Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI)

  • Review
  • Intervention

Authors


Abstract

Background

Traditional monitoring of ovarian hyperstimulation during in vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) treatment has included transvaginal ultrasonography (TVUS) plus serum estradiol levels to ensure safe practice by reducing the incidence and severity of ovarian hyperstimulation syndrome (OHSS) whilst achieving the good ovarian response needed for assisted reproduction treatment. 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 methods

We searched the Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, the National Research Register, and web-based trial registers such as Current Controlled Trials. The last search was conducted in May 2014. 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the identified trials and background papers were checked and authors were contacted to identify relevant published and unpublished data.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

Three review authors independently selected the studies, extracted data and assessed risk of bias. They resolved disagreements by discussion with the rest of the authors. Outcomes data were pooled and summary statistics were presented when appropriate. The quality of the evidence was rated using the GRADE methods.

Main results

With this update, four new studies were identified resulting in a total of six trials including 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. Pooled data showed no evidence of a difference in clinical pregnancy rate per woman between monitoring with TVUS only and combined monitoring (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 that compared with women with a 34% chance of clinical pregnancy using monitoring with TVUS plus serum estradiol, the clinical pregnancy rate in women using TVUS only was between 29% and 44%.

There was no evidence of a difference between the groups in the reported cases of OHSS (OR 1.03; 95% CI 0.48 to 2.20; six studies; N = 781; I² = 0%; low quality evidence), suggesting that compared with women with a 4% chance of OHSS using monitoring with TVUS plus serum estradiol, the OHSS rate in women monitored by TVUSS only was between 2% and 8%.

There was no evidence of a difference between the groups in the mean number of oocytes retrieved pre woman (mean difference (MD) 0.32; 95% CI -0.60 to 1.24; five studies; N = 596; I² = 17%; 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.

Authors' conclusions

This review update found no evidence from randomised trials to 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. A combined monitoring protocol including both TVUS and serum estradiol may need to be retained as precautionary good clinical practice and as a confirmatory test in a subset of women to identify those at high risk of OHSS. An economic evaluation of the costs involved with the two methods and the views of the women undergoing cycle monitoring would be welcome.

Plain language summary

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 ovarian hyperstimulation. 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 May 2014.

Key results: none of the six studies reported our primary outcome of live birth rate. Pooled data showed no evidence of a difference in clinical pregnancy rate between monitoring with TVUS only and monitoring with TVUS plus estradiol measurement (odds ratio (OR) 1.10; 95% CI 0.79 to 1.54; four studies; N = 617; I² = 5%; low quality evidence). Our findings suggest that compared with women with a 34% chance of clinical pregnancy using monitoring with TVUS plus serum estradiol, the clinical pregnancy rate in women using TVUS only was between 29% and 44%. There was no evidence of a difference in OHSS between the two arms (OR 1.03; 95% CI 0.48 to 2.20; six studies; N = 781; I² = 0%; low quality evidence), suggesting that compared with women with a 4% chance of OHSS using monitoring with TVUS plus serum estradiol, the OHSS rate in women monitored by TVUS only was between 2% and 8%.

Quality of the evidence: the evidence was of low quality. Limitations included imprecision and potential bias due to unclear 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.