Gene Expression Profiles and Structural/Functional Features of the Peri-Implantation Endometrium in Natural and Gonadotropin-Stimulated Cycles

Abstract

It has been speculated that controlled ovarian hyperstimulation (COH), as performed during in vitro fertilization therapy, may negatively affect embryo implantation. The objective of this prospective and randomized study was to investigate gene expression profiles of the human endometrium during the window of implantation of gonadotropin-stimulated COH cycles compared with temporally matched natural cycles (d 21). Analysis was performed with high-density oligonucleotide microarrays. In addition, other structural and functional features of the endometrium were investigated. Results corroborated that COH cycles depicted advancement of pinopodes appearance, histological features, and steroid receptor down-regulation when compared with natural cycles. These changes were associated with significant, albeit small, variations in gene expression (18 genes/expressed sequence tags and -1.55- to +3.40-fold changes). Second, there were significant changes in gene expression when comparing cycles using a GnRH agonist vs. a GnRH antagonist (13 genes/expressed sequence tags and +1.42- to +2.10-fold changes). This is the first attempt to elucidate gene expression profiles of the endometrium during COH cycles. The observed differences in gene expression in COH cycles using state-of-the-art protocols may not have a major functional impact on embryo implantation.

Impact of serum estradiol levels on the implantation rate of cleavage stage cryopreserved-thawed embryos transferred in programmed cycles with exogenous hormonal replacement

“…The mechanisms by which estrogen and P4 act are highly complex and involve multiple nuclear receptors as well as recently described membrane receptors. It is agreed that controlled ovarian hyperstimulation as performed for IVF leads to histopathologic changes and variations in gene expression profiles of the endometrium when compared to natural cycles [11,30,31]. The effect of markedly supraphysiologic levels of E 2 and various degrees of endometrial histological advancement have been well characterized [11,12].…”

“…It is agreed that controlled ovarian hyperstimulation as performed for IVF leads to histopathologic changes and variations in gene expression profiles of the endometrium when compared to natural cycles [11,30,31]. The effect of markedly supraphysiologic levels of E 2 and various degrees of endometrial histological advancement have been well characterized [11,12]. However, the enigma is still present: what is the true impact of variable degrees of embryoendometrium developmental asynchrony derived from IVF, hyperestrogenism and early luteal progesterone support in the presence of published high clinical embryo implantation rates?…”

“…There is also much debate about the impact of hyperestrogenism on endometrial development and implantation, particularly when controlled ovarian hyperstimulation is used in conjunction with fresh embryo transfers [9][10][11]. Data from our program has provided evidence that high levels of E 2 and also a high cumulative E 2 exposure during the entire follicular phase of gonadotropin-stimulated IVF cycles may have detrimental effects on implantation [12,13].…”

Clinical view of the ineffectiveness of IVF problem with endometrial receptivity

“…Такое мнение ученых иллю-стрирует то, что доза гонадотропинов или длительность стимуляции приводит к активации транскрипции генов, ко-торые не вовлечены в рецептивность в физиологических условиях. С другой стороны, 22% генов имеют менее актив-ную экспрессию в эндометрии в стимулированных циклах, что демонстрирует частичное подавление экспрессии ге-нов при стимуляции функции яичников.Был исследован профиль экспрессии генов в эндометрии в натуральном цикле (ЛГ + 8) в сравнении с последующим стимулированным циклом (ХГч + 9) в протоколах с а-ГнРГ и ант-ГнРГ, с поддержкой прогестероном лютеиновой фазы или без нее [52]. Как заключили исследователи, несмотря на то, что стимуляция функции яичников вызывает струк-турные и функциональные изменения в эндометрии, отли-чия в экспрессии генов были минимальными.…”

Influence Analysis on Discriminant Coordinates

“…Linear discriminant analysis (LDA), DC (also named canonical variates), and logistic discrimination are probably the most frequently used in differential diagnosis. Mirkin et al (2004), DC in a study of human endometrium; Galanaud et al (2006), DA for a noninvasive diagnostic assessment of brain tumors; Struijk et al (2006), a new method for discriminating between people with a normal genotype and those with the congenital long-QT syndrome; Guo et al (2007) and Perelman et al (2003), DA in microarray data, all illustrate relevant applications of DA in biomedical research.…”