Transdermal estrogen gel and oral aspirin combination therapy improves fertility prognosis via the promotion of endometrial receptivity in moderate to severe intrauterine adhesion

Abstract

Intrauterine adhesion (IUA) is one of the most common gynecological diseases in women of reproductive age. IUA, particularlyin moderate to severe forms, accounts for a large percentage of infertility cases. Clinically, the first-line treatment strategy for IUA is transcervical resection of adhesion (TCRA), followed by adjuvant postoperative treatment. Estrogen is one of the classic chemotherapies used following TCRA and contributes to preventing re-adhesion following surgery. However, estrogen has limited effects in promoting pregnancy, which is the ultimate goal for IUA management. In the present study, a transdermal estrogen gel and oral aspirin combination therapy was used in patients with IUA following TCRA. Compared with in the control group (transdermal estrogen only therapy), the combination therapy significantly increased endometrial receptivity marker (αvβ٣ and laminin) expression in endometrium tissues. Additionally, ultrasonic examination revealed the pulsatility index and resistant index of the uterine artery were lower in the combination therapy group. Combination therapy promoted angiogenesis and prevented fibrosis following TCRA more effectively than estrogen-only therapy. Collectively, the evaluation indices, including American Fertility Society score, endometrial parameters and pregnancy rate, indicated that patients with combination therapy had better prognoses in endometrial repair and pregnancy. In conclusion, postoperative combination therapy with transdermal estrogen gel and oral aspirin may be more efficacious in enhancing endometrial receptivity by increasing uterine blood and angiogenesis, contributing to improved fertility prognosis. The findings of the present study may provide novel guidance to the clinical treatment of IUA.

Aspirin inhibits endometrial fibrosis by suppressing the�TGF‑β1‑Smad2/Smad3 pathway in intrauterine adhesions

“…It is worth noting that combination therapy with oestrogen and aspirin may improve the rate of pregnancy in patients with IUA (28). However, an additional study indicated that there was no significant improvement in the pregnancy rate and live birth rate following additional low dose aspirin (23).…”

“…At present, there is increasing evidence that aspirin has a preventative effect in colorectal cancer and other types of cancer (35). Recent studies have suggested that aspirin is more effective in preventing adhesion recurrence following TcRA surgery, as it can increase endometrial angiogenesis (28). A prospective study revealed that aspirin combined with an intrauterine balloon and intrauterine device significantly increased endometrial thickness following TcRA surgery, and AFS scores and menstrual scores also improved significantly (23).…”

“…A prospective study revealed that aspirin combined with an intrauterine balloon and intrauterine device significantly increased endometrial thickness following TcRA surgery, and AFS scores and menstrual scores also improved significantly (23). Chi et al (28) demonstrated that compared with transdermal oestrogen alone therapy, transdermal oestrogen combined with aspirin following TcRA surgery resulted in an improved effect on increasing the endometrial thickness, increasing menstrual flow, preventing adhesion recurrence and improving endometrial receptivity, which may be associated with increased uterus intimal angiogenesis and decreased resistant index and pulsatility index in uterine arteries. The endometrial repair time following TcRA surgery is usually ~2 months (36).…”

“…Endometrial fibrosis is considered to be a key pathological event in the development of IUAs (38). Previous studies have demonstrated that aspirin may decrease fibrotic markers, including TGF-β, connective tissue growth factor (cTGF), collagen I and collagen III, in endometrial tissue (28), but the specific mechanism of action remains unclear. The results of the present study revealed that the expression of cOL1A1, α-SMA and FN in the endometrium of the aspirin group was decreased, thereby indicating an active role in the anti-fibrosis process.…”

Effects of early second‐look hysteroscopy combined with intrauterine balloon dilatation on reproductive outcomes for women with intrauterine adhesions

“…The use of low‐dose aspirin to reduce the risk of thrombosis caused by estrogen has also been gaining attention; furthermore, aspirin facilitates blood supply to the uterine artery and spiral artery, promoting endometrial growth . Further studies have reported that postoperative application of aspirin might enhance endometrial receptivity and improve reproductive outcomes in IUA cases …”