Current Development Follicular development: Lessons learned from human in vitro fertilization Alan H. DeChemey, M.D., Basil C. Tarlatzis, M.D.,* and Neri Laufer, M.D.** New Haven, Cminecticut In vitro fertilization has offered new insights into our understanding of ovulation induction, folliculogenesis, and luteal phase events. This new information is provided by the ability to precisely study these cycles in a frequent and sequential fashion through the use Of peripheral blood markers, ultrasound evaluation, and follicular fluid constituents and cell culture techniques, as well as direct observation of the oocyte, fertilization, and cleavage. In these stimulated cycles the follicular phase serum estradiol levels in conjunction with ultrasound were evaluated; a poor correlation was shown between follicle size and number and estrogen production. This distinct dyssynchrony suggests the recruitment of a number of cohorts of follicles in each stimulated cycle. From the biochemical mar1<ers in follicular fluid, cyclic adenosine monophosphate has a distinct predictive value in regard to pregnancy in in vitro fertilization- embryo transfer cycles. In the luteal phase, the mass effect of aspiration of great numbers of granulosa cells, the effect of supplemental progesterone, and the influence of high follicular phase estradiol levels remain controversial and, therefore, a less clear cut pattern emerges. Variations in the protocol have not greatly improved the major problems of folliculogenesis associated with ovulation induction and an in vitro fertilization-embryo transfer program, that is, follicular asynchrony and luteal phase deficiency. (AM J 0BSTET GYNECOL 1985;153:911·23.) Key words: Folliculogenesis, in vitro fertilization Although there are many methods of induction of ovulation in an in vitro fertilization-embryo transfer program, this report concentrates on the use of human menopausal gonadotropins (hMG, Pergonal, Serono Laboratories, Inc., Randolph, Massachusetts) alone. This schedule is used for two major reasons: (l) In a system as tenuous as an in vitro fertilization-embryo transfer program, the more variables that one can con- trol, the better one can study the various components of the system. (2) Laufer et al.' reported that clomi- phene had an adverse effect on mouse embryo growth in vitro that was dose-related. The protocol used has been described as a high-dose hMG tegimen 2 and is illustrated in Fig. l. Ovarian stim- ulation is induced by three ampules of hMG per day, 225 IU of follicle-stimulating hormone (FSH) and lu- teinizing hormone (LH), given from the third day of From the Department of Obstetrics and Gynecology, Yale University School of Medicine. Reprint requests: Alan H. DeCherney, M.D., Department of Obstetrics and Gynecology, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06510. *Basil C. Tarlatzis is a Lalor Foundation Fellow. **Neri Laufer was an Andrew W. Mellon Fellow. the cycle for 5 days. Thereafter, hMG is continued for another l to 3 days, depending on the individual's re- sponse. Human chorionic gonadotropin (hCG), 10,000 IU, is administered intramuscularly 24 hours after the last hMG injection, when at least two large follicles (> 1.5 em in diameter) are visualized on ultrasonogra- phy and serum estradiol levels are higher than 400 pg/ml. Laparoscopy is performed 36 to 38 hours after hCG administration and the content of all visible fol- licles is aspirated. 3 • 1 Follicular phase In the induction of ovulation for in vitro fertiliza- tion-embryo transfer, there are three major aims. The is to obtain as many oocytes for fertilization as possible since it has been demonstrated by several au- thors that the number of embryos up to five correlates well with the subsequent pregnancy rate.'· 6 Another goal must be to achieve synchronization in oocyte ma- turity; the more synchronized the oocytes, the greater the ability to determine when insemination should take place. The third consideration is to obtain oocytes of good quality and to decrease the incidence of degen- erated and atretic eggs. The parameters that can be 911