Role of Endometrial Scratch in UnExplained infertility (RESCUE); A Randomized Clinical Trial

Background Endometrial natural killer (NK) is thought to play a role in implantation and maintenance of a healthy pregnancy. However, their immunological role in unexplained infertility is yet unknown. The aim of the current study was to investigate the role of endometrial injury in treatment of unexplained infertility and to have more insight on the potential underlying mechanisms of its action methodology randomized controlled trial (RCT) done at Minia university hospital, diagnostic laparoscopy was done for both study and control group, study group had gentle scratch and specimens were sent for histopathological examination while control group had Laparoscopy only .Patients in both groups were followed up at the outpatient clinic for 3 months to assess if pregnancy achieved or not. Patients in the study group who had not achieved pregnancy had a repeated scratch using a pipelle sampler which was also sent for histopathology. Patients were counselled for intrauterine insemination (IUI) with ovulation induction while patient in control group had been counselled for IUI and ovulation induction only. Patients in both groups were followed up for further 3 months to assess patients who achieved pregnancy either naturally or after IUI . Results Baseline characteristics were comparable in both groups. Clinical pregnancy rate (CPR) was significantly higher in scratch group compared with the control group (22%; vs. 7.4%, P = 0.001) in the first three months of follow up. After second scratch and IUI cycles cumulative pregnancy rate was significantly higher in the scratch group compared with the control group (36.7% , vs. 16.2%,, P = 0.001). The mean time achieve pregnancy was found to be significantly shorter in the scratch group as compared to the control group (102 days vs.49.5 days, P = 0.01). Conclusion: Endometrial natural killer cells might play a crucial role in endometrial receptivity and therefore embryo implantation. Endometrial scratch could promote the recruitment of endometrial NK cells and give a more favourable results as regard clinical pregnancy in patients with unexplained infertility. Registration number PACTR201604001405465

The Current Role of Induced Endometrial Trauma (Endometrial Scratch) in Women Undergoing Infertility Treatment

Induced endometrial trauma, otherwise known as endometrial scratch is a simple technique that has been rapidly adopted into clinical practice, mainly for women having IVF treatment, in an attempt to increase pregnancy rates. The introduction of endometrial scratch followed early reports of improved clinical pregnancy rates in women with repetitive implantation failure after having the procedure and follows on from evidence from animal models in the early 20th century suggesting that mechanical trauma to the endometrium can induce decidual changes. Due to the ease and low cost of the procedure, it has been rapidly adopted as an add-on to fertility treatments, in many cases where evidence is still lacking. Despite the initial publication of a large number of studies that demonstrated encouraging improvements in pregnancy rates in women who underwent this procedure, these studies were mainly limited by the small sample sizes and heterogeneity of their study populations, leading to limited validity of the evidence provided by these studies. More recently, three large randomized controlled studies have been published that paint a different picture regarding the value of this procedure. This article explores the evolution of the evidence and the current state of endometrial scratch as an adjuvant therapy for women undergoing IVF treatment.

Comparing Two Types of Endometrial Scratch Before Embryo Transfer: A Prospective Randomized Pilot Study

Purpose: Although endometrial scratch may improve outcomes in certain groups of women undergoing assisted reproductive technology (ART), the type of endometrial procedure has not been specified. Our objective was to determine if two types of endometrial scratch prior to embryo transfer result in similar implantation and live birth rates. Also, to determine if patients experience similar pain from both types of endometrial scratch.Methods: This was a prospective, non-blinded, randomized controlled trial with parallel treatment arms of women undergoing blastocyst embryo transfer. Patients underwent endometrial scratch with either vigorous Pipelle curette or four-quadrant scratch with the Shepard insemination catheter.Results: There were 78 patients in the Pipelle curette group and 92 in the Shepard catheter group. There was no difference in implantation rates for the two groups (56.5% ±48 for Pipelle curette group vs. 59.7%±52 for Shepard catheter group, p-value 0.9). Live birth rates were also similar for the two groups (48.1% ±50 for Pipelle curette group vs. 46.8%±50 for Shepard catheter group, p-value 0.7). Mean pain score was significantly less for the Shepard catheter group than for the Pipelle curette group (3.0±2.4 vs. 3.9±2.2, p-value 0.01).Conclusions: Our study demonstrates no difference in implantation or live birth rates for two types of endometrial scratch. There was a difference in patient pain scales with endometrial scratch by a Shepard insemination catheter having a significantly lower pain score than by Pipelle curette. This data gives guidance as to the type of endometrial scratch to be performed prior to ART.

Experiences of trial participants and site staff of participating in and running a large randomised trial within fertility (the endometrial scratch trial): a qualitative interview study

ObjectivesTo explore the experiences of endometrial scratch (ES) trial participants and site staff of trial recruitment and participation, in order to improve the experience of participants in future trials.DesignQualitative study of a subset of participants in the ES randomised controlled trial and a subset of trial site staff.SettingA purposeful sample of 9 of the 16 UK Fertility Units that participated in the trial.ParticipantsA purposeful sample of 27 trial participants and 7 site staff.ResultsParticipants were largely happy with the recruitment practices, however, some were overwhelmed with the amount of information received. Interviewees had positive preconceptions regarding the possible effect of the ES on the outcome of their in vitro fertilisation (IVF) cycle, which often originated from their own internet research and seemed to be exacerbated by how site staff described the intervention. Some participants appeared to not understand that receiving the ES could potentially reduce their chances of a successful IVF outcome. Those randomised to the control arm discussed feeling discontent; site staff developed mechanisms of dealing with this.ConclusionsA lack of equipoise in both study participants and the recruiting site staff led to trial participants having positive preconceptions of the potential impact of the ES on their upcoming IVF cycle. Trial participants may not have understood the potential harms of participating in a randomised trial. The trial information sheet did not clearly state this; further research should assess how such information should be presented to potential participants, to proportionately present the level of risk, but to not unduly discourage participation. The amount of information fertility patients require about a research study should also be investigated, in order to avoid participants feeling overwhelmed by the amount of information they receive prior to starting IVF.Trial registration numberISRCTN23800982.

P–305 The expression of innate immune factors in the eutopic endometrium of women with endometriosis

Study question Is the expression of IL–17A and antimicrobial peptides (AMPs) altered in endometriosis? Summary answer IL–17A protein levels were similar in the endometrium of women with and without endometriosis but the expression of several AMPs was reduced in endometriosis. What is known already Chronic inflammation and aberrant immune signalling in the eutopic endometrium underlies the pathophysiology of endometriosis. Endometrial IL–17 levels have previously been shown by our group to be negatively correlated with successful pregnancy. IL–17 has also been associated with endometriosis. Among its immunomodulatory functions, IL–17 regulates the expression of several antimicrobial peptides (AMPs), highly conserved proteins that are involved in the innate immune response. Despite the well accepted paradigm of immune dysregulation in endometriosis, surprisingly little is known about the relationship between endometrial IL–17, AMPs and endometriosis, particularly in the context of infertility. Study design, size, duration This was a prospective cohort study. Endometrial biopsy samples were collected at the time of endometrial scratch testing, or during elective laparoscopy, over a 15-month period. The aim was to evaluate and compare IL–17A protein levels and the expression of specific AMPs (SLPI, elafin, beta-defensin 1, S100A7, S100A8, S100A9) [MW1] , in the endometrium of patients with endometriosis, and those without the disease. Participants/materials, setting, methods Thirty-two patients were recruited for the study, with 26 included in the final analysis. Biopsies were obtained at the time of planned endometrial scratch (mid-luteal phase) prior to ART (n = 7), or at the time of laparoscopy (n = 19). RNA was extracted and Q-PCR analysis for AMP transcript levels was performed. ELISA was carried out to quantify levels of IL–17A in endometrial tissue in a subgroup (n = 17). Main results and the role of chance: In our cohort IL–17A protein levels were not significantly different in the endometrium of patients with disease compared to those without (p = 0.3636). The expression of the AMPs elafin, SLPI, BD1 and S100A9, as measured by a Q-PCR transcript profiling approach, were found to be significantly reduced in the eutopic endometrium in cases of endometriosis as compared to cases without endometriosis. There was no significant difference in AMP expression between disease stages. No demonstrable difference in IL–17A protein levels, or AMP expression was detected between the proliferative and secretory phases of the menstrual cycle. Limitations, reasons for caution Numbers may not have been large enough to fully evaluate the impact of endometriosis stage or the effect of cycle phase. While all patients with endometriosis had surgical confirmation of disease, not all patients in the control cohort had a laparoscopy, though they had no clinical features suggestive of endometriosis. Wider implications of the findings: Our findings indicate that the innate immune environment of the eutopic endometrium is altered in endometriosis. Endometrial expression of AMPs was diminished in endometriosis, independent of disease stage. This work supports the model of dysregulated innate immune system in endometriosis, and reveals AMPs as novel immune players in disease pathogenesis. Trial registration number Not applicable