nafarelin and cetrorelix

Granulosa cells control oocyte maturation through paracrine signalling and changes to the microenvironment around the oocyte. Apoptosis occurs as a physiological mechanism of granulosa cell renewal, but how it relates with the ovarian response to induced ovulation is still unclear. Therefore, this study evaluated apoptosis-related gene expression levels in granulosa cells of patients undergoing controlled ovarian stimulation. We enrolled prospectively 59 consecutive IVF patients referred to a tertiary academic hospital for couple infertility treatment. Luteinized granulosa cells were isolated from follicular fluid and the RNA was extracted, reverse-transcribed and the gene expression of apoptosis inducers (caspase-3, caspase-8 and bax) and inhibitor (Bcl-2) was quantified by real-time polymerase chain reaction. Caspase-3 gene expression correlated negatively with the number of pre-ovulatory follicles (Spearman's r =  -0.308), the number of collected oocytes (r =  -0.451), the number of mature oocytes (r =  -0.526), the number of fertilized oocytes (r =  -0.439) and the number of viable embryos (r =  -0.443, all statistically significant at p < 0.02 level). No such associations were found with caspase-8, bax or bcl-2. These preliminary findings suggest that increased caspase-3 gene expression in granulosa cells is associated with a worse ovulatory response in humans.

Topics: Caspase 3; Chorionic Gonadotropin; Cohort Studies; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Gene Expression Regulation, Enzymologic; Gonadotropin-Releasing Hormone; Granulosa Cells; Humans; Nafarelin; Oocytes; Ovulation Induction

The paper presents a differential equation model for the feedback mechanisms between gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), development of follicles and corpus luteum, and the production of estradiol (E2), progesterone (P4), inhibin A (IhA), and inhibin B (IhB) during the female menstrual cycle. Compared to earlier human cycle models, there are three important differences: The model presented here (a) does not involve any delay equations, (b) is based on a deterministic modeling of the GnRH pulse pattern, and (c) contains less differential equations and less parameters. These differences allow for a faster simulation and parameter identification. The focus is on modeling GnRH-receptor binding, in particular, by inclusion of a pharmacokinetic/pharmacodynamic (PK/PD) model for a GnRH agonist, Nafarelin, and a GnRH antagonist, Cetrorelix, into the menstrual cycle model. The final mathematical model describes the hormone profiles (LH, FSH, P4, E2) throughout the menstrual cycle of 12 healthy women. It correctly predicts hormonal changes following single and multiple dose administration of Nafarelin or Cetrorelix at different stages in the cycle.

Topics: Biological Availability; Cell Membrane; Computer Simulation; Corpus Luteum; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Menstrual Cycle; Models, Biological; Nafarelin; Time Factors

We report our experience on the efficacy of a new regimen of the GnRH antagonist, cetrorelix, and recombinant FSH, Gonal-F, for controlled ovarian stimulation in a donor oocyte programme.. Six oocyte donors were commenced on Gonal-F (150 IU) and two on Gonal-F 225 IU daily on day 4 together with cetrorelix 0.25 mg daily on day 8 until the day of administration of hCG. Six premenopausal recipients were down-regulated with intranasal Nafarelin 400 micro g twice daily; two women with premature menopause did not require down-regulation for synchronization between donor and recipient cycles. The median (range) of oocytes retrieved and the median (range) fertilization rates were 7 (3-13) and 50% (0-71%) respectively. With the exception of a recipient who had failed fertilization, seven recipients had two embryos transferred. The median (range) number of days of ovarian stimulation, cetrorelix administration and number of Gonal-F ampoules administered for ovarian stimulation were 9 (7-12) days, 5 (3-8) and 18 (14-24) respectively. The clinical pregnancy rate per cycle was 50% (4/8) and one of the latter women miscarried at eight weeks gestation. Three women (37.3%) had full term deliveries.. This preliminary study has shown that using a combination of cetrorelix and Gonal-F resulted in a high pregnancy rate, reduced the duration of treatment for the donor and simplified oocyte donation.

Topics: Adult; Chorionic Gonadotropin; Embryo Transfer; Female; Fertilization in Vitro; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Humans; Middle Aged; Nafarelin; Oocyte Donation; Ovulation Induction; Pregnancy; Pregnancy Outcome; Tissue and Organ Harvesting