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      Effect of Exogenous Luteinizing Hormone (LH) Supplementation on Clinical Pregnancy of Patients Receiving Long-Acting Gonadotropin-Releasing Hormone Agonist (GnRHa) Cycles: A Retrospective Cohort Study

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          Abstract

          Purpose

          Timely and moderate luteinizing hormone (LH) secretion plays critical roles in follicle development and maturation. However, the role of LH supplementation in in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) cycles remains unclear. Can LH supplementation improve the clinical outcomes of patients who receive long-acting gonadotropin-releasing hormone agonist (GnRHa) pituitary downregulation in IVF/ICSI-ET cycles?

          Patients and Methods

          This is a retrospective cohort study of 2600 long-acting GnRHa down-regulated IVF/ICSI cycles from 2017 to 2020 in our reproductive medicine centre of Nanjing Drum Tower Hospital. Total cycles were divided into two groups according to LH supplementation or not. In addition, we conducted a secondary analysis that used propensity-score matching to reduce the effects of confounding.

          Results

          Exogenous LH addition was not significantly correlated with the clinical pregnancy rate (OR=0.910, 95% CI: 0.623–1.311, p=0.61) in logistic regression analysis. After propensity-score matching, we also found no significant association between LH supplementation and the clinical pregnancy rate (OR=0.792, 95% CI: 0.527–1.191, p=0.26).

          Conclusion

          There is no obvious effect of exogenous LH supplementation on the clinical pregnancy rate in non-selective patients receiving long-acting GnRHa IVF/ICSI-ET cycles, which suggests that exogenous LH addition is not always needed, which can help us avoid drug overuse to a certain extent.

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          Most cited references34

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          Gonadotropic control of ovarian follicular growth and development.

          S.G. Hillier (2001)
          Development-related paracrine cues that sensitize follicles to follicle stimulating hormone (FSH) and luteinizing hormone (LH) are crucial to the emergence of a single dominant follicle in each ovulatory menstrual cycle. Sex steroids, insulin-like growth factors and members of the transforming growth factor-beta superfamily are key players in the follicular paracrine system. FSH acts through membrane-associated granulosa cell receptors (FSHR) to stimulate granulosa cell proliferation and differentiation. The most responsive follicle at the beginning of the cycle is the first to produce estrogen and express granulosa cell LHR. Paracrine signalling activated by FSH and LH sustains growth and oestrogen secretion until an ovulation-inducing LH surge is discharged by the pituitary gland. LH then reprograms granulosa cell function, leading to terminal differentiation (luteinization) rupture of the follicle wall, and release of the fertilizable egg. The genes regulated by the LH surge orchestrate profound changes in sex steroid production, metabolism and action which are necessary for ovulation. Preovulatory granulosa cells also increase their ability to metabolise cortisone to cortisol, which may be part of a local anti-inflammatory mechanism to promote rapid healing of the ruptured ovarian surface.
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            The use of recombinant luteinizing hormone in patients undergoing assisted reproductive techniques with advanced reproductive age: a systematic review and meta-analysis.

            Micah J Hill, Eric Levens, Gary J. Levy … (2012)
            To evaluate the effect of recombinant LH in assisted reproduction technology (ART) cycles in patients of advanced reproductive age. A systematic review and meta-analysis. Published randomized controlled clinical trials comparing recombinant LH plus recombinant FSH versus recombinant FSH only in patients of advanced reproductive age. Patients 35 years and older undergoing assisted reproduction. Recombinant LH plus recombinant FSH controlled ovarian hyperstimulation (COH) versus recombinant FSH stimulation only in assisted reproduction cycles. Implantation and clinical pregnancy. Seven trials were identified that met inclusion criteria and comprised 902 assisted reproduction technology cycles. No differences in serum E(2) on the day of hCG administration were reported in any trials. Two trials reported lower oocyte yield and one trial reported lower metaphase II oocyte yield in the recombinant LH-supplemented group. One trial reported higher fertilization rates in the recombinant LH-supplemented group. In a fixed effect model, implantation was higher in the recombinant LH-supplemented group (odds ratio 1.36, 95% confidence interval 1.05-1.78). Similarly, clinical pregnancy was increased in the recombinant LH-supplemented group (odds ratio 1.37, 95% confidence interval 1.03-1.83). The addition of recombinant LH to ART cycles may improve implantation and clinical pregnancy in patients of advanced reproductive age. Copyright © 2012 American Society for Reproductive Medicine. All rights reserved.
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              Exogenous luteinizing hormone in controlled ovarian hyperstimulation for assisted reproduction techniques.

              Luca Gianaroli, Anna Ferraretti, Valeria Farfalli … (2004)
              To investigate the role of exogenous LH in controlled ovarian hyperstimulation for assisted reproductive technologies. Prospective randomized study. SISMER fertility unit. Women showing a hyporesponsiveness to FSH under GnRH agonist down-regulation were randomized into three groups: group A (n = 54) received an increased dosage of FSH; group B (n = 54) was administered recombinant LH in addition to the increased dose of FSH; group C (n = 22) was given additional FSH and LH using hMG as a combined drug. Fifty-four age-matched women with no need to increase the FSH dose were included as a control group (D). None. Implantation and live birth rate per started cycles. In group B, the pregnancy and implantation rates were statistically higher when compared with groups A and C and did not differ from the control group for normal response. The live birth rate was similar in groups B and D but was half as high in groups A and C. Hyporesponsiveness to FSH could be related to iatrogenic LH deficiency that, in turn, could affect oocyte competence. Addition of a small amount of recombinant LH is able to rescue oocyte competence to produce viable embryos.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Womens Health
                Journal ID (iso-abbrev): Int J Womens Health
                Journal ID (publisher-id): ijwh
                Title: International Journal of Women's Health
                Publisher: Dove
                ISSN (Electronic): 1179-1411
                Publication date (Electronic): 13 December 2022
                Publication date Collection: 2022
                Volume: 14
                Pages: 1691-1700
                Affiliations
                [1 ]Center for Reproductive Medicine and Obstetrics and Gynecology, Drum Tower Clinic Medical College of Nanjing Medical University , Nanjing, People’s Republic of China
                [2 ]Reproductive Medicine Center, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School , Nanjing, People’s Republic of China
                [3 ]Center for Molecular Reproductive Medicine, Nanjing University , Nanjing, People’s Republic of China
                Author notes
                Correspondence: Jun Xing; Na Kong, Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School , Nanjing, People’s Republic of China, Tel +8625-8310-6666-70261, Fax +8625-8310-7188, Email xing.jun@msn.com; xtalkn@163.com
                Author information
                http://orcid.org/0000-0003-4402-6256
                http://orcid.org/0000-0002-6613-1957
                Article
                Publisher ID: 388726
                DOI: 10.2147/IJWH.S388726
                PMC ID: 9759025
                PubMed ID: 36536609
                SO-VID: 6d043b13-30a7-486b-8f9f-4719f5b7a16f
                Copyright © © 2022 Huang et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 15 September 2022
                Date accepted : 06 December 2022
                Page count
                Figures: 1, Tables: 6, References: 34, Pages: 10
                Funding
                Funded by: National Natural Science Foundation of China, open-funder-registry 10.13039/501100001809;
                Funded by: Reproductions Research Program of Young and Middle-aged Physicians and China Health Promotion Foundation;
                This work was supported by the National Natural Science Foundation of China (81801530) and Reproductions Research Program of Young and Middle-aged Physicians and China Health Promotion Foundation (BJHPA-2022-SHZHYXZHQNYJ-LCH-002). There is no conflict of interests.
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Obstetrics & Gynecology
                Keywords: lh supplementation,long-acting gnrha,clinical pregnancy rate,logistic regression analysis,propensity-score matching
                Data availability:
                ScienceOpen disciplines: Obstetrics & Gynecology
                Keywords: lh supplementation, long-acting gnrha, clinical pregnancy rate, logistic regression analysis, propensity-score matching

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