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Frozen embryo transfers in IVF linked to greater risk of maternal hypertension

Implications rise with increasing use of embryo freezing in assisted reproduction

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Concerns have been raised that pregnancies derived from frozen embryo transfers in IVF might increase the maternal risk of hypertensive disorders.

Pre-eclampsia is one such condition that causes high blood pressure during pregnancy and after labour and which may have severe consequences for both the mother and the foetus.

The concerns have been raised in recent observational studies comparing the outcomes of fresh and frozen transfers, which, by definition, are subject to statistically confounding variables. Sibling comparisons can remove much of this confounding.

The extensive study based on real-life registry data and a comparison of maternal complications in sibling pregnancies indicate that pregnancies following frozen embryo transfer (FET) do indeed have a substantially higher risk of hypertensive disorders than naturally conceived pregnancies.

This same raised risk was also found in a sub-group analysis of sibling births, which was designed to eliminate the effect of any parental factors in the results.

“Our findings are important because the number of FETs is rapidly increasing throughout the world,” says the study’s first author, Dr Sindre H. Petersen from the Norwegian University of Science and Technology.

He has presented the study results at the 38th annual meeting of ESHRE in Milan on behalf of the Committee of Nordic Assisted Reproductive Technology and Safety group which monitors the health of mothers and children born after assisted reproduction in the Nordic countries.

According to the latest registry report from ESHRE, the proportion of FET cycles relative to fresh is still on the rise in Europe. In 2017 the proportion was 49 per cent, against 38 per cent in 2014. Similar trends are present in the US and most high-income countries.

FETs are increasingly common because of improved cryopreservation methods, facilitation of single embryo transfer, reduction of ovarian hyperstimulation, and the elective freezing of all embryos.

The study analysed more than 4.5 million singleton pregnancies in the registries of three Nordic countries with delivery between 1988 and 2015. Of the conceptions following assisted reproduction, 78, 300 were after fresh embryo transfer and 18,037 were after FET.

The registry birth references – largely unique to the Nordic countries – also allowed the identification of 33,209 sibling deliveries following either fresh or frozen embryo transfer, and natural conception.

“This study was by far the largest sibling analysis to date investigating the association between assisted reproduction treatments and hypertensive disorders in pregnancy,” Dr Petersen adds.

Results of the study showed that the risk of hypertensive disorders in pregnancy were almost twice as high in the pregnancies following FET that in pregnancies following a natural conception. However, the risk of hypertensive disorders in pregnancies following fresh embryo transfer pregnancies was comparable to naturally conceived pregnancies.

Hypertensive disorders in pregnancy comprise gestational hypertension and pre-eclampsia, and the more rare but severe conditions of eclampsia and Hemolysis-Elevated-Liver-enzymes-Low-Platelets (HELLP) syndrome.

Adjustments for maternal body mass index, smoking and time between deliveries did not affect the end results, nor did other methods of assisted reproduction (IVF, ICSI, duration of embryo culture or number of embryos transferred).

Dr Petersen says that the design of the study was not able to assess the relative merits of embryo freezing against the higher risk of hypertensive disorders, but notes that “cryopreservation has facilitated the highly favourable single embryo transfer approach, improving foetal and maternal outcomes by avoiding multiple pregnancies”.

Recent studies have suggested that the risk of hypertensive disorders in FET pregnancies may be associated with therapies to prepare the uterus for embryo implantation. These are usually given in the form of hormone replacement therapy in what has become known as a ‘programmed’ or ‘artificial’ cycle – in which there is no naturally developing corpus luteum to provide hormonal support for the pregnancy.

The presence of a corpus luteum – a mass of cells that forms in an ovary responsible for the production of the hormone progesterone during early pregnancy – is one potentially important difference between natural conception and fresh embryo transfers, on the one hand and FETs, on the other, says Petersen.

He adds: “In our analysis all natural conceptions and fresh embryo transfer pregnancies had a corpus luteum, while a subset of the FET pregnancies did not.

“However, we expect from previous Danish and Swedish publications that in our study, only 15-30 per cent of FET pregnancies were in artificial cycles, which seems unlikely to drive the entirety of the strong association in our results.

“It thus seems possible that some inherent aspect of the freezing and thawing process, for example epigenetic changes, might be responsible as well.”

The doctor has pointed out that it is too early to recommend changes to treatment strategies based solely on this study, and that there are still good reasons why frozen embryo transfers are increasingly used, especially in their facilitation of single embryo transfer.

“I am confident that a well-grounded and individualised decision of whether to go for a fresh or a frozen cycle can be made after dialogue between the clinician and the couple,” he concludes.

“Our study can contribute to informed decision-making for patients and clinicians.”

Pregnancy

Women’s health strategy a ‘missed opportunity,’ RCM says

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The Royal College of Midwives (RCM) has referred to the women’s health strategy as a ‘missed opportunity’ to address maternity services. 

The renewed strategy was released by the government this week, with the aim of putting women’s experiences at the centre of care and ensuring they are “better heard and served”.

However, the government stated that because of ongoing investigations into maternity services across the country, the strategy “does not seek to address safety in maternity and neonatal services”.

The RCM described this as a “missed opportunity” and urged the government to ensure that, following the inquiries, maternity is placed “at the very heart” of the strategy.

Gill Walton, RCM chief executive, said the college was “deeply disappointed” that maternity services “do not feature as a headline priority” in the renewed strategy.

She said: “This is a significant missed opportunity and one that is very difficult to understand.

“Pregnancy, birth and the postnatal period are not a footnote in women’s health – they are one of the most significant and consequential phases of a woman’s life.

“A strategy that treats maternity as an afterthought is not truly a women’s health strategy at all. It is exactly the kind of thinking that has allowed maternity services to reach the point they are at today.”

Walton acknowledged that the strategy contained commitments on ensuring women’s voices shape their care, on supporting families through pregnancy loss and on the principle that services should be held accountable when they fail to listen to women.

She added: “But a strategy that addresses one part of women’s health while leaving maternity care behind is only doing half the job.”

Walton urged the government to ensure that this is addressed when the ongoing investigations into maternity care conclude, with any recommendations placed “at the very heart of this strategy with the seriousness and urgency that women, families and midwives deserve”.

In the foreword to the renewed plans, health and social care secretary Wes Streeting referred to the ongoing independent National Maternity and Neonatal Investigation as action being taken by the government to improve safety in maternity services.

The strategy also refers to the new National Maternity and Neonatal Taskforce, chaired by Streeting, which aims to help deliver “safer, more equitable care” for women, babies and families.

The foreword said that, because of ongoing initiatives, it was “important that this work continues without restriction and that the government can properly respond to the findings”.

It added: “This renewed women’s health strategy therefore does not seek to address safety in maternity and neonatal services other than that related to women’s health before and during pregnancy and the actions we are taking immediately to improve maternity and neonatal care.”

The strategy does, however, include plans to prioritise health education in schools, communities and healthcare settings to “empower women” with the “knowledge and tools they need to help control their fertility” and “prepare for the best pregnancy outcomes.

It also promises to provide women with access to “safe and high-quality contraception, abortion care, fertility services, preconception care and support after pregnancy loss in convenient settings.

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Pregnancy

Scotland to publish dedicated miscarriage patient charter

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Scotland is set to publish the UK’s first dedicated miscarriage patient charter, giving women and families clear information on NHS care and support.

Commissioned by the Scottish Government and developed with baby-loss charities Tommy’s, Held In Our Hearts and the Miscarriage Association, the charter sets out minimum standards for compassionate, clinically appropriate and culturally competent miscarriage care across Scotland.

It builds on the Scottish Government’s Delivery Framework for Miscarriage Care, which has already changed practice across NHS boards.

Jenni Minto, Scottish public health and women’s health minister, said: “Miscarriage is devastating, and for too long women have not had the care and support they deserve.

“That is changing. Scotland will become the first country in the UK to publish a miscarriage patient charter, meaning women know exactly how they will be supported by health services following their loss.”

Unlike previous UK-wide norms, where women were typically offered enhanced support only after three miscarriages, Scotland’s approach means women can receive appropriate support after their first miscarriage.

The charter also sets out clear rights and expectations so every woman, regardless of location or circumstance, understands the care she should receive.

It includes access to private rooms in hospitals rather than busy clinical areas or maternity settings, progesterone treatment where clinically appropriate, compassionate and culturally competent bereavement support, and clear information in 18 languages, including British Sign Language and audio formats.

Progesterone is a hormone that growing evidence suggests may help reduce the risk of miscarriage in certain cases when given to women who meet specific clinical criteria.

The Scottish Government said the charter is designed to ensure personalised, respectful care and to address long-standing inequalities experienced by women during miscarriage.

It is intended to provide clarity on the support women can expect, consistent standards across all NHS boards, stronger awareness and confidence among healthcare professionals, and better access to emotional and practical support services.

Charities involved in its development said many women still report feeling dismissed, uninformed or unsupported during miscarriage.

They said the new charter marks an important step towards making sure every woman feels heard, respected and cared for.

The charter aligns with Scotland’s wider Women’s Health Plan, which is improving care across reproductive, menstrual, maternal and perinatal health.

Recent national developments include greater investment in women’s health services, improved training for healthcare staff, new digital and in-person support tools, and targeted action to reduce inequalities in access and outcomes.

Together, these measures aim to create a more compassionate and equitable women’s health system.

Minto said: “This charter is a landmark moment.

“It tells women clearly what they should expect from their NHS, and it holds services to account for delivering it.

“Scotland is leading the way, and I am proud of the progress NHS boards and our charity partners have made together.”

The model is expected to inform wider UK discussions on miscarriage support, bereavement care and early pregnancy services.

The charter will be made publicly available, offering women, partners and families clear guidance on their rights and the standards they can expect when seeking care.

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Motherhood

The maternity care crisis hiding in plain sight

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By Adrianne Nickerson, founder and CEO, Oula

The numbers get the headlines. Maternal mortality rates. Access deserts. Workforce shortages. These are real and urgent problems, but they’re not the whole story.

There’s a quieter breakdown happening inside routine appointments, and it’s driving outcomes in ways that never show up in formal reports.

Women describe maternity care that feels rushed and transactional.

They talk about repeating their medical history at every visit, leaving appointments with questions they never got to ask, and receiving advice so generic it doesn’t seem to account for their actual lives.

These aren’t just complaints about bedside manner. They’re signals that the system is losing the thread, and when that happens, clinical risk follows.

A patient who doesn’t feel heard may decide a new symptom isn’t worth mentioning.

A patient who leaves an appointment without clear next steps may wait too long to call when something changes. These small moments of disconnection are where complications quietly take shape.

The system is structured to rush

This isn’t about individual clinicians failing women. It’s about a care model built around short, physician-led visits with limited coordination across roles — applied to pregnancies that are often medically and emotionally complex.

Clinicians are covering more ground in less time, and patients feel that compression. Women in marginalised communities feel it most acutely.

Reports of dismissal and bias are well-documented, and the consequences compound: when trust erodes, communication breaks down, and the window for early intervention narrows.

What women are actually asking for

Younger women in particular are entering maternity care with different expectations. They want explanations for recommendations, not just instructions.

They want to understand tradeoffs and have their preferences carry forward from one visit to the next. They’re not looking to reduce medical oversight, they’re looking for care that makes sense as a whole.

That’s driving real interest in collaborative care models that bring OBs, midwives, nurses, and behavioural health professionals into a coordinated framework.

When roles are clear and communication is shared rather than siloed, the experience changes, and so do outcomes.

Experience is clinical performance

Health systems are sophisticated at tracking infection rates and readmissions. The experience of care deserves the same level of attention, because it’s often where the clinical picture first starts to slip.

The fixes aren’t mysterious. A longer first visit can prevent confusion that compounds over months. Integrated mental health support surfaces concerns that might otherwise go unspoken.

Clear communication across the care team eliminates the mixed messages that erode confidence.

Postpartum services like pelvic floor therapy and lactation support – when easy to access and clearly explained – extend the impact of care well beyond delivery.

Workforce shortages and financial pressure make all of this harder. They also make it more urgent.

When women feel respected and informed, they raise concerns earlier, follow care plans more consistently, and seek help sooner.

That’s not a soft outcome – that’s how complications get prevented.

Simply put: adjusting how care is delivered is one of the most direct ways to improve clinical outcomes.

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