Premature rise of progesterone during ovarian stimulation

Abstract

Premature rise of progesterone in controlled ovarian stimulation cycles influences IVF outcome. Several authors failed to demonstrate any negative impact while others reported the detrimental effect associated with progesterone rise (pre-ovulatory). It seems that P rise >1.5 ng/ml may have deleterious effect on endometrial receptivity, accelerating the endometrial maturation process that desynchronizes the crosstalk between the embryo and endometrium during implantation. This decreases the pregnancy rate. Progesterone elevations on the day of hCG in GnRH analogue cycles are the result of the ovarian stimulation itself, driven by high follicle- stimulating hormone dosages, high oestradiol levels, the increased number of follicles and oocytes, increased sensitivity of LH receptor of the granulosa cells to FSH or poor ovarian response with increased LH sensitivity. To prevent the premature rise of progesterone in COS, we should use milder stimulation protocols, earlier trigger of ovulation in high responders and single-blastocyst transfer on day 5. The optimal GnRH analogue protocols during the entire stimulation period appear to be the long agonist as well as 'long' and long GnRH antagonist regimens (oral contraceptive pre-treated fixed antagonist regime). The most appropriate choice to avoid the negative effects of follicular progesterone elevations is to cancel fresh embryo transfer and to transfer frozen-thawed embryos in natural cycles. Premature luteinization (PL) refers to a rise in serum progesterone (P) levels on the day of hCG administration. Most studies used an absolute P level on the day of hCG administration as an indicator of PL, and the cut-off level differed from 0.8 to 2 ng/mL. Some authors defined PL as a P/E2 ratio of >1. There is a marked variation in the incidence (13-71 %) of PL due to discrepancies in definition, population characteristics and/or treatment protocols. The pathogenesis of PL in COH is still poorly understood. Several hypotheses may be considered to explain this phenomenon: elevation of follicular LH levels, serum accumulation of HCG from HMG, increased LH receptor sensitivity of the granulosa cells to FSH or poor ovarian response with increased LH sensitivity. The consequences of this premature elevation of serum P on IVF outcome remain controversial. Attempts to prevent COH include use of low-dose hCG alone in the late COH stages, flexible antagonist protocol, use of mifepristone, aspiration of a single leading follicle and hCG administration when the levels of serum P exceeded 1.0 ng/mL.