Definitions used in pregnancy and pregnancy diagnosis
Definitions Used in Pregnancy
• Gestational Age (Menstrual Age): The time from the start of the last menstrual period to the expected due date (approximately 10 months, 40 weeks or 280 days).
• Age at Ovulation (Postconceptional Age): Time from fertilization to expected due date (approximately 9.5 months or 38 weeks or 265 days).
• Embryonic Period: It starts 2 weeks after conception and ends at the end of 8 weeks. During this period, organogenesis is completed.
• Fetal Period: It is the period starting 8 weeks after conception.
• Antenatal Period: It is the period from conception to birth.
• Perinatal Period: It is the period from the end of the 20th week of pregnancy until the completion of the 28th day after delivery.
• Gravida: A woman who is currently pregnant or has had a previous pregnancy (it doesn't matter how their pregnancy ended).
► Nulligravida: A woman who is not currently pregnant and has never been pregnant before.
► Primigravida: A woman who has had her first pregnancy.
► Multigravida: A woman who has had multiple pregnancies.
• Parity: These are still or live births after the 20th gestational week.
► Nullipar: Women who have not given birth above the 20th gestational week (women who have not completed a pregnancy other than abortion or ectopic pregnancy).
► Primiparous: A woman who has given birth at 20 weeks of gestation or above (live or dead, one or more babies).
► Multiparous: Two or more women who have given birth above the 20th week of pregnancy.
The number of pregnancies reaching the 20th week determines the parity, not the number of babies born. Women who have given birth to twins once after 20 weeks of gestation are primiparous women.
• Term Birth: births between weeks 37-42.
• Preterm Birth: It is the birth that takes place before 37th gestational week.
► Early pretem; Those born before the 34th week of pregnancy is completed.
► Late Preterm; Those born before the 34th to 36th week is completed.
• Postterm Birth: It is the birth that takes place after the 42nd gestational week.
• trimester; Pregnancy consists of three parts called trimesters.
► I.Trimester: 0-14. between weeks
► II.Trimester: 15-28. between weeks
► III. Trimester: 29-42. between weeks
• Perinatal Mortality: Neonatal deaths occurring between the 20th week of pregnancy and the first 28th day after birth.
• Maternal Mortality Rate: Includes maternal deaths due to reproductive process per 100,000 live births.
Cardiovascular diseases, obstetric hemorrhages and infections are among the most common causes of maternal mortality.
Diagnosing Pregnancy
Suspicious symptoms and signs suggesting pregnancy
► Nausea and vomiting
► Frequent urination
► Fatigue and weakness
► Menstrual delay
► Changes in the breasts (mastodynia, colostrum secretion)
► Skin changes (chloasma, linea nigra, striae, telangiectasia)
► Purplish discoloration of the vaginal mucosa and cervix (Chadwick sign)
► Detection of fetal movements (18-20 weeks in primigravids, 16-18 weeks in multigravids)
► Excessive softening of the isthmus (Hegar sign)
► Uterine souffle (murmur parallel to maternal heartbeat)
► Positive hCG test in blood or urine
Positive Findings Confirming Pregnancy
► Hearing the fetal heartbeat (8 weeks with Doppler, 18 weeks with auscultation)
► Determination of active fetal movements by the examiner (20th week)
► Seeing the fetus sonographically or radiographically
MATERNAL PLACENTAL FETAL UNIT
Fertilization and Implantation
• After the mature oocyte fertilizes in the tube, it turns into a zygote (diploid cell with 46 chromosomes). Each cell formed by the mitotic division of the zygote is called a blastomere, and as the division continues, a morula consisting of 16 blastomeres is formed. Morula approximately 3-4 days after fertilization. days later it descends into the uterine cavity. With the accumulation of fluid between the blastomeres in the morula, the cell turns into a blastocyst (with 58-256 blastomeres).
• On the fourth day, 5 cells located in the inner part of the 58-cell blastula will provide embryo development (embryoblast), and 53 cells located outside will develop trophoblast.
• By the fifth day, 8 cells of the 107-cell blastocyst are responsible for embryo formation (embryoblast), while the outer 99 cells form trophoblasts. During this period, the blastocyst gets rid of the surrounding zona pellucida, and as a result, it secretes cytokines (IL la and IL-113) and hCG that will enable it to be accepted by the endometrium. The response of the endometrium to these signals from the blastocyst is the release of leukemia inhibitory factor, colony stimulating factor and follistatin. Maternal recognition of pregnancy occurs by signals emitted by the blastocyst.
Against antigenic incompatibility between mother and fetus (semiallogeneic fetal graft), its immunological recognition allows HLA-G (HLA-G2 isoform) found in extravillous cytotrophoblasts.
• 6-7 days after fertilization. The blastocyst implants into the endometrium. Implantation takes place in 3 phases;
► Apposition - attachment of the blastocyst to the uterine wall; often in the posterior upper part of the uterus
► Adhesion - Increase in endometrial integrins
► Invasion
The most suitable period for endometrial receptivity for implantation is the 20-24th of the cycle. between days.
Loss of microvilli and cilia in epithelial surface cells is required for endometrial receptivity. In addition, protrusions towards the lumen on the apical cell surfaces begin to become prominent and these are called pinopods.
decidua
• Decidua is the special and highly modified endometrial tissue of pregnancy. The decidual reaction (decidualization) is the transformation of the secretory endometrium into decidual and occurs with estrogen, progesterone, androgen and factors secreted from the implanted blastocyst. Decidua secretes large amounts of prolactin.
• Decidua anatomically consists of three parts.
► Decidua basalis to the section just below the blastocyst implantation,
► Decidua capsullaris, which surrounds the developing blastocyst and separates it from the uterine cavity,
► The part that covers the entire remaining endometrium is called the decidua parietalis.
• In the first weeks of pregnancy, there is a space between the decidua capsullaris and the decidua parietalis because the gestational sac cannot fill the entire uterine cavity. 14-16 days of pregnancy. The growing sac fills the uterine cavity and the uterine cavity is completely obliterated as a result of the fusion of the decidua capsullaris and the decidua parietalis. The structure formed by two combined decidua is called decidua vera.
• Where the invading trophoblasts meet the decidua, there is a zone of fibrinoid degeneration, called the Nitabuch layer. In cases where the decidua is detective, such as placenta accreta, this layer is not observed.
trophoblasts
• The formation of the placenta begins with the trophectoderm that differentiates for the first time at the morula stage. As a result of this differentiation, the trophoblastic layer surrounding the blastocyst is formed. On the 8th day after fertilization, trophoblasts differentiate into outer multinuclear syncytiotrophoblasts and inner mononuclear cytotrophoblasts.
• Upon completion of implantation, these trophoblasts differentiate into villous and extravillous trophoblasts.
► Villous trophoblasts form the chorionic villi in the placenta and their primary function is the transport of oxygen and nutrients between the mother and the fetus.
► Extravillous trophoblasts penetrate the spiral arterioles by invading the maternal decidua and myometrium. Extravillous trophoblasts are also divided into two groups.
0 Interstitial trophoblasts invade the decidua, penetrate the myometrium, and form giant cells in the placental bed and surround the spiral arterioles.
0 Endovascular trophoblasts penetrate the lumen of spiral arterioles.
• After erosion of the endometrial epithelium, the blastocyst invades deeply and is completely covered by the endometrium on the 10th day after fertilization.
• As the blastocyst and trophoblasts grow, one end of this mass moves into the uterine cavity and the other end is buried deep into the endometrium. Chorionic villi invading the decidua basalis form the chorion frondosum (the fetal component of the placenta). As the embryo grows, blood circulation is restricted on the side of the chorionic layer facing the endometrial cavity. Therefore, the growth of the villi on the decidua capsullaris side stops and they begin to degenerate. As a result, this part of the chorion (chorion laeve) begins to form the avascular fetal membranes.
• The chorion is primarily a protective tissue layer and provides immunological acceptance. It also contains enzymes that deactivate uteotonins (prostaglandin dehydrogenase, oxytocinase and enkephalinase).
Invasion of trophoblasts is mediated by the proteolytic enzymes they secrete and the proteinases they activate in the endometrium. There are many adhesive molecules that keep invading trophoblasts attached to the maternal decidua, the most important of which is fetal fibronectin, also known as trophoblast adhesive.
Placenta
• About 12 days after implantation, primary chorionic villi begin to appear in the placenta. Secondary villi are formed when solid trophoblasts are surrounded by mesenchymal cords originating from the extraembryonic mesoderm. The villi that emerge after angiogenesis begins in the mesenchymal nucleus are called tertiary villi.
• Approximately 15 days after implantation, maternal blood begins to fill the intervillous space, and on the 7th day, fetal blood vessels become functional and true placental circulation begins.
• The inner surface of the villi is covered with cytotrophoblasts (Langhans cells), and the outer surface is covered with syncytium (syncytiotrophoblasts) and are syncytiotrophoblasts that are in direct contact with the maternal blood in the placenta.
• Placental cotyledons: Each cotyledon is a functional unit fed by chorionic villi. It is seen in the form of lobes on the maternal face, and their number varies between 10 and 38. The number of cotyledons remains the same throughout pregnancy.
• Term placenta weighs approximately 500 g and is 20 cm in diameter and 2 cm in thickness. As the placenta ages, there is a decrease in cytotrophoblasts and stroma, structural changes (thinning) in syncytiotrophoblasts, and an increase in Hoffbauer cells (fetal macrophages).
• If a section is taken from the fetal side of the placenta to the maternal side, it includes the amnion, chorion (frondosum), chorionic villi, decidua (basalis), and myometrium, respectively.
• The maternal face contains the cotyledons and the fetal face contains the amnion. Fetal chorionic vessels pass under the amnion. Fetal deoxygenated blood travels to the placenta via bilateral umbilical arteries, which are branches of the hypogastric artery. Oxygenated blood returns to the fetus via a single umbilical vein. There are chorionic arteries and veins on the fetal face.
In the placenta, maternal blood directly washes the villous trophoblasts, but does not mix with fetal blood in the fetal capillaries in the villi (haemochorial).
• In the placenta, maternal and fetal blood are separated from each other by the fetomaternal barrier. Until the third month of pregnancy, this barrier contains syncytiotrophoblasts, cytotrophoblasts, embryonic mesoderm and fetal capillary endothelium (hemodicorial),
After 3 months, cytotrophoblasts lose their continuity and disappear (hemomonochorial). Maternal blood is poured into the intervillous space. Fetal blood is in chorionic villi.
amnion
• Amnion in the 7th-8th days of embryonic life. It appears as a small vesicle between the embryonic cell mass and adjacent trophoblastic cells. There are no smooth muscle cells, nerves, lymphatics and blood vessels in the structure of the amnion. The amnion internally surrounds the fetal surface of the placenta, the umbilical cord, and remains in a sac around the fetus.
Synthesis and Secretions of the Amnion
a) From Epithelial Cells:
1. Metalloproteinase-1 tissue inhibitor
2. IL-8
3. PGE2
4. Fetal fibronectin
5. Endothelin
6. Parathyroid hormone-like protein
7. Natriuretic peptide
8.CRH
b) From Mesenchymal Cells:
1. Type I, III interstitial collagens
2. IL-6, IL-8
3. PGE2
4. Monocyte chemoattractant protein-1
Umbilical Cord (Funis)
• The umbilical cord consists of two arteries (carrying deoxygenated blood) and a vein (carrying oxygenated blood). During its formation, the right umbilical vein usually disappears and the left umbilical vein remains open. It contains Wharton gel, which is an extracellular matrix. The most common anomaly is single umbilical artery.
Placental Hormones
Human Chorionic Gonadotropin (hCG)
► hCG is a glycoprotein hormone with a weight of 36,000-40,000 Da. It has a heterodimer structure and consists of beta and alpha subunits. A single gene on the 6th chromosome encodes the a subunits of hCG, TSH, FSH and LH hormones. The beta subunit is encoded by 6 different regions on chromosome 19.
► hCG is largely synthesized from trophoblasts in the placenta by stimulation of placental GnRH.
► The hCG level in maternal blood is increased in multiple pregnancies, erythroblastosis fetalis accompanied by fetal hemolytic anemia, presence of fetus with Down syndrome and gestational trophoblastic diseases. On the other hand, its level decreases in pregnancy losses and ectopic pregnancies.
► It can be detected in maternal serum or urine 8-9 days after ovulation with a sensitive test. 60-70 from the last menstrual period. It reaches its maximum level of 100,000 mIU/mL by day 10 (week 10). The doubling time is approximately 48 hours in the first 10 weeks of pregnancy. It then declines to the lowest level by week 16 and remains at these levels throughout the pregnancy. On day 14, it drops below 5 mIU/mL in maternal serum.
► Its half-life is 36 hours. 30% of hCG is metabolized by the kidneys and the remainder is metabolized by the liver.
► Functions of hCG:
0 The most important effect is to ensure that the corpus luteum continues to function.
0 It directly stimulates the release of testosterone from the fetal testicles.
0 Stimulates the maternal thyroid gland.
0 Provides the release of relaxin from the corpus luteum.
0 Increases vasodilation in the uterine vascular bed.
It provides relaxation of myometrial smooth muscle cells.
human placental lactogen (hPL)
► It has been named as hPL (chorionic somatomammotropin) due to its patent lactogenic effects and its growth hormone-like structure (96% common).
► It is in the structure of non-glycosylated polypeptide.
► hPL; It is synthesized in trophoblasts in the placenta. It can be detected in maternal serum from the 3rd week of pregnancy and gradually increases to reach its peak level at 34th week. is the hormone secreted in the highest amount in pregnant women and its release is directly proportional to the placental mass.
► The half-life is 10-30 minutes.
► functions of hPL:
0 Providing free fatty acids for nutritional purposes to the fetus through maternal lipolysis.
0 More glucose to the fetus by inhibition of peripheral glucose uptake
0 Increase in maternal insulin levels with the effect of insulin resistance, resulting in increased protein synthesis and supply of amine acid to the fetus.
0 Patent is an angiogenic hormone that increases fetal vascularization.
0 Leptin inhibition
Chorionic Adrenocorticotropin (Acth) and Corticotropin Releasing Hormone (CRH)
► Placenta! The physiological effect of ACTH is not fully known. Placental ACTH is not under feedback regulation of corticosteroids. Placenta! Placenta from ACTH release! CRH is responsible.
While cortisol suppresses CRH with (-) feedback in the hypothalamus; It increases CRH release with (+) feedback in the placenta.
► While the CRH level is 5-10 pmol/L in the serum of a non-pregnant woman, this level rises to 100 pmol/L in pregnant women and to 500 pmol/L at the beginning of the third trimester. With the onset of labor, a 2-3-fold increase in CRH level is detected.
CRH is thought to be the factor that initiates labor.
relaxin
► It is a peptide hormone that is structurally similar to insulin and IGF. It is produced by the corpus luteum, decidua and placenta . 4-5. It appears in the maternal serum in the 10th weeks, peaks at the 10th week and decreases until the term.
► Relaxin is effective in providing myometrial relaxation in early pregnancy. Relaxin has important effects on renal hemodynamics, increasing glomerular filtration rate and decreasing osmolarity. In addition, it has a role in preparing the connective tissue in the genital area for birth and in reducing the vascular resistance in the uterine artery. However, it is not associated with peripheral joint elasticity.
leptin
► Since it is secreted in both cytotrophoblasts and syncytiotrophoblasts in the placenta, in addition to adipose tissue, its amounts in pregnancy are quite high.
progesterone
► Progesterone, which is produced from the corpus luteum with hCG stimulation for the first 7 weeks, is produced from syncytiotrophoblasts in the placenta after this week.
estrogens
► The placenta can synthesize very high amounts of estrogen. Neither cholesterol nor progesterone act as precursors for estrogen biosynthesis in trophoblasts. The placenta cannot synthesize cholesterol from acetate and does not contain 17a-hydroxylase and 17,20-lyase (CYP17) enzymes that are absolutely necessary for the production of sex steroids. Therefore, in the placenta, 21-carbon steroids cannot be reduced to 19-carbon steroids.
► DHEA-S acts as the major precursor of estrogens during pregnancy, the major source of which in pregnancy is the fetal adrenal gland. Therefore, the main source of estrogen produced by the placenta in pregnant women is the fetal adrenal gland.
► In the placenta, DHEA-S is converted to estradiol (E2) by 4 critical enzymes found in syncytiotrophoblasts.
0 First, the steroid sulfatase enzyme converts DHEA-S to DHEA,
0 Subsequently, the 3(3-OHSD enzyme converts DHEA to androstenedione,
0 The generated androstenedione is converted to estrone (EI) by the cytochrome P450 aromatase (CYP19) enzyme.
0 This is converted to the end product estradiol (E2) by the 17(3-OHSD enzyme).
► Some of the DHEA-S is hydroxylated with the 16a-hydroxylase enzyme in the fetal liver and comes to the placenta in the form of 160H-DHEA-S. As a result of the reaction of this androgen with 4 enzymes, estriol (E3) is formed.
► All these steps show that the placenta and fetus (adrenal gland and liver) play a role together in the biosynthesis of estrogens. Estrogens delivered to the fetus are inactivated by hydroxylation in the fetal liver and the fetus is protected from excessive feminization. In this process, estriol is reduced to oesterol (E4).
There is no 3 beta-OHSD (Delta5-4 isomerase) enzyme activity in the fetal zone of the fetal adrenal gland. Therefore, progesterone and androstenedione synthesis in the fetal adrenal gland is limited. Steroid sulfotransferase activity in the fetal adrenal gland is very high.
Since placenta and fetus coexist in E3 synthesis, E3 is an indicator of normal functioning of the fetoplacental unit.
Situations where E3 increases
1. Fetal erythroblastosis (placental hypertrophy i)
2. Multiple pregnancies
Cases where E3 is down
1. Fetal death
2. Fetal anencephaly
3. Fetal adrenal hypoplasia
4. Fetal-placental sulfatase deficiency
5. Fetal-placental aromatase deficiency
6. Trisomy 21 (Down syndrome)
7. Maternal use of glucocorticoids
8. Mother's Addison's disease
9. Gestational trophoblastic neoplasms
Very low maternal serum estriol level (<0.25 MOM}, Smith Lemli-Opitz Syndrome (7-dehydrocholesterol reductase gene mutation), X-linked ichthyosis (steroid sulfatase deficiency}, congenital adrenal hypoplasia, adrenocorticotropin deficiency, hypothalamic corticotropin deficiency, and anencephaly associated with.
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Hormones
during pregnancy |
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fetal compartment |
placental compartment |
maternal compartment |
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Alpha-fetoprotein |
hypothalamic hormones |
Decidual proteins |
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GnRH |
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CRH |
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TRH |
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Somatostatin |
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GHRH |
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Pituitary hormones |
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hCG |
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hPL |
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GH variant |
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PTH-like protein |
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ACTH |
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Oxytocin |
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Other proteins |
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Opiates |
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Prorenin |
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beta 1 pregnancy-specific glycoproteins |
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PAPP-A |
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Activin |
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inhibin |
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Follistatin |
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Relaxin |
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Calcitonin |
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Leptin |
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Atrial natriuretic peptide |
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Neuropeptide Y |
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growth factors |
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IGF-1 |
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IGF-2 |
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Epidermal growth factor |
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Fibroblast growth factor |
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Platelet-derived growth factor |
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Transforming growth factor a, B |
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cytokines |
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interleukin |
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Interferon |
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Tissue necrosis factor-alpha |
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Colony stimulating factor-1 |
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