scholarly journals Clinical applications of endometrial receptivity tests in patients with recurrent implantation failure

2021 ◽  
Vol 16 (1) ◽  
pp. 79-85
Author(s):  
Ioan BOLEAC ◽  
◽  
Manuela NEAGU ◽  
Anca CORICOVAC ◽  
Dorina CODREANU ◽  
...  

Recurrent implantation failure is represented by the failure to achieve a clinical pregnancy after transfer of at least 4 good-quality embryos in a minimum of 3 fresh or frozen cycles in a woman under the age of 40 years. One of the recent approaches in studying the window of implantation was building the expression profile of the genes of the endometrial cells. We performed a retrospective study which investigated if endometrial receptivity tests improved the outcomes of IVF procedures in patients with recurrent implantation failure. We enrolled 47 couples with RIF and divided them in 2 groups: the first group of 22 couples performed the ERA test and the embryo transfer according to the result of the test; the second group of 27 couples had the embryo transfer done without the ERA test. Our conclusion was that the ERA test did not improve the outcomes for patients with recurrent implantation failure.

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
S Ahuja ◽  
A Taranissi ◽  
M Taranissi

Abstract Study question Do the serum progesterone levels on the day of the endometrial receptivity analysis (ERA) biopsy correlate with the results of the ERA? Summary answer Serum progesterone levels on the day of the endometrial receptivity analysis biopsy do not correlate with the biopsy results. What is known already Endometrial receptivity is a time sensitive window characterised by maturation of the endometrium, during which the trophectodermal cells attach to the endometrial cells and invade the endometrial stromal vasculature. Progesterone is an essential element for receptivity and pregnancy. There is no consensus regarding the optimal progesterone levels in the luteal phase, for a successful pregnancy. Endometrial receptivity analysis is a diagnostic tool developed by profiling the transcriptome of over 238 genes that are expressed at different stages of the endometrial cycle. The results are reported as receptive, pre-receptive, early receptive, etc and are used to direct a personalised embryo transfer. Study design, size, duration We report a prospective study of 30 patients with a history of recurrent implantation failure (RIF). They underwent ERA testing in a medicated cycle, between early 2018 and late 2020. Participants/materials, setting, methods A large proportion of the patients we treat in our clinic (ARGC) have recurrent implantation failure. Thirty patients with RIF underwent ERA testing in a medicated cycle.They all followed the same protocol with down regulation, followed by estrogenic preparation for about 12–14 days, followed by progesterone for about 120 hours. An endometrial biopsy was taken at about 120 hours after progesterone exposure. Main results and the role of chance An ERA result was available on 28/30 patients. Eighteen were reported to be pre-receptive, seven receptive, 3 early receptive and 2 could not be analysed. The progesterone levels within 24 hours of the biopsy for the pre-receptive group ranged from 21.2–472 nmol/l, for the receptive group ranged from 27.8–152 nmol/l and for the early receptive group ranged from 54.9–162 nmol/l. Though the number of cases is small, we found no co-relation between the serum progesterone levels with the ERA results. Eighteen women underwent an embryo transfer based on the ERA results (pET-personalised embryo transfer). Eleven were positive with four live births, one early ongoing pregnancy, three miscarriages, one ectopic pregnancy, two biochemical pregnancies and seven negative results. Seven women had euploid embryo transfers-three had live births, one is viable at 11 weeks, one had a missed miscarriage and two were negative. There are no studies correlating the serum progesterone levels and the ERA results. In practice, we plan embryo transfers for women in frozen cycles by monitoring the serum progesterone levels alongside the day of the cycle. Hence, we wanted to review if the combination of the progesterone levels along with biopsy results would allow us the improve the results further. Limitations, reasons for caution This is a small study. Larger datasets are required to draw meaningful conclusions. Wider implications of the findings: If the above findings are confirmed by larger studies, we may not need to monitor serum progesterone levels during ERA biopsy cycles. Trial registration number NA


2021 ◽  
pp. 1-7
Author(s):  
Yuta Kasahara ◽  
Tomoko Hashimoto ◽  
Ryo Yokomizo ◽  
Yuya Takeshige ◽  
Koki Yoshinaga ◽  
...  

Background:The clinical value of personalized embryo transfer (pET) guided by the endometrial receptivity analysis (ERA) tests for recurrent implantation failure (RIF) cases is still unclear. The aim of this study is to clarify the efficacy of ERA leading to personalization of the day of embryo transfer (ET) in RIF patients. Methods: A retrospective study was performed for 94 patients with RIF who underwent ERA between July 2015 and December 2019. Pregnancy outcomes in a previous vitrified-warmed blastocyst transfer (previous VBT) and a personalized vitrified-warmed blastocyst transfer (pVBT) in identical patients were compared. The details of each pVBT were further analyzed between patients in a non-displaced group, which indicated “receptive” cases in ERA results and those who were in the displaced group, which indicated “non-receptive” cases. Results:When the pregnancy rate, both per patient and per transfer cycle, of previous VBT and pVBT were compared, a significant increase in pVBT was observed between the two methods (5.3% vs. 62.8%, 4.4% vs. 47.9%, respectively). The pregnancy rates, implantation rates, and clinical pregnancy rates of the first pVBT were significantly higher in the displaced group than the non-displaced group. The cumulative ongoing pregnancy rate of the displaced group tended to be higher compared to that of the non-displaced group in the first pVBT, although the difference was not statistically significant (51.0% vs. 31.1%, [Formula: see text] = 0.06). Conclusions:Our study demonstrates that pVBT guided by ERA tests may improve pregnancy outcomes in RIF patients whose window of implantation (WOI) is displaced, and its effect may be more pronounced at the first pVBT. The displacement of WOI may be considered to be one of the causes of RIF, and its adjustment may contribute to the improvement of pregnancy outcomes in RIF patients.


mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Min Fu ◽  
Xiaowei Zhang ◽  
Yiheng Liang ◽  
Shouren Lin ◽  
Weiping Qian ◽  
...  

ABSTRACT Recurrent implantation failure (RIF) refers to repeated failure to become pregnant after transferring embryos with normal morphology. However, the pathogenesis of RIF remains unrevealed, especially for those without any pathological features. In this study, we characterized the vaginal microbiota and metabolomes of patients with unexplained RIF, while patients who achieved clinical pregnancy in the first frozen embryo transfer (FET) cycle were used as controls. Based on 16S rRNA gene sequencing of the vaginal microbiota, the vaginal Lactobacillus showed a significant positive correlation with the pregnancy rate, and the RIF group presented higher microbial α-diversity than the control group (P value = 0.016). The metabolomic profile identified 2,507 metabolites, of which 37 were significantly different between the two groups (P value < 0.05, variable importance for the projection [VIP] > 1). Among them, 2′,3-cyclic UMP and inositol phosphate were the top two metabolites that were higher in the RIF group, while glycerophospholipids and benzopyran were important metabolites that were lower in the RIF group. A lack of lysobisphosphatidic acid and prostaglandin metabolized from glycerophospholipids will lead to deferred implantation and embryo crowding. Benzopyran, as a selective estrogen receptor modulator, may affect the outcome of pregnancy. All of the changes in metabolite profiles may result in or from the differential microbiota compositions in RIF patients. In conclusion, significant differences were presented in the vaginal microbiota and metabolomes between patients with unexplained RIF and women who became pregnant in the first FET cycle. For the first time, this study elaborates the possible pathogenesis of RIF by investigating the vaginal microbiota and metabolites in RIF patients. IMPORTANCE In vitro fertilization-embryo transfer (IVF-ET) is now widely applied for treating infertility, and unexplained recurrent implantation failure (RIF) has become a substantial challenge. We hypothesize that vaginal microbial dysbiosis is associated with RIF, as it is linked to many female reproductive diseases. In this study, we characterized the vaginal microbiota and metabolomes of patients with unexplained RIF, while patients who achieved clinical pregnancy in the first IVF cycle were set as controls. In general, significant differences were discovered in the vaginal microbiota and metabolomes between the two groups. This study is the first detailed elaboration of the vaginal microbiota and metabolites associated with RIF. We believe that our findings will inspire researchers to consider the dynamics of microbiomes related to the microenvironment as a critical feature for future studies of nosogenesis not only for RIF but also for other reproductive diseases.


2021 ◽  
Author(s):  
ling CUI ◽  
Fang Wang ◽  
Yonghong Lin

Abstract Background: To assess the effect of intrauterine administration of seminal plasma for patients with recurrent implantation failure before frozen-thawed embryo transfer. Methods: Trial design: This is a parallel group, randomized (1:1 allocation ratio) controlled trial.Participants: All patients will be recruited from Chengdu Women’s and Children’s Central Hospital. Inclusion criteria: 1. Women after IVF/ICSI treatment in Chengdu Women’s and Children’s Central Hospital. 2.Infertile women with a history of recurrent implantation failure. 3.Infertile couples (both male and female) aged between 20 and 39 years;4. Couples who have at least 1 good quality embryos for transfer. 5. Males had negative in infectious disease test. 6. The males have semen. 7. Women who intend to undergo FET after IVF or ICSI or pre-implantation genetic testing for aneuploidy (PGT-A). 8. Competent and able to give informed consent. Intervention and comparator: Treatment group receiving intrauterine administration of seminal plasma before frozen-thawed embryo transfer. Main outcomes: Clinical pregnancy after frozen-thawed embryo transfer. Randomisation: Patients will be randomly allocated to either treatment or control group at 1:1 ratio. Random numbers will be generated by using software SPSS 25.0 performed by an independent statistician from Chengdu Women’s and Children’s Central Hospital. Blinding (masking): Only the data analyst will be blinded to group assignment. Numbers to be randomised (sample size): To account for a 10% dropout rate, we will recruit 174 patients (87 in each group). Trial status: The date of approval is 31rd May 2021, version 2.0. Recruitment started on 1rd June and is expected to end in July 2022. Discussion: Intrauterine administration of seminal plasma before frozen-thawed embryo transfer of patients with recurrent implantation failure may improve clinical pregnancy rate, it has great Page 2 of 14 significance for assisted reproduction. Trial registration: The study protocol has been approved by the ethics committees at Chengdu Women’s and Children’s Central Hospital. The trial was registered at the Chinese Clinical Trial Registry ChiCTR2100046803. Registered on 28 May 2021.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Y Jia ◽  
Y L Sha ◽  
Z Qiu ◽  
Y H Guo ◽  
A X Tan ◽  
...  

Abstract Study question To quantify the effectiveness of endometrial receptivity analysis (ERA)-guided personalized embryo transfer (pET) in Chinese women. Summary answer ERA-guided pET may remarkably improve pregnancy and implantation rates among Chinese women with Recurrent implantation failure (RIF). What is known already RIF is a major cause of infertility, and endometrial receptivity is widely accepted to impact implantation failure. Precision prediction of the WOI, the time when the endometrium is most receptive to the implantation of the embryo, is, therefore, of great significance to improve implantation prospects. Previous studies have shown the effectiveness of ERA for the prediction of the WOI, and how pET, timed by ERA, improves implantation and pregnancy rates; however, the efficacy of ERA-guided pET remains unknown for Chinese women. Study design, size, duration Patients in Chengdu Xi’nan Gynecology Hospital (Chengdu, China) who were undergoing frozen embryo transfer (FET) at the blastocyst stage on day five or day six during the period from November 2019 through September 2020 were recruited for this study. A total of 145 eligible patients were included in the study and assigned to the ERA group (n = 67) or the control group (n = 78). Clinical pregnancy outcomes were compared between the two groups. Participants/materials, setting, methods Endometrial specimens were collected the from ERA group. Total RNA was extracted from endometrial specimens, the transcriptomic sequencing data were processed using RNA-Seq and the endometrial receptivity status was assessed by the ERA predictor. The endometrium was classified as receptive or non-receptive according to the ERA assessment, and pET was done at the time determined by ERA in the ERA group. Subjects in the control group did not receive ERA and underwent blastocyst transfer normally. Main results and the role of chance The demographic and clinical characteristics were comparable between the ERA and control groups (P &gt; 0.05). The ERA test identified 10.45% of samples as receptive and 89.55% of samples as non-receptive in the ERA group, with 70.15% of samples presenting a pre-receptive profile. We observed higher cumulative pregnancy (74.63% vs. 64.10%) and cumulative implantation rate (47.32% vs. 21.68%) rates, and a lower biochemical pregnancy rate (18.00% vs. 34.00%) in the ERA group when compared to the control group (P &lt; 0.05). Additionally, we found higher pregnancy (67.16% vs. 39.74%) and implantation (46.54% vs. 16.94%) rates as well as a lower biochemical pregnancy rate (17.78% vs. 45.16%) after the first ERA test in the ERA group when compared to the control group (P &lt; 0.01). Limitations, reasons for caution First, this is a retrospective analysis, which is relatively more biased than prospective clinical trials. Second, the study sample is considerably small. Third, only 10.45% of the subjects were identified as presenting a receptive profile, which limits the comparisons of clinical outcomes between patients with receptive and non-receptive endometria. Wider implications of the findings: This study demonstrates that the ERA test helps to determine the optimal timing for embryo transfer, improve pregnancy and implantation rates in patients with RIF, and guides the clinical application of the ERA test. Trial registration number approval No. 2020–018


2019 ◽  
Vol 37 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Zhenhong Shuai ◽  
Xuemei Li ◽  
Xuelian Tang ◽  
Fang Lian ◽  
Zhengao Sun

Objective: To evaluate the effect of transcutaneous electrical acupuncture stimulation (TEAS) on pregnancy outcomes in patients with recurrent implantation failure (RIF) undergoing in vitro fertilisation (IVF). Methods: A total of 122 women with RIF undergoing fresh embryo transfer cycle IVF were randomly allocated to a TEAS or mock TEAS (MTEAS) group. Gonadotrophin therapy using a long protocol was provided in both groups. TEAS consisted of 30 min of stimulation (9–25 mA, 2 Hz) at SP6, CV3, CV4 and Zigong from day 5 of the ovarian stimulation cycle once every other day until the day of embryo transfer. The patients in the control group received MTEAS. Implantation, clinical pregnancy and live birth rates were compared. Results: In the TEAS group, the implantation rate, clinical pregnancy rate and live birth rate (24.3%, 32.8% and 27.9%, respectively) were significantly higher than in the MTEAS group (12.1%, 16.4% and 13.1%, respectively). Conclusions: TEAS significantly improves the clinical outcomes of subsequent IVF cycles among women who have experienced RIF. Trial registration number: ChiCTR-TRC-14004730.


Zygote ◽  
2016 ◽  
Vol 24 (5) ◽  
pp. 742-747 ◽  
Author(s):  
Katalin Kanyo ◽  
Jozsef Zeke ◽  
Rita Kriston ◽  
Zoltan Szücs ◽  
Sandor Cseh ◽  
...  

SummaryBiochemical modifications of zona pellucida (ZP) result in zona hardening. Zona hardening (ZH) is induced by several factors such as advancing maternal age,in vitroculture conditions and cryopreservation and adversely effects implantation. The objective of the clinical study was to determine whether or not laser-assisted hatching (LAH) applied on day 3 frozen embryos improves the outcome of frozen embryo transfer (FET) cycles in patients with recurrent implantation failure and/or advanced female age. In total, 413 patients of different ages with recurrent implantation failure (maximum three cycles) were involved into the study. Patients were allocated randomly into LAH and control groups. On the day of FET, after thawing and just before FET, the ZP was thinned using a laser system. In the control group no treatment was applied on frozen embryo before transfer. The main outcome measures were clinical pregnancy rate. Overall, the results indicate a tendency that LAH increased (P= 0.08) clinical pregnancy. However, for patients older than 37 years, LAH increased pregnancy rates significantly (P= 0.03). In the LAH and control groups, the age of patients and the number of transferred embryos influenced pregnancy rates (P= 0.01). For patients older than 37 years, no effect of number of transferred embryos was detected (P= 0.14). The incidence of multiple pregnancies also increased in the LAH group (P= 0.01). In conclusion, in older woman, to overcome the negative effect of zona hardening, LAH could be performed on frozen embryos as a routine strategy before FET in frozen cycles in order to increase the possibility of pregnancy formation.


2018 ◽  
Vol 5 (3) ◽  
pp. 125-133
Author(s):  
I. Boleac ◽  
Manuela Neagu ◽  
R. Ene ◽  
Alina Busan - Pîrvoiu ◽  
Dorina Codreanu ◽  
...  

Recurrent implantation failure refers to a failure to achieve a clinical pregnancy after transfer of atleast four good-quality embryos in a minimum of three fresh or frozen cycles in a woman under theage of 40 years. We present this retrospective study, in which we proposed local endometrial injuryfor the management of the uterine factors in the case of 30 couples with recurrent implantationfailure. Our conclusion was that local endometrial injury improved the clinical pregnancy rate forthese couples, especially when the study population met specific criteria.


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