The sufferers in a single group were co-treated with letrozole and gonadotropins through the ovarian stimulation as well as the sufferers in the various other group were treated with gonadotropins just. amounts in the follicular liquids of regular responders treated with letrozole and gonadotropins through the ovarian excitement with sufferers treated with gonadotropins just. Methods An individual center, prospective scientific trial. We gathered follicular liquid from 26 sufferers, on the GnRH antagonist process, dual triggered with GnRH and hCG agonist. The sufferers in a single group had been co-treated with letrozole and gonadotropins through the ovarian excitement and the sufferers in the various other group had been treated with gonadotropins just. VEGF, PEDF, estrogen, progesterone and testosterone amounts were measured by ELISA 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 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 NBQX murine findings, 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 hyperstimulation syndrome showed a lower NBQX 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.RB, JM, AJ, NG and RC helped with the study design, data analysis, interpretation and manuscript editing. with gonadotropins only. Methods A single center, prospective clinical trial. We collected follicular fluid from 26 patients, on a GnRH antagonist protocol, dual triggered with hCG and GnRH agonist. The patients in one group were co-treated with letrozole and gonadotropins during the ovarian stimulation and the patients in the other group were treated with gonadotropins only. VEGF, PEDF, estrogen, progesterone and testosterone levels were measured by ELISA kits. Results The age of the NBQX 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 th rowspan=”1″ colspan=”1″ P NBQX /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, 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 hyperstimulation syndrome showed a lower incidence of OHSS in women receiving Rabbit Polyclonal to DRD4 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 lowering serum estrogen concentrations in the early follicular phase, letrozole causes secretion of more FSH and LH, which acts directly on the granulosa cells and may be responsible for the increased secretion of VEGF. In addition, we found higher.