Induction of Ovulation in the Human by Human Pituitary Gonadotropin 101 



fluid was often found, probably originating from the ruptured follicles. The 

 stimulated ovaries were very fragile and ruptured easily upon handling. Two 

 to three weeks later the enlarged ovaries were reduced in size and could not 

 be felt by pelvic examination. 



DISCUSSION 



The enlargement of the ovaries and the high excretion of estrogen following 

 the administration of FSH indicated that a large number of follicles were 

 stimulated. During a normal menstrual cycle several follicles are brought 

 to a certain point of maturation and then undergo atresia while a single one 

 takes the lead to its full development. It was likely that the exogenous FSH 

 disturbed this mechanism and brought all the stimulated follicles to full 

 maturation. When these matured follicles were exposed to the luteinizing 

 factor, luteinization occurred in all of them at the same time which resulted 

 in several ovulations and corpora lutea formations. Whether these enlarged 

 follicles were able to deliver normal ova was questionable. It might be 

 suggested that the rapid growth and the changes in intrafoUicular pressure 

 distributed the normal development of the ova. However, at least in two cases 

 the induced ova were fertilized and developed into normal fetuses. 



The primordial follicles of the ovaries, as was shown in this study, have to 

 be stimulated by the exogenous FSH for about 6 days before the luteinizing 

 factor is effective. When the follicles reached this state of maturation 

 luteinization took place very rapidly and a corpus luteum was formed within 

 24 hr. The luteinization of the ovaries was followed by a severe pain in the 

 lower abdomen. 



The strong effect of the exogenous FSH on the ovaries might indicate that 

 the doses were too large or that the hormone was administered during too 

 long a time. In several cases half the dose (5 mg) was administered without 

 any effect. It was possible that the first doses of FSH have to be rather large 

 in order to initiate follicular growth. After the follicles have been stimulated, 

 smaller doses might be sufficient. Furthermore, the period of 10 days might 

 also be too long, for the maturation necessary for the luteinization to occur 

 was reached already within 6 days. After an ovulation has occurred the 

 remaining follicles are still responsive to FSH stimulation and continue 

 growing and produce large amounts of estrogen. 



The tremendous rise in pregnanediol excretion seen in a couple of cases 

 suggests that the amount of HCG administered might also be too large. In 

 one case where a single corpus luteum was found, the pregnanediol excretion 

 was 8 mg per 48 hr which was a quite normal level during the luteal phase. 

 The high level of 100 to 140 mg per 48 hr found in one case might indicate 

 that 10 to 15 corpora lutea had been formed. In a patient operated upon this 

 suggestion was confirmed; the high excretion of 80 mg of pregnanediol was 



