The first patients have been dosed in a UK miscarriage trial testing a new intravaginal drug delivery platform for threatened miscarriage.

The FREEDOM study is evaluating 400mg progesterone Callavid in patients diagnosed with luteal phase insufficiency, a condition in which progesterone levels may be too low to support early pregnancy, increasing the risk of infertility and recurrent miscarriage.

Callavid uses a patented leak-free, tampon-like design intended to address the limitations of current vaginal treatments, which rely on self-administered pessaries, or vaginal suppositories, that can leak and may move during use.

The device is being developed by London-based Calla Lily Clinical Care, a medical technology company focused on women’s health. The trial is funded by the National Institute for Health and Care Research and run in collaboration with the Trial Management Unit at University Hospitals Coventry and Warwickshire NHS Trust.

According to the company, Callavid is positioned to become the world’s first drug-device combination product to support treatment of threatened miscarriage, as well as luteal phase support as part of assisted reproductive technologies, including in vitro fertilisation, or IVF.

The Government’s Renewed Women’s Health Strategy for England cites estimates ranging from 120,000 to 250,000 cases of miscarriage a year in the UK. Administering 400mg micronised progesterone twice daily is recommended by the National Institute for Health and Care Excellence for women who have suffered a previous miscarriage and experience bleeding during early pregnancy, known clinically as threatened miscarriage.

Current pessary delivery methods can result in uncertain placement and movement during use. These limitations can reduce the efficiency and consistency of drug absorption, potentially compromising delivery of the intended dose, and patients are regularly advised to lie horizontal for extended periods after each administration.

The FREEDOM trial is led by professor Siobhan Quenby MBE, an authority on miscarriage and preterm birth, and an honorary consultant at University Hospitals Coventry and Warwickshire NHS Trust. The study aims to evaluate safety, user acceptability and progesterone absorption, with the goal of providing evidence of improved usability in self-administration.

Quenby commented: “Through my clinical practice, I see the difficulties patients face with existing vaginal progesterone products at an already very stressful time. Callavid offers a promising new solution to ensure delivery of the correct progesterone dosage and give women greater confidence in their treatment. There is genuine excitement among both clinicians and patients at the prospect of Callavid progressing into clinical trials.”

Dr Lara Zibners, co-founder and chair of Calla Lily Clinical Care, added: “As a physician and entrepreneur, I believe we have a responsibility to create more effective, patient-centred solutions in women’s health. Having been through seven rounds of IVF myself, I have experienced how difficult progesterone treatment can be, and I am proud to be advancing an innovation shaped by both medical insight and lived experience.”

Thang Vo-Ta, co-founder and chief executive of Calla Lily Clinical Care, said: “Dosing the first patients in the FREEDOM study marks a critical milestone for Calla Lily Clinical Care. Callavid represents a differentiated delivery modality for a broad range of therapeutics in the pharma pipeline, and will create new opportunities to extend the lifecycle of existing drugs. This trial is a key step in demonstrating Callavid’s massive potential.”

A rare pregnancy complication has led to emergency surgery, including hysterectomies, after staff failed to detect it in affected women.

Scores of women have come forward to tell their stories of how they were affected by placenta accreta spectrum, or PAS, since the launch in February of a campaign to raise awareness among NHS staff and mothers-to-be of the dangers it poses.

One of them lost so much blood while giving birth that she has had to give up working as an NHS operating theatre nurse and suffers from PTSD.

Another lost six litres of blood and blames her daughter’s cerebral palsy on the stroke the child had while hospital staff were battling to save her life after an emergency caesarean section. Others have suffered permanent damage to their bladder or bowels.

Erin Cooper was never assessed for PAS even though she regularly bled heavily from 26 weeks into her pregnancy until she delivered her baby by emergency C-section at 33 weeks in 2024.

She said: “What I didn’t know, what no one had diagnosed, was that my placenta was abnormally and dangerously attached.

“The haemorrhage was catastrophic. I lost 4.5 litres of blood. I needed a massive blood transfusion, 13 units in total, and to save my life they had to perform a hysterectomy.

“It was like a murder scene. I now have PTSD around blood. I was a theatre nurse. I’ve had to change jobs and can no longer work in a patient-facing role.

“I get panicky when I hear sirens. I can’t drive past the hospital without feeling like I’m about to have a panic attack.

“I feel a deep loss of my womanhood. I’m now going into early menopause. Not a day goes by when I don’t think about being infertile at 33.”

PAS is associated with a history of C-section birth, while assisted fertility using in vitro fertilisation also increases the risk.

It occurs when the placenta, which gives the foetus nutrients and oxygen, grows too deeply into the wall of the woman’s uterus and blocks some or all of the cervix.

This makes the usual separation of the placenta from the uterus during birth difficult.

One hundred women who are concerned about how medical teams dealt with their PAS have contacted Amisha and Nik Adhia, who set up the Action for Accreta campaign.

The couple have collated the women’s experiences into a dossier of stories that vividly illustrate how often the condition goes undetected and the appalling physical consequences for those involved.

Seventy-five of the 100 cases are from around the UK and the others from abroad. In other cases, mothers suffered permanent damage to their bladder or bowels.

Six out of 10 of the 100 women say their PAS went undiagnosed, increasing the risk of them bleeding to death.

The 100 cases reveal “a dangerous gap in maternity care” and “systemic failures” that should prompt UK hospitals to do much more to train staff how to spot and treat PAS once it is diagnosed, say campaigners.

Politicians from all the main parties at Westminster are supporting their call for a major overhaul in how the NHS manages the condition.

Chloe Robinson from Burnley was taken to hospital in the middle of the night when she began bleeding heavily at home at 34 weeks pregnant in July 2024.

She said: “In theatre they discovered I had placenta accreta, something no one had suspected.

“They had to get several members of staff who were on call into the hospital because they weren’t prepared. I lost six litres of blood and had a hysterectomy to save my life.

“My daughter had a stroke, which I believe was due to the traumatic birth [and] she now has cerebral palsy.

“If they had found the condition before, none of this may have happened.”

A woman is at higher risk of PAS if she has had a previous birth by caesarean section because the placenta of her new pregnancy can attach itself to the scar of her C-section.

It is unclear exactly why IVF seems to also heighten the risk of the condition.

Doctors believe that the process of transferring and implanting an embryo into the woman during treatment may explain it, though they add that the extra risk posed by IVF is “small”.

Jeremy Hunt, the ex-health secretary who chairs Westminster’s all party parliamentary group on patient safety, urged NHS leaders to learn from the stories.

“Nik and Amisha have highlighted an important and under-recognised issue in maternity care,” she said.

“These stories and the Action for Accreta campaign highlight worrying gaps in how PAS is identified, recorded and managed across the NHS.

“Addressing these will require a more consistent, system-wide approach, including improved data, training and clinical preparedness.”