scholarly journals Recurrent Implantation Failure—Is It the Egg or the Chicken?

Life ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 39
Author(s):  
Paul Pirtea ◽  
Dominique de Ziegler ◽  
Jean Marc Ayoubi

Recurrent implantation failure (RIF) is an undefined, quite often, clinical phenomenon that can result from the repeated failure of embryo transfers to obtain a viable pregnancy. Careful clinical evaluation prior to assisted reproduction can uncover various treatable causes, including endocrine dysfunction, fibroid(s), polyp(s), adhesions, uterine malformations. Despite the fact that it is often encountered and has a critical role in Assisted Reproductive Technique (ART) and human reproduction, RIF’s do not yet have an agreed-on definition, and its etiologic factors have not been entirely determined. ART is a complex treatment with a variable percentage of success among patients and care providers. ART depends on several factors that are not always known and probably not always the same. When confronted with repeated ART failure, medical care providers should try to determine whether the cause is an embryo or endometrium related. One of the most common causes of pregnancy failure is aneuploidy. Therefore, it is likely that this represents a common cause of RIF. Other RIF potential causes include immune and endometrial factors; however, with a very poorly defined role. Recent data indicate that the possible endometrial causes of RIF are very rare, thereby throwing into doubt all endometrial receptivity assays. All recent reports indicate that the true origin of RIF is probably due to the “egg”.

2020 ◽  
Author(s):  
D Cimadomo ◽  
L Craciunas ◽  
N Vermeulen ◽  
K Vomstein ◽  
B Toth

Abstract STUDY QUESTION What is the global variability in recurrent implantation failure (RIF) definition, investigation and therapy, currently offered to patients undergoing IVF? SUMAMRY ANSWER Definitions, diagnostic investigations and treatments offered to RIF patients differ widely amongst assisted reproduction healthcare professionals and clinical guidelines on RIF are urgently needed. WHAT IS KNOWN ALREADY RIF affects around 10% of patients undergoing IVF worldwide. There is no consensus on the definition of RIF, its diagnostic investigations or the therapeutic options, which leads to inconsistencies in clinical practice. STUDY DESIGN, SIZE, DURATION A cross-sectional study of clinicians and embryologists was conducted between May and June 2020. The survey included 43 questions aimed at understanding participants’ background and their current practice with regards to defining, investigating and managing RIF. The questions were designed by the European Society of Human Reproduction and Embryology (ESHRE) Special Interest Group (SIG) on implantation and early pregnancy following three consensus meetings. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 8579 ESHRE members from 6916 IVF centers were invited to participate using two global email calls based on their pre-specified interest in implantation and early pregnancy. SurveyMonkey and SPSS were used for data collection and analysis, respectively. Furthermore, differences were reported in the answers of European and non-European professionals, as well as between public and private settings and among clinicians clustered according to the average number of RIF patients treated per year. MAIN RESULTS AND THE ROLE OF CHANCE The final data set included 735 clinicians and 300 embryologist or IVF-biologists. The majority defines RIF based on the number of failed embryo transfers (ETs) with the most common threshold adopted being three ETs both fresh and frozen. More than two-thirds take lifestyle factors into account, mainly drugs, smoking and BMI. The highest consensus on which diagnostic investigations should be performed was reached for anatomical malformations and gynecological aspects focusing on hydrosalpinx, Asherman’s syndrome, endometrial thickness and endometriosis. Concerning treatment of RIF patients, the highest consensus was reached for preconceptional therapies, including BMI adjustment, smoking and endometritis followed by therapies during IVF procedures. LIMITATIONS, REASONS FOR CAUTION The response rate was relatively low, but comparable to other surveys. WIDER IMPLICATIONS OF THE FINDINGS A consensus on definition, diagnosis and treatment of RIF would help to reduce costly, time-consuming and poorly validated approaches. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used. B.T. received support from Bayer for Clinical trials concerning endometriosis and Ferring for clinical trials concerning ovarian stimulation. She received reimbursement for travel expenses from Astropharm, Ferring. Dr Kade and is a shareholder of Reprognostics. She is a board member of the Austrian Society for Obstetrics and Gynecology (OEGGG), the associate head of the ‘Reproduktionsmedizinische Zentren Baden-Württemberg’ (RZBW), a member of guideline group of the German Society for Obstetrics and Gynecology (DGGG) and an editorial board member of the following journals: American Journal of Reproductive Immunology (AJRI), Archives of Gynecology and Obstetrics. All the other authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A.


Reproduction ◽  
2019 ◽  
Vol 158 (3) ◽  
pp. 247-255
Author(s):  
Su Liu ◽  
Hongxia Wei ◽  
Yuye Li ◽  
Lianghui Diao ◽  
Ruochun Lian ◽  
...  

During pregnancy, the maternal immune system must tolerate the persistence of semi-allogeneic fetus in the maternal tissue. Inadequate recognition of fetal antigens may lead to pregnancy complications, such as recurrent miscarriage (RM) and recurrent implantation failure (RIF). Dendritic cells (DCs) are key regulators of protective immune responses and the development and maintenance of tolerance. Regarding that DCs are important in the establishment of immune tolerance in human pregnancy, it would be important to study the microenvironment in which DCs reside or are activated may affect their functions toward tolerance rather than active immune response. IL-10 plays a critical role in the maintenance of normal pregnancy, and the increased production of IL-10 is associated with successful pregnancy. In this study, we provide an in-depth comparison of the phenotype and cytokine production by DC-10 and other DC subsets, such as iDC and mDC. CD14+ monocyte-derived DCs were differentiated in the presence of IL-10 (DC-10) in vitro from ten normal fertile controls, six RM women and seven RIF women, and characterized for relevant markers. DC-10 was characterized by relatively low expression of costimulatory molecule CD86, as well as MHC class II molecule HLA-DR, high expression of tolerance molecules HLA-G, ILT2, ILT4 and immunosuppressive cytokine IL-10, but produced little or no proinflammatory cytokines, such as TNF-α, IL-6 and IL-12p70. Our study provides a better understanding of the phenotypical properties of DC-10, which may participate in the complex orchestration that leads to maternal immune tolerance and homeostatic environment in human pregnancy.


Author(s):  
Jiaxing Li ◽  
Jia Qi ◽  
Guangxin Yao ◽  
Qinling Zhu ◽  
Xinyu Li ◽  
...  

Decidualization is driven by differentiation of human endometrial stromal cells (ESCs), and is a prerequisite for successful implantation and establishment of pregnancy. The critical role of impaired decidualization in women suffered recurrent implantation failure (RIF) has been established, while the underlying mechanism is poorly understood. In the present study, we verified the essential role of Sirtuin1 (SIRT1) in regulating differentiation and maintaining reactive oxygen species (ROS) homeostasis of human ESCs during decidualization. The abundance of SIRT1 was decreased in RIF patients both in the endometria during window of implantation phase and in the decidualized ESCs. Downregulation of SIRT1 disrupted the intracellular ROS homeostasis during decidualization of ESC, manifested as the accumulation of intracellular ROS level and the reduction of antioxidant stress molecules. Elimination of ROS with N-acetyl-L-cysteine (NAC) could rescued the decidualization inhibition caused by SIRT1 knockdown. Further, we explored the insufficient expression of SIRT1 in ESC affected the deacetylation of forkhead box O1 (FOXO1), and thus inhibited the transcriptional activity of FOXO1. This could account for the dysregulation of intracellular ROS homeostasis during decidualization and decreased expression of decidual markers. Collectively, our findings provided insight into the role of down-regulated SIRT1 in the poor decidual response of ESCs in RIF patients.


2016 ◽  
pp. 80-84
Author(s):  
Thi Tam An Nguyen ◽  
Minh Tam Le ◽  
Ngoc Thanh Cao

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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