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.”

GLP-1 drugs taken before conception were not linked to higher pregnancy risks in new research, which suggested they may even offer some protection.

Women of reproductive age are increasingly prescribed GLP-1 drugs for weight-management support, but the risks and benefits of using them before pregnancy remain poorly understood.

The findings support continuing the use of GLP-1 medicines in women with metabolic risk factors who are considering pregnancy, said Cara Dolin, a maternal-fetal medicine specialist and co-author of the research, which was presented at the Society of Maternal-Fetal Medicine pregnancy meeting in February 2026.

“While there’s more research to be done, this data provides some reassurance that it is not harmful to be taking a GLP-1 if you’re planning a pregnancy, and that having done so may in fact benefit you by optimising your preconception metabolic health.”

The researchers examined electronic medical records for patients with a pre-pregnancy BMI of more than 30 who delivered at more than 20 weeks’ gestation. The data were reviewed for two studies: one assessed the link between pre-pregnancy GLP-1 use and the risk of gestational diabetes, while the second looked at the risk of severe maternal morbidity in patients with obesity.

Women with obesity, diabetes, cardiovascular disease and other cardiometabolic disorders have a higher risk of pregnancy complications including preeclampsia, gestational diabetes, stillbirth, caesarean section and other outcomes. While GLP-1 medicines can help manage these conditions, they are contraindicated during pregnancy, and women are typically advised to stop the medication two months before trying to conceive.

However, stopping the drugs can often lead to rebound weight gain or worsening metabolic health. A 2025 study suggested this rebound worsened some pregnancy outcomes, but the risks and benefits are still poorly understood, Dolin said.

“There is a lot we just don’t know, which is why we wanted to look at our experience here with our Cleveland Clinic patients and see whether taking GLP-1 drugs before pregnancy was causing harm or if it was beneficial and helping patients have healthier pregnancies.”

Researchers analysed data for more than 8,000 women who had obesity but did not have diabetes before they became pregnant. They compared outcomes for 208 women who had been prescribed GLP-1 receptor agonists before pregnancy with those who had not been prescribed the medication.

Women in the GLP-1 group had more risk factors heading into pregnancy. They tended to be older and have a higher body mass index, higher rates of bariatric surgery and chronic high blood pressure, and present earlier for prenatal care.

However, outcomes for the two groups were similar. Researchers found that the GLP-1 group did not have higher rates of gestational diabetes, severe maternal morbidity or other adverse maternal outcomes, suggesting that the medication may have helped mitigate elevated risk factors.

“I think this is a really important signal, and it may reflect that these patients were able to optimise their metabolic health prior to conception.”

“It shows there’s potential to use these drugs in a more targeted way with patients who are planning a pregnancy and have these different comorbidities and obesity.”

While the findings suggest that using GLP-1 drugs before pregnancy may be beneficial in women with metabolic risk factors, having a plan to stop the medicines before conception is essential, Dolin noted. In some cases, patients may be moved to an alternative medication that is safe for pregnancy and can be used to help manage their metabolic health during pregnancy.

Providers with patients who are taking GLP-1 medicines and planning a pregnancy should consider referral to a maternal-fetal medicine specialist for pre-pregnancy counselling.

“We can have a nuanced conversation with the patient about taking the medication, what the benefits are, what the potential risks are, and help them formulate a plan to transition off the medication once they’re ready to start trying to conceive,” she said.