scholarly journals Down-regulation of S100P induces apoptosis in endometrial epithelial cell during GnRH antagonist protocol

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dan Zhang ◽  
Mi Han ◽  
Mingjuan Zhou ◽  
Mengyu Liu ◽  
Yan Li ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Gnrh Agonist ◽  
Cell Apoptosis ◽  
Gnrh Antagonist ◽  
Endometrial Receptivity ◽  
Endometrial Epithelial Cell ◽  
Ishikawa Cells ◽  
Gnrh Antagonist Protocol ◽  
Antagonist Protocol

Abstract Background The gonadotropin-releasing hormone (GnRH) antagonist protocol for in vitro fertilization (IVF) often leads to lower pregnancy rates compared to the GnRH agonist protocol. Decreased endometrial receptivity is one reason for the lower success rate, but the mechanisms underlying this phenomenon remain poorly understood. The S100 calcium protein P (S100P) is a biomarker for endometrial receptivity. Both GnRH antagonist and S100P are involved in mediating cell apoptosis. However, the involvement of S100P in reduced endometrial receptivity during the GnRH antagonist protocol remains unclear. Methods Endometrial tissue was collected at the time of implantation window from patients undergoing the GnRH agonist (GnRH-a) or GnRH antagonist (GnRH-ant) protocols, as well as from patients on their natural cycles. Endometrial cell apoptosis and expression levels of S100P, HOXA10, Bax, and Bcl-2 were assessed. Ishikawa cells were cultured to evaluate the effects that GnRH antagonist exposure or S100P up- or down- regulation had on apoptosis. Results Endometrial tissue from patients in the GnRH-ant group showed elevated apoptosis and decreased expression of the anti-apoptotic marker Bcl-2. In addition, endometrial expression of S100P was significantly reduced in the GnRH-ant group, and expression of HOXA10 was lower. Immunofluorescence colocalization analysis revealed that S100P was mainly distributed in the epithelium. In vitro experiments showed that knockdown of S100P in Ishikawa cells induced apoptosis, decreased expression of Bcl-2, while overexpression of S100P caused the opposite effects and decreased expression of Bax. Furthermore, endometrial epithelial cells exposed to GnRH antagonist expressed lower levels of S100P and Bcl-2, increased expression of Bax, and had higher rates of apoptosis. The increased apoptosis induced by GnRH antagonist treatment could be rescued by overexpression of S100P. Conclusions We found that GnRH antagonist treatment induced endometrial epithelial cell apoptosis by down-regulating S100P, which was detrimental to endometrial receptivity. These results further define a mechanistic role for S100P in contributing to endometrial apoptosis during GnRH antagonist treatment, and suggest that S100P is a potential clinical target to improve the success of IVF using the GnRH antagonist protocol.

scholarly journals A Flexible Multidose GnRH Antagonist versus a Microdose Flare-Up GnRH Agonist Combined with a Flexible Multidose GnRH Antagonist Protocol in Poor Responders to IVF

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Gayem İnayet Turgay Çelik ◽  
Havva Kömür Sütçü ◽  
Yaşam Kemal Akpak ◽  
Münire Erman Akar
Keyword(s):  
Gnrh Agonist ◽  
Gnrh Antagonist ◽  
Poor Responders ◽  
Vitro Fertilization ◽  
Significant Difference ◽  
Gnrh Antagonist Protocol ◽  
Group 2 ◽  
Antagonist Protocol ◽  
Group 1

Objective. To compare the effectiveness of a flexible multidose gonadotropin-releasing hormone (GnRH) antagonist against the effectiveness of a microdose flare-up GnRH agonist combined with a flexible multidose GnRH antagonist protocol in poor responders to in vitro fertilization (IVF).Study Design. A retrospective study in Akdeniz University, Faculty of Medicine, Department of Obstetrics and Gynecology, IVF Center, for 131 poor responders in the intracytoplasmic sperm injection-embryo transfer (ICSI-ET) program between January 2006 and November 2012. The groups were compared to the patients’ characteristics, controlled ovarian stimulation (COH) results, and laboratory results.Results. Combination protocol was applied to 46 patients (group 1), and a single protocol was applied to 85 patients (group 2). In group 1, the duration of the treatment was longer and the dose of FSH was higher. The cycle cancellation rate was significantly higher in group 2 (26.1% versus 38.8%). A significant difference was not observed with respect to the number and quality of oocytes and embryos or to the number of embryos transferred. There were no statistically significant differences in the hCG positivity (9.5% versus 9.4%) or the clinical pregnancy rates (7.1% versus 10.6%).Conclusion. The combination protocol does not provide additional efficacy.

scholarly journals Microdose Flare-up Gonadotropin-releasing Hormone (GnRH) Agonist Protocol and GnRH Antagonist Protocol: Effects on In-vitro Fertilization in Patients with Poor-responder Diagnosis According to Bologna Criteria

2021 ◽  
Vol 3 (2) ◽  
pp. 1-5
Author(s):  
Gökşen Görgülü ◽  
Merve Çakır Köle ◽  
Oya Aldemir ◽  
Emre Köle ◽  
Serdar Dilbaz
Keyword(s):  
In Vitro Fertilization ◽  
Pregnancy Rate ◽  
Gnrh Agonist ◽  
Gnrh Antagonist ◽  
Gonadotropin Releasing Hormone ◽  
Clinical Pregnancy ◽  
Vitro Fertilization ◽  
Gnrh Antagonist Protocol ◽  
Antagonist Protocol

Objective: The aim of the study was to evaluate microdose flare-up Gonadotropin-Releasing Hormone (GnRH) agonist protocol and GnRH antagonist protocol with respect to their effects on in-vitro fertilization (IVF) results in patients with poor ovarian response according to the Bologna Criteria. Material Methods: This was a retrospective cohort study conducted in the Assisted Reproduction clinic of University of Health Sciences, Etlik Zübeyde Hanım Gynaecology Training and Research Hospital. A total of 645 patients who had been diagnosed as poor responders in our clinic, between 2007 and 2018, and received treatment with either microdose flare-up GnRH agonist protocol (n=250, 38.8%) or GnRH antagonist protocol (n=395, 61.2%), were included in the study. Results: The mean age of the study group was 34.5±5.5 years. Comparisons showed that IVF cycle cancellation frequency (p<0.01), third day estradiol level (p=0.04) and third day follicle stimulating hormone level (p<0.01) were significantly greater in patients who underwent the microdose flare-up protocol. In the GnRH antagonist group, the number of surviving children (p=0.01), antral follicle count (p<0.01), follicle count on day of human chorionic gonadotropin (hCG) administration (p<0.01), endometrial thickness on hCG day (p<0.01), number of oocytes collected (p<0.01), mature oocyte count (p<0.01), embryo transfer number (p<0.01) were higher compared to the microdose flare-up protocol group. The two groups were similar in terms of clinical pregnancy rate. Conclusions: In terms of clinical pregnancy rate, the IVF results of microdose flare-up and GnRH antagonist protocols are similar. Further studies are needed to reach more comprehensive results on the subject.

scholarly journals A Novel Nomogram for Individualized Gonadotropin Starting Dose in GnRH Antagonist Protocol

2021 ◽  
Vol 12 ◽  
Author(s):  
Yubin Li ◽  
Yuwei Duan ◽  
Xi Yuan ◽  
Bing Cai ◽  
Yanwen Xu ◽  
...  
Keyword(s):  
Regression Model ◽  
Ovarian Stimulation ◽  
Multivariate Regression ◽  
Gnrh Antagonist ◽  
Bootstrap Resampling ◽  
Multivariate Regression Model ◽  
Starting Dose ◽  
Gnrh Antagonist Protocol ◽  
Antagonist Protocol

Controlled ovarian stimulation (COS) is one of the most vital parts of in vitro fertilization-embryo transfer (IVF-ET). At present, no matter what kinds of COS protocols are used, clinicians have to face the challenge of selection of gonadotropin starting dose. Although several nomograms have been developed to calculate the appropriate gonadotropin starting dose in gonadotropin releasing hormone (GnRH) agonist protocol, no nomogram was suitable for GnRH antagonist protocol. This study aimed to develop a predictive nomogram for individualized gonadotropin starting dose in GnRH antagonist protocol. Single-center prospective cohort study was conducted, with 198 women aged 20-45 years underwent IVF/intracytoplasmic sperm injection (ICSI)-ET cycles. Blood samples were collected on the second day of the menstrual cycle. All women received ovarian stimulation using GnRH antagonist protocol. Univariate and multivariate analysis were performed to identify predictive factors of ovarian sensitivity (OS). A nomogram for gonadotropin starting dose was developed based on the multivariate regression model. Validation was performed using concordance statistics and bootstrap resampling. A multivariate regression model based on serum anti-Müllerian hormone (AMH) level, antral follicle count (AFC), and body mass index (BMI) was developed and accounted for 59% of the variability of OS. An easy-to-use predictive nomogram for gonadotropin starting dose was established with excellent accuracy. The concordance index (C-index) of the nomogram was 0.833 (95% CI, 0.829-0.837). Internal validation using bootstrap resampling further showed the good performance of the nomogram. In conclusion, gonadotropin starting dose in antagonist protocol can be predicted precisely by a novel nomogram.

P–464 What is the optimal ovarian stimulation (OS) protocol for women who undergo planned oocyte cryopreservation (POC)?

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
S Delattre ◽  
L Strypstein ◽  
P Drakopoulos ◽  
S Mackens ◽  
S D Rijdt ◽  
...  
Keyword(s):  
Gnrh Agonist ◽  
Ovarian Reserve ◽  
Multivariate Regression ◽  
Gnrh Antagonist ◽  
Oocyte Cryopreservation ◽  
P Value ◽  
Oocyte Yield ◽  
First Choice ◽  
Gnrh Antagonist Protocol ◽  
Antagonist Protocol

Abstract Study question When repeated cycles of OS for planned oocyte cryopreservation using a standard GnRH antagonist protocol are required, can OS protocol modifications improve oocyte yield? Summary answer Compared to repeating a standard GnRH antagonist protocol, switching to a long GnRH agonist protocol for POC results in a higher number of cryopreserved oocytes. What is known already The total number of cryopreserved oocytes is a key parameter of POC programs because of its association with livebirth. A substantial proportion of women embarking on POC will undergo repeated cycles of OS to reach their desired target number of vitrified oocytes. According to recent guidelines, the GnRH antagonist protocol with GnRH agonist triggering is considered the first choice protocol for POC, because of its safety profile and convenience. However, in women with normal ovarian reserve, the long GnRH agonist protocol results in a higher number of oocytes retrieved. Evidence regarding the optimal protocol for POC is limited. Study design, size, duration This is a single-centre, retrospective cohort study including 283 women who had a first cycle for POC using a standard GnRH antagonist protocol and who requested a second OS cycle to increase their total number of vitrified oocytes for later use. The choice of protocol for the second cycle was left at the discretion of the reproductive medicine specialist. All OS cycles took place between January 2009 and December 2019 in a tertiary referral hospital. Participants/materials, setting, methods After ovarian reserve testing, the first cycle OS was performed using rFSH or HPhMG in a GnRH antagonist protocol. For the second cycle, a GnRH antagonist protocol with or without antagonist pretreatment, or a long GnRH agonist protocol was prescribed. The primary outcome was the number of mature oocytes (MII) vitrified per cycle. Cycle characteristics were compared. Data were assessed by generalized estimating equation (GEE) regression analysis adjusting for covariates. Main results and the role of chance In total, 226 (79.9%) women had a GnRH antagonist protocol and 57 (20.1%) had a long GnRH agonist protocol in their second OS cycle for POC. Overall, mean age was 36.6±2.4 years. The median (CI) number of mature oocytes vitrified after the second OS cycle was significantly higher than that after the first cycle [8 (5–11) vs. 7 (4–10), p &lt; 0.001]. According to GEE multivariate regression, adjusting for relevant confounders, switching from a GnRH antagonist protocol in the first cycle to a long GnRH agonist protocol in the second cycle was the only significant predictor of the number of vitrified oocytes after the subsequent cycle (coefficient 1.59, CI 0.29–2.89, p-value = 0.017). Age, AFC, initial dose and type of gonadotropins did not predict the number of vitrified oocytes. None of the women developed moderate or severe OHSS. Similarly, of 174 women who underwent their first OS cycle with a standard GnRH antagonist protocol, 133 women (76.4%) had the same protocol for their second cycle and 41 women (23.6%) an additional three-day course of GnRH antagonist pretreatment. According to GEE multivariate regression, this protocol modification did not result in more mature oocytes available for vitrification (coefficient –0.25, CI –1.86–1.36, p-value = 0.76). Limitations, reasons for caution These data should be interpreted with caution because of the retrospective design and limited sample. Although more oocytes were obtained with a long GnRH agonist protocol we have no data on livebirth in women returning to use their oocytes to support the choice for a specific OS protocol for POC. Wider implications of the findings: Although oocyte yield in the context of POC is an important parameter that may be modulated by the choice of OS protocol, the ultimate outcome measure of a successful POC program is livebirth after oocyte vitrification. Future research of oocyte parameters reflecting oocyte quality is paramount. Trial registration number Not applicable

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