Anastasios Tranoulis1, Alexandros Laios2, Andreas Pampanos3, Drakoulis Yannoukakos4, Dimitrios Loutradis5, Lina Michala5. 1. Department of Obstetrics and Gynaecology, St. James's University Hospital, Leeds Teaching Hospitals, Leeds, United Kingdom. Electronic address: tasostranoulis@yahoo.com. 2. Department of Obstetrics and Gynaecology, St. James's University Hospital, Leeds Teaching Hospitals, Leeds, United Kingdom. 3. Department of Genetics, Alexandra Hospital, University of Athens, Athens, Greece. 4. Molecular Diagnostics Laboratory, INRaSTES, National Center for Scientific Research "Demokritos", Aghia Parasevi, Athens, Greece. 5. Department of Reproductive Endocrinology, Alexandra Hospital, University of Athens, Athens, Greece.
Abstract
OBJECTIVE: To systematically review and appraise the existing evidence in relation to the efficacy and safety of pulsatile gonadotropin-releasing hormone (pGnRH) for the treatment of women with hypothalamic amenorrhea (HA). DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): A total of 35 studies (three randomized and 32 observational) encompassing 1,002 women with HA. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Primary outcomes: ovulation rate (OvR), pregnancy per ovulatory cycle rate (POR), and live birth per ovulatory cycle rate (LBOR). SECONDARY OUTCOMES: multiple gestation (MG), ovarian hyperstimulation syndrome (OHSS), and superficial thrombophlebitis (ST) rates. The summary measures were expressed as proportions and 95% confidence intervals (CI). RESULT(S): Pulsatile GnRH treatment appears to achieve high OvRs. A trend toward high PORs and LBORs among women with HA is demonstrated. SC pGnRH achieves comparable OvR compared with IV pGnRH. The incidence of OHSS is low and of mild severity. Treatment with pGnRH is associated with low but slightly higher MG rates compared with the general population. IV administered pGnRH is rarely associated with ST. CONCLUSION(S): The high OvRs leading to a high rate of singleton pregnancies and the low likelihood of OHSS render the pGnRH treatment modality both effective and safe for the treatment of women with HA of either primary or secondary origin.
OBJECTIVE: To systematically review and appraise the existing evidence in relation to the efficacy and safety of pulsatile gonadotropin-releasing hormone (pGnRH) for the treatment of women with hypothalamic amenorrhea (HA). DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): A total of 35 studies (three randomized and 32 observational) encompassing 1,002 women with HA. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Primary outcomes: ovulation rate (OvR), pregnancy per ovulatory cycle rate (POR), and live birth per ovulatory cycle rate (LBOR). SECONDARY OUTCOMES: multiple gestation (MG), ovarian hyperstimulation syndrome (OHSS), and superficial thrombophlebitis (ST) rates. The summary measures were expressed as proportions and 95% confidence intervals (CI). RESULT(S): Pulsatile GnRH treatment appears to achieve high OvRs. A trend toward high PORs and LBORs among women with HA is demonstrated. SC pGnRH achieves comparable OvR compared with IV pGnRH. The incidence of OHSS is low and of mild severity. Treatment with pGnRH is associated with low but slightly higher MG rates compared with the general population. IV administered pGnRH is rarely associated with ST. CONCLUSION(S): The high OvRs leading to a high rate of singleton pregnancies and the low likelihood of OHSS render the pGnRH treatment modality both effective and safe for the treatment of women with HA of either primary or secondary origin.