Patient's Preferences About Subcutaneous or Vaginal Progesterone Administration for Luteal Phase Support (PROPER-1)

Patient's Preferences About Subcutaneous or Vaginal Progesterone Administration for Luteal Phase Support: Prospective Randomized Trial.

Luteal phase support in "in vitro fertilization" (IVF) cycles has been shown to improve pregnancy rates and became a standard of treatment, and progesterone is the first choice considering its safety profile and effectiveness. There are many studies demonstrating that vaginal progesterone is equally efficacious and better tolerated compared to intramuscular progesterone for luteal phase support in IVF cycles. Conversely, although different studies showed that subcutaneous progesterone is equally efficacious compared to vaginal progesterone, patient use satisfaction and compliance were less studied with few evidences are available, that may guide the choice of vaginal progesterone instead of subcutaneous progesterone and other way around. Considering the paucity of published data about the patient's preference and use satisfaction about subcutaneous progesterone, the investigators will conduct a prospective randomized study aimed to compared adverse effects rates, impact on quality of life, use satisfaction and administration preference in women undergoing luteal phase support with vaginal progesterone versus subcutaneous progesterone during IVF cycles, that may guide the choice for luteal phase support in IVF cycles.

Study Overview

• Status: Completed
• Conditions: In Vitro Fertilization; Progesterone; Luteal Phase Support
• Intervention / Treatment: Drug: Subcutaneous Progesterone; Drug: Vaginal progesterone

• Study Type: Interventional
• Enrollment (Actual): 149
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Verona, Italy, 37125
    • AOUI Verona - University of Verona - Department of Obstetrics and Gynecology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Infertile women candidate to undergo fresh IVF cycles

Exclusion Criteria:

• day-3 follicle-stimulating hormone (FSH) levels over 15 IU/L
• clinically relevant systemic disease (e.g., uncontrolled thyroid and adrenal dysfunction, an organic intracranial lesion such as a pituitary tumor, insulin-dependent diabetes mellitus, cancers)
• hypersensitivity to any of the study drugs
• contraindications to use the study drugs
• surgical or medical condition that would interfere with absorption, distribution, metabolism, or excretion of the study drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Subcutaneous progesterone; After standard stimulating protocol for IVF, beginning on the day of oocyte retrieval allocated patients receive subcutaneous progesterone (Pleyris, IBSA Farmaceutici, Italia) 25 mg one time per day (every day at the same time, according to patient's availability and preference) for at least 8 gestational weeks or confirmation of a negative pregnancy test performed 14 days after oocyte retrieval.	Drug: Subcutaneous Progesterone; Subcutaneous progesterone (Pleyris, IBSA Farmaceutici, Italia) 25 mg one time per day (every day at the same time, according to patient's availability and preference).
Active Comparator: Vaginal progesterone; After standard stimulating protocol for IVF, beginning on the day of oocyte retrieval allocated patients receive micronized vaginal progesterone (Progeffik, EFFIK Spa, Italia) 200 mg three times per day (every 8 hours) for at least 8 gestational weeks or confirmation of a negative pregnancy test performed 14 days after oocyte retrieval.	Drug: Vaginal progesterone; Micronized vaginal progesterone (Progeffik, EFFIK Spa, Italia) 200 mg three times per day (every 8 hours).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Grade of use satisfaction reported by the patients	Patients will be asked how satisfied they are by the use of progesterone product that they receive in the luteal phase. Their satisfaction responses will be recorded on a scale of 1 to 3, with 1 being ''least satisfied'' and 3 being ''most satisfied'.	At the human chorionic gonadotropin test performed after 14 days of progesterone use
Grade of quality of life impairment reported by the patients	Patients will be asked whether work life, social life, sexual life, and personal hygiene are perceived impaired by the progesterone treatment that they received. The answer for each item is "yes" or "no".	At the human chorionic gonadotropin test performed after 14 days of progesterone use
Adverse effects (AEs)	Patients will be asked to report experienced AEs. The investigated AEs are sleepiness, dizziness, headache, bowel dysfunctions, breast pain/tension, weight changes, mood disorders, skin irritation, and vaginal discharge. The answer for each item is "yes" or "no".	At the human chorionic gonadotropin test performed after 14 days of progesterone use

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progesterone administration route that the patients prefer	Patients of subcutaneous progesterone arm and who had previously used vaginal progesterone will be asked which administration route they prefer.	At the human chorionic gonadotropin test performed after 14 days of progesterone use
Implantation rate	Rate of positive human chorionic gonadotropin test	At the human chorionic gonadotropin test performed after 14 days of progesterone use
Clinically pregnancy rate	Rate of evolving pregnancy at ultrasound	At 6 week from oocyte retrieval
live birth rate	Rate of baby delivered after 24 gestational weeks	At nine months from oocyte retrieval

Collaborators and Investigators

• Sponsor: Universita di Verona
• Investigators: Principal Investigator: Ricciarda Raffaelli, M.D., Universita di Verona; Principal Investigator: Rossana Di Paola, M.D., Universita di Verona; Principal Investigator: Antonio Simone Laganà, Università degli Studi dell'Insubria; Principal Investigator: Francesca Parissone, M.D., Universita di Verona; Study Director: Stefano Zaffagnini, M.D., AOUI Verona; Study Director: Massimo Franchi, M.D., Universita di Verona

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Actual): March 1, 2019
• Study Completion (Actual): July 1, 2019

Study Registration Dates

• First Submitted: October 31, 2018
• First Submitted That Met QC Criteria: November 6, 2018
• First Posted (Actual): November 8, 2018

Study Record Updates

• Last Update Posted (Actual): May 18, 2022
• Last Update Submitted That Met QC Criteria: May 11, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: subcutaneous; progesterone; vaginal; in vitro fertilization; luteal phase support
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: PROPER-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No