Duration of luteal support with progesterone pessaries to improve the success rates in assisted conception

The proportion of all randomised women that continue successfully to a viable pregnancy (at least one fetus with FHR >100 beats minute) on transabdominal / transvaginal ultrasound at 10 weeks post embryo transfer / 12 weeks gestation (i.e. at the end of 8 weeks supplementary trial treatment).

The following clinical estimates are available. The success rate at the biochemical testing stage is approximately 32.5%. Currently without further progesterone supplementation, 80% of these women will carry on successfully with a viable pregnancy (25.8% of clinical pregnancy rate) whilst 20% of these women will miscarry. We anticipate that an increase of 10% from the biochemical to the clinical pregnancy rate would be clinically important and therefore justify an additional 8 weeks of supplementation with progesterone, in other words, a reduction of 10% in the miscarriage rate.

1. Viable pregnancy (at least one fetus with FHR>100 beats per minute) on transvaginal ultrasound at 5 weeks post embryo transfer / 7 weeks gestation (i.e. at the end of 3 weeks supplementary trial treatment).
2. Relationship of serum markers (Estradiol, progesterone, Inhibin A, Inhibin B, Actavin A. free B-HCG and PAPP-A) taken at 5 and 10 weeks post embryo transfer with treatment allocation, primary outcome and secondary outcomes
3. A pelvic Doppler will be performed to determine if the blood velocity in the uterine artery is different in the two groups. This will be performed at 5 and 10 weeks post embryo transfer.
4. Side effects: A visual analogue score relating to the following side effects will be completed at both 5 weeks and 10 weeks post embryo transfer; nausea, bloating, vaginal discharge and vaginal irritation.
5. Antenatal Down’s Screening Outcomes - Antenatal Down’s screening results for all patients will be monitored, including individual serum quantification for double, triple, quadruple screening and nuchal translucency.
6. Neonatal outcomes - Outcome data regarding the child will be collected at delivery (Table 6). A standard neonatal examination will be conducted. Women will be asked to inform the study team of the outcome of the routine neonatal examination. Excessive androgenisation would be an important adverse outcome of supplementary progesterone and this would be detected by routine neonatal examination. Long term follow-up of the child may also be conducted as a separate study. Women will be asked to whether they consent to being contacted in future about long-term follow-up studies.
Some neonatal and other pregnancy outcomes will be captured in Trusts that do not recruit to this trial. We will identify a local contact and R&D contact in each Trust in order to obtain the necessary approvals. At each site that will contribute data to the outcomes clinicians will be following their routine clinical practice. Consent to participate in the study will not be sought at sites that contribute to data collection about outcomes and study medication will not be administered at these sites. Thus, the sites that contribute to data collection about outcomes will be exempt from site-specific assessment as part of approval by the Research Ethics Committee.
7. Compliance data - Patient compliance with using pessaries is recorded at each visit. A secondary analysis may look at the effect of compliance on the primary outcome.