Mid-luteal serum progesterone concentrations govern implantation rates for cryopreserved embryo transfers conducted under hormone replacement

Abstract

This study explores the relevance of mid-luteal serum hormonal concentrations in cryopreserved embryo transfer cycles conducted under hormone replacement therapy (HRT) control and which involved single-embryo transfer (SET) of 529 vitrified blastocysts. Widely ranging mid-luteal oestradiol and progesterone concentrations ensued from the unique HRT regimen. Oestradiol had no influence on clinical pregnancy or live birth rates, but an optimal progesterone range between 70 and 99 nmol/l (P < 0.005) was identified in this study. Concentrations of progesterone below 50 nmol/l and above 99 nmol/l were associated with decreased implantation rates. There was no clear interaction between oestradiol and progesterone concentrations but embryo quality grading did show a significant influence on outcomes (P < 0.001 and P = 0.002 for clinical pregnancy and live birth rates, respectively). Multiple comparison analysis showed that the progesterone effect was influential regardless of embryo grading, body mass index or the woman's age, either at vitrification or at cryopreserved embryo transfer. The results support the argument that careful monitoring of serum progesterone concentrations in HRT-cryopreserved embryo transfer is warranted and that further studies should explore pessary adjustments to optimize concentrations for individual women to enhance implantation rates.

Vitrified-warmed single-embryo transfers may be associated with increased maternal complications compared with fresh single-embryo transfers

“…Furthermore, vitrified-warmed blastocysts were graded twice -once prior to vitrification and again after warming with a possibly slightly poorer grade after warming and prior to transfer. While pregnancy and live birth rates are not the focus of our study, they may be affected by this difference in embryo quality (Yovich et al, 2015). Perinatal outcome, however, is most probably not affected by embryo quality as we previously reported (Oron et al, 2014).…”

Luteal phase progesterone and oestradiol after ovarian stimulation: relation to response and prediction of pregnancy

“…Indeed, the same range of progesterone at blastocyst transfer was seen regardless of clinical outcome ( Table 2). Earlier studies of natural conceptions in patients undergoing, and not undergoing, assisted reproduction techniques (Hull et al, 1982;Yovich et al, 1985aYovich et al, , 2015, have suggested the existence of an optimal range of luteal phase serum progesterone with an upper and a lower limit. Our data failed to support the concept of an optimal range after ovarian stimulation, as concentrations were almost identical in pregnant and non-pregnant women, and implantation rates were good, despite progesterone concentrations being eight-to nine-fold higher than in natural conception cycles (Hull et al, 1982).…”

“…A recent review of progesterone use after gonadotrophin releasing hormone agonist (GnRH) triggering, suggests an optimal threshold of 32-40 ng/ml of mid-luteal progesterone (Yding Andersen and Vilbour Andersen, 2014). Using oestrogen and progesterone therapy for frozen embryo transfers, Yovich et al (2015) found that a mid-luteal progesterone level between 22 and 31 ng/ml was associated with the best live birth rates. An optimal range of luteal phase steroid secretion may also exist after conventional assisted reproduction techniques with HCG triggering.…”

Micro-dose hCG as luteal phase support without exogenous progesterone administration: mathematical modelling of the hCG concentration in circulation and initial clinical experience

“…The lower pregnancy rates of the GnRHa trigger appear to be associated to a low mid-luteal phase progesterone level and probably reflect too low stimulation of the CL. Several studies have now suggested that in connection with ovarian stimulation (OS), the mid-luteal phase concentration of progesterone should exceed 100 nmol/l in order to reduce the risk of early pregnancy loss and augment reproductive outcome [12][13][14]. This concentration of progesterone is difficult to obtain through vaginal or intra-muscular administration alone and necessitates a direct stimulation of the CL with either rLH or hCG.…”