maternal obesity and risk of spontaneous abortion

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Symposium Abstracts / Journal of Reproductive Immunology 90 (2011) 131–163 139 S16 Recurrent pregnancy loss in obese women-is it an inde- pendent risk factor? M. Metwally Ninewells Hospital and the University of Dundee, Dundee, United Kingdom Introduction: There is significant evidence from the lit- erature to suggest an increased risk of miscarriage in obese women. The mechanism for this relationship is still largely unknown but may be a result of an adverse effect on the embryo, endometrium or both. Materials and methods: In this presentation we explore the findings of several studies from our group as well as others that have attempted to explore this complex association. Results: Firstly we explore the epidemiological rela- tionship between obesity and miscarriage by evidence from two studies. The first was a meta-analysis of the cur- rent literature that showed obesity to be associated with a small but significant risk of miscarriage both in the general population and in women undergoing assisted conception. The second was a retrospective study of 844 pregnan- cies from women suffering from recurrent miscarriage. The results again demonstrated that obesity causes a small but significant increased risk of miscarriage in the subsequent pregnancy. We then go on to explore the possible mech- anisms behind this increased miscarriage risk. Findings from a retrospective study of endometrial function in the peri-implantation period demonstrated a significant nega- tive correlation between endometrial glandular leukaemia inhibitory factor (LIF) concentrations and BMI. Yet another study describing the protein profile in the perimplantation endometrium showed that obesity was associated with a positive effect on haptoglobin expression. Both LIF and haptoglobin are inflammatory markers and point to a pos- sible local inflammatory endometrial condition in obese women. Our final study examined the effect of obesity on embryo quality in women undergoing in Vitro Fertilisation and showed that obesity is associated with poorer embryo quality in patients less than 35 years of age. Conclusions: Findings from these studies as well as from other groups demonstrate that obesity increases the risk of miscarriage as a result of an adverse effect on both the endometrium and developing embryo. More studies are needed to examine the exact nature of these defects but preliminary evidence points to a possible inflammatory condition. doi:10.1016/j.jri.2011.06.018 S17 Obesity, inflammation and early pregnancy loss F.C. Denison MRC Centre for Reproductive Health, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh, United King- dom Maternal obesity is the commonest co-morbidity in pregnancy and currently affects one in five of the antenatal population. In early pregnancy, maternal obesity is associ- ated with an increased risk of miscarriage, and congenital anomalies in the offspring. Later in pregnancy, maternal obesity is associated with increased risk of gestational diabetes, pre-eclampsia, peripartum complications, still- birth and fetal macrosomia. However, the mechanisms that link poor obstetric outcome to pre-pregnancy obesity are not well understood. This paper will review the evidence base for maternal and fetal factors, which have been sug- gested as mediating adverse pregnancy outcome. These will include systemic inflammation, endothelial dysfunc- tion, maternal metabolism, oocyte and embryo quality and the endometrial receptivity. doi:10.1016/j.jri.2011.06.019 S18 Maternal obesity and risk of spontaneous abortion A. Aghamohammadi , A. Zafari, A. Rajabi Islamic Azad University, Sari Branch, Iran Introduction: Because of the increasing epidemic of obesity and the fact that obesity is linked with several known disorders, there has been concern that obesity may have effects on pregnancy. The purpose of this study was to determine whether obesity increases the risk of sponta- neous abortion. Material and methods: In this cohort study, nulliparous pregnant women who presented to perinatal care center Imam Khomeyni hospital Sari Iran were included in this study. Weight and height in all women were measured. The omission measures of the sample was included these cases: all the woman under 20 years and beyond 35, smoking and addicted women, pregnancy with the fertility aid methods, multigravida in present pregnancy, suffering from known physical and mental diseases, uterine pathology or clinical history of antiphospholipid antibodies or recurrent abor- tion. Spontaneous abortion rates were compared among the four BMI groups: normal weight, overweight, obese and morbidly obese. Chi-Square and Odds-Ratio were used in this study. Results: There were significant differences in abor- tion rates between the morbidly obese (42.1%), the obese (25.3%), and the normal (12.3%) and overweight (14.7%) groups. Compared with the normal weight group, the obese and morbidly obese had a significant increase in the risk of spontaneous abortion. Conclusions: Our findings showed that obesity is a risk factor for spontaneous abortion. Therefore, obese patients

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Page 1: Maternal obesity and risk of spontaneous abortion

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Symposium Abstracts / Journal of Re

16

ecurrent pregnancy loss in obese women-is it an inde-endent risk factor?

. Metwally

Ninewells Hospital and the University of Dundee, Dundee,nited Kingdom

Introduction: There is significant evidence from the lit-rature to suggest an increased risk of miscarriage in obeseomen. The mechanism for this relationship is still largelynknown but may be a result of an adverse effect on thembryo, endometrium or both.

Materials and methods: In this presentation wexplore the findings of several studies from our group asell as others that have attempted to explore this complex

ssociation.Results: Firstly we explore the epidemiological rela-

ionship between obesity and miscarriage by evidencerom two studies. The first was a meta-analysis of the cur-ent literature that showed obesity to be associated with amall but significant risk of miscarriage both in the generalopulation and in women undergoing assisted conception.he second was a retrospective study of 844 pregnan-ies from women suffering from recurrent miscarriage. Theesults again demonstrated that obesity causes a small butignificant increased risk of miscarriage in the subsequentregnancy. We then go on to explore the possible mech-nisms behind this increased miscarriage risk. Findingsrom a retrospective study of endometrial function in theeri-implantation period demonstrated a significant nega-ive correlation between endometrial glandular leukaemianhibitory factor (LIF) concentrations and BMI. Yet anothertudy describing the protein profile in the perimplantationndometrium showed that obesity was associated withpositive effect on haptoglobin expression. Both LIF andaptoglobin are inflammatory markers and point to a pos-ible local inflammatory endometrial condition in obeseomen. Our final study examined the effect of obesity on

mbryo quality in women undergoing in Vitro Fertilisationnd showed that obesity is associated with poorer embryouality in patients less than 35 years of age.

Conclusions: Findings from these studies as well asrom other groups demonstrate that obesity increases theisk of miscarriage as a result of an adverse effect on bothhe endometrium and developing embryo. More studiesre needed to examine the exact nature of these defects

ut preliminary evidence points to a possible inflammatoryondition.

oi:10.1016/j.jri.2011.06.018

ve Immunology 90 (2011) 131–163 139

S17

Obesity, inflammation and early pregnancy loss

F.C. Denison

MRC Centre for Reproductive Health, University of Edinburgh,Queen’s Medical Research Institute, Edinburgh, United King-dom

Maternal obesity is the commonest co-morbidity inpregnancy and currently affects one in five of the antenatalpopulation. In early pregnancy, maternal obesity is associ-ated with an increased risk of miscarriage, and congenitalanomalies in the offspring. Later in pregnancy, maternalobesity is associated with increased risk of gestationaldiabetes, pre-eclampsia, peripartum complications, still-birth and fetal macrosomia. However, the mechanisms thatlink poor obstetric outcome to pre-pregnancy obesity arenot well understood. This paper will review the evidencebase for maternal and fetal factors, which have been sug-gested as mediating adverse pregnancy outcome. Thesewill include systemic inflammation, endothelial dysfunc-tion, maternal metabolism, oocyte and embryo quality andthe endometrial receptivity.

doi:10.1016/j.jri.2011.06.019

S18

Maternal obesity and risk of spontaneous abortion

A. Aghamohammadi ∗, A. Zafari, A. Rajabi

Islamic Azad University, Sari Branch, Iran

Introduction: Because of the increasing epidemic ofobesity and the fact that obesity is linked with severalknown disorders, there has been concern that obesity mayhave effects on pregnancy. The purpose of this study wasto determine whether obesity increases the risk of sponta-neous abortion.

Material and methods: In this cohort study, nulliparouspregnant women who presented to perinatal care centerImam Khomeyni hospital Sari Iran were included in thisstudy. Weight and height in all women were measured. Theomission measures of the sample was included these cases:all the woman under 20 years and beyond 35, smoking andaddicted women, pregnancy with the fertility aid methods,multigravida in present pregnancy, suffering from knownphysical and mental diseases, uterine pathology or clinicalhistory of antiphospholipid antibodies or recurrent abor-tion. Spontaneous abortion rates were compared amongthe four BMI groups: normal weight, overweight, obese andmorbidly obese. Chi-Square and Odds-Ratio were used inthis study.

Results: There were significant differences in abor-tion rates between the morbidly obese (42.1%), the obese(25.3%), and the normal (12.3%) and overweight (14.7%)groups. Compared with the normal weight group, the obese

and morbidly obese had a significant increase in the risk ofspontaneous abortion.

Conclusions: Our findings showed that obesity is a riskfactor for spontaneous abortion. Therefore, obese patients

Page 2: Maternal obesity and risk of spontaneous abortion

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140 Symposium Abstracts / Journal of Re

should be required to reduce weight before becoming preg-nant.

Keywords: Spontaneous abortion; Obesity

doi:10.1016/j.jri.2011.06.020

S19

Oxidative stress, innate immunity and sperm quality

M. Kurpisz a,∗, F. Monika a, P. Małgorzata b, J. Piotr c

a Institute of Human Genetics, Pol. Acad. Sci., Poznan, Polandb Laboratory of Histology and Developmental Biology,Pomeranian Medical University, Szczecin, Polandc Department of Infertility and Reproductive Endocrinology,Poznan Medical University, Poznan, Poland

Introduction: Oxidative stress underlies a wide rangeof pathologies including male reproductive system. It isusually associated to inflammation of reproductive tract,it may be also idiopathic (unknown reason) or endogenousdue to inefficiency of antioxidative system which in normalcircumstances may counterattack subclinical conditions ofdiseases. Since ‘male factor’ of infertility is still on rise themolecular background of this phenomenon must be care-fully elucidated.

Material and methods: We selected a group of indi-viduals with inflammatory processes and divided theminto normozoospermic males and men with pathologi-cal spermiogram. Pro-inflammatory cytokines (IL-1, IL-6,TNF�) were evaluated by ELISA as well as pro-oxidants(xanthine oxidase) and antioxidants (superoxide dis-mutase, catalase) either spectrophotometrically or bychemilumenscence. In another cohort, infertile malesapproaching an assisted reproductive clinic were evaluatedfor aerobic and anaerobic bacteria, malonylodialdehydecontent (MDA) in semen and cytokines (IL-8), and theseparameters were correlated with fertilized versus non-fertilized group. In another set of studies, we have animatedin situ inflammation of semen using collected normo-zoospermic samples, leukocytes (WBC), selected bacteriastrains and combinations of pro-inflammatory cytokines(IL-6 + IL-8, IL-12 + IL-18) while evaluating ROS secretion,MDA levels as well as apoptosis in TUNEL and Comet assaysto confirm earlier in situ observations. Lastly we have exam-ined sperm membrane integrity (live/dead sperm viabilityassay and by merocyanine 540) and mitochondrial activity(JC-1 and NADH-dependent NBT assay).

Results: We have discovered an interesting pattern ofreactions in in situ inflammation of the genitourinary tractwhile examining fertile versus infertile individuals. In thefirst cohort, IL-6 was elevated while in the second cohort,IL-1 and TNF� have been observed. Oxido-sensitive indicesin semen behaved differently in these cohorts—infertilemales had clear inefficiency of enzymatic antioxidantsthus requiring supplementary therapy. In ART scenario,almost 80% of individuals had a history of infection andelevated IL-8 while MDA levels were inversely related

with penetration of oocytes in IVF. Animation of inflam-matory conditions in vitro revealed clear and active effectof selected bacteria strains on ROS release while after addi-

ve Immunology 90 (2011) 131–163

tion of leukocytes, this effect was significantly augmentedwhen looking at MDA levels. An indirect effect of cytokineson oxidative stress was also documented. Selected combi-nations of cytokines (IL-6 + IL-8, IL-12 + IL18) exerted a cleareffect on apoptosis in both applied assays. Additionally allbacteria strains utilised (aerobes and anaerobes) signifi-cantly affected sperm plasma architecture while clearlydecreasing the sperm population with high mitochondrialtransmembrane potential.

Conclusions: These in vivo, in situ and in vitro studiesconfirmed each other and validated a suspicion that oxida-tive stress is linked mostly with innate immunity affectingthe interplay between bacteria, leukocytes and cytokinesand deteriorating sperm quality. Observation of redox bal-ance in semen may be particularly useful in male idiopathicinfertility. Further link between oxidative stress, spermquality and its possible implications on pregnancy mustbe also considered.

doi:10.1016/j.jri.2011.06.021

S20

Ovarian reserve and early pregnancy: the clinical rela-tion between oocyte quantity and oocyte quality

M.L. Haadsma a,∗, H. Groen b, M.J. Heineman c,d, T.M.Mooij e, C.B. Lambalk f, F.J.M. Broekmans g, F.E. vanLeeuwen e, A. Hoek c

a Department of Genetics, University Medical Center Gronin-gen, University of Groningen, The Netherlandsb Department of Epidemiology, University Medical CenterGroningen, University of Groningen, The Netherlandsc Department of Obstetrics and Gynaecology, UniversityMedical Center Groningen, University of Groningen, TheNetherlandsd Department of Obstetrics and Gynaecology, Academic Med-ical Center, Amsterdam, The Netherlandse Department of Epidemiology, Netherlands Cancer Institute,Amsterdam, The Netherlandsf Department of Obstetrics and Gynaecology, Vrije UniversiteitMedical Center, Amsterdam, The Netherlandsg Department of Reproductive Medicine and Gynaecology,University Medical Center Utrecht, The Netherlands

Introduction: As the age of a woman increases, hermonthly chance to conceive declines, whereas her chanceof having a miscarriage or a child with a chromoso-mal abnormality increases. This phenomenon of femalereproductive ageing is attributed to a decline in boththe quantity and the quality of a woman’s oocytes. Thedecrease in oocyte quantity eventually leads to menopause.The decrease in oocyte quality is caused by an increase inmeiotic errors, resulting in oocytes with a deviant num-ber of chromosomes. It is unknown whether the decline inoocyte quantity is related to the decline in oocyte quality. Ifso, the estimated number of remaining oocytes of a womanmay be predictive for her chance of conception, miscarriage

or a child with a chromosomal aberration.

Materials and methods: We performed several stud-ies on the clinical relation between oocyte quantity and