Prenatal diagnosis of 18p deletion and 8p trisomy syndrome: literature review and report of a novel case.

18p deletion syndrome constitutes one of the most frequent autosomal terminal deletion syndromes, affecting one in 50,000 live births. The syndrome has un-specific clinical features which vary significantly between patients and may overlap with other genetic conditions. Its prenatal description is extremely rare as the fetal phenotype is often not present during pregnancy. Trisomy 8p Syndrome is characterized by heterogenous phenotype, with the most frequent components to be cardiac malformation, developmental and intellectual delay. Its prenatal diagnosis is very rare due to the unspecific sonographic features of the affected fetuses. We present a very rare case of a fetus with multiple anomalies diagnosed during the second trimester whose genomic analysis revealed a 18p Deletion and 8p trisomy Syndrome. This is the first case where this combination of DNA mutations has been described prenatally and the second case in general. The presentation of this case, as well as the detailed review of all described cases, aim to expand the existing knowledge regarding this rare condition facilitating its diagnosis in the future.

Sperm DNA Fragmentation: Unraveling Its Imperative Impact on Male Infertility Based on Recent Evidence.

Male factors may be present in up to 50-70% of infertile couples and the prevalence of male infertility accounts for 20-30% of infertility cases. Understanding the mechanisms and causes behind male infertility remains a challenge, but new diagnostic tools such as DNA fragmentation might aid in cases where the routine semen analysis is insufficient. DNA fragmentation, which refers to damages or breaks of the genetic material of the spermatozoa, is considered one of the main causes of male infertility due to impaired functional capability of sperm. The aim of the present narrative review is to investigate and enlighten the potential correlation between DNA fragmentation and male infertility parameters such as the seminal profile and the reproductive outcomes. Comprehensive research in PubMed/Medline and Scopus databases was conducted and 28 studies were included in the present review. Fourteen studies provided data regarding the impact of DNA fragmentation and seminal parameters and showed a correlation of significantly lower sperm count, lower concentration, motility, and abnormal morphology with an increased DNA fragmentation index (DFI). Similarly, 15 studies provided data regarding the impact of DFI on reproductive outcomes. Two studies showed higher aneuploidy rates with higher DFI values, and seven studies showed significantly lower pregnancy rates and live birth rates with higher DFI values. Ultimately, the studies included in this review highlight, collectively, the importance of measuring sperm DFI in the assessment of male infertility. Further studies are needed to explore the effectiveness of interventions aiming to reduce DFI levels.

Fish DNA Sensors for Authenticity Assessment-Application to Sardine Species Identification.

Food and fish adulteration is a major public concern worldwide. Apart from economic fraud, health issues are in the forefront mainly due to severe allergies. Sardines are one of the most vulnerable-to-adulteration fish species due to their high nutritional value. Adulteration comprises the substitution of one fish species with similar species of lower nutritional value and lower cost. The detection of adulteration, especially in processed fish products, is very challenging because the morphological characteristics of the tissues change, making identification by the naked eye very difficult. Therefore, new analytical methods and (bio)sensors that provide fast analysis with high specificity, especially between closely related fish species, are in high demand. DNA-based methods are considered as important analytical tools for food adulteration detection. In this context, we report the first DNA sensors for sardine species identification. The sensing principle involves species recognition, via short hybridization of PCR-amplified sequences with specific probes, capture in the test zone of the sensor, and detection by the naked eye using gold nanoparticles as reporters; thus, avoiding the need for expensive instruments. As low as 5% adulteration of Sardina pilchardus with Sardinella aurita was detected with high reproducibility in the processed mixtures simulating canned fish products.

Hacking macrophages to combat cancer and inflammatory diseases - Current advances and challenges.

Recently, immunotherapy has been served as the treatment of choice for various human pathophysiologies, including inflammatory diseases and cancer. Though most of the current approaches target the lymphoid compartment, macrophages intimately implicated in the induction or resolution of inflammation have rationally gained their place into the therapeutics arena. In this review, I discuss the past and novel ground-breaking strategies focusing on macrophages in different human diseases and highlight the current challenges and considerations underlying their translational potentials.

The role of gut microbiome in prevention, diagnosis and treatment of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a common metabolic disease associated with maternal and foetal complications; gut microbiome might participate in GDM pathogenesis. Possible biological links include short chain fatty acids, incretin hormones, bile acids homeostasis and peroxisome proliferator-activated receptor gamma deficiency. Gut microbiome differs in patients with GDM even in early pregnancy, but no differences are observed five years postpartum. Patients have enriched Verrucomicrobia phylum, Christensenellaceae and Lachnospiraceae families, Haemophilus, Prevotella, Actinomyces, Collinsella and Ruminococcus genera during pregnancy. Clostridiales order, Alistipes, Faecalibacterium, Blautia, Eubacterium and Roseburia genera are depleted. However, there is great heterogeneity in the reviewed studies and scientific data on the use of gut microbiome characteristics and related biomarkers in GDM risk stratification and diagnosis are scarce. Probiotics and synbiotics have been tested for prevention and treatment for GDM with limited efficacy. Future studies should explore the effect of probiotics administration at first trimester of pregnancy and their value as adjuvant therapy.

Cadherin-11 as a therapeutic target in chronic, inflammatory rheumatic diseases.

Cadherin-11 has been identified as a key regulator of synovial architecture mediating contact between Fibroblast-like Synoviocytes and organization in the lining layer. A central role for cadherin-11 has also been suggested in the formation of the rheumatoid pannus. Therapeutic targeting of cadherin-11 results in amelioration of autoimmune experimental arthritis, as well as of experimental fibrosis. In addition, cadherin-11 expression is upregulated in the synovium of patients with chronic inflammatory arthritis, whereas detection of cadherin-11 mRNA transcripts in the peripheral blood has been associated with more severe disease phenotypes in two prototypic conditions of chronic joint inflammation and fibrosis, namely, rheumatoid arthritis and systemic sclerosis, respectively. Currently, a monoclonal antibody against cadherin-11 is in early phases of clinical trials in patients with rheumatoid arthritis. Herein, we review the current knowledge regarding the potential role of cadherin-11 in pathogenesis, as well as a biomarker and therapeutic target in chronic inflammatory rheumatic diseases.

Dynamic sentinel lymph node biopsy for penile cancer: a comparison between 1- and 2-day protocols.

OBJECTIVE: To determine the outcome of clinically negative node (cN0) patients with penile cancer undergoing dynamic sentinel node biopsy (DSNB), comparing the results of a 1- and 2-day protocol that can be used as a minimal invasive procedure for staging of penile cancer. PATIENTS AND METHODS: This is a retrospective analysis of 151 cN0 patients who underwent DSNB from 2008 to 2013 for newly diagnosed penile cancer. Data were analysed per groin and separated into groups according to the protocol followed. The comparison of the two protocols involved the number of nodes excised, γ-counts, false-negative rates (FNR), and complication rates (Clavien-Dindo grading system). RESULTS: In all, 280 groins from 151 patients underwent DSNB after a negative ultrasound ± fine-needle aspiration cytology. The 1-day protocol was performed in 65 groins and the 2-day protocol in 215. Statistically significantly more nodes were harvested with the 1-day protocol (1.92/groin) compared with the 2-day protocol (1.60/groin). The FNRs were 0%, 6.8% and 5.1%, for the 1-day protocol, 2-day protocol, and overall, respectively. Morbidity of the DSNB was 21.4% for all groins, and 26.2% and 20.1% for the 1-day and 2-day protocols, respectively. Most of the complications were of Clavien-Dindo Grade 1-2. CONCLUSIONS: DSNB is safe for staging patients with penile cancer. There is a trend towards a 1-day protocol having a lower FNR than a 2-day protocol, albeit at the expense of a slightly higher complication rate.

The role of the insulin-like growth factor-1 system in breast cancer.

IGF-1 is a potent mitogen of major importance in the mammary gland. IGF-1 binding to the cognate receptor, IGF-1R, triggers a signaling cascade leading to proliferative and anti-apoptotic events. Although many of the relevant molecular pathways and intracellular cascades remain to be elucidated, a growing body of evidence points to the important role of the IGF-1 system in breast cancer development, progression and metastasis. IGF-1 is a point of convergence for major signaling pathways implicated in breast cancer growth. In this review, we provide an overview and concise update on the function and regulation of IGF-1 as well as the role it plays in breast malignancies.

Increased messenger RNA levels of the mesenchymal cadherin-11 in the peripheral blood of systemic sclerosis patients correlate with diffuse skin involvement.

OBJECTIVES: Cadherin-11 is a cell-cell adhesion molecule also involved in cellular migration and invasion. Experimental studies implicated this molecule in inflammatory arthritis and fibrosing conditions. Moreover, cadherin-11 protein is hyper-expressed on fibroblasts and macrophages in the skin of systemic sclerosis (SSc) patients, whereas the respective mRNA levels correlate with skin thickness. Herein, we searched for possible cadherin-11 expression also in cells that circulate in SSc peripheral blood. METHODS: Cadherin-11 mRNA was quantified by real-time reverse transcription-polymerase chain reaction in 3 ml blood samples obtained from 71 SSc patients (aged 53±2 years, 65 women) and 35 control non-SSc patients with Raynaud's phenomenon. RESULTS: Cadherin-11 mRNA transcripts were detected in blood samples from 39% of patients with diffuse SSc, versus 16% of those with limited SSc, versus 6% and 16% of patients with idiopathic or associated with other connective tissue diseases Raynaud's phenomenon, respectively (p=0.049). Cadherin-11 mRNA levels in SSc patients were increased by 3.74-fold comparing to controls (p=0.036). By multivariate logistic regression analysis we found that diffuse skin involvement correlated, independently of age, gender, disease duration, lung involvement, digital ulcers, inflammatory indices or anti-Scl-70 autoantibody presence, with cadherin-11 mRNA positivity (p=0.028), but also with increased cadherin-11 mRNA levels (≥3-fold of non-SSc levels, p=0.011). CONCLUSIONS: Cadherin-11 may be hyper-expressed in the peripheral blood of diffuse SSc patients. Studies on the origin and possible pathogenic function of these circulating cells may shed light into the complex disease pathogenesis and further support the notion that cadherin-11 is a potential therapeutic target in SSc.

The role of estrogen receptor ß in prostate cancer.

Although androgen receptor (AR) signaling is the main molecular tool regulating growth and function of the prostate gland, estrogen receptor ß (ERß) is involved in the differentiation of prostatic epithelial cells and numerous antiproliferative actions on prostate cancer cells. However, ERß splice variants have been associated with prostate cancer initiation and progression mechanisms. ERß is promising as an anticancer therapy and in the prevention of prostate cancer. Herein, we review the recent experimental findings of ERß signaling in the prostate.

Uterus Transplantation as Infertility Treatment in Gynecological Cancer Survivors: A Systematic Review.

Background: The aim of this systematic review is to summarize the evidence regarding the acceptance of uterine transplantation as infertility treatment among gynecological cancer survivors, surgical and pregnancy outcomes post-transplantation for gynecological cancer survivors, as well as relevant adverse events. Methods: PubMed and Embase were searched for records published since 2000, and extensive reference screening was performed. Results: Out of 1901 unique records identified, 7 are included in this review; 4 examined the proportion of gynecological cancer survivors among applicants for uterine transplantation, 2 examined rejection rates, pregnancy rates, and outcomes after uterine transplantation among gynecological cancer survivors, and 2 reported the frequency of relevant adverse events. Among the applicants, 60/701 (8.6%) were gynecological cancer survivors, only 1 transplanted patient was a cervical cancer survivor and achieved two live births after eight embryo transfers, and 2/27 (7.4%) of uterus transplantation recipients were diagnosed with CIN post-transplantation. Conclusions: Uterus transplantation can be regarded as an infertility treatment for absolute uterine factor infertility (AUFI), although only one gynecological cancer survivor has received a uterus transplantation. The efficacy, safety, and ethical considerations for gynecological cancer survivors need to be addressed for uterine transplantation to become an infertility treatment option for AUFI among gynecological cancer survivors.

Increased prevalence of negative pregnancy and fetal outcomes in women with primary adrenal insufficiency. A systematic review and meta-analysis.

Maternal primary adrenal insufficiency (PAI) during pregnancy, due to either Addison disease (AD) or congenital adrenal hyperplasia (CAH), is rare. Only few studies have examined the subsequent important outcomes of maternal glucocorticoid and mineralocorticoid deficiencies during pregnancy upon the fetus and the neonate. Therefore, this systematic review and meta-analysis evaluated the impact of these deficiencies, with data from PubMed/Medline, Cochrane/CENTRAL, and Google Scholar. A total of 31 studies were included for qualitative analysis and 11 for quantitative analysis. Studies examining the prevalence of spontaneous abortion, preterm birth, the occurrence of small for gestational age (SGA) neonates, as well as the neonatal birth weight were included. The systematic review revealed a substantial number of spontaneous abortions, preterm births and SGA neonates in pregnant women with PAI. The meta-analysis showed a mean spontaneous abortion prevalence of 18%, 18% and 17% in women with PAI, AD or CAH, respectively. The mean preterm birth prevalence was 11% when women with AD or CAH were analyzed together, and 13% and 9% in women with AD or CAH, respectively, when these women were analyzed separately. The mean prevalence of SGA neonates was 8% when women with AD or CAH were analyzed together, and 5% and 10% in women with AD or CAH, respectively, when these women were analyzed separately. The mean fetal birth weight was within normalcy in all women with PAI, as well as in women with AD or CAH. In conclusion the executed systematic review of 31 studies followed by a meta-analysis of 11 studies in pregnant women with PAI has shown a greater prevalence of pregnancies with negative outcome (spontaneous abortion, preterm birth) and of negative fetal outcome (SGA) in women with either AD or CAH, as compared to control pregnant women.

Visceral Leishmaniasis in a Twin Pregnancy: A Case Report and Review of the Literature.

Visceral leishmaniasis (VL), often referred to as kala-azar, is quite rare in developed countries during pregnancy. Only few studies have evaluated its impact on perinatal outcome. It is caused primarily by Leishmania donovani or Leishmania infantum and presents with a wide spectrum of clinical manifestations from cutaneous ulcers to multisystem disease. Differential diagnosis is challenging as symptoms and signs are insidious, mimicking other diseases. Misdiagnosis can result in severe adverse perinatal outcomes, even maternal/neonatal death. Early treatment with liposomal amphotericin-B (LAmB) is currently the first choice with adequate effectiveness. We report a rare case of VL in a twin pregnancy with onset at the second trimester, presenting with periodic fever with rigors, right flank pain, and gradual dysregulation of all three cell lines. The positive rK39 enzyme-linked immunosorbent assay test confirmed the diagnosis. Treatment with LAmB resulted in clinical improvement within 48 h and in the delivery of two late-preterm healthy neonates with no symptoms or signs of vertical transmission. The one-year follow-up, of the mother and the neonates, was negative for recurrence. To our knowledge, this is the first reported case of VL in a twin pregnancy, and consequently treatment and perinatal outcome are of great importance.

Anastrozole monotherapy further improves near-adult height after the initial combined treatment with leuprorelin and anastrozole in early-maturing girls with compromised growth prediction: results from the second phase of the GAIL study.

Background: The first phase of the GAIL study ("Girls treated with an Aromatase Inhibitor and Leuprorelin," ISRCTN11469487) has shown that the combination of anastrozole and leuprorelin for 24 months is safe and effective in improving the predicted adult height (PAH) in girls with early puberty and compromised growth prediction by +1.21 standard deviation score (SDS; +7.51 cm) compared to inhibition of puberty alone, +0.31 SDS (+1.92 cm). Objectives and hypotheses: In the second phase of the GAIL study, we assessed the adult height (AH)/near-adult height (NAH) at the end of the first phase and, in addition, the efficacy of anastrozole monotherapy thereafter in further improving NAH. Methods: We measured the AH (age 16.5 years)/NAH [bone age (BA), 15 years] of the 40 girls included, divided into two matched groups: group A (20 girls on anastrozole + leuprorelin) and group B (20 girls on leuprorelin alone). Group A was further randomized into two subgroups: A1 and A2. Group A1 (n = 10), after completion of the combined therapy, received anastrozole 1 mg/day as monotherapy until BA 14 years, with a 6-month follow-up. Group A2 (n = 10) and group B (n = 20), who received only the combined treatment and leuprorelin alone, respectively, were recalled for evaluation of AH/NAH. Results: AH or NAH exceeded the PAH at the completion of the 2-year initial phase of the GAIL study in all groups, but the results were statistically significant only in group A1: NAH-PAH group A1, +3.85 cm (+0.62 SDS, p = 0.01); group A2, +1.6 cm (+0.26 SDS, p = 0.26); and group B, +1.7 cm (+0.3 SDS, p = 0.08). The gain in group A1 was significantly greater than that in group A2 (p = 0.04) and in group B (p = 0.03). Anastrozole was determined to be safe even as monotherapy in Group A1. Conclusions: In early-maturing girls with compromised growth potential, the combined treatment with leuprorelin and anastrozole for 2 years or until the age of 11 years resulted in a total gain in height of +9.7 cm when continuing anastrozole monotherapy until the attainment of NAH, as opposed to +7.4 cm if they do not continue with the anastrozole monotherapy and +3.6 cm when treated with leuprorelin alone. Thus, the combined intervention ends at the shortest distance from the target height if continued with anastrozole monotherapy until BA 14 years.

Molecular Rapid Test for Identification of Tuna Species.

Tuna is an excellent food product, relatively low in calories, that is recommended for a balanced diet. The continuously increasing demand, especially for bluefin-tuna-based food preparations, and its relatively high market price make adulteration by intentionally mixing with other lower-priced tunas more prospective. The development of rapid methods to detect tuna adulteration is a great challenge in food analytical science. We have thus developed a simple, fast, and low-cost molecular rapid test for the visual detection of tuna adulteration. It is the first sensor developed for tuna authenticity testing. The three species studied were Thunnus thynnus (BFT), Thunnus albacares, and Katsuwonus pelamis. DNA was isolated from fresh and heat-treated cooked fish samples followed by PCR. The PCR products were hybridized (10 min) to specific probes and applied to the rapid sensing device. The signal was observed visually in 10-15 min using gold nanoparticle reporters. The method was evaluated employing binary mixtures of PCR products from fresh tissues and mixtures of DNA isolates from heat-treated tissues (canned products) at adulteration percentages of 1-100%. The results showed that the method was reproducible and specific for each tuna species. As low as 1% of tuna adulteration was detected with the naked eye.

Immunotherapy in Cervical and Endometrial Cancer: Current Landscape and Future Directions.

Gynecological cancers pose a significant burden on women's health worldwide, necessitating innovative treatment approaches. Immunotherapy has emerged as a promising strategy, harnessing the body's immune system to combat cancer. This review aims to provide a comprehensive overview of the current landscape and future directions of immunotherapy in cervical and endometrial cancer. Methods: A thorough literature search was conducted to identify relevant studies and clinical trials. The main methods and treatments employed in immunotherapy for cervical and endometrial cancer, including immune checkpoint inhibitors, cancer vaccines, and adoptive cell therapies, are briefly described. Results: Immune checkpoint inhibitors, such as anti-PD-1/PD-L1 antibodies, have shown remarkable clinical efficacy in certain gynecological malignancies, particularly in advanced or recurrent cases. Additionally, ongoing research on cancer vaccines and adoptive cell therapies holds promise for personalized and targeted treatment options.

The Impact of Human Papillomavirus Infections on Recurrent Pregnancy Loss: A Review of the Literature.

Human papillomavirus (HPV) infections are significantly associated with multiple adverse reproductive outcomes such as miscarriages. Pregnant women are more susceptible to an HPV infection and its prevalence increases as pregnancy progresses. In this present review, we summarize the existing evidence indicating the potential impact of an HPV infection on the occurrence of recurrent pregnancy loss (RPL). Comprehensive research of the literature was performed in the Medline/PubMed and Scopus databases. A total of 185 articles were identified and 40 full-text articles were assessed. Four studies were eligible to be included in this literature review. To our knowledge, this is the first review aiming to summarize the current state of evidence regarding the possible association of HPV infections and RPL. Recurrent pregnancy loss constitutes a distressing reproductive event and scientific research has made significant efforts to determine the causes and mechanisms that could lead to RPL. It is still unclear whether the papillomavirus infection is associated with an increased risk for recurrent miscarriages. Research in the field revealed conflicting results and their deductions are limited by methodological limitations. Given the high prevalence of HPV infections and their potential role in the occurrence of adverse outcomes during pregnancy, further research is required to clarify the possibility of an HPV infection being a potential risk factor for recurrent miscarriages.

Fungal polysaccharides from Inonotus obliquus are agonists for Toll-like receptors and induce macrophage anti-cancer activity.

Fungal polysaccharides can exert immunomodulating activity by triggering pattern recognition receptors (PRRs) on innate immune cells such as macrophages. Here, we evaluate six polysaccharides isolated from the medicinal fungus Inonotus obliquus for their ability to activate mouse and human macrophages. We identify two water-soluble polysaccharides, AcF1 and AcF3, being able to trigger several critical antitumor functions of macrophages. AcF1 and AcF3 activate macrophages to secrete nitric oxide and the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Combined with interferon-γ, the fungal polysaccharides trigger high production of IL-12p70, a central cytokine for antitumor immunity, and induce macrophage-mediated inhibition of cancer cell growth in vitro and in vivo. AcF1 and AcF3 are strong agonists of the PRRs Toll-like receptor 2 (TLR2) and TLR4, and weak agonists of Dectin-1. In comparison, two prototypical particulate ß-glucans, one isolated from I. obliquus and one from Saccharomyces cerevisiae (zymosan), are agonists for Dectin-1 but not TLR2 or TLR4, and are unable to trigger anti-cancer functions of macrophages. We conclude that the water-soluble polysaccharides AcF1 and AcF3 from I. obliquus have a strong potential for cancer immunotherapy by triggering multiple PRRs and by inducing potent anti-cancer activity of macrophages.

Association between cytokine polymorphisms and recurrent pregnancy loss: A review of current evidence.

Cytokines are a type of protein that play an important role in the immune response and can also affect many physiological processes in the body. Cytokine polymorphisms refer to genetic variations or mutations that occur within the genes that code for cytokines, which may affect the level of cytokine production and function. Some cytokine polymorphisms have been associated with an increased risk of developing certain diseases, while others may be protective or have no significant effect on health. In recent years, the role of cytokine polymorphisms in the development of recurrent pregnancy loss (RPL) has been studied. RPL or miscarriage is defined as the occurrence of two or more consecutive pregnancy losses before the 20th week of gestation. There are diverse causes leading to RPL, including genetic, anatomical, hormonal, and immunological factors. With regard to cytokine polymorphisms, a few of them have been found to be associated with an increased risk of RPL, for instance, variations in the genes that code for interleukin-6, tumor necrosis factor-alpha, and interleukin-10. The exact mechanisms by which cytokine polymorphisms affect the risk of recurrent miscarriage are still being studied, and further research is essential to fully understand this complex condition. This brief review aims to summarize the recent literature on the association between cytokine polymorphisms and RPL.

Intraovarian Platelet-Rich Plasma Administration for Anovulatory Infertility: Preliminary Findings of a Prospective Cohort Study.

Background/Objectives: Infertility constitutes a significant challenge for couples around the world. Ovarian dysfunction, a major cause of infertility, can manifest with anovulatory cycles, elevated follicle-stimulating hormone levels, and diminished ovarian reserve markers such as anti-Müllerian hormone (AMH) levels or the Antral Follicle Count (AFC). Blood-derived therapies including platelet-rich plasma (PRP) have been used in fertility treatments in women with low ovarian reserve or premature ovarian insufficiency. This prospective clinical cohort study aims to assess the effects of intraovarian PRP therapy on ovarian function in women diagnosed with anovulatory cycles. Methods: The preliminary findings of this prospective cohort study are based on the first 32 patients enrolled. In this study, patients over 40 years old with anovulatory infertility were included. Venous blood samples were collected from each participant for the preparation of autologous platelet-rich plasma (PRP). Each participant received two courses of intraovarian PRP injections using a transvaginal ultrasound-guided approach. Serum levels of reproductive hormones before and after PRP intervention were measured. Results: This study's results demonstrate a significant improvement in ovarian physiology following transvaginal ultrasound-guided PRP infusion. A 75% increase in Antral Follicle Count (AFC) was observed, which was statistically significant. Furthermore, statistically significant reductions in follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin levels were observed. Serum Vitamin D 1-25 levels were substantially increased after the injection. Conclusions: These findings highlight the beneficial impact of intraovarian PRP injection in optimizing ovarian function and other metabolic parameters. However, the published literature on this subject is limited and further clinical studies should be conducted to confirm the role of intraovarian PRP in fertility treatments.