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Background: One of the most important population challenges during the last three decades has been the significant decrease in the fertility rate worldwide. Since the validity and reliability of the Male and Female Fertility Knowledge Inventories (MFKI and FFKI) have not been determined in Iran, we conducted this study to assess psychometric characteristics of the MFKI and FFKI in couples in Tabriz and Urmia, Iran. Methods: This was a cross-sectional study, as the first part (quantitative phase) of a sequential explanatory mixed-method study. The current study was done on 1200 participants (600 women with their husbands) living in the northwestern region of Iran, between January 2023 and September 2023. The psychometric properties of the Persian version of the tool (MFKI and FFKI) were performed in 5 stages, including translation process, content validity, face validity, construct validity and reliability assesment. Results: In this study, the CVI, CVR, and impact scores of the MFKI tool were equal to 0.90, 0.88, 3.26 and CVI, CVR, and Impact scores of the FFKI tool were respectively equal to 0.95, 0.91 and 3.59, that it indicated a satisfactory level of content and face validity. Then, to check the construct validity, the results of the exploratory factor analysis of the MFKI tool on 13 items led to the identification of 3 factors, including Environment and reproductive health (ERH), Lifestyle factors (LSF) and Sperm quality (SQ), which explained 66% of the cumulative variance. The results of the exploratory factor analysis of the FFKI tool on 15 items led to the identification of 4 factors, including Reproductive health (RH), Lifestyle factors (LSF), Chance of conception (CHC) and Ovarian reserve and preservation (ORP), which explained 68% of the cumulative variance. Conclusions: The findings of this study indicated that the Persian version of MFKI and FFKI has acceptable psychometric properties to measure the awareness of Iranian couples regarding fertility, which can be used as a screening tool for fertility knowledge by health care professionals and also as a reliable tool in research. Plain English summary: The right to sexual and reproductive health (SRH) is considered one of the basic rights of couples all over the world. Increasing childbearing age is a global social issue. In spite of the policies of having children in the previous decade, fertility reduction and involuntary childlessness are still the foremost global health problems. The fertility rate in Iran has reduced significantly in the last thirty years. This reduction can be attributed not only to economic difficulties but also to the postponement of marriage and having children, as well as infertility issues, which, by increasing the awareness of couples about fertility, seems to be able to overcome this problem to some extent. Consequently, we decided to conduct this study with the aim of determining the psychometric properties of the Male and Female Fertility Knowledge Inventories (MFKI and FFKI) in Iranian couples. The results of the current study revealed that this questionnaire, having acceptable psychometric properties to evaluate the state of awareness of Iranian couples regarding fertility, can be used as a valid and reliable tool in Iranian couples. It appears that it is essential for health care providers to play an active role in advising couples about the appropriate age of fertility, the problems of delay in having children, overcoming the value of having few children in society. Accordingly, health policymakers should recommend the use of valid screening tools to identify the knowledge of women and men about fertility in health centers. [ABSTRACT FROM AUTHOR]

Background: Semen quality significantly influences conception, and its preservation is crucial for couples seeking pregnancy. We investigated dietary and lifestyle risk factors impacting semen quality. Methods: A total of 466 males from the Guangzhou Women and Children's Medical Center's pre-pregnancy consultation clinic were recruited between January 2021 and March 2023 for inclusion. Semen analysis was performed, and diet and lifestyle data were gathered via questionnaire. Logistic regression was utilized to examine the link between diet, lifestyle variables, and semen quality. Results: Smoking worsened progressive sperm motility (38.0% vs. 36.0%, t = 2.262; P = 0.049). Alcohol consumption impaired progressive motility (40.5 ± 17.8% vs. 34.7 ± 16.1%, t = 3.396; P < 0.001) and total motility (56.0% vs. 64.0%; P = 0.001). Using plastic beverage bottles for oil or seasonings lowered sperm concentrations (40.4% vs. 59.0% vs. 65.5%; P = 0.032). A sweet diet correlated with higher total sperm motility (55.0% vs. 60.0%, 62.0% vs. 63.2%; P = 0.017). Higher milk product intake improved sperm concentration (41.6106vs. 63.7106 vs. 66.1*106; P = 0.021) and motility (54.5% vs. 56.0% vs. 63.0%; P = 0.033). More frequent egg consumption increased semen volume (3.1 mL vs. 3.8 mL vs. 4.0 mL; P = 0.038). Roughage intake enhanced sperm concentration (160.8106 vs. 224.6106; P = 0.027), and adequate sleep improved progressive sperm motility rate (35.4% ± 18.2% vs. 40.2 ± 16.3%, F = 3.747; P = 0.024) and total motility (52.7% vs. 61.5%; P = 0.013). The regression model showed that using plastic containers for condiments was a protective factor for semen volume (OR: 0.12; CI 0.03–0.55; P = 0.006), sperm concentration (OR: 0.001, CI 0.00–0.30; P = 0.012), and count (OR: 0.12, CI 0.03–0.48; P = 0.003). Milk and egg consumption were also protective for semen volume (OR: 0.18, CI 0.06–0.51; P = 0.001 and OR: 0.11, CI 0.03–0.55; P = 0.006, respectively), while sufficient sleep benefitted total sperm motility (OR: 0.47, CI 0.24–0.95; P = 0.034). Conclusions: Smoking and drinking, type of condiment container, diet preference, sleep duration, and milk, roughage, and egg consumption may reduce semen quality. [ABSTRACT FROM AUTHOR]

Background: The desire for fertility is the manifestation of yearning for immortality. Infertility and assisted reproductive technology (ART) expose couples to great affective, anxiety, stress, and financial burden. Increasing evidence emphasize the impact of lifestyle on infertility. One of the most crucial factors affecting the fertility process is the nutrition patterns, the amount and quality of physical activities, emotional problems management; modulate stressors, relief from anxiety, and the living conditions of couples. Most ART treatment interventions in Iran are not integrated into lifestyle programs. Therefore, this research will investigate the impact of mixed fertility health-promoting programs in couples who use ARTs. Methodology/Design: This study entails three steps. The first step includes the systematic review of literature on a health-promoting lifestyle in infertile couples undergoing ARTs, a systematic review of observational studies and interventions in couple's lifestyle, then, a systematic review of qualitative studies on infertility in couples and their lifestyle, and in the final step couple's life style literature systematically will evaluate in Iran. In case of failure to obtain the required results from systematic reviews, cross-sectional studies will be carried out to determine the lifestyle of infertile couples receiving ARTs. In the second stage, by holding a panel of experts, an intervention is planned based on the results of the previous stages in order to improve the lifestyle of couples. In the final step, the designed intervention will be administered as a random clinical trial—on ART candidates, in intervention or control groups in one of Iran University of Medical Sciences hospitals. Afterward, the data's will be evaluated by using standard questionnaires, that include health-promoting lifestyle questionnaire (HPLII), Beck's depression inventory (BDI), international physical activity questionnaire—short form (IPAQ-SF), and food frequency questionnaire (FFQ). The statistical analysis will be carried out in SPSS software. During the study, subjects meeting the inclusion criteria were randomly selected and randomized into the intervention and control groups. The health-promoting lifestyle training program will be executed for the intervention group while the standard care program is administered to the control group. The content of this program will be obtained from the consensus opinions of the expert panel. The program includes diet recommendations, physical activity, and stress management. Appropriate time, frequency, duration and number of activities will be considered. Communication with subjects will be possible through private meeting special comfort room. Support to the participants will also be through clinical visits social media, SMS and phone calls. Nutritional changes, physical activity amount, anxiety and stress level, abdominal circumference (AC), and body mass index (BMI) will be measured after the completion of the specified time interval. The initial outcome includes examining chemical pregnancy (2 weeks after the transmission) and clinical pregnancy by ultrasound (6 weeks after). The secondary outcome will be live birth rate. Retrieved oocyte and embryo numbers will also be reported. Discussion: Health-promoting lifestyle programs are essential in assisted reproductive technologies to improve pregnancy results and live birth. These programs in association with in-vitro fertilization (IVF) influence the outcome of fertilization. In addition, enhancing parental health leads to healthy pregnancy outcome. Despite the frequency of lifestyle risk factors, employing proper methods helps reduce anxiety and stress, modify dietary patterns, and perform qualitatively and quantitatively balanced physical activities. In addition, having coping skills and mental health management methods, in nowadays modern world challenges seems crucial and effective in solving fertility problems and reducing them before pregnancy. Plain Language Summary: For most people, children are the meaning of life. In some cultures, children are regarded as a family function and thus infertility is displeasing problem. In public believes, children are divine blessings. Not having children signifies a sick body and incomplete identity, which give rise to psychological and socio-economic consequences. Studies show that fertility and childbearing are biomarkers of survival and affect infertile men and women subconsciously. Since childbearing is one of the most crucial pillars of human marital life, an increase in infertile cases and use of ARTs by infertile couples, the lack of physical activity, sedentary lifestyle, unhealthy diet, stress, anxiety, and psychological problems caused by infertility problems, and the side effects of using ARTs preoccupy couples and distract their attention from healthy lifestyle and well-being issues. Despite the crucial importance of prevention in the modern world and the cost-effectiveness of prevention till treatment, numerous research findings expressing the importance of health education and disease ameliorates. These dimensions are still overlooked. Considering the importance of the issue, to the reduction of damages caused by chronic diseases, such as preventable NCDs problems including infertility, to promote fertility results, improving before conception. Oocyte retrieving time and in window period could improve embryo-maternal outcomes. Ensures couples' health, increases individuals' life satisfaction, and promotes health and lifespan of individuals, which is the ultimate goal of the healthcare system are the other purpose of health promoting process. It seems that health promotion lifestyle programs in Iran for infertile couples have not yet been integrated. Therefore, the combination of these programs with ART can be effective in achieving the goals of improving reproductive health. This research seeks to promote programs based on improving the health of infertile couples, increasing childbearing and increasing live births in people who are candidates for ART. A mixed study in the first step will be carried out by a systematic review of studies on ART candidate couples 'lifestyles. If the desired results are not achieved, a cross-sectional study will be conducted. In the second step, an intervention will be designed and developed to execute the lifestyle program following the specialists' opinions concerning nutrition, physical activity, and stress management. The next step will be carried out by implementing RCT. This intervention will be executed and evaluated at the end. [ABSTRACT FROM AUTHOR]

Background: Seasonal patterns of preterm birth were identified in previous studies, but the effect of conception season on preterm birth has not been extensively studied. Based on the notion that the etiological roots of preterm birth lie in the beginning of pregnancy, we did a population-based retrospective cohort study in Southwest China to examine the effects of season of conception and month of conception on preterm birth. Methods: We did a population-based retrospective cohort study in women (aged 18–49) who participated in the NFPHEP from 2010 to 2018, and had a singleton livebirth in southwest China. According to the time of the last menstruation reported by the participants, month of conception and season of conception were then ascertained. We used multivariate log-binomial model to adjust the potential risk factors for preterm birth and obtained adjusted risk ratio (aRR) and 95% confidence intervals (95%CI) for conception season, conception month and preterm birth. Results: Among 194 028 participants, 15 034 women had preterm birth. Compared with pregnancies that were conceived in the summer, pregnancies that were conceived in the spring, autumn and winter had the higher risk of preterm birth (Spring: aRR = 1.10, 95% CI: 1.04–1.15; Autumn: aRR = 1.14, 95% CI: 1.09–1.20; Winter: aRR = 1.28, 95% CI: 1.22–1.34) and also had a higher risk of early preterm birth (Spring: aRR = 1.09, 95% CI: 1.01–1.18; Autumn: aRR = 1.09, 95% CI: 1.01–1.19; Winter: aRR = 1.16, 95% CI: 1.08–1.25). Pregnancies in December, and January had a higher risk of preterm birth and early preterm birth than pregnancies that were conceived in July. Conclusions: Our study found that preterm birth was significantly related to season of conception. Preterm and early preterm birth rates were the highest among pregnancies that were conceived in winter, and the lowest among pregnancies in summer. [ABSTRACT FROM AUTHOR]

Background: Duplications of the long arm of chromosome 3 are rare, and associated to a well-defined contiguous gene syndrome known as partial trisomy 3q syndrome. It has been first described in 1966 by Falek et al., and since then around 100 patients have been reported. Clinical manifestations include characteristic facial dysmorphic features, microcephaly, hirsutism, congenital heart disease, genitourinary anomalies, hand and feet abnormalities, growth disturbances and intellectual disability. Most of cases are due to unbalanced translocations, inherited from a parent carrying a balanced aberration (reciprocal translocation or inversion), and rarely the genomic anomaly arises de novo. Very few studies report on the prenatal identification of such rearrangements. Case presentation: Hereby, we report on a newborn with a rare pure duplication of the long arm of chromosome 3. Noninvasive prenatal test (cell free fetal DNA analysis on maternal blood), performed for advanced parental age and use of assisted reproductive technique, evidenced a partial 3q trisomy. Then, invasive cytogenetic (standard and molecular) investigations, carried out through amniocentesis, confirmed and defined a 3q27.1-q29 duplication spanning 10.9 Mb, and including about 80 genes. Our patient showed clinical findings (typical facial dysmorphic features, esotropia, short neck, atrial septal defect, hepatomegaly, mild motor delay) compatible with partial trisomy 3q syndrome diagnosis, in addition to pre- and postnatal overgrowth. Conclusions: Advanced parental age increases the probability of chromosomal and/or genomic anomalies, while ART that of epigenomic defects. Both conditions, thus, deserve more careful prenatal monitoring and screening/diagnostic investigations. Among the latter, cell free fetal DNA testing can detect large segmental aneuploidies, along with chromosomal abnormalities. It identified in our patient a wide 3q rearrangement, then confirmed and defined through invasive molecular cytogenetic analysis. Neonatologists and pediatricians must be aware of the potential risks associated to duplication syndromes. Therefore, they should offer to affected subjects an adequate management and early and careful follow-up. These may be able to guarantee to patients satisfactory growth and development profiles, prevent and/or limit neurodevelopmental disorders, and timely recognition of complications. [ABSTRACT FROM AUTHOR]

Background: Abortion stigma likely affects the terminology abortion patients, providers and the public use or avoid using to refer to abortion care. Knowing the terminology people seeking abortion prefer could help inform the language used in clinical interactions and improve patients' experiences with abortion care. However, research in the U.S. has not examined patients' preferences in this area or whether terminology preferences vary by participant characteristics, in the way that experiences of stigma vary across different contexts and communities. This study aims to describe preferred terminology among people presenting for abortion care and to explore the pregnancy-related characteristics associated with these preferences. Methods: We surveyed abortion patients about their experiences accessing abortion care, including preferred terms for the procedure. Respondents could mark more than one term, suggest their own term, or indicate no preference. We recruited people ages 15–45 seeking abortion from four U.S. abortion facilities located in three states (California, Illinois, and New Mexico) from January to June 2019. We used descriptive statistics and multivariable multinomial logistic regression to explore associations between respondents' pregnancy-related characteristics and their preferred terminology. Results: Among the 1092 people approached, 784 (77%) initiated the survey and 697 responded to the terminology preference question. Most participants (57%, n = 400) preferred only one term. Among those participants, "abortion" (43%) was most preferred, followed by "ending a pregnancy" (29%), and "pregnancy termination" (24%). In adjusted multivariable models, participants who worried "very much" that other people might find out about the abortion (29%) were significantly more likely than those who were "not at all" worried (13%) to prefer "ending a pregnancy" over having no preference for a term (adjusted relative risk ratio: 2.68, 95% Confidence Interval: 1.46–4.92). Conclusions: People seeking abortion have varied preferences for how they want to refer to their abortions, in particular if they anticipate abortion stigma. Findings can be useful for clinicians and researchers so that they can be responsive to people's preferences during clinical interactions and in the design and conduct of abortion research. [ABSTRACT FROM AUTHOR]

Background: Retained products of conception can occur with induced abortion during early-term pregnancy, induction of labor during mid-term pregnancy, drug-induced abortion, miscarriage, cesarean delivery, or full-term normal delivery. Compared with traditional dilation and curettage, hysteroscopy is a safer and more effective treatment method for retained products of conception. This study aimed to report the efficacy of hysteroscopy for treating retained products of conception and to share our new clinical perspectives. Methods: This retrospective, single-center study was conducted at a tertiary hospital in Chengdu, China. We included 36 patients with retained products of conception who underwent hysteroscopy at our hospital. Results: Our study reported a complete removal rate of 80.5% (29/36) with one procedure. The normal menstruation recovery rate during 1 year of follow-up was 91.6% (33/36). A low rate of postoperative intrauterine adhesions (2.8% [1/36]) was also reported. Conclusion: Our retrospective study elucidated the use of hysteroscopy for retained products of conception. We also shared new perspectives regarding hysteroscopy and optimal surgical methods for treating retained products of conception as well as our experience treating residual products with hysteroscopy. To our knowledge, no other study has shared similar experiences. [ABSTRACT FROM AUTHOR]

Background: Alterations in the epigenome are a risk factor in multiple disease states. We have demonstrated in the past that disruption of the epigenome during early pregnancy or periconception, as demonstrated by altered methylation, may be associated with both assisted reproductive technology and undesirable clinical outcomes at birth, such as low birth weight. We have previously defined this altered methylation, calculated based on statistical upper and lower limits of outlier CpGs compared to the population, as an 'outlier methylation phenotype' (OMP). Our aim in this study was to determine whether children thus identified as possessing an OMP at birth by DNA methylation in cord blood persist as outliers in early childhood based on salivary DNA methylation. Results: A total of 31 children were included in the analysis. Among 24 children for whom both cord blood DNA and salivary DNA were available, DNA methylation patterns, analyzed using the Illumina Infinium MethylationEPIC BeadChip (850 K), between cord blood at birth and saliva in childhood at age 6–12 years remain stable (R2 range 0.89–0.97). At birth, three out of 28 children demonstrated an OMP in multiple cord blood datasets and hierarchical clustering. Overall DNA methylation among all three OMP children identified as outliers at birth was remarkably stable (individual R2 0.908, 0.92, 0.915), even when only outlier CpG sites were considered (R2 0.694, 0.738, 0.828). Conclusions: DNA methylation signatures in cord blood remain stable over time as demonstrated by a strong correlation with epigenetic salivary signatures in childhood. Future work is planned to identify whether a clinical phenotype is associated with OMP and, if so, could undesirable clinical outcomes in childhood and adulthood be predicted at birth. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a common gynecologic disorder related to abnormal circadian rhythm. Therefore, we aimed to find whether the level of melatonin, a rhythm regulating hormone changed in the ovarian microenvironment in this disease.Methods: The melatonin concentrations in follicular fluid (FF) were measured in 35 PCOS and 36 non-PCOS women undergoing in vitro fertilization (IVF) treatment.Results: The FF melatonin concentration was significantly lower in PCOS women than non-PCOS women (p = 0.045) and it was found positively correlated with serum basal FSH level (r = 0.308, p = 0.013). In IVF procedures, there was no significant difference in the fertilization rate of oocytes between the two groups, but the high-quality embryogenesis rate on the third day of the PCOS group was significantly lower than that of the control group (p = 0.042), which showed a weak positive correlation with the FF melatonin concentration (rs = 0.240, p = 0.044). Furthermore, there was no significant difference in overall pregnancy outcome. The PSQI questionnaire showed that sleep disorders were more likely to exist in the PCOS group, though there was no significant difference.Conclusion: The obtained results suggested PCOS women had lower melatonin concentrations in the ovarian microenvironment. [ABSTRACT FROM AUTHOR]

Background: Female sex workers (FSW) in sub-Saharan Africa are disproportionately affected by HIV and are critical to engage in HIV prevention, testing and care services. We describe the design of our evaluation of the 'AMETHIST' intervention, nested within a nationally-scaled programme for FSW in Zimbabwe. We hypothesise that the implementation of this intervention will result in a reduction in the risk of HIV transmission within sex work.Methods: The AMETHIST intervention (Adapted Microplanning to Eliminate Transmission of HIV in Sex Transactions) is a risk-differentiated intervention for FSW, centred around the implementation of microplanning and self-help groups. It is designed to support uptake of, and adherence to, HIV prevention, testing and treatment behaviours among FSW. Twenty-two towns in Zimbabwe were randomised to receive either the Sisters programme (usual care) or the Sisters programme plus AMETHIST. The composite primary outcome is defined as the proportion of all FSW who are at risk of either HIV acquisition (HIV-negative and not fully protected by prevention interventions) or of HIV transmission (HIV-positive, not virally suppressed and not practicing consistent condom use). The outcome will be assessed after 2 years of intervention delivery in a respondent-driven sampling survey (total n = 4400; n = 200 FSW recruited at each site). Primary analysis will use the 'RDS-II' method to estimate cluster summaries and will adapt Hayes and Moulton's '2-step' method produce adjusted effect estimates. An in-depth process evaluation guided by our project trajectory will be undertaken.Discussion: Innovative pragmatic trials are needed to generate evidence on effectiveness of combination interventions in HIV prevention and treatment in different contexts. We describe the design and analysis of such a study.Trial Registration: Pan African Clinical Trials Registry PACTR202007818077777 . Registered on 2 July 2020. [ABSTRACT FROM AUTHOR]

Background: Some persons conceived with donor gametes react negatively when they found their birth via donor conception. They request access to information about and seek to communicate with the donor. However, some countries mandate donor anonymity. Other countries allow donor-conceived persons to access donor information, but they can only use this access if their parents have disclosed donor conception to them. We investigated a thorny issue of donor conception: whether donor conception should be shifted from an anonymous basis to a non-anonymous basis.Methods: We review the issues and concerns regarding donor conception. We then consider the impact of direct-to-consumer genetic testing on donor conception, as well as the influence of donor conception on offspring's identity and the potential of different types of donors. To discuss the future policy of donor conception, the policies on the anonymity of gamete donors were investigated using publicly-available documents in 15 countries.Results: The aim of mandating donor anonymity is to protect the privacy of the donor and intended parents. However, the diffusion of direct-to-consumer genetic testing may make it impossible to maintain anonymity. Birth via donor conception shapes the offspring's identity, and the donor may further influence the development of offspring's identity through communications. It remains important to disclose donor conception to donor-conceived offspring and to provide them with donor information. However, that information might be insufficient for some donor-conceived persons. Here are benefits to having open-identity donors and known donors. Such donors can make an agreement with the parents regarding future communication with the offspring, although both sides should respect privacy. Subsequent counseling for all parties involved can result in better tripartite communication agreements.Conclusions: In sum, ethical and practical issues that complicate donor anonymity are driving a shift to non-anonymous donor conception, in which all parties come to a communication agreement. To pave the way for such a donor conception system, transitional measures can be put into place. For countries that already adopted non-anonymous donor conception, ensuring the communication agreements is important to protect the rights of parents, donor, and offspring. [ABSTRACT FROM AUTHOR]

Background: A significant proportion (20-59%) of people living with HIV in sub-Saharan Africa desire childbearing, are of reproductive age, and are in sero-different relationships (~50%). Thus it is plausible that some portion of new HIV transmissions are due to attempts to become pregnant. Safer conception (SC) methods that effectively reduce the risk of HIV transmission exist and can be made available in resource-constrained settings. Few studies in the region, and none in Botswana, have quantitatively examined the correlates of information, motivation, and behavioral skills for SC uptake.Methods: We surveyed 356 women living with HIV from 6/2018 to 12/2018 at six public-sector health clinics in Gaborone, Botswana. Participants were 18-40 years old, not pregnant, and desired future children or were unsure about their childbearing plans. We examined correlates of SC information, motivation, and behavioral skills using nested linear regression models, adjusting for socio-demographic, interpersonal, and structural variables.Results: Knowledge of SC methods varied widely. While some SC methods were well known (medical male circumcision by 83%, antiretroviral therapy for viral suppression by 64%), most other methods were known by less than 40% of participants. Our final models reveal that stigma as well as relationship and partner factors affect SC information, motivation, and behavioral skills. Both internalized childbearing stigma (ß=-0.50, 95%CI:-0.17, -0.02) and perceived community childbearing stigma were negatively associated with SC information (ß=-0.09, 95%CI:-0.80, -0.21). Anticipated (ß=-0.06, 95%CI:-0.12, -0.003) and internalized stigma (ß=-0.27, 95%CI:-0.44; -0.10) were associated with decreased SC motivation, while perceived community childbearing stigma was associated with increased SC motivation (ß=0.07, 95%CI:0.02, 0.11). Finally, internalized childbearing stigma was associated with decreased SC behavioral skills (ß=-0.80, 95%CI: -1.12, -0.47) while SC information (ß=0.24, 95%CI:0.12, 0.36), motivation (ß=0.36, 95%CI:0.15, 0.58), and perceived partner willingness to use SC (ß=0.47, 95%CI:0.36, 0.57) were positively associated with behavioral skills CONCLUSIONS: Low SC method-specific information levels are concerning since almost half (47%) of the study participants reported they were in sero-different relationships and desired more children. Findings highlight the importance of addressing HIV stigma and partner dynamics in interventions to improve SC information, motivation, and behavioral skills. [ABSTRACT FROM AUTHOR]

Background: Research has indicated a lack of disease-specific reproductive knowledge among patients with Inflammatory Bowel Disease (IBD) and this has been associated with increased "voluntary childlessness". Furthermore, a lack of knowledge may contribute to inappropriate medication changes during or after pregnancy. Decision aids have been shown to support decision making in pregnancy as well as in multiple other chronic diseases. A published decision aid for pregnancy in IBD has not been identified, despite the benefit of pre-conception counselling and patient desire for a decision support tool. This study aimed to develop and test the feasibility of a decision aid encompassing reproductive decisions in the setting of IBD.Methods: The International Patient Decision Aid Standards were implemented in the development of the Pregnancy in IBD Decision Aid (PIDA). A multi-disciplinary steering committee was formed. Patient and clinician focus groups were conducted to explore themes of importance in the reproductive decision-making processes in IBD. A PIDA prototype was designed; patient interviews were conducted to obtain further insight into patient perspectives and to test the prototype for feasibility.Results: Issues considered of importance to patients and clinicians encountering decisions regarding pregnancy in the setting of IBD included fertility, conception timing, inheritance, medications, infant health, impact of surgery, contraception, nutrition and breastfeeding. Emphasis was placed on the provision of preconception counselling early in the disease course. Decisions relating to conception and medications were chosen as the current focus of PIDA, however content inclusion was broad to support use across preconception, pregnancy and post-partum phases. Favourable and constructive user feedback was received.Conclusions: The novel development of a decision aid for use in pregnancy and IBD was supported by initial user testing. [ABSTRACT FROM AUTHOR]

Background: The fear of infertility or delayed return to fertility is a common barrier to contraceptive use in sub-Saharan Africa, particularly among young or nulliparous women. Global evidence on return to pregnancy after method discontinuation suggests these fears may be misplaced; yet the topic has not been widely studied in sub-Saharan Africa nor by age and parity group. Methods: Reproductive calendar data from recent Demographic and Health Surveys of 15 sub-Saharan African countries were used to analyze time-to-pregnancy following discontinuation of a contraceptive method with the reason to become pregnant. The probability of pregnancy at 12 months was estimated using single-decrement life tables run by type of method discontinued, age and parity. Results are presented by region: francophone West Africa, anglophone West Africa and East Africa. Results: The 12-month probability of pregnancy after discontinuation of contraception to become pregnant was 73.0% in francophone West Africa, 78.8% in anglophone West Africa, and 82.0% in East Africa. Our results showed significant regional differences in return to pregnancy by 12 months, with probabilities in francophone West Africa being significantly lower than in anglophone West Africa or East Africa. A lower return to pregnancy by 12 months was seen among women ages 35–49 years and was lowest after discontinuation of a hormonal method for all age groups. Differences by parity group were only evident after discontinuation of hormonal methods in francophone West Africa. Conclusions: Sustainable gains in increasing contraceptive uptake, especially among youth, may be difficult to achieve without information and counseling that address concerns about infertility and potential delays in return to pregnancy following use of hormonal methods. Plain English summary: The fear of infertility or delayed return to fertility is a common barrier to contraceptive use in sub-Saharan Africa, particularly among young or childless women. Global evidence on the time it takes to become pregnant after the discontinuation of a contraceptive method suggests these fears may be misplaced; yet the topic has not been widely studied in sub-Saharan Africa. Data from recent Demographic and Health Surveys of 15 sub-Saharan African countries were used to analyze the time it takes to become pregnant after discontinuation of a contraceptive method with the reason to become pregnant. The probability of becoming pregnant by 12 months was estimated using a life table approach. Results were compared by type of method discontinued, age and whether women had any children, in three regions of sub-Saharan Africa. Our findings show that the 12-month probability of pregnancy after discontinuation of contraception to become pregnant was 73.0% in francophone West Africa, 78.8% in anglophone West Africa, and 82.0% in East Africa. A lower return to pregnancy by 12 months was seen among women ages 35–49 years and was lowest after discontinuation of a hormonal method for all age groups. Differences by whether women had any children were only evident after discontinuation of hormonal methods in francophone West Africa. The findings indicate that sustainable gains in increasing contraceptive uptake, especially among youth, may be difficult to achieve without information and counseling that address concerns about infertility and potential delays in return to pregnancy following use of hormonal methods. [ABSTRACT FROM AUTHOR]

Background: Safer conception counseling (SCC) to promote the use of safer conception methods (SCM) is not yet part of routine family planning or HIV care. Guidelines for the use of SCM have been published, but to date there are no published controlled evaluations of SCC. Furthermore, it is unknown whether standard methods commonly used in resource constrained settings to integrate new services would be sufficient, or if enhanced training and supervision would result in a more efficacious approach to implementing SCC.Methods: In a hybrid, cluster randomized controlled trial, six HIV clinics were randomly assigned to implement the SCC intervention Our Choice using either a high (SCC1) or low intensity (SCC2) approach (differentiated by amount of training and supervision), or existing family planning services (usual care). Three hundred eighty-nine HIV clients considering childbearing with an HIV-negative partner enrolled. The primary outcome was self-reported use of appropriate reproductive method (SCM if trying to conceive; modern contraceptives if not) over 12 months or until pregnancy.Results: The combined intervention groups used appropriate reproductive methods more than usual care [20.8% vs. 6.9%; adjusted OR (95% CI)=10.63 (2.79, 40.49)], and SCC1 reported a higher rate than SCC2 [27.1% vs. 14.6%; OR (95% CI)=4.50 (1.44, 14.01)]. Among those trying to conceive, the intervention arms reported greater accurate use of SCM compared to usual care [24.1% vs. 0%; OR (95% CI)=91.84 (4.94, 1709.0)], and SCC1 performed better than SCC2 [34.6% vs. 11.5%; OR (95% CI)=6.43 (1.90, 21.73)]. The arms did not vary on modern contraception use among those not trying to conceive. A cost of $631 per person was estimated to obtain accurate use of SCM in SCC1, compared to $1014 in SCC2.Conclusions: More intensive provider training and more frequent supervision leads to greater adoption of complex SCM behaviors and is more cost-effective than the standard low intensity implementation approach.Trial Registration: Clinicaltrials.gov, NCT03167879 ; date registered May 23, 2017. [ABSTRACT FROM AUTHOR]

Background: For couples affected by HIV, and serodifferent couples in particular, pregnancy desire is often juxtaposed against the risk of HIV transmission between the couple and the potential neonate leading to thinking about measures to minimize risk of HIV transmission. We assess the use of fertility awareness methods [FAM] and evaluate the drivers of alignment between indicators of fertility and sexual behavior among HIV-serodifferent couples desiring pregnancy. Methods: HIV-serodifferent couples from Thika, Kenya were enrolled into an open-label pilot evaluation of safer conception strategies. Women responded to daily 7-item short message service [SMS] surveys on FAM and sexual activity. Menstrual cycles were categorized as having condomless sex aligned, not aligned, or partially aligned to the predicted peak fertility. We used binomial logit models with generalized estimating equations to assess alignment between condomless sex during peak fertility days and FAM results. We used Cox proportional hazards to compare pregnancy incidence among months with sex and peak fertility aligned and mis-aligned. Results: A total of 6929 SMS surveys across 252 menstrual cycles of 65 women were included. Reporting "sticky" cervical mucus (adjusted odds ratio [aOR]: 2.25, 95% confidence interval [95% CI]: 1.30, 3.90) and positive ovulation prediction kit [OPK] result (aOR: 2.07, 95% CI: 1.11, 3.86) were associated with increased likelihood of alignment of condomless sex during peak fertility. Pregnancy incidence was statistically similar among periods with sex aligned and not aligned with peak fertility. Conclusions: Among women engaged in a comprehensive safer conception program, a moderate percentage of women aligned condomless sex and predicted peak fertility days at least once. While FAM, particularly cervical mucus and OPK, are an inexpensive option for couples to consider using as a component of their safer conception strategies, antiretroviral-based strategies remain important to minimize risk. [ABSTRACT FROM AUTHOR]

Background: The health of a woman before conception not only influences the outcome of her pregnancy but also the lifelong health of mother and child. Many women in the UK are inadequately prepared for pregnancy, with reports of a high prevalence of smoking, low folic acid supplement use, and suboptimal diet and physical activity. Get Ready! will link an online digital tool to identify women planning pregnancy most at risk of complications with a personalised intervention to improve health behaviours and biomarkers of metabolic health. Methods: Women planning pregnancy will be identified from a free and widely used online preconception tool. A short online screening questionnaire will then be used to recruit women considered to be at high metabolic risk. Eligibility criteria include resident in the UK, age > 18–< 50 years, BMI ≥ 23 kg/m2 (South Asian) or ≥ 25 kg/m2 (all other ethnicities), and plus one or more of the following: 1st degree relative with type 2 diabetes, previous gestational diabetes (GDM), previous baby > 4 kg, or high risk ethnicity for GDM. Eligible women who consent to participate will be enrolled in a commercially available preconception intervention (Prepare Plans, LiveSmart UK Ltd). Following an online health assessment and home blood test, women will be provided with individualised lifestyle advice and coaching by dietitians. Process evaluation will provide an assessment of implementation of the intervention. Change in health behaviours and biomarkers of metabolic health will also be examined. Discussion: Suboptimal health behaviours amongst women planning pregnancy are widely prevalent in the UK. Personalised health checks and coaching are especially important for women at risk of pregnancy complications. Get Ready! introduces a novel approach to identifying high risk women planning pregnancy and provision of a targeted intervention. Registration: Trial sponsor: King's College London. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrinopathies in women during the reproductive age. Herbal medicines are used increasingly alone or in supplement with chemical medicines for the treatment of different diseases and dysfunctions. This study was aimed to evaluate the effects of lutein and nettle (Urtica dioica) extract on the biochemical parameters and the reproductive function in the PCOS model of mice. Methods: Following the induction of PCOS by dehydroepiandrosterone (DHEA), the mice (n = 98) were randomly assigned into seven groups, each consisting of fourteen mice; the groups were included control group (received solvent), PCOS group (received 6 mg/100 g B.W/day IP, DHEA for 21 days), PCOS+ Nettle extract (200 and 400 mg/kg), PCOS+ Lutein (125 and 250 mg/kg), and PCOS+ NL (200 mg/kg nettle extract and 125 mg/kg lutein). The nettle extract and lutein were administrated using gavage for 30 consecutive days after PCOS induction. Malondialdehyde (MDA), total antioxidant capacity (TAC), and estrogen were measured in serum, ovary, and uterus samples by the ELISA method. The total number of oocytes, oocyte quality, fertilization rate, 2-cell blastocyst, and arrested embryos (type I, type II, and type III) were also investigated. Results: A combination treatment of the nettle and lutein produced the lowest concentration of MDA in comparison to other groups which affected by the PCOS. The lowest level of TAC was observed in the PCOS group without treatment. The number of oocytes, oocyte quality, fertilization rate, and 2-cell blastocyst were significantly higher in the control group, but the lowest values were observed in the PCOS group without any treatment. Conclusions: The most favorable findings include improving antioxidant capacity, oocyte and embryo quality were observed in the PCOS+ 125 L group. [ABSTRACT FROM AUTHOR]

Background: Hypothermic preservation of boar semen is considered a potential method for omitting antibiotics from insemination doses, thereby contributing to the global antibiotic resistance defence strategy. The main challenges are chilling injury to spermatozoa and bacterial growth during semen storage leading to reduced fertility. Objectives: To examine chilling injury and the number and type of bacteria in boar semen stored at 5 °C in the absence of antibiotics, and to assess the applicability of hypothermic semen storage under field conditions. Material and methods: Boar ejaculates were extended with AndroStar® Premium, stored at 17 °C with and at 5 °C without antibiotics and tested for functional sperm parameters by flow cytometry. Raw semen and extended samples were investigated bacteriologically. Fertility was evaluated after once-daily inseminations of 194 sows in a field study. Results: Lethal sperm damage assessed by motility and membrane integrity was low throughout storage in both experimental groups. Sublethal chilling effects based on the decrease of viable spermatozoa with low membrane fluidity were higher (P < 0.05) up until 72 h in sperm stored at 5 °C compared to 17 °C but did not differ after 144 h. After 72 h, incubation in capacitating medium for 60 min induced a similar decrease in viable sperm with high mitochondria membrane potential and low cytosolic calcium in both groups. In semen stored at 5 °C, bacteria counts were below 103 CFU/mL and the bacteria spectrum was similar to that of raw semen. In 88% of 34 boars, cooled semen fulfilled the requirements for insemination. Fertility was high and did not differ (P > 0.05) between sow groups inseminated with semen stored antibiotic-free at 5 °C and semen stored at 17 °C with antibiotics. Conclusion: Despite subtle chilling effects and low bacterial numbers, antibiotic-free hypothermic storage of boar semen offers the possibility to reduce the use of antibiotics in pig insemination. However, strict sanitary guidelines must be maintained and further evidence of efficiency under field conditions is considered desirable. [ABSTRACT FROM AUTHOR]

Background: HIV-related maternal deaths and HIV infection among infants remain unacceptably high across sub-Saharan Africa despite increased antenatal care attendance and provision of antiretroviral therapy to pregnant women. In the Jamii Bora ("Better Family" in Swahili) Study, we seek to test the efficacy of an interdependence theory-based couple intervention. The intervention reaches pregnant women and male partners through home visits by male-female pairs of lay health workers. The aim is to increase access to home-based couples' HIV testing and counseling services to improve family health.Methods: This is a three-arm randomized control trial among 1080 pregnant women 15 years of age or older, living with their male partners, and who have not undergone couples' HIV testing and counseling in Kisumu and Migori Counties in Kenya. Couples will be randomized into three groups: home-based couple visits, HIV self-testing kits for couple use, or standard care (male partner clinic invitation letters). Participants will be followed up to 18 months postpartum. The study has three aims: in aim 1, we will determine the effects of the intervention on our primary outcome of couple HIV testing, compared to HIV self-testing kits and standard care; in aim 2, we will examine the intervention impact on HIV prevention behaviors, facility delivery, and postnatal healthcare utilization, as well as secondary health outcomes of maternal viral suppression and HIV-free child survival up to 18 months for couples living with HIV; and in aim 3, we will compare the cost-effectiveness of the home-based couple intervention to the less resource-intensive strategies used in the other two study arms. Assessments with couples are conducted at baseline, late pregnancy, and at months 3, 6, 12, and 18 after birth.Discussion: The results from this study will inform decision-makers about the cost-effective strategies to engage pregnant couples in the prevention of mother-to-child transmission and family health, with important downstream benefits for maternal, paternal, and infant health.Trial Registration: ClinicalTrials.gov NCT03547739 . Registered on May 9, 2018. [ABSTRACT FROM AUTHOR]

Objective: With the ongoing COVID-19 pandemic, large numbers of people will receive one of the several medications proposed to treat COVID-19, including patients of reproductive age. Given that some medications have shown adverse effects on sperm quality, there might be a transgenerational concern. We aim at examining the association between drugs proposed to treat COVID-19 when taken by the father around conception and any pre-term birth or major birth defects in offspring in a nation-wide cohort study using Danish registry data. Offspring whose father filled at least one prescription of the following medications in the 3 months preceding conception were considered exposed: chloroquine, hydroxychloroquine, losartan, azithromycin, naproxen, dexamethasone and prednisone. Results: For azithromycin and naproxen, large numbers of offspring were exposed (> 1800 offspring), and we found no association with adverse birth outcomes. For chloroquine, losartan and dexamethasone, exposure was intermediate (~ 900 offspring), and there was no statistically significant association with birth defects. For hydroxychloroquine and prednisone, exposure was limited (< 300 offspring). Our evidence suggests that azithromycin and naproxen are safe with respect to pre-term birth and birth defects. For the other drugs investigated larger exposures are needed for conclusive statements. [ABSTRACT FROM AUTHOR]

Background: To examine the differences between pregnant women who underwent embryo transfer (ET) and those who conceived naturally, as well as differences in their respective babies, and to determine the causes for these differences, to provide recommendations for women who are planning to undergo ET.Methods: A retrospective cohort study was performed of women who had received ET and those who had natural conception (NC) who received medical services during pregnancy and had their babies delivered at the Shunde Women and Children's Hospital of Guangdong Medical University, China between January 2016 and December 2018. In line with the requirements of the ethics committee, before the formal investigation, we first explained the content of the informed consent of the patient to the patient, and all the subjects included agreed to the content of the informed consent of the patient. Respondents agreed to visit and analyze their medical records under reasonable conditions. Each case in an ET group of 321 women was randomly matched with three cases of NC (963 cases) who delivered on the same day. The demographic information, past history, pregnancy and delivery history, and maternal and neonatal outcomes of the two groups were compared using univariate analysis.Results: Age, duration of hospitalization, number of pregnancies, number of miscarriages, induced abortion, ectopic pregnancy, gestational diabetes mellitus, preeclampsia, gestational anemia, pregnancy risk, mode of fetal delivery, and number of births were significantly different between the two groups (all P < 0.05). However, there were no significant differences in the disease, allergy, infection and blood transfusion histories of the pregnant women, or differences in prevalence of gestational hypothyroidism, gestational respiratory infection, premature rupture of membrane, placental abruption, fetal death, stillbirth, amniotic fluid volume and amniotic fluid clarity between the two groups (all P > 0.05). The percentages for low birth weight and premature birth were significantly higher in the ET group than in the NC group. In contrast, infant gender and prevalence of fetal macrosomia, fetal anomaly, neonatal asphyxia, and extremely low birth weight were not significantly different between the two groups (all P > 0.05).Conclusions: The clinical outcomes of mothers and the birth status of infants were better in the NC group than in the ET group. Maternal health must be closely monitored and improved in the ET group to reduce the incidence of gestational comorbidity and enhance the quality of fetal life. [ABSTRACT FROM AUTHOR]

Background: Female infertility is a worldwide concern and the etiology of infertility has not been thoroughly demonstrated. Although the mouse is a good model system to perform functional studies, the differences between mouse and human also need to be considered. The objective of this study is to elucidate the different molecular mechanisms underlying oocyte maturation and fertilization between human and mouse. Results: A comparative transcriptome analysis was performed to identify the differentially expressed genes and associated biological processes between human and mouse oocytes. In total, 8513 common genes, as well as 15,165 and 6126 uniquely expressed genes were detected in human and mouse MII oocytes, respectively. Additionally, the ratios of non-homologous genes in human and mouse MII oocytes were 37 and 8%, respectively. Functional categorization analysis of the human MII non-homologous genes revealed that cAMP-mediated signaling, sister chromatid cohesin, and cell recognition were the major enriched biological processes. Interestingly, we couldn't detect any GO categories in mouse non-homologous genes. Conclusions: This study demonstrates that human and mouse oocytes exhibit significant differences in gene expression profiles during oocyte maturation, which probably deciphers the differential molecular responses to oocyte maturation and fertilization. The significant differences between human and mouse oocytes limit the generalizations from mouse to human oocyte maturation. Knowledge about the limitations of animal models is crucial when exploring a complex process such as human oocyte maturation and fertilization. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to explore the correlation between serum vitamin D levels in couples undergoing in-vitro fertilisation (IVF) and normal fertilisation process.Methods: Between March 2016 and March 2017, we performed a prospective cohort study at an academic reproductive medicine centre to measure serum 25-hydroxyvitaminD (25-OHD) levels of 1232 couples before controlled ovarian stimulation. Generalized linear regression and binary multivariate logistic regression were employed to assess whether 25-OHD levels in men and women correlated with normal fertilisation rates and low fertilisation rate (LFR).Results: Serum 25-OHD levels in women were classified into three groups: Group A, less than 10%; Group B, between 10 and 90%; and Group C, greater than 90%. Using generalized linear regression, we observed that female 25-OHD levels were related to normal fertilisation rates. Adjusted normal fertilisation rates from Group A to Group C in women were 59.50, 62.72, and 66.13%, respectively (P = 0.007). After binary logistic regression analysis, for women, compared with Group C, the ORs for LFR were 4.814 in Group A (95% CI, 1.266-18.309, P = 0.021) and were 3.204 in Group B (95% CI, 0.949-10.812, P = 0.061). Male 25-OHD levels were not related to the probability of low fertilisation rate (P > 0.05).Conclusions: Circulating 25-OHD concentrations in women appear to be associated with normal fertilisation rates and low fertilisation rates in IVF cycles, but not in men. A further randomized controlled trial with vitamin D supplementation is needed to demonstrate whether female vitamin D levels exert an effect on the normal fertilisation process.Trial Registration: https://clinicaltrials.gov/;NCT03305510; Registered 08 October 2017 - Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Health prior to conception can significantly impact offspring health, however, a clear definition of the attributes of the preconception population is currently lacking. We aimed to use existing literature to explore the concept and attributes of a preconception population by: [1] identifying characteristics and research recruitment methods; and [2] generating an attribute-based working definition of a preconception population.Methods: A rapid review of current literature using CINAHL and the subject heading 'pre-pregnancy care' was conducted (Stage 1). Data extracted included definitions of preconception, participant inclusion/exclusion criteria, participant characteristics, and recruitment methods. Stage 2 involved a wider search of relevant publications beyond peer-reviewed literature followed by a concept analysis of the phrase "preconception population" applying Walker and Avant's framework (Stage 2).Results: Twenty-three papers (19 studies) were included in Stage 1. "Preconception" was explicitly defined in one study. Twelve studies specified participants must be planning a pregnancy. Stage 2 included 33 publications. Four key perspectives for the concept of the preconception population were derived: [1] intentional; [2] potential; [3] public health; and [4] life course.Conclusions: Adopting these perspectives may allow researchers to accurately define, identify and recruit preconception populations and to develop interventions that are appropriately broad or tailored depending on population needs. We hope the definitions will facilitate research with this population and will subsequently improve the wellbeing of preconception men and women, which is essential to ensuring the health of future generations. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy (ART) demonstrates high efficacy in reducing the risk of HIV transmission to sexual partners. However, it is not clear if the use of pre-exposure prophylaxis (PrEP) in HIV-1-serodiscordant couples is necessary during natural conception when the HIV-positive partner exhibits a suppressed viral load. The purpose of this study was to assess the role of PrEP during natural conception in this population.Methods: A retrospective, multicenter study was conducted in a cohort of HIV-1-serodiscordant couples (positive man, negative woman) with childbearing desires. HIV-positive male partners were treated with ART and achieved viral suppression for more than half a year. The HIV-negative female partners were either treated with PrEP or not treated with PrEP, and outcomes were compared between the two treatment groups.Results: Of 246 HIV-1-serodiscordant couples in whom the HIV-positive partner achieved viral suppression, 104 seronegative women were treated with PrEP during natural conception and 142 seronegative women were not treated with PrEP. There were 410 condom-less sexual acts in couples treated with PrEP and 615 condom-less sexual acts in couples not treated with PrEP. We observed no instances of HIV transmission in HIV-1-serodiscordant couples with or without the use of PrEP during the process of natural conception.Conclusions: Our results show that PrEP had minimal influence in reducing the risk of HIV transmission during natural conception in HIV-1-serodiscordant couples with a stably suppressed viral load. Thus, it may be an acceptable option for HIV-negative partners to not use PrEP during the process of natural conception if the HIV-positive partner has achieved viral suppression for more than half a year. [ABSTRACT FROM AUTHOR]

Background: Recent human transcriptomic analyses revealed a very large number of testis-enriched genes, many of which are involved in spermatogenesis. This comprehensive transcriptomic data lead us to the question whether positive selection was a decisive force influencing the evolution and variability of testis-enriched genes in humans. We used two methodological approaches to detect different levels of positive selection, namely episodic positive diversifying selection (i.e., past selection) in the human lineage within primate phylogeny, potentially driven by sperm competition, and recent positive directional selection in contemporary human populations, which would indicate adaptation to different environments. Results: In the human lineage (after correction for multiple testing) we found that only the gene TULP2, for which no functional data are yet available, is subject to episodic positive diversifying selection. Using less stringent statistical criteria (uncorrected p-values), also the gene SPATA16, which has a pivotal role in male fertility and for which episodes of adaptive evolution have been suggested, also displays a putative signal of diversifying selection in the human branch. At the same time, we found evidence for recent positive directional selection acting on several human testis-enriched genes (MORC1, SLC9B1, ROPN1L, DMRT1, PLCZ1, RNF17, FAM71D and WBP2NL) that play important roles in human spermatogenesis and fertilization. Most of these genes are population-specifically under positive selection. Conclusion: Episodic diversifying selection, possibly driven by sperm competition, was not an important force driving the evolution of testis-enriched genes in the human lineage. Population-specific, recent positive directional selection suggests an adaptation of male reproductive genes to different environmental conditions. Positive selection acts on eQTLS and sQTLs, indicating selective effects on important gene regulatory functions. In particular, the transcriptional diversity regulated by sQTLs in testis-enriched genes may be important for spermatocytes to respond to environmental and physiological stress. [ABSTRACT FROM AUTHOR]

Background: Women with hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH) experience more frequent and severe angioedema attacks compared with men. Fluctuations in female sex hormones can influence HAE attack frequency and severity. Subcutaneous C1-INH (C1-INH [SC]) is indicated as routine prophylaxis to prevent HAE attacks. In this post hoc subgroup analysis, we evaluated the efficacy and safety of C1-INH (SC) in female subjects with HAE-C1INH enrolled in an open-label extension of the pivotal phase III COMPACT trial. Methods: In this multicenter, randomized, parallel-arm trial, eligible subjects (age ≥ 6 years with ≥ 4 attacks over 2 consecutive months) received C1-INH (SC) 40 IU/kg or 60 IU/kg twice weekly for 52 to 140 weeks. Analyses of efficacy endpoints were performed for all female subjects and those of childbearing age (age ≥ 15 to ≤ 45 years), including subjects who became pregnant during the evaluation period. Results: Overall, 91% (69/76) of female subjects were classified as responders (≥ 50% reduction in HAE attacks relative to the pre-study period); 82% experienced < 1 attack/4 weeks. The median number of attacks/month was 0.10, with 96% median reduction in attacks relative to the pre-study period. Results were similar in the subgroup of subjects of childbearing age. Four women who became pregnant during the trial and were exposed to C1-INH (SC) during the first trimester delivered healthy babies with no congenital abnormalities. Conclusions: C1-INH (SC) prophylaxis was safe and effective in women with HAE-C1INH, including those of childbearing age. Four women exposed to C1-INH (SC) during the first trimester had uneventful pregnancies and delivered healthy babies. Trial registration Clinicaltrials.gov identifier NCT02316353 (Registered December 10, 2014); https://clinicaltrials.gov/ct2/show/NCT02316353. [ABSTRACT FROM AUTHOR]

Background: The period from conception to two years of life denotes a critical window of opportunity for promoting optimal growth and development of children. Poor nutrition and health in women of reproductive age and during pregnancy can negatively impact birth outcomes and subsequent infant survival, health and growth. Studies to improve birth outcomes and to achieve optimal growth and development in young children have usually tested the effect of standalone interventions in pregnancy and/or the postnatal period. It is not clearly known whether evidence-based interventions in the different domains such as health, nutrition, water sanitation and hygiene (WASH) and psychosocial care, when delivered together have a synergistic effect. Further, the effect of delivery of an intervention package in the pre and peri-conception period is not fully understood. This study was conceived with an aim to understand the impact of an integrated intervention package, delivered across the pre and peri-conception period, through pregnancy and till 24 months of child age on birth outcomes, growth and development in children.Methods: An individually randomized controlled trial with factorial design is being conducted in urban and peri-urban low- to mid-socioeconomic neighbourhoods in South Delhi, India. 13,500 married women aged 18 to 30 years will be enrolled and randomized to receive either the pre and peri-conception intervention package or routine care (first randomization). Interventions will be delivered until women are confirmed to be pregnant or complete 18 months of follow up. Once pregnancy is confirmed, women are randomized again (second randomization) to receive either the intervention package for pregnancy and postnatal period or to routine care. Newborns will be followed up till 24 months of age. The interventions are delivered through different study teams. Outcome data are collected by an independent outcome ascertainment team.Discussion: This study will demonstrate the improvement that can be achieved when key factors known to limit child growth and development are addressed together, throughout the continuum from pre and peri-conception until early childhood. The findings will increase our scientific understanding and provide guidance to nutrition programs in low- and middle-income settings.Trial Registration: Clinical Trial Registry - India #CTRI/2017/06/008908; Registered 23 June 2017, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies. [ABSTRACT FROM AUTHOR]

Background: It is well-established that couples' fecundities vary widely. Each couple has a relatively constant monthly probability of conceiving, which can vary from zero to quite high. This underlying probability is usually expressed as the time (number of menstrual cycles) the couple requires to conceive. Couples with high fecundity will, on average, need fewer cycles than couples with low fecundity. It is also well-documented that almost all human populations exhibit seasonal variation in births. Most European countries show seasonal variation that usually peak in the spring and are the lowest during the last quarter of the year. The increasingly strong pattern of depressed birth rates in November and December is likely explained by the December–January cut-off threshold for Swedish pupils' school entry and their parents increasing awareness of the negative effects on school outcomes for children who are juniors in the school-entry cohort they belong to. To actively plan births for a specific time of the year, couples need to have some knowledge of the time required for them to conceive. Methods: We use the duration between marriage of childless couples and first birth as a proxy measure of couples' fecundity. Based on this time-to-pregnancy measure we study to what extent couples' capacity to conceive affects the seasonality of their second births. We hypothesize that in a society with highly controlled fertility and a strong norm of having at least two children, sub-fertile couples will on average show less seasonal variation in second births. Sub-fertile couples, requiring more time to conceive the first time, will be less likely to try to target a desired birth month for their second child because doing so could jeopardize fulfilling their desired family size. We apply multinomial logistic regressions on 81,998 Swedish couples who married while being childless and subsequently gave birth to at least two children between 1990 and 2012, to investigate fecundity's role in seasonal variation in second births. Results: We found that seasonal variation in second births was strongly associated with couples' observed fecundity, measured as the duration between marriage formation and first birth. Our results support the hypothesis that sub-fertile couples, requiring more time to conceive the first time, show less seasonal variation in second births. The seasonal variations in second order births among couples with normal fecundity shows some similarities to traditional patterns as seen in agricultural and industrial societies of the past, with high numbers of births during the spring, and low numbers during the last quarter of the year. However, two important differences are notable. The characteristic Christmas peak in September has vanished, and the low birth rates in November and December come out much stronger than in the past. Conclusions: The birth seasonality among couples with normal fecundity are what we would expect if couples actively plan their births according to the cut-off date for Swedish pupils' school entry. We argue that our findings support the notion that scheduled childbirth is a reality in contemporary sociality. [ABSTRACT FROM AUTHOR]

Background: This study assessed the effects of propolis alone or combined with insulin on maternal status, pregnancy outcomes and placental oxidative stress in streptozotocin-induced diabetic rats. Methods: Forty female rats were randomly assigned into five groups (n = 8/group) i.e. non-DM (non-diabetes), DM (diabetes), DM + Propolis (diabetes on propolis orally); DM + Insulin (diabetes on insulin subcutaneously) and DM + Combined (diabetes on propolis and insulin) groups. Propolis and insulin were given at 300 mg/kg/day orally and 5.0 IU/kg/day subcutaneously, respectively, for 4 weeks. Results: Fasting blood glucose, conception period, implantation losses, foetal blood glucose and placental oxidative stress markers such as malonaldehyde and protein carbonyl were significantly higher while maternal weight gain, foetal body weight and total antioxidant capacity were significantly lower in DM group compared with non-DM group. These changes were significantly improved in rats treated with propolis or insulin alone with greater significant effects in rats treated with both propolis and insulin. Conclusion: This study may suggest the protective effects of propolis against DM-induced impaired pregnancy outcomes and placental oxidative stress with greater effects when combined with insulin. [ABSTRACT FROM AUTHOR]

Objectives: Primary Objective: To determine if pre-exposure prophylaxis (PrEP) with 400mg hydroxychloroquine (HCQ), taken orally once daily reduces microbiologically confirmed COVID-19 among front line health care workers at high risk for SARS-CoV-2 exposure. Secondary Objectives: To compare the following between study arms: adverse events; symptomatic COVID-19; duration of symptomatic COVID-19; days hospitalized attributed to COVID-19; respiratory failure attributable to COVID-19 requiring i) non-invasive ventilation or ii) intubation/mechanical ventilation; mortality attributed to COVID-19, number of days unable to work attributed to COVID-19, seroconversion (COVID-19 negative to COVID-19 positive over the study period); ability of participant plasma to neutralize SARS-CoV-2 virus in vitro; To describe short-term psychological distress associated with risk of COVID-19 exposure at 1, 60, 120 days of the study. To explore laboratory markers within participants with confirmed COVID-19: including circulating markers of host immune and endothelial activation in participant plasma and their correlation with disease severity and outcome TRIAL DESIGN: The HEROS study is a two-arm, parallel-group, individually randomized (1:1 allocation ratio), placebo controlled, participant and investigator-blinded, multi-site superiority trial of oral HCQ 400 mg taken once daily for 90 days as PrEP to prevent COVID-19 in health care workers at high risk of SARS-CoV-2 exposure. At 90 days, there is an open label extension wherein all participants are offered a one-month course of HCQ 400mg once daily for PrEP of COVID-19.Participants: Frontline HCWs aged 18 years of age or older, at high risk of SARS-CoV-2 exposure (including staff of emergency departments, intensive care units, intubation teams, COVID-wards, and staff deployed to Long Term Care facilities) of five academic hospitals in downtown Toronto, Canada. Exclusion criteria include: currently pregnant, planning to become pregnant during the study period, and/or breast feeding; known hypersensitivity/allergy to hydroxychloroquine or to 4-aminoquinoline compounds; current use of hydroxychloroquine; known prolonged QT syndrome and/or baseline resting ECG with QTc>450 ms and/or concomitant medications which simultaneously may prolong the QTc that cannot be temporarily suspended/replaced; known pre-existing retinopathy, G6PD deficiency, porphyria, liver disease including cirrhosis, encephalopathy, hepatitis or alcoholism, diabetes on oral hypoglycemics or insulin, or renal insufficiency/failure; disclosure of self-administered use of hydroxychloroquine or chloroquine within 12 weeks prior to study; confirmed symptomatic COVID-19 at time of enrollment.Intervention and Comparator: Intervention: hydroxychloroquine, 400mg (2 tablets) orally per day. Comparator: placebo, two tablets visually identical to the intervention, orally per day MAIN OUTCOMES: The primary outcome is microbiologically confirmed COVID-19 (i.e. SARS-CoV-2 infection). This is a composite endpoint which includes positive results from any validated SARS-CoV-2 diagnostic assay including detection of viral RNA, and/or seroconversion. Participants will be assessed at baseline, and then undergo monthly follow-up at day 30, 60, and 90, 120. At each visit, participants will provide an oropharyngeal sample, blood sample, and will undergo electrocardiogram monitoring of the QTc interval. Secondary outcome measures include: adverse events; symptom duration of COVID-19; days of hospitalization attributed to COVID-19; respiratory failure requiring ventilator support attributed to COVID-19; mortality attributed to COVID-19; total days off work attributed to COVID-19; seropositivity (reactive serology by day 120); and short term psychological impact of exposure to SARS-CoV-2 at day 1, 60, 120 days using the K10, a validated measure of non-specific psychological distress.Randomisation: Within each site, participants will be individually randomized to either the intervention arm with HCQ or the placebo arm using a fixed 1:1 allocation ratio using an interactive web-based response system to ensure concealment of allocation. Randomization schedules will be computer-generated and blocked using variable block sizes.Blinding (masking): All participants, research coordinators, technicians, clinicians and investigators will be blinded to the participant allocation group. Numbers to be randomised (sample size) N=988, randomised into two groups of 494 patients.Trial Status: This summary describes protocol version No. 1.6, May 15, 2020. Recruitment is ongoing - started April 20, 2020 and anticipated end date is July 30, 2021 TRIAL REGISTRATION: ISRCTN.com Identifier: ISRCTN14326006, registered April 14, 2020.Full Protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). [ABSTRACT FROM AUTHOR]

Background: Vasectomy is one of the permanent methods of contraception; however, the risk of conception still exists. Early failure, defined as a postoperative semen analysis showing persistent motile sperm, occurs in 1 in every 250 patients. Late failure, defined as the rejoining of the severed ends of the vas deferens, occurs in 1 in every 2000 patients.Case Presentation: A healthy 37-year-old British male presented to our clinic because his wife had conceived seven years after he had undergone a vasectomy. The result of his semen analysis after the vasectomy was negative, and the histopathological report confirmed that the sample contained tissue from both the left and right vas deferens. His wife conceived seven years after the procedure, and semen analysis at that time confirmed a total of 0.5 million sperm per milliliter of semen in a total semen sample of 6.3 ml. The total number of motile sperm recorded was 2.5 million.Conclusion: This case shows that late recanalization can occur up to seven years after a vasectomy. Patients should be informed prior to the procedure that late recanalization, although rare, may still occur. Post-vasectomy paternity necessitates further counseling to ensure that the patient and the patient's partner fully understand the implications and options available to them. [ABSTRACT FROM AUTHOR]

Background: Chromosome translocations are rare but frequently associated with infertility. The objective of this study is to investigate the feasibility of using chromosomal microarray analysis (CMA) on products of conception (POC) samples as an indicator of parental balanced translocation. From January 2011 to December 2016, CMA using Affymetrix Cytoscan™750K array was performed on 1294 POC samples in our hospital. Karyotyping and fluorescence in situ hybridization (FISH) using parental blood samples were performed to validate the origin of subchromosomal copy number variations (CNVs). Results: In the 1294 cases of POCs, we detected CNVs of terminal duplication and deletion that imply unbalanced translocation derivatives in 16 cases, and accurate diagnosis with the parental study was made in all the cases by karyotyping and/or FISH. In 10/16 (62.5%) of these cases, CNVs were inherited from one carrier parent of balanced translocation (Cases 1 to 10), while 6/16 (37.5%) cases occurred de novo (Cases 11 to 16). Conclusion: This study clearly illustrated the importance of the utilization of CMA on POC, followed by parental karyotyping and FISH to better characterize CNVs. This approach is especially useful for couples in whom one partner carries a cryptic/submicroscopic balanced translocation but has an apparently normal karyotype. [ABSTRACT FROM AUTHOR]

Background: Embryo implantation is crucial for animal reproduction. Unsuccessful embryo implantation leads to pregnancy failure, especially in human-assisted conception. Environmental factors have a profound impact on embryo implantation. Because people are being exposed to more light at night, the influence of long-term light exposure on embryo implantation should be explored. Methods: The effects of long photoperiodic exposure and melatonin on embryo implantation and offspring growth were examined. Long photoperiodic exposure (18:6 h light:dark) was selected to resemble light pollution. Melatonin (10-2, 10-3, 10-4,10-5 M) was added to the drinking water of mice starting at Day 1 (vaginal plugs) until delivery. Results: Melatonin treatment (10-4,10-5 M) significantly increased litter sizes compared to untreated controls (12.9 ± 0. 40 and 12.2 ± 1.01 vs. 11.5 ± 0.43; P < 0.05). The most effective concentration of melatonin (10-4 M) was selected for further investigation. No remarkable differences were found between melatonin-treated mice and controls in terms of the pups' birth weights, weaning survival rates, and weaning weights. Long photoperiodic exposure significantly reduced the number of implantation sites in treated mice compared to controls (light/dark, 12/12 h), and melatonin rescued this negative effect. Mechanistic studies revealed that melatonin enhanced the serum 17β-estradiol (E2) levels in the pregnant mice and upregulated the expression of the receptors MT1 and MT2 and p53 in uterine tissue. All of these factors may contribute to the beneficial effects of melatonin on embryo implantation in mice. Conclusion: Melatonin treatment was associated with beneficial effects in pregnant mice, especially those subjected to long photoperiodic exposure. This was achieved by enhanced embryo implantation. At the molecular level, melatonin administration probably increases the E2 level during pregnancy and upregulates p53 expression by activating MT1/2 in the uterus. All of the changes may improve the microenvironment of the uterus and, thus, the outcomes of pregnancy. [ABSTRACT FROM AUTHOR]

Background: Sperm cryopreservation is the most effective method to preserve male fertility but this is normally used for motile spermatozoa. Thus, only motile spermatozoa are used for cryopreservation in most reproductive medicine centers worldwide. The immotile spermatozoa from some problematic patients are usually discarded, resulting in a missed opportunity of sterility cryopreservation for future assisted reproductive treatments. Many studies have shown that successful fertilization can be obtained after selection of viable sperm from the completely immotile spermatozoa before ICSI. Whether the completely immotile spermatozoa are worth of freezing has not been realized The aim of this study is to explore the clinical value of cryopreservation of immotile spermatozoa. Methods: Completely immotile spermatozoa were collected and frozen, and subsequently viable but immotile frozen-thawed spermatozoa were selected by laser plus for ICSI. Main outcomes included spermatozoa survival index, fertilization rate and good quality embryo rate. Results: After identification by laser, the fresh samples of spermatozoa presented with a mean survival rate of 54. 86% and 26.05%, and this was reduced to 44.13% and 18.13% in frozen-thawed spermatozoa samples, which showed a frozen-thawed spermatozoa survival index of 0.80 and 0.70 in the testicular and ejaculate sperm, respectively. There were no statistically differences in fertilization rate (80% vs80.51%, 75.00% vs 81.48%), cleavage rate (95.45% vs 98.95%, 100.00% vs 95.45%) and good quality embryo rate (40.48% vs 52.13%, 33.33%vs38.10%) between the frozen-thawed immotile spermatozoa group and the routine fresh immotile spermatozoa ICSI group in both testicular and ejaculate sperm, respectively. Conclusions: The results of the study show that completely immotile spermatozoa can be frozen in order to preserve male fertility as long as viable spermatozoa are present. This procedure provides a further possibility for fertility preservation for patients with completely immotile spermatozoa. [ABSTRACT FROM AUTHOR]

Background: Unintended repeat conceptions can result in emotional, psychological and educational harm to young women, often with enduring implications for their life chances. This study aimed to identify which young women are at the greatest risk of repeat unintended pregnancies; which interventions are effective and cost-effective; and what are the barriers to and facilitators for the uptake of these interventions.Methods: We conducted a mixed-methods systematic review which included meta-analysis, framework synthesis and application of realist principles, with stakeholder input and service user feedback to address this. We searched 20 electronic databases, including MEDLINE, Excerpta Medica database, Applied Social Sciences Index and Abstracts and Research Papers in Economics, to cover a broad range of health, social science, health economics and grey literature sources. Searches were conducted between May 2013 and June 2014 and updated in August 2015.Results: Twelve randomised controlled trials (RCTs), two quasi-RCTs, 10 qualitative studies and 53 other quantitative studies were identified. The RCTs evaluated psychosocial interventions and an emergency contraception programme. The primary outcome was repeat conception rate: the event rate was 132 of 308 (43%) in the intervention group versus 140 of 289 (48%) for the control group, with a non-significant risk ratio (RR) of 0.92 [95% confidence interval (CI) 0.78-1.08]. Four studies reported subsequent birth rates: 29 of 237 (12%) events for the intervention arm versus 46 out of 224 (21%) for the control arm, with an RR of 0.60 (95% CI 0.39-0.93). Many repeat conceptions occurred in the context of poverty, low expectations and aspirations and negligible opportunities. Qualitative and realist evidence highlighted the importance of context, motivation, future planning and giving young women a central and active role in the development of new interventions.Conclusions: Little or no evidence for the effectiveness or cost-effectiveness of any of the interventions to reduce repeat pregnancy in young women was found. Qualitative and realist evidence helped to explain gaps in intervention design that should be addressed. More theory-based, rigorously evaluated programmes need to be developed to reduce unintended repeat pregnancy in young women.Trial Registration: PROSPERO, CRD42012003168 . Cochrane registration number: i = fertility/0068. [ABSTRACT FROM AUTHOR]

Background: Traditional testing of miscarriage products involved culture of tissue followed by G-banded chromosome analysis; this approach has a high failure rate, is labour intensive and has a resolution of around 10 Mb. G-banded chromosome analysis has been replaced by molecular techniques in some laboratories; we previously introduced a QF-PCR/MLPA testing strategy in 2007. To improve diagnostic yield and efficiency we have now updated our testing strategy to a more comprehensive QF-PCR assay followed by array CGH. Here we describe the results from the last 5 years of service. Methods: Fetal tissue samples and products of conception were tested using QF-PCR which will detect aneuploidy for chromosomes 13, 14, 15, 16, 18, 21, 22, X and Y. Samples that were normal were then tested by aCGH and all imbalance >1Mb and fully penetrant clinically significant imbalance <1Mb was reported. Results: QF-PCR analysis identified aneuploidy/triploidy in 25.6% of samples. aCGH analysis detected imbalance in a further 9.6% of samples; this included 1.8% with submicroscopic imbalance and 0.5% of uncertain clinical significance. This approach has a failure rate of 1.4%, compared to 30% for G-banded chromosome analysis. [ABSTRACT FROM AUTHOR]

Background: For peritoneal dialysis patients, the likelihood of conception is low and the probability of getting through the pregnancy successfully is even lower. Almost 60 years after the first reported case of a successful pregnancy in a dialysis patient, many issues concerning pregnancy in dialysis patients remain unresolved. Our patient's pregnancy is considered high risk as she has end stage renal failure and falls in the category of advance maternal age for pregnancy. We describe here the course of her uneventful pregnancy which we hope will contribute to the overall knowledge and management of pregnancy in elderly patients receiving peritoneal dialysis.Case Presentation: We report a successful elderly multigravid pregnancy, in a patient undergoing continuous ambulatory peritoneal dialysis (CAPD). Her pregnancy was detected early and she was closely managed by the nephrologist and obstetrician. She tolerated the same PD prescription throughout 36 weeks of pregnancy with daily ultrafiltration of 500-1500mls. Her blood pressure remained well controlled without the need of any antihypertensive medication. Her total Kt/V ranged from 1.93 to 2.73. Her blood parameters remained stable and she was electively admitted at 36 weeks for a trans-peritoneal lower segment caesarian section and bilateral tubal ligation.Conclusions: At the age of 42, our case is the oldest reported successful pregnancy in a patient on peritoneal dialysis. With careful counselling and meticulous follow up, we have shown that woman in the early stage of end stage renal failure can successfully deliver a full term baby without any complications. Therefore, these women should not be discourage from conceiving even if they are in advanced maternal age for pregnancy. [ABSTRACT FROM AUTHOR]

Background: Mammalian development in utero is absolutely dependent on proper placental development, which is ultimately regulated by the placental genome. The regulation of the placental genome can be directly studied by exploring the underlying organisation of the placental transcriptome through a systematic analysis of gene-wise co-expression relationships. Results: In this study, we performed a comprehensive analysis of human placental co-expression using RNA sequencing and intergrated multiple transcriptome datasets spanning human gestation. We identified modules of co-expressed genes that are preserved across human gestation, and also identifed modules conserved in the mouse indicating conserved molecular networks involved in placental development and gene expression patterns more specific to late gestation. Analysis of co-expressed gene flanking sequences indicated that conserved co-expression modules in the placenta are regulated by a core set of transcription factors, including ZNF423 and EBF1. Additionally, we identified a gene co-expression module enriched for genes implicated in the pregnancy pathology preeclampsia. By using an independnet transcriptome dataset, we show that these co-expressed genes are differentially expressed in preeclampsia. Conclusions: This study represents a comprehensive characterisation of placental co-expression and provides insight into potential transcriptional regulators that govern conserved molecular programs fundamental to placental development. [ABSTRACT FROM AUTHOR]

Background: Conception is a fundamental trait for successful cattle reproduction. However, conception rates in Japanese Black cattle have been gradually declining over the last two decades. Although conception failures are mainly caused by embryonic mortality, the role of maternal genetic factors in the process remains unknown. Copy number variation (CNV), defined as large-scale genomic structural variants, contributes to several genetic disorders. To identify CNV associated with embryonic mortality in Japanese Black cattle, we evaluated embryonic mortality as a categorical trait with a threshold model and conducted a genome-wide CNV association study for embryonic mortality using 791 animals. Results: We identified a deleted-type CNV ranging from 378,127 to 412,061 bp on bovine chromosome 8, which was associated with embryonic mortality at 30-60 days after artificial insemination (AI). The CNV harbors exon 2 to 6 of ANNEXIN A10 (ANXA10). Analysis of sequence traces from the CNV identified that 63 bp reads bridging the breakpoint were present on both sides of the CNV, indicating that the CNV was generated by non-allelic homologous recombination using the 63 bp homologous sequences. Western blot analysis showed that the CNV results in a null allele of ANXA10. This association was replicated using a sample population size of 2552 animals. To elucidate the function of ANXA10 in vivo, we generated Anxa10 null mice using the CRISPR/Cas9 system. Crossbreeding experiments showed that litter size from crosses of both Anxa10 -/- and Anxa10 +/- females had fewer pups than did Anxa10 +/+ females, and embryos of Anxa10 -/- females died between implantation stages E4.5 and E12.5. These results indicate that loss of maternal Anxa10 causes embryonic mortality. Conclusions: This study identified a deleted-type CNV encompassing ANXA10 in cows that was associated with embryonic mortality at 30-60 days after AI. Using a mouse model, we confirmed that litter sizes were smaller in crosses of both Anxa10 -/- and Anxa10 +/- females relative to those of wild females. These results indicate that ANXA10 is a maternal factor that is critical for embryo development. [ABSTRACT FROM AUTHOR]

Background: To examine transient environmental exposures and their relationship with human fecundity, exposure assessment should occur optimally at the time of conception in both members of the couple. We performed an observational, prospective cohort study with biomonitoring in both members of a heterosexual couple trying to conceive. Couples collected urine, saliva, and semen specimens for up to two menstrual cycles on days corresponding to the time windows of fertilization, implantation, and early pregnancy, identified based on the woman's observations of her cervical fluid.Results: Three hundred nine eligible couples were screened between 2011 and 2015, of which 183 enrolled. Eleven couples (6.0 %) withdrew or were lost to follow up. The most successful and cost effective recruiting strategies were word of mouth (40 % of participating couples), posters and flyers (37 %), and targeted Facebook advertising (13 %) with an overall investment of $37.35 spent on recruitment per couple. Both men and women collected ≥97.2 % of requested saliva samples, and men collected ≥89.9 % of requested semen samples. Within the periovulatory days (±3 days), there was at least one urine specimen collected by women in 97.1 % of cycles, and at least one by men in 91.7 % of cycles. Daily compliance with periovulatory urine specimens ranged from 66.5 to 92.4 % for women and from 55.7 to 75.0 % for men. Compliance was ≥88 % for questionnaire completion at specified time points.Conclusions: Couples planning to conceive can be recruited successfully for periconceptional monitoring, and will comply with intensive study protocols involving home collection of biospecimens and questionnaire data. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is a significant risk factor for cardiovascular disease (CVD) in later life. Pentraxin 3 (PTX3) is an essential component of innate immunity and independently associated with the risk of developing vascular events. The aim of the study was to examine the relationships between GDM, cardiovascular risk, and plasma PTX3 in pregnancy and at 5 years after the index pregnancy. Methods: This population-based prospective cohort included 300 women who had an oral glucose tolerance test (OGTT) during pregnancy. Five years later, the OGTT was repeated along with dual-energy x-ray absorptiometry, lipid analysis, and pulse wave velocity analysis. Fasting PTX3 levels were measured four times during pregnancy and at follow-up. Results: PTX3 levels were lower early in pregnancy and at 5 years follow-up in women who developed GDM. PTX3 levels throughout pregnancy were associated with body mass index. Low PTX3 levels in early pregnancy were predictive of an increased apoB/apoA ratio at 5-year follow-up. PTX3 at 5-year follow-up was inversely correlated with multiple metabolic risk factors for CVD, including body composition, arterial stiffness, dyslipidemia and previous GDM. Conclusions: Our results show that flow plasma concentration of PTX3 in early pregnancy is associated with sub-sequent development of GDM and with an enhanced risk for CVD as estimated by an elevated apoB/apoA ratio at 5 years postpartum. [ABSTRACT FROM AUTHOR]

Periconceptional supplementation could extend the period over which maternal and fetal nutrition is improved, but there are many challenges facing early-life intervention studies. Periconceptional trials differ from pregnancy supplementation trials, not only because of the very early or pre-gestational timing of nutrient exposure but also because they generate subsidiary information on participants who remain non-pregnant. The methodological challenges are more complex although, if well designed, they provide opportunities to evaluate concurrent hypotheses related to the health of non-pregnant women, especially nulliparous adolescents. This review examines the framework of published and ongoing randomised trial designs. Four cohorts typically arise from the periconceptional trial design--two of which are non-pregnant and two are pregnant--and this structure provides assessment options related to pre-pregnant, maternal, pregnancy and fetal outcomes. Conceptually the initial decision for single or micronutrient intervention is central--as is the choice of dosage and content--in order to establish a comparative framework across trials, improve standardisation, and facilitate interpretation of mechanistic hypotheses. Other trial features considered in the review include: measurement options for baseline and outcome assessments; adherence to long-term supplementation; sample size considerations in relation to duration of nutrient supplementation; cohort size for non-pregnant and pregnant cohorts as the latter is influenced by parity selection; integrating qualitative studies and data management issues. Emphasis is given to low resource settings where high infection rates and the possibility of nutrient-infection interactions may require appropriate safety monitoring. The focus is on pragmatic issues that may help investigators planning a periconceptional trial. [ABSTRACT FROM AUTHOR]

Background: The introduction of home digital ovulation tests (OTs) has provided a simple solution for women wishing to optimise the timing of intercourse when trying to conceive. However, despite this, very little is understood about women's experiences of using these tests. Methods: We carried out qualitative, semi-structured telephone interviews with women who were seeking to conceive (not actively undergoing clinical investigation/fertility treatment) from the general UK population. The interviews were conducted following participation in a randomised controlled trial (RCT) in which participants were either provided with digital home OTs to assist in timing intercourse (n = 18) or advised to have intercourse every 2-3 days (n = 18). The interviews were digitally recorded, transcribed and then analysed using Framework analysis to identify the themes. Results: Data saturation was reached after 36 interviews. The use of the OT appeared to elicit 10 key themes, which could be described within the context of three overarching issues: 1) a positive impact (understanding the menstrual cycle, confirming when ovulating, emotional support, improving the relationship), 2) a negative impact (changing sex life and relationship with their partner, the emotional consequences of prolonged use, questions and uncertainty about what their results mean for them) and 3) the experiences of trying to conceive in general (use of clinical guidance and emotional experience). Conclusions: Overall, the use of home OTs were found to affect women's thoughts and feelings in multiple ways during attempts to conceive. Although some women reported a range of negative experiences when using OTs, they also reported similar negative experiences when trying to conceive without using the tests. However, there were many positive themes associated with OT use, including an increased understanding of the menstrual cycle, confirmation of ovulation timing and providing a source of help and support when trying to conceive. Overall, when women are trying to conceive, ensuring they have access to high-quality information, including use of OT, may be of benefit to help address some of the questions and uncertainties that were raised by the participants in this study. Trial registration number: NCT01084304 [ABSTRACT FROM AUTHOR]

Early equine pregnancy shares many features with that of more intensively assessed domestic animals species, but there are also characteristic differences. Some of those are poorly understood. Descent of the equine conceptus into the uterine lumen occurs at day 5 to 6 after ovulation but is only possible when the embryo secretes prostaglandin E2. Although maintenance of equine pregnancy probably involves secretion of a conceptus derived anti-luteolytic factor, this agent has not been identified. Rapid growth, conceptus mobility and presence of an acellular capsule at the time of maternal recognition of pregnancy, i.e. between days 12 and 14, are prerequisites to avoid pregnancy loss. Progesterone together with 5a-pregnanes is secreted by the corpus luteum and induces the production of endometrial histotroph which is responsible for conceptus nutrition until placention. A stable contact between the outer trophoblast layer of the allantochorion and the luminal epithelium of the endometrium is not established before days 40 to 42 of pregnancy. [ABSTRACT FROM AUTHOR]

Background: Allergic diseases such as asthma and allergic rhinitis constitute asignificant burden of disease among women of childbearing age and those who arepregnant. Adequately managing these conditions is paramount in reducing negativefetal outcomes as well as maternal complications during pregnancy. However, thepotential for harm to both the mother and fetus demands carefully balancing efficacyand safety of treatment. Allergen immunotherapy (AIT) has emerged as a relativelysafe and efficacious mode of therapy in both children and adults. AIT has also beenconsidered for use during pregnancy. Methods: A review of the literature wasconducted for data regarding the safety of initiation and continuation of AIT duringpregnancy as well as the effect of AIT on the development of atopy in offspring. MEDLINE and the Cochrane Library were searched for clinical trials, randomizedcontrol trials, observational studies and journal articles in English using the terms"Pregnancy" and "Immunotherapy" from 1900 to present. This yielded 4 studies(totaling 422 pregnancies receiving AIT) investigating the continuation of AIT inpregnancy, 2 (totaling 31 pregnancies receiving AIT) evaluating AIT initiation duringpregnancy and 5 observing the effect of AIT on atopy in offspring. Results: No significant difference was found in the incidence of prematurity, hypertension (HTN)/proteinuria, congenital malformations or perinatal deaths betweenthe women continued on AIT (both subcutaneous (SC) IT and sublingual (SL) IT toinhalant allergens as well as venom IT) during pregnancy and controls. Similarly, therewas no significant difference in maternal or fetal complications between pregnantwomen initiated on AIT and controls. Among the few pregnant women (10/453pregnancies) who experienced generalized reactions while receiving AIT, none werefound to have fetal complications. Neither SCIT nor SLIT during pregnancy altered therisk of developing atopic disease in offspring. Conclusions: Based on these data, the continuation of AIT during pregnancyappears safe. Furthermore, the few data available suggest that the initiation of AITduring pregnancy might also be safe, however, more data is required for a definitiveconclusion. Lastly, available studies do not show a convincing reduction in thedevelopment of atopy in offspring from the administration of AIT during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Unintended pregnancies (mistimed or unwanted during the time of conception) can result in adverse outcomes both to the mother and to her newborn. Further research on identifying the characteristics of unintended pregnant women who are at risk is warranted. The present study aims to examine the prevalence and predictors of unintended pregnancy among Canadian women.Methods: The analysis was based on the 2006 Maternity Experiences Survey targeting women who were at least 15 years of age and who had a singleton live birth, between February 15, 2006 to May 15, 2006 in the Canadian provinces and November 1, 2005 to February 1, 2006 for women in the Canadian territories. The primary outcome was the mother's pregnancy intention, where unintended pregnancy was defined as women who wanted to become pregnant later or not at all. Sociodemographic, maternal and pregnancy related variables were considered for a multivariable logistic regression.Results: Adjusted Odds Ratios (OR) and 95% Confidence Intervals (95% CI) were reported. Overall, the prevalence of unintended pregnancy among Canadian women was 27%. The odds of experiencing an unintended pregnancy were statistically significantly increased if the mother was: under 20 years of age, immigrated to Canada, had an equivalent of a high school education or less, no partner, experienced violence or abuse and had 1 or more previous pregnancies. Additionally, mothers who reported smoking, drinking alcohol and using drugs prior to becoming pregnant, were all associated with an increased likelihood of experiencing an unintended pregnancy.Conclusion: The study findings constitute the basis for future research into these associations to aid in developing effective policy changes and interventions to minimize the odds of experiencing an unintended pregnancy and its associated consequences. [ABSTRACT FROM AUTHOR]