Embryo freezing for preventing ovarian hyperstimulation syndrome

Abstract

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic potentially life threatening condition resulting from an excessive ovarian stimulation. Its reported incidence varies from one percent to ten percent of in vitro fertilization (IVF) cycles. The factors leading to this syndrome have not been completely explained. It seems likely that the release of vasoactive substances, secreted by the ovaries under human chorionic gonadotropin (hCG) stimulation plays a key role in triggering this syndrome. The hallmark of this condition, is a massive shift of fluid from the intra-vascular compartment to the third space resulting in profound intra-vascular depletion and haemoconcentration. To evaluate (i) the effectiveness of cryopreservation (embryo freezing) for the prevention of OHSS when compared with human intra-venous albumin infusion (ii) the effectiveness of the elective cryopreservation (embryo freezing ) of all embryos for the prevention of OHSS when compared with fresh embryo transfer. We searched the Cochrane Menstrual Disorders and Subfertility Review Group specialised register of controlled trials up to April 2007. In addition, MEDLINE (PUBMED 1985 to March 2007), EMBASE (1985 to April 2007), CINAHL (1985 to March 2007) and the National Research Register (April 2007) were searched. Randomised controlled trials (RCTs) in which either human intra-venous albumin or cryopreservation of all embryos were used as a therapeutic approach to OHSS were included. The women were women of reproductive age who were down regulated by gonadotrophin-releasing hormone-analogue (GnRH-a), undergoing superovulation in in vitro fertilization and or intra-cytoplasmic sperm injection (IVF and or ICSI) cycles. Two review authors, Mr N.N. Amso (NNA) and Dr A. D'Angelo (ADA) scanned the titles and the abstracts of the reports identified by electronic searching in order to find relevant papers. One reviewer (ADA) obtained copies of the full text articles and made copies for the other reviewer (NNA) in which details of authors, institution, results and discussion were removed in order to assess their eligibility for inclusion . Disagreements were resolved by discussion. Additional information on the trial methodology or data were requested by writing to the corresponding authors directly. The interventions compared were cryopreservation (embryo freezing) versus intra-venous human albumin administration and elective cryopreservation of all embryos versus fresh embryo transfer. The primary outcomes were: incidence of moderate and severe OHSS versus nil and or mild OHSS, clinical pregnancies and or woman. The secondary outcomes were: number of oocytes retrieved, number of oocytes fertilized, number of embryos transferred, number of embryos frozen, multiple pregnancy rate, live birth rate, number of women admitted to the hospital as inpatient or outpatient and time to the next menstrual period (resolution time). Statistical analysis was performed in accordance with the Cochrane Menstrual Disorders and Subfertility Group guidelines. No new studies were identified for inclusion in the update therefore the of seventeen studies originally identified in the review published issue 2, 2002. It therefore remains that two studies of which met our inclusion criteria one study was included where cryopreservation (embryo freezing) was compared with intra-venous human albumin administration (Shaker 1996) and one study was included where elective cryopreservation of all embryos was compared with fresh embryo transfer (Ferraretti 1999). When cryopreservation was compared with intra-venous human albumin administration no difference was found in all the outcomes examined between the two groups. When elective cryopreservation of all embryos was compared with fresh embryo transfer no difference was found in all the outcomes examined between the two groups. This updated of the review (D'Angelo 2002) has showed that there is insufficient evidence to support routine cryopreservation and insufficient evidence for the relative merits of intra-venous albumin versus cryopreservation.