Self-sampling to increase participation in cervical cancer screening: an RCT comparing home mailing, distribution in pharmacies, and recall letter.

BACKGROUND: We performed a multicentre randomised controlled trial to evaluate the effect on participation in organised screening programmes of a self-sampling device mailed home or picked up at a pharmacy compared with the standard recall letter. METHODS: Women aged 30-64 non-responding to screening invitation were eligible. Response rate to first invitation ranged from 30% to 60% between centres. The control was the standard reminder letter to undergo the test used by the programme (Pap test in three centres and HPV DNA test in three other centres). Home mailing of the self-sampler was preceded by a letter with a leaflet about HPV. The analysis was intention-to-treat. RESULTS: In all, 14 041 women were randomised and recruited: 5012 in the control arm, 4516 to receive the self-sampler at home, and 4513 to pick up the self-sampler at a pharmacy. Participation was 11.9% in the control, 21.6% (relative participation: 1.75; 95% CI 1.60-1.93) in home, and 12.0% (relative participation: 0.96; 95% CI 0.86-1.07) in the pharmacy arms, respectively. The heterogeneity between centres was high (excess heterogeneity of that expected due to chance, i.e., I(2), 94.9% and 94.1% for home and pharmacy arm, respectively). The estimated impact on the overall coverage was +4.3% for home mail self-sampling compared with +2.2% for standard reminder. CONCLUSIONS: Home mailing of self-sampler proved to be an effective way to increase participation in screening programmes, even in those with HPV as primary testing. Picking up at pharmacies showed effects varying from centre to centre.

Validation, Deployment, and Real-World Implementation of a Modular Toolbox for Alzheimer's Disease Detection and Dementia Risk Reduction: The AD-RIDDLE Project.

The Real-World Implementation, Deployment, and Validation of Early Detection Tools and Lifestyle Enhancement (AD-RIDDLE) project, recently launched with the support of the EU Innovative Health Initiative (IHI) public-private partnership and UK Research and Innovation (UKRI), aims to develop, test, and deploy a modular toolbox platform that can reduce existing barriers to the timely detection, and therapeutic approaches in Alzheimer's disease (AD), thus accelerating AD innovation. By focusing on health system and health worker practices, AD-RIDDLE seeks to improve and smooth AD management at and between each key step of the clinical pathway and across the disease continuum, from at-risk asymptomatic stages to early symptomatic ones. This includes innovation and improvement in AD awareness, risk reduction and prevention, detection, diagnosis, and intervention. The 24 partners in the AD-RIDDLE interdisciplinary consortium will develop and test the AD-RIDDLE toolbox platform and its components individually and in combination in six European countries. Expected results from this cross-sectoral research collaboration include tools for earlier detection and accurate diagnosis; validated, novel digital cognitive and blood-based biomarkers; and improved access to individualized preventative interventions (including multimodal interventions and symptomatic/disease-modifying therapies) across diverse populations, within the framework of precision medicine. Overall, AD-RIDDLE toolbox platform will advance management of AD, improving outcomes for patients and their families, and reducing costs.

[Cigarette smoking and fertility in women and men]. / Tabac et fertilité chez la femme et l'homme.

Cigarette smoking consequences on female and male reproduction have been evaluated for twenty years only and thus poorly spread in the general population. However, several studies have noticed noxious effects of tobacco before and after conception, in both women and men, from smokers gametes to their offspring. This negative impact occurs in spontaneous as well as in assisted reproduction (ART). For women, pregnancy rate is decreased, early spontaneous abortions are increased and ovarian reserve is altered. For men, standard sperm parameters are modified and spermatozoon nuclear quality is compromised. One of the mechanisms involved in those anomalies could be the oxidative stress produced by some cigarette smoking components. The consequences on smokers offspring are hardly evaluated yet: pathologies of the respiratory system, decrease of fecundity and cancers outcomes. In conclusion, it seems obvious that smokers - men as women - have to quit smoking before having a parental project.

[Consequences of cigarette smoking on male fertility]. / Conséquences du tabac sur la fertilité masculine.

The different studies conducted over the last fifteen years on the consequences of cigarette smoking on male fertility have shown a decrease of sperm quality in smokers. In fact, the components of cigarette smoke pass through the blood-testis barrier and thus induce an alteration of sperm parameters and nucleus quality of the spermatozoa. Beyond this decrease of sperm quality, cigarette smoking also appears to have an impact on the smoker's offspring: lower embryo quality, increased risks to develop a childhood cancer. The pathophysiologic mechanisms are not yet clearly understood, but one of the most likely hypotheses is the production of an oxidative stress which is responsible for DNA fragmentation compromising the chances of pregnancy. In addition to the spermogram, further tests available in specialized laboratories can be prescribed to evaluate spermatozoal DNA fragmentation (TUNEL Assay, SCSA...). Antioxidant treatment can be administrated to reduce DNA fragmentation and increase the chances of pregnancy.

[Ovarian autoimmunity and ovarian pathologies: antigenic targets and diagnostic significance]. / Auto-immunité anti-ovarienne et pathologies ovariennes: cibles antigéniques et implications diagnostiques.

The involvement of serum anti-ovarian autoantibodies (AOA) in ovarian pathology still remains controversial. In some cases of clinically patent ovarian failure, there seems to be a causal relationship between AOA and the ovarian disease. In patients with various organ-specific or systemic autoimmune diseases, or with unexplained, repeated reproductive failure, but otherwise normal ovarian function, it is even more difficult to determine the significance of AOA for several reasons: i) AOA recognize many different antigenic targets in the ovary ii) the antiovarian response may be transient or variable with time iii) the presence of AOA does not imply their aetiopathogenic role in the disease. The present paper reviews the clinical significance of AOA based on their ovarian targets as far as they have been identified until now.

CD4-like molecules in human sperm.

The expression of a molecule recognized by CD4 monoclonal antibodies was investigated on human sperm using immunolabelling, biochemical and immunochemical methods. Flow cytometry detected a significant fluorescence signal. SDS-PAGE analysis and Western blotting identified a molecule of 60 kDa, consistent with a CD4-like structure as confirmed after selective immunoseparation. Additional bands reacting with anti-CD4 were found in sperm extracts (73 kDa) and seminal fluid (90 kDa). These data indicate that sperm express a molecule similar to the receptor for HIV described on mononuclear cells.

Expression of sex hormone-binding globulin (SHBG) in human granulosa-lutein cells.

Sex hormone-binding globulin (SHBG) was classically thought to be a plasma steroid-carrying protein of hepatic origin, but recently, locally produced, membrane-bound SHBG has been shown to influence cell functions in several steroid-responsive tissues. In the ovary, SHBG is known to be present in the follicular fluid, but information about a possible intracellular presence of SHBG in this organ is still very scarce. In this study the presence of SHBG was assessed by immunohistochemistry in human granulosa-lutein cells (GLC) collected by follicle puncture for in vitro fertilization. SHBG was detected in the cytoplasm of GLC before and after in vitro culture for up to 96 h. The presence of full-length SHBG messenger RNA was demonstrated in GLC by reverse transcription-polymerase chain reaction (RT-PCR) in both cultured and uncultured cells. These results demonstrate a local synthesis of SHBG in GLC and raise the question of the physiological significance of these findings in follicular physiology.

Do prophylactic prostaglandins reduce the transfusion rate at cesarean section in high-order multiple pregnancies?

OBJECTIVE: Cesarean section is the more usual mode of delivery in high-order multiple pregnancy (> or =3). Excessive uterine distension increases the risk of bleeding and the need for transfusion. The aim of this study was to investigate if prophylactic use of prostaglandins at cesarean section for high-order multiple pregnancies reduces blood loss and transfusion requirement based on historic data. STUDY DESIGN: We studied a prospective series of 28 parturients with high-order multiple pregnancy (group 2) who were treated, after clamping the last umbilical cord, with oxytocin (5IU intravenous then 35IU in a 24h infusion) combined with intravenous prostaglandin. A comparable retrospective series of 14 patients (group 1) had been given oxytocin alone at the same dose. Postoperative serum hemoglobin and transfusion rate as well as adverse effects were compared between the two groups. Student's t-test was used to compare continuous variables. Chi square test and Fisher exact test were used to compare categorical variables. RESULTS: The two groups were comparable for anthropometric data and duration of pregnancy. None of the patients in group 2 required red cell transfusion while 21.4% of those in group 1 required transfusion. A significant lower decrease of postoperative haemoglobin is noted in group 2 (P=0.0006). Multivariate analysis using variables significant at univariate analysis and pre-eclampsia confirmed this difference. There were no adverse reactions to treatment. CONCLUSION: In our experience, prophylactic prostaglandin infusion at cesarean section in high-order multiple pregnancy is associated with a lower need for per operative red cell transfusion and a higher postoperative hemoglobin level. This observation merits confirmation in larger studies.

[The role of the gynecologist in first aid in cases of sexual violence. A protocol proposal]. / Il ruolo del ginecologo di Pronto Soccorso nei casi di violenza sessuale. Proposta di protocollo.

The aim of this report is to provide a medical form to use in case of sexual assault, prepared taking into consideration the information lacking at present in most medical reports on the subject. This call for the necessity to conform the medical approach to the same protocol which may also be used from the forensic medicine point of view. More precise information should be obtained about the assault and the injuries inflicted, and also an immediate psychological support should be given to the victim. This information will then serve as a guide to the medical staff.

[Is there a future for Fallopian tube insemination in women?]. / L'insémination tubaire chez la femme a-t-elle un avenir?

In unselected patients, the pregnancy rate after intrauterine insemination (i.u.i.) seldom goes beyond 10-15% per cycle. An insufficient number of spermatozoa at the fertilization site has been hypothesized for a long time to explain the low efficacy of this technique. Thus, the introduction of a larger number of male gametes into the female tubes has been thought of to give better results since the late eighties. First, a direct tubal catheterisation has been proposed for injection of spermatozoa, either by laparoscopy or transvaginally under ultrasound guidance or by tactile sensation. However, these procedures have been abandoned because of some severe traumatic and infectious complications. Alternatively, a spermatozoa suspension of several millilitres can be injected under pressure into the uterine cavity while sealing the cervical os, by various systems. This technique called Fallopian sperm perfusion (FSP) has yielded some interesting results, particularly in unexplained infertility. Nevertheless, the superiority of FSP over i.u.i. still remains controversial. This review describes the current knowledge about intratubal insemination and its potential role in the management of human infertility.

[Ovarian puncture in fertilization in vitro: what analgesia?]. / Ponction ovarienne en fécondation in vitro: quelle analgésie?

UNLABELLED: We compared two techniques of local anesthesia used in transvaginal ultrasound guided oocyte recovery in in vitro fertilization: paracervical lidocaïne block versus vaginal application of Emla, a topical anesthesic cream. STUDY DESIGN: The study included 103 patients divided in two groups. Pain was evaluated by visual analog scale and questionnaire. RESULTS: Univariate analysis showed that the patients were satisfied with neither of the two protocols. Multivariate analysis revealed paracervical lidocaïne block to be superior. The premedication appeared inadequate. CONCLUSION: We decide to use paracervical lidocaïne block and to improve the premedication. Indications for general and locoregional anesthesia were also enlarged. A new study showed a significantly greater patient satisfaction. One variable analysis indicated that no one of these protocols satisfied our patients.

[What are the antigenic targets in the ovary?]. / Quelles cibles antigéniques dans l'ovaire?

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.

[Anti-ovarian antibodies and in vitro fertilization: cause or consequence?]. / Anticorps anti-ovaires et fécondation in vitro: cause ou conséquence?

OBJECTIVES: To assess anti-ovarian antibodies (AOA) in serum samples at various times of in vitro fertilization (IVF) attempts to determine whether ovarian stimulation could result in the production of such autoantibodies in women. PATIENTS AND METHODS: Prospective study on 134 patients and 138 IVF cycles using a classical long protocol. For each attempt, four serum samples were obtained, respectively, at the onset of downrelation (S1), end of downregulation (S13), after 7 days of follicular stimulation (S21) and the day of follicular puncture (SP). Five hundred and fifty two samples were tested with an enzyme-linked immunosorbent assay for three isotypes (IgG, IgA, IgM) of AOA. RESULTS: In the whole group, mean concentrations of AOA for each isotype were compared group by group: S1-S13, S1-S21, S1-SP, S13-S21, S13-SP, S21-SP. Not any significant difference was observed whatever the isotype considered. DISCUSSION AND CONCLUSION: This study shows the absence of influence of endogenous or exogenous ovarian stimulation by gonadotropins on anti-ovarian autoimmunity.

[Ectopic pregnancy: contribution of paraclinical investigations, ultrasonography excluded]. / Grossesse extra-utérine: apport des examens paracliniques hors échographie.

Because a misdiagnosis of ectopic pregnancy (EP) exposes patients to a vital risk, paraclinical exams have to be highly specific and as sensitive as possible. As the accuracy of diagnostic tools depends on the prevalence of the disease in different patient groups, clinical signs have to be considered when analyzing the literature (symptom-free women, complaints, risk factors...). In the first part of this review, various diagnostic tools are reviewed and the particular features of EP after assisted reproduction techniques are taken into account. The evaluation of serum quantitative betahCG level is primordial. In difficult cases when transvaginal ultrasound does not detect an intrauterine gestational sac, repeated betahCG measurements and determination of serum progesterone levels allow to evaluate the viability of an early pregnancy. If ultrasound diagnosis cannot be obtained without significant delay, culdocentesis is easy to perform and has a good positive predictive value. However, the detection of intrauterine chorionic villi is only of limited diagnostic value, whereas hysteroscopy may be of interest in some cases. In the second part an analysis of algorithms in the diagnostic management of EP is carried out. Currently, a standard protocol should not be applied for all patients and specific algorithms have to be defined according to the prevalence of EP in the treated population.

[Management of ovarian cysts: consequences of ovarian surgery on fertility]. / Prise en charge du kyste de l'ovaire: conséquences de la chirurgie ovarienne sur la fertilité.

Surgery remains an important tool for the management of ovarian cysts. The question is whether patients of reproductive age should be given conservative treatment or undergo unilateral oophorectomy according to infertility risk. The literature is too sparse to conclude, but there are two arguments favoring conservative treatment: i) unilateral ovariectomy may impair residual ovarian function, ii) reduction of ovarian follicular number appears to be associated with increased risk of trisomy 21 in offspring.

[The genetic basis of premature ovarian failure]. / Les bases génétiques de la défaillance ovarienne prématurée.

Premature ovarian failure is defined by the association of amenorrhea, elevated levels of serum gonadotropins and hypoestrogenism occuring before the age of forty. In a growing number of these cases, genetic disorders have been shown to be involved. Cytogenetic abnormalities predominantly concern the X chromosome, including Turner syndrome, but also rearrangements such as deletions and X-autosome translocations. Molecular investigation of these abnormalities has led to the identification of a number of candidate genes most of them still having unknown functions. Testing for premutation of the FMR1 gene, whose full mutation determines the fragile X syndrome, is particularly worthwhile in these patients because of its high frequency, not only among the patients with ovarian failure but also in the general population. Other, much less frequent mutations have been located for example in the gonadotropin and gonadotropin receptor genes and their study contributes to the understanding of ovarian physiology. Here we review most of the etiologies which have to be taken in account in the genetic screening of premature ovarian failure patients.

[Negative impact of cigarette smoking on male fertility: from spermatozoa to the offspring]. / Impact négatif du tabac sur la fertilité masculine: des spermatozoïdes à la descendance.

Cigarette smoking has negative effects on male fertility. Recent studies showed an active transfer of several components of cigarettes through the blood-testis barrier. The presence of these components in the seminal plasma may induce a degradation of sperm parameters and nuclear quality of spermatozoa, and compromise the chances of pregnancy. Moreover, smoking may have a negative impact on the smokers'offspring: poor quality embryos, development of childhood cancers. Oxidative stress-induced DNA damage seems to be one of the major causes of sperm quality alteration. Several methods are now available to analyze the degree of DNA fragmentation. In order to optimize the success rate of assisted reproduction technologies, the deleterious effects of smoking on male fertility and the necessity of cessation have to be explained in detail to these patients.

Impact of folate and homocysteine metabolism on human reproductive health.

Folates belong to the vitamin B group and are involved in a large number of biochemical processes, particularly in the metabolism of homocysteine. Dietary or genetically determined folate deficiency leads to mild hyperhomocysteinemia, which has been associated with various pathologies. Molecular mechanisms of homocysteine-induced cellular dysfunction include increased inflammatory cytokine expression, altered nitric oxide bioavailability, induction of oxidative stress, activation of apoptosis and defective methylation. Whereas the involvement of folate metabolism and homocysteine in ageing-related diseases, in several developmental abnormalities and in pregnancy complications has given rise to a large amount of scientific work, the role of these biochemical factors in the earlier stages of mammalian reproduction and the possible preventive effects of folate supplementation on fertility have, until recently, been much less investigated. In the present article, the possible roles of folates and homocysteine in male and female subfertility and related diseases are systematically reviewed, with regard to the epidemiological, pathological, pharmacological and experimental data of the literature from the last 25 years.

Pathophysiology of impaired ovarian function in galactosaemia.

Classical galactosaemia is an inherited inborn error of the major galactose assimilation pathway, caused by galactose-1-phosphate uridyltransferase (GALT) deficiency. Many GALT mutations have been described, with different clinical consequences. In severe forms, newborns present with a life-threatening, acute toxic syndrome that rapidly regresses under a galactose-restricted diet. However, long-term complications, particularly cognitive and motor abnormalities, as well as hypergonadotrophic hypogonadism in female patients are still unavoidable. The pathogenesis of galactose-induced ovarian toxicity remains unclear but probably involves galactose itself and its metabolites such as galactitol and UDP-galactose. Possible mechanisms of ovarian damage include direct toxicity of galactose and metabolites, deficient galactosylation of glycoproteins and glycolipids, oxidative stress and activation of apoptosis. As there is no aetiological treatment, clinical management of ovarian failure in galactosaemic patients principally relies on hormonal replacement therapy to induce pubertal development and to prevent bone loss and other consequences of estrogen deprivation. Further investigations will be necessary to better understand the metabolic flux of galactose through its biochemical pathways and the mechanisms of these secondary complications. The aim of this article is to present an extensive review on the pathogenesis and clinical management of galactose-induced premature ovarian failure.