Discussions 211 



is sxiggested by Dr. Gemzell's studies. He has overcome the genetic teadeacy for 

 monofollicuJar development by increasing circulating levels and or by altering ratios 

 of pituitary gonadotropins to levels that are apparently out of the normally produced, 

 genetically established range (1 refer here to the frequent observation at laparotomy of 

 multiple-follicle-stimulation and not to the single case of twinning, interesting thou^ 

 it may hc). It would seem that the phenotypic expression of this character controlling 

 multiplicity of oviilations may simply be in the normal gonadotropin levels for diflFerent 

 races or families or, more Ukely, the sensitivity of the developing follicles to a given 

 level of gonadotropins. The faa that no large differences in "normal" gonadotropin 

 excretion levels have been found among various races may reflect the grossness of 

 our present gonadotropin assays. 



Chairman Astwood : There are a couple of brief comments, I believe, that may be made 

 at this time. 



Dr. Duncan E. Rftd: I would Uke to ask Dr. Gemzell whether he has attempted to 

 prolong the normal menstrual cycle with himian chorionic gonadotropin. Also, I 

 should like to know if he has treated women, who might be classified as "chronic 

 aborters"', during the critical period of implantation and early placentatkm by 

 administering human chorionic gonadotropin in the hope of prolonging the cmpos 

 luteimi imtU such time as the syncyiium began to produce sufBcient amotmts of sex 

 steroids. 



Dr. Claude A. VniFF: May I ask a question? I would like to know whether Dr. Gemzell 

 has used any of the LH, which is a by-product of his preparation of FSH, following 

 the administration of FSH, instead of using the chorionic gonadotropin. 



I noted in yoiu" preparation the LH does come out in a separate fraction. 



The other question I have is this. Did this lady who produced the twins have any 

 family history of twinning? 



Dr. Janxt Mc.ARTHt,"R : I w-as intrigued by the mention in Dr. Gemzell's abstract of an 

 inhibitor)" aaion of progesterone given concomitantly with FSH. Would you be 

 willing to discuss this a little further? 



Dr. Carl Gemzell: In answer to Dr. Reid's question, we found liia: if FSH wus adminis- 

 tered after an ovtilation w^as brought about, it was possible to prolong the c>"cle. As 

 long as FSH was administered, there w^s an increa-e in follicular size and estrogen 

 excretion and no bleeding occurred, ^"hen the administration of FSH ceased, a 

 menstrual bleeding occurred, usually within one week. 



We have speculated whether it is necessary to add something more for the corpus 

 hiteum to function and produce steroids. However, when we measured the urinary 

 excretion of steroids there was always a large amount of progesterone produced. The 

 corpora lutea produced in this way lasted about two weeks and when the pregnanediol 

 excretion ceased, a bleeding occurred within one or two da.ys. 



It is difficult to state exactly when an OMiladon takes place following the adminis- 

 tration of FSH. In tw o cases we gave HCG intravenously 24 hr after the last injection 

 of FSH and collected the urine in 3 8-hr samples. Unfortunately both of these womm 

 had already ovulated on the administration of FSH alone, ^^'e are planning similar 

 experiments in order to find out just how long a lime it wiU take to in<htce oviilation 

 in ovaries which have been primed with FSH. 



^"hen HCG was administered to women wiio had been treated with FSH they 

 consistently felt a severe pain in the abdomen about eight to ten hours later. It may 

 be suggested that this pain indicates the luteinization of the ovaries. 



\N e have not done any work on the purification of human pituitary LH but we are 

 collecting the fractions which contain the LH activity. 



The w Oman w ho delivered twins had had no previous record of twins in her family. 



■^^e have treated a number of amenorrheic women with progesterone and FSH in 

 order to find out if the ovarian response was the same as following the administration 

 of FSH alone. The first 5 women treated showed no ovarian response and we thou^ 



