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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 -
Reproductive Toxicology (Elmsford, N.Y.) Jan 2012It is clear that cocaine and cocaine metabolites are present in the placenta and may harm the fetus. The results of the experimental manipulation of cocaine exposure are... (Review)
Review
It is clear that cocaine and cocaine metabolites are present in the placenta and may harm the fetus. The results of the experimental manipulation of cocaine exposure are not reported in the literature in a consistent manner. We conducted a systematic review of selected articles that demonstrated the analytical detection of cocaine and its metabolites in the placenta and that were published from January 1, 1956-June 30, 2011 using Medline, Toxline and Scopus databases. The collected data confirm that the placenta does not act as a barrier to fetal exposure, that cocaine quickly crosses the placenta and that one of the essential roles of the placenta is to metabolize cocaine during pregnancy. Our systematic review summarized the results showing that cocaine, benzoylecgonine and norcocaine are stored in the myometrium and the placental membrane and maintain continuous drug delivery to the amniotic fluid (and to the fetus) probably via diffusion.
Topics: Amniotic Fluid; Animals; Biological Assay; Biotransformation; Central Nervous System Stimulants; Cocaine; Cocaine-Related Disorders; Diffusion; Female; Fetal Blood; Humans; Maternal-Fetal Exchange; Myometrium; Placenta; Placental Circulation; Pregnancy; Pregnancy Complications
PubMed: 22094170
DOI: 10.1016/j.reprotox.2011.10.012 -
International Journal of Molecular... Aug 2018Growing evidence supports a role of vitamin D (VD) in reproductive health. Vitamin D receptor (VDR) is expressed in the ovary, endometrium, and myometrium. The... (Review)
Review
Growing evidence supports a role of vitamin D (VD) in reproductive health. Vitamin D receptor (VDR) is expressed in the ovary, endometrium, and myometrium. The biological actions of VD in fertility and reproductive tissues have been investigated but mainly using animal models. Conversely, the molecular data addressing the mechanisms underlying VD action in the physiologic endometrium and in endometrial pathologies are still scant. Levels of VDR expression according to the menstrual cycle are yet to be definitively clarified, possibly being lower in the proliferative compared to the secretory phase and in mid-secretory compared to early secretory phase. Endometrial tissue also expresses the enzymes involved in the metabolism of VD. The potential anti-proliferative and anti-inflammatory effects of VD for the treatment of endometriosis have been investigated in recent years. Treatment of ectopic endometrial cells with 1,25(OH)₂D₃ could significantly reduce cytokine-mediated inflammatory responses. An alteration of VD metabolism in terms of increased 24-hydroxylase mRNA and protein expression has been demonstrated in endometrial cancer, albeit not consistently. The effect of the active form of the vitamin as an anti-proliferative, pro-apoptotic, anti-inflammatory, and differentiation-inducing agent has been demonstrated in various endometrial cancer cell lines.
Topics: Endometriosis; Endometrium; Female; Fertility; Humans; Menstrual Cycle; Myometrium; Receptors, Calcitriol; Signal Transduction; Vitamin D
PubMed: 30096760
DOI: 10.3390/ijms19082320 -
Archives of Gynecology and Obstetrics Dec 2015Misoprostol, a prostaglandin derivative, reduces blood flow to uterus, facilitating every surgical operation on myometrium. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Misoprostol, a prostaglandin derivative, reduces blood flow to uterus, facilitating every surgical operation on myometrium.
METHOD
PubMed, Scopus and Cochrane databases were systematically searched and five studies met the inclusion criteria for our meta-analysis.
RESULTS
In total, 283 patients were included. The intention to treat population included 142 patients. The mean age of the patients was 34 years old. The vaginal route of administration was preferred in 117 out of 142 patients and the rectal route in 25 patients. Three studies were included in the analysis regarding duration of operation, estimated blood loss, preoperative/postoperative hemoglobin, transfusions needed and febrile morbidity. No significant difference was observed between vaginal suppository and placebo group concerning the duration of operation, the fall of preoperative hemoglobin, transfusions needed and the febrile morbidity. Regarding the estimated blood loss, the mean difference observed between the misoprostol and placebo groups was -148.55 mL per operation (95 % CI, -233.10 to -64), p < 0.001. As far as the postoperative Hgb, the misoprostol group presented significantly smaller reduction, 0.68 gr/dL per operation (95 % CI, 0.38-0.97), p < 0.001.
CONCLUSION
Easy to use, minor or no side effects, and good clinical outcomes are the properties that render misoprostol useful in the realization myomectomy independently of the surgical technique applied.
Topics: Abortifacient Agents, Nonsteroidal; Administration, Intravaginal; Blood Loss, Surgical; Blood Transfusion; Female; Humans; Leiomyoma; Misoprostol; Treatment Outcome; Uterine Myomectomy
PubMed: 26041328
DOI: 10.1007/s00404-015-3779-x -
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 -
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 -
Obstetrics and Gynecology Dec 2016To evaluate the accuracy of saline infusion sonohysterography in comparison with transvaginal ultrasonography for diagnosing polyps and submucosal leiomyomas in women... (Review)
Review
OBJECTIVE
To evaluate the accuracy of saline infusion sonohysterography in comparison with transvaginal ultrasonography for diagnosing polyps and submucosal leiomyomas in women with abnormal uterine bleeding.
DATA SOURCES
We searched the databases MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov as well as citations and reference lists to the end of November 2015.
METHODS OF STUDY SELECTION
Two authors screened 5,347 citations for eligibility. We included randomized controlled trials or prospective cohort studies published in English, assessing the accuracy of saline infusion sonohysterography and transvaginal ultrasonography for diagnosing polyps and submucosal leiomyomas in women with abnormal uterine bleeding. We considered studies using histopathologic specimens obtained at either hysteroscopy or hysterectomy as criterion standard.
TABULATION, INTEGRATION, AND RESULTS
Twenty-five studies were eligible. Two authors extracted data and assessed the quality of included studies. Bivariate random-effects models were used to compare the different tests and evaluate sources of heterogeneity. Saline infusion sonohysterography was superior to transvaginal ultrasonography with pooled sensitivity and specificity of 0.92 and 0.89 compared with 0.64 and 0.90, respectively (P<.001). Transvaginal ultrasound sensitivity for diagnosing polyps was particularly low (0.51). Saline infusion sonohysterography was also compared with hysteroscopy in seven studies and had similar sensitivity but inferior specificity (0.93 and 0.83 compared with 0.95 and 0.90, respectively, P=.007). All three procedures were well-tolerated by women. Saline infusion sonohysterography was successfully completed in 95% of women. Technical variations such as the use of balloon catheters were not found to affect diagnostic accuracy.
CONCLUSION
Transvaginal ultrasonography lacks sensitivity to be used alone to exclude the presence of polyps and leiomyomas in women with abnormal uterine bleeding. Although less specific than hysteroscopy, saline infusion sonohysterography offers a similar detection rate and permits concomitant visualization of the ovaries and myometrium. Cost, convenience, and tolerability of different imaging techniques require further evaluation.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO International prospective register of systematic reviews, http://www.crd.york.ac.uk/PROSPERO, CRD42016034005.
Topics: Endosonography; Female; Humans; Hysteroscopy; Leiomyoma; Polyps; Sensitivity and Specificity; Sodium Chloride; Ultrasonography; Uterine Hemorrhage; Uterine Neoplasms
PubMed: 27824761
DOI: 10.1097/AOG.0000000000001776 -
American Journal of Obstetrics and... Dec 2016Determining the depth of villous invasiveness before delivery is pivotal in planning individual management of placenta accreta. We have evaluated the value of various... (Review)
Review
BACKGROUND
Determining the depth of villous invasiveness before delivery is pivotal in planning individual management of placenta accreta. We have evaluated the value of various ultrasound signs proposed in the international literature for the prenatal diagnosis of accreta placentation and assessment of the depth of villous invasiveness.
OBJECTIVE
We undertook a PubMed and MEDLINE search of the relevant studies published from the first prenatal ultrasound description of placenta accreta in 1982 through March 30, 2016, using key words "placenta accreta," "placenta increta," "placenta percreta," "abnormally invasive placenta," "morbidly adherent placenta," and "placenta adhesive disorder" as related to "sonography," "ultrasound diagnosis," "prenatal diagnosis," "gray-scale imaging," "3-dimensional ultrasound", and "color Doppler imaging."
STUDY DESIGN
The primary eligibility criteria were articles that correlated prenatal ultrasound imaging with pregnancy outcome. A total of 84 studies, including 31 case reports describing 38 cases of placenta accreta and 53 series describing 1078 cases were analyzed. Placenta accreta was subdivided into placenta creta to describe superficially adherent placentation and placenta increta and placenta percreta to describe invasive placentation.
RESULTS
Of the 53 study series, 23 did not provide data on the depth of villous myometrial invasion on ultrasound imaging or at delivery. Detailed correlations between ultrasound findings and placenta accreta grading were found in 72 cases. A loss of clear zone (62.1%) and the presence of bridging vessels (71.4%) were the most common ultrasound signs in cases of placenta creta. In placenta increta, a loss of clear zone (84.6%) and subplacental hypervascularity (60%) were the most common ultrasound signs, whereas placental lacunae (82.4%) and subplacental hypervascularity (54.5%) were the most common ultrasound signs in placenta percreta. No ultrasound sign or a combination of ultrasound signs were specific of the depth of accreta placentation.
CONCLUSION
The wide heterogeneity in terminology used to describe the grades of accreta placentation and differences in study design limits the evaluation of the accuracy of ultrasound imaging in the screening and diagnosis of placenta accreta. This review emphasizes the need for further prospective studies using a standardized evidence-based approach including a systematic correlation between ultrasound signs of placenta accreta and detailed clinical and pathologic examinations at delivery.
Topics: Delivery, Obstetric; Female; Humans; Imaging, Three-Dimensional; Myometrium; Placenta Accreta; Pregnancy; Severity of Illness Index; Ultrasonography, Doppler, Color; Ultrasonography, Prenatal
PubMed: 27473003
DOI: 10.1016/j.ajog.2016.07.044 -
Ultrasound in Obstetrics & Gynecology :... Nov 2022To evaluate and compare the diagnostic test accuracy (DTA) of three-dimensional transvaginal ultrasound (3D-TVS) and magnetic resonance imaging (MRI) for deep myometrial... (Meta-Analysis)
Meta-Analysis Review
Three-dimensional transvaginal ultrasound vs magnetic resonance imaging for preoperative staging of deep myometrial and cervical invasion in patients with endometrial cancer: systematic review and meta-analysis.
OBJECTIVES
To evaluate and compare the diagnostic test accuracy (DTA) of three-dimensional transvaginal ultrasound (3D-TVS) and magnetic resonance imaging (MRI) for deep myometrial infiltration (DMI) and cervical invasion for preoperative staging and surgery planning in patients with endometrial cancer (EC).
METHODS
This systematic review and meta-analysis investigated the DTA of MRI and 3D-TVS for DMI and cervical invasion in patients with EC. A literature search was performed using MEDLINE, Scopus, EMBASE, ScienceDirect, The Cochrane library, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, EU Clinical Trials Register and World Health Organization International Clinical Trials Registry Platform to identify relevant studies published between January 2000 and December 2021. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool.
RESULTS
Five studies, including a total of 450 patients, were included in the systematic review. All five studies compared the DTA of 3D-TVS vs MRI for DMI, and three studies compared the DTA of 3D-TVS vs MRI for cervical invasion. Pooled sensitivity, positive likelihood ratio and negative likelihood ratio for detecting DMI using 3D-TVS were 77% (95% CI, 66-85%), 4.57 and 0.31, respectively. The respective values for detecting DMI on MRI were 80% (95% CI, 73-86%), 4.22 and 0.24. Bivariate metaregression indicated a similar DTA of 3D-TVS and MRI (P = 0.80) for the correct identification of DMI. Pooled ln diagnostic odds ratio for detecting cervical invasion was 3.11 (95% CI, 2.09-4.14) for 3D-TVS and 2.36 (95% CI, 0.90-3.83) for MRI. The risk of bias was low for most of the four domains assessed in QUADAS-2.
CONCLUSION
3D-TVS demonstrated good diagnostic accuracy in terms of sensitivity and specificity for the evaluation of DMI and cervical invasion, with results comparable with those of MRI. Thus, we confirmed the potential role of 3D-TVS in the preoperative staging and surgery planning in patients with EC. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Pregnancy; Female; Humans; Neoplasm Invasiveness; Myometrium; Endometrial Neoplasms; Ultrasonography; Magnetic Resonance Imaging; Sensitivity and Specificity; Neoplasm Staging
PubMed: 35656849
DOI: 10.1002/uog.24967 -
Ultrasound in Obstetrics & Gynecology :... Jul 2014To assess systematically the performance of prenatal magnetic resonance imaging (MRI) in diagnosing the presence, degree and topography of disorders of invasive... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess systematically the performance of prenatal magnetic resonance imaging (MRI) in diagnosing the presence, degree and topography of disorders of invasive placentation and to explore the role of the different MRI signs in predicting these disorders. The diagnostic accuracy of ultrasound and MRI in the detection of invasive placentation was also compared.
METHODS
MEDLINE, EMBASE, CINAHL and The Cochrane Library, including The Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and The Cochrane Central Register of Controlled Trials, were searched electronically utilizing combinations of the relevant medical subject heading terms, keywords and word variants for 'invasive placentation' and 'magnetic resonance imaging'. Only prospective studies reporting a diagnosis of invasive placentation at the time of MRI and retrospective studies in which the radiologist was blinded to the final results were included in the analysis. The MRI signs explored were: uterine bulging, heterogeneous signal intensity, dark intraplacental bands on T2 weighted sequences, focal interruption of the myometrium and tenting of the bladder. Summary estimates of sensitivity, specificity, positive and negative likelihood ratios (LR+, LR-) and diagnostic odds ratio (DOR) were based, depending on the number of studies, upon DerSimonian-Laird random-effect or hierarchical summary receiver-operating characteristics models.
RESULTS
A total of 18 studies involving 1010 pregnancies at risk for invasive placentation were included. The overall diagnostic accuracy of MRI in detecting the presence of invasive placentation was: sensitivity, 94.4% (95% CI, 86.0-97.9%); specificity, 84.0% (95% CI, 76.0-89.8%); LR+, 5.91 (95% CI, 3.73-9.39); LR-, 0.07 (95% CI, 0.02-0.18); DOR, 89.0 (95% CI, 22.8-348.1). MRI had a high predictive accuracy in assessing both the depth and topography of placental invasion. All five MRI signs showed good predictive accuracy in the diagnosis of disorders of invasive placentation. There was no difference in either the sensitivity (P = 0.24) or the specificity (P = 0.91) between ultrasound and MRI for the detection of invasive placentation.
CONCLUSIONS
Prenatal MRI is highly accurate in diagnosing disorders of invasive placentation. Ultrasound and MRI have comparable predictive accuracy. Large population-based studies are needed in order to assess whether ultrasound can predict the depth and topography of placental invasion as reliably as can MRI.
Topics: Female; Humans; Magnetic Resonance Imaging; Models, Statistical; Placenta Accreta; Pregnancy; Prenatal Diagnosis; Sensitivity and Specificity
PubMed: 24515654
DOI: 10.1002/uog.13327