GnRH agonist versus GnRH antagonist in IVF/ICSI cycles with recombinant LH supplementation: DNA fragmentation and apoptosis in granulosa cells

Lavorato, Heloisa Lopes; Oliveira, J.B.A.; Petersen, Claudia G.; Vagnini, L.D.; Mauri, A.L.; Cavagna, M.; Baruffi, R.L.R.; Franco, J.G.

doi:10.1016/j.ejogrb.2012.07.014

Cited by 15 publications

(11 citation statements)

References 20 publications

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“…Conversely, FF cfDNA content did not differ according to the type of COS protocols (agonist versus antagonist). In agreement, similar apoptosis levels were detected in granulosa cells exposed to agonist or antagonist treatments [ 43 ].…”

Section: Discussionsupporting

confidence: 79%

Cell-free DNA in Human Follicular Microenvironment: New Prognostic Biomarker to Predict in vitro Fertilization Outcomes

et al. 2015

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Cell-free DNA (cfDNA) fragments, detected in blood and in other biological fluids, are released from apoptotic and/or necrotic cells. CfDNA is currently used as biomarker for the detection of many diseases such as some cancers and gynecological and obstetrics disorders. In this study, we investigated if cfDNA levels in follicular fluid (FF) samples from in vitro fertilization (IVF) patients, could be related to their ovarian reserve status, controlled ovarian stimulation (COS) protocols and IVF outcomes. Therefore, 117 FF samples were collected from women (n = 117) undergoing IVF/Intra-cytoplasmic sperm injection (ICSI) procedure and cfDNA concentration was quantified by ALU-quantitative PCR. We found that cfDNA level was significantly higher in FF samples from patients with ovarian reserve disorders (low functional ovarian reserve or polycystic ovary syndrome) than from patients with normal ovarian reserve (2.7 ± 2.7 ng/μl versus 1.7 ± 2.3 ng/μl, respectively, p = 0.03). Likewise, FF cfDNA levels were significant more elevated in women who received long ovarian stimulation (> 10 days) or high total dose of gonadotropins (≥ 3000 IU/l) than in women who received short stimulation duration (7–10 days) or total dose of gonadotropins < 3000 IU/l (2.4 ± 2.8 ng/μl versus 1.5 ± 1.9 ng/μl, p = 0.008; 2.2 ± 2.3 ng/μl versus 1.5 ± 2.1 ng/μl, p = 0.01, respectively). Finally, FF cfDNA level was an independent and significant predictive factor for pregnancy outcome (adjusted odds ratio = 0.69 [0.5; 0.96], p = 0.03). In multivariate analysis, the Receiving Operator Curve (ROC) analysis showed that the performance of FF cfDNA in predicting clinical pregnancy reached 0.73 [0.66–0.87] with 88% specificity and 60% sensitivity. CfDNA might constitute a promising biomarker of follicular micro-environment quality which could be used to predict IVF prognosis and to enhance female infertility management.

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Section: Discussionsupporting

confidence: 79%

Cell-free DNA in Human Follicular Microenvironment: New Prognostic Biomarker to Predict in vitro Fertilization Outcomes

et al. 2015

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“…GnRH-a protocol [23-27]: The pituitary downregulation began during the luteal phase of the previous menstrual cycle with the GnRH-a leuprolide acetate (leuprolide acetate; Lupron®; Abbott, Brazil) at a dose of 1 mg/day for 14 days. The ovaries were then stimulated with a fixed dose of 150–225 IU of recombinant FSH (rFSH; Gonal F®; Serono, Brazil) and 75 IU/day of recombinant luteinising hormone (rLH; Luveris®; Serono, Brazil) for a period of 7 days.…”

Section: Methodsmentioning

confidence: 99%

“…GnRH-ant protocol [23-27]: On day 3 of the cycle, ovarian stimulation was induced with a fixed dose of 150–225 IU of rFSH and 75 IU/day of rLH for a period of 5 days. The decision on the starting dose of FSH was based on patient’s age.…”

Section: Methodsmentioning

confidence: 99%

A new ovarian response prediction index (ORPI): implications for individualised controlled ovarian stimulation

Oliveira

Baruffi

Petersen

et al. 2012

Reprod Biol Endocrinol

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BackgroundThe objective was to present a new ovarian response prediction index (ORPI), which was based on anti-Müllerian hormone (AMH) levels, antral follicle count (AFC) and age, and to verify whether it could be a reliable predictor of the ovarian stimulation response.MethodsA total of 101 patients enrolled in the ICSI programme were included. The ORPI values were calculated by multiplying the AMH level (ng/ml) by the number of antral follicles (2–9 mm), and the result was divided by the age (years) of the patient (ORPI=(AMH x AFC)/Patient age).ResultsThe regression analysis demonstrated significant (P<0.0001) positive correlations between the ORPI and the total number of oocytes and of MII oocytes collected. The logistic regression revealed that the ORPI values were significantly associated with the likelihood of pregnancy (odds ratio (OR): 1.86; P=0.006) and collecting greater than or equal to 4 oocytes (OR: 49.25; P<0.0001), greater than or equal to 4 MII oocytes (OR: 6.26; P<0.0001) and greater than or equal to 15 oocytes (OR: 6.10; P<0.0001). Regarding the probability of collecting greater than or equal to 4 oocytes according to the ORPI value, the ROC curve showed an area under the curve (AUC) of 0.91 and an efficacy of 88% at a cut-off of 0.2. In relation to the probability of collecting greater than or equal to 4 MII oocytes according to the ORPI value, the ROC curve had an AUC of 0.84 and an efficacy of 81% at a cut-off of 0.3. The ROC curve for the probability of collecting greater than or equal to 15 oocytes resulted in an AUC of 0.89 and an efficacy of 82% at a cut-off of 0.9. Finally, regarding the probability of pregnancy occurrence according to the ORPI value, the ROC curve showed an AUC of 0.74 and an efficacy of 62% at a cut-off of 0.3.ConclusionsThe ORPI exhibited an excellent ability to predict a low ovarian response and a good ability to predict a collection of greater than or equal to 4 MII oocytes, an excessive ovarian response and the occurrence of pregnancy in infertile women. The ORPI might be used to improve the cost-benefit ratio of ovarian stimulation regimens by guiding the selection of medications and by modulating the doses and regimens according to the actual needs of the patients.

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“…32 The GnRH agonist, on the other hand, is administered for a longer duration throughout the cycle, competitively blocking the ovarian FSH receptors and suppressing the ovarian response to the gonadotropins. 33 However, most of the studies have not found any difference in response to either protocols. 8,22,30,34 Several studies found that the total duration of stimulation and total dosage of gonadotropins in the antagonist group was much less than that in long agonist group.…”

Section: Discussionmentioning

confidence: 96%

Is there a perfect protocol for patients with low ovarian reserve: a retrospective study comparing antagonist or agonist protocol in patients with low ovarian reserve

Rai¹,

Khandavalli²

2020

Int J Reprod Contracept Obstet Gynecol

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Background: The high prevalence of infertility has made it a major healthcare problem in the present era. A majority of patients presenting with infertility have poor ovarian reserve (POR). Patients with POR are challenging to treat due to reduced treatment success and high cycle cancellation rate as there is no uniform definition and treatment protocol for these patients. The present retrospective study was performed to compare the pregnancy outcome between a long agonist protocol and flexible antagonist protocol in patients with POR. Patients with AMH ≤1.5 ng/mL and AFC ≤4 was included in the study. Controlled ovarian hyperstimulation is the basis of any in vitro fertilisation (IVF) procedure. There is no universally accepted ideal stimulation protocol for patients with POR, and it remains a challenge.Methods: This was a retrospective study covering the period from May 2019 to March 2020. Ninety-nine patients with low ovarian reserve (AMH ≤1.5 ng/mL and AFC ≤4) were included in the study. The patients underwent GnRH agonist/GnRH antagonist stimulation protocol using recombinant FSH. Demographic characteristics like age, BMI, duration of infertility was comparable. Total days of stimulation, total Gonadotropin dose used and clinical pregnancy rate in both the protocols was analyzed. Difference between the two groups was considered statistically significant at p-value <0.05.Results: Fifty-three patients underwent antagonist stimulation protocol and forty-six long agonist protocol. The clinical pregnancy rate was 37.7% (20/53) and 32.6% (15/46) in antagonist and agonist protocol respectively (p-value=0.5983). Pregnancy rate was higher in the antagonist group but the difference was not statistically significant.Conclusions: Antagonist protocol could marginally increase pregnancy rate in patients with low ovarian reserve. However, patients with poor ovarian reserve require a tailor-made protocol.

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GnRH agonist versus GnRH antagonist in IVF/ICSI cycles with recombinant LH supplementation: DNA fragmentation and apoptosis in granulosa cells

Abstract: The results suggest that therapy with either an agonist or antagonist of GnRH is associated with comparable levels of DNA fragmentation and apoptosis in granulosa cells in ICSI cycles supplemented with rLH.

Cited by 15 publications

References 20 publications

Cell-free DNA in Human Follicular Microenvironment: New Prognostic Biomarker to Predict in vitro Fertilization Outcomes

Cell-free DNA in Human Follicular Microenvironment: New Prognostic Biomarker to Predict in vitro Fertilization Outcomes

A new ovarian response prediction index (ORPI): implications for individualised controlled ovarian stimulation

Is there a perfect protocol for patients with low ovarian reserve: a retrospective study comparing antagonist or agonist protocol in patients with low ovarian reserve

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