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Embryonic Ages & Stages (A Note from EHD)

There is international agreement among embryologists that human development during the embryonic period be divided into 23 stages (which were initially proposed by Mall, described by Streeter, amended by O'Rahilly, and then amended and finalized by O'Rahilly and Müller in 1987).1 These have come to be known as Carnegie Stages. Particular internal and external features are required for inclusion in any given embryonic stage. These development stages are independent of age and length. The use of the term "stage" should be reserved for reference to this system per O'Rahilly and Müller in multiple publications.

Along with near universal acceptance of the human embryonic staging system, multiple age assignments have been proposed for many of the embryonic stages. Streeter believed the embryonic period spanned a 47- to 48-day period instead of the 56-day period which is widely accepted today. The Endowment for Human Development adopts the convention set forth by O'Rahilly and Müller in 1987 which has received widespread, but not universal, acceptance. O'Rahilly and Müller have since proposed amending this convention several times in light of more recent transvaginal ultrasound data through a personal communication with Dr. Josef Wisser in 19922 and others. The age differences are primarily limited to Carnegie stages 6 through 15 inclusive. Their new proposal and the slight adjustments during the past decade are provided for the interested reader.

One line of reasoning in favor of the traditional age estimates is as follows: The onset of embryonic cardiac contraction (onset of the heartbeat) has long been described as a Carnegie Stage 10 or possibly a very late Stage 9 event.3 We report this event occurring at an age of 3 weeks, 1 day (22 days) postfertilization using the 1987 aging estimates. Consistent with the 1987 convention, Kurjak and Chervenak4 cite a study by Neiman5 documenting cardiac activity at 22 days postfertilization. Wisser and Dirschedl reported using transvaginal ultrasound to visualize the embryonic heartbeat 23 days postfertilization in two embryos fertilized in vitro "with exactly known … age" and "in embryos from 2 mm of greatest length onwards."6 Tezuka et al. reported the earliest cardiac activity at 23 days postfertilization in embryos conceived naturally.7 Schats et al. reported the earliest cardiac activity at 25 days after follicle aspiration in embryos conceived in vitro.8 These findings most closely coincide with the 1987 age convention which is why EHD and perhaps others have continued to use the 1987 convention. Others may report the onset of cardiac contraction occurring at 28 or 29 days or even 30 days as shown below.

There is considerable variation in normal human development during the postnatal period. The prenatal period is no different with variations in the size, rate of growth, and order of appearance of some structures or functions. No one knows the exact age range for each stage with absolute certainty. These age estimates will likely be modified in the future as additional knowledge is gained.

O'Rahilly and Müller's Age Assignments for Carnegie Stages, 1987 to 2010

Carnegie
Stage
Number
of Somites
Greatest
Length (mm)
1987 Age 9
Convention
(in PF Days*)
1999 Age 10
Estimates
(in PF Days*)
2001 Age 11
Estimates
(in PF Days*)
2006 Age12
Estimates
(in PF Days*)
2010 Age13
Estimates
(in PF Days*)
1   0.1 - 0.15 1 - 1 - 1
2   0.1 - 0.2 1½ - 3 2 - 3 2 - 3 - 2 - 3
3   0.1 - 0.2 4 4 - 5 4 - 5 - 4 - 5
4   0.1 - 0.2 5 - 6 6 6 - 6
5   0.1 - 0.2 7 - 12 7 - 12 - - -
5a   0.1 7 - 8 - 7 - 8 - 7 - 8
5b   0.1 9 - 9 - 9?
5c   0.15 - 0.2 11 - 12 - 11 - 12 - 11 - 12?
6   0.2 13 17 17 - 16 - 18?
6a   - - - - - -
6b   - - - - - -
7   0.4 16 19 19 - 18 - 21?
8   1.0 - 1.5 18 23 - 23 21 - 25
8a   - - - 23 - -
8b   - - - 23 - -
9 1-3 1.5 - 2.5 20 26 25 25 25 - 27
10 4-12 2 - 3.5 22 29 28 28 28 - 30?
11 13-20 2.5 - 4.5 24 30 29 29 28 - 30
12 21-29 3 - 5 26 31 30 30 29 - 31
13 30+ 4 - 6 28 32 32 32 30 - 33
14   5 - 7 32 33 33 33 33 - 35
15   7 - 9 33 35 36 36 35 - 37
16   8 - 11 37 37 38 39 37 - 40
17   11 - 14 41 40 41 - 39 - 42
18   13 - 17 44 42 44 44 42 - 45
19   16 - 18 47½  44 46 46 45 - 47
20   18 - 22 50½  47 49 49 47 - 50
21   22 - 24 52 50 51 51 49 - 52
22   23 - 28 54 52 53 53 52 - 55
23   27 - 31 56½  56 56 56 53 - 58

* PF Days = Postfertilization Days

Footnotes
1 O'Rahilly and Müller, 2001. 3.
2 O'Rahilly and Müller, 1999a. 13.
3 Campbell, 2004. 14; Carlson, 2004. 430; de Vries and Saunders, 1962. 96; Gardner and O'Rahilly, 1976. 583; Gilbert-Barness and Debich-Spicer, 1997. 650; Gittenger-de Groot et al., 2000. 17; van Heeswijk et al., 1990. 151; Kurjak, Chervenak, 1994. 439; Navaratnam, 1991. 147-148; O'Rahilly and Müller, 1987. 99; Wisser and Dirschedl, 1994. 108.
4 Kurjak, Chervenak, 1994. 439.
5 Neiman HL, 1990. 22.
6Quotes from Wisser and Dirschedl, 1994. 108.
7 Tezuka et al., 1991. 211.
8 Schats et al., 1990. 989.
9 O'Rahilly and Müller, 1987. 3. Greatest length data is essentially uniform throughout the various texts.
10 O'Rahilly and Müller, 1999a. Various pages.
11 O'Rahilly and Müller, 2001. 490. Table A-1 – essentially unchanged from the 1996 edition. The 2001 convention differs only slightly from the 1999 convention as shown.
12 O'Rahilly and Müller, 2006. 12 (Table 8-1).
13 O'Rahilly R, Müller F, 2010. 75.