scholarly journals Alterations in Vaginal Microbiota and Associated Metabolome in Women with Recurrent Implantation Failure

mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Min Fu ◽  
Xiaowei Zhang ◽  
Yiheng Liang ◽  
Shouren Lin ◽  
Weiping Qian ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Inositol Phosphate ◽  
Clinical Pregnancy ◽  
Vaginal Microbiota ◽  
Control Group ◽  
Rrna Gene ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Critical Feature ◽  
Α Diversity

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.

Vaginal microbiota alterations in women with recurrent implantation failure and the associated metabolome

2019 ◽  
Author(s):  
Min Fu ◽  
Xiaowei Zhang ◽  
Weiping Qian ◽  
Yiheng Liang ◽  
Shouren Lin ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Vaginal Microbiota ◽  
Control Group ◽  
P Value ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Vitro Fertilization ◽  
Α Diversity ◽  
Rdna Sequencing

Abstract In vitro fertilization-embryo transfer (IVF-ET) is now widely applied in treating infertility. As the number of IVF cycles continues to increase, recurrent implantation failure (RIF) has become a big challenge. The cause of RIF is very complex and remains largely unrevealed, especially for those without any pathological features. It has been proved that vaginal microbiota is associated with many female reproductive diseases, such as pregnancy-related diseases, sexually transmitted diseases, tubal factor infertility, and first trimester miscarriage after in vitro fertilization (IVF) and so on. Hence, vaginal microbiota and its metabolome may also relate to RIF. In this study, we characterized the vaginal microbiota and metabolome of patients with unexplained RIF, while patients who achieved clinical pregnancy in the first IVF cycle were used as controls. Results Based on 16S rDNA sequencing of the vaginal microbiota, the RIF group presented higher microbial α-diversity than the control group (0.80±0.50 vs 0.50±0.39, P-value=0.016) and harbored more non-Lactobacillus microorganisms, including 25 significantly increased genera of both aerobic and anaerobic bacteria. The metabolomic profile showed that the relative abundances of 37 metabolites among 2,507 metabolites were significantly different between the two groups. Among them, 2',3-cyclic UMP and phosphoinositide were the top two metabolites significantly upregulated in the RIF group, while glycerophospholipids and benzopyran were important metabolites that were significantly downregulated. Lysobisphosphatidic acid (LPA) and prostaglandin (PG) metabolized from glycerophospholipids are key factors affecting implantation and decidualization. Benzopyran, as a selective estrogen receptor modulator (SERM), may affect the outcome of pregnancy. All of the metabolome outcomes may result in or from the differential microbiota composition in the RIF patients. Conclusions In conclusion, significant differences were presented in the vaginal microbiota and metabolome between RIF patients and women who became pregnant in the first IVF cycle, which are related to embryo implantation. This study not only deeply investigates the relationship between RIF and the vaginal microbial community and its metabolites but also provides a profound understanding of the pathogenesis of RIF.

scholarly journals Transcutaneous electrical acupuncture point stimulation improves pregnancy outcomes in patients with recurrent implantation failure undergoing in vitro fertilisation and embryo transfer: a prospective, randomised trial

2019 ◽  
Vol 37 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Zhenhong Shuai ◽  
Xuemei Li ◽  
Xuelian Tang ◽  
Fang Lian ◽  
Zhengao Sun
Keyword(s):  
Embryo Transfer ◽  
Live Birth ◽  
Pregnancy Outcomes ◽  
Clinical Pregnancy ◽  
In Vitro Fertilisation ◽  
Control Group ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Electrical Acupuncture

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.

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 ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Embryo Transfer ◽  
Expression Profile ◽  
Clinical Applications ◽  
Endometrial Receptivity ◽  
Clinical Pregnancy ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Endometrial Cells

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.

scholarly journals Effect of Intrauterine Administration of Seminal Plasma for Patients with Recurrent Implantation Failure Before FET: Study Protocol for a Prospective Randomised Controlled Trial

2021 ◽  
Author(s):  
ling CUI ◽  
Fang Wang ◽  
Yonghong Lin
Keyword(s):  
Embryo Transfer ◽  
Study Protocol ◽  
Seminal Plasma ◽  
Controlled Trial ◽  
Clinical Pregnancy ◽  
Implantation Failure ◽  
Central Hospital ◽  
Recurrent Implantation Failure ◽  
Frozen Thawed Embryo Transfer ◽  
Thawed Embryo Transfer

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.

P–392 Clinical outcomes of endometrium receptivity analysis(ERA) testing in patients with repeated IVF failures

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
W J Yang ◽  
F Lu ◽  
L Che. yu ◽  
Y. Y Hsuan ◽  
C Chin. Hung ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Clinical Outcomes ◽  
Embryo Transfer ◽  
Clinical Pregnancy ◽  
Control Group ◽  
Implantation Failure ◽  
Single Center ◽  
Implantation Window ◽  
Ivf Failure ◽  
Endometrium Receptivity

Abstract Study question Is ERA testing different between RIF patients with control group? Summary answer In RIF patients, there were more chances of non-receptive endometrium. ERA testing may be helpful for the patients with repeated IVF failure. What is known already: The endometrium receptivity analysis testing might have the ability to detect the implantation window. In repeat implantation failure patients, detecting of precisely implantation window may have some benefits. Study design, size, duration This was a single-center retrospective observational study. Two hundred and forty-nine patients who underwent ERA testing following frozen-thawed embryo transfer in our center were including in this study between January 2019 and May 2020. Participants/materials, setting, methods 181 patients having unexplained repeated IVF failure (RIF group, at least tow implantation failure) and 68 patients having no experience with embryo transfer (Control group) who underwent ERA testing were including in this study. Both of Patients having a receptive (R) ERA and having a non-receptive (NR) ERA underwent a personalized embryo transfer (pET) on ERA. ERA results and clinical outcomes compared between RIF group and control group were analyzed by Chi-square test. Main results and the role of chance The proportion of R/NR results were 33:35 for the RIF group and 118:63 for the Control group, demonstrating the displacement of the window of implantation in patients with RIF. Our results revealed an endometrial factor in 51% RIF patients, which was significantly greater than the Control group 34.8% (P = 0.02). Among the patients with NR ERA result, there are not significantly difference in clinical pregnancy rate in the RIF group compared with control group (57.1%. vs. 61.9%). The clinical pregnancy rate of the patients with receptive ERA result also is comparable in both group (70.3% vs. 66.7%). Limitations, reasons for caution This is a retrospective, single center study with limited case number. There were may some bias with ERA testing errors. Wider implications of the findings: In RIF patients, there were more chances of non-receptive endometrium. ERA testing may be helpful for the patients with repeated IVF failure. Larger randomized studies are required to validate these results. Trial registration number 18MMHISO70e

P–313 Endometrial receptivity analysis for personalized embryo transfer in patients with recurrent implantation failure: a retrospective analysis of a Chinese cohort

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Y Jia ◽  
Y L Sha ◽  
Z Qiu ◽  
Y H Guo ◽  
A X Tan ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Retrospective Analysis ◽  
Embryo Transfer ◽  
Chinese Women ◽  
Endometrial Receptivity ◽  
Control Group ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Biochemical Pregnancy ◽  
Implantation Rates

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

scholarly journals The impact of laser-assisted hatching on the outcome of frozen human embryo transfer cycles

Zygote ◽  
2016 ◽  
Vol 24 (5) ◽  
pp. 742-747 ◽  
Author(s):  
Katalin Kanyo ◽  
Jozsef Zeke ◽  
Rita Kriston ◽  
Zoltan Szücs ◽  
Sandor Cseh ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Pregnancy Rates ◽  
Clinical Pregnancy ◽  
Assisted Hatching ◽  
Implantation Failure ◽  
Control Groups ◽  
Recurrent Implantation Failure ◽  
Zona Hardening ◽  
Frozen Embryos ◽  
And Control

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.

Experience of using time-lapse microscopy in IVF and ICSI programs

2020 ◽  
pp. 47-50
Author(s):  
N. V. Saraeva ◽  
N. V. Spiridonova ◽  
M. T. Tugushev ◽  
O. V. Shurygina ◽  
A. I. Sinitsyna
Keyword(s):  
Pregnancy Rate ◽  
Embryo Transfer ◽  
Selection Procedure ◽  
Time Lapse ◽  
Single Embryo Transfer ◽  
Main Group ◽  
Clinical Pregnancy ◽  
Control Group ◽  
Time Lapse Microscopy

In order to increase the pregnancy rate in the assisted reproductive technology, the selection of one embryo with the highest implantation potential it is very important. Time-lapse microscopy (TLM) is a tool for selecting quality embryos for transfer. This study aimed to assess the benefits of single-embryo transfer of autologous oocytes performed on day 5 of embryo incubation in a TLM-equipped system in IVF and ICSI programs. Single-embryo transfer following incubation in a TLM-equipped incubator was performed in 282 patients, who formed the main group; the control group consisted of 461 patients undergoing single-embryo transfer following a traditional culture and embryo selection procedure. We assessed the quality of transferred embryos, the rates of clinical pregnancy and delivery. The groups did not differ in the ratio of IVF and ICSI cycles, average age, and infertility factor. The proportion of excellent quality embryos for transfer was 77.0% in the main group and 65.1% in the control group (p = 0.001). In the subgroup with receiving eight and less oocytes we noted the tendency of receiving more quality embryos in the main group (р = 0.052). In the subgroup of nine and more oocytes the quality of the transferred embryos did not differ between two groups. The clinical pregnancy rate was 60.2% in the main group and 52.9% in the control group (p = 0.057). The delivery rate was 45.0% in the main group and 39.9% in the control group (p > 0.050).

THE EFFECT OF ASSISTED HATCHING IN FROZEN-THAWED EMBRYO TRANSFER CYCLES

2016 ◽  
pp. 80-84
Author(s):  
Thi Tam An Nguyen ◽  
Minh Tam Le ◽  
Ngoc Thanh Cao
Keyword(s):  
Embryo Transfer ◽  
Zona Pellucida ◽  
Assisted Hatching ◽  
Implantation Failure ◽  
Multiple Pregnancies ◽  
Recurrent Implantation Failure ◽  
Key Words Laser ◽  
Implantation And Pregnancy Rates ◽  
Frozen Thawed Embryo Transfer ◽  
Thawed Embryo Transfer

Background: Laser assisted hatching technique based on the hypothesis to make an artificial hole on zona pellucida (ZP) that can help embryo hatching out of ZP easily. This technique has been shown to increase implantation and pregnancy rates in women of advanced age, in women with recurrent implantation failure and following the transfer of frozen–thawed embryos. This study described the outcome of frozen–thawed embryo transfers with laser assisted hatching (LAH), which is one of the safest method in nowadays. Purpose: To assess the effect of assisted hatching technique on the clinical outcomes in vitrified-warmed transfer cycles. Method: A total of 65 thawed-transfer cycles with 153 thawed-embryos undertaken within a 12-month period were analysed, Assisted hatching with laser zona thinning was performed with one-quarter of the zona pellucida circumference. The overall thawed-embryos (day 3) were kept in culture overnight. Patient were prepared the suitable endometrium and transferred embryos advantageously. Results: In which, having the rate of survival embryos were 143 occupying 94.3%, the percentage of grade 1 and 2 embryos occupied 55.9% and 29,3% respectively, and that were enrolled LAH before transfering of frozen–thawed embryos. The average transferred embryos were 2.4±0.8, The rate of implantation per transferred embryos and per transferred embryos cycles was 19.5% and 43.1% respectively. The rate of clinical pregnancies per embryo transfer cycles occupied 33.8% with percentage of early miscarriages (biochemical pregnancies and early clinical miscarriages) was 12.3%. The rate of ongoing pregnancies was 30.8% and multiple pregnancies was low just 12.3%. This result was equal or higher than other researchs in embryos transfer had or no LAH. Conclusion: LAH contributed to stable frozen–thawed embryos transfer effectiveness. Key words: Laser assisted hatching, frozen–thawed embryos transfer, zona pellucida (ZP)

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