Transplantation of umbilical cord-derived mesenchymal stem cells promotes the recovery of thin endometrium in rats

The endometrium plays a critical role in embryo implantation and pregnancy, and a thin uterus is recognized as a key factor in embryo implantation failure. Umbilical cord mesenchymal stem cells (UC-MSCs) have attracted interest for the repair of intrauterine adhesions. The current study investigated the repair of thin endometrium in rats using the UC-MSCs and the mechanisms involved. Rats were injected with 95% ethanol to establish a model of thin endometrium. The rats were randomly divided into normal, sham, model, and UC-MSCs groups. Endometrial morphological alterations were observed by hematoxylin–eosin staining and Masson staining, and functional restoration was assessed by testing embryo implantation. The interaction between UC-MSCs and rat endometrial stromal cells (ESCs) was evaluated using a transwell 3D model and immunocytochemistry. Microarray mRNA and miRNA platforms were used for miRNA-mRNA expression profiling. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses were performed to identify the biological processes, molecular functions, cellular components, and pathways of endometrial injury and UC-MSCs transplantation repair and real-time quantitative reverse transcription PCR (qRT-PCR) was performed to further identify the expression changes of key molecules in the pathways. Endometrium thickness, number of glands, and the embryo implantation numbers were improved, and the degree of fibrosis was significantly alleviated by UC-MSCs treatment in the rat model of thin endometrium. In vitro cell experiments showed that UC-MSCs migrated to injured ESCs and enhanced their proliferation. miRNA microarray chip results showed that expression of 45 miRNAs was downregulated in the injured endometrium and upregulated after UC-MSCs transplantation. Likewise, expression of 39 miRNAs was upregulated in the injured endometrium and downregulated after UC-MSCs transplantation. The miRNA-mRNA interactions showed the changes in the miRNA and mRNA network during the processes of endometrial injury and repair. GO and KEGG analyses showed that the process of endometrial injury was mainly attributed to the decomposition of the extracellular matrix (ECM), protein degradation and absorption, and accompanying inflammation. The process of UC-MSCs transplantation and repair were accompanied by the reconstruction of the ECM, regulation of chemokines and inflammation, and cell proliferation and apoptosis. The key molecules involved in ECM-receptor interaction pathways were further verified by qRT-PCR. Itga1 and Thbs expression decreased in the model group and increased by UC-MSCs transplantation, while Laminin and Collagen expression increased in both the model group and MSCs group, with greater expression observed in the latter. This study showed that UC-MSCs transplantation could promote recovery of thin endometrial morphology and function. Furthermore, it revealed the expression changes of miRNA and mRNA after endometrial injury and UC-MSCs transplantation repair processed, and signaling pathways that may be involved in endometrial injury and repair.

Comparison of Frozen Embryo Transfer Outcomes Between Uterine Infusion of Granulocyte Colony-Stimulating Factor and Growth Hormone Application in Patients With Thin Endometrium: A Retrospective Study

ObjectiveTo investigate the effect of two treatments on the outcome of freeze-thaw embryo transfer for pregnancy assistance in thin endometrium.MethodsA retrospective study was conducted on 66 patients who failed in the first cycle treated in the reproductive medicine center of the Second Hospital of Hebei Medical University from January 2018 to December 2019. Granulocyte colony stimulating factor (G-CSF) was used through cavity infusion in one group (n=25, and growth hormone (GH) was subcutaneously injected in the group (n=41). The clinical data of the two groups were compared, including morphology and thickness of the endometrium, biochemical pregnancy rate, clinical pregnancy rate, implantation rate, miscarriage rate, and live birth rate in each period of the hormone replacement cycle.ResultsThere was no significant difference in age, BMI, AMH, FSH, LH, E2, infertility years, number of transferred embryos, basal endometrium, and thickness of endometrium on the day of P administration before and after treatment (P> 0.05). After treatment, compared to the GH group, the G-CSF group presented higher biochemical pregnancy rate (56% versus 48.8%; P=0.569), clinical pregnancy rate (52% versus 46.3%; P=0.655), implantation rate (34.8% versus 27.5%; P=0.391), and live birth rate (40% versus 31.7%; P=0.493), but the differences were not statistically significant (P > 0.05). On the 5th day of treatment, the endometrial thickness in the G-CSF group was thinner than that in the GH group (4.83 ± 0.85 versus 5.75 ± 1.27; P< 0.05), but it had no correlation with pregnancy outcome (P > 0.05). There was no significant difference in endometrial thickness between the two groups on the 7th, 9th day of treatment and the day of P administration (P > 0.05). On the 5th day of treatment, the proportion of endometrial type A morphology in the GH group was significantly higher than that in the G-CSF group (P < 0.05), while the type B morphology in the G-CSF group was significantly higher than that in the GH group (P< 0.05).ConclusionAlthough G-CSF and GH may not have a role in increasing endometrium, both of them can improve the pregnancy outcomes of patients with thin endometrium in the FET cycle. And the effects of the two treatments were similar.

Effectiveness of Intrauterine Infusion of Autologous Platelet-Rich Plasma in the Treatment of Thin Endometrium of Infertile Women

One of the key factors in implantation and pregnancy is endometrium. Sufficiently great percentage of in vitro fertilization failure is because of the endometrial receptivity therefore, high quality embryo and adequate receptive endometrial growth are important for successful implantation. Platelet rich plasma has beneficial effect in advancement of endometrial thickness for women with thin endometrial thickness. PRP can be used in various medical conditions including patients with refractory endometrium as a complementary therapy to conventional treatment. Aim: To determine the effectiveness of intrauterine infusion of autologous platelet-rich plasma in the treatment of thin endometrium of infertile women. Objectives: To identify infertile female patients with inadequate endometrial growth (less than 7 mm) in the past frozen embryo transfer (FET) cycles despite standard treatments. To observe intrauterine infusion of autologous platelet-rich plasma (PRP) in these infertile female patients with thin endometrium. To determine the effectiveness of intrauterine infusion of autologous PRP in the treatment of thin endometrium of infertile women during In vitro fertilization (IVF). Methods: It is a prospective observational study. Present study will be carried out with 30 patients. Women having inappropriate endometrial thickness of less than 7 mm, in past FET cycles will be included. Sonographic machine will be used; to measure endometrial thickness by an expert Gynecologist, where thickest part of uterus will be measured in longitudinal axis. Expected Results: It is expected that intra uterine infusion of PRP will be effective in thickening of endometrial wall in patients with thin endometrium. Once the results are satisfactory it can be helpful for endometrial preparation in reproduction techniques. Conclusion: Present study is purposed to testify PRP as a novel method for advancement of reproductive medicine, it will be helpful to overcome with the issues such as inadequate thickness of endometrium, poor response to conventional therapy and increase clinical pregnancies and live births positively.

Effectiveness of Cryopreservation in Patients of Young Reproductive Age with the Risk of Ovarian Hyperstimulation, "Thin" Endometrium and Previous IVF Failures

The article provides an analysis of clinical, anamnestic and laboratory parameters for patients of young reproductive age who participated in IVF programs and have cryopreserved embryos. The main reasons for embryo cryopreservation were prevention of OHSS, "thin" endometrium and "previous IVF failures." It has been found that the patients from the group of transfer cancellation due to prevention of ovarian hyperstimulation had a higher ovarian reserve, a larger number of eggs, fresh and frozen embryos, and shorter shelf life of frozen embryos. All embryos were of the best quality (corresponding to the day of cultivation); the “post-thaw cultivation” technique was applied. During stimulation, lower amounts of gonadotropins were used. Patients with thin endometrium and previous IVF failures demonstrated slow growth of follicles, which required a higher course dose of gonadotropins with the addition of LH-containing preparations. Regardless of the group, in most cases, frozen/thawed embryos were transferred at the blastocyst stage (Day 5). The pregnancy rate was high in patients at risk of OHSS and with thin endometrium (48.6%, 48.0%). Patients with IVF failures had a lower pregnancy rate; this is due to endometrial pathology in the medical history, a smaller number of antral follicles, oocytes, fresh and frozen embryos, and longer shelf life of frozen embryos.

PSYCHOLOGICAL CHARACTERISTICS OF WOMEN WITH THIN ENDOMETRIUM: CLINICAL CASES

Психологическим фактором, ассоциированным с этим нарушением, может стать представление женщины о том, что опасной для ее физического здоровья является сама беременность. Причиной таких представлений является сформировавшееся в личной истории женщины убеждение в том, что ее организм не сможет выносить беременность. Случай первый: «Анорексички не беременеют».

Birth of a healthy infant after bone marrow-derived cell therapy

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.