Higher cumulative doses of common fertility drug clomiphene citrate may increase pregnancy loss risks, according to new research.

Around one in six people experience infertility, with irregular or absent ovulation among the most common causes.

Clomiphene citrate has long been a mainstay of fertility treatment, but Adelaide University research has raised concerns about higher cumulative doses.

The new study found that high doses of clomiphene citrate accumulated over multiple fertility treatment cycles could increase the risk of pregnancy loss.

Lead author associate professor Sheree Boulet said the findings showed a clear dose-response relationship, meaning the risks increased as cumulative exposure rose.

She said: “Women who received higher cumulative doses of clomiphene citrate experienced progressively greater risks of adverse pregnancy outcomes.

“We examined more than 21,000 embryo transfer cycles across four cumulative dose categories and found that increasing the dose did not significantly improve the chance of a live birth.

“Our findings suggest there may be a point where increasing the dose offers little additional benefit while exposing women to greater risk, highlighting the importance of carefully balancing effectiveness with safety when making treatment decisions.”

Supported by the NHMRC and conducted in partnership with Boston University and the Centers for Disease Control and Prevention, researchers analysed 21,004 IVF embryo transfer cycles in the US.

Women receiving cumulative doses of 500mg to 749mg of clomiphene citrate had a 12 per cent higher risk of miscarriage, while those receiving 750mg to 999mg had a 38 per cent higher risk.

Women receiving cumulative doses of 750mg or more were also more than twice as likely to have twins or other multiple births.

Rates of spontaneous abortion, another term for miscarriage, increased as the dose rose.

Researchers also recorded more than a threefold increase in stillbirth at the highest dose, although the finding was not statistically significant because that dose was rare. Larger studies are needed to confirm the association.

The finding is consistent with an earlier Adelaide University study that showed a doubling of neonatal death in pregnancies involving clomiphene citrate. Neonatal death means the death of a baby shortly after birth.

Higher cumulative doses did not improve the chance of a live birth, but did increase twinning, which raises the risk of adverse outcomes for both mother and child.

Clomiphene citrate is one of the world’s most widely prescribed fertility drugs. It has been prescribed to millions of women worldwide since 1967 and remains a recommended first-line treatment for ovulation induction.

The drug is recognised as an essential medicine by the World Health Organization. It works by stimulating the ovaries to release eggs, increasing the chance of pregnancy.

Women who do not respond to lower doses, or who require multiple treatment cycles, may receive progressively higher cumulative doses over time.

The findings build on a series of studies from Adelaide University’s Robinson Research Institute linking clomiphene citrate with increased risks of pregnancy loss, stillbirth, perinatal death and some birth defects.

Experimental studies in mice supported these findings, showing that higher doses reduced successful pregnancies and were associated with pregnancy loss, impaired fetal growth and developmental abnormalities.

Professor Michael Davies, senior researcher and co-author of all the studies, said the latest work builds on more than two decades of Adelaide-led research into the safety of fertility treatments.

He said: “Clomiphene citrate has been used by many women since 1967, but it has never been comprehensively evaluated in large prospective clinical trials.

“Our studies indicate that women respond differently to clomiphene citrate and that increasing cumulative doses may increase the risk of adverse pregnancy outcomes without improving the likelihood of a live birth.

“The findings confirm and extend our previous studies in both human and mouse models which highlight the need to better understand the dose-response relationship and whether more personalised dosing strategies could improve safety.

“Until we can better understand these differences, it remains important that clinicians rigorously follow manufacturer’s safety recommendations and avoid unnecessarily increasing cumulative doses.

“The same questions are now being asked of newer ovulation-inducing medications, so any move away from clomiphene citrate should also be guided by robust evidence rather than assumptions about safety.”

Women should not feel pressured into an “ideal birth”, health secretary Yvette Cooper has said as she promised major maternity reform.

Cooper has returned to the Department of Health and Social Care 27 years after serving as public health minister under Tony Blair.

She said maternity and child health would be a major focus of her new role, alongside significant reforms to social care.

In an interview with the Guardian, Cooper said the changes should address any pressure on women to pursue a particular birth experience.

Families affected by maternity failures have repeatedly raised concerns that some units were reluctant to escalate medical interventions because of a preference for more natural births.

Cooper said: “I would worry about any mum feeling pressurised that there is somehow a kind of an ideal birth experience to live up to when it’s always different in every case, and you have to follow the evidence, you have to have informed choice.”

As one of her first actions as health secretary, Cooper said she intended to reintroduce binding national maternity standards.

The standards were dismantled during early Conservative NHS reforms and replaced with fragmented arrangements managed separately by individual hospital trusts.

A new maternity taskforce will draft the standards, which will have five central aims.

These include ending regional differences in levels of care and tackling racial inequalities linked to poorer outcomes in deprived areas, particularly for Black and Asian women.

Patient experiences will also form part of how standards are measured, while new targets will aim to identify underperformance before a major scandal develops.

Cooper, who became the first minister to take maternity leave while serving as a junior health minister in the early 2000s, said reports into maternity scandals had been “traumatic” to read and showed that systemic change was needed.

She said: “We’ve always said the NHS is about the cradle to the grave. I want to make it a personal crusade to put the cradle back at the heart of the NHS, and to have much more focus around maternity and child health, the very beginning of a family’s life, making that much more central to the priorities of the NHS, giving it the priority that it really deserves.”

Cooper said discussions about how maternity services could better listen to mothers’ needs had been taking place for the past two decades.

However, she said the emphasis on placing women and families at the centre of care appeared to have been lost.

She said: “It feels incomprehensible that we could be in this situation in the 2020s. I went back to look at some of the things that we’d done 25 years ago.

“And what did strike me was how much we were talking then about women and families being at the centre of care and about listening to women’s views.

“It is really shocking and distressing feeling that has somehow been lost in some of the maternity units where actually it should be the central issue.

“I had a direct interest. I was pregnant at the time. But I am really struck by it now, just feeling like there is this big gap in the priorities that the NHS has been focused on.”

Cooper said she was determined to provide a robust response to Donna Ockenden’s investigations into maternity failures at Shrewsbury and Telford and Nottingham, alongside Baroness Valerie Amos’s national investigation into England’s maternity system.

The investigations highlighted systemic clinical errors, understaffing and toxic institutional cultures. They found that hundreds of infant and maternal deaths were directly linked to failures to listen to mothers and defensive attempts to protect institutions.

Amos’s review faced criticism, including the resignation of an expert adviser over the lack of explicit warnings about “normal birth ideology”.

Families also questioned whether the review’s proposed statutory maternity commissioner would have sufficient independence.

Cooper said she remained committed to introducing the role.

She said: “In the end, the most important people in the maternity services are the mothers, babies, the families. But the point of having a maternity commissioner is to make sure that those issues are championed as part of an NHS.”

She also said reforms needed to address an oppositional culture between doctors and midwives in some trusts over when medical intervention during birth may be necessary.

Cooper said: “The thing that struck me most was the sense of women feeling they weren’t being listened to … And I think that probably does go back to issues around culture.”

Cooper, who served as foreign secretary until recently, said she was prepared for a difficult period in the health role as she sought to implement Andy Burnham’s social care reforms.

She said she remained committed to establishing the national care service announced by the prime minister the previous week.

A longstanding ally of former prime minister Keir Starmer and a former rival of Burnham in the 2015 Labour leadership contest, Cooper said she believed the change of prime minister had been necessary.

She said: “Of course it’s not easy. I really did not think it was possible to win the election when I came back into the shadow cabinet in 2022. It’s only because of what Keir did that we managed to win.

“But we had very difficult local election results … we have to respond to that. But I think we’ve got a sense of energy now.

“All of the things that Andy wants to focus on and drive are also just very much the things that that people are concerned about across the country.”

Daily beetroot juice may help support kidney health during pregnancy in women with chronic kidney disease, early research suggests.

Pregnancy puts additional strain on the kidneys. Around half of women with moderate to severe chronic kidney disease experience a decline in kidney function while pregnant.

Despite these risks, outcomes for pregnant women with the condition have changed little over the past 30 years.

Many medicines used to manage kidney disease are also unsuitable during pregnancy, meaning women often need to stop taking them for at least nine months.

Researchers at King’s College London examined whether dietary nitrate from beetroot juice could offer a simple and safe way to support kidney function during pregnancy.

Beetroot juice is naturally rich in nitrate, which the body converts into nitric oxide. Nitric oxide widens blood vessels and improves blood flow, which could reduce the strain placed on the kidneys during pregnancy.

The study involved 108 pregnant women with stage 2 to 5 chronic kidney disease across eight UK hospitals.

Before reaching 25 weeks of pregnancy, participants were randomly assigned to receive either standard care or a daily beetroot juice supplement containing dietary nitrate.

The study was mainly designed to assess whether a larger clinical trial would be practical. However, the findings also suggested possible benefits for mothers and babies.

Kate Bramham, consultant nephrologist at King’s College Hospital, professor at King’s College London and senior author of the study, said: “For women living with chronic kidney disease, pregnancy has always meant navigating a difficult trade-off between preserving their own health and keeping their baby safe, often with few tools to do both.

“These results are an encouraging first step towards a low-cost, low-risk intervention that could genuinely make a difference for this group of women, who have been underserved by research for far too long.”

Women receiving beetroot juice experienced around 70 per cent fewer serious adverse events overall than those receiving standard care. Of the serious adverse events that occurred, around half affected newborn babies.

Among women with more advanced kidney disease, researchers also observed trends towards better kidney function after pregnancy, fewer newborn admissions to neonatal care and a reduced need for blood pressure medication during pregnancy.

The researchers found no safety concerns linked to beetroot juice supplementation during pregnancy, including no increase in hyperkalaemia, which means unusually high potassium levels in the blood.

There have been concerns that beetroot juice could increase the risk of hyperkalaemia in pregnant women with chronic kidney disease, with some online advice recommending that they avoid it. However, no increase was recorded among women receiving the supplement.

Dr Priscilla Smith, a nephrologist, King’s College London PhD student and first author of the study, said: “Pregnancy can put additional stress on the kidneys, and for women with chronic kidney disease there are currently limited options to protect kidney function during this time.

“Our findings suggest beetroot juice could offer a simple and accessible approach that is safe and worth exploring further.”

The researchers said larger clinical trials are now needed to determine whether beetroot juice can significantly reduce kidney function decline and improve long-term outcomes for mothers and babies.

If confirmed, the intervention could offer an inexpensive and widely available way to support women with chronic kidney disease during pregnancy, when safe treatment options remain limited.

The research was supported by funding from Kidney Research UK.

Dr Andrew Webb, clinical senior lecturer at King’s College London and a co-author of the study, said: “By increasing nitric oxide production, dietary nitrate from beetroot juice may help improve blood vessel function and support kidney health.

“These early findings provide an important foundation for future research into protecting women with chronic kidney disease during pregnancy and their babies.”