Fertility
Higher doses of common fertility drug may increase pregnancy risks

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.”
Fertility
NHS IVF access review launched in Scotland
Fertility
Jersey PMOS clinic a ‘good start’

Jersey is launching a pilot PMOS health check clinic for women to improve follow-up care and access to specialist support.
The clinic will operate at the Assisted Reproductive Unit in St Brelade from October, providing health checks rather than diagnosing or treating the condition.
Women with polyendocrine metabolic ovarian syndrome (PMOS) will need to see their GP before being referred to the service.
Jessica Pinel, chair of PMOS Jersey, described the service as “a good start” but said more could be done.
She said the clinic was in line with draft guidance from the UK’s National Institute for Health and Care Excellence (NICE), which advises annual checks to identify health issues associated with the condition.
Pinel was diagnosed with PMOS in 2023 after spending more than £3,100 on treatment.
She said: “We need to realise that cost may be a barrier to people getting support, even if the cost is going to their GP. But I think we do have to be grateful that we have had this service approved.
“Because the clinic is part of the government health system, it allows for referrals to be made into different pathways like endocrinology, dermatology, so it could actually allow for better support and reduce costs for women with PMOS.
“I think it’s great to see things moving forward and, for women who are newly diagnosed, there’s going to be a more joined-up approach and we’re now taking the long-term health consequences of PMOS more seriously.”
PMOS, which was renamed from polycystic ovary syndrome (PCOS) in May, is a metabolic condition that changes how the ovaries work and affects up to one in eight women, according to the UK’s NHS.
The new name was introduced to reflect the condition’s effects across the body. PMOS has been linked to infertility and weight gain.
The Jersey government said the clinic would help women access further care for PMOS and associated conditions, including type 2 diabetes.
Screening clinic nurse Corrinne Purdy said reviews would take a holistic approach, covering medication, height and weight, sleep, management of the condition, fertility aspirations and mental health.
She said: “We will see whether they’re getting on alright with their medication, how they’re feeling about themselves; we will do height and weight reviews, we will ask them questions about their sleep, how they’re managing their condition.
“We will also speak to them about any particular fertility aspirations and how they’re getting with their mental health as well.”
Purdy said PMOS had been “overlooked” for a long time and that many women struggle with associated symptoms.
The government said women who require specialist management for heavy menstrual bleeding, fertility concerns or other gynaecological conditions would be referred to the appropriate specialist service.
It said existing waiting lists for gynaecology or surgical capacity would not be affected because additional clinical capacity had been identified.
Assistant Minister for Health and Social Services Andy Howell said many women “have been suffering” with PMOS and that the trial was intended to show “that we’re taking them seriously and they’re not going to be dismissed”.
Howell said funding for the clinic would be “managed within the budget that we have at the moment, so it’s not going to cost us any more”.
The Health Department was allocated £381m for 2026 as part of the government’s 2026-2029 budget.
The clinic will also offer investigations including ultrasound scans and endometrial biopsies during the same visit.
Howell said Jersey would base its review of the service on NICE guidance, while Pinel said feedback from women using the clinic would be shared with practitioners to help improve the support provided.
Fertility
Scotland’s birth rate hits record low for third year running

Scotland recorded its lowest number of births for a third consecutive year in 2025, with 45,067 live births registered.
The total was almost 696 fewer than the previous year and the lowest annual figure since records began in 1855.
Deaths also outnumbered births for the 11th consecutive year, with the gap between the two generally widening since 2014.
Registrar General and National Records of Scotland chief executive Alison Byrne said: “This is the eleventh year in a row where deaths have outnumbered births and the third in a row where we have a new record low for the number of births in Scotland.
“Generations of change are captured in these figures.
“This data will inform debate and decision-making across the public and private sectors, as we consider what this means for our future.”
Figures published by the National Records of Scotland (NRS) show the country’s total fertility rate fell to 1.23 in 2025, from 1.24 in 2024.
The total fertility rate measures the average number of children born to each woman. A rate of around 2.1 is needed for a population to replace itself without migration.
Scotland’s 2025 figure was the lowest since the start of the NRS-published time series in 1951. The country’s fertility rate was last above 2.1 in 1973.
Despite the decline in births, Scotland’s population increased slightly in the year to June 2025, driven by migration.
The annual figures also showed an increase in stillbirths, from 159 in 2024 to 188 in 2025.
This represented 4.2 stillbirths for every 1,000 live and stillbirths, compared with 3.5 in 2024. The 2024 figure was the joint lowest stillbirth rate recorded for any year and remains historically low.
The infant death rate fell from 3.5 per 1,000 live births in 2024 to 3.3 in 2025.
Adoptions declined from 369 in 2024 to 340 in 2025.
Meanwhile, 27,191 marriages took place in Scotland during 2025, 236 more than the previous year. Four per cent were same-sex marriages and 96 per cent were mixed-sex marriages.
Civil partnerships increased to 944, the highest number since 2006, the first full year in which civil partnerships were available.
The figures form part of the NRS annual release covering births, marriages, deaths and other vital life events in Scotland.
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