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Human Reproduction Update Nov 2022To provide the optimal milieu for implantation and fetal development, the female reproductive system must orchestrate uterine dynamics with the appropriate hormones...
BACKGROUND
To provide the optimal milieu for implantation and fetal development, the female reproductive system must orchestrate uterine dynamics with the appropriate hormones produced by the ovaries. Mature oocytes may be fertilized in the fallopian tubes, and the resulting zygote is transported toward the uterus, where it can implant and continue developing. The cervix acts as a physical barrier to protect the fetus throughout pregnancy, and the vagina acts as a birth canal (involving uterine and cervix mechanisms) and facilitates copulation. Fertility can be compromised by pathologies that affect any of these organs or processes, and therefore, being able to accurately model them or restore their function is of paramount importance in applied and translational research. However, innate differences in human and animal model reproductive tracts, and the static nature of 2D cell/tissue culture techniques, necessitate continued research and development of dynamic and more complex in vitro platforms, ex vivo approaches and in vivo therapies to study and support reproductive biology. To meet this need, bioengineering is propelling the research on female reproduction into a new dimension through a wide range of potential applications and preclinical models, and the burgeoning number and variety of studies makes for a rapidly changing state of the field.
OBJECTIVE AND RATIONALE
This review aims to summarize the mounting evidence on bioengineering strategies, platforms and therapies currently available and under development in the context of female reproductive medicine, in order to further understand female reproductive biology and provide new options for fertility restoration. Specifically, techniques used in, or for, the uterus (endometrium and myometrium), ovary, fallopian tubes, cervix and vagina will be discussed.
SEARCH METHODS
A systematic search of full-text articles available in PubMed and Embase databases was conducted to identify relevant studies published between January 2000 and September 2021. The search terms included: bioengineering, reproduction, artificial, biomaterial, microfluidic, bioprinting, organoid, hydrogel, scaffold, uterus, endometrium, ovary, fallopian tubes, oviduct, cervix, vagina, endometriosis, adenomyosis, uterine fibroids, chlamydia, Asherman's syndrome, intrauterine adhesions, uterine polyps, polycystic ovary syndrome and primary ovarian insufficiency. Additional studies were identified by manually searching the references of the selected articles and of complementary reviews. Eligibility criteria included original, rigorous and accessible peer-reviewed work, published in English, on female reproductive bioengineering techniques in preclinical (in vitro/in vivo/ex vivo) and/or clinical testing phases.
OUTCOMES
Out of the 10 390 records identified, 312 studies were included for systematic review. Owing to inconsistencies in the study measurements and designs, the findings were assessed qualitatively rather than by meta-analysis. Hydrogels and scaffolds were commonly applied in various bioengineering-related studies of the female reproductive tract. Emerging technologies, such as organoids and bioprinting, offered personalized diagnoses and alternative treatment options, respectively. Promising microfluidic systems combining various bioengineering approaches have also shown translational value.
WIDER IMPLICATIONS
The complexity of the molecular, endocrine and tissue-level interactions regulating female reproduction present challenges for bioengineering approaches to replace female reproductive organs. However, interdisciplinary work is providing valuable insight into the physicochemical properties necessary for reproductive biological processes to occur. Defining the landscape of reproductive bioengineering technologies currently available and under development for women can provide alternative models for toxicology/drug testing, ex vivo fertility options, clinical therapies and a basis for future organ regeneration studies.
Topics: Animals; Female; Humans; Pregnancy; Bioengineering; Embryo Implantation; Genitalia, Female; Reproduction; Uterus
PubMed: 35652272
DOI: 10.1093/humupd/dmac025 -
European Journal of Obstetrics,... Aug 2023Leiomyomas (fibroids), the most common benign solid tumours in females, originate from the myometrium and are associated with poor quality of life for patients. The... (Review)
Review
BACKGROUND
Leiomyomas (fibroids), the most common benign solid tumours in females, originate from the myometrium and are associated with poor quality of life for patients. The current management of uterine leiomyomas mainly includes surgical interventions such as hysterectomy and myomectomy, either by laparoscopy or laparotomy, which have several complications and are not ideal for preserving fertility. Therefore, there is a need to develop or repurpose medical treatments that do not require surgical intervention.
OBJECTIVE
Many drugs are used to treat the symptoms associated with uterine fibroids. The main objective of this systematic review is to give an up-to-date account of potential pharmacological agents (non-surgical methods) for the management of uterine leiomyomas.
SEARCH STRATEGY
PubMed was searched for scientific and clinical literature using the keyword 'uterine fibroids' along with the drug names described in each section. For example, 'uterine fibroids' and 'ulipristal acetate' were the keywords used to search for literature on ulipristal acetate (UPA).
RESULTS
Various preclinical and clinical studies have shown that some drugs and herbal formulations exhibit activity in the management of uterine leiomyomas. Recent studies found that drugs such as UPA, elagolix, EC313, asoprisnol, nutritional supplements and herbal preparations were helpful in treating the symptoms associated with uterine leiomyomas.
CONCLUSION
Many drugs show efficacy in patients with symptomatic uterine fibroids. UPA is one of the most studied and prescribed medicines for uterine fibroids; however, its usage has been restricted due to a few recent incidences of hepatic toxicity. Herbal drugs and natural supplements have also shown promising effects on uterine fibroids. The synergistic effects of nutritional and herbal supplements have been reported in certain cases, and should be studied in detail. Further research is warranted to identify the mode of action of the drugs, and to determine the precise conditions that would explain the causes of toxicity in some patients.
Topics: Female; Humans; Uterine Neoplasms; Quality of Life; Leiomyoma; Uterine Myomectomy; Acetates
PubMed: 37385088
DOI: 10.1016/j.ejogrb.2023.06.021 -
International Journal of Gynaecology... May 2022Despite the high prevalence of adenomyosis in hysterectomy specimens of endometrial carcinoma (EC) patients, the relationship between adenomyosis and EC prognosis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite the high prevalence of adenomyosis in hysterectomy specimens of endometrial carcinoma (EC) patients, the relationship between adenomyosis and EC prognosis appears unclear.
OBJECTIVE
To assess the prognostic value of coexistent adenomyosis in patients with EC.
METHODS
A systematic review and meta-analysis was performed by searching six electronic databases for studies reporting data on prognosis of EC patients with and without coexistent adenomyosis. Studies with patient selection based on prognostic factors were excluded. Pooled univariate hazard ratio (HR) analyses for overall survival (OS) and disease-free survival (DRF) were performed, using EC patients without adenomyosis as a control group. For DFS, pooled multivariate HR analysis was also evaluable.
RESULTS
Three studies of 2505 EC patients (553 with and 1952 without adenomyosis) were included. Compared with EC patients without adenomyosis, EC patients with coexistent adenomyosis showed a pooled HR of 0.533 (CI 95%, 0.329-0.864) for OS at univariate analysis; 0.536 (CI 95%, 0.334-0.859) for DFS at univariate analysis; and 0.875 (CI 95%, 0.331-2.315) for DFS at multivariate analysis.
CONCLUSION
In EC patients with coexistent adenomyosis, the risk of death is halved compared with EC patients without adenomyosis. However, the independence of this association needs to be verified in future studies.
Topics: Adenomyosis; Disease-Free Survival; Endometrial Neoplasms; Female; Humans; Prognosis; Progression-Free Survival
PubMed: 34228822
DOI: 10.1002/ijgo.13818 -
The Cochrane Database of Systematic... Dec 2021Dysmenorrhoea (period pain) is a common condition with a substantial impact on the well-being and productivity of women. Primary dysmenorrhoea is defined as recurrent,... (Review)
Review
BACKGROUND
Dysmenorrhoea (period pain) is a common condition with a substantial impact on the well-being and productivity of women. Primary dysmenorrhoea is defined as recurrent, cramping pelvic pain that occurs with periods, in the presence of a normal uterus, ovaries and fallopian tubes. It is thought to be caused by uterine contractions (cramps) associated with a high level of production of local chemicals such as prostaglandins. The muscle of the uterus (the myometrium) responds to these high levels of prostaglandins by contracting forcefully, causing low oxygen levels and consequently pain. Nifedipine is a calcium channel blocker in widespread clinical use for preterm labour due to its ability to inhibit uterine contractions in that setting. This review addresses whether this effect of nifedipine also helps with relief of the uterine contractions during menstruation OBJECTIVES: To assess the effectiveness and safety of nifedipine for primary dysmenorrhoea.
SEARCH METHODS
We searched for all published and unpublished randomised controlled trials (RCTs) of nifedipine for dysmenorrhoea, without language restriction and in consultation with the Cochrane Gynaecology and Fertility Group (CGF) Information Specialist. The following databases were searched to 25 November 2021: the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase, PsycINFO, and CINAHL. Also searched were the international trial registers: ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal, the Web of Science, OpenGrey, LILACS database, PubMed and Google Scholar. We checked the reference lists of relevant articles.
SELECTION CRITERIA
We included RCTs comparing nifedipine with placebo for the treatment of primary dysmenorrhoea.
DATA COLLECTION AND ANALYSIS
The primary outcomes to be assessed were pain, and health-related quality of life. Secondary outcomes were adverse effects, satisfaction, and need for additional medication. The two review authors independently assessed the included trials. There were insufficient data to allow meaningful meta-analysis.
MAIN RESULTS
The evidence assessed was of very low quality overall. We examined three small RCTs, with a total of 106 participants. Data for analysis could be extracted from only two of these trials (with a total of 66 participants); two trials were published in the 1980s, and the third in 1993. Nifedipine may be effective for "any pain relief" compared to placebo in women with primary dysmenorrhoea (odds ratio (OR) 9.04, 95% confidence interval (CI) 2.61 to 31.31; 2 studies, 66 participants; very low-quality evidence). The evidence suggests that if the rate of pain relief using placebo is 40%, the rate using nifedipine would be between 64% and 95%. For the outcome of "good" or "excellent" pain relief, nifedipine may be more effective than placebo; the confidence interval was very wide (OR 43.78, 95% CI 5.34 to 259.01; 2 studies, 66 participants; very low-quality evidence). We are uncertain if the use of nifedipine was associated with less requirement for additional analgesia use than placebo (OR 0.54, 95% CI 0.07 to 4.20, 1 study, 42 participants; very low-quality evidence). Participants indicated that they would choose to use nifedipine over their previous analgesic if the option was available. There were similar levels of adverse effects and menstruation-related symptoms in the placebo and intervention groups (OR 0.94, 95% CI 0.08 to 10.90; 1 study, 24 participants; very low-quality evidence); if the chance of adverse effects with placebo is 80%, the rate using nifedipine would be between 24% and 98%. There were no results regarding formal assessment of health-related quality of life.
AUTHORS' CONCLUSIONS
The evidence is insufficient to confirm whether nifedipine is a possible medical treatment for primary dysmenorrhoea. The trials included in this review had very low numbers and were of low quality. Notably, there was a large imbalance in numbers randomised between placebo and treatment groups in one of the two trials with data available for analysis. While there was no evidence of a difference noted in adverse effects between groups, more data from larger participant numbers are needed for this outcome. Larger, more well-conducted trials are required to elucidate the potential role of nifedipine in the treatment of this common condition, as it could be a useful addition to the therapeutic options available if shown to be well tolerated and effective. The safety of nifedipine in women of reproductive age is well established from trials of its use in preterm labour, and clinicians are accustomed to off-label use for this indication. The drug is inexpensive and readily available. Other options for relief of primary dysmenorrhoea are not suitable for all women; NSAIDs and the oral contraceptive pill (OCP) are contraindicated for some women, and the OCP is not suitable for women who are trying to conceive. In addition, the trials examined suggest there may be a participant preference for nifedipine.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Dysmenorrhea; Female; Humans; Infant, Newborn; Menstruation; Nifedipine; Pelvic Pain; Pregnancy
PubMed: 34921554
DOI: 10.1002/14651858.CD012912.pub2 -
Journal of Obstetrics and Gynaecology :... Jul 2022A caesarean section may lead to a defect of the myometrium at the site of the uterine scar. The association with abnormal uterine bleeding or impaired fertility has been...
A caesarean section may lead to a defect of the myometrium at the site of the uterine scar. The association with abnormal uterine bleeding or impaired fertility has been demonstrated. Hysteroscopic remodelling reportedly reduces the symptoms. To review the available literature reporting on hysteroscopic treatment of these defects in symptomatic women with abnormal uterine bleeding or impaired fertility. A systematic search of PubMed and Cochrane databases has been performed until January 2021, including 27 articles. Hysteroscopic remodelling relieved symptoms of abnormal uterine bleeding in 60-100% and 25-100% of women with impaired fertility conceived within the follow up period. No major complications were reported. Hysteroscopic remodelling seems a treatment option in the management of symptomatic caesarean scar defects. Long-term follow-up and larger studies are needed to evaluate the effect on abnormal uterine bleeding as well as on reproductive outcomes.
Topics: Cesarean Section; Cicatrix; Female; Humans; Hysteroscopy; Pregnancy; Uterine Hemorrhage
PubMed: 35014923
DOI: 10.1080/01443615.2021.2003310 -
International Journal of Environmental... Feb 2022Adenomyosis is a common benign gynecological condition, defined as an extension of endometrial tissue into the myometrium. Some studies suggest that adenomyosis could be... (Review)
Review
Adenomyosis is a common benign gynecological condition, defined as an extension of endometrial tissue into the myometrium. Some studies suggest that adenomyosis could be a favorable prediction factor associated with survival outcomes in endometrial cancer. The aim of our systematic review was to investigate the current knowledge regarding adenomyosis and a possible molecular mechanism of carcinogenesis in adenomyotic lesions. In addition, the long-term prognosis for patients with endometrial cancer and coexisting adenomyosis (and endometriosis) was a key point of the research. The current literature was reviewed by searching PubMed, using the following phrases: "adenomyosis and endometrial cancer" and "malignant transformation of adenomyosis". According to the literature, genetic mutations, epigenetic changes, and inactivation of specific tumor suppressor genes in adenomyosis are still poorly understood. Data regarding the influence of adenomyosis on survival outcomes in endometrial cancer seem to be contradictory and require further clinical and molecular investigation.
Topics: Adenomyosis; Endometrial Neoplasms; Endometriosis; Endometrium; Female; Humans; Myometrium; Risk Factors
PubMed: 35206475
DOI: 10.3390/ijerph19042294 -
BMC Medical Genomics Jun 2015Preterm birth (PTB), or birth before 37 weeks of gestation, is the leading cause of newborn death worldwide. PTB is a critical area of scientific study not only due to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Preterm birth (PTB), or birth before 37 weeks of gestation, is the leading cause of newborn death worldwide. PTB is a critical area of scientific study not only due to its worldwide toll on human lives and economies, but also due to our limited understanding of its pathogenesis and, therefore, its prevention. This systematic review and meta-analysis synthesizes the landscape of PTB transcriptomics research to further our understanding of the genes and pathways involved in PTB subtypes.
METHODS
We evaluated published genome-wide pregnancy studies across gestational tissues and pathologies, including those that focus on PTB, by performing a targeted PubMed MeSH search and systematically reviewing all relevant studies.
RESULTS
Our search yielded 2,361 studies on gestational tissues including placenta, decidua, myometrium, maternal blood, cervix, fetal membranes (chorion and amnion), umbilical cord, fetal blood, and basal plate. Selecting only those original research studies that measured transcription on a genome-wide scale and reported lists of expressed genetic elements identified 93 gene expression, 21 microRNA, and 20 methylation studies. Although 30 % of all PTB cases are due to medical indications, 76 % of the preterm studies focused on them. In contrast, only 18 % of the preterm studies focused on spontaneous onset of labor, which is responsible for 45 % of all PTB cases. Furthermore, only 23 of the 10,993 unique genetic elements reported to be transcriptionally active were recovered 10 or more times in these 134 studies. Meta-analysis of the 93 gene expression studies across 9 distinct gestational tissues and 29 clinical phenotypes showed limited overlap of genes identified as differentially expressed across studies.
CONCLUSIONS
Overall, profiles of differentially expressed genes were highly heterogeneous both between as well as within clinical subtypes and tissues as well as between studies of the same clinical subtype and tissue. These results suggest that large gaps still exist in the transcriptomic study of specific clinical subtypes as well in the generation of the transcriptional profile of well-studied clinical subtypes; understanding the complex landscape of prematurity will require large-scale, systematic genome-wide analyses of human gestational tissues on both understudied and well-studied subtypes alike.
Topics: DNA Methylation; Female; Gene Expression Profiling; Gene Expression Regulation, Developmental; Genome-Wide Association Study; Humans; Phenotype; Placenta; Pregnancy; Premature Birth; Risk Factors; Term Birth; Transcriptome
PubMed: 26044726
DOI: 10.1186/s12920-015-0099-8 -
Seminars in Reproductive Medicine May 2020To summarize and update our current knowledge regarding adenomyosis diagnosis, prevalence, and symptoms. Systematic review of PubMed between January 1972 and April 2020....
To summarize and update our current knowledge regarding adenomyosis diagnosis, prevalence, and symptoms. Systematic review of PubMed between January 1972 and April 2020. Search strategy included: "adenomyosis [MeSH Terms] AND (endometriosis[MeSH Term OR prevalence study [MeSH Terms] OR dysmenorrhea[Text Word] OR prevalence[Text Word] OR young adults [Text Word] OR adolesce* [Text Word] OR symptoms[Text Word] OR imaging diagnosis [Text Word] OR pathology[Text Word]. Articles published in English that addressed adenomyosis and discussed prevalence, diagnosis, and symptoms were included. Included articles described: pathology diagnosis, imaging, biopsy diagnosis, prevalence and age of onset, symptoms, and concomitant endometriosis. Sixteen articles were included in the qualitative analysis. The studies are heterogeneous when diagnosing adenomyosis with differing criteria, protocols, and patient populations. Prevalence estimates range from 20% to 88.8% in symptomatic women (average 30-35%) with most diagnosed between 32-38 years old. The correlation between imaging and pathology continues to evolve. As imaging advances, newer studies report younger symptomatic women are being diagnosed with adenomyosis based on both magnetic resonance imaging (MRI) and/or transvaginal ultrasound (TVUS). High rates of concomitant endometriosis create challenges when discerning the etiology of pelvic pain. Symptoms that are historically attributed to endometriosis may actually be caused by adenomyosis. Adenomyosis remains a challenge to identify, assess and research because of the lack of standardized diagnostic criteria, especially in women who wish to retain their uterus. As noninvasive diagnostics such as imaging and myometrial biopsies continue to improve, younger women with variable symptoms will likely create criteria for diagnosis with adenomyosis. The priority should be to create standardized histopathological and imaging diagnoses to gain deeper understandings of adenomyosis.
Topics: Adenomyosis; Adolescent; Adult; Diagnosis, Differential; Disease Progression; Dysmenorrhea; Dyspareunia; Endometriosis; Female; Humans; Infertility, Female; Magnetic Resonance Imaging; Menorrhagia; Myometrium; Ultrasonography; Young Adult
PubMed: 33352607
DOI: 10.1055/s-0040-1721795 -
Gynecological Endocrinology : the... Sep 2016Adenomyosis is a heterogeneous gynaecologic condition with a range of clinical presentations, the most common being heavy menstrual bleeding and dysmenorrhoea; however,... (Review)
Review
Adenomyosis is a heterogeneous gynaecologic condition with a range of clinical presentations, the most common being heavy menstrual bleeding and dysmenorrhoea; however, patients can also be asymptomatic. Several studies support the theory that adenomyosis results from invasion of the endometrium into the myometrium, causing alterations in the junctional zone. These changes are commonly seen on imaging studies, such as transvaginal ultrasound and magnetic resonance imaging. The aim of this review is to discuss the medical approach to the management of adenomyosis symptoms, including pain and abnormal uterine bleeding. The standard treatment of adenomyosis is hysterectomy, but there is no medical therapy to treat the symptoms of adenomyosis while still allowing patients to conceive. Medical therapies using suppressive hormonal treatments, such as continuous use of oral contraceptive pills, high-dose progestins, selective oestrogen receptor modulators, selective progesterone receptor modulators, the levonorgestrel-releasing intrauterine device, aromatase inhibitors, danazol, and gonadotrophin receptor hormone agonists can temporarily induce regression of adenomyosis and improve the symptoms.
Topics: Adenomyosis; Female; Humans
PubMed: 27379972
DOI: 10.1080/09513590.2016.1197200 -
BioMed Research International 2022This is the first meta-analysis that assessed the association between maternal smoking and the risk of placenta accreta spectrum (PAS), so this study was aimed at... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is the first meta-analysis that assessed the association between maternal smoking and the risk of placenta accreta spectrum (PAS), so this study was aimed at investigating the association between maternal smoking and PAS based on observational studies. PAS is defined as a severe obstetric complication due to the abnormal invasion of the chorionic villi into the myometrium and uterine serosa.
METHODS
We searched electronic bibliographic databases including PubMed, Web of Science, Scopus, Science Direct, and Google Scholar until January 2022. The results were reported using a random effect model. The chi-square test and the statistic were used to assess heterogeneity. Egger's and Begg's tests were used to examine the probability of publication bias. All statistical analyses were performed at a significance level of 0.05 using Stata software, version 11.
RESULTS
Based on the random effect model, the estimated OR of the risk of PAS associated with smoking was 1.21 (95% CI: 1.02, 1.41; = 4.7%). Subgroup analysis was conducted based on study design, and the result showed that the association between smoking and PAS among cohort studies was significant 1.35 (95% CI: 1.15, 1.55; = 0.0%).
CONCLUSION
Our results suggested that maternal smoking is a risk factor for the PAS. There was no heterogeneity among studies that reported an association between smoking and the PAS. The Newcastle-Ottawa Scale (NOS) was used to measure study quality.
Topics: Chi-Square Distribution; Cohort Studies; Female; Humans; Observational Studies as Topic; Placenta Accreta; Pregnancy; Risk Factors; Smoking
PubMed: 35860796
DOI: 10.1155/2022/2399888