Objective:

2

To evaluate the efficacy and safety of Chinese medicine (CM) improving pregnancy outcomes after surgery for endometriosis-associated infertility.

Methods:

2

A multicenter

randomized

doubleblind placebo parallel controlled clinical trial was designed. A total of 202 patients who had laparoscopy for endometriosis-associated infertility with qi stagnation and blood stasis syndrome were included and randomly divided into the CM treatment group and placebo control group at a ratio of 1:1 using a central block randomization from May 2014 to September 2017

101 patients in each group. The two groups received continuous intervention at 1–5 days after surgery

for 6 menstrual cycles. Before ovulation

the CM group was treated Huoxue Xiaoyi Granule (活血消异颗粒); after ovulation

Bushen Zhuyun Granule (补肾助孕颗粒) was involved. The control group was treated with placebo. Transvaginal ultrasonography was performed every menstrual cycle during the treatment

and female hormone levels in the follicular and luteal phases were measured during the 1st

3rd and 6th menstrual cycles. The analysis was continued until pregnancy. The primary outcomes were clinical pregnancy rate and pregnancy outcome

and the secondary outcomes were follicular development and endometrial receptivity. Safety evaluations were performed before and after treatment.

Results:

2

(1) Clinical pregnancy and live birth rates: the clinical pregnancy and live birth rates of the CM group were significantly higher than those of the placebo group [44.6% (45/101) vs. 29.7% (30/101)

34.7% (35/101) vs. 20.8% (21/101)

both

P

<

0.05]. (2) Follicle development: the incidence of dominant follicles

rate of cumulative cycle ovulation

and rate of cumulative cycle mature follicle ovulation were significantly higher in the CM group than those in the placebo group [93.8% (350/373) vs. 89.5% (341/381)

80.4% (275/342) vs. 69.1% (253/366)

65.8% (181/275) vs 56.1% (142/253)

P

<

0.05 or

P

<

0.01]). The incidence of cumulative cycle luteinized unruptured follicle syndrome was significantly lower in the CM group than in the placebo group [11.7% (40/342) vs. 17.8% (65/366)

P

<

0.05). (3) Endometrial receptivity: after treatment

both endometrial types and endometrial blood flow types in the CM group were mainly types A and B

while those in the placebo group were mainly types B and C

with a significant difference between the two groups (both

P

<

0.05). (4) Adverse events: the incidence of adverse events between the two groups was not significantly different (

P

>

0.05).

Conclusion:

2

Strategies for activating blood circulation-regulating Gan (Liver)-tonifying Shen (Kidney) sequential therapy can effectively improve the clinical pregnancy rate and live birth rate of endometriosis-associated infertility with qi stagnation and blood stasis after laparoscopy

improve follicular development

promote ovulation

improve endometrial receptivity

while being a safe treatment option. (Trial registration No. NCT02676713)