Role of hormonal and inflammatory alterations in obesity-related reproductive dysfunction at the level of the hypothalamic-pituitary-ovarian axis.
Goldsammler Michelle,Merhi Zaher,Buyuk Erkan
Reproductive biology and endocrinology : RB&E
BACKGROUND:Besides being a risk factor for multiple metabolic disorders, obesity could affect female reproduction. While increased adiposity is associated with hormonal changes that could disrupt the function of the hypothalamus and the pituitary, compelling data suggest that obesity-related hormonal and inflammatory changes could directly impact ovarian function. OBJECTIVE:To review the available data related to the mechanisms by which obesity, and its associated hormonal and inflammatory changes, could affect the female reproductive function with a focus on the hypothalamic-pituitary-ovarian (HPO) axis. METHODS:PubMed database search for publications in English language until October 2017 pertaining to obesity and female reproductive function was performed. RESULTS:The obesity-related changes in hormone levels, in particular leptin, adiponectin, ghrelin, neuropeptide Y and agouti-related protein, are associated with reproductive dysfunction at both the hypothalamic-pituitary and the ovarian levels. The pro-inflammatory molecules advanced glycation end products (AGEs) and monocyte chemotactic protein-1 (MCP-1) are emerging as relatively new players in the pathophysiology of obesity-related ovarian dysfunction. CONCLUSION:There is an intricate crosstalk between the adipose tissue and the inflammatory system with the HPO axis function. Understanding the mechanisms behind this crosstalk could lead to potential therapies for the common obesity-related reproductive dysfunction.
10.1186/s12958-018-0366-6
Leptin and reproduction.
Clarke I J,Henry B A
Reviews of reproduction
In the few years since leptin was identified as a satiety factor in rodents, it has been implicated in the regulation of various physiological processes. Leptin has been shown to promote sexual maturation in rodent species and a role in reproduction has been investigated at various sites within the hypothalamo-pituitary-gonadal axis. This review considers the evidence that leptin (or alteration in amount of body fat) can affect reproduction. There is evidence that leptin plays a permissive role in the onset of puberty, probably through action on the hypothalamus, where leptin receptors are found in cells that express appetite-regulating peptides. There is little evidence that leptin has a positive effect on the pituitary gonadotrophs and the gonads. There is also very little indication that leptin acts in an acute manner to regulate reproduction in the short term. It seems more likely that leptin is a 'barometer' of body condition that sends signals to the brain. Studies in vitro have shown negative effects on ovarian steroid production and there are no reports of effects on testicular function. Leptin concentrations in plasma increase in women during pregnancy, owing to production by the placenta but the functional significance of this is unknown. A number of factors that affect the production and action of leptin have yet to be studied in detail.
10.1530/ror.0.0040048
Obesity induces ovarian inflammation and reduces oocyte quality.
Snider Alexandria P,Wood Jennifer R
Reproduction (Cambridge, England)
In the United States, 36.5% of women between the ages of 20 and 39 years are obese. This obesity results in not only metabolic disorders including type II diabetes and cardiovascular disease, but also impaired female fertility. Systemic and tissue-specific chronic inflammation and oxidative stress are common characteristics of obesity. This is also true in the ovary. Several studies have demonstrated that pro-inflammatory cytokines and reactive oxygen species alter estrous cyclicity, steroidogenesis and ovulation. Inflammation and oxidative stress also impair meiotic and cytoplasmic maturation of the oocyte which reduces its developmental competence for fertilization and pre-implantation embryo development. Interestingly, there is recent evidence that obesity- and/or polycystic ovary syndrome (PCOS)-dependent changes to the gut microbiome contributes to ovarian inflammation, steroidogenesis and the expression of mRNAs in the oocyte. However, several gaps remain necessitating future studies to identify inflammation, oxidative stress and gut microbiome mechanisms that reduce ovarian function and oocyte quality.
10.1530/REP-18-0583
Obesity and reproductive dysfunction in women.
Moran Lisa J,Dodd Jodie,Nisenblat Victoria,Norman Robert J
Endocrinology and metabolism clinics of North America
Overweight and obesity are significant and increasing health problems associated with increased risks of morbidity, quality of life, and metabolic and reproductive health consequences. In women, being overweight or obese is associated with impaired fertility and decreased chance of conception both in natural and assisted reproductive technology births. During pregnancy, overweight and obesity are associated with increased risk of adverse maternal and infant health outcomes. Attention to weight loss before conception may improve fertility and maternal and infant health outcomes during pregnancy.
10.1016/j.ecl.2011.08.006
Obesity and reproductive function: a review of the evidence.
Klenov Violet E,Jungheim Emily S
Current opinion in obstetrics & gynecology
PURPOSE OF REVIEW:Over the last decade, the evidence linking obesity to impaired reproductive function has grown. In this article, we review this evidence and discuss the underlying pathophysiology. RECENT FINDINGS:Obese women are less likely than normal-weight women to achieve pregnancy. Female obesity adversely affects reproductive function through alterations in the hypothalamic-pituitary-ovarian axis, oocyte quality, and endometrial receptivity. It is unclear which mechanism contributes the most to subfecundity, and it is likely a cumulative process. Emerging data highlight the contribution of male obesity to impaired reproductive function and that couple obesity has synergistic adverse effects. Once pregnant, obese women are at higher risk for adverse pregnancy outcomes. Weight loss improves reproductive potential in obese patients. As obese women surpass 35 years of age, age may be more important than body mass index in determining reproductive potential. SUMMARY:Obstetrician gynecologists need to be aware of the negative impact of obesity on reproductive function so that they appropriately counsel their patients. Further work is needed to clarify the underlying pathophysiology responsible for adverse effects of obesity on reproduction so that novel treatment approaches may be developed.
10.1097/GCO.0000000000000113
Impact of obesity on female fertility and fertility treatment.
Zain Murizah M,Norman Robert J
Women's health (London, England)
Obesity and overweight are common conditions that have consequences not only on general health but also to a great extent on reproductive health. There is a high prevalence of obese women in the infertile population and numerous studies have highlighted the link between obesity and infertility. Obesity contributes to anovulation and menstrual irregularities, reduced conception rate and a reduced response to fertility treatment. It also increases miscarriage and contributes to maternal and perinatal complication. Reduction of obesity, particularly abdominal obesity, is associated with improvements in reproductive functions; hence, treatment of obesity itself should be the initial aim in obese infertile women before embarking on ovulation-induction drugs or assisted reproductive techniques. While various strategies for weight reduction, including diet, exercise, pharmacological and surgical intervention exist, lifestyle modification continues to be of paramount importance.
10.2217/17455057.4.2.183
Position of the American Dietetic Association and American Society for Nutrition: obesity, reproduction, and pregnancy outcomes.
, ,Siega-Riz Anna Maria,King Janet C
Journal of the American Dietetic Association
Given the detrimental influence of maternal overweight and obesity on reproductive and pregnancy outcomes for the mother and child, it is the position of the American Dietetic Association and the American Society for Nutrition that all overweight and obese women of reproductive age should receive counseling on the roles of diet and physical activity in reproductive health prior to pregnancy,during pregnancy, and in the inter conceptional period, in order to ameliorate these adverse outcomes. The effect of maternal nutritional status prior to pregnancy on reproduction and pregnancy outcomes is of great public health importance. Obesity in the United States and worldwide has grown to epidemic proportions, with an estimated 33% of US women classified as obese. This position paper has two objectives: (a) to help nutrition professionals become aware of the risks and possible complications of overweight and obesity for fertility,the course of pregnancy, birth outcomes, and short- and long-term maternal and child health outcomes;and (b) related to the commitment to research by the American Dietetic Association and the American Society for Nutrition, to identify the gaps in research to improve our knowledge of the risks and complications associated with being overweight and obese before and during pregnancy.Only with an increased knowledge of these risks and complications can health care professionals develop effective strategies that can be implemented before and during pregnancy as well as during the inter conceptional period to ameliorate adverse outcomes.
Weight loss improves reproductive outcomes in obese women undergoing fertility treatment: a randomized controlled trial.
Sim K A,Dezarnaulds G M,Denyer G S,Skilton M R,Caterson I D
Clinical obesity
For women attempting pregnancy, obesity reduces fertility and is an independent risk factor for obstetric and neonatal complications. The aim of this evaluator-blinded, randomized controlled trial was to evaluate a weight loss intervention on pregnancy rates in obese women undertaking fertility treatment. Forty-nine obese women, aged ≤ 37 years, presenting for fertility treatment were randomized to either a 12-week intervention (n = 27) consisting of a very-low-energy diet for the initial 6 weeks followed by a hypocaloric diet, combined with a weekly group multidisciplinary programme; or a control group (n = 22) who received recommendations for weight loss and the same printed material as the intervention. Anthropometric and reproductive parameters were measured at baseline and at 12 weeks. The 22 women who completed the intervention had greater anthropometric changes (-6.6 ± 4.6 kg and -8.7 ± 5.6 cm vs. -1.6 ± 3.6 kg and -0.6 ± 6.3 cm) compared with the control group (n = 17; P < 0.001). The intervention group achieved a pregnancy rate of 48% compared with 14% (P = 0.007), took a mean two fertility treatment cycles to achieve each pregnancy compared with four in the control group (P = 0.002), and had a marked increase in the number of live births (44% vs. 14%; P = 0.02). A group weight loss programme, incorporating dietary, exercise and behavioural components, is associated with a significant improvement in pregnancy rates and live births in a group of obese women undergoing fertility treatment.
10.1111/cob.12048
[Obesity and reproduction: a literature review].
Le Goff S,Lédée N,Bader G
Gynecologie, obstetrique & fertilite
Obesity is a growing public health problem because of the morbimortality factors linked to it. In obstetrics and gynecology, consequences on fertility and contraception are notable: infertility, low assisted reproductive technologies (ART) results, miscarriages, congenital abnormalities, obstetrical and neonatal complications, low hormonal contraception efficacy. These effects are partially corrected by weight loss which can be achieved by behavioural, medical or surgical treatment. Gynaecologists should always participate in a multidisciplinary management of obesity before hormonal contraception or ART.
10.1016/j.gyobfe.2008.03.005
The impact of obesity on reproduction in women.
Al-Nuaim Lulu A
Saudi medical journal
Obesity can impact on reproductive functions by causing hormonal imbalance and ovulatory dysfunction. Furthermore, obesity is associated with a range of adverse health consequences. There is a tight coupling between the reproductive system and energy balance. Obesity results from chronic imbalance between energy intake and energy expenditure, and therefore changes in energy expenditure impact on the reproductive system. Physical activity, through its effect on energy expenditure, plays an imperative role in maintaining energy balance and thus improving health. It is therefore recommended that weight loss is the best and the cheapest therapy for infertile obese women.
Female obesity is negatively associated with live birth rate following IVF: a systematic review and meta-analysis.
Sermondade Nathalie,Huberlant Stéphanie,Bourhis-Lefebvre Vanessa,Arbo Elisangela,Gallot Vanessa,Colombani Marina,Fréour Thomas
Human reproduction update
BACKGROUND:A worldwide increase in the prevalence of obesity has been observed in the past three decades, particularly in women of reproductive age. Female obesity has been clearly associated with impaired spontaneous fertility, as well as adverse pregnancy outcomes. Increasing evidence in the literature shows that obesity also contributes to adverse clinical outcomes following in vitro fertilization (IVF) procedures. However, the heterogeneity of the available studies in terms of populations, group definition and outcomes prevents drawing firm conclusions. A previous meta-analysis published in 2011 identified a marginal but significant negative effect of increased female body mass index (BMI) on IVF results, but numerous studies have been published since then, including large cohort studies from national registries, highlighting the need for an updated review and meta-analysis. OBJECTIVE AND RATIONALE:Our systematic review and meta-analysis of the available literature aims to evaluate the association of female obesity with the probability of live birth following IVF. Subgroup analyses according to ovulatory status, oocyte origin, fresh or frozen-embryo transfer and cycle rank were performed. SEARCH METHODS:A systematic review was performed using the following key words: ('obesity', 'body mass index', 'live birth', 'IVF', 'ICSI'). Searches were conducted in MEDLINE, EMBASE, Cochrane Library, Eudract and clinicaltrial.gov from 01 January 2007 to 30 November 2017. Study selection was based on title and abstract. Full texts of potentially relevant articles were retrieved and assessed for inclusion by two reviewers. Subsequently, quality was assessed using the Newcastle-Ottawa Quality Assessment Scales for patient selection, comparability and assessment of outcomes. Two independent reviewers carried out study selection and data extraction according to Cochrane methods. Random-effect meta-analysis was performed using Review Manager software on all data (overall analysis), followed by subgroup analyses. OUTCOMES:A total of 21 studies were included in the meta-analysis. A decreased probability of live birth following IVF was observed in obese (BMI ≥ 30 kg/m2) women when compared with normal weight (BMI 18.5-24.9 kg/m2) women: risk ratio (RR) (95% CI) 0.85 (0.82-0.87). Subgroups analyses demonstrated that prognosis was poorer when obesity was associated with polycystic ovary syndrome, while the oocyte origin (donor or non-donor) did not modify the overall interpretation. WIDER IMPLICATIONS:Our meta-analysis clearly demonstrates that female obesity negatively and significantly impacts live birth rates following IVF. Whether weight loss can reverse this deleterious effect through lifestyle modifications or bariatric surgery should be further evaluated.
10.1093/humupd/dmz011
Impact of Female Obesity on Cumulative Live Birth Rates in the First Complete Ovarian Stimulation Cycle.
Ding Wen,Zhang Fu-Li,Liu Xiao-Cong,Hu Lin-Li,Dai Shan-Jun,Li Gang,Kong Hui-Juan,Guo Yi-Hong
Frontiers in endocrinology
Female overweight/obesity has been reported to be associated with compromised pregnancy outcomes in fresh embryo transfer cycles. It is unclear whether the cumulative live birth rate (CLBR) is adversely affected after all viable embryos are transferred from the first ovarian stimulation cycle. To investigate whether the CLBR was compromised in obese women. A total of 9,772 young women underwent their first IVF/ICSI cycles from January 2012 to October 2017. Pregnancy outcomes were compared according to female BMI. Among 1,671 women with polycystic ovary syndrome (PCOS), those with a BMI ≥ 28 kg/m had a lower cumulative clinical pregnancy rate (CCPR) and CLBR during the first complete ovarian stimulation cycle. Additionally, the pregnancy loss rate was increased in this group, although the difference was not significant. Among the 8,101 women without PCOS, the CCPR and CLBR of obese patients was also significantly decreased, and this group also showed increased pregnancy loss rates. Moreover, overweight women also had a decreased CLBR. Female obesity adversely affected the CLBR after utilizing the viable embryos from first oocytes retrieval.
10.3389/fendo.2019.00516
Female obesity and infertility.
Talmor Alon,Dunphy Bruce
Best practice & research. Clinical obstetrics & gynaecology
Infertility affects one in seven couples, and its rate is on the increase. Ovulatory defects and unexplained causes account for >50% of infertile aetiologies. It is postulated that a significant proportion of these cases are either directly or indirectly related to obesity. The prevalence of overweight and obese men and women has topped 50% in some developed countries. Obesity is on the increase worldwide; in turn, the consequences in terms of the associated morbidity and mortality have also been increasing. Obesity is associated with various reproductive sequelae including anovulation, subfertility and infertility, increased risk of miscarriage and poor neonatal and maternal pregnancy outcomes. Thus, the combination of infertility and obesity poses some very real challenges in terms of both the short- and long-term management of these patients. The mechanism with which obesity impacts female reproductive function is summarised in this review.
10.1016/j.bpobgyn.2014.10.014