Scientists have suggested that a new drug could help improve the odds of successful IVF treatment, after initial trials showed it boosted the rate of embryo implantation during IVF and led to a 7% increase in live births.
For their study, the researchers set out to test whether the drug, the first of its kind and which has a direct effect on the inner lining of the womb, could improve the embryo implantation process during fertility treatment.
Known as OXO-001 and created by Spanish biotech company Oxolife, the pill had already gone through safety checks in pre-clinical trials, reports The Independent.
The study enrolled 96 infertile women aged 40 and under who were receiving fertility treatment – either IVF or intracytoplasmic sperm injection (ICSI) with donor eggs – at 28 centres across Europe between September 2021 and January 2023.
They were either given a placebo or OXO-001, taken twice daily one menstrual cycle before the embryo transfer and five weeks after.
The researchers found “ongoing pregnancy rates” measured 10 weeks after embryo transfer were 46.3% for patients treated with OXO-001 compared with 35.7% for those on the placebo.
This is a “clinically significant finding”, academics said, presenting their study to the European Society of Human Reproduction and Embryology’s (ESHRE) 40th annual meeting in Amsterdam last week.
There was also a clinically meaningful increase in the number of mothers who went on to have a live birth, they said.
The live birth rate was 42.6% for women who took OXO-001 compared with 35.7% among those who took the placebo, according to the abstract, which is also being published in the journal Human Reproduction.
Side-effects were similar in both the placebo group and the group receiving the new treatment, the most common being headaches, nausea, vomiting, gastrointestinal issues and dizziness, and most of which were mild to moderate.
The drug will now be tested in a phase three clinical trial, and will include women who are using their own eggs.
Oxolife chief executive Dr Agnes Arbat said: “Most rounds of IVF or ICSI still end in failure, often because a viable embryo does not implant.
“A simple-to-take pill that materially improves the chance of success would therefore be of huge benefit to those who want a baby. This proof-of-concept phase two study shows that hope is now a step closer.”
A separate study presented to the the ESHRE meeting suggested women who were exposed to air pollution before starting IVF might have lower odds of a successful outcome.
Researchers studied data on air pollution levels and compared these with information on when women had their eggs collected during the IVF process.
They examined data from 1 835 patients in Perth, Australia, who underwent a total of 2 155 IVF cycles with frozen embryo transfers over eight years.
They also looked at air pollution concentrations at four different times before the women had their eggs retrieved – 24 hours; two weeks; four weeks and three months.
Those exposed to the highest levels of a type of air pollution called PM10 in the two weeks before egg retrieval had 38% lower odds of a subsequent live birth, compared with those exposed to the lowest levels of pollution.
Those exposed to PM2.5 in the three months before egg retrieval also had lower odds of live birth.
Study details
Efficacy results from the phase II randomised clinical trial: OXO-001 in infertile women undergoing egg donation IVF/ICSI
A Arbat, J Bellver, J Garcia-Velasco et al.
Published in Human Reproduction on 10 July 2024
Abstract
Study question
Does OXO-001 increase implantation and pregnancy rates in women undergoing egg donation IVF/ICSI and embryo transfer (ET) compared to placebo?
Summary answer
This proof-of-concept (PoC) prospective randomised and controlled study shows that OXO-001 treatment increases implantation and pregnancy rates in infertile women undergoing IVF/ICSI with studied doses.
What is known already
OXO-001 is a drug being developed as an innovative treatment to enhance embryo implantation through a direct effect on the endometrium. Preclinical results show an increase in embryo implantation and viability. Moreover, they show that OXO-001 is safe for the mother, the foetuses, and the newborns without any deleterious effect on the development, viability, and implantation potential of OXO-001-exposed embryos. Neither conceptus development nor morphological disturbances have been observed in the deciduas of treated-pregnant mice. Furthermore, clinical trials confirmed that OXO-001 has the necessary wide safety margin and non-complex kinetics, allowing further research on its therapeutic potential in infertility.
Study design, size, duration
It was a randomised, double-blind, placebo-controlled, and multicentre phase II clinical trial with three parallel arms conducted at 28 European centre (September/2021-January/2023. EudraCT Num:2021-000001-25). A subset of women ≤40 years were analysed. A total of 173 were randomised in the three study arms (Placebo, 200 and 300mg/day OXO-001). Treatment started one menstrual cycle before the ET cycle and continued until 5 weeks after ET. The results of this communication are focused on the 300mg/day dose.
Participants/materials, setting, methods
Patients were infertile women (18-40 years; BMI 18-30 kg/m2) eligible for a fresh-single blastocyst (day 5 and ≥3BB) ET resulting from a donor egg. Exclusion criteria include gynaecological abnormalities and history of ≥ 2 failed ET, among others. The primary endpoint was ongoing pregnancy rate (OPR). Secondary included biochemical and clinical pregnancy (BPR and CPR), live birth rate (LBR), and safety and tolerability of OXO-001.
Main results and the role of chance
111 women were randomised, and 96 performed a single ET (42 Placebo, 54 OXO-001 300mg/day). Higher BPR, CPR, OPR, and LBR per delivery after were observed in the OXO-001 group versus placebo (75.9% vs. 52.4%*, 50.0% vs. 37.5%, 46.3% vs. 35.7%, 42.6% vs. 35.7%, respectively. *p<0.05). The logistic regression analysis showed a statistically significant difference in the BPR for OXO-001 versus placebo (OR 3.03, 95% CI 1.17-7.85; p = 0.022), and a clinically meaningful difference for CPR, OPR, and LBR after a single ET. In safety evaluation, the frequency of treatment-emergent adverse events (TEAEs) assessed as at least possibly related to the study medication were similar between groups (14 for OXO-001 and 10 for placebo). Most TEAEs were mild or moderate in severity. The most common TEAES were headache, nausea and vomiting, gastrointestinal and dizziness. The assigned study medication was well tolerated, and relevant changes in laboratory analyses (haematology and biochemical profile) were not observed.
Limitations, reasons for caution
This PoC study was designed to define clinically meaningful differences in fertility outcomes and find patient profiles. It was not empowered to find statistical differences in the OPR. An empowered phase III study is needed to confirm the positive results from phase II.
Wider implications of the findings
This phase II PoC has achieved its objectives showing that OXO-001 increases more than 10% pregnancy rates in infertile women undergoing IVF/ICSI, with a safe and well-tolerated profile. This is a step forward toward the first therapeutic tool to increase embryo implantation and ET success.
The Independent article – New pill can increase IVF success rates, study suggests (Open access)
See more from MedicalBrief archives:
Frozen eggs more efficient than IVF for older women – US study
Biotech company plans to create embryos for organ harvesting
IVF mis-selling concerns brings fertility treatment guidelines for UK consumers