Altered Kinetics of Pituitary Response to Gonadotropin-Releasing Hormone in Women with Variant Luteinizing Hormone: Correlation with Ovulatory Disorders

Takahashi, Kentaro; Karino, Kenji; Kanasaki, Haruhiko; Miyazaki, Kohji

doi:10.1159/000075194

Cited by 5 publications

(2 citation statements)

References 27 publications

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“…Moreover, observational trials suggest that v-betaLH is related to a reduced gonadal function and subfertility [21]. Finally, differences in the circulatory kinetics between the two types of LH may explain the diversities in LH function between patients with ovulatory disorders and women with normal ovulatory cycles [22]. This study confirms that v-betaLH carriers need a higher FSH dose during COS, supporting the idea that this polymorphism represents a biologically less active form of LH, unable to adequately support FSH activity during follicular stimulation.…”

Section: Discussionmentioning

confidence: 99%

A common polymorphic allele of the LH beta-subunit gene is associated with higher exogenous FSH consumption during controlled ovarian stimulation for assisted reproductive technology

Alviggi

Pettersson

Longobardi

et al. 2013

Reprod Biol Endocrinol

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BackgroundV-betaLH is a common genetic variant of LH caused by two polymorphic base changes in the beta subunit gene, altering the amino acid sequence (Trp8Arg and Ile15Thr). In a previous-preliminary trial performed in women undergoing IVF, it was demonstrated that carriers of v-betaLH show sub-optimal ovarian response to a standard long GnRH-agonist down -regulation protocol when stimulated with pure recombinant FSH (r-hFSH). The aim of this study was to confirm the hypothesis that women with v-betaLH display hypo-sensitivity to exogenous FSH in a larger IVF population and to explore the frequency of this variant in a Danish female population.MethodsIn the present study, the effect of v-betaLH was retrospectively investigated in a larger series of women undergoing controlled ovarian stimulation (COS) and, for the first time, in a Danish IVF population. A total of 220 normogonadotrophic women following a long GnRH-agonist down-regulation protocol received an individualized dose of r-hFSH (100 IU and 375 IU s.c. daily) according to antral follicle count, baseline FSH, body mass index and age. The LH genotype was assessed in all patients by immunofluorometric assay.ResultsV-betaLH was present in 11% of patients, whereas the allelic frequency was 12%. The study population was divided into two groups according to their LH genotype. Group A consisted of 196 wt/wt women. Group B included 24 individuals with v-betaLH (21 heterozygous and 3 homozygous). No statistically significant differences in the mean number of oocytes retrieved, fertilization rate and pregnancy rate per cycle were observed between groups. However, Group B received a significantly higher cumulative-dose of r-hFSH than Group A (2435.86 +/− 932.8 IU versus 1959.8 +/− 736.45 p = 0.048). When one-way ANOVA in a within design was applied, the LH genotype had a statistically significant effect (p < 0.01) on the cumulative dose of r-hFSH, showing a progressive increase from wt/wt (1959.8 +/− 736.45 IU) to v-betaLH hetero- (2267.5 +/− 824.3) and homozygotic women (3558.3 +/− 970.9).ConclusionsThese results confirm that carriers exhibit hypo-sensitivity to exogenous FSH during COS, documenting that the frequency of v-betaLH in Denmark is similar to a number of European countries.

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Section: Discussionmentioning

confidence: 99%

A common polymorphic allele of the LH beta-subunit gene is associated with higher exogenous FSH consumption during controlled ovarian stimulation for assisted reproductive technology

Alviggi

Pettersson

Longobardi

et al. 2013

Reprod Biol Endocrinol

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“…It is clearly known that female sex hormone level in the circulation vary during different reproductive stages of females such as pre menarche, post-menarche, pregnancy, lactation and menopause (Takahashi et al, 2004). Their hormonal system consists of three different factors viz.…”

Section: Th« Orimljll Anthropologistmentioning

confidence: 99%

A Study on Prevalence of Sex Chromatin during Different Reproductive Stage of Bengalee Hindu Caste Females

Mukherjee

2013

The Oriental Anthropologist: A Bi-annual International Journal

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Human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. The differential behaviour of the two X chromosome of female cells has biological implications. During the long evolutionary process of humankind, the X chromosome has generated and recruited a disproportionately high number of functional retro-posed genes where as the autosomes experienced tower gene turnover. Recent enquiries have revealed a surprisingly large number of naturally occurring anti-sense transcripts, but their functions remain largely undiscovered. A well documented case occurs in X inactivation, the mechanism by which X-linked gene expression is equalized between XX females and XY males. The anti-sense gene determines X chromosome choice and represses the non-coding silencer. This process of chromosome inactivation (XCI) is a remarkable example of long range, mono-allelic gene silencing and facultative heterochromatin formation. The X chromosome inactivation is initiated from X inactivation centre (XIC), usually found near the centromere. The inactivated X chromosome usually lies along the edge of the interphase nucleus in tightly condensed states. An effect of hormonal factors on the frequency of sex chromatin has been a subject matter of importance since long. The present study was conducted to evaluate the prevalence of sex chromatin and its spatial organization within the nucleus among Bengalee Hindu caste females of different age groups. Buccal smear samples were collected from 150 females belonging to five different reproductive stages of their life- pre-menarchial, post menarchal, pregnant, lactating and menopausal 30 samples were chosen from each of these groups. The remits indicated differential prevalence of sex chromatin among the participants at different reproductive stages. The present study demonstrated that the prevalence of sex chromatin was significantly lowest p<0.001) and highest (p<0.001) among the pre-menarchial females and lactating mothers respectively. On the other hand, the menopausal women revealed significantly lower prevalence (p<0.001) of sex chromatin compared to the participants of rest of the reproductive categories. Furthermore, the present study revealed that the spatial organization differ significantly among different reproductive stages. These results suggested possible association between the presence of steroid hormone receptors and the prevalence of sex chromatin.

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Suboptimal response to GnRHa long protocol is associated with a common LH polymorphism

Alviggi¹,

Clarizia²,

Pettersson³

et al. 2009

Reproductive BioMedicine Online

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The aim of this observational preliminary trial was to estimate the association between the most common polymorphism of LH (LH-beta variant: v-betaLH), with different profiles of ovarian response to recombinant human FSH (rhFSH). A total of 60 normogonadotrophic patients undergoing a gonadotrophin-releasing hormone analogue long down-regulation protocol followed by stimulation with recombinant human FSH (rhFSH) for IVF/intracytoplasmic sperm injection, and in whom at least five oocytes were retrieved were retrospectively included. On the basis of the total rhFSH consumption, patients were divided into three groups: Group A: 22 women requiring a cumulative dose of rhFSH >3500 IU; Group B: 15 patients requiring 2000-3500 IU; Group C (control): 23 women requiring <2000 IU. The presence of v-betaLH was evaluated using specific immunoassays. Peak oestradiol concentrations were significantly lower in Group A when compared with both groups B (P < 0.05) and C (P < 0.001). Group A had a significantly lower (P < 0.05) number of oocytes retrieved (7.3 +/- 1.5, 11.7 +/- 2.4 and 14.7 +/- 4.1 in the three groups, respectively). Seven carriers (31.8%) of v-betaLH were found in Group A, whereas only one variant (6.7%) was observed in Group B; no variant was detected in Group C. These preliminary results suggest that v-betaLH is more frequent in women with ovarian resistance to rhFSH.

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Altered Kinetics of Pituitary Response to Gonadotropin-Releasing Hormone in Women with Variant Luteinizing Hormone: Correlation with Ovulatory Disorders

Cited by 5 publications

References 27 publications

A common polymorphic allele of the LH beta-subunit gene is associated with higher exogenous FSH consumption during controlled ovarian stimulation for assisted reproductive technology

A common polymorphic allele of the LH beta-subunit gene is associated with higher exogenous FSH consumption during controlled ovarian stimulation for assisted reproductive technology

A Study on Prevalence of Sex Chromatin during Different Reproductive Stage of Bengalee Hindu Caste Females

Suboptimal response to GnRHa long protocol is associated with a common LH polymorphism

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