Induction of Ovulation in the Human by Human Pituitary Gonadotropin 193 



These findings suggest that in order to obtain chnical effects with gonado- 

 tropin preparations from human pituitaries or urine should be used. 

 Gonadotropins from the urine of castrated or menopausal women, which 

 have mainly FSH activity, have been available for a long time, but the 

 preparations are of low biological activity and their clinical effects are 

 unsatisfactory. An FSH preparation obtained from human pituitaries was 

 found to be quite active (4). When administered over long periods of time 

 it did not evoke any formation of antigonadotropic factors. 



A difficult problem in clinical practice is to prove if and when an ovulation 

 takes place. Spontaneous ovulations do give rise to a number of signs that 

 separately or together give rather good evidence — the rise in body tempera- 

 ture, the secretory reaction of the endometrium and the changes in vaginal 

 smear and cervical secretion. These signs are all due to the release of free 

 progesterone from a fresh corpus luteum. 



In the case of ovulation induced by exogenous gonadotropins, however, 

 these signs may not be valid. The normal physiological functions of the 

 ovaries require certain ratios of FSH to LH and a slight change in these 

 ratios may change the secretion of the ovaries. Administered in unphysio- 

 logical doses, they may be effective in maturing the follicles without actually 

 bringing about an ovulation. It is also possible that exogenous gonadotropins 

 disturb the normal mechanism of ovulation in which a group of follicles are 

 brought to a certain point of maturation and then undergo atresia while the 

 favored one will continue to full development. Instead, the gonadotropins 

 may bring several follicles to full maturation and thus bring hormone 

 production to levels far above the normal. 



The evidence for ovulation presented previously at this Conference is 

 from carefully controlled animal experiments. Our results of gonadotropin 

 studies in the human are somewhat less straightforward owing to the various 

 conditions and the differences in the material. Clinical studies are often 

 fraught with difficulties that are for the most part insurmountable. Every 

 examination must be carried out in the interest of the patient and has to be 

 justified from the point of diagnosis or treatment. Thus, in most cases, 

 the proof of ovulation must rest on circumstantial rather than direct 

 evidence. 



The only absolute proofs of ovulation following the administration of 

 gonadotropin are pregnancy or a fresh corpus luteum. To confirm a corpus 

 luteum an abdominal exploration is usually necessary although sometimes 

 culdoscopy may suffice. 



We hesitate to employ surgical operations because the stimulated ovaries 

 are very fragile and easily damaged. Furthermore, since surgical intervention 

 is seldom justified, we have usually relied on circumstantial evidence such as 

 an increase in pregnanediol excretion or secretory reaction of the 

 endometrium. 



