Dipeptidyl peptidase-4 inhibitor: Sitagliptin down-regulated toll-like receptor 4 signaling pathway to reduce uterine injury in rats.

Objectives: Uterine ischemia is a common problem with ongoing controversy about its pathogenesis and prevention. The present study aimed to investigate the protective role of sitagliptin against uterine ischemia-reperfusion injury (IRI). Materials and Methods: Rats were allocated into 4 groups: control, sitagliptin (SIT) (5 mg/kg), IR; ischemia was induced followed by reperfusion, and IR+SIT; SIT was administered 1 hr before IRI. Uteri were removed for histopathological and biochemical observations. Malondialdehyde (MDA), total nitrites (NOx), reduced glutathione (GSH), superoxide dismutase (SOD) activity, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and toll-like receptor 4 (TLR4) were all measured. Hematoxylin and eosin (H&E) stain, Periodic acid-Schiff stain (PAS), and caspase-3 immunostaining were applied. Results: In the IR+SIT group; NOx, GSH, and SOD activities increased significantly. Meanwhile, the levels of MDA, TNF-α, IL-6, TLR4, and caspase-3 immunoexpression showed a significant reduction, as compared with the IR group. In the IR+SIT group, an improvement in the histopathological picture was noticed. Conclusion: The results showed that sitagliptin confers protection against uterine IRI through anti-oxidant, anti-inflammatory, and anti-apoptotic effects with a possible role for TLR4.

Leukotriene Receptor Antagonist, Montelukast Ameliorates L-NAME-Induced Pre-eclampsia in Rats through Suppressing the IL-6/Jak2/STAT3 Signaling Pathway.

AIMS: To investigate the potential protective role of montelukast (Mont) in the pre-eclampsia rat model induced by L-NG-Nitro arginine methyl ester (L-NAME). METHODS AND MATERIALS: Thirty-two pregnant female albino Wistar rats were assigned to four groups: the control group: pregnant rats received vehicles; the Mont group: pregnant rats received Mont (10 mg/kg/day, p.o.) from the 6th to the 18th day of gestation; the L-NAME group: pregnant rats received L-NAME (50 mg/kg/day, i.p.) from the 9th to the 18th day of gestation; the Mont/L-NAME group: pregnant rats received Mont (10 mg/kg/day, p.o.) from the 6th to the 18th day of gestation and L-NAME (50 mg/kg/day, i.p.) from the 9th to the 18th day of gestation. Placental, hepatic, and renal malondialdehyde (MDA), total nitrites (NOx), interleukin 6 (IL-6), and tumor necrosis factor (TNF)-α were determined. Serum alanine transaminase (ALT), aspartate transaminase (AST), creatinine, urea, 24-h urinary protein, and the placental growth factor (PGF) were measured. Histopathological examinations of the placental, hepatic, and renal tissues were also performed. In addition, placental, hepatic, and renal Janus kinase 2 (Jak2) and signal transducer and activator of transcription 3 (STAT3) immunoblotting were performed. KEY FINDINGS: Mont improves oxidative stress, IL-6, TNF-α, ALT, AST, creatinine, urea, 24-h urinary protein, PGF, Jak2, and STAT3 which were all affected by L-NAME. Moreover, the histopathological assessment indicated that Mont restored the normal architecture that was markedly disturbed by L-NAME. SIGNIFICANCE: Mont exerted the biochemical and histopathological amelioration of L-NAME-caused pre-eclampsia through its anti-inflammatory, anti-oxidant function and suppression of the IL-6/Jak2/STAT3 signaling pathway.

Retraction Note to: The effect of endometrial injury on first cycle IVF/ICSI outcome: A randomized controlled trial.

[This retracts the article DOI: 10.29252/ijrm.14.3.193.].

Impact of domestic violence against pregnant women in Minia governorate, Egypt: a cross sectional study.

BACKGROUND: Domestic violence is a common problem that is related to many serious short-term and long-term health hazards around the world. METHODS: During obtaining the medical history from the participants, the questions used to assess the abuse were derived from the widely used Abuse Assessment Screen (AAS). Potential risk factors including a variety of socio-demographic and reproductive health-relation indicators were assessed. The influence of violence on the pregnancy outcome was determined by the continuous follow-up till giving birth. RESULTS: 513 pregnant women were included. The prevalence of violence among them was 50.8%. The prevalence of physical, sexual, verbal, and emotional abuse was 30.2, 20, 41.7, and 45.4% respectively. Exposure to violence during pregnancy had significant effects on the women and their pregnancy outcome in the form of development of vaginal infection (P-value =0.036), vaginal bleeding (P-value = 0.008), preterm labour (P-value = 0.003), premature rupture of membrane (P-value = 0.001). CONCLUSION: Violence against pregnant women in Minia Governorate, Egypt is common especially emotional violence and it has many adverse effects on the women and their pregnancy outcome. One of the most important risk factors is the fear of the husband which makes violence a continuous vicious circle.

The value of serum progesterone level on day of human chorionic gonadotrophin administration / metaphase II oocyte ratio in predicting IVF/ICSI outcome in patients with normal ovarian reserve.

BACKGROUND: The clinical implication of the increased serum progesterone level on the day of HCG administration in assisted reproduction treatment (ART) is still controversial. The current study aimed to compare the predictive value of serum progesterone on day of HCG administration / metaphase II oocyte (P/MII) ratio on IVF/ ICSI outcome to serum progesterone (P) level alone and the ratio of serum progesterone/estradiol level (P/E2) ratio in prediction of pregnancy rates after ART. MATERIAL & METHODS: Two hundred patients admitted to the IVF/ICSI program at Minia IVF center in Egypt in the period from October 2016 to May 2018 were included in this study. Serum Progesterone (P) and Estradiol (E2) levels were estimated on the day of HCG administration. The ratio between serum P and the number of MII oocytes (P/MII ratio) was calculated and the predictive values of the three parameters (P, P/E2 ratio and P/MII ratio) in prediction of cycle outcomes were measured. RESULTS: P/ MII oocyte ratio was significantly lower in patients who attained clinical pregnancy (n = 97) as compared with those who couldn't whilst there was no significant difference in P and P/E2 ratio between the two groups. Using a cut off value of 0.125, the sensitivity and specificity of progesterone/ MII ratio in prediction of no pregnancy in IVF/ICSI were 75.7 and 77.1% respectively with the area under The Receiver operating curve (ROC-AUC) = 0.808. The respective values of the ROC-AUC for the P and P/E2 ratio were 0.651 and 0.712 with sensitivity and specificity of 71.2 and 73.5%for P level and of 72.5 and 75.3% for P/E2 ratio. Implantation or clinical pregnancy rates were significantly different between patients with high and low P/MII ratio irrespective of day of embryo transfer (day 3 or 5). CONCLUSIONS: In patients with normal ovarian response, serum progesterone on day of HCG / MII oocyte ratio can be a useful predictor of pregnancy outcomes and in deciding on freezing of all embryos for later transfer instead of high progesterone level alone.

The acceptability of using IUDs among Egyptian nulliparous women: a cross-sectional study.

BACKGROUND: Although intrauterine contraceptive device is highly effective, safe, long term and reversible method of contraception, the general population and physicians refuse. IUDs for nulliparous women due to persistent rumors about its side effects and complications. The aim of this study was to assess the acceptability of IUD use in nulliparous women by both women and health care providers in Egypt. METHODS: Five hundred thirty nulliparous women and 200 physicians were interviewed in 10 family planning clinics in Suez and Minia cities - Egypt. The knowledge and attitudes of women and health care providers towards IUD use in nulliparous women were assessed through a well designed questionnaire over 2 years. Those women who accepted using IUD were then followed up for 6 months. RESULTS: Most of nulliparous women sought for contraception reported a negative impression of IUD method (96.2%). 82.5% of physicians had the same attitude. The reasons for refusing IUD among nulliparous women are fear of side effects including infection (52.8%), and bleeding (37.7%).Also, fear of subsequent infertility 51.9% of women. Regarding the providers, increased pelvic inflammatory disease (PID) represented the highest percentage (70%) for non acceptability, followed by difficult insertion (52.5%). Ninety women who accepted use IUD were followed up 6 months later, 94.4% were still using the method and77.8% were happy with the results. CONCLUSION: The main barriers that hinder the use of IUD in nulliparous women are the women insufficient knowledge and attitude of their physicians. Good client counseling. Good training for physician to improve their experience would help increase the use of such effective and safe method.

The effect of uterine artery ligation in patients with central placenta pevia: a randomized controlled trial.

BACKGROUND: Placenta previa is major obstetric surgical risk as it is associated with higher percentage of intraoperative and postpartum hemorrhage (PPH), increased requirement of blood transfusion and further surgical procedures. The current study aimed to evaluate uterine artery ligation prior to uterine incision as a procedure to minimize blood loss during cesarean section in patients with central placenta previa. METHODS: One hundred and four patients diagnosed with central placenta previa antenatally and planned to have elective caesarean section were recruited from the antenatal clinic at Minia Maternity University hospital. Patients were randomly allocated into either ligation group or control group. RESULTS: Both groups were similar regarding demographic features and preoperative risk factors for bleeding. The intraoperative blood loss was significantly lower in the ligation group as compared with the control group (569.3 ± 202.1 mL vs. 805.1 ± 224.5 mL respectively, p = 0.002). There was a significant increase in the requirement for blood transfusion in the control group as compared with the ligation group (786 ± 83 mL vs. 755 ± 56 mL respectively, p = 0.03) Three cases in the control group required further surgical interventions to control intraoperative bleeding, while no cases in the ligation required further surgical techniques and that was statistically significant (p = 0.001). CONCLUSION: Uterine artery ligation prior to uterine incision may be a helpful procedure to minimize intraoperative and postpartum blood loss in cases with central placenta previa. TRIAL REGISTRATION: Retrospectively registered in ClinicalTrials.gov Identifier: NCT02002026 - December 8, 2013.

Risk factors and outcome of patients with eclampsia at a tertiary hospital in Egypt.

BACKGROUND: Eclampsia is a major cause of maternal and neonatal morbidity and mortality in low and middle income countries. The aim of this study was to assess the risk factors and maternal and perinatal outcome in patients with eclampsia in order to get reliable data that helps in reducing the incidence and improving the outcome in an area with high incidence of eclampsia. METHODS: Retrospective study including 250 patients diagnosed with eclampsia at Minia Maternity University Hopsital, Minia, Egypt in the period between January 2013 and December 2014.We analyzed the data obtained from medical records of these patients including patient characteristics, medical, obstetric, current pregnancy history, data on hospital admission, treatment given at hospital and maternal and perinatal outcome. Statistical analysis was done using SPSS version 21. RESULTS: During the study period, 21690 women gave birth in the hospital; of which 250 cases of eclampsia were diagnosed (1.2%).Four women died (case fatality rate 1.6%). The main risk factors identified were young age, nulliparity, low level of education, poor ante-natal attendance and pre-existing medical problems. The most common complication was HELLP syndrome (15.6%). Magnesium sulphate therapy was given to all patients but there was lack of parenteral anti-hypertensive therapy. Forty six cases delivered vaginally (18.4%). Assisted delivery was performed in 22 (8.8%) cases and caesarean section in 177 (70.8%) cases; 151(60.4%) primary caesarean sections and 26 (10.4%) intra-partum. Perinatal deaths occurred in 11.9% on cases. Prematurity and poor neonatal services were the main cause. CONCLUSION: Morbidity and mortality from eclampsia are high in our setting. Improving ante-natal and emergency obstetric and neonatal care is mandatory to improve the outcome.

Does laparoscopy still has a role in modern fertility practice?

BACKGROUND: More than 3 decades after the introduction of in vitro fertilization (IVF) and despite the improved success rates of assisted reproductive technologies, the argument for performing laparoscopy as a part of the infertility workup still stands. OBJECTIVE: To evaluate the role of laparoscopy±hysteroscopy in diagnosis and management of infertility in our setting in view of modern fertility practice. MATERIALS AND METHODS: This case control study was carried out on 600 infertile women subjected to laparoscopy or combined laparoscopy and hysteroscopy at endoscopy unit in Minia University Hospital, Egypt during the period from January 2012 to December 2014. RESULTS: The causes of infertility as identified by laparoscopy±hysteroscopy were polycystic ovary syndrome (25.1%), tubal factor (30%), uterine cause (4%), and endometriosis (2.7%). No cause was identified in 38.2% of cases. Based on operative findings, women were treated with different options. Expectant management was used in 92 cases (15.3%). Ovulation induction with anti-estrogens or gonadotropins was used in 372 cases (62%). Sixty cases (10%) had intrauterine insemination and sixty four cases (10.7%) underwent in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) treatment. Within 1 yr after laparoscopy, 180 cases achieved pregnancy (30%). The most favorable outcome was recorded in women with unexplained infertility (36.7% of cases got pregnant) followed by women with polycystic ovary syndrome (27.8%). Participants with uterine and tubal infertility factor achieved pregnancy in 25% and 22.8% of cases, respectively. The worst outcome was recorded in women with endometriosis. CONCLUSION: Laparoscopy still has an important role in the diagnosis and treatment of infertility.

The effect of endometrial injury on first cycle IVF/ICSI outcome: A randomized controlled trial.

BACKGROUND: Implantation remains a limiting step in IVF/ICSI. Endometrial injury isa promising procedure aiming at improving the implantation and pregnancy rates after IVF/ICSI. OBJECTIVE: The aim of this study was to evaluate the effect of endometrial injury induced in precedingcycle on IVF/ICSI outcome. MATERIALS AND METHODS: Four hundred patients undergoing their first IVF/ICSI cycle in two IVF units in Minia, Egypt were randomly selected to undergo either endometrial injury in luteal phase of preceding cycle (intervention group) or no treatment (control group). Primary outcome wasthe implantation and live birth ratesWhile the secondary outcome was clinical pregnancy, miscarriage, multiple pregnancy rates, pain and bleeding during and after procedure. RESULTS: Implantation and live birth rates were significantly higher in intervention compared with control group (22.4% vs. 18.7%, p=0.02 and 67% vs. 28%, p=0.03), respectively. There was also a significant reduction in miscarriage rate in intervention group (4.8% vs. 19.7%, respectively, p<0.001). CONCLUSION: Endometrial injury in preceding cycle improves the implantation rate and live birth rate and reduces the miscarriage rate per clinical pregnancy in patients undergoing their first IVF/ICSI cycle.

Nitric oxide donors improve the ovulation and pregnancy rates in anovulatory women with polycystic ovary syndrome treated with clomiphene citrate: A RCT.

BACKGROUND: Clomiphene citrate (CC) is the first line agent used for ovulation induction in patients with polycystic ovarian syndrome (PCOS). However, there is marked discrepancy between the ovulation and pregnancy rates achieved, which may be attributed to the undesirable effect of CC on cervical mucus and endometrium. OBJECTIVE: The aim of this study was to evaluate the effect of Isosorbid monoitrate (ISMN) as nitric oxide (NO) donors on the ovulation and pregnancy rates in an ovulatory women with PCOS treated with CC. MATERIALS AND METHODS: Ninety patients with PCOS were randomly allocated into three groups. Patients in group A) were treated with 100 mg CC for five days starting from the fifth day of the cycle. Patients in group B) and C) received 10 mg and 20 mg of ISMN respectively in addition to CC, applied vaginally till the diagnosis of ovulation. RESULTS: There was a significant increase in the ovulation and pregnancy rates in the patients treated with CC+ISMN as compared with patients treated with CC alone (p< 0.001). CONCLUSION: Concomitant use of NO with CC seems to improve the ovulation and pregnancy rates in the patients with PCOS with no significant increase in side effects as compared with CC alone.

The influence of circulating anti-Müllerian hormone on ovarian responsiveness to ovulation induction with gonadotrophins in women with polycystic ovarian syndrome: a pilot study.

BACKGROUND: Women with polycystic ovarian syndrome (PCOS) are known to have elevated circulating Anti-Müllerian hormone (AMH), which has been found to desensitize ovarian follicles to follicle stimulating hormone (FSH). The purpose of this study was to investigate the impact of high circulating AMH on ovarian responsiveness to ovulation induction with gonadotrophins in PCOS women. METHODS: This prospective observational pilot study was conducted in two collaborating Fertility Centres in the UK and Egypt. The study included 20 consecutive anovulatory women with PCOS who underwent 34 cycles of human menopausal gonadotrophin (hMG) ovarian stimulation using chronic low-dose step up protocol. Blood samples were collected for the measurement of serum AMH concentrations in the early follicular (day 2-3) phase in all cycles of hMG treatment. The serum levels of AMH were compared between cycles with good vs. poor response. The good response rates and the total dose and duration of hMG treatment were compared between cycles with high vs. low serum AMH concentrations. RESULTS: Cycles with poor response (no or delayed ovulation requiring >20 days of hMG treatment) had significantly (p = .007) higher median{range} serum AMH concentration (6.5{3.2-13.4}ng/ml) compared to that (4.0{2.2-10.2}ng/ml) of cycles with good response (ovulation within 20 days of hMG treatment). ROC curve showed AMH to be a useful predictor of poor response to hMG stimulation (AUC, 0.772; P = 0.007). Using a cut-off level of 4.7 ng/ml, AMH had a sensitivity of 100% and specificity of 58% in predicting poor response. The good response rate was significantly (p < .001) greater in cycles with lower AMH (<4.7 ng/ml) compared to that in those with AMH > = 4.7 ng/ml (100% vs. 35%, respectively). All cycles with markedly raised serum AMH levels (> 10.2 ng/ml) were associated with poor response. Cycles with high AMH (> = 4.7 ng/ml) required significantly (p < .001) greater amounts (median {range}, 1087{450-1650}IU) and longer duration (20 {12-30}days) of hMG stimulation than cycles with lower AMH (525 {225-900}IU and 8{6-14}days). CONCLUSIONS: PCOS women with markedly raised circulating AMH seem to be resistant to hMG ovulation induction and may require a higher starting dose.

The predictive value of circulating anti-Müllerian hormone in women with polycystic ovarian syndrome receiving clomiphene citrate: a prospective observational study.

CONTEXT: Elevated serum anti-Müllerian hormone (AMH) concentration in women with polycystic ovarian syndrome (PCOS) is known to lower sensitivity of ovarian follicles to circulating FSH. This effect may compromise the outcome of clomiphene citrate (CC) ovulation induction. OBJECTIVE: The objective of the study was to investigate the impact of high circulating AMH on the outcome of CC ovulation induction in women with PCOS. DESIGN: This was a prospective cohort observational study. SETTING: The study was conducted at the Fertility Unit, Derby, United Kingdom. PATIENTS: Sixty anovulatory women with PCOS participated in the study. INTERVENTIONS: Serum AMH concentrations were measured on cycle day 2 during 187 CC cycles. These concentrations were compared between responders and nonresponders. The receiver-operating characteristic curve was used to evaluate the prognostic value of circulating AMH. The success rates of CC were compared between patients with high vs low AMH levels. The dose of CC required to achieve ovulation was correlated with serum AMH concentrations. MAIN OUTCOME MEASURES: Ovulation and pregnancy rates were measured. RESULTS: Serum AMH concentrations were significantly (P < .001) lower in responders (achieving ovulation) vs nonresponders (mean ± SEM, 2.5 ± 0.1 vs 5.8 ± 0.7 ng/mL, respectively). Similarly, serum AMH concentrations were significantly (P = .046) lower in pregnant (3.0 ± 0.4 ng/mL) vs nonpregnant patients (4.4 ± 0.5 ng/mL). There was a significant (P = .02) gradient increase of serum AMH levels with the increasing dose of CC required to achieve ovulation. The receiver-operating characteristic curve showed AMH to be a useful predictor of no ovulation (area under the curve, 0.809; P < .001) with a useful cutoff level of 3.4 ng/mL. Ovulation and pregnancy rates were significantly higher (97%, P < .001, and 46%, P = .034) in patients with low AMH (<3.4 ng/mL) vs women with AMH 3.4 ng/mL or greater (48% and 19%). CONCLUSION: PCOS women with high circulating AMH (≥ 3.4 ng/mL) seem to be resistant to CC and may require a higher starting dose.