Talk:1987 Developmental Stages In Human Embryos - Introduction

From Embryology

Ronan O'Rahilly

Fabiola Müller

Developmental stages in human embryos: revised and new measurements

Cells Tissues Organs. 2010;192(2):73-84. doi: 10.1159/000289817. Epub 2010 Feb 26.

O'Rahilly R1, Müller F.


The staging of human embryos, as distinct from seriation, depends on a morphological scheme devised by Streeter and completed by O'Rahilly, who proposed the term Carnegie stages. To avoid misconceptions and errors, and to place new findings in perspective, it is necessary to summarize the essentials of the Carnegie system: (1) Twenty-three stages cover the embryonic period, i. e. the first 8 postfertilizational weeks of development. (2) The system is based on internal as well as external features, and the use of only external criteria is subject to serious limitations. For example, precise delineation of stages 19-23 and of the embryonic-fetal transition depends on histological examination. (3) Prenatal measurements are not an integral component of the staging system, and hence a stage should never be assigned merely on the basis of embryonic length. A 20-mm embryo, for example, could belong to any of three stages. Measurements, however, are important for the assessment of age, and very few measurements are available for staged embryos. Presented here and based on accurate staging are the maximum diameter of the chorionic sac, the crown-heel length, the greatest length exclusive of the lower limbs, the biparietal diameter, the head circumference, the length of the hindbrain, the total length of the brain, and the lengths of the limbs as well as of their segments, including the foot length. (4) Prenatal ages are also not an integral part of the staging system and hence a stage should never be assigned merely on the basis of prenatal age. Ages, however, are of clinical importance and their estimate has been rendered more precise by accurate timing of fertilization followed by ultrasonography. Prenatal age is postfertilizational and hence some 2 weeks less than the postmenstrual interval. The term gestational age is ambiguous and should be discarded. Presented here is a new graph showing proposed estimates of age in relation to stages and based on current information. Copyright 2010 S. Karger AG, Basel.

PMID 20185898


Fig. 0-1. Diagram of endometrial-decidual and embryonic-fetal relationships in relation to time. The second ovulation shown, which is followed by fertilization, is that from which postovulatory age is calculated. The last menstrual period (L.M.P.), which occurred a variable time previously, marks the beginning of the “gestational interval” (asterisk), as defined by Treloar, Behn, and Cowan (1967), who consider pregnancy (gestation) to begin with implantation, whereas others use fertilization as the starting point. Postconceptual hemorrhage in phase with menstruation would result in an apparently short gestational interval. On the other hand, an unrecognized abortion preceding pregnancy, if no menstruation intervened, would result in an apparently long gestational interval. Such possibilities, together with variability in both premenstrual and postmenstrual phases of the cycle, render menstrual data unsatisfactory in the assessment of embryonic age.

Fig. 0-2. The length of the embryonic disc from stage 5 to stage 11, approximately 1–3½ postovulatory weeks, based on the measurements of 81 embryos. Most of the specimens may be expected to fall within the shaded band, but extreme values are indicated by the five vertical lines. At 1 week the diameter of the disc is approximately 0.1 mm. At 2 weeks the disc is about 0.2 mm in length. At 3 weeks the embryonic length has increased to about 1.5–2 mm. The measurements at later stages are shown in figure 0-3.

Fig. 0-3. The length of the embryo from stage 8 to stage 23, approximately 2½to 8 postovulatory weeks, based on the measurements of more than 100 specimens that had been graded as excellent in quality. The measurements at earlier stages are shown in figure 0-2. The maximum diameter of the chorion has also been included (based on 200 specimens graded as either good or excellent): the shaded band includes approximately 80 percent of the specimens. At 4 weeks the embryo is about 5 mm in length and the chorion about 25 mm in diameter. At 8 weeks the embryo is about 30 mm in length, and the chorion is about 65 mm in diameter.

Fig. 0-4. The relative size of the embryo and the chorion at weekly intervals. The stages shown are 6, 10, 13, 16, 17, 20, and 23. The drawings are at approximately the scale of the actual specimens.

Table 0-1. Developmental Stages in Human Embryos

Carnegie Stage Pairs of Somites Size (mm) Age* (days) Features 1 0.1-0.15 1 Fertilization. 2 0.1-0.2 1½-3 From 2 to about 16 cells. 3 0.1-0.2 4 Free blastocyst. 4 0.1-0.2 5-6 Attaching blastocyst. 5 0.1-0.2 7-12 Implanted although previllous. 5a 0.1 7-8 Solid trophoblast. 5b 0.1 9 Trophoblastic lacunae. 5c 0.15-0.2 11-12 Lacunar vascular circle. 6 0.2 13 Chorionic villi; primitive streak may appear. 6a Chorionic villi. 6b Primitive streak. 7 0.4 16 Notochordal process. 8 1.0-1.5 18 Primitive pit; notochordal and neurenteric canals; neural folds may appear. 9 1-3 1.5-2.5 20 Somites first appear. 10 4-12 2-3.5 22 Neural folds begin to fuse; 2 pharyngeal bars; optic sulcus. 11 13-20 2.5-4.5 24 Rostral neuropore closes; optic vesicle. 12 21-29 3-5 26 Caudal neuropore closes; 3-4 pharyngeal bars; upper limb buds appearing. 13 30-? 4-6 28 Four limb buds; lens disc; otic vesicle. 14 5-7 32 Lens pit and optic cup; endolymphatic appendage distinct. 15 7-9 33 Lens vesicle; nasal pit; antitragus beginning; hand plate; trunk relatively wider; future cerebral hemispheres distinct. 16 8-11 37 Nasal pit faces ventrally; retinal pigment visible in intact embryo; auricular hillocks beginning; foot plate. 17 11-14 41 Head relatively larger; trunk straighten nasofrontal groove distinct; auricular hillocks distinct; finger rays. 18 13-17 44 Body more cuboidal; elbow region and toe rays appearing; eyelid folds may begin; tip of nose distinct; nipples appear; ossification may begin. 19 16-18 47½ Trunk elongating and straightening. 20 18-22 50½ Upper limbs longer and bent at elbows. 21 22-24 52 Fingers longer; hands approach each other, feet likewise. 22 23-28 54 Eyelid and external ear more developed. 23 27-31 56½ Head more rounded; limbs longer and more developed.

  • Olivier and Pineau (1962) for stages 11-23. Miscellaneous sources for stages 1-10.

Table 0-2. List of Discarded and Replaced Terms

Alternative, Inappropriate, or Incorrect Terms Terms Used Here Blastocoel Blastocystic cavity Blastopore Primitive pit Blastula Blastocyst Branchial Pharyngeal; visceral Chorda dorsalis Notochord Embryonic shield Embryonic disc (including cloacal membrane) Formative cells Epiblast Gastrulation Not used Germ disc Epiblast Gestational age Not used Head process Notochordal process Horizon Stage Medullary- groove and folds Neural groove and folds Menstrual age Not used Morula Late stage 2 embryo Ovum (egg) Oocyte; ootid; embryo Perivitelline space Subzonal space Placode Plate or disc Pronephros Rostralmost part of mesonephros Tail Not used Ultimobranchial Telopharyngeal Vitellus Ooplasm; cytoplasm Yolk sac Umbilical vesicle