None listed
Conditions
Brief summary
FETs using HRT stimulation occur with no corpus luteum. This means endometrial growth, maturation and maintenance is entirely dependent on the effect of HRT for at least the first 2-5 weeks post-transfer. By 10 weeks post-transfer the placenta is producing adequate hormone to support the endometrium. Although intramuscular progesterone treatment is popular in North America, in Australia and Europe vaginal preparations are preferred. Natural and HRT FET cycles have been compared and show equivalent live birth rates on meta-analysis. The local experience at Monash IVF is different, with a significantly lower live birth rate for HRT compared to natural FETs (14.5% vs 22.4% - OR 0.59 (0.55-0.62)) for all comers. This difference is maintained when 20 potential confounding factors are allowed for using logistic regression (patient age; number of embryos transferred, embryo maturity etc) with an adjusted odds ratio of 0.55 (0.48-0.64). A recent publication from Yovich (2015) showed a significantly higher live birth rate in women undergoing HRT FETs, where the mid-luteal phase serum progesterone was >50 nmol/L. Review of the Monash IVF dataset investigating serum progesterone concentrations after 14-18 days of treatment in HRT FETs confirmed a significantly higher live birth rate (26.4% vs 11.3%). A shortcoming of measuring progesterone both at mid-luteal and Day 14-18, is that the opportunity to change management and improve outcome has potentially already passed. A further retrospective review of Monash IVF HRT FET cycles investigating progesterone dosage, Day 14-18 serum progesterone and live birth rates, suggested that dose frequency may be as important of actual dosage. This study aims to investigate “at risk” women with low serum progesterone (<50 nmol/L), but measure this after 2 days of treatment and then assess the effect of adding an extra dose of progesterone each day upon the live birth rate.
Interventions
Participants will be randomised to receive either an extra progesterone 400mg pessary or a placebo pessary for 12 weeks. For patients on a twice daily dose this study pessary will be used at midday. Those on a thrice daily dose will use the extra study pessary in the late evening. This aims to leave unchanged the timing of initial active pessaries for patients where a placebo pessary is added, so that there is no change to the background dosing. We do not intend to monitor compliance of partic
Participants will be randomised to receive either an extra progesterone 400mg pessary or a placebo pessary for 12 weeks. For patients on a twice daily dose this study pessary will be used at midday. Those on a thrice daily dose will use the extra study pessary in the late evening. This aims to leave unchanged the timing of initial active pessaries for patients where a placebo pessary is added, so that there is no change to the background dosing. We do not intend to monitor compliance of participants with the allocated intervention. Participation will be viewed on an ‘intention to treat’ analysis.
Sponsors
Monash IVF Pty Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Is a female receiving single embryo FET with HRT at Monash IVF 2. Is between the age of 18 and 45 years 3. Has provided informed consent 4. Speaks sufficient English to provide informed consent 5. Has been prescribed an initial progesterone pessary dose of 400mg bd or tds and is obtaining these pessaries from Slade pharmacy 6. Low serum progesterone levels at Day 2 of progesterone treatment (<50nmol/L)
Exclusion criteria
• Already completed an HRT FET cycle in this study • Planned double embryo transfer.
Outcome results
None listed