IUI With Letrozole Versus in Natural Cycle

Study Overview
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Brief Summary
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Rationale Intrauterine insemination (IUI) is the treatment of first choice for couples with unexplained and mild male factor infertility in many countries, but it is controversial whether ovarian stimulation improves fertility outcomes. In recent retrospectively collected data, we found that in couples with unexplained and mild male factor infertility undergoing IUI, ovarian stimulation with letrozole increased live birth rate as compared to natural cycle IUI without substantially increasing the multiple pregnancy rate. We therefore intend to perform a randomized clinical trial (RCT) on the subject in five reproductive medical centers in different cities in China. Objective To test the hypothesis that in couples with unexplained or mild male factor infertility scheduled for an IUI program ovarian stimulation with letrozole increases the live birth rate as compared to natural cycle treatment. Study design Multicenter randomized controlled trial. Study population Women diagnosed with unexplained or mild male factor infertility scheduled for treatment with IUI. Intervention Women will be randomized for ovarian stimulation with letrozole or to natural cycle IUI. In the group allocated to ovarian stimulation, women will receive oral tablets letrozole 5 mg daily from cycle day 3 for 5 days. We will treat the couples for 3 cycles, with a time horizon of 4 months. Main study parameters/endpoints Primary outcome is live birth resulting from conception within 4 months after randomization. Secondary endpoints are clinical pregnancy, multiple pregnancy, miscarriage rates, pregnancy complications, time to pregnancy leading to live birth. Nature and extent of the burden and risks associated with participation, benefit and group relatedness The strategies compared are already broadly applied in current practice. No additional risks are expected. There is no benefit for participants, but the results may benefit future infertile couples.

Official Title
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Intrauterine Insemination With Letrozole Versus Intrauterine Insemination in Natural Cycle. A Muticenter Randomized Controlled Trial

Conditions
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Intrauterine Insemination, Unexplained Infertility

Intervention / Treatment
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* Drug: Letrozole


Participation Criteria
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Eligibility Criteria
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Inclusion criteria In order to be eligible to participate in this study, a participating couple must meet all of the following criteria: Being diagnosed with unexplained or mild male infertility At least one sided tubal patency, established according to local protocol Normal or mild impairment of semen quality defined as total motile sperm count (TMSC) no less than 5million, based on at least one recent semen analysis Exclusion criteria A potential participant who meets any of the following criteria will be excluded from study participation: Woman with double sided tubal pathology Women with irregular cycles, PCOS or other endocrine disorders Man with impaired semen quality: total motile sperm count (TMSC) less than 5million

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: letrozole group<br>Women will be given IUI treatment with ovarian stimulation with letrozole 5mg/day starting from day 3 of menstrual cycle for 5 days. | Drug: Letrozole<br>* Women will be randomized to the group with ovarian stimulation with letrozole or the group without stimulation.<br>|
| No Intervention: natural cycle group<br>Women will be given IUI treatment without ovarian stimulation. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| live birth rate | Primary outcome is live birth resulting from conception within 4 months after randomization. | 14 months |