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Objectives: Endometrial scratching (ES) and/or intravenous intralipid therapy (in cases of increased uterine natural killer cells, uNKs) are still conducted in several fertility centers as "add-on" treatments in patients undergoing ART, although convincing evidence for beneficial effects is lacking. Study design: In this retrospective study, associations between ES treatment or additional intralipid therapy and pregnancy and live birth rates of 1,546 patients undergoing 2,821 IVF-/ICSI-treatment cycles with fresh or frozen embryo transfers in a German fertility-center between 1st January 2014 and 31th May 2017 were analyzed. Results: Overall pregnancy and live birth rates for all 2,821 treatment cycles (468 cycles with ES) were 32.8% and 23.5%. There were no statistically significant differences in pregnancy or live birth rates between first treatment cycles with and without ES (p = 0.915 and p = 0.577) or between second cycles following an unsuccessful first cycle with and without ES (p = 0.752 and p = 0.623). These results were confirmed using multivariable generalized estimating equations (GEE) models accounting for non-independency of multiple treatment cycles per patients that included all cycles and showed no significant effect of ES on pregnancy (p = 0.449) or live birth rates (p = 0.976). Likewise, a GEE model revealed no significant effect of intralipid treatment on pregnancy (p = 0.926) and live birth rates (p = 0.727). Conclusions: Our results reveal no evidence that ES increases the pregnancy or live birth rates in women undergoing their first or further IVF cycle with fresh or frozen embryo transfer. Intralipid treatment was also not beneficial. Even if patients explicitly ask for it, these procedures are not recommended outside of clinical studies. [ABSTRACT FROM AUTHOR]

ObjectivesEndometrial scratching (ES) and/or intravenous intralipid therapy (in cases of increased uterine natural killer cells, uNKs) are still conducted in several fertility centers as “add-on” treatments in patients undergoing ART, although convincing evidence for beneficial effects is lacking.Study designIn this retrospective study, associations between ES treatment or additional intralipid therapy and pregnancy and live birth rates of 1,546 patients undergoing 2,821 IVF-/ICSI-treatment cycles with fresh or frozen embryo transfers in a German fertility-center between 1st January 2014 and 31th May 2017 were analyzed.ResultsOverall pregnancy and live birth rates for all 2,821 treatment cycles (468 cycles with ES) were 32.8% and 23.5%. There were no statistically significant differences in pregnancy or live birth rates between first treatment cycles with and without ES (p = 0.915 and p = 0.577) or between second cycles following an unsuccessful first cycle with and without ES (p = 0.752 and p = 0.623). These results were confirmed using multivariable generalized estimating equations (GEE) models accounting for non-independency of multiple treatment cycles per patients that included all cycles and showed no significant effect of ES on pregnancy (p = 0.449) or live birth rates (p = 0.976). Likewise, a GEE model revealed no significant effect of intralipid treatment on pregnancy (p = 0.926) and live birth rates (p = 0.727).ConclusionsOur results reveal no evidence that ES increases the pregnancy or live birth rates in women undergoing their first or further IVF cycle with fresh or frozen embryo transfer. Intralipid treatment was also not beneficial. Even if patients explicitly ask for it, these procedures are not recommended outside of clinical studies.

Background: Induced endometrial injury is a technique described that have positive impact on implantation. The aim ofthis study was to investigate whether hysteroscopic endometrial fundal incision (EFI) in oocyte recipients before embryotransfer increases pregnancy and live birth rates or not.Materials and Methods: A prospective study was conducted between 2014 and 2019 at an in vitro fertilization (IVF) unitin Greece. As part of the protocol, hysteroscopy and EFI were offered to all the egg recipients and the outcomes comparedwith those from an older cohort from the same Unit not undergoing hysteroscopy.Results: In total, 332 egg recipients participated in the study; 114 of them underwent EFI prior to embryo transfer. Bothgroups were similar in terms of age, years of infertility, duration of hormone replacement treatment (HRT) and numberof blastocysts transferred. In the EFI group, minor anomalies were detected and treated in 6.1% (n=7) of the participants.Moreover, pregnancy test was positive in 73.7% of the women in the hysteroscopy group compared to 57.8% in the nonhysteroscopygroup (P=0.004). Live birth rate was also higher (56.1 vs. 42.2%, P=0.016) in the EFI group compared tothe non-hysteroscopy one.Conclusion: Apart from the obvious benefit of recognizing obscured anomalies, requiring surgical correction, it appearsthat in oocyte recipients prior to embryo transfer, EFI might improve uterine receptivity and reproductive outcomes.

Background: Induced endometrial injury is a technique described that have positive impact on implantation. The aim of this study was to investigate whether hysteroscopic endometrial fundal incision (EFI) in oocyte recipients before embryo transfer increases pregnancy and live birth rates or not. Materials and Methods: A prospective study was conducted between 2014 and 2019 at an in vitro fertilization (IVF) unit in Greece. As part of the protocol, hysteroscopy and EFI were offered to all the egg recipients and the outcomes compared with those from an older cohort from the same Unit not undergoing hysteroscopy. Results: In total, 332 egg recipients participated in the study; 114 of them underwent EFI prior to embryo transfer. Both groups were similar in terms of age, years of infertility, duration of hormone replacement treatment (HRT) and number of blastocysts transferred. In the EFI group, minor anomalies were detected and treated in 6.1% (n=7) of the participants. Moreover, pregnancy test was positive in 73.7% of the women in the hysteroscopy group compared to 57.8% in the nonhysteroscopy group (P=0.004). Live birth rate was also higher (56.1 vs. 42.2%, P=0.016) in the EFI group compared to the non-hysteroscopy one. Conclusion: Apart from the obvious benefit of recognizing obscured anomalies, requiring surgical correction, it appears that in oocyte recipients prior to embryo transfer, EFI might improve uterine receptivity and reproductive outcomes. [ABSTRACT FROM AUTHOR]

Yin-Ling Xiu, Kai-Xuan Sun, Qian Zhang, Yu-Hong Xiao, Xue Bai, Yong Chen, Meng-Si Zhao, Yue-Xin Yu Center of Reproductive Medicine, General Hospital of Northern Theatre Command, Shenyang, 110016, People’s Republic of ChinaCorrespondence: Yue-Xin Yu, Center of Reproductive Medicine, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang, 110016, People’s Republic of China, Tel +86-18809881296, Email yuyuexinpingan@163.comAim: To compare the pregnancy outcomes of frozen-thawed embryo transfer (FET) cycles among women with repeated implantation failure (RIF) treated with various endometrial preparation protocols.Methods: A total of 605 women with RIF were retrospectively recruited between January 2017 and December 2020 from Northern Theater General Hospital. Patients were divided into natural cycles, hormone replacement therapy (HRT) cycles, depot gonadotropin-releasing hormone (GnRH) agonist-HRT, and endometrial scratching (ES) plus depot GnRH agonist-HRT. The primary endpoint was clinical pregnancy rate, while secondary endpoints included live birth rate and pain assessment.Results: Of the 605 recruited patients, 63 were undergoing natural cycles, 281 were treated with HRT cycles, 141 treated with depot GnRH agonist-HRT, and 120 treated with ES combined with depot GnRH agonist-HRT. There were significant differences among protocols on clinical pregnancy rate (P=0.029), while no significant difference was observed among protocols on live birth rates (P=0.108). Multivariate analyses suggested that HRT (odds ratio [OR]: 0.50; 95% confidence interval [CI]: 0.28– 0.89; P=0.019) and depot GnRH agonist-HRT (OR: 0.49; 95% CI: 0.27– 0.91; P=0.021) cycles were associated with a lower clinical pregnancy rate as compared with natural cycles, while no significant difference between ES combined with depot GnRH agonist-HRT and natural cycles for clinical pregnancy rates (OR: 0.72; 95% CI: 0.38– 1.36; P=0.313). Moreover, the HRT (OR: 0.70; 95% CI: 0.39– 1.28; P=0.239), depot GnRH agonist-HRT (OR: 0.67; 95% CI: 0.35– 1.29; P=0.229), and ES combined with depot GnRH agonist-HRT (OR: 1.11; 95% CI: 0.58– 2.14; P=0.754) cycles had no significant effects on live birth rate as compared with natural cycles. A total of 87.50% patients treated with ES combined with depot GnRH agonist-HRT reported pain during the procedure.Conclusion: ES and depot GnRH agonists could be considered for RIF women with high-quality blastocysts, 14 days after verified transplantation failure.Keywords: endometrial scratching, depot GnRH agonist, repeated implantation failure, blastocysts, clinical pregnancy rate, live birth rate

Abstract Research question To evaluate the role of endometrial scratching performed prior to an embryo transfer cycle on the probability of pregnancy compared to placebo/sham or no intervention. Design A computerized literature (using a specific search strategy) search was performed across the databases MEDLINE, EMBASE, COCHRANE CENTRAL, SCOPUS and WEB OF SCIENCE up to June 2023 in order to identify randomized controlled trials (RCTs) evaluating the effect of endometrial scratching prior to an embryo transfer cycle on the probability of pregnancy, expressed either as live birth, ongoing pregnancy or clinical pregnancy (in order of significance) compared to placebo/sham or no intervention. Data were pooled using random-effects or fixed-effects model, depending on the presence or not of heterogeneity. Heterogeneity was assessed using the I 2 statistic. Subgroup analyses were performed based on the population studied in each RCT, as well as on the timing and method of endometrial biopsy. Certainty of evidence was assessed using the GRADEPro tool. Results The probability of live birth was significantly higher in embryo transfer cycles after endometrial scratching as compared to placebo/sham or no intervention (relative risk-RR: 1.12, 95% CI: 1.05–1.20; heterogeneity: I2=46.30%, p

Abstract Background Endometrial scratching (ES) or injury is intentional damage to the endometrium performed to improve reproductive outcomes for infertile women desiring pregnancy. Moreover, recent systematic reviews with meta-analyses and randomized controlled trials demonstrated that ES is not effective, data on the safety are limited, and it should not be recommended in clinical practice. The aim of the current study was to assess the view and behavior towards ES among fertility specialists throughout infertility centers in Italy, and the relationship between these views and the attitudes towards the use of ES as an add-on in their commercial setting. Methods Online survey among infertility centers, affiliated to Italian Society of Human Reproduction (SIRU), was performed using a detailed questionnaire including 45 questions with the possibility to give “closed” multi-choice answers for 41 items and “open” answers for 4 items. Online data from the websites of the infertility centers resulting in affiliation with the specialists were also recorded and analyzed. The quality of information about ES given on infertility centers websites was assessed using a scoring matrix including 10 specific questions (scored from 0 to 2 points), and the possible scores ranged from 0 to 13 points (‘excellent’ if the score was 9 points or more, ‘moderate’ if the score was between 5 and 8, and ‘poor’ if it was 4 points or less). Results The response rate was of 60.6% (43 questionnaires / 71 infertility SIRU-affiliated centers). All included questionnaires were completed in their entirety. Most physicians (~ 70%) reported to offer ES to less than 10% of their patients. The procedure is mainly performed in the secretory phase (69.2%) using pipelle (61.5%), and usually in medical ambulatory (56.4%) before IVF cycles to improve implantation (71.8%) without drugs administration (e.g., pain drugs, antibiotics, anti-hemorrhagics, or others) before (76.8%) or after (64.1%) the procedure. Only a little proportion of infertility centers included in the analysis proposes formally the ES as an add-on procedure (9.3%), even if, when proposed, the full description of the indications, efficacy, safety, and costs is never addressed. However, the overall information quality of the websites was generally “poor” ranging from 3 to 8 and having a low total score (4.7 ± 1.6; mean ± standard deviation). Conclusions In Italy, ES is a procedure still performed among fertility specialists for improving the implantation rate in IVF patients. Moreover, they have a poor attitude in proposing ES as an add-on in the commercial setting.

BACKGROUND In IVF/ICSI treatment, the process of embryo implantation is the success rate-limiting step. Endometrial scratching has been suggested to improve this process, but it is unclear if this procedure increases the chance of implantation and live birth (LB) and, if so, for whom, and how the scratch should be performed. OBJECTIVE AND RATIONALE This individual participant data meta-analysis (IPD-MA) aims to answer the question of whether endometrial scratching in women undergoing IVF/ICSI influences the chance of a LB, and whether this effect is different in specific subgroups of women. After its incidental discovery in 2000, endometrial scratching has been suggested to improve embryo implantation. Numerous randomized controlled trials (RCTs) have been conducted, showing contradicting results. Conventional meta-analyses were limited by high within- and between-study heterogeneity, small study samples, and a high risk of bias for many of the trials. Also, the data integrity of several trials have been questioned. Thus, despite numerous RCTs and a multitude of conventional meta-analyses, no conclusion on the clinical effectiveness of endometrial scratching could be drawn. An IPD-MA approach is able to overcome many of these problems because it allows for increased uniformity of outcome definitions, can filter out studies with data integrity concerns, enables a more precise estimation of the true treatment effect thanks to adjustment for participant characteristics and not having to make the assumptions necessary in conventional meta-analyses, and because it allows for subgroup analysis. SEARCH METHODS A systematic literature search identified RCTs on endometrial scratching in women undergoing IVF/ICSI. Authors of eligible studies were invited to share original data for this IPD-MA. Studies were assessed for risk of bias (RoB) and integrity checks were performed. The primary outcome was LB, with a one-stage intention to treat (ITT) as the primary analysis. Secondary analyses included as treated (AT), and the subset of women that underwent an embryo transfer (AT+ET). Treatment-covariate interaction for specific participant characteristics was analyzed in AT+ET. OUTCOMES Out of 37 published and 15 unpublished RCTs (7690 participants), 15 RCTs (14 published, one unpublished) shared data. After data integrity checks, we included 13 RCTs (12 published, one unpublished) representing 4112 participants. RoB was evaluated as 'low' for 10/13 RCTs. The one-stage ITT analysis for scratch versus no scratch/sham showed an improvement of LB rates (odds ratio (OR) 1.29 [95% CI 1.02–1.64]). AT, AT+ET, and low-RoB-sensitivity analyses yielded similar results (OR 1.22 [95% CI 0.96–1.54]; OR 1.25 [95% CI 0.99–1.57]; OR 1.26 [95% CI 1.03–1.55], respectively). Treatment-covariate interaction analysis showed no evidence of interaction with age, number of previous failed embryo transfers, treatment type, or infertility cause. WIDER IMPLICATIONS This is the first meta-analysis based on IPD of more than 4000 participants, and it demonstrates that endometrial scratching may improve LB rates in women undergoing IVF/ICSI. Subgroup analysis for age, number of previous failed embryo transfers, treatment type, and infertility cause could not identify subgroups in which endometrial scratching performed better or worse. The timing of endometrial scratching may play a role in its effectiveness. The use of endometrial scratching in clinical practice should be considered with caution, meaning that patients should be properly counseled on the level of evidence and the uncertainties. [ABSTRACT FROM AUTHOR]

Research question: To evaluate the role of endometrial scratching performed prior to an embryo transfer cycle on the probability of pregnancy compared to placebo/sham or no intervention. Design: A computerized literature (using a specific search strategy) search was performed across the databases MEDLINE, EMBASE, COCHRANE CENTRAL, SCOPUS and WEB OF SCIENCE up to June 2023 in order to identify randomized controlled trials (RCTs) evaluating the effect of endometrial scratching prior to an embryo transfer cycle on the probability of pregnancy, expressed either as live birth, ongoing pregnancy or clinical pregnancy (in order of significance) compared to placebo/sham or no intervention. Data were pooled using random-effects or fixed-effects model, depending on the presence or not of heterogeneity. Heterogeneity was assessed using the I2 statistic. Subgroup analyses were performed based on the population studied in each RCT, as well as on the timing and method of endometrial biopsy. Certainty of evidence was assessed using the GRADEPro tool. Results: The probability of live birth was significantly higher in embryo transfer cycles after endometrial scratching as compared to placebo/sham or no intervention (relative risk-RR: 1.12, 95% CI: 1.05–1.20; heterogeneity: I2=46.30%, p<0.001, 28 studies; low certainty). The probability of ongoing pregnancy was not significantly difference between the two groups (RR: 1.07, 95% CI: 0.98–1.18; heterogeneity: I2=27.44%, p=0.15, 11 studies; low certainty). The probability of clinical pregnancy was significantly higher in embryo transfer cycles after endometrial scratching as compared to placebo/sham or no intervention (RR: 1.12, 95% CI: 1.06–1.18; heterogeneity: I2=47.48%, p<0.001, 37 studies; low certainty). A subgroup analysis was performed based on the time that endometrial scratching was carried out. When endometrial scratching was performed during the menstrual cycle prior to the embryo transfer cycle a significantly higher probability of live birth was present (RR: 1.18, 95% CI:1.09-1.27; heterogeneity: I2=39.72%, p<0.001, 21 studies; moderate certainty). On the contrary, no effect on the probability of live birth was present when endometrial injury was performed during the embryo transfer cycle (RR: 0.87, 95% CI: 0.67-1.15; heterogeneity: I2=65.18%, p=0.33, 5 studies; low certainty). In addition, a higher probability of live birth was only present in women with previous IVF failures (RR: 1.35, 95% CI: 1.20-1.53; heterogeneity: I2=0%, p<0.001, 13 studies; moderate certainty) with evidence suggesting that the more IVF failures the more likely endometrial scratching to be beneficial (p=0.004). The number of times endometrial scratching was performed, as well as the type of instrument used did not appear to affect the probability of live birth. Conclusions: Endometrial scratching during the menstrual cycle prior to an embryo transfer cycle can lead to a higher probability of live birth in patients with previous IVF failures. PROSPERO registration: PROSPERO CRD42023433538 (18 Jun 2023) [ABSTRACT FROM AUTHOR]

Background: Endometrial scratching (ES) or injury is intentional damage to the endometrium performed to improve reproductive outcomes for infertile women desiring pregnancy. Moreover, recent systematic reviews with meta-analyses and randomized controlled trials demonstrated that ES is not effective, data on the safety are limited, and it should not be recommended in clinical practice. The aim of the current study was to assess the view and behavior towards ES among fertility specialists throughout infertility centers in Italy, and the relationship between these views and the attitudes towards the use of ES as an add-on in their commercial setting. Methods: Online survey among infertility centers, affiliated to Italian Society of Human Reproduction (SIRU), was performed using a detailed questionnaire including 45 questions with the possibility to give "closed" multi-choice answers for 41 items and "open" answers for 4 items. Online data from the websites of the infertility centers resulting in affiliation with the specialists were also recorded and analyzed. The quality of information about ES given on infertility centers websites was assessed using a scoring matrix including 10 specific questions (scored from 0 to 2 points), and the possible scores ranged from 0 to 13 points ('excellent' if the score was 9 points or more, 'moderate' if the score was between 5 and 8, and 'poor' if it was 4 points or less). Results: The response rate was of 60.6% (43 questionnaires / 71 infertility SIRU-affiliated centers). All included questionnaires were completed in their entirety. Most physicians (~ 70%) reported to offer ES to less than 10% of their patients. The procedure is mainly performed in the secretory phase (69.2%) using pipelle (61.5%), and usually in medical ambulatory (56.4%) before IVF cycles to improve implantation (71.8%) without drugs administration (e.g., pain drugs, antibiotics, anti-hemorrhagics, or others) before (76.8%) or after (64.1%) the procedure. Only a little proportion of infertility centers included in the analysis proposes formally the ES as an add-on procedure (9.3%), even if, when proposed, the full description of the indications, efficacy, safety, and costs is never addressed. However, the overall information quality of the websites was generally "poor" ranging from 3 to 8 and having a low total score (4.7 ± 1.6; mean ± standard deviation). Conclusions: In Italy, ES is a procedure still performed among fertility specialists for improving the implantation rate in IVF patients. Moreover, they have a poor attitude in proposing ES as an add-on in the commercial setting. [ABSTRACT FROM AUTHOR]

Abstract Background To assess the efficacy of dysdrogesterone in the treatment of chronic endometritis (CE) treated with antibiotic in premenopausal women with endometrial polyps (EPs). Methods Routine detection of endometrium was simultaneously conducted to determine whether there was CE by syndecan-1 (CD138), while women underwent hysteroscopic polypectomy in our hospital. Antibiotic was given for the treatment of CE. A total of 235 premenopausal women with CE who underwent hysteroscopic polypectomy were enrolled in the retrospective observational study. In the control group, single antibiotic was given for the treatment of CE form January 2016 to December 2018, and in the treatment group additional dydrogesterone was used from January 2019 to November 2020. Comparison of cure rates of CE with different treatment regimens was performed. Results The cure rates of CE in dydrogesterone and antibiotic combination group and the single antibiotic group were 85.2% and 74.3%, respectively, with overall cure rate of 80.0% (188/235). The combination group showed better effects regarding the cure rate of CE (P

Endometrial scratching is intentional injury of the endometrium intended to improve the reproductive outcomes of infertile women who seek pregnancy. In recent years, several randomized controlled trials, systematic reviews, and meta-analyses of trials have been published, reporting controversial results. Some authors have recommended against endometrial scratching in clinical practice, while others have recommended its application to specific categories of patients. This article aimed to provide a critical analysis of the old and new available evidence, to assist physicians interpreting the published data, and to generate insights for future research on the topic. [ABSTRACT FROM AUTHOR]

ObjectiveEndometrial scratching (ES) during hysteroscopy before embryotransfer (ET) remains doubtable on whether it benefits the reproductive outcomes. The optimal technique is not clear and repeated implantation failure as a challenging field in in vitro fertilization (IVF) seems to be the springboard for clinicians to test its effectiveness.MethodsMedline, PMC, ScienceDirect, Scopus, CENTRAL, Google Scholar were searched from their inception up to April 2023 for studies to evaluate the effectiveness of adding endometrial scratching during hysteroscopy before ET.ResultsThe initial search yielded 959 references, while 12 eligible studies were included in the analyses, involving 2,213 patients. We found that hysteroscopy and concurrent ES before ET resulted in a statistically significant improvement in clinical pregnancy rate (CPR) [RR = 1.50, (95% CI 1.30–1.74), p

Abstract Objective True identity and specific set of markers to enrich endometrial stem cells still remains elusive. Present study was undertaken to further substantiate that very small embryonic-like stem cells (VSELs) are the true and elusive stem cells in adult mice endometrium. Methods This was achieved by undertaking three sets of experiments. Firstly, SSEA-1+ and Oct-4 + positive VSELs, sorted from GFP mice, were transplanted into the uterine horns of wild-type Swiss mice and GFP uptake was studied within the same estrus cycle. Secondly, uterine lumen was scratched surgically and OCT-4 expressing stem/progenitor cells were studied at the site of injury after 24–72 h. Thirdly, OCT-4 expression was studied in the endometrium and myometrium of adult mice after neonatal exposure to estradiol (20 µg/pup/day on days 5–7 after birth). Results GFP + ve VSELs expressing SSEA-1 and Oct-4 engrafted and differentiated into the epithelial cells lining the lumen as well as the glands during the estrus stage when maximum remodeling occurs. Mechanical scratching activated tissue-resident, nuclear OCT-4 positive VSELs and slightly bigger ‘progenitors’ endometrial stem cells (EnSCs, cytoplasmic OCT-4) which underwent clonal expansion and further differentiated into luminal and glandular epithelial cells. Neonatal exposure to endocrine disruption resulted in increased numbers of OCT-4 positive VSELs/EnSCs in adult endometrium. Discussion Results support the presence of functionally active VSELs in adult endometrium. VSELs self-renew and give rise to EnSCs that further differentiate into epithelial cells under normal physiological conditions. Also, VSELs are vulnerable to endocrine insults. To conclude VSELs are true and elusive uterine stem cells that maintain life-long uterine homeostasis and their dysregulation may result in various pathologies. Graphical Abstract

Background: To assess the efficacy of dysdrogesterone in the treatment of chronic endometritis (CE) treated with antibiotic in premenopausal women with endometrial polyps (EPs).Methods: Routine detection of endometrium was simultaneously conducted to determine whether there was CE by syndecan-1 (CD138), while women underwent hysteroscopic polypectomy in our hospital. Antibiotic was given for the treatment of CE. A total of 235 premenopausal women with CE who underwent hysteroscopic polypectomy were enrolled in the retrospective observational study. In the control group, single antibiotic was given for the treatment of CE form January 2016 to December 2018, and in the treatment group additional dydrogesterone was used from January 2019 to November 2020. Comparison of cure rates of CE with different treatment regimens was performed.Results: The cure rates of CE in dydrogesterone and antibiotic combination group and the single antibiotic group were 85.2% and 74.3%, respectively, with overall cure rate of 80.0% (188/235). The combination group showed better effects regarding the cure rate of CE (P < .05). Multivariate analysis confirmed that the cure rate of CE was not affected by age, body mass index, number of EPs, the status of estrogen receptor and the status of progesterone receptor. Conversely, dydrogesterone and endometrial scratching were beneficial factors for cure rate increase with antibiotic treatment.Conclusion: Combination of dydrogesterone and antibiotic was more effective for cure rate of CE than antibiotic alone in premenopausal women after hysteroscopic polypectomy. Endometrial scratching also contributed to the cure rate increase with antibiotic treatment. [ABSTRACT FROM AUTHOR]

This retrospective cohort study aimed to evaluate the effect of hysteroscopy and endometrial scratching (ES) in patients with recurrent implantation failure (RIF) who do not have an intracavity pathology. The authors retrospectively collected data of patients between 2014 and 2019 from a single centre. The study analysed 350 unexplained RIF patients, of whom, 225 underwent hysteroscopy and endometrial scratching, and 125 did not have a hysteroscopy prior to an IVF cycle. Pregnancy rates among post endometrial scratching and no endometrial scratching cycles were 35.6% versus 27.2%, (p =.048), clinical pregnancy rates were 32.9% versus 21.6% (p =.026) and live birth rates were 26.2% versus 19.2% (p =.039). Although it is not possible to distinguish whether hysteroscopy or injury is effective in improving live birth results, the authors thought that endometrial injury with gentle conventional curettage is effective in patients with recurrent implantation failure. What is already known on this subject? Hysteroscopy and endometrial injury improve pregnancy outcomes in IVF cycles, but definitive conclusions have been uncertain. What do the results of this study add? The study showed that endometrial injury with gentle conventional curettage during hysteroscopy significantly improved the pregnancy rates of RIF patients compared to the non-hysteroscopy group. What are the implications of these findings for clinical practice and/or further research? In cases of recurrent implantation failure, even if hysteroscopy findings are normal, endometrial scratching in the follicular phase increases pregnancy rates compared to the non-hysteroscopy group. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether endometrial scratching increases the chance of live birth in women with unexplained infertility attempting to conceive without assisted reproductive technology.Design: Randomized, placebo-controlled, participant-blind, multicenter international trial.Setting: Fertility clinics.Patient(s): Women with a diagnosis of unexplained infertility trying to conceive without assistance.Intervention(s): Participants were randomly assigned to receive an endometrial biopsy or a placebo procedure (placement of a biopsy catheter in the posterior fornix, without inserting it into the external cervical os). Both groups performed regular unprotected intercourse with the intention of conceiving over three consecutive study cycles.Main Outcome Measure(s): The primary outcome was live birth.Result(s): A total of 220 women underwent randomization. The live birth rate was 9% (10 of 113 women) in the endometrial-scratch group and 7% (7 of 107 women) in the control group (adjusted OR, 1.39; 95% CI, 0.50-4.03). There were no differences between the groups in the secondary outcomes of clinical pregnancy, viable pregnancy, ongoing pregnancy, and miscarriage. Endometrial scratching was associated with a higher pain score on a 10-point scale (adjusted mean difference, 3.07; 95% CI, 2.53-3.60).Conclusion(s): This trial did not find evidence that endometrial scratching improves the live birth rate in women with unexplained infertility trying to conceive without assistance.Clinical Trial Registration Number: Australian New Zealand Clinical Trials Registry ACTRN12614000656639. [ABSTRACT FROM AUTHOR]

Objective: True identity and specific set of markers to enrich endometrial stem cells still remains elusive. Present study was undertaken to further substantiate that very small embryonic-like stem cells (VSELs) are the true and elusive stem cells in adult mice endometrium. Methods: This was achieved by undertaking three sets of experiments. Firstly, SSEA-1+ and Oct-4 + positive VSELs, sorted from GFP mice, were transplanted into the uterine horns of wild-type Swiss mice and GFP uptake was studied within the same estrus cycle. Secondly, uterine lumen was scratched surgically and OCT-4 expressing stem/progenitor cells were studied at the site of injury after 24–72 h. Thirdly, OCT-4 expression was studied in the endometrium and myometrium of adult mice after neonatal exposure to estradiol (20 µg/pup/day on days 5–7 after birth). Results: GFP + ve VSELs expressing SSEA-1 and Oct-4 engrafted and differentiated into the epithelial cells lining the lumen as well as the glands during the estrus stage when maximum remodeling occurs. Mechanical scratching activated tissue-resident, nuclear OCT-4 positive VSELs and slightly bigger 'progenitors' endometrial stem cells (EnSCs, cytoplasmic OCT-4) which underwent clonal expansion and further differentiated into luminal and glandular epithelial cells. Neonatal exposure to endocrine disruption resulted in increased numbers of OCT-4 positive VSELs/EnSCs in adult endometrium. Discussion: Results support the presence of functionally active VSELs in adult endometrium. VSELs self-renew and give rise to EnSCs that further differentiate into epithelial cells under normal physiological conditions. Also, VSELs are vulnerable to endocrine insults. To conclude VSELs are true and elusive uterine stem cells that maintain life-long uterine homeostasis and their dysregulation may result in various pathologies. [ABSTRACT FROM AUTHOR]

Does endometrial scratching improve the chance of a live birth in women with polycystic ovary syndrome (PCOS) undergoing ovulation induction and trying to conceive? An international, multicentre, randomized, sham-controlled trial across six fertility clinics in three countries (New Zealand, UK and Brazil). Women with a diagnosis of PCOS who were planning to commence ovulation induction cycles (at least three cycles) in order to conceive were randomly assigned to receive the pipelle (scratch) procedure or a sham (placebo) procedure in the first cycle of ovulation induction. Women kept a diary of ovulation induction and sexual intercourse timing over three consecutive cycles and pregnancies were followed up to live birth. Primary outcome was live birth and secondary outcomes were clinical pregnancy, ongoing pregnancy, multiple pregnancy, adverse pregnancy outcomes, neonatal outcomes, bleeding following procedure and pain score following procedure. A total of 117 women were randomized; 58 to the scratch group and 59 to the sham group. Live birth occurred in 11 (19%) women in the scratch group and 14 (24%) in the sham group (odds ratio 0.76, 95% confidence interval [CI] 0.30–1.92). Secondary outcomes were similar in each group. Significantly higher pain scores were reported in the scratch group (adjusted mean difference 3.2, 95% CI 2.5–3.9) when measured on a visual analogue scale. No difference was detected in live birth rate for women with PCOS who received an endometrial scratch when trying to conceive using ovulation induction; however, uncertainty remains due to the small sample size in this study. [ABSTRACT FROM AUTHOR]

Introduction: Endometrial injury (ES) has been suggested as intervention to increase probability of pregnancy in women undergoing assisted reproductive technologies. Majority of studies reported that ES improves outcome in Invitro fertilisation,Intrauterine Insemination(IUI) and natural conceptions: however, the size and quality of studies are poor which questions the presence of any beneficial effect. The present study was done to evaluate the effect of endometrial scratching on pregnancy rate after previous failed Intrauterine Insemination and to assess the pain and bleeding following the procedure.Material and Methods: Randomized controlled trial. One hundred sixty-eight women (Eighty-four in each group) with primary/secondary infertility were recruited and randomized into intervention and control group using block randomization. Intervention group underwent ES using pipelle's canula on D8 or D9 of menstrual cycle. Three cycles of ovulation induction with Clomiphene citrate and gonadotrophins followed by IUI was done. The primary end point was clinical pregnancy rate. Pain and bleeding after the procedure were evaluated as secondary outcomes.The study was conducted from June 2017 to June 2019.Main Results: The cumulative clinical pregnancy rate in ES group was 22.2 % in comparison 9.8 % in control group. In the intent to treat analysis, with a p value of 0.03 calculated from Chi-square test(p < 0.05) there was statistically significant difference in the pregnancy rate between Intervention and Control group. Efficacy of intervention was found to be Fourteen Percent (14 %). Fifty-one women (63 %) had marked a VAS pain score of 4-5 and Twelve women(12.2 %) experienced mild spotting post procedure. Two patients in ES group had miscarriage and no case of multiple pregnancy in both the groups.Conclusion: Endometrial Scratching improves clinical pregnancy rate in patients with Unexplained infertility and mild male factor infertility with previous failed IUI cycles. ES will be an inexpensive alternative to IVF for couples after IUI failures especially in developing countries, with an acceptable pregnancy rate and does not demand any special qualification or equipment and can be trained easily in primary settings. Larger and adequately powered studies are needed to elucidate the beneficial effects of endometrial scratching on implantation. [ABSTRACT FROM AUTHOR]

Abstract Background It is still unclear whether endometrial injury (EI) has a beneficial effect on reproductive outcomes, and if so, the optimal procedure characteristics are not clear. All previous papers concluded that more research is needed, and as additional studies were recently published, the insights on EI have changed significantly. Methods Searches were conducted in MEDLINE, Embase, Web of Science, and Cochrane Library, to identify randomized controlled trials examining the EI effect on IVF outcomes in women at least one previous failed cycle. Results 2015 references were identified through database searching. Ultimately, 17 studies were included, involving 3016 patients. Clinical pregnancy rate (CPR) (RR = 1.19, [95% CI 1.06–1.32], P = .003) and live birth rate (LBR) (RR = 1.18, [95%CI 1.04–1.34], P = .009) were significantly improved after EI. Number of previous failed cycles, maternal age, and hysteroscopy were found to be relevant confounders. Higher CPR and LBR were found when EI was performed twice, while performing EI once did not significantly improve reproductive rates. Conclusion According to the present meta‐analysis, EI may be offered to younger patients with few previous failed cycles and should be additionally studied in an RCT comparing different timing and more than one EI before treatment.

Abstract Background The effects of endometrial scratching (ES) on embryo implantation have been studied for many years. Several studies have shown better outcomes when performed on patients undergoing intrauterine insemination and in vitro fertilization (IVF) cycles, but many other reports have not been able to find these differences. As far as cycles with donor eggs are concerned, reported evidence is scarce. Our aim in this trial is to determine if ES is useful for those patients undergoing IVF cycles with donor eggs, in order to assure a greater homogeneity in embryo quality and endometrial preparation. Methods This single centre randomized controlled trial will include patients undergoing an egg donation cycle, meeting the inclusion criteria and who accept to participate in the study. Once informed consent is signed, patients will be randomly allocated to the study arm (group A) and then receive ES in the luteal phase of the cycle prior to embryo transfer, or the control arm (group B) without any intervention. All cycle data will be collected and analyzed to obtain the clinical pregnancy and the live birth rates in the two groups. Discussion Several studies have tried to determine the effectiveness of an ES in IVF cycles, but it is still unclear due to the heterogeneity of these reports. The aim of this study is to determine if there are differences in clinical pregnancy rate and live birth rate in egg donor cycles, when comparing an ES performed in the preceding luteal phase versus no intervention, given that embryo quality and endometrial preparation protocols will be comparable. Trial registration Ethical approval of version 2.0 of this trial was obtained on the 13th January 2017. It was retrospectively registered on the 5th April 2017 as the ENDOSCRATCH Trial ( NCT03108157 ) in ClinicalTrials.gov.

Study Question: What is the prevalence and pattern of IVF add-on use in Australia?Summary Answer: Among women having IVF in the last 3 years, 82% had used one or more IVF add-on, most commonly acupuncture, preimplantation genetic testing for aneuploidy and Chinese herbal medicine.What Is Known Already: IVF add-ons are procedures, techniques or medicines which may be considered nonessential to IVF, but usually used in attempts to improve the probability of conception and live birth. The use of IVF add-ons is believed to be widespread; however, there is little information about the prevalence and patterns of use in different settings.Study Design, Size, Duration: An online survey was distributed via social media to women in Australia who had undergone IVF since 2017. Women were excluded if they were gestational surrogates, used a surrogate, or underwent ovarian stimulation for oocyte donation or elective oocyte cryopreservation only. The survey was open from 21 June to 14 July 2020.Participants/materials, Setting, Methods: Survey questions included demographics, IVF and medical history, and use of IVF add-ons including details of the type of add-on, costs and information sources used. Participants were also asked about the relative importance of evidence regarding safety and effectiveness, factors considered in decision-making and decision regret.Main Results and the Role Of Chance: A total of 1590 eligible responses were analysed. Overall, 82% of women had used one or more add-ons and these usually incurred an additional cost (72%). Around half (54%) had learned about add-ons from their fertility specialist, and most reported that the decision to use add-ons was equally shared with the specialist. Women placed a high level of importance on scientific evidence for safety and efficacy, and half (49%) assumed that add-ons were known to be safe. Most women experienced some regret at the decision to use IVF add-ons (66%), and this was more severe among women whose IVF was unsuccessful (83%) and who believed that the specialist had a larger contribution to the decision to use add-ons (75%).Limitations, Reasons For Caution: This retrospective survey relied on patient recall. Some aspects were particularly prone to bias such as contributions to decision-making. This approach to capturing IVF add-on use may yield different results to data collected directly from IVF clinics or from fertility specialists.Wider Implications Of the Findings: There is a very high prevalence of IVF add-on use in Australia which may be generalisable to other settings with similar models of IVF provision. Although women placed high importance on scientific evidence to support add-ons, most add-ons do not have robust evidence of safety and effectiveness. This suggests that IVF patients are not adequately informed about the risks and benefits of IVF add-ons, or are not aware of the paucity of evidence to support their use.Study Funding/competing Interest(s): This research was supported by a McKenzie Postdoctoral Fellowship Grant (University of Melbourne), a Department of Obstetrics and Gynaecology Innovation Grant (University of Melbourne) and an NHMRC Investigator Grant (APP1195189). A.P. declares that he provides fertility services at Melbourne IVF (part of Virtus Health). J.W. reports grants from Wellcome Trust, during the conduct of the study, and that publishing benefits his career. The remaining authors report no conflict of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: In vitro fertilisation (IVF) 'add‐ons' are extra (non‐essential) procedures, techniques or medicines, which usually claim to increase the chance of a successful IVF outcome. Use of IVF add‐ons is believed to be widespread in many settings; however, information about add‐on availability in Australasia is lacking. Aims: To understand which add‐ons are advertised on Australasian IVF clinic websites, and what is the evidence for their benefit. Materials and Methods: A systematic assessment of website content was undertaken between December 2019–April 2020, capturing IVF add‐ons advertised, including costs, claims of benefit, statements of risk or limitations, and evidence of effectiveness for improving live birth and pregnancy. A literature review assessed the strength and quality of evidence for each add‐on. Results: Of the 40 included IVF clinics websites, 31 (78%) listed one or more IVF add‐ons. A total of 21 different add‐ons or add‐on groups were identified, the most common being preimplantation genetic testing for aneuploidies (offered by 63% of clinics), time‐lapse systems (33%) and assisted hatching (28%). In most cases (77%), descriptions of the IVF add‐ons were accompanied by claims of benefit. Most claims (90%) were not quantified and very few referenced scientific publications to support the claims (9.8%). None of the add‐ons were supported by high‐quality evidence of benefit for pregnancy or live birth rates. The cost of IVF add‐ons varied from $0 to $3700 (AUD/NZD). Conclusions: There is widespread advertising of add‐ons on IVF clinic websites, which report benefits for add‐ons that are not supported by high‐quality evidence. [ABSTRACT FROM AUTHOR]

Background: Following recent publications regarding the use of the controversial procedure, endometrial scratching (ES), we wish to gain insights into in vitro fertilization (IVF) clinicians’ knowledge and practice, including an updated literature review, current versus past utilization, patient selection, timing and frequency. Methods: Internet-based self-report multiple-choice/multiple-answer survey of IVF clinics. Results: Of the 143 IVF units completing the survey, 119 have used ES in IVF/intrauterine insemination (IUI). Of the respondents with ES experience, 94% recommended ES to patients with repeated implantation failure, 32.3% to patients with a thin endometrium, and 3.5% to general IVF/IUI patients. The majority of respondents performed ES only once prior to an IVF cycle. Of current or past ES users, 73% stopped or reduced ES frequency after reading recent ES-related publications. This was despite the finding that 57.2% believed that ES increased implantation and live-birth likelihood in selected IVF/IUI patients. Conclusions: Despite previous widespread utilization of ES, the lack of consensus regarding patient selection, timing, and benefits of the procedure, has prompted many IVF clinicians who used the procedure in the past to abandon the intervention. According to our study, ES is practiced most commonly for patients with repeated implantation failure and performed once during the luteal phase. Further research is needed to obtain definitive practice guidelines based on ES successes and failures–specifically a prospective randomized controlled study according to the methodology used by Barash et al., original publication.

Objective: This study evaluated the effect of endometrial injury on pregnancy outcomes in patients with a poor ovarian response (POR), based on the Bologna criteria, who underwent intracytoplasmic sperm injection (ICSI) cycles. Material and Methods: Sixty-eight patients were enrolled in this retrospective cohort study. All patients in the endometrial scratching group (group 1, n=32) and control group (group 2, n=36) underwent office hysteroscopy in the early follicular phase of the cycle before controlled ovarian stimulation. Group 1 also underwent endometrial scratching. The main outcome measure was the ongoing pregnancy rate. Results: The study groups had similar baseline demographics, including age, body mass index, duration of infertility, number of ICSI cycles, and hormone levels. However, the antral follicle count was significantly higher in group 1 than in group 2 (4.2±1.9 vs 3.3±1.8; p<0.05). There were no significant group differences in ovarian stimulation characteristics (ovarian stimulation time, trigger day endometrial thickness, number of metaphase II oocytes), number of embryos transferred, or the ratio of embryo transfer on days 3 and 5. Moreover, there were no significant differences between groups 1 and 2 in the rates of chemical pregnancy (25% vs 19.4%), clinical pregnancy (15.6% vs 11.1%) or ongoing pregnancy (9.4% vs 8.3%) (p>0.05 for all). Conclusion: Endometrial scratching did not improve pregnancy outcomes for patients meeting the Bologna criteria for a POR to ICSI cycles using fresh embryo transfer and the GnRH antagonist protocol. [ABSTRACT FROM AUTHOR]

Introduction: The menstrual cycle is regulated by a complex interplay between endometrial epithelial cells, endothelial cells, immune cells, and sex hormones. To communicate, cells secrete cytokines that have multiple and diverse effects on recipient cells. Knowledge of how these cells interact in the uterus is insufficient. Menstrual blood is easily accessible and provides a source to study menstrual cycle physiology. This study aimed to determine the cytokine profile in menstrual blood plasma and investigate the differences in cytokine profiles between menstrual and peripheral blood plasma. Several previous studies indicate an improved chance of embryo implantation after endometrial scratching. Consequently, our secondary aim was to compare the menstrual blood cytokine profile before and after luteal phase endometrial scratching.Material and Methods: Nineteen healthy donors collected menstrual blood for the first 24 hours of menstruation in two sequential cycles. Matched peripheral blood was taken at the same time. An endometrial biopsy was performed at cycle day 7-9 post ovulation in between the two collection times. A Luminex multiplex assay was performed in one batch analyzing a predetermined group of cytokines in plasma.Results: Peripheral blood plasma and menstrual blood plasma showed substantial significant differences in cytokine profile. In menstrual blood plasma, C5/C5a, interleukin-6 (IL-6), IL-1β, and CXCL8 were detected in high concentrations, whereas IL-2, IL-12p70, XCL1/Lymphotactin, and interferon-γ were low. The most pronounced median differences between menstrual and peripheral blood plasma were found for IL-6, IL-1β, and CXCL8. The cytokine profiles of menstrual blood plasma were similar between the individual donors and did not differ over two subsequent cycles. None of the cytokines analyzed in menstrual blood plasma differed significantly before or after luteal phase endometrial scratching (P < .01).Conclusions: Our results demonstrate that the menstrual blood cytokine profile is distinctly different from peripheral blood plasma and that the inter-individual difference in menstrual blood cytokine profile in healthy donors is limited and stable over time. The small injury caused by an endometrial biopsy does not change the cytokine profile in the subsequent menstrual cycle. Our study provides new insights into menstrual cycle physiology. [ABSTRACT FROM AUTHOR]

Objective: To study the effect of local endometrial scratching on the outcomes of intrauterine insemination cycle. Design: Randomized controlled trial. Study setting: Department of Obstetrics & Gynecology, JN Medical College, Aligarh Muslim University, Aligarh. Materials and methods: A total of 77 patients were enrolled in the study. Patients undergoing controlled ovarian stimulation with intrauterine insemination were randomly allocated in two groups. In group A (n=31), endometrial scratching was carried out on D8/ D9 of same menstrual cycle in which intrauterine uterine insemination (IUI) was performed and in group B (control group; n=31), endometrial scratching was not performed. Primary outcome was measured by pregnancy rate, while secondary outcome was measured by endometrial indices. Results: Pregnancy rate was 16.2% in group A in which endometrial scratching was carried out in IUI cycle, whereas in group B, pregnancy rate was 9.6%. Although in group A, pregnancy rate was higher when compared with group B, the results were not statistically significant (P > 0.05). The mean endometrial thickness of women in group A was 9.329±0.934 which was significantly higher than endometrial thickness of group B, that is, 7.72±2.0. In group A, greater number of women (41.93%, n=13) had zone 3 endometrial flow than group B (19.35%, n=6). However, the difference was not statistically significant (P > 0.05). Conclusion: Endometrial scratching in follicular phase in the same cycle of stimulation with IUI gives better pregnancy rate in comparison with IUI without endometrial scratching. However, the results can be of proven clinical significance only if larger group of population is studied. [ABSTRACT FROM AUTHOR]

Abstract Recurrent implantation failure (RIF) refers to cases in which women have had three failed in vitro fertilization (IVF) attempts with good quality embryos. The definition should also take advanced maternal age and embryo stage into consideration. The failure of embryo implantation can be a consequence of uterine, male, or embryo factors, or the specific type of IVF protocol. These cases should be investigated to determine the most likely etiologies of the condition, as this is a complex problem with several variables. There are multiple risk factors for recurrent implantation failure including advanced maternal age, smoking status of both parents, elevated body mass index, and stress levels. Immunological factors such as cytokine levels and presence of specific autoantibodies should be examined, as well as any infectious organisms in the uterus leading to chronic endometritis. Uterine pathologies such as polyps and myomas as well as congenital anatomical anomalies should be ruled out. Sperm analysis, pre-implantation genetic screening and endometrial receptivity should be considered and evaluated, and IVF protocols should be tailored to specific patients or patient populations. Treatment approaches should be directed toward individual patient cases. In addition, we suggest considering a new initial step in approach to patients with RIF, individualized planned activities to activate the brain's reward system in attempt to improve immunological balance in the body.

Abstract Background In the Netherlands, couples with unexplained infertility and a good prognosis to conceive spontaneously (i.e. Hunault > 30%) are advised to perform timed intercourse for at least another 6 months. If couples fail to conceive within this period, they will usually start assisted reproductive technology (ART). However, treatment of unexplained infertility by ART is empirical and can involve significant burdens. Intentional endometrial injury, also called ‘endometrial scratching’, has been proposed to positively affect the chance of embryo implantation in patients undergoing in vitro fertilization (IVF). It might also be beneficial for couples with unexplained infertility as defective endometrial receptivity may play a role in these women. The primary aim of this study is to determine whether endometrial scratching increases live birth rates in women with unexplained infertility. Method A multicentre randomized controlled trial will be conducted in Dutch academic and non-academic hospitals starting from November 2017. A total of 792 women with unexplained infertility and a good prognosis for spontaneous conception 30%) will be included, of whom half will undergo endometrial scratching in the luteal phase of the natural cycle. The women in the control group will not undergo endometrial scratching. According to Dutch guidelines, both groups will subsequently perform timed intercourse for at least 6 months. The primary endpoint is cumulative live birth rate. Secondary endpoints are clinical and ongoing pregnancy rate; miscarriage rate; biochemical pregnancy loss; multiple pregnancy rate; time to pregnancy; progression to intrauterine insemination (IUI) or IVF; pregnancy complications; complications of endometrial scratching; costs and endometrial tissue parameters associated with reproductive success or failure. The follow-up duration is 12 months. Discussion Several small studies show a possible beneficial effect of endometrial scratching in women with unexplained infertility trying to conceive naturally or through IUI. However, the quality of this evidence is very low, making it unclear whether these women will truly benefit from this procedure. The SCRaTCH-OFO trial aims to investigate the effect of endometrial scratching on live birth rate in women with unexplained infertility and a good prognosis for spontaneous conception

Objective: The objective of the study was (1) “to evaluate the therapeutic efficacy of endometrial scratching in repeated controlled ovarian stimulation (COS) failure cycles.” And (2) “to compare differences in pregnancy outcome by endometrial scratching in early (D2–D4) and late follicular phases (D7–D9) of the same stimulation cycle.” Materials and Methods: Women attending infertility clinic in a tertiary care center and who have two or more repeated COS failure cycles and planned for COS with intrauterine insemination (IUI) were included in the study which is a prospective parallel, interventional, single-blinded, randomized control study, in 1:1 allocation ratio. A total of 165 patients were recruited and randomly allocated into three groups: Group A (n = 55) underwent endometrial scratching on D2–D4 of the same COS cycle, Group B (n = 55) on D7–D9, and Group C (n = 55) no intervention done. All the patients underwent COS according to standard protocol followed by IUI. Results: Clinical pregnancy rate was 12.73% (odds ratio [OR] =0.87 95% confidence interval [CI] =0.288–2.55, P = 1), 16.36% (OR = 1.15; 95% CI = 0.40–3.23, P = 1), and 14.54%, respectively, in Group A, B, and C, respectively (P = 0.86), as per intention to treat analysis. Using Chi-square test, P value between Group A and B was 0.787, between Group A and C was 1.000, and between Group B and C was 1.000. As per protocol analysis, clinical pregnancy rate was 13.46% (OR = 0.83; 95% CI = 0.27–2.5, P = 0.74), 19.57% (OR = 1.3 95%; CI = 0.45–3.73, P = 0.41), and 15.69%. Using Chi-square test, P value between Group A and B was 0.588, between Group A and C was 0.967, and between Group B and C was 0.815. No abortions and multiple pregnancies occurred in either of the groups. Conclusion: The effect found was of good quantum in Group B as per protocol analysis which could be of clinical relevance if larger sample size would have been taken. Endometrial scratching is a cost-effective and easy technique which may improve clinical pregnancy rates in previous COS failure cycles, but more trials are needed to be conducted using larger sample size to achieve the improved and significant outcome.

The potential benefit of endometrial scratching (ES) on embryo implantation is still a controversial subject. At present, the single retrospective study in egg donor IVF cycles concluded that ES has no beneficial effect. Our objective was to determine if there are differences in clinical pregnancy rates (CPR) in egg donor cycles when an ES is performed. This is a randomized controlled trial (RCT) in egg donor IVF patients conducted at ProcreaTec Fertility Center in Madrid. Three hundred fifty-two patients were included in total. One hundred sixty-one patients completed the protocol in group A and 172 patients in group B. Patients allocated to group A received an ES in the luteal phase of the cycle preceding the embryo transfer cycle. Group B patients did not receive any intervention. Primary outcome of this RCT was CPR. Secondary outcomes were implantation (IR), miscarriage (MR), ongoing pregnancy (OPR), multiple pregnancy (MulPR), and live birth rates (LBR). CPR was 104 of 161 (64.6%) in group A and 102 of 172 (59.3%) in group B (RR 1.09, 95% confidence interval (CI) (0.92–1.29); p = 0.378). OPR, MR, MulPR, and LBR were also comparable. No major complications were detected after ES and pregnancy complications were comparable. Our results show that there is no beneficial role of ES in egg donor IVF cycles, considering these patients as the ideal model as they share homogeneous embryo quality and endometrial preparation protocols. This trial was registered on April 5, 2017, as the ENDOSCRATCH trial (NCT03108157). [ABSTRACT FROM AUTHOR]

Background: It is still unclear whether endometrial injury (EI) has a beneficial effect on reproductive outcomes, and if so, the optimal procedure characteristics are not clear. All previous papers concluded that more research is needed, and as additional studies were recently published, the insights on EI have changed significantly. Methods: Searches were conducted in MEDLINE, Embase, Web of Science, and Cochrane Library, to identify randomized controlled trials examining the EI effect on IVF outcomes in women at least one previous failed cycle. Results: 2015 references were identified through database searching. Ultimately, 17 studies were included, involving 3016 patients. Clinical pregnancy rate (CPR) (RR = 1.19, [95% CI 1.06–1.32], P =.003) and live birth rate (LBR) (RR = 1.18, [95%CI 1.04–1.34], P =.009) were significantly improved after EI. Number of previous failed cycles, maternal age, and hysteroscopy were found to be relevant confounders. Higher CPR and LBR were found when EI was performed twice, while performing EI once did not significantly improve reproductive rates. Conclusion: According to the present meta‐analysis, EI may be offered to younger patients with few previous failed cycles and should be additionally studied in an RCT comparing different timing and more than one EI before treatment. [ABSTRACT FROM AUTHOR]

Objective: Endometrial scratch injury (ESI) has been proposed to improve endometrial receptivity and thereby increase implantation rates in assisted reproductive technology (ART) treatment. ESI has been widely incorporated into clinical practice despite inconclusive evidence of its effect on reproductive outcomes. We aimed to assess pregnancy and live birth rates in subfertile women receiving ESI before IVF treatment in comparison to controls.Study Design: This was a randomised controlled trial (RCT) with no blinding of participants, investigators or health care personnel. Women in ART treatment were allocated to either office hysteroscopy with ESI (ESI group) or no intervention (control group). In total 184 women in IVF/ICSI treatment with minimum one previous failed IVF/ICSI cycle, were included in the final analysis. The primary outcome was positive serum hCG (s-hCG). Secondary outcomes were ongoing pregnancy and live birth rate. Only per-protocol analyses were performed as all patients included at one centre had to be excluded. The trial is registered at ClinicalTrials.gov, NCT01743391.Results: Our results showed a non-significant increase in positive s-hCG (OR 1.23, 95 % CI (0.65-2.33)), ongoing pregnancy (OR 1.52, 95 % CI (0.73-3.17)), and live birth rates (OR 1.69, 95 % CI (0.78-3.64)) per randomised woman between the ESI and the control group.Conclusion: We observed no significant differences in positive s-hCG or other reproductive outcomes in the ESI vs. the control group. While the crude estimates of positive reproductive outcomes were higher in the ESI group, statistical significance was not reached, and the study was not powered to show smaller differences. However, data from this study will be re-evaluated in the context of an individual participant data meta-analysis (IPD-MA) of RCTs on ESI. [ABSTRACT FROM AUTHOR]

Background: The effects of endometrial scratching (ES) on embryo implantation have been studied for many years. Several studies have shown better outcomes when performed on patients undergoing intrauterine insemination and in vitro fertilization (IVF) cycles, but many other reports have not been able to find these differences. As far as cycles with donor eggs are concerned, reported evidence is scarce. Our aim in this trial is to determine if ES is useful for those patients undergoing IVF cycles with donor eggs, in order to assure a greater homogeneity in embryo quality and endometrial preparation.Methods: This single centre randomized controlled trial will include patients undergoing an egg donation cycle, meeting the inclusion criteria and who accept to participate in the study. Once informed consent is signed, patients will be randomly allocated to the study arm (group A) and then receive ES in the luteal phase of the cycle prior to embryo transfer, or the control arm (group B) without any intervention. All cycle data will be collected and analyzed to obtain the clinical pregnancy and the live birth rates in the two groups.Discussion: Several studies have tried to determine the effectiveness of an ES in IVF cycles, but it is still unclear due to the heterogeneity of these reports. The aim of this study is to determine if there are differences in clinical pregnancy rate and live birth rate in egg donor cycles, when comparing an ES performed in the preceding luteal phase versus no intervention, given that embryo quality and endometrial preparation protocols will be comparable.Trial Registration: Ethical approval of version 2.0 of this trial was obtained on the 13th January 2017. It was retrospectively registered on the 5th April 2017 as the ENDOSCRATCH Trial (NCT03108157) in ClinicalTrials.gov. [ABSTRACT FROM AUTHOR]

Study Question: Does intentional endometrial injury (scratching) during the follicular phase of ovarian stimulation (OS) increase the clinical pregnancy rate (CPR) in ART?Summary Answer: CPR did not vary between the endometrial injury and the control group, but the trial was underpowered due to early termination because of a higher clinical miscarriage rate observed in the endometrial injury arm after a prespecified interim analysis.What Is Known Already: Intentional endometrial injury has been put forward as an inexpensive clinical tool capable of enhancing endometrial receptivity. However, despite its widespread use, the benefit of endometrial scratching remains controversial, with several recent randomized controlled trials (RCTs) being unable to confirm its added value. So far, most research has focused on endometrial scratching during the luteal phase of the cycle preceding the one with embryo transfer (ET), while only a few studies investigated in-cycle injury during the follicular phase of OS. Also, the persistence of a scratch effect in subsequent treatment cycles remains unclear and possible harms have been insufficiently studied.Study Design, Size, Duration: This RCT was performed in a tertiary hospital setting between 3 April 2014 and 8 October 2017. A total of 200 women (100 per study arm) undergoing IVF/ICSI in a GnRH antagonist suppressed cycle followed by fresh ET were included.Participants/materials, Setting, Methods: Participants were randomized with a 1:1 allocation ratio to either undergo a pipelle endometrial biopsy between Days 6 and 8 of OS or to be in the control group.The primary outcome was CPR. Secondary outcomes included biochemical pregnancy rate, live birth rate (LBR), early pregnancy loss (biochemical pregnancy losses and clinical miscarriages), excessive procedure pain/bleeding and cumulative reproductive outcomes within 6 months of the study cycle.Main Results and the Role Of Chance: The RCT was stopped prematurely by the trial team after the second prespecified interim analysis raised safety concerns, namely a higher clinical miscarriage rate in the intervention group. The intention-to-treat CPR was similar between the biopsy and the control arm (respectively, 44 versus 40%, P = 0.61, risk difference = 3.6 with 95% confidence interval = -10.1;17.3), as was the LBR (respectively, 32 versus 36%, P = 0.52). The incidence of a biochemical pregnancy loss was comparable between both groups (10% in the intervention group versus 15% in the control, P = 0.49), but clinical miscarriages occurred significantly more frequent in the biopsy group (25% versus 8%, P = 0.032). In the intervention group, 3% of the patients experienced excessive procedure pain and 5% bleeding. The cumulative LBR taking into account all conceptions (spontaneous or following ART) within 6 months of randomization was not significantly different between the biopsy and the control group (54% versus 60%, respectively, P = 0.43).Limitations, Reasons For Caution: The trial was stopped prematurely due to safety concerns after the inclusion of 200 of the required 360 patients. Not reaching the predefined sample size implies that definite conclusions on the outcome parameters cannot be drawn. Furthermore, the pragmatic design of the study may have limited the detection of specific subgroups of women who may benefit from endometrial scratching.Wider Implications Of the Findings: Intentional endometrial injury during the follicular phase of OS warrants further attention in future research, as it may be harmful. These findings should be taken in consideration together with the growing evidence from other RCTs that scratching may not be beneficial.Study Funding/competing Interest(s): This study was supported by 'Fonds Wetenschappelijk Onderzoek' (FWO, Flanders, Belgium, 11M9415N, 1524417N). None of the authors have a conflict of interest to declare with regard to this study. [ABSTRACT FROM AUTHOR]

To evaluate the pregnancy rate and serum cytokines (IL6 & TNF) in a group of unexplained infertile patients after minimal Endometrial scratching. This study was conducted in the Al-Alwia teaching hospital and a privet center of IVF in Baghdad, from January 2016 till December 2017; 108 patients were involved in this study as they had unexplained infertility, then all patients underwent a hysteroscopy and endometrial scratching. Cytokines (TNF and IL6) were measured in serum before and after endometrial scratching. The calculations for the relative risk (beneficial risk) for pregnancy was highest for spontaneous group, followed by IUI group, and lowest in IVF group. It was found that there was a highly significant difference in serum TNF & IL6 after endometrial scratching. Endometrial scratching increase pregnancy rate in all study groups but spontaneous > IUI > IVF-ET. It causes a significant increment in serum concentrations of TNF-á and IL-6. Higher levels of TNF-á and IL-6 were associated with better pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Endometrial scratching (ES) using a biopsy catheter prior to the IVF cycle in the repeated implantation failure (RIF) population has been suggested, but no convincing evidence of its benefit has been presented until now.Methods: A retrospective mono-center study among 300 consecutive IVF-RIF cycles following evaluation of the ovarian reserve, hysterosalpingography or hysteroscopy, pelvic ultrasound, thrombophilia evaluation, karyotyping and assessment of male sperm parametrs. The findings within normal limits. All the patients offered ES, 78 consented and underwent ES prior to their next IVF cycle.Results: A comparison of treatment outcomes between the post-ES cycles (n = 78) and the non-ES cycles (222) demonstrated the following: 34 (43.5%) versus 14 (6.3%) conceptions, respectively (p = 0.001) and 30 (38.4%) versus 2 (0.9%) clinical pregnancies, respectively (p < 0.001%), emphasizing an extremely high biochemical pregnancy rate among the non-ES cycles. Implantation rate was 19.7% versus 0.4%, respectively (p < 0.001) and live birth rate was 33.33% (26 newborns) versus 0.45% (1 newborn), respectively (p < 0.001). Since there were more embryos available for transfer and more top-quality embryos in the post-ES-IVF conception cycles, the role of ES became questionable. A multivariate analysis that included ES and the percentage of top-quality embryos demonstrated that ES was an independent factor highly correlated with conception in this particular RIF population.Conclusions: ES proved to be an efficient tool in a particular subgroup of RIF patients with fertility investigation results within normal limits, an optimal ovarian response to gonadotropins, and a high percentage of top-quality embryos. Nevertheless, the results should not be overestimated, since the study has limitations related to its retrospective model. [ABSTRACT FROM AUTHOR]

Abstract Background Success rates of assisted reproductive techniques (ART) are approximately 30%, with the most important limiting factor being embryo implantation. Mechanical endometrial injury, also called ‘scratching’, has been proposed to positively affect the chance of implantation after embryo transfer, but the currently available evidence is not yet conclusive. The primary aim of this study is to determine the effect of endometrial scratching prior to a second fresh in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle on live birth rates in women with a failed first IVF/ICSI cycle. Method Multicenter randomized controlled trial in Dutch academic and non-academic hospitals. A total of 900 women will be included of whom half will undergo an endometrial scratch in the luteal phase of the cycle prior to controlled ovarian hyperstimulation using an endometrial biopsy catheter. The primary endpoint is the live birth rate after the 2nd fresh IVF/ICSI cycle. Secondary endpoints are costs, cumulative live birth rate (after the full 2nd IVF/ICSI cycle and over 12 months of follow-up); clinical and ongoing pregnancy rate; multiple pregnancy rate; miscarriage rate and endometrial tissue parameters associated with implantation failure. Discussion Multiple studies have been performed to investigate the effect of endometrial scratching on live birth rates in women undergoing IVF/ICSI cycles. Due to heterogeneity in both the method and population being scratched, it remains unclear which group of women will benefit from the procedure. The SCRaTCH trial proposed here aims to investigate the effect of endometrial scratching prior to controlled ovarian hyperstimulation in a large group of women undergoing a second IVF/ICSI cycle. Trial registration NTR 5342 , registered July 31st, 2015. Protocol version Version 4.10, January 4th, 2017.

Endometrial scratching (ES) has been proposed as a useful technique to improve outcomes in in vitro fertilization (IVF) cycles, particularly in patients with previous implantation failures. Our objective was to determine if patients undergoing egg-donor IVF cycles had better live birth rates after ES, according to their previous implantation failures. Secondary outcomes were pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, and multiple pregnancy rate. We analysed the results of 352 patients included in the Endoscratch Trial (NCT03108157). A total of 209 were patients with one or no previous implantation failures (105 with an ES done in the previous cycle, group A1, and 104 without ES, group B1), and 143 were patients with at least two previous failed implantations (71 patients with ES, group A2, and 72 without ES, group B2). We found an improvement in pregnancy rates (62.9% in group A1 vs. 55.8% in group B1 vs. 70.4% in group A2 vs. 76.4% in group B2, p = 0.028) in patients with at least two previous implantation failures, but this difference was not statistically different when we compared clinical pregnancy rates (59.1% vs. 51.0% vs. 64.8% vs. 68.1% in groups A1, B1, A2 and B2, respectively, p = 0.104) and live birth rates (52.4% vs. 43.3% vs. 57.8% vs. 55.6% in groups A1, B1, A2 and B2, respectively, p = 0.218). According to these results, we conclude that there is no evidence to recommend ES in egg-donor IVF cycles, regardless of the number of previous failed cycles.

Objective: To study whether endometrial scratching in the luteal phase before ovarian stimulation increases clinical pregnancy rates in women with one or more previous implantation failures.Design: A nonblinded multicenter randomized clinical trial.Setting: Fertility clinics.Patient(s): Three hundred four eligible patients scheduled for IVF/intracytoplasmic sperm injection were randomized. The intervention group (n = 151) underwent endometrial scratching in the luteal phase before controlled ovarian stimulation, while no intervention was performed in the control group (n = 153).Intervention(s): Endometrial scratching with a Pipelle de Cornier catheter in the luteal phase before ovarian stimulation.Main Outcome Measure(s): Clinical pregnancy rate and prenatal and birth data.Result(s): There was no overall significant improvement in clinical pregnancy rates between the control and intervention groups (38.5% vs. 44.4%; relative risk = 1.15; confidence interval [0.86-1.55]). However, subgroup analyses revealed that women with three or more previous implantation failures had a significant increase in clinical pregnancy rate (31.1% vs. 53.6%; relative risk = 1.72; confidence interval [1.05-2.83]) after scratching. No difference was seen as regards prenatal and birth data between the two groups.Conclusion(s): Endometrial scratching in the luteal phase before ovarian stimulation significantly enhances the clinical pregnancy rate in women with three or more prior implantation failures. This result seems to corroborate previous reports, which found that particularly women with repeated implantation failure seem to gain a positive effect from endometrial scratching. Importantly, there were no significant differences in prenatal data and birth data between the groups.Clinical Trial Registration Number: NCT01963819. [ABSTRACT FROM AUTHOR]

Study Question: Do randomised controlled trials (RCTs) evaluating endometrial scratching suffer from methodological issues including insufficient trial registration, statistical errors or irreproducibility, randomisation errors or miscellaneous issues?Summary Answer: The majority of RCTs investigating endometrial scratching have methodological issues.What Is Known Already: A large number of small RCTs investigating the effectiveness of endometrial scratching prior to in vitro fertilisation (IVF) and intrauterine insemination (IUI)/intercourse have reported favourable findings. Subsequently, systematic reviews incorporating these RCTs yielded meta-analyses in favour of endometrial scratching. Endometrial scratching has been widely adopted by infertility specialists around the world. Recently, an international RCT including 1364 women reported no benefit from endometrial scratching before IVF.Study Design, Size, Duration: We evaluated several methodological issues of RCTs investigating the effectiveness of endometrial scratching prior to IVF and IUI/intercourse. We identified 25 RCTs for IVF and 12 RCTs for IUI/intercourse with full-text publication.Participants/materials, Setting, Methods: We assessed the RCTs on the following criteria: adequacy of trial registration, statistical issues (description of statistical methods and reproducibility of univariable statistical analysis), excessive similarity or difference in baseline characteristics that is not compatible with chance (Monte Carlo simulations and Kolmogorov-Smirnov test) and miscellaneous methodological issues.Main Results and the Role Of Chance: Of 25 RCTs evaluating endometrial scratching prior to IVF, only eight (32%) had adequate trial registration. In total, 10 (40%) RCTs had issues regarding statistical methods. Nine (69%, 13 applicable) RCTs had at least one inconsistency between reported and reproduced univariable statistical analysis for categorical baseline/intermediate characteristics. Statistical results of at least one outcome were not reproducible in 14 (74%, 19 applicable) RCTs. Only two (8%) RCTs had none of the above issues. Suggested by the simulations, these RCTs did not significantly violate the null hypothesis that the baseline characteristics were the results of a properly conducted randomisation process (P = 0.4395).Of 12 IUI/intercourse RCTs, only 2 (17%) had adequate trial registration. In total, five (42%) studies had issues of statistical methods. Inconsistency between reported and reproduced univariable analysis for baseline/intermediate categorical variable(s) was found in four (57%, 7 applicable) RCTs. Statistical analysis was not reproducible for at least one outcome in eight (80%, 10 applicable) studies. All RCTs had at least one of the above issues. These RCTs were inconsistent with the null hypothesis that their baseline characteristics were the results of proper randomised allocation (P = 1.659*10-7).Limitations, Reasons For Caution: We were unable to assess RCTs which were not published as full-text papers. We could not analyse individual participant data to investigate possible reasons for statistical inconsistencies. The method to infer the likelihood of proper random sampling rests on assumptions including independent baseline characteristics, simple randomisation and no publication bias.Wider Implications Of the Findings: The methodological issues common to RCTs evaluating endometrial scratching may have biased the results of the trials. Further development and validation of these novel methods may be helpful for the critical appraisal of RCTs.Study Funding/competing Interest(s): No external funding was sought to support this work. B.W.M. is supported by a National Health Medical Research Council (NHMRC) Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck and Guerbet. D.W. is supported by a grant from the Paracelsus Medical University Salzburg, Austria (PMU Research Fund-PMU FFF Number: L-18/02/006-WET) and by Drs Haackert Foundation, Germany. S.L. is an author of a trial included in this study, an author of an included systematic review and a Cochrane editor. All other authors have no conflicts of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the impact of endometrial thickness (EMT) during menstruation and endometrial scratching on the pregnancy in frozen–thawed embryo transfer (FET). Methods: About 1298 patients receiving FET were retrospectively analyzed and divided according to EMT on the 4th or 5th day of menstruation. Group A: EMT ≤ 3.0 mm; Group B: EMT 3.1–5.0 mm; Group C: EMT 5.1–7.0 mm and Group D: EMT > 7.0 mm. Patients in Group D were further divided to scratching group and nonscratching group. Endometrial growth was defined as the change in EMT from 4th or 5th day of menstruation to the day of embryo transferred. Results: We found no significant differences in general conditions among four groups (P > 0.05). The average EMT during menstruation and differences in inter‐group endometrial growth of four groups had statistical significance (P < 0.05). The pregnancy rate and implantation rate of Group D were significantly lower than other groups (P < 0.001). Pregnancy rate (68.29% vs 53.26%) and implantation rate (52.67% vs 36.34%) in endometrial scratching group were higher than those in nonscratching group (P < 0.05). Conclusion: Higher EMT during menstruation adversely affects pregnancy outcomes following FET. Endometrial scratching may improve the receptivity of endometrium and increase the rate of embryo implantation and pregnancy. [ABSTRACT FROM AUTHOR]

Background: Endometrial injury is an intentional damage made to the endometrium, usually produced by a Pipelle catheter. Over the last two decades, endometrial injury has been studied to improve implantation rates and decrease the incidence of implantation failure in invitro fertilization (IVF) cycles. Recently, additional studies of endometrial injury, performed not only in patients with implantation failure but also in intrauterine insemination cycles, have been conducted, and the endometrial injury made by hysteroscopy has been researched. The evidence describing the impact of endometrial injury is controversial; therefore, we conducted a systematic review and meta-analysis to examine the issue.Objective and Rationale: Our objective is to review the research that has been done until now and perform a meta-analysis regarding endometrial injury and its influence on implantation success and pregnancy rates in patients with at least one failed IVF cycle. In particular, we aim to study the efficacy of the procedure and look for confounding factors, such as maternal age, in assessing the efficacy of endometrial injury.Search Methods: The systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Study protocol can be assessed at PROSPERO International prospective register of systematic reviews (registration number CRD42018092773). Searches were conducted by an experienced research librarian in the following databases: MEDLINE(R) using the OvidSP interface and PUBMED, Embase, Web of Science and Cochrane Library. This review considered for inclusion randomized-controlled trials examining the success of performing local endometrial injury on IVF outcomes in women with previous failed IVF cycles.Outcomes: Ten studies, comprising a total of 1260 patients, were selected. Overall, when studying the effect of endometrial injury on clinical pregnancy rates (CPRs) and live birth rates (LBRs), higher rates were shown in the endometrial injury group. However, endometrial injury did not significantly improve CPRs and LBRs, when considering sub-group analyses of studies including patients with two or more failed IVF cycles, studies examining older patients or studies which did not include hysteroscopy. There was no significant difference found regarding multiple pregnancy rates, while a handful of studies showed an improvement in miscarriage rates.Wider Implications: Endometrial injury should be used restrictively and not routinely in clinics. Maternal age and number of previous failed treatment cycles may be contributing factors which can influence the results when studying the effect of endometrial local injury. It is possible that the relative contribution of endometrial receptivity to the chances of implantation decreases with any additional failed cycle. The optimal study to prove the efficacy of local endometrial injury on implantation and pregnancy rates, should be a random-controlled trial studying the effect of local endometrial injury in oocyte donation cycles, in recipients with repeated implantation failure. This kind of study will conclude whether local endometrial injury is an efficient procedure with minimum confounding factors, and may assist in defining the population, even outside of donation cycles, that will benefit from the procedure. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the effect of endometrial scratching in patients with or without prior failed ART cycles on live birth (LBR) and clinical pregnancy rates (CPR)? SUMMARY ANSWER It remains unclear if endometrial scratching improves the chance of pregnancy and, if so, for whom. WHAT IS KNOWN ALREADY Endometrial scratching is hypothesized to improve embryo implantation in ART. Multiple studies have been published, but it remains unclear if endometrial scratching actually improves pregnancy rates and, if so, for which patients. STUDY DESIGN, SIZE, DURATION For this review, a systematic search for published articles on endometrial scratching and ART was performed on 12 February 2018, in Pubmed, Embase and the Cochrane Library. PARTICIPANTS/MATERIALS, SETTING, METHODS Randomized controlled trials (RCTs) that evaluated endometrial scratching in the cycle prior to the stimulation cycle and reported CPR or LBR were included. RCTs investigating the effect of scratching during the stimulation cycle, or prior to cryo-thaw cycles were excluded. Studies were assessed using the Cochrane Risk of Bias tool. The effect of scratching was assessed for three different patient groups: patients with no prior IVF/ICSI treatment (Group 0), patients with one failed full IVF/ICSI cycle, including cryo-thaw cycles (Group 1) and patients with two or more failed full IVF/ICSI cycles (Group 2). A meta-analysis was performed when statistical heterogeneity was low; otherwise, a descriptive analysis was performed. MAIN RESULTS AND THE ROLE OF CHANCE Fourteen RCTs involving 2537 participants were included. Most RCTs contained a high or unclear risk of bias on one or more items. Substantial clinical and statistical heterogeneity was present; therefore meta-analysis for LBR and CPR could only be performed on Group 1. For this group, no differences between scratch and control were found for both LBR (risk ratio (RR) 1.01 [95%CI 0.68–1.51]) and CPR (RR 1.04 [95%CI 0.74–1.45]). For Groups 0 and 2, pooled analysis could not be performed, and for both groups the results of the individual RCTs were negative, neutral and positive. Miscarriage and multiple pregnancy rates were evaluated for the three groups (0, 1 and 2) together. Both outcomes were not significantly different between scratch and control (miscarriage rate RR 0.82 [95%CI 0.57–1.17] and multiple pregnancy rate RR 1.06 [95%CI 0.84–1.35]). Subgroup analysis, excluding trials with a risk of unintentional endometrial injury in the control group, was performed for Group 0 and 2 for LBR and CPR, and for the overall groups for miscarriage rate and multiple pregnancy rate. This reduced the heterogeneity and allowed for pooled analysis in these subgroups. Results of pooled analysis for the subgroups of Group 0 and 2 showed no significant difference for LBR, but CPR was significantly improved after endometrial scratching (Group 0 RR 1.28 [95%CI 1.02–1.62] and Group 2 RR 2.03 [95%CI 1.20–3.43]). Subgroup analysis of the overall groups showed no significant difference for miscarriage and multiple pregnancy rate. LIMITATIONS REASONS FOR CAUTION The main limitations were that many RCTs had a high or unclear risk of bias on one or several items, clinical heterogeneity was still present despite categorizing into three populations, and that not all RCTs could be included in the analyses because separate data for our three groups could not be provided. WIDER IMPLICATIONS OF THE FINDINGS It remains unclear if endometrial scratching improves the chance of pregnancy for women undergoing ART and, if so, for whom. This means endometrial scratching should not be offered in daily practice until results from large and well-designed RCTs and an individual patient data analysis become available. STUDY FUNDING/COMPETING INTERESTS No specific funding was sought for the study. The Department of Reproductive Medicine and Gynaecology funds of the University Medical Center of Utrecht were used to support the authors throughout the study period and preparation of the manuscript. None of the authors has a conflict of interest to declare. REGISTRATION NUMBER Not applicable. [ABSTRACT FROM AUTHOR]

Background: Induced endometrial injury is a technique described that have positive impact on implantation. The aim of this study was to investigate whether hysteroscopic endometrial fundal incision (EFI) in oocyte recipients before embryo transfer increases pregnancy and live birth rates or not., Materials and Methods: A prospective study was conducted between 2014 and 2019 at an in vitro fertilization (IVF) unit in Greece. As part of the protocol, hysteroscopy and EFI were offered to all the egg recipients and the outcomes compared with those from an older cohort from the same Unit not undergoing hysteroscopy., Results: In total, 332 egg recipients participated in the study; 114 of them underwent EFI prior to embryo transfer. Both groups were similar in terms of age, years of infertility, duration of hormone replacement treatment (HRT) and number of blastocysts transferred. In the EFI group, minor anomalies were detected and treated in 6.1% (n=7) of the participants. Moreover, pregnancy test was positive in 73.7% of the women in the hysteroscopy group compared to 57.8% in the nonhysteroscopy group (P=0.004). Live birth rate was also higher (56.1 vs. 42.2%, P=0.016) in the EFI group compared to the non-hysteroscopy one., Conclusion: Apart from the obvious benefit of recognizing obscured anomalies, requiring surgical correction, it appears that in oocyte recipients prior to embryo transfer, EFI might improve uterine receptivity and reproductive outcomes.

Background: In IVF/ICSI treatment, the process of embryo implantation is the success rate-limiting step. Endometrial scratching has been suggested to improve this process, but it is unclear if this procedure increases the chance of implantation and live birth (LB) and, if so, for whom, and how the scratch should be performed., Objective and Rationale: This individual participant data meta-analysis (IPD-MA) aims to answer the question of whether endometrial scratching in women undergoing IVF/ICSI influences the chance of a LB, and whether this effect is different in specific subgroups of women. After its incidental discovery in 2000, endometrial scratching has been suggested to improve embryo implantation. Numerous randomized controlled trials (RCTs) have been conducted, showing contradicting results. Conventional meta-analyses were limited by high within- and between-study heterogeneity, small study samples, and a high risk of bias for many of the trials. Also, the data integrity of several trials have been questioned. Thus, despite numerous RCTs and a multitude of conventional meta-analyses, no conclusion on the clinical effectiveness of endometrial scratching could be drawn. An IPD-MA approach is able to overcome many of these problems because it allows for increased uniformity of outcome definitions, can filter out studies with data integrity concerns, enables a more precise estimation of the true treatment effect thanks to adjustment for participant characteristics and not having to make the assumptions necessary in conventional meta-analyses, and because it allows for subgroup analysis., Search Methods: A systematic literature search identified RCTs on endometrial scratching in women undergoing IVF/ICSI. Authors of eligible studies were invited to share original data for this IPD-MA. Studies were assessed for risk of bias (RoB) and integrity checks were performed. The primary outcome was LB, with a one-stage intention to treat (ITT) as the primary analysis. Secondary analyses included as treated (AT), and the subset of women that underwent an embryo transfer (AT+ET). Treatment-covariate interaction for specific participant characteristics was analyzed in AT+ET., Outcomes: Out of 37 published and 15 unpublished RCTs (7690 participants), 15 RCTs (14 published, one unpublished) shared data. After data integrity checks, we included 13 RCTs (12 published, one unpublished) representing 4112 participants. RoB was evaluated as 'low' for 10/13 RCTs. The one-stage ITT analysis for scratch versus no scratch/sham showed an improvement of LB rates (odds ratio (OR) 1.29 [95% CI 1.02-1.64]). AT, AT+ET, and low-RoB-sensitivity analyses yielded similar results (OR 1.22 [95% CI 0.96-1.54]; OR 1.25 [95% CI 0.99-1.57]; OR 1.26 [95% CI 1.03-1.55], respectively). Treatment-covariate interaction analysis showed no evidence of interaction with age, number of previous failed embryo transfers, treatment type, or infertility cause., Wider Implications: This is the first meta-analysis based on IPD of more than 4000 participants, and it demonstrates that endometrial scratching may improve LB rates in women undergoing IVF/ICSI. Subgroup analysis for age, number of previous failed embryo transfers, treatment type, and infertility cause could not identify subgroups in which endometrial scratching performed better or worse. The timing of endometrial scratching may play a role in its effectiveness. The use of endometrial scratching in clinical practice should be considered with caution, meaning that patients should be properly counseled on the level of evidence and the uncertainties., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Objective: Evaluation of endometrial scratching on pregnancy rates after IUI and comparing levels and distribution of IL-6 (inflammatory molecule) and E-Cadherin (adhesion molecule) by immunohistochemistry. Study design: Randomized case control study. Study design: Randomized case control study. Setting: Tertiary care hospital of Delhi, India. Material and methods: 240 women (120 in each group) with previous failed IUI cycles were enrolled. Study group patients were subjected to endometrial scratch by ''Pipelle" on postovulatory day 6-8 in the preceding cycle. IUI was performed after controlled ovarian stimulation with gonadotropins. 20 patients of study group in whom IUI was cancelled underwent repeat scratch on postovulatory day 6-8. Levels and distribution of IL-6 and E-Cadherin were evaluated by Immunohistochemistry before and after the scratch. Main outcome: Comparison of pregnancy rates in women undergoing IUI after endometrial scratching with women undergoing IUI alone. Results and conclusion: There were 19 (19%) clinical pregnancies in the study group and 8 (7.6%) in the control group. There was a significant difference in between both the groups (p = 0.022). Number of pregnancies in unexplained infertility patients was 22.66% in study and 9.5% in control group (p = 0.0291). There was significant increase in score for IL-6 and E-Cadherin in both glands and stroma after scratching. Endometrial scratch is a simple, practical, cost effective and outpatient procedure which may increase pregnancy rates in previous failed IUI cycles. Increased intensity of staining; shift of major part of staining from gland or stroma in pre scratch samples to both glands and stroma in post scratch samples; and increased stromal decidualization point towards increased endometrial receptivity. [ABSTRACT FROM AUTHOR]