Abstract
Luteal phase deficiency (LPD) is described as a condition of insufficient progesterone exposure to maintain a regular secretory endometrium and allow for normal embryo implantation and growth. Recently, scientific focus is turning to understand the physiology of implantation, in particular the several molecular markers of endometrial competence, through the recent transcriptomic approaches and microarray technology. In spite of the wide availability of clinical and instrumental methods for assessing endometrial competence, reproducible and reliable diagnostic tests for LPD are currently lacking, so no type-IA evidence has been proposed by the main scientific societies for assessing endometrial competence in infertile couples. Nevertheless, LPD is a very common condition that may occur during a series of clinical conditions, and during controlled ovarian stimulation (COS) and hyperstimulation (COH) programs. In many cases, the correct approach to treat LPD is the identification and correction of any underlying condition while, in case of no underlying dysfunction, the treatment becomes empiric. To date, no direct data is available regarding the efficacy of luteal phase support for improving fertility in spontaneous cycles or in non-gonadotropin induced ovulatory cycles. On the contrary, in gonadotropin in vitro fertilization (IVF) and non-IVF cycles, LPD is always present and progesterone exerts a significant positive effect on reproductive outcomes. The scientific debate still remains open regarding progesterone administration protocols, specially on routes of administration, dose and timing and the potential association with other drugs, and further research is still needed.
Highlights
Multiple uses of progesterone and progestogens for women’s health in clinical practice are recognized
This study has shown that controlled ovarian stimulation (COS) regimens affect the transcriptomic pattern of endometrial cells in comparison with natural cycles; in particular, there were numerous differences in the main systems involved in the implantation process, such as the TGFb signaling pathway, the complement and coagulation cascades and leukocyte transendothelial migration [34]
New and different regimens have been proposed for a greater luteal phase support in GnRH-a triggering: the intensive or “American” approach which consists of an aggressive steroidal support with adjuvant low-dose human chorionic gonadotropin (hCG) trigger only in selected cases, such as women with peak serum E2 less than 4000 pg/ml on the day of trigger, and the moderate or the “European” approach which promotes the production of endogenous steroids by the corpus luteum via exogenous hCG supplementation, immediately after the oocyte retrieval, at dose low enough to avoid the development of ovarian hyperstimulation syndrome (OHSS) [108]
Summary
Multiple uses of progesterone and progestogens for women’s health in clinical practice are recognized. A recent meta-analysis concluded that progesterone support did not benefit the clinical pregnancy rate in patients undergoing ovulation induction with CC (RR 0.89, 95 % CI 0.47 to 1.67) nor a significant difference in miscarriage per cycle between the two groups (OR 1.03, 95 % CI 0.52 to 2.04) [13].
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