Is progesterone elevation on the day of human chorionic gonadotrophin administration associated with the probability of pregnancy in in vitro fertilization? A systematic review and meta-analysis

Abstract

The role of progesterone elevation on in vitro fertilization (IVF) outcome has remained a debatable issue for several years. The aim of this systematic review and meta-analysis was to evaluate whether progesterone elevation on the day of human chorionic gonadotrophin (hCG) administration is associated with the probability of pregnancy. Eligible studies were considered those in which patients did not participate more than once. A literature search in MEDLINE, EMBASE and CENTRAL identified 12 eligible studies, 10 of which were retrospective. The majority (n = 10) of these studies did not detect a statistically significant association between progesterone elevation and the probability of pregnancy. Meta-analysis was performed only for the studies (n = 5) that provided data on clinical pregnancy per patient reaching hCG administration for final oocyte maturation. No statistically significant association between progesterone elevation and the probability of clinical pregnancy was detected (Odds ratio: 0.75, 95% confidence interval 0.53-1.06; P = 0.10). This finding persisted in the sensitivity analyses performed, which excluded the studies that did not report clearly that measurement of progesterone did not affect patients' management and those that did not report definition of clinical pregnancy. In addition, subgroup analyses were conducted on the basis of type of gonadotrophin-releasing hormone GnRH analogue used and on the value of serum threshold used to classify patients in those with or without progesterone elevation. These analyses, however, did not materially change the results obtained. In conclusion, the best available evidence does not support an association between progesterone elevation on the day of hCG administration and the probability of clinical pregnancy in women undergoing ovarian stimulation with GnRH analogues and gonadotrophins for IVF.

“Premature luteinization” in the era of GnRH analogue protocols: time to reconsider

“…Dragging the term of "premature luteinization" from the pre-to the GnRH analogue era is confusing and inadequate and other terminology should be looked for. The need for an appropriate nomenclature and definition that will reflect accurately this phenomenon and be able to guide investigators to examine the effect of P elevation on ART outcome, which is still to be very much controversial [1][2][3], is prominently needed. Table 1 summarizes the different terms of P elevation before hCG administration, that have been recently suggested in the literature.…”

“…Premature luteinization 2. Elevated progesterone on the day of hCG administration [1,2,25] 3. Pre-hCG progesterone elevation [20] 4.…”

“…During the GnRH analogue era the term of premature luteinization was nonintentionally dragged from the previous period with the same definition. Although most investigators still apply an absolute P level on hCG day as an indication for elevated P level, the cut-off point has differed considerably between one study and another ranging from 0.9 to 2.0 ng/mL [1,10]. Most recent studies have suggested that a cut-off point of 1.25 [16] or 1.5 ng/mL [2], may differentiate more properly in their detrimental effect on endometrial receptivity, however this should be investigated further taking into account the type of gonadotropin and GnRH analogue (agonist or antagonist) employed.…”

“…More than two decades have passed since the GnRH agonist was brought into practice and more than one decade since the GnRH antagonist was commenced, however moderate P elevation, before the day of hCG administration, is continuing to complicate a significant part of ART cycles employing both protocols, ranging from 12.4 to 52.3% [1].…”

“…While some investigators advocate no affect on the probability of clinical pregnancy achievement [1] others support an adverse effect on ART outcome through a detrimental effect on endometrial receptivity [2,3].…”