Bio-identical progesterone (PRG) is an exogenous female steroidal hormone which is used for treatment of polycystic ovary syndrome (PCOS). However, it suffers from poor bioavailability due to hepatic ...metabolism and poor solubility. The target of this work was to evaluate and statistically optimize PRG-loaded nanovesicle transethosomes (NVTEs) based in mucoadhesive gel for transvaginal delivery of PRG as potential luteal-phase support. A 2
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full factorial design was used to explore the effect of phosphatidylcholine (PC), Tween 80, cetyltrimethyl ammonium bromide and ethanol concentration on particle size, entrapment efficiency (EE%), % in vitro PRG release after 24 h and transvaginal flux. PRG-loaded NVTEs were prepared by injection sonication method. The results revealed that the mean particle sizes ranged from 133.3 ± 3.42 to 349.5 ± 1.24 nm, zeta potential ranged from -23.5 ± 3.84 to +74.6 ± 4.97 mV, EE% ranged from 87.93 ± 3.58 to 97.05 ± 2.61%, % PRG release ranged from 50.9 ± 2.75 to 90.69 ± 2.07 and transvaginal flux ranged from 0.274 ± 0.03 to 0.531 ± 0.04 mg/cm
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/h. The optimized formulation was subjected to transmission electron microscope for morphological examination and then incorporated in the mucoadhesive vaginal gel using Carbopol 974, hydroxyl propyl methylcellulose and sodium alginate. The optimized formulation was clinically studied in anovulatory PCOS and showed a significant increase in the serum PRG, endometrial thickness, echogenicity degree and the pregnancy rate. Briefly, PRG-loaded NVTEs vaginal gel might be a promising formulation for luteal phase support and increase pregnancy rate in anovulatory PCOS.
Background: Several parameters were proposed to predict the impact of premature luteinization on intracytoplasmic sperm injection (ICSI) outcomes such as isolated progesterone (P) level, progesterone ...to oocyte ratio, and progesterone/estradiol ratio (P/E2). Aim: The aim of this study is to compare the predictive value of P/E2 ratio and isolated P level on the ovulation triggering day for pregnancy outcomes in fresh GnRH antagonist ICSI cycles. Settings and Design: A retrospective cohort study conducted in a university-affiliated in vitro fertilization center between January 2017 and April 2019. Methods: The study included women who underwent their first- or second-ranked GnRH antagonist ICSI cycles with day-3 embryo transfer. P/E2 ratio was calculated as (P ng/mL × 1000)/E2 (pg/mL). Cutoff values of ≥1.5 ng/ml for high P (HP) and ≥0.55 for HP/E2 ratio were chosen based on the literature. Statistical Analysis: A receiver operating curve was performed to detect the predictability of serum P/E2 and P for the ongoing pregnancy rate. First, patients were divided according to either P level (low P < 1.5 ng/mL and HP ≥1.5 ng/mL) or P/E2 ratio (low P/E2 <0.55 and HP/E2 ≥ 0.55). Patients were further divided into four subgroups: (Group A: HP and HP/E2 ratio, Group B: low P and low P/E2 ratio, Group C: HP only, and Group D: HP/E2 only). A multivariate regression analysis models were used to account for the effect of the cycle confounders on the likelihood of pregnancy. Results: A total of 402 ICSI cycles were analyzed. The area under the curve was 0.67 and 0.59 for P/E2 and P, respectively. P/E2 showed a significant association with ongoing pregnancy (adjusted odds ratios aOR: 0.409, 95% confidence interval CI 0.222-0.753, P = 0.004) while HP revealed no significant predictive value (aOR: 0.542, 95% CI 0.284-1.036, P = 0.064) after the multivariate analysis. Conclusions: P elevation may not present as an independent predictor for cycle outcomes. P/E2 ratio has a better prognostic value than P alone in predicting pregnancy of GnRH antagonist cycles.
The impact of the prematurely elevated serum progesterone on the late follicular phase, commonly known as premature luteinization (PL), is a matter of continuing debate. Available evidence supports ...that serum progesterone ≥ 1.5 ng/ml on the day of ovulation triggering could reduce the pregnancy potential in fresh in vitro fertilization (IVF) cycles by jeopardizing endometrial receptivity. Causes of PL during ovarian stimulation are unclear. Recent studies point toward the daily follicle-stimulating hormone dosage, duration of controlled ovarian stimulation, number of oocytes retrieved, and peak estradiol level as factors affecting the incidence of PL. Emerging data show additional influence on embryo quality. The prevention of PL has been challenging. The key elements in preventing PL include individualization of ovarian stimulation according to patient’s ovarian reserve, proper ovulation trigger timing, and use of medications such as corticosteroids and metformin. Embryo cryopreservation with deferred embryo transfer is the established strategy to overcome PL, yet it is an extra burden to the IVF laboratory and increased cost for patients. Herein, we review the up-to-date knowledge of this frequent IVF problem including causes, proposed diagnostic criteria, and its impact on endometrial receptivity, embryo quality, and pregnancy outcomes. The preventive measures and rescue strategies are also discussed.
Background: Postpartum hemorrhage (PPH) is a direct cause of maternal death all over the world. A Bakri balloon is recommended by American College of Obstetricians and Gynecologists (ACOG) and World ...Health Organization (WHO) as a treatment line for PPH unresponsive to uterotonics. We carried out a systematic review to assess the safety and effectiveness of Bakri balloon in the management of PPH.
Methods: We searched PubMed, SCOPUS, central Cochrane, and Web of Science, from 2001 to 2018 for randomized controlled trials (RCTs) and observational studies to assess the safety and effectiveness of Bakri balloon on refractory PPH.
Results: Twenty-eight articles were included for analysis. The primary indication for the use of a Bakri balloon tamponade was PPH. Only 67.9% (19/28) quantified the estimate blood loss necessary to use the balloon. Uterine atony was the underlying cause of PPH in 75% (21/28) of studies. Most of the studies on Bakri balloon are followed by vaginal birth (3/4). Bakri balloon displacement from the uterine cavity was reported by five publications, with the overall rate being 9% (95% CI: 5-15%). Hysterectomy was necessary for 1% (95% CI: 0-8%) of the women who required the balloon.
Conclusions: Bakri balloon seems to be a less effective tool for management of PPH either after vaginal or cesarean delivery.
To evaluate tissue concentration of 1, 25 dihydroxyvitamin D3, and gene expression level of CYP27B1 that codes for 1-α hydroxylase (vitamin D activating enzyme), and CYP24A1 that codes for ...24-hydroxylase (vitamin D catabolizing enzyme) in human uterine leiomyoma (ULM), its adjacent myometrium (Myo-F), and normal myometrium (Myo-N).
Levels of 1, 25 dihydroxyvitamin D3 were measured using HPLC and Diode detectors whereas CYP27B1, and CYP24A1 expressions were assessed using Real-Time PCR in ULM, Myo-F, and Myo-N. Non-parametric statistics were used.
ULMs contained significantly less 1, 25 dihydroxy vitamin D3 compared to Myo-F (3.0, IQR: 1.0–9.0 versus 6.0, IQR: 3.0–13.0 μg/ kg, P value is 0.03). No significant difference was detected between ULM and Myo-N, or Myo-F and Myo-N. Intratumoral level of the active form of vitamin D did not differ according to the type of ULM (submucous or interstitial/subserous), or to the ULM volume. CYP27B1 was expressed in ULM (2.17, IQR: 0.65–4.9), Myo-F (4.94, IQR: 1.04–22.59), and Myo-N (0.99, IQR: 0.49–1.71) to a comparable level. CYP24A1 expression was significantly higher in ULM compared to Myo-N (2.00, IQR: 0.69–10.77 versus 0.22, IQR: 00- 0.96, respectively, P value is 0.04).
Human ULMs contain significantly lower 1, 25 dihydroxyvitamin D3 than its adjacent myometrium. ULM, Myo-F, and Myo-N express CYP27B1 and CYP24A1. ULMs express significantly higher level of CYP24A1 than normal myometrium indicating that over expression of 24-hydroxylase is a mechanism by which ULMs sustain a relative state of hypovitaminosis D.
Background: Periventricular hemorrhage (PVH) is common in early preterm neonates but much less common in term and late preterm neonates. The aim of this study was to identify the risk factors and ...outcomes of PVH in term and late preterm neonates in a tertiary care center in Upper Egypt. Methods: A total of 33 term and late preterm (≥ 34 weeks of gestation) neonates (18 females and 15 males) admitted at the neonatal intensive care unit (NICU) of Sohag University Hospital and diagnosed with PVH from January 2016 to October 2018 were included in this prospective study. The neonates with major congenital malformation of the nervous system were excluded. The risk factors for PVH were ascertained, and the diagnosis was confirmed by transcranial ultrasound, computed tomography or magnetic resonance imaging. The outcomes were assessed at discharge time and the age of 6 months. Results: ThePVH was diagnosed in 5.9% of the neonates. The median of age was 12 days (age range: 2-28 days) at presentation, and convulsions were the most frequent presentations followed by poor suckling and pallor. The risk factors for PVH included prolonged prothrombin time, thrombocytopenia, non-administration of vitamin K, and prolonged labor in 54.5%, 30 %, 30 %, and 27.3% of the cases, respectively. Moreover, 26 (78.7 %) cases were discharged with good conditions, and 7 (21.2 %) subjects died in the NICU. The investigation of the patients’ follow-up at the age of 6 months revealed neurological impairments in 36 % of the survivors. Grade IV and III PVH had mortality rates of 66.67% and 18.75%, respectively (P=0.009). Neurodevelopmental impairments were more frequent in Grade III and IV (P=0.002). Conclusion: The incidence of PVH was 5.9% among term and late preterm neonates admitted to our NICU. Coagulation disorders and prolonged labor were the leading risk factors. Most patients had favorable outcomes, and one-third of the cases had neurodevelopmental impairments. In addition, mortality was reported in one-fifth of the neonates. Severe grades of PVH had the worst outcomes.
Premature luteinization (PL) is not unusual in
fertilization (IVF) and could not be wholly avoided by using either gonadotropin-releasing hormone (GnRH) agonists or GnRH antagonist regimens. The ...study aims to evaluate metformin's efficacy in preventing PL in fresh GnRH antagonist intracytoplasmic sperm injection (ICSI) cycles with cleavage-stage embryo transfer.
This randomized, double-blind, placebo-controlled trial was conducted in a tertiary university IVF center. We recruited infertile women who were scheduled to perform their first or second ICSI trial. Eligible women were recruited and randomized in a 1:1 ratio into two groups. Metformin was administered in a dose of 1500 mg per day since the start of contraceptive pills in the cycle antecedent to stimulation cycle until the day of ovulation triggering, while women in the placebo group received a placebo for the same regimen and duration. The primary outcome was the incidence of PL, defined as serum progesterone (P) on the triggering day ≥1.5 ng/mL. Secondary outcomes comprised the live birth, ongoing pregnancy, implantation, and good-quality embryos rates.
The trial involved 320 eligible participants (n=160 in each group). Both groups had comparable stimulation days, endometrial thickness, peak estradiol levels, number of oocytes retrieved, and number of mature oocytes. Metformin group experienced lower level of serum P (P<0.001) and incidence of PL (10 vs. 23.6%, P=0.001). Moreover, lower progesterone/estradiol (P/E) ratio and progesterone to mature oocyte index (PMOI) (P=0.002 and P=0.002, respectively) were demonstrated in women receiving metformin. Metformin group generated a better rate of goodquality embryos (P=0.005) and ongoing pregnancy (43.8 vs. 31.8%, P=0.026). A similar trend, though of borderline significance, was observed in the live birth rate in favor of metformin administration (38.15 vs. 27.5%, P=0.04).
Metformin could be used in patients with potential PL to improve fresh cycle outcomes by preventing PL (Registration number: NCT03088631).
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