THE IMPACT OF LUTEINIZED UNRUPTURED FOLLICLE (LUF) ON OUTCOME OF CONTROLLED OVARIAN STIMULATION: IS THERE A RELATION TO STIMULATION PROTOCOL ?

Introduction : LUF is a form of anovulation and a subtle cause of female infertility. The syndrome cannot be diagnosed by traditional progesterone-dependent ovulation detection methods. Without the use of either transvaginal ultrasound (TVS) or laparoscopy as well as progesterone assay, LUF syndrome may go unnoticed.
Objective : To assess the prevalence of LUF and the effect of stimulation protocol on its development as diagnosed by serial TVS and midluteal progesterone (MLP).
Patients and Methods : A total of 300 cycles in 228 patients were monitored for various causes of infertility under different stimulation protocols: clomiphene citrare (CC)/HCG, or CC plus HMG/HCG, or HMG/HCG. Serial TVS was started from days -5 to days +5 (The day of HCG trigger of ovulation was cycle day zero). MLP was measured on day +7. TVS evidence of LUF was persistence of unruptured preovulatory follicle(s) up to day +5 together with bichemical evidence of luteinization (MLP > 1 ng/mL. Luteal phase length was measured to identify short luteal phase defect. Normal ovulatory cycle was diagnosed by TVS evidence of follicular rupture (visible corpus luteum with or without free fluid in DP) and biochemical evidence of good luteal function (MLP > lOng/ml) Luteal phase defect (LPD) was diagnosed by MLP1 ng/ml.
Results : Of the total 300 cycles in 228 patients, 16 cycles in 15 patients were diagnosed as LUF giving a prevalence of 9% of cycles. Mean MLP was significantly lower in LUF cycles compared to normal ovulatory cycles (9.1±5.9 vs 21.9+1212 ng/mL respectively) (P<0.001). CC/HCG protocol was used in 48% of LUF cycles compared to 18.6% of normal cycles (P<0.001), while CC plus HMG/HCG or HMG/HCG were used in (40%, 36.9% in LUF and, normal ovulatory cycles respectively) (P=0.07). The percentage of PCOD cases was not significantly different in both groups (40% & 31% in LUF & normal ovulatroy cycles respectively). Although CC stimulation was used in 154/228 first cycles (35%) and 49/70 repeat cycles (35%), only 2 cases had recurrent LUF in first and repeat cycles of same patients. Although mean luteal phase length was not significanlty different (14.3±2.5 days vs 15.7+2.5) days in LUF and normal cycles respectively), 60% of LUF cases had MLP < 10 ng/ml (compared to none of the normal control. Cycle pregnancy rate was 21% in the normal cycles and zero in LUF cycles.
Conclusions : LUF as a clinical entity is to be suspected in cases treated by controlled ovarian stimulation employing CC and HCG protocol. About two thirds of LUF cases are associated with luteal phase defect. Our Data showed that LUF in stimulated cycles is a transient cycle phenomena related to subtle cycle features rather than constant patient feature and is not a persistent cause of female infertility. It also has an undermining effect on Ihc outcome of treatment cycles in terms of midluteal phase progesterone level and pregnancy rale. Both LUF and lutcal phase defect associated with CC/HCG stimulation partly explain the discrepancy between ovulation rale delected by hormone assay and pregnancy rate. Combined serial ultrasound monitoring and midluteal progesterone assay are essential for diagnosis oi luteinized unruptured follicle.