Download SOWH OBF 1 Pre-‐Pregnancy, Conception, and Fetal Development

SOWH OBF Pre-­‐Pregnancy, Conception, and Fetal Development Pre-­‐Pregnancy Menstrual Cycle Uterine Cycle Ovarian Cycle Pre-­‐Pregnancy Care Higher Body Mass and Infertility Intense Exercise and Infertility Conception Treatments for Infertility Fertilization Ectopic Pregnancy Cleavage Implantation Placenta Cervical Mucus Plug Factors Affecting Normal Fetal Development General Low Birth Rate and Fetal Growth Restrictions Nervous, Cardiovascular, and Respiratory Systems Normal Fetal Development First, Second, and Third Trimesters Pre-­‐Pregnancy Menstrual Cycle • Menstrual cycle frequency ranges from 15-­‐45 days • Average menses lasts 4-­‐6 days Uterine Cycle (Decherney 2007; Blackburn, 2007) The uterine cycle is regulated by estrogen and progesterone. • Proliferative Phase: Day 1-­‐Day14  Endometrium regenerates and thickens  Purpose: Restore uterine lining after menstruation  Phase length varies • Secretory Phase: Day 14-­‐Day 28  Purpose: Prepares the uterine lining for implantation  After ovulation, progesterone and estrogen produced by the corpus luteum cause the endometrium to become more vascularized  The endometrium secretes a clear fluid  If fertilization does not occur, then the endometrium is shed through menstruation  Phase length typically 14 days Ovarian Cycle (Decherney 2007, Blackburn 2007) • Follicular Phase  Follicular maturation OBF Pre-­‐Read 1 Pre-­‐Pregnancy, Conception, and Fetal Devlopment S Giglio, K Fisher, D Cathcart 1 SOWH OBF •
o 1 follicle containing an immature ovum begins development at the beginning of the cycle o FSH stimulation helps to mature the follicle o FSH and LH secretion increases during the follicular phase  Ovulation o LH secretion peaks 12-­‐24 hours before ovulation o LH peak triggers rupture of the follicle at approximately day 14 of the cycle. Ovum is released, picked up by the fimbriae and transported through the oviducts to the uterus Luteal Phase • Development of the corpus luteum o Luteal cells of the corpus luteum secrete estrogen and progesterone • Corpus luteum will degenerate if fertilization does not occur Prepregnancy Care • Women should consult with a physician before becoming pregnant for a medical evaluation • Birth Control (American College of Obstetrics and Gynecology)  The purpose of discontinuing oral contraceptives before attempting to conceive: o It takes a few months to resume ovulation o Menstrual cycle may be irregular – making it more difficult to conceive immediately after stopping the pill o Taking oral contraceptives within the few months before conception is not linked to birth defects, according to ACOG  Remove Intrauterine devices before attempting to conceive which can lead to infections or pregnancy loss • Regular Exercise  Exercise before and during pregnancy reduces risk of abnormal glucose tolerance and gestational diabetes, as physical activity can reduce blood glucose levels (Oken 2006)  Higher body mass index may increase the risk of late fetal death and preterm delivery (Cnattingius 1998)  Pelvic floor muscle exercise during pregnancy may reduce the risk of stress incontinence after delivery. (Morkved 2003)  May reduce risk for back pain during pregnancy. (Borg-­‐Stein 2005)  The course of labor after endurance exercise during pregnancy (Clapp 1990) o 131 well-­‐conditioned recreational athletes who had an uneventful first half of pregnancy. o 87 women continued to exercise regularly at or above 50% of their preconceptional level throughout pregnancy o 44 women discontinued their regular exercise regimen before the end of the first trimester. o Incidence of preterm labor was similar in the two groups (9%). 2 OBF Pre-­‐Read 1 Pre-­‐Pregnancy, Conception, and Fetal Devlopment S Giglio, K Fisher, D Cathcart SOWH OBF •
o Labor began significantly earlier in the exercise group (277 ± 6 vs 282 ± 6 days). o The exercising women had a lower incidence of • Abdominal (6% vs 30%) and vaginal (6% vs 20%) operative delivery • Active labor was shorter (264 ± 149 vs 382 ± 275 min) in those who were delivered vaginally. o Clinical evidence of acute fetal stress was less frequent in the exercise group (50% vs 26%), o Birth weight was reduced in exercise group (3369 ± 318 vs 3776 ± 401 gm). Nutrition (Decherney 2007; Blackburn, 2007)  Iron: Recommended intake for women is 12-­‐18g/day; iron requirements increase during pregnancy o Can decrease the risk of iron deficiency anemia  Protein Intake: 46-­‐60g/day for women of childbearing age; protein is essential for growth of fetal tissue  Calcium: 1000mg/day for women of childbearing age; this may be increased to 1500mg/day during the later months of pregnancy and during lactation to prevent demineralization of the maternal skeleton  Folic Acid: 400mg/day to prevent neural tube defects; this should begin preferably 3 months prior to pregnancy; folic acid is necessary for DNA synthesis o Prenatal vitamins usually contain 1g of folate Higher Body Mass Index and Infertility (Rich-­‐Edwards 2002) • Being overweight (BMI>25) increases the risk of ovulatory infertility  Normal BMI = 18.5-­‐24.9 • Obesity may disrupt ovarian function by:  Depression of sex hormone binding globulin  Increase insulin resistance  Hypoandrogenism: Thought to contribute to polycystic ovarian syndrome • In women who are overweight, physical activity may reduce the risk of ovulatory infertility by improving insulin sensitivity and decreasing adiposity Intense Exercise and Infertility (Warren 2001; Morris 2006) • Theory that exercise affects the hypothalamic-­‐pituitary axis by disturbing GnRH pulse generator  If energy expenditure is greater than dietary intake, then there is gonadotropin-­‐
releasing hormone (GnRH) suppression  This limits pituitary secretion of lutenizing hormone (LH) which reduces ovarian stimulation and estradiol production  This can cause suppression of menstrual cycles, delayed menarche or amenorrhea  Theory that caloric deficit is more important than the exercise itself  Infertility occurs due to inadequate luteal phase or anovulation  Weight gain of 1-­‐2kg or 10% decrease in exercise load may restore ovulation OBF Pre-­‐Read 1 Pre-­‐Pregnancy, Conception, and Fetal Devlopment S Giglio, K Fisher, D Cathcart 3 SOWH OBF Conception Treatments for Infertility (ACOG, 2007) • Infertility is defined as inability to conceive after 12 months of unprotected sex • Medication to induce ovulation  Clomiphene citrate  Gonadotropins • Surgery to open blocked fallopian tubes • Treat endometriosis • Artificial Insemination: sperm placed in the uterus not by sexual means • Assisted Reproductive Technology (ART)  In vitro fertilization: sperm and eggs are placed together in a dish to fertilize, then embryos are placed back inside the woman’s uterus to grow  Exercising 4 or more hours per week for 1-­‐9 years and participating in cardiovascular exercise before beginning in vitro fertilization may reduce chances of successful live birth (Warren & Perlroth 2001; Morris 2006) o Many women are advised to be on pelvic rest after in vitro until pregnancy is established • Manual therapy for infertility (Wurn 2004)  Studied the effectiveness of manual soft tissue therapy in: o Facilitating natural fertility o Improving in vitro fertilization in women with a history of adhesions  53 infertile patients o 17 trying to conceive naturally o 36 planning IVF within 15 months  Inclusion in study was inability to conceive after 12 months of unprotected intercourse and suspected or confirmed pelvic adhesions  Treatments were designed to treat o Biomechanical problems within the pelvis, sacrum, coccyx o Restricted soft tissue or visceral mobility  Results o 10 in the first group became pregnant within 1 year • 9 had full term deliveries o In the second group, 25 patients were available for follow up • There were 22 clinical pregnancies in 33 embryo transfers • Age adjusted expected number is 12.7  Odds ratio for a successful pregnancy in a cycle (manual treatment: no treatment) is 3.20  Only therapists trained to do visceral mobilizations should attempt to improve fertility in a patient by using manual therapy Fertilization (Toot 2004) • At time of ovulation, female reproductive tract characteristics are ideal for sperm penetration 4 OBF Pre-­‐Read 1 Pre-­‐Pregnancy, Conception, and Fetal Devlopment S Giglio, K Fisher, D Cathcart SOWH OBF •
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40-­‐300 million sperm are deposited in the vagina; less than 200 reach the egg Ova are usually fertilized within 12 hours of ovulation, usually in the fallopian tube Fertilization occurs as the acrosome (on the head of the sperm) burrows its way into the oocyte Changes in the oocyte membrane prevent entrance of additional sperm •
Ectopic Pregnancy • Occurs when the baby starts to develop outside the uterus • Most common site is in the fallopian tube • Occurs in 1 in every 40-­‐100 pregnancies • Caused by any condition which impedes the movement of the fertilized egg through the tube  Scarring from past ectopic pregnancy, infection or surgery  Endometriosis  Increased risk with in vitro fertilization  Increased risk in women taking hormones (BCP) • Can occur after tubal ligation; most pregnancies that occur 2-­‐3 years after tubal sterilization will be ectopic Cleavage (Toot 2004) • Cleavage follows fertilization • Consists of a rapid succession of mitotic divisions developing a morula • The outer cells of the morula secrete fluid • This develops a single fluid-­‐filled cavity or blastocyst Implantation (Toot 2004) • Fertilized ovum reaches the endometrial cavity about 3 days after ovulation • Transport is promoted by progesterone and prostaglandins • Embryo (blastocyst) reaches the uterine cavity and undergoes further development for 2-­‐3 days before implanting • Space develops within the layers of blastocyst cells forming the amniotic cavity • Minute amounts of hCG appear in the maternal serum Placenta (Toot 2004) • The blastocyst burrows deeper into the endometrium • Solid primitive villi form • First distinguished the 12th day of fertilization • Maternal venous sinus are tapped about day 15 • By day 17 fetal and maternal blood vessels are functional and placental circulation is established • Placenta previa occurs when the placenta grows in the lowest part of the uterus and covers all or part of the opening to the cervix  Varying degrees OBF Pre-­‐Read 1 Pre-­‐Pregnancy, Conception, and Fetal Devlopment S Giglio, K Fisher, D Cathcart 5 SOWH OBF 
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o Marginal – placenta is against cervix but not over it o Partial – placenta covers part of the opening o Complete – placenta covers the entire opening of the cervix Prevalence is 1 in 200 pregnancies More common in women who have: o An abnormally developed uterus o Many previous pregnancies o Multiple gestation o Scarring of the uterine wall from previous pregnancies, cesareans, uterine surgery or abortions Symptoms include sudden, painless vaginal bleeding that often occurs near the end of the second trimester or beginning of the third trimester; it may be self limiting but may be the beginning of labor Usually diagnosed on routine ultrasound exam Women with asymptomatic previa can continue with normal activities with a repeat ultrasound at 28 weeks (Sakornbut 2007) o If the previa persists into the 3rd trimester the patient must be on pelvic rest and hospitalization is necessary if significant bleeding occurs o Pelvic rest requires that the patient stop intercourse • Orgasm causes the uterus to contract but generally do not result in a change in cervical dilation or effacement • Prostaglandins in seminal fluid can cause increased uterine activity and if near term can result in cervical dilatation or effacement Cervical Mucous Plug • A plug of mucous that forms to protect the normally sterile uterine cavity from the vagina (Hein 2002) • Formed due to hyperplasia of the cervical glands as a result of increased hormones • Serves as a mechanical and chemical barrier to infection Factors Affecting Normal Fetal Development • General Low Birth Weight and Fetal Growth Restrictions (Mongelli 2000)  WHO definitions: o Low birth weight = less than 2500 grams (5.5 lb) o Very low birth weight = less than 1500 grams (3.3 lb)  Low birth weight for gestational age may or may not be due to intrauterine growth restriction (IUGR)  There are no universal definitions for intrauterine growth restriction (Williams Obstetrics 1997) o Poor growth of a baby in utero for any reason o Fetus weight is below the 10th percentile o Symmetric 6 OBF Pre-­‐Read 1 Pre-­‐Pregnancy, Conception, and Fetal Devlopment S Giglio, K Fisher, D Cathcart SOWH OBF 
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• All organs reduced in size • Usually due to insult early in pregnancy – chemical exposure, virus o Asymmetric • Abdomen smaller than the head and brain • Usually due to insult later in pregnancy (3rd trimester) –anything that would interfere with placental function Risk Factors for IUGR (Williams Obstetrics 1997) o Maternal weight of less than 100 pounds o Poor nutrition o Social isolation o Fetal infections o Birth defects/chromosomal abnormalities o Use of drugs, cigarettes and/or alcohol o Pre-­‐eclampsia, Gestational hypertension o Chronic hypoxia (higher altitudes) o Placental abnormalities o Umbilical cord abnormalities o Multiple pregnancy Birth weight itself does not account for gestational age. o Babies small due to genetic factors have fewer risks than those due to intrauterine growth restriction Birth weight at term is correlated more strongly to maternal characteristics and the intrauterine environment. SGA may be attributed to poor overall maternal nutrition, specific nutritional deficiencies, or exposure to a toxin. (Rice 2000) Toxicants that may cause intrauterine growth retardation include alcohol, cigarette smoking, PCBs, lead. (Rice 2000) Nervous System (Rice 2000)  In general, if exposure to environmental toxicants occurs before or after an organ develops, it is less vulnerable to perturbation than if exposure occurs during development of the organ.  Prenatal exposure to alcohol or cigarette smoking; postnatal exposure to lead during developmental years. o Deficits in IQ, attention problems, increased impulsivity, and deficits of executive function.  Small for gestational age (SGA) is a risk factor for behavioral problems later in life. Cardiovascular System & Glucose Metabolism (Godfrey 2000; Rich-­‐Edwards 1997; McCance 1994; Lithell 1996)  Small for gestational age (SGA) is linked to coronary heart disease, high blood pressure and hypertension, altered glucose metabolism later in life  Such findings are less notable with some larger studies (Murphy 2006) Respiratory System (Murphy 2006) OBF Pre-­‐Read 1 Pre-­‐Pregnancy, Conception, and Fetal Devlopment S Giglio, K Fisher, D Cathcart 7 SOWH OBF 
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Contradictory data: increased risk of developing asthma and having reduced lung function is noted neonates that are small or large for birth weight Death from COPD later in life related to lower birth weight Normal Fetal Development (Regan 2005, Murkoff 2002) First Trimester • Months 1-­‐3 or weeks 1-­‐13  0-­‐6 weeks o By the 3rd week, the newly fertilized egg has floated into the uterus and embedded itself in the lining. o Three layers of cells develop to create different parts of the embryo’s body: 1. Outer layer (ectoderm) becomes skin, hair, nails, nipples, tooth enamel, eye lenses, nervous system and brain. 2. Middle layer (mesoderm) becomes skeleton, muscles, heart, blood vessels, and reproductive organs. 3. Inner layer (endoderm) becomes respiratory and digestive systems, liver, pancreas, stomach, bowel, urinary tract and bladder. o At this point cells are programmed for what they will become and cannot become another type of cell. o Early formation of the neural tube and brain are established. o Needs are met by the yolk sac until the placenta is fully developed. o The embryo floats in an amniotic sac, which is covered by an outer protective sac called the chorion.  6-­‐10 weeks o By week 10, the embryo is considered a fetus. o It can respond to touch. o Heart has four chambers and heart rate is 180 bpm. o Limbs begin to develop and the tail disappears. o Head grows more rapidly than other parts of the body to accommodate for the brain. o Brain and spinal cord differentiate from the neural tube. o Primitive facial bones develop and fuse together, with facial features becoming more recognizable. o Inner ear starts to form. o Taste buds and tooth buds exist.  10-­‐13 weeks o All vital body organs are in place. o The fetal head accounts for 1/3 of crown to rump length (CRL). o Neck supports the head. o Facial bones are completely formed. o Eyes, inner ear, and middle ear are fully developed. 8 OBF Pre-­‐Read 1 Pre-­‐Pregnancy, Conception, and Fetal Devlopment S Giglio, K Fisher, D Cathcart SOWH OBF o
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Fetal skin is thin, transparent and permeable to amniotic fluid. Ossification of bones begins at 12 weeks. Fetus exhibits vigorous, jerky movements and exhibits early reflexes. Ovaries or testes have fully formed. The heart is fully formed; heart rate is 110-­‐160 bpm. Second Trimester • Months 4-­‐6 or weeks 14-­‐26  13-­‐17 weeks o Facial and ear features are more pronounced. Eyebrows and eyelashes begin to develop. o All connections in the brain, nerves, and muscles have been made. Myelin begins to develop. o Muscles are able to contract and relax. o The hands grasp whatever they come in contact with. o The placenta continues to grow. o The kidneys begin to filter amniotic fluid swallowed by the baby. o The fetus begins to shed skin cells (important with amniocentesis testing).  17-­‐21 weeks o Head is now in better proportion to the rest of the body. o Legs are now longer than the arms. o Lungs, digestive tract, nervous system, and immune systems are starting to mature. o Skeleton can now be seen clearly on X-­‐ray. o Sexual organs are well developed. Ovaries, all eggs, and uterus are fully formed. Testes have not descended yet; but a scrotal swelling and rudimentary penis are visible on ultrasound. o Eyelids are closed, but eyeballs can roll side to side. The retina is light-­‐
sensitive. o Taste buds are well developed. o The fetus is able to hear the mother’s heart beating, blood pulses, and digestive noises, as well as loud sounds outside the mother’s body. o Thin layers of body fat begin to develop and the baby is covered with lanugo hair. o The placenta is now fully developed functionally and continues to grow.  21-­‐26 weeks o Two distinct layers of skin, epidermis and dermis, have developed. The skin is now covered with lanugo and vernix, a thick waxy protective coating. o Movements become more deliberate and sophisticated. o By 24 weeks, EEG brainwaves are similar to those of a newborn infant. o Eyelids will be open by the end of this period. o Cycle of sleeping and waking is developing. o Fetal heart rate is 140-­‐150 bpm. OBF Pre-­‐Read 1 Pre-­‐Pregnancy, Conception, and Fetal Devlopment S Giglio, K Fisher, D Cathcart 9 SOWH OBF o The baby begins to practice breathing movements as amniotic fluid helps develop more alveoli. o The limit of potential fetal viability outside the womb is currently approximately 24 weeks. Third Trimester • Months 7-­‐9 or weeks 27-­‐40  26-­‐30 weeks o Body weight and length increases. o As additional fat is deposited under the skin, the baby begins to lose its lanugo hair. o Testes begin to descend into the scrotum. o Eyes will begin to blink and baby is more aware of differences in light. o Movements become much more noticeable to the mother as the size of the baby overtakes the amount of amniotic fluid. o Fetal bone marrow has taken over as the main producer of the baby’s red blood cells. o The brain and nervous system continue to become more intricate and sophisticated.  30-­‐ 35 weeks o The brain and nervous system are fully developed o The lungs are maturing very quickly. Fetal adrenal glands produce cortisol to stimulate the production of surfactant in the fetal lungs. o Adrenal glands also produce large quantities of an androgen-­‐like hormone (DHEAS) in boys and girls. In boys, testes are producing testosterone. o Baby’s movements are strong but slower due to cramped space in the uterus. o By week 35, most babies lie longitudinally (vertically). Risk of abnormal position is increased with polyhydramnios, placenta previa, and multiple fetuses.  35-­‐40 weeks o Baby is likely (and hopefully) in head-­‐down position. o Baby continues to gain weight steadily, mostly due to continued fat deposition. o Movement should continue as before, though with less freedom for the baby. o Most of the lanugo hair has disappeared. Some vernix remains to assist of passage through the birth canal. o Lungs are now fully mature and surfactant continues to be produced. o Heart rate is 110-­‐150 bpm. o Digestive system is now ready to accept liquid foods. Intestines are filled with meconium. • Meconium plug normally will pass in the first few days after birth, though may pass while in utero if the baby becomes distressed. 10 OBF Pre-­‐Read 1 Pre-­‐Pregnancy, Conception, and Fetal Devlopment S Giglio, K Fisher, D Cathcart SOWH OBF o Testes complete their descent into the scrotum. o Immune system is now capable of protecting against a variety of infections. o Fetal skull remains unfused until after birth to allow passage through the birth canal. o By the 36th (in first pregnancies) to the 40th week, the fetal head normally will become engaged in the pelvis for delivery. o By 42 weeks, the placenta begins to lose its efficient functioning, and induction is likely for the health of the baby. References American College of Obstetrics and Gynecology. Treating infertility. 2007 http://www.acog.org/publications/patient_education/bp137.cfm Accessed October 1, 2008. Blackburn S, editor. Maternal, Fetal & Neonatal Physiology. 3rd ed. St Louis, Missouri: Elsevier Saunders, 2007. Borg-­‐Stein J, Dugan S, Gruber J. Musculoskeletal aspects of pregnancy. American Journal of Physical Medicine and Rehabilitation. 2005; 84:180-­‐92. Clapp, J.F. The course of labor after endurance exercise during pregnancy. American Journal of Obstetrics and Gynecology.1990; 163: 1799-­‐1805. Cnattingius S, Bergstrom R, Lipworth L, Kramer M. Prepregnancy weight and the risk of adverse pregnancy outcomes. New England Journal of Medicine 1998; 338(3):147-­‐152. Decherney A, Nathan L, Goodwin T, Laufer N, editors. Current Diagnosis & Treatment Obstetrics & Gynecology. 10th ed. New York: McGraw-­‐Hill, 2007. Godfrey KM, Barker DJP. Fetal nutrition and adult disease. Am J Clin Nutr. 2000; 71 (suppl): 1344S-­‐52S. Hein M, Valore EV, Helmig RB, Uldejerg N, Ganz T. Antimicrobial factors in the cervical mucus plug. Am J Obstet Gynecol. 2002 Jul; 187(1):137-­‐44 Lithell HO, McKeigue PM, Berglund L, Mohsen R, Lithell U-­‐B, Leon DA. Relation of size at birth to non-­‐
insulin dependent diabetes and insulin concentrations in men aged 50-­‐60 years. BMJ. 1996; 312: 406-­‐
410. McCance DR, Pettit DJ, Hanson RL, Jacobsson LTH, Knowler WC, Bennett PH. Birth weight and non-­‐insulin dependent diabetes: ‘thrifty genotype’, ‘thrifty phenotype’, or ‘surviving small baby genotype’? BMJ. 1994; 308: 942-­‐945. Mongelli M, Gardosi J. Fetal Growth. Current Opinion in Ob & Gyn. 2000; 12: 111-­‐115. Morkved S, Bo K, Schei B, Salvesen K. Pelvic floor muscle training during pregnancy to prevent urinary incontinence: A single-­‐blind randomized controlled trial. Obstetrics and Gynecology 2003; 101(2):313-­‐319. Morris S, Missmer S, Cramer D, Powers R, McShane P, Hornstein M. Effects of lifetime exercise on the outcome of in vitro fertilization. Obstetrics and Gynecology 2006; 108(4):938-­‐945. OBF Pre-­‐Read 1 Pre-­‐Pregnancy, Conception, and Fetal Devlopment S Giglio, K Fisher, D Cathcart 11 SOWH OBF Murkoff H, Eisenberg A, Hathaway S. What to Expect When You’re Expecting. New York: Workman Publishing. 2002. Murphy VE, Smith R, Giles WB, Clifton VL. Endocrine Regulation of Human Fetal Growth: The Role of the Mother, Placenta, and Fetus. Endocrine Reviews. 2006; 27(2): 141-­‐169. Oken E, Ning Y, Rifas-­‐Shiman S, Radesky J, Rich-­‐Edwards J, Gillman M. Associations of physical activity and inactivity before and during pregnancy. Obstetrics and Gynecology 2006; 108(5):1200-­‐1207. Regan L. I’m Pregnant: A Week-­‐by-­‐Week Guide From Conception to Birth. London: Dorling Kindersley Limited. 2005. Rice D, Barone Jr S. Critical Periods of Vulnerability for the Developing Nervous System: Evidence from Humans and Animal Models. Environmental Health Perspectives. 2000; 108(3): 511-­‐533. Rich-­‐Edwards J, Spiegelman D, Garland M, Hertzmark E, Hunter D, Colditz G, et al. Physical activity, body mass index, and ovulatory disorder infertility. Epidemiology 2002; 13:184-­‐190. Rich-­‐Edwards JW, Stampfer MJ, Manson JAE, et al. Birth weight and the risk of cardiovascular disease in a cohort of women followed up since 1976. BMJ. 1997; 315: 396-­‐400. Sakornbut E, Leeman L, Fontaine P. Late pregnancy bleeding. Am Fam Physician. 2007 Apr 15; 75(8):1199-­‐
206 Toot PF, Lu JKH. “Female Reproductive Physiology.” Essentials of Obstetrics and Gynecology, 4th ed. Ed. Hacker NF, Moore GL, Gambone JC. Philadelphia, PA: Elsevier Saunders, 2004. 41-­‐44. Warren M, Perlroth N. The effects of intense exercise on the female reproductive system. Journal of Endocrinology 2001; 170:3-­‐11. th
Williams Obstetrics. 20 edition. 1997. Appleton and Lange. Stamford Connecticut. Wurn B, Wurn L, Roscow A. Treating Female Infertility and Improving IVF Pregnancy Rates With a Manual Physical Therapy Technique. MedGen Med. 2004;6(2):51 12 OBF Pre-­‐Read 1 Pre-­‐Pregnancy, Conception, and Fetal Devlopment S Giglio, K Fisher, D Cathcart