How common is natural conception in women who have had a livebirth via assisted reproductive technology? Systematic review and meta-analysis.

STUDY QUESTION: What is the proportion of women who experience natural conception after a livebirth via assisted reproductive technology (ART)? SUMMARY ANSWER: Current evidence suggests that natural conception pregnancy may occur in at least one in five women after having a baby via IVF or ICSI. WHAT IS KNOWN ALREADY: It is widely known that some women having babies via ART go on to conceive naturally. This reproductive history is of media interest and often described as 'miracle' pregnancies. STUDY DESIGN, SIZE, DURATION: A systematic review with meta-analysis was carried out. Ovid Medline, Embase, and PsycINFO were searched until 24 September 2021 for English language, human studies from 1980. Search terms were used for the concepts of natural conception pregnancy, assisted reproduction, and livebirth. PARTICIPANTS/MATERIALS, SETTING, METHODS: The inclusion criterion was studies with an outcome measure of the proportion of women experiencing natural conception pregnancy after an ART livebirth. Quality of studies was assessed using the Critical Appraisal Skills Programme cohort study checklist or AXIS Appraisal tool for cross-sectional studies, and a risk of bias assessment was carried out. No studies were excluded based on quality. Random-effects meta-analyses were adopted to produce a pooled effect estimate of the proportion of natural conception pregnancy after ART livebirth. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1108 distinct studies were identified, resulting in 54 studies after screening by title and abstract. Eleven studies including 5180 women were selected for this review. The included studies were mostly of moderate quality with a maximum follow-up period ranging from 2 to 15 years. Four studies reported natural conception livebirths which were used as known underestimates of natural conception pregnancies. The pooled estimate for the proportion of women having natural conception pregnancies after ART livebirth was 0.20 (95% CI, 0.17-0.22). LIMITATIONS, REASONS FOR CAUTION: The studies varied widely according to methodology, population, cause of subfertility, type and outcome of fertility treatment, and length of follow-up, leading to potential bias relating to confounding, selection bias, and missing data. WIDER IMPLICATIONS OF THE FINDINGS: Current evidence suggests that contrary to widely held views, natural conception pregnancy after ART livebirth is far from rare. National, data-linked studies are needed to provide more accurate estimates of this incidence and analysis of associated factors and trends over time to facilitate tailored counselling of couples considering further ART. STUDY FUNDING/COMPETING INTEREST(S): This work was conducted as part of an academic clinical fellowship awarded to AT by the National Institute for Health Research (NIHR). NIHR has had no input into the study design, data collection, and analysis, nor the writing of this study. No authors have any conflicts of interest. REGISTRATION NUMBER: PROSPERO (CRD42022322627).

Pre-pregnancy health of women with pre-existing diabetes or previous gestational diabetes: Analysis of pregnancy risk factors and behavioural data from a digital tool.

AIMS: To examine health behaviours and risk factors in women with pre-existing diabetes or previous gestational diabetes mellitus who are planning pregnancy. METHODS: Health behaviour, risk factor and demographic data obtained from a digital pregnancy planning advisory tool (Tommy's charity UK) were analysed. Descriptive statistical analysis was performed, stratified by diabetes type. RESULTS: Data from 84,359 women, including 668 with type 1 diabetes, 707 with type 2 diabetes and 1785 with previous gestational diabetes obtained over a 12-month period (September 2019-September 2020) were analysed. 65%, 95%CI (61,68%) of women with type 2 diabetes and 46%, 95%CI (43,48%) with previous gestational diabetes were obese (BMI ≥30 kg/m2 ), compared with 26%, 95%CI (26,26%) without diabetes. Use of folic acid supplements was low; 41%, 95%CI (40,41%) of women without diabetes and 42%, 95%CI (40,45%) with previous gestational diabetes reported taking folic acid (any dose) while 47%, 95%CI (43.50%) women with type 1 diabetes and 44%, 95%CI (40,47%) women with type 2 diabetes respectively reported taking the recommended dose (5 mg). More women with type 1 diabetes and type 2 diabetes reported smoking (20%, 95%CI [17,23%] and 23%, 95%CI [20,26%] respectively) and taking illicit/recreational drugs (7%, 95%CI [6,10%] and 9%, 95% CI [7,11%]) compared to women without diabetes (smoking 17%, 95% CI [16,17%], drug use 5%, 95%CI [5,5%]). Alcohol consumption, low levels of physical activity and of fruit and vegetable intake were also evident. CONCLUSIONS: This study highlights the potential of online pregnancy planning advisory tools to reach high-risk women and emphasises the need to improve pre-pregnancy care for women with pre-existing diabetes and previous gestational diabetes, many of whom are actively seeking advice. It is also the first to describe pre-pregnancy health behaviours in women with previous gestational diabetes.

The physical-mental health interface in the preconception period: analysis of 131 182 women planning pregnancy in the UK.

OBJECTIVE: The physical and mental health of women prior to conception can have a significant impact on pregnancy and child outcomes. Given the rising burden of non-communicable diseases, the aim was to explore the relation between mental health, physical health and health behaviour in women planning a pregnancy. METHODS: Cross-sectional analysis of responses from 131 182 women to a preconception health digital education tool, providing data on physical and mental health and health behaviour. Logistic regression was used to explore associations between mental health and physical health variables. RESULTS: Physical health conditions were reported by 13.1% and mental health conditions by 17.8%. There was evidence for an association between self-reported physical and mental health conditions (odds ratio [OR] 2.22, 95% CI 2.14-2.3). Those with a mental health condition were less likely to engage with healthy behaviour at preconception such as folate supplementation (OR 0.89, 95% CI 0.86-0.92) and consumption of the recommended amount of fruit and vegetables (OR 0.77, 95% CI 0.74-0.79). They were more likely to be physically inactive (OR 1.14, 95% CI 1.11-1.18), smoke tobacco (OR 1.72, 95% CI 1.66-1.78) and use illicit substances (OR 2.4, 95% CI 2.25-2.55). CONCLUSIONS: Greater recognition of mental and physical comorbidities is needed and closer integration of physical and mental healthcare in the preconception period, which could support people to optimise their health during this time and improve long-term outcomes.

Women's preconception health in England: a report card based on cross-sectional analysis of national maternity services data from 2018/2019.

OBJECTIVE: To present the first national-level report card on the state of women's preconception health in England. DESIGN: Cross-sectional population-based study. SETTING: Maternity services, England. POPULATION: All pregnant women in England with a first antenatal (booking) appointment recorded in the national Maternity Services Dataset (MSDS) from April 2018 to March 2019 (n = 652 880). METHODS: We analysed the prevalence of 32 preconception indicator measures in the overall population and across socio-demographic subgroups. Ten of these indicators were prioritised for ongoing surveillance based on modifiability, prevalence, data quality and ranking by multidisciplinary UK experts. RESULTS: The three most prevalent indicators were the proportion of the 22.9% of women who smoked 1 year before pregnancy who did not quit smoking before pregnancy (85.0%), those who had not taken folic acid supplementation before pregnancy (72.7%) and previous pregnancy loss (38.9%). Inequalities were observed by age, ethnicity and area-based deprivation level. The ten indicators prioritised were not taking folic acid supplementation before pregnancy, obesity, complex social factors, living in the most deprived areas, smoking around the time of conception, overweight, pre-existing mental health condition, pre-existing physical health condition, previous pregnancy loss and previous obstetric complication. CONCLUSIONS: Our findings suggest important opportunities to improve the state of preconception health and reduce socio-demographic inequalities for women in England. In addition to MSDS data, other national data sources that record further and possibly better quality indicators could be explored and linked to build a comprehensive surveillance infrastructure.

Predictive ability of the Desire to Avoid Pregnancy scale.

BACKGROUND: A longstanding gap in the reproductive health field has been the availability of a screening instrument that can reliably predict a person's likelihood of becoming pregnant. The Desire to Avoid Pregnancy Scale is a new measure; understanding its sensitivity and specificity as a screening tool for pregnancy as well as its predictive ability and how this varies by socio-demographic factors is important to inform its implementation. METHODS: This analysis was conducted on a cohort of 994 non-pregnant participants recruited in October 2018 and followed up for one year. The cohort was recruited using social media as well as advertisements in a university, school, abortion clinic and outreach sexual health service. Almost 90% of eligible participants completed follow-up at 12 months; those lost to follow-up were not significantly different on key socio-demographic factors. We used baseline DAP score and a binary variable of whether participants experienced pregnancy during the study to assess the sensitivity, specificity, area under the ROC curve (AUROC) and positive and negative predictive values (PPV and NPV) of the DAP at a range of cut-points. We also examined how the predictive ability of the DAP varied according to socio-demographic factors and by the time frame considered (e.g., pregnancy within 3, 6, 9 and 12 months). RESULTS: At a cut-point of 2 on the 0-4 range of the DAP scale, the DAP had a sensitivity of 0.78, a specificity of 0.81 and an excellent AUROC of 0.87. In this sample the cumulative incidence of pregnancy was 16% (95%CI 13%, 18%) making the PPV 43% and the NPV 95% at this cut-point. The DAP score was the factor most strongly associated with pregnancy, even after age and number of children were taken into account. The association between baseline DAP score and pregnancy did not differ across time frames. CONCLUSIONS: This is the first study to assess the DAP scale as a screening tool and shows that its predictive ability is superior to the limited pre-existing pregnancy prediction tools. Based on our findings, the DAP could be used with a cut-point selected according to the purpose.

Interventions to support contraceptive choice and use: a global systematic map of systematic reviews.

BACKGROUND: To review the highest level of available evidence, a systematic map identified systematic reviews that evaluated the effectiveness of interventions to improve contraception choice and increase contraception use. METHODS: Systematic reviews published since 2000 were identified from searches of nine databases. Data were extracted using a coding tool developed for this systematic map. Methodological quality of included reviews was assessed using AMSTAR 2 criteria. FINDINGS AND CONCLUSION: Fifty systematic reviews reported evaluations of interventions for contraception choice and use addressing three domains (individual, couples, community); Meta-analyses in 11 of the reviews mostly addressed interventions for individuals. We identified 26 reviews covering High Income Countries, 12 reviews covering Low Middle-Income Countries and the rest a mix of both. Most reviews (15) focussed on psychosocial interventions, followed by incentives (6) and m-health interventions (6). The strongest evidence from meta-analyses is for the effectiveness of motivational interviewing, contraceptive counselling, psychosocial interventions, school-based education, and interventions promoting contraceptive access, demand-generation interventions (community and facility based, financial mechanisms and mass media), and mobile phone message interventions. Even in resource constrained settings, community-based interventions can increase contraceptive use. There are gaps in the evidence on interventions for contraception choice and use, and limitations in study designs and lack of representativeness. Most approaches focus on individual women rather than couples or wider socio-cultural influences on contraception and fertility. This review identifies interventions which work to increase contraception choice and use, and these could be implemented in school, healthcare or community settings.

SARS-CoV-2 infection in the first trimester and the risk of early miscarriage: a UK population-based prospective cohort study of 3041 pregnancies conceived during the pandemic.

STUDY QUESTION: Does maternal infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the first trimester affect the risk of miscarriage before 13 week's gestation? SUMMARY ANSWER: Pregnant women with self-reported diagnosis of SARS-CoV-2 in the first trimester had a higher risk of early miscarriage. WHAT IS KNOWN ALREADY: Viral infections during pregnancy have a broad spectrum of placental and neonatal pathology. Data on the effects of the SARS-CoV-2 infection in pregnancy are still emerging. Two systematic reviews and meta-analyses reported an increased risk of preterm birth, caesarean delivery, maternal morbidity and stillbirth. Data on the impact of first trimester infection on early pregnancy outcomes are scarce. This is the first study, to our knowledge, to investigate the rates of early pregnancy loss during the SARS-CoV-2 outbreak among women with self-reported infection. STUDY DESIGN, SIZE, DURATION: This was a nationwide prospective cohort study of pregnant women in the community recruited using social media between 21 May and 31 December 2020. We recruited 3545 women who conceived during the SARS-CoV-2 pandemic who were <13 week's gestation at the time of recruitment. PARTICIPANTS/MATERIALS, SETTING, METHODS: The COVID-19 Contraception and Pregnancy Study (CAP-COVID) was an on-line survey study collecting longitudinal data from pregnant women in the UK aged 18 years or older. Women who were pregnant during the pandemic were asked to complete on-line surveys at the end of each trimester. We collected data on current and past pregnancy complications, their medical history and whether they or anyone in their household had symptoms or been diagnosed with SARS-CoV-2 infection during each trimester of their pregnancy. RT-PCR-based SARS-CoV-2 RNA detection from respiratory samples (e.g. nasopharynx) is the standard practice for diagnosis of SARS-CoV-2 in the UK. We compared rate of self-reported miscarriage in three groups: 'presumed infected', i.e. those who reported a diagnosis with SARS-CoV-2 infection in the first trimester; 'uncertain', i.e. those who did not report a diagnosis but had symptoms/household contacts with symptoms/diagnosis; and 'presumed uninfected', i.e. those who did not report any symptoms/diagnosis and had no household contacts with symptoms/diagnosis of SARS-CoV-2. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 3545 women registered for the CAP-COVID study at <13 weeks gestation and were eligible for this analysis. Data for the primary outcome were available from 3041 women (86%). In the overall sample, the rate of self-reported miscarriage was 7.8% (238/3041 [95% CI, 7-9]). The median gestational age (GA) at miscarriage was 9 weeks (interquartile range 8-11). Seventy-seven women were in the 'presumed infected' group (77/3041, 2.5% [95% CI 2-3]), 295/3041 were in the uncertain group (9.7% [95% CI 9-11]) and the rest in the 'presumed uninfected' (87.8%, 2669/3041 [95% CI 87-89]). The rate of early miscarriage was 14% in the 'presumed infected' group, 5% in the 'uncertain' and 8% in the 'presumed uninfected' (11/77 [95% CI 6-22] versus 15/295 [95% CI 3-8] versus 212/2669 [95% CI 7-9], P = 0.02). After adjusting for age, BMI, ethnicity, smoking status, GA at registration and the number of previous miscarriages, the risk of early miscarriage appears to be higher in the 'presumed infected' group (relative rate 1.7, 95% CI 1.0-3.0, P = 0.06). LIMITATIONS, REASONS FOR CAUTION: We relied on self-reported data on early pregnancy loss and SARS-CoV-2 infection without any means of checking validity. Some women in the 'presumed uninfected' and 'uncertain' groups may have had asymptomatic infections. The number of 'presumed infected' in our study was low and therefore the study was relatively underpowered. WIDER IMPLICATIONS OF THE FINDINGS: This was a national study from the UK, where infection rates were one of the highest in the world. Based on the evidence presented here, women who are infected with SARS-CoV-2 in their first trimester may be at an increased risk of a miscarriage. However, the overall rate of miscarriage in our study population was 8%. This is reassuring and suggests that if there is an effect of SARS-CoV-2 on the risk of miscarriage, this may be limited to those with symptoms substantial enough to lead to a diagnostic test. Further studies are warranted to evaluate a causal association between SARS-CoV-2 infection in early pregnancy and miscarriage risk. Although we did not see an overall increase in the risk of miscarriage, the observed comparative increase in the presumed infected group reinforces the message that pregnant women should continue to exercise social distancing measures and good hygiene throughout their pregnancy to limit their risk of infection. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by a grant from the Elizabeth Garrett Anderson Hospital Charity (G13-559194). The funders of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report. J.A.H. is supported by an NIHR Advanced Fellowship. A.L.D. is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support to J.A.H. and A.L.D. as above; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work. TRIAL REGISTRATION NUMBER: N/A.

Contraception after in vitro fertilisation (IVF): a qualitative study of the views of women who have had spontaneous pregnancies after successful IVF.

BACKGROUND: The use of in vitro fertilisation (IVF) has increased rapidly since its inception in 1978. Women seeking IVF have a wide range of subfertility causes including unexplained subfertility. A growing subgroup of women seek treatment for other reasons than fertility problems, for example, women in same sex relationships and single women. This study aims to better understand the contraceptive needs of women after successful IVF pregnancy in order to improve service delivery and prevent unplanned and rapid-repeat pregnancies. METHODS: A qualitative study of views of women who have had spontaneous pregnancies after successful IVF. Participants were recruited using purposive and snowballing sampling methods from social media and peer networks. The framework method was used for analysis using NVivo12. RESULTS: The sample comprised 21 interviewees from the United Kingdom (UK), having a range of spontaneous pregnancy outcomes, including single and multiple livebirths, miscarriage, ectopic pregnancy and termination of pregnancy. Contraceptive choices were subject to a complex and dynamic interaction of influencing factors including beliefs regarding subfertility, desire for children and views on contraception. None of the women recalled receiving any information or useful counselling about contraception during fertility or maternity care. After IVF pregnancy, most women (n = 16) used no or ineffective contraception. Spontaneous pregnancy was not universally welcomed in this group and inter-pregnancy intervals were often short (n = 16, less than 18 months). Even after subsequent spontaneous pregnancy, use of contraception and the most effective methods remained low. Women held persistent beliefs regarding their subfertility despite subsequent spontaneous pregnancy. They associated aspects of the IVF process with a sense of personal failure, despite an ultimately "successful" outcome of livebirth. These aspects may reinforce their self-belief in subfertility. Other barriers to contraception use in women having IVF included: lack of knowledge of likelihood of spontaneous pregnancy, lack of contraceptive experience and inherent incentives towards shorter inter-pregnancy intervals. CONCLUSIONS: The contraceptive needs of women having IVF pregnancies are real and are being overlooked. Fertility services should take responsibility for providing information on the risks of subsequent spontaneous pregnancy. Maternity and community healthcare professionals must address women's perceptions of their fertility in order to engage them in contraception counselling.

Women who have difficulty getting pregnant may choose to use fertility treatment to help. Fertility treatment known as 'in vitro fertilisation', or IVF, was developed around 40 years ago and has been increasingly used ever since. Over 8 million babies have been born this way around the world. There are many different reasons why women can have problems getting pregnant and in a quarter of cases the cause is never found. We know that some women, who have babies using IVF, get pregnant again afterwards without fertility treatment. Getting pregnant again quickly, or when a woman isn't ready, can be worse for the health of the mother and child. Therefore, this study aims to understand what contraception women need after IVF to plan and space their future pregnancies. We spoke to 21 women who became pregnant without fertility treatment after having their first babies using IVF. Although most of these women had not been using contraception after their first baby, they were shocked to get pregnant again as they firmly believed they could not get pregnant without fertility treatment. Most of these pregnancies had happened quickly and not all the women were happy to be pregnant again. These women were not given the information they needed about their chances of getting pregnant after IVF without fertility treatment. Fertility and maternity services must close this gap. Health professionals also need to explore women's beliefs about their own fertility after IVF before they can start to have helpful conversations about contraception.

What does family building mean? A qualitative exploration and a new definition: a UK-based study.

BACKGROUND: The importance of improving men's and women's knowledge of sexual and reproductive health has been emphasised in numerous global health policies. Fertility awareness literature highlights a disproportionately higher number of articles related to pregnancy-prevention compared to pregnancy-planning, which is justifiable in many contexts. However, recent concerted effort to improve fertility-awareness warrants a closer investigation of basic reproductive health terminologies. The objective of this study is to explore participants' views of "family building" and provide a definition. METHODS: We conducted 35 qualitative in-depth interviews on men, women and healthcare professionals who were sampled from a UK cross-sectional survey. We asked participants about terms such as 'family planning' and 'family building' to elicit views and explored the appropriateness of the term "family building." Data were transcribed and analysed via Framework analysis. RESULTS: When asked what 'family planning' meant to them, study participants stated that the term meant the avoidance of pregnancy. They viewed it as an "umbrella term for the use of contraception methods," that "paradoxically, the term family planning almost has a negative connotation regarding having a family," but could not state similar terminology for planning a family. Reasons cited for this perspective include the focus of school education and usage in clinical settings. CONCLUSIONS: In the absence of an explicit definition in literature, we generated a new definition for family building as follows: "Family building refers to the construction or formation of a family, which can include steps or actions taken by an individual towards having children. In contrast to family planning, the intent focuses on pregnancy planning and childbearing rather than pregnancy prevention. However, it can also include actions taken to space the number of children one has." Some balance in the global public health messages, including bridging the gap in reproductive health literature, policies, processes and practices may contribute to the effort to improve fertility knowledge. Use of appropriate terminologies help optimise reproductive health services in order to enable men and women achieve their desired fertility intentions, whatever they may be. Trial registration Not applicable.

Global health policies have emphasised the importance of improving individual's knowledge of sexual and reproductive health. Fertility awareness literature highlights a disproportionately higher number of articles related to pregnancy-prevention compared to pregnancy-planning, which is justifiable in many contexts. However, the recent concerted effort to improve fertility awareness warrants a closer investigation of basic terminologies in the field. For example, although the term family planning encompasses attaining the desired number of children and spacing pregnancies, it is almost synonymous with not having children, while there is currently no widely accepted equivalent terminology for planning to have children, either in general usage or clinical settings. We conducted 35 qualitative in-depth interviews on men, women and healthcare professionals who were sampled from a UK cross-sectional survey. When asked what 'family planning' meant to them, study participants stated avoidance of pregnancy. They viewed it as an "umbrella term for the use of contraception methods", that "paradoxically, the term family planning almost has a negative connotation regarding having a family," but could not state similar terminology for planning a family. We introduced family building and provided a new definition. We believe that some balance in the global public health messages, including revisiting widely used terminologies can help bridge the gap in reproductive health literature, and contribute to the effort to improve fertility knowledge. Additionally, this has implications for promotion of preconception and optimising reproductive health in relevant policies, processes and practices, in order to help people achieve their desired fertility intentions, whatever they may be.

Factors influencing contraception choice and use globally: a synthesis of systematic reviews.

BACKGROUND: Unintended pregnancy has a huge adverse impact on maternal, child and family health and wealth. There is an unmet need for contraception globally, with an estimated 40% of pregnancies unintended worldwide. METHODS: We systematically searched PubMed and specialist databases for systematic reviews addressing contraceptive choice, uptake or use, published in English between 2000 and 2019. Two reviewers independently selected and appraised reports and synthesised quantitative and qualitative review findings. We mapped emergent themes to a social determinants of health framework to develop our understanding of the complexities of contraceptive choice and use. FINDINGS: We found 24 systematic reviews of mostly moderate or high quality. Factors affecting contraception use are remarkably similar among women in very different cultures and settings globally. Use of contraception is influenced by the perceived likelihood and appeal of pregnancy, and relationship status. It is influenced by women's knowledge, beliefs, and perceptions of side effects and health risks. Male partners have a strong influence, as do peers' views and experiences, and families' expectations. Lack of education and poverty is linked with low contraception use, and social and cultural norms influence contraception and expectations of family size and timing. Contraception use also depends upon their availability, the accessibility, confidentiality and costs of health services, and attitudes, behaviour and skills of health practitioners. INTERPRETATION: Contraception has remarkably far-reaching benefits and is highly cost-effective. However, women worldwide lack sufficient knowledge, capability and opportunity to make reproductive choices, and health care systems often fail to provide access and informed choice.

Use of effective contraception following provision of the progestogen-only pill for women presenting to community pharmacies for emergency contraception (Bridge-It): a pragmatic cluster-randomised crossover trial.

BACKGROUND: Unless women start effective contraception after oral emergency contraception, they remain at risk of unintended pregnancy. Most women in the UK obtain emergency contraception from community pharmacies. We hypothesised that pharmacist provision of the progestogen-only pill as a bridging interim method of contraception with emergency contraception plus an invitation to a sexual and reproductive health clinic, in which all methods of contraception are available, would result in increased subsequent use of effective contraception. METHODS: We did a pragmatic cluster-randomised crossover trial in 29 UK pharmacies among women receiving levonorgestrel emergency contraception. Women aged 16 years or older, not already using hormonal contraception, not on medication that could interfere with the progestogen-only pill, and willing to give contact details for follow-up were invited to participate. In the intervention group, women received a 3-month supply of the progestogen-only pill (75 µg desogestrel) plus a rapid access card to a participating sexual and reproductive health clinic. In the control group, pharmacists advised women to attend their usual contraceptive provider. The order in which each pharmacy provided the intervention or control was randomly assigned using a computer software algorithm. The primary outcome was the use of effective contraception (hormonal or intrauterine) at 4 months. This study is registered, ISRCTN70616901 (complete). FINDINGS: Between Dec 19, 2017, and June 26, 2019, 636 women were recruited to the intervention group (316 [49·6%], mean age 22·7 years [SD 5·7]) or the control group (320 [50·3%], 22·6 years [5·1]). Three women (one in the intervention group and two in the control group) were excluded after randomisation. 4-month follow-up data were available for 406 (64%) participants, 25 were lost to follow-up, and two participants no longer wanted to participate in the study. The proportion of women using effective contraception was 20·1% greater (95% CI 5·2-35·0) in the intervention group (mean 58·4%, 48·6-68·2), than in the control group (mean 40·5%, 29·7-51·3 [adjusted for recruitment period, treatment group, and centre]; p=0·011).The difference remained significant after adjusting for age, current sexual relationship, and history of effective contraception use, and was robust to the effect of missing data (assuming missingness at random). No serious adverse events occurred. INTERPRETATION: Provision of a supply of the progestogen-only pill with emergency contraception from a community pharmacist, along with an invitation to a sexual and reproductive health clinic, results in a clinically meaningful increase in subsequent use of effective contraception. Widely implemented, this practice could prevent unintended pregnancies after use of emergency contraception. FUNDING: National Institute for Health Research (Health Technology Assessment Programme project 15/113/01).

Health behaviours in 131,182 UK women planning pregnancy.

BACKGROUND: A woman's health at the time of conception lays the foundation for a healthy pregnancy and the lifelong health of her child. We investigated the health behaviours of UK women planning pregnancy. METHODS: We analysed survey data from the 'Planning for Pregnancy' online tool (Tommy's, UK). We described all women planning pregnancy and compared the frequency of non-adherence to preconception recommendations in women who had already stopped contraception (active planners) and those who had not (non-active planners). RESULTS: One hundred thirty-one thousand one hundred eighty-two women from across the UK were included, of whom 64.8% were actively planning pregnancy. Of the whole cohort, twenty percent were smokers and less than one third took folic acid supplements (31.5%). Forty two percent engaged in less than the recommended 150 min of weekly physical activity and only 53.3% consumed five portions of fruit or vegetables 4 days a week. Smokers were 1.87 times more likely to be active planners than non-smokers (95% CI 1.79-1.94), and women who took folic acid were 7 times more likely to be active planners (95% CI 6.97-7.59) compared to women who did not. Smoking, drug use and lack of folic acid supplementation were common in younger women and those who were underweight. CONCLUSIONS: This unique survey of UK women has identified poor adherence to preconception recommendations in those planning pregnancies and supports the need for a greater public health focus on preconception health. This study provides a contemporary basis from which to inform preconception health advice and a benchmark to measure changes over time.

Preconception health in England: a proposal for annual reporting with core metrics.

There is growing interest in preconception health as a crucial period for influencing not only pregnancy outcomes, but also future maternal and child health, and prevention of long-term medical conditions. Successive national and international policy documents emphasise the need to improve preconception health, but resources and action have not followed through with these goals. We argue for a dual intervention strategy at both the public health level (eg, by improving the food environment) and at the individual level (eg, by better identification of those planning a pregnancy who would benefit from support to optimise health before conception) in order to raise awareness of preconception health and to normalise the notion of planning and preparing for pregnancy. Existing strategies that target common risks factors, such as obesity and smoking, should recognise the preconception period as one that offers special opportunity for intervention, based on evidence from life-course epidemiology, developmental (embryo) programming around the time of conception, and maternal motivation. To describe and monitor preconception health in England, we propose an annual report card using metrics from multiple routine data sources. Such a report card should serve to hold governments and other relevant agencies to account for delivering interventions to improve preconception health.

Before the beginning: nutrition and lifestyle in the preconception period and its importance for future health.

A woman who is healthy at the time of conception is more likely to have a successful pregnancy and a healthy child. We reviewed published evidence and present new data from low-income, middle-income, and high-income countries on the timing and importance of preconception health for subsequent maternal and child health. We describe the extent to which pregnancy is planned, and whether planning is linked to preconception health behaviours. Observational studies show strong links between health before pregnancy and maternal and child health outcomes, with consequences that can extend across generations, but awareness of these links is not widespread. Poor nutrition and obesity are rife among women of reproductive age, and differences between high-income and low-income countries have become less distinct, with typical diets falling far short of nutritional recommendations in both settings and especially among adolescents. Several studies show that micronutrient supplementation starting in pregnancy can correct important maternal nutrient deficiencies, but effects on child health outcomes are disappointing. Other interventions to improve diet during pregnancy have had little effect on maternal and newborn health outcomes. Comparatively few interventions have been made for preconception diet and lifestyle. Improvements in the measurement of pregnancy planning have quantified the degree of pregnancy planning and suggest that it is more common than previously recognised. Planning for pregnancy is associated with a mixed pattern of health behaviours before conception. We propose novel definitions of the preconception period relating to embryo development and actions at individual or population level. A sharper focus on intervention before conception is needed to improve maternal and child health and reduce the growing burden of non-communicable diseases. Alongside continued efforts to reduce smoking, alcohol consumption, and obesity in the population, we call for heightened awareness of preconception health, particularly regarding diet and nutrition. Importantly, health professionals should be alerted to ways of identifying women who are planning a pregnancy.

Origins of lifetime health around the time of conception: causes and consequences.

Parental environmental factors, including diet, body composition, metabolism, and stress, affect the health and chronic disease risk of people throughout their lives, as captured in the Developmental Origins of Health and Disease concept. Research across the epidemiological, clinical, and basic science fields has identified the period around conception as being crucial for the processes mediating parental influences on the health of the next generation. During this time, from the maturation of gametes through to early embryonic development, parental lifestyle can adversely influence long-term risks of offspring cardiovascular, metabolic, immune, and neurological morbidities, often termed developmental programming. We review periconceptional induction of disease risk from four broad exposures: maternal overnutrition and obesity; maternal undernutrition; related paternal factors; and the use of assisted reproductive treatment. Studies in both humans and animal models have demonstrated the underlying biological mechanisms, including epigenetic, cellular, physiological, and metabolic processes. We also present a meta-analysis of mouse paternal and maternal protein undernutrition that suggests distinct parental periconceptional contributions to postnatal outcomes. We propose that the evidence for periconceptional effects on lifetime health is now so compelling that it calls for new guidance on parental preparation for pregnancy, beginning before conception, to protect the health of offspring.

Intervention strategies to improve nutrition and health behaviours before conception.

The nutritional status of both women and men before conception has profound implications for the growth, development, and long-term health of their offspring. Evidence of the effectiveness of preconception interventions for improving outcomes for mothers and babies is scarce. However, given the large potential health return, and relatively low costs and risk of harm, research into potential interventions is warranted. We identified three promising strategies for intervention that are likely to be scalable and have positive effects on a range of health outcomes: supplementation and fortification; cash transfers and incentives; and behaviour change interventions. On the basis of these strategies, we suggest a model specifying pathways to effect. Pathways are incorporated into a life-course framework using individual motivation and receptiveness at different preconception action phases, to guide design and targeting of preconception interventions. Interventions for individuals not planning immediate pregnancy take advantage of settings and implementation platforms outside the maternal and child health arena, since this group is unlikely to be engaged with maternal health services. Interventions to improve women's nutritional status and health behaviours at all preconception action phases should consider social and environmental determinants, to avoid exacerbating health and gender inequalities, and be underpinned by a social movement that touches the whole population. We propose a dual strategy that targets specific groups actively planning a pregnancy, while improving the health of the population more broadly. Modern marketing techniques could be used to promote a social movement based on an emotional and symbolic connection between improved preconception maternal health and nutrition, and offspring health. We suggest that speedy and scalable benefits to public health might be achieved through strategic engagement with the private sector. Political theory supports the development of an advocacy coalition of groups interested in preconception health, to harness the political will and leadership necessary to turn high-level policy into effective coordinated action.

Evaluation of the Krio Language Version of the London Measure of Unplanned Pregnancy in Western Area, Sierra Leone.

New ways of measuring pregnancy planning/intention such as the London Measure of Unplanned Pregnancy (LMUP), which recognise the complexity of the construct, are being adopted worldwide. The aim of this study was to evaluate the psychometric properties of the Krio version of the LMUP in Sierra Leone. An interviewer-administered version of the LMUP was translated into Krio and pre-tested with 12 pregnant women. Field testing involved 172 pregnant women aged 15-42, with 87 completing a re-test. Completion rates of LMUP items were 100%. LMUP scores 1-12 were captured. Reliability: the scale was internally consistent (Cronbach's alpha 0.84) and stable (weighted Kappa 0.93). Construct validity: all hypotheses were confirmed. Principal components analysis revealed five items (items 2-6) related to one construct. Mokken scaling procedure selected the same five items. Removal of item 1 (which had 97% endorsement of the _no contraception' response option) brought about only a very slight improvement in LMUP performance, therefore we recommend retaining all six items. The Krio LMUP is reliable, valid and suitable to use in Sierra Leone.

Non-adherence to basal insulin among patients with type 2 diabetes in a US managed care population: Results from a patient survey.

The aim of this study was to assess insulin non-adherence among patients with type 2 diabetes (T2DM) to better understand relationships between adherence, basal insulin (BI) usage, and patient experiences. A cross-sectional survey of patients with T2DM using BI was conducted. Adherence was measured by the Morisky Medication Adherence Scale 8-Items (MMAS-8). Low adherence (LA) was defined as MMAS-8 score < 6, high adherence (HA) as MMAS-8 score = 8, and medium adherence as MMAS-8 score = 6 to < 8. Patients with MMAS-8 scores = 6 to < 8 were excluded from the analysis. Of 400 completed surveys, 395 patients (98.8%) completed all MMAS-8 items, 112 with LA, 134 with HA. Compared with HA patients, greater proportions of LA patients followed more complex BI dosing patterns (57.1% vs. 39.5%, P = 0.014), had some difficulty calculating their correct BI dose (40.2% vs. 6.8%, P < 0.001), reported having missed ≥1 dose per month (79.3% vs. 12.6%, P < 0.001), and temporarily stopped BI in the past year (23.2% vs. 0.7%, P < 0.001). In conclusion, understanding patients' experiences with BI therapy can help formulate strategies to improve adherence.

Pregnancy Intention and Pregnancy Outcome: Systematic Review and Meta-Analysis.

Introduction Previous systematic reviews concluded that rigorous research on the relationships between pregnancy intentions and pregnancy outcomes is limited. They further noted that most studies were conducted in high-income countries and had methodological limitations. We aim to assess the current evidence base for the relationship between pregnancy intention and miscarriage, stillbirth, low birthweight (LBW) and neonatal mortality. In March 2015 Embase, PubMed, Scopus and PsychInfo were searched for studies investigating the relationship between pregnancy intention and the outcomes of interest. Methods Studies published since 1975 and in English, French or Spanish were included. Two reviewers screened titles and abstracts, read the full text of identified articles and extracted data. Meta-analyses were conducted where possible. Results Thirty-seven studies assessing the relationships between pregnancy intention and LBW were identified. A meta-analysis of 17 of these studies found that unintended pregnancies are associated with 1.41 times greater odds of having a LBW baby (95%CI 1.31, 1.51). Eight studies looking at miscarriage, stillbirth or neonatal death were found. The limited data concerning pregnancy loss and neonatal mortality precluded meta-analysis but suggest these outcomes may be more common in unintended pregnancies. Discussion While there seems to be an increased risk of adverse pregnancy outcome in unintended pregnancies, there has been little improvement in either the quantity of evidence from low-income countries or in the quality of evidence generally. Longitudinal studies of pregnancy intention and pregnancy outcome, where pregnancy intention is assessed prospectively with a validated measure and where analyses include confounding or mediating factors, are required in both high- and low-income countries.

The importance of unresolved fatigue in depression: costs and comorbidities.

OBJECTIVE: To assess the cost outcomes of patients with a history of depression and clinically significant fatigue. METHODS: Adults with ≥ 2 claims with depression diagnosis codes identified from the HealthCore Integrated Research Database were invited to participate in this study linking survey data with retrospective claims data (12-mo presurvey and postsurvey periods). Patient surveys included measures for depression (Quick Inventory of Depressive Symptomatology), fatigue (Fatigue Associated with Depression Questionnaire), anxiety (7-item Generalized Anxiety Disorder scale), sleep difficulty (Athens Insomnia Scale), and pain (Brief Pain Inventory). After adjusting for demographic and clinical characteristics using propensity scores, postsurvey costs were compared between patients with and without fatigue using nonparametric bootstrapping methods. RESULTS: Of the 1982 patients who had completed the survey and had complete claims data, 653 patients had significant levels of fatigue. Patients with fatigue reported significantly higher scores, indicating greater severity, on measures of depression, pain, sleep difficulty, and anxiety (all p < 0.05). These patients also had higher levels of overall medication use and were more likely to have lower measures of socioeconomic status than patients without significant levels of fatigue (all p < 0.05). Mean annual total costs were greater for patients with fatigue than those without fatigue ($14,462 vs $9971, respectively, p < 0.001). These cost differences remained statistically significant after adjusting for clinical and demographic differences. CONCLUSIONS: Clinically significant fatigue appears to add to the economic burden of depression. This reinforces the need for aggressive treatment of all symptoms and further examination of the variability of this relationship as patients approach remission.