Prospective multicenter observational real-world study to assess the use, efficacy and safety profile of follitropin delta during IVF/ICSI procedures (DELTA Study).

OBJECTIVE: To describe the use, efficacy and safety profile of follitropin delta in women undergoing IVF/ICSI in routine clinical practice after one treatment cycle. STUDY DESIGN: This was a French multicenter, prospective, observational study conducted in 14 fertility centers between June 2020 and June 2021. During this period, 248 women undergoing IVF or ICSI were treated with follitropin delta for the first time. Women were followed up to 10-11 weeks after the first fresh or frozen embryo transfer. The main outcomes were use of dosing algorithm, follitropin delta dosing patterns, ovarian response, pregnancy, and adverse drug reactions in routine clinical practice. RESULTS: The analyzable population consisted of 223 patients with mean ± SD age of 33.0 ± 4.4 years, body weight of 65.7 ± 11.8 kg, and the median (IQR) AMH level was 2.6 (1.5-4.0) ng/mL. For 193 patients (86.5 %) it was the first IVF/ICSI cycle and for 30 (13.5 %) the second. The algorithm was used for the calculation of the starting dose for 88.3 % of the patients. The mean daily starting dose of follitropin delta was 11.4 ± 4.1mcg for the whole analyzable population and 14.4 ± 5.2 mcg for the sub-group of 26 patients dosed without the algorithm. The mean duration of stimulation with follitropin delta was 10.8 ± 5.2 days. The mean total dose of follitropin delta administered was 122.2 ± 80.0 mcg. An antagonist protocol was used in 90.3 % of patients. The mean ± SD number of oocytes retrieved among patients that started stimulation was 11.3 ± 6.8 and 46.1 % of patients achieved the targeted response of the algorithm of 8-14 oocytes retrieved. A fresh transfer was performed for 77.6 % of patients; the mean ± SD number of embryos transferred was 1.3 ± 0.5. The implantation rate was 36.0 %. Per started cycle, clinical pregnancy was reported in 35.0 % of the patients and ongoing pregnancy in 29.6 %. In total, 5 patients (2.2 %) reported an event of OHSS. CONCLUSION: Clinical results as collected in routine clinical practice are promising, showing a favorable effectiveness-safety profile of follitropin delta for a very varied patient population (including anovulatory PCOS, very poor responders, or non-IVF naïve patients). These real-world data complement results from clinical trials and provide useful information for usual clinical practice within a heterogeneous population group.

Improving water, sanitation, and hygiene (WASH), with a focus on hand hygiene, globally for community mitigation of COVID-19.

Continuity of key water, sanitation, and hygiene (WASH) infrastructure and WASH practices-for example, hand hygiene-are among several critical community preventive and mitigation measures to reduce transmission of infectious diseases, including COVID-19 and other respiratory diseases. WASH guidance for COVID-19 prevention may combine existing WASH standards and new COVID-19 guidance. Many existing WASH tools can also be modified for targeted WASH assessments during the COVID-19 pandemic. We partnered with local organizations to develop and deploy tools to assess WASH conditions and practices and subsequently implement, monitor, and evaluate WASH interventions to mitigate COVID-19 in low- and middle-income countries in Latin America and the Caribbean and Africa, focusing on healthcare, community institution, and household settings and hand hygiene specifically. Employing mixed-methods assessments, we observed gaps in access to hand hygiene materials specifically despite most of those settings having access to improved, often onsite, water supplies. Across countries, adherence to hand hygiene among healthcare providers was about twice as high after patient contact compared to before patient contact. Poor or non-existent management of handwashing stations and alcohol-based hand rub (ABHR) was common, especially in community institutions. Markets and points of entry (internal or external border crossings) represent congregation spaces, critical for COVID-19 mitigation, where globally-recognized WASH standards are needed. Development, evaluation, deployment, and refinement of new and existing standards can help ensure WASH aspects of community mitigation efforts that remain accessible and functional to enable inclusive preventive behaviors.

Evaluation of SARS-CoV-2 in semen, seminal plasma, and spermatozoa pellet of COVID-19 patients in the acute stage of infection.

To date, there is limited information about the presence of SARS-CoV-2 in semen especially in the acute phase of the infection. While available data from cohort studies including a total of 342 patients in the acute or recovery phase of the infection are reassuring, one study mentioned detecting virus in the semen of 6/38 COVID-19 patients. Here we assessed SARS-CoV-2 presence in the semen of COVID-19 positive patients in the acute stage of infection, within 24 hours of the positive nasopharyngeal swabs. Semen, seminal plasma and spermatozoa pellet were screened for SARS-CoV-2 and manual or airborne contamination during semen sampling. Among the 32 COVID-19 volunteers, the median interval from the onset of symptoms to semen collection was 4 days [IQR: 0-8]. Only one presented positive SARS-CoV-2 PCR in semen and seminal plasma fractions, although the spermatozoa pellet was negative. Viral cultures were all negative. We observed slightly higher concentrations of bacterial DNA in the SARS-CoV-2 positive specimen than in all negative samples. The bacteria identified neither confirm nor rule out contamination by oropharyngeal secretions during collection. SARS-CoV-2 was rarely present in semen during the acute phase of the disease. This very rare situation could be connected to oral or manual contamination during semen collection. The possible presence of SARS-CoV-2 in semen calls for nasopharyngeal viral testing and strict hygiene protocols during semen collection before assisted reproductive attempts.

Live birth after intrauterine insemination: is there an upper cut-off for the number of motile spermatozoa inseminated?

RESEARCH QUESTION: To date, most studies have investigated the minimum number of spermatozoa available for intrauterine insemination (IUI), with no data on the maximum number of motile spermatozoa inseminated (NMSI) having been published. This study aimed to determine whether an upper cut-off for the NMSI during IUI exists above which the live birth rate (LBR) is negatively affected. DESIGN: Retrospective analysis of autologous IUI cycles performed between January 2010 and July 2018 in women <43 years old with a NMSI >1 million. The main outcome was the LBR per IUI cycle as a function of the NMSI. RESULTS: A total of 2592 IUI cycles performed in 1017 couples were included. The LBR increased with NMSI up to 30 million without any upper threshold (AUC = 0.5441). The LBR per IUI cycle were 14.5%, 17.9% and 22.7% for NMSI of >1 to ≤10, >10 to ≤20 and >20 to ≤30 million, respectively (P = 0.003). By univariate analysis, the NMSI, female age, number of mature follicles and oestradiol concentrations on day of ovulation triggering, cycle number and infertility aetiology influenced the LBR. Multivariate analysis showed that the LBR was 1.49 and 1.78 times higher when IUI was performed with a NMSI >10 to ≤20 million (odds ratio [OR] 1.49; 95% confidence interval [CI] 1.10-2.02]) and >20 to ≤30 million (OR 1.78; 95% CI 1.08-2.94), respectively, compared with IUI with a NMSI >1 to ≤10 million. CONCLUSIONS: The LBR after IUI can be optimized by inseminating a maximum of motile spermatozoa up to 30 million. Thus, in this specific cohort, IUI preparations should not be diluted when more than 10 million motile spermatozoa are obtained.

Engineering of Antimicrobial Surfaces by Using Temporin Analogs to Tune the Biocidal/antiadhesive Effect.

Proliferation of resistant bacteria on biomaterials is a major problem leading to nosocomial infections. Due to their broad-spectrum activity and their ability to disrupt bacterial membranes through a rapid membranolytic mechanism, antimicrobial peptides (AMPs) are less susceptible to the development of bacterial resistance and therefore represent good candidates for surface coating strategies to prevent biofilm formation. In this study, we report on the covalent immobilization of temporin-SHa, a small hydrophobic and low cationic antimicrobial peptide exhibiting broad-spectrum activity, and (SHa) analogs on modified gold surfaces. Several analogs derived from SHa with either a carboxamidated ([K³]SHa, d-[K³]SHa) or a carboxylated C-terminus ([K³]SHa-COOH) were used to achieve peptide grafting on gold surfaces modified by a thiolated self-assembled monolayer (SAM). Surface functionalization was characterized by polarization modulation infrared reflection absorption spectroscopy (PM-RAIRS) and X-ray photoemission spectroscopy (XPS). The antibacterial properties of the temporin-functionalized surfaces were tested against the Gram-positive Listeria ivanovii. Direct visualization of the peptide effects on the bacterial membrane was investigated by scanning electron microscopy equipped with a field emission gun (SEM-FEG). All active temporin analogs were successfully grafted and display significant antibacterial activity (from 80 to 90% killing efficiency) in addition to a 2-fold decrease of bacterial adhesion when all d-SHa analogs were used.

European species of the Gnaphosa alpica complex (Araneae, Gnaphosidae).

Members of the genus Gnaphosa belong to the largest gnaphosid spiders. They are particularly interesting in nature conservation as their distribution is mainly restricted to disappearing natural non-forest habitats. In Europe, several Gnaphosa species groups occur. The exclusively Palaearctic group G. bicolor is characterised by a retrolaterally-shifted embolus, which occupies at least part of the middle one-third of the palpal bulb; females have laterally expanded epigyne and often have very elongated median epigynal ducts (Ovtsharenko et al. 1992). So far four species of this group have been identified in Europe, with a fifth species found in Central Asia (G. tarabaevi Ovtsharenko, Platnick Song, 1992). Two of the European species, G. bicolor (Hahn, 1831) and G. badia (L. Koch, 1866), are well known and their taxonomy and nomenclature is stable, but the same does not hold true for the other two.

On the identity of the Palearctic species of the wolf spider genus Trebacosa (Araneae: Lycosidae).

In this paper we propose Trebacosa brunhesi Villepoux, 2007 as a junior synonym of Trebacosa europaea Szinetár & Kan-csal, 2007 based on the examination of specimens from all the localities from where those species are known. Illustration of the type species of the genus, Trebacosa marxi (Stone, 1890) and specimens from all known localities of T. europaea are given to show both the inter- and the intraspecific differences of the genus. Scanning electron micrographs were used to illustrate the detailed structure of the female's genitalia.

Intracytoplasmic morphologically selected sperm injection (IMSI) after repeated IVF or ICSI failures: a prospective comparative study.

OBJECTIVE: Sperm morphology plays a significant role in assisted reproductive technologies and is associated with high implantation rates. The objective of this study was to evaluate the outcome of intracytoplasmic morphologically selected sperm injection (IMSI) after repeated failures of conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) techniques. STUDY DESIGN: In a prospective study in which couples acted as their own controls, 75 infertile couples were offered IMSI after at least two previous IVF or ICSI failures. The main outcome measures were embryo quality and number of blastocysts obtained. RESULTS: The percentage of top quality embryos obtained at day 2 was increased in IMSI compared to IVF/ICSI cycles (89.8% versus 79.8%; p=0.009). Extended embryo culture was possible in 41.3% of IMSI cycles versus 26.7% of IVF/ICSI cycles (p=0.04), and the mean number of blastocysts obtained was higher in IMSI cycles (1.5±1.9) than in IVF/ICSI cycles (1.0±1.2) (p=0.03). Moreover, IMSI resulted in clinical pregnancy and birth rates of respectively 29.3% and 18.6%. CONCLUSION: After two or three IVF/ICSI failures, IMSI seems to give better embryo quality and more blastocysts, which allow more embryo transfers at the blastocyst stage. This study supports the use of sperm ultramorphology examination as an independent test to be proposed after repeated IVF or ICSI failures.

Adverse effects of hepatitis B virus on sperm motility and fertilization ability during IVF.

The consequences of hepatitis B virus (HBV) infection for fertility are still unclear. Spermatozoa with decreased motility have been reported in HBV-infected patients. It has been demonstrated in vitro that HBV S protein has adverse effects on human sperm function with consequences for fertilization. In a case-control study design, 32 IVF cycles in couples with male HBV infection were compared with 64 cycles in non-infected couples, matched for age, time period, cycle rank and sperm parameters on the day of oocyte retrieval. Sperm motility before selection was significantly reduced in the HBV group (36.3 ± 11.6% versus 45.3 ± 14.4%,P = 0.003). A low fertilization rate (LFR) was more frequently observed in the HBV group (34.4% versus 15.6%, P = 0.036) and was associated with a decreased number of embryos available for transfer, although embryo quality on day 2 or 3 was not different.Implantation and pregnancy rates were comparable between groups. This study shows that HBV has a deleterious effect on sperm motility in vivo and that couples whose male partner is infected have a higher risk of LFR after IVF, a risk which is independent from the initial sperm motility.

Endometrial vascularity by three-dimensional power Doppler ultrasound and cytokines: a complementary approach to assess uterine receptivity.

INTRODUCTION: Uterine receptivity was assessed simultaneously by measurement of vasoactive cytokines possibly involved in development of spiral arteries and by assessment of endometrial and uterine arterial blood flow. The objective was to explore the relationship between cytokine-related dysregulation and endometrial vascularisation in women with repeated implantation failures after in vitro fertilisation embryo transfer (IVF-ET). MATERIALS AND METHODS: We studied 40 women with recurrent IVF/ICSI-ET failures, despite replacement of more than 10 embryos of 'good quality', and 8 fertile controls. Three-dimensional ultrasound with power angiography was performed to record the sub-endometrial vascular flow index (VFI) and uterine artery pulsatility index prior to endometrial biopsy at day 21-23 of a monitored natural cycle. Endometrial IL-18, IL-18BP and IL-15 mRNA expression was assessed by real-time PCR, and the number of CD56(+) cells determined by immunochemistry. RESULTS: IL-18 and IL-15 mRNA expression was significantly different between the two groups. The range of variation in vascular imaging data was increased in the implantation failure (IF) group. The mRNA ratio for IL-15, but not the other cytokines, correlated with sub-endometrial vascular flow (r=0.65; p<0.001). This ratio correlated also with the mean number of CD56(+) cells per high-power field (r=0.41; p=0.005). Both IL-18 and IL-18BP mRNA expression was significantly negatively correlated with mean uterine artery pulsatility index (r=-0.37 and -0.43; p=0.02 and 0.01, respectively). CONCLUSION: Comprehensive ultrasonographic indicators appear to be related to various mechanisms, including insufficient or excessive uterine NK cell recruitment and inadequate endothelial vascular remodelling. New molecular tools may be useful in providing greater precision of uterine receptivity than ultrasonic indicators alone.

Uterine receptivity and cytokines: new concepts and new applications.

The implantation process, currently thought to be the most critical step in achieving a successful early pregnancy, remains one of the most important unsolved processes in reproductive medicine. It depends on uterine-dependent and embryo-specific events, which need to be critically coordinated. Early embryo signaling following a maternal hormonal or cytokine-mediated preparation phase seems to be involved in stages immediately before, during and just after the apposition step to permit adequate proliferation of the stroma. Our objective is to develop guidelines and diagnostic tools pertinent to appreciate uterine receptivity. We will focus our attention on the uterine luminal environment at the time of oocyte retrieval and on the monitoring of the endometrium using three-dimensional ultrasound associated with digital technology and cytokine quantification by real-time PCR during the implantation window in an IVF/ICSI population. There is an accumulating body of data which strongly suggests that both implantation and uterine receptivity are controlled, primarily, though not exclusively, by locally acting growth factors and cytokines, some under steroid control. Some specific cytokines (IL-12, IL-15 and IL-18) in the luminal environment and in the endometrium allow a distinct pattern of abnormal uterine receptivity. The identification of these distinct patterns of abnormal uterine receptivity and of the mechanisms leading to the abnormal angiogenesis before implantation strongly suggest that no single therapeutic scheme can correct all cases of implantation failure and should be adapted for each patient especially in the case of unexplained infertility.

Difficult management of recurrent catamenial pneumothorax.

Catamenial pneumothorax is an uncommon disease whose management is not consensual. We report the case of a patient who experienced several episodes of pneumothorax. She was initially treated by repair of diaphragmatic defects and hormonal treatment. During the therapeutic amenorrhea, no recurrence occurred. However, each cessation of medical therapy was followed by recurrence. Finally, talc pleurodesis and tubal ligature were performed without any recurrence in the subsequent 12 months. This report outlines the great difficulties that can be encountered in the management of patients with catamenial pneumothorax.