Effects of letrozole and clomiphene citrate on the expression of HOXA10 and integrin αvβ3 in uterine epithelium of rats

Bao, Shenghua; Sheng, Shi; Peng, Yi; Lin, Qi

doi:10.1016/j.fertnstert.2007.11.024

Cited by 34 publications

(25 citation statements)

References 29 publications

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“…A key regulator of the anb3 integrin is the transcription factor, HOXA10 (Daftary et al, 2002), which is also reduced in mild endometriosis (Szczepanska et al, 2010). Letrozole treatment has been shown to increase anb3 expression, compared with clomiphene citrate in the rat uterus model (Bao et al, 2009). The increase in integrin expression in response to letrozole in natural cycles, reflects the improved implantation and pregnancy rates noted during IVF in patients who took letrozole.…”

Section: Discussionmentioning

confidence: 99%

Endometrial receptivity defects during IVF cycles with and without letrozole

et al. 2012

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background: Our aim was to study ways to improve IVF success rates in women with suspected endometrial receptivity defects. methods: We conducted a retrospective cohort study examining the effect of letrozole (aromatase inhibitor) on integrin expression as a marker of endometrial receptivity. We compared IVF outcomes in 97 infertile women who had undergone anb3 integrin assessment by immunohistochemistry in mid-luteal endometrial biopsies. Of 79 women undergoing standard IVF, 29 (36.7%) lacked normal integrin expression. Eighteen other women with low integrin were studied after receiving letrozole during early IVF stimulation. An independent set of anb3 integrin-negative patients (n ¼ 15) who had undergone repeat endometrial biopsy for integrin testing while taking letrozole were re-evaluated.results: Clinical pregnancy and delivery rates were higher in women with normal anb3 integrin expression compared with those who were integrin negative [20/50 (40%) versus 4/29 (13.8%); P ¼ 0.02 and 19/50 (38%) versus 2/29 (7%); P , 0.01, respectively]. In 18 women who received letrozole early in IVF, 11 conceived (61.1%; P , 0.001) compared with integrin-negative patients who did not receive letrozole. In integrin-negative women who were rebiopsied on letrozole, 66.7% reverted to normal integrin expression. Positive endometrial aromatase immunostaining using a polyclonal antibody was a common finding in infertile patients compared with controls.conclusions: Lack of endometrial anb3 integrin expression is associated with a poor prognosis for IVF that might be improved with letrozole co-treatment. Prospective studies are needed to confirm and extend these findings but the data suggest that aromatase expression may contribute to implantation failure in some women.

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Section: Discussionmentioning

confidence: 99%

Endometrial receptivity defects during IVF cycles with and without letrozole

et al. 2012

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“…We think that letrozole resulted in comparable pregnancy rate as clomiphene citrate, in spite of less number of mature oocytes induced, because it has no adverse effect on endometrium. Boa et al found that the markers of endometrial receptivity (HOXA10 and integrin alpha (v) beta (3)) in rats were suppressed by clomiphene citrate and not affected by letrozole [24]. Moreover, Cortinez reported that letrozole administration in infertile ovulatory women was associated with in-phase histological dating of endometrium and normal pinopode expression [10].…”

Section: Discussionmentioning

confidence: 99%

Extended letrozole regimen versus clomiphene citrate for superovulation in patients with unexplained infertility undergoing intrauterine insemination: A randomized controlled trial

Fouda

Sayed

2011

Reprod Biol Endocrinol

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BackgroundThe aim of this randomized controlled trial was to compare the efficacy of extended letrozole regimen with clomiphene citrate in women with unexplained infertility undergoing superovulation and intrauterine insemination (IUI).MethodsTwo hundred and fourteen patients with unexplained infertility were randomized into two equal groups using computer generated list and were treated by either letrozole 2.5 mg/day from cycle day 1 to 9 (extended letrozole group, 211 cycles) or clomiphene citrate 100 mg/day from cycle day 3 to 7 (clomiphene citrate group,210 cycles). Intrauterine insemination was performed 36 to 40 hours after HCG administration.ResultsBoth groups were comparable with regard to number of mature follicles (2.24 +/- 0.80 Vs 2.13 +/- 0.76) and the day of HCG administration. Serum estradiol was significantly greater in clomiphene citrate group (356 +/- 151 Vs 822 +/- 302 pg/ml, P = < 0.001) and the endometrial thickness was significantly greater in extended letrozole group (9.10 +/- 1.84 Vs 8.18 +/- 1.93 mm, P = < 0.001).The pregnancy rate per cycle and cumulative pregnancy rate were significantly greater in extended letrozole group (18.96% Vs 11.43% and 37.73% Vs 22.86%, respectively).ConclusionThe extended letrozole regimen had a superior efficacy as compared with clomiphene citrate in patients of unexplained infertility undergoing superovulation and IUI.Trial registrationClinicalTrials.gov, NCT01232075

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“…A recent study in a rat model suggests that ovarian stimulation with CC has a suppressive effect on integrin and HOXA10 expression, when compared to letrozole [Bao et al 2009]. In addition to the molecular markers, fully developed pinopods were also observed to be maximally expressed in unexplained infertile women stimulated with letrozole ( Figure 1).…”

Section: Discussionmentioning

confidence: 85%

“…Cortinez and co-workers [2005], have evaluated the clinical response and endometrial morphology during the implantation window with letrozole in infertile ovulatory women. The effects of letrozole on the expression of a v b 3 integrin and HOXA10 gene in the uterine epithelium of rats have been investigated and compared with that of CC [Bao et al 2009]. In a recent retrospective study, the effect of letrozole on integrin expression as a marker of endometrial receptivity was examined [Miller et al 2012].…”

Section: Introductionmentioning

confidence: 99%

Endometrial receptivity markers in infertile women stimulated with letrozole compared with clomiphene citrate and natural cycles

Ganesh

Chauhan²,

Chakravarty

et al. 2013

Systems Biology in Reproductive Medicine

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Though various advantages associated with the use of letrozole as an ovulation inducing drug are documented, there is inadequate information regarding its effect on endometrial receptivity. Expression of endometrial receptivity markers including a v b 3 integrin, L-selectin, LIF, and pinopods during the implantation window in infertile women stimulated with letrozole or clomiphene citrate (CC), and spontaneous cycles is investigated. A total of 36 women were included in the study out of which 16 women were diagnosed with primary unexplained infertility and the other 20 women with severe oligoasthenozoospermic/azoospermic male partners. Both groups were sub-divided into three groups; women stimulated with letrozole, or with CC, and the third group was allowed to ovulate spontaneously (natural cycles). Women having natural cycles and not given any drug were considered as controls. Once ovulation was confirmed by ultrasonography, endometrial samples were collected on the seventh day post-ovulation and analyzed. In women with unexplained infertility treated with letrozole and CC, epithelial and stromal expression of a v b 3 integrin, L-selectin, leukemia inhibitory factor (LIF), and pinopod formation was found to be significantly higher as compared to controls. Expression of these receptivity markers was found to be comparable amongst the letrozole, CC, and control groups in women with severe oligoasthenozoospermic/azoospermic male partners. Cell cycle analysis showed similar cell cycle phase fractions on comparing the CC and the letrozole groups. Stimulation with letrozole and CC appears to enhance endometrial receptivity in women with unexplained infertility. However, letrozole and CC did not have any significant effect on the endometrial receptivity markers of women with severe oligoasthenozoospermic/azoospermic male partners.

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Effects of letrozole and clomiphene citrate on the expression of HOXA10 and integrin αvβ3 in uterine epithelium of rats

Cited by 34 publications

References 29 publications

Endometrial receptivity defects during IVF cycles with and without letrozole

Endometrial receptivity defects during IVF cycles with and without letrozole

Extended letrozole regimen versus clomiphene citrate for superovulation in patients with unexplained infertility undergoing intrauterine insemination: A randomized controlled trial

Endometrial receptivity markers in infertile women stimulated with letrozole compared with clomiphene citrate and natural cycles

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