O-026 RCT of INTRA - Uterine administration of granulocyte colony-stimulating factor (G-CSF) before embryo-transfer in resistant thin endometrium in IVF-ICSI cycles
Authors: Jindal P C , Singh R , Singh M 
Published: June 2022

Abstract

Study question
Does intrauterine administration of G-CSF (granulocyte-colony-stimulating factor) prior to Embryo-Transfer in patients with resistant thin endometrium improve endometrial thickness and pregnancy rate in IVF-ICSI cycles?

Summary answer
Yes, Intrauterine administration of G-CSF(granulocyte colony-stimulating factor) before embryo transfer in resistant thin endometrium increases endometrial thickness and improves the pregnancy-rate in IVF-ICSI cycles.

What is known already
Optimal endometrial thickness reflects adequate maturation, which is a key factor for implantation.
Proliferative and secretory changes at the endometrial lining are the result of a complex intrauterine environment where sex steroid hormones and local factors play important role.
Lucena et al. found that the uterine-infusion of G-CSF increased endometrial thickness resulting in a successful pregnancy .
Li et al. evaluated the effectiveness of G-CSF in a thin endometrium in frozen ET-cycles.
The implantation and pregnancy rates were significantly higher (Scarpellini & Sbracia 2012,et al.2015), whereas did not affect endometrial thickness, implantation, or pregnancy rates (Barad et al. 2014, Li et al. 2014).

Study design, size, duration
86 Infertile patients with thin endometrium below 45 years age (2018 to 2021) were included in this study, in whom traditional treatment with estradiol, sildenafil etc had been unsuccessful.
Patients were randomly divided into two groups using computer generated list after proper consent .The study group received intrauterine- G-CSF and control group received placebo (saline) before Embryo Transfer in IVF-ICSI cycles.

Primary Outcome
Endometrial-thickness, Implantation & Pregnancy rates.

Secondary-outcome
Abortion-rate

Participants/materials, setting, methods
The study group (n = 43) received intrauterine infusion of 300 microgramme/1ml of G-CSF, and the control group (n = 43) underwent placebo-saline infusion before Embryo-Transfer.
G-CSF was administered by an intrauterine catheter by slow instillation on the day of hCG administration.
If the endometrium had not reached at least a 7-mm within 48 h, a second dose was administered following oocyte retrieval.

Main results and the role of chance
The endometrial growth was significantly different in the two groups, with an improvement in the G-CSF group.
Endometrial expansion to Optimal thickness occurred within approximately 48 -72 hour after G-CSF instillation.
In all subjects, at the time of administration of G-CSF, endometrial thickness was 6.43 ± 1.49 mm, and,after G-CSF administration, it increased significantly to 8.11 ± 1.42 mm.
The IR and PR were statistically significantly higher in the group receiving intrauterine G-CSF (22% and 33%, respectively) as compared to the control group (08% and 14%, respectively).
Abortion Rates were comparable in both the groups and difference was not significant.
Endometrial instillation of G-CSF may be effective in expanding chronically unresponsive thin endometrium, resistant to conventional remedies.
This treatment needs more multicentric trials to assess its potential in improving the implantation chances in IVF-ICSI cycles, thereby improving pregnancy rates.
Uterine perfusion or SC injection with G-CSF represents a promising new tool for intractable problem of thin endometrium . Proliferative and secretory changes in the endometrial lining are the result of a complex intrauterine environment where sex steroid hormones and different local factors play an important role for endometrial thickening.

Limitations, reasons for caution
Our study is not without limitations.
We did not have a large number of patients.
The main strengths of study were its RCT design to evaluate the efficacy of intrauterine G-CSF administration on IVF success. Further more RCT are required to establish the best route and dose of GCSF administration in thin-endometrium.

Wider implications of the findings
Several methods have been proposed, to increase endometrial-thickness in women undergoing IVF-ICSI . These therapies included -tocopherol, pentoxifylline, low-dose aspirin, sildenafil citrate, estradiol administration and hCG priming.Our study using Intra-Uterine instillation of G-CSF represents a promising and cost-effective therapy for the currently most intractable problem of resistant, thin endometrium.

Trial registration number
not applicable