Circulating progesterone levels and ongoing pregnancy rates in controlled ovarian stimulation cycles for in vitro fertilization: analysis of over 4000 cycles

The influence of elevated serum progesterone levels during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles on pregnancy rates is a matter of continued debate among fertility clinicians. Efforts to resolve this question have been impeded by the various assays used to measure progesterone and the different, arbitrary threshold values for defining 'high' progesterone levels. A non-interventional, retrospective, observational, single-centre cohort study evaluated the relationship between serum progesterone levels on the day of human chorionic gonadotrophin (hCG) administration and the ongoing pregnancy rate in 4032 patients undergoing IVF/ICSI cycles using gonadotrophin-releasing hormone (GnRH) analogues for pituitary down-regulation. Ongoing pregnancy rates were inversely associated with serum progesterone levels on the day of hCG (P < 0.001 for overall trend), irrespective of the GnRH analogue used for pituitary down-regulation. Patients with serum progesterone levels < 1.5 ng/ml had significantly higher ongoing pregnancy rates than those with progesterone levels > 1.5 ng/ml (31.0 versus 19.1%; P = 0.00006); odds ratio, 0.53 (95% confidence interval, 0.38-0.72). Multivariate regression analysis showed that daily follicle-stimulating hormone dose, number of oocytes and estradiol values on the day of hCG administration were positively associated with progesterone levels (P < 0.0001 for all). Serum progesterone levels were significantly greater in women treated with GnRH agonists (n = 1177) versus antagonists (n = 2855; 0.84 +/- 0.67 versus 0.75 +/- 0.66 ng/ml; P = 0.0003). Elevated serum progesterone levels on the day of hCG administration is associated with reduced ongoing pregnancy rates. In particular, serum progesterone levels of > 1.5 ng/ml were associated with lower ongoing pregnancy rates following IVF/ICSI cycles irrespective of the GnRH analogue used for pituitary down-regulation.