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Preconception BMI linked to fertility and miscarriage risks

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Preconception BMI outside the healthy range is linked to longer time to pregnancy and higher miscarriage risk, new research has revealed.

The study followed 3,033 pregnancy or preconception episodes among couples in Rotterdam between August 2017 and July 2021, examining how body mass index (BMI) – weight relative to height – affects fertility.

Women had a median age of 31.6 years and men 33.4. BMI categories were underweight (under 18.5), normal (18.5–24.9), overweight (25–29.9) and obese (30 or greater).

Fecundability – the chance of conceiving in one menstrual cycle – declined with each BMI unit for both sexes.

Women with obesity had a 28 per cent lower chance of conceiving than women of normal weight, while overweight women had a 12 per cent reduction.

Overweight and obese men had an 11 per cent reduction compared with normal-weight men.

The researchers wrote: “A better understanding of the separate and combined associations of BMI in women and men with fertility and miscarriage outcomes is needed to develop novel targeted population strategies to optimise BMI from the preconception period onward.”

Of the cases studied, 17.8 per cent of women were classed as subfertile, meaning conception took more than 12 months. In addition, 11.3 per cent of pregnancies ended in miscarriage, defined as loss before 22 weeks’ gestation.

Underweight women had nearly twice the risk of subfertility compared with normal-weight women.

Overweight women faced a 35 per cent higher risk, while women with obesity had a 67 per cent higher risk.

Miscarriage risks were also higher outside the healthy BMI range: overweight women had a 49 per cent higher risk and women with obesity a 44 per cent higher risk than normal-weight women.

The median time to pregnancy across all participants was 3.7 months. The study also recorded use of assisted reproductive technology, including in vitro fertilisation, among couples struggling to conceive.

The investigators concluded: “Optimising BMI from the preconception period onward in women and men might be an important strategy to improve fertility and pregnancy outcomes.”

Cancer

Research uncovers potential new target for breast cancer therapy

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Targeting CD1d altered immune cells slowed tumour growth and improved immunotherapy responses in mouse models of breast cancer, researchers found.

The findings suggest blocking the molecule could make the environment around breast tumours more favourable to anti-cancer immune responses.

Further work is needed to understand how these immune changes occur and how the approach could be safely used in patients.

Researchers from King’s College London, the Francis Crick Institute and University College London investigated how immune cells inside breast tumours influence cancer growth.

They focused on myeloid cells, a group of immune cells found in large numbers within tumours that can either support an immune attack against cancer or contribute to tumour growth and immune evasion.

The team examined CD1d, a molecule found on the surface of myeloid and other immune and tissue cells that helps regulate immune responses.

When CD1d was genetically removed from cells in a mouse model of breast cancer, the mice were more resistant to tumour growth. Researchers also saw changes in myeloid cell populations, including increased activity among cells that can help attack cancer.

The team then blocked CD1d using an antibody and again observed changes in myeloid cells and slower tumour growth. Blocking CD1d also improved responses to immunotherapy in the mouse model.

Researchers used single-cell RNA sequencing, a technique that examines gene activity in individual cells, to investigate the immune changes in more detail.

They identified a population of myeloid cells called monocytes that expressed genes associated with inflammation, an important part of the immune response. These cells were particularly important in restricting tumour growth in the mouse models.

A similar pattern of gene activity was identified in data from human breast cancer tumours. Its presence in myeloid cells was associated with positive responses to immunotherapy in breast cancer patients.

However, the findings in people were based on gene expression data and did not test CD1d-targeting treatment in patients.

Professor Patricia Barral, professor of immunobiology at King’s College London and senior author of the study, said: “Many breast cancers do not respond well to current immunotherapies.

“Our findings reveal a previously unrecognised mechanism by which immune cells within tumours are regulated.

“While CD1d is best known for helping immune cells recognise lipid molecules, we found that it also plays a role in shaping the behaviour of myeloid cells within tumours.

“These findings suggest that targeting the immune cells that surround and support tumours could boost anti-cancer immunity and potentially improve treatment responses in the future.”

Researchers now plan to investigate how the immune changes occur and how they can be safely harnessed in patients.

They also want to examine whether targeting CD1d could enhance existing treatments and influence treatment responses in different cancer types.

The work was supported by UKRI BBSRC, Breast Cancer Now and the Cancer Research UK City of London Centre.

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Menopause

Menopause frequently missing from electronic health records – study

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Menopause is often absent from women’s electronic health records, a study of nearly 396,000 women has found.

Researchers found menopause appeared almost seven times more often in participant surveys than in electronic health records (EHRs).

The findings suggest important reproductive health information, including age at menopause, may often be missing from health records used for research.

Audrey Hendricks, associate professor of bioinformatics at CU Anschutz and the study’s principal investigator, said: “Ultimately, we cannot study what we do not measure. We cannot treat what we do not know.

“Menopause has enormous implications for women’s health, but if we don’t consistently capture when menopause occurs and other important reproductive health information, we limit our ability to understand how this transition affects disease risk and health outcomes.”

Researchers at the University of Colorado Anschutz analysed data from women taking part in the National Institutes of Health’s All of Us Research Program.

They compared menopause information reported by participants in surveys with menopause diagnoses recorded in their electronic health records.

Around 193,000 menopause observations were identified in survey data, compared with approximately 28,000 diagnoses in EHR data.

Menopause was documented in electronic health records for only about 7 per cent of women in the dataset.

Nearly all participants with a menopause diagnosis recorded in their EHR also reported menopause in survey data. However, substantially fewer women had menopause documented in their health records.

Other important information was also frequently unavailable, including age at menopause, which researchers may use when examining links between menopause and chronic disease risk.

Menopause is a physiological transition that can affect cardiometabolic health and many other aspects of women’s health.

Researchers said relatively little is known about how factors including the timing and type of menopause influence health outcomes across diverse populations.

Large-scale programmes such as All of Us combine participant surveys, electronic health records and genomic data, but menopause-related research depends on relevant reproductive health information being available.

Missing menopause information can make it harder to investigate how the transition relates to health and disease.

The findings may also help researchers using All of Us data define menopause-related study populations, design studies and estimate how many participants are needed.

Hendricks said: “We have an enormous opportunity to use large-scale datasets to understand women’s health across the menopause transition and to identify who may be at greater risk for disease.

“But we need to make sure that the information researchers need is actually being collected.

“We must do a better job of capturing women’s health information, including reproductive health and measures related to menopause.”

Researchers said more complete and consistent collection of menopause and reproductive health information could help future studies examine factors such as age at menopause and their relationship with disease risk and health outcomes.

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Insight

Fertility rate in England and Wales hits record low, new figures reveal

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The fertility rate in England and Wales fell to a record low of 1.39 children per woman in 2025, down from 1.41 a year earlier.

New figures show that parts of London and cities with major universities accounted for many of the areas with the lowest local fertility rates.

The City of London recorded the lowest rate in 2025 at 0.37 children per woman, followed by Cambridge at 0.87 and the London boroughs of Islington and Westminster at 0.90.

The Office for National Statistics (ONS) defines the fertility rate as the average number of live children women would expect to have over their childbearing lives.

Brighton & Hove recorded a rate of 0.95, followed by Southwark at 0.97 and Norwich at 0.98.

Exeter, Oxford and York, along with the London boroughs of Camden and Hammersmith & Fulham, each recorded 1.01 children per woman.

At the other end of the table, Pendle in Lancashire and Luton in Bedfordshire had the highest rate at 1.93.

They were followed by Oldham in Greater Manchester at 1.87, Bradford in West Yorkshire at 1.84 and Barking & Dagenham in London at 1.83.

The overall fertility rate for England and Wales declined from 1.41 in 2024 to 1.39 in 2025.

A rate of around 2.1 is needed for a population to remain stable over time when the impact of migration is excluded.

Twelve of the 25 local authorities with the lowest fertility rates in 2025 were in London.

In Wales, Swansea recorded the lowest fertility rate at 1.18, while Carmarthenshire, the Isle of Anglesey and Newport each had the highest rate at 1.48.

There were 585,396 live births in England and Wales in 2025, down from 594,677 in 2024 and the lowest number since 1977.

Live births fell across every region in England. The West Midlands recorded the largest percentage decline at 3.1 per cent, while the North East had the smallest at 0.3 per cent.

The average age of parents also increased slightly.

Mothers had a provisional standardised mean age of 31.1 in 2025, compared with 31.0 in 2024. Fathers had an average age of 34.0, up from 33.9.

In 1975, the average age was 26.4 for mothers and 29.5 for fathers.

The proportion of births where the mother was born outside the UK also increased, from 20.8 per cent in 2005 to 27.5 per cent in 2015 and 34.6 per cent in 2025.

India was the most common country of birth for non-UK-born mothers in 2025 for the fourth consecutive year.

It was followed by Pakistan, Nigeria and Romania.

In 2025, 56.4 per cent of births were to parents who were both born in the UK, down from 62.7 per cent in 2015.

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