Obs/Gyn studies

Objective
To confirm or refute that a mild IVF protocol lead to a higher ongoing pregnancy rate compared to conventional treatment in poor responders

Study design
International multicentre randomized controlled study

Group 1: 197 patients will undergo one cycle mild IVF

Group 2: 197 patients will undergo one cycle of conventional IVF

Study population
Patients with expected or non expected poor response

Expected

- Aged women =< 35 years.

- Women who have a raised basal day 3 FSH level > 10 IU/mL irrespective of age.

- Women who have a low antral follicular count < 5 follicles.

Unexpected:

- Women aged < 35 years old.

- Women who responded poorly during their first IVF cycle i.e. total gonadotrophin dose used > 3000 IU FSH for follicle growth

- Women who have low oocyte yield < 3-5 follicles despite high daily stimulation dose.

- Women who have their IVF cycle cancelled due to a low estradiol level < 300-850 pg/ml.

Intervention
Couples are allocated 1:1 to a treatment consisting of one cycle of mild ovarian stimulation IVF-ET plus subsequent cryo-cycles with OCP plus 150IU FSH plus GnRH antagonist or one cycle of conventional controlled ovarian hyperstimulation IVF-ET followed by plus subsequent cryo-cycles with long GnRH agonist plus 450IU HMG.

Outcome measures
Primary outcome parameter

Ongoing pregnancy (OPR) per women randomised (defined as a viable pregnancy of at least 10 weeks of gestation).

.Secondary outcome parameters

- Clinical pregnancy, defined as any registered embryonic heartbeat at sonography.

- Biochemical pregnancy ((defined as an increase in serum HCG or a positive pregnancy test)

- Multiple pregnancy, defined as registered heartbeat of at least two foetuses at 6-8 weeks of gestation.

- Miscarriage rate

- Fertilization rate

- Number of oocytes

- Number of metaphase II oocytes

- Number of embryos

- Number of ET

- Number of embryos frozen

- Total FSH dose used for ovarian stimulation

- Cancellation rate

- Drop-out rate

- Costs

- Patient discomfort/distress during IVF treatment.

Power/data analysis

Considering an ongoing pregnancy rate of 15 % in both treatment groups, with an alpha of 5% and a beta of 20%, 197 patients per group are required to exclude a difference of 10% to the determent of the new protocol. Therefore we need to include 394 couples in total.

Economic evaluation
The time horizon for the economic evaluation will be ongoing pregnancy rate (OPR) after one cycle of treatment. The cost analysis will be performed from a medical perspective, i.e. only direct costs of medical interventions will be calculated. Standardized unit costs will be calculated based on actual expenses made during the study. Subsequently, unit costs will be applied to resource use as observed during the study. Resource utilization will be documented using individual patient data in the case record forms.
Resource unit prices will reflect the unit of staff, materials, equipment, depreciation, and overhead. Costs will be presented in (Egyptian pound; Euros and others).

The cost analysis will be designed as a cost minimization analysis if ongoing pregnancy rate are comparable between the study groups. If not, a cost-effectiveness analysis will be performed. The cost-effectiveness ratio will be calculated as the ratio of the difference in total costs to the difference in proportion ongoing pregnancy per the treatment groups.

To quantify the uncertainty (the confidence interval) of the cost-effectiveness ratio bootstrap analysis will be used. Results will be presented with and without discounting. Sensitivity analyses will be performed on costs and pregnancy rates of the different treatment strategies.

Projectleaders

Prof. Dr: Fulco van der Veen (MD, PhD)

Center for Reproductive Medicine Dept. Obstetrics and Gynecology

Academic Medical Center Amsterdam

F.vanderVeen@amc.uva.nl

Mohamed A.F.Youssef, MD, Assistant lecturer ,

Dept. Obstetrics and Gynaecology,

Kasr-Alainy Hospitals,

Faculty of Medicine- Cairo University,

Cairo, Egypt.

m.a.youssef@amc.uva.nl / mmfatah@yahoo.com

Madelon van Wely, PhD, Epidemiologist,