We sought to assess the safety and effectiveness of flushing follicles as part of egg collection in women undergoing treatments to help them get pregnant (assisted reproductive technology (ART)).
Couples who have difficulty becoming pregnant naturally may choose to have treatments (interventions) to help them get pregnant. These interventions are known as assisted reproductive technology (ART). One type of ART is in vitro fertilisation (IVF). During IVF, ovarian stimulation is performed using hormones to stimulate multiple eggs to develop within follicles located in each ovary. After ovarian stimulation, a needle guided by ultrasound is inserted into each follicle in order to collect these eggs. Instead of using only suction to obtain the contents of follicles (aspiration), it has been proposed that flushing the follicles after aspiration may lead to collection of more eggs and therefore higher chances of becoming pregnant and having a baby. This technique is called follicular flushing.
We included 15 studies that randomly assigned a total of 1643 women to follicular aspiration alone or follicular flushing after aspiration. To see if there was a difference between the two techniques, we wanted to look at the main results of live birth rate (number of babies born per 1000 women) and miscarriage rate (number of miscarriages per 1000 women). We carried out a comprehensive search to identify all relevant research in the field in July 2021.
Four studies reported on the main result of live birth rate. It is uncertain whether follicular flushing has an impact on live birth rate compared with aspiration alone. This suggests that if a live birth rate of approximately 30% is seen with aspiration alone, the equivalent live birth rate with follicular flushing lies between 20% and 39%. One study reported on miscarriage rate, although the certainty of the evidence was low, preventing us from drawing any conclusions with confidence. Nevertheless, the data suggest that if the miscarriage rate is approximately 1% with aspiration alone, the equivalent rate with follicular flushing lies between 0% and 22%.
We are also uncertain of the impact of follicular flushing on the number of eggs retrieved, the number of embryos, or the clinical pregnancy rate compared to aspiration alone. Although the certainty of evidence was low, it appears that follicular flushing takes longer to perform than aspiration alone. The available evidence was insufficient to permit any firm conclusions with respect to adverse events or safety.
More research is needed to find out whether any specific patient groups would benefit from follicular flushing.
Certainty of the evidence
The certainty of evidence for the main outcome of live birth rate was moderate. The certainty of evidence for the other outcomes ranged from very low to low. The main limitations of included studies were lack of blinding (the process of preventing women participating in the trial and research staff from being aware of the intervention used), inconsistency (differences across studies), and imprecision (insufficient data).
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.
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.
To assess the safety and efficacy of follicular flushing as compared with aspiration only performed in women undergoing ART.
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.
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.
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.
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.