Dydrogesterone Versus Intravaginal Progesterone in the Luteal Phase Support

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

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.)

Study Overview

• Status: Completed
• Conditions: Luteal Phase Defect
• Intervention / Treatment: Drug: Oral dydrogesterone; Drug: Crinone 8% gel

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 Type: Interventional
• Enrollment (Actual): 853
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Croatia
  • Zagreb, Croatia, 10000
    • University Hospital Center Sisters of Mercy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: 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

Publications and helpful links

General Publications

• Tomic V, Tomic J, Klaic DZ, Kasum M, Kuna K. Oral dydrogesterone versus vaginal progesterone gel in the luteal phase support: randomized controlled trial. Eur J Obstet Gynecol Reprod Biol. 2015 Mar;186:49-53. doi: 10.1016/j.ejogrb.2014.11.002. Epub 2014 Nov 20.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (ACTUAL): October 1, 2013
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: August 9, 2010
• First Submitted That Met QC Criteria: August 9, 2010
• First Posted (ESTIMATE): August 10, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): January 29, 2014
• Last Update Submitted That Met QC Criteria: January 27, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: tolerability; safety; IVF; pregnancy rate; luteal phase support; vaginal progesterone; oral progesterone
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone; Dydrogesterone
• Other Study ID Numbers: KBSM-0010