A THERAPEUTIC ROLE OF PROLACTIN SUPPLEMENTATION IN OVARIAN STIMULATION FOR IN-VITRO FERTILIZATION - THE BROMOCRIPTINE-REBOUND METHOD

In a prospective randomized study, we examined whether a novel method of ovarian stimulation, the bromocriptine-rebound method, improves in vitro fertilization (IVF) outcomes compared with the conventional long protocol using GnRH agonist and human menopausal gonadotropin (hMG). Ovulatory women with previous failed IVF-embryo transfer using the lon g protocol were prospectively assigned to either the bromocriptine-reb ound method (group 1, 82 cycles) or the long protocol (group 2, 80 cyc les). The bromocriptine-rebound method was the same as the long protoc ol, except that bromocriptine was administered daily from day 4 of the preceding cycle until 7 days before hMG stimulation. The numbers of f ollicles, fertilized oocytes, and embryos with superior morphology wer e higher in group 1 than in group 2. The rates of clinical pregnancy a nd live birth delivery per cycle were significantly higher in group 1 (38% and 33%, respectively) than in group 2 (21% and 1996, respectivel y). The mean concentration of serum PRL during hMG administration was significantly higher in group 1 than group 2. A significant correlatio n between the number of superior embryos and PRL concentrations was ob served in group 1, but not in group 2. Next, we performed a retrospect ive study to investigate how the bromocriptine-rebound method exerts i ts beneficial effects. In the initial IVF with the long protocol, the mean concentration of serum PRL during hMG administration and the expr ession of PRL receptor (PRLr) messenger ribonucleic acid (mRNA) in gra nulosa cells were significantly higher in nonpregnant patients than in pregnant ones. When IVF was repeated with the bromocriptine-rebound m ethod in the nonpregnant patients, the expression of PRLr mRNA decreas ed significantly. In conclusion, the bromocriptine-rebound method enha nces embryonic development and the rate of live birth delivery in pati ents with previous failed IVF using the long protocol. We hypothesize that in the nonpregnant patients using the long protocol, the serum PR L concentration and PRLr mRNA expression are increased to compensate f or poor postreceptor responsiveness of granulosa cells to PRL during o ocyte maturation. The bromocriptine-rebound method may improve oocyte maturation in such patients by restoring postreceptor responsiveness o f granulosa cells to PRL during the hypoprolactinemic period and incre asing the PRL concentration by a rebound phenomenon after discontinuat ion of bromocriptine.