Follicular progesterone elevations with ovulation induction for IVF

Abstract

The purpose of this review is to analyse the sources and effects of follicular progesterone elevations during ovarian stimulation, with the underlying mechanisms and preventive strategies on the in vitro fertilisation pregnancy outcome. In the early follicular phase, a flare-up effect of gonadotrophin releasing hormone (GnRH) agonists and incomplete luteolysis in GnRH antagonist regimens can result in significant elevations of progesterone. In the late follicular phase, progesterone elevations in GnRH analogue cycles are the result of the ovarian stimulation itself, driven by high follicle stimulating hormone dosage, estradiol levels, the number of follicles and oocytes. It seems that progesterone elevations (> or = 1.5 ng/mL or 4.77 nmol/L) have a detrimental effect on the outcome of pregnancy, accelerating the endometrial maturation. 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. To prevent follicular phase elevations it might be preferable to 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.

Comparison of progesterone measurement on day of, and day after, HCG administration in IVF–embryo transfer cycles

“…In addition, we also found that progesterone rises rapidly just before and after HCG administration, and increased by about five-fold over a 24-h period. The mechanism of P elevation on the day of HCG administration and the relationship to the LH activity has been addressed in a recent review, which suggested that premature luteinization is a misnomer and that the elevated progesterone is direct consequence of FSH stimulation and multiple follicle development (Kasum et al, 2014).…”

Letrozole Supplementation and the Increased Risk of Elevated Progesterone Levels on Trigger Day

“…Many studies have shown that progesterone produced in IVF/ICSI is related to the number of follicles ( 23 , 24 ). In this study, we hypothesised that late elevations in follicular blood progesterone might be owing to the following reasons: 1) An increase in progesterone secretion from the recruited follicles; the greater the number of follicles, the higher the progesterone level, which could be induced by any protocol; 2) pathological progestogen, which is related to the premature luteinisation of follicles and decreased follicle quality.…”

The Ideal Stimulation Protocol: Is There One?

“…In the late follicular phase, progesterone elevations in GnRH analog cycles are the result of the ovarian stimulation itself, driven by high follicle stimulating hormone dosage, estradiol levels, and the numbers of follicles and oocytes. It seems that progesterone elevations (C 1.5 ng/mL or 4.77 nmol/L) have a detrimental effect on the outcome of pregnancy, accelerating the endometrial maturation [32,33]. 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.…”

“…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. To prevent follicular-phase elevations, it might be preferable to use milder stimulation protocols, earlier trigger of ovulation in high responders, and single-blastocyst transfer on day 5 [32]. The optimal GnRH analog protocols during the entire stimulation period appear to be the long agonist as well as ''long'' and long GnRH antagonist regimens [33].…”