Progesterone Luteal Support in Unexplained Infertility Management
Trial Snapshot
- Phase
- Phase 3
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 640
- Primary Endpoint
- Pregnancy occurring within 6 months after randomisation, leading to a live birth.
Study Overview
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.
Detailed Description
Rationale
Progesterone is a critical hormone in the luteal phase, facilitating endometrial secretory transformation, decidualization, implantation, and early pregnancy maintenance. A previous systematic review suggested that progesterone insufficiency may contribute to reduced implantation potential and lower pregnancy rates in women with unexplained infertility (UI). Additional support for the importance of luteal function in fertility is provided by studies demonstrating improved outcomes following progesterone supplementation in various fertility treatments, including intrauterine insemination (IUI) during mildly stimulated cycles, (natural)-cycle cryoembryo transfers and early gestation.
The present study aims to determine whether progesterone supplementation during the luteal phase in women with UI, managed expectantly through ovulation testing and timed intercourse, can increase live birth rates. A previous pilot randomised controlled trial (the PINC trial) indicated a potential benefit of luteal phase support (LPS) in this population (odds ratio 2.38, 95% CI 0.78-7.24), though the study was underpowered, included only three menstrual cycles, and lacked placebo blinding, thereby limiting the strength of the evidence and supporting the need for a large, high-quality study.
The hypothesis is that the addition of progesterone during expectant management in UI will lead to an absolute increase of 10% in cumulative live birth rate. LPS is expected to be cost-effective, by reducing the need for invasive fertility treatment such as IUI or IVF, thereby shortening time to pregnancy and decreasing the emotional, psychological, and financial burden of infertility care. Given the low cost and ease of home administration, the impact of LPS on total healthcare is expected to be minimal. The overall estimated budget impact of the addition of LPS in UI management is ±11.6 million euros per year.
Trial design
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 43 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Outcomes
Primary Outcomes
Pregnancy occurring within 6 months after randomisation, leading to a live birth.
Time Frame: within 6 months after randomisation
Secondary Outcomes
- 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)
- Time to pregnancy(Within 6 months after randomisation)
- Pregnancy loss(within 6 months after randomisation)
- Pregnancy complications(within 6 months after randomisation)
- Perinatal outcomes(within 6 months after randomisation)
- Type of delivery(within 6 months after randomisation)
- Side effects(During the 6-month study period)
- Compliance to therapy(During the 6-month study period)
- Number of adverse events and serious adverse events.(During the 6-month study period)
- Quality of life assessed at time of randomisation, and 6 and 18 months after randomisation(assessed at time of randomisation, and 6 and 18 months after randomisation)
- Progression to (MOH)IUI/IVF/ICSI(within six months after randomisation)
- Use of ART and (ongoing) pregnancy achieved(after the six-month study period and within 12 months follow up.)
- Budget impact(over the 6-month study period)
- Cost-effectiveness analyses using live birth rates and costs(over the 6-month study period)
Investigators
Simone Broer
Principal Investigator
UMC Utrecht