SY 2011-201

Subject: Obstetrics - Gynecology Topic: Fetal Development Lecturer: Dr. Labios Date of Lecture: 12/13/2011 Transcriptionist: Dazed and confused Editor: Beach Bunny Pages: 12 Fetal Growth and Development Differentiate the various terms used to determine the age and duration of pregnancy Correlate the clinical significance of the various morphologic changes at various stages of fetal development Relate fetal nutrition with specific placental function Determine the clinical relevance of the various physiologic changes of the fetus Describe the development of the fetal reproductive system. Determination of Gestational Age (aka, Menstrual Age) Calculated from LNMP (last normal menstrual period), or 2 weeks prior to ovulation and fertilization and 3 weeks prior to implantation. LNMP used generally because most women know their LNMP. If cycle is irregular or unknown LNMP, ultrasound is main determinant of fetal age supplemented with PE and history. Other terms: Ovulation age Postconceptional age Both are determined by LNMP 2 weeks. Average duration is 280 days (40 weeks) Corresponds to 9 1/3 calendar months Corresponds to 10 lunar months. 1 lunar month = 28 days. Naegeles Rule: A quick estimate of the due date of a pregnancy based on menstrual data. 1st day of LMP + 7 days 3 months Eg, LMP = 10/01/11 10 3/01 +7/11 + 1 = 7/08/2012 as expected date of delivery (EDD). Some texts may refer to it as EDC, or estimated date of confinement. For the month: 10 3 = 7 For the day: 1 + 7 = 8 For the year, please take into consideration that the average pregnancy lasts 9-1/3 months or 280 days. So any LMP after March 26 (which is the 85th day of the year), will have an EDD in the next year. So in this case add +1 to the current year. 2011 + 1 = 2012. Average, women will deliver within 3 weeks of EDD, ie, 37 40 weeks. Postdatism: >42 weeks, or delivery after 2 weeks of EDD. Trimester of Pregnancy The period of gestation can also be divided into 3 units of 3 calendar months (13 weeks) each. Some texts use 14 weeks. These 3 trimesters have some important obstetrical milestones. Eg, 1st trimester is embryogenesis and is vulnerable to teratogens. 2nd trimester is when maternal adaptation begins and where maternal testing is performed, ie, glucose test. 3rd trimester: fetus is now usually viable. Morphological Growth Ovum Zygote Blastocyst Embryo fetus

Phases of development within 2 weeks after ovulation 1. Fertilization 2. Formation of free blastocyst 3. Implantation of blastocyst Primitive chorionic villi are formed soon after implantation. With the development of chorionic villi, it is conventional to refer to the products of conception not as fertilized ovum, or zygote but as an embryo. Conception Conception occurs when the sperm meets and penetrates the ovum, or egg. Also known as fertilization. Ovum (Egg) The ovum is the female reproductive cell Barely visible to the naked eye Chief characteristics Round 0.01mm in diameter Consistency of stiff jelly Contributes 23 chromosomes Zygotic Period Conception 1st week Definition: a fertilized egg with 46 chromosomes Genetic potential determined at this time Egg is 2.5 mm in diameter at end of 1st week Mitosis occurs in this period By ultrasound, can see a chorionic sac or pregnancy sac. Embryonic Period Commences at the beginning of the 3rd week after ovulation and fertilization (which coincides in time with the expected day that the next menstruation would have started). Pregnancy test is positive Embryonic disc is well defined Chorionic sac is 1 cm in diameter By end of 4th week after ovulation: Chorionic sac/gestational sac = 2 3 cm in diameter Embryo = 4 5 mm in length Positive cardiac pulsations Partitioning of the primitive heart Arm and leg buds are present Amnion is beginning to unsheathe the body stalk By the end of 6th week after fertilization: Embryo = 22 24 mm in length Heart is completely formed Fingers and toes are present Arms bend at the elbows Upper lip is complete External ear starts to develop 8th week after fertilization End of embryonic period Beginning of fetal period Embryo fetus = 4 cm long Major portion of lung development is yet to occur 10 weeks by menstrual age Fetal Period

Consists of growth and maturation of structures that were formed during the embryonic period Length Characteristics 12 weeks 6 to 7 (+)centers of ossification; fingers and toes; skin and nails; cm movement; genitalia 16 weeks 12 cm Weight = 110 gm 20 weeks 16 cm Weight = 300 gm; skin less transparent; lanugo covers the entire body; scalp hair 24 weeks 21 cm Weight = 630 gm; skin is wrinkled; fat deposition begins; bronchi, bronchioles, alveolar duct development is nearly completed 28 weeks 25 cm Weight = 1100 gm; skin is red covered with vernix caseosa; papillary membrane has just disappeared from the eyes 32 weeks 28 cm Weight = 1800 gm; skin is still red and wrinkled 36 weeks 32 cm Weight = 2500 gm; skin wrinkling is lost 40 weeks 36 cm Weight = 3400 gm **Note: Crown rump length is more accurate than standing height when measuring the length of the fetus. Below: This is the table from Williams that Doc compared to the above table. What he highlights: 14 weeks: sex is distinguishable. At around 24 weeks, the weight is 3x the length. 28 weeks: there is an exponential growth in weight. Note: According to Doc, the below weights were based on specimens preserved in formalin. So fresh specimens will be 5% less in weight.

The Fetal Head Represented by the skull and face Skull is composed of following bones: 2 frontal 2 parietal 2 temporal Upper portion of occipital bone Wings of sphenoid From an obstetrical viewpoint, the size of the head is important because an essential feature of labor is the adaptation between the fetal head and the maternal body pelvis. Skull bones are separated by membranous spaces called sutures: Frontal: between the 2 frontal bones

Sagittal: between the 2 parietal bones 2 coronal: between frontal and parietal 2 lambdoid: between the posterior margins of the parietal bones and upper margin of the occipital bone Frontal and coronal sutures are the most important sutures Fontanel: an area that is being formed by several sutures; irregular space which is enclosed by a membrane. Greater or anterior: lozenge shaped space that is situated at the junction of the sagittal and the coronal sutures Lesser or posterior: small triangular area at the intersection of the sagittal and lambdoid sutures. Temporal or casserian: Temporal fontanels have no diagnostic significance It is important to differentiate these fontanels from each other via internal examination to determine the proper alignment of the fetal head.

Critical Diameters of the Fetal Head Average Location length Occipitofrontal 11.5 cm From the root of the nose to the most prominent portion of the occipital bone Biparietal 9.5 cm From one parietal bone to the other Bitemporal 8.0 cm Between 2 temporal bones Occipitotemporal 12.5 cm From chin to the most prominent portion of occiput Suboccipitobreg 9.5 cm From middle of large fontanel to the matic undersurface of the occipital bone just where it joins the neck **Note: The babys head would need to flex for the shortest circumference to pass through the bony pelvis. If the sinciput is presenting, the occipitofrontal diameter will have difficulty passing through the bony pelvis.

Circumference of the Fetal Head Plane of the occipitofrontal diameter The greatest circumference of the fetal head Averages 34.5 cm Plane of the occipitobregmatic diameter The smallest circumference of the fetal head Averages 32 cm The bones of the cranium are normally connected only by a thin layer of fibrous tissue that allows considerable shifting or sliding of each bone to accommodate the size and shape of the maternal pelvis. This intrapartum process is termed molding. Placental Role in Fetal Growth The placenta is the organ of transfer between mother and fetus At the maternal fetal interface, there is transfer of oxygen and nutrients from the mother to the fetus. Conversely, there is transfer of CO2 and other metabolic wastes from fetus to mother. There are no direct communications between the fetal blood, which is contained in the fetal capillaries in the intravillous space of the chorionic villi and the maternal blood which remains in the intervillous space.

The Intervillous space: Maternal blood Substances transferred from mother to fetus first enter the intervillous space and are then transported to syncytiotrophoblast. Substances transported from the fetus to the mother are transferred from the synctitium into the same space. There are no direct communications between the fetal blood, which is contained in the fetal capillaries in the intravillous space of the chorionic villi, and the maternal blood, which remains in the intervillous space. Thus, the chorionic villi and the intervillous space, together, function for the fetus as lung, gastrointestinal tract, and kidney. Placental Transfer Substances that pass from maternal blood to fetal blood must traverse: 1. Synctiotrophoblast 2. Stroma of the intravillous space 3. Fetal capillary wall This histologic barrier separates blood in the maternal and fetal circulations. The syncytiotrophoblast actively or passively permits, facilitates, and adjusts the amount and rate of transfer of a wide range of substances to the fetus. This transfer is dependent on the total surface area of chorionic villi With close correlation to fetal weight Total surface at term has been estimated to be 10m2. Regulation of Placental Transfer is Dependent on at least 10 variables: 1. Concentration of substance in the maternal plasma. 2. Rate of maternal flow. Eg, hypertensive mother will have chance of intrauterine blood flow. 3. Area available for exchange across the villous trophoblast. Eg, some hypertensive disorders may lead to hypoplacentosisintrauterine BF. Eg, in gestational diabetes, there is hyperplacentosisin exchange and bigger baby may result. 4. Physical properties of tissue barrier 5. Capacity of the biochemical machinery of the placenta 6. Amount of substance metabolized 7. Area available for exchange across the fetal capillaries. 8. Concentration of substance in the fetal blood 9. Binding or carrier proteins 10.Rate of fetal blood flow

Mechanism of Transfer 1. Diffusion Mechanism of transfer of low molecular weight compounds: oxygen, CO2, water, most electrolytes, anesthetic gases Also glycerol 2. Facilitated diffusion - glucose 3. Active transport - ions Placenta as the Fetal Lung: O2 Transfer of oxygen across the placenta is blood flow limited Supplies 8 ml O2/min/kg of fetal weight Average oxygen saturation of intervillous blood = 65 75% Partial pressure (pO2) = 30 35 mmHg Transfer of fetal CO2 is by diffusion, which is more rapid than O2 Near term, pCO2 in the UA = 48 mmHg or about 5 mmHg more than in the maternal intervillous blood. Fetal blood has less affinity for CO2 than does maternal blood, thereby favoring exchange Mild hyperventilation by the pregnant woman results in a fall in pCO2 favoring a transfer of CO2 from the fetal compartment to maternal blood Fetal Nutrition Largely dependent on maternal food intake, nutritional status 3 major maternal storage depots: the liver, muscle, and adipose tissue Storage hormone insulin

Maternal source of energy 1. Glucose as glycogen, mainly stored in liver and muscle 2. Amino acids as protein 3. Free fatty acids from adipose tissue Glucose and fetal growth Glucose is a major nutrient for fetal growth and energy Human placental lactogen (hPL) blocks the peripheral uptake and use of glucose while promoting the mobilization and use of free fatty acids by maternal tissues Glucose transfer across cell membranes is accomplished by a carrier mediated, stereo specific nonconcentrating process of facilitated diffusion With 14 separate transport proteins (GLUTs) GLUT 1 and GLUT 3 transport D glucose Located in the plasma membrane of the microvilli of human synctiotrophoblast Free Fatty Acids and Triglycerides Neutral fat (triacylglycerols) does not cross the placenta Glycerol passes by simple diffusion Fatty acids also synthesized in the placenta Lipoprotein lipase is present on the maternal but not on the fetal side This arrangement should favor hydrolysis of triacylglycerols in the maternal intervillous space while preserving these neutral lipids in the fetal blood. Fatty acids transferred to the fetus can be converted to triacylglycerol in the fetal liver. The LDL particle from maternal plasma bind to specific LDL receptors in the coated pit regions of microvilli on the maternal facing side of synctiotrophoblast. Taken up by receptor mediated endocytosis The placental uptake and use of low density lipoprotein for fetal assimilation of essential fatty acids and amino acids. The LDL particles from maternal plasma bind to specific LDL receptors in the coated pit regions of microvilli on the maternal facing side of synctiotrophoblast. This is taken up by receptor mediated endocytosis.

The apoprotein and cholesterol esters of LDL are hydrolyzed lysosomal enzymes in the syncytium to give: 1. Cholesterol for progesterone synthesis 2. Free amino acids 3. Essential fatty acids, primarily linoleic acid

Proteins Limited transfer of larger proteins across the placenta Exceptions are: IgG cross the placenta in large amounts via endocytosis via trophoblast Fc receptors. So it is present in approximately the same presentation in cord and placental sera. IgA and IgM of maternal origin are excluded from the fetus. Retinol binding proteins Ions and trace metals Iodide transport = carrier mediated, energy requiring active process Zinc in the fetal plasma also are greater than those in maternal plasma Copper levels in fetal plasma are less than those in maternal plasma

Placental Sequestration of Heavy Metals Heavy metal - binding protein Metallothionein 1 = expressed in human syncytiotrophoblast Binds zinc, copper, lead, and cadmium. Cadmium is found in people who smoke, so excess cadmium can lead to poor placental growth. Metallothionein 1 binds cadmium for this reason. Vitamins Vitamin A (retinol) Greater concentration in fetus than maternal plasma Bound to retinol binding protein and prealbumin Vitamin C (ascorbic acid) Transfer from mother to fetus is accompanied by an energy dependent, carrier mediated process Vitamin D (cholecalciferol [1, 25 dihydroxycholecalciferol]) Greater concentration in maternal plasma than fetus 1 hydroxylation of 25 hydroxyvitamin D3 takes place in placenta and in decidua Fetal 1. 2. 3. 4. 5. 6. 7. 8. Physiology Amniotic fluid Fetal circulation Fetal blood Fetal immune response Nervous system/sensory organs Gastrointestinal system Urinary system Pulmonary system

Amniotic Fluid Early pregnancy = ultrafiltrate of maternal plasma Beginning 2nd trimester = similar to fetal plasma. At this point it consists mostly of extracellular fluid that diffuses through the skin and thus reflects the composition of fetal plasma. After 20 weeks = composed largely of fetal urine because cornification of fetal skin prevents diffusion of ECF. The fetal kidneys start producing urine of 12 weeks, and by 18 weeks they are producing 7 to 14 ml/day. Serves to cushion the fetus for musculoskeletal development, protection from trauma Maintains temperature

EGF and EGF like growth factors (transforming growth factor ) may promote growth and differentiation of lungs and GIT Volume: Increases to 10 ml/week at 8 weeks Increases up to 60 ml/week at 21 weeks Then declines to steady state at 33 weeks Role in pulmonary development Draining off amniotic fluid, chronically draining pulmonary fluid through the trachea, and by physically preventing the chest excursion that mimics breathing may lead to pulmonary hypoplasia

Fetal Circulation Fetal blood does not need to enter the lungs to be oxygenated Fetal heart chambers work in parallel not in series Ventricles of heart work in parallel not series. Well oxygenated blood enters left ventricle, which supplies the heart and the brain, and less oxygenated blood enters the left ventricle and supplies the rest of the body. These separate circulations are maintained by structures if the right atrium, which effectively directs blood to either the left atrium or the right ventricle. LA RA via the foramen ovale. The blood is partitioned according to its oxygen content in the IVC. The well oxygenated blood tends to course along the medial aspect of IVC and the less oxygenated blood stays along the lateral wall. This facilitates shunting into opposites sides of the heart. Once this blood enters the right atrium, the configuration the crista dividends preferentially shunts the well oxygenated blood from the medial side of the IVC and ductus venosus into the foramen ovale. After oxygen is extracted from the blood, it reenters the right heart via the SVC. 90% of blood exiting the right ventricle is then shunted through the ductus arteriorsus to the descending aorta. The less oxygenated blood coursing the lateral wall of the IVC enters the right atrium, then enters the right ventricle. The SVC courses inferiorly and anteriorly as it enters the right atrium, ensuring that less well oxygenated blood returning from the brain and upper body will be shunted to the right ventricle. After birth: Umbilical vessels Ductus arteriosus Constrict or collapse Foramen ovale Ductus venosus Hypogastric (aka, umbilical) arteries obliterated within 3 to 4 days after birth become umbilical ligaments Umbilical vein forms the ligamentum teres. Umbilical vein divides into ductus venosus and portal sinus. Portal sinus supplies the liver and some nutrients are extracted there. It then feeds into the IVC. Ductus constricts by a 10 to 96 hours, anatomically closed by 2 to 3 weeks, to become ligamentum venosum Fetal blood Hemopoiesis: Sites Yolk sac Liver: More important in early stages Bone marrow: More important in later development Sites of hemopoiesis synthesized at various stages of fetal development (see figure below) The first erythrocytes are nucleated and macrocytic Mean cell volume = 180 fL and decreases to 105 115 fL at term Hemoglobin = 12 g/dL midpregnancy, 18 g/dL at term

Erythropoiesis Mostly influenced by fetal erythropoietin as maternal erythropoietin does not cross the placenta. Production is influenced by testosterone, estrogen, prostaglandin, thyroid hormone, and lipoprotein The fetal liver appears to be an important source until renal production begins Fetal blood volume At term = 78 ml/kg (Usher and associates, 1963) Volume of blood of fetal origin = 45 ml/kg (Gruenwald, 1967) Fetoplacental blood volume = 125 ml/kg Fetal coagulation factors Embryo = no hemostatic proteins Fetus at 12 weeks = starts producing normal, adult type, procoagulant, fibrinolytic and anticoagulant proteins Maternal proteins do not cross Factors that are low in cord blood: II, VII, IX, X, XI, XII, XIII, and fibrinogen

Fetal Immune Response Immunoglobulin G Main Ig in the fetus, in the absence of infection Maternal source transferred across the placenta by receptor mediated process in synctiotrophoblast IgG transport begins at 16 weeks, bulk acquired during the last 4 weeks of pregnancy, adult values are not attained until 3 years of age. Transfer can be harmful like in D- antigen isoimmunization resulting in HDN (hemolytic disease of the newborn) Immunoglobulin M Not transported from mother to fetus Increased levels are found in newborns with rubella, CMV, or toxoplasmosis Immunoglobulin A Ingested in colostrums, provides protection against enteric infections Lymphocytes B lymphocytes appear in liver by 9 weeks, present in blood and spleen by 12 weeks T lymphocytes begin to leave the thymus at about 14 weeks Despite this the newborn responds poorly to immunization, and especially poorly to bacterial capsular polysaccharides

This may be due to either deficient response of newborn B cells to polyclonal activators or lack of T cells that proliferate in response to specific stimuli

Nervous System and Sensory Organs Spinal cord relation to vertebral column: Embryo = entire length By 24 weeks = S1 At birth = L3 Adult = L1 Myelination begins in the middle of gestation Synaptic function is developed by the 8th week to demonstrate flexion of the neck and trunk At 10 weeks, local stimuli may evoke squinting, opening of the mouth, incomplete finger closure, and flexion of the toes. Swallowing 10 weeks Respiration 14 to 16 weeks Rudimentary taste 7 weeks buds Sucking ability 24 weeks Ability to hear sound 24 to 26 weeks Eye sensitivity 28 weeks Gastrointestinal System Swallowing begins at 10 to 12 weeks Effect on amniotic fluid volume Early pregnancy = little effect Late pregnancy: if swallowing is inhibited, polyhydramnios is common. So if there is a lot of fluid on US, GI tract is examined via US. Meconium Whenever the fetus swallows the amniotic fluid containing meconium is saved in the gut, ie, glycerophospholipids, cells, lanugo. Meconium is greenish in color due to biliverdin. So how do you know fetus passes meconium? The amniotic fluid should also be greenish. Mechanism of passage of meconium: Normal bowel via vagal stimulation When hypoxia stimulates vasopressin hormone from fetal pituitary gland. Small bowel obstruction Congenital florid diarrhea Urinary System Anatomical development Kidney and ureter = develop from intermediate mesoderm Bladder and urethra = develop from urogenital sinus Bladder = develops in part from the allantois Physiological development Kidneys = receive between 2 and 4% cardiac output. Newborn receives 15 18% Renal vascular resistance is high and the filtration fraction is low GFR = less than 0.1 mL/min to 0.3 mL/min at 20 weeks Decreased in cases of hemorrhage of hypoxia, growth restricted infants, and infants of diabetic mother Urine formation Starts at 12 weeks By 18 weeks = 7 to 14 mL/day At term = 27 mL/day or 650 mL/day furosemide

uteroplacental insufficiency, fetal stress

Pulmonary System Immaturity of the lung = RDS (Respiratory Distress Syndrome) Fetal lung mature function Anatomical and morphological development Capacity for surfactant formation 3 stages of lung development (Moore, 1983) 1. Pseudoglandular = 5th to 17th week 2. Canalicular = 16 25 weeks, bronchiole formation 3. Terminal sac = pulmonary alveoli; type II cells begin to produce surfactant Clinical correlation (+)renal agenesis No amniotic fluid is present from the beginning of lung growth Fetus with membrane rupture before 20 weeks Normal bronchial branching and cartilage development but has immature alveoli Membrane rupture after 24 weeks Little long term effect on pulmonary structure Surfactant A substance formed specifically in the type II pneumocytes that line the alveoli Uncoils form the lamellar bodies, and spreads to line the alveolus Prevents the collapse of terminal sacs or alveoli during expiration At birth, the terminal sacs must remain expanded despite the pressure imparted by the tissue to air interface With the first breath, surfactant uncoils from the lamellar bodies, and spreads to line the alveolus to prevent alveolar collapse during expiration. Composition: Protein (10%) Lipid (90%) 80% are phosphatidylcholines (lecithins) The principal active lecithin is dipalmitoylphosphatidylcholine (DPPC) 50% Phosphatidylglycerol (PG) 8 to 15% Corticosteroids and fetal lung maturation For pregnancy less than 32 weeks: Betamethasone 12 mg, IM, 2 doses, 24 hours apart Dexamethasone, 5 mg, IM, q12h x 4 doses Possible side effects: neurodevelopmental anomalies in the newborn, infection Fetal Gender 1963: Carr quoted 106 males/100 females 1998: Davis reported a significant decline in male births since 1950 in Denmark, Sweden, Netherlands, US, Germany, Norway, and Finland 1997: In Canada, the proportion of males has dropped by 2.2 male births per 1000 live births. In the Atlantic region, the decline was 5.6 males per 1000 Gender assignment at birth Basic requirements for gender assignment Karyotypic sex Gonadal sex Hormonal milieu Anatomy Possibilities for surgical correction Chromosomal gender Genetic gender XX or XY is established at the time of fertilization Gonadal Gender At 6 weeks after conception if a Y chromosome is present, the gonads develop into testis

Testes development if the SRY gene (sex determining region) is expressed Phenotypic Gender After gonadal gender is established, this is established rapidly. Male phenotypic sexual differentiation is directed by the function of the fetal testis In the absence of a testis, female differentiation ensues irrespective of the genetic gender Development and differentiation of the internal and external genitalia to male phenotype is dependent on testicular function. On the contrary, fetal ovary is not required for female sexual differentiation. Mllerian Inhibiting Substance Acts locally as a paracrine factor to cause regression of Mllerian duct, preventing the development of uterus, Fallopian tube, and upper vagina Produced by Sertoli cells of the seminiferous tubules Fetal testosterone secretion Acts directly on the Wolffian duct to effect the development of the vas deferens, epididymis, and seminal vesicles Enters the fetal blood and acts on the anlagen of the external genitalia Genital ambiguity of the newborn Result of either of the 2: 1. Excessive androgen action in an embryo fetus that was destined to be female 2. Inadequate androgen representation for one destined to be male 4 clinically defined categories: 1. Female pseudohermaphrodite: (+)uterus 2. Male pseudohermaphrodite: (-)uterus 3. Dysgenetic gonads 4. True hermaphrodite

Note: This is where Doc ends the lecture. The following are pulled from old notes for the sake of completion. However, these were not discussed in the actual lecture. Category 1: Female Pseudohermaphroditism Mllerian-inhibiting substance is not produced Androgen exposure of the embryo-fetus is excessive, but variable, for a fetus genetically predestined to be female The karyotype is 46,XX Ovaries are present Uterus, FT, and upper vagina are developed Fetal Growth and Development Page 11 of 11 Causes: Congenital adrenal hyperplasia excessive ACTH stimulation of the fetal adrenal glands secretion of large amounts of cortisol precursor, like androstenedione converted to testosterone in extra adrenal fetal tissues. Transfer of androgen from maternal compartments = ovarian tumors (theca lutein cyst, luteoma, arrhenoblastoma-Sertoli leydig cell tumor, hilar cell tumor Drugs ingested in pregnancy - synthetic progestin or anabolic steroids Category 2: Male Pseudohermaphroditism Production of Mllerian-inhibiting substance Incomplete but variable androgenic representation for a fetus predestined to be male The karyotype is 46,XY The presence of testes or no gonads Uterus, FT, and upper vagina do not develop

These subjects have a spectrum of phenotypes that varies from a normal female with absent uterus, FT, and upper vagina, to a normal male phenotype with anorchia (congenital absence of the testes) Causes: Androgen Insensitivity Syndrome Incomplete Androgen Insensitivity, familial male pseudohermaphroditism type 1 (Reifenstein Syndrome), 5 a-reductase deficiency

Category 3: Dysgenetic Gonads Mllerian-inhibiting substance is not produced Fetal androgen exposure is variable The karyotype varies among subjects and is commonly abnormal Neither normal ovaries nor testes are present but rarely both ovarian and testicular tissues are found Turners syndrome (46X) Most common form phenotype is female secondary gender characteristics do not develop at the time of expected puberty Category 4: True Hermaphroditism The guidelines for category 3 are met Have both ovarian and testicular tissues, and in particular, germ cells (ova and sperm) of both sexes are found in the abnormal gonads Preliminary diagnosis Physical examination Ultrasound evaluation (+) uterus = consider Female Pseudohermaphroditism, testicular or gonadal dysgenesis or true hermaphroditism (-) uterus = Male pseudohermaphroditism ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~End of Transcription~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ To this end we always pray for you, that our God will make you worthy of His calling and may fulfill every resolve for good and every work of faith by His power, so that the name of our Lord Jesus may be glorified in you, and you in Him, according to the grace of our God and the Lord Jesus Christ. 2 Thessalonians 1:11-12