,3.12),P = 0.0002) and reduced endometrial artery RI compared to the non-Met group (SMD = − 2.83, 95% CI: (− 5.06, − 0.59), P = 0.01). As expected, metformin also improved CPR and reduced MR in PCOS patients as a result, clinical pregnancy rate (risk ratio [RR] = 1.26, 95% CI: 1.11–1.43, P = 0.0003), and miscarriage rate (RR = 0.73, 95% CI:0.58–0.91, P = 0.006). Conclusion Metformin may improve endometrial receptivity (ER) in PCOS patients by increasing EMT and reducing endometrial artery RI. However, the level of most original studies was low, with small sample sizes. More large-scale, long-term RCTs with rigorous methodologies are needed.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jian-Chun Li ◽  
Yan-Hong Wang ◽  
li-Ying Peng ◽  
Yun Zhou ◽  
Shi-Bin Chao

BackgroundIn recent years frozen-thawed embryo transfer (FET) has played an increasingly important role in ART, but there is limited consensus on the most effective method of endometrial preparation (EP) for FET. Inspired by significantly higher implantation rate and clinical pregnancy rate of the depot GnRH-a protocol, we proposed a novel EP protocol named down-regulation ovulation-induction (DROI) aimed to improve pregnancy outcomes of FET.MethodsThis was a single-center, randomized controlled pilot trial. A total of 307 patients with freeze-all strategy scheduled for first FET were enrolled in the study. A total 261 embryos were transferred in DROI-FET group including 156 patients and 266 embryos were transferred in mNC-FET group including 151 patients. Reproductive outcomes were compared between the two groups.ResultsThe basic characteristics of patients, and the average number, quality and stage of embryos transferred were comparable between the two groups. Our primary outcome, implantation rate(IR) in DROI-FET group, was significantly higher than that of the mNC-FET group (54.41% versus 35.71%, P<0.01). The clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR) in DROI-FET group was also higher than that in mNC-FET group (69.87% versus 50.33%, P<0.01; 64.10% versus 42.38%, P<0.01).Conclusion(s)Compared to existing endometrial preparation methods, the DROI protocol might be the more efficient and promising protocol.


Author(s):  
Zhiqin Bu ◽  
Xinhong Yang ◽  
Lin Song ◽  
Beijia Kang ◽  
Yingpu Sun

Abstract Background The aim of this study was to explore the impact of endometrial thickness change after progesterone administration on pregnancy outcome in patients transferred with single frozen-thawed blastocyst. Methods This observational cohort study included a total of 3091 patients undergoing their first frozen-thawed embryo transfer (FET) cycles between April 2015 to March 2019. Endometrial thickness was measured by trans-vaginal ultrasound twice for each patient: on day of progesterone administration, and on day of embryo transfer. The change of endometrial thickness was recorded. Results Regardless of endometrial preparation protocol (estrogen-progesterone/natural cycle), female age, body mass index (BMI), and infertility diagnosis were comparable between patients with an increasing endometrium on day of embryo transfer and those without. However, clinical pregnancy rate increases with increasing ratio of endometrial thickness. Compared with patients with Non-increase endometrium, those with an increasing endometrium on day of embryo transfer resulted in significantly higher clinical pregnancy rate (56.21% vs 47.13%, P = 0.00 in estrogen-progesterone cycle; 55.15% vs 49.55%, P = 0.00 in natural cycle). Conclusions In most patients, endometrial thickness on day of embryo transfer (after progesterone administration) increased or kept being stable compared with that on day of progesterone administration. An increased endometrium after progesterone administration was associated with better pregnancy outcome.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Karagianni ◽  
A Papatheodorou ◽  
N Christoforidis ◽  
A Chatziparasidou

Abstract Study question Does artificial collapse of human blastocysts before vitrification affect the post warming quality of embryos and/or the reproductive outcome? Summary answer This study suggests that artificial collapse with laser pulse before vitrification significantly benefits blastocyst quality post-warming without improving reproductive outcome. What is known already The efficiency of vitrification of blastocysts can be influenced by various factors, such as the stage of the expansion and the quality of the embryos. Expanded blastocysts seem to be more sensitive and prone to cryo-injury during vitrification because of the large amount of blastocoelic fluid which may cause insufficient dehydration. Artificial collapse (AC) with micro-needles or with laser pulse can improve the vitrification procedure and protect the expanded blastocysts from cryoinjuries by reducing the fluid of the blastocoel. Study design, size, duration This prospective randomized study was performed at Embryolab Fertility Clinic, in Thessaloniki, Greece between July 2020 and November 2020 and included 94 ICSI treatments with no fresh embryo transfer. Patients with more than 4 blastocysts were randomized and allocated to the study (AC) group or control group. Randomization list was created by a computer-based program. The embryos were vitrified at the blastocyst stage and the best 1–2 embryos were transferred in a subsequent cycle. Participants/materials, setting, methods Patients were divided in two groups: AC group (n = 46) where 1 or 2 best expanded blastocysts were artificially collapsed by a laser pulse before vitrification and control group (n = 48) where the corresponding best expanded embryos remained untreated before vitrification. The embryos were graded according to Gardner’s criteria and vitrified using open system. Quality of embryos, pregnancy rate and clinical pregnancy rate from the first warming cycle were the parameters that were analyzed using z-test. Main results and the role of chance The analyzed embryos were in total 171, 85 in the AC group and 86 in the control group. The day 5 embryos in each group were 6.89 (±3.41) and 6.50 (±3.38) and the number of embryos per embryo transfer was 1.85 (±0.36) and 1.79 (±0.41) respectively. Cryoinjury was determined as the presence of degenerated cell in ICM or TE. In the AC group cryo-injury was significantly lower than in the control group [31.11% with at least 1 embryo per embryo transfer and 52.08% respectively (p = 0.0356), 6.67% with cryo-injury in both embryos and 14.58% respectively (p < 0.0001), 8.89% with cryo-injury in ICM and 10.42% respectively (p < 0.0001), 15.56% with cryo-injury in trophectoderm and 27.08% respectively (p < 0.0001), and 6.67% with cryo-injury in both ICM and trophectoderm and 12.50% respectively (p < 0.0001)]. Pregnancy rate (positive b-hcg) was not significantly different between the two groups (62.22% in AC group and 76.09% in control group, p = 0.1479), nor was the clinical pregnancy rate (52.38% and 60.87% in AC and control group respectively, p = 0.4208). Limitations, reasons for caution The number of cases included in this study was limited and the live birth rate was not yet available. More prospective randomized studies are needed in order to validate the benefit of artificial collapse before the vitrification procedure. Wider implications of the findings: Laser artificial Collapse does not compromise expanded blastocyst quality, on the contrary it seems to reduce the amount of cryoinjury observed post warming. Whether it can improve the reproductive outcome, remains to be examined in larger scale studies. Trial registration number Not applicable


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