Monitoring of stimulated cycles in fertility treatment involving in vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI)

Review question: can ultrasound alone be used safely without adding estradiol blood test measurements to monitor women undergoing controlled ovarian hyperstimulation during IVF and ICSI? We reviewed the evidence on monitoring women undergoing controlled ovarian hyperstimulation as part of IVF or ICSI by transvaginal ultrasound (TVUS) only versus traditional combined monitoring (TVUS) and blood hormone (estradiol) levels.

Background: Assisted reproduction techniques such as IVF and ICSI involve a process called controlled ovarian stimulation. The ovaries are artificially stimulated to produce follicles and then ovulation (release of a mature ovum or egg) is induced so that eggs can be retrieved for use in either IVF or ICSI to produce embryos in the laboratory. Traditionally women undergoing controlled ovarian hyperstimulation prior to ovulation induction have been monitored by TVUS and measurement of the hormone estradiol level in their blood. The aim of monitoring is to detect the optimum time to induce ovulation (by the administration of human chorionic gonadotrophin or luteinising hormone) and to determine an adequate response to ovarian hyperstimulation to allow egg retrieval, but importantly also to identify women at risk of the potentially serious rare condition of ovarian hyperstimulation syndrome (OHSS). It has been suggested that a simplified protocol of monitoring by TVUS alone may reduce unnecessary anxiety and operational costs during IVF and ICSI.

Study characteristics: we included six randomised controlled trials conducted in the UK, France, Spain, Israel and the US, including 781 women. They compared monitoring with TVUS only versus TVUS plus serum estradiol concentration in women undergoing ovarian hyperstimulation for IVF and ICSI treatment. The evidence was current to March 2020.

Key results: none of the six studies reported our primary outcome of live birth rate. Only four of the six studies reported pregnancy rate per woman; we are uncertain of the effect of monitoring with TVUS only versus TVUS plus estradiol measurement on clinical pregnancy rate per woman. Our findings suggest that in women with a 36% chance of clinical pregnancy using monitoring with TVUS plus serum estradiol, the clinical pregnancy rate using TVUS only would be between 31% and 46%.

We are uncertain of any effect in the mean number of oocytes retrieved per woman.

We are uncertain whether monitoring with TVUS only versus TVUS plus estradiol measurement affected the incidence of OHSS. The evidence suggested that in women with a 4% chance of OHSS using monitoring with TVUS plus serum estradiol, the OHSS rate monitored by TVUS only would be between 2% and 8%. The cycle cancellation rate was similar in both arms of two studies reporting this outcome.

Quality of the evidence: the evidence was of low quality. Limitations included imprecision and potential bias due to unclear description of randomisation methods, allocation concealment and blinding, as well as differences in the treatment protocols. Quality assessment was hampered by a lack of methodological descriptions in several studies. Two studies reported funding by pharmaceutical companies, whereas the remaining four studies did not report their sources of funding.

Authors' conclusions: 

This review update found no new randomised trials. Evidence from the six studies previously identified did not suggest that combined monitoring by TVUS and serum estradiol is more efficacious than monitoring by TVUS alone with regard to clinical pregnancy rates and the incidence of OHSS. The number of oocytes retrieved appeared similar for both monitoring protocols. The data suggest that both these monitoring methods are safe and reliable. However, these results should be interpreted with caution because the overall quality of the evidence was low. Results were compromised by imprecision and poor reporting of study methodology. The choice of one or the other method may depend upon the convenience of its use, and the associated costs. An economic evaluation of the costs involved with the two methods and the views of the women undergoing cycle monitoring would be welcome.

Read the full abstract...
Background: 

Monitoring of in vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) is necessary to detect as well as reduce the incidence and severity of ovarian hyperstimulation syndrome (OHSS) whilst achieving the optimal ovarian response needed for assisted reproduction treatment. Traditional monitoring of ovarian hyperstimulation during in vitro fertilisation IVF and ICSI treatment has included transvaginal ultrasonography (TVUS) plus serum estradiol levels . The need for combined monitoring (using TVUS and serum estradiol) during ovarian stimulation in assisted reproduction is controversial. It has been suggested that combined monitoring is time consuming, expensive and inconvenient for women and that simplification of IVF and ICSI therapy by using TVUS only should be considered. 

Objectives: 

To assess the effect of monitoring controlled ovarian hyperstimulation (COH) in IVF and ICSI cycles in subfertile couples with TVUS only versus TVUS plus serum estradiol concentration, with respect to rates of live birth, pregnancy and OHSS.

Search strategy: 

In this update conducted in March 2020, two review authors searched the Cochrane Gynaecology and Fertility Group's Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, the National Research Register, and web-based trial registers. There was no language restriction applied. All references in the identified trials and background papers were checked and authors were contacted to identify relevant published and unpublished data.

Selection criteria: 

Only randomised controlled trials that compared monitoring with TVUS only versus TVUS plus serum estradiol concentrations in women undergoing COH for IVF and ICSI treatment were included.

Data collection and analysis: 

Two review authors (IK, AW) independently selected the studies, extracted data and assessed risk of bias. We resolved disagreements by discussion. Outcomes data were pooled and summary statistics were presented when appropriate. The quality of the evidence was rated using the GRADE methods.

Main results: 

We did not identify any new eligible studies in this update in 2020. The evidence based on the six trials identified in 2014 remained unchanged. They included 781 women undergoing monitoring of COH with either TVUS alone or a combination of TVUS and serum estradiol concentration during IVF or ICSI treatment.

None of the six studies reported our primary outcome of live birth rate. Two studies presented pregnancy rate per initiated cycle and per embryo transfer, respectively. Four studies reported pregnancy rate per woman with pooled data; we are uncertain of the effect of monitoring with TVUS only versus combined monitoring on clinical pregnancy rate per woman (odds ratio (OR) 1.10; 95% confidence interval (CI) 0.79 to 1.54; four studies; N = 617; I² = 5%; low quality evidence). This suggests in women with a 36% chance of clinical pregnancy using monitoring with TVUS plus serum estradiol, the clinical pregnancy rate using TVUS only would be between 31% and 46%.

We are uncertain of any effect in the mean number of oocytes retrieved per woman (mean difference (MD) 0.32; 95% CI -0.60 to 1.24; five studies; N = 596; I² = 17%; low quality evidence). 

We are uncertain whether monitoring with TVUS only versus combined monitoring affected the incidence of OHSS (OR 1.03; 95% CI 0.48 to 2.20; six studies; N = 781; I² = 0%; low quality evidence), suggesting that in women with a 4% chance of OHSS using monitoring with TVUS plus serum estradiol, the OHSS rate monitored by TVUS only would be between 2% and 8%.

The cycle cancellation rate was similar in both arms of two studies (0/34 versus 1/31, 1/25 versus 1/25; OR 0.57; 95% CI 0.07 to 4.39; N = 115; I² = 0%; low quality evidence). 

The evidence was low quality for all comparisons. Limitations included imprecision and potential bias due to unclear randomisation methods, allocation concealment and blinding, as well as differences in treatment protocols. Quality assessment was hampered by the lack of methodological descriptions in several studies.

Share/Save