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Journal of Assisted Reproduction and... Jan 2022Platelet-rich plasma (PRP) therapy has been used as an adjunct to fertility treatments in women with very low ovarian reserve and premature ovarian insufficiency. Recent... (Review)
Review
PURPOSE
Platelet-rich plasma (PRP) therapy has been used as an adjunct to fertility treatments in women with very low ovarian reserve and premature ovarian insufficiency. Recent literature in both humans and animals suggest that intraovarian PRP administration in the setting of poor ovarian reserve may help ovarian function and increase the chances of pregnancy.
METHODS
A comprehensive literature search through PubMed, MEDLINE databases, and recent abstracts published at relevant society meetings was performed and resulted in 25 articles and 2 abstracts published that studied effect of PRP on the ovaries for the purpose of reproduction.
RESULTS
This review article presents all the data published to date pertaining to intraovarian PRP injection and pregnancy, both naturally and after in vitro fertilization. It also presents the most recent data on the use of ovarian PRP in in vitro and animal model studies highlighting the possible mechanisms by which PRP could impact ovarian function.
CONCLUSIONS
Even though recent commentaries questioned the use of PRP as an "add-on" therapy in fertility treatment because it has not been thoroughly studied, the recent basic science studies presented here could increase awareness for considering more serious research into the efficacy of PRP as an adjunct for women with poor ovarian reserve, premature ovarian insufficiency, and even early menopause who are trying to conceive using their own oocytes. Given its low-risk profile, the hypothetical benefit of PRP treatment needs to be studied with larger randomized controlled trials.
Topics: Adult; Drug Administration Routes; Female; Humans; Ovary; Ovulation Induction; Platelet-Rich Plasma
PubMed: 35175511
DOI: 10.1007/s10815-021-02385-w -
Journal of Clinical Research in... Jul 2018Abnormal uterine bleeding (AUB) is the most common gynecologic complaint of adolescents admitted to hospital. Heavy menstrual bleeding (HMB) is the most frequent... (Review)
Review
Abnormal uterine bleeding (AUB) is the most common gynecologic complaint of adolescents admitted to hospital. Heavy menstrual bleeding (HMB) is the most frequent clinical presentation of AUB. Anovulatory cycles, owing to immature hypothalamic-pituitary-ovarian axis, is the leading etiology of HMB and there is an accompanying bleeding disorder in almost 20% of patients with HMB. Additionally, endocrine disorders such as hypothyroidism, hyperprolactinemia and polycystic ovary syndrome are possible causes of AUB. Exclusion of bleeding disorders, especially of von Willebrand disease is important for diagnosis and treatment of HMB, particularly in cases with AUB, which has been present since menarche. Management of HMB is based on the underlying etiology and severity of the bleeding. After other causes are excluded, anovulatory heavy bleeding can be treated successfully with combined oral contraceptives and iron supplementation either as an outpatient or in hospital depending on the clinical findings and level of anemia. The epidemiology, clinical presentation, diagnostic approach and treatment of HMB is discussed and our clinical experience in this field is presented in this review.
Topics: Adolescent; Female; Humans; Uterine Hemorrhage
PubMed: 29537383
DOI: 10.4274/jcrpe.0014 -
Cancer Cell May 2022Despite repeated associations between T cell infiltration and outcome, human ovarian cancer remains poorly responsive to immunotherapy. We report that the hallmarks of...
Despite repeated associations between T cell infiltration and outcome, human ovarian cancer remains poorly responsive to immunotherapy. We report that the hallmarks of tumor recognition in ovarian cancer-infiltrating T cells are primarily restricted to tissue-resident memory (TRM) cells. Single-cell RNA/TCR/ATAC sequencing of 83,454 CD3CD8CD103CD69 TRM cells and immunohistochemistry of 122 high-grade serous ovarian cancers shows that only progenitor (TCF1) tissue-resident T cells (TRM cells), but not recirculating TCF1 T cells, predict ovarian cancer outcome. TRM cells arise from transitional recirculating T cells, which depends on antigen affinity/persistence, resulting in oligoclonal, trogocytic, effector lymphocytes that eventually become exhausted. Therefore, ovarian cancer is indeed an immunogenic disease, but that depends on ∼13% of CD8 tumor-infiltrating T cells (∼3% of CD8 clonotypes), which are primed against high-affinity antigens and maintain waves of effector TRM-like cells. Our results define the signature of relevant tumor-reactive T cells in human ovarian cancer, which could be applicable to other tumors with unideal mutational burden.
Topics: CD8-Positive T-Lymphocytes; Female; Humans; Immunologic Memory; Lymphocytes, Tumor-Infiltrating; Memory T Cells; Ovarian Neoplasms
PubMed: 35427494
DOI: 10.1016/j.ccell.2022.03.008 -
Frontiers in Immunology 2022Tumor-infiltrating lymphocytes (TILs), frontline soldiers of the adaptive immune system, are recruited into the tumor site to fight against tumors. However, their small... (Review)
Review
Tumor-infiltrating lymphocytes (TILs), frontline soldiers of the adaptive immune system, are recruited into the tumor site to fight against tumors. However, their small number and reduced activity limit their ability to overcome the tumor. Enhancement of TILs number and activity against tumors has been of interest for a long time. A lack of knowledge about the tumor microenvironment (TME) has limited success in primary TIL therapies. Although the advent of engineered T cells has revolutionized the immunotherapy methods of hematologic cancers, the heterogeneity of solid tumors warrants the application of TILs with a wide range of specificity. Recent advances in understanding TME, immune exhaustion, and immune checkpoints have paved the way for TIL therapy regimens. Nowadays, TIL therapy has regained attention as a safe personalized immunotherapy, and currently, several clinical trials are evaluating the efficacy of TIL therapy in patients who have failed conventional immunotherapies. Gaining favorable outcomes following TIL therapy of patients with metastatic melanoma, cervical cancer, ovarian cancer, and breast cancer has raised hope in patients with refractory solid tumors, too. Nevertheless, TIL therapy procedures face several challenges, such as high cost, timely expansion, and technical challenges in selecting and activating the cells. Herein, we reviewed the recent advances in the TIL therapy of solid tumors and discussed the challenges and perspectives.
Topics: Female; Humans; Lymphocytes, Tumor-Infiltrating; Immunotherapy; Melanoma; Ovarian Neoplasms; T-Lymphocytes; Tumor Microenvironment
PubMed: 36389779
DOI: 10.3389/fimmu.2022.1018962 -
Acta Medica Portuguesa Mar 2021Abnormal uterine bleeding is the most common complaint that motivates female adolescents to seek medical advice. Abnormal uterine bleeding has a significant impact on... (Review)
Review
Abnormal uterine bleeding is the most common complaint that motivates female adolescents to seek medical advice. Abnormal uterine bleeding has a significant impact on quality of life, promoting school absenteeism and limitations in social life. Moreover, episodes can vary from mild to life threatening events if not recognized and treated promptly. Healthcare providers should be able to distinguish between a normal and abnormal menstrual pattern, as this may provide early diagnosis of a potential health concern. The PALM-COEIN classification system should be used in the evaluation. Anovulation is the most frequent cause, frequently due to immaturity of the hypothalamic-pituitary-ovarian axis. A careful history and physical examination are crucial in the differential diagnosis. Management is based on both the underlying cause and the severity of bleeding. Most patients improve with pharmacological treatment, frequently requiring a multidisciplinary approach. First line treatment consists of hormonal therapy. Surgery is rarely needed. Although the prevalence of abnormal uterine bleeding is higher in adolescents compared to adults, most recommendations are not specific for this age, which makes the diagnosis and management challenging. The literature reveals lack of standardized care for adolescents and regimens vary widely. Future studies on efficacy and safety of treatments specifically in adolescents are needed.
Topics: Adolescent; Adult; Blood Coagulation Disorders; Female; Humans; Menorrhagia; Metrorrhagia; Quality of Life; Uterine Diseases; Uterine Hemorrhage
PubMed: 34214420
DOI: 10.20344/amp.12829 -
Drugs Oct 2022An oral fixed-dose combination of relugolix/estradiol/norethisterone (also known as norethindrone) acetate (Ryeqo; Myfembree) has been approved for the management of... (Review)
Review
An oral fixed-dose combination of relugolix/estradiol/norethisterone (also known as norethindrone) acetate (Ryeqo; Myfembree) has been approved for the management of heavy menstrual bleeding associated with uterine fibroids in the USA and management of moderate to severe symptoms of uterine fibroids in the EU. Relugolix is a gonadotropin releasing hormone (GnRH) receptor antagonist that decreases serum estradiol and progesterone concentrations to postmenopausal levels. The addition of estradiol/norethisterone acetate to relugolix ameliorates relugolix-induced bone loss and hot flush. In the two phase 3 LIBERTY trials, relugolix + estradiol/norethisterone substantially decreased menstrual bleeding and improved a range of other uterine fibroid symptoms in women with uterine fibroids-associated heavy menstrual bleeding. The combination was generally well tolerated, with vasomotor symptoms being the most common adverse reaction. Treatment with this combination for over up to 2 years did not induce a clinically meaningful bone loss in the majority of women. Relugolix/estradiol/norethisterone acetate, with its convenient once-daily administration, is a useful addition to current pharmacological treatment options for premenopausal women with symptomatic uterine fibroids.
Topics: Female; Humans; Norethindrone Acetate; Menorrhagia; Uterine Neoplasms; Leiomyoma; Norethindrone; Estradiol; Acetates
PubMed: 36331779
DOI: 10.1007/s40265-022-01790-4 -
Human Reproduction (Oxford, England) Jun 2021The prospect of ovarian rejuvenation offers the tantalising prospect of treating age-related declines in fertility or in pathological conditions such as premature...
The prospect of ovarian rejuvenation offers the tantalising prospect of treating age-related declines in fertility or in pathological conditions such as premature ovarian failure. The concept of ovarian rejuvenation was invigorated by the indication of the existence of oogonial stem cells (OSCs), which have been shown experimentally to have the ability to differentiate into functional follicles and generate oocytes; however, their clinical potential remains unknown. Furthermore, there is now growing interest in performing ovarian rejuvenation in situ. One proposed approach involves injecting the ovary with platelet rich plasma (PRP). PRP is a component of blood that remains after the in vitro removal of red and white blood cells. It contains blood platelets, tiny anucleate cells of the blood, which are responsible for forming athrombus to prevent bleeding. In addition, PRP contains an array of cytokines and growth factors, as well as a number of small molecules.The utility ofPRP has been investigatedin a range of regenerative medicine approaches and has been shown to induce differentiation of a range of cell types, presumably through the action of cytokines. A handful ofcasereports have described the use of PRP injections into the ovaryin the human, and while these clinical data report promising results, knowledge on the mechanisms and safety of PRP injections into the ovary remain limited.In this article, we summarise some of the physiological detail of platelets and PRP, before reviewing the existing emerging literature in this area. We then propose potential mechanisms by which PRP may be eliciting any effects before reflecting on some considerations for future studies in the area. Importantly, on the basis of our existing knowledge, we suggest that immediate use of PRP in clinical applications is perhaps premature and further fundamental and clinical research on the nature of ovarian insufficiency, as well as the mechanism by which PRP may act on the ovary, is needed to fully understand this promising development.
Topics: Female; Humans; Platelet-Rich Plasma; Primary Ovarian Insufficiency; Rejuvenation; Reproduction
PubMed: 33963408
DOI: 10.1093/humrep/deab106 -
Canadian Medical Association Journal Nov 1964Ataxia-telangiectasia is a syndrome of progressive cerebellar ataxia and other neurological manifestations associated with conjunctival and cutaneous telangiectases and...
Ataxia-telangiectasia is a syndrome of progressive cerebellar ataxia and other neurological manifestations associated with conjunctival and cutaneous telangiectases and with recurrent sino-pulmonary infections. Immunological and endocrine abnormalities occur. Two girls with this disease are described. The first had only minor respiratory infections; her serum proteins and immunity responses appeared normal. The second had recurrent pulmonary infections and bronchiectasis; she also exhibited sclerodermatous changes, poor development of secondary sexual characteristics with low urinary excretion of 17-ketosteroids, and lymphopenia. Autopsy at 17 years showed bilateral ovarian dysgerminomata and excessive cutaneous collagen as well as atrophy, and perhaps hypoplasia, of adrenals, thymus, spleen and lymphoid tissue (after steroid therapy). The cerebellum exhibited cortical degeneration. Both lungs were fibrotic with old and recent bronchopneumonia and bronchiectasis. The left lung was studied by injection of a latex preparation; no arteriovenous aneurysms were found, but the smaller pulmonary vessels showed some unusual morphological characteristics.
Topics: 17-Ketosteroids; Adolescent; Ataxia; Ataxia Telangiectasia; Atrophy; Blood Protein Electrophoresis; Bronchiectasis; Cerebellar Diseases; Child; Conjunctiva; Dysgerminoma; Eosinophils; Female; Genetics, Medical; Humans; Hypogonadism; Immunoelectrophoresis; Infant; Infant, Newborn; Leukocyte Count; Lymphocytes; Neoplasms, Germ Cell and Embryonal; Neurologic Manifestations; Ovarian Neoplasms; Pathology; Pulmonary Circulation; Pulmonary Fibrosis; Scleroderma, Systemic; Telangiectasis; Urine
PubMed: 14229760
DOI: No ID Found -
Frontiers in Endocrinology 2023Premature ovarian insufficiency (POI) is one of the most common causes of female infertility and the etiology is highly heterogeneous. Most cases are idiopathic and the...
BACKGROUND
Premature ovarian insufficiency (POI) is one of the most common causes of female infertility and the etiology is highly heterogeneous. Most cases are idiopathic and the pathogenesis remains unclear. Previous studies proved that the immune system plays a crucial role in POI. However, the precise role of immune system remains unclear. This study aimed to analyze the characteristics of peripheral blood mononuclear cells (PBMC) from patients with POI by single-cell RNA sequencing (scRNA-seq) and to explore the potential involvement of immune response in idiopathic POI.
METHODS
PBMC was collected from three normal subjects and three patients with POI. PBMC was subjected to scRNA-seq to identify cell clusters and differently expressed genes (DEGs). Enrichment analysis and cell-cell communication analysis were performed to explore the most active biological function in the immune cells of patients with POI.
RESULTS
In total, 22 cell clusters and 10 cell types were identified in the two groups. Compared with normal subjects, the percentage of classical monocytes and NK cells was decreased, the abundance of plasma B cells was increased, and CD4/CD8 ratio was significantly higher in POI. Furthermore, upregulation of and downregulation of , and were identified, which were enriched in NK cell-mediated cytotoxicity, antigen processing and presentation, and IL-17 signaling pathway. Among them, and were respectively the most significantly upregulated and downregulated genes among all cell clusters of POI. The strength of cell-cell communication differed between the healthy subjects and patients with POI, and multiple signaling pathways were assessed. The TNF pathway was found to be unique in POI with classical monocytes being the major target and source of TNF signaling.
CONCLUSIONS
Dysfunction of cellular immunity is related to idiopathic POI. Monocytes, NK cells, and B cells, and their enriched differential genes may play a role in the development of idiopathic POI. These findings provide novel mechanistic insight for understanding the pathogenesis of POI.
Topics: Humans; Female; Leukocytes, Mononuclear; Menopause, Premature; Primary Ovarian Insufficiency; Immune System Diseases; Sequence Analysis, RNA
PubMed: 37223018
DOI: 10.3389/fendo.2023.1129657 -
Ultrasound in Obstetrics & Gynecology :... Aug 2022The primary aim of this study was to describe the ultrasound features of various endometrial and other intracavitary pathologies in women without abnormal uterine... (Observational Study)
Observational Study
OBJECTIVES
The primary aim of this study was to describe the ultrasound features of various endometrial and other intracavitary pathologies in women without abnormal uterine bleeding (AUB) using the International Endometrial Tumor Analysis (IETA) terminology. The secondary aim was to compare our findings with published data on women with AUB.
METHODS
This was a prospective observational study of women presenting at one of seven centers specialized in gynecological ultrasonography, from 2011 until 2018, for indications unrelated to AUB. All patients underwent transvaginal ultrasound using the IETA examination and measurement techniques. Ultrasonography was performed as part of routine gynecological examination or follow-up of non-endometrial pathology, or as part of the work-up before undergoing treatment for infertility, uterine prolapse or ovarian pathology. Ultrasound findings were described using the IETA terminology. Endometrial sampling was performed after the ultrasound scan. The histological endpoints were endometrial atrophy, proliferative or secretory endometrium, endometrial hyperplasia without atypia, endometrial polyp, intracavitary leiomyoma, endometrial intraepithelial neoplasia (EIN), endometrial cancer (EC) and insufficient tissue. The findings in our cohort of women without AUB were compared with those in a published cohort of women with AUB who were examined with transvaginal ultrasound between 2012 and 2015 using the same IETA examination technique and terminology.
RESULTS
In this study (IETA3), we included 1745 women without AUB who underwent a standardized transvaginal ultrasound examination followed by either endometrial sampling with histological diagnosis (n = 1537) or at least 1 year of clinical and ultrasound follow-up (n = 208). Of these, 858 (49.2%) women were premenopausal and 887 (50.8%) were postmenopausal. Histology showed the presence of EC and/or EIN in 29 (1.7%) women, endometrial polyps in 1028 (58.9%), intracavitary myomas in 66 (3.8%), proliferative or secretory changes or hyperplasia without atypia in 144 (8.3%), endometrial atrophy in 265 (15.2%) and insufficient tissue in five (0.3%). Most cases of EC or EIN (25/29 (86.2%)) were diagnosed after menopause. The mean endometrial thickness in women with EC or EIN was 11.2 mm (95% CI, 8.9-13.6 mm), being on average 2.4 mm (95% CI, 0.3-4.6 mm) thicker than their benign counterparts. Women with malignant endometrial pathology manifested more frequently non-uniform echogenicity (22/29 (75.9%)) than did those with benign endometrial pathology (929/1716 (54.1%)) (difference, +21.8% (95% CI, +4.2% to +39.2%)). Moderate to abundant vascularization (color score 3-4) was seen in 31.0% (9/29) of cases with EC or EIN compared with 12.8% (220/1716) of those with a benign outcome (difference, +18.2% (95% CI, -0.5% to +36.9%)). Multiple multifocal vessels were recorded in 24.1% (7/29) women with EC or EIN vs 4.0% (68/1716) of those with a benign outcome (difference, +20.2% (95% CI, +4.6% to +35.7%)). A regular endometrial-myometrial junction was seen less frequently in women with EC or EIN (19/29 (65.5%)) vs those with a benign outcome (1412/1716 (82.3%)) (difference, -16.8% (95% CI, -34.2% to +0.6%)). In women with endometrial polyps without AUB, a single dominant vessel was the most frequent vascular pattern (666/1028 (64.8%)). In women with EC, both in those with and those without AUB, the endometrium usually manifested heterogeneous echogenicity, but the endometrium was on average 8.6 mm (95% CI, 5.2-12.0 mm) thinner and less intensely vascularized (color score 3-4: difference, -26.8% (95% CI, -52.2% to -1.3%)) in women without compared to those with AUB. In both pre- and postmenopausal women, asymptomatic endometrial polyps were associated with a thinner endometrium, and they manifested more frequently a bright edge, a regular endometrial-myometrial junction and a single dominant vessel than did polyps in symptomatic women, and they were less intensely vascularized.
CONCLUSIONS
We describe the typical ultrasound features of EC, polyps and other intracavitary histologies using IETA terminology in women without AUB. Our findings suggest that the presence of asymptomatic polyps or endometrial malignancy may be accompanied by thinner and less intensely vascularized endometria than their symptomatic counterparts. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Atrophy; Endometrial Hyperplasia; Endometrial Neoplasms; Endometrium; Female; Humans; Male; Polyps; Ultrasonography; Uterine Diseases; Uterine Hemorrhage; Uterine Neoplasms
PubMed: 35385178
DOI: 10.1002/uog.24910