The role of parity in the relationship between endometriosis and pregnancy outcomes: a systematic review and meta-analysis.

Abstract: Endometriosis is a chronic and debilitating condition which can affect the entire reproductive life course of women with a potentially detrimental effect on pregnancy. Pregnancy (and increasing parity) can affect endometriosis by modulating disease severity and suppressing symptoms. Multiparous women could be less likely to suffer from endometriosis-related pregnancy complications than primiparous women. We aimed to systematically review the evidence examining the role of parity in the relationship between pregnancy outcomes and endometriosis. A systematic search of MEDLINE, EMBASE, CINAHL, Web of Science, and Cochrane Library was performed from inception to May 2022. We searched for experimental and observational studies. Grading of Recommendations, Assessment, Development, and Evaluation was used to assess the quality of evidence with the risk of bias in non-randomised studies of interventions tool incorporated. Eleven studies were included in the meta-analysis. Primiparous women with endometriosis had almost double the risk of hypertensive disorders of pregnancy (OR: 1.99, 95% CI: 1.50-2.63, P < 0.001) compared to multiparous women with endometriosis. Primiparous women with endometriosis were at significantly increased risk of preterm delivery, caesarean delivery, and placenta praevia compared to primiparous women without endometriosis. There were no significant differences in outcomes when multiparous women with endometriosis were compared to multiparous women without endometriosis. There is limited evidence to suggest that primiparous women with endometriosis may be at higher risk of adverse pregnancy outcomes compared to multiparous women. The modulatory role of parity in the pathophysiology of endometriosis and its impact on pregnancy outcomes should be investigated. Lay summary: Endometriosis can adversely affect pregnancy and cause complications that can affect both mother and baby. The severity and symptoms of endometriosis are lessened in pregnancy and with increasing births. Women who have previously given birth could experience fewer pregnancy complications than women giving birth for the first time. We reviewed the literature to compare pregnancy outcomes in women with endometriosis by whether they had given birth before or not. Our review included 11 studies. More women with endometriosis giving birth for the first time had blood pressure disorders in pregnancy than women with endometriosis who had given birth before. First-time mothers with endometriosis tended to have a baby born early, caesarean delivery, and an abnormally located placenta compared to those without endometriosis. This study supports the theory that women with endometriosis in their first pregnancy are at higher risk of complications and may benefit from additional monitoring.

The increased trafficking of the calcium channel subunit alpha2delta-1 to presynaptic terminals in neuropathic pain is inhibited by the alpha2delta ligand pregabalin.

Neuropathic pain results from damage to the peripheral sensory nervous system, which may have a number of causes. The calcium channel subunit alpha(2)delta-1 is upregulated in dorsal root ganglion (DRG) neurons in several animal models of neuropathic pain, and this is causally related to the onset of allodynia, in which a non-noxious stimulus becomes painful. The therapeutic drugs gabapentin and pregabalin (PGB), which are both alpha(2)delta ligands, have antiallodynic effects, but their mechanism of action has remained elusive. To investigate this, we used an in vivo rat model of neuropathy, unilateral lumbar spinal nerve ligation (SNL), to characterize the distribution of alpha(2)delta-1 in DRG neurons, both at the light- and electron-microscopic level. We found that, on the side of the ligation, alpha(2)delta-1 was increased in the endoplasmic reticulum of DRG somata, in intracellular vesicular structures within their axons, and in the plasma membrane of their presynaptic terminals in superficial layers of the dorsal horn. Chronic PGB treatment of SNL animals, at a dose that alleviated allodynia, markedly reduced the elevation of alpha(2)delta-1 in the spinal cord and ascending axon tracts. In contrast, it had no effect on the upregulation of alpha(2)delta-1 mRNA and protein in DRGs. In vitro, PGB reduced plasma membrane expression of alpha(2)delta-1 without affecting endocytosis. We conclude that the antiallodynic effect of PGB in vivo is associated with impaired anterograde trafficking of alpha(2)delta-1, resulting in its decrease in presynaptic terminals, which would reduce neurotransmitter release and spinal sensitization, an important factor in the maintenance of neuropathic pain.