Intrauterine Flushing With Follicular Fluid Plus Granulosa Cells

Evaluation of Implantation and Clinical Pregnancy After Intrauterine Flushing of Infertile Patients With Follicular Fluid Plus Granulosa Cells- Randomized Controlled Trial

One hundred forty patients with male factor infertility are randomized into two groups. In the study group, flushing the endometrial cavity with 2ml of clear follicular fluid with granulose cells will be performed using an IUI catheter after ovum pick-up While in the control group, no flushing of the endometrial cavity with FF is done. The implantation rates and pregnancy rates in both groups will be assessed.

Study Overview

• Status: Completed
• Conditions: Embryo Implantation; Follicular Fluid; Granulosa Cell
• Intervention / Treatment: Biological: Intrauterine flushing of follicular fluid with granulosa cells

Detailed Description

This study is a randomized clinical trial to investigate implantation rate and clinical pregnancy after intrauterine flushing of infertile patients with follicular fluid plus granulosa cells - Randomized controlled trials. The study protocol is approved by the Ethics Committee (Institutional Review Board) of Royan institute and all participants provide informed consent.

The main objective of this study is evaluation of implantation rate and clinical pregnancy after flushing of uterine in infertile patients with follicular fluid plus granulosa cells in IVF/ ICSI cycles.

Material and methods: In a randomized clinical trial, 140 patients with Male factor infertility referring to infertility clinic of Royan Institute, Iran, who received ovarian stimulation with antagonist and agonist protocol, will be randomly assigned to two groups: in case group, if the follicular fluid of two clear dominant follicles contain at least 2 COC, after removal of the COCs, follicular fluid will be collected Endometrial cavity flushing with 2 ml of follicular fluid will be performed by IUI caterer. In control group only catheterization of uterine cavity will be performed. Primary outcome is comparison of implantation rate between case and control group. Secondly outcome is assessment of clinical pregnancy rate in both groups.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Parvaneh Afsharian; Phone Number: +9821- 23562000; Email: pafshar@royaninstitute.org

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Royan Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 38 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Normal Hormonal profile (FSH, LH, AMH) and normal AFC
2. Normal ovarian reserve
3. Age 20-38 years
4. Regular menstrual cycle
5. IVF / ICSI or IVF or ICSI cycles with agonist and antagonist protocol
6. Existence of at least 2 oocytes in dominant follicular fluids

Exclusion Criteria:

1. Presence of Endometriosis and Endometrioma
2. Hydrosalpinx
3. OHSS (Ovarian Hyper Stimulating Syndrome)
4. Tubal factor infertility
5. Male factor infertility with azoospermia
6. Low/Poor Response
7. Myoma with a compression effect or submocusa myometrium
8. Intra mural or subserouse Myoma > 5cm
9. Presence of untreated Thyroid, Diabetic and Hepatitis diseases, vaginal infection.
10. Endometrial tuberculosis
11. The follicular fluid which contains any oocyte or contaminated with blood will be discarded

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intrauterine flushing follicular fluid; Women underwent intrauterine flushing with follicular fluid plus granulosa cells	Biological: Intrauterine flushing of follicular fluid with granulosa cells; All patients in case and control groups will receive agonist and antagonist protocol. Ovarian stimulation will be carried out when pituitary desensitization is achieved and is continued until the day of hCG administration. COCs aspiration will be performed 34-36h after hCG injection. Clear Follicular Fluids (without blood cells) which contain COCs will be used. Endometrial flushing after oocyte retrieval with 2 ml of clear FF plus granulose cells will be performed by an IUI catheter. The control group included 70 women who would not have FF endometrial flushing. In both groups, embryo transfer will be carried out 2-3 days later. Luteal phase support will be started the day after ovum pick up by the vaginal administration of progesterone daily for 16 days and will continued for up to12 weeks if pregnancy occurred. Pregnancy was diagnosed by measurement of β-hCG level and later was confirmed by Transvaginal sonography.
No Intervention: Without intrauterine flushing with follicular fluid; Women without intrauterine flushing with follicular fluid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Implantation rates	Implantation rate was measured as the number of gestational sacs observed, divided by the number of embryos transferred	Day 35-42 post ovum pick-up (OPU) (34-36 hours post recombinant human choriogonadotropin day [approximately 28 days])

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical pregnancy rate	The observation of gestational sac on ultrasound examination two-three weeks after positive serum βhCG	4-6 weeks after embryo transfer

Collaborators and Investigators

• Sponsor: Royan Institute
• Investigators: Study Chair: Maryam Hafezi, Department of Endocrinology and Female Infertility

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): January 1, 2023

Study Registration Dates

• First Submitted: September 1, 2019
• First Submitted That Met QC Criteria: September 1, 2019
• First Posted (Actual): September 4, 2019

Study Record Updates

• Last Update Posted (Actual): March 14, 2023
• Last Update Submitted That Met QC Criteria: March 11, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Manifestations; Flushing
• Other Study ID Numbers: Infertility-Uterine flushing

Drug and device information, study documents

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