Empty Follicle Syndrome in Poly Cystic Ovarian Syndrome Patients After GnRH Agonist Trigger at a Tertiary Level Infertility Centre: A Prospective Cohort Study

Objectives To analyse the incidence and underlying physiology of Empty Follicular Syndrome (EFS) following gonadotropin-releasing hormone (GnRH) agonist trigger in Polycystic Ovarian Syndrome (PCOS) patients at a tertiary-level infertility centre in India. Material and Methods A prospective cohort study was conducted amongst 225 PCOS patients diagnosed as per Rotterdam’s criteria during the period between January 1, 2017, and December 31, 2019, at a tertiary care infertility centre in New Delhi, India. Controlled ovarian hyperstimulation (COH) using a fixed GnRH antagonist protocol was followed for all patients, concluding with a GnRH agonist trigger. In cases where no oocytes were obtained during ovum pick-up from the first ovary, serum progesterone (P4) levels were assessed to differentiate between genuine EFS (S. P4 >3.5 ng/ml) and false EFS (S. P4 <3.5 ng/ml). Rescue human chorionic gonadotropin (hCG) trigger was given in cases of false EFS and oocyte retrieval was planned 35 hours after the trigger. Segmentation of the cycle was done, and frozen embryo transfer was scheduled for a subsequent cycle. Results EFS following GnRH agonist trigger was seen in 3.11% (7/225) of PCOS patients undergoing in vitro fertilisation (IVF) at our centre. The age, body mass index, parity, and the type and duration of infertility were comparable between the EFS group and the non-EFS group. No significant differences were observed in serum follicle-stimulating hormone, anti-mullerian hormone, or antral follicle count between the two groups. However, patients in the EFS group needed significantly higher doses of gonadotropins (2500 ± 743 IU vs. 1850 ± 690 IU; p = 0.02) and experienced a longer stimulation period (11.6 ± 1.79 days vs. 9.5 ± 1.2 days; p = 0.001) compared to those in the Non-EFS group. Among the seven EFS cases, five cases (71.43%) were determined to be false EFS, while two cases (28.57%) were classified as genuine EFS with no identifiable aetiology. Of the five false EFS cases, four patients had successful egg retrieval following a rescue hCG trigger, and two of these patients (40%) achieved clinical pregnancy. In cases of genuine EFS, the subsequent cycle was managed using a GnRH antagonist protocol with a dual trigger. Egg retrieval was successful in one patient, while the other experienced a recurrence of genuine EFS. Conclusion Based on our experience at a specialised infertility care centre in India, EFS appears to be an uncommon event in PCOS patients undergoing IVF after a GnRH agonist trigger. False EFS may yield positive outcomes with the use of a rescue trigger, while genuine EFS is mostly associated with intrinsic ovarian dysfunction.