Therapeutic role of granulocyte-colony stimulating factor and aspirin in unexplained recurrent pregnancy loss: a retrospective study.

Abstract

Background: Recurrent pregnancy loss (RPL), the loss of two or more clinically confirmed pregnancies, is observed in approximately 1%-5% of couples trying to conceive. Immune dysfunction is increasingly recognized as a contributing factor. This study evaluated pregnancy outcomes among women with unexplained RPL treated with combined recombinant human granulocyte-colony stimulating factor (rhG-CSF) and low-dose aspirin, while acknowledging that the evidence base for rhG-CSF in unexplained RPL remains uncertain.

Methods: In this retrospective study, 300 women aged 18-45 years with at least two consecutive unexplained pregnancy losses were treated with subcutaneous rhG-CSF and low-dose aspirin. Eligible women had documented ovulation, no major uterine abnormality, and no male-factor infertility. Source records were reviewed for mode of conception; all 300 index pregnancies were documented as spontaneous conceptions, and no pregnancies achieved by assisted reproductive technology (ART) were included. rhG-CSF was initiated on the sixth day after ovulation and continued until menstruation or completion of 9 gestational weeks; aspirin 75 mg/day was initiated at the same post-ovulatory time point and continued until 36 gestational weeks unless pregnancy loss or a safety indication required discontinuation. Clinical pregnancy, live birth, miscarriage, stillbirth, neonatal outcomes, and adverse events were assessed. Maternal age was treated as a clinically relevant covariate. Analyses were conducted using IBM SPSS version 27.

Results: Live birth at or after 20 weeks of gestation occurred in 211/300 women (70.3%) according to the institutional obstetric registry definition used in the source records. All index pregnancies were verified as spontaneous conceptions, with no ART pregnancies included. Clinical pregnancy, defined as an intrauterine gestational sac with fetal cardiac activity at 6-7 gestational weeks, was observed in 99.3% of participants. In the age-adjusted model, a higher pretreatment systolic/diastolic ratio remained associated with lower odds of live birth (adjusted OR = 0.34, 95% CI 0.22-0.52, p < 0.001), while increasing maternal age was also associated with lower live-birth odds (adjusted OR per year = 0.94, 95% CI 0.89-0.99, p = 0.031). The miscarriage rate was 29.7%, median neonatal birth weight was 3,012 g, and congenital anomalies were documented in 12.6% of recorded neonatal outcomes.

Conclusion: In this retrospective cohort, combined rhG-CSF and aspirin therapy was associated with improved uterine Doppler indices and a 70.3% live-birth rate among women with unexplained RPL. Because the study lacked an untreated control group and rhG-CSF use for unexplained RPL remains off-label with conflicting trial evidence, these findings should be interpreted cautiously and confirmed in adequately powered controlled studies.