Value of Follicular Flushing. Randomised Controlled Trial

Does Addition of Follicular Flushing to the Initial Aspiration Lead to Higher Numbers of Oocytes Retrieved in Women Undergoing Oocyte Retrieval? A Randomized Controlled Trial

The purpose of this study is to evaluate whether the addition of follicular flushing to the initial aspiration during oocyte retrieval increases the number of oocytes retrieved in women undergoing ovarian stimulation.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Procedure: Experimental: Follicular aspiration with addition of follicular flushing.

Detailed Description

There is an ongoing debate regarding the effectiveness of follicular flushing during oocyte retrieval. Currently published studies and metanalyses suggest that follicular flushing does not improve live birth rate, clinical pregnancy rate or the number of oocytes retrieved. However, currently published studies may be confounded by the types of needle used, aspiration pressures, number of times flushing is repeated, etc. Additionally, follicular flushing should be examined in specific patient populations according to their response to ovarian stimulation.

In the current study, each woman will have one ovary (right or left) randomly assigned to be aspirated with or without the addition of follicular flushing. This study design ensures that clinical and demographic characteristics of the couple will not affect the outcomes evaluated. The primary endpoints will be the number of oocytes retrieved per ovary assigned to each group. Secondary outcomes will be the oocyte recovery rate (oocytes retrieved per follicle aspirated) oocyte maturation rate, fertilization rate, and embryo development per ovary assigned to each group.

The study population will include three subgroups according to observed ovarian response to ovarian stimulation (poor responders, normal responders, hyper responders). Assuming a minimum clinically significant difference in oocyte yield of 1 oocyte, a sample size of twenty patients per subgroup is required to yield 80% power.

Patients aged <43 years with the presence of at least one follicles >11mm in each ovary on the day of triggering final oocyte maturation will be eligible for inclusion in the study. 60 patients (20 in each of the aforementioned subgroup) will be recruited and just prior to oocyte retrieval their left and right ovaries will be randomly allocated into flushing or the no-flushing group. In both ovaries all follicles greater than 11mm will be punctured by the same 16G double lumen needle, using the same aspiration pressure. In the flushing group, flushing will be performed up to a maximum of five times or until a cumulus oocyte complex (COC) is retrieved.

In the control group all follicles greater than 11mm will be aspirated by the same double lumen needle and no flushing will be performed.

All COCs will be grouped according to the ovary they originated from by the embryologists and their development will be recorded until Day 3 following fertilization (Number of MII oocytes, number of fertilized oocytes, number good quality Day 3 embryos).

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tryfon G Lainas, PhD; Phone Number: +302107236333; Email: tlainas@eugonia.com.gr
• Study Contact Backup: Name: George T Lainas, PhD; Phone Number: +302107236333; Email: ggslns@gmail.com

Study Locations

• Greece
  • Athens, Greece, 11528
    • Eugonia Unit of Assisted Reproduction

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Presence of both ovaries
• 18-43 years old
• At least one follicle >11mm present in each ovary on day of triggering final oocyte maturation.

Exclusion Criteria:

• Ovarian surgery
• Monofolicular development

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: Follicular aspiration with addition of follicular flushing.; All follicles will be aspirated with the addition of follicular flushing if necessary (up to 5 times per follicle)	Procedure: Experimental: Follicular aspiration with addition of follicular flushing.; Follicular flushing if necessary up to 5 times using a double lumen needle for oocyte recovery
No Intervention: Follicular aspiration only.; All follicles will be aspirated and no flushing will be applied.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of oocytes retrieved	Number of oocytes retrieved per ovary randomised	During oocyte collection (usually 10-30 minutes)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oocyte recovery rate	Number of oocytes retrieved per follicle aspirated	During oocyte collection (usually 10-30 minutes)
Oocyte maturation rate	Number of mature (metaphase-II) oocytes divided by the number of oocytes retrieved per ovary randomised	During oocyte denudation (usually 10-30 minutes)
Fertilization rate	Number of fertilised (2PN) oocytes divided by the number of matured oocytes retrieved per ovary randomised	During fertilisation check (usually 10 minutes)
Percentage of good quality embryos on day 2/3	Number of good quality embryos divided by the number of fertilized oocytes per ovary randomised	During embryo evaluation (usually 10 minutes)

Collaborators and Investigators

• Sponsor: Eugonia

Publications and helpful links

General Publications

• von Horn K, Depenbusch M, Schultze-Mosgau A, Griesinger G. Randomized, open trial comparing a modified double-lumen needle follicular flushing system with a single-lumen aspiration needle in IVF patients with poor ovarian response. Hum Reprod. 2017 Apr 1;32(4):832-835. doi: 10.1093/humrep/dex019.
• Franasiak JM. Follicular flushing: time to look elsewhere to improve in vitro fertilisation outcomes? BJOG. 2017 Jul;124(8):1197. doi: 10.1111/1471-0528.14628. No abstract available.
• Roque M, Sampaio M, Geber S. Follicular flushing during oocyte retrieval: a systematic review and meta-analysis. J Assist Reprod Genet. 2012 Nov;29(11):1249-54. doi: 10.1007/s10815-012-9869-9. Epub 2012 Oct 13.

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2022
• Primary Completion (Actual): December 30, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: July 15, 2022
• First Submitted That Met QC Criteria: July 21, 2022
• First Posted (Actual): July 26, 2022

Study Record Updates

• Last Update Posted (Actual): March 30, 2023
• Last Update Submitted That Met QC Criteria: March 29, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Oocyte Retrieval; Follicular Flushing
• Additional Relevant MeSH Terms: Skin Manifestations; Infertility; Flushing
• Other Study ID Numbers: Flushing RCT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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