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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 -
Frontiers in Oncology 2022Observational studies suggested that systemic lupus erythematosus (SLE) might be associated with increased cancer incidence and cancer-related death, however, the...
BACKGROUND
Observational studies suggested that systemic lupus erythematosus (SLE) might be associated with increased cancer incidence and cancer-related death, however, the results are inconsistent. We aim to comprehensively estimate the causal relationships between SLE and cancer morbidity and mortality using a meta-analysis of cohort studies and Mendelian randomization.
METHODS
A systematic search was conducted using PubMed to identify cohort studies published before January 21, 2021. Meta-analysis was performed to calculate relative risk (RR) and corresponding 95% confidence intervals (CI). In addition, we further evaluated the potentially causal relationships identified by cohort studies using two-sample Mendelian randomization.
RESULTS
A total of 48 cohort studies involving 247,575 patients were included. We performed 31 main meta-analysis to assess the cancer risk and three meta-analyses to evaluate cancer mortality in SLE patients. Through meta-analyses, we observed an increased risk of overall cancer (RR=1.62, 95%CI, 1.47-1.79, <0.001) and cancer-related death (RR=1.52, 95%CI, 1.36-1.70, <0.001) in patients with SLE. Subgroup analysis by site-specific cancer showed that SLE was a risk factor for 17 site-specific cancers, including six digestive cancers (esophagus, colon, anus, hepatobiliary, liver, pancreatic), five hematologic cancers (lymphoma, Hodgkin's lymphoma, non-Hodgkin lymphoma, leukemia, multiple myeloma), as well as cancer in lung, larynx, cervical, vagina/vulva, renal, bladder, skin, and thyroid. In addition, further mendelian randomization analysis verified a weakly association between genetically predisposed SLE and lymphoma risk (odds ratio=1.0004, =0.0035).
CONCLUSIONS
Findings from our study suggest an important role of SLE in carcinogenesis, especially for lymphoma.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, CRD42021243635.
PubMed: 35600353
DOI: 10.3389/fonc.2022.860794 -
The vaginal microbiome and the risk of preterm birth: a systematic review and network meta-analysis.Scientific Reports May 2022Preterm birth is a major cause of neonatal morbidity and mortality worldwide. Increasing evidence links the vaginal microbiome to the risk of spontaneous preterm labour... (Meta-Analysis)
Meta-Analysis
Preterm birth is a major cause of neonatal morbidity and mortality worldwide. Increasing evidence links the vaginal microbiome to the risk of spontaneous preterm labour that leads to preterm birth. The aim of this systematic review and network meta-analysis was to investigate the association between the vaginal microbiome, defined as community state types (CSTs, i.e. dominance of specific lactobacilli spp, or not (low-lactobacilli)), and the risk of preterm birth. Systematic review using PubMed, Web of Science, Embase and Cochrane library was performed. Longitudinal studies using culture-independent methods categorizing the vaginal microbiome in at least three different CSTs to assess the risk of preterm birth were included. A (network) meta-analysis was conducted, presenting pooled odds ratios (OR) and 95% confidence intervals (CI); and weighted proportions and 95% CI. All 17 studies were published between 2014 and 2021 and included 38-539 pregnancies and 8-107 preterm births. Women presenting with "low-lactobacilli" vaginal microbiome were at increased risk (OR 1.69, 95% CI 1.15-2.49) for delivering preterm compared to Lactobacillus crispatus dominant women. Our network meta-analysis supports the microbiome being predictive of preterm birth, where low abundance of lactobacilli is associated with the highest risk, and L. crispatus dominance the lowest.
Topics: Female; Humans; Infant, Newborn; Lactobacillus; Lactobacillus crispatus; Microbiota; Network Meta-Analysis; Pregnancy; Premature Birth; Vagina
PubMed: 35562576
DOI: 10.1038/s41598-022-12007-9 -
Frontiers in Medicine 2022Pelvic organ prolapse (POP) affects many women and contributes significantly to a decrease in their quality of life causing urinary and/or fecal incontinence, sexual...
Pelvic organ prolapse (POP) affects many women and contributes significantly to a decrease in their quality of life causing urinary and/or fecal incontinence, sexual dysfunction and dyspareunia. To better understand POP pathophysiology, prevention and treatment, many researchers resorted to evaluating animal models. Regarding this example and because POP affects principally older women, our aim was to provide an overview of literature on the possible biomechanical changes that occur in the vaginas of animal models and their supportive structures as a consequence of aging. Papers published online from 2000 until May 2021 were considered and particular attention was given to articles reporting the effects of aging on the microscopic structure of the vagina and pelvic ligaments in animal models. Most research has been conducted on rodents because their vagina structure is well characterized and similar to those of humans; furthermore, they are cost effective. The main findings concern protein structures of the connective tissue, known as elastin and collagen. We have noticed a significant discordance regarding the quantitative changes in elastin and collagen related to aging, especially because it is difficult to detect them in animal specimens. However, it seems to be clear that aging affects the qualitative properties of elastin and collagen leading to aberrant forms which may affect the elasticity and the resilience of tissues leading to pelvic floor disease. The analysis of histological changes of pelvic floor tissues related to aging underlines how these topics appear to be not fully understood so far and that more research is necessary.
PubMed: 35492348
DOI: 10.3389/fmed.2022.863945 -
American Journal of Obstetrics and... Sep 2022To assess the efficacy and safety of vaginal progesterone to prevent recurrent preterm birth and adverse perinatal outcomes in singleton gestations with a history of... (Meta-Analysis)
Meta-Analysis Review
Does vaginal progesterone prevent recurrent preterm birth in women with a singleton gestation and a history of spontaneous preterm birth? Evidence from a systematic review and meta-analysis.
OBJECTIVE
To assess the efficacy and safety of vaginal progesterone to prevent recurrent preterm birth and adverse perinatal outcomes in singleton gestations with a history of spontaneous preterm birth.
DATA SOURCES
MEDLINE, Embase, LILACS, and CINAHL (from their inception to February 28, 2022), Cochrane databases, Google Scholar, bibliographies, and conference proceedings.
STUDY ELIGIBILITY CRITERIA
Randomized controlled trials that compared vaginal progesterone to placebo or no treatment in asymptomatic women with a singleton gestation and a history of spontaneous preterm birth.
METHODS
The primary outcomes were preterm birth <37 and <34 weeks of gestation. The secondary outcomes included adverse maternal and perinatal outcomes. Pooled relative risks with 95% confidence intervals were calculated. We assessed the risk of bias in the included studies, heterogeneity (I test), small-study effects, publication bias, and quality of evidence; performed subgroup and sensitivity analyses; and calculated 95% prediction intervals and adjusted relative risks.
RESULTS
Ten studies (2958 women) met the inclusion criteria: 7 with a sample size <150 (small studies) and 3 with a sample size >600 (large studies). Among the 7 small studies, 4 were at high risk of bias, 2 were at some concerns of bias, and only 1 was at low risk of bias. All the large studies were at low risk of bias. Vaginal progesterone significantly decreased the risk of preterm birth <37 weeks (relative risk, 0.64; 95% confidence interval, 0.50-0.81; I=75%; 95% prediction interval, 0.31-1.32; very low-quality evidence) and <34 weeks (relative risk, 0.62; 95% confidence interval, 0.42-0.92; I=66%; 95% prediction interval, 0.23-1.68; very low-quality evidence), and the risk of admission to the neonatal intensive care unit (relative risk, 0.53; 95% confidence interval, 0.33-0.85; I=67%; 95% prediction interval, 0.16-1.79; low-quality evidence). There were no significant differences between the vaginal progesterone and the placebo or no treatment groups in other adverse perinatal and maternal outcomes. Subgroup analyses revealed that vaginal progesterone decreased the risk of preterm birth <37 weeks (relative risk, 0.43; 95% confidence interval, 0.33-0.55; I=0%) and <34 weeks (relative risk, 0.27; 95% confidence interval, 0.15-0.49; I=0%) in the small but not in the large studies (relative risk, 0.98; 95% confidence interval, 0.88-1.09; I=0% for preterm birth <37 weeks; and relative risk, 0.94; 95% confidence interval, 0.78-1.13; I=0% for preterm birth <34 weeks). Sensitivity analyses restricted to studies at low risk of bias indicated that vaginal progesterone did not reduce the risk of preterm birth <37 weeks (relative risk, 0.96; 95% confidence interval, 0.84-1.09) and <34 weeks (relative risk, 0.90; 95% confidence interval, 0.71-1.15). There was clear evidence of substantial small-study effects in the meta-analyses of preterm birth <37 and <34 weeks of gestation because of funnel plot asymmetry and the marked differences in the pooled relative risks obtained from fixed-effect and random-effects models. The adjustment for small-study effects resulted in a markedly reduced and nonsignificant effect of vaginal progesterone on preterm birth <37 weeks (relative risk, 0.86; 95% confidence interval, 0.68-1.10) and <34 weeks (relative risk, 0.92; 95% confidence interval, 0.60-1.42).
CONCLUSION
There is no convincing evidence supporting the use of vaginal progesterone to prevent recurrent preterm birth or to improve perinatal outcomes in singleton gestations with a history of spontaneous preterm birth.
Topics: Female; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Pregnancy; Premature Birth; Progesterone; Vagina
PubMed: 35460628
DOI: 10.1016/j.ajog.2022.04.023 -
Frontiers in Microbiology 2022Genital mycoplasmas (GM), such as , and are commonly associated with spontaneous preterm labor (SPTL), spontaneous preterm birth (PTB), and preterm prelabor rupture of... (Review)
Review
Genital Mycoplasmas and Biomarkers of Inflammation and Their Association With Spontaneous Preterm Birth and Preterm Prelabor Rupture of Membranes: A Systematic Review and Meta-Analysis.
Genital mycoplasmas (GM), such as , and are commonly associated with spontaneous preterm labor (SPTL), spontaneous preterm birth (PTB), and preterm prelabor rupture of membranes (PPROM). This study determined the association between GM and such adverse pregnancy outcomes. We searched for studies published 1980-2019 in MEDLINE, EMBASE, and Web of Science. Studies were eligible when GM was detected during pregnancy. We included 93 and 51 studies in determining the prevalence and the inflammatory biomarkers associated with GM, respectively, using the "metafor" package within R. The protocol was registered with PROSPERO (registration no. CRD42016047297). Women with the studied adverse pregnancy outcomes had significantly higher odds of presence with GM compared to women who delivered at term. For PTB, the odds ratios were: (OR: 2.25; CI: 1.35-3.75; : 44%), (OR: 2.04; CIL 1.18-3.53; : 20%), (OR: 1.75; CI: 1.47-2.07; : 0%), (OR: 1.50; CI: 1.08-2.07; : 58%). SPTL had significantly higher odds with (OR: 1.96; CI: 1.19-3.23; : 1%) or (OR: 2.37; CI: 1.20-4.70; : 76%) compared to women without SPTL. Women with PPROM had significantly higher odds with (OR: 2.09; CI: 1.42-3.08; : 0%) than women without PPROM. However, our subgroup analysis based on the diagnostic test and the sample used for detecting GM showed a higher prevalence of GM in maternal samples than in fetal samples. GM presence of the cervix and vagina was associated with lower odds of PTB and preterm labor (PTL). In contrast, GM presence in the AF, fetal membrane, and placenta was associated with increased odds of PTB and PTL. However, genital mycoplasmas may not elicit the massive inflammation required to trigger PTB. In conclusion, GM presence in the fetal tissues was associated with significantly increased odds of PTB and PTL.
PubMed: 35432251
DOI: 10.3389/fmicb.2022.859732 -
BMC Pregnancy and Childbirth Mar 2022Screening for maternal anogenital Group B streptococci (GBS) colonization in pregnancy with initiation of intravenous intrapartum antibiotic prophylaxis as indicated has... (Meta-Analysis)
Meta-Analysis
Vaginal-perianal or vaginal-perineal compared with vaginal-rectal culture-based screening for Group B Streptococci (GBS) colonization during the third trimester of pregnancy: a systematic review and meta-analysis.
BACKGROUND
Screening for maternal anogenital Group B streptococci (GBS) colonization in pregnancy with initiation of intravenous intrapartum antibiotic prophylaxis as indicated has led to a significant reduction in the incidence of neonatal GBS infection. This study aims to evaluate the agreement between vaginal-perianal or vaginal-perineal culture and the more typically used vaginal-rectal culture for screening for maternal anogenital GBS colonization in the third trimester of pregnancy.
METHODS
Eligible English-language studies published until January 2020 were retrieved from Scopus, Web of Science, PubMed, Embase, and ClinicalTrials.gov databases. Studies were compiled that assessed for GBS colonization utilizing vaginal-perianal or vaginal-perineal culture and vaginal-rectal culture during the third trimester of pregnancy. Nonoriginal research articles and studies that did not assess pregnant patients, did not use culture-based screening, or did not compare vaginal-perianal or vaginal-perineal culture with vaginal-rectal culture were excluded. The search identified 559 articles with three prospective cohort studies that met inclusion criteria, including 643 participants. Quality was assessed using the Newcastle-Ottawa Scale, and risk of bias was assessed using the Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. Patient characteristics and associated pain with specimen collection were abstracted. Meta-analyses of both the raw agreement and the Cohen's kappa statistic were performed.
RESULTS
Within the three included studies, the range of GBS detection was 17.6-34.0%, consistent with the anticipated prevalence of GBS colonization reported in earlier publications. For both raw agreement and Cohen's kappa coefficient, the test for heterogeneity was not significant, indicating low heterogeneity among studies. The pooled estimate of the raw agreement was 0.97 (95%CI 0.95-0.98) and of the Cohen's kappa coefficient was 0.91 (95% CI: 0.87-0.95), indicating (according to the Landis and Koch criteria) an "almost perfect" agreement between the compared clinical tests. In the two studies that assessed procedure-related patient discomfort, vaginal-rectal swabbing caused more discomfort.
CONCLUSION
Use of vaginal-perineal culture for assessment of maternal GBS colonization is comparable to the more typically utilized vaginal-rectal culture and is associated with less discomfort.
Topics: Female; Humans; Mass Screening; Perineum; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, Third; Rectum; Specimen Handling; Streptococcal Infections; Streptococcus agalactiae; Vagina
PubMed: 35287615
DOI: 10.1186/s12884-022-04546-w -
Revista Da Associacao Medica Brasileira... Feb 2022
Meta-Analysis
Topics: Administration, Oral; Antifungal Agents; Candidiasis, Vulvovaginal; Female; Humans; Recurrence; Vagina
PubMed: 35239893
DOI: 10.1590/1806-9282.20210916 -
Journal of Personalized Medicine Feb 2022(1) Background: Granulomatosis with polyangiitis (GPA) is a necrotizing vasculitis that mimics gynecologic cancer. In GPA patients, the genitourinary system is affected... (Review)
Review
(1) Background: Granulomatosis with polyangiitis (GPA) is a necrotizing vasculitis that mimics gynecologic cancer. In GPA patients, the genitourinary system is affected in <1%. The objective of the study was to provide a systematic review of the literature of GPA patients with gynecological involvement. (2) Methods: PubMed and Embase were searched from inception to July 2021 for GPA patients with gynecological involvement Medical Subject Headings (MeSH) and free-text terms. Exclusion criteria were other language, review articles, pregnancy, fertility, or male patients. Data were extracted on clinical evolution, symptoms, examinations findings, diagnosis delay, treatment, outcome, patient status, and follow-up. (3) Results: Seventeen studies included data from patients with GPA and primary or relapsed gynecological involvement. 68% of the authors of this review thought the patient had cancer. The main gynecological symptom is bleeding, but exclusive gynecologic symptomatology is rare (ENT: 63%, lungs: 44%, kidneys-urinary tract: 53%). GPA could affect all areas of the genital tract, but the most frequent location is the uterine cervix. Medical treatment for GPA is effective. (4) Conclusions: GPA of the female genital tract must be considered when biopsies of an ulcerated malignant-appearing cervical or vaginal mass are negative for malignancy even when they are unspecific. Rheumatology consultation is indicated.
PubMed: 35207776
DOI: 10.3390/jpm12020289 -
International Urogynecology Journal Jul 2022To clarify which parameters are associated with unsuccessful pessary fitting for pelvic organ prolapse (POP) at up to 3 months follow-up. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To clarify which parameters are associated with unsuccessful pessary fitting for pelvic organ prolapse (POP) at up to 3 months follow-up.
METHODS
Embase, PubMed and Cochrane CENTRAL library were searched in May 2020. Inclusion criteria were: (1) pessary fitting attempted in women with symptomatic POP; (2) pessary fitting success among the study outcomes with a maximal follow-up of 3 months; (3) baseline parameters compared between successful and unsuccessful group. A meta-analysis was performed using the random effects model.
MAIN RESULTS
Twenty-four studies were included in the meta-analysis. Parameters associated with unsuccessful pessary fitting were: age (OR 0.70, 95% CI 0.56-0.86); BMI (OR 1.35, 95% CI 1.08-1.70); menopause (OR 0.65 95% CI 0.47-0.88); de novo stress urinary incontinence (OR 5.59, 95% CI 2.24-13.99); prior surgery, i.e. hysterectomy (OR 1.88, 95% CI 1.48-2.40), POP surgery (OR 2.13, 95% CI 1.34-3.38), pelvic surgery (OR 1.81, 05% CI 1.01-3.26) and incontinence surgery (OR 1.87, 95% CI 1.08-3.25); Colorectal-Anal Distress Inventory-8 scores (OR 1.92, 95% CI 1.22-3.02); solitary predominant posterior compartment POP (OR 1.59, 95% CI 1.08-2.35); total vaginal length (OR 0.56, 95% CI 0.32-0.97); wide introitus (OR 4.85, 95% CI 1.60-14.68); levator ani avulsion (OR 2.47, 95% CI 1.35-4.53) and hiatal area on maximum Valsalva (OR 1.89, 95% CI 1.27-2.80).
CONCLUSION
During counselling for pessary treatment a higher risk of failure due to the aforementioned parameters should be discussed and modifiable parameters should be addressed. More research is needed on the association between anatomical parameters and specific reasons for unsuccessful pessary fitting.
Topics: Female; Humans; Pelvic Floor; Pelvic Organ Prolapse; Pessaries; Urinary Incontinence, Stress; Vagina
PubMed: 35037973
DOI: 10.1007/s00192-021-05015-2