Evaluation of the relationship between ovarian reserve with congenital anomalies and intramural uterine leiomyoma among infertile women: a cross-sectional study.

BACKGROUND: Ovarian reserve is a crucial indicator of a woman's fertility potential, which is determined by the quality and quantity of antral follicles and oocytes. However, certain factors such as endometriosis, pelvic inflammatory disease, myoma, and the natural process of aging can lead to a poor ovarian response to stimulation, reducing a woman's chances of conceiving. OBJECTIVE: To evaluate the effect of uterus congenital anomalies and uterine leiomyoma are associated on ovarian reserve. METHODS: The present cross-sectional study was performed on 321 infertile women in three groups consisted of 97 infertile women with intramural uterine leiomyoma and 81 infertile women with uterine anomalies and 143 infertile women without uterine anomalies and uterine leiomyoma during 2017-2019 in Royan Center. Sampling method was continuous and available. Data collection tool in this study was a questionnaire which was in two parts of individual variables and the second part was related to ultrasound results (number of antral follicles and ovarian volume) and laboratory tests (Anti-Mullerian Hormone (AMH) and Follicle-stimulating Hormone (FSH)). Ovarian reserve parameters were measured in three groups on the third day of the cycle in both groups. Data analysis was performed using SPSS software version 21. Quantitative variables were analyzed using t-test, qualitative variables were analyzed using chi-square test. RESULTS: The results of in laboratory parameters showed that there was no statistically significant difference between the three groups in FSH (2.35 ± 1.55, 2.07 ± 1.81, 2.31 ± 1.93) and AMH (6.84 ± 2.75,7.52 ± 3.14,6.93 ± 3.04), respectively (P > 0.05). The results of sonographic variables also showed that the variables include number of antral follicles in right ovarian, number of antral follicles in left ovarian have statistically significant between the three groups (5.73 ± 2.69,4.84 ± 3.14,6.66 ± 3.13), respectively (P < 0.05). CONCLUSION: The results of the present study showed that uterine abnormalities and uterine leiomyoma with different mechanisms such as reduce of antral follicle numbers and the effect on uterine and ovarian blood flow lead to a decrease in ovarian reserve and infertility. Therefore, treatment and surgery can reduce these effects and improve the fertility of the affected women.

Clinical and laboratory findings following transplantation of allogeneic adipose-derived mesenchymal stromal cells in knee osteoarthritis, a brief report.

BACKGROUND: Mesenchymal stromal cells (MSCs) injection has been proposed as an innovative treatment for knee osteoarthritis (KOA). Since, allogeneic MSCs can be available as off-the-shelf products, they are preferable in regenerative medicine. Among different sources for MSCs, adipose-derived MSCs (AD-MSCs) appear to be more available. METHODS: Three patients with KOA were enrolled in this study. A total number of 100 × 106 AD-MSCs was injected intra-articularly, per affected knee. They were followed up for 6 months by the assessment of clinical outcomes, magnetic resonance imaging (MRI), and serum inflammatory biomarkers. RESULTS: The primary outcome of this study was safety and feasibility of allogeneic AD-MSCs injection during the 6 months follow-up. Fortunately, no serious adverse events (SAEs) were reported. Assessment of secondary outcomes of visual analogue scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and knee osteoarthritis outcome score (KOOS) indicated improvement in all patients. Comparison between baseline and endpoint findings of MRI demonstrated a slight improvement in two patients. In addition, decrease in serum cartilage oligomeric matrix protein (COMP) and hyaluronic acid (HA) indicated the possibility of reduced cartilage degeneration. Moreover, quantification of serum interleukin-10 (IL-10) and interleukin-6 (IL-6) levels indicated that the host immune system immunomodulated after infusion of AD-MSCs. CONCLUSION: Intra-articular injection of AD-MSCs is safe and could be effective in cartilage regeneration in KOA. Preliminary assessment after six-month follow-up suggests the potential efficacy of this intervention which would need to be confirmed in randomized controlled trials on a larger population. TRIAL REGISTRATION: This study was registered in the Iranian registry of clinical trials (https://en.irct.ir/trial/46) in 24 April 2018 with identifier IRCT20080728001031N23.

Mesenchymal Stromal Cell Therapy Improves Refractory Perianal Fistula in Crohn's Disease: Case Series Clinical Interventional Study.

Objective: Perianal fistulas in Crohn's disease (CD) are the main challenges in inflammatory bowel diseases (IBDs). Some of the fistulas are refractory to any therapeutic strategy. The aim of this study was to evaluate the therapeutic effects of mesenchymal stromal cells (MSCs) as a novel promising modality for the treatment of fistulizing CD. Materials and Methods: This case series clinical interventional study was conducted from 2014 to 2017 at Shariati Hospital, an IBD referral center in Tehran, Iran. Refractory adult patients with CD who had draining perianal fistulas were enrolled in this study. All patients were examined by a colorectal surgeon and the fistula imaging studies were performed by pelvic magnetic resonance imaging (MRI). After autologous bone marrow (BM) aspiration and MSCs isolation, the cells were cultured and passaged under current good manufacturing practice (cGMP) conditions. Four intra-fistula injections of cells, each containing 40×106 MSCs suspended in fibrin glue, were administered by an expert surgeon every 4 weeks. Procedure safety, feasibility and closure of the perianal fistulas at week 24 were assessed. Clinical examination and MRI findings were considered as the primary end points. Results: In total, 5 patients (2 males and 3 females) were enrolled in this study. No adverse events were observed during the six-month follow-up in these patients. Both the Crohn's Disease Activity Index (CDAI) and Perianal Disease Activity Index (PDAI) scores decreased in all patients after cell injections and one patient achieved complete remission with closure of fistulas, discontinuation of fistula discharge, and closure of the external opening. Conclusion: Local injection of MSCs combined with fibrin glue is potentially a safe and effective therapeutic approach for complex perianal fistulas in patients with CD.

Does amniotic fluid sludge result in preterm labor in pregnancies after assisted reproduction technology? A nested Case - Control study.

OBJECTIVE: to investigate the relationship between the Amniotic fluid Sludge exposure during pregnancy and the Preterm Labor (PTL) in pregnant women who had undergone Assisted Reproductive Technology procedures (ART) in Royan institute. MATERIALS AND METHODS: It was a nested case-control study that was conducted on 110 eligible pregnant women who had undergone IVF procedure in Royan institute, Tehran, Iran. The final sample size was 63 subjects with Amniotic fluid Sludge and 67 subjects with normal Amniotic fluid. Delivery before 37 of gestation was considered as PTL.The study was approved by the ethics committee of the Royan institute and the written consent form was filled by participants. Data was entered to the SPSS (version 21, SPSS, Inc.). The baseline characteristics of the participants were described as absolute (n) and relative (%) frequencies for the covariates. Man Whitney and T-Test were used to compare the mean of covariates and the P-value lower than 0.05 was considered significant. The prevalence of the PTL was compared between two groups. RESULTS: The mean Gestational Age at delivery in case and control group were 36.46 ± 3.45 and 38.03 ± 1.61, respectively which was significant (p = .01). The prevalence of PTL in case and control group were 23.8% and 10.4% respectively which was significant (p = .04). The percentage of cases with cervical length less than 30 (mm) in case and control group were 28.6% and 10.4%, respectively (p = .008) and the percentage of cerclage in case and control group were 33.3% and 7.5% respectively, (p = .00) which were significant statistically. CONCLUSION: The amniotic fluid sludge has a direct effect on the cervical length of pregnancies after ART. In such cases, PTB will be probable in the presence of sludge in spite of preventive treatments such as cerclage.

Autologous bone marrow-derived CD133 cells with core decompression as a novel treatment method for femoral head osteonecrosis: a pilot study.

BACKGROUND: Avascular necrosis (AVN) of femoral head is a progressive bone disease due to ischemia of femoral head; patients experience pain and they can not do normal activity. There is not an effective way to treat the cause of this disease. In recent studies, treatment of this disease using pluripotent stem cell-derived mesenchyme is safe and effective, but this method needs more investigation. In this study, the safety and efficacy of CD133+ cells were evaluated as a novel method of stem cell therapy to treat AVN. METHODS: In this prospective quasi-experimental study, the participants were selected among patients with AVN who were referred to the Royan Cell Therapy Center. Autologous bone marrow-derived CD133+ cells were injected into the necrotic site of the femoral head during core decompression (CD). The Visual Analogue Scale (VAS), Harris Hip Score (HHS), Western Ontario and McMaster Universities Arthritis Index (WOMAC) and walking distance (WD) were measured before and 2, 6 and 12 months after CD. RESULTS: Overall, nine patients (six men and three women) were investigated in this study. Their mean age was 26 years old. All of them significantly improved in VAS, HHS, WOMAC and WD scores and they could do more activity without pain. Also, imaging findings demonstrated significant reductions in joint injuries. Significant complications were not seen in patients. DISCUSSION: This prospective quasi-experimental study demonstrated that, in patients with AVN, a single bone marrow-derived CD133+ cell injection into the necrotic site of the femoral head during CD is safe and effective in providing significant, clinically relevant pain relief and patients could do more activity over 2, 6 and 12 months. This pilot study suggested further clinical trials over an extended assessment period to approve bone marrow-derived CD133+ cell injection to treat AVN.

Intra-articular knee implantation of autologous bone marrow-derived mesenchymal stromal cells in rheumatoid arthritis patients with knee involvement: Results of a randomized, triple-blind, placebo-controlled phase 1/2 clinical trial.

BACKGROUND: In this study, we intend to assess the safety and tolerability of intra-articular knee implantation of autologous bone marrow-derived mesenchymal stromal cells (MSCs) in patients with rheumatoid arthritis (RA) and to determine the preliminary clinical efficacy data in this population. The trial registration numbers are as follows: Royan Institute Ethics Committee: AC/91/1133; NCT01873625. METHODS: This single-center, randomized, triple-blind, placebo-controlled phase 1/2 clinical trial randomized RA patients with knee involvement to receive either an intra-articular knee implantation of 40 million autologous bone marrow-derived MSCs per joint or normal saline (placebo). Patients were followed up for 12 months to assess therapy outcomes. RESULTS: A total of 30 patients, 15 in the MSC group and 15 in the placebo group, enrolled in this study. There were no adverse effects reported after MSC administration or during follow-up. Patients who received MSCs had superior findings according to the Western Ontario and McMaster Universities Arthritis Index (WOMAC), visual analogue scale (VAS), time to jelling and pain-free walking distance. However, this improvement could not be significantly sustained beyond 12 months. The MSC group exhibited improved standing time (P = 0.01). In addition, the MSCs appeared to contribute to reductions in methotrexate and prednisolone use. CONCLUSION: Intra-articular knee implantation of MSCs appeared to be safe and well tolerated. In addition, we observed a trend toward clinical efficacy. These results, in our opinion, have justified the need for further investigations over an extended assessment period with larger numbers of RA patients who have knee involvement.

Imaging and Clinical Data of Placental Site Trophoblastic Tumor: A Case Report.

Placental site trophoblastic tumor (PSTT) is a very rare variant of gestational trophoblastic tumor. It can occur after normal termination of pregnancy or spontaneous abortion and ectopic or molar pregnancy. There is a wide range of clinical manifestations from a benign condition to an aggressive disease with fatal outcome. One of the most important characteristics of PSTT, unlike other forms of gestational trophoblastic diseases (GTD) is the presence of low beta-subunit of human chorionic gonadotropin (ß-hCG) levels because it is a neoplastic proliferation of intermediate trophoblastic cells. However, human placental lactogen (hPL) is increased on histologic section and in the serum of patients too. We present a case of PSTT and discuss the differential diagnosis in order to further familiarize physicians with the diagnosis and treatment of this disease. It has a varied clinical spectrum and usually presents with irregular vaginal bleeding or amenorrhea. Diagnosis is confirmed by dilatation and curettage (D and C) and hysterectomy. Because chemotherapy is not effective, surgery is the cornerstone of treatment. This case is presented because it is a rare neoplasm with different treatments and it should be differentiated from molar pregnancy.

Long-Term Follow-up of Intra-articular Injection of Autologous Mesenchymal Stem Cells in Patients with Knee, Ankle, or Hip Osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a debilitating disease that typically affects a large number of the middle-aged and elderly population. Current treatment strategies have had limited success in these patients. This study aims to investigate the safety of treatment with autologous bone marrow (BM)-derived mesenchymal stem cells (MSCs) transplanted in patients with OA of the knee, ankle, or hip. METHODS: We enrolled 18 patients with different joint involvements (knee, ankle, or hip OA) and one was lost to follow-up. BM samples were taken from the patients, after which BM-derived MSCs were isolated and cultured. Each patient received one MSC injection. Patients were followed with clinical examinations, MRI and laboratory tests at 2, 6, 12, and 30 months post-transplantation. RESULTS: We observed no severe adverse events such as pulmonary embolism, death, or systemic complications. A limited number of patients had very minor localized adverse effects such as rash and erythema. There were no changes in liver function, hematology, or biochemistry analyses before and after cell therapy. There was no evidence of tumor or neoplastic changes in the patients during the 30-month follow-up period. All patients exhibited therapeutic benefits such as increased walking distance, decreased visual analog scale (VAS), and total Western Ontario and McMaster Universities OA Index (WOMAC) scores which were confirmed by MRI. CONCLUSIONS: Our study has shown that injection of MSCs in different OA affected joints is safe and therapeutically beneficial. However, further studies are needed with larger sample sizes and longer follow-up periods to confirm these findings.

Chromosomally and Anatomically Normal Fetuses With Increased First Trimester Nuchal Translucency Conceived by ICSI.

Nuchal translucency (NT) measurements in the first trimester screening between 11 and 14 weeks' gestation are regarded as a clear marker for aneuploidies. The presence of a thickened NT, even if the karyotype is normal, can be associated with structural abnormalities. Having an abnormal screening of NT, parents and physicians could face dilemma over abortion particularly in a case of IVF/ICSI fetuses. Measurement of the NT thickness combined with biochemical markers has a false-positive rate of 5%. Hereby we present six cases of chromosomally normal fetuses with an increased NT thickness in the first trimester, a normal karyotype and normal follow-up scans, who had a good prognosis for a normal early childhood. This report may help increase the confidence of couples who are reluctant to terminate the pregnancy.

Comparison of two dimensional and live three dimensional ultrasounds for the diagnosis of septated uterus.

BACKGROUND: Traditionally, septate uterus was diagnosed with invasive method like hysterosalpingography and hysteroscopy. Nowadays transvaginal ultrasonography was reported to be a sensitive tool for detection of septate uterus too. OBJECTIVE: The objective of the present study was to evaluate the application of two dimensional ultrasound (2-DUS) and real time three dimensional ultrasound (3-DUS) in differentiating various type of septated uterus. Hysteroscopy confirmation was assigned as the gold standard. MATERIALS AND METHODS: This retrospective study was performed among 215 infertile women with suspected septate uterus from October 2008 to July 2012. An inclusion criterion was septated uterus based on HSG or experiencing abortion, preterm labor, or recurrent IVF failure. Fusion anomalies were excluded from the study (unicornuate, bicornuate and didelphys anomalies). The results of 3D and 2D sonographies were compared, while they were confirmed by hysteroscopy result in detection of septated uterus. Kappa index for agreement between 2DUS and hysteroscopy, as well as 3-DUS and hysteroscopy in detection of septate uterus was carried out. By receiver operating characteristic (ROC) curve, cut off points for predicting the kind of anomalies were proposed. RESULTS: The women were evaluated by 2-DUS (n=89) and (II) 3-DUS (n=126). All women underwent hysteroscopy, following 2-DUS and 3-DUS at the same or subsequent cycle. The results of kappa (K) index were 0.575 and 0.291 for 3-DUS and hysteroscopy, as well as 2-DUS and hysteroscopy, respectively. Also, the cutoff points were 27% for arcuate and subseptate, and 35% for differentiating septate and subseptate. CONCLUSION: Real time 3-DUS has better ability for visualization both uterine cavity and the fundal uterine, so it has higher agreement in detection of septate uterus than 2-DUS.

Sonographic findings in partial type of trisomy 18.

Trisomy 18 (Edwards syndrome) is the second most common trisomy among live born fetuses, with poor prognosis. Estimate of its incidence is between 1 in 4000- 16000 live births. Most of the chromosomal abnormalities in fetuses are detected by prenatal ultrasound findings in the first and second trimesters. In this case re- port, we present a partial type of trisomy 18 occurring through de novo unbalanced translocation of chromosomes 18 and 21. The ultrasound features enabling the early detection of trisomy 18 include a delayed ossification of calvarium combined with early onset of fetal growth restriction (FGR) and the absence of nasal bone through performing triple test followed by amniocentesis. Finally, the parents decided to terminate the pregnancy.

Uterine cavity assessment in infertile women: Sensitivity and specificity of three-dimensional Hysterosonography versus Hysteroscopy.

BACKGROUND: Assessment of uterine abnormalities is a core part in infertility evaluation. OBJECTIVE: The aim of this study was to evaluate the sensitivity and specificity of three-dimensional hysterosonography (3-DHS) in the diagnosis of uterine abnormalities in infertile women. MATERIALS AND METHODS: The infertile women who visited Royan Institute and referred to 3-DHS consecutively, prior to in vitro fertilization, from 2010-2011 included in this cross-sectional study. For patients who underwent hysteroscopy in addition to 3-DHS (214/977), the verification bias adjusted sensitivity and specificity of 3-DHS which were calculated by global sensitivity analysis method. Hysteroscopy was used as the gold standard for diagnosis of uterine abnormalities. Histological diagnosis of resected endometrial tissues by hysteroscopy was assessed and the adjusted sensitivity and specificity of 3-DHS and hysteroscopy in detection of polyp or hyperplasia were determined. Histopathologic results were considered as the gold standard for diagnosis of polyp or hyperplasia. RESULTS: The overall sensitivity and specificity for 3-DHS in diagnosis of uterine anomalies considering hysteroscopy as the gold standard were 68.4% and 96.3% respectively. Sensitivity and specificity of hysteroscopy in diagnose of polyp or hyperplasia was calculated at 91.3% and 81.4% respectively. Sensitivity and specificity of 3-DHS in diagnosis polyps or hyperplasia was calculated at 91.4% and 80.2 % respectively. CONCLUSION: The results of present study proved that, compared to hysteroscopy; 3-DHS has a reliable specificity for diagnosis of uterine abnormalities. Sensitivity and specificity of 3-DHS and hysteroscopy in detecting polyp or hyperplasia regarding histopathology as the gold standard was the same.

Diagnostic accuracy of transvaginal sonography in the detection of uterine abnormalities in infertile women.

BACKGROUND: Accurate diagnosis of uterine abnormalities has become a core part of the fertility work-up. A variety of modalities can be used for the diagnosis of uterine abnormalities. OBJECTIVES: This study was designed to assess the diagnostic accuracy of transvaginal ultrasonography (TVS) in uterine pathologies of infertile patients using hysteroscopy as the gold standard. PATIENTS AND METHODS: This was a cross-sectional study carried out in the Department of Reproductive Imaging at Royan Institute from October 2007 to October 2008. In this study, the medical documents of 719 infertile women who were investigated with transvaginal ultrasound (TVS) and then hysteroscopy were reviewed. All women underwent hysteroscopy in the same cycle time after TVS. Seventy-six out of 719 patients were excluded from the study and 643 patients were studied. TVS was performed in the follicular phase after cessation of bleeding. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for TVS. Hysteroscopy served as the gold standard. RESULTS: The overall sensitivity, specificity, positive and negative predictive values for TVS in the diagnosis of uterine abnormality was 79%, 82%, 84% and 71%, respectively. The sensitivity and PPV of TVS in detection of polyp were 88.3% and 81.6%, respectively. These indices were 89.2% and 92.5%, respectively for fibroma, 67% and 98.3%, respectively for subseptated uterus and 90.9% and 100%, respectively for septated uterus. Adhesion and unicornuated uterus have the lowest sensitivity with a sensitivity of 35% and PPV of 57.1%. CONCLUSION: TVS is a cost-effective and non-invasive method for diagnosis of intrauterine lesions such as polyps, submucosal fibroids and septum. It is a valuable adjunctive to hysteroscopy with high accuracy for identification and characterization of intrauterine abnormalities. This may lead to a more precise surgery plan and performance.

Application of 3D Ultrasonography in Detection of Uterine Abnormalities.

Structural pathologies in the uterine cavity such as müllerian duct anomalies (MDAs) and intrauterine lesions (fibroids, polyps, synechiae) may have important roles in subinfertility, implantation failure and pregnancy outcome. Various imaging modalities such as hysterosalpingography (HSG), sonography, laparoscopy and hysteroscopy are used in the evaluation of MDAs and intrauterine lesions. Recently, three-dimensional ultrasound (3DUS) has been introduced as a non-invasive, outpatient diagnostic modality. With increased spatial awareness, it is superior to other techniques used for the same purpose.