The impact of ovarian stimulation for IVF on the developing embryo

Purpose To investigate whether serum Anti-Müllerian hormone (AMH) on day 3 could predict controlled ovarian stimulation and reproductive outcomes in women with polycystic ovary syndrome. Methods A total of 164 PCOS patients undergoing their first IVF treatment cycle were prospectively included. Serum AMH levels on cycle day 3 was measured. The controlled ovarian stimulation and clinical outcomes for the study population were divided according to the <25th, 25 to 75th, or >75th percentile of serum day-3 AMH. Results Estradiol levels on hCG day and the number of retrieved oocytes significantly increased with increasing serum AMH levels, while total consumption of gonadotropin dose showed a significant decrease (P<0.05). Fertilization rate and the number of good quality embryos were comparable among the low, average and high groups (P>0.05). Embryo implantation rates in the high AMH group was significantly inferior to those with low and average AMH concentration (27 versus 48.8 and 50%, P<0.01). Clinical pregnancy rates was lower in the high AMH group than that of the low and average group (45.9 versus 65 and 66.7%, P00.09), but this difference was only close to statistical significance. In addition, ordinal regression analysis indicated that LH level was the only independent predictor of embryo implantation rates (P00.017). Conclusions In PCOS women, AMH levels on day 3 of the IVF stimulation cycle positively predict ovarian response to gonadotrophins. However, the women with high AMH levels had a significantly decreased IR, which may be due to remarkably increased LH concentrations.Keywords Anti-Müllerian hormone . Assisted reproduction . Polycystic ovary syndrome . Serum AMH Anti-Müllerian hormone (AMH), also known as Müllerian inhibiting substance (MIS), is producted specifically by granulose cells of early developing pre-antral and small antral follicles in the ovary, and declines with advancing age. AMH has therefore been proposed as a novel clinical marker of ovarian reserve [1]. Another major reason for the interest in AMH is the fact that serum AMH levels are increased significantly in women with polycystic ovary syndrome (PCOS) when compared with normoovulatory women [2,3].PCOS is the most frequent cause of anovulatory infertility and hyperandrogenism in young women [4]. Women with this syndrome are characterized by an excessive number of small antral follicles (2-3 fold that of normal ovaries) [5]. As an exclusively granulosa cell product, it was initially proposed that the rise in serum AMH in PCOS was a consequence of the increased small antral follicle number in these ovaries [6]. The Capsule In PCOS women, high AMH levels on day 3 of the IVF stimulation cycle predict high ovarian response to gonadotrophins, but low embryo implantation rates.

Section: Discussionmentioning

confidence: 99%

Correlation of serum Anti-Müllerian hormone concentrations on day 3 of the in vitro fertilization stimulation cycle with assisted reproduction outcome in polycystic ovary syndrome patients

Wei

Gong

2012

“…However, it can affect oocyte maturation and subsequent embryo development. Artificial induction of ovulation with high doses of gonadotrophins has been demonstrated to decrease the viability of embryos and induce oocyte aneuploidy [3,4]. In animal models, COH was shown to induce the incidence of aberrant methylation patterns in mouse two-cell embryos and the placenta [5], and affect sperm methylation patterns in the second generation of offspring [6].…”

Section: Introductionmentioning

confidence: 99%

Preliminary proteomic analysis on the alterations in follicular fluid proteins from women undergoing natural cycles or controlled ovarian hyperstimulation

Zhang

et al. 2015

Purpose To study the differences in protein expression profiles of follicular fluid (FF) between controlled ovarian hyperstimulation (COH) and natural ovulatory cycles. Methods Twelve infertile women undergoing in vitro fertilization and embryo transfer (IVF-ET), with matched clinical information, were retrospectively recruited in the IVF center of our university hospital, including six undergoing COH and another six with natural cycles. FF was sampled from dominant follicles with mature oocytes. Protein expression profiles in each FF sample were analyzed respectively using twodimensional gel electrophoresis. Differentially expressed proteins were identified using matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF MS) and validated by western blotting. Differentially expressed proteins were further analyzed using Ingenuity Pathway Analysis (IPA) software.Results Two proteins were downregulated and 11 proteins were upregulated (change ≥1.5-fold, P<0.05) in the COH group. We identified one down-egulated and seven upregulated proteins using MALDI-TOF MS. Four differentially expressed proteins, including transferrin, complement component C3 (C3), haptoglobin and alpha-1-antitrypsin (AAT), were further validated by rate nephelometry and western blotting analyses. The IPA analysis revealed a significant network involved in the humoral immune and inflammatory responses. Conclusions The eight differentially expressed proteins were related to immune and inflammatory responses in the ovary. Our results provide new insights into the influence of COH on follicular (spp) development and IVF outcomes.

“…In fact, although pharmacological doses of FSH alone are capable of stimulating ovarian follicular development, LH is strictly necessary to achieve final follicular maturation and oocyte fertilization [4,11]. Standard stimulation regimens typically use exogenous FSH or human menopausal gonadotropin (hMG) in conjunction with gonadotropin-releasing hormone agonists (GnRH-a) to suppress endogenous gonadotropin release [50]. Down-regulation with GnRH-a in some normogonadotrophic women may result in a profound suppression of endogenous LH concentration impairing adequate E 2 synthesis.…”

Section: Introductionmentioning

confidence: 99%

Follicular fluid hormonal profile and cumulus cell gene expression in controlled ovarian hyperstimulation with recombinant FSH: effects of recombinant LH administration

Barberi

Ermini

Morelli

et al. 2012

Purpose Down-regulation with gonadodropin-releasing agonist (GnRH-a) protocol during IVF stimulation leads to a severe endogenous LH suppression, which may affect the follicular development. The aim of the study was to evaluate the effects of recombinant LH (r-LH) administration, during late follicular development stages, in recombinant FSH (r-FSH) stimulated cycles on follicular fluid (FF) parameters and on cumulus cell quality. Methods Twenty patients undergoing IVF were stimulated in a long GnRH agonist protocol with r-FSH alone or with r-LH supplementation when the leading follicle reached diameter of 14 mm. FF was collected at the time of oocyte retrieval from 32 follicles ≥ 18 mm. Serum FSH, LH, estradiol (E 2 ), and progesterone (P 4 ) were evaluated on the day of hCG administration. Intra-follicular E 2 , P 4 , AMH and TGF-β were assayed. Total RNA from 18 individual cumuli was isolated for gene expression analyses. Results R-LH increased FF P 4 levels. FF TGF-β levels and PTGS2 and HAS2 expression in cumulus cells (CCs) positively correlated with increased P 4 levels observed in FFs, while a negative correlation was found between P 4 and AMH levels. Conclusions FF positive correlation between P 4 and TGF-β levels and CC expression of PTGS2 and HAS2 suggest an association with a better follicle quality. In addition, our data suggest that late follicular phase r-LH supplementation leads to a more advanced stage of follicular maturation.