1004 



SPERM, OVA, AND PREGNANCY 



cated that the dosage varied with the stage 

 of pregnancy. An adequate dose of approxi- 

 mately 1 mg. progesterone in the early 

 stages of pregnancy needs to be increased 

 to 5 mg. in the later stages (Allen and 

 Heckel, 1939; ComTier and Kehl, 1938a, b). 

 These investigators also revealed that an 

 optimal effect could be obtained by using a 

 progesterone-estrogen combination in the 

 ratio of 750 to 1. Chang (1951) transferred 

 ova to nonovulated intact rabbits and noted 

 that massive doses in the order of 25 mg. 

 macrocrystalline progesterone injected for 

 three times were required to obtain a 50 per 

 cent maintenance of pregnancy. He also re- 

 ported that under the conditions of his ex- 

 periment an initially high dose was needed 

 for the passage of the ova, implantation, 

 and early maintenance. Since then, further 

 experimentation, especially on other spe- 

 cies, has revealed a significant role by estro- 

 gen in enhancing the pregnancy-maintain- 

 ing action of progesterone. 



A vast literature exists for the human 

 being on the prevention of threatened abor- 

 tion by progesterone which is beyond the 

 scope of this review. Variation from nega- 

 tive results to excellent maintenance is re- 

 ported. It is obvious that a great deal of 

 variability exists here and, to some extent, 

 this is explained by a need for more objec- 

 tive criteria in evaluating threatened abor- 

 tion and the therapy (Guterman and Tul- 

 sky, 1949). It is obvious that if the 



TABLE 16.12 

 Maintenance of pregnancy in the rat castrated on 



the 12th day of gestation 



(From J. Yochim and M. X. Zarrow, Fed. Proc, 



18, 174, 1959.) 



threatened abortion were the result of some 

 disturbance other than progesterone, that 

 progesterone therapy might be without suc- 

 cess. Indirect evidence for the need for 

 progesterone to maintain a successful preg- 

 nancy in the human being and for the lack 

 of need for the corpus luteum once preg- 

 nancy is established has been presented by 

 Tulsky and Koff (1957). Corpora lutea 

 were removed from day 35 to day 77 of 

 pregnancy in 14 women. Two of the women 

 exhibited spontaneous abortion and a 

 marked drop in pregnanediol excretion. The 

 remaining 12 maintained a normal preg- 

 nancy and pregnanediol excretion. The data 

 can be interpreted to indicate a need for 

 progesterone during pregnancy and that 

 this need can be met by a nonovarian 

 source, i.e., the i)lacenta. 



In both the rat and mouse, successful 

 maintenance of pregnancy after castration 

 has been obtained with progesterone or a 

 combination of progesterone and estrogen. 

 However, partial maintenance following 

 castration can be obtained in the rat under 

 special circumstances. Haterius (1936) re- 

 moved all the fetuses except one and left all 

 placentas intact. Under these conditions the 

 remaining fetus was carried beyond term. 

 Alexander, Fraser and Lee (1955) found 

 that castration of the rat on the 9th day 

 resulted in 100 per cent abortion, whereas 

 60 per cent of the fetuses were retained until 

 term if castration was on the 17th day. 

 Dosage of progesterone as high as 5 to 10 

 mg. daily following castration the 9th day 

 gave only partial maintenance. It is possible 

 that better results would have followed 

 multiple daily injections. Yochim and Zar- 

 row (1959) castrated rats on day 12 of ges- 

 tation and obtained a pregnancy index (no. 

 of fetuses alive at day 20 h- no. of implanta- 

 tion sites at day 12) of 0.741 when 2 mg. 

 progesterone were gi^'en in two divided 

 daily doses and 0.495 when 1.5 mg. proges- 

 terone was given (Table 16.12). However, 

 the addition of 0.1 /^.g. estradiol daily 

 markedly enhanced the action of the proges- 

 terone so that a pregnancy index of 0.9, i.e., 

 equivalent to the normal controls, was ob- 

 tained with 1.5 mg. progesterone. 



Finally, Hall (1957) has indicated that 

 relaxin synergizes with estradiol and pro- 

 gesterone in the maintenance of jiregnancy 



