Dydrogesterone Versus Intravaginal Progesterone in the Luteal Phase Support

Study Overview
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Brief Summary
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The purpose of this study is to compare efficacy and tolerability of the dydrogesterone and the vaginal progesterone, used for luteal phase support. (Initial start date was January 2009 but not for patients' recruitment only for paper work, documents, team organization, statistical pre-work actions and to gain the official approval of Institutional Review Board. The recruitment started in October 2010 and continued until October 2013.)

Detailed Description
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The use of gonadotropin-releasing hormone (GnRH) agonists in the ovarian stimulation, which prevents a premature surge of luteal hormone (LH), ultimately leads to suppression of the pituitary gland and high levels of estrogen observed during induced cycles result in inhibiting effect on the implantation of human embryos. The luteal support in in-vitro-fertilization (IVF) cycles can be prolonged using human chorion gonadotropin(hCG) and/or progesterone. Since it has been noted that the use of hCG was related with higher risks of the onset of ovarian hyperstimulation syndrome (OHSS), progesterone is nowadays a product of choice in luteal support. Currently vaginal progesterone is widely used, since the classic oral progesterone results in low bioavailability and lower pregnancy rate and the intramuscular progesterone (IM-P) daily injections are painful and may cause abscesses, inflammatory reactions and local soreness. However, standard protocol for luteal phase support has not been established (i.e. optimal dosage, route or duration). Dydrogesterone is a retroprogesterone with good oral bioavailability. Oral administration is clear advantage, due to expected higher patient compliance and better tolerability than currently used vaginal or IM-P. We hypothesize that dydrogesterone has the same efficacy as vaginal progesterone but better tolerability due to less side effects.

Official Title
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Oral Dydrogesterone Versus Vaginal Progesterone Gel in the Luteal Phase Support: Randomized Controlled Trial

Conditions
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Luteal Phase Defect

Intervention / Treatment
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* Drug: Oral dydrogesterone
* Drug: Crinone 8% gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: routine ovulation induction protocol with GnRH agonist less than three prior IVF cycles at least three aspirated oocytes BMI <35 kg/m2 age <45 years Exclusion Criteria: history of dysfunctional uterine bleeding acute urogenital disease recurrent miscarriage previous allergic reactions to a progesterone products

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Oral dydrogesterone<br>Study group receiving 2x10mg of oral dydrogesterone until a pregnancy test or in the case of pregnancy until 10 week. | Drug: Oral dydrogesterone<br>* oral-2x10mg<br>* Other names: Duphastone (Solvay Pharmaceuticals);|
| Active Comparator: Crinone 8% vaginal gel<br>Control group is receiving vaginal gel, 1x90mg, until a pregnancy test or in the case of pregnancy until 10 week. | Drug: Crinone 8% gel<br>* vaginal-1x90mg<br>* Other names: Crinone 8% gel (Fleet Laboratories Ltd., Watford, UK);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ongoing pregnancy rate | Ongoing pregnancy rate is defined by the presence of gestational sac(s) with viable fetal heart beats at 12 weeks' gestation by transvaginal ultrasound. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events | The side effects included the occurrence of headache, somnolence, nausea, abdominal pain, bloating, dizziness, headache, breast fullness, perineal irritation, vaginal discharge and bleeding, interference with coitus. | 10 weeks | 
| Satisfaction | Satisfaction score is determinate on the 5-point level scale with 1 being absolutely satisfied and 5 being absolutely dissatisfied and tolerability by yes and now answers regarding side effects that the supplements could cause. | 10 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IVF, luteal phase support, oral progesterone, vaginal progesterone, pregnancy rate, safety, tolerability