In Estimated Good Prognosis Patients Could Unexpected “Hyporesponse” to Controlled Ovarian Stimulation be Related to Genetic Polymorphisms of FSH Receptor?

Alviggi, Carlo; Caprio, Francesca; Gizzo, Salvatore; Noventa, Marco; Strina, Ida; Pagano, Tiziana; Rosa, Pasquale De; Carbone, Ilma Floriana; Colacurci, Nicola; Placido, Giuseppe De

doi:10.1177/1933719116630419

Cited by 44 publications

(48 citation statements)

References 29 publications

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“…In a 2013 sizeable longitudinal study, we found that a common LH beta subunit variant was associated with increased FSH consumption during OS ( 29 ). In another study, we found that the prevalence of hypo-response was higher in G allele carriers of a common FSH receptor (FSHR) polymorphism (p.N680SA > G, rs6166) than in wild-type haplotypes ( 30 ). Furthermore, in vitro studies using human granulosa cells demonstrated that p.N680SA>G G homozygous showed higher resistance to FSH stimulation than p.N680SA>G A homozygous carriers at the FSH receptor level ( 31 , 32 ).…”

Section: Pathogenesis Of Hypo-responsementioning

confidence: 96%

Understanding Ovarian Hypo-Response to Exogenous Gonadotropin in Ovarian Stimulation and Its New Proposed Marker—The Follicle-To-Oocyte (FOI) Index

Esteves²,

et al. 2018

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Hypo-responsiveness to controlled ovarian stimulation is an undervalued topic in reproductive medicine. This phenomenon manifests as a low follicles output rate (FORT) with a discrepancy between the relatively low number of pre-ovulatory follicles which develop following ovarian stimulation as compared to the number of antral follicles available at the start of stimulation. The pathophysiology mechanisms explaining the ovarian resistance to gonadotropin stimulation are not fully understood, but the fact that both hypo-responders and normal responders share similar phenotypic characteristics suggests a genotype-based mechanism. Indeed, existing evidence supports the association between specific gonadotropin and their receptor polymorphisms and ovarian hypo-response. Apart from genotypic trait, environmental contaminants and oxidative stress might also be involved in the hypo-response pathogenesis. The ratio between the number of oocytes collected at the ovum pick up and the number of antral follicles at the beginning of OS [Follicle to oocyte index (FOI)] is proposed as a novel parameter to assess the hypo-response. Compared with traditional ovarian reserve markers, FOI might reflect most optimally the dynamic nature of follicular growth in response to exogenous gonadotropin. In this review, we contextualize the role of FOI as a parameter to identify this condition, discuss the underlying mechanisms potentially implicated in the pathogenesis of hypo-response, and appraise possible the treatment strategies to overcome hyper-responsiveness to gonadotropin stimulation.

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Section: Pathogenesis Of Hypo-responsementioning

confidence: 96%

Understanding Ovarian Hypo-Response to Exogenous Gonadotropin in Ovarian Stimulation and Its New Proposed Marker—The Follicle-To-Oocyte (FOI) Index

Esteves²,

et al. 2018

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“…The presence of genetic mutations or single nucleotide polymorphisms of Gn and their receptors can influence ovarian sensitivity to Gn stimulation (17,18). Apart from genotypic traits, there is also evidence to suggest that environmental contaminants and oxidative stress are involved in the hyporesponse pathogenesis (19)(20)(21).…”

Section: Discussionmentioning

confidence: 99%

Follicular Output Rate and Follicle-to-Oocyte Index of Low Prognosis Patients According to POSEIDON Criteria: A Retrospective Cohort Study of 32,128 Treatment Cycles

et al. 2020

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Objective: To investigate ovarian sensitivity in subgroups of patients with a low prognosis, as defined by the POSEIDON criteria, undergoing in vitro fertilization treatment and measures to improve ovarian sensitivity in these patients. Design: We conducted a retrospective cohort analysis. Setting: The study was conducted at an IVF clinic in a public hospital. Patients: A total of 32,128 fresh IVF cycles from January 2014 to October 2018 at a single IVF clinic were included in the analysis. Patients with a low prognosis were categorized into four groups based on the POSEIDON criteria. Interventions: None. Main Outcome Measure: The primary outcome measures were the follicular output rate (FORT) and the follicle-to-oocyte index (FOI). Results: The FORTs in the order from the highest to the lowest were 1.18 in group 3, 0.98 in group 4, 0.76 in group 1, and 0.68 in group 2. The trend in the FOI values was consistent with that in the FORTs. Among patients with poor ovarian sensitivity, 58.41% of patients with FORTs ≥ 0.30 in the second cycle underwent an adjustment to the ovarian stimulation (OS) protocol and 41.59% underwent an adjustment to the gonadotropin (Gn) starting dose. Among patients with normal ovarian sensitivity, 43.56% of those with FORTs ≥ 0.80 in the second cycle underwent an adjustment to the OS protocol and 56.44% underwent an adjustment to the Gn starting dose. Conclusion: Ovarian sensitivity was the highest in group 3 (young women with poor ovarian reserve), followed by groups 4 (women at advanced age with poor ovarian reserve) and 1 (young women with good ovarian reserve), and it was the lowest in group 2 (women at advanced age with good ovarian reserve). For patients with poor ovarian sensitivity, it is preferred to recommend an adjustment to the OS protocol, while for those with normal ovarian sensitivity, adjusting the Gn starting dose is preferred.

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“…Ovarian response in IVF is clearly dependent on the genotype of the FSH receptor (30) . Different variants in receptor genotype have been related to different basal FSH levels and to different numbers of FSH ampoules needed to achieve adequate ovarian response in IVF (31) .…”

Section: Discussionmentioning

confidence: 99%

Antral Follicle Count versus Basal Follicle Stimulating Hormone as Predictors of Ovarian Response in Women Undergoing Superovulation with Long Protocol for Assisted Reproduction

El-Maeboud

Elbohoty

El-Alim

et al. 2017

Egyptian Journal of Hospital Medicine

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Background: the prediction of ovarian response before undertaking the expensive IVF treatment is quite important; it seemed that Patient characteristics, rather than the stimulation protocol are the determinant of the individual response. Advance identification of patient who will elicit a poor response or hyper response to standard treatment would be of great clinical advantage. Several parameters have been postulated as predictors of the ovarian response. Aim of work: to compare between bFSH and AFC in predicting the ovarian response in women undergoing super-ovulation with long protocol for assisted reproduction. Patients and Methods: this is an observational cohort study that included 80 infertile women who performed IVF/ICSI. It took place at Assisted Reproductive Technology (ART) Unit. Ain shams University Maternity hospital. No extra interventional measures were taken in the study apart from routine investigations and procedures done during ART therapy, being already approved in signed consent to undergo treatment. Patients who are fulfilling the inclusion and exclusion criteria were enrolled in the study. They all underwent superovulation with long GnRH agonist. They were followed up through the stimulation protocol steps, then data were analysed. Results: all basal measured data such as Age p. value =0.035, AFC p. value =0.000, basal FSH p. value =0.000 and basal E2 p. value =0.020 showed statistical significant difference between the good responders and poor responders when both groups were compared, When we apply ROC curve to compare between AFC and basal FSH as regards both (good and poor responders) to detect which one of them is better, there was no statistical significance difference between them with p. value = 0.371, the best cut off point for AFC as a predictor for good responders was found > 3 follicles with sensitivity of 90.5%, specificity of 94.1% and area under curve (AUC) of 97.5%, while while the best cut off point for basal FSH level was found ≤ 8 with sensitivity of 77.78%, specificity of 100% and AUC of 93.7%. Conclusion: AFC and basal FSH are good predictors of ovarian response in women undergoing superovulation with long protocol. There was no absolute superiority of AFC on basal FSH in predicting ovarian response. Age and basal E2 are also considered good predictors of ovarian response.

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In Estimated Good Prognosis Patients Could Unexpected “Hyporesponse” to Controlled Ovarian Stimulation be Related to Genetic Polymorphisms of FSH Receptor?

Cited by 44 publications

References 29 publications

Understanding Ovarian Hypo-Response to Exogenous Gonadotropin in Ovarian Stimulation and Its New Proposed Marker—The Follicle-To-Oocyte (FOI) Index

Understanding Ovarian Hypo-Response to Exogenous Gonadotropin in Ovarian Stimulation and Its New Proposed Marker—The Follicle-To-Oocyte (FOI) Index

Follicular Output Rate and Follicle-to-Oocyte Index of Low Prognosis Patients According to POSEIDON Criteria: A Retrospective Cohort Study of 32,128 Treatment Cycles

Antral Follicle Count versus Basal Follicle Stimulating Hormone as Predictors of Ovarian Response in Women Undergoing Superovulation with Long Protocol for Assisted Reproduction

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