Obesity Affects Endometrial Receptivity by Displacing the Window of Implantation

Bellver, José; Marín, Carlos; Lathi, Ruth B.; Murugappan, Gayathree; Labarta, Elena; Vidal, C.; Gilés, Juan; Cabanillas, Sergio; Marzal, Alicia; Galliano, Daniela; Ruiz-Alonso, María; Simón, Carlos; Valbuena, Diana

doi:10.1007/s43032-021-00631-1

Cited by 37 publications

(21 citation statements)

References 42 publications

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“…In a natural cycle, or in a hormonally prepared endometrium, embryo-endometrium synchronization could be achieved in obese women by normalizing the timing of endometrial receptivity, as occurs with frozen embryo transfers. However, in molecular terms, a dysregulation of gene expression during the window of implantation (WOI) has been described in hormonally prepared endometria of obese women, especially in association with metabolic disturbances and with a dominant pattern of delayed receptivity as ERA tests have been found more frequently prereceptive [59][60][61]. In this way, an endometrial disturbance may persist even in the absence of the supraphysiologic steroid levels reached during ovarian stimulation.…”

Section: The Uterus and Its Environmentmentioning

confidence: 99%

BMI and miscarriage after IVF

Bellver

2022

Current Opinion in Obstetrics &Amp; Gynecology

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Purpose of reviewTo summarize recent findings related to the risk of miscarriage in women with elevated BMI undergoing IVF, and the mechanisms involved in said risk.Recent findingsMiscarriage rates are increased in overweight and obese women in both natural and assisted reproduction. Oocyte and embryo quality assessed according to classic morphological static parameters does not seem to be affected by excessive female body weight. Despite the initial lack of consensus between studies regarding embryo morphokinetics in obese women, blastocyst formation and quality have recently been shown to be similar across BMI groups, even in the case of euploid embryos. However, some metabolomic differences have been described in oocytes and embryos from obese women, thus pointing to a functional alteration. In women with elevated BMI, the percentage of aneuploid embryos is similar to that of normal weight women, and rates of miscarriage are higher, despite the transfer of euploid embryos. Therefore, the origin of the increased pregnancy loss rate after IVF in these women may be related to metabolomic, epigenetic or mitochondrial oocyte and embryo disturbances, or to the abnormal endocrine, metabolic and inflammatory uterine environment induced by obesity, which seems to be also responsible for other numerous complications during pregnancy and the in-utero fetal programming of postnatal diseases. A displacement of the window of implantation in obese women undergoing artificial endometrial preparation has recently been described and may be related to the poorer embryo implantation rates and increased risk of miscarriage observed following fresh and frozen embryo transfers with autologous oocytes, and with donated ova in recipients with extremely high BMI.SummaryFemale obesity is related to poorer outcome in natural and assisted conception, including an increased risk of miscarriage. Embryo morphology, assessed by conventional methods or by morphokinetics, does not seem to be affected by excess weight, with similar blastocyst formation and quality than normal weight women reported in IVF cycles. Embryo aneuploidy is not increased, and higher miscarriages rates are seen after euploid embryo transfer in obese women. Disturbances of the uterus or its environment induced by female obesity seem to be the most likely cause of the increased risk of miscarriage, although metabolomic, epigenetic or mitochondrial oocyte and embryo dysfunction cannot be ruled out as cannot congenital anomalies. In the context of all the above, weight reduction before pregnancy should be advised in obese women trying to become pregnant.

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Section: The Uterus and Its Environmentmentioning

confidence: 99%

BMI and miscarriage after IVF

Bellver

2022

Current Opinion in Obstetrics &Amp; Gynecology

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“…This association corroborates the hypothesis that the impairment of these interconnected phenomena could be one of the mechanisms that lead to a poor reproductive outcome and early pregnancy loss in females with high-fat diet habits [ 222 ]. To continue, a decreased endometrial decidualization was also observed in obese women due to high-fat habits [ 223 , 224 , 225 , 226 ]. The pathogenesis of this phenomenon can consist of a high level of proinflammatory cytokines and an overexpression of pathways related to immune response and ROS production, inducing endothelial dysfunction [ 223 ].…”

Section: High-fat Diet Impact On Oocyte Developmental Competencementioning

confidence: 99%

High-Fat Diet and Female Fertility across Lifespan: A Comparative Lesson from Mammal Models

et al. 2022

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Female reproduction focuses mainly on achieving fully grown follicles and competent oocytes to be successfully fertilized, as well as on nourishing the developing offspring once pregnancy occurs. Current evidence demonstrates that obesity and/or high-fat diet regimes can perturbate these processes, leading to female infertility and transgenerational disorders. Since the mechanisms and reproductive processes involved are not yet fully clarified, the present review is designed as a systematic and comparative survey of the available literature. The available data demonstrate the adverse influences of obesity on diverse reproductive processes, such as folliculogenesis, oogenesis, and embryo development/implant. The negative reproductive impact may be attributed to a direct action on reproductive somatic and germinal compartments and/or to an indirect influence mediated by the endocrine, metabolic, and immune axis control systems. Overall, the present review highlights the fragmentation of the current information limiting the comprehension of the reproductive impact of a high-fat diet. Based on the incidence and prevalence of obesity in the Western countries, this topic becomes a research challenge to increase self-awareness of dietary reproductive risk to propose solid and rigorous preventive dietary regimes, as well as to develop targeted pharmacological interventions.

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“…A wide range of disorders were associated with obesity, including chronic low-grade inflammation, metabolic syndrome, diabetes, cardiovascular disease, and infertility (1)(2)(3)(4). Recent retrospective population studies have found that obese patients have poor endometrial receptivity (5), poor embryo quality (6,7), low oocyte maturation rates (8), and subsequently, low pregnancy rate (9,10) and high abortion rate (11,12). Nevertheless, the etiology for poor reproductive ability in obese women remains largely unclear.…”

Section: Introductionmentioning

confidence: 99%

Decreased DNA Repair Ability: A Mechanism for Low Early Embryonic Development Potential of Oocytes From Overweight Patients After Fertilization in IVF Cycles

Wang

Zhu

et al. 2021

Front. Endocrinol.

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BackgroundWhether female BMI impacts the DNA repair ability in the oocytes after fertilization has not been investigated. The aim of this study is to assess the early embryo quality and reproductive outcomes of oocytes from overweight women when fertilized with sperm with varying degrees of DNA fragmentation.MethodsA total number of 1,612 patients undergoing fresh autologous in vitro fertilization (IVF) cycles was included. These patients were divided into two groups according to maternal body mass index (BMI): normal weight group (18.5–24.9 kg/m2; n=1187; 73.64%) and overweight group (≥25 kg/m2; n=425; 26.36%). Each group was then subdivided into two groups by sperm DNA fragmentation index (DFI): low fragmentation group (<20% DFI, LF) and high fragmentation group (≥20% DFI, HF). Laboratory and clinical outcomes were compared between subgroups.ResultsFor the normal-weight group, there was no statistical significance in embryo quality and reproductive outcomes between the LF and HF groups. But in the overweight group, significantly lower fertilization rate (LF: 64%; HF: 59%; p=0.011), blastocyst development rate (LF: 57%; HF: 44%; p=0.001), as well as high-quality blastocyst rate (LF: 32%; HF: 22%; p=0.034) were found in the HF group, despite the similar pregnancy rates (LF: 56%; HF: 60%; p=0.630).ConclusionsDecreased DNA repair activity in oocytes may be a possible mechanism for the low early development potential of embryos from overweight patients in in vitro fertilization cycles.

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Obesity Affects Endometrial Receptivity by Displacing the Window of Implantation

Cited by 37 publications

References 42 publications

BMI and miscarriage after IVF

BMI and miscarriage after IVF

High-Fat Diet and Female Fertility across Lifespan: A Comparative Lesson from Mammal Models

Decreased DNA Repair Ability: A Mechanism for Low Early Embryonic Development Potential of Oocytes From Overweight Patients After Fertilization in IVF Cycles

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