Intrauterine Insemination With Letrozole Versus in Natural Cycle

Intrauterine Insemination With Letrozole Versus Intrauterine Insemination in Natural Cycle. A Randomised Controlled Trial

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, investigators 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. Investigators therefore perform a randomized clinical trial (RCT) on the subject in the Centre of Reproductive Medicine, Peking University Third Hospital, Beijing, 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 Randomized clinical 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 3-5 for 5 days. Investigators will treat the couples for 3 cycles, with a time horizon of 4 months.

Main study parameters/endpoints Primary outcome is ongoing pregnancy leading to live birth. Secondary endpoints are clinical pregnancy, multiple pregnancy, miscarriage rates, pregnancy complications and patients' costs.

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 subfertile couples.

Study Overview

• Status: Completed
• Conditions: Infertility; Intrauterine Insemination
• Intervention / Treatment: Drug: letrozole

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100191
      • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Being diagnosed with unexplained or mild male subfertility
• At least one sided tubal patency, established according to local protocol
• Normal or mild impairment of semen quality defined as a TMSC of 3 million or more based on at least one semen analysis

Exclusion Criteria:

• Woman with double sided tubal pathology
• Women with irregular cycles, PCOS or other endocrine disorders
• Impaired semen quality: pre-wash TMSC <3 million.

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
Experimental: letrozole group; letrozole 5mg/day starting from day 3 of menstrual cycle for 5 days	Drug: letrozole; Women will be randomizedfor ovarian stimulation with letrozole or to natural cycle IUI.
No Intervention: natural cycle group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ongoing pregnancy	Primary outcome is ongoing pregnancy leading to live birth	3 months

Collaborators and Investigators

• Sponsor: Peking University Third Hospital
• Investigators: Principal Investigator: Shuo Huang, PhD, Peking University Third Hospital

Publications and helpful links

General Publications

• Franik S, Le QK, Kremer JA, Kiesel L, Farquhar C. Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2022 Sep 27;9:CD010287. doi: 10.1002/14651858.CD010287.pub4. Review.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2018
• Primary Completion (Actual): June 30, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: February 25, 2018
• First Submitted That Met QC Criteria: March 4, 2018
• First Posted (Actual): March 6, 2018

Study Record Updates

• Last Update Posted (Actual): February 8, 2021
• Last Update Submitted That Met QC Criteria: February 5, 2021
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole
• Other Study ID Numbers: IUI-letrozole/natural cycle

Drug and device information, study documents

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