Ovulation triggering with GnRH agonist vs. hCG in the same egg donor population undergoing donor oocyte cycles with GnRH antagonist: a prospective randomized cross-over trial.

OBJECTIVE: To compare fertilization, implantation and pregnancy rates in donor oocyte cycles triggered for final oocyte maturation with either human chorionic gonadotropin (hCG) or gonadotropin releasing hormone (GnRH) agonist in the same donor population in two sequential stimulation cycles. DESIGN: Prospective randomized cross-over trial. SETTING: Private infertility clinic. PATIENT(S): Eighty-eight stimulation cycles in 44 egg donors. INTERVENTIONS: Controlled ovarian hyperstimulation (COH) with GnRH antagonist protocol triggered with hCG or GnRH agonist (leuprolide acetate 0.15 mg) in the same egg donors in two consecutive cycles. MAIN OUTCOME MEASURE(S): The primary outcome measure was the proportion of mature and fertilized oocytes per donor cycle. Secondary outcome measures were implantation and pregnancy rates in the recipients and incidence of ovarian hyperstimulation syndrome (OHSS) in oocyte donors. RESULT(S): The proportion of mature oocytes, fertilized oocytes and mean embryo scores were comparable between the two triggering agents. While implantation (36.53% vs, 32.93%), pregnancy (69.08% vs. 68.81%) and clinical pregnancy (41.3% vs. 40.2%) rates were comparable for the groups, the incidence of OHSS was significantly lower in GnRH than in hCG triggered cycles. CONCLUSION(S): Fertilization, implantation and pregnancy rates from donor oocytes stimulated with GnRH antagonist protocol were identical for donor cycles triggered with hCG and GnRH agonist. GnRH antagonist triggering in egg donors was associated with lower rates of OHSS.

Outcome of assisted reproduction treatment in patients with endometrial thickness less than 7 mm.

Endometrial thickness is one of the parameters contributing to the outcome of assisted reproduction treatment. The aim of the current study was to investigate the pregnancy rate and the outcome when the endometrial thickness was <7 mm during a treatment cycle. Treatments conducted between January 2000 and December 2004 at the German Hospital in Istanbul were reviewed retrospectively. A total of 175 embryo transfer cycles with an endometrial thickness of <7 mm on the day of oocyte retrieval were assessed. The 175 oocyte retrieval-embryo transfer cycles resulted in 53 pregnancies (30%), of which 11% were biochemical pregnancies, 26% were miscarriages and 58% were delivered. The clinical pregnancy rate was 26%, miscarriage rate was 31% and live birth rate was 17%. However, the results were quite good when the patient age was <35 years or the number of oocytes retrieved was over five or the number of available embryos to transfer was three or more. In conclusion, when the endometrial thickness is <7 mm during an treatment cycle, the couple should be informed about the chance of pregnancy and the outcome. In a young normoresponder woman with at least three embryos available for transfer, transfer could be carried out, otherwise embryo freezing should be recommended.

Comparison of agonistic flare-up-protocol and antagonistic multiple dose protocol in ovarian stimulation of poor responders: results of a prospective randomized trial.

The management of poor responders in IVF has always been a big problem. The ideal approach has yet to be formulated. In this study we aim to compare two alternative stimulation protocols. A total of 48 poor responder patients described from previous cycles were included and grouped into two: group I consisted of 24 patients in 24 cycles in which leuprolide acetate (40 microg s.c. per day) was initiated on cycle day 2 followed by exogenous gonadotrophins on cycle day 3; group II consisted of 24 patients in 24 cycles in which ovarian stimulation included gonadotrophin-releasing hormone (GnRH) antagonist (cetrorelix, 0.25 mg daily during late follicular phase) administration. While only the oestradiol concentrations on the day of HCG were lower in group II compared with group I, the clinical pregnancy and implantation rates among groups did not show any significance. The impact of these two regimens in ovarian stimulation of poor responders seem to be same and to establish these results further randomized studies with larger sample sizes are required.

Addition of GnRH antagonist in cycles of poor responders undergoing IVF.

Concern about the use of gonadotrophin-releasing hormone (GnRH) agonists in ovarian stimulation of poor responder IVF patients has arisen from the claim that GnRH agonists might have a direct deleterious effect through their receptors on the ovary. In this study, we compared two ovarian stimulation protocols in which no GnRH agonists were used. In all, 40 patients with a poor response in previous treatment cycles were included. They were divided into two groups: group I (n = 20) received ovarian stimulation for 20 cycles, without the addition of either GnRH agonist or antagonist; while group II (n = 20) patients received ovarian stimulation for 20 cycles, including the administration of a GnRH antagonist (Cetrorelix, 0.25 mg daily) during the late follicular phase. There was no statistically significant difference between the groups for mean age, duration of infertility, baseline FSH concentration, cancellation rate, number of ampoules of gonadotrophin used, number of mature oocytes retrieved, oestradiol concentrations on the day of injection of human chorionic gonadotrophin (HCG), fertilization rate and number of embryos transferred. The clinical pregnancy and implantation rates in group II appeared higher than in group I, but were not significantly different (20 and 13.33% compared with 6.25 and 3.44% respectively). The addition of GnRH antagonists to ovarian stimulation protocols might be a new hope for poor responder IVF patients, but this report is preliminary and further controlled randomized prospective studies with larger sample sizes are required.

Corticotropin-releasing factor inhibits luteinizing hormone-stimulated P450c17 gene expression and androgen production by isolated thecal cells of human ovarian follicles.

Recently, we reported that the thecal compartment of the human ovary contains a CRF system replete with gene expression and protein for corticotropin-releasing factor (CRF), CRF-Receptor 1 (CRF-R1), and the blood-derived high affinity CRF binding protein (CRF-BP). Granulosa cells are devoid of the CRF system. The parallel increases in intensity of CRF, CRF-R1, and 17 alpha-hydroxylase messenger ribonucleic acid (mRNA) and proteins in thecal cells with follicular maturation suggest that the intraovarian CRF system may play an autocrine role regulating androgen biosynthesis, with a downstream effect on estrogen production by granulosa cells. The functionality of the ovarian CRF system may be conditioned by the relative presence of plasma-derived CRF-BP by virtue of its localization of protein, but not transcript in thecal cells and its ability to compete with CRF for the CRF receptor. To further these findings, in the present study we have examined the effect of CRF on LH-stimulated 17 alpha-hydroxylase (P450c17) gene expression and androgen production by isolated thecal cells from human ovarian follicles (11-13 mm). During the 48-h culture, addition of LH (10 ng/mL) to the medium increased by 5- and 6-fold dehydroepiandrosterone and androstenedione production by thecal cells. Remarkably, the LH-stimulated, but not basal, androgen production was inhibited by CRF in a time- and dose-dependent manner. The half-maximal (ID50) effect dose of CRF occurred at 5 x 10(-8) mol/L, and at a maximal concentration of 10(-6) mol/L, CRF completely inhibited LH-stimulated androgen production. This inhibitory effect of CRF became evident at 12 h (45%), and by 24 h the effect was more pronounced, with a 70% reduction from baseline. As determined by Northern analyses, CRF dose dependently decreased LH-stimulated P450c17 mRNA levels, with a maximal inhibition of 85% P450c17 gene expression at a CRF concentration of 10(-6) mol/L. With the addition of 10(-6) mol/L of the antagonist alpha-helical CRF-(9-41), the inhibitory effect of CRF was partially reversed for both P450c17 mRNA (75%) and androgen production (50%), indicating the CRF-R1-mediated event. In conclusion, the present study demonstrated a potent inhibitory effect of CRF on LH-stimulated dehydroepiandrosterone and androstenedione production that appears to be mediated through the reduction of P450c17 gene expression. Thus, the ovarian CRF system may function as autocrine regulators for androgen biosynthesis in the thecal cell compartment to maintain optimal substrate for estrogen biosynthesis by granulosa cells. Further studies to define the role of CRF-BP in the endocrine modulation of the intraovarian CRF system are needed.