• BMB Reports
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• v.51 no.5
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• pp.225-229
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• 2018

In humans, hormonal regulation is crucial for the preparation of uterine environment leading to either successful implantation or menstrual cycle. Estrogen is a pivotal female steroid hormone that regulates the uterine dynamics along with progesterone in the estrous and menstrual cycles in humans. Estrogen signals act via nuclear estrogen receptor or membrane-bound receptor. The membrane-bound estrogen receptor plays a crucial role in the rapid response of estrogen in the uterine epithelium. Recently, RASD1 has received attention as a novel signal transducer of estrogen in various systems including female reproductive organs. In this review, we discuss the regulation of estrogen and RASD1 signaling in the uterus and also provide insights into RAS as a novel signaling molecule in repeated implantation failure.

• Clinical and Experimental Reproductive Medicine
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• v.44 no.2
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• pp.105-110
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• 2017

Objective: The purpose of this study was to evaluate the efficacy of frozen mixed double-embryo transfer (MDET; the simultaneous transfer of day 3 and day 5 embryos) in comparison with frozen blastocyst double-embryo transfer (BDET; transfer of two day 5 blastocysts) in patients with repeated implantation failure (RIF). Methods: A total of 104 women with RIF who underwent frozen MDET (n = 48) or BDET (n = 56) with excellent-quality embryos were included in this retrospective analysis. All frozen embryo transfers were performed in natural cycles. The main outcome measures were the implantation rate, clinical pregnancy rate, multiple pregnancy rate, and miscarriage rate. These measures were compared between the patients who underwent MDET or BDET using the chi-square test or the Fisher exact test, as appropriate. Results: The implantation and clinical pregnancy rates were significantly higher in patients who underwent MDET than in those who underwent BDET (60.4% vs. 39.3%, p=0.03 and 52.1% vs. 30.4%, p=0.05, respectively). A significantly lower miscarriage rate was observed in the MDET group (6.9% vs. 10.7%, p=0.05). In addition, the multiple pregnancy rate was slightly, but not significantly, higher in the MDET group (27.1% vs. 25.0%). Conclusion: MDET was found to be significantly superior to double blastocyst transfer. It could be regarded as an appropriate approach to improve in vitro fertilization success rates in RIF patients.

• The Journal of Korean Obstetrics and Gynecology
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• v.37 no.2
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• pp.120-134
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• 2024

Objectives: This research aimed at investigating the trends of acupuncture treatment for Recurrent Implantation Failure (RIF) patients in IVF. Methods: Studies were searched from PubMed, Cochrane Library, EMBASE, CNKI up to April 2024. Terms as 'Implantation failure', 'Recurrent implantation failure', 'Repeated implantation failure', 'RIF' and 'Acupuncture', 'Electroacupuncture', 'Needling' were used. Results: Of 136 screened, 10 studies are selected and analyzed. Studies were conducted using manual acupuncture and electroacupuncture. The results showed that acupuncture (electroacupuncture) treatment for RIF patients is effective in improving clinical pregnancy rate, endometrial blood flow, uterus morphology, endometrium thickness. The most frequently used acupoints were 三陰交 (SP6) and 子宮 (EX-CA1). Conclusions: Included studies showed that acupuncture (electroacupuncture) might have effect on RIF. Further research and meta-analysis should be conducted to verify its therapeutic mechanisms and safety.

• Clinical and Experimental Reproductive Medicine
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• v.48 no.3
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• pp.203-210
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• 2021

We performed a systematic review and meta-analysis to evaluate whether intralipid administration improved the outcomes of in vitro fertilization. Online databases (PubMed, Cochrane Library, Medline, and Embase) were searched until March 2020. Only randomized controlled trials (RCTs) that assessed the role of intralipid administration during in vitro fertilization were considered. We analyzed the rates of clinical pregnancy and live birth as primary outcomes. Secondary outcomes included the rates of chemical pregnancy, ongoing pregnancy, and missed abortion. We reviewed and assessed the eligibility of 180 studies. Five RCTs including 840 patients (3 RCTs: women with repeated implantation failure, 1 RCT: women with recurrent spontaneous abortion, 1 RCT: women who had experienced implantation failure more than once) met the selection criteria. When compared with the control group, intralipid administration significantly improved the clinical pregnancy rate (risk ratio [RR], 1.48; 95% confidence interval [CI], 1.23-1.79), ongoing pregnancy rate (RR, 1.82; 95% CI, 1.31-2.53), and live birth rate (RR, 1.85; 95% CI, 1.44-2.38). However, intralipid administration had no beneficial effect on the miscarriage rate (RR, 0.75; 95% CI, 0.48-1.17). A funnel plot analysis revealed no publication bias. Our findings suggest that intralipid administration may benefit women undergoing in vitro fertilization, especially those who have experienced repeated implantation failure or recurrent spontaneous abortion. However, larger, well-designed studies are needed to confirm these findings.

• Clinical and Experimental Reproductive Medicine
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• v.51 no.3
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• pp.260-267
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• 2024

Objective: This study investigated the metabolic status of the spent culture media from embryos of patients with repeated implantation failure (RIF) undergoing in vitro fertilization-intracytoplasmic sperm injection cycles in comparison with the embryos from healthy fertile women. Methods: Metabolite levels in spent culture media were assessed and compared between embryos from RIF patients (n=35) and oocyte donors as controls (n=15). Protein levels of insulin-like growth factor 1 (IGF-1) were determined using Western blotting. Concentrations of glucose, pyruvate, and lactate were measured using spectrophotometry. Ionic colorimetric assay kits were utilized to analyze the concentrations of sodium, chloride, calcium, and magnesium ions. High-performance liquid chromatography was employed to measure the concentrations of glutamic acid, aspartic acid, methionine, phenylalanine, and histidine. Results: Glucose consumption and lactate secretion were higher in the control group than in the RIF group. The magnesium concentration was significantly higher in the control group than in the RIF group, but glutamic acid and aspartic acid concentrations were lower in the control group than in the RIF patients (p<0.05). The levels of IGF-1, sodium, calcium, chloride, methionine, histidine, and phenylalanine did not show statistically significant differences between the two groups. Conclusion: The metabolic profile of the culture medium of the embryos in the RIF group differed from that of the control group. These findings suggest potential factors that may affect implantation capacity in RIF patients and provide a new perspective on embryo selection.

• Clinical and Experimental Reproductive Medicine
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• v.25 no.2
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• pp.123-128
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• 1998

Implantation rates remain low following human in vitro fertilization (IVF). Suboptimal culture conditions may limit the ability of embryos to hatch as blastocysts, and artificial opening of the zona pellucida has been proposed as a means to promote subsequent hatching (assisted hatching). In this study, assisted hatching (AH) by zona drilling using acidic Tyrode's solution was performed in 320 patients, due to their age of more than 38 years (group A), the thick zona pellucida (group Z; $ZP\geq0.18{\mu}m$), and failures in implantation more than 3 times in previous IVF-ET trial (group P). This study was designed firstly, to study the effects of AH on the outcomes of IVF-ET according to the indications and secondly, to verify the appropriate application of AH. The results were as follows; 1. There was no difference in pregnancy rate between AH group (26.6%) and non-AH group (26.5%). 2. Assisted hatching (AH) showed significantly higher pregnancy rate of the patients with thick zona pellucid a than those of the patients with age factor and with the history of repeated implantation failure. But in the patients with age factor only, AH resulted in higher pregnancy rate. 3. Interestingly, the patients with complex factors including zona factor (Z: 33.9%; ZA: 30.4%; ZP: 31.6%; ZAP: 21.4%) showed higher pregnancy rates than other complex factors excluding zona factor (A: 24.4%, P: 0%; AP: 10.8%). From these results, AH is more helpful to the patients with thick zona pellucida rather than patients with older age and/or previous repeated implantation failure.

• Clinical and Experimental Reproductive Medicine
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• v.43 no.4
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• pp.185-192
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• 2016

Chronic endometritis (CE) is a condition involving the breakdown of the peaceful co-existence between microorganisms and the host immune system in the endometrium. A majority of CE cases produce no noticeable signs or mild symptoms, and the prevalence rate of CE has been found to be approximately 10%. Gynecologists and pathologists often do not focus much clinical attention on CE due to the time-consuming microscopic examinations necessary to diagnose CE, its mild clinical manifestations, and the benign nature of the disease. However, the relationship between CE and infertility-related conditions such as repeated implantation failure and recurrent miscarriage has recently emerged as an area of inquiry. In this study, we reviewed the literature on the pathophysiology of CE and how it may be associated with infertility, as well as the literature regarding the diagnosis and treatment of CE. In addition, we discuss the value of hysteroscopic procedures in the diagnosis and treatment of CE.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.41
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• pp.27.1-27.9
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• 2019

Background: Implants are becoming the first choice of rehabilitation for tooth loss. Even though they have a high success rate, failures still occur for many reasons. The objective of this study is to analyze the reasons for recurring failure at the same site and the results of re-implantation. Methods: Thirteen patients (11 males and 2 females, mean age 60 ± 9.9 years) who experienced implant surgery failure at the same site (same tooth extraction area) two or more times in the Department of Oral and Maxillofacial Surgery, Seoul National University Bundang Hospital, between 2004 and 2017 were selected. The medical records on a type, sites, diameter, and length of implants; time and estimated cause of failure; and radiographs were reviewed. Data were collected and analyzed retrospectively, and the current statuses were evaluated. Results: A total of 14 implants experienced failure in the same site more than two times. Twelve implants were placed in the maxilla, while 2 implants were placed in the mandible. The maxillary molar area was the most common site of failure (57.1%), followed by the mandibular molar, anterior maxilla, and premolar areas (14.3% each). The first failure occurred most commonly after prosthetic treatment (35.7%) with an average period of failure of 3.8 months after loading. Ten cases were treated as immediate re-implantation, while the other 4 were delayed reimplantation after an average of 3.9 months. The second failure occurred most commonly after prosthetic treatment (42.9%), with an average of 31 months after loading; during the healing period (42.9%); and during the ongoing prosthetic period (14.3%). In 3 cases (21.4%), the treatment plan was altered to an implant bridge, while the other 11 cases underwent another implant placement procedure (78.6%). Finally, a total of 9 implants (64.3%) survived, with an average functioning period of 60 months. Conclusions: Implants can fail repeatedly at the same site due to overloading, infection, and other unspecified reasons. The age and sex of the patient and the location of implant placement seem to be associated with recurring failure. Type of implant, bone augmentation, and bone materials used are less relevant.

• Clinical and Experimental Reproductive Medicine
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• v.50 no.4
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• pp.277-284
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• 2023

Objective: In this retrospective study, we analyzed factors influencing the ongoing pregnancy rate (PR) in women with repeated implantation failure (RIF) undergoing embryo transfer with endometrial receptivity array (ERA). Methods: Eighty-three consecutive personalized embryo transfers (pETs) with ERA, from 54 women with RIF, were selected from June 2020 to April 2022. Vitrified blastocyst transfer was timed based on ERA results. Results: The ongoing PR per pET was 33.7%. Using ERA, the endometrium was identified as pre-receptive in 26 cycles, early receptive in 25 cycles, receptive in 31 cycles, and late receptive in one cycle. With cycles categorized into three receptivity phases (pre-receptive, early receptive, or receptive), no significant differences were found in the clinical PR (27.3%, 55.6%, and 40%, respectively) or ongoing PR (9.1%, 55.6%, and 40%, respectively) after a single blastocyst transfer. Similarly, no significant differences were observed in the clinical PR or ongoing PR after the transfer of two or more blastocysts. Among women with ongoing pregnancy relative to those without, age at first pET was significantly lower (35 years vs. 39 years, p=0.001), while blastocyst score (23 vs. 18, p=0.012) and the proportion of blastocyst scores >18 (71.4% vs. 38.9%, p=0.005) were significantly higher. In multiple logistic regression analysis, the woman's age (odds ratio [OR], 0.814; 95% confidence interval [CI], 0.706 to 0.940; p=0.005) and blastocyst score >18 (OR, 3.052; 95% CI, 1.075 to 8.665; p=0.036) were identified as significant factors influencing ongoing pregnancy. Conclusion: In pET with ERA, ongoing pregnancy was closely associated with woman's age and blastocyst quality.

• Clinical and Experimental Reproductive Medicine
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• v.44 no.1
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• pp.1-7
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• 2017

The task force of the Korean Society for Reproductive Immunology recommends intravenous immunoglobulin G treatment in women with reproductive failure, including recurrent pregnancy loss and/or repeated implantation failure, who show cellular immune factors such as abnormal natural killer cell levels, natural killer cell cytotoxicity, and/or type 1 T helper immunity.