Does LH supplementation in poor responders affect granulosa cells apoptosis rate in ART? A prospective randomised controlled trial

The aim was to compare granulosa cell's (GCs) apoptosis rate with (group A) or without (group B) luteinising hormone (LH) supplementation in poor ovarian responders (PORs) during controlled ovarian stimulation (COS). After oocyte retrieval, the follicular fluid was analysed by cytoflowmetry. Primary outcomes were GCs apoptosis rate in terms of viability, early apoptosis, late apoptosis and necrosis. Secondary outcome was clinical pregnancy rate. The viability was 96.7{IQR: 8} and 83.5{IQR: 20} for groups A and B, respectively (p < .001). Late apoptosis rates were significantly lower in group A (median 1.5, {IQR: 3.1}) than group B (median 9.5, {IQR: 20.6}) (p < .001). Median early apoptosis rates were 1.4 {IQR: 2.9} and 5.2 {IQR: 6.5} for group A and B respectively (p = .04). No significant difference was observed in the clinical pregnancy rate. Although LH seems necessary in PORs to decrease late granulosa apoptosis rates, this does not improve clinical pregnancy rates.IMPACT STATEMENT What is already known on this subject? LH supplementation during COS has long been an issue in PORs to overcome the rFSH responsiveness due to the LH polymorphism. LH receptors have also been on GCs and their expression increases in preovulatory follicles. GCs apoptosis rates may show the oocyte quality and reproductive potential of oocyte retrieved and the requirement for LH supplementation. What do the results of this study add? The present study shows that LH supplementation during COS for PORs promotes the GC viability and reduces early/late apoptosis rates. Similarly, the number of MII oocytes was significantly higher in the LH regimen group. However, there was no significant difference in terms of clinical pregnancy rates. What are the implications of these findings for clinical practice and/or further research? The oocyte quality parameters such as higher GC viability and lower GC early/late apoptosis rates verify the LH supplementation in PORs during COS. However, the limited size of this study requires further multi-centre research in a larger cohort of patients. Results obtained with a sensitive and validated method will help clinicians to make better decisions in patient care.

Automated summary

The study demonstrates that LH supplementation during COS for PORs improves GC viability and reduces early/late apoptosis rates, leading to a higher number of MII oocytes. However, this does not result in a significant difference in clinical pregnancy rates. Further multi-centre research is needed to validate these findings.