Motives for desiring children among individuals of different sexual-romantic orientations: a cross-sectional study.

PURPOSE: Little is known about the reasoning behind the desire to have children in non-heterosexual individuals. This study compares the motives of different sexual-romantic orientations and their preferred ways of fulfilling this desire. METHODS: This was a monocentric cross-sectional study. Subjects were recruited via social media, personal contacts and queer organisations in Switzerland. An anonymous questionnaire comprised general questions about the participant's background, a validated survey about the desire to have children and additional non-validated questions addressing the impact of sexual-romantic orientation on the desire to have children. The inclusion criteria were adults without children and a completed questionnaire. RESULTS: Of 837 participants, 642 were included in the study. Four groups of sexual-romantic orientations consisted of more than 35 participants: bisexual-biromantic (n = 38), heterosexual-heteroromantic (n = 230), homosexual-homoromantic (n = 159) and pansexual-panromantic (n = 55). Subgroups with a positive wish for a child rated all motives in the same order and with minimal numeric difference. The most important aspect seemed to be emotional involvement. Non-heterosexual-heteroromantic showed concerns about adverse reactions regarding their wish for a child. All orientations hoped for a biological child. CONCLUSION: Our findings about bi-, hetero-, homo- and pansexual people and their motives for a desire to have children agree with the existing literature about hetero, homo and bisexual. The impact of the fear of adverse reaction and discrimination has been discussed before and is supported by our data. We suggest better support before and during the realization of the wish for a child as well as support for non-traditional aspiring parents.

"I noticed that when I have a good supervisor, it can make a Lot of difference." A Qualitative Study on Guidance of Employees with a Work Disability to Improve Sustainable Employability.

PURPOSE: For employees with a work disability adequate daily guidance from supervisors is key for sustainable employability. Supervisors often lack expertise to guide this group of employees. Mentorwijs (literal translation: Mentorwise) is a training for supervisors to improve the guidance of employees with a work disability. The aim of this study was to investigate the experiences of employees with a work disability regarding: (1) the guidance from their supervisors (who followed the Mentorwijs training), (2) which differences they notice in the guidance due to the Mentorwijs training, and (3) what kind of aspects they consider important in their guidance to achieve sustainable employability. METHODS: A qualitative study was performed with semi-structured (group) interviews among twenty-one employees with a work disability. Thematic analysis was performed to analyze the data. RESULTS: Themes that followed from the interviews were: (1) work tasks and conditions can facilitate or hinder sustainable employability: (2) relationships among employees and with supervisors can affect sustainable employability; (3) a desire for new opportunities and challenges; and (4) a need for supervisor skills to facilitate sustainable employability, i.e. appreciation, availability of help, dealing with problems, listening, attitude and communication. According to employees, changes were mainly noticed in supervisor skills. CONCLUSIONS: Employees with a work disability were very satisfied with the guidance of supervisors who followed the Mentorwijs training. To improve sustainable employability, training of supervisors should focus more on adequate work conditions, providing employees opportunities to learn new work tasks and improving supervisors' skills regarding appreciation, attitude and communication.

Determinants of transplantation success with cryopreserved ovarian tissue: data from 196 women of the FertiPROTEKT network.

STUDY QUESTION: What are the pregnancy and live birth rates for ovarian tissue transplantation and which factors are associated with the success rate? SUMMARY ANSWER: Pregnancy and live birth rates per transplanted woman are 32.7% and 26.5% and success rate is associated with female age and first versus repeated transplantation. WHAT IS KNOWN ALREADY: Live birth rates after ovarian tissue transplantations have been reported to be between around 24% and 41% per patient. Success rates seem to be negatively associated with increasing female age at the time of tissue cryopreservation and with pelvic radiation. Success rates are apparently not reduced after overnight transportation of ovarian tissue before freezing. STUDY DESIGN, SIZE, DURATION: Registry analysis of 244 transplantations in 196 women, performed by 26 FertiPROTEKT network centres from 2007 to 2019 with follow-up till December 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Orthotopic ovarian tissue transplantations were performed in 196 women, 191 with previous malignant and 5 with previous non-malignant diseases. Size of transplanting centres varied between 1 and 100 transplantations per centre (median: 2). Factors possibly associated with success rate such as female age, first and repeated transplantation, experience of the transplanting centre and overnight transportation of the ovarian tissue before freezing were analysed. MAIN RESULTS AND THE ROLE OF CHANCE: Average age of all 196 transplanted women was 31.3 years (SD 5.2; range 17-44) at the time of cryopreservation of tissue and 35.9 years (SD 4.8; range 23-47) at the time of transplantation. Pregnancy rate was 30.6% (95% CI, 24.2-37.6%) per first transplantation and 32.7% (95% CI, 26.1-39.7%) per patient. Pregnancy rate was higher after first transplantation (30.6% (95% CI, 24.2-37.6%)) compared to second and subsequent transplantations (11.8% (95% CI, 3.3-27.5%)). Live birth rate per first transplantation was 25.0% (95% CI, 19.1-31.7%) and per patient 26.5% (95% CI, 20.5-33.3%). Success rate decreased with increasing age at the time of ovarian tissue freezing. Live birth rate was 28.2% (95% CI, 20.9-36.3%) in women <35 years and 16.7% (95% CI, 7.9-29.3%) in women >35 years. Pregnancy rates after first transplantation were higher in centres who had performed ≥10 transplantations (35.1%) compared to centres with <10 transplantation (25.4%) (P = 0.12). Corresponding live birth rates were 27.0% and 18.6%. Success rates were not different in women with and without overnight transportation of tissue before cryopreservation. LIMITATIONS, REASONS FOR CAUTION: The data were drawn from a registry analysis. Data such as ovarian reserve and premature ovarian insufficiency were not available for all women. Data might be influenced by different follow-up policies of the centres. WIDER IMPLICATIONS OF THE FINDINGS: The study reveals the high potential of ovarian tissue freezing and transplantation, but only if freezing is performed in younger women. The study suggests focus should be placed on the first and not on repeated transplantations. It also opens the discussion of whether transplantation should rather be performed by experienced centres. STUDY FUNDING/COMPETING INTEREST(S): No funding. No competing interests. TRIAL REGISTRATION NUMBER: N/A.

Hexagonal Prisms Form in Water-Ice Clouds on Mars, Producing Halo Displays Seen by Perseverance Rover.

Observations by several cameras on the Perseverance rover showed a 22° scattering halo around the Sun over several hours during northern midsummer (solar longitude 142°). Such a halo has not previously been seen beyond Earth. The halo occurred during the aphelion cloud belt season and the cloudiest time yet observed from the Perseverance site. The halo required crystalline water-ice cloud particles in the form of hexagonal columns large enough for refraction to be significant, at least 11 µm in diameter and length. From a possible 40-50 km altitude, and over the 3.3 hr duration of the halo, particles could have fallen 3-12 km, causing downward transport of water and dust. Halo-forming clouds are likely rare due to the high supersaturation of water that is required but may be more common in northern subtropical regions during northern midsummer.

The impact of micronized progesterone on cardiovascular events - a systematic review.

Biologically identical menopausal hormone therapy (MHT) including micronized progesterone (MP) has gained much attention. We aimed to assess the impact of MP in combined MHT on venous and arterial thromboembolism (VTE/ATE) (e.g. deep venous thrombosis/pulmonary embolism, myocardial infarction [MI] and ischemic stroke). Articles were eligible if they provided endpoints regarding cardiovascular events and use of exogenous MP. Literature searches were designed and executed for the databases Medline, Embase, CINAHL, the Cochrane Library, ClinicalTrials.gov and interdisciplinary database Web of Science. Twelve studies consisting of randomized controlled trials (RCTs), case-control studies and prospective or retrospective cohort studies were included, and risk of bias was assessed. Only a minority assessed thromboembolic events as a primary endpoint, showing that in contrast to norpregnane derivatives, primary and recurrent VTE risk was not altered by combining estrogens with MP, which was also true for ischemic stroke risk. Similarly, in placebo-controlled RCTs assessing VTE/ATE as adverse events there were no significant intergroup differences. Studies on MI as a primary endpoint are missing. In conclusion, while available data suggest that MP as a component in combined MHT may have a neutral effect on the vascular system, more RCTs investigating the impact of MP alone or in combined MHT on vascular primary endpoints are needed.

Role of the mTOR Signalling Pathway During Extracellular Acidosis in Tumour Cells.

The metabolic microenvironment of solid tumours is often dominated by extracellular acidosis which results from glycolytic metabolism. Acidosis can modulate gene expression and foster the malignant progression. The aim of the study was to analyse the effects of extracellular acidosis on the mTOR signalling pathway, an important regulator of anabolic and catabolic processes like cell proliferation and autophagy. The study was performed in two tumour cell lines, AT-1 prostate and Walker-256 mammary carcinoma cells. Cells were incubated at pH 7.4 or 6.6 for 3 h and 24 h. Then RNA and protein were extracted and analysed by qPCR and western blot. mTOR and P70-S6 kinase (P70-S6K), an important downstream target of mTOR, as well as the autophagic flux were studied. The effect of acidosis on P70S6K phosphorylation was compared to pharmacological mTOR inhibition with LY294002 and rapamycin. In both cell lines the total mTOR expression was not altered by acidosis, however, the mTOR phosphorylation was reduced after 3 h but not after 24 h. The P70S6K phosphorylation was reduced at both time points comparable to changes by pharmacological mTOR inhibitors. The autophagic flux, also a target of mTOR and measured by LC3-II expression, was increased in both cell lines after 24 h of acidosis. The results of this study indicate that mTOR signalling is inhibited by extracellular acidosis which then lead to a reduced activity of the P70-S6 kinase (modulating gene expression) and increased autophagy possibly mediated by ULK1/2 activity. These finding may offer new perspectives for therapeutic interventions in acidic tumours.

Impact of progesterone on skin and hair in menopause - a comprehensive review.

In clinical practice, micronized progesterone (MP) is frequently recommended to treat signs and symptoms of skin and hair aging in menopausal women. The aim of this comprehensive review was to evaluate whether topically or systemically applied MP may effectively prevent or slow down signs of skin and hair aging. Three out of six identified studies reported an impact of MP on skin aging markers in menopausal women. Of these, two studies reported a benefit: one for topically applied MP, another for systemically applied combined menopausal hormone therapy (MHT) comprising MP as progestogen for endometrial protection. Tolerability and safety of MP were good. However, there was no study investigating the impact of MP on menopausal scalp hair. In conclusion, delay of skin aging comprises lifestyle adjustment, antioxidants, and several esthetic procedures. In menopausal women, MHT displays beneficial effects on skin aging. There is poor quality but promising scientific evidence for MP displaying anti-aging skin effects in menopausal women. However, good quality studies are needed.

Follicular flushing leads to higher oocyte yield in monofollicular IVF: a randomized controlled trial.

STUDY QUESTION: Does follicular flushing increase the number of mature oocytes in monofollicular IVF? SUMMARY ANSWER: Follicular flushing increases the number of mature oocytes in monofollicular IVF. WHAT IS KNOWN ALREADY: Flushing increases neither the oocyte yield nor the pregnancy rate in polyfollicular IVF or in poor responder patients. In monofollicular IVF, the effect of flushing has so far been addressed by two studies: (i) a prospective study with minimal stimulation IVF demonstrated an increased oocyte yield, and (ii) a retrospective study with natural cycle (NC)-IVF showed an increased oocyte yield and an increased transfer rate. STUDY DESIGN, SIZE, DURATION: Randomized controlled trial including 164 women who were randomized for either aspiration with or without flushing from 2016 to 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Infertile women 18-42 years of age with an indication for IVF treatment at a university-based infertility unit. Women undergoing monofollicular IVF were randomized to either follicular aspiration only or follicular aspiration directly followed by five follicular flushes at a 1:1 ratio. The intervention was done without anaesthesia, using a gauge 19 single-lumen needle. Flushing volume was calculated (sphere formula) based on the size of the follicle. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 164 women were included; 81 were allocated to 'aspiration only' and 83 to additional 'flushing'. Primary analysis was based on the intention-to-treat: oocyte yield, defined as the collected mature oocyte rate, was higher (n = 64/83, 77.1%) in the flushing group compared to the aspiration only group (n = 48/81, 59.3%, adjusted risk difference (RD): 18.2% (95% CI 3.9-31.7%), P-value = 0.02). In the flushing group, most oocytes were retrieved within the first three flushes (63/83, 75.8%). Fertilization rate was higher in the flushing group (n = 53/83, 63.9% vs n = 38/81, 46.9%; adjusted RD: 16.8% (96% CI 1.5-31.4%), P = 0.045). Transfer rate was also higher in the flushing group (n = 52/83, 62.7% vs n = 38/81, 46.9%; RD: 15.71 (95% CI 0.3-30.3%)), but the difference was not significant (P = 0.06). The clinical pregnancy rate n = 9/83 versus n = 9/81 (RD: -0.3% (95% CI -9.9% to 9.5%)) and live birth rate n = 7/83 versus n = 8/81 (RD: -1.5% (95% CI -10.4% to 7.1%)) were not significantly different between the flushing and the aspiration group. The median duration of the intervention was significantly longer with flushing (2.38 min; quartiles 2.0, 2.7) versus aspiration only (0.43 min; quartiles 0.3, 0.5) (P < 0.01). There was no significant difference in the mean (±SD) visual analogue scales pain score between the follicular flushing (3.4 ± 1.8) and the aspiration group (3.1 ± 1.89). LIMITATIONS, REASONS FOR CAUTION: Blinding of the procedure was not possible. WIDER IMPLICATIONS OF THE FINDINGS: Our study proved that flushing of single follicles in NC-IVF increases the oocyte yield. In contrast to polyfollicular IVF flushing seems to be beneficial in a monofollicular setting if the technique used in our study (single-lumen needle, 5 flushings with flushing volume adaptation) is applied. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the financial sources of the division and in part by a research grant provided by NMS Biomedical SA, Switzerland. The company did not have any roles in design or conduct of the study or in the preparation of the manuscript. The authors have no other conflicts of interest. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT02641808. TRIAL REGISTRATION DATE: 29 December 2015. DATE OF FIRST PATIENT'S ENROLMENT: 22 August 2016.

Serum anti-Müllerian hormone concentration and follicle density throughout reproductive life and in different diseases-implications in fertility preservation.

STUDY QUESTION: How do anti-Müllerian hormone (AMH) serum concentrations and follicle densities (FDs) change with age and disease and what are the implications for fertility preservation? SUMMARY ANSWER: AMH concentrations and FD do not correlate in young women, and AMH but not FD is reduced in some diseases, limiting the value of AMH as a predictive parameter of ovarian tissue transplantation. WHAT IS KNOWN ALREADY: AMH is widely used as a parameter to estimate the ovarian reserve. However, the reliability of AMH to predict total number of follicles and the FD is questionable. Women with lymphoma and leukaemia have been shown to have reduced AMH concentrations, but it is unknown if the FD is also reduced. In fertility preservation it is essential to estimate the correct total number of follicles and the FD, as ovarian tissue should only be cryopreserved if ovarian reserve is high. Furthermore, the amount of tissue to be transplanted should be based on the estimation of the real FD. STUDY DESIGN, SIZE, DURATION: This retrospective observational study included 830 women (mean ± SD age, 28.2 ± 6.81 years; range, 4-43 years) with malignant (n = 806) and benign (n = 24) diseases who cryopreserved tissue in a single centre as part of a national fertility preservation programme. Females with ovarian surgery or known predispositions for a reduced ovarian reserve were excluded. AMH concentrations and FD were evaluated from March 2011 to September 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: AMH concentrations were analysed before gonadotoxic therapies. Standardized biopsies, obtained from different areas of ovarian cortex, were collected. FD was analysed after tissue digestion and calcein staining and was expressed as average number of primordial and primary follicles count per 3 mm biopsy and per cubic millimeter tissue. AMH concentrations and FD were analysed in relation to age and diagnosis group. Both parameters were age adjusted, and associations between the different diagnosis groups and AMH versus FD were assessed. MAIN RESULTS AND THE ROLE OF CHANCE: Mean ± SD AMH concentration was 3.1 ± 2.81 g/ml, mean FD per 3 mm biopsy was 137 ± 173.9 and 19.4 ± 24.60 per mm3. Maximum AMH concentrations were found in children and teenagers at the age of 6-10 years (5.71 ng/ml) and in adults at the age of 21-25 years (3.33 ng/ml). FD was highest in young children up to an age of 15 years and decreased with increasing age. AMH and FD were not correlated in women ≤20 years and weakly to moderately correlated in women 21-40 years (r = 0.24-0.39). Age-adjusted correlations between AMH and FD were demonstrated in several diagnosis groups such as breast cancer, leukaemia, sarcoma, gastrointestinal cancer and gynaecological cancer but not in the groups exhibiting Hodgkin's and non-Hodgkin's lymphoma, cerebral cancer, other types of malignancies and other types of benign diseases. Further statistical analysis supported the finding that, in some diagnosis groups such as Hodgkin's lymphoma and in gynaecological cancer, AMH concentrations but not FDs are reduced, questioning the prognostic accuracy of AMH for the FD in these diseases. LIMITATIONS, REASONS FOR CAUTION: Even though biopsies were taken from different sites, heterogenous distribution of follicles might have had some effect on the accuracy of the analysis. WIDER IMPLICATION OF THE FINDINGS: AMH should be used with care to estimate the total ovarian reserve and FD of cancer patients in young women in some diseases. Therefore, calculating the amount of ovarian tissue to be transplanted based solely on AMH might be inaccurate whereas FD might be a better parameter. STUDY FUNDING/COMPETING INTEREST(S): The study did not receive any exterior funding.

Effectiveness of seminal plasma in in vitro fertilisation treatment: a systematic review and meta-analysis.

BACKGROUND: With in vitro fertilization (IVF) techniques, only 20-25% of the transferred embryos lead to a pregnancy. OBJECTIVE: To evaluate the beneficial effects of seminal plasma (SP) or semen applied at the time of oocyte aspiration or embryo transfer. SEARCH STRATEGY: Electronic databases were searched from their inception up to August 2017. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) evaluating the effects of SP or semen in IVF treatment. Trials were considered if women were exposed to any kind of SP or semen (either SP/semen injection or sexual intercourse) around the time of oocyte pickup and embryo transfer. DATA COLLECTION AND ANALYSIS: The primary outcome was clinical pregnancy rate (CPR). MAIN RESULTS: Eight RCTs on women undergoing IVF (2128 in total) were included in the meta-analysis. Women randomized in the intervention group had a significantly higher CPR compared with controls (30.0 versus 25.1%; RR 1.20; 95% CI, 1.04-1.39). No significant differences were found in the secondary outcomes, including livebirth rate, biochemical pregnancy, miscarriage, multiple pregnancies, and birth weight. The subgroup analyses (four RCTs, 780 participants), including only those RCTs in which prepared undiluted SP was injected just after oocyte pickup, conformed with the overall analysis for the primary outcome (46.3 versus 37.2%; RR 1.23; 95% CI, 1.05-1.45). CONCLUSION: Because intravaginal or intracervical SP application around the time of oocyte pickup is associated with higher CPR, local application SP may be considered as a potential treatment to improve implantation. TWEETABLE ABSTRACT: SP at the time of oocyte pickup is associated with higher CPR.

Bridging between load-flow and Kuramoto-like power grid models: A flexible approach to integrating electrical storage units.

In future power systems, electrical storage will be the key technology for balancing feed-in fluctuations. With increasing share of renewables and reduction of system inertia, the focus of research expands toward short-term grid dynamics and collective phenomena. Against this backdrop, Kuramoto-like power grids have been established as a sound mathematical modeling framework bridging between the simplified models from nonlinear dynamics and the more detailed models used in electrical engineering. However, they have a blind spot concerning grid components, which cannot be modeled by oscillator equations, and hence do not allow one to investigate storage-related issues from scratch. Our aim here is twofold: First, we remove this shortcoming by adopting a standard practice in electrical engineering and bring together Kuramoto-like and algebraic load-flow equations. This is a substantial extension of the current Kuramoto-like framework with arbitrary grid components. Second, we use this concept and demonstrate the implementation of a storage unit in a wind power application with realistic feed-in conditions. We show how to implement basic control strategies from electrical engineering, give insights into their potential with respect to frequency quality improvement, and point out their limitations by maximum capacity and finite-time response. With that, we provide a solid starting point for the integration of flexible storage units into Kuramoto-like grid models enabling to address current problems like smart storage control, optimal siting, and rough cost estimations.

Week 96 results of the randomized, multicentre Maraviroc Switch (MARCH) study.

OBJECTIVES: The Maraviroc Switch (MARCH) study week 48 data demonstrated that maraviroc, a chemokine receptor-5 (CCR5) inhibitor, was a safe and effective switch for the ritonavir-boosted protease inhibitor (PI/r) component of a two nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI] plus PI/r-based antiretroviral regimen in patients with R5-tropic virus. Here we report the durability of this finding. METHODS: MARCH, an international, multicentre, randomized, 96-week open-label switch study, enrolled HIV-1-infected adults with R5-tropic virus who were stable (> 24 weeks) and virologically suppressed [plasma viral load (pVL) < 50 HIV-1 RNA copies/mL]. Participants were randomized to continue their current PI/r-based regimen (PI/r) or to switch to MVC plus two N(t)RTIs (MVC) (1:2 randomization). The primary endpoint was the difference in the proportion with pVL < 200 copies/mL at 96 weeks. The switch arm was defined as noninferior if the lower limit of the 95% confidence interval (CI) for the difference was < -12% in the intention-to-treat (ITT) population. Safety endpoints (the difference in the mean change from baseline or a comparison of proportions) were analysed as key secondary endpoints. RESULTS: Eighty-two (PI/r) and 156 (MVC) participants were randomized and included in the ITT analysis; 71 (87%) and 130 (83%) were in follow-up and on therapy at week 96. At week 96, 89.0% and 90.4% in the PI/r and MVC arms, respectively, had pVL < 50 copies/mL (95% CI -6.6, 10.2). Moreover, in those switching away from PI/r, there were significant reductions in mean total cholesterol (differences 0.31 mmol/L; P = 0.02) and triglycerides (difference 0.44 mmol/L; P < 0.001). Changes in CD4 T-cell count, renal function, and serious and nonserious adverse events were similar in the two arms. CONCLUSIONS: MVC as a switch for a PI/r is safe and effective at maintaining virological suppression while having significant lipid benefits over 96 weeks.

Optimizing the impact of alcohol and drug screening and early intervention in a high-risk population receiving services in New York City sexual health clinics: A process and outcome evaluation of Project Renew.

Unhealthy substance use is associated with increased rates of STDs, including HIV. Within three high-risk New York City (NYC) sexual health clinics between 2008 and 2012 (n = 146,657), 17% of patients screened positive for a current SUD but only 5.3% ever received prior treatment. The goal of Project Renew was to expand the reach of substance use early intervention services within and across sexual health clinics citywide and decrease substance use, poor mental health, and risky sexual behavior. To accomplish this goal, Screening, Brief Intervention, and Referral to Treatment (SBIRT), an evidence-based substance use early intervention model, was implemented in all eight NYC sexual health clinics February 2012-January 2015. Clinic patients were screened for substance misuse using the AUDIT/DAST-10, and those who screened positive were eligible for on-site brief intervention. Overall, 130,597 substance misuse screenings were conducted (66,989, or 51%, positive), and 17,474 on-site brief interventions and 1238 referrals were provided (not unique to individual patients). A 10% sample of 14,709 unique patients who screened positive were interviewed using a federal data collection tool at baseline and six months later to assess changes in substance use, sexual risk behaviors, mental health, and health status (n = 1328). At six-month follow-up, patients reported reduced substance use, less sexual activity, improved overall health, and fewer days of depression and anxiety compared to measures at baseline (p < 0.05). Based on positive results, Project Renew SBIRT services have been sustained, ensuring essential care which may help prevent acquisition of HIV/STDs among a large population of high-risk New Yorkers.

Trends in proportion of older HIV-infected people in care in Latin America and the Caribbean: a growing challenge.

We aimed to quantify the proportion of people receiving care for HIV-infection that are 50 years or older (older HIV patients) in Latin America and the Caribbean between 2000 and 2015 and to estimate the contribution to the growth of this population of people enrolled before (<50yo) and after 50 years old (yo) (⩾50yo). We used a series of repeated, cross-sectional measurements over time in the Caribbean, Central and South American network (CCASAnet) cohort. We estimated the percentage of patients retained in care each year that were older HIV patients. For every calendar year, we divided patients into two groups: those who enrolled before age 50 and after age 50. We used logistic regression models to estimate the change in the proportion of older HIV patients between 2000 and 2015. The percentage of CCASAnet HIV patients over 50 years had a threefold increase (8% to 24%) between 2000 and 2015. Most of the growth of this population can be explained by the increasing proportion of people that enrolled before 50 years and aged in care. These changes will impact needs of care for people living with HIV, due to multiple comorbidities and high risk of disability associated with aging.

Fertility preservation: ovarian response to freeze oocytes is not affected by different malignant diseases-an analysis of 992 stimulations.

PURPOSE: To study if ovarian response is affected by the type of disease if fertility preservation is required. METHODS: A registry of the trinational fertility preservation network FertiPROTEKT including 992 patients aged 18-40 years undergoing ovarian stimulation and follicle aspiration for fertility preservation from 1/2007 until 3/2016 was analysed. The number of collected oocytes, days of stimulation, total gonadotropin dosage and gonadotropin dosage per day were evaluated. RESULTS: Total oocyte number was negatively correlated with increasing age (r = 0.237, p < 0.0001). Oocyte numbers were in women < 26 years 15.4 ± 8.8, 26-30 years 13.1 ± 8.5, 31-35 years 12.2 ± 7.7 and 36-40 years 9.9 ± 8.0. Age-adjusted oocyte numbers were not different in women with Hodgkin's lymphoma (12.6 ± 8.8), non-Hodgkin's lymphoma (12.4 ± 8.2), leukaemia (11.7 ± 8.2), sarcoma (11.8 ± 8.2), cerebral cancer (16.5 ± 8.1), gastrointestinal cancer (13.2 ± 8.1) gynaecological cancer (10.8 ± 8.2) and other types of malignancies (15.8 ± 8.1) apart from ovarian cancer with lower oocyte yield (7.3 ± 8.3, p < 0.001) compared to women with breast cancer (13.3 ± 8.8). The total gonadotropin dose used for stimulation was only elevated in Hodgkin's and non-Hodgkin's lymphoma compared to women with breast cancer (p < 0.05). Oocyte yield was lower in women with versus without ovarian cancer (p < 0.0001). CONCLUSIONS: As ovarian response is not affected by the type of cancer, ovarian stimulation can be performed with the same oocyte yield in different malignant diseases. However, oocyte yield is reduced if ovarian surgery is required and in older women.

Practical recommendations for fertility preservation in women by the FertiPROTEKT network. Part I: Indications for fertility preservation.

PURPOSE: Most guidelines about fertility preservation are predominantly focused on scientific evidence, but are less practically orientated. Therefore, practically oriented recommendations are needed to support the clinician in daily practice. METHODS: A selective literature search was performed based on the clinical and scientific experience of the authors, focussing on the most relevant diseases and gynaecological cancers. This article (Part I) provides information on topics that are essential for the fertility preservation indication, such as disease prognosis, disease therapy and its associated risks to fertility, recommending disease-specific fertility preservation measures. Part II specifically focusses on fertility preservation techniques. RESULTS: In breast cancer patients, fertility preservation such as ovarian tissue and oocyte cryopreservation is especially recommended in low-stage cancer and in women < 35 years of age. In Hodgkin's lymphoma, the indication is mainly based on the chemotherapy regime as some therapies have very low, others very high gonadotoxicity. In borderline ovarian tumours, preservation of fertility usually is achieved through fertility sparing surgery, ovarian stimulation may also be considered. In cervical cancer, endometrial cancer, rheumatic diseases and other malignancies such as Ewing sarcoma, colorectal carcinoma, non-Hodgkin lymphoma, leukaemia etc., several other factors must be considered to enable an individual, stage-dependent decision. CONCLUSION: The decision for or against fertility preservation depends on the prognosis, the risks to fertility and individual factors such as prospective family planning.

The Anticaries Efficacy of a 1.5% Arginine and Fluoride Toothpaste.

Dental caries remains a world-wide disease despite the global distribution of fluoride. It has become apparent that the introduction of significant levels of sugar (fermentable carbohydrate) into the diet has resulted in a change in the biofilm, encouraging acid formation. Further, there has been a shift in the microbiota in the biofilm to a flora that produces acid, and thrives and reproduces in an acidic environment. The management of caries activity under these conditions has focused on brushing to remove the biofilm with fluoride pastes, and high-dose fluoride treatments. Kleinberg, in the 1970s, identified an arginine-containing compound in saliva that several oral biofilm bacterial species metabolize to produce base. Multiple in situ and in vivo studies have been conducted, and have discussed the ability of multiple bacteria to increase the resting pH of the biofilm and even reduce the decrease in pH when the biofilm is challenged with glucose. This shift in resting pH can shift the level of caries formation by the biofilm. Here, we present 8 clinical studies, with different clinical designs, measuring different clinical outcomes, for a diverse, world-wide population. Each of these studies demonstrates reductions in caries formation beyond that seen with fluoride alone and several demonstrate the reversal of early caries lesions. Significant clinical research has been shown that 1.5% arginine combined with fluoride toothpaste has superior anti-caries efficacy to toothpaste containing fluoride alone.

Gonadotrophin stimulation in IVF alters the immune cell profile in follicular fluid and the cytokine concentrations in follicular fluid and serum.

Study question: Are the immune cell profiles and the cytokine concentrations in follicular fluid (FF) and serum at the preovulatory stage different in conventional exogenous gonadotrophin stimulated IVF (c-IVF) compared with natural cycle IVF (NC-IVF)? Summary answer: The cell counts of CD45+ leucocytes and T cell subpopulations and the cytokine concentrations in FF and serum are different in c-IVF compared to NC-IVF. What is known already: FF-derived cells are heterogeneous. Immune cells are involved in intra-ovarian processes and cytokines are required for normal follicular development. Gonadotrophins stimulate the regulatory intrafollicular system and influence the local distribution of immune cells and the intrafollicular release of cytokines. Administration of exogenous gonadotrophins may have a significant effect on this local regulatory system, which then in turn could influence oocyte quality. Study design, size, duration: The study included 105 patients, 69 undergoing c-IVF and 36 undergoing NC-IVF. c-IVF was performed by exogenous ovarian stimulation with hMG and GnRH antagonists. Participants/materials, setting, methods: FF samples were collected from the first dominant follicle in c-IVF without pooling and from single leading preovulatory follicles in NC-IVF. Three different approaches were used to analyze FF samples: (i) microscopic investigation of CD45+ leucocytes, (ii) fluorescence-activated cell sorting to determine CD19+ B cells and CD3+ T cells including T cell subpopulations (CD4+, CD8+), and (iii) evaluation of tumour necrosis factor-alpha (TNF-α), interferon-gamma (INF-γ), interleukins (IL)-2, -6, -8, -10 and vascular endothelial growth factor (VEGF) levels in matched FF and serum samples using the Bio-Plex® platform. Main results and the role of chance: FF obtained from c-IVF contained proportionally more CD45+ leucocytes (P = 0.0384), but fewer CD8+ cytotoxic T cells than FF from NC-IVF. CD3+ T lymphocytes were the most common type of lymphocytes, and the number thereof was comparable in the two study groups. In c-IVF, serum VEGF levels were higher (P = 0.007) than in NC-IVF while FF contained marginally decreased concentrations of IL-8 in c-IVF in comparison to NC-IVF. The cytokine concentration gradient between FF and serum in c-IVF was 10-fold for IL-8 and 8-fold for VEGF and thereby markedly lower than in NC-IVF, where the differences were 32-fold and 30-fold, respectively. Strong positive correlations were determined between FF- IL-10 and FF- VEGF in c-IVF (r = 0.85, P < 0.0001) and in NC-IVF (r = 0.81, P < 0.0001). Large scale data: N/A. Limitations, reasons for caution: The ovulation of NC-IVF follicles was induced by the exogenous administration of hCG, which means that the environment did not fully correspond to the physiological situation. Wider implications of the findings: The differences in the immune profile and the cytokine concentrations in c-IVF and NC-IVF follicles support the hypothesis that conventional ovarian stimulation affects indirectly and heterogeneously the intrafollicular milieu, and thereby possibly affects the oocyte quality and the IVF outcome. However, further studies are needed to confirm our findings and to refine stimulation protocols in the context of optimizing the intrafollicular environment during oocyte maturation. Study funding/competing interest(s): The study was supported by a research grant from IBSA Institut Biochimique SA and MSD Merck Sharp & Dohme GmbH. The authors are clinically involved in low dose mono-follicular stimulation and IVF-therapies, using gonadotrophins from all gonadotrophins distributors on the Swiss market, including Institut Biochimique SA and MSD Merck Sharp & Dohme GmbH.

Two-year development of children conceived by IVM: a prospective controlled single-blinded study.

STUDY QUESTION: Is there a difference in mental development of children conceived by IVM in comparison to IVF or ICSI, independently, at the age of 2 years? SUMMARY ANSWER: No differences could be found in mental development of IVM children compared to IVF and IVM children compared to ICSI as well. WHAT IS KNOWN ALREADY: Only few retrospective or non-controlled studies addressed the health of IVM children and did not show a negative impact of the IVM procedure. STUDY DESIGN, SIZE, DURATION: Prospective controlled single-blinded study including 63 pregnancies (21 per IVM, IVF and ICSI groups) with 70 children expected. Examinations of 62 embryos at first trimester screening, of 57 fetuses at 21st week of pregnancy, of 60 children at birth and of 37 children at their second birthday were performed during the study period from January 2009 until October 2016. Bayley score at the age of 2 was the primary outcome parameter. Data of 40 children after spontaneous conception from a previous prospective unrelated study were further used as control at 2 years examination and compared to the pooled ART group (IVM, IVF and ICSI). PARTICIPANTS/MATERIALS, SETTING, METHODS: Twenty-one IVM pregnancies achieved in the study period were included. For each of them, the following IVF- and ICSI pregnancies were recruited as controls. Ultrasound examinations during pregnancy, examinations of newborns and of children around their second birthday were done by blinded prenatal specialists, pediatricians and neuropediatricians, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: Children conceived after IVM did not show differences during embryonic development, at birth nor in their neuropediatric development at the age of 2 compared to their counterparts after IVF and after ICSI (Bayley score 91.3 ± 21.0 for IVM, 96.8 ± 13.2 for IVF and 103.9 ± 13.1 for ICSI) and of the pooled ART group compared to children after spontaneous conception (96.6 ± 16.4 ART and 103.2 ± 9.4 spontaneous conception). When analyzing singleton pregnancies only, again no differences during pregnancy, at birth and at their 2-year evaluation were detected between IVM versus IVF and IVM versus ICSI. LIMITATIONS, REASONS FOR CAUTION: Due to the small sample size data must be interpreted with caution. To allow a confirmative answer that there are no health risks for children conceived by IVM, large multicenter cohort or registry-based studies are urgently needed. WIDER IMPLICATIONS OF THE FINDINGS: The study adds further information to previous uncontrolled or retrospective studies, which were unable to detect risks for the health of IVM children. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by the 'Deutsche Forschungsgemeinschaft' (DFG): STR 387/4-1. G.R. receives royalties from Pearson Assessment Germany (editor fee for Bayley-III). The other authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Follicular flushing in natural cycle IVF does not affect the luteal phase - a prospective controlled study.

In contrast to multifollicular IVF, follicular flushing seems to increase the efficacy of monofollicular IVF treatments such as natural cycle IVF (NC-IVF). However, because follicular flushing causes loss of granulosa cells, it might negatively affect luteal phase length and endocrine function of the luteal body. A prospective cohort Phase II study was performed in 24 women undergoing NC-IVF. Women underwent a reference cycle with human chorionic gonadotrophin-induced ovulation without follicle aspiration and analysis of the length of the luteal phase and luteal concentrations of progesterone and oestradiol. In addition, they underwent a NC-IVF cycle which was performed identically but follicles were aspirated and flushed three times. The luteal phase was shorter in 29.2%, equal in 16.7% and longer in 50.0% of cases following flushing of the follicles. Overall, neither difference in luteal phase length was significant [median duration (interquartile range) in reference cycle: 13 (12; 14.5), IVF (flushing) cycle: 14 (12.5; 14.5), median difference (95% CI): 0.5 (-0.5 to 1.5)] nor median progesterone and oestradiol concentrations. In conclusion, follicular flushing in NC-IVF affects neither the length of the luteal phase nor the luteal phase concentrations of progesterone and oestradiol, questioning the need for luteal phase supplementation.