A systematic review was conducted of the influence of local endometrial injury (LEI) on the outcome of the subsequent IVF cycle. MEDLINE, EMBASE, the Cochrane Library, National Research Register, ISI Conference Proceedings, ISRCTN Register and Meta-register were searched for randomized controlled trials to October 2011. The review included all trials comparing the outcome of IVF treatmentin patients who had LEI in the cycle preceding their IVF treatment with controls in which endometrial injury was not performed. The main outcome measures were clinical pregnancy and live birth rates. In total, 901 participants were included in two randomized (n = 193) and six non-randomized controlled studies (n = 708). The quality of the studies was variable. Meta-analysis showed that clinical pregnancy rate was significantly improved after LEI in both the randomized (relative risk, RR, 2.63, 95% CI 1.39–4.96, P = 0.003) and non-randomized studies (RR 1.95, 95% CI 1.61–2.35, P < 0.00001). The improvement did not reach statistical significance in the one randomized study which reported the live birth rate (RR 2.29, 95% CI 0.86–6.11). Robust randomized trials comparing a standardized protocol of LEI before IVF treatment with no intervention in a well-defined patient population are needed.
The endometrium is the lining of the womb where the embryo implants. Endometrial surface injury is a simple office procedure. We reviewed the literature to find out if performing endometrial surface injury before an IVF treatment cycle improves its outcome. Our review found that when endometrial surface injury was performed before an IVF treatment cycle, there was a significant improvement in the outcome of that treatment cycle. We recommend this question is addressed in a well-conducted randomized study to confirm the findings of our review.
Introduction
Implantation remains the rate-limiting step towards the establishment of pregnancy during IVF treatment. Successful implantation is a complex process that requires effective interaction of a competent embryo and receptive endometrium at the molecular level. To date, most attempts to improve the IVF implantation rate have focused on embryonic factors, such as extended embryo culture, blastocyst selection and transfer, assisted hatching and preimplantation aneuploidy screening. In contrast, only a few interventions have been proposed to improve endometrial receptivity, despite evidence that up to two-thirds of implantation failures could be secondary to insufficient receptivity (Simon et al., 1998).
One of the proposed interventions designed to promote the development of a receptive endometrium is to induce local endometrial injury (LEI) prior to starting an IVF cycle. The relationship between endometrial injury and successful implantation was observed initially in the animal model and subsequently examined in several clinical studies in different IVF populations (Almog et al., 2010, Barash et al., 2003, Friedler et al., 1993, Li and Hao, 2009).
This study sought to systematically review and summarize existing evidence related to the impact of LEI on the outcome of IVF treatment to further guide clinical practice.
Section snippets
Literature search methodology
This study searched in MEDLINE (1966-December 2011), EMBASE (1974-December 2011), Cochrane Library (1970–2011) and the National Research Register for relevant studies. The search also included ISI Conference Proceedings since 1990, as well as databases for registration of ongoing and archived randomized controlled trials (RCT) namely ISRCTN Register and Meta-register for RCT. A combination of Medical Subject Headings (MeSH) and text words were used to generate two subsets of citations, one
Results
The process of literature identification and selection is summarized in Figure 1. Of the 130 citations identified in the search, 15 were selected during the initial screening and, on examination of full manuscripts, eight articles including a total of 901 participants satisfied the selection criteria for this review. A ninth study of endometrial injury (Huang et al., 2011) was excluded as the LEI procedure was combined with a hysteroscopy in the intervention group.
This study found two
Discussion
Several interventions have been proposed to increase IVF success rates, but very few are directed towards improving endometrial receptivity. Data presented in this systematic review and meta-analysis suggest a beneficial effect of LEI performed prior to ovarian stimulation on the clinical pregnancy and live birth rates after IVF. This positive impact was consistent among the randomized and non-randomized studies in the clinical pregnancy rate, but did not reach statistical significance in the
Acknowledgement
The authors are especially grateful to the authors of the studies included in this review, who provided additional data.
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Although the intrauterine administration of PBMCs activated by hCG significantly increased the pregnancy and live birth rates in our included studies, we noted that the control group comprised patients without intrauterine administration in six studies and patients with intrauterine PBS in one study. The operation of intrauterine administration might cause endometrial trauma, which would influence the clinical outcomes (El-Toukhy et al., 2012; Panagiotopoulou et al., 2015). Therefore, further research on patients receiving intrauterine administration of PBMCs cultured in isolation, as a control group, should be encouraged to eliminate the effects of the operation and determine the exact role of hCG in this therapy.
The purpose of this study was to assess whether intrauterine administration of peripheral blood mononuclear cells (PBMCs) activated by human chorionic gonadotropin (hCG) could improve the pregnancy and live birth rates in women with repeated implantation failure (RIF), and whether the parameters of co-culture of hCG and PBMCs would affect the clinical outcomes. Six databases (PubMed, Ovid, Medline, NCBI, Cqvip and Wanfang) were searched up to October 2020 by two independent reviewers. Seven studies were included according to specific inclusion and exclusion criteria. A meta-analysis showed that the pregnancy and live birth rates were significantly increased in the case group compared with the control group (odds ratio [OR]: 3.43, 95 % confidence interval [CI]: 1.78–6.61; P = 0.0002 and OR: 2.79, 95 % CI: 1.09–7.15; P = 0.03), especially when hCG was cultured with PBMCs for 48 h or PBMCs administration was performed two or three days before embryo transfer (ET). Neither the dosage of the hCG co-cultured with PBMCs nor the mean concentration of the administered PBMCs appeared to influence the therapeutic efficiency. In conclusion, intrauterine administration of PBMCs co-cultured with hCG for 48 h, conducted two or three days before ET, could be an effective therapy for women experiencing RIF. Due to the limitations of sample size and quality of the included studies, further high-quality studies with large sample sizes are warranted to optimize the parameters of hCG and PBMC co-culture to help more RIF patients benefit from this therapy.
2020, European Journal of Obstetrics and Gynecology and Reproductive Biology
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.
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.
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.
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.
Tarek El-Toukhy is a consultant in reproductive medicine and surgery and preimplantation genetic diagnosis (PGD) at the Assisted Conception Unit and PGD Centre at Guy’s and St Thomas’ Hospital in London. His clinical and research interests are in the fields of recurrent IVF implantation failure, prevention of ovarian hyperstimulation syndrome, embryo freezing, PGD and minimal access surgery. He has published over 80 original articles, reviews and opinion papers.
