Levonorgestrel-releasing intrauterine device-wearing women express contraceptive glycodelin A in endometrium during midcycle: another contraceptive mechanism?

Abstract

Intrauterine devices (IUDs) exert contraceptive action by interfering with sperm transport, ovum development, fertilization and implantation. Glycodelin A (GdA) is a uterine glycoprotein that has local contraceptive activity by inhibiting sperm-egg binding. GdA is normally absent from endometrium during the fertile midcycle and it is not expressed until the fifth postovulatory day. The phase of menstrual cycle addressed in this study covers the phase when conception is most likely to follow an unprotected intercourse and when GdA is normally absent. We present here evidence that levonorgestrel-releasing IUD (LNg-IUD) is accompanied by 'inappropriate' expression of GdA in endometrium between days 7 and 16 of the menstrual cycle (six out of six cases). The same was also found in copper-releasing IUD (Cu-IUD)-wearing women, but less frequently (four out of 11 cases, P < 0.0345, Fisher's exact test). In-situ hybridization localized GdA mRNA into endometrial glands in the midcycle endometrium, confirming the cellular site of synthesis. Based on the potent inhibitory activity of GdA on sperm-egg binding, the presence of GdA in uterine glands of IUD wearers may lead to prior exposure of sperm to contraceptive GdA, thus contributing to the contraceptive activity of the IUD.

Mise au point sur la contraception intra-utérine en 15 questions-réponses

“…Ces phé nomè nes ré sultent essentiellement de l'interaction du lé vonorgestrel avec les ré cepteurs à la progesté rone, qui provoque une diminution de l'activité mitotique des cellules endomé triales [6]. En outre, le SIUl induirait l'expression d'une glycoproté ine, la glycodé line A, un inhibiteur physiologique de la fé condation (blocage de l'interaction spermatozoïde-ovocyte II), expression qui contribuerait à renforcer l'effet contraceptif du SIUl [7]. Enfin, lorsque le taux plasmatique de lé vonorgestrel est supé rieur à 200 pg/mL, on observe une augmentation des indices de pulsatilité des artè res uté rines en phase luté ale, atteignant des valeurs semblables à celles observé es physiologiquement en dé but de cycle.…”

Glycodelin in reproductive endocrinology and hormone-related cancer

“…Therefore, absence or low abundance of glycodelin-A in endometrium during the periovulatory fertile window is biologically meaningful (55). Certain progestin-based contraceptives increase endometrial glycodelin-A secretion over the fertile midcycle (68), possibly contributing to the contraceptive effect.…”

Glycodelin: A Major Lipocalin Protein of the Reproductive Axis with Diverse Actions in Cell Recognition and Differentiation

“…Intrauterine contraception. The use of a levonorgestrelreleasing intrauterine device (IUD) is consistently accompanied by "inappropriate" expression of glycodelin-A in endometrium between d 7 and 16 of the menstrual cycle (168). Also, women using the copper-releasing IUD occasionally express "inappropriate" glycodelin at this phase of the cycle, but this is less frequent than in women with a hormonereleasing IUD.…”