Is intrauterine insemination a viable treatment option for women over 43 years old? An analysis by ovarian stimulation protocol and sperm source

PurposeThe aim of this study was to determine how female age at the end of the reproductive spectrum effects success of natural cycle intrauterine insemination (IUI) or IUI in combination with ovarian stimulation.MethodsWe performed a retrospective cohort study of women 43 years of age and older at the time of IUI in a single academic fertility center between January 2011 and March 2018. Primary outcomes were both pregnancies and live births per cycle of IUI. Data are presented as percentage or mean ± SD. Fisher exact and chi-squared analyses were performed.ResultsThere were 9334 IUI cycles conducted during the study period. Of these cycles, 325 IUIs (3.5%) were for women aged 43 years and over at the time of insemination (43.6 ± 0.8, range 43 to 47 years). Analysis of these 325 IUI cycles revealed 5 biochemical pregnancies (1.5%) and only 1 live birth (0.3%). The pregnancy rate did not differ between IUIs using donor sperm (N = 1/49, 2.0%) compared to IUIs with partner sperm (N = 4/276, 1.4%). The pregnancy rate did not differ between IUIs with gonadotropins (N = 2/211, 0.9%), clomiphene or letrozole (N = 2/78, 2.6%), or natural cycle (N = 1/36, 2.8%).ConclusionsThe use of intrauterine inseminations in women 43 years of age and older is an ineffective treatment strategy. This is irrespective of the use of ovarian stimulation or donor sperm. Costly gonadotropin injections did not increase the chance of pregnancy nor did oral medication when compared to natural cycle IUIs.     

Prevention of immune precipitation by purified components of the alternative pathway

The role of the alternative pathway in complement-mediated prevention of immune precipitation has been investigated by the use of BSA-anti-BSA immune complex (IC) purified components. For immune precipitation to be prevented all six alternative pathway components (C3, factors B D, P, H and I) were required. In the absence of one or both of the control proteins H and I, excessive fluid phase turnover of C3 occurred with precipitation of IC. Kinetic studies showed that in the presence of the control proteins, an initial phase of precipitation occurred, and was followed by a phase of resolubilization of IC. When the efficiency of classical and alternative pathways in the prevention of immune precipitation was compared it was found that the classical pathway proteins were more effective than the alternative pathway components. A reaction mixture containing the components of both pathways was no better than the classical pathway protein alone. 125I-C3 was bound to IC which had been rendered soluble in the presence of classical or alternative pathway components. A molar ratio of two molecules C3b:five molecules IgG was calculated. Other complement components which were bound to IC which had been formed in the presence of serum were C1q, C4, C2, C3, C5, P and H. Factors B and I were not detected. Our findings suggest that the alternative pathway is of secondary importance to the classical pathway in the prevention of immune precipitation.     

Glucocorticoid blockade does not abrogate tumor-induced cachexia

Cancer-induced cachexia is a common manifestation observed in patients with malignancies. Elevated levels of circulating glucocorticoids and interleukin-6 (IL-6) have been observed in cancer patients with cachexia and are implicated as major mediators in this process. The purpose of this study was to investigate the role of circulating glucocorticoid levels as primary mediators in cancer-induced cachexia. We evaluated whether inhibition of glucocorticoids with the receptor antagonist RU-486 could abrogate the detrimental wasting of muscle and adipose tissues seen in a well-characterized murine tumor-induced cachexia model. Mice (12/group) were randomized to control, tumor-bearing, control + vehicle, or tumor-bearing + glucocorticoid receptor antagonist groups. Circulating serum glucocorticoid and IL-6 levels were measured in addition to multiple body composition parameters, such as total body weight, lean body mass, and adipose content. The results of this study indicate a significant physiological alteration in the tumor-bearing host that causes severe and detrimental changes in body composition parameters. Regression analysis demonstrated a significant correlation between increased circulating glucocorticoid levels and alterations in body composition parameters. These observed defects were not abrogated with the administration of a glucocorticoid receptor antagonist. We therefore conclude that the untoward effects of tumor-induced cachexia are not mediated primarily by the peripheral effects of high circulating glucocorticoid levels but may involve a complex interaction with IL-6.     

Biological Evidence for a Neurodevelopmental Model of Pediatric Bipolar Disorder

Bipolar disorder (BD) is a chronic illness with high morbidity and mortality. Pediatric onset BD has a more severe course of illness with higher rates of relapse and psychosocial impairment. Discovering interventions early in the course of BD in youth is paramount to preventing full illness expression and improve functioning in these individuals throughout the lifespan. It is therefore important to understand the mechanisms involved in the development of BD in order to determine which youth are at most risk and provide biological targets for early intervention. To serve this cause, we propose a neurodevelopmental model of BD, based on the existing data that implicate prefrontal - subcortical network dysfunction, caused by pre-existing genetic susceptibility and triggered by pathological reactions to stress and chronic inflammatory processes.     

Mortality in bullous pemphigoid: A systematic review and meta‐analysis of standardized mortality ratios

There are inconsistent data on mortality rates in patients with bullous pemphigoid (BP). Trends in mortality in BP throughout the years are yet to be established. The aim of the present study was to study the mortality in BP patients relative to the general population and to estimate trends in standardized mortality over the past 30 years. We performed a systematic review and meta‐analysis of observational studies in Medline, Embase and Scopus (1823–2017). Reference lists of included studies were also searched for eligible studies. Quality of evidence was assessed using the Newcastle–Ottawa Scale (NOS). A meta‐analysis was performed using random‐effects models to estimate pooled standardized mortality ratios (SMR) with 95% confidence intervals (CI). Meta‐regression models were used to investigate the secular trends in SMR. Ten studies were included covering the period 1960–2015 (1736 patients, 746 deaths). Pooled all‐cause SMR was 3.6 (95% CI, 2.6–5.0). There was no trend in all‐cause SMR across the last three decades (regression coefficient 0.02 [change in logSMR/year]; 95% CI, 0.04–0.08; P = 0.545). In conclusion, there is a 3.6‐fold increased mortality among patients with BP as compared with the age‐matched general population. The excess mortality in BP has not changed significantly over the past 30 years.     

Risk factors for early postpartum hemorrhage (PPH) in the first vaginal delivery,and obstetrical outcomes in subsequent pregnancy

Objective: To investigate risk factors for postpartum hemorrhage (PPH) in vaginal deliveries and the influence of previous PPH on the subsequent pregnancy.

Study design: A retrospective cohort study including first singleton deliveries between the years 1988 and 2012 was performed comparing deliveries with and without PPH. In addition, perinatal outcomes of the subsequent pregnancy were evaluated. Multivariable analysis was performed to control for confounders.

Results: PPH complicated 0.8% of all first vaginal deliveries. Significant risk factors for PPH in vaginal delivery, using a multiple logistic regression model, were: post-term pregnancy, fertility treatments, hypertensive disorders, labor dystocia during the 2nd, and perineal tears grade 2 and 3, respectively. Previous PPH was found to be an independent risk factor for PPH in the subsequent pregnancy. Moreover, previous PPH was found to be a significant risk factor for cesarean section (CS) deliver, to complicate delivery with revision of uterus cavity, anemia, and to require blood transfusion.

Conclusion: Previous PPH poses a risk for recurrent PPH in subsequent delivery and an increased risk for CS. As PPH remains one of the major causes of maternal morbidity, this study strengthens the need for a comprehensive evaluation of prior PPH as a major risk factor for PPH recurrence.     

Treatment of Induced Murine SLE with a Peptide Based on the CDR3 of an Anti-DNA Antibody Reverses the Pattern of Pathogenic Cytokines

A peptide based on the complementarity determining region (CDR) 3 of a pathogenic anti-DNA monoclonal antibody that bears the 16/6 idiotype (Id) was shown previously to be a dominant T-cell epitope in experimental SLE, and to be capable of inhibiting SLE-associated responses. When injected, concomitant with active immunization with the pathogenic human anti-DNA, 16/6 Id + mAb, pCDR3 inhibited the proliferation of LN-derived T cells stimulated in vitro with the 16/6 Id mAb. The inhibition of the specific proliferative responses could be reversed by the addition of exogenous IL-2 to the cultures. Analysis of secreted cytokine profile in supernatants of these cultures demonstrated that pCDR3 treatment reduced significantly the levels of both IL-2 and IFN- &#110 that were elevated further in cells of the 16/6 Id-immunized mice. The CDR3-based peptide was shown here to immunomodulate in vivo experimental SLE, induced by the human anti-DNA 16/6 Id + antibody. The beneficial effects of pCDR3 on the clinical manifestations of SLE were associated with downregulation of the Th1-type (IL-2, IFN- &#110 ) and proinflammatory (TNF- &#102 ) cytokines, whereas the immunosuppressive cytokine TGF- &#103 was up regulated.     

Single port laparoscopic sacrohysteropexy in a young patient presenting with grade III uterine prolapse and rectocele

Introduction

Uterine preservation in patients with uterine prolapse is a common practice in the last decade and the reconstructive pelvic operation can be done either by vaginal, abdominal or laparoscopic approach. In young patients, uterine preservation is a legitimate option and one of the proposed operations is sacro-hystero-pexy. Single Port Laparoscopy (SPL) is a relatively new technique. This is a case of a young patient presented with grade III uterine prolapse and rectocele.

Methods

The video presents the surgical technique of sacro-hystero-pexy as was described in 2001 by von Theobald, adapted specifically for the SPL technique.

Conclusions

The Single Port laparoscopy is an advanced laparoscopic technique. This video demonstrate that scaro-hystero-pexy can be done safely and efficacy with Single Port Laparoscopy without prolonging the operation time significantly.