Pedro N Barri, Buenaventura Coroleu, Francisca Martinez
Service of Reproductive Medicine, Department of Obstetrics and Gynecology
Hospital Universitario Quirón Dexeus, Barcelona, Spain
The supraphysiological steroid concentrations and consequent LH supression which are common in IVF cycles, causes disruptions to the luteal phase leading to inadequate endometrial development and asynchrony in the embryo – endometrium dialogue (Fauser and Devroey 2003; Bourgain and Devroey 2003) (Fig. 1). Although there is a rapid recovery of the pituitary in GnRh antagonists cycles luteal support remains mandatory in the majority of IVF cycles (Fatemi et al. 2007)
Luteal supplementation with human chorionic gonadotropin (HCG) has proven efficient in overcoming luteal phase defects, however this treatment is frequently associated with an increased risk of ovarian hyperstimulation syndrome (OHSS) for this reason the most widely used form of luteal support is progesterone.. Natural progesterone administered by the vaginal route has been the most commonly used protocol for luteal support. Recent developments will allow to use new subcutaneous preparations that will improve patients’ compliance.
We know that inadverted GnRH agonist administration in the luteal phase does not interfere the evolution of a pregnancy after ART. For these reasons some authors suggested that GnRH agonist administration in luteal phase can enhance implantation. Recent studies and metaanalyses have shown that the use of GnRH for luteal support could improve the pregnancy rate obtained (Van der Linden et al 2011). Nevertheless considering the heterogeneity of the different trials, we relieve that it is too premature to recommend the use of GnRH agonist for luteal support. Additional randomized and controlled trials are mandatory to obtain evidence-based recommendations.
Accepting the fact that progesterone still is the gold standard for the luteal support of the majority of IVF cycles, the question nowadays is to tailor new protocols for cycles in which triggering has been carried out with a bolus of GnRH agonist (Humaidan et al 2011), clinical approach that is becoming more and more popular in the recent years not only for patients at high risk of OHSS but also for postponing embryo transfer for an artificial cycle (Fig.2).
Finally, which is the ideal dose of progesterone and for how long? A growing body of evidence is supporting this concept and adds to this concern that progesterone supplementation might be necessary for luteal support but could be unnecessary for early pregnancy. The challenge today is not only to reduce the duration of progesterone treatment in early pregnancy but probably clarify its use for luteal support in terms of products, dose and route of administration.
BIBLIOGRAPHY
- Fauser B.C., Devroey P ( 2003) Reproductive biology and IVF: Ovarian stimulation and luteal phase consequences, Trends in Endocrinology and Metabolism 14-5:236-42
- Fatemi H., Popovic-Todorovic B., Papanikolaou E., Donoso P., Devroey P. (2007) An update of luteal phase support in stimulated IVF cycles. Hum. Reprod. Update 13-6:581-90
- Bourgain C., Smitz J.,Devroey P. ( 2003) Metaanalysis on luteal support Hum. Reprod. 18-3: 656-7
- Van der Linden M.,Buckingham K., Farquhar C., Kremer JA., Metwally M. (2011) Luteal phase support for assisted reproduction cycles Cochrane Database of Systematic Reviews (5-10)
- Humaidan P., Kol S., Papanikolaou E., and Copenhagen GnRH triggering workshop group, Hum. Reprod. Update 98:510-24