Ovarian hyperstimulation affects fluid transporters in the uterus: a potential mechanism in uterine receptivity

2014 ◽  
Vol 26 (7) ◽  
pp. 982 ◽  
Author(s):  
Laura A. Lindsay ◽  
Christopher R. Murphy
Keyword(s):  
Implantation Rate ◽  
Normal Pregnancy ◽  
Controlled Ovarian Hyperstimulation ◽  
Fertility Treatment ◽  
Ovarian Hyperstimulation ◽  
Potential Mechanism ◽  
Uterine Receptivity ◽  
Aquaporin 5 ◽  
Uterine Fluid ◽  
Luminal Epithelial Cells

Controlled ovarian hyperstimulation is commonly used in fertility treatment. Evidence suggests that this could alter the endometrial environment and influence implantation rate. However, the mechanisms underlying this disruption are unknown. A recently developed rat ovarian hyperstimulation (OH) model found alterations in the localisation and expression of several molecules associated with implantation, as well as an increase in luminal fluid at the time of implantation. The present study investigated the effects of OH in rats on the expression of fluid-transporting molecules aquaporin 5 (AQP5) and claudin 4. The expression of these proteins was investigated in uterine luminal epithelial cells of rats undergoing OH and compared with normal pregnancy. There was a significant increase in AQP5 protein in OH rats at the time of implantation, along with a loss of the mesometrial staining gradient, which is thought to contribute to implantation position. At the same time, there was a significant decrease in claudin 4 protein. These results suggest that OH in rats causes a dysregulation in uterine fluid dynamics through modifications to fluid-transporting molecules, resulting in an unfavourable implantation environment for the blastocyst.

scholarly journals Controlled Ovarian Hyperstimulation Protocol in Infertile Patients During the COVID-19 Pandemic

2021 ◽  
Vol 12 ◽  
Author(s):  
Fei Li ◽  
HuiXia Zhang ◽  
WeiYi Shi ◽  
YiFang Wu ◽  
Ye Tian ◽  
...  
Keyword(s):  
Endometrial Thickness ◽  
Management Strategies ◽  
Implantation Rate ◽  
Controlled Ovarian Hyperstimulation ◽  
Ovarian Hyperstimulation ◽  
Down Regulation ◽  
Cycle Number ◽  
Full Dose ◽  
Infertility Patients

Objectives: To explore the appropriate controlled ovarian hyperstimulation (COH) protocols in infertility patients who received the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatments during the COVID-19 pandemic.Materials and Methods: This retrospective cohort study evaluated the efficiency of the early follicular-phase long-acting GnRH-agonist long (EFLL) protocol (a new protocol developed by Chinese clinicians), prolonged pituitary down-regulation of EFLL protocol (Pro-EFLL), and the GnRH-ant protocol for couples meeting the study criteria between February 2020 and June 2020 who were treated by the First Affiliated Hospital of Zhengzhou University during the COVID-19 pandemic, and compared the pregnancy rates and miscarriage rates per fresh transfer cycle, number of retrieved oocytes, endometrial thickness on the day of hCG injection and the number of fertilized oocytes, mature oocytes, fertilized oocytes, and transferable embryos among the three protocols.Results: We found that the prolonged pituitary down-regulation during the COVID-19 pandemic by utilizing a full-dose of GnRH-a administrated in infertility patients were no differences in clinical outcomes than other protocols, The prolonged pituitary down-regulation protocol and EFLL protocol were associated with a higher Endometrial thickness on the day of hCG injection (12.67 ± 2.21 vs. 12.09 ± 2.35 vs. 10.79 ± 2.38, P < 0.001), retrieved oocytes (14.49 ± 6.30 vs. 15.02 ± 7.93 vs. 10.06 ± 7.63, P < 0.001), mature oocytes (11.60 ± 5.71 vs. 11.96 ± 6.00 vs. 7.63 ± 6.50, P < 0.001), fertilized oocytes (9.14 ± 5.43 vs. 8.44 ± 5.34 vs. 5.42 ± 5.20, P < 0.001), and transferable embryos (4.87 ± 2.96 vs. 6.47 ± 5.12 vs. 3.00 ± 3.28 vs. P < 0.001) in the GnRH-antagonist protocol.Conclusion: We recommend that patients start Gn injections 33–42 days after a pituitary downregulated full dose (3.75 mg) of gonadotropin-releasing hormone agonist during the COVID-19 pandemic, even a delay of 2–4 weeks does not affect the implantation rate. The study can provide a more detailed estimate and clinical management strategies for infertile couples during the COVID-19 pandemic.

scholarly journals Uterine focal adhesions are retained at implantation after rat ovarian hyperstimulation

Reproduction ◽  
2016 ◽  
Vol 152 (6) ◽  
pp. 753-763 ◽  
Author(s):  
Laura A Lindsay ◽  
Samson N Dowland ◽  
Christopher R Murphy
Keyword(s):  
Plasma Membrane ◽  
Focal Adhesions ◽  
Normal Pregnancy ◽  
Controlled Ovarian Hyperstimulation ◽  
Ovarian Hyperstimulation ◽  
Integrin Β1 ◽  
Tem Analysis ◽  
Basal Plasma Membrane ◽  
Basal Plasma ◽  
Basal Portion

Controlled ovarian hyperstimulation is an essential component of IVF techniques to ensure proliferation and development of multiple ovarian follicles, but the effects of these hormones on the endometrium are largely unknown. During normal pregnancy in rats, there are significant changes in the basal plasma membrane of uterine epithelial cells (UECs) at the time of receptivity, including loss of focal adhesions. This enables the UECs to be removed from the implantation chamber surrounding the blastocyst, thus allowing invasion into the underlying stroma. This study investigated the influence of ovarian hyperstimulation (OH) on the basal plasma membrane of UECs during early pregnancy in the rat. Immunofluorescence results demonstrate the presence of paxillin, talin, integrin β1 and phosphorylated FAK (Y397FAK) in the basal portion of UECs at the time of implantation in OH pregnancy. TEM analysis demonstrated a flattened basal lamina and the presence of focal adhesions on the basal surface at this time in OH pregnancy. Significantly low full-length paxillin, high paxillin δ and integrin β1 were seen at the time of implantation in OH compared with those in normal pregnancy. The increase in paxillin δ suggests that these cells are less mobile, whereas the increase in integrin β1 and Y397FAK suggests the retention of a stable FA complex. Taken together with the increase in morphological focal adhesions, this represents a cell type that is stable and less easily removed for blastocyst implantation. This may be one mechanism explaining lower implantation rates after fresh embryo transfers compared with frozen cycles.

scholarly journals Influence of short-term ovarian stimulation on bone metabolism in women undergoing fertility treatment

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Anna Ritzinger ◽  
Monika Schmidmayr ◽  
Bernd Lesoine ◽  
Vanadin Seifert-Klauss
Keyword(s):  
Bone Resorption ◽  
Bone Metabolism ◽  
Ovarian Stimulation ◽  
Luteal Phase ◽  
Influencing Factor ◽  
Controlled Ovarian Hyperstimulation ◽  
Fertility Treatment ◽  
Ovarian Hyperstimulation ◽  
Short Term ◽  
Down Regulation

Abstract Objectives Hormonal disturbances during menopause are an established influencing factor on bone health, but the role of controlled ovarian hyperstimulation for fertility treatment remains unclear. To evaluate the influence of ovarian stimulation on bone metabolism with particular regard to serum follicle-stimulating hormone (FSH) levels this prospective observational study was conducted. Methods A total of 71 women underwent controlled ovarian hyperstimulation with recombinant FSH (rFSH) or human menopausal gonadotropin (HMG) (FSH + LH) administered in individual doses, with gonadotropin-releasing hormone (GnRH) agonist down-regulation initiated in the luteal phase of the previous cycle. At four time points (start of down-regulation [T1], start of ovarian stimulation [T2], oocyte retrieval [T3] and luteal phase of the stimulation cycle [T4]), luteinizing hormone (LH), FSH, estradiol (E2), osteocalcin (OC), bone-specific alkaline phosphatase (BAP), as well as the bone resorption markers β-isomerized C-terminal telopeptide of type I collagen (β-CTX) and tartrate-resistant acid phosphatase (TRACP) were measured. Results The cyclic variations in FSH levels had a positive effect on the concentration profile of the bone resorption marker β-CTX (p=0.0001). Supraphysiologic estradiol levels showed a negative association with osteocalcin concentrations (p=0.017), and significantly lower OC and TRACP levels were observed at T4 compared to T1. By group comparison, women treated with rFSH presented with a higher bone turnover than the HMG group at the end of a stimulation cycle (T4). Conclusions Our results show that FSH is a significant influencing factor of bone metabolism. Overall, there was no evidence of enhanced bone resorption under short-term ovarian stimulation therapy. Further studies with bigger sample sizes are warranted to validate these results.

scholarly journals Expression of E-Cadherin in Pig-Tailed Monkey (Macaca nemestrina) Endometrium after Controlled Ovarian Hyperstimulation

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Nurhuda Sahar ◽  
R. Muharam ◽  
Andhea Debby Pradhita ◽  
Rosalina Thuffi ◽  
Wa Ode Zulhulaifah ◽  
...  
Keyword(s):  
Success Rate ◽  
Steroid Hormones ◽  
Implantation Rate ◽  
Controlled Ovarian Hyperstimulation ◽  
Macaca Nemestrina ◽  
Control Group ◽  
Ovarian Hyperstimulation ◽  
Cycle Group ◽  
Rate Research ◽  
E Cadherin

An increase of steroid hormones in controlled ovarian hyperstimulation (COH) procedures is reducing the success rate in assisted reproductive technology (ART), and this includes the pregnancy rate and/or implantation rate. Research has found that the decrease in the success rate occurred due to the decreased expression of the protein that is needed to prepare the endometrium so that the embryo could attach. The aim of the study was to analyse the changes in E-chaderin expression due to COH and its relations with increased level of steroid hormones as one of the proteins in the endometrium. There were 13 samples of stored biological tissue from Macaca nemestrina endometrial tissue; came from one group of natural cycles as the control group ( n = 4 ) and three groups of stimulated cycles. The first stimulated cycle group was injected by a 30 IU dose of rFSH ( n = 2 ). The second stimulated cycle group was injected by a 50 IU dose of rFSH ( n = 4 ). The third stimulated cycle group was injected by a 70 IU dose of rFSH ( n = 3 ). The expression of E-cadherin was measured by the immunohistochemistry (IHC) technique. Estradiol (E2) and progesterone (P4) levels were assessed using ELISA and have already been done. The IHC staining expression of E-cadherin was found in the cytoplasm of glandular epithelium. Immunostaining measurement used the H_SCORE. We found that the expression of E-cadherin within the group was not significantly different ( p value: 0.178). Similarly, both the correlation between the estradiol level with E-cadherin and the correlation between the progesterone level with E-cadherin were not significantly different ( p value: 0.872 and p value: 0.836). The conclusion is that the level of E-Cadherin expression in the endometrium that were taken in themiddle secretion phase not affected by the dose regimen that given. In addition, the level of expression is not influenced by the increase of serum E2 and P4 levels.

scholarly journals Traditional Chinese Medicine, the Zishen Yutai Pill, Ameliorates Precocious Endometrial Maturation Induced by Controlled Ovarian Hyperstimulation and Improves Uterine Receptivity via Upregulation of HOXA10

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Qi Gao ◽  
Lu Han ◽  
Xiumei Li ◽  
Xia Cai
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Target Gene ◽  
Controlled Ovarian Hyperstimulation ◽  
Reproductive Technology ◽  
Ovarian Hyperstimulation ◽  
Uterine Receptivity ◽  
Rt Pcr ◽  
Implantation Rates ◽  
Important Marker

Controlled ovarian hyperstimulation (COH) is widely used in assisted reproductive technology (ART), but it often leads to precocious maturation of the endometrium such that it impairs embryonic implantation and limits pregnancy rates. Previous studies have shown the traditional Chinese medicine, the Zishen Yutai pill (ZYP), to be effective in treatment of threatened as well as recurrent miscarriages, and it can improve embryonic implantation rates in patients undergoing IVF treatment. In the present study, the ZYP has been found to ameliorate precocious endometrial maturation in a mouse model of different COH. Molecular evaluations, real-time PCR, relative RT-PCR, Western blotting, and immunohistochemistry have indicated that the ZYP increased the expression of HOXA10, an important marker of uterine receptivity. Elevation of HOXA10 led to further upregulation of its target gene, integrinβ3, and downregulation of EMX2, two additional markers of uterine receptivity. In this way, the ZYP may mitigate COH-induced precocious maturation of the endometrium and improve uterine receptivity by upregulating HOXA10.

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