Steroid receptor expression in late follicular phase endometrium in GnRH antagonist IVF cycles is already altered, indicating initiation of early luteal phase transformation in the absence of secretory changes
- PMID: 15705618
- DOI: 10.1093/humrep/deh793
Steroid receptor expression in late follicular phase endometrium in GnRH antagonist IVF cycles is already altered, indicating initiation of early luteal phase transformation in the absence of secretory changes
Abstract
Background: Ovarian stimulation for IVF profoundly alters the early luteal phase endometrial development. It has been hypothesized that this process has already started in the late follicular phase, as the endometrium has already been exposed to high steroid concentrations since that phase. The aim of the present study was to prospectively investigate the effect of multi-follicular ovarian stimulation for IVF on the late follicular phase endometrium histology and the expression of estrogen receptor (ER) and progesterone receptor (PR).
Methods: In a cross-over study, 11 infertile women with normal ovulatory function, participating in an IVF programme and treated with GnRH antagonist/recombinant FSH ovarian stimulation, were enrolled in the study. Endometrial biopsies were taken in a natural cycle on the day of the onset of the surge of the LH, and in a subsequent stimulation cycle on the day of hCG administration for final oocyte maturation. Endometrial histological dating was carried out according to Noyes' criteria. Immunohistochemistry was performed, using commercially available antibodies for ER and PR endometrial expression. The immunohistochemical signal was recorded in 1000 epithelial cells in each compartment (glands and stroma). Endometrial expression for each of the two receptors was graded on a scale of 0-3, based on the intensity of nuclear staining. Then a score range between 0 and 3000 was recorded, and expressed as a mean score per 1000 stroma or glandular cells per sample (range: 0-3).
Results: Histological examination of biopsies both in natural and stimulated cycles showed no secretory changes. However, in stimulated cycles, PR expression was significantly up-regulated compared to natural cycles in both glands (1.67 versus 1.34, P < 0.05) and stroma (1.98 versus 1.62, P < 0.05), whereas ER was down-regulated in glands (1.15 versus 1.43, P < 0.05). In IVF cycles, the progesterone measurements, although within normal values (range 0.8-1.4 microg/l), were significantly higher than in natural cycles (0.99 vs 0.63 microg/l, respectively, P = 0.008). An ongoing pregnancy rate of 37.5% was achieved in the stimulated cycles.
Discussion: Although the current study found no early secretory transformation in stimulated endometria before hCG administration, the ER and PR expression in these endometria is similar to the one described during the first days of the luteal phase in natural cycles. Supraphysiological concentrations of estradiol and subtle progesterone rises in the late follicular phase might be responsible for this modulated steroid receptor profile. This phenomenon indicates accentuated maturation of the endometrium in IVF cycles from the pre-ovulatory phase onwards.
Similar articles
-
GnRH antagonists in ovarian stimulation for IVF.Hum Reprod Update. 2006 Jul-Aug;12(4):333-40. doi: 10.1093/humupd/dml001. Epub 2006 Mar 27. Hum Reprod Update. 2006. PMID: 16567347 Review.
-
Prolongation of follicular phase by delaying hCG administration results in a higher incidence of endometrial advancement on the day of oocyte retrieval in GnRH antagonist cycles.Hum Reprod. 2005 Sep;20(9):2453-6. doi: 10.1093/humrep/dei069. Epub 2005 May 12. Hum Reprod. 2005. PMID: 15890735 Clinical Trial.
-
[Optimizing ovarian stimulation for IVF using GnRH antagonists].J Gynecol Obstet Biol Reprod (Paris). 2004 Oct;33(6 Pt 2):3S42-5. J Gynecol Obstet Biol Reprod (Paris). 2004. PMID: 15643688 Review. French.
-
Accelerated endometrial maturation in the luteal phase of cycles utilizing controlled ovarian hyperstimulation: impact of gonadotropin-releasing hormone agonists versus antagonists.Fertil Steril. 2004 Jul;82(1):167-71. doi: 10.1016/j.fertnstert.2003.11.050. Fertil Steril. 2004. PMID: 15237007
-
Nonsupplemented luteal phase characteristics after the administration of recombinant human chorionic gonadotropin, recombinant luteinizing hormone, or gonadotropin-releasing hormone (GnRH) agonist to induce final oocyte maturation in in vitro fertilization patients after ovarian stimulation with recombinant follicle-stimulating hormone and GnRH antagonist cotreatment.J Clin Endocrinol Metab. 2003 Sep;88(9):4186-92. doi: 10.1210/jc.2002-021953. J Clin Endocrinol Metab. 2003. PMID: 12970285 Clinical Trial.
Cited by
-
Hormonal profile in early luteal phase after triggering ovulation with gonadotropin-releasing hormone agonist in high-responder patients.Front Endocrinol (Lausanne). 2022 Aug 15;13:834627. doi: 10.3389/fendo.2022.834627. eCollection 2022. Front Endocrinol (Lausanne). 2022. PMID: 36046787 Free PMC article.
-
Poor ovarian response and the possible role of natural and modified natural cycles.Ther Adv Reprod Health. 2022 Jan 14;16:26334941211062026. doi: 10.1177/26334941211062026. eCollection 2022 Jan-Dec. Ther Adv Reprod Health. 2022. PMID: 35072076 Free PMC article. Review.
-
Endometrial changes in estrogen and progesterone receptor expression during implantation in an oocyte donation program.Exp Ther Med. 2020 Dec;20(6):178. doi: 10.3892/etm.2020.9308. Epub 2020 Oct 12. Exp Ther Med. 2020. PMID: 33101468 Free PMC article.
-
Reduced live birth rates in frozen versus fresh single cleavage stage embryo transfer cycles: A cross -sectional study.Int J Reprod Biomed. 2020 Jul 22;18(7):491-500. doi: 10.18502/ijrm.v13i7.7366. eCollection 2020 Jul. Int J Reprod Biomed. 2020. PMID: 32803114 Free PMC article.
-
Elective cryopreservation of all day 5 blastocysts is more effective than using day 6 blastocysts for improving pregnancy outcome in stimulated cycles.Reprod Med Biol. 2008 Apr 17;7(2):75-83. doi: 10.1111/j.1447-0578.2008.00203.x. eCollection 2008 Jun. Reprod Med Biol. 2008. PMID: 29662418 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials