Metformin administration in patients with polycystic ovary syndrome who receive gonadotropins for in vitro fertilization cycles: 10-year experience in a large infertile population.

The study aim was to evaluate our personal experience regarding the use and the reproductive effect of metformin administration in a large population of infertile patients with polycystic ovary syndrome (PCOS) undergoing gonadotropins ovarian stimulation for in vitro fertilization (IVF). Infertile patients with PCOS undergoing gonadotropins ovarian stimulation with (metformin group, n = 191) or without (control group, n = 187) metformin and IVF were evaluated. Treatment characteristics, patients' data and reproductive outcomes were evaluated. In all cases, metformin with an immediate-release formulation was administered, and in most of cases it was given as pre- and co-treatment (74.9%) and at a dosage of 1700 mg/day (59.7%). Stimulation length and gonadotropins doses were significantly (p < 0.05) higher in metformin group than in control group. The number of dominant follicles on day of ovarian maturation triggering and peak oestradiol levels were significantly (p < 0.05) lower in metformin group than in control group. Cycle cancellation rate under metformin resulted significantly influenced by interaction with body mass index (BMI), age and basal follicle-stimulating hormone (FSH) levels. Notwithstanding, metformin use in infertile PCOS patients who receive gonadotropins for IVF is not standardized, it seems to modulate the ovarian response to stimulation. This effect may benefit or harm on the basis of ovarian reserve and patients' characteristics.

Preimplantation genetic diagnosis for the treatment of failed in vitro fertilization-embryo transfer and habitual abortion.

OBJECTIVE: To apply preimplantation genetic diagnosis (PGD) for the treatment of patients with a history of failed IVF-ET or habitual aborters. DESIGN: Prospective clinical study. SETTING: Tertiary center for assisted reproduction. PATIENT(S): Ninety-four couples with failed IVF-ET after >2 IVF cycles and 64 couples with >2 spontaneous abortions. INTERVENTION(S): Patients were prepared for oocyte retrieval using standard controlled ovarian hyperstimulation protocols after standard laboratory techniques. Blastomeres from 6- to 8-cell embryos were analysed using fluorescence in situ hybridization with commercial chromosomal probes, and normoploid embryos were transferred on day 3 after fertilization. MAIN OUTCOME MEASURE(S): Pregnancy and implantation rates and live births. RESULT(S): Both 3- and 5-probe PGD resulted in a significantly higher outcome than controls for failed IVF-ET. Five-probe PGD appeared to be more suitable for habitual aborters. CONCLUSION(S): This pilot study suggests that 3-probe PGD is a valid option for failed IVF-ET patients. The use of five or more probes is indicated for habitual aborters.

Does metformin affect the ovarian response to gonadotropins for in vitro fertilization treatment in patients with polycystic ovary syndrome and reduced ovarian reserve? A randomized controlled trial.

OBJECTIVE: To evaluate the effects of metformin on the ovarian response to gonadotropins given for in vitro fertilization (IVF) programs in patients with polycystic ovary syndrome (PCOS) and reduced ovarian reserve. DESIGN: Prospective, parallel, randomized, double-blind, placebo-controlled clinical trial. SETTING: Academic departments of obstetrics and gynecology, and a private IVF center. PATIENT(S): Primary infertile patients with PCOS older than 35 years and/or with a basal follicle-stimulating hormone (FSH) level higher than 10 IU/L who were scheduled for IVF cycles. INTERVENTION(S): Gonadotropin-releasing hormone agonist flare-up protocol and high starting doses of recombinant FSH plus metformin or placebo tablets. MAIN OUTCOME MEASURE(S): Primary end point: cancellation rate for low ovarian response. Secondary end-points: other clinical, biochemical, and reproductive data. RESULT(S): Enrollment was stopped after 88 participants had been randomized and analyzed due to an unacceptable increased risk of poor ovarian response in the metformin arm. Statistically significant differences between the metformin and placebo groups were observed in the dose of gonadotropins used, peak estradiol levels, and the number of dominant follicles, retrieved oocytes, and metaphase II oocytes. CONCLUSION(S): In patients with PCOS and reduced ovarian reserve, metformin worsened the response to gonadotropins, and its administration should be stopped before the start of controlled ovarian hyperstimulation for IVF programs. CLINICAL TRIALS IDENTIFICATION NUMBER: NCT01208740.

Metformin reduces risk of ovarian hyperstimulation syndrome in patients with polycystic ovary syndrome during gonadotropin-stimulated in vitro fertilization cycles: a randomized, controlled trial.

OBJECTIVE: To test whether metformin administration reduces the incidence of ovarian hyperstimulation syndrome (OHSS) in infertile high-risk patients with polycystic ovary syndrome (PCOS) who have been treated with gonadotropins for IVF. DESIGN: Parallel, randomized, double-blind, placebo-controlled clinical trial. SETTING: Academic departments, general hospital, and IVF centers. PATIENT(S): One hundred twenty patients with PCOS at high risk for OHSS. INTERVENTION(S): Gonadotropins ovarian stimulation for IVF and metformin (500 mg three times daily) or placebo tablets (three times daily). MAIN OUTCOME MEASURE(S): The primary end point of the current clinical trial was the rate of OHSS. Anthropometric and reproductive data were evaluated. RESULT(S): The total OHSS and cancellation rates were significantly reduced in patients treated with metformin. The relative risk for OHSS was of 0.28 (95% confidence interval, 0.11-0.67). With metformin the stimulation length and the total amount of gonadotropins used were significantly increased, whereas the peak E(2) levels were significantly reduced. CONCLUSION(S): In patients with PCOS who are at high risk for OHSS and who have been stimulated with gonadotropins for IVF cycles, metformin reduces the risk of OHSS by modulating the ovarian response to the stimulation. REGISTRATION ID NUMBER FROM CLINICALTRIALS.GOV: NCT01233206.

Effectiveness of presacral neurectomy in women with severe dysmenorrhea caused by endometriosis who were treated with laparoscopic conservative surgery: a 1-year prospective randomized double-blind controlled trial.

OBJECTIVE: The purpose of this study was to assess the effectiveness of presacral neurectomy in women with severe dysmenorrhea caused by endometriosis that was treated with conservative surgical intervention. STUDY DESIGN: One hundred forty-one sexually active women of fertile age with chronic severe dysmenorrhea caused by endometriosis were treated with conservative laparoscopic surgery. Patients were assigned randomly to not receive (group A) or receive (group B) presacral neurectomy. At 6 and 12 months after the surgical procedures, the cure rate was evaluated in each patient. The frequency and severity of dysmenorrhea, dyspareunia, and chronic pelvic pain were also evaluated at the same time intervals. RESULTS: The cure rate was significantly higher in group B compared with group A at a follow-up examination at 6 months (87.3% vs 60.3%) and 12 months (85.7% vs 57.1%). At follow-up visits, the frequency and severity of dysmenorrhea, dyspareunia, and chronic pelvic pain were significantly lower in both groups compared with baseline values; in particular, significantly lower values were observed in group B versus group A for the severity. CONCLUSION: Presacral neurectomy improves the cure rate in women who are treated with conservative laparoscopic surgery for severe dysmenorrhea caused by endometriosis.

Zygote versus embryo transfer: a prospective randomized multicenter trial.

PURPOSE: To determine the efficiency of transferring human zygotes as opposed to human day 2 or 3 embryos. METHODS: A prospective, randomized, Multicenter trial. Patients were randomized into zygote or embryo transfer. Patients were prepared for oocyte retrieval using standardized protocols. Oocyte retrieval was performed under general anesthesia. Oocytes and spermatozoa were treated using standard laboratory techniques. All protocols were coordinated by the coordinating center. RESULTS: A total of 386 patients were included in the trial. Pregnancy rates were 36.5% after zygote transfer and 42% after embryo transfer. Implantation rates were equivalent (17%) in both groups. CONCLUSIONS: No general difference was observed for zygote or embryo transfer. The results suggest that zygote transfer is a valid alternative to embryo transfer.