The effect of excess body fat on female and male reproduction

Mintziori, Gesthimani; Nigdelis, Meletios P.; Mathew, Hannah; Mousiolis, Athanasios; Goulis, Dimitrios G.; Mantzoros, Christos S.

doi:10.1016/j.metabol.2020.154193

Cited by 58 publications

(41 citation statements)

References 176 publications

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“…Moreover, the present findings may help policymakers and healthcare professionals implement measures to attenuate the risk of ‘low-prognosis’ and potentially refine reproductive planning. Awareness campaigns emphasizing the adverse effects of advanced maternal age and diminished ovarian reserve have been explored, as has the potential positive impact of lifestyle changes on pregnancy ( Vause et al , 2009 ; Deatsman et al , 2016 ; Revelli et al , 2016 ; Kudesia et al , 2018 ; Salih et al , 2019 ; Mintziori et al , 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Cumulative delivery rate per aspiration IVF/ICSI cycle in POSEIDON patients: a real-world evidence study of 9073 patients

Esteves¹,

Yaralı́

Vuong

et al. 2021

Human Reproduction

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STUDY QUESTION What is the cumulative delivery rate (CDR) per aspiration IVF/ICSI cycle in low-prognosis patients as defined by the Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria? SUMMARY ANSWER The CDR of POSEIDON patients was on average ∼50% lower than in normal responders and varied across POSEIDON groups; differences were primarily determined by female age, number of embryos obtained, number of embryo transfer (ET) cycles per patient, number of oocytes retrieved, duration of infertility, and BMI. WHAT IS KNOWN ALREADY The POSEIDON criteria aim to underline differences related to a poor or suboptimal treatment outcome in terms of oocyte quality and quantity among patients undergoing IVF/ICSI, and thus, create more homogenous groups for the clinical management of infertility and research. POSEIDON patients are presumed to be at a higher risk of failing to achieve a live birth after IVF/ICSI treatment than normal responders with an adequate ovarian reserve. The CDR per initiated/aspiration cycle after the transfer of all fresh and frozen–thawed/warmed embryos has been suggested to be the critical endpoint that sets these groups apart. However, no multicenter study has yet substantiated the validity of the POSEIDON classification in identifying relevant subpopulations of patients with low-prognosis in IVF/ICSI treatment using real-world data. STUDY DESIGN, SIZE, DURATION Multicenter population-based retrospective cohort study involving 9073 patients treated in three fertility clinics in Brazil, Turkey and Vietnam between 2015 and 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants were women with infertility between 22 and 42 years old in their first IVF/ICSI cycle of standard ovarian stimulation whose fresh and/or frozen embryos were transferred until delivery of a live born or until all embryos were used. Patients were retrospectively classified according to the POSEIDON criteria into four groups based on female age, antral follicle count (AFC), and the number of oocytes retrieved or into a control group of normal responders (non-POSEIDON). POSEIDON patients encompassed younger (<35 years) and older (35 years or above) women with an AFC ≥5 and an unexpected poor (<4 retrieved oocytes) or suboptimal (4–9 retrieved oocytes) response to stimulation, and respective younger and older counterparts with an impaired ovarian reserve (i.e. expected poor responders; AFC <5). Non-POSEIDON patients were those with AFC ≥5 and >9 oocytes retrieved. CDR was computed per one aspirated cycle. Logistic regression analysis was carried out to examine the association between patient classification and CDR. MAIN RESULTS AND ROLE OF CHANCE The CDR was lower in the POSEIDON patients than in the non-POSEIDON patients (33.7% vs 50.6%; P < 0.001) and differed across POSEIDON groups (younger unexpected poor responder [Group 1a; n = 212]: 27.8%, younger unexpected suboptimal responder [Group 1b; n = 1785]: 47.8%, older unexpected poor responder [Group 2a; n = 293]: 14.0%, older unexpected suboptimal responder [Group 2b; n = 1275]: 30.5%, younger expected poor responder [Group 3; n = 245]: 29.4%, and older expected poor responder [Group 4; n = 623]: 12.5%. Among unexpected suboptimal/poor responders (POSEIDON Groups 1 and 2), the CDR was twice as high in suboptimal responders (4–9 oocytes retrieved) as in poor responders (<4 oocytes) (P = 0.0004). Logistic regression analysis revealed that the POSEIDON grouping, number of embryos obtained, number of ET cycles per patient, number of oocytes collected, female age, duration of infertility and BMI were relevant predictors for CDR (P < 0.001). LIMITATIONS, REASONS FOR CAUTION Our study relied on the antral follicle count as the biomarker used for patient classification. Ovarian stimulation protocols varied across study centers, potentially affecting patient classification. WIDER IMPLICATIONS OF THE FINDINGS POSEIDON patients exhibit lower CDR per aspirated IVF/ICSI cycle than normal responders; the differences are mainly determined by female age and number of oocytes retrieved, thereby reflecting the importance of oocyte quality and quantity. Our data substantiate the validity of the POSEIDON criteria in identifying relevant subpopulations of patients with low-prognosis in IVF/ICSI treatment. Efforts in terms of early diagnosis, prevention, and identification of specific interventions that might benefit POSEIDON patients are warranted. STUDY FUNDING/COMPETING INTEREST(S) Unrestricted investigator-sponsored study grant (MS200059_0013) from Merck KGaA, Darmstadt, Germany. The funder had no role in study design, data collection, analysis, decision to publish or manuscript preparation. S.C.E. declares receipt of unrestricted research grants from Merck and lecture fees from Merck and Med.E.A. H.Y. declares receipt of payment for lectures from Merck and Ferring. L.N.V. receives speaker fees and conferences from Merck, Merck Sharp and Dohme (MSD) and Ferring and research grants from MSD and Ferring. J.F.C. declares receipt of statistical services fees from ANDROFERT Clinic. T.M.H. received speaker fees and conferences from Merck, MSD and Ferring. P.H. declares receipt of unrestricted research grants from Merck, Ferring, Gedeon Richter and IBSA and lecture fees from Merck, Gedeon Richter and Med.E.A. C.A. declares receipt of unrestricted research grants from Merck and lecture fees from Merck. The remaining authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER N/A.

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Section: Discussionmentioning

confidence: 99%

Cumulative delivery rate per aspiration IVF/ICSI cycle in POSEIDON patients: a real-world evidence study of 9073 patients

Esteves¹,

Yaralı́

Vuong

et al. 2021

Human Reproduction

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“…Adipose tissue contributes to the pathophysiology of a variety of cardiometabolic disorders, such as atherosclerosis, obesity, diabetes mellitus, and the metabolic syndrome (1). Several common conditions in women are influenced by the amount and biological activity of fat tissue, such as menstrual cycle disorders, infertility, polycystic ovary syndrome (PCOS) as well as gestational diabetes (2). The menopausal transition is also characterized by prominent fat tissue changes, with visceral redistribution and increased metabolic perturbance (3).…”

Section: Introductionmentioning

confidence: 99%

D-Chiro-Inositol Regulates Insulin Signaling in Human Adipocytes

et al. 2021

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D-Chiro-Inositol (D-Chiro-Ins) is a secondary messenger in the insulin signaling pathway. D-Chiro-Ins modulates insulin secretion, the mitochondrial respiratory chain, and glycogen storage. Due to these actions D-Chiro-Ins has been proposed to correct defective insulin function in a variety of conditions characterized by metabolic dysfunction, such as polycystic ovary syndrome (PCOS), obesity, gestational diabetes and fat accumulation at menopause. Since it is unclear whether D-Chiro-Ins directly acts on adipocytes, we aimed to study D-Chiro-Ins’s actions on adipocyte viability, proliferation, differentiation, and insulin-related protein expression using a human adipocyte cell line derived from Simpson–Golabi–Behmel Syndrome (SGBS) which fully differentiates to mature adipocytes. Throughout differentiation, cells were treated with D-Chiro-Ins, 17β-estradiol (E2) or Insulin. Cell viability and proliferation were not affected by D-Chiro-Ins, then D-Chiro-Ins promoted cell differentiation only during the final days of the process, while E2 enhanced it from the first phases. D-Chiro-Ins stimulated lipid storage and the production of big lipid droplets, thus reducing the content of free fatty acids. We also found that D-Chiro-Ins, either alone or in combination with insulin and E2 increased the expression and activation of insulin receptor substrate-1 (IRS1) and glucose transporter type 4 (GLUT4). In conclusion, this work shows that D-Chiro-Ins plays a direct role in the differentiation and in the function of human adipocytes, where it synergizes with insulin and estrogen through the recruitment of signal transduction pathways involved in lipid and glucose storage. These findings give clear insights to better understand the actions of D-Chiro-Ins on fat metabolism in women in physiology and in a variety of diseases.

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“…Our findings may help decision-makers and practitioners implement measures to mitigate the risk of low-prognosis and optimize reproductive planning. Awareness campaigns highlighting the adverse impact of advanced female age and impaired ovarian reserve on reproductive success (35,36), the effect of lifestyle changes (37)(38)(39)(40), and the role of treatment strategies to improve treatment success could be explored (41)(42)(43)(44)(45)(46). Although the impact of the above interventions on POSEIDON prevalence rates remains mostly unknown, our data suggest that the "low-prognosis" burden could be prevented at least partially by treating patients earlier.…”

Section: Clinical Importancementioning

confidence: 88%

Low Prognosis by the POSEIDON Criteria in Women Undergoing Assisted Reproductive Technology: A Multicenter and Multinational Prevalence Study of Over 13,000 Patients

Esteves¹,

Yaralı́

Vuong

et al. 2021

Front. Endocrinol.

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ObjectiveTo estimate the prevalence of low-prognosis patients according to the POSEIDON criteria using real-world data.DesignMulticenter population-based cohort study.SettingsFertility clinics in Brazil, Turkey, and Vietnam.PatientsInfertile women undergoing assisted reproductive technology using standard ovarian stimulation with exogenous gonadotropins.InterventionsNone.Main outcome measuresPer-period prevalence rates of POSEIDON patients (overall, stratified by POSEIDON groups and by study center) and the effect of covariates on the probability that a patient be classified as “POSEIDON”.ResultsA total of 13,146 patients were included. POSEIDON patients represented 43.0% (95% confidence interval [CI] 42.0–43.7) of the studied population, and the prevalence rates varied across study centers (range: 38.6–55.7%). The overall prevalence rates by POSEIDON groups were 44.2% (group 1; 95% CI 42.6–45.9), 36.1% (group 2; 95% CI 34.6–37.7), 5.2% (group 3; 95% CI 4.5–6.0), and 14.4% (group 4; 95% CI: 13.3–15.6). In general, POSEIDON patients were older, had a higher body mass index (BMI), lower ovarian reserve markers, and a higher frequency of female factor as the primary treatment indication than non-POSEIDON patients. The former required larger doses of gonadotropin for ovarian stimulation, despite achieving a 2.5 times lower number of retrieved oocytes than non-POSEIDON patients. Logistic regression analyses revealed that female age, BMI, ovarian reserve, and a female infertility factor were relevant predictors of the POSEIDON condition.ConclusionsThe estimated prevalence of POSEIDON patients in the general population undergoing ART is significant. These patients differ in clinical characteristics compared with non-POSEIDON patients. The POSEIDON condition is associated with female age, ovarian reserve, BMI, and female infertility. Efforts in terms of diagnosis, counseling, and treatment are needed to reduce the prevalence of low-prognosis patients.

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The effect of excess body fat on female and male reproduction

Cited by 58 publications

References 176 publications

Cumulative delivery rate per aspiration IVF/ICSI cycle in POSEIDON patients: a real-world evidence study of 9073 patients

Cumulative delivery rate per aspiration IVF/ICSI cycle in POSEIDON patients: a real-world evidence study of 9073 patients

D-Chiro-Inositol Regulates Insulin Signaling in Human Adipocytes

Low Prognosis by the POSEIDON Criteria in Women Undergoing Assisted Reproductive Technology: A Multicenter and Multinational Prevalence Study of Over 13,000 Patients

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