Are Phosphodiesterase Type 5 Inhibitors Associated with Vision‐Threatening Adverse Events? A Critical Analysis and Review of the Literature

IntroductionPhosphodiesterase type 5 (PDE5) inhibitors are the first line drugs for treatment of erectile dysfunction. Sildenafil (Viagra^R), tadalafil (Cialis^R), and vardenafil (Levitra^R) are from the same class of drugs that inhibit PDE5. Transient visual symptoms such as change in color perception and increased light sensitivity are well‐known adverse effects of these drugs and occur in 3–11% of sildenafil users. Vision‐threatening (serious) ocular complications, such as nonarteritic ischemic optic neuropathy and cilio‐retinal artery occlusion have rarely been reported in PDE5 inhibitor users.AimsTo highlight and analyze the most recently published case literature on serious ocular complications of PDE5 inhibitors.MethodsSearch of the peer‐reviewed English literature was conducted using Medline. The following databases also were searched: Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Global Health, and MD Consult. The causality assessment of the reported adverse drug reactions was analyzed by applying both the World Health Organization (WHO) Probability Scale and the criteria utilized by the National Registry of Drug‐Induced Ocular Side Effects.Main Outcome MeasuresTo scientifically and objectively find out if PDE5 inhibitors are associated with vision‐threatening ocular complications.ResultsEight case reports of serious PDE5 inhibitor‐associated ocular complications were identified since January 2006 until February 2011. Case reports included cases of anterior and posterior nonarteritic ischemic optic neuropathy, central retinal vein occlusion, cilio‐retinal artery occlusion, acute angle closure glaucoma and optic atrophy after sildenafil use.ConclusionThere is lack of conclusive evidence to indicate a direct cause–effect relationship between PDE5 inhibitor use and vision‐threatening ocular events. Men who use PDE5 inhibitors appear to suffer vision‐threatening complications at the same frequency as the general population. However, minor visual adverse effects occur in 3–11% of users and they are transient and reversible. Azzouni F and Abu samra K. Are phosphodiesterase type 5 inhibitors associated with vision‐threatening adverse events? A critical analysis and review of the literature. J Sex Med 2011;8:2894–2903.     

The Efficacy and Safety of Ospemifene in Treating Dyspareunia Associated with Postmenopausal Vulvar and Vaginal Atrophy: A Systematic Review and Meta‐Analysis

IntroductionOspemifene, a novel selective estrogen receptor modulator, has been developed for the treatment of vulvovaginal atrophy and dyspareunia in postmenopausal women.AimWe carried out a systematic review and meta‐analysis to assess the efficacy and safety of the drug for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy.MethodsA literature review was performed to identify all published randomized double‐blind, placebo‐controlled trials of ospemifene for the treatment of vulvovaginal atrophy and dyspareunia. The search included the following databases: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. A systematic review and meta‐analysis was conducted.Main Outcome MeasuresSix publications involving a total of 1,772 patients were used in the analysis, including three randomized controlled trials (RCTs) that were short‐term (12 weeks) comparisons of ospemifene with placebo and three RCTs that were long‐term (1 year) comparisons of ospemifene with placebo.ResultsFor the comparison of short‐term ospemifene with placebo, parabasal cells (the standardized mean difference [SMD] = −37.5, 95% confidence interval [CI] = −41.83 to −33.17, P < 0.00001), superficial cells (SMD = 9.24, 95% CI = 7.70 to 10.79, P < 0.00001), vaginal PH (SMD = −0.89, 95% CI = −0.98 to −0.80, P = 0.00001), and dyspareunia (SMD = −0.37, 95% CI = −0.43 to −0.30, P = 0.00001) indicated that ospemifene was more effective than the placebo. For the comparison of long‐term ospemifene with placebo, endometrial thickness (SMD = 0.90, 95% CI = 0.58 to 1.23, P = 0.00001), treatment emergent adverse event, discontinuations due to adverse event, and serious adverse event indicated that ospemifene was generally safe.ConclusionsThis meta‐analysis indicates that ospemifene to be an effective and safe treatment for dyspareunia associated with postmenopausal vulvar and vaginal atrophy. Cui Y, Zong HT, Yan HL, Li N, and Zhang Y. Treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy: A systematic review and meta‐analysis. J Sex Med 2014;11:487–497.     

Classical Cesarean: What Are the Maternal and Infant Risks Compared With Low Transverse Cesarean in Preterm Birth,and Subsequent Uterine Rupture? A Systematic Review and Meta-analysis

ObjectivesClassical cesarean section may be associated with increased short- and long-term risks. The objectives of this study were to review the following systematically: first, the short-term maternal and infant risks with preterm classical compared with low transverse cesarean sections; and second, the risk of spontaneous or early-labour uterine rupture.Data sourcesMedline, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from January 1980 to July 2018.Study selectionA total of 772 studies were independently screened by two reviewers, and 91 full texts were reviewed. The review included nine studies comparing outcomes after preterm classical versus low transverse cesarean section and 15 studies addressing subsequent pregnancy outcomes.Data synthesisOur primary short-term outcomes were maternal death and intensive care unit (ICU) admission. For subsequent pregnancies, our primary outcome was the risk of spontaneous or early-labour uterine rupture. The data were synthesized using random effects, and odds ratios (ORs) and 95% confidence intervals (CIs) were generated. There were no significant differences between preterm classical and low transverse cesarean sections in the odds of maternal death (OR 2.38; 95% CI 0.15–38.07) or ICU admission (adjusted OR 2.38; 95% CI 0.42–13.35). A subgroup from 28 to 31 weeks gestation had increased risks of endometritis, transfusion, and ICU admission with the classical incision. The low vertical incision was associated with a lower odds of organ injury than was the low transverse incision. The incidence of uterine rupture following the classical incision without a trial of labour was 1%.ConclusionPreterm classical cesarean section is not associated with significantly increased risks, but data are scarce. Subsequent uterine rupture risk when not planning a trial of labour is 1%.     

What are the required components of pre- and post-test counseling?

Prenatal care providers are faced with a myriad of decisions about how to offer genetic screening and testing in ways that are appropriate to their patient population and their workflow. Among the critical issues brought to the forefront of rapidly advancing genetic and genomic technologies is the importance of pre- and post-test counseling. This document is a synthesis of proceedings of a workshop sponsored by the American College of Obstetricians and Gynecologists, the American College of Medical Genetics and Genomics, and the Society for Maternal-Fetal Medicine, on January 24-25, 2017, during which invited experts discussed required components of pre- and post-test counseling and associated concerns in the provision of prenatal care.     

What are the antigenic targets in the ovary?

The ovary can be the target of an autoimmune disease involving many different autoantigens. The clinical feature of this disease often results in premature ovarian failure or infertility and may be either isolated or associated with other autoimmune pathologies, especially with adrenal autoimmunity. The diagnosis of an autoimmune mechanism relies on the presence of anti-ovarian antibodies, whose prevalence is quite variable according to the different methods used to detect them, and to the different stages of the disease. In addition, their clinical significance is not always clear, as to their pathologic or epiphenomenal nature. However, the study of these autoantibodies has led to the identification of some of their antigenic targets which have to be known for a better understanding of the pathologic mechanisms involved. This paper reviews anti-steroid producing cells, anti-gonadotrophin receptor, anti-gonadotrophin, anti-corpus luteum, anti-zona pellucida and anti-oocyte antibodies.     

Fathers in the birth room: What are they expecting and experiencing? A phenomenological study

Objective

to explore the role, expectations and meanings that individual fathers ascribe to their presence at birth.

Design

a Heideggerian phenomenological approach utilising in-depth interviews at two different time points.

Setting

large tertiary maternity unit in the North West of England.

Participants

11 first-time fathers accessed through hospital-based parentcraft sessions.

Findings

four main themes were evident: fathers' disconnection with pregnancy and labour; fathers on the periphery of events during labour; control; and fatherhood beginning at birth and reconnection.

Key conclusions

birth is the moment that fathers ascribe as the beginning of fatherhood. However, through their lack of knowledge and perceived control, they struggle to find a role there.

Implications for practice

midwives are ideally placed to help fathers to find a role through parentcraft and encouraging participation at birth.     

What Is the Impact of the Internet on Decision‐Making in Pregnancy? A Global Study

Abstract: Background: Women need access to evidence‐based information to make informed choices in pregnancy. A search for health information is one of the major reasons that people worldwide access the Internet. Recent years have witnessed an increase in Internet usage by women seeking pregnancy‐related information. The aim of this study was to build on previous quantitative studies to explore women’s experiences and perceptions of using the Internet for retrieving pregnancy‐related information, and its influence on their decision‐making processes. Methods: This global study drew on the interpretive qualitative traditions together with a theoretical model on information seeking, adapted to understand Internet use in pregnancy and its role in relation to decision‐making. Thirteen asynchronous online focus groups across five countries were conducted with 92 women who had accessed the Internet for pregnancy‐related information over a 3‐month period. Data were readily transferred and analyzed deductively. Results: The overall analysis indicates that the Internet is having a visible impact on women’s decision making in regards to all aspects of their pregnancy. The key emergent theme was the great need for information. Four broad themes also emerged: “validate information,”“empowerment,”“share experiences,” and “assisted decision‐making.” Women also reported how the Internet provided support, its negative and positive aspects, and as a source of accurate, timely information. Conclusion: Health professionals have a responsibility to acknowledge that women access the Internet for support and pregnancy‐related information to assist in their decision‐making. Health professionals must learn to work in partnership with women to guide them toward evidence‐based websites and be prepared to discuss the ensuing information. (BIRTH 38:4 December 2011)     

Endometriosis and IVF: are agonists really better? Analysis of 1180 cycles with the propensity score matching

Abstract

Objective: To compare the outcomes of patients with confirmed endometriosis undergoing in vitro fertilization (IVF)-embryo transfer (ET) treated with either gonadotropin-releasing hormone agonist (GnRHa) or gonadotropin-releasing hormone antagonist (GnRHant) using the propensity score (PS) matching.

Design: Observational, retrospective analysis from January 2000 to December 2010.

Setting: Private tertiary fertility clinic.

Patient(s): Patients with endometriosis confirmed by ultrasound or surgery (American Fertility Society; AFS grades I–IV) that underwent an IVF-ET, stimulated with standard controlled ovarian hyperstimulation (COH) and GnRHa or GnRHant.

Intervention(s): A PS was assigned to all patients, which calculates the conditional probability of receiving a certain treatment; a higher PS (1) meant a higher probability of receiving treatment with GnRHa, and a lower PS (0) meant a higher probability of receiving GnRHant. The PS was calculated with a logistic regression model adjusted specifically for age, follicle stimulating hormone, antral follicle count and previous IVF cycles. All patients were divided into three groups according to their PS.

Main outcome measure(s): pregnancy rate (PR) per cycle.

Results: 1180 patients were analyzed. Raw PR per cycle was 41.8% and 23.4%, and PR per ET was 44.3 and 27%, respectively. PR per cycle: 41.9 versus 30% in group A; in group B, 39.7% versus 36.4% and in group C, 15.4% versus 18.9%. The overall odds ratio for PR adjusted by PS was 1.10 [0.58–2.19].

Conclusions: After matching patients by PS, PR after COH with either GnRHa or GnRHant may be equally effective.     

What are the individual perceptions of patients with borderline tumours of the ovary in regard to pathogenesis and prognosis? A structured survey on 60 women

The traditional notion that a family is built around and based on blood or genetic ties is challenged when assisted human reproduction utilizing donor gametes is used. A focus on the family?–?in contrast to the individual?–?requires from medicine an extension of thinking in which a model that incorporates treating infertility and building a family becomes the norm. Such a model will require that attention is given to the psychological and social needs of the would-be parents, thus enabling them to approach their family building with confidence. This confidence is expected to carry through to their sharing with their offspring the nature of their family building and thus avoid the stigma that leads to secrecy. Research relating to dimensions of family building when donor insemination has been used is reviewed. The impact of professional attitudes, along with the policies adopted by governments concerning access to genetic information for offspring, significantly influences the families built with assistance of donor gametes or embryos. The evolution of professional thinking in this area is reviewed, along with the increasing involvement of governments.     

What are the individual perceptions of patients with borderline tumours of the ovary in regard to pathogenesis and prognosis? A structured survey on 60 women

Limited data exist about the perception of patients with borderline ovarian tumours (BOT). We assessed the individual perception of patients with BOT, with special focus on the biological-behaviour of the disease. Sixty patients with BOT who underwent surgery during January 2001 to June 2009 were interviewed by a 9-item-questionnaire, at the earliest, 12 months postoperatively. The aim was to assess their estimation regarding the malignant potential of BOT, its impact on their future fertility, the risk of recurrence and death and the possible causes of BOT. Seventeen women incriminated occupational-stress as a causative factor; 8 women genetic-predisposition, and 7 women personal-stress. Only 10 (16.7%) patients evaluated the BOT malignant potential as equivalent to that of a benign ovarian-cyst, while 28 (46.7%) and 20 (33.3%) patients believed carrying the same or equivalent recurrence- and mortality-risk, respectively, like patients with ovarian cancer (OC). Most fertile patients (19/23; 82.6%) felt adequately informed about the impact of BOT on their future fertility, while four patients stated being insufficiently informed. Despite the overall favourable BOT prognosis, affected patients appear to correlate their malignant potential close to that of OC with an equivalent high risk of recurrence. However, patients do not expect to die of BOT. There is a high need to intensify information process regarding BOT. Future trials are warranted to evaluate whether this may substantially influence the patients' perspectives.     

Genetics of Preeclampsia: What are the Challenges?

Despite recent efforts to identify susceptibility gènes of preeclampsia, the genetic determinants of the condition remain ill-defined, as is the situation for most disorders of complex inheritance patterns. The angiotensinogen, factor V, and methylenetetrahydrofolate reductase genes have been investigated in different populations, as have other genes involved in blood pressure, vascular volume control, thrombophilia, lipid metabolism, oxidative stress, and endothelial dysfunction. The study of the genetics of complex traits is faced with both methodological and genetic issues; these include adequate sample size to allow for the identification of modest genetic effects, of gene-gene and gene-environment interactions, the study of adequate quantitative traits and extreme phenotypes, haplotype analyses, statistical genetics, genome-wide (hypothesis- free) versus candidate-gene (hypothesis-driven) approaches, and the validation of positive associations. The use of genetically well-characterized populations showing a founder effect, such as the French-Canadian population of Quebec, in genetic association studies, may help to unravel the susceptibility genes of disorders showing complex inheritance, such as preeclampsia. It is necessary to better evaluate the role of the fetal genome in the resulting predisposition to preeclampsia and its complications. Eventually, we may be able to integrate genetic information to better identify the women at risk of developing preeclampsia, and to improve the management of those suffering from this condition.     

What are the real risks for breast cancer?

There is a steady drumbeat of peer-reviewed medical articles relating risks of breast cancer from a variety of factors. Whether or not the reported factors are under the control of any given individual, they have been trumpeted by the lay media and are responsible for the understandable finding among women that breast cancer generates more anxiety than heart disease, even though the number of US women who died of heart disease in 2010 is over seven and a half times the number who fell victim to breast cancer. This article attempts to reduce the anxiety-inducing barrage of these reports by orienting physicians to better understand the validity of reported breast cancer risk factors. We hope to provide this understanding by: explaining the difference between relative and absolute risk, encouraging application of the 95% confidence interval to better evaluate the statistical validity of any given risk factor; placing the reported risk factors in the context of an accepted risk factor like cigarette smoking and lung cancer; and communicating the limits of statistical validity in the absence of reproducibility. This review will, to a small degree, provide a balance to the reports currently dominating the literature.     

Female Sexual Dysfunction and Diabetes: A Systematic Review and Meta‐Analysis

IntroductionSexual dysfunction is reported in diabetic women (female sexual dysfunction [FSD]).AimTo examine the frequency of FSD in diabetic women, and its clinical or metabolic correlates, through meta‐analysis of available studies.MethodsWe searched in MEDLINE, EMBASE, Cochrane Library, and in reference lists of articles and systematic reviews; we considered human clinical studies published as full articles reporting on FSD in diabetic and control women. In total, we considered 26 studies, including 3,168 diabetic and 2,823 control women.Main Outcome MeasuresFrequency of FSD and score of Female Sexual Function Index (FSFI) as a function of study size, patient details (age, body mass index [BMI], duration of diabetes, metabolic control [HbA1c], chronic complications, Beck Depression Inventory [BDI] score).ResultsFrequency of FSD was higher in type 1 (OR [95%CI] 2.27 [1.23, 4.16]), in type 2 diabetes (2.49 [1.55, 3.99]), and in “any diabetes” (type 1 and 2) women (2.02 [1.49, 2.72]) than in controls for any duration of diabetes. FSFI was lower in type 1 (?0.27 [?0.41, ?0.12]), in type 2 diabetes (?0.65 [?0.75, ?0.54]), and in “any diabetes” women (?0.80 [?0.88, ?0.71]) than in controls. Depression was significantly more frequent in diabetic than in control women. At meta‐regression only BMI was significantly associated with effect size (P = 0.005). At weighed regression, the only significant association was found between age and FSFI (P = 0.059). The limitations were as follows: only studies of observational nature were available, and heterogeneity was seen among studies.ConclusionsFSD is more frequent in diabetic than in control women, but it is still poorly understood; low FSFI is associated with high BMI. Further studies are necessary to better understand risk factors for FSD in diabetic women.     

Menstruation in Adolescents: What Do We Know? and What Do We Do with the Information?

The menstrual cycle has been recognized as a vital sign that gives information about the overall health of an adolescent or young adult female. Significant deviations from monthly cycles can signal disease or dysfunction. This review highlights the evidence based parameters for normal puberty, menarche, cyclicity, and amount of bleeding. The review addresses sources of information available online, noting inaccuracies that appear in web sites, even and especially those targeting adolescents. The review includes a call to action to provide accurate information about the menstrual cycle as a VITAL SIGN.     

What are the factors associated with the follow-up preferences of women in long-term remission from gynaecological cancer?

We set out to examine factors associated with follow up preferences of women attending routine hospital follow up after treatment for early stage gynaecological cancer. This was a retrospective cohort study, using hospital records and questionnaire data, and was based in North Staffordshire, UK. Fifty-four women, who had undergone successful treatment for early stage gynaecological cancer and currently attending routine hospital follow up appointments, were studied. Follow-up preferences were established using a specially designed questionnaire. A questionnaire package containing psychological and demographic measures was used. Clinical details including site and stage of disease, treatment and follow-up type were obtained from medical records. There were no significant demographic or clinical differences between the women with preference for hospital follow-up and those women with a preference for discharge. Women with a preference for follow-up were found to have significantly higher anxiety (as measured by the MAC anxiety scale). These results were not found for the other anxiety scales (STAI and HADS). Three predictor variables (MAC anxiety, Education and Car ownership) were found to predict significantly group membership. It is not possible to predict follow-up needs using demographic, clinical or psychological factors. Follow-up needs are achieved through effective medical communication. The role of the specialist nurse is implicated. A larger scale study is necessary to elaborate this preliminary research.