The Treatment of Tubal Inflammatory Infertility using Yinjia Tablets through EGFR/MEK/ERK Signaling Pathway based on Network Pharmacology.

Background: Salpingitis obstructive infertility (SOI) refers to infertility caused by abnormal conditions such as tubal adhesion and blockage caused by acute and chronic salpingitis. SOI has a serious impact on women's physical and mental health and family harmony, and it is a clinical problem that needs to be solved urgently.

Objective: The purpose of the present study was to explore the potential pharmacological mechanisms of the Yinjia tablets (Yin Jia Pian, YJP) on tubal inflammation.

Methods: Networks of YJP-associated targets and tubal inflammation-related genes were constructed through the STRING database. Potential targets and pathway enrichment analysis related to the therapeutic efficacy of YJP were identified using Cytoscape and Database for Annotation, Visualization, and Integrated Discovery (metascape). E. coli was used to establish a rat model of tubal inflammation and to validate the predictions of network pharmacology and the therapeutic efficacy of YJP. H&E staining was used to observe the pathological changes in fallopian tubes. TEM observation of the ultrastructure of the fallopian tubes. ELISA was used to detect the changes of IL-6 and TNF-α in fallopian tubes. Immunohistochemistry was used to detect the expression of ESR1. The changes of Bcl-2, ERK1/2, p-ERK1/2, MEK, p-MEK, EGFR, and p-EGFR were detected by western blot.

Results: Through database analysis, it was found that YJP shared 105 identical targets with the disease. Network pharmacology analysis showed that IL-6, TNF, and EGFR belong to the top 5 core proteins associated with salpingitis, and EGFR/MEK/ERK may be the main pathway involved. The E. coli-induced disease rat model of fallopian tube tissue showed damage, mitochondrial disruption, and increased levels of the inflammatory factors IL-6 and TNF-α. Tubal inflammatory infertility rats have increased expression of Bcl-2, p-ERK1/2, p-MEK, and p-EGFR, and decreased expression of ESR1. In vivo, experiments showed that YJP improved damage of tissue, inhibited shedding of tubal cilia, and suppressed the inflammatory response of the body. Furthermore, YJP inhibited EGFR/MEK/ERK signaling, inhibited the apoptotic protein Bcl-2, and upregulated ESR1.

Conclusion: This study revealed that YJP Reducing tubal inflammation and promoting tissue repair may be associated with inhibition of the EGFR/MEK/ERK signaling pathway.

Polycystic ovaries and herbal remedies: A systematic review.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects one in every 15 women worldwide. This disorder is mainly characterized by increased levels of male hormones (androgens), acne, and hirsutism, and can lead to long-term insulin resistance, miscarriage, or even infertility in women. PCOS is a disorder that can be treated with natural and allopathic remedies that work against the PCOS mechanism. The present study reviews previous studies on the treatment of PCOS using natural drugs. METHODS: The data in this study were collected from articles published in reputable databases including ScienceDirect, PubMed, Google Scholar, and SID in the field of medicinal plants from 1990 to 2021. RESULTS: A review of the literature showed that plants such as aloe vera and chamomile improve fertility by increasing the number of ovarian follicles. Besides, Vitex agnus-castus and octane reduce hirsutism by reducing testosterone and androgen levels. It was also shown that liquorice, ginseng, cinnamon, and de chiro Inositol improve the adverse effects of diabetes caused by PCOS by lowering lipid and blood glucose levels. Moreover, Stachys lavandulifolia and fennel are effective in changing endometrial tissue parameters in PCOS by reducing estrogen and hyperplasia. CONCLUSIONS: Various studies have shown that herbal medicines can improve PCOS symptoms in women with minimal side effects but a longer treatment cycle.

Effects of L-carnitine supplementation for women with polycystic ovary syndrome: a systematic review and meta-analysis.

Background: Polycystic ovary syndrome (PCOS) is a disorder in reproductive age women and is characterized by hyperandrogenic anovulation and oligo-amenorrhea, which leads to infertility. Anovulation in PCOS is associated with low follicle-stimulating hormone levels and the arrest of antral follicle development in the final stages of maturation. L-carnitine (LC) plays a role in fatty acid metabolism, which is found to be lacking in PCOS patients. This systematic review and meta-analysis aimed to determine the effectiveness of LC supplementation for patients with PCOS. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Psychological Information Database (PsycINFO), and the World Health Organization International Clinical Trials Registry Platform for all randomized control trials, comparing LC alone or in combination with other standard treatments for the treatment of PCOS from inception till June 2021. We independently screened titles and abstracts to identify available trials, and complete texts of the trials were checked for eligibility. Data on the methods, interventions, outcomes, and risk of bias from the included trials were independently extracted by the authors. The estimation of risk ratios and mean differences with a 95 percent confidence interval (CI) was performed using a random-effects model. Results: Nine studies with 995 participants were included in this review. Five comparison groups were involved. In one comparison group, LC reduced the fasting plasma glucose (FPG) (mean differences (MD) -5.10, 95% CI [-6.25 to -3.95]; P = 0.00001), serum low-density lipoprotein (LDL) (MD -25.00, 95% CI [-27.93 to -22.07]; P = 0.00001), serum total cholesterol (MD -21.00, 95% CI [-24.14 to -17.86]; P = 0.00001), and serum triglyceride (TG) (MD -9.00, 95% CI [-11.46 to -6.54]; P = 0.00001) with moderate certainty of evidence. Another comparison group demonstrated that LC lowers the LDL (MD -12.00, 95% CI [-15.80 to -8.20]; P = 0.00001), serum total cholesterol (MD -24.00, 95% CI [-27.61 to -20.39]; P = 0.00001), and serum TG (MD -19.00, 95% CI [-22.79 to -15.21]; P = 0.00001) with moderate certainty of evidence. Conclusion: There was low to moderate certainty of evidence that LC improves Body Mass Index (BMI) and serum LDL, TG, and total cholesterol levels in women with PCOS.

Rescue of obesity-induced infertility in female mice by silencing AgRP neurons.

Obesity impacts multiple sites of the hypothalamus-pituitary gland-ovary axis (HPO axis) and has become a leading cause of female infertility. However, the critical hypothalamic neurons that participate in the development of obesity-induced infertility have not been well defined yet. Previous studies suggested that metabolic-sensing agouti-related peptide-expressing (AgRP) neurons in the arcuate nucleus (ARC) are hyperactive in diet-induced obesity (DIO) mice. We hypothesize that these neurons may convey metabolic dysfunction onto the HPO axis and contribute to obesity-induced infertility's pathophysiological process. To determine if AgRP neurons in obesity play a necessary role in the development of reproductive impairment in obesity, we used the chemogenetic method to normalize the neuronal activity of AgRP neurons in DIO female mice and test if their fertility can be restored. Our results indicated that chemogenetic inhibition of AgRP neurons could fully rescue the reproductive performance of DIO female mice, as manifested by recovered sex hormonal levels, ovulation, and fecundity. Moreover, we assayed serum AgRP levels in normal-weight and obese women and found elevated AgRP levels in obese subjects, suggesting the correlation between obesity and AgRP neuronal hyperactivity. Our results indicated that AgRP neurons constitute a central node connecting metabolism and reproduction, and dysfunctions of these neurons play a crucial role in reproductive impairment induced by metabolic abnormalities.

Comparative risk reduction of complications pertaining to polycystic ovarian syndrome by multiple treatment options.

The aim of study was to find effective treatment option which reduces the risk of complications among patients of polycystic-ovarian-syndrome. A cross-sectional study was conducted from January-2019 to December-2019. Data was collected from 200 patients that have visited hospitals and clinics located in Karachi. A questionnaire was used in the survey. Collected data was analyzed with SPSS-22. Hormonal-imbalance (p=0.0001), polycystic-ovaries (p=0.008), irregular-menstruation (p=0.0001), obesity (p=0.0001), diabetes (p=0.0001) and infertility (p=0.014) significantly treated by allopathic-medications. Hormonal-imbalance (p=0.025), polycystic-ovaries (p=0.0001), irregular-menstruation (p=0.0001), obesity (p=0.046), diabetes (p=0.001), acne (p=0.046), anxiety (p=0.014), depression (p=0.014) and eating disorder (p=0.046) significantly treated by homeopathic-medications. Polycystic-ovaries (p=0.0001), irregular-menstruation (p=0.0001), obesity (p=0.014), diabetes (p=0.0001) and acne (p=0.014) significantly treated by herbal-medications. Allopathic treatment was found effective in reducing risk of complication associated with PCOS; hormonal-imbalance (59%), hirsutism (42%), obesity (89%), diabetes (90%), hypertension (17%), infertility (60%) and anxiety (75%). Risk reduction of complications by Homeopathic treatment; polycystic-ovaries (54%), irregular menstruation (91%) and depression (43%). Combination treatment was found effective in reducing the risk of acne (43%) and eating disorder (100%). Allopathic treatment is effective in reducing the majority of risks of complications and the complications of polycystic-ovaries-syndrome can be significantly controlled with the homeopathic mode of treatment.

Exploring the facilitators and barriers to using an online infertility risk prediction tool (FoRECAsT) for young women with breast cancer: a qualitative study protocol.

INTRODUCTION: As cancer treatments may impact on fertility, a high priority for young patients with breast cancer is access to evidence-based, personalised information for them and their healthcare providers to guide treatment and fertility-related decisions prior to cancer treatment. Current tools to predict fertility outcomes after breast cancer treatments are imprecise and do not offer individualised prediction. To address the gap, we are developing a novel personalised infertility risk prediction tool (FoRECAsT) for premenopausal patients with breast cancer that considers current reproductive status, planned chemotherapy and adjuvant endocrine therapy to determine likely post-treatment infertility. The aim of this study is to explore the feasibility of implementing this FoRECAsT tool into clinical practice by exploring the barriers and facilitators of its use among patients and healthcare providers. METHODS AND ANALYSIS: A cross-sectional exploratory study is being conducted using semistructured in-depth telephone interviews with 15-20 participants each from the following groups: (1) premenopausal patients with breast cancer younger than 40, diagnosed within last 5 years, (2) breast surgeons, (3) breast medical oncologists, (4) breast care nurses (5) fertility specialists and (6) fertility preservation nurses. Patients with breast cancer are being recruited from the joint Breast Service of three affiliated institutions of Victorian Comprehensive Cancer Centre in Melbourne, Australia-Peter MacCallum Cancer Centre, Royal Melbourne Hospital and Royal Women's Hospital, and clinicians are being recruited from across Australia. Interviews are being audio recorded, transcribed verbatim and imported into qualitative data analysis software to facilitate data management and analyses. ETHICS AND DISSEMINATION: The study protocol has been approved by Melbourne Health Human Research Ethics Committee, Australia (HREC number: 2017.163). Confidentiality and privacy are maintained at every stage of the study. Findings will be disseminated through peer-reviewed scholarly and scientific journals, national and international conference presentations, social media, broadcast media, print media, internet and various community/stakeholder engagement activities.

The therapeutic dimension of research about spirituality: Particularities of cancer, mental health and infertility.

Healthcare is moving from a biomedical paradigm into a holistic paradigm, which includes all dimensions and needs of patients and families. Health conditions may trigger a spiritual journey for believers or non-believers bringing to light the nature of the human being and its vulnerable condition. Healthcare professionals are full participants in this life and health scenario and have an unquestionable duty related to the provision of spiritual care, on the basis of legislation, ethical codes, and on research evidence. Researchers are seizing better and broader knowledge about spirituality in healthcare, and research about this phenomenon is growing internationally. But, spirituality is considered complex, an area of intimacy and deep subjective meaning. These factors may raise some ethical concerns when submitting research projects to the ethics committees. In this paper, the authors share their experience in research about spirituality in the beginning of life issues/infertility and with adults with severe health conditions, and describe participants' perspectives on research engagement.

A 7-year follow-up study of the Mindfulness-Based Program for Infertility: Are there long-term effects?

The Mindfulness-Based Program for Infertility (MBPI) was developed for people facing infertility and proved effective in cultivating mindfulness skills, improving infertility self-efficacy, and decreasing depression, shame, entrapment, and defeat feelings. Fifty-five women attended the MBPI sessions and completed self-report measures of depression, anxiety, mindfulness, and experiential avoidance at post-MBPI (T1), 6-month follow-up (T2), and 7-year follow-up (T3). There were significant direct time effects regarding experiential avoidance (F = 3.81; p < 0.033; ηp 2  = 0.08), the mindfulness facets describing (F = 3.54; p = 0.037; ηp 2  = 0.13), acting with awareness (F = 6.87; p = 0.002; ηp 2  = 0.22), nonjudging of inner experience (F = 10.66; p < 0.001; ηp 2  = 0.31), and depressive symptoms (F = 4.85; p = 0.020; ηp 2  = 0.10). There was an increase in the describing facet from T1 to T3 (p = 0.036). The act with awareness facet increased from T1 to T2 (p = 0.010) and from T1 to T3 (p = 0.007), as well as the nonjudging of inner experience facet (T1 to T2 [p = 0.030] and T1 to T3 [p = 0.002]). Experiential avoidance decreased from T1 to T3 (p = 0.022) and depressive symptoms from T1 to T2 (p = 0.019). Post-MBPI scores were maintained at T2 and T3 concerning anxiety symptoms and the observing and no-reactivity mindfulness facets. There were long-term effects of MBPI on mindfulness and experiential avoidance. Moreover, therapeutic gains were maintained regarding depression and anxiety symptoms, independently of the reproductive outcome.

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.

A Dyadic Approach to Infertility Stress, Marital Adjustment, and Depression on Quality of Life in Infertile Couples.

PURPOSE: This study was conducted to examine the level of infertility stress, marital adjustment, depression, and quality of life in infertile couples and assess the actor and partner effects in these areas using the actor-partner interdependence model. DESIGN: Cross-sectional study. METHOD: Participants were 121 infertile couples. After pilot study, data were collected from November 2012 to March 2013 using the following questionnaires: the Fertility Quality of Life, Fertility Problem Inventory, Revised Dyadic Adjustment Scale, and Beck Depression Inventory. FINDINGS: There was a gender difference in infertility stress, depression, and quality of life. Infertility stress had actor and partner effects on the quality of life. Marital adjustment had an actor effect on the quality of life for the wives. Depression had actor and partner effects on quality of life for the wives, but only an actor effect for the husbands. CONCLUSION: This study found that there were actor and partner effects of infertility stress, marital adjustment, and depression on the quality of life in infertile couples. These findings may help nurses be aware of such effects and can be used as a baseline data in the development of nursing interventions for infertile couples.

Perception of a single-session pre-in vitro fertilisation counselling service and attitudes towards support group: a survey of patients in Singapore.

INTRODUCTION: This study aimed to investigate patients' evaluation of a compulsory pre-in vitro fertilisation (IVF) counselling session in Singapore and determine their attitudes towards attending a support group during IVF treatment. METHODS: 464 patients due to undergo their first IVF treatment were recruited at the Clinic for Human Reproduction, National University Hospital, Singapore. Prior to IVF treatment, all patients attended a counselling session conducted by a clinical psychologist trained in infertility counselling. The Depression Anxiety Stress Scales 21 was used to measure patients' psychological symptoms of depression, anxiety and stress. A feedback form was administered after the session to determine their evaluation of the session and interest in attending a support group. RESULTS: After the pre-IVF counselling session, 90.9% of patients reported that the session was useful, with over 80% of participants reporting that the session had helped them to better prepare for the IVF treatment, enhanced their coping and enabled them to better communicate their needs to their spouse. Overall, 64.1% of patients expressed interest in attending a support group, with male patients showing more interest. Financial resources and the level of psychological symptoms experienced were found to influence patients' motivation to attend a support group. CONCLUSION: The single pre-IVF counselling session was well received and found to be useful by patients. Hence, it is recommended that IVF counselling be made an essential part of the holistic care given to patients undergoing IVF, particularly those who experience higher levels of distressing psychological symptoms.

Screening, brief intervention, and referral to treatment for opioid and other substance use during infertility treatment.

Opioid use and misuse have reached epidemic proportions in the United States, especially in women of childbearing age, some of whom seek infertility treatments. Substance use is much more common than many of the conditions routinely screened for during the preconception period, and it can have devastating consequences for the woman and her family. Substance use can worsen infertility, complicate pregnancy, increase medical problems, and lead to psychosocial difficulties for the woman and her family. The reproductive endocrinologist thus has an ethical and medical duty to screen for substance use, provide initial counseling, and refer to specialized treatment as needed. This article provides an overview of screening, brief intervention, and referral to treatment (SBIRT), a public health approach shown to be effective in ameliorating the harms of substance use.

Fertility issues in patients with hematologic malignancies.

An essential component of a cancer patient's comprehensive care is addressing potential threats to his or her reproductive health. Providers should discuss the risk of infertility with newly diagnosed patients and offer the chance to consult with a reproductive specialist as early as possible. Standard fertility preservation options include embryo or oocyte cryopreservation for women and sperm banking for men; all options for pre-pubertal children are experimental. Patients with hematologic malignancies are a distinct population in whom standard options may present special challenges, and alternative management strategies are being explored. Unique approaches in hematologic malignancy patients include experimental techniques, such as hormonal therapy, referrals to reproductive specialists after cancer treatment, or discontinuation of tyrosine kinase inhibitor therapy in appropriate chronic myelogenous leukemia patients. Importantly, expedited communication between hematologists and reproductive specialists may greatly enhance the quality of care for these patients. Facilitation of referrals will both improve the quality-of-life and expand the prospect of parenthood in survivors. There are ample opportunities to advance the field of oncofertility through additional research, especially in hematologic malignancy patients.

Prevalence of cervical insufficiency in polycystic ovarian syndrome.

BACKGROUND: Pregnant women with polycystic ovarian syndrome (PCOS) experience a greater rate of adverse obstetrical outcomes compared with non-PCOS women. We examined the prevalence and incidence of cervical insufficiency (CI) in a community cohort of pregnant women with and without PCOS. METHODS: A retrospective cohort study was conducted within a large integrated health care delivery system among non-diabetic PCOS women with second or third trimester delivery during 2002-2005 (singleton or twin gestation). PCOS was defined by Rotterdam criteria. A non-PCOS comparison group matched for delivery year and hospital facility was used to estimate the background rate of CI. Women were designated as having new CI diagnosed in the index pregnancy (based on cervical dilation and/or cervical shortening) and prior CI based on prior diagnosis of CI with prophylactic cerclage placed in the subsequent pregnancy. RESULTS: We identified 999 PCOS women, of whom 29 (2.9%) had CI. There were 18 patients with new CI and 11 with prior CI having prophylactic cerclage placement; four CI patients had twin gestation. In contrast, only five (0.5%) non-PCOS women had CI: two with new CI and three with prior CI. The proportion of newly diagnosed incident CI (1.8 versus 0.2%) or prevalent CI (2.9 versus 0.5%) was significantly greater for PCOS compared with non-PCOS pregnant women (both P < 0.01). Among PCOS women, CI prevalence was particularly high among South Asians (7.8%) and Blacks (17.5%) compared with Whites (1%) and significantly associated with gonadotropin use (including in vitro fertilization). Overall, the PCOS status was associated with an increased odds of prevalent CI pregnancy (adjusted odds ratio 4.8, 95% confidence interval 1.5-15.4), even after adjusting for maternal age, nulliparity, race/ethnicity, body mass index and fertility treatment. CONCLUSION: In this large and ethnically diverse PCOS cohort, we found that CI occurred with a higher than expected frequency in PCOS women, particularly among South Asian and Black women. PCOS women with CI were also more likely to have received gonadotropin therapy. Future studies should examine whether natural and hormone-altered PCOS is a risk factor for CI, the role of race/ethnicity, fertility drugs and consideration for heightened mid-trimester surveillance in higher risk subgroups of pregnant women with PCOS.

Impact of a group mind/body intervention on pregnancy rates in IVF patients.

OBJECTIVE: To determine if women who were randomized to a mind/body program before starting their first IVF cycle would have higher pregnancy rates than control subjects. DESIGN: Randomized, controlled, prospective study. SETTING: Private academically affiliated infertility center. PATIENT(S): A total of 143 women aged≤40 years who were about to begin their first IVF cycle. INTERVENTION(S): Subjects were randomized to a ten-session mind/body program (MB) or a control group and followed for two IVF cycles. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate. RESULT(S): Only 9% of the MB participants had attended at least one-half of their sessions at cycle 1 start. Pregnancy rates for cycle 1 were 43% for all subjects; 76% of the MB subjects had attended at least one-half of their sessions at cycle 2 start. Pregnancy rates for cycle 2 were 52% for MB and 20% for control. CONCLUSION(S): MB participation was associated with increased pregnancy rates for cycle 2, prior to which most subjects had attended at least half of their sessions.

Laparoscopic laser treatment of endometriosis with the Nd:YAG sapphire probe.

Laparoscopic surgery with the Nd:YAG laser generator and a sapphire probe was performed in 43 women for relief of pain and/or infertility associated with endometriosis and in two other women for treatment of an asymptomatic adnexal enlargement. More than half of the patients had American Fertility Society endometriosis scores of stage III or IV. Results of uterosacral denervation for pain relief were excellent, and eight of 17 patients who were attempting pregnancy with follow-up for 6 months conceived. A touch technique, reduced smoke production, and delivery via a flexible fiber constitute advantages to the surgeon compared with carbon dioxide systems.