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. 2022 Nov 21;11(11):CD004634.
doi: 10.1002/14651858.CD004634.pub4.

Follicular flushing during oocyte retrieval in assisted reproductive techniques

Ektoras X Georgiou  1 , Pedro Melo  2 , Ying C Cheong  3 , Ingrid E Granne  4
Affiliations

Follicular flushing during oocyte retrieval in assisted reproductive techniques

Ektoras X Georgiou et al. Cochrane Database Syst Rev. .

Abstract

Background: Follicular aspiration under transvaginal ultrasound guidance is routinely performed as part of assisted reproductive technology (ART) to retrieve oocytes for in vitro fertilisation (IVF). The process involves aspiration of the follicular fluid followed by the introduction of flush, typically culture media, back into the follicle followed by re-aspiration. However, there is a degree of controversy as to whether this intervention yields a larger number of oocytes and is hence associated with greater potential for pregnancy than aspiration only.

Objectives: To assess the safety and efficacy of follicular flushing as compared with aspiration only performed in women undergoing ART.

Search methods: We searched the following electronic databases up to 13 July 2021: the Cochrane Gynaecology and Fertility Specialised Register of Controlled Trials, CENTRAL (containing output from two trial registries and CINAHL), MEDLINE, Embase, and PsycINFO. We also searched LILACS, Google Scholar, and Epistemonikos. We reviewed the reference lists of relevant papers and contacted experts in the field to identify further relevant studies.

Selection criteria: We included randomised controlled trials (RCTs) that compared follicular aspiration and flushing with aspiration alone in women undergoing ART using their own gametes. Primary outcomes were live birth rate and miscarriage rate per woman randomised.

Data collection and analysis: Two review authors independently assessed studies identified by search against the inclusion criteria, extracted data, and assessed risk of bias. A third review author was consulted if required. We contacted study authors as needed. We analysed dichotomous outcomes using Mantel-Haenszel odds ratios (ORs), 95% confidence intervals (CIs), and a fixed-effect model, and we analysed continuous outcomes using mean differences (MDs) between groups presented with 95% CIs. We examined the heterogeneity of studies via the I2 statistic. We assessed the certainty of evidence using the GRADE approach.

Main results: We included 15 studies with a total of 1643 women. Fourteen studies reported outcomes per woman randomised, and one study reported outcomes per ovary. No studies were at low risk of bias across all domains; the main limitation was lack of blinding. The certainty of the evidence ranged from moderate to very low, and was downgraded for risk of bias, imprecision, and inconsistency. We are uncertain of the effect of follicular flushing on live birth rate compared to aspiration alone (OR 0.93, 95% CI 0.59 to 1.46; 4 RCTs; n = 467; I2 = 0%; moderate-certainty evidence). This suggests that with a live birth rate of approximately 30% with aspiration alone, the equivalent live birth rate with follicular flushing lies between 20% and 39%. We are uncertain of the effect of follicular flushing on miscarriage rate compared to aspiration alone (OR 1.98, 95% CI 0.18 to 22.22; 1 RCT; n = 164; low-certainty evidence). This suggests that with a miscarriage rate of approximately 1% with aspiration alone, the equivalent miscarriage rate with follicular flushing lies between 0% and 22%. We are uncertain of the effect of follicular flushing on oocyte yield (MD -0.47 oocytes, 95% CI -0.72 to -0.22; 9 RCTs; n = 1239; I2 = 61%; very low-certainty evidence); total number of embryos (MD -0.10 embryos, 95% CI -0.34 to 0.15; 2 RCTs; n = 160; I2 = 58%; low-certainty evidence); and clinical pregnancy rate (OR 1.12, 95% CI 0.85 to 1.51; 7 RCTs; n = 939; I2 = 46%; low-certainty evidence). The duration of the retrieval process may be longer with flushing (MD 175.44 seconds, 95% CI 152.57 to 198.30; 7 RCTs; n = 785; I2 = 87%; low-certainty evidence). It was not possible to perform a meta-analysis for adverse events, although individual studies reported on outcomes ranging from depression and anxiety to pain and pelvic organ injury.

Authors' conclusions: The effect of follicular flushing on both live birth and miscarriage rates compared with aspiration alone is uncertain. Although the evidence does not permit any firm conclusions on the impact of follicular flushing on oocyte yield, total number of embryos, number of cryopreserved embryos, or clinical pregnancy rate, it may be that the procedure itself takes longer than aspiration alone. The evidence was insufficient to permit any firm conclusions with respect to adverse events or safety.

Trial registration: ClinicalTrials.gov NCT02277210.

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Conflict of interest statement

EG has no interests to declare.

PM has no interests to declare.

YC is a consultant for Complete Fertility, and has received lecture fees from Merck (to April 2021).

IG is a principal investigator on a project grant from Bayer. She declares that she has not received the funds personally and cannot access or control the spending of the moneys.

Figures

1
1
Study flow diagram.
2
2
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
3
3
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
4
4
Forest plot of comparison: 1 Follicular flushing, outcome: 1.1 Live birth rate.
5
5
Forest plot of comparison: 1 Follicular flushing, outcome: 1.2 Miscarriage rate.
6
6
Forest plot of comparison: 1 Follicular flushing, outcome: 1.2 Oocyte yield per woman randomised (normally distributed data).
7
7
Forest plot of comparison: 1 Follicular flushing, outcome: 1.4 Duration of oocyte retrieval (normally distributed data; seconds).
8
8
Forest plot of comparison: 1 Follicular flushing, outcome: 1.8 Clinical pregnancy rate per woman randomised.
9
9
Forest plot of comparison: 1 Follicular flushing, outcome: 1.10 Adverse events (continuous data).
10
10
Forest plot of comparison: 1 Follicular flushing, outcome: 1.11 Adverse events (dichotomous data).
1.1
1.1. Analysis
Comparison 1: Follicular flushing, Outcome 1: Live birth rate
1.2
1.2. Analysis
Comparison 1: Follicular flushing, Outcome 2: Miscarriage rate
1.3
1.3. Analysis
Comparison 1: Follicular flushing, Outcome 3: Oocyte yield per woman randomised (normally distributed data)
1.5
1.5. Analysis
Comparison 1: Follicular flushing, Outcome 5: Duration of oocyte retrieval (normally distributed data; seconds)
1.7
1.7. Analysis
Comparison 1: Follicular flushing, Outcome 7: Total number of embryos (normally distributed data)
1.9
1.9. Analysis
Comparison 1: Follicular flushing, Outcome 9: Number of embryos cryopreserved per woman randomised (normally distributed data)
1.11
1.11. Analysis
Comparison 1: Follicular flushing, Outcome 11: Clinical pregnancy rate per woman randomised
1.12
1.12. Analysis
Comparison 1: Follicular flushing, Outcome 12: Ongoing pregnancy rate per woman randomised
1.13
1.13. Analysis
Comparison 1: Follicular flushing, Outcome 13: Adverse events (continuous data)
1.14
1.14. Analysis
Comparison 1: Follicular flushing, Outcome 14: Adverse events (dichotomous data)
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References

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