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Boosting immune cell tolerance may help prevent early pregnancy loss

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Recurrent pregnancy loss can be devastating and exert a major impact on women, their partners, and society more broadly, but currently there are few options for effective therapies.

Over several years, there has been mounting evidence that a deficiency in special immune cells called T-regulatory (Treg) cells, which are essential for preparing the uterus for receptive embryo implantation, are a factor in early pregnancy loss.

A new study in The American Journal of Pathology, details evidence in a pre-clinical animal model that boosting these cells improves the chance of healthy pregnancy. The work raises the prospect of evaluating this intervention in women who are prone to experience early pregnancy loss, a common condition affecting natural conception and women undergoing in vitro fertilization (IVF).

Lead investigator Sarah A. Robertson, PhD, The Robinson Research Institute and School of Biomedicine, the University of Adelaide, Australia, explained: “Previous studies have found low numbers of Treg cells in women who experienced early pregnancy loss as well as changes that lead Treg cells to have functional problems that are reminiscent of autoimmune diseases.

“This can impair the implantation process and suppress development of the early placenta. Therefore, Treg cells provide an attractive target for interventions to improve maternal immune tolerance and protect against pregnancy disorders caused by immune imbalance in at-risk women.”

The researchers utilized a mouse model of early pregnancy loss to test a new candidate treatment intervention in which the cytokine interleukin-2 (IL-2) is combined with specific antibodies to target Treg cells. Like humans with recurrent pregnancy loss, the mice have an immune defect that arises at conception and results in later feotal loss.

The researchers administered the IL-2 antibody complex (called IL-2/JES6-1) in the time between conception and embryo implantation to the miscarriage-prone mice and also in mice that have had healthy pregnancies. They observed significant changes to the number and phenotype of the Treg cells in the uterus, blood, and other tissues in both groups of mice.

The expanded pool of Treg cells exhibited features that are characteristic of robust pregnancy tolerance and were effective in preventing generation of detrimental effector T cells that threaten pregnancy success. Importantly, the miscarriage-prone mice showed markedly improved pregnancy outcomes after treatment, and their miscarriage rate was consistently reduced from 30 per cent to 11 per cent, which is within the normal range for mice.

Professor Robertson added: “The results show that efficacy of the IL-2/JES6-1 treatment might be achieved with lower doses, which will likely be important as we consider how to translate the findings to human application.

“Another notable observation was that treatment in very early pregnancy, even before the embryos commence implantation, has a profound effect on the progression of the pregnancy with lasting benefit into late gestation.

“This is consistent with growing evidence pointing to embryo implantation and early placental development being the turning point for pregnancy success.”

The study demonstrates the potential of targeting Treg cells and provides pivotal evidence to justify human studies; however, it will be important to undertake clinical trials to assemble evidence of safety and benefit in humans before the treatment can be recommended.

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Insight

Higher nighttime temps linked to increased risk of autism diagnosis in children – study

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Nighttime temperatures during pregnancy may be linked to a higher chance of an autism diagnosis in children, a recent study suggests.

The research tracked nearly 295,000 mother-child pairs in Southern California from 2001 to 2014 and linked warmer overnight temperatures with higher risk in early and late pregnancy.

Children of mothers exposed to higher than typical nighttime temperatures during weeks one to 10 of pregnancy had a 15 per cent higher risk of an autism diagnosis.

Exposure during weeks 30 to 37 was linked to a 13 per cent higher risk.

 Lead author David Luglio, a post-doctoral fellow at Tulane University, said: “A key takeaway is that we identified specific windows when a mother and her developing child can be most affected by exposures to higher nighttime temperatures.

“This is critical and hopefully can help mothers prepare accordingly.”

The study is described as the first to examine how temperature may affect fetal neurodevelopment, the process by which a baby’s brain and nervous system form during pregnancy.

Extreme temperatures linked to increased risk were classified as above the 90th percentile, meaning 3.6°F hotter than average, and the 99th percentile, 5.6°F above average.

The association held even after researchers accounted for factors such as neighbourhood conditions, vegetation and fine-particle air pollution.

The study could not account for other factors such as access to air conditioning. Researchers did not find the same association with daytime temperatures, potentially because people spend more time away from home during the day.

“Heat waves are becoming more frequent, and people may only think of the dangers of daytime heat exposure,” said Mostafijur Rahman, assistant professor of environmental health sciences at Tulane University.

“These results indicate a strong association between high nighttime temperatures during pregnancy and autism risk in children and show that we need to think about exposure to heat around the clock.”

The study did not examine how higher temperatures at night might affect prenatal development, though Luglio said it is possible that warmer nights disrupt sleep for pregnant mothers.

Previous research has suggested insufficient sleep during pregnancy may be linked to a higher risk of neurocognitive delays in children.

“Extreme heat exposure during pregnancy has been linked to a range of adverse health outcomes, including prenatal neurodevelopment delays and complications with an embryo’s development of a central nervous system,” Luglio said.

“The goal of our study was to specifically explore the link between prenatal heat exposure and autism diagnoses for the first time.”

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Fertility

Most NHS regions in England limit IVF to single cycle, research finds

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Nearly 70 per cent of NHS regions in England fund only one IVF cycle for women under 40, breaking national guidelines, new research has found.

Twenty-nine of the 42 integrated care boards, which control local NHS budgets, now offer only one round of treatment, after four reduced access in the past year.

National Institute for Health and Care Excellence (Nice) guidelines recommend three full cycles for women under 40 who have been unable to conceive for two years.

Only two of England’s 42 integrated care boards have policies consistent with these guidelines, which they are not legally obliged to follow.

The research was conducted by the Progress Educational Trust, a fertility charity.

Sarah Norcross, the director of PET, said the impact was “devastating” for couples struggling with infertility.

She said: “Infertility is already incredibly stressful for people, and it puts them under even more pressure, because there is so much riding on whether that one NHS-funded cycle is going to work.

“And for some people, that will be their only chance, because private fertility treatment is so expensive.”

The data showed regional variations, with the whole of the north-west offering just one cycle.

“It’s a postcode lottery, and we’re seeing a race to the bottom,” said Norcross.

Of the 29 integrated care boards that offer a single cycle, 19 provide only a partial cycle, where not all viable embryos created are transferred.

There was just one recent example of improved services, from NHS South East London, which in July 2024 went from one partial to two full cycles.

The NHS estimates that about one in seven couples may have difficulty achieving a pregnancy. One cycle of IVF can cost from £5,000 at a private clinic.

Fertility rates in England and Wales have fallen since 2010 to 1.41 children per woman in 2024, the lowest on record and below the replacement level of 2.1 at which a population is stable without immigration.

Health minister Karin Smyth said in a written parliamentary answer last month that it was “unacceptable” that access to NHS-funded fertility services varied across the country.

Revised Nice fertility guidelines are due this spring, but Norcross said changing them seemed pointless.

She said: “Fertility treatment has always been a Cinderella service. It’s always been the one they’ve chosen to cut or to ignore.

“Nice has recommended three full NHS-funded cycles, for women under 40, for more than 20 years. This has never been implemented across England, unlike in Scotland.”

Norcross advocated centralised commissioning and replicating Scotland’s approach, which included financial modelling and a phased implementation starting with two cycles to avoid long waits, moving up to three once capacity was achieved.

“It is a tried and tested plan that England could follow,” Norcross added.

A Department of Health and Social Care spokesperson said: “We recognise access to fertility treatment varies across the country and we are working with the NHS to improve consistency.

“Nice provides clear clinical guidelines, and we expect integrated care boards to commission treatment in line with these.

“Updated Nice fertility guidelines are expected this spring and we will continue to support NHS England to make sure the guidance is fully considered in local commissioning decisions.”

An NHS England spokesperson said: “These clinical services are commissioned by integrated care boards for their area based on the needs of the local population and prioritisation of resources available.

“All ICBs have a responsibility to ensure services are provided fairly and are accessible by different population groups.”

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Fertility

France urges 29-year-olds to start families now

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France is urging 29-year-olds to have children as part of a 16-point plan to boost fertility and raise birth rates.

Health officials say the aim is to prevent men and women facing fertility problems later in life and thinking “if only I had known”.

The strategy comes as the country, like many western nations including the UK, faces tumbling birth rates.

The trend is creating concerns about how governments can fund pensions and healthcare for ageing populations with fewer younger working people paying taxes.

But policies to raise fertility rates globally have produced limited results, and critics of the scheme suggest better housing and maternity provision could be more effective.

The government will send out “targeted, balanced, and scientifically sound information” to young people on issues including sexual health and contraception.

The material “will also reiterate that fertility is a shared responsibility between women and men,” the country’s health ministry said.

The plan includes efforts to increase the number of egg-freezing centres from 40 to 70. The process involves extracting and storing a woman’s eggs for potential future use.

The country’s health system already provides free egg-freezing for people aged 29 to 37, a service that costs about £5,000 per round in the UK.

The country’s fertility rate of 1.56 children per woman is below the 2.1 needed to maintain a stable population.

However, it is higher than rates in China, Japan and South Korea, and the UK, where the latest figures show it dropped to a record low of 1.41 in England and Wales by 2024.

Professor François Gemenne, who specialises in sustainability and migration at HEC Paris Business School, told Sky News: “This is something that demographers had known for a long time, but the fact that there were more deaths than births in France last year created a shock effect.”

He said the country’s “demographic worry” is exacerbated by the design of its pensions system and its “obsession with immigration and the fear of being ‘replaced'”.

The plan also includes a new national communication campaign, a “My Fertility” website advising on the effects of smoking, weight and lifestyle, and school lessons for children about reproductive health.

The health ministry has acknowledged its maternal and infant mortality rates are higher than neighbouring countries and is beginning a review of perinatal care to address the “concerning” situation.

Channa Jayasena, professor in reproductive endocrinology at Imperial College London, told Sky News: “On the female side, societal changes leading to older age of motherhood are certainly important.

He said obesity was also a problem as it increased women’s risk of polycystic ovary syndrome and endometriosis.

Allan Pacey, professor of andrology (male reproductive health) at Manchester University, said for most people globally, deciding to have children was “down to [non-medical] factors such as better access to education, career opportunities, taxation, housing, mortgages, finance, etc.”

“Medicine can’t help with those things,” Pacey added.

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