The effect of icariin for infertile women with thin endometrium: A protocol for systematic review.

BACKGROUND: Thin endometrium, defined as <7 mm of the endometrial thickness around ovulation period, had been identified as a negative factor on pregnancy rate of infertile women. It was considered to be the toughest part in treatment of infertility, because there was a lack of significant effect, although many drugs had been already used. Icariin was one of the major bioactive pharmaceutical constituent extracted from the Chinese herb "Ying Yang Huo," in the genus of Epimedium, and some randomized controlled trials reported its application for thin endometrium. There is no systematic review focusing on the effective of icariin in treating infertile women with thin endometrium, so our review aims to explore it. METHODS: The bibliographic database and electronic library will be systematically searched online, such as MEDLINE, EMBASE, Web of Science, Clinicaltrails.org., China National Knowledge Infrastructure Database (CNKI), Wan fang Database, China Biology Medicine Database (CBM), VIP Science Technology Periodical Database, and Cochrane Library. And the reference listed for potential literatures of included studies will be scanned additionally. Related randomized controlled trials (RCTs) will be collected and selected before January 4, 2020. Trials will be screened by independent reviewers, and the literature will be search in English or Chinese, with the search terms as "Icariin," "Epimedium," "infertile women," "female infertility," "endometrium," "pregnancy rate." The software for Systematic review and Meta-analysis is RevMan 5.3. The protocol and the systematic review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement. RESULT AND CONCLUSION: The efficacy of icariin to treat thin endometrium will be evaluated, and the conclusion will be published to help clinicians determine treatment strategy for infertile women with thin endometirum by providing medical evidence. REGISTRATION INFORMATION: PROSPERO CRD42019148977.

Traditional Chinese herb for low endometrial receptivity and its effect on pregnancy: Protocol for a systematic review and meta-analysis.

BACKGROUND: Low endometrial receptivity is associated with infertility in women through multiple and complex mechanisms. Existing treatments are not always effective. Symptomatic drugs such as estradiol valerate and/or aspirin do not completely solve the problem. Traditional Chinese herbs have been widely used in infertility and uterine disease including low endometrial receptivity. However, their effectiveness and safety are still obscure and deserve further investigation. OBJECTIVE: To assess the effect and safety of traditional Chinese herbs in treating low endometrial receptivity. METHODS: We will summarize and meta-analyze randomized controlled trials (RCTs) of traditional Chinese herbs for the treatment of low endometrial receptivity. RCTs comparing traditional Chinese herbs with blank control, placebo, or conventional therapies will be included. RCTs comparing traditional Chinese herbs plus conventional therapies with conventional therapies alone will also be included. The following electronic databases will be searched: PubMed, Cochrane Library, EMBASE, CNKI, CBM, VIP, and WANFANG DATA. The methodological quality of RCTs will be assessed using the Cochrane risk assessment tool. All trials included will be analyzed according to the criteria of the Cochrane Handbook. Review Manager 5.3, R-3.5.1 software will be used for publication bias analysis. GRADE pro GDT web solution will be used for evidence evaluation. RESULTS: This review will evaluate the effects of traditional Chinese herbs on estradiol, progesterone, thickness, volume, and perfusion index(PI) of the endometrium, pregnancy rate, and symptoms. CONCLUSIONS: This review will provide clear evidence to assess the effectiveness and safety of traditional Chinese herbs for low endometrial receptivity. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/M85VT.

Acupuncture in improving endometrial receptivity: a systematic review and meta-analysis.

BACKGROUND: This systematic review aimed at summarizing and evaluating the evidence of randomized controlled trials (RCTs) using acupuncture to improve endometrial receptivity (ER). METHODS: We searched 12 databases electronically through August 2018 without language restrictions. We included RCTs of women of infertility due to low ER, and excluded infertility caused by other reasons or non-RCTs. Two independent reviewers extracted the characteristics of studies and resolved the differences through consensus. Data were pooled and expressed as standard mean difference (SMD) or mean difference (MD) for continuous outcomes and risk ratio (RR) for dichotomous outcomes, with 95% confidence interval (CI). RESULTS: We found very low to moderate level of evidence that acupuncture may improve pregnancy rate (RR = 1.23 95%CI[1.13, 1.34] P < 0.00001) and embryo transfer rate (RR = 2.04 95%CI[1.13, 3.70] P = 0.02), increase trilinear endometrium (RR = 1.47 95%CI [1.27, 1.70] P < 0.00001), thicken endometrium (SMD = 0.41 95% CI [0.11, 0.72] P = 0.008), reduce resistive index (RI) (MD = -0.08 95% CI [- 0.15, - 0.02] P = 0.01), pulse index (PI) (SMD = -2.39 95% CI [- 3.85, - 0.93] P = 0.001) and peak systolic velocity/ end-diastolic blood velocity (S/D) (SMD = -0.60 95% CI [- 0.89, - 0.30] P < 0.0001), compared with medication, sham acupuncture or physiotherapy. Acupuncture was statistically significant as a treatment approach. CONCLUSION: The efficacy and safety of acupuncture on key outcomes in women with low ER is statistically significant, but the level of most evidence was very low or low. More large-scale, long-term RCTs with rigorous methodologies are needed.

[Research progress on roles of vitamin D in endometriosis].

In addition to regulating calcium and phosphorus metabolism to maintain strong bones, vitamin D also has immune regulating and anti-inflammatory effects. Moreover, it is related to chronic inflammatory diseases, autoimmune diseases and cancer. Many studies indicate the roles of vitamin D in the development and progression of endometriosis including the effects on modulation of immune responses, inflammation reactions, cell proliferation and apoptosis, angiogenesis, adhesion and invasion. Vitamin D supplementation can relieve pain and improve endometrial receptivity associated with endometriosis and play a preventive and therapeutic role. This paper summarizes the roles of vitamin D in endometriosis.

Review of Endometriosis Diagnosis through Advances in Biomedical Engineering.

Endometriosis is characterized as the ectopic presence of endometrium in various locations within the abdominal cavity, such as the fallopian tube, the pouch of Douglas, the ovaries, outside the ovaries, and more. The inner lining of the uterus, endometrium, is a dynamic tissue that undergoes morphological and functional changes cyclically. The proliferation of endometrial cells during menstruation is influenced by increasing circulating estrogen levels. Adult progenitor stem cells are likely responsible for this remarkable regenerative capacity and hence, enhanced capacity to generate endometriosis. This chronic estrogen-dependent disease is characterized by the ectopic endometrial implant. The disorder occurs in 6%-10% of reproductive-aged women and in 35%-50% of women with pelvic pain and infertility. Currently, the preferred diagnostic methods are laparoscopic inspection by transvaginal ultrasound, MRI, and sensors. Diagnoses with transvaginal ultrasound have 92.7% sensitivity and 97% specificity in detecting endometriotic lesions. On average, MRI diagnoses of DIE have 74% sensitivity and 95% specificity. Lastly, chemical sensors have 91.7% sensitivity and 90.0% specificity in detecting endometriosis. The standard of care includes personalizing the treatment plan based on the individual's set of symptoms and their severity. Advances in biomedical engineering have aided professionals in personalizing the course of treatments as well as to increasing the quality of life of these patients through various therapies for managing pain. Because no one theory provides a full explanation for the manifestation of the disease, hormonal therapies, targeted therapeutics, and surgical options have emerged as elements of disease management. Clinicians are in the process of developing advanced pharmaceutical drugs with specific orphan target receptors of the ectopic tissue. Possible complications that accompany the condition include dyspareunia, hyperalgesia, infertility, and many others.

Tratamiento con plasma autólogo rico en plaquetas en una paciente estéril con un endometrio refractario / Treatment with rich platelets autologous plasma in a sterile patient with suspected refractory endometrium

Paciente de 36 años con esterilidad primaria de 2 años. Tras estudio completo se decide donación de ovocitos. En los controles se observa un grosor endometrial adelgazado. Con el diagnóstico de endometrio refractario, se realiza un tratamiento con estrógenos a altas dosis, vitamina E y pentoxifilina durante 3 meses. Como el grosor endometrial no aumenta, asociamos AAS. Finalmente se administra intraútero plasma autólogo rico en plaquetas. A las 96 horas se observa un endometrio de 7,3 mm, transfiriéndose dos embriones vitrificados, resultando en un aborto bioquímico. Discusión: El tratamiento médico del endometrio refractario constituye un reto. Existen numerosas opciones terapéuticas, hormonales y no hormonales. Sin embargo, la mayoría de estas opciones están escasamente evaluadas por lo que se requieren de estudios mejor diseñados y con mayor tamaño muestral (AU)

36 years old patient with primary sterility of 2 years. An oocyte donation was decided after the study. An endometrial thickness slimmed was observed in different visits. With the diagnosis of refractory endometrium, a treatment was performed with high-dose estrogen, vitamin E and pentoxifylline for 3 months. As the endometrial thickness did not increase, we associated AAS. Finally intrauterine platelet-rich autologous plasma was administered. At 96 hours 7.3 mm of endometrium was observed, two vitrified embryos transferred, resulting in a biochemical abortion. Discussion: The medical treatment of refractory endometrium is a challenge. There are many therapies, hormonal and nonhormonal options. However, most of these options are poorly evaluated so they require better designed studies and larger sample size (AU)

Effects of conservative laparoscopic endometrial cystectomy and use of kidney-reinforcing and blood activating traditional Chinese medicine on ovarian functions.

This study investigated functional changes in the ovaries of women who have had conservative laparoscopic endometrial cystectomy and the effects of traditional kidney-reinforcing and blood-activating Traditional Chinese Medicine (TCM) on ovarian function. Seventy female patients who underwent laparoscopic endometrial cystectomy were randomized into two groups: TCM group receiving kidney-reinforcing and blood-activating Chinese medicine (N = 35) and control group receiving only routine follow-up (N = 35). The serum levels of all study participants were measured for follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and inhibin B (INHB) prior to and after endometrial surgery. Postoperative menstruation conditions were also assessed. Compared to preoperative conditions, both LH and FSH levels during the postoperative 1st month increased in both groups, while E2 and INHB levels decreased (P < 0.05). In the TCM group, in contrast to the control group and the postoperative 1st month, we observed a decrease in LH and FSH levels during the postoperative 4th month, while E2 and INHB levels increased (P < 0.05). In this study, we found that certain TCM prescriptions lowered postoperative serum FSH and LH levels and increased the serum INHB and basal E2 levels, thereby improving the ovarian reserve.

Clinical observations of sequential therapy with Chinese medicine and hysteroscopic mechanical stimulation of the endometrium in infertile patients with repeated implantation failure undergoing frozen-thawed embryo transfer.

OBJECTIVES: To investigate the clinical effect of sequential therapeutic intervention Yupei Qisun [compensating for weakness by invigorating Kidney (Shen) and Spleen (Pi) in advance] in Chinese medicine (CM) and hysteroscopic endometrial mechanical stimulation on the treatment of infertile patients with repeated implantation failure (RIF); and to study the differences in patients' endometrial thickness and type on the day of embryo transfer, serum hormone levels on embryo transfer day and clinical pregnancy outcomes. METHODS: In the clinical study, 168 frozen-thawed embryo transfer (FET) cycles for couples with RIF conforming to the research protocol were randomly divided into three groups: a CM group with 56 cycles (CM combined with FET), a hysteroscopy group with 55 cycles (hysteroscopic endometrial mechanical stimulation), and a control group with 57 cycles (conventional FET). Differences in endometrial thickness on the embryo transfer day, levels of serum estradiol (E2) and progesterone (P) on the embryo transfer day, the E2/P ratio on the embryo transfer day, biochemical and clinical pregnancy rates, implantation rate, abnormal pregnancy rate and other indices were compared among the three groups. RESULTS: Endometrial thickness, E2 and P levels, and the E2/P ratio on embryo transfer day and other factors had no significant differences among groups. The biochemical pregnancy, clinical pregnancy, and implantation rates of the CM and hysteroscopy groups were significantly higher than the control group (P<0.05), and there were no significant differences between these two groups. The abnormal pregnancy rate had no significant difference among the three groups. CONCLUSIONS: Sequential therapy of Yupei Qisun could significantly improve the clinical outcomes of rif-fet cycles, being equivalent to hysteroscopic endometrial mechanical stimulation, and provided a reliable method to treat such infertile couples.

The effect of sacral nerve stimulation on uterine activity: a pilot study.

INTRODUCTION: Sacral nerve stimulation (SNS) is a treatment for consecutive therapy resistant faecal incontinence or constipation. Little is known about the effects of SNS on uterocervical function. Therefore, it is advised to turn off the stimulator during pregnancy or to wait with permanent implantation of the stimulator until family completion. Diagnostic ultrasound provides an, non-invasive, opportunity to study various aspects of uterine activity. The purpose of this pilot study was to assess the influence of SNS on endometrial waves of the nonpregnant uterus by ultrasound recordings. METHOD: Six patients with an implanted SNS were included. Ultrasound recordings were performed with the stimulator turned off and in three stimulation frequencies. Uterine activity is described as wave frequency and wave direction. RESULTS: All three premenopausal patients showed endometrial activity with the stimulator turned off. This activity was maintained with the stimulator turned on in two patients, but disappeared in one patient. All three postmenopausal patients had no endometrial activity with the stimulator turned off. In one patient there was activity with the stimulator turned on at a frequency of 21 Hz. CONCLUSION: We have shown some effect of SNS on uterine activity. In premenopausal women we discovered that SNS seems to exhibit no effect or an inhibitory effect rather than an excitatory effect on uterine activity. Based on the preliminary results of this study, we can not recommend any guidelines for SNS usage during conception and pregnancy. A larger study in premenopausal women with SNS is needed to investigate the significance of these changes.

The use of a combination of pentoxifylline and tocopherol in women with a thin endometrium undergoing assisted conception therapies--a report of 20 cases.

An optimal thickness of the endometrium is considered to be one of the prerequisites for successful implantation of the embryo. A retrospective analysis was carried out to investigate the use of Pentoxyfylline and tocopherol in improving the endometrial thickness in cases that are unresponsive to conventional therapy. Twenty women with thin endometrium (<6 mm) undergoing either ovulation induction or frozen embryo transfer cycles were prescribed 800 mg of PTX and 1000 IU of Vit E daily. In 11 cases, the etiology for thin endometrium was unknown. The known causes included Turners' syndrome (3), Kallman's syndrome (1), idiopathic hypogonadotrophic hypogonadism (2), premature ovarian failure (1) and Asherman's syndrome (2), none of which had responded to conventional hormonal stimulation. The mean duration of treatment was 8.1 months (+/-4.5, range 1-18 months). The mean thickness of endometrium before and after treatment was 4.37 mm (+/-1.5 mm) and 6.05 mm (+/-1.83 mm), respectively (p = 0.001, 95% CI 0.84-2.5). Overall, 14 (73.7%) women showed improvement in endometrial thickness which was the primary outcome. Pregnancy occurred in eight women (40%) of which three were natural, one had ovulation induction and another five had frozen embryo transfers. We conclude that a combination of pentoxyfylline and tocopherol may improve endometrial growth in resistant cases that are unresponsive to conventional therapy.

A simulation of gas-based, endometrial-ablation therapy.

The method of numerical simulation has been employed to evaluate the use of a gas as a heating medium for endometrial ablation for the treatment of menorrhagia and uterine fibroids. The simulations encompassed fluid flow and heat transfer within the gaseous medium which serves to heat the uterine lining and the coupled heat conduction in the uterine tissue. For the case study featured here, helium at a temperature of 140 degrees C was employed as the heating medium. A total therapy duration of 6 min was modeled. The outcome of the simulation has provided quantitative information about the detailed necrosis depths that can be attained by the application of the therapy. In particular, necrosis depths on the order of 5 mm were achieved. It was also shown that by making use of a tailored pattern of fluid flow within the uterine cavity, particular zones on the uterine lining such as fibroids can be selectively targeted. Furthermore, the duration of the therapy needed to achieve a desired degree of necrosis can be predicted in advance. The advantages of a gas-based therapy relative to a liquid-based therapy are identified. Significant among these is the capability of the gas-based therapy to target specific zones which require treatment, while sparing healthy tissue. Another significant advantage of gas-based therapy is that it enables the use of higher temperatures which, in turn, allows the therapeutic process to be performed in a shorter time duration.

[Using of Therma-Choice system in treatment of metrorrhagia in case of porphyria]. / Therma-Choice w leczeniu krwawien z macicy w przypadku porfirii.

The authors present the use of Uterine Balloon Therapy in the long term metrorrhagia resistant to conservative treatment, in the case of porphyria. The method was used on a 44 year old female, suffering from acute intermittent liver porphyria for 9 years.

High omega-3:omega-6 fatty acid ratios in culture medium reduce endometrial-cell survival in combined endometrial gland and stromal cell cultures from women with and without endometriosis.

OBJECTIVE: To study the effects of omega-3 and omega-6 polyunsaturated fatty acid (PUFA) on in vitro proliferation of endometrial cells and their production of the cytokine interleukin-8 (IL-8). DESIGN: In vitro study. SETTING: Obstetrics and gynecology department, University of Aberdeen. PATIENT(S): Women attending an infertility clinic. INTERVENTION(S): In vitro cell cultures using culture mediums supplemented with normal and high ratios of omega-3 PUFA and omega-6 PUFA. MAIN OUTCOME MEASURE(S): In vitro survival and production of IL-8 by dispersed endometrial cells. RESULT(S): In vitro survival of endometrial cells from women with and without endometriosis was significantly reduced in the presence of high omega-3:omega-6 PUFA ratios compared with cells incubated in the absence of fatty acids, in balanced omega-3:omega-6 PUFA ratios, and in high omega-6:omega-3 PUFA ratios. Endometrial cells from women with endometriosis secreted higher concentrations of IL-8, especially in the presence of high omega-3:omega-6 PUFA ratios. CONCLUSION(S): omega-3 PUFA may have a suppressive effect on the in vitro survival of endometrial cells and omega-3 PUFA be useful in the management of endometriosis by reducing the inflammatory response and modulating cytokine function.

Endometrial effects of etonogestrel (Implanon) contraceptive implant.

The subdermal contraceptive implant etonogestrel (Implanon; NV Organon International, Oss, The Netherlands) exerts complex effects on the endometrium. These include direct effects on the endometrium through endometrial progestin target sites, and indirect effects through suppression of the hypothalamic-pituitary-ovarian axis. The resulting effects are categorized by alterations in endometrial histology, endometrial thickness, dysmenorrhoea and menstrual bleeding pattern. The exact mechanism of action of progestins on the endometrium has not been determined. The contraceptive effect in Implanon users is mainly due to inhibition of ovulation. Current research is concentrating on the potential of the progestin implant to modify endometrial vascular, angiogenic, steroid receptor and proto-oncogene function. These processes may be involved in the causation of progestin-induced breakthrough bleeding.

A heat transfer model of thermal balloon endometrial ablation.

A heat transfer model was developed for thermal balloon endometrial ablation treatment for menorrhagia. The model includes heat conduction through the uterus wall, cooling due to blood perfusion through the uterine tissue and the contribution of metabolic heat generation. A parameter sensitivity study indicated that metabolic heat generation had a minimal effect, but model predictions were sensitive to blood perfusion rate. However, within the range of expected perfusion rates, the model calculates damage depths (3-6 mm) close to the range for effective treatment. Using a blood perfusion rate of 0.0028 m(3)t m(-3)b s(-1), the predicted burn depth (4 mm) correlated well with experimental measurements (4.2 +/- 0.6 mm) reported elsewhere for a treatment temperature of 92 degrees C and time of 6 mins (Neuwirth, R. S. et al. The endometrial ablator: A new instrument. Obstet. Gynecol. 83:792-796, 1994). If no vaporization of water in the tissue occurs, the model predicts that the same burn depth of 4 mm can be obtained with increased treatment temperature (130 degrees C) and shorter treatment time (1.4 min). Steeper temperature profiles through the uterine wall suggest that, in the absence of other changes due to higher temperatures, the deeper layers of the myometrium and the serosa would be protected from thermal damage when using higher treatment temperatures for a shorter duration. However, if vaporization occurs at 105 degrees C, the model predicts little benefit in using treatment temperatures above 120 degrees C up to 160 degrees C. For further validation of the model, in vivo studies using the high temperature treatments are needed to measure temperature profiles through the uterine wall, blood perfusion rates, and the other effects of temperature on uterine tissue.

Endometrial destruction by hyperthermia--a possible treatment of menorrhagia. An experimental study.

BACKGROUND: Treatment of menorrhagia by heat-destruction of the endometrium, intended to be an alternative to hysterectomy, was investigated in an experimental study. METHOD: A specially designed catheter (CavatermTM) with a silicone balloon containing a self-regulating containing heating element is inserted into the uterus, filled with glycine to a pressure of around 180 mmHg and heated to about 75 degrees C. We investigated the treatment effect in vitro in five extirpated uteri (series A) and in vivo in three patients treated peroperatively just before hysterectomy, temperatures being monitored in the surrounding tissues (series B). In both series we monitored the following variables: heating-power, balloon-pressure, temperature of the heating element (around 85 degrees C) and the temperatures at five locations from top to bottom of the balloon surface. RESULTS: After 30 min in vitro treatment at 75 degrees C, the endometrium was partly destructed, and condensed. Histological examination showed smooth muscle cells to be destroyed to a depth of 2-5 mm close to the endometrium. With in vivo treatment for 30 min at a heating power of about 20 W (resulting in balloon surface temperatures of 58-65 degrees C), the increases in temperature of the surrounding tissue were too small to measure accurately (+/-1 degree C). Histological examination showed destruction of cells in the corpus uteri to a maximum depth of 8 mm. CONCLUSION: Findings in in vitro and in vivo experiments suggest that 30 min heating of the endometrium to 58-65 degrees C with an intrauterine silicone balloon filled with a liquid to a pressure of 180 mmHg exerts therapeutic effects on both endometrium and uterine cavity smooth muscle cells without damage to surrounding tissues.