Efficacy of intra-ovarian injection of autologous platelet-rich plasma in women with poor responders: a systematic review and meta-analysis.

CONTEXT: The effect of platelet-rich plasma (PRP) on ovarian reserve markers in poor ovarian response (POR) is challenging. AIM: This systematic review and meta-analysis was, therefore, designed to evaluate the effectiveness of intra-ovarian injection of autologous PRP on improving ovarian reserve markers and assisted reproductive technology (ART) outcomes in infertile women with POR. METHODS: A systematic search was conducted for the efficacy of intra-ovarian injection of autologous PRP on the improvement of ovarian reserve markers and ART outcomes in infertile women with POR. The methodological quality of the included studies was checked and eligible studies were included in the meta-analysis to find pooled results. Keywords were primary ovarian insufficiency, premature menopause, poor responder, poor ovarian response, diminished/decreased ovarian reserve, platelet-rich plasma, and intra-ovarian or a combination of them. The effect of PRP on fertility indices was evaluated using the standardized mean difference (SMD). The analysis was performed through STATA version 13. KEY RESULTS: 13 studies containing 1289 patients were included. Mean age, body mass index (BMI) and duration of infertility was 37.63 ± 2.66 years, 24 ± 1.23 kg/m2 and 4.79 ± 1.64 years, respectively. Most of the studies measured the outcomes 2-3/3 months after intra-ovarian injection of autologous PRP. The antral follicular count (AFC) after treatment by PRP is higher with an SMD of 0.95 compared to before treatment. The day 3 follicle-stimulating hormone (FSH) after treatment by PRP is lower with an SMD of - 0.25 compared to before treatment. The day 3 estradiol (E2) after treatment by PRP is higher with an SMD of 0.17 compared to before treatment. The anti-Mullerian hormone (AMH) after treatment by PRP is higher with an SMD of 0.44 compared to before treatment. The total oocytes number after treatment by PRP is higher with an SMD of 0.73 compared to before treatment. The number of MII oocytes after treatment by PRP is higher with an SMD of 0.63 compared to before treatment. The number of cleavage-stage embryos after treatment by PRP is higher with an SMD of 1.31 compared to before treatment. The number of day 5 embryo after treatment by PRP is higher with an SMD of 1.28 compared to before treatment. Pooled estimation of a meta-analysis of prevalence studies reported a prevalence of 22% for clinical pregnancy, 5% for spontaneous pregnancy and 21% for ongoing pregnancy following PRP therapy. CONCLUSION: Intra-ovarian injection of PRP improved ovarian reserve markers with increasing AFC, serum level of AMH and day 3 E2 and decreasing serum level of day 3 FSH. In addition, this treatment improved ART outcomes through the increasing of number total oocytes, number of MII oocytes, number of cleavage-stage embryos and number of day 5 embryos in POR women. IMPLICATIONS: Although treatment of POR women remains challenging, the use of intra-ovarian injection of autologous PRP in POR patients prior to IVF/ICSI cycles is a sign of new hope for increasing the success of IVF/ICSI. However, further well-organized, randomized controlled trials should be conducted to substantiate this result and recommend intra-ovarian injection of PRP as part of routine treatment in women with POR.

Effects of moderate COVID-19 infection on semen oxidative status and parameters 14 and 120 days after diagnosis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus causing coronavirus disease 2019 (COVID-19). Because COVID-19 is a multisystem infection, there are some concerns regarding its possible effects on male fertility. This study aimed to investigate the effects of COVID-19 on semen oxidative status and parameters 14 and 120 days after diagnosis in patients presenting with moderate infection (defined as respiratory symptoms, with or without fever, with Spo2 <93% and >90% and lung involvement <50%). Semen samples were obtained from 20 participants at two time points: the first sample on Day 14 and the second on Day 120 after diagnosis. Semen parameters (sperm concentration, motility, morphology, and viability) were evaluated, as were levels of seminal reactive oxygen species (ROS), malondialdehyde (MDA), total antioxidant capacity (TAC) and sperm DNA fragmentation. Semen parameters, including sperm motility and DNA integrity, improved at 120 days after the COVID-19 diagnosis relative to values at 14 days. In addition, ROS and MDA levels were significantly reduced in patients 120 days after infection, and TAC increased at 120 days compared with 14 days (during the acute stage of infection). In conclusion, the present study shows that the detrimental effects of COVID-19 on sperm properties caused by oxidative stress decrease up to Day 120 after diagnosis.

Effect of vitrification on biogenesis pathway and expression of development-related microRNAs in preimplantation mouse embryos.

Vitrification of embryos has been known as the most efficient cryopreservation method in assisted reproductive technology clinics. Vitrification of preimplantation embryo might be associated with altered gene expression profile and biochemical changes of vitrified embryos. Stringent regulation of gene expression in early embryonic stages is very critical for normal development. In the present study, we investigated the effect of vitrification on the canonical miRNA biogenesis pathway, and also the expression of developmental related miRNAs, in 8-cell and blastocyst mouse embryos. Although the expression pattern of the miRNA biogenesis pathway genes differed between 8-cell and blastocyst mouse embryos, vitrification did not affect the expression level of these genes in preimplantation embryos. The expression levels of miR-21 and let-7a were significantly decreased in vitrified 8-cell embryos and fresh blastocysts when compared with fresh 8-cell embryos. The expression of Stat3 was significantly reduced in blastocysts after vitrification. The alteration in the expression pattern of miRNAs, due to their mode of action, can affect broad downstream key developmental signaling pathways. Therefore, the blastocyst stage is the preferred point for embryo vitrification as they are less susceptible to cryo-damages regarding the stability of miRNAs related to the developmental and implantation competence of embryo.

Stem cell therapy for lung diseases: From fundamental aspects to clinical applications.

The respiratory system is a complex group of organs in the human body, all of which are necessary in breathing. Due to its special anatomy and composition, after exposure to various damaging factors such as micro particles, carbon granules and toxic gases, the respiratory system can be affected by a variety of damage without return to its original state. Currently, the prevalence of lung diseases, including asthma, and chronic obstructive pulmonary diseases, such as emphysema, has increased remarkably. New therapeutic approaches are desperately needed to discover regenerative medicine approaches, especially cell therapy. This review summarizes the recent advances in stem cell treatments and the research efforts conducted through the application of stem cell therapy for respiratory system diseases. In particular, researchers have used animal models to gather data about treating lung injury by stem cell transplantation. This review concentrated on the findings about route, timing and adjustment of cell transplantation dose, optimum stem cell type selection and potency marker of cells as therapeutic agents. These factors are essential subjects for approval and clinical transplantation. The current clinical trials aiming at treatment of lung diseases by stem cells are mentioned and discussed.

Urinary Tract Infection in Infants <1 Month of Age: Demographic, Clinical, and Microbiological Characteristics.

BACKGROUND: This cross-sectional study was conducted on 232 infants aged <1 month with proven UTI admitted to three major teaching hospitals for the period 2010-2018 to assess clinical, demographic, and laboratory findings of urinary tract infection in this age group. METHODS: All information was extracted from the medical records. Urinary tract infection was defined as ≥ 50,000 colony-forming units per milliliter of a single uropathogen isolated from a catheterized or suprapubic aspiration or greater than 100,000 colony-forming units per milliliter from a midstream, clean-catch sample. RESULTS: The most common pathogen isolated was E. coli (78.4%), followed by Enterobacter and Klebsiella, accounting for 12.1 and 4.7% respectively. The main presenting clinical manifestation was jaundice, which was found in 54.7% of cases; it was followed by restlessness (45.6%) and fever (40%). CONCLUSION: During infancy, the signs and symptoms of UTI are often nonspecific and although urine culture is a gold standard diagnostic tool specimen collection is challenging and urine contamination is common in children, therefore it makes the diagnosis difficult. UTI in infants may indicate underlying genitourinary abnormalities; therefore, appropriate diagnosis and immediate initiation of antibiotic therapy are crucial to decrease long-term complications like renal scarring. According to our study, the most common clinical features were jaundice, restlessness, and fever, therefore it is suggested that urine culture should be performed for all infants presenting with these signs and symptoms.

Comparing the effect of sequential embryo transfer versus double blastocyst embryo transfer on pregnancy outcomes in intracytoplasmic sperm injection (ICSI) cycles in patients with repeated implantation failure: A randomized controlled trial.

OBJECTIVE: Recurrent implantation failure (RIF) is the main challenge in assisted reproductive technology (ART) practice. Sequential embryo transfer, in which both, cleavage-stage embryo on day 3 and blastocyst on day 5, are sequentially transferred in the same cycle, has been suggested for increasing embryo implantation in RIF patients. The aim of the present study was to compare the effect of sequential embryo transfer versus double blastocyst embryo transfer on pregnancy outcomes in intracytoplasmic sperm injection (ICSI)/frozen embryo transfer (FET) cycles in RIF patients. MATERIALS AND METHODS: This prospective study was enrolled 224 RIF patients undergoing ICSI/FET cycles and randomly divided to sequential and control groups. In sequential group, embryo transfer was conducted on day 3 (cleavage stage) and day 5 (blastocyst stage). In control group, two top-quality blastocysts were transferred on day 5. RESULTS: Two hundred and two couples accomplished the trial, and their data were analyzed. Results demonstrated that sequential embryo transfer on day 3 and day 5 compared to double blastocyst transfer on day 5 significantly increased implantation rate, clinical pregnancy rate and ongoing pregnancy rate in RIF patients (p-value = 0.0142, p-value = 0.0154, p-value = 0.0201, respectively). However, there were no significant differences in terms of chemical pregnancy rate, multiple pregnancy rate, miscarriage rate and ectopic pregnancy rate in the studied groups. CONCLUSION: Sequential embryo transfer is associated with improved pregnancy outcomes in RIF patients. Further prospective studies with larger sample sizes are required to validate these results.

The relationship between sex steroids (E2, progesterone, and AMH) levels and severity and fatality of COVID-19: A systematic review.

Sex steroids are powerful modulators of the immune system and they may affect the immune response and inflammatory consequences of COVID-19. This systematic review aims to explore the impact of sex steroids on COVID-19 mortality and complications. We looked up the keywords of the study in Scopus, PubMed, and Web of Science. All related original articles published in English, as of October 16, 2021, were reviewed to be included in our research. Concerns regarding the effect of sex hormones on COVID-19, eight full texts have been identified for the conclusion. In these studies, the relationship between estradiol and COVID-19 mortality has been mentioned. The most significant findings were the higher COVID-19 mortality rate in men, compared to women; also, in menopausal women compared to younger women and who received estradiol. In two studies, oral contraceptive pills had a protective effect on the morbidity of SARS-CoV-2 infection. In a randomized controlled trial, subcutaneous injection of progesterone in hospitalized men significantly reduced their symptoms and need for oxygen therapy. Hormone replacement therapy was positively associated with reducing COVID-19 symptoms. Although the results were insufficient for a conclusion, this study represents estrogen as an appropriate pharmacological method for preventing and diminishing the inflammation related to COVID-19 disease. However, future prospective studies and clinical trials are needed to clarify and approve this protective effect.

Effects of Adjuvant Growth Hormone Therapy on Poor Ovarian Responders in Assisted Reproductive Technology.

Objective:The present study aimed to evaluate the effect of adjuvant growth hormone (GH) therapy in antagonist protocol aiming to improve ovarian response and clinical outcomes of women with poor ovarian response. Methodology:This clinical trial was a single-center study, controlled with equal randomization, which was carried out in Avicenna Infertility Clinic, Tehran, Iran. Totally, 118 patients were randomly allocated to either the intervention or the control group. The intervention group received GH and gonadotropin in gonadotropin-releasing hormone (GnRH) antagonist protocol (GH/GnRHant), while the control group received gonadotropin in GnRH antagonist protocol (GnRHant). Results:The results revealed that the number of days of gonadotropin administration significantly decreased (p-value = 0.040) in the GH/GnRHant group compared to the GnRHant group. Also, our study findings showed that a number of top-quality day 3 embryos and clinical pregnancy rate were higher in the GH/GnRHant group (p-value = 0.007) compared to the GnRHant group (p-value = 0.036). However, there was no significant difference between the two groups in terms of number of received gonadotropin ampoules, number of retrieved MI and MII oocytes, chemical pregnancy rate, ongoing pregnancy rate and live birth rate. Conclusion:These results suggest that adjuvant GH therapy in antagonist protocol in women with a history of poor ovarian response is effective to decrease the number of days of received gonadotropin ampoules and improve pregnancy rate.

The Effects of Autologous Platelet-Rich Plasma on Pregnancy Outcomes in Repeated Implantation Failure Patients Undergoing Frozen Embryo Transfer: A Randomized Controlled Trial.

Repeated implantation failure (RIF) is a disorder in which good-quality embryos fail to implant in the endometrium following several in vitro fertilization (IVF) cycles. This study aimed to evaluate the efficiency and safety of intrauterine infusion of platelet-rich plasma (PRP) in improvement of pregnancy outcomes in RIF patients undergoing frozen embryo transfer (FET). A total of 438 women with a history of RIF undergoing FET were assessed for eligibility to enter the study. Patients were randomly assigned to the intervention (PRP) and control groups. The intervention group received an intrauterine infusion of 0.5 ml PRP 48 h before embryo transfer while the control group received standard treatment. The rates of chemical and clinical pregnancy were defined as the primary outcome values. All women were followed up until the study endpoints that included the number of neonates born and pregnancy-related complications. Three hundred and ninety-three participants accomplished the study and their data were analyzed. The chemical pregnancy, clinical pregnancy, and live birth rates were higher in the PRP group than control group (p value: <0.0001; p value: <0.0001; p value: <0.0001 respectively). However, there were no significant differences between the two groups in terms of multiple pregnancies and pregnancy complications except for spontaneous abortion. The spontaneous abortion rate was significantly higher in the control group compared to the PRP group (p value = 0.0262). These results suggest that intrauterine infusion of PRP is an effective and safe route to improve pregnancy outcomes in RIF patients undergoing FET.

Effect of 1,25(OH)2-vitamin D3 on decidualization of human endometrial stromal cells.

Decidualization is the differentiation of endometrial stromal cells (eSC) to rounded, epithelioid-like cells during menstrual cycle and pregnancy. The impairment of this process leads to infertility and a variety of pregnancy disorders, including recurrent miscarriages and uteroplacental disorders. The aim of this study was to evaluate the effect of 1,25(OH)2-vitamin D3 (VD) on transformation of primary eSC into decidual cells. After isolation of eSC from biopsy samples of healthy fertile women and their characterization, the cells were cultured and propagated, and confluent cultures were decidualized for 12 days with progesterone (P4) and estradiol (E2) in presence or absence of VD. Prolactin (PRL) concentration was measured every 48 h in culture medium of eSCs, and ultrastructural changes were evaluated at the end of treatment. The results showed that PRL concentration in culture medium of eSCs was significantly increased in VD-treated decidual cells compared to control groups in a time-dependent manner. Ultrastructural analysis demonstrated that VD enhances many of the ultrastructural changes of decidualized cells including expansion of rough endoplasmic reticulum (rER), increased lipid droplets and high number of euchromatin round nuclei. These results suggest that VD may play an important role during early pregnancy by promoting cellular transformation associated with decidualization.

A comparative study of post-warming survival rates and clinical outcomes of human blastocysts vitrified/warmed by CryoTouch and Cryotop methods.

OBJECTIVE: Advances in embryo culture conditions and the development of vitrification as a revolutionary cryopreservation method have allowed for routine use of blastocyst transfer in assisted reproduction technology (ART) cycles. Several vitrification/warming media and devices have been introduced for commercial use so far. The aim of this retrospective study was to compare post-warming survival rates and clinical outcomes of human blastocysts vitrified/warmed by two different commercial methods (CryoTouch and Cryotop) during ART cycles. METHODS: This retrospective study assessed a total of 50 frozen embryo transfer (FET) cycles conducted on 56 warmed blastocysts between January 2018 and December 2020. Post-warming blastocyst survival rates and clinical outcomes including clinical pregnancy and live birth rates were calculated after single blastocyst transfer cycles. RESULTS: The results revealed no significant differences between two groups in post-warming survival rate (p-value=0.8381), clinical pregnancy rate (p-value=0.8157) and live birth rate (p-value=0.7041). CONCLUSIONS: Post-warming survival rates and clinical outcomes were comparable with no significant difference in blastocysts vitrified/warmed by CryoTouch and Cryotop commercial methods.

Disorders of sex development and female reproductive capacity: A literature review.

Disorders of sex development (DSD) are a wide-ranging group of complex conditions that influence chromosomal, gonadal, and phenotypic sex. The prevalence of DSD is very low, but affected patients deserve individualized management to improve psychological, sexual, and reproductive outcomes. This review aims to clarify the fertility potential of DSD patients who can be reared as females and their chance of becoming pregnant, especially using assisted reproductive techniques (ART). Due to the effects of DSD on internal and external genital organs, these conditions result in varying degrees of fertility potential. Fertility rate depends on the phenotype and is inversely related to the severity of the disorder. Reproductive endocrinologists and infertility specialists must be considered active partners of the interdisciplinary treatment team. With current advances in ART, pregnancy is more achievable in patients who were considered infertile at first glance. Due to the complexity of the medical management in DSD patients, more studies should be conducted to conclusively suggest the best choice for improving their fertility potential.Abbreviations: AIS: Androgen Insensitivity Syndrome; AMH: Anti-Müllerian Hormone; ART: Assisted Reproductive Technology; ASRM: American Society for Reproductive Medicine; CAH: Congenital Adrenal Hyperplasia; CAIS: Complete Androgen Insensitivity Syndrome; DHT: Dihydrotestosterone; DSD: Disorders of Sexual Development; FSH: Follicle Stimulating Hormone; GD: Gonadal Dysgenesis; ICSI: Intracytoplasmic Sperm Injection; IUGR: Intrauterine Growth Restriction; IVF: In Vitro Fertilization; IVF-ET: IVF and Embryo Transfer; LH: Luteinizing Hormone; MGD: Mixed Gonadal Dysgenesis; MRI: Magnetic Resonance Imaging; MRKH: Mayer-Rokitansky-Kuster-Hauser; US: Ultrasonography; HSG: Hysterosalpingography; PAIS: Partial Androgen Insensitivity Syndrome; PGD: Preimplantation Genetic Diagnosis; POR: P450 Oxidoreductase; PROM: Premature Rupture of Membranes; TS: Turner Syndrome; 17ß-HSD III: 17ß-Hydroxysteroid Dehydrogenase III; 21-OHD: 21-hydroxylase deficiency; 5α-RD-2: 5α-reductase-2.

The impact of congenital uterine abnormalities on pregnancy and fertility: a literature review.

Congenital abnormalities of the uterus result primarily from embryological maldevelopment of the paramesonephric ducts and have been associated with pregnancy complications, reduced fertility, and other adverse fetal outcomes. While such abnormalities are rare, affected patients should be correctly managed to improve psychological, sexual, and reproductive outcomes. This review intends to elucidate the impact of congenital uterine abnormalities on fertility and pregnancy outcomes. We also present the available management methods and discuss the role of assisted reproductive technologies (ART) to benefit affected women. This review clearly shows that although these disorders are generally not lethal, they critically impact the patient's reproductive health. The fertility rate of patients with uterine congenital abnormalities depends on the severity of the condition. Reproductive endocrinologists and infertility specialists must be considered as active parts of the interdisciplinary treatment team for such patients. ART practices are reasonably successful at managing fertility problems of women with these abnormalities.

Evaluation of Expression and Phosphorylation of Progesterone Receptor in Endometrial Stromal Cells of Patients with Recurrent Implantation Failure Compared to Healthy Fertile Women.

Recurrent implantation failure (RIF) is the repeated failure of good-quality embryos in implantation process following several assisted reproduction cycles. Disruption of the endometrial receptivity is one of the main causes of RIF. Progesterone plays a pivotal role in the endometrial receptivity through the regulation of gene expression pattern by binding to its receptors in the endometrial cells. The aim of this study was to evaluate the expression level of progesterone receptor (PR) and its phosphorylated form in the endometrial stromal cells (eSC) of RIF patients and compare it to the eSC of healthy fertile women as control group. After isolation of the eSC from biopsy samples of RIF patients and healthy fertile women and their characterization, expression levels of PR mRNA, PR protein, and phospho-Ser294 PR protein were evaluated by quantitative real-time PCR and immunofluorescence staining, respectively. The results demonstrated a significant reduction in PR mRNA expression (P < 0.01.) and phospho-Ser294 PR protein (P < 0.05) level in RIF patients compared to the control group. These data for the first time suggest that the expression of PR and its phosphorylated form are impaired in RIF patients. Therefore, designing therapeutic methods for improving PR expression status and its regulation in the endometrium of RIF patients may help in improving the final reproductive outcomes of these cases.

Pyrvinium pamoate induces in-vitro suppression of IL-6 and IL-8 produced by human endometriotic stromal cells.

Endometriosis, a chronic inflammatory disease, is identified by the presence of endometrial tissue outside the uterus. The prevalence of this disease among reproductive-age women is almost 10-15%. High levels of IL-6 and IL-8 have been found in the peritoneal fluid (PF) of women with endometriosis and are involved in its pathogenesis. Isolated stromal cells from 12 ectopic and eutopic endometrial biopsies of women with ovarian endometrioma and also 12 endometrial biopsies of nonendometriotic controls were treated with 1.1 µM pyrvinium pamoate, a Wnt/ß-catenin signaling pathway inhibitor, for 72 hrs. Before treatment, mRNA gene expression and secretion of IL-6 and IL-8 were significantly higher in ectopic (EESCs) than eutopic (EuESCs) and control (CESCs) endometrial stromal cells. After treatment, mRNA gene expression and also secretion of IL-6 and IL-8 were significantly reduced. Our Findings showed that pyrvinium pamoate suppresses the mRNA gene expression and secretion of IL-6 and IL-8 in human endometriotic stromal cells. Additional investigations on this compound are required before clinical application.

Effect of 1,25(OH)2-vitamin D3 on expression and phosphorylation of progesterone receptor in cultured endometrial stromal cells of patients with repeated implantation failure.

Repeated implantation failure (RIF) occurs in a condition when good quality embryos fail to implant in the endometrium following several in vitro fertilization (IVF) cycles. Suboptimal endometrial receptivity is one of the main underlying factors that causes this failure. Progesterone is the key regulator of endometrial receptivity which regulates gene expression through binding to its receptors in the endometrial stromal cells (eSC). The aim of this study was to evaluate the effect of 1,25(OH)2-vitamin D3 on progesterone receptor (PR) expression level and its phosphorylation on Ser294 residues in eSC of RIF patients and healthy fertile women. After isolation of the eSC from biopsy samples of RIF patients and healthy fertile women and their characterization, the cells were incubated with vitamin D3 and the expression level of PR mRNA, PR protein and phospho-Ser294 PR protein were evaluated after treatment. The results showed that vitamin D3 treatment increases PR mRNA and protein level and phospho-Ser294 PR protein level in the isolated eSC of both RIF patients and the control group. These results suggest that vitamin D3 may possibly play a key role during the embryo implantation process by affecting the expression pattern and regulatory modifications of the PR in the eSC.