Glucocorticoid supplementation for IVF/ICSI

Review question

Does glucocorticoid supplementation improve outcomes in women undergoing controlled ovarian stimulation during in-vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) cycles?

We reviewed the evidence on women having a glucocorticoid component added to the usual ovarian stimulation protocols versus those that received only the standard traditional ovarian stimulation protocols.

Background

Ovarian response to stimulation during IVF and ICSI cycles plays an important role in determining live birth rates. Most ovarian stimulation regimens administer a combination of hormones to stimulate the ovaries, suppress the pituitary gland and prevent surges of natural hormones that may be detrimental to egg maturation. Various add-on (adjuvant) treatments during ovarian stimulation have been used in an attempt to improve this process, and it has been suggested that the addition of a glucocorticoid component may improve results.

Study characteristics

We found four randomised controlled trials (RCTs), but useable data were available for only two of these. The trials compared adjuvant treatment with systemic glucocorticoids during ovarian stimulation for IVF cycles versus no placebo. The evidence is current to October 2016.

Key results

Two RCTs were included in our analyses (310 women). For the outcome of live birth, data were available for only 212 women, as the larger study had data available from only one study centre.

There was no conclusive evidence of a difference in the primary outcome of live birth rate and the secondary outcome of clinical pregnancy rate. Our findings suggest that if the chance of live birth with placebo is assumed to be 15%, the chance following supplementation would be between 7% and 31%, and that if the chance of clinical pregnancy with placebo is assumed to be 24%, the chance following treatment with supplementation would be between 23% and 47%. There was also insufficient evidence to determine whether there was any difference between the groups in the multiple-pregnancy rate or miscarriage rate. Neither of the studies reported ovarian hyperstimulation syndrome (OHSS) or side-effects.

Thus, the safety and effectiveness of glucocorticoid administration in women undergoing controlled ovarian hyperstimulation for IVF/ICSI cycles (until the day of oocyte retrieval) is unclear due to the small number of studies and low event rates. Whilst glucocorticoids possibly increase the clinical pregnancy rate, there may be little or no impact on the live birth rate.

Quality of the evidence

The evidence was rated as low or very low quality for all outcomes, mainly due to imprecision, with low sample sizes and few events.

Authors' conclusions: 

The safety and effectiveness of glucocorticoid administration in women undergoing controlled ovarian hyperstimulation for IVF/ICSI cycles (until the day of oocyte retrieval) is unclear due to the small number of studies and low event rates. Whilst glucocorticoids possibly increase the clinical pregnancy rate, there may be little or no impact on live birth rate. More research is needed.

Read the full abstract...
Background: 

Ovarian response to stimulation during in-vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) plays an important role in determining live birth rates. Adjuvant treatments during ovarian stimulation that have different modes of action have been used to improve ovarian response to stimulation and outcome of IVF. Glucocorticoids (GCs) are a class of steroid hormones that have been used either alone or in combination with other stimulatory regimens in order to improve folliculogenesis and pregnancy rates. However, considerable uncertainty remains over whether administration of glucocorticoid during ovarian stimulation until oocyte recovery is superior to no glucocorticoid in improving live birth rates in women undergoing IVF/ICSI.

Objectives: 

To determine the safety and effectiveness of systemic glucocorticoids during ovarian stimulation for IVF and ICSI cycles.

Search strategy: 

We searched the Cochrane Gynaecology and Fertility Group Specialised Register, the Cochrane Central Register of Studies Online (CRSO), MEDLINE, Embase, CINAHL and PsycINFO from inception to 10 October 2016. We handsearched reference lists of articles, trial registers and relevant conference proceedings and contacted researchers in the field.

Selection criteria: 

We included randomised controlled trials (RCTs) comparing adjuvant treatment with systemic glucocorticoids during ovarian stimulation for IVF or ICSI cycles versus no adjuvant treatment.

Data collection and analysis: 

Two review authors independently selected studies, assessed risk of bias and extracted the data. Our primary outcome was live birth. Secondary outcomes included clinical pregnancy, multiple pregnancy, miscarriage, ovarian hyperstimulation syndrome (OHSS) and side-effects. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) and pooled the data using a fixed-effect model. The quality of the evidence was assessed using GRADE methods.

Main results: 

Four RCTs were included in the review (416 women). The trials compared glucocorticoid supplementation during IVF stimulation versus placebo. Two of the studies had data in a form that we could not enter into analysis, so results include data from only two trials (310) women. For the outcome of live birth, data were available for only 212 women, as the larger study had data available from only one study centre.

One of the studies gave inadequate description of randomisation methods, but the other was at low risk of bias in all domains. The evidence was rated as low or very low quality for all outcomes, mainly due to imprecision, with low sample sizes and few events.

There was insufficient evidence to determine whether there was any difference between the groups in live birth rate (OR 1.08, 95% CI 0.45 to 2.58; 2 RCTs, n = 212, I2 = 0%, low-quality evidence). Our findings suggest that if the chance of live birth with placebo is assumed to be 15%, the chance following supplementation would be between 7% and 31%. There was no conclusive evidence of a difference in the clinical pregnancy rate (OR 1.69, 95% CI 0.98 to 2.90; 2 RCTs, n = 310, I2 = 0%, low-quality evidence).The evidence suggests that if the chance of clinical pregnancy with placebo is assumed to be 24%, the chance following treatment with glucocorticoid supplementation would be between 23% and 47%. There was also insufficient evidence to determine whether there was any difference between the groups in multiple-pregnancy rate (OR 3.32 , 95% CI 0.12 to 91.60; 1 RCT , n = 20, very low-quality evidence) or miscarriage rate (OR 1.00, 95% CI 0.05 to 18.57; 1 RCT, n = 20, very low-quality evidence). Neither of the studies reported OHSS or side-effects.

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