Neuromuscular Electrical Stimulation and Biofeedback Therapy to

Improve Endometrial Growth in Patients with Thin Endometrium

A Randomized Controlled Study

Madafeitom Meheza Abide Bodombossou Djobo, Xiaoli Chen, Zhuangyu He, Xiaomiao Zhao,

Shaoqing Chen, Qingxue Zhang and Dongzi Yang

Department of Obstetrics and Gynecology, Reproductive Center, Memorial Hospital of Sun Yat-Sen University,

Guangzhou, Guangdong, China

1 INTRODUCTION

Thin endometrium at time of ovulation can be a

concern and may be one of the principal causes of

embryo implantation failure, poor placental

development and miscarriage in assisted

reproductive technologies (ART). The aim of this

study is to evaluate the efficacy of non-invasive

NMES in the management of thin endometrium

patients with history of at least two previous ART

cycles failure in which the optimum endometrium

thickness was less or equal to 7 mm.

2 METHOD

This was an open label, randomized controlled trial,

interventional study, parallel assignment, comparing

NMES with ASA in fertility unit, Memorial Hospital

of Sun Yat-Sen University. Allocation to groups was

by concealment. 115 patients with thin endometrium

(≤7mm) and history of infertility were recruited for

this work. NMES group received intermittent

vaginal NMES according to the manufacturer’s

recommended protocol for 20 to 30 minutes, 3 to 4

times during one menstruation cycle from day 9-10

to human chorionic gonadotropin (hCG)

administration day and in comparison, a similar

group of subjects received ASA (100mg/day from

day 9 or day 10 until the day of pregnancy test). Pre

and post-treatment endometrium thickness,

endometrial volume and Power Doppler

Angiography (PDA) related parameters measured by

three-dimensional ultrasound using a 4D

sonographic scanner (Voluson 730/ Voluson E8, GE

Medical Systems, Kretz Ultrasound, Zipf,

Austria) equiped with an automatic 6-12 MHz 4D

probe at day 9-10 and at hCG administration day.

Data analysis was performed using Mann–Whitney

U-test and chi-square test where appropriated.

3 RESULTS AND DISCUSSION

A total of 55 and 48 women were randomized to

NMES therapy and ASA treatment groups

respectively and effectively participated to the study

and were further analysed. The mean age of the

study population was 30.74 ± 4.52 (range 21-39).

The women in this study had mixed diagnosis.

51/103(50%) had primary infertility. 45 women out

of 103 were diagnosed polycystic ovary syndrome

(PCOS). 42 had tubal occlusion, and 71 with male

factor. Their mean ages were 30.32 ± 4.57 and 31.23

± 4.47 years for NMES and ASA group respectively.

Their mean body mass indexes (BMI) were 20.78 ±

3.24 and 21.82 ± 2.92 kg/m2 for NMES and ASA

respectively. The endometrium was thicker in the

NMES group compared with that in ASA group

[8.00 versus 7.72; P=0.028]. 32/55(58%) developed

endometrial thickness equal to or more than 8 mm

after NMES therapy in the NMES group and

16/48(33%) in ASA group. The endometrial and

sub-endometrial volumes at final point also differ

significantly between groups [2.58 versus 2.28;

P=0.008 and 1.40 versus 1.21; P=0.001 for

endometrial volume and sub-endometrial volume

respectively. The two groups did not differ

significantly regarding endometrial vascularization

index (VI) and vascularization flow index (VFI) at

final point. But in another hand, endometrial flow

index (FI), sub-endometrial vascularization

index(sub-VI), sub-endometrial flow index (sub-FI)

and sub-endometrial vascularization flow index

(sub-VFI) differed statistically between groups

(P=0.032, P=0.022, P=0.006 and P=0.018

respectively).

A good quality of endometrium is of great

significance to human reproduction and therefore

plays an important role as well as a good quality

Meheza Abide Bodombossou Djobo M., Chen X., He Z., Zhao X., Chen S., Zhang Q. and Yang D..

Neuromuscular Electrical Stimulation and Biofeedback Therapy to Improve Endometrial Growth in Patients with Thin Endometrium - A Randomized

Controlled Study.

 2013 SCITEPRESS (Science and Technology Publications, Lda.)

embryo. Normally, in response to oestrogen, the

uterine lining or endometrium grows about 1-2mm

every other day. Thin endometrium more commonly

occurs when the basal germinal endometrium, from

which the full endometrial layer develops, is

compromised in its response to oestrogen by damage

or reduced blood flow. Many studies have been

reported that a poor uterine receptivity in women

with thin endometrium is associated with the

impairment of blood flow impedance through the

endometrium(Khairy,2007)(Sher,2002).Despite

advancement of the ART, therapy for thin

endometrium have gone without significant change

for some women over the past few decades. One

major impediment to treating women with this

condition is the large range of aetiologies associated

to thin endometrium. NMES is the application of

electrical current to the pelvic floor muscles. NMES

combined with biofeedback may be useful in that the

electrical stimulation provides a passive contraction

that increases awareness of pelvic floor muscle

contractions in general. In a recently published pilot

study, we have shown that NMES) could be one of

effective options to manage women with thin

endometrium (Bodombossou-Djobo,2011). To our

knowledge, this is the first randomized trial

examining the effect of NMES compared to ASA on

endometrium thickness. Our main outcome of

interest in this trial was the change in endometrial

thickness and volume along with associated

vascularization indices in the two groups. The data

in this study have showed that NMES improved

endometrial thickness, endometrial volume and

endometrial vascularization in women with thin

endometrium. There was no consistent decrease in

impedance to uterine spiral arteries blood flow from

baseline to final point in aspirin group patients. In

contrast to these findings, there was a decrease in PI

and RI values after NMES therapy in NMES group

patients. This makes us believed that NMES not

only improved endometrial thickness but also

decreased PI and RI in patients with thin

endometrium.

It is currently unclear how NMES exerted its

action on the endometrium in term of mechanism

but the hypothesis was that by stimulating uterine

smooth muscle to repeated contraction and

relaxation, there will be an increased in blood supply

towards the whole endometrial and the sub-

endometrial regions that leads to peripheral tissue

trophicity. By this hypothetical mechanism, NMES

will likely correct the impairment of uterine blood

flow and will increase the endometrial thickness.

4 CONCLUSIONS

Our randomized controlled trial showed better

endometrial thickness, endometrial volume and

vascularization in NMES group than that in aspirin

group. However, more studies with greater sample

size and with uniformity regarding treatment

protocols are needed for the implementation of the

new therapy in clinic.

REFERENCES

Khairy, M. et al., 2007. Aspirin in women undergoing in

vitro fertilization treatment: a systematic review and

meta-analysis. Fertil Steril, 2007. 88(4): p. 822-31.

Sher, G. and J. D. Fisch., 2002. Effect of vaginal sildenafil

on the outcome of in vitro fertilization (IVF) after

multiple IVF failures attributed to poor endometrial

development. Fertil Steril, 2002. 78(5): p. 1073-6.

Bodombossou-Djobo, M. M. et al., 2011. Neuromuscular

electrical stimulation and biofeedback therapy may

improve endometrial growth for patients with thin

endometrium during frozen-thawed embryo transfer: a

preliminary report. Reprod Biol Endocrinol. 9: p. 122.