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      Progesterone levels on the human chorionic gonadotropin trigger day affect the pregnancy rates for embryos transferred at different stages of development in both general and selected IVF/ICSI populations

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          Abstract

          Background

          Two meta-analyses have shown that pregnancy and birth rates are significantly higher after blastocyst transfer than after cleaved embryo transfer. Other studies have revealed that a serum progesterone level > 1.5 ng/ml on the trigger day is responsible for premature luteinization and is associated with a low pregnancy rate. The objectives of this retrospective study were to determine whether blastocyst transfer gave higher pregnancy rates than cleaved embryo transfer at day 3 in both the general and selected IVF/ICSI populations, and whether the serum progesterone level influenced the pregnancy rate.

          Method

          We studied IVF/ICSI cycles with GnRH antagonist - FSH/hMG protocols in a general population ( n = 1210) and a selected “top cycle” population ( n = 677), after blastocyst transfer on day 5 or cleaved embryo transfer on day 3. The selected couples had to meet the following criteria: female age < 35, first or second cycle, and one or two embryos transferred. We recorded predictive factors for pregnancy and calculated the progesterone to oocyte index (POI), the progesterone:estradiol ratio (P:E2 ratio), and the progesterone to follicle (> 14 mm) index (PFI).

          Results

          In the general population, the clinical pregnancy rate was significantly higher after blastocyst transfer (33.3%) than after cleaved embryo transfer (25.3%; p <  0.01); the same was true for the birth rate (32.1 and 22.8%, respectively, p <  0.01). The differences between blastocyst and embryo transfer groups were not significant in the selected population (respectively 35.7% vs. 35.8% for the clinical pregnancy rate, and 33.9 and 34.9% for the birth rate). The serum progesterone levels on the eve of the trigger day and on the day itself were significantly lower in the pregnant women ( p <  0.01). We found a serum progesterone threshold of 0.9 ng/ml, as also reported by other researchers. The POI and the PFI appear to have predictive value for cleaved embryos transfers.

          Conclusions

          Blastocyst transfers were associated with higher clinical pregnancy and birth rates than cleaved embryo transfers in a general population but not in a selected population. The serum progesterone levels on the eve of the trigger day and on the day itself predicted the likelihood of pregnancy.

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          Most cited references55

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          The International Glossary on Infertility and Fertility Care, 2017 † ‡ §

          Abstract STUDY QUESTION Can a consensus and evidence-driven set of terms and definitions be generated to be used globally in order to ensure consistency when reporting on infertility issues and fertility care interventions, as well as to harmonize communication among the medical and scientific communities, policy-makers, and lay public including individuals and couples experiencing fertility problems? SUMMARY ANSWER A set of 283 consensus-based and evidence-driven terminologies used in infertility and fertility care has been generated through an inclusive consensus-based process with multiple stakeholders. WHAT IS KNOWN ALREADY In 2006 the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) published a first glossary of 53 terms and definitions. In 2009 ICMART together with WHO published a revised version expanded to 87 terms, which defined infertility as a disease of the reproductive system, and increased standardization of fertility treatment terminology. Since 2009, limitations were identified in several areas and enhancements were suggested for the glossary, especially concerning male factor, demography, epidemiology and public health issues. STUDY DESIGN, SIZE, DURATION Twenty-five professionals, from all parts of the world and representing their expertise in a variety of sub-specialties, were organized into five working groups: clinical definitions; outcome measurements; embryology laboratory; clinical and laboratory andrology; and epidemiology and public health. Assessment for revisions, as well as expansion on topics not covered by the previous glossary, were undertaken. A larger group of independent experts and representatives from collaborating organizations further discussed and assisted in refining all terms and definitions. PARTICIPANTS/MATERIALS, SETTING, METHODS Members of the working groups and glossary co-ordinators interacted through electronic mail and face-to-face in international/regional conferences. Two formal meetings were held in Geneva, Switzerland, with a final consensus meeting including independent experts as well as observers and representatives of international/regional scientific and patient organizations. MAIN RESULTS AND THE ROLE OF CHANCE A consensus-based and evidence-driven set of 283 terminologies used in infertility and fertility care was generated to harmonize communication among health professionals and scientists as well as the lay public, patients and policy makers. Definitions such as ‘fertility care’ and ‘fertility awareness’ together with terminologies used in embryology and andrology have been introduced in the glossary for the first time. Furthermore, the definition of ‘infertility’ has been expanded in order to cover a wider spectrum of conditions affecting the capacity of individuals and couples to reproduce. The definition of infertility remains as a disease characterized by the failure to establish a clinical pregnancy; however, it also acknowledges that the failure to become pregnant does not always result from a disease, and therefore introduces the concept of an impairment of function which can lead to a disability. Additionally, subfertility is now redundant, being replaced by the term infertility so as to standardize the definition and avoid confusion. LIMITATIONS, REASONS FOR CAUTION All stakeholders agreed to the vast majority of terminologies included in this glossary. In cases where disagreements were not resolved, the final decision was reached after a vote, defined before the meeting as consensus if passed with 75%. Over the following months, an external expert group, which included representatives from non-governmental organizations, reviewed and provided final feedback on the glossary. WIDER IMPLICATIONS OF THE FINDINGS Some terminologies have different definitions, depending on the area of medicine, for example demographic or clinical as well as geographic differences. These differences were taken into account and this glossary represents a multinational effort to harmonize terminologies that should be used worldwide. STUDY FUNDING/COMPETING INTERESTS None. TRIAL REGISTRATION NUMBER N/A.
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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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              Serum progesterone level effects on the outcome of in vitro fertilization in patients with different ovarian response: an analysis of more than 10,000 cycles.

              To investigate the relationship between serum P levels on the day of hCG administration and pregnancy outcomes in different responders undergoing IVF. Retrospective study. Teaching hospital. A total of 11,055 women who underwent their first IVF/intracytoplasmic sperm injection cycles and a subgroup of 4,021 women undergoing frozen-embryo transfer (FET) cycles. Patients underwent IVF-ET with the long GnRH agonist protocol. The ovarian response was classified as high (≥ 20 oocytes; n = 2,023), poor (≤ 4 oocytes; n = 827), or intermediate (remaining cases; n = 8,205) according to the number of oocytes retrieved. Clinical outcomes of IVF-ET and FET cycles were analyzed according to plasma P levels. Ongoing pregnancy rates (PRs). Ongoing PRs in fresh cycle were inversely associated with serum P levels on the day of hCG administration for all patients. Different P threshold concentrations were determined according to different ovarian response: We proposed a serum P level of 1.5 ng/mL as the threshold for poor responders, 1.75 ng/mL for intermediate responders, and 2.25 ng/mL for high responders. Our study does not show negative results for elevated P levels on oocyte performance in terms of fertilization, cleavage rate, or PR of FET cycles within different ovarian responses, offering no evidence for a detrimental effect of high P on oocyte quality. Elevated P levels on the day of hCG administration negatively influence PR regardless of different ovarian responses, although increased P threshold concentration is associated with better ovarian responses. The detrimental effect of P elevation on PR seems to be unrelated to oocyte quality in all responders. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                philippe.merviel@chu-brest.fr
                Journal
                BMC Pregnancy Childbirth
                BMC Pregnancy Childbirth
                BMC Pregnancy and Childbirth
                BioMed Central (London )
                1471-2393
                6 May 2021
                6 May 2021
                2021
                : 21
                : 363
                Affiliations
                GRID grid.411766.3, ISNI 0000 0004 0472 3249, Department of Gynecology, Obstetrics and Reproductive Medicine, , Brest University Hospital, ; 2 avenue Foch, F-29200 Brest, France
                Author information
                http://orcid.org/0000-0003-0184-0880
                Article
                3832
                10.1186/s12884-021-03832-3
                8101180
                33957886
                f983c9a7-b4ca-464e-8e07-b60e801b59b7
                © The Author(s) 2021

                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
                : 16 September 2020
                : 26 April 2021
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2021

                Obstetrics & Gynecology
                ivf/icsi,pregnancy,progesterone,blastocyst,cleaved embryo
                Obstetrics & Gynecology
                ivf/icsi, pregnancy, progesterone, blastocyst, cleaved embryo

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