• "Gametogenesis, fertilization, cleavage, gastrulation"
• Or paste the list of topics from your textbook/notes

Pharyngeal Arches and Their Derivatives

Overview

• The Developing Human: Clinically Oriented Embryology

Structure of a Typical Pharyngeal Arch

1. Neural crest cells - migrate into the arches during week 4 and form skeletal structures (cartilage, bone), dermis, and smooth muscle of the head/neck
2. Paraxial and lateral plate mesoderm - form the muscular core of each arch

• An aortic arch artery (arising from the truncus arteriosus)
• A cartilaginous skeletal element
• A cranial nerve (special visceral efferent fibers)
• A muscle primordium

Cross-section through the embryo at the pharyngeal gut level, showing the arch components and their layer arrangement - Langman's Medical Embryology

The Six Pharyngeal Arches in Detail

Arch 1 - The Mandibular Arch

• Dorsal end forms the malleus and incus (middle ear ossicles)
• Middle portion regresses, but its perichondrium persists as the anterior ligament of malleus and sphenomandibular ligament
• Mandible develops by intramembranous ossification of mesenchyme surrounding Meckel's cartilage (not directly from it)
• Maxillary process mesenchyme forms the premaxilla, maxilla, zygomatic bone, and part of temporal bone by membranous ossification

• Muscles of mastication (temporalis, masseter, medial and lateral pterygoids)
• Mylohyoid
• Anterior belly of digastric
• Tensor tympani
• Tensor veli palatini

Arch 2 - The Hyoid Arch

• Stapes (middle ear ossicle)
• Styloid process of temporal bone
• Stylohyoid ligament
• Lesser cornu (horn) of hyoid bone
• Upper part of body of hyoid bone

• Muscles of facial expression (frontalis, orbicularis oculi, orbicularis oris, buccinator, etc.)
• Stapedius
• Stylohyoid
• Posterior belly of digastric
• Auricular muscles (external ear)

Arch 3

• Lower part of the body of hyoid bone
• Greater cornu (horn) of hyoid bone

• Stylopharyngeus (the only muscle derived from arch 3)

Arch 4

• Thyroid cartilage (superior cornu)
• Contributes to cricoid, arytenoid, corniculate, and cuneiform cartilages

• Cricothyroid
• Levator veli palatini
• Constrictors of the pharynx (superior, middle, inferior)

Arch 5

Arch 6

• Cricoid cartilage
• Arytenoid, corniculate, and cuneiform cartilages

• Intrinsic muscles of the larynx (except cricothyroid)
• Striated muscles of the esophagus

Summary Table of Derivatives

Cartilage Derivatives - Visual Summary

Pharyngeal Pouches (Endodermal Derivatives)

Pharyngeal Clefts (Ectodermal Derivatives)

Clinical Correlates

1. First Arch Syndrome

• Treacher Collins Syndrome (Mandibulofacial Dysostosis): Autosomal dominant; mutation in TCOF1 gene (encodes treacle protein involved in ribosomal RNA biogenesis). Features: malar hypoplasia, down-slanting palpebral fissures, lower eyelid defects, deformed external ears, possible middle/inner ear defects.
• Pierre Robin Sequence: Micrognathia (small mandible) → posterior tongue displacement → bilateral cleft palate. Most cases are de novo; rarely autosomal dominant.

2. DiGeorge Syndrome (22q11.2 Deletion Syndrome)

• Absent/hypoplastic thymus → T-cell immunodeficiency
• Absent/hypoplastic parathyroids → hypoparathyroidism, hypocalcemia
• Cardiac outflow tract defects (aortic arch anomalies, VSD, truncus arteriosus)
• Facial features: shortened philtrum, low-set ears, nasal clefts

3. Branchial (Lateral Cervical) Cysts and Fistulas

Memory Aids

V - VII - IX - X(sup) - X(rec) "Very Fine Girls Are Exceptional"

Stapedius, Stylohyoid, Posterior belly digastric, Auricular, muscles of facial expression (All = CN VII)

Malleus, Incus, Sphenomandibular ligament, Temporal bone (part)

Gastrulation

Definition and Timing

• Occurs during week 3 of development
• The embryo during this stage is called a gastrula
• It is the most significant developmental event of the third week and is the beginning of morphogenesis (development of body form)
• Key signaling molecules: BMPs, FGF8, Sonic Hedgehog (Shh), Wnt, Tbx16, Tgifs
• The Developing Human: Clinically Oriented Embryology, Langman's Medical Embryology

Background: The Bilaminar Disc

• Epiblast (upper layer) - columnar cells forming the floor of the amniotic cavity
• Hypoblast (lower layer) - cuboidal cells forming the roof of the umbilical vesicle (yolk sac)

Step 1: Formation of the Primitive Streak

• Epiblast cells proliferate and migrate toward the median plane at the caudal end
• This forms a thickened linear band called the primitive streak
• As the streak elongates caudally, its cranial end enlarges to form the primitive node (Hensen's node)
• The primitive node has a central depression called the primitive pit; the streak itself has a midline groove called the primitive groove, with slightly elevated edges called primitive ridges

• Establishes the embryo's axes: once it appears, you can identify cranial/caudal ends, dorsal/ventral surfaces, and right/left sides
• The caudal end of the streak marks the future tail end; the cranial end marks the head end

Step 2: Invagination and Formation of Germ Layers

1. It downregulates E-cadherin - loosening cell-cell adhesion between epiblast cells, allowing them to detach and migrate
2. It regulates BRACHYURY (T) expression - specifying cells into mesoderm

Step 3: Spread of Mesoderm and Fate Map

• Cranially, they pass on either side of the prechordal plate (a midline region of tightly adherent ecto-endoderm that forms just cranial to the oropharyngeal membrane)
• Laterally, they establish contact with extraembryonic mesoderm covering the yolk sac and amnion
• Cranially and caudally, two membrane regions remain without mesoderm between them:
  • Oropharyngeal membrane (cranially) - future mouth opening
  • Cloacal membrane (caudally) - future anal/urogenital openings

Epiblast Fate Map (ingression through different streak levels)

Step 4: Formation of the Notochord

1. These cells first intercalate into the hypoblast, creating a transient notochordal plate
2. As endoderm cells replace the hypoblast, the notochordal plate cells proliferate and detach, forming a solid cellular rod - the definitive notochord
3. The notochord initially forms a hollow tube (the notochordal canal), which temporarily communicates with the amniotic cavity above and the umbilical vesicle below through the neurenteric canal
4. The floor of the canal degenerates, forming a flat notochordal plate, which then folds in on itself to create the solid notochord
5. The neurenteric canal normally obliterates once notochord development is complete

Functions of the Notochord:

• Defines the primordial longitudinal axis of the embryo and gives it rigidity
• Acts as the primary inducer in the early embryo - induces the overlying ectoderm to thicken into the neural plate (primordium of the CNS)
• Contributes to the nucleus pulposus of intervertebral discs in adults
• Largely degenerates as vertebral bodies form around it

What the Three Germ Layers Give Rise To

Growth of the Embryonic Disc

• The disc is initially flat and nearly round; it elongates with a broad cranial end and narrow caudal end
• Growth occurs mainly in the cephalic region - driven by continuous cell migration from the primitive streak in the cranial direction
• The primitive streak remains relatively fixed in size at the caudal end
• By the end of week 4, the primitive streak shows regressive changes, rapidly shrinks, and disappears
• Development proceeds in a cephalocaudal direction: cranial germ layers differentiate by mid-week 3, while caudal regions are still forming germ layers by the end of week 4

Clinical Correlates

1. Caudal Dysgenesis (Sirenomelia)

• Hypoplasia and fusion of lower limbs (mermaid-like appearance)
• Vertebral abnormalities
• Renal agenesis
• Imperforate anus
• Genital anomalies

2. Sacrococcygeal Teratoma

3. Teratogenic Sensitivity

4. Laterality Defects

• Situs inversus - complete mirror-image reversal of all organs
• Situs ambiguus (heterotaxy) - discordant organ positioning, with possible isomerisms or inversions of the heart chambers, associated with congenital heart defects

5. Notochordal Remnant Tumors (Chordomas)

Summary: Key Events Week by Week

Spermatogenesis and Oogenesis

PART 1: SPERMATOGENESIS

Definition and Overview

• Costanzo Physiology 7th Edition, Guyton and Hall Textbook of Medical Physiology

Location: The Seminiferous Tubule

• Sertoli cells - large supporting cells with overflowing cytoplasm that surround, nurture, and regulate all developing germ cells
• Leydig (interstitial) cells - in the connective tissue between tubules; produce testosterone under LH stimulation
• A blood-testis barrier formed by tight junctions between Sertoli cells, dividing the tubule into a basal compartment (spermatogonia) and an adluminal compartment (all later stages)

Three Phases of Spermatogenesis

Phase 1 - Mitotic Proliferation (Spermatogonia)

• Junqueira's Basic Histology

Phase 2 - Meiotic Divisions (Spermatocytes)

• Primary spermatocyte (2n, 4C = diploid, 4N DNA) → 2 secondary spermatocytes (haploid, 2N DNA)
• This is the longest phase - primary spermatocytes spend ~3 weeks in prolonged prophase I (leptotene → zygotene → pachytene → diplotene → diakinesis)
• Crossing-over (recombination) occurs during prophase I, generating genetic diversity

• Each secondary spermatocyte → 2 spermatids (haploid, 1N DNA)
• Final result: 4 haploid spermatids from each primary spermatocyte
• Of the 4 spermatids: 2 carry the X chromosome, 2 carry the Y chromosome

Phase 3 - Spermiogenesis (Transformation of Spermatids → Spermatozoa)

1. Acrosome formation - Golgi apparatus vesicles merge over the nucleus to form the acrosomal cap (contains hyaluronidase, acrosin, neuraminidase, phospholipase A, and esterases)
2. Nuclear condensation - Nucleus becomes elongated and compact (histones replaced by protamines)
3. Flagellum development - Centrioles organize the axoneme (9+2 microtubule arrangement) that forms the tail
4. Mitochondrial sheath - Mitochondria migrate to wrap around the proximal tail → middle piece
5. Loss of excess cytoplasm - Residual cytoplasm shed as residual bodies (phagocytosed by Sertoli cells)

Structure of a Mature Spermatozoon

Hormonal Regulation of Spermatogenesis

Sperm Transport and Maturation

• They acquire forward motility and fertilizing capacity over ~2 weeks
• They can be stored for several months while remaining viable
• Capacitation (final activation) occurs in the female reproductive tract over 4-6 hours: inhibitory seminal factors are washed away, cholesterol is withdrawn from sperm membrane, Ca²⁺ influx increases, and the acrosomal membrane fuses with the outer sperm membrane

• Seminal vesicles (60%): fructose (energy), prostaglandins, fibrinogen, citrate
• Prostate (30%): citrate, calcium, alkaline enzymes (neutralizes acid, increases motility)
• Bulbourethral glands (5%): mucus

PART 2: OOGENESIS

Definition and Key Contrast with Spermatogenesis

Prenatal Phase: Oogonia → Primary Oocytes

1. Primordial germ cells migrate from the dorsal endoderm of the yolk sac along the mesentery of the hindgut to the germinal epithelium of the ovarian cortex
2. They divide mitotically to produce oogonia - peak at ~7 million oogonia by weeks 20-24 of gestation
3. From week 8-9 onward, oogonia begin entering meiosis I, becoming primary oocytes
4. Meiosis is immediately arrested in late prophase I (dictyotene stage) - this suspended state can last up to 50 years (until menopause)
5. Connective tissue cells surround each primary oocyte to form a primordial follicle (primary oocyte + single layer of flattened granulosa cells)
6. By birth: only ~1-2 million primary oocytes remain (massive atresia reduces the pool)
7. No new oogonia are produced after birth - females work from this fixed, declining pool

Postnatal Phase: Follicular Development and Ovulation

Stage 1 - Primordial → Primary → Secondary Follicle (Years)

• Granulosa cells proliferate and become cuboidal → columnar
• Primary oocyte grows and develops zona pellucida (glycoprotein coat: ZP1, ZP2, ZP3)
• Theca interna cells differentiate and begin steroid production
• Granulosa cells begin secreting fluid
• Duration: 13-50 years (minimum age at first ovulation to menopause)

Stage 2 - Secondary → Graafian (Antral) Follicle (70-85 days)

• Occurs only during reproductive period
• Fluid accumulates in a central cavity - the antrum (contains steroids, mucopolysaccharides, proteins, FSH)
• Follicle reaches 2-5 mm diameter - called a Graafian follicle
• Several follicles enter this stage each cycle

Stage 3 - Dominant Follicle Selection and Ovulation (5-7 days before ovulation)

• A single dominant follicle achieves dominance; its cohorts undergo atresia
• Within 48 hours, dominant follicle grows to ~20 mm
• On day 14 of a 28-day cycle, the LH surge triggers ovulation
• The primary oocyte COMPLETES meiosis I just before ovulation:
  • → Secondary oocyte (retains most cytoplasm) + 1st polar body (extruded, degenerates)
• The secondary oocyte then enters meiosis II but arrests again at metaphase II

Meiotic Arrests Summarized

Comparison of Oocyte Numbers Through Life

Corpus Luteum

• Secretes progesterone and estrogen to prepare the endometrium for implantation
• If fertilization occurs: hCG from the trophoblast maintains the corpus luteum until the placenta takes over hormone production (~weeks 8-10)
• If no fertilization: corpus luteum degenerates after ~14 days → corpus albicans → progesterone withdrawal → menstruation

Hormonal Regulation of Oogenesis / Ovarian Cycle

Clinical Correlates

Yolk Sac (Umbilical Vesicle) and Twin Pregnancy

PART 1: THE YOLK SAC (UMBILICAL VESICLE)

Terminology

• The Developing Human: Clinically Oriented Embryology

Formation: Primary vs. Secondary Umbilical Vesicle

Primary Umbilical Vesicle (Day 8-12)

• After implantation, cells from the hypoblast (lower layer of the bilaminar disc) migrate around the inside of the cytotrophoblast shell
• These cells form a thin membrane lining the blastocyst cavity, creating the primary umbilical vesicle
• The bilaminar disc - composed of epiblast (above) and hypoblast (below) - forms the roof of this vesicle

Secondary Umbilical Vesicle (Day 13-14)

• As the extraembryonic coelom (chorionic cavity) forms and enlarges, it pinches and compresses the primary vesicle
• Extraembryonic endodermal cells migrating from the hypoblast form a smaller, secondary umbilical vesicle - this is what is commonly called "the yolk sac"
• A portion of the primary vesicle is pinched off and remains as a small remnant outside the secondary vesicle
• The secondary vesicle is surrounded by extraembryonic splanchnic mesoderm

Structure

• Inner layer: Extraembryonic endoderm (continuous with the embryonic endoderm)
• Outer layer: Extraembryonic splanchnic mesoderm

Functions of the Yolk Sac

Fate of the Yolk Sac

• Gradually becomes smaller as the embryo grows and folds
• By week 6-7, the vitelline (omphalomesenteric) duct - which connects it to the gut - normally obliterates
• The yolk sac eventually becomes a small vestigial structure lying outside the embryo within the umbilical cord
• It is usually no longer detectable ultrasonographically after 12 weeks

Clinical Relevance of Yolk Sac Remnant

Ultrasonographic Significance

• The secondary yolk sac is visible on transvaginal ultrasound as early as 5 weeks' gestation - the first structure identified within the gestational sac
• A visible yolk sac confirms an intrauterine pregnancy
• Abnormal yolk sac (too large >6mm, too small, irregular shape, or absent) is associated with early pregnancy failure/miscarriage
• The yolk sac and the embryo/fetal heartbeat together are the key first-trimester ultrasound landmarks

PART 2: TWIN PREGNANCY

Incidence and Classification

Two fundamental types:

Dizygotic (DZ) Twins

• Always dichorionic - diamniotic (two separate chorionic and amniotic sacs)
• Placentas may be separate or fused (secondary fusion after close implantation)
• May be same sex or opposite sex
• No more genetically alike than any two siblings

• Asian populations: ~1 in 500
• White populations: ~1 in 125
• Some African populations: ~1 in 20
• Hereditary tendency - recurrence ~3x that of general population; influenced by mother's genotype (not father's)
• Associated with: advanced maternal age, multiparity, gonadotropin-stimulating drugs (clomiphene), ART/IVF

Monozygotic (MZ) Twins

MZ Twin Types Based on Timing of Split

Membrane Structure Summary Table

• MZ: 1% monoamniotic-monochorionic; 64% diamniotic-monochorionic; 25% fused placentas; 10% separate placentas
• DZ: 40% fused placentas; 60% separate placentas

Clinical Complications of Twin Pregnancy

1. Twin-to-Twin Transfusion Syndrome (TTTS)

• Occurs in 10-15% of monochorionic-diamniotic (MCDA) twins
• Caused by unidirectional arteriovenous anastomoses in the shared placenta - arterial blood from one twin shunts into the venous circulation of the other
• Donor twin: small, pale, anemic, oligohydramnios, IUGR
• Recipient twin: large, polycythemic, polyhydramnios, cardiac overload, risk of congestive heart failure
• Placenta: pale portion (donor) vs. dark red (recipient)
• Treatment: Fetoscopic laser coagulation of placental vascular anastomoses (gold standard)
• Lethal if untreated in severe cases: anemia → death of donor; CCF → death of recipient

2. Cord Entanglement (MCMA twins)

• Monoamniotic twins share one amniotic sac → umbilical cords can intertwine
• Fetal mortality rates increased by up to 10% due to cord compression/interruption
• Management: close ultrasound surveillance; often planned delivery at 34 weeks

3. IUGR and Growth Discordance

• One twin may be significantly smaller, especially in MCDA twins
• Growth discordance >20% weight difference is clinically significant

4. Conjoined Twins

• Arise from incomplete division of the embryonic disc after day 13
• Named by site of union:

• Incidence: ~1 in 50,000-100,000 births
• Parasitic (heteropagus) twins (1:1,000,000): severely defective twin is attached to and dependent on the cardiovascular system of the complete twin

5. Anastomosis and Erythrocyte Mosaicism (DZ twins)

• In DZ twins with fused placentas, vascular anastomoses may result in erythrocyte mosaicism - each twin has two red blood cell populations with different blood groups
• Unlike in cattle, female DZ twins with a male co-twin do not develop masculinization (no freemartin effect in humans)

6. Discordance in MZ Twins

• Somatic mutations post-zygotic splitting
• Uneven X-chromosome inactivation (lyonization) in female MZ twins
• Epigenetic differences
• Vascular abnormalities during development
• Chromosome aberrations originating in one blastocyst after the split

7. Early Death of a Twin ("Vanishing Twin")

• One twin dies early in pregnancy and is resorbed
• Common - seen on early ultrasound but not at delivery
• Clinical concern: if CVS or amniocentesis samples extraembryonic tissue from the resorbed twin, prenatal cytogenetic results may not match the live-born infant's karyotype

Determining Zygosity

• All DZ twins are dichorionic, but ~35% of MZ twins are also dichorionic
• A dichorionic placenta cannot rule out MZ twinning
• Definitive zygosity determination: DNA molecular markers (any two non-MZ individuals will show differences in a large panel of DNA markers)
• Same sex, monochorionic → almost certainly MZ
• Opposite sex → always DZ

• Kidney/bone marrow organ transplantation (MZ twins are ideal donors)
• Risk counseling for genetic conditions
• Understanding disease concordance/discordance

Superfecundation and Superfetation

• Superfecundation: Fertilization of two oocytes by two different sperms (possibly from different fathers) at different times within the same ovulatory cycle. DZ twins with different fathers have been confirmed by genetic markers.
• Superfetation: Fertilization at different times in different menstrual cycles - extremely rare in humans; would require two implantations at different developmental stages in the same uterus.

Implantation

Definition and Timing

• The Developing Human: Clinically Oriented Embryology, Langman's Medical Embryology

Prerequisites for Implantation

1. Blastocyst Activation ("Hatching")

• After reaching the uterine cavity at day 4-5, the blastocyst must hatch from the zona pellucida
• Zona pellucida is dissolved by proteolytic enzymes (strypsin) secreted by the blastocyst
• Hatching exposes the trophoblast directly to the endometrial surface
• The blastocyst orients itself with the embryoblast (inner cell mass) pole - the polar trophoblast - facing the endometrium

2. Endometrial Receptivity - "Window of Implantation"

• The endometrium is only receptive for a brief 2-3 day window in the mid-luteal phase (days 20-24 of a 28-day cycle)
• This window is created by the synergistic action of progesterone (P4) and estradiol (E2) from the corpus luteum
• Progesterone triggers:
  • Cessation of endometrial proliferation
  • Transformation of stromal cells into large secretory decidual cells (decidualization)
  • Influx of specialized immune cells (uterine NK cells, macrophages)
  • Expression of surface adhesion molecules and signaling molecules

• Creasy & Resnik's Maternal-Fetal Medicine

Stages of Implantation: Day-by-Day Sequence

Day 6-7: Apposition and Initial Adhesion

• The zona-free blastocyst loosely appositions itself to the endometrial epithelium
• The polar trophoblast (over the ICM) aligns with the luminal epithelium
• This is a non-firm, reversible contact

Day 8: Adhesion and Early Invasion

• Single layer of mononucleated cells
• Mitotically active - cells divide and migrate outward into the syncytiotrophoblast
• Trophoblast fusion regulated by the cyclic AMP pathway
• Source of new cells for syncytiotrophoblast

• Rapidly expanding multinucleated mass with no cell boundaries
• Formed by fusion of cytotrophoblast cells (which lose their individual membranes)
• No mitotic figures in syncytiotrophoblast - it grows only by incorporation of new cytotrophoblast cells
• Actively secretes enzymes that digest and invade the endometrial connective tissue
• Produces hCG (human chorionic gonadotropin)

• Two layers form: epiblast (tall columnar cells, facing amnion) and hypoblast (cuboidal cells, facing blastocyst cavity)
• A small slit - the primordium of the amniotic cavity - appears within the epiblast
• Amnioblasts (epiblast cells adjacent to the cytotrophoblast) line the forming amniotic cavity

Day 9: Lacunar Stage

• The blastocyst is more deeply embedded in the endometrium
• The surface epithelium defect is closed by a fibrin coagulum (closing plug)
• Vacuoles appear in the syncytiotrophoblast at the embryonic pole → fuse to form lacunae (spaces)
• This marks the lacunar stage of trophoblast development
• Cells from the hypoblast migrate to line the inside of the cytotrophoblast, forming the exocoelomic (Heuser) membrane → together with the hypoblast, this forms the primitive umbilical vesicle (primary yolk sac)

Days 11-12: Uteroplacental Circulation Established

• Blastocyst is completely embedded in endometrial stroma; surface epithelium nearly fully covers the original defect
• Syncytiotrophoblast penetrates deeper into stroma and erodes the endothelial lining of maternal capillaries
• Maternal capillaries become engorged → called sinusoids
• Syncytial lacunae become continuous with sinusoids → maternal blood flows freely into the lacunar system → establishes the uteroplacental circulation
• Extraembryonic mesoderm forms from cells between the exocoelomic membrane and inner trophoblast; extraembryonic coelomic spaces begin to appear within it
• The syncytiotrophoblast begins eroding endometrial glands → glycogen-rich secretions flood the lacunae, providing early nutrition to the embryo
• Decidual reaction in the endometrium: stromal cells accumulate glycogen and lipids, become polyhedral (decidual cells); later spreads throughout the entire endometrium

Day 13: Completion of Implantation

• Surface defect in endometrium has healed completely
• Occasional bleeding from increased blood flow into lacunae may occur around day 28, potentially confused with menstruation → can cause inaccuracy in estimated delivery date
• Cytotrophoblast cells proliferate locally and penetrate into syncytiotrophoblast → form cellular columns surrounded by syncytium → primary chorionic villi (first stage in placenta development)
• Secondary yolk sac forms (definitive yolk sac); the primary yolk sac is largely pinched off and leaves a remnant
• Extraembryonic coelomic spaces fuse to form the extraembryonic coelom (chorionic cavity)
• The connecting stalk forms - suspending the embryo, amnion, and yolk sac within the chorionic sac

hCG and the Rescue of the Corpus Luteum

• hCG enters maternal blood via the lacunar system
• It rescues the corpus luteum from regression, which would otherwise occur at day 23-24 (without pregnancy)
• The corpus luteum continues secreting progesterone and estrogen → maintains the endometrium and prevents menstruation
• hCG levels rise exponentially in early pregnancy, doubling every 48-72 hours → forms the basis of urine and blood pregnancy tests
• Enough hCG is produced by end of week 2 to give a positive pregnancy test, even before the woman knows she is pregnant

Molecular Summary of the Implantation Sequence

Normal vs. Abnormal Implantation Sites

Normal Site

• Posterior wall of upper body of uterus, close to midline (most common)
• Anterior wall also acceptable

Low Implantation → Placenta Previa

• Blastocyst implants in the lower uterine segment
• As the placenta grows, it overlies the internal cervical os → placenta previa
• Presents with painless antepartum hemorrhage; may require cesarean delivery

Abnormal Implantation Sites → Ectopic Pregnancy

• Previous ectopic pregnancy (highest risk)
• Pelvic inflammatory disease (PID) - tubal scarring/adhesions
• Endometriosis
• Previous tubal surgery
• In utero DES exposure
• IVF/ART (incidence ~3/1000)
• IUCD (intrauterine contraceptive device)

• No embryo heartbeat + diameter <3 cm: methotrexate (1-2 oral/IM doses)
• Rupture or failed medical treatment: salpingectomy / salpingostomy (surgical)
• Heterotopic pregnancy (simultaneous intrauterine + ectopic): surgical removal of ectopic tube without disturbing the intrauterine pregnancy

The Decidua

Summary Timeline