In vivo and in vitro effects of cord blood hematopoietic stem and progenitor cell (HSPC) expansion using valproic acid and/or nicotinamide.

BACKGROUND: High self-renewal capacity and most permissive nature of umbilical cord blood (CB) results with successful transplant outcomes but low hematopoietic stem and progenitor cell (HSPC) counts limits wider use. In order to overcome this problem ex vivo expansion with small molecules such as Valproic acid (VPA) or Nicotinamide (NAM) have been shown to be effective. To the best of our knowledge, the combinatory effects of VPA and NAM on HSPC expansion has not been studied earlier. The aim of this study was to analyze ex vivo and in vivo efficacy of VPA and NAM either alone or in combination in terms of expansion and engraftment. METHODS: A total of 44 CB units were included in this study. To determine the ex vivo and in vivo efficacy, human CB CD34+ cells were expanded with VPA and/or NAM and colony forming unit (CFU) assay was performed on expanded HSPC. Xenotransplantation was performed simultaneously by intravenous injection of expanded HSPC to NOD-SCID gamma (NSG) mice (n = 22). Significance of the difference between the expansion groups or xenotransplantation models was analyzed using t-test, Mann-Whitney, ANOVA or Kruskal-Wallis tests as appropriate considering the normality of distributions and the number of groups analyzed. RESULTS: In vitro CD34+ HSPC expansion fold relative to cytokines-only was significantly higher with VPA compared to NAM [2.23 (1.07-5.59) vs 1.48 (1.00-4.40); p < 0.05]. Synergistic effect of VPA+NAM has achieved a maximum relative expansion fold at 21 days (D21) of incubation [2.95 (1.00-11.94)]. There was no significant difference between VPA and VPA+NAM D21 (p = 0.44). Fold number of colony-forming unit granulocyte-macrophage (CFU-GM) colonies relative to the cytokine-only group was in favor of NAM compared to VPA [1.87 (1.00-3.59) vs 1.00 (1.00-1.81); p < 0.01]. VPA+NAM D21 [1.62 (1.00-2.77)] was also superior against VPA (p < 0.05). There was no significant difference between NAM and VPA+NAM D21. Following human CB34+ CB transplantation (CBT) in the mouse model, fastest in vivo leukocyte recovery was observed with VPA+NAM expanded cells (6 ± 2 days) and the highest levels of human CD45 chimerism was detectable with VPA-expanded CBT (VPA: 5.42 % at day 28; NAM: 2.45 % at day 31; VPA+NAM 1.8 % at day 31). CONCLUSION: Our study results suggest using VPA alone, rather than in combination with NAM or NAM alone, to achieve better and faster expansion and engraftment of CB HSPC.

The Role of the Supine Empty Stress Test in the Evaluation of Women with Stress Urinary Incontinence: A Retrospective Cohort Study.

The International Continence Society recommends the supine empty stress test (SEST) as an accessory test in the evaluation of women with urinary incontinence, especially for the presence of intrinsic sphincter deficiency (ISD). The aim of this study was to investigate the relationship between the SEST and clinical findings in women diagnosed with stress urinary incontinence with single voiding cycle ambulatory urodynamics (AUM). AUM tracings of patients with lower urinary tract symptoms (LUTS = Lower urinary tract symptoms) (n = 513) were retrospectively reviewed, and 364 charts with urodynamic SUI were analyzed. Demographics, examination findings, scores of the Sandvik Incontinence Severity Index and validated questionnaires, and AUM findings were compared between SEST-positive and -negative groups. Additionally, the diagnostic accuracy of the SEST in the diagnosis of low abdominal leak point pressure (ALPP ≤ 60 cm H2O) in women with pure urodynamic SUI was calculated. The SEST was positive in 41.8% (n = 152) of the cohort. Women with a positive SEST had higher scores on the Sandvik severity index (9.2 ± 3.6 vs. 7.5 ± 3.8, p = 0.003) and lower ALPP (79.6 ± 29.3 vs. 98.4 ± 31.3, p < 0.001). The negative predictive value of the SEST for ISD was found to be 92.4%. Thus, the SEST seems to be an objective clinical test reflecting urinary incontinence severity while excluding the presence of ISD.

Do the Ultrasonographic Measures of Midurethral Sling Location Relate With Surgical Outcomes?

IMPORTANCE: The proper placement of a midurethral sling (MUS) is the key factor for a successful surgical outcome. OBJECTIVE: This study aimed to evaluate the relationship of perineal ultrasonographic measures of the tape location with subjective and objective outcomes after MUS surgery at midterm follow-up of women. METHODS: The tape percentile (TP; total urethral length/bladder neck tape distance×100) and urethra tape distance (UTD; the shortest distance from the longitudinal smooth muscle complex of the urethra to the midpoint of the tape) were correlated with midterm surgical success. Patient satisfaction measured with the visual analog scale (VAS) was considered as the primary outcome. The presence of stress urinary incontinence on direct questioning, the Urinary Distress Inventory 6 (UDI-6) scores, findings of the cough stress test, free uroflowmetry, postvoid residual volume, and single-cycle voiding ambulatory urodynamic monitoring (AUM) were the other outcomes. RESULTS: Seventy-eight women were evaluated at a mean follow-up of 4.4 ±3.3 years. Women who were highly satisfied (VAS ≥ 8) had a significantly higher TP (64.7% vs 50.8%, P < 0.001) and lower UTD (3.6 vs 4.5 mm, P = 0.018). Irritative, stress, and obstructive scores at UDI-6 increased as the tape was located closer to the bladder neck (P < 0.001, P < 0.001 and P = 0.044, respectively), and stress symptoms decreased with a tape closer to the urethra (P < 0.001). Women with detrusor overactivity at AUM were found to have a lower TP (P < 0.001). CONCLUSION: The perineal ultrasonographic evaluation of tape location with UTD and TP seems to be well correlated with the women's midterm MUS surgical outcomes.

The association of coital incontinence with clinical factors and single voiding cycle ambulatory urodynamic monitoring findings in women.

Introduction: Coital incontinence (CI) is a frequent problem in women with urinary incontinence (UI) with significant impact on female sexuality and quality of life. The underlying mechanism is controversial; it has been known that CI is associated with both stress urinary incontinence (SUI) and detrusor overactivity (DO). However, recently it has been reported that CI is mainly related with SUI and urethral incompetence, but not with DO. Ambulatory urodynamic monitoring (AUM) has been shown to be a sensitive tool for the detection of DO. The aim of this study was to investigate the clinical risk factors for CI and the association of CI with urodynamic diagnoses at single voiding cycle AUM. Methods: Records of sexually active women with urinary incontinence attending the urogynaecology unit of a university hospital, who completed the PISQ-12 were reviewed retrospectively (n = 1,005). Patients were grouped using the 6th question; patients answering "never" to this question were considered as continent during coitus (n = 591) and patients reporting any urinary leakage at coitus were considered to have CI (n = 414). Demographics, clinical examination findings, incontinence severity measured by the Sandvik Incontinence Severity Index, scores of Turkish validated questionnaires (PFDI-20, IIQ-7, OAB-V8, and PISQ-12) and single voiding cycle AUM findings were compared, and univariate and multivariate logistic regression analyses were performed. Results: Among all sexually active women with UI, 41.2% had CI; UI was more severe, symptom bother was higher, related quality of life (p < 0.001) and sexual function were worse (≤0.018) in these women. Younger age (OR 0.967, p < 0.001), history of vaginal delivery (OR 2.127, p = 0.019), smoking (OR 1.490, p = 0.041), postural UI (OR 2.012, p = 0.001), positive cough stress test (OR 2.193, p < 0.001), and positive SEST (OR 1.756, p = 0.01) were found as independent clinical factors associated with CI. Urodynamic SUI (OR 2.168, p = 0.001) and MUI (OR 1.874, p = 0.002) were found as significant and independent urodynamic diagnoses associated with CI, whereas no association was found with DO or UUI. Conclusion: Both clinical and AUM findings supported that CI is a more severe form of UI that it is mainly related with SUI and urethral incompetence, but not with UUI or DO.

Current developments in artificial intelligence from obstetrics and gynecology to urogynecology.

In today's medical practice clinicians need to struggle with a huge amount of data to improve the outcomes of the patients. Sometimes one clinician needs to deal with thousands of ultrasound images or hundred papers of laboratory results. To overcome this shortage, computers get in help of human beings and they are educated under the term "artificial intelligence." We were using artificial intelligence in our daily lives (i.e., Google, Netflix, etc.), but applications in medicine are relatively new. In obstetrics and gynecology, artificial intelligence models mostly use ultrasound images for diagnostic purposes but nowadays researchers started to use other medical recordings like non-stress tests or urodynamics study results to develop artificial intelligence applications. Urogynecology is a developing subspecialty of obstetrics and gynecology, and articles about artificial intelligence in urogynecology are limited but in this review, we aimed to increase clinicians' knowledge about this new approach.

Impact of pelvic floor distress on non-invasive urodynamic findings in women.

OBJECTIVE (S): To compare non-invasive urodynamic findings in women with and without pelvic floor distress and to investigate the patient characteristics affecting maximum flow rates. STUDY DESIGN: This is a retrospective study including data derived from a prospective cohort study evaluating free uroflowmetry findings in asymptomatic and symptomatic women with urinary dysfunction attending the gynecology outpatient clinic for routine annual control, infertility, abnormal uterine bleeding and pelvic floor dysfunction. Data regarding baseline characteristics, questionnaires, urogynecologic examination findings and free uroflowmetry results were retrieved. Women were grouped according to the Turkish validated Pelvic Floor Distress Inventory (PFDI-20); women who scored 0 or 1 points for each item ("no" or "not at all") were considered as asymptomatic in terms of pelvic floor dysfunction, and women who scored 2 or more points to any item were accepted as symptomatic. Baseline characteristics, clinical examination findings and free uroflowmetry data were compared among the groups using Student's-t or Mann-Whitney U tests, Chi-square test or Fisher's exact tests, where appropriate. Correlations and their significance, and patient characteristics affecting Qmax were investigated using the Pearson test. A multiple linear regression model was used to identify independent factors affecting Qmax. RESULTS: The study population (n = 186) comprised asymptomatic (n = 70, 37.6%) and symptomatic (n = 116, 62.4%) women according to the scores of the PFDI-20. Corrected Qmax, TQmax, Tvv and PVR were found significantly lower in asymptomatic women (p ≤ 0.001). In asymptomatic women, PVR was <100 mL in 98.5%, and <50 mL in 80%. In multivariate linear regression analysis parity, obstructive subscale score of the UDI-6, previous mid-urethral sling surgery and hysterectomy were found to affect Qmax negatively, whereas VV was found to affect Qmax positively. CONCLUSION(S): Although significantly different, overlapping wide ranges of non-invasive urodynamic findings have been observed in women with and without pelvic floor distress in the present study population. Maximum urinary flow rates were significantly affected by patient characteristics such as parity, obstructive symptoms, prior incontinence surgery and hysterectomy. There is need for further larger studies considering all possible factors that may affect voiding.

Current status of stem cell treatments and innovative approaches for stress urinary incontinence.

Stem cells are capable of self-renewal, differentiation, and the promotion of the release of chemokines and progenitor cells essential for tissue regeneration. Stem cells have the potential to develop into specialized cells if given the right conditions, to self-renew and maintain themselves, to generate a large number of new differentiated cells if injured, and to either generate new tissues or repair existing ones. In the last decade, it has become clear that treating lower urinary tract dysfunction with the patient's own adult stem cells is an effective, root-cause method. Regenerative medicine is predicated on the idea that a damaged rhabdosphincter can be repaired, leading to enhanced blood flow and improved function of the sphincter's exterior (striated) and internal (smooth) muscles. Stem cell therapy has the potential to cure stress urinary incontinence according to preclinical models. In contrast, stem cell treatment has not been licensed for routine clinical usage. This article reviews the current state of stem cell for stres urinary incontinence research and recommends future avenues to facilitate practical uses of this potential therapy modality.

Changes of pelvic organ prolapse and pelvic floor dysfunction throughout pregnancy in singleton primigravidas: A prospective cohort study.

OBJECTIVE: To document the deterioration in pelvic organ support occurring throughout all trimesters during the first pregnancy of women with no known risk factors. Secondarily to make a comprehensive review in order to verify the current findings and methodologies of similar studies in the literature. STUDY DESIGN: In this prospective study, forty-one primigravid women with a singleton pregnancy were recruited during their first trimester. During follow-up pelvic organ support changes were documented by using Pelvic Organ Prolapse Quantification (POP-Q) system. Additionally, pelvic floor muscle strength examination, by modified Oxford scoring (MOS), and symptom assessment by Pelvic Floor Distress Inventory-Short Form (PFDI-20) were performed at three time points: first (T1), second (T2), and third trimester (T3) (n = 33). The Wilcoxon test was performed to test the significance of pairwise differences. Spearman correlation coefficient was estimated to determine the linear association of the findings. RESULTS: Both distal and proximal anterior and posterior vaginal walls (Points Aa, Ba, Ap and Bp) with cervix (C) descended towards the hymen, throughout first pregnancy with a significant caudal shift on progressing from T2 to T3 (p ≤ 0.017). Posterior fornix (Point D) made a non-significant cranial shift (p = 0.527). The genital hiatus, perineal body and total vaginal length increased significantly (p ≤ 0.001). No significant difference in MOS was observed throughout pregnancy. The scores of PFDI-20 with all its domains worsened significantly during pregnancy, especially in T3 (p ≤ 0.011). Moderate correlations were observed between posterior vaginal descent and anorectal symptoms (rho 0.427, p < 0.05), and between the changes in genital hiatus and prolapse symptoms (rho 0.406, p < 0.05). CONCLUSION: A significant descent both in all compartments of vaginal wall and perineum with an increase in total vaginal length, was observed together with an associated pelvic floor dysfunction throughout the first pregnancy of women.

A prediction model for detrusor overactivity at ambulatory urodynamics in women with urinary incontinence.

OBJECTIVE(S): To develop a multivariable model using both clinical examination findings and validated questionnaires' scores for predicting the presence of detrusor overactivity observed during ambulatory urodynamic monitoring in women with urinary incontinence. STUDY DESIGN: The study population was chosen from a registry of women evaluated with urodynamics for urinary incontinence retrospectively. Data for baseline characteristics, clinical findings, and ambulatory urodynamic records were evaluated for all women included to the study. Urodynamic data were obtained by retrospective review of urodynamic traces with a standardized protocol during single voiding cycle, compatible to the standards of International Continence Society (ICS) for ambulatory urodynamic monitoring. RESULTS: A total of 395 women with urinary incontinence were included in the study. Detrusor overactivity was diagnosed in 57.1% of women included to the study. Clinical factors positively associated with detrusor overactivity were higher body-mass index (OR = 1.10; 95% CI 1.03-1.15, p < 0.001), higher OAB-V8 (Overactive bladder awareness tool - version 8) scores (OR = 1.04; 95% CI 1.01-1.06, p < 0.001) and presence of urgency urinary incontinence (OR = 2.39; 95% CI 1.47-3.81, p < 0.001). The presence of postural urinary incontinence (OR = 0.51; 95%CI 0.28-0.90, p = 0.021) and insensible loss of urine (OR = 0.33; 95%CI 0.27-0.93, p = 0.005) had negative associations with detrusor overactivity in the final multivariate logistic regression analysis. CONCLUSION(S): BMI, OAB-V8 scores, urgency urinary incontinence, postural urinary incontinence and insensible loss of urine were associated with the presence of detrusor overactivity according to our prediction model. However, the overall model accuracy suggests urodynamic studies are still needed for a definitive diagnosis. Nevertheless, the prediction may be beneficial for selecting a subgroup of women who are unlikely to benefit from ambulatory urodynamic monitoring for the diagnosis of detrusor overactivity.

Comparison of patient reported outcomes, pelvic floor function and recurrence after laparoscopic sacrohysteropexy versus vaginal hysterectomy with McCall suspension for advanced uterine prolapse.

OBJECTIVE: To compare medium/long-term outcomes in terms of pelvic floor function, patient reported prolapse recurrence and repeat prolapse surgery after laparoscopic sacrohysteropexy (LSHP) and vaginal hysterectomy with McCall suspension (VH&McCall) which is the most commonly performed surgical option for severe uterine prolapse from past to present. STUDY DESIGN: Files of patients who underwent LSHP and VH&McCall for advanced utero-vaginal prolapse (stage 3 & 4) at the Department of Gynecology in Ankara University School of Medicine between 2008 and 2018 were reviewed (n = 517). Data of women who were followed up for at least 1-year and containing both the full-filled Patient Global Impression of Improvement (PGI-I) survey and Turkish validated Pelvic Floor Distress Inventory-20 (PFDI-20), were included. RESULTS: A total of 132 women were included in the study; 46 women who underwent LSHP and 86 women who underwent VH&McCall. Even though the median age of the LSHP group was significantly lower than the median age of VH&McCall group (42 vs. 67 years; P<;0.001), recurrence and repeat surgery rates were found to be similar after both surgical approaches as well as the scores of PGI-I and PFDI-20. However, in women who were operated before their sixties, symptomatic recurrence was found to be significantly lower after LSHP than VH&McCall (16.2 % vs. 47.4 %, respectively; P = 0.024) as well as repeat prolapse surgery (2.7 % vs. 26.3 %, respectively; P = 0.014). PGI-I and PFDI-20 scores also suggested better pelvic floor function after LSHP significantly (p = 0.004 & p = 0.003 respectively). When adjusted for age, VH&McCall significantly increased the risk of symptomatic prolapse recurrence compared to LSHP (OR: 4.65; 95 % CI: 1.326-16.312; P = 0.016). CONCLUSION: LSHP and VH&McCall might seem to be surgical options for individualized management with similar pelvic floor function & recurrence in the medium/long-term follow-up, but the age adjusted risk analysis showed higher rates of symptomatic recurrence after VH&McCall. Moreover, the better outcomes after LSHP in the younger subset, revealed the need of further clarification with well-designed prospective studies.

Comparison of alternative ßhCG follow-up protocols after single-dose methotrexate therapy for tubal ectopic pregnancy.

PURPOSE: To evaluate the performances of five different ßhCG follow-up protocols after single-dose methotrexate therapy for tubal ectopic pregnancy (EP). METHODS: Data of patients who received single-dose methotrexate therapy for tubal EP at a university hospital between January 2011 and July 2016 were reviewed. A 'successful methotrexate treatment' was defined if the EP treated with no need for surgery. The performances of different protocols were tested by comparing with the currently used '15% ßhCG decrease between days 4 and 7' protocol. The tested follow-up protocols were '20, 25%, and any ßhCG decrease between days 0/1 and 7' and '20% and any ßhCG decrease between days 0/1 and 4'. RESULTS: Among the 96 patients evaluated, 12 (12.5%) required second dose. Totally, 91 (94.8%) patients treated successfully with no need for surgery. Four patients were operated within 4 days following the second dose. One patient who did not need second dose according to the standard follow-up protocol was operated on the 10th day due to rupture (specificity = 80%). Two protocols, namely '20% ßhCG decrease between days 0/1 and 7' and 'any ßhCG decrease between days 0/1 and 7' did not show statistically significant differences from the index protocol regarding the number of patients who should be assigned to 2nd dose. CONCLUSIONS: 'Any ßhCG decrease between days 0/1 and 7' protocol may substitute the currently used one to decide second dose methotrexate in tubal EP management. Omitting 4th day measurement seems to be more convenient and cost effective.

Nomogram with potential clinical use to predict lymph node metastasis in endometrial cancer patients diagnosed incidentally by postoperative pathological assessment.

PURPOSE: To determine the clinical and pathological risk factors for lymph node metastasis (LNM) in patients with endometrial cancer and to create a nomogram to predict LNM in patients without surgical staging. METHODS: All patients with endometrial adenocarcinoma who were treated surgically at a university based gynecologic oncology clinic between January 2011 and December 2014 were recruited. Women with endometrial adenocarcinoma who were surgically staged including lymphadenectomy were included in the study. Data regarding clinical and pathological risk factors were recorded. The histopathologic slides from the staging surgeries were re-evaluated microscopically by a gynecologic pathologist for all parameters along with lymphovascular space invasion (LVSI). RESULTS: A total of 279 patients with endometrial cancer were analyzed. Among those, 31 (11.1%) had lymph node metastasis. According to the univariate analyses, elevated CA 125 (>35 U/mL), LVSI, myometrial invasion ≥50%, grade 3 disease, non-endometrioid type, and cervical stromal involvement were significantly associated with LNM. The multivariate logistic regression analysis showed that LVSI, non-endometrioid type, elevated CA 125, and cervical stromal involvement increased the risk of LNM. However, myometrial invasion and grade did not significantly affect the risk of LNM. A nomogram to predict LNM was constructed using these factors (concordance index 0.92). CONCLUSIONS: LVSI is the most important predictor for LNM. The present nomogram can be useful to decide if adjuvant therapy is required for patients who undergo simple hysterectomy for a benign etiology and incidentally diagnosed with endometrial cancer by pathological evaluation.

Effects of obstetric gel on the process and duration of labour in pregnant women: Randomised controlled trial.

The present study investigated maternal and neonatal outcomes in pregnant women who used obstetric lubricant gels during active labour. This prospective randomised controlled study included 180 pregnant women. Women were randomly assigned to two groups during the first-stage of labour. Pregnant women in the obstetric gel group received standard antepartum care plus vaginal application of obstetric gel. Women in the control group received standard antepartum care without obstetric gel. Mean duration of the second stage of labour was significantly shorter in the obstetric gel group than control group (45 ± 34 min vs. 58 ± 31 min, respectively; p = .005). Mean APGAR values at 5 min were significantly higher in the obstetric gel group (9.5 ± 0.6 vs. 9.2 ± 0.7; p = .0014). Among nulliparous women, mean duration of the second stage of labour was significantly shorter in the gel group than control group (53 ± 52 min vs. 83 ± 45 min, respectively; p = .003). Using obstetric gel at the beginning of the first stage decreases the length of the second stage of labour, particularly in nulliparous women, and may be associated with an improved APGAR score at 5 min. Impact statement A limited number of studies in the literature have demonstrated that obstetric gels shorten the second stage of labour and are protective for the pelvic floor. The results of this study show that using obstetric gel shortens the second stage of labour in only nulliparous, but not multiparous women. In addition, a significant improvement in the 5 min APGAR score was seen in the neonates of women who used obstetric gel. The application of obstetric gels during the labour of nulliparous women may be a useful clinical practice and may have a widespread use in the future.

Lower serotonin level and higher rate of fibromyalgia syndrome with advancing pregnancy.

OBJECTIVE: The aim of the study is to investigate the relationship between changes in serotonin levels during pregnancy and fibromyalgia syndrome (FS) and the relationships between FS and the physical/psychological state, biochemical and hormonal parameters, which may be related to the musculoskeletal system. STUDY DESIGN: This study is a prospective case-control study conducted with 277 pregnant women at the obstetric unit of Ankara University Faculty of Medicine, in the period between January and June 2015. FS was determined based on the presence or absence of the 2010 ACR diagnostic criteria and all the volunteers were asked to answer the questionnaires as Fibromyalgia Impact Criteria (FIQ), Widespread Pain Index (WPI), Symptom Severity Scale (SS), Beck Depression Inventory and Visual Analog Scale (VAS). Biochemical and hormonal markers (glucose, TSH, T4, Ca (calcium), P (phosphate), PTH (parathyroid hormone) and serotonin levels) relating to muscle and bone metabolism were measured. RESULTS: In the presence of fibromyalgia, the physical and psychological parameters are negatively affected (p < 0.001). There was no significant difference between the fibromyalgia and control groups in terms of glucose, Ca (calcium), P (phosphorus), PTH (parathyroid hormone), TSH (thyroid stimulant hormone), fT4 (free T4) levels (p = 0.060, 0.799, 0.074, 0.104, 0.797, 0.929, respectively). A reduction in serotonin levels may contribute to the development of fibromyalgia but this was not statistically significant. The Beck Depression Inventory scale statistically showed that increasing scores also increase the risk of fibromyalgia (p <0.001). CONCLUSION: Our study has shown that serotonin levels in women with FS are lower than the control group and that serotonin levels reduce as pregnancy progresses. Anxiety and depression in pregnant women with FS are higher than the control group. The presence of depression increases the likelihood of developing FS at a statistically significant level. Serotonin impairment also increases the chance of developing FS, but this correlation has not been shown to be statistically significant.

Final oocyte maturation with two different GnRH agonists in antagonist co-treated cycles at risk of ovarian hyperstimulation syndrome.

Triptorelin 0.2 mg and leuprolide 1 mg subcutaneous injections for triggering final follicular maturation were compared in patients with a high risk for ovarian hyperstimulation syndrome (OHSS). Infertile patients treated with GnRH antagonist protocol between January 2014 and March 2016 were recruited. Patients with high serum oestradiol levels on HCG day (>3000 pg/ml) indicating a risk of OHSS consisted of the study groups (A and B). Patients with serum oestradiol levels less than 3000 pg/ml consisted of the control group (C). A single injection of 0.2 mg triptorelin, 1 mg leuprolide and 10000 IU HCG were administered for final oocyte triggering in groups A (n = 63), B (n = 74) and C (n = 131), respectively. Demographic parameters were comparable between the groups. No cases of severe or moderate OHSS occurred in any group. The clinical pregnancy rates were 31.7%, 37.8% and 32.8% in groups A, B and C, respectively. Both injections had comparable efficacy in clinical outcome and OHSS risk. Regardless of preferred drug, GnRH agonist trigger for final oocyte maturation seems to be safe for patients with high OHSS risk, and can be safely used in fresh embryo transfer cycles.

Does adding endometrial scratching to diagnostic hysteroscopy improve pregnancy rates in women with recurrent in-vitro fertilization failure?

OBJECTIVE: To investigate the effect of additional endometrial scratching procedure during hysteroscopy on assisted reproductive technology (ART) cycle outcomes in repeated implantation failure (RIF) patients without endometrial or uterine abnormalities on hysteroscopic evaluation. MATERIALS AND METHODS: Three hundred and forty-five RIF patients who underwent ART at a university-based infertility clinic between January 2011 and June 2015 were recruited in this retrospective cohort study. Uterine cavities of all included patients were evaluated by diagnostic hysteroscopy 7-14 days prior to the subsequent ART cycle. Women without endometrial abnormalities were allocated into two groups; the scratching group was consisted of patients who underwent endometrial scratching by using monopolar electric energy with needle forceps during hysteroscopy, and the control group was consisted of patients who underwent only diagnostic hysteroscopy. RESULTS: The implantation rate was significantly higher in the scratching group than the control group (37.7% versus 24.5%; p = 0.04). Clinical and ongoing pregnancy rates were also found to be significantly higher in the scratching group than the control group (37.7% versus 27.6%; p = 0.03; and 33.3% versus 23%; p = 0.03, respectively). CONCLUSION: Endometrial scratching during diagnostic hysteroscopy seems to enhance implantation and as well pregnancy rates in comparison to diagnostic hysteroscopy alone.

Dual trigger with gonadotropin-releasing hormone agonist and recombinant human chorionic gonadotropin improves in vitro fertilization outcome in gonadotropin-releasing hormone antagonist cycles.

AIM: The aim of this study was to evaluate whether dual trigger with leuprolide acetate plus recombinant human chorionic gonadotropin (hCG) improves in vitro fertilization outcome in gonadotropin-releasing hormone antagonist cycles. METHODS: A total of 156 patients diagnosed with mild male factor, unexplained or tubal factor infertility were enrolled in the study. All subjects were allocated into one of two groups: the dual trigger group (leuprolide acetate 500 µg + recombinant hCG 250 µg) and the standard group (recombinant hCG 250 µg) according to the selected trigger method. Oocyte trigger was performed when at least three follicles >17 mm were observed. Pregnancy rate, number of collected oocytes, number of metaphase II oocytes, number of grade-A embryos, cycle cancellation rate, and ovarian hyperstimulation syndrome rate were the main outcome measures for the study. RESULTS: The mean number of grade-A embryos (1.6 ± 1.5 vs 1.1 ± 1.4, P = 0.01) and of metaphase II oocytes (7.9 ± 4.6 vs 6.3 ± 5.8, P = 0.02) was significantly higher in the dual-trigger group. Pregnancy rate was significantly higher in the dual-trigger group than in the standard group (54.8 vs 37.5%, P = 0.006). Two cases of mild ovarian hyperstimulation syndrome were observed in each group. CONCLUSION: This novel and more physiological trigger approach using 500 µg leuprolide acetate plus 250 µg recombinant hCG may lead to an increase in the number of metaphase II oocytes, grade-A embryos, and may improve pregnancy rates.

Should we interpret the results of 'two-step' glucose screening again according to the obstetric outcomes?

We aimed to re-evaluate the 'two-step' antenatal glucose screening programme in relation to maternal and foetal outcomes in pregnant women screened for gestational diabetes mellitus and to compare maternal and foetal outcomes between different groups divided according to glucose tolerance test results. Two-thousand four-hundred and two pregnant women attending for antenatal care were recruited retrospectively for the study. Mean birthweight for pregnancies with single-value abnormality (SVA) in 100-g oral glucose tolerance test (OGTT) was significantly higher than the control group [3420 ± 378 vs. 3294 ± 444]. We found a significantly higher rate of macrosomia in the subgroup of 50-g glucose challenge test (GCT) between 130 and 140 mg/dl [9.7% vs. 4.8%]. Pregnant women whose 50-g GCT results are between 130 and 140 mg/dl or who have SVA in 100-g OGTT not only have gestational diabetes, but are also at increased risk for diabetic complications.

Heavy metal and trace element concentrations in blood and follicular fluid affect ART outcome.

OBJECTIVES: To assess the effects of heavy metal and trace element concentrations in blood and follicular fluid on assisted reproductive technology cycle outcome. STUDY DESIGN: A prospective study was conducted between January 2012 and July 2012 in a university hospital infertility clinic. One hundred and one patients with unexplained infertility who underwent intracytoplasmic sperm injection using GnRH-antagonist protocol were recruited. Concentrations of four toxic metals (Cd, Pb, Hg, As) and three trace elements (Cu, Zn, Fe) were measured both in blood and follicular fluid specimens. Patients were evaluated in two groups; the study group consisted of patients with ongoing pregnancy (n=20) and the reference group consisted of patients experienced assisted reproductive technology failure, miscarriage or biochemical pregnancy (n=81). RESULTS: Demographics and cycle parameters were comparable between the groups except for median number of day 3 Grade A embryos. Statistically significant negative correlations were found between blood Pb levels and number of MII oocytes, implantation, clinical pregnancy and ongoing pregnancy rates. Results of the log binomial regression revealed 2.2% lower risk for ongoing pregnancy for each 1µg/dL higher blood Pb concentration while holding the other variables in the model constant (RR 0.978; 95% CI 0.956-0.998; P=.041). Also, the results revealed 71.9% lower risk for ongoing pregnancy for each 1µg/dL higher follicular fluid Cu concentration while holding the other variables in the model constant (RR 0.288; 95% CI 0.085-0.92; P=.039). CONCLUSION: Blood concentrations of Pb and follicular fluid concentrations of Cu seem to have significant impacts on assisted reproductive technology cycle outcome.

Is omitting the 3rd hour measurement in the 100 g oral glucose tolerance test feasible?

BACKGROUND: To evaluate the diagnostic value of the 3rd hour plasma glucose level in the 100 g oral glucose tolerance test (OGTT). METHODS: Records of all pregnant patients with abnormal 50 g glucose challenge test (GCT) between January 2005 and December 2013 were reviewed (n=1963). The 100 g OGTT results were analyzed separately for both Carpenter & Couston (CC) and National Diabetes Data Group (NDDG) criteria. RESULTS: The number of patients diagnosed with gestational diabetes mellitus (GDM) was 297 (15.1%) according to CC criteria and 166 (8.4%) according to NDDG criteria. The 1st hour plasma glucose level showed the highest correlation with GDM diagnosis (ρ=0.595 for CC and ρ=0.567 for NDDG). However, the 3rd hour plasma glucose level showed the weakest correlation with GDM diagnosis (ρ=0.216 for CC and ρ=0.213 for NDDG). The 3rd hour value of 100 g OGTT was one of the two elevated measurements in 10.8% of patients when CC criteria are used and in 13.8% of patients when NDDG criteria are used. CONCLUSION: Omitting 3rd hour plasma glucose measurement in 100 g OGTT results in unacceptable rates of underdiagnosed patients.