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      Adverse impact of elevated serum progesterone and luteinizing hormone levels on the hCG trigger day on clinical pregnancy outcomes of modified natural frozen-thawed embryo transfer cycles

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          Abstract

          Research question

          The relationship between serum progesterone (P) and luteinizing hormone (LH) levels on the human chorionic gonadotropin (hCG) trigger day and the clinical pregnancy outcomes in modified natural frozen-thawed embryo transfer (mNC-FET) cycles are controversial.

          Design

          This was a retrospective study of 788 mNC-FET cycles. A smooth fitting curve and threshold effect analysis was performed to identify the effect of serum P and LH levels measured on the hCG day on the clinical pregnancy rate (CPR) and live birth rate (LBR) of mNC-FET cycles.

          Results

          The CPR and LBR decreased significantly when the LH level on the hCG day was greater than or equal to 32 IU/L. Further subgroup analysis showed that the CPR decreased significantly when the P level on the hCG day was equal to or greater than 1 ng/mL. When the P level was lower (< 1 ng/mL), the patients with an LH level greater than or equal to 32 IU/L had reduced CPR and LBR in mNC-FET cycles.

          Conclusion

          Applying the hCG trigger on a day with a higher P level (≥ 1 ng/mL) leads to a decreased CPR and LBR. hCG administration with a higher LH level (≥ 32 IU/L) also leads to a decreased CPR and LBR in mNC-FET cycles when the P level is less than 1 ng/mL.

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          Most cited references28

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          ART in Europe, 2014: results generated from European registries by ESHRE†

          What are the European trends and developments in ART and IUI in 2014 as compared to previous years?
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            Cycle regimens for frozen-thawed embryo transfer.

            Among subfertile couples undergoing assisted reproductive technology (ART), pregnancy rates following frozen-thawed embryo transfer (FET) treatment cycles have historically been found to be lower than following embryo transfer undertaken two to five days following oocyte retrieval. Nevertheless, FET increases the cumulative pregnancy rate, reduces cost, is relatively simple to undertake and can be accomplished in a shorter time period than repeated in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles with fresh embryo transfer. FET is performed using different cycle regimens: spontaneous ovulatory (natural) cycles; cycles in which the endometrium is artificially prepared by oestrogen and progesterone hormones, commonly known as hormone therapy (HT) FET cycles; and cycles in which ovulation is induced by drugs (ovulation induction FET cycles). HT can be used with or without a gonadotrophin releasing hormone agonist (GnRHa). This is an update of a Cochrane review; the first version was published in 2008.
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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.

                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                01 December 2022
                2022
                : 13
                : 1000047
                Affiliations
                [1] 1 Center for Reproductive Medicine and Obstetrics and Gynecology, Drum Tower Clinic Medical College of Nanjing Medical University , Nanjing, China
                [2] 2 Reproductive Medicine Center, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School , Nanjing, China
                [3] 3 Center for Molecular Reproductive Medicine, Nanjing University , Nanjing, China
                Author notes

                Edited by: Eytan R. Barnea, BioIncept, LLC, United States

                Reviewed by: Bindu Menon, University of Toledo, United States; Yingchun Su, First Affiliated Hospital of Zhengzhou University, China

                *Correspondence: Jingyu Liu, lianjing1216@ 123456hotmail.com ; Na Kong, xtalkn@ 123456163.com

                †These authors have contributed equally to this work and share first authorship

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

                Article
                10.3389/fendo.2022.1000047
                9751419
                36531505
                d4c632f2-6888-4f45-860b-e06a1316c6b1
                Copyright © 2022 Huang, Shen, Shi, Shan, Yan, Liu and Kong

                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
                : 21 July 2022
                : 22 November 2022
                Page count
                Figures: 3, Tables: 3, Equations: 0, References: 28, Pages: 7, Words: 3536
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 81801530, 81601246
                Categories
                Endocrinology
                Original Research

                Endocrinology & Diabetes
                modified natural cycle,frozen-thawed embryo transfer,serum progesterone level,serum luteinizing hormone level,clinical pregnancy rate,live birth rate

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