Effects of different progesterone levels on reproductive outcomes in assisted reproductive technologies: from molecular basis to treatment strategies

Figures & data

Table 1. Factors contributing to progesterone elevation in the late follicular phase [8–16].

Author, year	Risk factor	P4 level	Protocol used	Pregnancy rate
Bosch et al. 2010 [8]	Number of follicles	P4 elevated (on the day of HCG administration, >1.5 ng/mL)	GnRH agonists and antagonists	Lower
	Number of oocytes
	Daily FSH dose
Hill et al. 2015 [9]	Number of follicles	P4 elevated (on the day of HCG administration, >1.5 ng/mL)	GnRH agonists and antagonists	Lower (both cleavage- and blastocyst-stage ETs)
	Number of oocytes
	Total FSH dose
Hill et al. 2018 [10]	Number of follicles	P4 elevated (on the day of HCG administration)	GnRH agonists and antagonists	Lower
	Number of oocytes	Proportional change in live birth rate (from P4 >2.0 ng/mL)
	P4/oocyte ratio does not have effect
Koo et al. 2015 [11]	Total FSH dose, number of oocytes, E2 level	P4 elevated (>0.9 ng/mL)	GnRH antagonists	Lower
Kyrou et al. 2012 [12]	FSH-only protocols	P4 elevated (on the day of HCG administration, >1.5 ng/mL)	R-FSH + GnRH antagonist	Lower
	Number of follicles
Oktem et al. 2017 [13]	FSH-only protocols	P4 elevated: in ovarian tissue sample- effect of FSH on P4 production from human granulosa cells via upregulation of 3β-HSD expression and increasing its enzymatic activity	FSH	Not measured
Papaleo et al. 2014 [14]	Total dose of FSH	P4 elevated (on the day of HCG administration)	GnRH agonists and antagonists	Lower (cleavage- stage ETs)
	Basal P4 level
Venetis et al. 2015 [15]	Number of oocytes	P4 elevated (on the day of HCG administration, >1.5 ng/mL)	GnRH agonists and antagonists	Lower
	Number of follicles
	Total dose of FSH
Werner et al. 2014 [16]	LH addition	P4 reduced (<1.0 ng/mL when LH was used along with FSH)	GnRH agonists and antagonists	Not measured

Abbreviations: 3β-HSD, 3-beta-hydroxysteroid dehydrogenase; E2, estradiol; ET, embryotransfer; FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; HCG, human chorionic gonadotropin; LH, luteinizing hormone; P4, progesterone; R-FSH, recombinant follicle stimulating hormone.

Table 2. Progesterone at the beginning of the cycle as a marker for elevated progesterone in late follicular phase [14,17–22].

Author, year	Cycle day and P4 level	Protocol used	Pregnancy rate
Blockeel et al. 2011 [17]	2nd, P4 > 1,5 ng/mL (antagonist used to normalize P4 values)	rFSH + GnRH antagonist	No statistical significance
Hamdine et al. 2014 [18]	2nd, P4 > 1.5 ng/mL	rFSH + GnRH antagonist	Lower clinical and ongoing pregnancy rate, but the differences did not reach statistical significance
Kolibianakis et al. 2004 [19]	2nd, P4 > 1.5 ng/mL (antagonist used to normalize P4 values)	rFSH + GnRH antagonist	Lower clinical and ongoing pregnancy rates
Mutlu et al. 2017 [20]	2nd, P4>0.65 ng/mL (predictor for premature P4 rise >1.5 ng/mL)	rFSH, hMG + GnRH antagonist	No statistical significance
Papaleo et al. 2014 [14]	2nd, P4 >0.4 ng/mL (predictive factor for later elevated P4)	rFSH, Rfsh + rLH, hMG, GnRH agonist and antagonists	Lower when P4 before HCG administration is >1.35 ng/mL
Sims et al. 1994 [21]	2nd to 6th cycle day P4 >1 ng/mL	Leuprolide acetate + FSH	Lower clinical and ongoing pregnancy rate, but the differences did not reach statistical significance
Tang et al. 2007 [22]	4th, P4 >1 ng/mL	rFSH + GnRH agonist	Lower clinical and ongoing pregnancy rates

Abbreviations: FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; HCG, human chorionic gonadotropin; hMG, human menopausal gonadotropin; P4, progesterone; rFSH, recombinant follicle stimulating hormone; rLH, recombinant luteinizing hormone.

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