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      An Individualized Recommendation for Controlled Ovary Stimulation Protocol in Women Who Received the GnRH Agonist Long-Acting Protocol or the GnRH Antagonist Protocol: A Retrospective Cohort Study

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          Abstract

          Background

          The GnRH agonist long-acting protocol and GnRH antagonist protocol are widely used in ovarian stimulation. Which protocol eliciting higher live birth rate for IVF/ICSI patients with different ages, different ovarian reserves and different body mass index (BMI) has not been studied. However, among these protocols, the one that elicits higher live birth in IVF/ICSI patients with different ages, ovarian reserves and body mass indexes (BMI) has not been identified.

          Methods

          This was a retrospective cohort study about 8579 women who underwent the first IVF-ET from January, 2018 to August, 2021. Propensity Score Matching (PSM) was used to improve the comparability between two protocols.

          Results

          After PSM, significant higher live birth rates were found in the GnRH agonist long-acting protocol compared to GnRH antagonist protocol (44.04% vs. 38.32%) (p<0.001). Stratified analysis showed that for those with AMH levels between 3 ng/ml and 6 ng/ml, with BMI ≥ 24 kg/m 2 and were aged ≥ 30 years old, and for those women with BMI < 24kg/m 2 and were aged ≥30 years whose AMH levels were ≤ 3ng/ml, the GnRH agonist long-acting protocol was more likely to elicit live births [OR (95%CI), 2.13(1.19,3.80)], [OR (95%CI), 1.41(1.05,1.91)]. However, among women with BMI ≥ 24kg/m 2 and were aged ≥30 years whose AMH levels were ≤ 3ng/ml, the GnRH agonist long-acting protocol had a lower possibility of eliciting live births [OR (95%CI), 0.54(0.32,0.90)]. Also, among women with AMH levels between 3 ng/ml and 6 ng/ml, with BMI ≥ 24 kg/m 2 and with age < 30 years and for those with AMH levels between 3 ng/ml and 6 ng/ml, regardless of age, and with BMI<24kg/m2,, the possibility of live births was similar between the two protocols [OR (95%CI), 1.06(0.60,1.89)], [OR (95%CI), 1.38(0.97,1.97)], [OR (95%CI), 0.99(0.72,1.37)]. Among the women with AMH levels ≤ 3 ng/ml and with were aged < 30years, regardless of BMI, the possibility of live birth was similar between the two protocols [OR (95%CI), 1.02(0.68,1.54)], [OR (95%CI), 1.43(0.68,2.98)]. Moreover, among women with AMH levels ≥ 6ng/ml, the possibility of live birth was similar between the two protocols [OR (95%CI),1.42(0.75,2.69)], [OR (95%CI),1.02(0.19,5.35)], [OR (95%CI), 1.68(0.81,3.51)], [OR (95%CI), 0.51(0.10,2.55)].

          Conclusions

          The suitability of the GnRH agonist long-acting protocol or GnRH antagonist protocol to infertility patients is dependent on specific biological characteristics of the patients.

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          Most cited references43

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          The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting.

          Many variations in oocyte and embryo grading make inter-laboratory comparisons extremely difficult. This paper reports the proceedings of an international consensus meeting on oocyte and embryo morphology assessment. Background presentations about current practice were given. The expert panel developed a set of consensus points to define the minimum criteria for oocyte and embryo morphology assessment. It is expected that the definition of common terminology and standardization of laboratory practice related to embryo morphology assessment will result in more effective comparisons of treatment outcomes. This document is intended to be referenced as a global consensus to allow standardized reporting of the minimum data set required for the accurate description of embryo development.
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            Ovarian reserve testing: a user's guide.

            Ovarian reserve is a complex clinical phenomenon influenced by age, genetics, and environmental variables. Although it is challenging to predict the rate of an individual's ovarian reserve decline, clinicians are often asked for advice about fertility potential and/or recommendations regarding the pursuit of fertility treatment options. The purpose of this review is to summarize the state-of-the-art of ovarian reserve testing, providing a guide for the obstetrician/gynecologist generalist and reproductive endocrinologist. The ideal ovarian reserve test should be convenient, be reproducible, display little if any intracycle and intercycle variability, and demonstrate high specificity to minimize the risk of wrongly diagnosing women as having diminished ovarian reserve and accurately identify those at greatest risk of developing ovarian hyperstimulation prior to fertility treatment. Evaluation of ovarian reserve can help to identify patients who will have poor response or hyperresponse to ovarian stimulation for assisted reproductive technology. Ovarian reserve testing should allow individualization of treatment protocols to achieve optimal response while minimizing safety risks. Ovarian reserve testing may inform patients regarding their reproductive lifespan and menopausal timing as well as aid in the counselling and selection of treatment for female cancer patients of reproductive age who receive gonadotoxic therapy. In addition, it may aid in establishing the diagnosis of polycystic ovary syndrome and provide insight into its severity. While there is currently no perfect ovarian reserve test, both antral follicular count and antimüllerian hormone have good predictive value and are superior to day-3 follicle-stimulating hormone. The convenience of untimed sampling, age-specific values, availability of an automated platform, and potential standardization of antimüllerian hormone assay make this test the preferred biomarker for the evaluation of ovarian reserve in women.
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              Female obesity is negatively associated with live birth rate following IVF: a systematic review and meta-analysis

              A worldwide increase in the prevalence of obesity has been observed in the past three decades, particularly in women of reproductive age. Female obesity has been clearly associated with impaired spontaneous fertility, as well as adverse pregnancy outcomes. Increasing evidence in the literature shows that obesity also contributes to adverse clinical outcomes following in vitro fertilization (IVF) procedures. However, the heterogeneity of the available studies in terms of populations, group definition and outcomes prevents drawing firm conclusions. A previous meta-analysis published in 2011 identified a marginal but significant negative effect of increased female body mass index (BMI) on IVF results, but numerous studies have been published since then, including large cohort studies from national registries, highlighting the need for an updated review and meta-analysis. Our systematic review and meta-analysis of the available literature aims to evaluate the association of female obesity with the probability of live birth following IVF. Subgroup analyses according to ovulatory status, oocyte origin, fresh or frozen-embryo transfer and cycle rank were performed. A systematic review was performed using the following key words: (‘obesity’, ‘body mass index’, ‘live birth’, ‘IVF’, ‘ICSI’). Searches were conducted in MEDLINE, EMBASE, Cochrane Library, Eudract and clinicaltrial.gov from 01 January 2007 to 30 November 2017. Study selection was based on title and abstract. Full texts of potentially relevant articles were retrieved and assessed for inclusion by two reviewers. Subsequently, quality was assessed using the Newcastle-Ottawa Quality Assessment Scales for patient selection, comparability and assessment of outcomes. Two independent reviewers carried out study selection and data extraction according to Cochrane methods. Random-effect meta-analysis was performed using Review Manager software on all data (overall analysis), followed by subgroup analyses. A total of 21 studies were included in the meta-analysis. A decreased probability of live birth following IVF was observed in obese (BMI ≥ 30 kg/m2) women when compared with normal weight (BMI 18.5–24.9 kg/m2) women: risk ratio (RR) (95% CI) 0.85 (0.82–0.87). Subgroups analyses demonstrated that prognosis was poorer when obesity was associated with polycystic ovary syndrome, while the oocyte origin (donor or non-donor) did not modify the overall interpretation. Our meta-analysis clearly demonstrates that female obesity negatively and significantly impacts live birth rates following IVF. Whether weight loss can reverse this deleterious effect through lifestyle modifications or bariatric surgery should be further evaluated.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                22 July 2022
                2022
                : 13
                : 899000
                Affiliations
                [1] 1 Department of Obstetrics and Gynecology, Women and Children’s Hospital of Chongqing Medical University , Chongqing, China
                [2] 2 Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, School of Public Health , Chongqing, China
                [3] 3 Reproductive Medical Center, Chengdu Xinan Gynecological Hospital , Chengdu, China
                [4] 4 Department of Epidemiology, School of Public Health and Management, Research Center for Medicine and Social Development, Innovation Center for Social Risk Governance in Health, Chongqing Medical University , Chongqing, China
                [5] 5 The Department of Reproductive Medicine, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China
                [6] 6 Department of Gynecology, Chongqing Hospital of Traditional Chinese Medicine , Chongqing, China
                [7] 7 Infertility and Infertility Center, Chengdu Jinjiang Hospital for Women‘s and Children’s Health , Chengdu, China
                [8] 8 Reproductive Medical Center, Southwest Hospital, Army Medical University, Third Military Medical University , Chongqing, China
                Author notes

                Edited by: Yimin Zhu, Zhejiang University, China

                Reviewed by: Yong-Jiang Zhou, Hainan Medical University, China; Zi Yang, Peking University Third Hospital, China; Wei Wang, Second Hospital of Hebei Medical University, China

                *Correspondence: Wei He, anyhewei@ 123456163.com ; Qi Wan, wanqi123@ 123456163.com ; Yu-Bin Ding, dingyb@ 123456cqmu.edu.cn

                †These authors share first authorship

                This article was submitted to Reproduction, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2022.899000
                9355571
                35937797
                e2a0b22d-64f8-41dd-aba1-18bdbb71ae85
                Copyright © 2022 Chen, Meng, Zhong, Tang, Li, Feng, Adu-Gyamfi, Jia, Lv, Geng, Zhu, He, Wan and Ding

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 18 March 2022
                : 17 June 2022
                Page count
                Figures: 1, Tables: 4, Equations: 0, References: 43, Pages: 10, Words: 5835
                Categories
                Endocrinology
                Original Research

                Endocrinology & Diabetes
                gnrh agonist long-acting protocol,gnrh antagonist protocol,live birth rate,ovarian reserve,body mass index

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