Lower apoptosis rate in human cumulus cells after administration of recombinant luteinizing hormone to women undergoing ovarian stimulation for in vitro fertilization procedures

Ruvolo, Giovanni; Bosco, Liana; Pane, A.; Morici, Giovanni; Cittadini, E; Roccheri, Maria Carmela

doi:10.1016/j.fertnstert.2006.06.059

Cited by 113 publications

(108 citation statements)

References 15 publications

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“…These data are further supported by the fact that it has been shown that supplementation with r-LH during the late follicular phase significantly reduced the number of immature oocytes collected after pick-up, while it increased the number of embryos transferred [46] and reduced CC apoptosis [47].…”

Section: Discussionmentioning

confidence: 62%

“…However, in women above 35 years of age, poor responders, or with more severe pituitary GnRH-a suppression, stimulation with r-LH in the mid/late-follicular phase could be associated with improved results [6,12,24,34,37,40,41,47]. In a recent meta-analysis study it has been suggested that the supplementation with r-LH in patients of advanced reproductive age stimulated with r-FSH, may improve implantation and clinical pregnancy without affecting metaphase II (Met II) yield [31].…”

Section: Introductionmentioning

confidence: 99%

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Follicular fluid hormonal profile and cumulus cell gene expression in controlled ovarian hyperstimulation with recombinant FSH: effects of recombinant LH administration

Barberi

Ermini

Morelli

et al. 2012

J Assist Reprod Genet

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Purpose Down-regulation with gonadodropin-releasing agonist (GnRH-a) protocol during IVF stimulation leads to a severe endogenous LH suppression, which may affect the follicular development. The aim of the study was to evaluate the effects of recombinant LH (r-LH) administration, during late follicular development stages, in recombinant FSH (r-FSH) stimulated cycles on follicular fluid (FF) parameters and on cumulus cell quality. Methods Twenty patients undergoing IVF were stimulated in a long GnRH agonist protocol with r-FSH alone or with r-LH supplementation when the leading follicle reached diameter of 14 mm. FF was collected at the time of oocyte retrieval from 32 follicles ≥ 18 mm. Serum FSH, LH, estradiol (E 2 ), and progesterone (P 4 ) were evaluated on the day of hCG administration. Intra-follicular E 2 , P 4 , AMH and TGF-β were assayed. Total RNA from 18 individual cumuli was isolated for gene expression analyses. Results R-LH increased FF P 4 levels. FF TGF-β levels and PTGS2 and HAS2 expression in cumulus cells (CCs) positively correlated with increased P 4 levels observed in FFs, while a negative correlation was found between P 4 and AMH levels. Conclusions FF positive correlation between P 4 and TGF-β levels and CC expression of PTGS2 and HAS2 suggest an association with a better follicle quality. In addition, our data suggest that late follicular phase r-LH supplementation leads to a more advanced stage of follicular maturation.

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Section: Discussionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Follicular fluid hormonal profile and cumulus cell gene expression in controlled ovarian hyperstimulation with recombinant FSH: effects of recombinant LH administration

Barberi

Ermini

Morelli

et al. 2012

J Assist Reprod Genet

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“…Studies (Ruvolo et al 2007) also found a lower apoptosis rate in human cumulus cells after administration of recombinant LH to women undergoing ovarian stimulation for IVF procedures. Our results are in accordance with these results and supplied another direct evidence of LH as an anti-apoptosis factor in GCs.…”

Section: Discussionmentioning

confidence: 93%

PCSK6 regulated by LH inhibits the apoptosis of human granulosa cells via activin A and TGFβ2

Wang

Fan

et al. 2014

Journal of Endocrinology

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Mammalian proprotein convertases (PCs) play an important role in folliculogenesis, as they proteolytically activate a variety of substrates such as the transforming growth factor beta (TGFb) superfamily. PC subtilism/kexin 6 (PCSK6) is a member of the PC family and is ubiquitously expressed and implicated in many physiological and pathological processes. However, in human granulosa cells, the expression of the PC family members, their hormonal regulation, and the function of PCs are not clear. In this study, we found that PCSK6 is the most highly expressed PC family member in granulosa cells. LH increased PCSK6 mRNA level and PCSK6 played an anti-apoptosis function in KGN cells. Knockdown of PCSK6 not only increased the secretion of activin A and TGFb2 but also decreased the secretion of follistatin, estrogen, and the mRNA levels of FSH receptor (FSHR) and P450AROM (CYP19A1). We also found that, in the KGN human granulosa cell line, TGFb2 and activin A could promote the apoptosis of KGN cells and LH could regulate the follistatin level. These data indicate that PCSK6, which is regulated by LH, is highly expressed in human primary granulosa cells of pre-ovulatory follicles and plays important roles in regulating a series of downstream molecules and apoptosis of KGN cells.

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“…Ruvolo [28] suggested that supplementation with recombinant LH (recLH) during the proliferative phase improves some clinical parameters. In particular, the supplementation of recLH greatly reduces the number of picked-up immature oocytes, thus increasing the number of transferred embryos, which is negatively correlated with the risk of OHSS.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, the supplementation of recLH greatly reduces the number of picked-up immature oocytes, thus increasing the number of transferred embryos, which is negatively correlated with the risk of OHSS. In addition, the increase in pregnancy rates and implantation rates may be correlated with the reduction of apoptosis seen in the cumulus cells of patients treated with recLH [28].…”

Section: Discussionmentioning

confidence: 99%

Difference in mitochondrial gene expression in granulosa cells between recombinant FSH and hMG cycles under in vitro fertilization and transfer

Saito

Yamashita

Higuchi

et al. 2013

Reprod Medicine & Biology

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Purpose Examination of the mitochondrial mRNA expression in granulosa cells from an unspecified population of infertile patients to evaluate whether recombinant follicle stimulating hormone (recFSH) is more effective in producing higher quality embryo rates compared with human menopausal gonadotropin (hMG). Method Thirty-nine patients who underwent the in vitro fertilization and embryo transfer program were retrospectively examined. Patients were administered recFSH (n = 18) or hMG (n = 20) in a long protocol where GnRH agonist was used. Granulosa cells were obtained during oocyte retrieval and examined for mitochondria mRNA expression ratio against GAPDH. Expressions of mitochondria mRNA were evaluated by real-time PCR analysis. Results The high-quality embryo rate in the hMG cycle was higher than in the recFSH cycle, and the total dose of hMG showed a positive correlation with the expression level of mitochondrial genes in granulosa cells. Moreover, mitochondria mRNA expression was higher in the hMG cycle than in the recFSH cycle. Conclusions Compared with recFSH, hMG induces a higher mitochondrial gene expression ratio in granulosa cells at the time of oocyte retrieval and, therefore, may lead to higher quality embryo rates.

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Lower apoptosis rate in human cumulus cells after administration of recombinant luteinizing hormone to women undergoing ovarian stimulation for in vitro fertilization procedures

Cited by 113 publications

References 15 publications

Follicular fluid hormonal profile and cumulus cell gene expression in controlled ovarian hyperstimulation with recombinant FSH: effects of recombinant LH administration

Follicular fluid hormonal profile and cumulus cell gene expression in controlled ovarian hyperstimulation with recombinant FSH: effects of recombinant LH administration

PCSK6 regulated by LH inhibits the apoptosis of human granulosa cells via activin A and TGFβ2

Difference in mitochondrial gene expression in granulosa cells between recombinant FSH and hMG cycles under in vitro fertilization and transfer

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