Influence of Progesterone Withdrawal on Pregnancy‐Related Parameters During Post‐Implantation Early Pregnancy Loss

Abstract

Pharmacologically-induced luteolysis or treatment with an antiprogestin in early post-implantation pregnancy in dogs results in asynchronous death and resorption of conceptuses, indicating variable rates of response of individual conceptuses towards progesterone deficiency. This variability also seems to occur in bitches showing pregnancy failure in response to spontaneous luteal deficiency. In a total of 10 beagle pregnancies (two consecutive pregnancies of five bitches), abortifacient treatments beginning on day 24 after ovulation (ov) involved either administration of a progestin antagonist (total of six pregnancies, in three bitches) or a luteolytic regimen of prostaglandin F(2alpha)-analogue together with a dopamine agonist (total of four pregnancies, in two bitches). The outcomes were evaluated in relation to four control pregnancies in two bitches by assay of serum progesterone, prolactin and relaxin at selected time points or within selected time periods, by ultrasound of conceptuses including measurement of uterine blood flow, and parameters of the blood fibrinolytic system including plasma fibrinogen and plasminogen. The process of embryonic death and conceptus resorption was variable in onset and duration both in bitches that received the progesterone antagonist aglepristone (AGLE) and in those under the luteolytic treatment (cloprostenol combined with cabergoline). Pregnancy termination (death of all embryos or foetuses, respectively) occurred as early as day 29 and as late as day 41 after ov in AGLE-treated bitches, and not earlier than day 37 after ov in luteolytic-treatment bitches. Impending embryonic death was not predicted by changes in relaxin concentration, parameters of the fibrinolytic system, or in the perfusion of small uteroplacental vessels.

Characteristics of midluteal phase uterine artery hemodynamics in patients with recurrent pregnancy loss

“…A growing amount of studies have demonstrated that the impedance to uterine artery blood flow was significantly increased in RPL patients compared with controls . Impaired uterine artery blood perfusion is considered as a pathogenesis of RPL, which would affect the endometrial receptivity and play an important role in regulating successful pregnancy . However, Isaksson et al showed that there was no significant correlation between uterine artery blood perfusion and the occurrence of spontaneous fetal loss .…”

“…6,7,9,10 Impaired uterine artery blood perfusion is considered as a pathogenesis of RPL, which would affect the endometrial receptivity and play an important role in regulating successful pregnancy. 11,14 However, Isaksson et al showed that there was no significant correlation between uterine artery blood perfusion and the occurrence of spontaneous fetal loss. 15 We found that, during the midluteal phase, the mPI, mRI and mS/D values for uterine arteries were significantly higher in RPL patients compared with the controls, which was consistent with our previous preliminary findings.…”

“…17 It is worthy to mention that unexplained RPL patients also had significantly higher resistance to uterine artery blood flow than the controls, which is consistent with the findings of previous researches. 11,18 It therefore suggests that poor uterine perfusion in unexplained RPL patients might be one of the underlying pathologies. It provides a new insight on the treatment for unexplained RPL patients.…”

“…In addition, studies have found a significantly increased resistance to uterine artery blood flow in RPL patients with antiphospholipid syndrome (APS), Müllerian uterine anomalies or unexplained etiology in comparison to those in the control group . And some researchers believed that inadequate uterine artery blood perfusion could play a critical role in the pathogenesis of RPL …”

“…7,10 And some researchers believed that inadequate uterine artery blood perfusion could play a critical role in the pathogenesis of RPL. 11 Based on these observations, the present study aims to investigate the characteristics of the impedance to uterine artery blood flow during the midluteal phase and to explore the possible correlations between the resistance to uterine artery blood flow and the different etiologies of RPL.…”