3280?nmol/l, value /th /thead Age (years)36.3??3.935.8??3.7NSAMH (pmol/l)14.26??7.716.4??6.7NSFSH7.3??1.66.6??1.9NSEtiology for infertilityUnexplained-8 br / Male factor-3 br / Mechanical-0 br / Fertility preservation-2Unexplained-7 br / Male factor-3 br / Mechanical-1 br / Fertility preservation- 2NSLength of stimulation (days)9.4??1.810.7??1.7NSDosage of gonadotropins3085??6333294??917NSOocytes (n)11.7??5.712.1??6.1NS2PN(n)6.6??5.17.6??4.4NSBlastocysts (n)3.1??2.22.9??1.9NSBlastocyst rate (blast/2PN)46.9%38.1%NSE2 levels (pmol/l)1032??3758069??30680.001Ongoing Pregnancy rate5/11 (45.4%)4/11(36.3%)NS CCB02 Open in a separate window Table 2 The hormone levels in the follicular fluid from patients co-treated with letrozole and gonadotropins vs. during the ovarian stimulation and the patients in the CCB02 other group were treated with gonadotropins only. VEGF, PEDF, estrogen, progesterone and testosterone levels were measured by ELISA CCB02 kits. Results The age of the patients, the total dose of gonadotropins and the number of oocytes were comparable between the two groups. In the follicular fluid, the estrogen levels (2209?nmol/l vs. 3280?nmol/l, value /th /thead Age (years)36.3??3.935.8??3.7NSAMH (pmol/l)14.26??7.716.4??6.7NSFSH7.3??1.66.6??1.9NSEtiology for infertilityUnexplained-8 br / Male factor-3 br / Mechanical-0 br / Fertility preservation-2Unexplained-7 br / Male factor-3 br / Mechanical-1 br / Fertility preservation- 2NSLength of stimulation (days)9.4??1.810.7??1.7NSDosage of gonadotropins3085??6333294??917NSOocytes (n)11.7??5.712.1??6.1NS2PN(n)6.6??5.17.6??4.4NSBlastocysts (n)3.1??2.22.9??1.9NSBlastocyst rate (blast/2PN)46.9%38.1%NSE2 levels (pmol/l)1032??3758069??30680.001Ongoing Pregnancy rate5/11 (45.4%)4/11(36.3%)NS Open in a separate window Table 2 The hormone levels in the follicular fluid from patients co-treated with letrozole and gonadotropins vs. gonadotropins only thead th rowspan=”1″ colspan=”1″ /th th rowspan=”1″ colspan=”1″ Letrozole group (13) /th th rowspan=”1″ colspan=”1″ Control group (13) /th CCB02 th rowspan=”1″ colspan=”1″ P /th /thead Estrogen(nmol/l)2009??10343280??13710.01Testosterone(nmol/l)246.5??153.240.7??14.3 ?0.001Progesterone(mol/l)21.4??8.317.5??10.30.3 Open in a separate window The mean VEGF level (2992?pg/ml vs. 1812?pg/ml em p /em ?=?0.02) was significantly increased and the mean PEDF level (9.7?ng/ml vs 17.3?ng/ml p? ?0.001) was significantly decreased in the letrozole group (Table ?(Table33). Table 3 The VEGF and PEDF levels in the follicular fluid from patients co-treated with letrozole and gonadotropins vs. gonadotropins only thead th rowspan=”1″ colspan=”1″ /th th rowspan=”1″ colspan=”1″ Letrozole group (13) /th th rowspan=”1″ colspan=”1″ Control group (13) /th th rowspan=”1″ colspan=”1″ p /th /thead VEGF (pg/ml)2992??431.71812??462.40.02PEDF (ng/ml)9.7??5.717.3??8.4 ?0.001 Open in a separate window None of the patients in the study group or in the control group developed early or late OHSS. Discussion In contrast to observations in mice, we found that VEGF levels were increased and PEDF levels were decreased in the follicular fluids of patients treated with letrozole during the stimulation cycles, despite a significant suppression of estradiol concentration in follicular fluid. In the murine model, letrozole was administered only at the trigger day and not during the ovarian stimulation whereas in our current study, the patients were treated during the entire ovarian stimulation, which might explain the differences between the VEGF and PEDF levels observed. Similarly to the murine findings, CCB02 He et al. demonstrated a decrease in the VEGF serum levels after treatment with letrozole in the luteal phase. He found a dose dependent decrease in the levels of VEGF with increasing doses of letrozole administered in the luteal phase [11]. The findings of He et al. suggested that letrozole could decrease the risk of OHSS although it is not clear if the effect on VEGF and PEDF secretion was a direct action of letrozole or an indirect effect through a reduction in estradiol levels. A randomized controlled study in hyper-responder patients which aimed to compare the efficacy of letrozole to aspirin during the luteal phase in primary prevention of early ovarian FBXW7 hyperstimulation syndrome showed a lower incidence of OHSS in women receiving letrozole compared with aspirin [3]. In contrast to previous studies, the patients treated with letrozole had higher levels of VEGF in the serum compared to the patients not treated with letrozole. The authors hypothesized that the mechanism of lower incidence of OHSS was independent of VEGF but rather due to the induction of a luteolytic effect and lower estradiol concentrations which reduced the risk of early-onset OHSS (5). Although we didnt measure the VEGF or PEDF levels in the serum, we found increased VEGF and PEDF levels in the follicular fluid of letrozole treated patients at the time of oocyte retrieval. In the follicular phase, letrozole reduces serum estrogen levels which results in reduced negative feedback on gonadotrophin secretion from the hypothalamus-pituitary axis [12C14]. By.