The effect of aspirin on uterine arterial blood flow and endometrium in moderate and severe intrauterine adhesion after transcervical resection of adhesion: a systematic review and meta-analysis

Figures & data

Figure 1. Flow diagram of the study selection process.

Table 1. Characteristics of Included Studies.

Articles	Surgery	Age	Onset time	Experimental group	Control group	Results
Cheng (2021) [4]	Severe IUA	Control group: n = 37, mean age = 32.15 ± 3.65, mean BMI= 22.41 ± 0.75 kg/m^2, Experimental group: n = 37, mean age = 31.85 ± 3.34, mean BMI = 22.53 ± 0.69 kg/m^2	No mention	Oral Estradiol Tablets: 1 table/time, 2 times/d, Oral aspirin: 100 mg/time, 1 time/d, Oral Estrogen/ Progesterone Tablets: 10 mg/time (day 14 after surgery)	Oral Estradiol Tablets: 1 table/time, 2 times/d, Oral Estrogen/Progesterone Tablets: 10 mg/time (day 14 after surgery)	1. Clinical Effectiveness (p < .05) 2. PI, RI (p < .05) 3. TGF-β1, TIMP-1 (p < .05) 4. Adverse reactions (p > .05)
Li et al. (2021) [5]	Severe IUA	Control group: n = 53, mean age = 34.05 ± 5.64, mean BMI = 23.25 ± 1.68 kg/m^2, mean AFS = 10.23 ± 1.22 Experimental group: n = 53, mean age = 33.97 ± 5.71, mean BMI = 22.58 ± 1.47 kg/m^2, mean AFS = 10.03 ± 1.61	Control group: 6.35 ± 1.63 month Experimental group: 6.04 ± 1.55 month	Oral Estradiol Tablets: 1 mg/time, 2 times/d, Oral aspirin: 100 mg/d, Oral Estrogen/Progesterone Tablets: 10 mg/time (d 14 after surgery)	Oral Estradiol Tablets: 1 mg/time, 2 times/d, Oral Estrogen/Progesterone Tablets: 10 mg/time (day 14 after surgery)	1. Clinical Effectiveness (p < .05) 2. Uterine morphology and menstrual recovery (p < .05) 3.FI, PI, RI (p < .05)
Xue and Ruoyu (2020) [6]	Severe IUA	Control group: n = 40, mean age = 33.00 ± 4.92 Experimental group: n = 40, mean age = 32.85 ± 4.70	No mention	Oral Estrogen: 1 mg/time, 1 times/d, Oral Estradiol Tablets: 1 table/d, Oral aspirin: 100 mg/d	Oral Estrogen: 1 mg/time, 1 times/d, Oral Estradiol Tablets: 1 table/d	1. Menstrual improvement (p = .03) 2. Recurrence of uterine adhesions (p = .014) 3. Adverse reactions (p > .05)
Liu and Wang (2020) [7]	Hysteroscopic electric resection	Control group: n = 28, mean age = 41 Experimental group: n = 30, mean age = 41	No mention	Oral Estrogen: 2 mg/time, 2 times/d, Oral Progesterone: 10 mg/d, Oral aspirin: 100 mg/d	Oral Estrogen: 2 mg/time, 2 times/d, Oral Progesterone: 10 mg/d,	1. RI, PI (p < .05) 2. Endometrium thickness and FI (p < .05) 3. Menstrual and uterine status (p < .05)
Shihui and Qiong (2020) [8]	Moderate and serve IUA	Control group: n = 20, mean age = 30 ± 0.5 Experimental group: n = 30, mean age = 29 ± 0.3	No mention	Oral Estradiol Valerate: 2 mg/time, 1 times/d, Oral Progesterone Capsules: 10 mg/d, Oral aspirin: 75 mg/d	Oral Estradiol Valerate: 2 mg/time, 1 times/d, Oral Progesterone Capsules: 10 mg/d	1. Uterine status (p > .05) 2. Endometrium thickness (p < .05) 3. Menstrual improvement (p < .05) 4. Pregnancy (p < .05)
Liu et al. (2019) [9]	Moderate and Severe IUA	Control group: n = 20, mean age = 31.38 ± 5.61 Experimental group: n = 20, mean age = 39.47 ± 5.72	No mention	Oral Progesterone Capsules: 4 mg/d, Oral aspirin: 50 mg/d, Oral Duphaston (in last 7 d)	Oral Progesterone Capsules: 4 mg/d, Oral Duphaston (in last 7 d)	1. Clinical Effectiveness (p < .05) 2. Endometrium thickness, PI, and RT (p < .05) 3. MVD and VEGF of Endometrium (p < .05) 4. Pregnancy (p > .05)
Shi et al. (2019) [10]	Moderate and Severe IUA	Control group: n = 20, mean age = 32.30 ± 4.19, mean AFS = 7.97 ± 1.46 Experimental group: n = 20, mean age = 31.79 ± 4.94, mean AFS = 7.39 ± 1.80	No mention	Oral Estradiol Valerate: 1 mg/time, 2 times/d, Oral aspirin: 25 mg/time, 3 times/d, Oral Estradiol/Duphaston: 1 times/d	Oral Estradiol Valerate: 1 mg/time, 2 times/d, Oral Estradiol/Duphaston: 1 times/d (in last 10 d)	1. AFS (p < .05) 2. Menstrual improvement (p < .05) 3. Pregnancy (p < .05)
Zhong-Ping et al. (2019) [11]	Severe IUA	Control group: n = 24, mean age = 32.5 ± 3.1, mean MBI = 23.1 ± 3.0 kg/m^2 Experimental group: n = 24, mean age = 32.1 ± 3.4, MBI= 23.3 ± 3.4 kg/m^2	Control group: 6.72 ± 1.5 month Experimental group: 6.36 ± 1.5 month	Oral Estradiol Valerate: 2 mg/time, 1 times/d, Oral aspirin: 100 mg/time, 1 times/d, Oral progesterone: 100 mg/time, 2 times/d	Oral Estradiol Valerate: 2 mg/time, 1 times/d, Oral progesterone: 100 mg/time, 2 times/d	1. Clinical Effectiveness (p < .05) 2. Endometrium thickness, VI, FI, and VFI (p < .05)
Xiang and Ding (2018) [12]	Moderate and Severe IUA	Total= 137, mean age = 32.47 ± 5.2	No mention	Oral Estradiol Valerate: 2 mg/d, Oral aspirin: 80 mg/d, Oral Vitamin E: 100 mg/d, Oral Dragon Deer Pills: 3–5 pills/d	Oral Estradiol Valerate: 2–4 mg/d	1. Efficient uterine recovery (p < .05) 2. Menstrual improvement (p < .05) 3. Uterine adhesions without recurrence rate (p < .05) 3. Pregnancy (p < .05)
Zheng and Ming (2018) [13]	Serve IUA	Control group: n = 40, mean age = 32.1 ± 5.3, mean BMI = 23.6 ± 4.3 kg/m^2 Experimental group: n = 40, mean age = 31.8 ± 5.5, mean BMI = 23.1 ± 4.6 kg/m2	Control group: 7.1 ± 0.8 month Experimental group: 7.0 ± 1.0 month	Oral Estradiol Valerate: 9 mg/time, 1 times/d, Oral aspirin: 50 mg/d, Oral Medroxyprogesterone: 10 mg/d	Oral Estradiol Valerate: 9 mg/time, 1 times/d, Oral Medroxyprogesterone: 10 mg/d	1. VI, FI, VF, RI, and PI(p < .05) 2. Endometrium thickness (p < .05)
Ming et al. (2018) [14]	IUA	Control group: n = 21, mean age = 29.00 ± 4.23 Experimental group: n = 30, mean age= 25.00 ± 6.7	No mention	Oral Estradiol Valerate: 20 mg/8 h, Oral aspirin: 100 mg/d	Oral Estradiol Valerate: 20 mg/8 h, Oral aspirin: 100 mg/d	1. Endometrium thickness, RI, and PI (p < .05) 2. Clinical Effectiveness (p = 0.03)
Zhang and Yang (2017) [15]	Severe IUA	Control group: n = 35, mean age = 27.5 ± 4.6, mean BMI = 22.6 ± 1.9 kg/m^2 Experimental group: n = 28, mean age = 28.1 ± 4.9, mean BMI = 23.2 ± 1.6 kg/m^2	No mention	Fentanyl estrogen used vaginally: 1 mg/time, 2 times/d, Oral Duphaston: 10 mg/time, 2 times/d (after 17 d), oral aspirin: 75 mg/time, 1 time/d	Fentanyl estrogen used vaginally: 1 mg/time, 2 times/d, Oral Duphaston: 10 mg/time, 2 times/d (after 17 d),	1. Efficient uterine recovery (p > .05) 2. Menstrual improvement (p < .05) 3. Endometrium thickness (p > .05) 4. Pregnancy (p > .05)
Wen et al. (2017) [16]	Severe IUA	Control group: n = 60, mean age = 27.5 ± 4.6, mean BMI = 21.706 ± 1.404 kg/m^2, mean AFS = 10.423 ± 0.854 Experimental group: n = 65, mean age = 28.1 ± 4.9, mean BMI = 22.095 ± 1.439 kg/m^2, mean AFS = 10.219 ± 0.800	No mention	Oral Estradiol Valerate: 3 mg/time, 3 times/d, Oral aspirin: 75 mg/d	Oral Estradiol Valerate: 3 mg/time, 3 times/d	1. Endometrium thickness (p < .05) 2. Endometrial volume (p = .474) 3. RI and PI (p < .05) 4. Pregnancy (p < .05)
Chen et al. (2016) [17]	Severe IUA	Control group: mean age = 32.5 ± 5.6, mean BMI = 23.1 ± 4.6 kg/m^2 Experimental group: mean age = 32.1 ± 5.4, mean BMI = 22.8 ± 4.7 kg/m^2	Control group: 6.92 ± 0.92 month Experimental group: 6.26 ± 0.98 month	Oral Estradiol Valerate: 9 mg/d, Oral aspirin: 50 mg/d, oral MedroxyProgesterone: 10 mg/d	Oral Estradiol Valerate: 9 mg/d, oral MedroxyProgesterone: 10 mg/d	1. RI, PI, VI, FI and VFI (p <.05) 2. Smad2 and Smad3 (p < .05) 3. PAI-1, ADAM15 and AD- AM17 (p < .05)
Cao (2016) [18]	IUA	Control group: n = 41, mean age = 27.35 ± 4.23 Experimental group: n = 41, mean age = 28.88 ± 4.96	No mention	Oral Estradiol Valerate: 3 mg/time, 3 times/d, Oral aspirin: 50 mg/d, oral progesterone (after 21 d)	Oral Estradiol Valerate: 3 mg/time, 3 times/d, oral progesterone (after 21 d)	1. Endometrial volume (p < .05) 2. RI (p < .05) 3. Uterine status (p < .05) 4.Pregnancy (p < .05)
Chi et al. (2015) [19]	Severe IUA	n = 80, mean age = 27.4 ± 4.5	No mention	B: Oral Estradiol Valerate: 3 mg/time, 3 times/d, Oral aspirin: 50 mg/d C: Oral Estradiol Valerate: 3 mg/time, 3 times/d, Oral aspirin: 75 mg/d D: Oral Estradiol Valerate: 3 mg/time, 3 times/d, Oral aspirin: 100 mg/d,	A: Oral Estradiol Valerate: 3 mg/time, 3 times/d	1. Endometrial volume (p < .05) 2. RI, PI(p < .05) 3. Menstrual improvement (p < .05) 4. Uterine status (p < .05)
Chen et al. (2017) [2]	IUA	Control group: n = 30, mean age= 30.77 ± 4.4 Experimental group (group B): n = 32, mean age= 31.44 ± 5.3 Experimental group (group C): n = 35, mean age= 30.94 ± 4.87	No mention	Oral Estradiol Valerate: 3 mg/d, Oral aspirin: 1 mg/d, oral medroxyprogesterone: 10 mg/d (last 10 d)	Oral Estradiol Valerate: 3 mg/d, oral medroxyprogesterone: 10 mg/d (last 10 d)	1. Endometrium thickness (p < .05) 2. Pregnancy (p > .05)
Chi et al. (2018) [20]	Moderate and Severe IUA	Control group: n = 18, mean age= 30 ± 4.80 Experimental group: n = 20, mean age= 29 ± 5.81	No mention	Transdermal estrogen: 5 g/d, oral aspirin: 100 mg/d	Transdermal estrogen: 5 g/d	1. RI and PI 2. MVD
Zhang et al. (2020) [21]	Moderate and Severe IUA	Control group: n = 26, mean age= 28.15 ± 3.68, mean BMI= 22.16 ± 2.18 Experimental group: n = 28, mean age= 29.07 ± 4.25, mean BMI= 22.01 ± 1.99	No mention	Oral estradiol valerate: 4 mg/d, oral cyproterone acetate: 1 mg/d (last 10 d), oral aspirin: 100 mg/d	Oral estradiol valerate: 4 mg/d, oral cyproterone acetate: 1 mg/d (last 10 d)	1. menstrual period, menstrual volume, and postoperative average AFS score (p < .01) 2. endometrial thickness, no adhesion cases following operation (p < .05)

ET: endometrium thickness; PI: pulsatility index; RI: resistance index; MVD: endometrium microvessel density; VEGF: vascular endothelial growth factor; VI: Vascular index; FI: Blood flow Index; VFI: Vascular blood flow Index.

Table 2. Appraisal of methodological quality (Newcastle-Ottawa Scale) of included studies.

	Selection				Comparability	Outcome			Score
Study	Adequate definition of cases	Representativeness of the cases	Selection of controls	Definition of controls	Comparability control for the important factor	Ascertainment of exposure	Same method of ascertainment for cases and controls	Non-response rate
Cheng (2021) [4]	c	a*	b	a*	a*	a*	a*	b	5
Li et al. (2021) [5]	c	a*	b	a*	a*	a*	a*	b	5
Xue and Ruoyu (2020) [6]	a*	a*	b	a*	a*	a*	a*	b	7
Ting and Wang (2020) [7]	a*	a*	b	a*	a*	a*	a*	b	6
Shihui and Qiong (2020) [8]	a*	a*	b	a*	a*	b*	a*	b	6
Liu et al. (2019) [9]	a*	a*	b	a*	b*	a*	a*	b	6
Shi et al. (2019) [10]	a*	a*	b	a*	b*	a*	a*	a*	7
Zhong-Ping et al. (2019) [11]	a*	a*	b	a*	a*	a*	a*	b	6
Xiang and Ding (2018) [12]	a*	a*	b	a*	a*	a*	a*	b	6
Zheng and Ming (2018) [13]	a*	a*	b	a*	a*	a*	a*	b	6
Ming et al. (2018) [14]	c	a*	b	a*	a*	a*	a*	b	5
Zhang and Yang (2017) [15]	c	a*	b	a*	a*	a*	a*	b	5
Wen et al. (2017) [16]	a*	a*	b	a*	a*	a*	a*	b	6
Chen et al. (2016) [17]	a*	a*	b	a*	a*	a*	a*	b	6
Cao (2016) [18]	c	a*	b	a*	a*	a*	a*	b	5
Chi et al. (2015) [19]	c	a*	b	a*	a*	a*	a*	b	5
Chen et al. (2017) [2]	a*	a*	b	a*	a*	a*	a*	b	6
Chi et al. (2018) [20]	a*	a*	b	a*	a*	a*	a*	b	6
Zhang et al. (2020) [21]	a*	a*	b	a*	a*	a*	a*	b	6

a*: Category is addressed adequately; b: Comparability category is addressed adequately; c: Category is not adequately addressed.

*Scores can be calculated.

Figure 2. Changes of Endometrium thickness.

Figure 3. Blood flow Index.

Figure 4. Pulsatility index changes.

Figure 5. Resistance index changes.

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