The role of Cistanches Herba and its ingredients in improving reproductive outcomes: A comprehensive review.

BACKGROUND: Infertility patients account for an astonishing proportion of individuals worldwide. Due to its complex etiology and challenging treatment, infertility has imposed significant psychological and economic burdens on many patients. C. Herba (Cistanche tubulosa (Schenk) Wight and Cistanche deserticola Ma), renowned as one of the most prominent Chinese herbal medicines (CHMs), is abundant in diverse bioactive compounds that exhibit therapeutic effects on many diseases related to oxidative stress (OS) and disorders of sex hormone levels. OBJECTIVE: Due to the limited drugs currently used in clinical practice to improve reproductive outcomes and their inevitable side effects, developing safe and effective new medications for infertility is of significance. This article comprehensively reviewed the phytochemicals of C. Herba, focusing on their efficacy and mechanisms on infertility and their safety for the first time, aiming to offer valuable insights for the development and application of C. Herba, and for developing novel strategies for treating infertility. METHODS: We used "Cistanche" and its known bioactive components in combination with "sperm", "testicles", "epididymis", "ovaries", "uterus", and "infertility" as keywords to search in PubMed, Web of Science, Scopus and CNKI up to November 2023. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline was followed. RESULTS: The therapeutic effects of C. Herba on infertility are mainly attributed to echinacoside (ECH), verbascoside (VB), salidroside (SAL), polysaccharides, and betaine. They can effectively improve spermatogenic dysfunction, gonadal dysfunction and erectile dysfunction (ED) by exerting anti-oxidation, sex hormones regulation and anti-hypoxia. Moreover, they can also improve premature ovarian failure (POF), ovarian and uterine cancer, oocyte maturation by exerting anti-oxidation, anti-apoptosis, and anti-cancer. C. Herba and its active ingredients also exhibit pleasing safety. CONCLUSION: C. Herba is a promising source of natural medicine for infertility. Additionally, compared to current therapeutic drugs, its favorable safety also supports its development as a nutritional supplement. However, high-quality clinical studies are required to validate its effectiveness for the development of novel therapeutic strategies.

Sex differences in the cardiovascular effects of GnRH analogues.

The integral role of the hypothalamic-pituitary-gonadal axis in reproductive processes makes it a prime therapeutic target. By inhibiting sex steroid synthesis, gonadotropin-releasing hormone (GnRH) analogues are used in the management of cancers, benign neoplasms, infertility and gender dysphoria. However, the wide application of these therapeutics raises concerns regarding the unintended effects upon the cardiovascular system. In males with prostate cancer, GnRH analogues when used as an androgen deprivation therapy appear to increase the risk of cardiovascular disease, which is the leading cause of death in this population. Therefore, due to the utilisation of GnRH analogues across the lifespan and gender spectrum, this relationship merits discussion. Existing data suggest an association between GnRH analogues and major adverse cardiovascular events in males. Conversely, females receiving GnRH analogues for breast cancer treatment appear to be at an increased risk of developing hypertension. In this narrative review, we describe the uses of GnRH analogues in adults, adolescents and children. We discuss whether sex plays a role in the cardiovascular effects of GnRH analogues and explore the significance of sex hormone receptors in the vasculature. We also consider confounding factors such as malignancy, advanced age and infertility.

In vitro fertilisation for unexplained subfertility.

BACKGROUND: In vitro fertilisation (IVF) is a treatment for unexplained subfertility but is invasive, expensive, and associated with risks. OBJECTIVES: To evaluate the effectiveness and safety of IVF versus expectant management, unstimulated intrauterine insemination (IUI), and IUI with ovarian stimulation using gonadotropins, clomiphene citrate (CC), or letrozole in improving pregnancy outcomes. SEARCH METHODS: We searched following databases from inception to November 2021, with no language restriction: Cochrane Gynaecology and Fertility Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL. We searched reference lists of articles and conference abstracts. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing effectiveness of IVF for unexplained subfertility with expectant management, unstimulated IUI, and stimulated IUI. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. MAIN RESULTS: IVF versus expectant management (two RCTs) We are uncertain whether IVF improves live birth rate (LBR) and clinical pregnancy rate (CPR) compared to expectant management (odds ratio (OR) 22.0, 95% confidence interval (CI) 2.56 to 189.37; 1 RCT; 51 women; very low-quality evidence; OR 3.24, 95% CI 1.07 to 9.8; 2 RCTs; 86 women; I2 = 80%; very low-quality evidence). Adverse effects were not reported. Assuming 4% LBR and 12% CPR with expectant management, these would be 8.8% to 9% and 13% to 58% with IVF. IVF versus unstimulated IUI (two RCTs) IVF may improve LBR compared to unstimulated IUI (OR 2.47, 95% CI 1.19 to 5.12; 2 RCTs; 156 women; I2 = 60%; low-quality evidence). We are uncertain whether there is a difference between IVF and IUI for multiple pregnancy rate (MPR) (OR 1.03, 95% CI 0.04 to 27.29; 1 RCT; 43 women; very low-quality evidence) and miscarriage rate (OR 1.72, 95% CI 0.14 to 21.25; 1 RCT; 43 women; very low-quality evidence). No study reported ovarian hyperstimulation syndrome (OHSS). Assuming 16% LBR, 3% MPR, and 6% miscarriage rate with unstimulated IUI, these outcomes would be 18.5% to 49%, 0.1% to 46%, and 0.9% to 58% with IVF. IVF versus IUI + ovarian stimulation with gonadotropins (6 RCTs), CC (1 RCT), or letrozole (no RCTs) Stratified analysis was based on pretreatment status. Treatment-naive women There may be little or no difference in LBR between IVF and IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles: OR 1.19, 95% CI 0.87 to 1.61; 3 RCTs; 731 women; I2 = 0%; low-quality evidence; 1 IVF to 1 IUI cycle: OR 1.63, 95% CI 0.91 to 2.92; 2 RCTs; 221 women; I2 = 54%; low-quality evidence); or between IVF and IUI + CC (OR 2.51, 95% CI 0.96 to 6.55; 1 RCT; 103 women; low-quality evidence). Assuming 42% LBR with IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles) and 26% LBR with IUI + gonadotropins (1 IVF to 1 IUI cycle), LBR would be 39% to 54% and 24% to 51% with IVF. Assuming 15% LBR with IUI + CC, LBR would be 15% to 54% with IVF. There may be little or no difference in CPR between IVF and IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles: OR 1.17, 95% CI 0.85 to 1.59; 3 RCTs; 731 women; I2 = 0%; low-quality evidence; 1 IVF to 1 IUI cycle: OR 4.59, 95% CI 1.86 to 11.35; 1 RCT; 103 women; low-quality evidence); or between IVF and IUI + CC (OR 3.58, 95% CI 1.51 to 8.49; 1 RCT; 103 women; low-quality evidence). Assuming 48% CPR with IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles) and 17% with IUI + gonadotropins (1 IVF to 1 IUI cycle), CPR would be 44% to 60% and 28% to 70% with IVF. Assuming 21% CPR with IUI + CC, CPR would be 29% to 69% with IVF. There may be little or no difference in multiple pregnancy rate (MPR) between IVF and IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles: OR 0.82, 95% CI 0.38 to 1.77; 3 RCTs; 731 women; I2 = 0%; low-quality evidence; 1 IVF to 1 IUI cycle: OR 0.76, 95% CI 0.36 to 1.58; 2 RCTs; 221 women; I2 = 0%; low-quality evidence); or between IVF and IUI + CC (OR 0.64, 95% CI 0.17 to 2.41; 1 RCT; 102 women; low-quality evidence). We are uncertain if there is a difference in OHSS between IVF and IUI + gonadotropins with 1 IVF to 2 to 3 IUI cycles (OR 6.86, 95% CI 0.35 to 134.59; 1 RCT; 207 women; very low-quality evidence); and there may be little or no difference in OHSS with 1 IVF to 1 IUI cycle (OR 1.22, 95% CI 0.36 to 4.16; 2 RCTs; 221 women; I2 = 0%; low-quality evidence). There may be little or no difference between IVF and IUI + CC (OR 1.53, 95% CI 0.24 to 9.57; 1 RCT; 102 women; low-quality evidence). We are uncertain if there is a difference in miscarriage rate between IVF and IUI + gonadotropins with 1 IVF to 2 to 3 IUI cycles (OR 0.31, 95% CI 0.03 to 3.04; 1 RCT; 207 women; very low-quality evidence); and there may be little or no difference with 1 IVF to 1 IUI cycle (OR 1.16, 95% CI 0.44 to 3.02; 1 RCT; 103 women; low-quality evidence). There may be little or no difference between IVF and IUI + CC (OR 1.48, 95% CI 0.54 to 4.05; 1 RCT; 102 women; low-quality evidence). In women pretreated with IUI + CC IVF may improve LBR compared with IUI + gonadotropins (OR 3.90, 95% CI 2.32 to 6.57; 1 RCT; 280 women; low-quality evidence). Assuming 22% LBR with IUI + gonadotropins, LBR would be 39% to 65% with IVF. IVF may improve CPR compared with IUI + gonadotropins (OR 14.13, 95% CI 7.57 to 26.38; 1 RCT; 280 women; low-quality evidence). Assuming 30% CPR with IUI + gonadotropins, CPR would be 76% to 92% with IVF. AUTHORS' CONCLUSIONS: IVF may improve LBR over unstimulated IUI. Data should be interpreted with caution as overall evidence quality was low.

Optimism, Resilience, and Infertility-Specific Stress during Assisted Reproductive Technology / El optimismo, la resiliencia y el estrés especifico por infertilidad en la aplicación de las técnicas de reproducción asistida

Background: Infertility generates high levels of stress to women. The aim was to explore optimism and resilience among women undergoing assisted reproductive technology (ART). Method: Participants were recruited in a private fertility clinic. The sample consisted of 229 women under medical treatment for fertility who completed the following self-report instruments: a sociodemographic and clinical questionnaire, Resilience Scale (RS), Life Orientation Test (LOT-R), Perceived Stress Scale (PSS), and STAI State and STAI Trait. Results: Our data revealed that high resilience levels were associated with a reduced psychological stress (β = .02, p < .001, 95% CI [.34, .13]). A significant negative correlation between perceived stress and resilience (r = -.320, p = .001) was found. Conclusion: The findings highlight the protective mediating role of resilience when women are confronted with the negative effects of infertility diagnosis and assisted reproductive technology (ART), and therefore the potential utility of resilience to reduce infertility-specific stress. (AU)

Antecedentes: La infertilidad genera un nivel de estrés elevado en la mujer. El objetivo era explorar el optimismo y la resiliencia en las mujeres que se someten a técnicas de reproducción asistida (TRA). Método: Los participantes fueron reclutados en una clínica de fertilidad privada. La muestra estuvo conformada por 229 mujeres en tratamiento médico para de fertilidad que cumplimentaron los siguientes instrumentos de autoinforme: cuestionario sociodemográfico y clínico, Escala de Resiliencia (RS), Test de Orientación a la Vida (LOT-R), Escala de Estrés Percibido (PSS) y STAI Estado y Rasgo. Resultados: Los datos revelaron que un nivel elevado de resiliencia se asociaba con menos estrés psicológico (β = .02, p < .001, IC del 95 % [.34, .13]). Se obtuvo una correlación negativa significativa entre estrés percibido y resiliencia (r = -.320, p = .001). Conclusión: Los hallazgos resaltan el papel mediador protector de la resiliencia cuando las mujeres se enfrentan a los efectos negativos del diagnóstico de infertilidad y las técnicas de reproducción asistida (TRA) y, por lo tanto, la utilidad potencial de la resiliencia para reducir el estrés específico de la infertilidad. (AU)

Evidence-based complementary and alternative medicine conventional surgery combined with traditional Chinese medicinal retention enema for tubal obstructive infertility: A systematic review and meta-analysis.

BACKGROUND: Chinese medicinal retention enemas have gradually attracted the attention of clinicians as an alternative approach for tubal obstructive infertility. The purpose of this study was to investigate the efficacy and safety of conventional surgery combined with traditional Chinese medicinal retention enemas for the treatment of tubal obstructive infertility. MATERIALS AND METHODS: Eight electronic databases were searched from their inception to November 30, 2022. To assess the efficacy and safety of different treatments, following outcomes were measured: clinical pregnancy rate, clinical total effective rate, incidence of ectopic pregnancy, the improvement of Traditional Chinese Medicinal (TCM) symptoms, the improvement of the signs of obstructive tubal infertility and side effects. RESULTS: A total of 23 Randomized Controlled Trials (RCTs) with 1909 patients met the inclusion criteria. The pooled results showed a higher pregnancy rate in the experimental group than in the control group (RR 1.75, 95% CI [1.58, 1.94], Z = 10.55, P<0.00001). The clinical total effective rate in the experimental group was higher than that in the control group (RR 1.28, 95% CI [1.23, 1.34], Z = 11.07, P<0.00001). The incidence of ectopic pregnancy in the experimental group was lower than that in the control group (RR 0.40, 95% CI [0.20, 0.77], Z = -2.73, P = 0.01). CONCLUSION: Based on current evidence, we concluded that conventional surgery combined with traditional Chinese medicinal retention enema for tubal obstructive infertility was superior to conventional surgery alone in improving the clinical pregnancy rate, improving clinical total effective rate, improving TCM symptoms, improving the signs of obstructive tubal infertility and lowering the incidence of ectopic pregnancy. However, further clinical trials with high-quality methodologies need to be conducted.

Phytochemicals: Alternative for Infertility Treatment and Associated Conditions.

Infertility and obstetric complications have become global health issues in the past few years. Infertility is defined as the inability of a couple to conceive even after twelve months or more of regular and unprotected intercourse. According to WHO data published in the year 2020, 186 million people have infertility globally. Factors leading to infertility are variable in both males and females. But some common factors include smoking, alcohol consumption, obesity, and stress. Various synthetic drugs and treatment options are available that are effective in treating infertility, but their prolonged usage produces various unwanted adverse effects like hot flashes, mood swings, headaches, and weight gain. In extreme cases, these may also lead to the development of anxiety and depression. Herbal remedies have gained a lot of popularity over the years, and people's inclination toward them has increased all over the world. The prime reason is that these show significant therapeutic efficacy and have fewer side effects. The therapeutic efficacy of plants can be attributed to the presence of diverse phytochemical classes of constituents like alkaloids, flavonoids, and volatile oils. These secondary metabolites, or phytomolecules, can be used to develop herbal formulations. The review highlights the applications and mechanisms of action of various phytochemicals for treating infertility. Also, it focuses on the various future prospects associated with it.

Impact of preconception thyrotrophin on obstetric outcomes in the fertile population.

INTRODUCTION: There is evidence that subclinical hypothyroidism is associated with infertility, miscarriage and obstetric complications. However, there is controversy regarding the optimal TSH value in women seeking pregnancy. Current guidelines recommend that hypothyroid women with levothyroxine replacement who are planning pregnancy should optimise the dose of levothyroxine to achieve thyrotrophin (TSH) levels <2.5 mU/l, since these requirements increase in pregnancy, thus reducing the risk of TSH elevation during the first trimester. In women with infertility, who undergo highly complex treatments and have positive thyroid autoimmunity, values of TSH <2.5 mU/l prior to fertility treatment are suggested. Although this is a different population, these «optimal¼ TSH levels were also extended to euthyroid women without evidence of infertility, who are seeking pregnancy. OBJECTIVES: Determine whether preconception TSH levels between 2.5 and 4.64 mIU/l are associated with adverse obstetric outcomes in euthyroid women. MATERIALS AND METHODS: Retrospective cohort study. We evaluated 3265 medical records of pregnant women aged 18-40 years, euthyroid (TSH 0.5-4.64 mU/ml), with TSH measurement at least one year before gestation. 1779 met inclusion criteria. The population was divided according to categories: TSH 0.5-2.4 mU/l (optimal) and TSH 2.5-4.6 mU/l (suboptimal). Information on maternal and fetal obstetric outcomes was collected from each group. RESULTS: We found no statistical difference in the occurrence of adverse obstetric events between the two groups. There was also no difference when adjusting for thyroid autoimmunity, age, body mass index, previous diabetes and previous arterial hypertension. CONCLUSION: Our results suggest that the reference range of TSH used in the general population could be used in women seeking pregnancy, even in the presence of thyroid autoimmunity. Treatment with levothyroxine should be considered only in patients with special situations.

Trends in clomiphene citrate and gonadotropins use in women with infertility between 2010 and 2017: A population-based study in France.

PURPOSE: To describe temporal trends and assess factors associated with changes in the prescription of clomiphene citrate and gonadotropins between 2010 and 2017 in women with infertility aged 18-50 from metropolitan France. METHODS: 6321 prevalent women from a representative sample of the national medico-administrative database were identified. We performed a Cochran-Armitage trend test and calculated the rate ratios. A Poisson regression was used to derive the incidence rate ratios, for each treatment class. RESULTS: The prevalence rate and incidence rate of clomiphene citrate use significantly decreased by 20% (RR 0.80: 95% CI 0.71-0.90) and 23% (RR 0.77: 95% CI 0.66-0.89), respectively. Its initiation was higher in all age groups compared to the reference (18-24 years), with a downward gradient. It was also higher when the density of gynaecologists was higher and in disadvantaged areas. The prevalence rate and incidence rate of gonadotropin use increased by 11% (RR 1.11: 95% CI 1.01-1.22) and 33% (RR 1.33: 95% CI 1.14-1.55) respectively. Gonadotropin initiation was highest in the 31-35 age group, but it was also higher in the 25-30 and 36-40 age groups at a similar level (reference 18-24 years). Its initiation was higher when the density of gynaecologists was higher, but not associated with social deprivation. CONCLUSION: Our results showed an increase in gonadotropin use for infertility treatment in France during the 2010-2017 period and a decrease in clomiphene citrate use. Further work should be undertaken to analyse the use of these drugs in relation to women's care pathways.

Drug substitution and adjuvant therapy in patients with genetics related infertility: A review.

With the in-depth study of the human genome and the increasing popularity of gene sequencing, it has been gradually confirmed that genetics can play a crucial role in infertility. To provide references for clinical treatment, we have focused on genes and drug therapy for genetic infertility. This review recommends adjuvant therapy and drug substitution. Examples of these therapies include antioxidants (such as folic acid, vitamin D, vitamin E, inositol, coenzyme Q10 etc.), metformin, anticoagulants, levothyroxine, dehydroepiandrosterone, glucocorticoids, and gonadotropins etc. Based on the pathogenesis, we provide an overview of the current knowledge, including randomized controlled trials and systematic reviews, and predict potential target genes and signaling pathways, proposing possible future strategies for the use of targeted drugs to treat infertility. Non-coding RNAs are anticipated to become a novel target for the treatment of reproductive illnesses since they have a significant role in controlling the occurrence and development of reproductive diseases.

Rescuing fertility during COVID-19 infection: exploring potential pharmacological and natural therapeutic approaches for comorbidity, by focusing on NLRP3 inflammasome mechanism.

The respiratory system was primarily considered the only organ affected by Coronavirus disease 2019 (COVID-19). As the pandemic continues, there is an increasing concern from the scientific community about the future effects of the virus on male and female reproductive organs, infertility, and, most significantly, its impact on the future generation. The general presumption is that if the primary clinical symptoms of COVID-19 are not controlled, we will face several challenges, including compromised infertility, infection-exposed cryopreserved germ cells or embryos, and health complications in future generations, likely connected to the COVID-19 infections of parents and ancestors. In this review article, we dedicatedly studied severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virology, its receptors, and the effect of the virus to induce the activation of inflammasome as the main arm of the innate immune response. Among inflammasomes, nucleotide oligomerization domain-like receptor protein, pyrin domain containing 3 (NLRP3) inflammasome pathway activation is partly responsible for the inflicted damages in both COVID-19 infection and some reproductive disorders, so the main focus of the discussion is on NLRP3 inflammasome in the pathogenesis of COVID-19 infection alongside in the reproductive biology. In addition, the potential effects of the virus on male and female gonad functions were discussed, and we further explored the potential natural and pharmacological therapeutic approaches for comorbidity via NLRP3 inflammasome neutralization to develop a hypothesis for averting the long-term repercussions of COVID-19. Since activation of the NLRP3 inflammasome pathway contributes to the damage caused by COVID-19 infection and some reproductive disorders, NLRP3 inflammasome inhibitors have a great potential to be considered candidates for alleviating the pathological effects of the COVID-19 infection on the germ cells and reproductive tissues. This would impede the subsequent massive wave of infertility that may threaten the patients.

Granulosa tumor: two spontaneous pregnancies after combined medico-surgical treatment: case report and review of the literature.

BACKGROUND: Granulosa tumor is a rare tumor that arises from the mesenchyme and the sexual cord of the ovary. The prognosis is generally excellent, and treatment is mainly based on surgery, followed by chemotherapy depending on the extension of the disease. However, "the obstetrical prognosis" is compromised. CASE PRESENTATION: We report the case of a 32-year-old Caucasian patient who was diagnosed during a primary infertility assessment with an ultrasound image of a 39 mm organic left ovarian cyst confirmed on pelvic magnetic resonance imaging with infiltration of the uterosacral space. Tumor markers, including cancer antigen 125, alpha fetoprotein, and ß-human chorionic gonadotropin, were normal. Histological study of biopsies of the ovarian lesion taken during exploratory laparoscopy confirmed the diagnosis of adult granulosa tumor. After a normal extension assessment including a thoracoabdominopelvic computed tomography scan and a positron emission tomography scan, the patient underwent complete conservative surgery and the disease was classified as stage Ic. Three cycles of adjuvant chemotherapy according to the "BEP" protocol combining bleomycin, etoposide, and cisplatin were performed after oocyte cryopreservation. After a 5-year follow-up period, the patient had no sign of tumor progression and had two spontaneous pregnancies, the first occurring 3 months after the end of chemotherapy and the second 14 months later. CONCLUSION: Granulosa cell tumor remains a rare tumor whose management considerably compromises fertility and reduces the chances of having a spontaneous pregnancy. The particularity of our observation is that the diagnosis of the granulosa tumor was made following a primary infertility assessment and that the patient had two spontaneous pregnancies 3 months after the end of a medico-surgical treatment known to be very gonadotoxic.

Hypogonadism After Treatment for Medulloblastoma: Results From the SJMB03 Trial of Risk-Adapted Radiation Therapy.

PURPOSE: Our purpose was to estimate the cumulative incidence (CI) of hypogonadism in a cohort of pediatric patients treated for medulloblastoma with surgery, risk-adapted craniospinal irradiation, and dose-intensive chemotherapy. METHODS AND MATERIALS: Children and adolescents (n = 156) treated between 2003 and 2013 were evaluated for evidence of hypogonadism and infertility. Clinical information and mean radiation dose to the hypothalamus and gonads and cumulative doses of chemotherapy agents were recorded to estimate CI of hypogonadism and infertility with competing risks. RESULTS: The 5-year CI of hypogonadism was 71.25% (±6.76%) for women and 6.48% (±3.16%) for men (P < .0001) and 50.00% (±9.70%) for puberty age and 28.99% (±5.05%) for prepuberty age at treatment (P = .0068). The 5-year CI by gonadal radiation dose exposure (GRDE) was 61.11% (±12.13%) for high (>2 Gy), 61.18% (±12.92%) for intermediate (1-2 Gy), and 21.97% (±4.76%) for low (<1 Gy) (P < .0001). Sex, puberty status, GRDE, interval from treatment to puberty, and vincristine dose were associated with hypogonadism. Hypogonadism in female sex was highly correlated with GRDE, and dose to hypothalamus was significant when included in multivariable models or when used in models restricted to patients treated after the age of puberty. CI of infertility at 10 years was 55.36% (±14.07%) for women and 23.53% (±10.64%) for men (P = .0389) in a sample of 33 patients. CONCLUSIONS: In the setting of intensive chemotherapy, low-dose gonadal radiation exposure has a significant effect on gonadal function. Women and those achieving age of puberty at time of radiation therapy have a higher risk of hypogonadism. GRDE > 2 Gy was associated with hypogonadism for all groups and >1 Gy in prepubertal patients. Hypothalamus dose was significant when included in multivariable models that included postpubertal patients and those with lower GRDE.

Updates on Molecular Targets and Epigenetic-Based Therapies for PCOS.

Polycystic ovarian syndrome (PCOS) can cause infertility in females due to hyperandrogenism and neuroendocrine abnormalities. The aim of this study is to decipher the impact of endocrine variables, hyperandogenism, insulin resistance, oxidative stress, and dietary conditions in PCOS conditions, subsequently to depict the role of epigenetic factors relative to phenotypic manifestations in PCOS conditions. We have reviewed several metabolic milieus pertinent to PCOS conditions. Comparative efficacies of various PCOS therapies, and recent clinical recommendations for the effective management of PCOS and role of metabolic/endocrine variables in PCOS conditions were described. Comparative therapeutic effects were vividly delineated according to the variable pathophysiology and internal variables during PCOS syndrome on the female body through the formation of cascade of endocrine pathology, which affects working capacity and fosters redox stress-induced cardiovascular, neural, and liver abnormalities. GLP-1 agonists, insulin sensitizers (metformin), and diet and exercise regimens efficacy were explained in enhancing the fertility outcomes among the overweight or obese females with PCOS. Comprehensive appraisal of DNA methylation as epigenetic changes and the manifestations of methylated genes in PCOS conditions were discussed particularly to screen novel molecular targets for developing efficient diagnostic indicators for predicting PCOS risk or its progression. Due to the reversible nature of epigenetic modifications, it is possible to screen the "druggable" regions to target or to correct abnormalities in the gene expression subsequently to develop chromatin-modifying therapies against PCOS.

Low-dose clomiphene citrate does not reduce implantation and live birth rates in otherwise unstimulated modified natural cycle IVF-retrospective cohort study.

RESEARCH QUESTION: Does antioestrogen effect of clomiphene citrate (CC) on the endometrium reduce implantation and thereby decrease pregnancy and live birth rate per transferred embryo? METHODS: In this cohort, unstimulated IVF cycles modified with clomiphene citrate (CC-NC-IVF) and unstimulated, natural IVF cycles (NC-IVF) conducted between 2011 and 2016 were included. CC was applied in a dosage of 25mcg per day, starting on cycle day 7 until ovulation trigger day. Primary outcomes were clinical pregnancy rate, defined as amniotic sac visible in ultrasound, and live birth rate per transferred embryo. Miscarriage rate calculated as amniotic sac not ending in a live birth was secondary outcome. A modified mixed-effect Poisson regression model was applied, and adjustments were made for female age, parity, type and cause of infertility. Additionally, stratification by parity and age was performed. RESULTS: Four hundred and ninety-nine couples underwent a total of 1042 IVF cycles, 453 being NC-IVF and 589 being CC-NC-IVF cycles. Baseline characteristics of both groups did not differ. Addition of CC did neither decrease clinical pregnancy rate (aRR 0.86; 95% CI 0.67-1.12) nor live birth rate per transferred embryo (aRR 0.84; 95% CI 0.62-1.13) in comparison with NC-IVF. Miscarriage rate did not differ between CC-NC-IVF and NC-IVF (aRR 0.95; 95% CI 0.57-1.57). CONCLUSION: Low-dose CC does not reduce pregnancy or live birth rate per transferred embryo. It can be used in infertility treatment without negatively affecting the endometrium and implantation.

Nasturtium officinale L. and metformin alleviate the estradiol- induced polycystic ovary syndrome with synergistic effects through modulation of Bax/Bcl-2/p53/caspase-3 signaling pathway and anti-inflammatory and anti-oxidative effects.

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women, which is associated with metabolic, hereditary and hormonal disorders. The aim of this study was to evaluate the therapeutic effects of Nasturtium officinale L. (N. officinale) on biochemical and molecular parameters in estradiol-induced PCOS in rats. Seventy Wistar rats in 7 groups (n = 10) were randomly assigned to normal (NC), PCOS, metformin (MET - 300 mg/kg), N. officinale (50 and 100 mg/kg) and co-treatment with MET and N. officinale groups. After 21 days of treatment, biochemical parameters levels of estrogen, LH and FSH along with serum levels of (IL-6 and IL-1ß cytokines) and serum antioxidant parameters (enzymatic activity of catalase and superoxide dismutase) were measured. Finally, by measuring the expression of apoptosis related genes (Bax/Bcl-2/p53/caspase-3) with the help of real-time PCR and the expression of p53 with the help of immunohistochemistry in ovarian cells. N. officinale modulates hormones through its hypothalamic-pituitary-gonadal pathway with its synergistic effects along with MET. Also, in co-treatment groups (MET and N. officinale), the activity of serum antioxidant enzymes increased and also the serum level of inflammatory cytokines decreased. N. officinale, along with MET, amplified the Bax/Bcl2/p53/caspase-3 pathways, which eventually increased the number of p53 positive cells. These findings indicate that N. officinale extract along with MET can improve the physiological function of the ovaries in PCOS-induced disorders. PRACTICAL APPLICATIONS: Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women, which is associated with metabolic, hereditary and hormonal disorders. The extract of Nasturtium officinale L. was able to intensify mitochondrial apoptotic pathway in cystic follicles and prevent their formation. It seems that pro-drugs containing N. officinale along with effective commercial drugs in PCOS can help ovulation and fertility in woman with this disease.

Pharmacotherapy of infertility in Ghana: Why do infertile patients discontinue their fertility treatment?

BACKGROUND: Globally, millions of people of reproductive age experience infertility. With that notwithstanding, most infertile patients undergoing pharmacotherapy withdraw from treatment before achieving the desired outcome. The reasons for their withdrawal, particularly in sub-Saharan Africa, have not been well examined, hence the need for this study. OBJECTIVES: The aim of the study was to examine why infertile patients discontinue pharmacotherapy prior to achieving conception. METHODS: The study employed an exploratory qualitative design. Purposive sampling technique was used to recruit subjects into the study. Twenty infertile patients (fourteen females and six males) who discontinued their treatment, and eight attending health professionals who provided direct care to these patients were interviewed. Telephone and face-to-face interviews were conducted using a semi-structured interview guide. The data collected were transcribed, coded, and generated into themes using thematic content analysis. RESULTS: The major reasons for discontinuation of infertility treatment included lack of support from male partners, seeking alternative treatment, unmet outcome, poor medical services, distance, stigmatization, and relocation. CONCLUSIONS: Patients and healthcare personnel shared both similar and diverse views on reasons for discontinuation of infertility treatment that reflect situations in a typical African setting, most of which are not reported in existing studies. The outcome of this study will provide insight for fertility therapists and policy makers in designing appropriate measures to facilitate maximum compliance and improvement in treatment outcome.

Comparison of amphotericin B deoxycholate in combination with either flucytosine or fluconazole, and voriconazole plus flucytosine for the treatment of HIV-associated cryptococcal meningitis: a prospective multicenter study in China.

BACKGROUND: The most appropriate alternative to induction therapy for HIV-associated cryptococcal meningitis (CM) remains unclear when standard treatment is unavailable, inaccessible, intolerable, or ineffective. METHODS: A prospective, multi-centre cohort study was conducted to analyze the data of 156 HIV-infected patients with CM who were treated with amphotericin B deoxycholate (AmB-D) + flucytosine (5FC), voriconazole (VCZ) + 5FC, or AmB-D + Fluconazole (Flu) as induction regimens. Clinical efficacy, cumulative mortality, and adverse effects were compared among the three treatment groups. RESULTS: Fewer deaths occurred by week 4 and week 10 among patients receiving AmB-D + 5FC than among those receiving AmB-D + Flu [4 (5.1%) vs. 8 (16.0%) deaths by week 4; hazard ratio, 1.8; 95% confidence interval [CI], 1.0 to 3.3; p = 0.039; and 8 (10.3%) vs. 14 (28.0%) deaths by week 10; hazard ratio, 1.8; 95% CI, 1.1 to 2.7; p = 0.008, respectively]. AmB-D plus 5FC was found to result in significantly higher rates of cerebrospinal fluid (CSF) culture sterility (57.6% vs. 34% by week 2; 87.9% vs. 70% by week 10; p < 0.05 for both comparisons). However, the differences in CSF culture sterility and mortality between the VCZ + 5FC group and the AmB-D + 5FC group were not statistically significant. VCZ plus 5FC had a significantly advantageous effect on the incidence of new AIDS-defining illness and length of hospital stay, compared with AmB-D plus 5FC. Laboratory adverse events (grade 3 or 4), such as severe anemia, were less frequent with VCZ + 5FC use than with AmB-D combined with 5FC or Flu use. CONCLUSION: Our results suggest that AmB-D combined with 5FC remains the more efficacious induction regimen compared to AmB-D plus Flu, and that VCZ + 5FC might be a potential alternative when the standard regimen is not readily available, accessible, tolerated, or effective. CLINICAL TRIALS: Registration number, ChiCTR1900021195. Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362 .

Image Analysis of TVCDS in Infertile Patients with Polycystic Ovary Syndrome.

In order to analyze and examine the TVCDS images of infertile patients, this paper conducted an in-depth study based on the symptoms of polycystic ovary syndrome. Through the sample size estimation method, mathematical analysis, and other methods, the image examination of the polycystic ovary in TVCDS was successfully analyzed. 86 cases of infertile patients with PCS were divided into a control group treated with clomiphene alone and an observation group treated with clomiphene combined with TCM periodic therapy, with 43 patients in each group. The therapeutic effects of the two groups were compared and analyzed. Results show that the treatment effective rate and pregnancy success rate of the observation group were 95.35% and 88.37%, respectively, and those of the control group were 83.72% and 76.74%, respectively. The difference between the two groups was statistically significant (P < 0.05). It was understood that the main pathogenesis of polycystic ovary syndrome is the abnormal balance of kidney, qi, and blood meridians. Thus, the balance of kidney-anemone-chong Ren-uprisal is broken and the result is infertility symptoms or irregular menstruation. After a study on TVCDS in infertile patients, it was observed that the levels of progesterone (P) and luteinizing hormone (LH) in patients with irregular menstruation were significantly increased. The increase was higher than that in the control group, with an overall negative rate of 4.00%, compared with 18.00% of the control group, showing a significant difference. It also indicates that TVCDS image examination has a very significant effect on improving menstrual irregularities and reducing the incidence of adverse reactions.

Nonpharmacological Interventions for the Management of Testosterone and Sperm Parameters: A Scoping Review.

PURPOSE: Testosterone replacement and associated pharmacologic agents are effective strategies to treat male hypogonadism; however, nutraceutical agents and lifestyle modification approaches have gained medical interest. The purpose of this scoping review is to highlight the evidence (or lack thereof) of nutraceuticals and lifestyle modification approaches in the management of testosterone levels and sperm parameters. METHODS: A scoping review of nonpharmacologic interventions (supplements, herbal medicines, diets, sleep, and exercise) with the potential to improve male health was undertaken to elucidate changes in testosterone levels and sperm parameters in men with hypogonadism or infertility compared with healthy patients. FINDINGS: A multitude of nutraceuticals and functional nutrients are purported to stimulate testosterone production; however, only a select few have had promising results, such as zinc, vitamin D (in case of hypovitaminosis D), l-arginine, mucuna, and ashwagandha, based on well-controlled randomized clinical trials of men with low testosterone levels and related problems. Except for l-arginine, these natural agents, as well as tribulus and ω3 fatty acids, can improve some degree of sperm parameters in infertile men. Before implementing these nutraceutical agents, adequate sleep, exercise, and weight loss in patients with obesity are imperative. The effects of nonpharmacologic interventions on testosterone levels are modest and hence do not directly translate into clinical benefits. Correspondingly, androgen receptor content, but not endogenous androgens, has been regarded as the principal factor in muscle hypertrophy. IMPLICATIONS: A limited number of supplements and herbal medicines can be considered as adjunctive approaches in the management of testosterone levels and sperm parameters, primarily in men with low testosterone levels and infertility, whereas most nonpharmacologic supplements appear to lack evidence. Although proper physical exercise, sleep, and diet are indisputable approaches because of the general benefits to health, the use of nutraceuticals, if considered, must be personalized by physicians and/or registered dietitians.

Persea americana seed extract restores defective sperm quality and biochemical parameters relevant to reproduction in male wistar rats treated with cyclosporine A.

Studies have shown that some drugs impair spermatogenesis, thereby causing infertility. Thus, this study aims at investigating the effect of Persea americana seed extract on the male reproductive system in cyclosporine-induced rats. Thirty male albino rats were randomly divided into five groups; all groups were induced with cyclosporine except the control group. Group 3 was treated with 10 mg/kg of lisinopril, groups 4 and 5 received 50 and 100 mg/kg of PAE, respectively. The experiment lasted for 7 days. The antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)], and arginase activities were evaluated, nitric oxide (NO) and malondialdehyde (MDA) level of the penile tissue homogenate were determined with serum hormonal (follicle stimulating hormone, luteinizing hormone and testosterone) concentration and sperm quality. This study showed that cyclosporine induction caused a significant (p < .05) decrease in the SOD, CAT, sperm quality, NO, and hormonal level as compared to the control group, with a simultaneous increase in arginase activity and MDA level. However, treatment with PAE and lisinopril significantly (p < .05) increase antioxidant enzyme activities, sperm quality, NO, and serum hormonal level, with a decrease MDA level and arginase activity when compared with cyclosporine-induced group. This study showed that P. americana seed extract could be useful in the management of hormonal disruption resulting from oxidative stress in male folks. PRACTICAL APPLICATIONS: Some pharmaco-agents have been reported to alter spermatogenesis, thereby causing infertility. Plants represent natural resources use in the management of several human diseases from time immemorial. Persea americana seed is a part of the fruit that most people do throw away after consuming the edible portion of the fruit. However, the therapeutic and pharmacological activities of P. americana seed have been reported. Therefore, this study sought to investigate the effects of P. americana seed extract on cyclosporine-induced reprotoxicity.