Progesterone Luteal Support in Unexplained Infertility Management

NCT07738068 | Not Yet Recruiting Phase 3

• 2 other identifiers: V00039252026-525747-33-00
• Study Type: interventional
• Target: 640
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate whether progesterone in women with unexplained infertility can increases live birth rate. The main research question is: Does luteal phase support with progesterone increase the live birth rate among couples with unexplained infertility? The study compares progesterone with placebo to determine the effectiveness of progesterone in unexplained infertility. Study participants will:

• Perform home ovulation tests and maintain a digital diary to record menstrual cycles and study medication use.10
• Take progesterone or placebo twice daily during the luteal phase of each menstrual cycle for up to six months.11
• Continue usual medical care. No additional hospital visits or invasive procedures are required as part of the study.

Conditions

Infertility; Female Infertility; Subfertility; Infertility Primary; Infertility Secondary; Subfertility, Female

Keywords

infertility; Unexplained Infertility; Luteal Phase Support (LPS); Expectant Management; progesteron luteal support; progesteron; Progesterone (Utrogestan®)

Outcome Measures

Primary Outcomes (1)

• Pregnancy occurring within 6 months after randomisation, leading to a live birth.

  within 6 months after randomisation

Secondary Outcomes (18)

• Clinical pregnancy

  within 6 months after randomisation

• Ongoing pregnancy

  within 6 months after randomisation

• Biochemical pregnancy loss

  within 6 months after randomisation

• Miscarriage rates

  within 6 months after randomisation

• Multiple pregnancy rate

  within 6 months after randomisation

Study Arms (2)

1. The Progesterone Arm

EXPERIMENTAL

Female participants apply vaginal micronized progesterone (Utrogestan) during the luteal phase of their cycle, at a dosage of 300 mg twice daily

Drug: Utrogestan® 200 mg Soft Capsule

2. The Placebo (Control) Arm

PLACEBO COMPARATOR

Female participants apply a vaginal capsule (placebo) during the luteal phase of their cycle, at a dosage of 300 mg twice daily

Drug: Placebo soft capsule 200 mg

Interventions

Utrogestan® 200 mg Soft Capsule DRUG

progesteron versus placebo

1. The Progesterone Arm

Placebo soft capsule 200 mg DRUG

placebo

2. The Placebo (Control) Arm

Eligibility Criteria

• Age: 18 Years - 43 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Primary or secondary infertility for at least a period of 1 year Participants whose previous pregnancy was achieved through MOH-IUI or IVF are eligible to join the study, provided they are willing to continue expectant management for at least six months before considering any further fertility interventions
• Diagnosis of UI after infertility work-up, i.e.
• regular menstrual cycle ranging between 21-35 days,
• total motile sperm count ≥ 10 million/ml,
• no risk of tubal pathology (or in case of increased risk, tubal pathology uitgesloten middels tubal patency testing)
• A Hunault prognostic score ≥ 30% (calculated using the Hunault prediction model7, based on key prognostic factors including female age, subfertility duration, type of subfertility (primary or secondary), sperm motility and referral status),
• Assignment to expectant management during at least six months, in accordance with Dutch NVOG Guidelines (4).
• Female age ≥18 years old Female
• BMI \<45 kg/m2

You may not qualify if:

• Uncorrected uterine factors, such as endometrial polyps or submucosal fibroids,
• Insufficient knowledge or understanding of the Dutch or English language and not willing or able to receive study information via a certified translator
• Not able or willing to provide (written) informed consent
• Contraindications for vaginal progesterone, in particular: females with allergy to peanuts or soya.
• Formal diagnosis of endometriosis

Sponsors & Collaborators

• Simone Broer: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

MeSH Terms

Conditions

Infertility; Infertility, Female

Interventions

Utrogestan

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications

Study Officials

• Simone L. Broer, Gynaecologist, PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julie C.M. van de Wal, MD

CONTACT

+31650177981; j.c.m.vandewal-15@umcutrecht.nl

Katja C.E. Drechsel, MD, PhD

CONTACT

K.C.E.Drechsel-2@umcutrecht.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The PLUIM study is designed as a randomized, double-blind, multicenter superiority trial involving two parallel treatment arms

Study Record Dates

• First Submitted: July 22, 2026
• First Posted: July 30, 2026
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): January 1, 2031
• Last Updated: July 30, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share