Advertisement

The impact of food intake and social habits on embryo quality and the likelihood of blastocyst formation

Published:March 26, 2015DOI:https://doi.org/10.1016/j.rbmo.2015.03.007

      Abstract

      The aim of this study was to evaluate the influence of patients' lifestyle factors and eating habits on embryo development. A total of 2659 embryos recovered from 269 patients undergoing intracytoplasmic sperm injection cycles were included. The frequency of intake of food items and social habits were registered and its influences on embryo development evaluated. The consumption of cereals, vegetables and fruits positively influenced the embryo quality at the cleavage stage. The quality of the embryo at the cleavage stage was also negatively correlated with the consumption of alcoholic drinks and smoking habits. The consumption of fruits influenced the likelihood of blastocyst formation, which was also positively affected by the consumption of fish. Being on a weight-loss diet and consumption of red meat had a negative influence on the likelihood of blastocyst formation. The likelihood of blastocyst formation was also negatively influenced by the consumption of alcoholic drinks and by smoking habits. The consumption of red meat and body mass index had a negative effect on the implantation rate and the likelihood of pregnancy. In addition, being on a weight-loss diet had a negative influence on implantation rate. Our evidence suggests a possible relationship between environmental factors and ovary biology.

      Keywords

      Introduction

      Infertility affects between 8 and 16% of reproductive-aged couples (
      • Stephen E.H.
      • Chandra A.
      Declining estimates of infertility in the United States: 1982–2002.
      ). Over the past 2 decades, the use of assisted reproduction techniques has increased dramatically worldwide, and has made pregnancy possible for many infertile couples. Although high-quality embryos may be available for transfer, however, most in-vitro-produced embryos fail to implant (
      • de Mouzon J.
      • Goossens V.
      • Bhattacharya S.
      • Castilla J.A.
      • Ferraretti A.P.
      • Korsak V.
      • Kupka M.
      • Nygren K.G.
      • Andersen A.N.
      Assisted reproductive technology in Europe, 2007: results generated from European registers by ESHRE.
      ).
      The identification of factors that may influence the implantation of in-vitro-produced embryos is one of the most studied areas in assisted reproduction techniques. Special attention has been paid to the effects of the patient's lifestyle on the outcomes of assisted reproduction techniques. Lifestyle factors and nutritional status are known to be critical determinants of normal reproductive function (
      • Chavarro J.E.
      • Rich-Edwards J.W.
      • Rosner B.A.
      • Willett W.C.
      Protein intake and ovulatory infertility.
      ). Menopause has been reported to occur earlier (
      • Midgette A.S.
      • Baron J.A.
      Cigarette smoking and the risk of natural menopause.
      ) and conception to be delayed for over 1 year (
      • Baird D.D.
      • Wilcox A.J.
      Cigarette smoking associated with delayed conception.
      ) among smokers compared with non-smokers. Moreover, cigarette smoking may impair sperm motility, decrease antioxidant activity in the seminal plasma (
      • Pasqualotto F.F.
      • Umezu F.M.
      • Salvador M.
      • Borges Jr., E.
      • Sobreiro B.P.
      • Pasqualotto E.B.
      Effect of cigarette smoking on antioxidant levels and presence of leukocytospermia in infertile men: a prospective study.
      ) and lead to increased thickness of the zona pellucida (
      • Shiloh H.
      • Lahav-Baratz S.
      • Koifman M.
      • Ishai D.
      • Bidder D.
      • Weiner-Meganzi Z.
      • Dirnfeld M.
      The impact of cigarette smoking on zona pellucida thickness of oocytes and embryos prior to transfer into the uterine cavity.
      ).
      Obesity and low body weight may also impair fertility. A high body mass index (BMI) has been shown to adversely affect the outcomes of assisted reproduction technique treatment (
      • Fedorcsak P.
      • Dale P.O.
      • Storeng R.
      • Ertzeid G.
      • Bjercke S.
      • Oldereid N.
      • Omland A.K.
      • Abyholm T.
      • Tanbo T.
      Impact of overweight and underweight on assisted reproduction treatment.
      ,
      • Nichols J.E.
      • Crane M.M.
      • Higdon H.L.
      • Miller P.B.
      • Boone W.R.
      Extremes of body mass index reduce in vitro fertilization pregnancy rates.
      ), and physical activity positively affects embryo implantation and the chance of pregnancy (
      • Ferreira R.C.
      • Halpern G.
      • Figueira Rde C.
      • Braga D.P.
      • Iaconelli Jr., A.
      • Borges Jr., E.
      Physical activity, obesity and eating habits can influence assisted reproduction outcomes.
      ). Other aspects of the patient's diet may affect fertility, such as certain vitamins and food groups that could have a greater effect on reproductive health for both males and females (
      • Chavarro J.E.
      • Rich-Edwards J.W.
      • Rosner B.A.
      • Willett W.C.
      Dietary fatty acid intakes and the risk of ovulatory infertility.
      ,
      • Chavarro J.E.
      • Rich-Edwards J.W.
      • Rosner B.A.
      • Willett W.C.
      Protein intake and ovulatory infertility.
      ,
      • Keskes-Ammar L.
      • Feki-Chakroun N.
      • Rebai T.
      • Sahnoun Z.
      • Ghozzi H.
      • Hammami S.
      • Zghal K.
      • Fki H.
      • Damak J.
      • Bahloul A.
      Sperm oxidative stress and the effect of an oral vitamin E and selenium supplement on semen quality in infertile men.
      ,
      • Mendiola J.
      • Torres-Cantero A.M.
      • Vioque J.
      • Moreno-Grau J.M.
      • Ten J.
      • Roca M.
      • Moreno-Grau S.
      • Bernabeu R.
      A low intake of antioxidant nutrients is associated with poor semen quality in patients attending fertility clinics.
      ,
      • Silver E.W.
      • Eskenazi B.
      • Evenson D.P.
      • Block G.
      • Young S.
      • Wyrobek A.J.
      Effect of antioxidant intake on sperm chromatin stability in healthy nonsmoking men.
      ).
      Extended embryo culture and the transfer of blastocyst-stage embryos are associated with increased implantation rates compared with cleavage-stage embryo transfer (
      • Blake D.A.
      • Farquhar C.M.
      • Johnson N.
      • Proctor M.
      Cleavage stage versus blastocyst stage embryo transfer in assisted conception.
      ,
      • Papanikolaou E.G.
      • Kolibianakis E.M.
      • Tournaye H.
      • Venetis C.A.
      • Fatemi H.
      • Tarlatzis B.
      • Devroey P.
      Live birth rates after transfer of equal number of blastocysts or cleavage-stage embryos in IVF. A systematic review and meta-analysis.
      ). Prolonging the culture period allows for a better selection of embryos for transfer because laboratory assessment is undertaken after the embryonic genome has begun to be expressed (
      • Tesarik J.
      • Kopecny V.
      • Plachot M.
      • Mandelbaum J.
      Early morphological signs of embryonic genome expression in human preimplantation development as revealed by quantitative electron microscopy.
      ). Moreover, because of their high implantation rate, single-blastocyst transfers may increase the pregnancy rate and reduce the frequency of multiple gestations (
      • Gardner D.K.
      • Surrey E.
      • Minjarez D.
      • Leitz A.
      • Stevens J.
      • Schoolcraft W.B.
      Single blastocyst transfer: a prospective randomized trial.
      ,
      • Ryan G.L.
      • Sparks A.E.
      • Sipe C.S.
      • Syrop C.H.
      • Dokras A.
      • Van Voorhis B.J.
      A mandatory single blastocyst transfer policy with educational campaign in a United States IVF program reduces multiple gestation rates without sacrificing pregnancy rates.
      ). The proportion of embryos that develop to the blastocyst stage, however, is still variable (
      • Mercader A.
      • Garcia-Velasco J.A.
      • Escudero E.
      • Remohi J.
      • Pellicer A.
      • Simon C.
      Clinical experience and perinatal outcome of blastocyst transfer after coculture of human embryos with human endometrial epithelial cells: a 5-year follow-up study.
      ,
      • Schoolcraft W.B.
      • Gardner D.K.
      Blastocyst versus day 2 or 3 transfer.
      ,
      • Westphal L.M.
      • Hinckley M.D.
      • Behr B.
      • Milki A.A.
      Effect of ICSI on subsequent blastocyst development and pregnancy rates.
      ), and eventually, embryo transfer cancellation may occur in extended embryo culture programmes.
      Different factors may be responsible for the variation in the rate of blastocyst formation, such as the culture media (
      • Biggers J.D.
      • Racowsky C.
      The development of fertilized human ova to the blastocyst stage in KSOM(AA) medium: is a two-step protocol necessary?.
      ,
      • Macklon N.S.
      • Pieters M.H.
      • Hassan M.A.
      • Jeucken P.H.
      • Eijkemans M.J.
      • Fauser B.C.
      A prospective randomized comparison of sequential versus monoculture systems for in-vitro human blastocyst development.
      ,
      • Sepulveda S.
      • Garcia J.
      • Arriaga E.
      • Diaz J.
      • Noriega-Portella L.
      • Noriega-Hoces L.
      In vitro development and pregnancy outcomes for human embryos cultured in either a single medium or in a sequential media system.
      ), laboratory conditions (
      • Lane M.
      • Mitchell M.
      • Cashman K.S.
      • Feil D.
      • Wakefield S.
      • Zander-Fox D.L.
      To QC or not to QC: the key to a consistent laboratory?.
      ,
      • Meintjes M.
      • Chantilis S.J.
      • Douglas J.D.
      • Rodriguez A.J.
      • Guerami A.R.
      • Bookout D.M.
      • Barnett B.D.
      • Madden J.D.
      A controlled randomized trial evaluating the effect of lowered incubator oxygen tension on live births in a predominantly blastocyst transfer program.
      ,
      • Waldenstrom U.
      • Engstrom A.B.
      • Hellberg D.
      • Nilsson S.
      Low-oxygen compared with high-oxygen atmosphere in blastocyst culture, a prospective randomized study.
      ), oocyte quality (
      • Catala M.G.
      • Izquierdo D.
      • Rodriguez-Prado M.
      • Hammami S.
      • Paramio M.T.
      Effect of oocyte quality on blastocyst development after in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in a sheep model.
      ,
      • Lin Y.C.
      • Chang S.Y.
      • Lan K.C.
      • Huang H.W.
      • Chang C.Y.
      • Tsai M.Y.
      • Kung F.T.
      • Huang F.J.
      Human oocyte maturity in vivo determines the outcome of blastocyst development in vitro.
      ) or sperm origin (
      • Nilsson S.
      • Waldenstrom U.
      • Engstrom A.B.
      • Hellberg D.
      Single blastocyst transfer after ICSI from ejaculate spermatozoa, percutaneous epididymal sperm aspiration (PESA) or testicular sperm extraction (TESE).
      ). Less is known, however, about the influence of patients' lifestyle on embryo quality and blastocyst formation. Therefore, the goal of the present study was to evaluate whether patients' lifestyle factors and eating habits can influence embryo quality, the likelihood of blastocyst formation and clinical outcomes in patients undergoing assisted reproduction techniques.

      Materials and methods

      Study design

      The study included 2659 embryos recovered from 269 patients undergoing intracytoplasmic sperm injection (ICSI) cycles between January 2012 and July 2013. All patients completed a questionnaire with multiple-choice questions before the beginning of the treatment. The women were asked about the frequency of their consumption of many food items and about their social habits.
      The effects of dietary and social habits on embryo quality on day three and the likelihood of blastocyst formation were evaluated. To evaluate the effects of dietary and social habits on the likelihood of blastocyst formation, 1400 embryos cultured until day 5 of development were evaluated. Moreover, the influence of dietary and social habits on clinical pregnancy rates was also investigated.
      Clinical pregnancy was defined as the presence of fetal heart activity by ultrasound at 6 to 7 weeks of gestation after embryo transfer. Written informed consent was obtained, in which patients agreed to share the outcomes of their own cycles for research purposes, and the study was approved by the local Institutional Review Board on 19 December 2012.

      Food consumption and social habits frequency questionnaire

      All patients were interviewed face-to-face before the beginning of the treatment. The modified validated questionnaire (
      • Ribeiro A.C.
      • SávioII K.E.O.
      • Rodrigues M.L.C.F.
      • Costa T.H.M.
      • Schmitz B.A.
      Validation of a food frequency questionnaire for the adult population.
      ) contained multiple-choice questions about the average frequency of consumption of food items during the past year.
      The food categories investigated in the present study were cereals, vegetables, legumes, fruits, red and pork meat, chicken, fish, dairy products, chocolate, soft drinks, caffeine-containing soft drinks, alcoholic drinks, dietary sweetener and coffee.
      The frequency of food consumption was registered on a scale with five values, ranging from no consumption to repeated daily consumption. The specific categories were never or less than once per month; one to three times per month; once per week; two to four times per week; and every day.
      The questionnaires were completed by the same interviewer, and a different questionnaire recorded information on exercise, weight-loss dieting in the past 3 months, the number of meals eaten per day and smoking habits. In addition, BMI was measured.
      Exercising was recorded on the following scale: less than 1 h per week; 1 h per week; 2 h per week; 3 h per week; 4 h per week; and 5 h or more per week. Smoking habits were recorded as the number of cigarettes smoked per day, and BMI was measured based on weight/height2 and expressed as Kg/m2.

      Ovarian stimulation

      Ovarian stimulation was achieved by pituitary suppression using a gonadotrophin-releasing hormone antagonist (Cetrotide; Serono, Geneva, Switzerland), and the ovarian stimulation was performed using recombinant FSH (Gonal-F; Serono, Geneva, Switzerland).
      Follicular growth was monitored using transvaginal ultrasound examination starting on day 4 of gonadotrophin administration. When adequate follicular growth and serum oestradiol levels were observed, recombinant human chorionic gonadotrophin (HCG) (Ovidrel; Serono, Geneva, Switzerland) was administered to trigger the final follicular maturation. The oocytes were collected 35 h after HCG administration through transvaginal ultrasound ovum retrieval.

      Preparation of oocytes

      The retrieved oocytes were maintained in culture media (Global® for fertilization; LifeGlobal, CT, USA) supplemented with 10% protein supplement (LGPS; LifeGlobal, CT, USA) and covered with paraffin oil (Paraffin oil P.G.; LifeGlobal, CT, USA) for 2–3 h before removal of cumulus cells. The surrounding cumulus cells were removed after exposure to a HEPES-buffered medium containing hyaluronidase (80 IU/mL; LifeGlobal, CT, USA). The remaining cumulus cells were mechanically removed by gently pipetting with a hand-drawn Pasteur pipette (Humagen Fertility Diagnostics, Charlottesville, USA).
      Oocytes that were observed to have released the first polar body were considered mature and were used for ICSI, which is carried out for all IVF cycles in this centre.

      Intracytoplasmic sperm injection

      A micro-injedtion dish prepared with 4 µl droplets of buffered medium (Global® with HEPES; LifeGlobal, CT, USA) was used to carry out ICSI and covered with paraffin oil on a heated stage (37.0 ± 0.5°C) of an inverted microscope. About 16 h after ICSI, fertilization was confirmed by the presence of two pronuclei and the extrusion of the second polar body. The embryos were maintained in a 50 µl drop of culture medium (Global®; LifeGlobal, CT, USA) supplemented with 10% protein supplement and covered with paraffin oil in a humidified atmosphere under 6% CO2 at 37°C for 3 days.

      Embryo morphology evaluation

      Embryo morphology was assessed as follows: 16–18 h after ICSI ± 1 h; 44 h ± 1 h after ICSI, for day two evaluation; 68 h ± 1 h after ICSI, for day 3 evaluation; 116 h ± 2 h after ICSI for day 5 evaluation; and 120 h ± 2 h after ICSI for late day 5 evaluation (transfer time). Embryo morphology was carried out using an inverted Nikon Diaphot microscope (Eclipse TE 300; Nikon, Tokyo, Japan) with a Hoffmann modulation contrast system under ×400 magnification.
      To evaluate cleavage-stage morphology, the following parameters were recorded: the number of blastomeres; the percentage of fragmentation; the variation in blastomere symmetry; the presence of multinucleation; and the defects in the zona pellucida and cytoplasm. High-quality cleavage-stage embryos were defined as those with all of the following characteristics: eight to 10 cells on day 3; less than 15% fragmentation; symmetric blastomeres; the absence of multinucleation; colourless cytoplasm with moderate granulation and no inclusions; the absence of perivitelline space granularity; and the absence of zona pellucida dysmorphism. Embryos lacking any of these characteristics were considered to be of low quality.
      To evaluate blastocyst formation, the embryos were classified based on their degree of expansion and hatching status, as follows: (i) an early blastocyst with a blastocoel that was less than one-half of the volume of the embryo; (ii) a blastocyst with a blastocoel that was greater than one-half of the volume of the embryo; (iii) a full blastocyst with a blastocoel that completely filled the embryo; (iv) an expanded blastocyst; (v) a hatching blastocyst; and (vi) a hatched blastocyst. Full, expanded, hatching and hatched blastocysts were considered for the blastocyst group, and the other embryos were considered for the non-blastocyst group.

      Statistical analysis

      Regression analyses were conducted to study the influence of specific food and beverage intake on the cleavage-stage embryo quality, blastocyst formation, implantation and the likelihood of pregnancy. Binary regression analyses were used when consumption was analysed (dichotomous variable), and ordinal regression analyses were used when the frequency of consumption (ordinal variable) was analysed. All regression analyses were adjusted for maternal age, the number of retrieved oocytes and the fertilization rate, as these variables were considered to be potential confounders in the association between the factors evaluated and the outcomes. The results were expressed as odds ratios (OR), 95% confidence intervals (CI) and P-values. The results were considered to be significant at the 5% critical level (P < 0.05). The data analysis was conducted using Minitab Statistical Software (version 16).

      Results

      Influence of food intake and social habits on embryo quality and the likelihood of blastocyst formation

      The consumption of cereals (OR 1.34, CI 1.09 to 1.59; P = 0.016), vegetables (OR 1.25, CI 1.06 to 1.38; P = 0.025) and fruits (OR 1.38, CI 1.07 to 1. 71; P = 0.018) positively influenced the embryo quality at the cleavage stage. The quality of the embryo on day 3 was negatively correlated with the consumption of alcoholic drinks (OR 0.75, CI 0.62 to 0.95; P = 0.032) and with smoking habits (OR 0.95, CI 0.82 to 0.99; P = 0.044) (Table 1).
      Table 1Regression analysis of eating and social habits that may affect the cleavage-stage embryo quality.
      Response variablePredictor cariableORCI lowerCI upperP-value
      Cleavage-stage embryo qualityCereals1.341.091.590.016
      Vegetables1.251.061.380.025
      Legumes1.020.861.32NS
      Fruits1.381.071.710.018
      Red meat0.810.651.00NS
      Fish1.051.011.36NS
      Chicken1.000.801.26NS
      Dairy products1.010.801.27NS
      Chocolate1.160.941.43NS
      Alcoholic drinks0.750.620.950.032
      Soft drinks0.920.820.104NS
      Caffeine-containing soft drinks1.130.771.68NS
      Dietary sweetener0.890.761.25NS
      Coffee1.330.991.63NS
      Exercise1.070.841.36NS
      Weight-loss diet0.890.681.17NS
      Smoking0.950.820.990.044
      Meals per day0.980.971.02NS
      BMI0.990.961.01NS
      BMI = body mass index; CI = confidence interval; NS = not statistically significant; OR = odds ratio.
      The quality of embryo on cleavage stage and also the conversion of embryos into blastocyst was influence by some food intake and other habits. An increase chance of formation of blastocysts with a blastocoel that completely fills the embryo, expanded blastocysts, and a hatching or hatched blastocysts was observed among patients who consumed fruits (OR 1.32, CI 1.08 to 1.63; P = 0.008) or fish (OR 1.31, CI 1.05 to 1.66; P = 0.018). Being on a weight-loss diet (OR 0.78, CI 0.62 to 0.98; P = 0.046) and the consumption of red meat (OR 0.81, CI 0.65 to 0.99; P = 0.049) had a negative influence on the likelihood of blastocyst formation, and, in similarity to the cleavage-stage embryo quality, the likelihood of blastocyst formation was negatively influenced by the consumption of alcoholic drinks (OR 0.75, CI 0.62 to 0.95; P = 0.032) and by smoking habits (OR 0.76, CI 0.56 to 0.94; P = 0.045) (Table 2).
      Table 2Regression analysis of eating and social habits that may affect the likelihood of blastocyst formation.
      Response variablePredictor cariableORCI lowerCI upperP-value
      Likelihood of blastocyst formationCereals1.010.801.28NS
      Vegetables1.020.901.02NS
      Legumes1.880.881.33NS
      Fruits1.321.081.630.008
      Red meat0.810.650.990.049
      Fish1.311.051.660.018
      Chicken1.000.801.26NS
      Dairy products1.010.801.27NS
      Chocolate0.890.681.17NS
      Alcoholic drinks0.750.620.950.032
      Soft drinks0.920.820.104NS
      Caffeine-containing soft drinks1.130.771.68NS
      Coffee1.330.991.63NS
      Dietary sweetener1.250.981.55NS
      Exercise1.070.841.36NS
      Weight-loss diet0.780.620.980.046
      Smoking0.760.560.940.045
      Meals per day0.980.971.02NS
      BMI0.990.961.01NS
      BMI = body mass index; CI = confidence interval; NS = not statistically significant; OR = odds ratio.
      Although the blastocyst formation and the hatching status were correlated with food intake and social habits, no association with the blastocyst quality (inner cell mass and trophectoderm morphology) was observed.

      Influence of food intake and social habits on ICSI outcomes

      The consumption of red meat (OR 0.68, CI 0.48 to 0.89; P = 0.042), BMI (OR 0.43, CI 0.25 to 0.93; P = 0.046) and being on a weight-loss diet (OR 0.79, CI 0.56 to 0.97; P = 0.016) had a negative effect on the likelihood of clinical pregnancy (Table 3).
      Table 3Binary regression analysis of eating and social habits that may affect the likelihood of clinical pregnancy.
      Response variablePredictor cariableORCI lowerCI upperP-value
      Clinical pregnancyCereals1.590.732.48NS
      Vegetables1.670.874.32NS
      Legumes1.930.332.47NS
      Fruits0.620.281.35NS
      Red meat0.680.480.890.042
      Fish0.810.361.81NS
      Chicken0.980.661.02NS
      Dairy products0.710.331.55NS
      Chocolate1.060.631.77NS
      Alcoholic drinks1.020.691.50NS
      Soft drinks0.930.621.39NS
      Coffee0.830.541.26NS
      Caffeine-containing soft drinks1.230.881.45NS
      Dietary sweetener0.810.561.56NS
      Exercise1.690.862.70NS
      Weight-loss diet0.790.560.970.011
      Smoking0.860.381.93NS
      BMI0.430.250.930.046
      BMI = Body mass index; CI = Confidence interval; OR = odds ratio.

      Discussion

      Recent studies have shown that infertility has drastically increased over the past decades (
      • Bushnik T.
      • Cook J.L.
      • Yuzpe A.A.
      • Tough S.
      • Collins J.
      Estimating the prevalence of infertility in Canada.
      ). This can be explained by a number of reasons. In addition to the delay in childbearing observed with women being older when first attempting pregnancy, environmental factors have identified as affecting general health and the capacity to reproduce.
      In the present study, the effect of specific food and beverage intake and other social habits on embryo quality, the likelihood of blastocyst formation and ICSI outcomes was evaluated. The results showed that the quality of the embryo and the likelihood of blastocyst formation were negatively influenced by the consumption of alcoholic drinks and by smoking habits.
      Although it is well documented that cigarette smoke contains many harmful substances, more research is needed to establish a link to infertility (
      • Roth L.K.
      • Taylor H.S.
      Risks of smoking to reproductive health: assessment of women's knowledge.
      ). Strong evidence supports the adverse effects of smoking on fertility, acting through different pathways (
      • Augood C.
      • Duckitt K.
      • Templeton A.A.
      Smoking and female infertility: a systematic review and meta-analysis.
      ,
      • Sharara F.I.
      • Beatse S.N.
      • Leonardi M.R.
      • Navot D.
      • Scott Jr., R.T.
      Cigarette smoking accelerates the development of diminished ovarian reserve as evidenced by the clomiphene citrate challenge test.
      ,
      • Soares S.R.
      • Simon C.
      • Remohi J.
      • Pellicer A.
      Cigarette smoking affects uterine receptiveness.
      ).
      • Feichtinger W.
      • Papalambrou K.
      • Poehl M.
      • Krischker U.
      • Neumann K.
      Smoking and in vitro fertilization: a meta-analysis.
      suggested that smokers require more assisted reproduction technique cycles than non-smokers do to achieve a pregnancy. Together with our findings, this evidence suggests that the substances that are inhaled through cigarette smoking may affect a growing follicle during gametogenesis, affecting the quality of the oocyte and thus the quality of the embryo, its developmental competence and its implantation potential.
      In the present study, alcohol consumption in addition to cigarette smoking was shown to affect embryo development. Alcohol consumption has been reported to impair fertility, although the level of consumption associated with the risk is unclear. A high level of alcohol consumption is known to affect the fetus (
      • Goransson M.
      • Magnusson A.
      • Bergman H.
      • Rydberg U.
      • Heilig M.
      Fetus at risk: prevalence of alcohol consumption during pregnancy estimated with a simple screening method in Swedish antenatal clinics.
      ,
      • Krulewitch C.J.
      Alcohol consumption during pregnancy.
      ), but the effect on fertility at lower levels is still unknown. The mechanisms by which alcohol could impair conception are unclear but may include an alcohol-induced rise in oestrogen, which reduces FSH secretion, suppressing folliculogenesis (
      • Homan G.F.
      • Davies M.
      • Norman R.
      The impact of lifestyle factors on reproductive performance in the general population and those undergoing infertility treatment: a review.
      ).
      In the present study, the questionnaire was conducted before starting treatment. Even though the nutritionist counsels the patients to stop or at least reduce smoking and alcohol habits before and especially during the treatment, we were, unfortunately, unable to ensure that this happened. In fact, many times we did not know if patients were smoking at the time of treatment, and this is a drawback of these types of studies.
      Recently, the effect of pollutants and occupational factors on reproductive health has been a matter of debate. Environmental pollutants, such as methyl mercury, pesticides, lead, welding, organic solvents, radiation, xenoestrogens and household glues have been shown to have a negative effect on fertility (
      • Bretveld R.
      • Kik S.
      • Hooiveld M.
      • van Rooij I.
      • Zielhuis G.
      • Roeleveld N.
      Time-to-pregnancy among male greenhouse workers.
      ,
      • Foster W.G.
      • Neal M.S.
      • Han M.S.
      • Dominguez M.M.
      Environmental contaminants and human infertility: hypothesis or cause for concern?.
      ,
      • Homan G.F.
      • Davies M.
      • Norman R.
      The impact of lifestyle factors on reproductive performance in the general population and those undergoing infertility treatment: a review.
      ,
      • McDiarmid M.A.
      • Gardiner P.M.
      • Jack B.W.
      The clinical content of preconception care: environmental exposures.
      ,
      • Mendiola J.
      • Torres-Cantero A.M.
      • Moreno-Grau J.M.
      • Ten J.
      • Roca M.
      • Moreno-Grau S.
      • Bernabeu R.
      Exposure to environmental toxins in males seeking infertility treatment: a case-controlled study.
      ,
      • Mendola P.
      • Messer L.C.
      • Rappazzo K.
      Science linking environmental contaminant exposures with fertility and reproductive health impacts in the adult female.
      ). In the present study, the consumption of red meat had a negative effect on embryo development and the likelihood of pregnancy. This finding is consistent with the poor fertility associated with a higher intake of products that may contain xenoestrogens, and endocrine-disrupting compound (EDC). The use of these EDC compounds in the food industry may result in an increased level of sex steroids in processed foods, such as meat or milk (
      • Bushnik T.
      • Cook J.L.
      • Yuzpe A.A.
      • Tough S.
      • Collins J.
      Estimating the prevalence of infertility in Canada.
      ,
      • Fusani L.
      • Della Seta D.
      • Dessi-Fulgheri F.
      • Farabollini F.
      Altered reproductive success in rat pairs after environmental-like exposure to xenoestrogen.
      ,
      • Milnes M.R.
      • Bermudez D.S.
      • Bryan T.A.
      • Edwards T.M.
      • Gunderson M.P.
      • Larkin I.L.
      • Moore B.C.
      • Guillette Jr., L.J.
      Contaminant-induced feminization and demasculinization of nonmammalian vertebrate males in aquatic environments.
      ).
      In addition, the negative effect of the consumption of red meat on embryo development and the likelihood of pregnancy may be due to the increase in the absorption of advanced glycation end-products (AGE). These are compounds created through the non-enzymatic reaction between reducing sugars and free amino groups in proteins, lipids or nucleic acids (
      • Singh R.
      • Barden A.
      • Mori T.
      • Beilin L.
      Advanced glycation end-products: a review.
      ). Animal-derived foods that are high in fat and protein are generally rich in AGE and are also prone to new AGE formation during the cooking process (
      • Uribarri J.
      • Woodruff S.
      • Goodman S.
      • Cai W.
      • Chen X.
      • Pyzik R.
      • Yong A.
      • Striker G.E.
      • Vlassara H.
      Advanced glycation end products in foods and a practical guide to their reduction in the diet.
      ). Formation and accumulation of AGE occurs during normal ageing and may cause tissue and intracellular damage directly by macromolecular trapping and cross-linking and also indirectly by binding to specific AGE receptors (RAGE) on cell surfaces (
      • Thomas M.C.
      • Baynes J.W.
      • Thorpe S.R.
      • Cooper M.E.
      The role of AGEs and AGE inhibitors in diabetic cardiovascular disease.
      ).
      • Jinno M.
      • Takeuchi M.
      • Watanabe A.
      • Teruya K.
      • Hirohama J.
      • Eguchi N.
      • Miyazaki A.
      Advanced glycation end-products accumulation compromises embryonic development and achievement of pregnancy by assisted reproductive technology.
      suggested that AGE accumulation was highly correlated with poor follicular and embryonic development and with a lower likelihood of ongoing pregnancy.
      In a recent study by
      • Mendiola J.
      • Torres-Cantero A.M.
      • Moreno-Grau J.M.
      • Ten J.
      • Roca M.
      • Moreno-Grau S.
      • Bernabeu R.
      Food intake and its relationship with semen quality: a case-control study.
      , an association between semen quality and the consumption of foods containing processed meat (sausages and others) was observed, although the effect of these compounds on female fertility is less certain. It could be argued that partners usually share the same habits, so if one eats a certain group of foods, it is expected that the other may consume it as well. Therefore, the decreased embryo developmental competence and likelihood of pregnancy observed in these couples may be due to diminished sperm, rather than oocyte, quality.
      Other food items were associated with increased embryo quality and developmental potential. Intake of cereals, vegetables and fruits led to better embryo development. Although a strong correlation between maternal eating habits and pregnancy outcomes has been demonstrated (
      • Hambidge K.M.
      • Krebs N.F.
      • Westcott J.E.
      • Garces A.
      • Goudar S.S.
      • Kodkany B.S.
      • Pasha O.
      • Tshefu A.
      • Bose C.L.
      • Figueroa L.
      • Goldenberg R.L.
      • Derman R.J.
      • Friedman J.E.
      • Frank D.N.
      • McClure E.M.
      • Stolka K.
      • Das A.
      • Koso-Thomas M.
      • Sundberg S.
      Preconception maternal nutrition: a multi-site randomized controlled trial.
      ,
      • Ota E.
      • Tobe-Gai R.
      • Mori R.
      • Farrar D.
      Antenatal dietary advice and supplementation to increase energy and protein intake.
      ,
      • Sagedal L.R.
      • Overby N.C.
      • Lohne-Seiler H.
      • Bere E.
      • Torstveit M.K.
      • Henriksen T.
      • Vistad I.
      Study protocol: fit for delivery – can a lifestyle intervention in pregnancy result in measurable health benefits for mothers and newborns? A randomized controlled trial.
      ), the effect of female habits on conception success is still to be elucidated. Strong evidence shows, however, that a well-balanced, healthy diet is beneficial for general health (
      • Sanders T.A.
      Diet and general health: dietary counselling.
      ). Diet before pregnancy may also influence fetal well-being (
      • Imdad A.
      • Bhutta Z.A.
      Effect of balanced protein energy supplementation during pregnancy on birth outcomes.
      ,
      • Imdad A.
      • Yakoob M.Y.
      • Bhutta Z.A.
      The effect of folic acid, protein energy and multiple micronutrient supplements in pregnancy on stillbirths.
      ). In line with these findings, it is expected that reproductive performance may be positively influenced by the consumption of healthy food.
      In line with this, previous studies have reported that fruit and vegetable intake is associated with lower oxidative stress and improved antioxidant status (
      • Rink S.M.
      • Mendola P.
      • Mumford S.L.
      • Poudrier J.K.
      • Browne R.W.
      • Wactawski-Wende J.
      • Perkins N.J.
      • Schisterman E.F.
      Self-report of fruit and vegetable intake that meets the 5 a day recommendation is associated with reduced levels of oxidative stress biomarkers and increased levels of antioxidant defense in premenopausal women.
      ). Oxidative stress has been shown to cause defective embryo development in vitro (
      • Agarwal A.
      • Saleh R.A.
      • Bedaiwy M.A.
      Role of reactive oxygen species in the pathophysiology of human reproduction.
      ).
      • Bedaiwy M.A.
      • Elnashar S.A.
      • Goldberg J.M.
      • Sharma R.
      • Mascha E.J.
      • Arrigain S.
      • Agarwal A.
      • Falcone T.
      Effect of follicular fluid oxidative stress parameters on intracytoplasmic sperm injection outcome.
      reported that higher follicular fluid total antioxidant capacity and reactive oxygen species (ROS) levels are associated with pregnancy after ICSI. Endogenous ROS have been shown to play important roles as signalling molecules, during reproductive events. It has also been suggested that ROS are key signals in the initiation of apoptosis in antral follicles and granulosa cells of antral follicles. Additionally, high concentrations of antioxidants in oocytes are necessary for normal fertilization and subsequent preimplantation embryonic development (for review see
      • Devine P.J.
      • Perreault S.D.
      • Luderer U.
      Roles of reactive oxygen species and antioxidants in ovarian toxicity.
      ).
      Evidence suggests that couples undergoing infertility treatment are at increased risk for adverse reproductive effects from the widely distributed toxic elements such as mercury, lead, cadmium and arsenic (
      • Kim K.
      • Fujimoto V.Y.
      • Parsons P.J.
      • Steuerwald A.J.
      • Browne R.W.
      • Bloom M.S.
      Recent cadmium exposure among male partners may affect oocyte fertilization during in vitro fertilization (IVF).
      ). It has been reported that fish can be an exposure route for toxic chemicals, which confer risks for health outcomes (
      • Kim K.
      • Fujimoto V.Y.
      • Parsons P.J.
      • Steuerwald A.J.
      • Browne R.W.
      • Bloom M.S.
      Recent cadmium exposure among male partners may affect oocyte fertilization during in vitro fertilization (IVF).
      ,
      • Mahaffey K.R.
      • Clickner R.P.
      • Jeffries R.A.
      Adult women's blood mercury concentrations vary regionally in the United States: association with patterns of fish consumption (NHANES 1999–2004).
      ). The relationship between the risks and benefits of fish consumption, however, is complex. Consumption of fish and fish oils may be beneficial for early cognitive development and improve cardiovascular health in adults. A recent report demonstrated a positive effect of the consumption of fish oil on sperm parameters
      • Alizadeh A.
      • Esmaeili V.
      • Shahverdi A.
      • Rashidi L.
      Dietary fish oil can change sperm parameters and fatty acid profiles of ram sperm during oil consumption period and after removal of oil source.
      , in another study, showed that women with a high alpha-linolenic acid intake had a higher baseline oestradiol, and alpha-linolenic acid and docosahexaenoic acid intake may improve embryo morphology (
      • Hammiche F.
      • Vujkovic M.
      • Wijburg W.
      • de Vries J.H.
      • Macklon N.S.
      • Laven J.S.
      • Steegers-Theunissen R.P.
      Increased preconception omega-3 polyunsaturated fatty acid intake improves embryo morphology.
      ). This is in accordance with our findings, which demonstrated a positive relationship between the consumption of fish and the likelihood of blastocyst formation.
      Our results also demonstrated that the likelihood of blastocyst formation and the pregnancy rate were negatively affected in patients who reported being on a weight-loss diet. It is well known that the reproductive system is extremely sensitive to influences from the external environment and that the mechanisms responsible for the adjustment of reproductive function involve the availability of calories (
      • Martin G.B.
      • Rodger J.
      • Blache D.
      Nutritional and environmental effects on reproduction in small ruminants.
      ,
      • Wade G.N.
      • Jones J.E.
      Neuroendocrinology of nutritional infertility.
      ). These days, some people go through ‘miraculous-sounding diets that claim to melt off pounds within few days’. It is known, however, that eating disorders leading to weight loss are associated with a reduced frequency or the cessation of ovulation. Food is used as a source of energy for a variety of essential and non-essential functions. In times of deprivation, it is necessary to ration available oxidizable substrates in favour of essential functions that are required to sustain life. Reproduction is expendable at least in the short term and can be deferred until times are more favourable. Women with anovulation associated with excessive physical activity or who are underweight have low levels of leptin, LH and oestradiol. The frequency of gonadotrophin pulses is too low to sustain the development of antral follicles to the point of ovulation (
      • Sommer U.
      • Herscovitz H.
      • Welty F.K.
      • Costello C.E.
      LC-MS-based method for the qualitative and quantitative analysis of complex lipid mixtures.
      ). In some female athletes when energy expenditure is reduced, such as after an injury, menstrual cycles return (
      • Loucks A.B.
      Energy availability, not body fatness, regulates reproductive function in women.
      ).
      Additionally, obesity is an important cause of subfertility in many modern societies (
      • ESRHE
      Nutrition and reproduction in women.
      ). In the present study, BMI was shown to be inversely correlated with treatment success. This finding is in accordance with a previous report by our group, revealing that a high BMI may adversely affect the outcomes of assisted reproduction technique-based treatment (
      • Fedorcsak P.
      • Dale P.O.
      • Storeng R.
      • Ertzeid G.
      • Bjercke S.
      • Oldereid N.
      • Omland A.K.
      • Abyholm T.
      • Tanbo T.
      Impact of overweight and underweight on assisted reproduction treatment.
      ).
      Why the blastocyst formation chance was affected by some habits, but no correlation with the blastocyst quality was observed, is a matter of the debate. The most important of the reported advantages of blastocyst-stage transfer in IVF is that it yields a higher pregnancy rate than cleavage-stage embryo transfer. Previous studies have reported the importance of trophectoderm, but not inner cell mass morphology for blastocyst implantation (
      • Ahlstrom A.
      • Westin C.
      • Reismer E.
      • Wikland M.
      • Hardarson T.
      Trophectoderm morphology: an important parameter for predicting live birth after single blastocyst transfer.
      ,
      • Hill M.J.
      • Richter K.S.
      • Heitmann R.J.
      • Graham J.R.
      • Tucker M.J.
      • DeCherney A.H.
      • Browne P.E.
      • Levens E.D.
      Trophectoderm grade predicts outcomes of single-blastocyst transfers.
      ). More recently, however, it was shown that the blastocyst formation (expansion and hatching status) is the most important parameter affecting blastocyst implantation (
      • Van den Abbeel E.
      • Balaban B.
      • Ziebe S.
      • Lundin K.
      • Cuesta M.J.
      • Klein B.M.
      • Helmgaard L.
      • Arce J.C.
      Association between blastocyst morphology and outcome of single-blastocyst transfer.
      ). Therefore, it would be expected that specific food intake and social habits, which affects the cycle's outcomes, would preferably have an effect on the blastocyst formation expansion and hatching status rather than on the trophectoderm and inner cell mass morphology. There is, however, a need for increased knowledge of the effect of each specific morphology parameter at the blastocyst stage on the probability of successful implantation and pregnancy.
      One limitation of the present study is the lack of information concerning food intake and social habits in men, which would bias the results. We believe, however, that the oocyte quality plays a vital role in the blastocyst formation and embryo implantation; moreover, as discussed previously, it could be argued that partners usually share the same habits, so if one eats a certain group of foods, it is expected that the other may consume it as well.
      In summary, our findings have shown that embryo developmental potential and clinical outcomes may be influenced by food intake and social habits. These results suggest that couples seeking assisted reproduction techniques must be advised about the adverse effects of women's lifestyle on treatment success and highlight the importance of involving a nutritionist in assisted reproduction technique programmes.

      References

        • Agarwal A.
        • Saleh R.A.
        • Bedaiwy M.A.
        Role of reactive oxygen species in the pathophysiology of human reproduction.
        Fertil. Steril. 2003; 79: 829-843
        • Ahlstrom A.
        • Westin C.
        • Reismer E.
        • Wikland M.
        • Hardarson T.
        Trophectoderm morphology: an important parameter for predicting live birth after single blastocyst transfer.
        Hum. Reprod. 2011; 26: 3289-3296
        • Alizadeh A.
        • Esmaeili V.
        • Shahverdi A.
        • Rashidi L.
        Dietary fish oil can change sperm parameters and fatty acid profiles of ram sperm during oil consumption period and after removal of oil source.
        Cell. J. 2014; 16: 289-298
        • Augood C.
        • Duckitt K.
        • Templeton A.A.
        Smoking and female infertility: a systematic review and meta-analysis.
        Hum. Reprod. 1998; 13: 1532-1539
        • Baird D.D.
        • Wilcox A.J.
        Cigarette smoking associated with delayed conception.
        JAMA. 1985; 253: 2979-2983
        • Bedaiwy M.A.
        • Elnashar S.A.
        • Goldberg J.M.
        • Sharma R.
        • Mascha E.J.
        • Arrigain S.
        • Agarwal A.
        • Falcone T.
        Effect of follicular fluid oxidative stress parameters on intracytoplasmic sperm injection outcome.
        Gynecol. Endocrinol. 2012; 28: 51-55
        • Biggers J.D.
        • Racowsky C.
        The development of fertilized human ova to the blastocyst stage in KSOM(AA) medium: is a two-step protocol necessary?.
        Reprod. Biomed. Online. 2002; 5: 133-140
        • Blake D.A.
        • Farquhar C.M.
        • Johnson N.
        • Proctor M.
        Cleavage stage versus blastocyst stage embryo transfer in assisted conception.
        Cochrane Database Syst. Rev. 2007; (CD002118)
        • Bretveld R.
        • Kik S.
        • Hooiveld M.
        • van Rooij I.
        • Zielhuis G.
        • Roeleveld N.
        Time-to-pregnancy among male greenhouse workers.
        Occup. Environ. Med. 2008; 65: 185-190
        • Bushnik T.
        • Cook J.L.
        • Yuzpe A.A.
        • Tough S.
        • Collins J.
        Estimating the prevalence of infertility in Canada.
        Hum. Reprod. 2012; 27: 738-746
        • Catala M.G.
        • Izquierdo D.
        • Rodriguez-Prado M.
        • Hammami S.
        • Paramio M.T.
        Effect of oocyte quality on blastocyst development after in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in a sheep model.
        Fertil. Steril. 2012; 97: 1004-1008
        • Chavarro J.E.
        • Rich-Edwards J.W.
        • Rosner B.A.
        • Willett W.C.
        Dietary fatty acid intakes and the risk of ovulatory infertility.
        Am. J. Clin. Nutr. 2007; 85: 231-237
        • Chavarro J.E.
        • Rich-Edwards J.W.
        • Rosner B.A.
        • Willett W.C.
        Protein intake and ovulatory infertility.
        Am. J. Obstet. Gynecol. 2008; 198: 210e211-210e217
        • de Mouzon J.
        • Goossens V.
        • Bhattacharya S.
        • Castilla J.A.
        • Ferraretti A.P.
        • Korsak V.
        • Kupka M.
        • Nygren K.G.
        • Andersen A.N.
        Assisted reproductive technology in Europe, 2007: results generated from European registers by ESHRE.
        Hum. Reprod. 2012; 27: 954-966
        • Devine P.J.
        • Perreault S.D.
        • Luderer U.
        Roles of reactive oxygen species and antioxidants in ovarian toxicity.
        Biol. Reprod. 2012; 86: 27
        • ESRHE
        Nutrition and reproduction in women.
        Hum. Reprod. Update. 2006; 12: 193-207
        • Fedorcsak P.
        • Dale P.O.
        • Storeng R.
        • Ertzeid G.
        • Bjercke S.
        • Oldereid N.
        • Omland A.K.
        • Abyholm T.
        • Tanbo T.
        Impact of overweight and underweight on assisted reproduction treatment.
        Hum. Reprod. 2004; 19: 2523-2528
        • Feichtinger W.
        • Papalambrou K.
        • Poehl M.
        • Krischker U.
        • Neumann K.
        Smoking and in vitro fertilization: a meta-analysis.
        J. Assist. Reprod. Genet. 1997; 14: 596-599
        • Ferreira R.C.
        • Halpern G.
        • Figueira Rde C.
        • Braga D.P.
        • Iaconelli Jr., A.
        • Borges Jr., E.
        Physical activity, obesity and eating habits can influence assisted reproduction outcomes.
        Womens Health (Lond. Engl.). 2010; 6: 517-524
        • Foster W.G.
        • Neal M.S.
        • Han M.S.
        • Dominguez M.M.
        Environmental contaminants and human infertility: hypothesis or cause for concern?.
        J. Toxicol. Environ. Health B Crit. Rev. 2008; 11: 162-176
        • Fusani L.
        • Della Seta D.
        • Dessi-Fulgheri F.
        • Farabollini F.
        Altered reproductive success in rat pairs after environmental-like exposure to xenoestrogen.
        Proc. Biol. Sci. 2007; 274: 1631-1636
        • Gardner D.K.
        • Surrey E.
        • Minjarez D.
        • Leitz A.
        • Stevens J.
        • Schoolcraft W.B.
        Single blastocyst transfer: a prospective randomized trial.
        Fertil. Steril. 2004; 81: 551-555
        • Goransson M.
        • Magnusson A.
        • Bergman H.
        • Rydberg U.
        • Heilig M.
        Fetus at risk: prevalence of alcohol consumption during pregnancy estimated with a simple screening method in Swedish antenatal clinics.
        Addiction. 2003; 98: 1513-1520
        • Hambidge K.M.
        • Krebs N.F.
        • Westcott J.E.
        • Garces A.
        • Goudar S.S.
        • Kodkany B.S.
        • Pasha O.
        • Tshefu A.
        • Bose C.L.
        • Figueroa L.
        • Goldenberg R.L.
        • Derman R.J.
        • Friedman J.E.
        • Frank D.N.
        • McClure E.M.
        • Stolka K.
        • Das A.
        • Koso-Thomas M.
        • Sundberg S.
        Preconception maternal nutrition: a multi-site randomized controlled trial.
        BMC Pregnancy Childbirth. 2014; 14: 111
        • Hammiche F.
        • Vujkovic M.
        • Wijburg W.
        • de Vries J.H.
        • Macklon N.S.
        • Laven J.S.
        • Steegers-Theunissen R.P.
        Increased preconception omega-3 polyunsaturated fatty acid intake improves embryo morphology.
        Fertil. Steril. 2011; 95: 1820-1823
        • Hill M.J.
        • Richter K.S.
        • Heitmann R.J.
        • Graham J.R.
        • Tucker M.J.
        • DeCherney A.H.
        • Browne P.E.
        • Levens E.D.
        Trophectoderm grade predicts outcomes of single-blastocyst transfers.
        Fertil. Steril. 2013; 99: 1283-1289 e1281
        • Homan G.F.
        • Davies M.
        • Norman R.
        The impact of lifestyle factors on reproductive performance in the general population and those undergoing infertility treatment: a review.
        Hum. Reprod. Update. 2007; 13: 209-223
        • Imdad A.
        • Bhutta Z.A.
        Effect of balanced protein energy supplementation during pregnancy on birth outcomes.
        BMC Public Health. 2011; 11: S17
        • Imdad A.
        • Yakoob M.Y.
        • Bhutta Z.A.
        The effect of folic acid, protein energy and multiple micronutrient supplements in pregnancy on stillbirths.
        BMC Public Health. 2011; 11: S4
        • Jinno M.
        • Takeuchi M.
        • Watanabe A.
        • Teruya K.
        • Hirohama J.
        • Eguchi N.
        • Miyazaki A.
        Advanced glycation end-products accumulation compromises embryonic development and achievement of pregnancy by assisted reproductive technology.
        Hum. Reprod. 2011; 26: 604-610
        • Keskes-Ammar L.
        • Feki-Chakroun N.
        • Rebai T.
        • Sahnoun Z.
        • Ghozzi H.
        • Hammami S.
        • Zghal K.
        • Fki H.
        • Damak J.
        • Bahloul A.
        Sperm oxidative stress and the effect of an oral vitamin E and selenium supplement on semen quality in infertile men.
        Arch. Androl. 2003; 49: 83-94
        • Kim K.
        • Fujimoto V.Y.
        • Parsons P.J.
        • Steuerwald A.J.
        • Browne R.W.
        • Bloom M.S.
        Recent cadmium exposure among male partners may affect oocyte fertilization during in vitro fertilization (IVF).
        J. Assist. Reprod. Genet. 2010; 27: 463-468
        • Krulewitch C.J.
        Alcohol consumption during pregnancy.
        Annu. Rev. Nurs. Res. 2005; 23: 101-134
        • Lane M.
        • Mitchell M.
        • Cashman K.S.
        • Feil D.
        • Wakefield S.
        • Zander-Fox D.L.
        To QC or not to QC: the key to a consistent laboratory?.
        Reprod. Fertil. Dev. 2008; 20: 23-32
        • Lin Y.C.
        • Chang S.Y.
        • Lan K.C.
        • Huang H.W.
        • Chang C.Y.
        • Tsai M.Y.
        • Kung F.T.
        • Huang F.J.
        Human oocyte maturity in vivo determines the outcome of blastocyst development in vitro.
        J. Assist. Reprod. Genet. 2003; 20: 506-512
        • Loucks A.B.
        Energy availability, not body fatness, regulates reproductive function in women.
        Exerc. Sport Sci. Rev. 2003; 31: 144-148
        • Macklon N.S.
        • Pieters M.H.
        • Hassan M.A.
        • Jeucken P.H.
        • Eijkemans M.J.
        • Fauser B.C.
        A prospective randomized comparison of sequential versus monoculture systems for in-vitro human blastocyst development.
        Hum. Reprod. 2002; 17: 2700-2705
        • Mahaffey K.R.
        • Clickner R.P.
        • Jeffries R.A.
        Adult women's blood mercury concentrations vary regionally in the United States: association with patterns of fish consumption (NHANES 1999–2004).
        Environ. Health Perspect. 2009; 117: 47-53
        • Martin G.B.
        • Rodger J.
        • Blache D.
        Nutritional and environmental effects on reproduction in small ruminants.
        Reprod. Fertil. Dev. 2004; 16: 491-501
        • McDiarmid M.A.
        • Gardiner P.M.
        • Jack B.W.
        The clinical content of preconception care: environmental exposures.
        Am. J. Obstet. Gynecol. 2008; 199: S357-S361
        • Meintjes M.
        • Chantilis S.J.
        • Douglas J.D.
        • Rodriguez A.J.
        • Guerami A.R.
        • Bookout D.M.
        • Barnett B.D.
        • Madden J.D.
        A controlled randomized trial evaluating the effect of lowered incubator oxygen tension on live births in a predominantly blastocyst transfer program.
        Hum. Reprod. 2009; 24: 300-307
        • Mendiola J.
        • Torres-Cantero A.M.
        • Moreno-Grau J.M.
        • Ten J.
        • Roca M.
        • Moreno-Grau S.
        • Bernabeu R.
        Exposure to environmental toxins in males seeking infertility treatment: a case-controlled study.
        Reprod. Biomed. Online. 2008; 16: 842-850
        • Mendiola J.
        • Torres-Cantero A.M.
        • Moreno-Grau J.M.
        • Ten J.
        • Roca M.
        • Moreno-Grau S.
        • Bernabeu R.
        Food intake and its relationship with semen quality: a case-control study.
        Fertil. Steril. 2009; 91: 812-818
        • Mendiola J.
        • Torres-Cantero A.M.
        • Vioque J.
        • Moreno-Grau J.M.
        • Ten J.
        • Roca M.
        • Moreno-Grau S.
        • Bernabeu R.
        A low intake of antioxidant nutrients is associated with poor semen quality in patients attending fertility clinics.
        Fertil. Steril. 2010; 93: 1128-1133
        • Mendola P.
        • Messer L.C.
        • Rappazzo K.
        Science linking environmental contaminant exposures with fertility and reproductive health impacts in the adult female.
        Fertil. Steril. 2008; 89: e81-e94
        • Mercader A.
        • Garcia-Velasco J.A.
        • Escudero E.
        • Remohi J.
        • Pellicer A.
        • Simon C.
        Clinical experience and perinatal outcome of blastocyst transfer after coculture of human embryos with human endometrial epithelial cells: a 5-year follow-up study.
        Fertil. Steril. 2003; 80: 1162-1168
        • Midgette A.S.
        • Baron J.A.
        Cigarette smoking and the risk of natural menopause.
        Epidemiology. 1990; 1: 474-480
        • Milnes M.R.
        • Bermudez D.S.
        • Bryan T.A.
        • Edwards T.M.
        • Gunderson M.P.
        • Larkin I.L.
        • Moore B.C.
        • Guillette Jr., L.J.
        Contaminant-induced feminization and demasculinization of nonmammalian vertebrate males in aquatic environments.
        Environ. Res. 2006; 100: 3-17
        • Nichols J.E.
        • Crane M.M.
        • Higdon H.L.
        • Miller P.B.
        • Boone W.R.
        Extremes of body mass index reduce in vitro fertilization pregnancy rates.
        Fertil. Steril. 2003; 79: 645-647
        • Nilsson S.
        • Waldenstrom U.
        • Engstrom A.B.
        • Hellberg D.
        Single blastocyst transfer after ICSI from ejaculate spermatozoa, percutaneous epididymal sperm aspiration (PESA) or testicular sperm extraction (TESE).
        J. Assist. Reprod. Genet. 2007; 24: 167-171
        • Ota E.
        • Tobe-Gai R.
        • Mori R.
        • Farrar D.
        Antenatal dietary advice and supplementation to increase energy and protein intake.
        Cochrane Database Syst. Rev. 2012; (CD000032)
        • Papanikolaou E.G.
        • Kolibianakis E.M.
        • Tournaye H.
        • Venetis C.A.
        • Fatemi H.
        • Tarlatzis B.
        • Devroey P.
        Live birth rates after transfer of equal number of blastocysts or cleavage-stage embryos in IVF. A systematic review and meta-analysis.
        Hum. Reprod. 2008; 23: 91-99
        • Pasqualotto F.F.
        • Umezu F.M.
        • Salvador M.
        • Borges Jr., E.
        • Sobreiro B.P.
        • Pasqualotto E.B.
        Effect of cigarette smoking on antioxidant levels and presence of leukocytospermia in infertile men: a prospective study.
        Fertil. Steril. 2008; 90: 278-283
        • Ribeiro A.C.
        • SávioII K.E.O.
        • Rodrigues M.L.C.F.
        • Costa T.H.M.
        • Schmitz B.A.
        Validation of a food frequency questionnaire for the adult population.
        Revista de Nutrição. 2006; 19: 10-16
        • Rink S.M.
        • Mendola P.
        • Mumford S.L.
        • Poudrier J.K.
        • Browne R.W.
        • Wactawski-Wende J.
        • Perkins N.J.
        • Schisterman E.F.
        Self-report of fruit and vegetable intake that meets the 5 a day recommendation is associated with reduced levels of oxidative stress biomarkers and increased levels of antioxidant defense in premenopausal women.
        J. Acad. Nutr. Diet. 2013; 113: 776-785
        • Roth L.K.
        • Taylor H.S.
        Risks of smoking to reproductive health: assessment of women's knowledge.
        Am. J. Obstet. Gynecol. 2001; 184: 934-939
        • Ryan G.L.
        • Sparks A.E.
        • Sipe C.S.
        • Syrop C.H.
        • Dokras A.
        • Van Voorhis B.J.
        A mandatory single blastocyst transfer policy with educational campaign in a United States IVF program reduces multiple gestation rates without sacrificing pregnancy rates.
        Fertil. Steril. 2007; 88: 354-360
        • Sagedal L.R.
        • Overby N.C.
        • Lohne-Seiler H.
        • Bere E.
        • Torstveit M.K.
        • Henriksen T.
        • Vistad I.
        Study protocol: fit for delivery – can a lifestyle intervention in pregnancy result in measurable health benefits for mothers and newborns? A randomized controlled trial.
        BMC Public Health. 2013; 13: 132
        • Sanders T.A.
        Diet and general health: dietary counselling.
        Caries Res. 2004; 38: 3-8
        • Schoolcraft W.B.
        • Gardner D.K.
        Blastocyst versus day 2 or 3 transfer.
        Semin. Reprod. Med. 2001; 19: 259-268
        • Sepulveda S.
        • Garcia J.
        • Arriaga E.
        • Diaz J.
        • Noriega-Portella L.
        • Noriega-Hoces L.
        In vitro development and pregnancy outcomes for human embryos cultured in either a single medium or in a sequential media system.
        Fertil. Steril. 2009; 91: 1765-1770
        • Sharara F.I.
        • Beatse S.N.
        • Leonardi M.R.
        • Navot D.
        • Scott Jr., R.T.
        Cigarette smoking accelerates the development of diminished ovarian reserve as evidenced by the clomiphene citrate challenge test.
        Fertil. Steril. 1994; 62: 257-262
        • Shiloh H.
        • Lahav-Baratz S.
        • Koifman M.
        • Ishai D.
        • Bidder D.
        • Weiner-Meganzi Z.
        • Dirnfeld M.
        The impact of cigarette smoking on zona pellucida thickness of oocytes and embryos prior to transfer into the uterine cavity.
        Hum. Reprod. 2004; 19: 157-159
        • Silver E.W.
        • Eskenazi B.
        • Evenson D.P.
        • Block G.
        • Young S.
        • Wyrobek A.J.
        Effect of antioxidant intake on sperm chromatin stability in healthy nonsmoking men.
        J. Androl. 2005; 26: 550-556
        • Singh R.
        • Barden A.
        • Mori T.
        • Beilin L.
        Advanced glycation end-products: a review.
        Diabetologia. 2001; 44: 129-146
        • Soares S.R.
        • Simon C.
        • Remohi J.
        • Pellicer A.
        Cigarette smoking affects uterine receptiveness.
        Hum. Reprod. 2007; 22: 543-547
        • Sommer U.
        • Herscovitz H.
        • Welty F.K.
        • Costello C.E.
        LC-MS-based method for the qualitative and quantitative analysis of complex lipid mixtures.
        J. Lipid Res. 2006; 47: 804-814
        • Stephen E.H.
        • Chandra A.
        Declining estimates of infertility in the United States: 1982–2002.
        Fertil. Steril. 2006; 86: 516-523
        • Tesarik J.
        • Kopecny V.
        • Plachot M.
        • Mandelbaum J.
        Early morphological signs of embryonic genome expression in human preimplantation development as revealed by quantitative electron microscopy.
        Dev. Biol. 1988; 128: 15-20
        • Thomas M.C.
        • Baynes J.W.
        • Thorpe S.R.
        • Cooper M.E.
        The role of AGEs and AGE inhibitors in diabetic cardiovascular disease.
        Curr. Drug Targets. 2005; 6: 453-474
        • Uribarri J.
        • Woodruff S.
        • Goodman S.
        • Cai W.
        • Chen X.
        • Pyzik R.
        • Yong A.
        • Striker G.E.
        • Vlassara H.
        Advanced glycation end products in foods and a practical guide to their reduction in the diet.
        J. Am. Diet. Assoc. 2010; 110 (e912): 911-916
        • Van den Abbeel E.
        • Balaban B.
        • Ziebe S.
        • Lundin K.
        • Cuesta M.J.
        • Klein B.M.
        • Helmgaard L.
        • Arce J.C.
        Association between blastocyst morphology and outcome of single-blastocyst transfer.
        Reprod. Biomed. Online. 2013; 27: 353-361
        • Wade G.N.
        • Jones J.E.
        Neuroendocrinology of nutritional infertility.
        Am. J. Physiol. Regul. Integr. Comp. Physiol. 2004; 287: R1277-R1296
        • Waldenstrom U.
        • Engstrom A.B.
        • Hellberg D.
        • Nilsson S.
        Low-oxygen compared with high-oxygen atmosphere in blastocyst culture, a prospective randomized study.
        Fertil. Steril. 2009; 91: 2461-2465
        • Westphal L.M.
        • Hinckley M.D.
        • Behr B.
        • Milki A.A.
        Effect of ICSI on subsequent blastocyst development and pregnancy rates.
        J. Assist. Reprod. Genet. 2003; 20: 113-116

      Biography

      Daniela Braga obtained her DVM degree in 1998 at Paulista University Sao Paulo, Brazil. She is currently a PhD student at Universidade Federal Paulista – UNIFESP, head of the Scientific Research Department at Fertility – Centro de Fertilização Assistida and collaborator at the discipline of human assisted reproduction laboratory in the Instituto Sapientiae – Centro de Estudos e Pesquisa em Reprodução Assistida. Daniela Braga has published over 80 scietific papers in peer reviewed journals.