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A systematic review and meta-analysis of randomized controlled studies comparing follicular flushing versus aspiration during oocyte retrieval in IVF cycles

Contraception and Reproductive Medicine volume 10, Article number: 25 (2025) Cite this article

Abstract

Objectives

To assess the value of follicular flushing during ovum pick up compared to follicular aspiration in IVF cycles.

Search strategy

Screening of PubMed, Web Of Science, Cochrane, Scopus, and clinical trials registry from inception to October 2024. The search key words included follicular flushing, follicle aspiration, ovum pick up, oocyte retrieval, IVF, and their MeSH terms.

Selection criteria

This review included all RCTs that evaluated the use of follicular flushing during ovum pick-up. Seventeen studies including 2218 participants (1124 were subjected to follicular flushing and 1094 subjected to follicular aspiration) were included.

Data collection and analysis

The extracted data included the settings of the study, the number and characteristics of participants, intervention details including the number of flushes, and the suction pressure used, outcome parameters including number of retrieved oocytes, the oocyte/ follicle ratio, the number of MII oocytes, the time of the procedure, the fertilization, implantation, clinical pregnancy, chemical pregnancy, ongoing pregnancy, live birth, miscarriage and cancellation rates, and risk of bias assessment.

Main results

The number of retrieved and MII oocytes were evaluated in 14 and 11 studies with 1920 and 1588 participants and revealed a mean difference (MD) of 0.03 and 0.16 with [-0.50, 0.57] and [-0.29, 0.61] 95% CI (P value =0.9 and 0.48, I2 = 87% and 90%), respectively.

The fertilization and implantation rates were evaluated in 4 and 7 studies with 3331 and 1605 participants and revealed an Odd Ratio (OR) of 1.48 and 0.91 with [0.98, 2.24] and [0.55, 1.51] 95% CI (P value =0.06 and 0.72, I2 = 82% and 61%), respectively.

The clinical pregnancy rate was evaluated in 11 studies with 1542 participants and revealed an Odd Ratio (OR) of 1.23 with [0.86, 1.74] 95% CI (P value =0.26, I2 = 42%).

The ongoing pregnancy /livebirth rate was evaluated in 11 studies with 1266 participants and revealed an Odd Ratio (OR) of 1.07 with [0.80, 1.43] 95% CI (P value =0.65, I2 = 0%).

The time of the procedure was evaluated in 8 studies with 985 participants and revealed a mean difference (MD) of 178.58 with [98.23, 258.93] 95% CI (P value <0.001, I2 = 97%).

The cycle cancellation rate was evaluated in 5 studies with 856 participants and revealed an Odd Ratio (OR) of 0.66 with [0.45, 0.98] 95% CI (P value =0.04, I2 = 0%).

Conclusion

Follicular flushing during oocyte retrieval did not improve the number of retrieved oocytes, the oocyte retrieved over the aspirated follicles ration, the number of MII oocytes, the fertilization rate, implantation rate, clinical pregnancy, chemical pregnancy, ongoing pregnancy/livebirth, and miscarriage rates and associated with significant prolongation of the procedure. Cycle cancellation was significantly improved with follicular flushing in women with poor ovarian response.

Trial registration

Registration number CRD42024600698 date of registration 23/10/2024.

Introduction

IVF is a relatively complicated procedure that involves a series of stages. The number of oocytes obtained after the hormonal ovarian stimulation is very crucial in determination of IVF success [1].

Initially, ovum pick up was challenging and performed by either laparotomy or laparoscopy with less than 50 % success rate [2].

This rate was improved with the introduction of foot-controlled suction pressure control [3], and Teflon lined beveled aspiration needles [4].

Ovum pick up is usually performed under general anesthesia after 34 -38 hours of ovulation triggering [5].

The role of first come first serve is usually followed during ovum pick up to avoid intraovarian bleeding, inadvertent follicular rupture, and to ensure continuous visualization of the needle during aspiration to avoid pelvic organs and vessels injury [6].

Although ovum pick up is a relatively safe procedure, it may be associated with pain, infection (0.6%), vaginal bleeding (8.6%), and complications of the used anesthesia [7].

Several modifications were suggested to maximize the number of retrieved oocytes during ovum pick up especially in women with poor ovarian response [8]

The use of follicular flushing was introduced to reduce the risk of oocyte retention. However, the use of flushing may have a damaging effect on the retrieved oocytes. While some investigators suggested the use of follicular flushing in all women, others restricted its use to poor responders and another group rejected its use in all cases.

Older non RCTs suggested that follicular flushing increased the number of retrieved oocytes [9,10,11].

Subsequent studies yielded conflicting results regarding the benefits and risks of follicular flushing [12].

So, the conduction of this review was necessary to search for evidence regarding follicular flushing use during ovum pick up.

Objective

To evaluate the safety and efficacy of value of follicular flushing compared to follicular aspiration during ovum pick up in IVF cycles.

Methods

This study was prospectively registered following the PRISMA guidelines of randomized controlled studies with CRD42024600698 number.

Eligibility criteria, information sources, search strategy

Two authors independently searched the different databases including PubMed, Web Of Science, Cochrane, Scopus, and clinical trials registry from inception to October 2024. The search key words included follicular flushing, follicle aspiration, ovum pick up, oocyte retrieval, IVF, and their MeSH terms.

Study selection

This review included all RCTs that evaluated the use of follicular flushing and compared it to follicular aspiration during ovum pick-up step in IVF cycles without language restrictions. It included all studies regardless of the number of flushes, the suction pressure used and, in all participants, whether poor, normal, or high ovarian responders.

After completing the search, the same 2 authors independently screened the articles for possible inclusion in this review. Any disagreement between them was reviewed and evaluated by all other authors.

After establishment of the included studies, 2 authors independently extracted the data from the selected articles using an extraction data sheet. The sheet included the settings of the study, the number of randomized and analyzed participants, the inclusion and exclusion criteria of the participants, all the intervention details including the number of flushes, and the suction pressure used, outcome parameters including both primary and secondary ones, risk of bias assessment and trial registration details.

The reported outcomes included the number of retrieved oocytes, the oocyte/ follicle ratio, the number of MII oocytes, the time of the procedure, the fertilization, implantation, clinical pregnancy, chemical pregnancy, ongoing pregnancy, live birth, miscarriage, and cancellation rates.

The risk of bias assessment for the included studies followed the recommendations of the Cochrane Handbook of Systematic Reviews for evaluation of RCTs. These recommendations included assessment of the random sequence generation, allocation concealment, participants and outcome assessor blinding, incomplete and selective data reporting and assessment of other biases. GRADE analysis was used to assess the quality of evidence for each outcome. GRADE assessment included the number of the reporting studies, risk of bias, inconsistency of the reported outcome, indirectness of data, sample size, width of CI and publication bias.

Statistical analysis

The overall effect estimate for dichotomous and continuous variables was done through measurement of Odd Ratio and the mean differences with 95% CI for both, respectively. The fixed or random effect models were used in non-significant and significant studies heterogeneity, respectively. The heterogeneity was evaluated through assessed by Cochran’s Q test and I2 statistics. The level of significance was set at or below 0.05 for P value and at or above 40% for I2. All statistical calculations and subgroup analysis were done using the Review Manager (RevMan) version 5.4.1 (The Nordic Cochrane Centre, Cochrane Collaboration, 2020, Copenhagen, Denmark).

Results

Study selection, study characteristics:

The flow chart of the search process is shown in Figure 1.

Fig 1
figure 1

PRISMA flow chart

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Seventeen studies including 2218 participants (1124 were subjected to follicular flushing and 1094 subjected to follicular aspiration) were included in our meta-analysis [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29].

All the included studies were published in English language and conducted in a single center.

Four studies were conducted in USA [21,22,23, 27], 3 in Turkey [16,17,18], 2 in UK [19, 28] and one study was conducted in each of the following countries Australia [15], Brazil [14], Egypt [25], France [13], Germany [29], Italy [24], Greece [20] and Switzerland [26].

The included participants were poor ovarian responders in 8 studies [13, 14, 17, 21,22,23, 26, 29], normal responders in 1 study [16] and unspecified in relation to ovarian response in 8 studies [15, 18,19,20, 24, 25, 27, 28]. The suction pressure used in the included studies ranged between 80 mmHg and 220 mmHg. In 1 study the suction pressure was manually determined [27] and unspecified in 6 studies [15, 16, 18, 19, 23, 24].

The number of follicular flushes were 1 flush in 5 studies [13, 16, 18, 21, 27], 2 flushes in 2 studies [24, 25], 3 flushes in 4 studies [14, 17, 22, 29], 4 flushes in 1 study [23], 5 flushes in 4 studies [15, 19, 20, 26] and 6 flushes in 1 study [28].

The included studies characteristics including the settings, sample size, participants characteristics, details of interventions, study outcomes and trial registration details are presented in Table 1.

Table 1 Characteristics of the included studies
Full size table

The risk of bias is described in Figure 2.

Fig 2
figure 2

Risk of bias A graph B summary

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Synthesis of results

The number of retrieved oocytes was evaluated in 14 studies with 1920 participants (973 were subjected to follicular flushing and 947 were subjected to follicular aspiration) and revealed a mean difference (MD) of 0.03 with [-0.50, 0.57] 95% CI (P value =0.9, I2 = 87%) (Figure 3).

Fig 3
figure 3

The number of retrieved oocytes

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The oocyte/ follicle ratio was evaluated in 5 studies with 6051 participants (2985 were subjected to follicular flushing and 3066 were subjected to follicular aspiration) and revealed an Odd Ratio (OR) of 1.12 with [0.64, 1.96]95% CI (P value =0.7, I2 = 94%) (Figure 4).

Fig 4
figure 4

The oocyte/ follicle ratio

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The number of MII oocytes was evaluated in 11 studies with 1588 participants (806 were subjected to follicular flushing and 782 were subjected to follicular aspiration) and revealed a mean difference (MD) of 0.16 with [-0.29, 0.61] 95% CI (P value =0.48, I2 = 90%) (Figure 5).

Fig 5
figure 5

The number of MII oocytes

Full size image

The fertilization rate was evaluated in 4 studies with 3331 participants (1644 were subjected to follicular flushing and 1687 were subjected to follicular aspiration) and revealed an Odd Ratio (OR) of 1.48 with [0.98, 2.24] 95% CI (P value =0.06, I2 = 82%) (Figure 6).

Fig 6
figure 6

Fertilization rate

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The implantation rate was evaluated in 7 studies with 1605 participants (833 were subjected to follicular flushing and 772 were subjected to follicular aspiration) and revealed an Odd Ratio (OR) of 0.91 with [0.55, 1.51] 95% CI (P value =0.72, I2 = 61%) (Figure 7).

Fig 7
figure 7

Implantation rate

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The clinical pregnancy rate was evaluated in 11 studies with 1542 participants (787 were subjected to follicular flushing and 755 were subjected to follicular aspiration) and revealed an Odd Ratio (OR) of 1.23 with [0.86, 1.74] 95% CI (P value =0.26, I2 = 42%) (Figure 8).

Fig 8
figure 8

Clinical pregnancy rate

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The chemical pregnancy rate was evaluated in 3 studies with 539 participants (281 were subjected to follicular flushing and 258 were subjected to follicular aspiration) and revealed an Odd Ratio (OR) of 0.93 with [0.58, 1.49] 95% CI (P value =0.76, I2 = 37%) (Figure 9).

Fig 9
figure 9

Chemical pregnancy rate

Full size image

The ongoing pregnancy /livebirth rate was evaluated in 11 studies with 1266 participants (644 were subjected to follicular flushing and 622 were subjected to follicular aspiration) and revealed an Odd Ratio (OR) of 1.07 with [0.80, 1.43] 95% CI (P value =0.65, I2 = 0%) (Figure 10).

Fig 10
figure 10

Ongoing pregnancy/live birth rate

Full size image

The miscarriage rate was evaluated in 5 studies with 601 participants (303 were subjected to follicular flushing and 298 were subjected to follicular aspiration) and revealed an Odd Ratio (OR) of 1.01 with [0.21, 4.73] 95% CI (P value =0.99, I2 = 36%) (Figure 11).

Fig 11
figure 11

Miscarriage rate

Full size image

The time of the procedure was evaluated in 8 studies with 985 participants (504 were subjected to follicular flushing and 481 were subjected to follicular aspiration) and revealed a mean difference (MD) of 178.58 with [98.23, 258.93] 95% CI (P value <0.001, I2 = 97%) (Figure 12).

Fig 12
figure 12

Time of the procedure

Full size image

The cycle cancellation rate was evaluated in 5 studies with 856 participants (441 were subjected to follicular flushing and 415 were subjected to follicular aspiration) and revealed an Odd Ratio (OR) of 0.66 with [0.45, 0.98] 95% CI (P value =0.04, I2 = 0%) (Figure 13).

Fig 13
figure 13

Cancellation rate

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Subgroup analysis for different outcomes according to the ovarian response of participants and number of flushes is described in Table 2 and the quality of evidence using GRADE analysis is described in Table 3.

Table 2 Subgroup analysis of outcomes
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Table 3 GRADE quality of evidence
Full size table

Discussion

This meta-analysis confirmed that follicular flushing during oocyte retrieval did not improve any of the IVF cycle outcomes except the reduction of cycle cancellation rate (high evidence). The non improved outcomes included the number of retrieved oocytes (moderate evidence), the oocyte retrieved over the aspirated follicles ration (moderate evidence), the number of MII oocytes (high evidence), the fertilization rate (moderate evidence), implantation rate (moderate evidence), clinical pregnancy (high evidence), chemical pregnancy (moderate evidence), ongoing pregnancy/livebirth (high evidence), and miscarriage rates (moderate evidence).

Our review confirmed high evidence that the procedure of follicular flushing was associated with significant prolongation of the procedure of ovum pick up.

These findings were constant through all subgroup analysis with few exceptions. These include the higher number of oocytes retrieved in the flush group if the flush was done once, the fertilization rate being higher in the flush group in poor responders and in women who underwent one and five flushes, the implantation and clinical pregnancy rates being higher in the flush group after four flushes (however that was derived from Moklin and colleagues study only).

The lower cancellation rate was significantly evident in poor responders and after one flush only while it shows non-significant differences in other women.

Strengths and limitations

Our meta-analysis provides the largest evidence about the value of follicular flushing during ovum pick up. All available RCTs without any language limitations were included. Careful and complete data extraction, meticulous risk of bias assessment for all individual studies were done by 2 authors independently. All authors for the included articles were contacted via email for clarifications and any missing data. A GRADE assessment of the quality of evidence for all outcomes was achieved. Extensive subgroup data analysis was calculated for all the available outcomes according to the ovarian reserve nature of included participants and the number of flushes.

The main limitations of this significant heterogeneity among the included studies. Most of the studies lack blind nature through their risk of bias assessment. Not all studies reported the same outcomes and most of the studies focused on the number of oocytes and other laboratory data with less concentration on the clinical outcomes of the procedure, especially livebirth rates. We tried to overcome this heterogeneity through analysis of data using the random effect model and through extensive subgroup analysis. Although all authors were contacted several times, only few authors responded for data clarification. In this review, we failed to report the side effects and complications of the procedures as they were rarely reported by the included studies. However, that was not considered as a major limitation as the process of ovum pick up is relatively safe.

Comparison with existing reviews

The Martini and colleagues systematic review included 11 studies (1,178 cases). They found that follicular flushing was not associated with improvement in either livebirth or clinical pregnancy rates. They reported a lower number of retrieved oocytes and MII oocytes and longer duration of the procedure in women who underwent follicular flushing compared to those who underwent direct aspiration. Compared to our systematic reviews, not all outcomes were reported, and subgroup analysis was not done due to inclusion of smaller number of studies [12].

Neumann and colleagues in 2023 conducted a systematic review to assess the value of follicular flushing in poor responders. It included 6 RCTs. They reached a conclusion that the effect of follicular flushing in poor responders is uncertain. Their review included only 6 studies, and the clinically related outcomes as clinical pregnancy and livebirth rates were not assessed [30].

A recent Cochrane review included 15 studies (1643 women) compared to 17 studies (2218 participants) in our review. The authors concluded that the value of follicular flushing is questionable on laboratory outcomes such as the numbers of retrieved oocytes, total number, and number of cryopreserved embryos and clinical outcomes such as clinical pregnancy, livebirth, and miscarriage rates. Although the authors evaluated most of the clinical outcomes, other outcomes such as fertilization, implantation and cycle cancellation rates were not evaluated. Also, extensive subgroup analysis was not done [31].

Conclusion

This systematic review concluded that the practice of follicular flushing was not associated with improvement of IVF outcomes named the number of oocytes retrieved, the oocyte / follicle ratio, fertilization, implantation, clinical pregnancy, chemical pregnancy, live birth, and miscarriage rates. The cycle cancellation rate showed a significant improvement in follicular flushing in women with POR. The follicular flushing was associated with prolongation of the time of ovum pick up with expected prolongation of the anesthesia time and subsequently its complications and increase in the costs.

According to the current evidence, follicular flushing is not recommended during ovum pick up. We recommend a well-organized multicenter blinded RCTs conduction with standardization of the suction pressure and the number of flushes for each follicle to reach a solid conclusion about the use of follicular flushing especially in women with considerable risk of unfavorable outcomes as poor responders.

Data availability

No datasets were generated or analysed during the current study.

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Acknowledgements

None.

Clinical trial number

Not applicable.

Synopsis

Follicular flushing during ovum pick up did not improve the number of retrieved oocytes, the number of MII oocytes, fertilization, implantation, clinical pregnancy, ongoing pregnancy, or livebirth rates. Follicular flushing during ovum pick up did not improve the number of retrieved oocytes, the number of MII oocytes, fertilization, implantation, clinical pregnancy, ongoing pregnancy, or livebirth rates.

Manuscript data

A. Why was this study conducted?

To assess the value of follicular flushing during ovum pick up in IVF cycles.

B. What are the key findings?

•Follicular flushing during oocyte retrieval did not improve the laboratory assessed outcomes of IVF named number of retrieved oocytes, the oocyte retrieved over the aspirated follicles ration, the number of MII oocytes, the fertilization rate, implantation rate,

•Follicular flushing was not associated with improvement of clinical pregnancy, chemical pregnancy, ongoing pregnancy/livebirth, or miscarriage rates.

•The procedure of follicular flushing was associated with significant prolongation of the ovum pick up procedure.

C. What does this study add to what is already known?

•Our meta-analysis provides the largest available evidence about the value of follicular flushing during ovum pick up.

•The current evidence did not recommend the use of follicular flushing during ovum pick up as it was not associated with improvement of the number of retrieved oocytes, clinical, ongoing or livebirth rates.

•Large multicenter RCT with adequate blinding with standardization of the suction pressure and the number of flushes considering women with different ovarian responses is needed for proper evaluation of follicular flushing.

Funding

Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB).

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Authors and Affiliations

  1. Faculty of medicine, Cairo University, Cairo, Egypt

    Nour A El-Goly

  2. Department of Obstetrics and Gynecology, Kasr Al-Ainy Hospital, Cairo University, Cairo, Egypt

    Ahmed M Maged, Aimy Essam & Amira Shoab

  3. 11 Eid Mostafa Street, Haram, Giza, Egypt

    Ahmed M Maged

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  1. Nour A El-Goly
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  2. Ahmed M Maged
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  3. Aimy Essam
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  4. Amira Shoab
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Contributions

NAE data extraction, risk of bias assessment, revision and approval of manuscript AMM search, data analysis, writing, revision and approval of manuscript AE data analysis. writing, revision and approval of manuscript AS search, revision and approval of manuscript

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Correspondence to Ahmed M Maged.

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El-Goly, N.A., Maged, A.M., Essam, A. et al. A systematic review and meta-analysis of randomized controlled studies comparing follicular flushing versus aspiration during oocyte retrieval in IVF cycles. Contracept Reprod Med 10, 25 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s40834-025-00351-w

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  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s40834-025-00351-w

Keywords

Contraception and Reproductive Medicine

ISSN: 2055-7426

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