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      Short versus Long Gonadotropin-Releasing Hormone Analogue Suppression Protocols in IVF/ICSI Cycles in Patients of Various Age Ranges

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          Abstract

          Objective

          To compare the two GnRH-a protocols (long GnRH-a protocol and short GnRH-a protocol) for ovarian stimulation in IVF/ICSI cycles in patients of various age ranges.

          Methods

          A total of 5662 IVF-ET/ICSI cycles from 2010 to 2013 were retrospectively identified. The cycles were divided into two groups: a long protocol group and short protocol group. In each group, the patients were divided into four age ranges: <31 years, 31 to 35 years, 36 to 40 years, and >40 years. The duration of stimulation, total dose of Gn, implantation rate and pregnancy rate were compared.

          Results

          The total dose of Gn was significantly higher, and the duration of stimulation was significantly longer, in the long protocol group than in the short protocol group for all age ranges ( P<0.05). If the patients were of the same age range, the number of oocytes retrieved, MII oocytes, and high-quality embryos in the long protocol group were all significantly greater than those in the short protocol group ( P<0.05). In the long protocol group, the clinical pregnancy rates of the four age ranges were 52.76%, 44.33%, 36.15% and 13.33%, respectively, which were significantly higher than those in the short protocol group (33.33%, 24.58%, 22.49% and 8.72%, respectively; P<0.05). The same trend was also found in the implantation rates of the four age ranges. As the age increased, the clinical pregnancy and implantation rates, as well as the number of oocytes retrieved, MII oocytes, and high-quality embryos, of the long protocol group significantly decreased ( P<0.05).

          Conclusions

          Our study demonstrated that regardless of patient age, the long protocol was superior to the short protocol in terms of the number of retrieved oocytes, as well as the implantation and pregnancy rates.

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          Most cited references16

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          Clinical management of low ovarian response to stimulation for IVF: a systematic review.

          Poor response is not a rare occurrence in ovarian stimulation. Although not fully accepted, the most dominant criteria for poor ovarian response are small numbers of follicles developed or oocytes retrieved, and low estradiol (E2) levels after the use of a standard stimulation protocol. There is no ideal predictive test as the poor responder is revealed only during ovulation induction; however, increased levels of day 3 FSH and E2 as well as decreased levels of inhibin B can be used to assess ovarian reserve. Several protocols have been proposed for clinical management of low ovarian response in IVF. Although high doses of gonadotrophins have been used by the vast majority of authors, results have been controversial and prospective randomized studies have shown little or no benefit. The few available relevant studies do not indicate that recombinant FSH improves outcome. Flare-up GnRH agonist protocols (including all dosage varieties) produce better results than standard long luteal protocols. Luteal initiation GnRH agonist 'stop' protocols were shown to improve ovarian response according to prospective studies with historical controls, but this was not confirmed by well-designed prospective, randomized, controlled studies. The few available data obtained with GnRH antagonists have not shown any benefits. Adjuvant therapy with growth hormone (GH) or GH-releasing factors results in no significant improvement. The use of corticosteroids reduces the incidence of poor ovarian response in women undergoing IVF treatment. The limited data obtained with nitric oxide donors are encouraging. Pretreatment with combined oral contraceptives prior to stimulation may help ovarian response. No benefit was observed with standard use of ICSI or assisted hatching of zona pellucida. Finally, natural cycle IVF has produced results which are comparable with those obtained with stimulated cycles in true poor responders. Well-designed, large-scale, randomized, controlled trials are needed to assess the efficacy of these different management strategies.
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            Long gonadotropin-releasing hormone agonist versus short agonist versus antagonist regimens in poor responders undergoing in vitro fertilization: a randomized controlled trial.

            To compare the efficacy of the long GnRH agonist vs. the short GnRH agonist vs. the GnRH antagonist regimens in poor responders undergoing IVF. Randomized controlled trial. Tertiary referral fertility units. Women with previous poor ovarian response undergoing IVF. One hundred eleven women were randomized to the long GnRH agonist, short agonist, and antagonist regimens. The primary outcome was the number of oocytes retrieved. Secondary outcome measures were gonadotropin consumption, duration of stimulation, cycle cancellation rate, mature oocytes retrieved, fertilization rate, cycles reaching ET, and clinical and ongoing pregnancy rates. Number of oocytes retrieved was significantly higher with long GnRH agonist compared with the short agonist regimen (4.42 ± 3.06 vs. 2.71 ± 1.60), while there was no significant difference between long agonist and antagonist regimens (4.42 ± 3.06 vs. 3.30 ± 2.91). Duration of stimulation and total gonadotropin dose were significantly higher with long agonist compared with short agonist and antagonist regimens. The ongoing pregnancy rate was 8.1% with long and short agonist regimens and 16.2% with the antagonist regimen. Long GnRH agonist and antagonist regimens offer a suitable choice for poor responders, whereas the short agonist regimen may be less effective because of fewer eggs retrieved. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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              Women older than 40 years of age and those with elevated follicle-stimulating hormone levels differ in poor response rate and embryo quality in in vitro fertilization.

              To investigate whether IVF outcome of patients older than 40 years of age with basal FSH levels less than 15 IU/L differs from that in patients 40 years of age or younger with basal FSH levels of 15 IU/L or greater. Prospective observational study. Tertiary academic fertility center. Women 41 years of age or older with basal FSH levels less than 15 IU/L (n = 50), and women 40 years of age or younger with elevated basal FSH levels (n = 36) undergoing their first IVF cycle. IVF treatment using a long suppression protocol with recombinant FSH at a fixed starting dose of 150 IU/L. Ovarian response, ongoing pregnancy rates, and implantation rates. The high FSH group experienced more cycle cancellations due to absent follicular growth than did the high age group (31% vs. 8%). However, the high FSH group had better implantation rates per embryo (34% vs. 11%), higher ongoing rates per ET (40% vs.13%), and higher ongoing pregnancy rates per cycle (25% vs. 10%). In both groups, poor responders had lower pregnancy rates. The outcome of IVF differs between patients older than 40 years of age with normal FSH levels and relatively young patients with elevated FSH levels. This finding may have implications for the management of these patients.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                24 July 2015
                2015
                : 10
                : 7
                : e0133887
                Affiliations
                [1 ]Center for Reproductive Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
                [2 ]Center for Reproductive Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
                Institute of Zoology, Chinese Academy of Sciences, CHINA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JPO YBL YWX CQZ. Performed the experiments: JPO YWX. Analyzed the data: JPO WJX. Wrote the paper: WJX.

                Article
                PONE-D-15-19961
                10.1371/journal.pone.0133887
                4514806
                26208150
                960c14cb-97ed-4f80-aead-a3add2a21a15
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 9 May 2015
                : 2 July 2015
                Page count
                Figures: 10, Tables: 1, Pages: 11
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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