In spite of significant advances in the field of reproductive medicine, repeated implantation failure (RIF) is a challenging and extremely disappointing problem. The success of in vitro fertilization and embryo transfer (IVF-ET) cycles depends mainly on uterine receptivity and embryo quality. Successful evaluation of endometrial receptivity conducive to embryo implantation continues to be a challenge in assisted reproductive technology (ART). Several researcher groups have reported the successful use of granulocyte-colony stimulating factor (G-CSF) during IVF cycles in terms of achieving higher clinical pregnancy rates on account of increased endometrial thickness. Women who fail to achieve adequate endometrial thickness despite conventional treatment with high dose estrogen or those with a history of repeated implantation failures in spite of normal endometrial thickness often do not achieve pregnancy and resort to gestational surrogacy. A new therapeutic approach to achieve successful pregnancy in such patients would be very desirable.
To assess the efficacy of a single dose of intrauterine G-CSF on endometrial thickness, implantation and clinical pregnancy rates in women who either had a thin endometrium after estrogen priming (< 8 mm) or a history of repeated implantation failures at IVF, undergoing embryo transfer after 10 days of priming with oral estradiol and vaginal slidenafil.
Materials and methods
Two hundred and thirty-one women (between 24 and 46 years of age) undergoing IVF-ET were recruited for the study. All cases were prospectively studied at the Mumbai Fertility Clinic and IVF Center (a subdivision of Kamala Polyclinic and Nursing Home) over a period of 6 months from January to June 2014, after their written informed consent. Subgroup I consisted of 117 patients who had a persistently thin endometrium (< 8 mm) in spite of high dose oral estradiol valerate and vaginal sildenafil priming. Subgroup II consisted of 114 patients who had a history of repeated (two or more) implantation failures (RIF) at IVF-ET cycles despite adequate endometrium (≥8 mm). All were infused with a single dose of G-CSF (300 mcg) in the uterine cavity after 10 days of priming with oral estradiol valerate and vaginal sildenafil citrate. Endometrial thickness was reassessed 4 days after G-CSF instillation. This was followed by administration of intramuscular progesterone in oil (100 mg) daily with embryo transfer on day 5 of progesterone for all patients. All embryo transfers for patients undergoing oocyte donation or embryo donation were done at the 4-cell stage on day 2. All Frozen embryo transfers (FET) of vitrified embryos were at 8 cell stage. Estimation of serum beta hCG was at 14 days post-embryo transfer for all patients. Successful implantation and net clinical pregnancy rate was confirmed based on appearance of gestational sac on sonogram after 10 days and observation of fetal cardiac activity after 20 days of positive β-hCG results.
Out of total 231 patients recruited in the study, 95% patients from subgroup I (n = 111) and 94% patients from subgroup II (n = 107) showed mean increase in endometrial thickness by at least 2.5 mm within 4 days of G-CSF single dose instillation. A total of 218 patients from both subgroups underwent S. β-hCG estimation 14 days post IVF-ET. Out of 103 β-hCG positive patients, 83 showed net clinical pregnancy (fetal cardiac activity present) giving a net pregnancy rate of 38.07% for the whole study group with 37% in the subgroup with thin endometrium (< 8 mm) and 39.25% in the subgroup with adequate (≥8 mm) endometrium with history of two or more failed implantation at previous IVF-ET cycles. There were no adverse events for the whole study population.
There can be a strong possibility with a single dose of 300 mcg intrauterine infusion of G-CSF to achieve significant increase in the endometrial thickness with higher successful pregnancy rate among infertile women under- going IVF-ET cycles with a history of a persistently thin endometrium or repeated implantation failures (rather difficult to treat patients). G-CSF could be a valuable tool to consider before advising the option of surrogacy. In the absence of a control group, our conclusions warrant conduct of further studies.
How to cite this article
Shah J, Gangadharan A, Shah V. Effect of Intrauterine Instillation of Granulocyte Colony-stimulating Factor on Endometrial Thickness and Clinical Pregnancy Rate in Women undergoing in vitro Fertilization Cycles: An Observational Cohort Study. Int J Infertil Fetal Med 2014;5(3):100-106.