Depot and Daily GnRHa: Equally Effective for Long Down-Regulation Protocol?

For the long protocol of down regulation in in vitro fertilization (IVF) cycles, the effectiveness of depot and daily gonadotropin-releasing hormone agonists (GnRHa) are similar, reported the Cochrane Menstrual Disorders and Subfertility Group in an intervention review and meta-analysis.¹
   
Women undergoing IVF often use GnRHa to suppress ovarian activity through down regulation of the pituitary gland. Once this occurs, other fertility drugs, such as gonadotropins, are given to stimulate ovulation in a controlled manner. A number of protocols are used to achieve this, but there is a trend toward higher rates of clinical pregnancy when poor responders are treated with the long protocol.² The long protocol typically involves administering GnRHa until ovarian activity is suppressed, which usually occurs in about 2 weeks. This can be achieved by using daily low-dose injections or a single “depot” injection of higher doses of the drug.
   
The aim of this review was to compare a single depot dose of GnRHa with daily doses of GnRHa in women undergoing IVF. Sixteen studies were eligible for review. However, only 12 studies involving a total of 1366 women were considered suitable for the meta-analysis. All participants received either depot or daily GnRHa for long protocols in IVF treatment cycles. The variation in outcome reporting between studies made it difficult to establish whether there were any substantial differences between study groups.¹
   
Live birth rates and ongoing pregnancy rates varied little between women receiving depot GnRHa and daily GnRHa (odds ratio [OR], 0.95; 7 studies, 873 women), but substantial differences between study groups could not be ruled out. If women who received daily GnRHa injections had a 24% chance of achieving a live birth or ongoing pregnancy, then the corresponding chance of these outcomes in women receiving depot GnRHa would be 18% to 29%. This trend between study groups held for clinical pregnancy rates as well as rates of ovarian hyperstimulation syndrome (OHSS). For women in the daily group with a 30% chance of having a clinical pregnancy, the corresponding chance for women in the depot group was 25% to 35%. Of the women in the daily group who had a 3% chance of OHSS developing, the corresponding risk of OHSS in the depot group ranged from 1% to 6%.
   
The only significant difference between study groups was that women receiving depot administration of GnRHa, compared with those using daily GnRHa, needed significantly more units of gonadotropin over a longer period to achieve ovarian stimulation.

Pertinent Points:
- Although the outcomes related to depot and daily GnRHa use are similar, women who received depot GnRHa required more units of gonadotropins for a longer duration of use.
- Based on these findings, the use of depot GnRHa may increase the overall costs of IVF.

References:

1. Albuquerque LET, Tso LO, Saconato H, et al. Depot versus daily administration of gonadotrophin-releasing hormone agonist protocols for pituitary down regulation in assisted reproductive cycles. Cochrane Database Syst Rev. 2013;1. CD:002808. doi: 10.1002/14651858.CD002808.pub3.
2. Badawy A, Wageah A, El Gharib M, Osman EE. Strategies for pituitary down-regulation to optimize IVF/ICSI outcome in poor ovarian responders. J Reprod Infertil. 2012;13:124-130.