DISCUSSIONS 



Chairman: AsrwooD 



Chairman Astvv<x)d: Thank you very much for that fine presentation. Dr. Gemzell. I 

 think we might have a brief discussion, before going on to the next paper. Dr. Segal, 

 do you have any remarks to make at this time ? 



Dr. Sheldon Seg.al: Dr. Gemzell's interesting studies and the results he has recorded 

 speak for themselves so eloquently that there is very little left to question. I have but a 

 few minor points of interest to raise. Until now, when pituitar>- gonadotropins ha\e 

 been extracted from animal glands, we have been shackled, to a certain extent, by 

 the practical expedience- of using whate\ er glands that could be obtained under slaughter- 

 house conditions. This has made it almost impossible to extract separately male and 

 female pituitaries. Since the program of extracting himian piluitaries for gonadotropins 

 is still in its infanc>\ it might be possible to establish a collection procedure which 

 would permit taking advantage of sex-specific characteristics. All would agree, on the 

 basis of total gonadotropin assays, that quantitative differences exist and it is far 

 from imreasonable to assimie that qualitative differences might be imcovered which 

 would play an important role in the biologic activity of human pituitary extracts. I 

 would urge Dr. Gemzell to consider this possibility when making collections for future 

 extraaions. 



The results indicate that there was a remarkable imiformity in the time required 

 for ovxilation after the supplementing dose of HCG was administered. In most 

 instances it appeared to take approximately 10 hr. In a few cases, however, the evidence 

 did seem to indicate a longer period of delay. This final maturation period of the 

 follicle and enclosed ovum may be viewed as highly significant toward assuring the 

 egg normalcy. The condition of the released egg is particularly important in these 

 considerations since human gonadotropins will find widespread usage in cases of 

 infertility in which induced o%Tilations will be given the greatest opportunity for 

 subsequent fertilization and development. With this in mind, it would seem advisable 

 to eliminate the use of HCG as the supplementary, ovulation-inducing substance 

 and as soon as adequate supplies are available, establish the dosage levels required 

 to complete with pituitary gonadotropins, the entire process of follicle stimulation, 

 final maturation of the ovoim and ovxJation. The work reported by Dr. Simpson 

 earlier in this Conference could be used to great advantage in determining the dosage 

 ratios that would be required. In brief, I am contending that ovulation is a continuous 

 process including the various steps mentioned above. The gametes released following 

 the stimulation by human pituitarv- gonadotropin as an initial step followed by HCG 

 stimulation to carry the process to completion may not have the same opportunity 

 for normalcy as gametes that have developed completely under stimulation by pituitary 

 gonadotropins. 



My final comment is with respect to Dr. Gemzell's finding of multiple-follicle- 

 stimulation following the administration of human pituitary FSH. It raises an 

 interesting speculation on the possible phenotypic expression of a gene action known 

 to exist in humans. .Multiple or polyovular ovulations occur with familial and even 

 racial distribution. For example, they occur less frequently among Japanese families 

 than in Caucasians. To say that the phenomenon is controlled genetically, as all would 

 agree, does not delve very deeply toward understanding the physiologic differences 

 that exist at the level of the ovary. One could speculate in terms of gene penetrance, 

 postulating that the greater the penetrance the greater restriction placed on the number 

 of follicles stimulated at each cycle. The physiologic mechanism of the gene action 



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