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      Increasing dominant follicular proportion negatively associated with good clinical outcomes in normal ovarian responders using the depot GnRH agonist protocol: a large-sample retrospective analysis

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          Abstract

          Background

          Currently, there is no universal criteria for the trigger time of controlled ovarian hyperstimulation (COH), especially with the emerging depot GnRH agonist protocol. It is challenging to explore an indicator that is representative of target follicle cohort development as an alternative to the conventional approach of determining the trigger time based on a few leading follicles.

          Methods

          This was a large-sample retrospective analysis. Between January 2016 and January 2020, 1,925 young normal ovarian responders who underwent their first in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycle using the depot GnRH agonist protocol were included. They were divided into three groups based on the dominant follicular proportion (DFP, defined as the ratio of ≥ 18 mm dominant follicles/ ≥ 14 mm large follicles on the human chorionic gonadotropin (HCG) day; Group A: < 30%; Group B: 30%−60%; and Group C: ≥ 60%). The binary logistic regression and multivariate linear regression were used to assess whether the DFP was associated with clinical pregnancy, the number of frozen blastocysts, the blastocyst formation rate, and the low number of frozen blastocysts.

          Results

          The logistic regression analysis showed that compared with Group A, the odds ratio (OR) for clinical pregnancy was 1.345 in Group B ( P = 0.023), and there was no statistical difference between Group C and Group A ( P = 0.216). The multivariate linear regression analysis showed that DFP was negatively associated with the number of frozen blastocysts (β ± SE: Group B vs. Group A = − 0.319 ± 0.115, P = 0.006; Group C vs. Group A = − 0.432 ± 0.154, P = 0.005) as well as the blastocyst formation rate (β ± SE: Group B vs. Group A = − 0.035 ± 0.016, P = 0.031; Group C vs. Group A = − 0.039 ± 0.021, P = 0.067). Furthermore, the OR for the low number of frozen blastocysts was 1.312 in Group B ( P = 0.039) and 1.417 in Group C ( P = 0.041) compared to Group A.

          Conclusions

          For young normal ovarian responders using the depot GnRH agonist protocol, increasing DFP might reduce the developmental potential of oocytes and reduce the number of available blastocysts, and this might result in a lower cumulative pregnancy rate. However, further confirmation using strict prospective randomised controlled studies is required.

          Supplementary information

          The online version contains supplementary material available at 10.1186/s13048-022-00973-7.

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          Most cited references23

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          Progesterone elevation and probability of pregnancy after IVF: a systematic review and meta-analysis of over 60 000 cycles.

          BACKGROUND The aim of this meta-analysis was to evaluate the association of progesterone elevation (PE) on the day of hCG administration with the probability of pregnancy in fresh, frozen-thawed and donor/recipient IVF cycles. METHODS A literature search in MEDLINE, SCOPUS, COCHRANE CENTRAL and ISI Web of Science was performed aiming to identify studies comparing the probability of pregnancy in patients with or without PE after ovarian stimulation with gonadotrophins and GnRH analogues. Standard meta-analytic methodology was used for the synthesis of results and meta-regression for exploration of heterogeneity. RESULTS Sixty-three eligible studies were identified evaluating 55 199 fresh IVF cycles, nine studies evaluating 7229 frozen-thawed cycles and eight studies evaluating 1330 donor/recipient cycles. In fresh IVF cycles, a decreased probability of pregnancy achievement was present in women with PE (when PE was defined using a threshold ≥ 0.8 ng/ml) when compared with those without PE. The pooled effect sizes were 0.8-1.1 ng/ml: odds ratio (OR) = 0.79; 1.2-1.4 ng/ml: OR = 0.67; 1.5-1.75 ng/ml: OR = 0.64; 1.9-3.0 ng/ml: OR: 0.68 (P < 0.05 in all cases). No adverse effect of PE on achieving pregnancy was observed in the frozen-thawed and the donor/recipient cycles. CONCLUSIONS Based on the analysis of more than 60 000 cycles, it can be supported that PE on the day of hCG administration is associated with a decreased probability of pregnancy achievement in fresh IVF cycles in women undergoing ovarian stimulation using GnRH analogues and gonadotrophins. On the other hand, an adverse effect of PE does not seem to be present in frozen-thawed and donor/recipient cycles.
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            The relationship between pregnancy outcome and smooth endoplasmic reticulum clusters in MII human oocytes.

            During ICSI, we occasionally observe pronucleus sized translucent vacuoles. We investigated why these vacuoles occur and determined the effect on pregnancy outcome. Translucent vacuole-positive oocytes and the corresponding cohort were examined by transmission electron microscopy (TEM) and histochemical staining with DiI and ER-Tracker. Stimulation methods, hormonal levels, patients' condition and grade of transferred embryos were compared between vacuole-positive and vacuole-negative cycles. By TEM, we confirmed that the vacuoles were tubular-type smooth endoplasmic reticulum clusters (sERCs). Numerous small sERCs were also observed in the oocytes from the same cohort. Veeck's grades of transferred embryos were higher in sERC-positive cycles and fertilization rate was similar to those of sERC-negative cycles. However, in sERC-positive cycles, significantly lower pregnancy and higher biochemical pregnancy rates were shown. Serum estradiol levels on the day of hCG administration were significantly higher in sERC-positive cycles. The presence of sERCs is associated with lower chances of successful pregnancy, even in sERC-negative oocytes from the same cohort that are transferred along with the sERC-positive oocytes. High estradiol levels could be one of the causes of sERC formation.
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              A quantitative assessment of follicle size on oocyte developmental competence.

              To quantitatively assess the impact of follicle size on oocyte maturation, fertilization, and embryo quality. Prospective study. Academic medical center. Couples undergoing ovarian stimulation and in vitro fertilization (IVF). A total of 235 cycles were monitored prospectively, and 2934 oocytes were collected from five groups of follicle size. Repeated measures multivariate analyses were used to compare the smaller follicle sizes with the lead follicle. Oocyte maturation, fertilization, and embryo quality. Compared with the lead follicular group (>18 mm), the odds of a mature oocyte from a 16 to 18 mm size follicle were 37% and declined progressively with each size. The odds of fertilization of oocytes from follicles 16 to 18 mm in size was 28% less than the lead group and decreased with each size. The rate of polyspermy with conventional insemination was increased for the smaller follicular groups (adjusted odds ratio = 2.37). Follicle size did not predict embryo cell number, but embryos from smaller follicles had a statistically significantly higher fragmentation compared with the lead group. The lead follicular group was most likely to have a mature oocyte that was capable of fertilization and best suited for development into a high-quality embryo. The smaller follicles were capable of producing metaphase II oocytes that could fertilize, but at rates approaching only 60% that of the lead follicular group.
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                Author and article information

                Contributors
                kunqian@tjh.tjmu.edu.cn
                Journal
                J Ovarian Res
                J Ovarian Res
                Journal of Ovarian Research
                BioMed Central (London )
                1757-2215
                13 April 2022
                13 April 2022
                2022
                : 15
                : 44
                Affiliations
                GRID grid.33199.31, ISNI 0000 0004 0368 7223, Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, , Huazhong University of Science and Technology, ; Wuhan, China
                Author information
                http://orcid.org/0000-0001-8063-457X
                Article
                973
                10.1186/s13048-022-00973-7
                9006398
                35418089
                d238bd89-dadc-48dc-a45a-b1e877706826
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 7 September 2021
                : 26 March 2022
                Funding
                Funded by: National Key Research and Development Project
                Award ID: 2018YFA0108401
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81571464
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2022

                Obstetrics & Gynecology
                ivf/icsi,controlled ovarian hyperstimulation,hcg trigger time,depot gnrh agonist protocol,dominant follicular proportion,clinical outcomes

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