Mesenchymal-epithelial transition (MET) is a mechanism of endometrial epithelial regeneration. It is also implicated in adenocarcinoma and endometriosis. Little is known about this process in normal uterine physiology. Previously, using pregnancy and menses-like mouse models, MET occurred only as an epithelial damage/repair mechanism. Here, we hypothesized that MET also occurs in other physiological endometrial remodeling events, outside of damage/repair, such as during the estrous cycle and adenogenesis (gland development). To investigate this, Amhr2-Cre-YFP/GFP mesenchyme-specific reporter mice were used to track the fate of mesenchymal-derived (MD) cells. Using EpCAM (epithelial marker), EpCAM+YFP+ MD-epithelial cells were identified in all stages of the estrous cycle except diestrus, in both postpartum and virgin mice. EpCAM+YFP+ MD-epithelial cells comprised up to 80% of the epithelia during estrogen-dominant proestrus and significantly declined to indistinguishable from control uteri in diestrus, suggesting MET is hormonally regulated. MD-epithelial cells were also identified during postnatal epithelial remodeling. MET occurred immediately after birth at postnatal day (P) 0.5 with EpCAM+GFP+ cells ranging from negligible (0.21%) to 82% of the epithelia. EpCAM+GFP+ MD-epithelial cells declined during initiation of adenogenesis (P8, avg. 1.75%) and then increased during gland morphogenesis (P14, avg. 10%). MD-epithelial cells expressed markers in common with non-MD-epithelial cells (e.g., EpCAM, FOXA2, ESR1, PGR). However, MD-epithelial cells were differentially regulated postnatally and in adults, suggesting a functional distinction in the two populations. We conclude that MET occurs not only as an epithelial damage/repair mechanism but also during other epithelial remodeling events, which to our knowledge has not been demonstrated in other tissues.\n

The purpose of the study was to investigate if adjuvant hormones after successful adhesiolysis lead to a reduction in spontaneous recurrence of adhesions and influence reproductive outcomes.

The aim of this prospective, randomized, controlled trial was to evaluate the efficacy of different doses of oestrogen treatment (2 mg and 6 mg daily) after hysteroscopic adhesiolysis in patients with moderate to severe adhesion according to the American Fertility Society (AFS) classification of intrauterine adhesions. A total of 121 patients were included in the final analysis. Fifty-nine patients received 2 mg oestrogen daily (low-dose group), and 62 received 6 mg oestrogen daily (high-dose group) for three cycles after surgery. Second- and third-look outpatient hysteroscopy was performed 4 and 8 weeks after the initial surgery. There was no difference in the menstrual pattern and AFS scores before and after surgery between the two groups, and AFS scores at the second- and third-look hysteroscopy were found to be significantly lower than the scores before surgery in both groups (both P < 0.01). While this study did not address the fundamental question of whether oestrogen adjuvant therapy prevents the recurrence of intrauterine adhesions, the findings do not support the use of high-dose oestrogen therapy after hysteroscopic adhesiolysis.Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

This randomized controlled trial (RCT) aimed to compare two different routes of postoperative estrogen treatment on the improvements of menstruation, postoperative endometrial thickness, and fertility outcomes in patients with moderate to severe intrauterine adhesions (IUA).

To evaluate the value of intrauterine platelet-rich concentrates among patients with intrauterine adhesions (IUAs) after hysteroscopic adhesiolysis.Four different databases (PubMed, Cochrane Library, Scopus, and ISI web of science) were searched for the available studies from inception to November 2021. We selected randomized clinical trials (RCTs) that compared platelet-rich concentrates in the intervention group versus no injection of platelet-rich concentrates in the control group among women with intrauterine adhesions after operative hysteroscopy. Revman software was utilized for performing our meta-analysis. Our primary outcomes were the adhesion score and incidence of recurrence of severe intrauterine adhesions postoperatively. Our secondary outcomes were the clinical pregnancy rate, menstrual flow duration in days, and menstrual flow amount (number of pads).Five RCTs met our inclusion criteria with a total number of 329 patients. We found that platelet-rich concentrates were linked to a significant reduction in the postoperative adhesion score (MD = -1.00, 95% CI [-1.68, -0.32], p = 0.004). Moreover, there was a significant reduction in the incidence of severe IUAs recurrence among the platelet-rich concentrates group (7.6%) compared to the control group (23.4%) after hysteroscopy (p = 0.001). The clinical pregnancy rate was significantly increased among the platelet-rich concentrates group (37.1%) in comparison with the control group (20.7%) after hysteroscopic adhesiolysis (p = 0.008). There were significant improvements in the menstrual flow duration and amount among the platelet-rich concentrates group (p < 0.001).Intrauterine placement of platelet-rich concentrates is an effective method for the treatment of intrauterine adhesions after hysteroscopy.Copyright © 2022 Elsevier B.V. All rights reserved.

What is the efficacy of platelet-rich plasma (PRP) in reducing adhesion reformation in women with moderate to severe intrauterine adhesions (IUA)?In this randomized controlled trial, women with moderate-to-severe IUA were recruited between November 2019 and June 2021 from a university hospital and randomized into the PRP or control group. The PRP group was treated using an intrauterine-suitable balloon combined with PRP infusion following hysteroscopic adhesiolysis, whereas the control group received only the former intervention. The reductions in adhesion scores from before to after surgery and the adhesion reformation rate were analysed.A total of 123 participants successfully completed the study (PRP group, 63; control group, 60). Age, pregnancy history, menstrual score and American Fertility Society score before surgery were not significantly different between the two groups. At the second-look hysteroscopy, the PRP group had a significantly greater reduction in adhesion score than the control group (7 versus 6, respectively; P = 0.027). The postoperative adhesion reformation rates in the PRP group and the control group were 20.6% and 30.0%, respectively (risk ratio 0.69, 95% confidence interval 0.27-1.38, P = 0.232; number needed to treat 10.6).Intrauterine PRP infusion seems to be beneficial in reducing postoperative adhesion reformation following hysteroscopic adhesiolysis.Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Intrauterine adhesion (IUA) is the most common cause of uterine infertility. This study aims to evaluate whether platelet-rich fibrin (PRF) treatment can stimulate damaged endometrium regeneration in rats.

To evaluate the efficacy and safety of autologous platelet‐rich fibrin (PRF) for the treatment of infertility with intrauterine adhesions.

To evaluate the efficacy of freeze-dried amnion graft for prevention of intrauterine adhesion (IUA) reformation after hysteroscopic adhesiolysis.A prospective randomized controlled trial was conducted among 88 women with severe IUAs who underwent hysteroscopic adhesiolysis at Beijing Obstetrics and Gynecology Hospital between July 15, 2015, and July 1, 2016. All participants had a balloon inserted into the uterine cavity for 1 week. Sterilized freeze-dried amnion graft covered the balloon portion of the Foley catheter among patients allocated to the amnion group (n=44), whereas patients in the control group (n=44) did not receive the graft. Follow-up hysteroscopy was performed 3 months after surgery. Preoperative and postoperative IUA scores, menstruation scores, and pregnancy rates were assessed.Both groups exhibited reductions in IUA scores and improvements in menstruation scores following treatment (P<0.001 for each measure). Compared with the control group, the amnion group had a lower IUA score (P=0.032) and a higher menstruation score (P<0.001) at follow-up. By contrast, the rates of IUA reformation and pregnancy were not significantly different between the two groups.Use of freeze-dried amnion graft was effective in reducing IUA reformation and improving menstruation (according to pictorial blood-loss assessment chart) following hysteroscopic adhesiolysis of severe IUAs. ClinicalTrials.gov: (NCT02496052).© 2017 International Federation of Gynecology and Obstetrics.

Various adjuvant therapies have failed to improve clinical symptoms and pregnancy rates among patients with moderate-to-severe intrauterine adhesion.To evaluate the ability of amniotic membrane to prevent the recurrence of intrauterine adhesion after hysteroscopic adhesiolysis.The Cochrane Library, Embase, and PubMed databases were searched for articles published before December 31, 2017, using the terms: ("amnion") and ("intrauterine adhesions" or "Asherman syndrome" or "IUA" or "endometrial injury" or "uterine adhesion" or "hysteroscopic" or "hysteroscopic adhesiolysis").Randomized controlled trials of amniotic membrane therapy after hysteroscopic adhesiolysis.Four studies were included in the meta-analysis (300 patients in total). Dichotomous outcomes were expressed as relative risk (RR) with 95% confidence intervals (CIs). Continuous variables were expressed as mean difference.Amniotic membrane increased menstrual blood volume after hysteroscopic adhesiolysis (mean difference 6.15, 95% CI 4.20-8.11; P<0.001). By contrast, this treatment did not affect the rates of intrauterine adhesion recurrence (RR 0.84, 95% CI 0.61-1.16; P=0.290); pregnancy (RR 1.40, 95% CI 0.78-2.50; P=0.260); or spontaneous abortion (RR 0.88, 95% CI 0.38-1.99; P=0.750).The use of amniotic membrane increased menstrual blood volume but failed to improve other measures assessed in the current meta-analysis.© 2018 International Federation of Gynecology and Obstetrics.

Does intrauterine infusion of granulocyte colony-stimulating factor (G-CSF) prevent adhesion reformation and promote endometrial growth after hysteroscopic adhesiolysis?

Does placing an intrauterine balloon for different durations (7, 14 or 28 days) affect the recurrence of intrauterine adhesions after hysteroscopic adhesiolysis?Prospective randomized control trial involving 138 patients recruited over a 12-month period and followed up post-operatively for 15 months. The primary outcome measure was the rate of adhesion reformation at third-look hysteroscopy.At third-look hysteroscopy, 8 weeks after the initial hysteroscopy, the adhesion recurrence rate in women who had an intrauterine balloon for 28 days (20%) was significantly (P < 0.01) lower than that of women who had the balloon for 14 days (55%) or 7 days (36.8%).Placing an intrauterine balloon for 28 days instead of 7 or 14 days after hysteroscopic adhesiolysis resulted in a greater reduction in the recurrence rate of adhesions. However, the study was underpowered to address whether the ongoing pregnancy rate could be improved by keeping the balloon in the uterine cavity for a longer period of time.Copyright © 2019. Published by Elsevier Ltd.

To highlight the efficiency of intrauterine device (IUD) guidance during hysteroscopic adhesiolysis for severe intrauterine adhesions.A prospective, randomized trial.Private tertiary and referral infertility clinic.Seventy-one subfertile patients who underwent hysteroscopic treatment of intrauterine synechiae or adhesions.Thirty-six women in group 1 were initially examined by laparoscopy-hysteroscopy at first look, and an IUD was inserted during hysteroscopic adhesiolysis. The adhesions were further lysed by the guidance of IUD during the second-look office hysteroscopy, 1 week later. Patients were prescribed 2 months of estrogen as well as P therapy, and the IUD was removed by the end of this period. The uterine cavity was evaluated, and adhesions were further lysed by a third-look office hysteroscopy, 1 week after the removal of IUD. Thirty-five women in group 2 were similarly examined by first-look office hysteroscopy, and an IUD was inserted during hysteroscopic adhesiolysis. These patients did not undergo early intervention of office hysteroscopy, 1 week after the first procedure. They also used 2 months of estrogen and P therapy. The IUD was removed by the end of this period, and the uterine cavity was evaluated and adhesions were further lysed during a second-look office hysteroscopy.Pregnancy rate and live birth rate.Spontaneous pregnancy rates after treatment were 17/36 (47.2%) and 11/35 (30%), and live birth rates were 10/36 (28%) and 7/35 (20%) in groups 1 and 2, respectively. These differences between the two groups were not statistically significant.The method described especially for early intervention may prevent complications during the treatment of severe intrauterine adhesions and may present a secure and effective alternative for constructive clinical outcomes.

To evaluate the efficacy and pregnancy outcomes of intrauterine balloon and intrauterine contraceptive devices in the prevention of adhesion reformation following hysteroscopic adhesiolysis in infertile women with moderate to severe intrauterine adhesion.