Granulocyte-colony stimulating factor administration for subfertile women undergoing assisted reproduction

Christian Medical College, Department of Reproductive Medicine, Ida Scudder Road, Vellore, Tamil Nadu, India, 632004. Christian Medical College, Cochrane South Asia, Prof. BV Moses Centre for Evidence-Informed Healthcare and Health Policy, Carman Block II Floor, CMC Campus, Bagayam, Vellore, India, 632002. King's College London, Division of Women's Health, Faculty of Life Sciences & Medicine, Strand, London, UK, WC2R 2LS.

The Cochrane database of systematic reviews. 2020;1:Cd013226
PICO Summary

Population

Subfertile women undergoing IVF treatment, (15 studies, n=1253).

Intervention

Granulocyte-colony stimulating factor (G-CSF) administration, (n=622).

Comparison

Placebo or no additional treatment during IVF (n=631).

Outcome

There was inadequate reporting of study methods and high risk of performance bias due to lack of blinding. None of the trials reported the primary effectiveness outcome of live-birth rate. Uncertain whether G-CSF administration improves ongoing pregnancy rate compared to control (RR 1.42. Uncertain whether G-CSF administration reduces miscarriage rate (Peto odds ratio 0.55); compared to the control group. Uncertain whether G-CSF administration improves overall clinical pregnancy rate compared to control (RR 1.63). Uncertain whether G-CSF administration improves clinical pregnancy rate compared to the control group (RR 1.11). G-CSF administration may improve clinical pregnancy rate in women with two or more previous IVF failures compared to the control group (RR 2.11). In subfertile women with thin endometrium, uncertain whether G-CSF administration improves clinical pregnancy rate compared to the control group (RR 1.58). No study reported on multiple pregnancy rate. Only four trials reported adverse events as an outcome, and none of them reported any major adverse events following either G-CSF administration or placebo/no treatment.
Abstract
BACKGROUND Granulocyte-colony stimulating factor (G-CSF) seems to play an important role in the process of embryo implantation and continuation of pregnancy. It has been used during in vitro fertilisation (IVF) treatment for subfertile women with chronically thin endometrium and those with previous multiple IVF failures. It is currently unknown whether G-CSF is effective in improving results following assisted reproductive technology (ART). OBJECTIVES To evaluate the effectiveness and safety of G-CSF in women undergoing ART. SEARCH METHODS We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform in February 2019. We searched reference lists of relevant articles and handsearched relevant conference proceedings. SELECTION CRITERIA Randomised controlled trials (RCTs) comparing G-CSF administration versus no treatment or placebo in subfertile women undergoing IVF treatment. DATA COLLECTION AND ANALYSIS Two review authors independently screened studies, extracted data, and assessed risk of bias. The primary outcomes were live-birth rate and miscarriage rate following G-CSF administration. We have reported ongoing pregnancy rate in cases where studies did not report live birth but reported ongoing pregnancy. Secondary outcomes were clinical pregnancy rate, multiple pregnancy rate, adverse events, ectopic pregnancy rate, small for gestational age at birth, abnormally adherent placenta, and congenital anomaly rate. We analysed data using risk ratio (RR), Peto odds ratio and a fixed-effect model. We assessed the quality of the evidence using the GRADE criteria. MAIN RESULTS We included 15 trials involving 622 women who received G-CSF and 631 women who received placebo or no additional treatment during IVF. The main limitations in the quality of the evidence were inadequate reporting of study methods and high risk of performance bias due to lack of blinding. We assessed only two of the 15 included trials as at a low risk of bias. None of the trials reported the primary effectiveness outcome of live-birth rate. We are uncertain whether G-CSF administration improves ongoing pregnancy rate compared to control in subfertile women undergoing ART (RR 1.42, 95% confidence interval (CI) 0.83 to 2.42; 2 RCTs; participants = 263; I(2) = 0%; very low-quality evidence). For a typical clinic with 14% ongoing pregnancy rate, G-CSF administration would be expected to result in ongoing pregnancy rates between 12% and 35%. We are uncertain whether G-CSF administration reduces miscarriage rate (Peto odds ratio 0.55, 95% CI 0.17 to 1.83; 3 RCTs; participants = 391; I(2) = 0%; very low-quality evidence) compared to the control group in subfertile women undergoing ART. We are uncertain whether G-CSF administration improves overall clinical pregnancy rate compared to control in subfertile women undergoing ART (RR 1.63, 95% CI 1.32 to 2.01; 14 RCTs; participants = 1253; I(2) = 13%; very low-quality evidence). For a typical clinic with 17% clinical pregnancy rate, G-CSF administration would be expected to result in clinical pregnancy rates between 23% and 35%. In the unselected IVF population, we are uncertain whether G-CSF administration improves clinical pregnancy rate compared to the control group (RR 1.11, 95% CI 0.77 to 1.60; 3 RCTs; participants = 404; I(2) = 0%; low-quality evidence). G-CSF administration may improve clinical pregnancy rate in women with two or more previous IVF failures compared to the control group (RR 2.11, 95% CI 1.56 to 2.85; 7 RCTs; participants = 643; I(2) = 0%; low-quality evidence). In subfertile women with thin endometrium undergoing ART, we are uncertain whether G-CSF administration improves clinical pregnancy rate compared to the control group (RR 1.58, 95% CI 0.95 to 2.63; 4 RCTs; participants = 206; I(2) = 30%; low-quality evidence). No study reported on multiple pregnancy rate. Only four trials reported adverse events as an outcome, and none of them reported any major adverse events following either G-CSF administration or placebo/no treatment. AUTHORS' CONCLUSIONS In subfertile women undergoing ART, we are uncertain whether the administration of G-CSF improves ongoing pregnancy or overall clinical pregnancy rates or reduces miscarriage rate compared to no treatment or placebo, whether in all women or those with thin endometrium, based on very low-quality evidence. Low-quality evidence suggests that G-CSF administration may improve clinical pregnancy rate in women with two or more IVF failures, but the included studies had unclear allocation concealment or were at high risk of performance bias.
Study details
Study Design : Systematic Review
Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine