scholarly journals Immediate versus delayed frozen embryo transfer in women following a failed IVF-ET attempt: a multicenter randomized controlled trial

Author(s):  
Jing-Yan Song ◽  
Feng-Yi Dong ◽  
Li Li ◽  
Xing-Xing Zhang ◽  
Ai-Juan Wang ◽  
...  

Abstract Background The optimal time at which to perform a frozen-thawed embryo transfer (FET) following a failed in-vitro fertilization-embryo transfer (IVF-ET) attempt remains elusive to most reproductive experts. Physicians often delay the introduction of FET due to concerns related to potential residual effects of ovarian hyperstimulation which may interfere with the regular menstrual cycle. Moreover, given that most of the published studies on the topic are retrospective and have inconsistent findings, it is crucial to develop evidence-based randomized control guides for clinical practice. Therefore, this well-designed randomized controlled trial (RCT) was conducted to determine whether it is necessary to delay FET for at least one menstrual cycle after the failure of fresh embryo transfer. Methods Infertile women eligible for IVF-ET were invited to participate in this multicenter, randomized, non-inferiority, parallel-group, unblinded, controlled trial at the academic fertility centers of four public hospitals in Chinese Mainland. Infertile women scheduled to receive their first FET cycle after a failed IVF-ET attempt were randomly assigned to either (a) the immediate FET group in which FET was performed in the first menstrual cycle following the failed IVF-ET cycle (n = 366) or (b) the delayed FET group in which FET was performed in the second or subsequent menstrual cycle following the failed IVF-ET cycle (n = 366). All FET cycles were performed during hormone replacement cycles for endometrial preparation. The primary outcome was the ongoing pregnancy, defined as a detectable fetal heart beat beyond twelve weeks of gestation. Secondary outcomes were other pregnancy-related outcomes, maternal and neonatal complications. Analysis was performed by both intention-to-treat and per-protocol principles. Results A total of 646 FETs were completed. The frequency of moderate to severe depression and high stress level prior to FET in delayed FET group were significantly higher than that in immediate FET group (10.6% vs 6.1%, p = 0.039; 30.3% vs 22.4%, p = 0.022, respectively). Immediate FET resulted in a higher frequency of clinical pregnancy than did delayed FET (41.7% vs 34.1%), for a relative risk (RR) of 1.23 (95% confidence interval [CI], 1.00-1.50; p = 0.045). Women who underwent immediate FET also had a lower frequency of biochemical pregnancy loss (11.7% vs. 30.6%), with a RR of 0.28 (95% CI 0.23–0.63, p < 0.001), and a higher frequency of embryo implantation (25.2% vs. 20.2%), with a RR of 1.25 (95% CI 1.01–1.53; p = 0.038). Although the ongoing pregnancy and live birth rates did not differ significantly between the immediate FET and delayed FET groups (37.1% vs 30.3%, RR 1.22, 95% CI 0.99–1.52, p = 0.067; 36.5% vs 30.0%, RR 1.22, 95% CI 0.98–1.52, p = 0.079, respectively), a multivariate logistic regression analysis adjusted for potential confounders such as depression and stress levels revealed that the immediate FET group had a significantly higher ongoing pregnancy and live birth rates than the delayed FET group (odds ratio 0.68, 95% CI 0.47–0.99, p = 0.041; odds ratio 0.67, 95% CI 0.46–0.96, p = 0.031). The risks of maternal and neonatal complications were comparable between the two groups. Conclusions In women with a previous failed IVF-ET attempt, immediate FET resulted in higher ongoing pregnancy and live birth rates than delayed FET. These findings warrant caution in the indiscriminate application of a delayed FET strategy when apparent risk of high stress level is perceived.

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jing-Yan Song ◽  
Feng-Yi Dong ◽  
Li Li ◽  
Xing-Xing Zhang ◽  
Ai-Juan Wang ◽  
...  

Abstract Background The optimal time at which to perform a frozen-thawed embryo transfer (FET) following a failed in-vitro fertilization-embryo transfer (IVF-ET) attempt remains elusive to most reproductive experts. Physicians often delay the introduction of FET due to concerns related to potential residual effects of ovarian hyperstimulation which may interfere with the regular menstrual cycle. Moreover, given that most of the published studies on the topic are retrospective and have inconsistent findings, it is crucial to develop evidence-based randomized control guides for clinical practice. Therefore, this well-designed randomized controlled trial (RCT) was conducted to determine whether it is necessary to delay FET for at least one menstrual cycle after the failure of fresh embryo transfer. Methods Infertile women eligible for IVF-ET were invited to participate in this multicenter, randomized, non-inferiority, parallel-group, unblinded, controlled trial at the academic fertility centers of four public hospitals in Chinese Mainland. Infertile women scheduled to receive their first FET cycle after a failed IVF-ET attempt were randomly assigned to either (a) the immediate FET group in which FET was performed in the first menstrual cycle following the failed IVF-ET cycle (n = 366) or (b) the delayed FET group in which FET was performed in the second or subsequent menstrual cycle following the failed IVF-ET cycle (n = 366). All FET cycles were performed during hormone replacement cycles for endometrial preparation. The primary outcome was the ongoing pregnancy, defined as a detectable fetal heart beat beyond twelve weeks of gestation. Secondary outcomes were other pregnancy-related outcomes, maternal and neonatal complications. Analysis was performed by both intention-to-treat and per-protocol principles. Results A total of 646 FETs were completed. The frequency of moderate to severe depression and high stress level prior to FET in delayed FET group were significantly higher than that in immediate FET group (10.6% vs 6.1%, p = 0.039; 30.3% vs 22.4%, p = 0.022, respectively). Immediate FET resulted in a higher frequency of clinical pregnancy than did delayed FET (41.7% vs 34.1%), for a relative risk (RR) of 1.23 (95% confidence interval [CI], 1.00–1.50; p = 0.045). Women who underwent immediate FET also had a lower frequency of biochemical pregnancy loss (11.7% vs. 30.6%), with a RR of 0.28 (95% CI 0.23–0.63, p < 0.001), and a higher frequency of embryo implantation (25.2% vs. 20.2%), with a RR of 1.25 (95% CI 1.01–1.53; p = 0.038). Although the ongoing pregnancy and live birth rates did not differ significantly between the immediate FET and delayed FET groups (37.1% vs 30.3%, RR 1.22, 95% CI 0.99–1.52, p = 0.067; 36.5% vs 30.0%, RR 1.22, 95% CI 0.98–1.52, p = 0.079, respectively), a multivariate logistic regression analysis adjusted for potential confounders such as depression and stress levels revealed that the immediate FET group had a significantly higher ongoing pregnancy and live birth rates than the delayed FET group (odds ratio 0.68, 95% CI 0.47–0.99, p = 0.041; odds ratio 0.67, 95% CI 0.46–0.96, p = 0.031). The risks of maternal and neonatal complications were comparable between the two groups. Conclusions In women with a previous failed IVF-ET attempt, immediate FET resulted in higher ongoing pregnancy and live birth rates than delayed FET. These findings warrant caution in the indiscriminate application of a delayed FET strategy when apparent risk of high stress level is perceived. Trial registration ChiCTR2000033313.


2021 ◽  
Author(s):  
Kathryn M Goldrick ◽  
Paul B Marshburn ◽  
Michelle L Matthews ◽  
Rebecca S Usadi ◽  
Margaret A Papadakis ◽  
...  

Abstract Purpose: Although endometrial scratch may improve outcomes in certain groups of women undergoing assisted reproductive technology (ART), the type of endometrial procedure has not been specified. Our objective was to determine if two types of endometrial scratch prior to embryo transfer result in similar implantation and live birth rates. Also, to determine if patients experience similar pain from both types of endometrial scratch.Methods: This was a prospective, non-blinded, randomized controlled trial with parallel treatment arms of women undergoing blastocyst embryo transfer. Patients underwent endometrial scratch with either vigorous Pipelle curette or four-quadrant scratch with the Shepard insemination catheter.Results: There were 78 patients in the Pipelle curette group and 92 in the Shepard catheter group. There was no difference in implantation rates for the two groups (56.5% ±48 for Pipelle curette group vs. 59.7%±52 for Shepard catheter group, p-value 0.9). Live birth rates were also similar for the two groups (48.1% ±50 for Pipelle curette group vs. 46.8%±50 for Shepard catheter group, p-value 0.7). Mean pain score was significantly less for the Shepard catheter group than for the Pipelle curette group (3.0±2.4 vs. 3.9±2.2, p-value 0.01).Conclusions: Our study demonstrates no difference in implantation or live birth rates for two types of endometrial scratch. There was a difference in patient pain scales with endometrial scratch by a Shepard insemination catheter having a significantly lower pain score than by Pipelle curette. This data gives guidance as to the type of endometrial scratch to be performed prior to ART.


Author(s):  
Racca Annalisa ◽  
Panagiotis Drakopoulos ◽  
Samuel dos Santos Ribeiro ◽  
Christophe Blockeel

Zygote ◽  
2021 ◽  
pp. 1-6
Author(s):  
Linjun Chen ◽  
Zhenyu Diao ◽  
Jie Wang ◽  
Zhipeng Xu ◽  
Ningyuan Zhang ◽  
...  

Summary This study analyzed the effects of the day of trophectoderm (TE) biopsy and blastocyst grade on clinical and neonatal outcomes. The results showed that the implantation and live birth rates of day 5 (D5) TE biopsy were significantly higher compared with those of D6 TE biopsy. The miscarriage rate of the former was lower than that of the latter, but there was no statistically significant difference. Higher quality blastocysts can achieve better implantation and live birth rates. Among good quality blastocysts, the implantation and live birth rates of D5 and D6 TE biopsy were not significantly different. Among fair quality and poor quality blastocysts, the implantation and live birth rates of D5 TE biopsy were significantly higher compared with those of D6 TE biopsy. Neither blastocyst grade nor the day of TE biopsy significantly affected the miscarriage rate. Neonatal outcomes, including newborn sex, gestational age, preterm birth, birth weight and low birth weight in the D5 and D6 TE biopsies were not significantly different. Both blastocyst grade and the day of TE biopsy must be considered at the same time when performing preimplantation genetic testing–frozen embryo transfer.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
R Heidenberg ◽  
A Lanes ◽  
E Ginsburg ◽  
C Gordon

Abstract Study question How do live birth rates differ in anovulatory women with polycystic ovary syndrome and hypothalamic hypogonadism compared to normo-ovulatory women undergoing fresh or frozen embryo transfer? Summary answer Live birth rates are similar among all groups undergoing fresh embryo transfer but are significantly lower in women with hypothalamic hypogonadism undergoing frozen embryo transfer. What is known already Conflicting data exist regarding pregnancy outcomes in patients with tubal factor infertility versus polycystic ovary syndrome (PCOS). Some studies demonstrate higher pregnancy and live birth rates for women with PCOS undergoing fresh embryo transfer, but other studies demonstrate no difference. Women with PCOS have higher live birth rates than those with tubal factor infertility when undergoing frozen embryo transfer. Fewer data are available regarding IVF outcomes in women with hypothalamic hypogonadism (HH) and tubal factor infertility. Several studies report comparable live birth rates with fresh embryo transfer, but there are no data on frozen embryo transfer outcomes. Study design, size, duration Retrospective cohort study of all fresh and frozen autologous embryo transfers performed for patients with oligo-anovulation (PCOS, n = 380 and HH, n = 39) and normo-ovulation (tubal factor infertility, n = 315) from 1/1/2012 to 6/30/2019. A total of 734 transfers from 653 patients were analyzed. Participants/materials, setting, methods Transfer outcomes, including implantation, miscarriage, clinical pregnancy and live birth rates, were assessed in fresh and frozen embryo transfer cycles. Adjusted relative risks (RR) and 95% confidence intervals (CI) were calculated adjusting for age, BMI, stimulation protocol, number of embryos transferred, embryo quality, endometrial stripe thickness and day of transfer. Poisson regression was used for counts and with an offset for ratios. Generalized estimating equations were used to account for patients contributing multiple cycles. Main results and the role of chance For fresh embryo transfer cycles, live birth rates are similar among patients with tubal factor infertility, PCOS and HH (29.5% vs. 37.9% vs. 35.9%, respectively, aRR 1.15 95% CI: 0.91–1.44 and aRR 1.23 95% CI: 0.81–2.00, respectively). When evaluating frozen embryo transfer cycles, patients with HH have lower live birth rates than patients with tubal factor infertility (26.5% vs. 42.6%, aRR 0.54 95% CI: 0.33–0.88) and patients with PCOS (26.5% vs. 46.7%, aRR 0.55 95% CI: 0.34–0.88). Additionally, patients with HH have higher chemical pregnancy rates and miscarriage rates than patients with tubal factor infertility (26.5% vs. 13.0% and 17.7% vs. 6.5%, respectively, RR 2.71 95% CI: 1.27–5.77 and RR 2.03 95% CI: 1.05–3.80, respectively). Point biserial correlation showed no significant correlation between live birth and endometrial stripe thickness in HH patients undergoing frozen embryo transfer (r = 0.028, p-value 0.876). Limitations, reasons for caution This study is limited by its retrospective nature and the small sample size of women with hypothalamic hypogonadism. Additionally, these data represent outcomes from a single academic center, so generalizability of our findings may be limited. Wider implications of the findings: Lower live birth rates for HH patients undergoing frozen embryo transfer cycles are not correlated with endometrial stripe thickness. This may be due to absent gonadotropin signaling on endometrial receptors. A prospective randomized trial of HH patients to modified natural versus programmed frozen embryo transfer would best support this hypothesis. Trial registration number Not applicable


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
S Vereeck ◽  
A Sugihara ◽  
D D Neubourg

Abstract Study question The purpose of this systematic review is to calculate dropout-rates of IVF/ICSI treatment by analysing the published cumulative live birth rates of IVF/ICSI treatment. Summary answer One out of three patients stop their treatment after their first IVF/ICSI cycle and dropout-rates tend to increase per consecutive cycle. What is known already Cumulative live birth rates (CLBRs) have created the possibility to present realistic probabilities of having a live birth after IVF/ICSI treatment. However, it is noted that a significant percentage of the patients stop their treatment before having a child (“dropout”). Possible reasons and predicting factors for dropout of treatment are already extensively investigated. However, only a few studies try to report about the incidence of dropout. Publications on CLBRs of large numbers of patients allow the extraction of dropout-rates. These rates will provide insight in the extent of the problem and could be used as a reference for interventional studies. Study design, size, duration Four databases (PubMed, The Cochrane Library, EMBASE, DoKS) were systematically searched from 1992 to December 2020. Search terms referred to “cumulative live birth” AND “ART/IVF/ICSI”. No restrictions were made on the type or language of publication. Studies were included if they reported absolute numbers of patients and live births per consecutive complete IVF/ICSI cycle or per consecutive embryo transfer cycle, starting from the first IVF/ICSI cycle for each patient. Participants/materials, setting, methods Dropout-rates per cycle were calculated in two manners: “intrinsic dropout-rate” with all patients that started the particular IVF/ICSI cycle in the denominator, and “potential dropout-rate” with all patients who did not achieve a live birth after IVF/ICSI (and potentially could have started a consecutive cycle) in the denominator. Dropout-rates were analysed for consecutive complete cycles and consecutive embryo transfer cycles, because these two manners are used in reporting CLBRs, often related to the reimbursement policy. Main results and the role of chance This review included 29 studies and almost 800,000 patients from different countries and registries. Regarding the patients who started their first IVF/ICSI cycle, trying to conceive their first child by IVF/ICSI, intrinsic dropout-rate was 33% (weighted average) after the first complete cycle, meaning they did not return for their second oocyte retrieval cycle. After the first embryo transfer cycle, intrinsic dropout-rate was 27% (weighted average), meaning those patients did not return for their next frozen-thawed embryo transfer cycle or for the next oocyte retrieval cycle. Regarding the patients who did not achieve a live birth after the first complete cycle, potential dropout-rate was 48% (weighted average), and 37% (weighted average) after the first embryo transfer cycle. Both potential and intrinsic dropout-rates for both consecutive complete and embryo transfer cycles tended to increase with cycle number. One study on second IVF/ICSI conceived children showed a potential dropout-rate after the first complete cycle of 29%. From studies on women &gt;40 years of age, the potential dropout-rate after the first complete cycle was 45% (weighted average) and from studies with the uses of testicular sperm extraction, the potential dropout-rate after the first complete cycle was 34% (weighted average). Limitations, reasons for caution Our analysis was hampered by the different ways of reporting on CLBRs (complete cycles versus embryo transfer cycles), informative censoring, patients changing clinics and spontaneous pregnancies. Dropout-rates were potentially overestimated given that spontaneous pregnancies were not taken into account. Wider implications of the findings: The extent of dropout in IVF/ICSI treatment is substantial and has an important impact on its effectiveness. Therefore, it is a challenge for fertility centers to try to keep patients longer on board, by taking into account the patients’ preferences and managing their expectations. Trial registration number PROSPERO Registration number: CRD42020223512


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
P Sokol ◽  
E Clu. Obradó ◽  
M Sol Inarejos ◽  
M Parrieg. Beltrán ◽  
F Martíne. Sa. Andrés ◽  
...  

Abstract Study question Are embryo quality and day of vitrification (Day 5, 6 or 7) associated with live birth rates (LBR) following single blastocyst transfer (SBT) in frozen embryo transfer cycle (FET)? Summary answer Both blastocyst quality and day of vitrification are significantly associated with LBRs, with very low LBR when poor quality embryos are frozen on day 6. What is known already Evidence suggests that chromosomal status (ploidy) is strongly associated with blastocyst morphology and good quality embryos are more likely to be euploid. Furthermore, previous studies have shown a relationship between the time that embryos need to reach blastocyst stage and their euploidy rate with slowly developing blastocysts showing higher rate of aneuploidy. Nonetheless, despite all this evidence little is known about the actual effect of the combination of blastocyst quality and day of its vitrification. The scope of this study was to quantify the actual effect of the embryo quality and day of vitrification on live birth rates following FET. Study design, size, duration Retrospective analysis of 1546 FET cycles with SBT conducted between 2017 and 2019 in the university-affiliated private clinic. The embryos used for FET were obtained from IVF/ICSI: with PGT (FET-PGT) or without PGT (FET0) or from donated oocytes (FET-DON). Participants/materials, setting, methods FET with natural, natural-modified and completely medicated cycles to prepare endometrial lining were included. Blastocysts were classified according to Spanish Association for the Study of Reproductive Biology (ASEBIR) classification, ranging from A (the highest) to D (the lowest). The impact on LBR of different subgroups, formed within FET-PGT, FET0, FET-DON groups due to different day of vitrification and blastocyst quality, was assessed, using logistic regression after adjusting for age, day of vitrification and embryo quality. Main results and the role of chance We included 1546 FET cycles. Of those, 543 (35%) corresponded to FET-PGT; 648 (42%) to FET0 and 355 (23%) to FET-DON cycles. Overall, 1051 (68%) embryos were frozen on day 5(D5), 472 (30.5%) on day 6(D6) and 23 (1.5%) on day 7(D7). As far as embryo quality was concerned, 215 (13.9%) grade A; 957 (61.9%) B; 371(24%) C and 3(0.2%) D blastocysts were transferred. LBRs were significantly different between different embryos frozen on D5 44.3%; on D6 28.8% and on D7 8.7%, p &lt; 0.001. When blastocyst quality was considered, LBR were 48.4% for grade A; 42.5% for B; 25.1% for C and 0% for D, p &lt; 0.001. After applying logistic regression analysis, the odds ratio (OR) for transferring D6-blastocyst was 1.08, 95% CI[0.45; 2.62] and blastocyst with grade B and C; 0.71, 95% CI[0.51; 1.00]; 0.57,95% CI[0.36; 0.88] respectively. However, after transferring D6-blastocyst graded as C, the OR was 0.33, 95% CI[0.12; 0.90]. Our predictive model showed that the impact of the embryo quality on LBR was sustained across three groups. Transfer of D5/D6 grade A blastocyst resulted in the highest, while D6-C in the lowest LBR in all the groups. In the latter case vitrification on D6 impaired additionally the outcome. Limitations, reasons for caution The study should be interpreted with caution due to its retrospective character and the assessment of blastocyst quality on the day of vitrification and not on the day its transfer. Wider implications of the findings: Our robust findings could be considered a useful tool for counselling couples who seek advice regarding their expected success rates in the setting of FET with SBT. The very low livebirth rates in low quality (C) slow developing (D6) embryos should be communicated to patients prior to planning a FET. Trial registration number Not applicable


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