Effect of endometrial mechanical stimulation in an unselected population undergoing in vitro fertilization: futility analysis of a double-blind randomized controlled trial

Abstract

Purpose Implantation failure is a major limiting factor of successful in vitro fertilization (IVF). The objective of this study was to determine if endometrial mechanical stimulation (EMS) by endometrial biopsy in the luteal phase of the cycle prior to embryo transfer (ET) improves clinical outcomes in an unselected subfertile population. Methods Double-blind, randomized controlled trial of EMS versus sham biopsy and odds of clinical pregnancy after IVF and embryo transfer. Secondary outcomes included spontaneous miscarriage and live birth. Results One hundred women enrolled and were randomized from 2013 to 2017. Enrollment was terminated after futility analysis showed no difference in clinical pregnancy between EMS versus control, 47.2% vs 61.7% (OR 0.55, 95% CI 0.25-1.23, p = 0.15). There were no significant differences between women who underwent EMS and those who did not in terms of positive pregnancy test 54.7% vs 63.8% (OR 0.69, 95% CI 0.31-1.53, p = 0.36), miscarriage 7.5% vs 2.1% (OR 3.76 95% CI 0.41-34.85, p = 0.22), or live birth 43.4% vs 61.7% (OR 0.48 95% CI 0.21-1.06, p = 0.07). Conclusions EMS in the luteal phase of the cycle preceding embryo transfer does not improve clinical outcomes in an unselected subfertile population and may result in a lower live birth rate. We caution the routine use of EMS in an unselected population.

The impact of endometrial injury on reproductive outcomes: results of an updated meta‐analysis

“…Finally, 17 references 12,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] comprising 3016 patients, 1498 in the EI group, and 1518 in the control group were included in our meta-analysis.…”

“…12,27,29,30,35 Due to high risk of bias in the randomization process and allocation according to the clinical case record number, the study published by Matsumato et al was excluded from our analysis. 36 Eleven studies included patients with at least one previous failed cycle, 12,[20][21][22]26,27,[29][30][31]33,35 four studies included patients with at least two previous failed cycles, [23][24][25]34 and the remaining two studies 28,32 included patients with at least three previous failed IVF cycles ( Table 1). Three studies, in addition to presenting the data for patients with at least one previous failed cycle, provided further data for patients with at least two previous failed cycles.…”

“…included patients with previous failed cycles as the included data originated from a subgroup analysis 27,29,30 (Table 1).…”

“…In the study published by Gibreel et al 31 As noted in Table 1, studies varied in inclusion criteria and in the EI procedure. Nine studies performed EI once on the luteal phase of the cycle preceding IVF treatment, [22][23][24]26,27,29,30,34,35 two studies performed EI once on the follicular phase, 25,32 one study performed EI once between day 3 of the cycle preceding the IVF cycle and day 3 of the IVF cycle, 12 three studies performed EI twice on the luteal phase 20,31,33 and two studies performed EI twice, once in the follicular phase and once in the luteal phase. 21,28 Figure 2 presents the risk of bias summary.…”

“…26,28,30,35 Unclear risk of reporting bias was also found in nine studies due to absent or retrospective clinical trial registration. 21,[23][24][25]27,29,[32][33][34] Other factors of bias were unclear in six studies that involved antibiotics, steroids, or hysteroscopy in their treatment protocol. 21,25,26,[31][32][33] Another five studies had unclear risk of bias due to the inclusion of a subgroup analysis.…”