A Phase 3 interventional study of Utrogestan® 200 mg Soft Capsule and Placebo soft capsule 200 mg in Infertility, Female Infertility and Subfertility, sponsored by Simone Broer. Not yet recruiting. Open to female participants aged 18 Years to 43 Years. Per ClinicalTrials.gov, last updated 2026-07-30.
Sponsored by Simone Broer · Phase 3, Interventional, and Treatment
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:
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
A randomised, controlled, double-blind, multicentre superiority trial will be conducted with two parallel, non-crossover treatment arms: (1) LPS and (2) placebo. All natural cycles occurring within 6 months after randomisation, monitored at home using LH-surge ovulation testing, are included in the study period. The follow up period continues for 12 months after end of the study period (i.e. up to 18 months after randomisation) to assess pregnancy outcomes and confirm live birth.
Trial population A total of 640 patients will be included, with 320 patients allocated to each treatment group.
Couples diagnosed with primary or secondary unexplained infertility, who have a good prognosis for achieving a live birth within the coming year (i.e. Hunault prognostic score ≥30%) and who are assigned to expectant management for at least six months in accordance with Dutch NVOG guidelines, are eligible for inclusion. Female eligibility criteria include an age range of 18-43 years and a body mass index (BMI) below 45kg/m2. A diagnosis of endometriosis will constitute an exclusion criterion.
Interventions
During six consecutive calendar months, participants will perform LH-surge testing via urinary ovulation tests at home, followed by progesterone or placebo treatment during the luteal phase of each menstrual cycle.
A dosage of 300 mg vaginal micronised progesterone twice daily (Utrogestan; Besins Healthcare, Ireland) will be administered in the treatment group, while matching vaginal placebo capsules will be administered in the control group.
Treatment will start on day 3 after a positive urinary LH-surge test and continue until the onset of menstruation, a negative pregnancy test performed 14 days after the positive LH-surge test, miscarriage, or a gestational age of 7+0 weeks. No additional hospital visits or laboratory tests will be required compared with standard care.
Participants are will be asked to use the vaginal capsules as prescribed and complete a medication diary to record compliance throughout the study period. In addition, participants receive short digital questionnaires: at randomisation (Q1, to assess baseline quality of life), at 6 months after randomisation (Q2, quality of life, compliance to therapy, side-effects), and 18 months after randomisation (Q3, determine pregnancy and neonatal outcomes of pregnancies achieved within 6 months after randomisation, determine use of ART treatment and conception during follow up period).
For pregnancies occurring during the six-month study period, the first pregnancy ultrasound will be scheduled at the hospital. Following confirmation of a viable pregnancy, additional antenatal care will be provided within the usual care setting, typically in primary care, unless medical indications require specialist care.
552 studies on the registry are indexed under Infertility, Female; 137 are open to participants now.
This study's planned enrollment of 640 is above the median of 100 across 378 interventional studies indexed under Infertility, Female.
Browse Infertility, Female studies →This is the only study on the registry with Simone Broer as lead sponsor.
Compared within Infertility, Female, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Infertility. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Diagnosis of UI after infertility work-up, i.e.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
progesteron versus placebo
placebo
Pregnancy occurring within 6 months after randomisation, leading to a live birth.
Time frame: within 6 months after randomisation
Clinical pregnancy
Time frame: within 6 months after randomisation
Ongoing pregnancy
Time frame: within 6 months after randomisation
Biochemical pregnancy loss
Time frame: within 6 months after randomisation
Miscarriage rates
Time frame: within 6 months after randomisation
Multiple pregnancy rate
of all achieved (ongoing) pregnancies
Time frame: within 6 months after randomisation
Time to pregnancy
Of all achieved (ongoing) pregnancies
Time frame: Within 6 months after randomisation
Pregnancy loss
of all achieved (ongoing) pregnancies
Time frame: within 6 months after randomisation
Pregnancy complications
of all achieved (ongoing) pregnancies
Time frame: within 6 months after randomisation
Perinatal outcomes
Of all achieved (ongoing) pregnancies
Time frame: within 6 months after randomisation
Type of delivery
of all achieved (ongoing) pregnancies
Time frame: within 6 months after randomisation
Side effects
Assessed using a monthly medication diary and a questionnaire administered 6 months after randomisation.
Time frame: During the 6-month study period
Compliance to therapy
Assessed using a monthly medication diary and a questionnaire administered 6 months after randomisation.
Time frame: During the 6-month study period
Number of adverse events and serious adverse events.
Time frame: During the 6-month study period
Quality of life assessed at time of randomisation, and 6 and 18 months after randomisation
using the FertiQoL questionnaire
Time frame: assessed at time of randomisation, and 6 and 18 months after randomisation
Progression to (MOH)IUI/IVF/ICSI
Time frame: within six months after randomisation
Use of ART and (ongoing) pregnancy achieved
Time frame: after the six-month study period and within 12 months follow up.
Budget impact
Time frame: over the 6-month study period
Cost-effectiveness analyses using live birth rates and costs
Time frame: over the 6-month study period
No study locations are listed for this record.
Plan to share: No
No publications or documents are linked to this record.
This study is not yet recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Utrogestan