Treatment Of Female Infertility Research Articles

Network pharmacology-based prediction and verification of the mechanism for Bushen Chengyun granule on low endometrial receptivity

Abstract Objective Bushen Chengyun granule (BCG) is an empirical treatment for female infertility (FI) caused by low endometrial receptivity (LER) involving a poorly understood mechanism. In this study, network pharmacology was used to explore the potential therapeutic mechanism of BCG on FI caused by LER. Methods The corresponding herb targets were obtained by conducting a search in the Traditional Chinese Medicine Systems Pharmacology Database and PubMed-reported literature. Disease targets were obtained from the following databases: Comparative Toxicogenomics Database, Human Phenotype Ontology, and Therapeutic Target Database. Treatments for LER using BCG have used target matching (BCG – LER target). Then, the predicted targets were uploaded to the Search Tool for the Retrieval of Interacting Genes/Proteins database for gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Furthermore, triptorelin acetate for injection + menotrophin + chorionic gonadotropin for injection were used to establish a mouse model of blastocyst implantation disorder and to evaluate the in vivo effect of BCG on blastocyst implantation. Results Overall, 156 bioactive chemical components and 1092 targets of BCG were identified. The results indicated that 482 biological processes (FDR Conclusions These findings reveal the potential therapeutic mechanism of BCG for female infertility involves low endometrial receptivity, which should be evaluated further.

Role of Laparoscopic Surgery in the Management of Female Infertility at the Department of Gynecology of Hôpital du Mali

Infertility is a socio-cultural drama in Africa, especially in Mali and remains difficult for couples to overcome. Laparoscopy, also called minimally invasive surgery or keyhole surgery, is an operative technique that permits to explore the pelvis and perform an appropriate therapeutic procedure. The objective of our work was to assess the role of laparoscopic surgery in the treatment of female infertility at Hopital du Mali. It was a retrospective descriptive study that was conducted over a period of 5 years (January 2013 to December 2018). Any patients followed for infertility and who underwent laparoscopic surgery in the gynecology department over a period of two (2) years were included. The outcome of laparoscopic surgery was evaluated in terms of conception of pregnancy. We had collected 103 infertile patients out of 2984, with a frequency of 3.45%. The mean age of our patients was 30.2 years. Housewives and out-of-school women accounted for 68.93% and 54.37% respectively. Nulligravida represented 41.75%. Regarding infertility, it was primary in 41.75% and secondary in 58.25%, with an average duration of 6.2 years. Systematic chlamydial serology was positive in 62.14% of our patients. Hysterosalpingography (HSG) revealed bilateral tubal obstruction in 53.33% of cases. Laparoscopy found tubal adhesions in 97.80% of cases. Adhesiolysis was the main procedure performed with 84.47% bilateral tubal patency achieved in the methylene blue test. Among our patients who had contracted a pregnancy (22.99%), 85% had carried their pregnancies to term. Tubal damage was the main cause of infertility. Adhesiolysis remains the main laparoscopic procedure for treatment.

Traditional Chinese Medicine Treatment Associated with Female Infertility in Taiwan: A Population‐Based Case‐Control Study

Background Traditional Chinese medicine (TCM) for the treatment of female infertility remains ambiguous. The aim of the present case-control study was to examine the association between TCM treatment and successful pregnancy among infertile women. Methods This population-based case-control study included the data from 2,627 infertile women with successful pregnancy and 2,627 infertile women without successful pregnancy using datasets from the Longitudinal Health Insurance Database 2000 of the National Health Insurance Research Database during 2000–2010. The odds ratios (ORs) and 95% confidence intervals (CIs) for the relationship between TCM use and successful pregnancy in infertility women were estimated using logistic regression. Results Patients who received TCM treatment significantly increased in successful pregnancy (OR = 1.48; 95% CI = 1.31–1.66), compared with patients without TCM. Si-Wu-Tang (OR = 4.25; 95% CI = 2.18, 8.30), Gui-Zhi-Fu-Ling-Wan (OR = 3.27; 95% CI = 2.13, 5.02), and Jia-Wei-Xiao-Yao-San (OR = 3.17; 95% CI = 2.35, 4.28) were the TCM agents that were most strongly associated with successful pregnancy among infertile women. Conclusions Our study findings indicate that TCM is associated with higher likelihood of successful pregnancy in infertile women, which is worthy of further investigation by randomized control trial.

Progress on Therapy of Infertility by Integrated Traditional Chinese and Western Medicine

Infertility is one of the difficult complicated diseases. Many couples suffer from it. The pathogenesis is very complicated. The imbalance or lesson of any link of the reproductive system can cause infertility. This paper summarizes the treatment of female infertility by integrated Traditional Chinese Medicine (TCM) and Western Medicine (WM) which can not only improve the ovulation rate and pregnancy rate, but also decrease the complications. The effects are better than that by TCM or WM only. Therefore, the coupling method is worth to be used widely in clinical practice.

Advances in human primordial follicle activation and premature ovarian insufficiency.

In women, the non-growing population of follicles that comprise the ovarian reserve is determined at birth and serves as the reservoir for future fertility. This reserve of dormant, primordial follicles and the mechanisms controlling their selective activation which constitute the committing step into folliculogenesis are essential for determining fertility outcomes in women. Much of the available data on the mechanisms responsible for primordial follicle activation focuses on a selection of key molecular pathways, studied primarily in animal models, with findings often not synonymous in humans. The excessive induction of primordial follicle activation may cause the development of premature ovarian insufficiency (POI), a condition characterised by menopause before age 40 years. POI affects 1-2% of all women and is accompanied by additional health risks. Therefore, it is critical to further our understanding of primordial follicle activation in order to diagnose, treat and prevent premature infertility. Research in primordial follicle activation has focused on connecting new molecules to already established key signalling pathways, such as phosphatidylinositol 3-Kinase (PI3K) and mammalian target of rapamycin (mTOR). Additionally, other aspects of the ovarian environment, such as the function of the extracellular matrix, in contributing to primordial follicle activation have gained traction. Clinical applications are examining replication of this extracellular environment through the construction of biological matrices mimicking the 3D ovary, to support follicular growth through to ovulation. This review outlines the importance of the events leading to the establishment of the ovarian reserve and highlights the fundamental factors known to influence primordial follicle activation in humans presenting new horizons for female infertility treatment.

In vitro fertilization outcome in women with endometrial tuberculosis and tubal tuberculosis

Purpose: To evaluate in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) outcome in women with genital tuberculosis (GTB).Methods: One hundred and fifty-five women with genital tuberculosis constituted the study group (Group A), consisting of 25 patients with endometrial tuberculosis (Group A1) and 130 patients with tubal tuberculosis (Group A2). Women with non-tuberculous tubal infertility were matched by age and study period served as controls (Group B).Results: Patients with GTB had significantly reduced endometrial thickness, high-quality embryos rate, implantation rate as compared with controls (p < .05), no differences were found in other pregnancy parameters. In addition, the endometrial thickness, fertilization rate, high-quality embryos rate and implantation rate were also significantly lower in women with endometrial tuberculosis as compared with controls. And the cumulative pregnancy rate in endometrial tuberculosis was significantly decreased compared with tubal tuberculosis and controls (p < .05). However, IVF/ICSI pregnancy outcomes in patients with tubal tuberculosis showed no difference as compared with controls (p > .05). Also, rates of miscarriage, preterm birth, obstetrical complications, and neonatal problems did not differ among three groups.Conclusions: In conclusion, IVF/ICSI-ET remains the most optimal method for the treatment of female infertility associated with tubal tuberculosis. However, patients with endometrium tuberculosis showed significantly reduced fertilization, implantation and cumulative pregnancy rates.

Using Mesenchymal Stem Cells to Treat Female Infertility: An Update on Female Reproductive Diseases.

Female infertility impacts the quality of life and well-being of affected individuals and couples. Female reproductive diseases, such as primary ovarian insufficiency, polycystic ovary syndrome, endometriosis, fallopian tube obstruction, and Asherman syndrome, can induce infertility. In recent years, translational medicine has developed rapidly, and clinical researchers are focusing on the treatment of female infertility using novel approaches. Owing to the advantages of convenient samples, abundant sources, and avoidable ethical issues, mesenchymal stem cells (MSCs) can be applied widely in the clinic. This paper reviews recent advances in using four types of MSCs, bone marrow stromal cells, adipose-derived stem cells, menstrual blood mesenchymal stem cells, and umbilical cord mesenchymal stem cells. Each of these have been used for the treatment of ovarian and uterine diseases, and provide new approaches for the treatment of female infertility.

Impact of circadian rhythms on female reproduction and infertility treatment success.

In recent years, new studies have investigated the role and influence of sleep on female fertility and early pregnancy outcomes, providing a growing body of knowledge demonstrating how regulation by sleep of hormones are important to reproduction, and how disruptions in sleep, circadian rhythms, and genes regulating circadian rhythmicity can negatively impact fertility and early pregnancy outcomes. This review aims to summarize the most recent research on the relationship among circadian rhythms, fertility, and early pregnancy outcomes in women, and to explore possible fertility interventions. Recent studies have found altered levels of FSH, LH, and prolactin with sleep disturbance or circadian dysrhythmia. Disruption of circadian rhythms in the form of shift work, jet lag, and daylight savings time changes have been associated with poorer fertility and early pregnancy outcomes. Alterations in the expression of circadian rhythm-regulating circadian locomotor output cycles kaput (CLOCK) genes have been associated with decreased fertility and increased rates of miscarriage. Overall, undisrupted sleep and circadian rhythmicity appear to optimize fertility and early pregnancy outcomes and may play an important role in the success of fertility treatment.

Ethnopharmacological Survey of Medicinal Plants Used in the Traditional Treatment of Female Infertility in Fez Region, Morocco

An ethnopharmacological survey was carried out among 224 informants to collect the information on medicinal plants used for the traditional treatment of female infertility in the Fes, Meknes and Boulemane region. In total, 63 plant species belonging to 29 families were used against female infertility. The most frequently cited plants wereLavandula officinalis(26.33%),Mentha pulegium(13.83%),Mentha suaveolens(11.16%),Rosmarinus officinalis(10.71%) andPetroselinum sativum(8.03%). Furthermore, the present study represents a useful documentation for the preservation of this knowledge about medicinal plants and for the amelioration of women reproductive health.

Use of Growth Hormone in the IVF Treatment of Women With Poor Ovarian Reserve

Growth hormone (GH) has been used as an adjunct in the field of female infertility treatment for more than 25 years, although, apart from treating women with GH deficiency its role has not yet been clarified. Contributing to this lack of clarity is that several underpowered studies have been performed on women undergoing IVF treatment, with a previous “poor response” to ovarian stimulation, which have suggested a favorable outcome. Meta-analysis of randomized controlled trials has demonstrated a benefit for the use of the adjunct growth hormone, in comparison to placebo; with reductions in the duration of ovarian stimulation required prior to oocyte retrieval, with a greater number of oocytes collected, and improvements in many of the early clinical parameters with the use of GH. However, no benefit of an increased chance of a live birth with the use of growth hormone for the “poor responding” patient has been determined. Consequently the role of GH to treat a woman with a poor response to ovarian stimulation cannot be supported on the basis of the available evidence. However, the place for GH in the treatment of women undergoing IVF may yet still be determined, as it is also used, without firm evidence of benefit; for women with poor embryonic development, poor endometrial development and for women who do not conceive despite multiple embryo transfers (recurrent implantation failure).

Role of hystero-laparoscopy with chromopertubation as a diagnostic cum therapeutic tool in evaluation and treatment of female infertility

Role of hystero-laparoscopy with chromopertubation as a diagnostic cum therapeutic tool in evaluation and treatment of female infertility

Surrogacy as protection of men’s paternal rights

The paper presents the main problems of legal regulation of surrogacy in the Russian Federation. One of the main problems of this direction is the legislative deprivation of the rights of single men to paternity by means of this method. According to the current legislation, namely Federal law № 323 of article 55 of paragraph 3 and 9, the right to surrogacy is held by either a man and a woman who are married or a single woman who cannot bear or give birth to a child for medical reasons. According to the Constitution, all rights and freedoms of citizens are equal, so it is illegal and unfair to deprive unmarried men who want to have offspring as much as women and have every right to be good fathers. In addition, for the treatment of female infertility developed a variety of auxiliary medical reproductive technologies, a number of which should be used in the work with the «strong» half of humanity pre-creating the necessary legislative framework that allows for all the necessary medical manipulation. The paper presents data on fertility, mortality, use of IVF and surrogacy in the United States of America. A comparative analysis of U.S. statistical data with official Russian statistics. The issue of adoption was touched upon, as in 2011 fewer children were born in the United States from surrogate mothers, which may be due to the popularity of adoption and guardianship. The arguments that focus on the need for timely legislative solutions to legal issues of surrogacy are presented.

Worldwide decline of IVF birth rates and its probable causes.

With steadily improving pregnancy and live birth rates, IVF over approximately the first two and a half decades evolved into a highly successful treatment for female and male infertility, reaching peak live birth rates by 2001–2002. Plateauing rates, thereafter, actually started declining in most regions of the world. We here report worldwide IVF live birth rates between 2004 and 2016, defined as live births per fresh IVF/ICSI cycle started, and how the introduction of certain practice add-ons in timing was associated with changes in these live birth rates. We also attempted to define how rapid worldwide ‘industrialization’ (transition from a private practice model to an investor-driven industry) and ‘commoditization’ in IVF practice (primary competitive emphasis on revenue rather than IVF outcomes) affected IVF outcomes. The data presented here are based on published regional registry data from governments and/or specialty societies, covering the USA, Canada, the UK, Australia/New Zealand (combined), Latin America (as a block) and Japan. Changes in live birth rates were associated with introduction of new IVF practices, including mild stimulation, elective single embryo transfer (eSET), PGS (now renamed preimplantation genetic testing for aneuploidy), all-freeze cycles and embryo banking. Profound negative associations were observed with mild stimulation, extended embryo culture to blastocyst and eSET in Japan, Australia/New Zealand and Canada but to milder degrees also elsewhere. Effects of ‘industrialization’ suggested rising utilization of add-ons (‘commoditization’), increased IVF costs, reduced live birth rates and poorer patient satisfaction. Over the past decade and a half, IVF, therefore, has increasingly disappointed outcome expectations. Remarkably, neither the profession nor the public have paid attention to this development which, therefore, also has gone unexplained. It now urgently calls for evidence-based explanations.

Impact of infertility and infertility treatments on quality of life and levels of anxiety and depression in women undergoing in vitro fertilization

This study aims to evaluate levels of anxiety and depression in women, correlated with infertility per se and with infertility treatments, highlighting predictors of higher levels of distress. Two validated standardized questionnaires, the Hospital Anxiety and Depression Scale (HADS) and the Fertility Quality of Life (FertiQoL), were administered to 89 women both before their first cycle of infertility treatment and again at the end of the ovarian stimulation for in vitro fertilization (IVF). Women's levels of anxiety were significantly higher before the treatment than during the treatment itself. Stratifying the women in three groups based on principal cause of infertility (male infertility, female infertility, or both male and female), we found significantly higher levels of anxiety and general distress in patients under treatment for female infertility. Higher anxiety levels in our sample before the treatment are probably an effect of not knowing what they are expected to do to solve their problem. Moreover, when the cause of infertility is exclusively female, women experience higher levels of anxiety and general distress both before and during the treatment, probably correlated to a sense of guilt. These data help the treating physician to better counsel patients and to provide a more focused psychological support.

Neurotrophins and glial cell line-derived neurotrophic factor in the ovary: physiological and pathophysiological implications.

BACKGROUNDNeurotrophins [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4)] and glial cell line-derived neurotrophic factor (GDNF) are soluble polypeptide growth factors that are widely recognized for their roles in promoting cell growth, survival and differentiation in several classes of neurons. Outside the nervous system, neurotrophin (NT) and GDNF signaling events have substantial roles in various non-neural tissues, including the ovary.OBJECTIVE AND RATIONALEThe molecular mechanisms that promote and regulate follicular development and oocyte maturation have been extensively investigated. However, most information has been obtained from animal models. Even though the fundamental process is highly similar across species, the paracrine regulation of ovarian function in humans remains poorly characterized. Therefore, this review aims to summarize the expression and functional roles of NTs and GDNF in human ovarian biology and disorders, and to describe and propose the development of novel strategies for diagnosing, treating and preventing related abnormalities.SEARCH METHODSRelevant literature in the English language from 1990 to 2018 describing the role of NTs and GDNF in mammalian ovarian biology and phenotypes was comprehensively selected using PubMed, MEDLINE and Google Scholar.OUTCOMESStudies have shown that the neurotrophins NGF, BDNF, NT-3 and NT-4 as well as GDNF and their functional receptors are expressed in the human ovary. Recently, gathered experimental data suggest putative roles for NT and GDNF signaling in the direct control of ovarian function, including follicle assembly, activation of the primordial follicles, follicular growth and development, oocyte maturation, steroidogenesis, ovulation and corpus luteum formation. Additionally, crosstalk occurs between these ovarian regulators and the endocrine signaling system. Dysregulation of the NT system may negatively affect ovarian function, leading to reproductive pathology (decreased ovarian reserve, polycystic ovary syndrome and endometriosis), female infertility and even epithelial ovarian cancers.WIDER IMPLICATIONSA comprehensive understanding of the expression, actions and underlying molecular mechanisms of the NT/GDNF system in the human ovary is essential for novel approaches to therapeutic and diagnostic interventions in ovarian diseases and to develop more safe, effective methods of inducing ovulation in ART in the treatment of female infertility.

Bioengineering the ovary to preserve and reestablish female fertility.

Different bioengineering strategies can be presently adopted and have been shown to have great potential in the treatment of female infertility and ovarian dysfunction deriving from chemotherapy, congenital malformations, massive adhesions as well as aging and lifestyle. One option is transplantation of fresh or cryopreserved organs/fragments into the patient. A further possibility uses tissue engineering approaches that involve a combination of cells, biomaterials and factors that stimulate local ability to regenerate/ repair the reproductive organ. Organ transplant has shown promising results in large animal models. However, the source of the organ needs to be identified and the immunogenic effects of allografts remain still to be solved before the technology may enter the clinical practice. Decellularization/ repopulation of ovary with autologous cells or follicles could represent an interesting, still very experimental alternative. Here we summarize the recent advancements in the bioengineering strategies applied to the ovary, we present the principles for these systems and discuss the advantages of these emerging opportunities to preserve or improve female fertility.

AMH as the primary marker for fertility.

In women, the anti-Müllerian hormone (AMH) is secreted by the granulosa cells of growing follicles. Its measurement is strongly correlated with antral follicle count and represents a reliable marker of ovarian reserve. It also has the advantage of being highly reproducible since it has little variation within and between cycles. However, although it seems to be a good quantitative reflection of the ovarian reserve, it does not assess oocyte or embryo quality. This drawback precludes any good prediction of female fertility in the general population as well as in specific subgroups of patients. However, the AMH assay can become an indirect marker of the remaining female fertile years in some cases such as in those women who are at risk for premature ovarian failure or in those suffering from polycystic ovary syndrome. Its interest is no more to be proven in assisted reproductive technology where it is a valuable aid to the choice of the proposed techniques, ovarian stimulation protocols and gonadotropin dosage. AMH is finally very informative in monitoring cancer patients having received gonadotoxic drugs or having undergone mutilating ovarian surgeries. In conclusion, although it cannot be considered as a reliable predictor of pregnancy in women, AMH is now a useful tool in the management and treatment of female infertility.

The place of ART in Africa

Since the birth of Louis Brown on July 25th, 1978 through in vetro fertilization, assisted reproductive technology (ART) now is widely used for the treatment of both male and female infertility. Today globally almost 2 million ART cycles are performed every year. Although Africa constitutes 16% of the world population, yet its share of ART is much less than its fair share of 320,000 cycles per year. There are several barriers to the wide application of ART in Africa. These include epidemiological, geographic, financial, and socio-cultured barriers in addition to the health education barrier, restrictive health policy barrier and health systems barrier. In Africa there is an increasing demand for ART. Africa, like many parts in the world, is witnessing a changing life style which affects fertility. In Africa infertility is a medico-socio cultural problem with sex-based sufferings. Furthermore there is a higher prevalence of STIs and postpartum and postabortion infections which contributes to both male and female infertility. This coupled with the fact that treatment of infertility is a human right issue which should not be discriminated on economic, geographic, or racial basis, necessitates finding ways to overcome such disparity in the provision of ART for infertile patients in Africa. The paper discusses the various possible ways to improve availability and access to ART in Africa. The infertile couples in Africa should not suffer the health, psychological, and societal burden of infertility simply because others in the African continent reproduce too many. The 2030 SDGs agenda has envisaged a better future. One where we collectively tear down the barriers and correct disparities, focusing first on those left further behind.

BMI1 Deficiency Results in Female Infertility by Activating p16/p19 Signaling and Increasing Oxidative Stress.

The polycomb repressor B lymphoma Mo-MLV insertion region 1 (BMI1) is a core composition of polycomb repressive complex 1 (PRC1) and contributes to diverse fundamental cellular processes including cell senescence, apoptosis and proliferation. To investigate the role and mechanism of BMI1 in maintaining normal female reproductive function, we compared the differences in reproductive phenotypes between Bmi1-deficient and wild-type female mice. The Bmi1-deficient female mice were then supplemented with N-acetylcysteine in their drinking water to explore whether antioxidant supplementation could improve reproductive dysfunction caused by BMI1 deficiency. The results revealed that Bmi1 deletion resulted in complete infertility in female mice, estrous cycle disorder, and follicular developmental disorders. The reactive oxygen species levels in the ovarian tissue were increased; the ability of antioxidant enzymes was downregulated; the expression levels of p19 and p53 proteins were significantly upregulated. We also found that oocytes derived from Bmi1-deficient mice could not develop into embryos by in vitro fertilization and in vitro culture of embryos. Furthermore, supplementation with the antioxidant NAC not only improved the reproductive defects caused by Bmi1 deletion, but also largely rescued the ability of Bmi1-deficient oocytes to develop into embryos in vitro. These results indicated that cells lacking Bmi1 resulted in female infertility by activating the p16/p19 signaling pathway, increasing oxidative stress and DNA damage, inhibiting granulosa cell proliferation, and inducing granulosa cell apoptosis. Thus, BMI1 may be a novel potential target for the clinical treatment of female infertility.

Reduced RNA expression of the FMR1 gene in women with low (CGGn&lt;26) repeats

Low FMR1 variants (CGGn<26) have been associated with premature ovarian aging, female infertility and poor IVF treatment success. Until now, there is little published information concerning possible molecular mechanisms for this effect. We wished to examine whether relative expression of RNA and the FMR1 gene’s fragile X mental retardation protein (FMRP) RNA isoforms differ in women with various FMR1 sub-genotypes (normal, low CGGn<26 and/or high CGGn≥34). This prospective cohort study was conducted between 2014 and 2017 in a clinical research unit of the Center for Human Reproduction in New York City. The study involved a total of 98 study subjects, including 18 young oocyte donors and 80 older infertility patients undergoing routine in vitro fertilization (IVF) cycles. The main outcome measure was RNA expression in human luteinized granulosa cells of 5 groups of FMRP isoforms. The relative expression of FMR1 RNA in human luteinized granulosa cells was measured by real-time PCR and a possible association with CGGn was explored. All 5 groups of FMRP RNA isoforms examined were found to be differentially expressed in human luteinized granulosa cells. The relative expression of four FMR1 RNA isoforms showed significant differences among 6 FMR1 sub-genotypes. Women with at least one low allele expressed significantly lower levels of all 5 sets of FRMP isoforms in comparison to the non-low group. While it would be of interest to see whether FMRP is also decreased in the low-group we recognize that in recent years it has been increasingly documented that information flow of genetics may be regulated by non-coding RNA, that is, without translation to a protein product. We, thus, conclude that various CGG expansions of FMR1 allele may lead to changes of RNA levels and ratios of distinct FMRP RNA isoforms, which could regulate the translation and/or cellular localization of FMRP, affect the expression of steroidogenic enzymes and hormonal receptors, or act in some other epigenetic process and therefore result in the ovarian dysfunction in infertility.