Dydrogesterone Versus Intravaginal Progesterone in the Luteal Phase Support

Sponsor

University of Zagreb (Other)

Overall Status

Completed

CT.gov ID

NCT01178931

Collaborator

(none)

853

Enrollment

Location

Arms

Duration (Months)

22.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.)

Condition or Disease	Intervention/Treatment	Phase
Luteal Phase Defect	Drug: Oral dydrogesterone Drug: Crinone 8% gel	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

853 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2010

Actual Primary Completion Date :

Oct 1, 2013

Actual Study Completion Date :

Dec 1, 2013

Arms and Interventions

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

Arm

Intervention/Treatment

Active Comparator: Oral dydrogesterone

Study group receiving 2x10mg of oral dydrogesterone until a pregnancy test or in the case of pregnancy until 10 week.

Drug: Oral dydrogesterone

oral-2x10mg

Other Names:

Duphastone (Solvay Pharmaceuticals)

Active Comparator: Crinone 8% vaginal gel

Control group is receiving vaginal gel, 1x90mg, until a pregnancy test or in the case of pregnancy until 10 week.

Drug: Crinone 8% gel

vaginal-1x90mg

Other Names:

Crinone 8% gel (Fleet Laboratories Ltd., Watford, UK)

Outcome Measures

Primary Outcome Measures

Ongoing pregnancy rate [12 weeks]
Ongoing pregnancy rate is defined by the presence of gestational sac(s) with viable fetal heart beats at 12 weeks' gestation by transvaginal ultrasound.

Secondary Outcome Measures

Number of participants with adverse events [10 weeks]
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.
Satisfaction [10 weeks]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Center Sisters of Mercy	Zagreb		Croatia	10000

Sponsors and Collaborators

University of Zagreb

Investigators

Principal Investigator: Jozo Tomic, M.D., Department of Human Reproduction, University Hospital Center Sisters of Mercy
Study Chair: Vlatka Tomic, M.D., Department of Human Reproduction, University Hospital Center Sisters of Mercy