Good endometrium is the prerequisite and guarantee for reproduction and maternal and child health. Endometrial injury caused by operation or non-operation can lead to menstrual irregularities, amenorrhea, abortion, infertility, and other gynecological diseases to bother women. Intrauterine adhesions (IUA) and thin endometrium are common diseases caused by abnormal repair after endometrium damage. The incidence of IUA is not low after uterine operative surgery, and the recurrence is pretty high after uterine adhesiolysis. At present, there were many methods for endometrial repair in clinic or in the laboratory, but the efficacy was different from methods to methods. They are mainly including estrogen therapy, stem cell therapy, complementary medicine therapy, and some physical barrier therapy. In order to guide the effective repair and regeneration of endometrium in clinic, this paper reviews the merit and demerit of these methods for endometrium regeneration and repair that have been proved to be effective in experiments and clinical in recent years.

Endometritis is defined as an infection or inflammation of the endometrium. Endometritis is of two types: acute and chronic. Acute endometritis is the symptomatic acute inflammation of the endometrium, which upon examination with a microscope shows micro-abscess and neutrophil invasion in the superficial endometrium. One of its most common manifestations is postpartum endometritis. Chronic endometritis is a silent disease usually diagnosed on the workup of secondary amenorrhoea and infertility. An important cause of chronic endometritis is tuberculosis, especially in developing nations. Chronic and acute endometritis have been associated with poor reproductive outcomes. Worse outcomes have been reported for individuals with chronic endometritis. This is a scoping review of endometritis and its impact on fertility.

Asherman's syndrome (AS) is caused by intrauterine adhesions and inactive endometrium from repeated curettage of the uterine endometrium. AS is a major cause of recurrent implantation failure and miscarriage and is very difficult to treat because of the poor recovery of endometrial basal cells. Platelet-rich plasma (PRP) has abundant growth factors that may induce angiogenesis and cell proliferation. Here, we demonstrate that human PRP (hPRP) significantly enhances angiogenesis to restore embryo implantation, leading to successful pregnancy in mice with AS. In mice with AS, hPRP treatment considerably reduced the expression of fibrosis markers and alleviated oligo/amenorrhea phenotypes. Mice with AS did not produce any pups, but the hPRP therapy restored their infertility. AS-induced abnormalities, such as aberrantly delayed embryo implantation and intrauterine growth retardation, were considerably eliminated by hPRP. Furthermore, hPRP significantly promoted not only the elevation of various angiogenic factors, but also the migration of endometrial stromal cells. It also increased the phosphorylation of STAT3, a critical mediator of wound healing, and the expression of tissue remodeling genes in a fibrotic uterus. PRP could be a promising therapeutic strategy to promote angiogenesis and reduce fibrosis in impaired uterine environments, leading to successful embryo implantation for better clinical outcomes in patients with AS.

Bone marrow-derived cell (BMDC) therapy has numerous applications as potential biological cells for use in regenerative medicine. Here, we present an original case of endometrial atrophy associated with genital tuberculosis in a woman who achieved a live birth with BMDC. This 27-year-old woman came to our center with endometrial atrophy and primary infertility. She had a past history of genital tuberculosis and amenorrhea. Her husband's semen quality was normal. The patient was counseled for hysteroscopy due to thin endometrium and advised in vitro fertilization (IVF) with donor eggs in lieu of poor ovarian reserve. Several attempts of IVF with hormone replacement therapy (HRT) were made, but the desired thickness of the endometrium was not achieved. Uterine artery injection of BMDC through interventional radiology was given, followed by HRT for three months, which resulted in improved endometrium. This was subsequently followed by IVF with donor egg. The treatment resulted in the conception and delivery of a 3.1-kg baby boy through lower segment caesarean section with no antenatal, intranatal or postnatal complications. Recently, there has been massive interest in stem cells as a novel treatment method for regenerative medicine, and more specifically for the regeneration of human endometrium disorders like Asherman syndrome and thin endometrium, which was the reason behind using this strategy for treatment.

Intrauterine adhesion (IUA), and its severe form Asherman syndrome (Asherman's syndrome), is a mysterious disease, often accompanied with severe clinical problems contributing to a significant impairment of reproductive function, such as menstrual disturbance (amenorrhea), infertility or recurrent pregnancy loss. Among these, its correlated infertility may be one of the most challenging problems. Although there are many etiologies for the development of IUA, uterine instrumentation is the main cause of IUA. Additionally, more complicated intrauterine surgeries can be performed by advanced technology, further increasing the risk of IUA. Strategies attempting to minimize the risk and reducing its severity are urgently needed. The current review will expand the level of our knowledge required to face the troublesome disease of IUA. It is separated into six sections, addressing the introduction of the normal cyclic endometrial repairing process and its abruption causing the formation of IUA; the etiology and prevalence of IUA; the diagnosis of IUA; the classification of IUA; the pathophysiology of IUA; and the primary prevention of IUA, including (1) delicate surgical techniques, such as the use of surgical instruments, energy systems, and pre-hysteroscopic management, (2) barrier methods, such as gels, intrauterine devices, intrauterine balloons, as well as membrane structures containing hyaluronate-carboxymethylcellulose or polyethylene oxide-sodium carboxymethylcellulose as anti-adhesive barrier.

Intrauterine adhesion (IUA) formation and the resulting Asherman's syndrome (AS) is an unfortunate clinical condition that occurs when the endometrium is damaged as a consequence of trauma, such as vigorous curettage, infection, or some Müllerian anomaly. The most frequent symptoms include hypo/amenorrhea, infertility, and adverse reproductive outcomes. Prevention of IUA formation is essential; however, when present, accurate diagnosis and surgical intervention (hysteroscopic adhesiolysis) are required. The outcome of this treatment is based on the technique and the extent of surgery performed which depends on the severity and complexity of the disease. Hence its classification becomes particularly important to determine a standardized therapy for each case and patient counseling regarding the prognosis. In this article, we aim to describe the IUAs classification systems that have been proposed comparing the merits and demerits of each one.

Endometrial-related disorders including Asherman's syndrome, thin endometrium, pelvic organ prolapse, and cesarean scar pregnancies can be accompanied by different symptoms such as amenorrhea, infertility, abnormal placental implantation and recurrent miscarriage. Different methods have been introduced to overcome these problems such as surgery and hormonal therapy but none of them has shown promising outcomes. On the other hand, the development of novel regenerative therapeutic strategies has opened new avenues for the treatment of endometrial-related deficiencies. In this regard, different types of scaffolds, acellular matrices and also cell therapy with adult or stem cells have been investigated for the treatment of endometrial-related deficiencies. In this paper, we review the current status of cell-based endometrium regeneration using scaffold dependent and scaffold-free methods and future perspectives in this field. Moreover, we discuss the endometrial diseases that can be candidates for cell-based treatments. Also, the cells with the potential for endometrial regeneration are explained.

Asherman's syndrome (AS) is characterized by intrauterine adhesions or fibrosis resulting from scarring inside the endometrium. AS is associated with infertility, recurrent miscarriage, and placental abnormalities. Although mesenchymal stem cells show therapeutic promise for the treatment of AS, the molecular mechanisms underlying its pathophysiology remain unclear. We ascertained that mice with AS, like human patients with AS, suffer from extensive fibrosis, oligo/amenorrhea, and infertility. Human perivascular stem cells (hPVSCs) from umbilical cords repaired uterine damage in mice with AS, regardless of their delivery routes. In mice with AS, embryo implantation is aberrantly deferred, which leads to intrauterine growth restriction followed by no delivery at term. hPVSC administration significantly improved implantation defects and subsequent poor pregnancy outcomes via hypoxia inducible factor 1α (HIF1α)-dependent angiogenesis in a dose-dependent manner. Pharmacologic inhibition of HIF1α activity hindered hPVSC actions on pregnancy outcomes, whereas stabilization of HIF1α activity facilitated such actions. Furthermore, therapeutic effects of hPVSCs were not observed in uterine-specific HIF1α-knockout mice with AS. Secretome analyses of hPVSCs identified cyclophilin-A as the major paracrine factor for hPVSC therapy via HIF1α-dependent angiogenesis. Collectively, we demonstrate that hPVSCs-derived cyclophilin-A facilitates HIF1α-dependent angiogenesis to ameliorate compromised uterine environments in mice with AS, representing the major pathophysiologic features of humans with AS.

Asherman syndrome is a rare acquired clinical condition resulting in the obliteration of the uterine cavity causedby the presence of partial or complete fibrous intrauterine adhesions involving at least two-thirds of the uterine cavity potentially obstructing the internal cervical orifice. Common reported symptoms of the disease are alterations of the menstrual pattern with decreased menstrual bleeding leading up to amenorrhoea and infertility. Hysteroscopy is currently considered the gold standard diagnostic and therapeutic approach for patients with intrauterine adhesions. An integrated approach, including preoperative, intraoperative and postoperative therapeutic measures, however, are warranted owing to the complexity of the syndrome. This review aims to summarize the most recent evidence on the recommended preoperative, intraoperative and postoperative procedures to restore the uterine cavity and a functional endometrium, as well as on the concomitant use of adjuvant therapies to achieve optimal fertility outcomes.

Transcervical resection of adhesion (TCRA) is the standard treatment for the intrauterine adhesions, but the recurrence of adhesions is a tough problem for the gynecologist. In addition, the therapeutic strategy after TCRA about prevention of recurrence remains controversial especially for the patients with moderate to severe intrauterine adhesions (IUAs). Hence, we designed this study to explore the safety and efficacy of fresh amnion grafts for preventing the recurrence after TCRA for patients with moderate to severe IUAs. One hundred patients with moderate to severe IUAs who presented with a history of hypomenorrhea, amenorrhea and infertility were included in the study from January 2015 to December 2017. Patients were divided into amnion group (52 patients) and chitosan group (48 patients). Fresh amnion grafts or intrauterine injections of chitosan were administered after TCRA. Transvaginal ultrasonography (TVUS) and hysteroscopy were performed at the first and third month after the operation. The surgical procedures for all patients were completed successfully without relevant complications. In amnion group, 8 patients exhibited relapse in the first month and 2 patients in three months after surgery; in chitosan group, 23 women exhibited relapse in the first month and 18 patients in three months after surgery. Statistical analysis revealed that the recurrence rate of adhesion in amnion group was significantly lower than those of chitosan group in the first and three months after surgery (P 1 = 0.000, P 2 = 0.000). After TCRA, fresh amnion graft plays a significant role in preventing further adhesions than injections of chitosan.

Vaginal stenosis or gynatresia is a congenital disease and it is part of Mayer-Rokitansky-Kustner-Hauser syndrome. Acquired vaginal stenosis is a rare complication of vaginal delivery and may be caused by an infection, charlatans, birth injury or postpartum hypoestrogeny. We report a case of postpartum complete vaginal stenosis secondary to vaginal injuries as a result of medical negligence. The study involved a 19 year old patient, who had had dead child born vaginally at home, presenting with a two-year history of secondary amenorrhea associated with chronic pelvic pain. The patient reported the occurrence of multiple not sutured vaginal tears. Pelvic MRI showed complete extended vaginal stenosis of about 25mm with upstream haematological retention and bilateral hematosalpinx. The patient underwent release of vaginal adhesions followed by regular vaginal dilation. Only two cases have been reported in the literature. Pain and dyspareunia were the most common symptoms. All cases were treated by a release of the synechias and vaginal dilation.

Asherman's syndrome (AS) is characterized by intrauterine adhesion or fibrosis resulting from damage to the endometrium, often leading to amenorrhea, infertility, or recurrent pregnancy loss. Although various therapeutic strategies for AS have been proposed, the options remain limited. New strategies such as bone marrow-derived mesenchymal stem cell (BM-MSC) therapy aim to potentiate the intrinsic capacity of endometrial regeneration. However, BM-MSC therapy has not been widely adopted mainly because it involves invasive and expensive procedures such as bone marrow biopsy and cell storing. On the other hand, platelet-rich plasma (PRP) is considered safe and affordable because it involves the less invasive procedure of blood collection from peripheral veins to produce PRP. To assess the effectiveness of human PRP infusion for endometrial regeneration, we established a murine model of injury-induced AS and evaluated endometrial morphology, expression of fibrosis-related factors, implantation sites (IS), and pregnancy outcomes associated with human PRP treatment. We found that treatment with human PRP was associated with improved endometrial morphology, reduced degree of fibrosis, and down-regulated expression of fibrosis-related factors in murine model of AS. Furthermore, human PRP treatment was associated with a higher number of IS and live-births. Our results suggest that human PRP treatment may become a valuable strategy to promote the regeneration of damaged endometrium and thus improve fertility and pregnancy outcomes in clinical practice.

This study aimed to investigate the efficacy of the transplantation of autologous adipose-derived stromal vascular fraction (AD-SVF) containing adipose stem cells (ASCs) in regenerating functional endometrium in patients with severe Asherman's syndrome (AS). This was a prospective clinical study involving six infertile women aged 20-44 years who were diagnosed with severe AS by hysteroscopy. Autologous AD-SVF were isolated from patient's adipose tissue obtained by liposuction and then transplanted into uterus by transcervical instillation using an embryo transfer catheter followed by estrogen hormone therapy. Endometrial growth and pregnancy outcomes were assessed after fresh or frozen embryo transfer. Of the five patients who remained in the study, two women who had amenorrhea resumed their menstruation with irregular scant bleeding. Three women with oligomenorrhea had increased menstrual amount. Before therapy, the maximum EMT measured ultrasonographically was 3.0 ± 1.0 mm (range: 1.7 to 4.4 mm), which significantly increased to 6.9 ± 2.9 mm (range: 5.2 to 12.0 mm, p = 0.043) after cell transplantation and hormone therapy. Five women had embryo transfer after therapy: one fresh and four frozen-thawed. One woman conceived but aborted spontaneously at 9-week gestation. AD-SVF is a safe and easily available cell product containing adipose-derived stem cells. Autologous transplantation of AD-SVF may regenerate damaged human endometrium and increase endometrial receptivity. Our study showed the feasibility of AD-SVF in restoring endometrial function and increasing endometrial thickness. This cell therapy may become a promising treatment for infertile women with endometrial dysfunction and needs further investigation.

Asherman syndrome consists in an acquired condition characterized by the development of fibrous intrauterine adhesions involving until two-thirds of the uterine cavity. Common signs of the syndrome are represented by alterations of regular menses, hypomenorrhea and amenorrhea. Moreover, women affected by Asherman syndrome, often struggle with fertility problems such as difficulty in spontaneous conceiving as well as complications including recurrent pregnancy loss and invasive placentation. The abnormality of the endometrial line consisting in insufficient thickness and/or endometrial trauma damaging the decidua basalis, are characteristic elements of the disease. Several studies have been conducted during the last ten years to find a solution restoring the regular endometrial line solving the fertility issue in Asherman women. Hormonal therapy as well as the use of stem cells seem to represent valid options to regenerate the endometrium opening a new scenario in the fertility treatment of these women. In this context, the presented study proposes an integrated approach to reach an adequate endometrial reconstitution and consequentially optimal fertility outcomes.

Asherman syndrome is a reproductive disorder characterized by intrauterine adhesions and amenorrhea, infertility, abnormal placentation, or pregnancy loss. Treatment of Asherman syndrome involves hysteroscopic lysis of adhesions. Many surgeons utilize postoperative measures such as hormone therapy, solid mechanical devices, or barrier gels to prevent recurrent adhesions in this setting. However, there is limited high-quality evidence to support their use. Additional research is needed on the safety and efficacy of these commonly used methods to guide patient care.

Approximately one-third of the world's population is infected with Mycobacterium tuberculosis, and it is a leading cause of infertility in endemic countries. The global incidence of tuberculosis (TB) is growing at approximately 0.4% per year, and much faster in sub-Saharan Africa. TB causing fertility is rare in developed countries. We present a case of genital tuberculosis causing Asherman's syndrome and resultant infertility. The patient is a 34-year-old P0 who presented to care after a prolonged period of secondary amenorrhea and infertility. She underwent a hysterosalpingogram which demonstrated no free spill and a diagnostic hysteroscopy which had findings of mottled endometrium. Pathology returned positive for Mycobacterium tuberculosis. The patient was treated with 9 months of antituberculous therapy. While she has not yet succeeded in becoming pregnant, the patient has started to notice cyclic spotting, indicating possible return of menses. This case highlights the importance of TB treatment and considering TB in patients who present with unexplained infertility.

Acquired gynatresia is a common gynecological condition in developing countries where puerperal complications and unskilled interventions prevail. A 23-year-old primipara who had spontaneous vaginal delivery complicated by gynatresia had vaginoplasty that failed due to erectile dysfunction in the spouse. She subsequently developed secondary amenorrhea and was relieved with dilatation and evacuation. She was planned for definitive surgery, however,she incidentally conceived with q pin-hole vagina. She was delivered of a live fetus at term via an elective cesarean section. This case is peculiar as spontaneous conception occurred with a pinhole opening. There is a need to adequately evaluate cases before definitive management to maximize success.

Asherman's syndrome (AS) is a partial or complete obliteration of the uterine cavity after intrauterine trauma. Approximately 90 % of severe AS cases occur after abortion curettage or postpartum curettage. Clinical signs and symptoms are abnormalities of the cycle (hypomenorrhoea or amenorrhoea) and fertility disorders. We have reviewed the recent literature on AS following the description of a typical clinical case. The management of AS is not easy. It must be done by experienced surgeons. Realization of several surgeries is sometimes mandatory, with the use of anti-adhesive devices between interventions. Its complex management encourages insistence on the avoidance of its risk factors.

Women with Asherman syndrome (AS) have intrauterine adhesions obliterating the uterine cavity. Hysteroscopic March classification describes the adhesions which graded in terms of severity. This study has been designed to assess the prevalence and association between of clinical presentations, potential causes, and hysteroscopic March classification of AS among infertile women with endometrial thickness.A retrospective descriptive study was carried out that included 41 women diagnosed with AS. All of the patients underwent evaluation and detailed history. All cases classified according to March classification of AS were recorded. Patients were divided into 2 groups based on measurement of endometrial thickness. Group A consisted of 26 patients with endometrial thickness ≤5 mm, and group B included 15 patients with endometrial thickness >5 mm.The prevalence of AS was 4.6%. Hypomenorrhea was identified in about 46.3%, and secondary infertility 70.7%. History of induced abortion, curettage, and postpartum hemorrhage were reported among 56.1%, 51.2%, and 31.7%, respectively. AS cases were classified as minimal in 34.1%, moderate 41.5%, and severe among 24.4% as per March classification. Amenorrhea was reported by 23.1% of women in group A, compared to 0% in group B (P = .002). Ten of 26 patients (38.5%) from group A had a severe form of March classification, compared with 0 of 15 patients (0%) in group B. This was statistically significant (P < .001).The thin endometrium associated with amenorrhea and severe form of March classification among patients with AS.

In developed countries Asherman's syndrome is almost always the result of a prior intrauterine operative trauma. This is often asymptomatic but may result in hypo- or amenorrhea and can contribute to infertility and pregnancy complications. We review their etiology, clinical implications, and systems proposed to classify their extent. The numerous methods reported for performing lysis of intrauterine adhesions are summarized along with clinical results. Current strategies to prevent recurrence of intrauterine adhesions have not been conclusively shown to be clinically effective, but the potential for endometrial regeneration using stem cells is an exciting modality under investigation.

Acquired vaginal stenosis is a rare obstructing anomaly, which can be caused by use of chemicals in the vagina. A 21-year-old gravida 1 para 1, presented with secondary amenorrhea and inability to have sexual intercourse, after normal spontaneous vaginal delivery complicated by post partum bleeding. The delivery was conducted by untrained traditional birth attendant at home. The wash cloth soaked with caustic soda was packed in the patient's vagina and was left in situ for 10 days, which ultimately led to the severe scarring and stenosis of the vagina. Patient underwent surgical management and the extensive vaginal adhesions were excised and a patent vagina was reconstructed. Patient then reported successful vaginal intercourse without dyspareunia. Post partum vaginal stenosis due to chemical vaginitis is rare. These cases can be prevented by adequate training of untrained health care workers.