A Therapeutic Role of Prolactin Supplementation in Ovarian Stimulation forin VitroFertilization: The Bromocriptine-Rebound Method

Abstract

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 long protocol were prospectively assigned to either the bromocriptine-rebound method (group 1, 82 cycles) or the long protocol (group 2, 80 cycles). The bromocriptine-rebound method was the same as the long protocol, except that bromocriptine was administered daily from day 4 of the preceding cycle until 7 days before hMG stimulation. The numbers of follicles, fertilized oocytes, and embryos with superior morphology were higher in group 1 than in group 2. The rates of clinical pregnancy and live birth delivery per cycle were significantly higher in group 1 (38% and 33%, respectively) than in group 2 (21% and 19%, respectively). The mean concentration of serum PRL during hMG administration was significantly higher in group 1 than group 2. A significant correlation between the number of superior embryos and PRL concentrations was observed in group 1, but not in group 2. Next, we performed a retrospective study to investigate how the bromocriptine-rebound method exerts its beneficial effects. In the initial IVF with the long protocol, the mean concentration of serum PRL during hMG administration and the expression of PRL receptor (PRLr) messenger ribonucleic acid (mRNA) in granulosa cells were significantly higher in nonpregnant patients than in pregnant ones. When IVF was repeated with the bromocriptine-rebound method in the nonpregnant patients, the expression of PRLr mRNA decreased significantly. In conclusion, the bromocriptine-rebound method enhances embryonic development and the rate of live birth delivery in patients with previous failed IVF using the long protocol. We hypothesize that in the nonpregnant patients using the long protocol, the serum PRL concentration and PRLr mRNA expression are increased to compensate for poor postreceptor responsiveness of granulosa cells to PRL during oocyte maturation. The bromocriptine-rebound method may improve oocyte maturation in such patients by restoring postreceptor responsiveness of granulosa cells to PRL during the hypoprolactinemic period and increasing the PRL concentration by a rebound phenomenon after discontinuation of bromocriptine.

High‐level synthesis of human prolactin in Chinese‐hamster ovary cells

“…Human prolactin (hPRL), a protein hormone primarily secreted by the anterior pituitary, has a remarkably wide spectrum of biological activities [1]. Whereas PRL is best known for its stimulation of lactation, and growth and development of the mammary gland [2], it has also been shown to mediate a variety of physiological processes, including growth and maturation of oocytes [3], immune modulation [4] and osmoregulation [5]. Basically a single‐chain protein with a molecular mass of 23000 Da and three intramolecular disulphide bridges, PRL shows significant molecular polymorphism, including a varying percentage of the glycosylated form, which could underlie its diverse properties [1].…”

Prolactin Relationship with Fertility and In Vitro Fertilization Outcomes—A Review of the Literature

“…The role of prolactin in restoring the responsiveness of granulosa cells to stimulation was explored in an older study. Thus, Jinno et al [ 87 ] proposed a new method of ovarian stimulation for IVF in patients with previous IVF failure, the bromocriptine rebound (BR) method [ 87 ]. They administrated bromocriptine from day 4 of the preceding cycle until 7 days before stimulation in patients treated with long agonist protocol and HMG.…”

“…They administrated bromocriptine from day 4 of the preceding cycle until 7 days before stimulation in patients treated with long agonist protocol and HMG. They reported that patients treated with the BR method had higher numbers of follicles, fertilized oocytes, embryos with superior morphology, clinical pregnancy and live birth rates in comparison with patients who did not receive bromocriptine ( Table 1 ) [ 87 ]. Prolactin levels were also significantly higher in patients treated with bromocriptine and were correlated with the number of superior embryos [ 87 ].…”

“…They reported that patients treated with the BR method had higher numbers of follicles, fertilized oocytes, embryos with superior morphology, clinical pregnancy and live birth rates in comparison with patients who did not receive bromocriptine ( Table 1 ) [ 87 ]. Prolactin levels were also significantly higher in patients treated with bromocriptine and were correlated with the number of superior embryos [ 87 ]. They also noticed that the mRNA prolactin receptors in granulosa cells were higher in non-pregnant patients before bromocriptine administration and that the mRNA prolactin receptors decreased after BR method treatment.…”

The Effect of Prolactin on the Quality of Heifer Oocytes Retrieved by Transvaginal Puncture of Follicles

“…К настоящему времени установлено, что гормон гипофиза пролактин (ПРЛ) влияет на овариальную функцию самок и может позитивно модулировать созревание ооцитов и их способность к эмбриональному развитию (17)(18)(19)(20). Рецепторы этого гормона или его мРНК выявлены в ооцитах и сопряженных с ними клетках кумулюса у различных видов млекопитающих, включая коров (20)(21)(22)(23).…”