Preconception Lecture-1 PDF

Preconception Lecture-1 NFS 526 Lifecycle Nutrition Nutrition Through the life cycle, Judith E Brown, 6th edition, 2018, Cengage Learning Publisher ISBN-10: 1-305-62800-4; ISBN-13: 978-1-305-62800-7 PART 1: REPRODUCTIVE...

Preconception Lecture-1 NFS 526 Lifecycle Nutrition Nutrition Through the life cycle, Judith E Brown, 6th edition, 2018, Cengage Learning Publisher ISBN-10: 1-305-62800-4; ISBN-13: 978-1-305-62800-7 PART 1: REPRODUCTIVE PHYSIOLOGY Definitions Fertility: the actual production of children Fecundity: the biological capacity to bear children Infertility: lack of conception after 1 year of unprotected intercourse 3  Statistics Percent of women aged 15-44 with impaired fecundity: 12.1% Percent of married women aged 15-44 that are infertile: 6.7% Percent of women aged 15-44 who have ever used infertility services: 12.0% Source: Key Statistics from the National Survey of Family Growth (data are for 2011-2015) Statistics 9-15% of couples in developed countries are involuntarily childless (infertile and/or infecund) Healthy couples have a 20-25% of chance of becoming pregnant within a given menstrual cycle 30-50% of conceptions are lost by resorption into the uterine wall within the first 6 weeks of conception 9% are lost to miscarriage in the first 20 weeks of pregnancy 5 Subfertility Reduced level of fertility characterized by unusually long time for conception Examples: Having multiple miscarriages Sperm abnormalities Infrequent ovulation ~18% of couples fall into this category due to delayed time to conception (12 months), or repeated, early pregnancy losses 6 Reproductive Physiology Puberty: Period in which humans become biologically capable of reproduction Ova: Eggs females produce & store within the ovaries Menstrual Cycle: ~4 week interval in which hormones direct buildup of blood & nutrient stores within uterus; ovum matures & is released 7 Reproductive Physiology Women are born with a lifetime supply of ova (~7 million) Chromosomes in ova may be damaged by: Oxidation Radioactive particle exposure Aging 8 Reproductive hormones Gonadotropin-releasing hormone (GnRH) Stimulates pituitary to release FSH and LH Follicle-stimulating hormone (FSH) Stimulates maturation of ovum & sperm Luteinizing hormone (LH) Stimulates secretion of estrogen, progesterone & testosterone 9 Reproductive hormones Estrogen Stimulates release of GnRH in follicular phase & follicle growth & maturation of follicle Stimulates vascularity & storage of glycogen & other nutrients within uterus Progesterone Prepares uterus for fertilized ovum, increases vascularity of endometrium, & stimulates cell division of fertilized ova 10  Two Phases of Menstrual Cycle Follicular Phase—(first half of menstrual cycle) Follicle growth & maturation Main hormones: GnRH, FSH, estrogen, & progesterone Luteal Phase—(last half of menstrual cycle) After ovulation Formation of corpus luteum  in estrogen & progesterone stimulate menstrual flow Prostaglandins & cramps 12 Male Reproductive System Reproductive capacity results from interplay between Hypothalamus Pituitary gland Testes Ongoing, not cyclic Involves GnRH, FSH and LH, as well as testosterone (androgens) Testosterone and androgens ( Dehydrotestosterone etc) stimulate the maturation and release of sperm from the testes Spermatogenesis- Formation and Maturation of the sperm mediated by testosterone. 13 Physiological factors contributing to normal fertility Normal menstrual cycle Production of ova Sperm maturation, production and storage Endocrine alterations Sperm motility Causes of infertility From: Infertility and Contraception Harrison's Principles of Internal Medicine, 19e, 2015 PART-2 NUTRITION-RELATED DISRUPTIONS IN FERTILITY  Nutrition-Related Disruptions in Fertility Under nutrition Weight loss Obesity High exercise levels Intake of specific foods & food components Alcohol, Caffeine, Nutrients, High Fat Diets Under nutrition and Fertility Chronic Rodents- Lesser Corpus luteum, lower weight gain during pregnancy (Alexandar et al 1988) Small impact on fertility and fecundity Higher likelihood of small frail infants, infant death during first year of life Acute Results in dramatic decline in fertility Is recovered with recovered food intake Reduces reproductive capacity by modifying hormonal signals that regulate ovulation and menstrual cycles in females Also impairs sperm maturation in males 19 Body Fat and Fertility Fat cells produce hormones: Estrogen Androgens Leptin Excessive and inadequate body fat levels will alter the hormone balance and affect the reproductive cycle 20 Body Fat and Fertility Critical level of body fat: BMI > 20 kg/m2 Triggers and sustains normal hormone production Exact % fat range is debatable http://pennshape.upenn.edu/files/pennshape/Body-Co mposition-Fact-Sheet.pdf Low body fat can lead to: Delayed onset of menstruation Amenorrhea Lowered libido Reduced sperm production 21 Body Fat and Fertility From: Rich-Edwards et al 2002 22  Recent Studies on Adiposity and Fertility Participants with obesity between ages 9 and 12 were more likely to report fertility difficulties ( Jacobs 2017) Higher overall adiposity, but not central adiposity, was associated with longer Time to pregnancy in Asian women ( Loy 2018) Men presenting with a BMI greater than 25 kg/m(2) have fewer chromatin-intact normal-motile sperm cells per ejaculate. ( Kort 2005) Both morbid obesity and being underweight have a negative effect on sperm quality, particularly epididymal maturation.( Luque 2017)  Adiposity and Fertility- Mechanisms Adipose tissue converts androgens to estrogen by aromatization. Body fat is thus a significant extragonadal source of estrogen Obese men have significantly lower circulating levels of testosterone Adiposity influences the direction of estrogen metabolism to more potent or less potent forms Leaner women make more catechol estrogens, the less potent form Obese women and girls have a diminished capacity for estrogen to bind sex- hormone-binding-globulin  Excess Fat mass and Infertility Increase in the number of fat cells results in a cascade of changes Increased leptin and insulin levels and a preferential increase in LH, but not FSH, levels. High insulin levels increases ovarian testosterone production/action. The net effect of these changes is to stimulate the partial development of follicles that secrete supranormal levels of testosterone, but which rarely ovulate (hence low progesterone). Insulin sensitivity and ovarian function Poretsky et al., 1999 Obesity and Fertility High Fat Diets and Fertility  Weight loss and Fertility In overweight/obese individuals Weight loss improves ovulation, menstrual irregularities, live birth, natural conception, reduced miscarraiges, ( Sim et al., 2014, Moran et al 2011) Energy restriction alone leads to improvement in reproductive parameters In men undergoing weight loss ( Mir 2018) DNA Fragmentation Index improved Improvement in morphology How effective are weight-loss interventions for improving fertility in women and men who are overweight or obese? Best et al 2017  Findings by Best et al 2017 A total of 40 studies were included, of which 14 were randomized control trials. Primary outcomes were pregnancy, live birth rate and weight change. In women, reduced calorie diets and exercise interventions were more likely than control interventions to result in pregnancy [risk ratio 1.59, 95% CI (1.01, 2.50)], and interventions resulted in weight loss and ovulation improvement, where reported. Miscarriage rates were not reduced by any intervention. WIDER IMPLICATIONS: Overweight and obese persons seeking fertility should be educated on the detrimental effects of fatness and the benefits of weight reduction, including improvement in pregnancy rates. A combination of a reduced calorie diet, by reducing fat and refined carbohydrate intake, and increased aerobic exercise should form the basis of programmes designed for such individuals. A lack of randomized studies in men and couples, and studies evaluating barriers to undertaking weight loss in infertile populations is evident, and future research should examine these issues further. Exercise and Fertility Physical fitness and exercise are associated with improved fertility outcomes E.g. Each hour of vigorous exercise/wk associated with 7% lower risk of ovulatory infertility (Rich-Edwards et al 2002) Mechanism- Exercise increases insulin sensitivity, which is related to ovarian function 32 Rich Edwards et al., 2002  Long term strenuous exercise HIE : High intensity exercise MIE : Moderate intensity exercise Oxidative Stress, Antioxidants and Fertility Antioxidants (e.g. Vitamins E, C, beta-carotene) protect reproductive cells from oxidative stress Free radicals can harm: Polyunsaturated fatty acids in sperm membranes, decreasing sperm motility and ability to fuse with egg DNA within the sperm cell Egg and follicular development Implantation of egg in uterine wall 35 Supplementation clinical trials and fertility Preliminary clinical trials show: Supplemental intakes of vitamin E and selenium improve sperm quality in infertile men Regular intake of vitamin C, E and beta carotene supplements increase sperm number and motility Zinc supplements improve sperm quality Recent meta analysis showed promise for use of Selenium, Zinc, CoQ10 and/or w-3 FA for sperm health 36 Caffeine and Fertility Epidemiological studies show high intakes are linked to reduced fertility http://www.cspinet.org/new/cafchart.htm Compared with nonsmoking women with a caffeine intake less than 300 mg/day, nonsmoking women who consumed 300-700 mg/day of caffeine had a fecundability odds ratio (FR) of 0.88 (95% confidence interval (CI), 0.60-1.31), while those with a higher consumption had an FR of 0.63 (95% CI, 0.25-1.60), after adjustments for body mass index, alcohol intake, diseases of the female reproductive organs, semen quality, and duration of the menstrual cycle ( Jensen 1998). There was no association between male caffeine and alcohol intake and semen quality. Male caffeine intake was negatively related to live birth after assisted reproductive technologies Adjusted live birth rate among couples with a male partner in the highest quartile of caffeine intake (≥272 mg/day) compared to couples with a male partner in the lowest quartile of intake ( or =6 units/d ( 90mg per unit) during pregnancy is associated with impaired fetal length growth. Caffeine exposure might preferentially adversely affect fetal skeletal growth ( Bakker 2010). Prospective birth cohort in Japan suggests that higher maternal total caffeine intake, mainly in the form of Japanese and Chinese tea, during pregnancy is associated with a greater risk of preterm birth (Okubo 2015) Adenosine receptor antagonist that may influence fertility by affecting ovulation, menstrual characteristics, sperm quality, sperm DNA damage. Alcohol and Fertility Alcohol intake alters the hormonal milieu Decreases estrogen and testosterone levels Disrupts menstrual cycle Disrupts testicular function How much? Not entirely clear. 1-5 drinks/week = ~40% decreased chance of conception Over 10 drinks/week = ~66% decreased chance of conception 39  Studies on Alcohol and fertility Live birth rate among couples with a male partner in the highest quartile of alcohol intake (≥22 g/day) compared to couples with a male partner in the lowest quartile of intake (