Comparing the results of human chorionic gonadotropin and dual triggering protocols in consecutive IVF cycles of women with poor ovarian response: A retrospective case-control study.

Comparing the results of human chorionic gonadotropin and dual triggering protocols in consecutive IVF cycles of women with poor ovarian response: A retrospective case-control study. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparing the results of human chorionic gonadotropin and dual triggering protocols in consecutive IVF cycles of women with poor ovarian response: A retrospective case-control study. MELIS GOKCE KOCER YAZICI, Gulcin Ozkara, Mert Yesiladali, Ece Gumusoglu Caglar, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3357308/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Bolus administration of GnRH analogs mimics physiological ovulation and adding GnRH-a to hCG (“dual triggering”) to induce final oocyte maturation stimulates the luteinizing hormone surge which improves IVF outcomes by decreasing immature oocyte rates. Effects of dual triggering on oocytes have been investigated in previous studies. However, retrieved oocytes in consecutive hCG and dual triggering cycles of poor responder(POR) patients has not been studied yet. In this study, we aimed to examine the retrieved/mature oocyte counts after administering hCG and dual triggering to POR patients in their consecutive IVF cycles. Method A total of 54 patients with two consecutive cycles within two years were included into this single-centered, retrospective cohort study that was conducted at Yeditepe University Hospitals, Istanbul, Turkey, between 2014 and 2021. All patients were diagnosed with POR according to the Bologna Criteria (2011). Dual vs hCG triggering protocols were compared using Wilcoxon test in terms of oocyte count and maturation. Results Although a statistically significant difference was observed between the ages of patients in their consecutive IVF cycles, it did not have a clinical significance (38.80±3.72 vs 38.17±3.75, p0.05). No statistically significant difference was found in terms of total and mature oocytes between two protocols. Conclusion The results demonstrated that the choice of triggering method, whether hCG or dual triggering, did not significantly influence neither the retrieved oocyte count nor maturation in POR patients. Poor ovarian response dual triggering IVF oocyte maturation MII/total oocyte ratio Introduction For many years, human chorionic gonadotropin (hCG) has been widely used in IVF treatments to stimulate oocyte maturation and ovulation triggering by mimicking reproductive physiology and influencing the natural luteinizing hormone (LH) surge. Luteotropic effects of hCG, with its long half-life, results in an intrauterine environment that is optimal for pregnancy. The extended half-life of hCG is, however, a key contributor to the increased risk of ovarian hyperstimulation syndrome (OHSS) [ 1 , 2 ]. Different medical approaches have been tried to prevent OHSS in oocyte pick up (OPU) cycles but no effective treatment method has been proven. To lower the incidence of OHSS, Shapiro et al. put forward the administration of low-dose hCG and GnRH-a on the same day of oocyte retrieval, so called dual triggering. Shortly after, it was shown that patients with a history of recurrent empty follicles and immature oocyte rates achieved better results after dual triggering in terms of mature oocytes (metaphase II, MII). In another study, Griffin et al. observed that by dual triggering, more mature oocytes were retrieved from the patients who had more than 25% of immature oocytes in their previous OPU cycles [ 3 ]. Studies until today aimed to investigate the effects of dual triggering to prevent OHSS in patients who have high, normal or low responses to controlled ovarian hyperstimulation (COH). By means of those studies, the effect of dual triggering on oocyte maturation has been brought to light. While investigating the live birth rates in patients who had normal response to dual triggering, Lin et al. found a statistically significant increase in the total number of oocytes and the number of mature (metaphase II, MII) oocytes retrieved [ 4 ]. Recently, the first prospective, double-blinded, randomized controlled study on normal responders to dual triggering (n: 155) demonstrated the increase in oocytes per follicle, MII oocytes and total oocyte counts, with no reported cases of OHSS (14). But the effects of different triggering methods on the same poor responder patients’ oocytes have not been evaluated and compared before. Our aim in this study is to apply two different triggering methods in consecutive COH cycles to poor responder patients and compare the oocyte counts, MII oocytes and MII/total oocyte ratios obtained after each COH cycle. Materials and Methods Patient Selection A total of 54 patients that had two consecutive treatment cycles were included into this single-centered, retrospective cohort study that was conducted at Yeditepe University Hospitals, Istanbul, Turkey, between 2014 and 2021. All patients were diagnosed with poor ovarian reponse according to the Bologna Criteria(2011)(Meeting 2 of 3: 1- Advanced maternal age (> 40 years) or any other risk factor for poor ovarian response (POR); 2- ≤ 3 oocyte retrieval in a previous traditional stimulation protocols; 3- Antral follicle count (AFC) ≤ 5–7 or anti-Müllerian hormone (AMH) < 0.5–1.1 ng/ml)[ 5 ]. Patients who had not meeting the above given criteria, and identified a genetic mutation regarding the oocyte maturation or had more than two years between those consecutive treatment cycles were excluded from the study. Treatment Protocol Patients were evaluated ultrasonographically on the 2nd or 3rd day of their menstrual cycle. COH was initiated to patients who did not have any contraindications for treatment. Appropriate dosage was determined according to the patients’ individual characteristics. Recombinant follicle stimulating hormone (rFSH) (GONAL-f, Merck-Serono) and/or human menopausal gonadotropin (HMG) (Merional, IBSA) were/was used for ovarian hyperstimulation. Patients who were scheduled for flexible GnRH-a protocol for pituitary suppression were evaluated ultrasonographically on the 5th or 6th days of their menstrual cycles. GnRH-a (Cetrotide, Merck-Serono or Orgalutran, MSD) was administered if at least one follicle was ≥ 14 mm. Ultrasonography was performed at regular intervals to follow up the follicular developments. When at least two dominant follicles of 17 mm’s were observed; standard hCG (Pregnyl 10.000 IU, Merck or Ovitrelle 500 mcg, Merck) or dual triggering was planned. Dual triggering was accomplished by the simultaneous injections of hCG (Pregnyl 10.000 IU, Merck or Ovitrelle 500 mcg, Merck) and GnRH-a (Gonapeptyl 0.2 mg, Ferring). OPU was performed 36–38 hours after ovulation triggering. Statistical Analysis Statistical analyses were performed using IBM Statistical Package for the Social Sciences (SPSS) Software Version 25. Non-parametric Wilcoxon signed ranks test was used for the comparisons of two different triggering protocols. P value of < 0.05 was considered as statistically significant. Primary outcome was the effect of dual triggering on oocyte maturation; hence on mature oocyte counts. Results Demographic and clinical characteristics of the patients were given in Table 1 . Vast majority of patients had 77.8% (n = 42) primary infertility and remaining ones had secondary infertility 22.2% (n = 12). Other concomitant pathologies to diminished ovarian reserve were 44.4% (n = 24) advanced maternal age, 3.7% endometrioma, 3.7% absolute tubal factor. Although a statistically significant difference was observed between the ages of patients in their consecutive IVF cycles (dual vs hCG triggering), it did not have a clinical significance (38.80 ± 3.72 vs 38.17 ± 3.75, p < 0.001, respectively). Anti mullerian hormone (AMH) (ng/ml) levels and body mass indexes (BMI) (kg/m 2 ) were found similar between dual and hCG triggering groups (AMH: 0.4565 ± 0.30 vs 0.4561 ± 0.30, BMI: 29.86 ± 3.76 vs 29.24 ± 4.23, respectively). Basal FSH and estradiol (E2) levels were not statistically significant between two treatment groups (p > 0.05). Total gonadotropin doses were higher in dual triggering group than hCG triggering group (3955.56 ± 963.78 vs 3619.81 ± 911.27, p = 0.011), however, stimulation days were similar (10.24 ± 1.45 vs 9.98 ± 1.18, respectively). No statistically significant difference was found between the dual triggering protocol and hCG protocol in different assisted reproductive technology (ART) cycles of the same patients in terms of total retrieved oocytes (Dual: 3.72 ± 2.96 vs hCG: 3.61 ± 2.13, p > 0.05, respectively) (Table 1 ). Table 1 Demographic and clinical characteristics of patients (n: 54) Dual Triggering hCG Triggering p value Age (years) 38.17 ± 3.75 38.17 ± 3.75 < 0.001 AMH (ng/ml) 0.45 ± 0.30 0.45 ± 0.30 NS Body Mass Index (BMI) (kg/m 2 ) 29.86 ± 3.76 29.24 ± 4.23 NS Basal FSH (mIU/mL) 10.74 ± 4.10 9.71 ± 3.85 NS Basal E2 (pg/ml) 36.76 ± 17.64 43.06 ± 19.52 NS Total Gonadotropin dose (Units) 3955.56 ± 963.78 3619.81 ± 911.27 0.011 Duration of stimulation (days) 10.24 ± 1.45 9.98 ± 1.18 NS Total retrieved oocytes (n) 3.72 ± 2.96 3.61 ± 2.13 NS MII oocyte (n) 2.88 ± 2.40 2.94 ± 1.95 NS Values were given as mean ± standard deviation (SD). AMH, anti-mullerian hormone; BMI, body mass index; FSH, follicle-stimulating hormone; E2, estradiol hormone; MII, metaphase II; NS, statistically non-significant; n, number. Bold values are statistically significant (p < 0.05). Discussion GnRH analogs have shown promise in reducing the risk of ovarian hyperstimulation syndrome (OHSS) associated with hCG triggering. The concept of dual triggering, combining GnRH-a and hCG, has gained attention for its potential to enhance IVF outcomes, especially in cases of poor ovarian response. While previous studies have indicated positive effects of dual triggering on oocyte maturation and overall IVF success, the current study underscores that such benefits might not extend uniformly to patients with poor ovarian response. As the landscape of IVF continues to evolve, further investigation is warranted to fully understand the nuances of triggering methods in different patient populations. By shedding light on the specific circumstances of poor responder patients, this study contributes to the broader dialogue surrounding IVF protocols and optimization of outcomes. However, it is important to note that this study focused solely on oocyte-related outcomes, and the potential impact on implantation, ongoing pregnancies, and live birth rates warrants additional exploration, especially considering the potential effects of GnRH-a triggering on luteal phase support and endometrial receptivity. Gonen et al. demonstrated the physiological effects of GnRH-a’s on follicle maturation and oocyte triggering [ 6 ]. Since LH surge occurred within natural limits, the risk of OHSS was shown to be lower with GnRH-a triggering. Later studies demonstrated that endogenous LH surge and the following increase in FSH due to GnRH-a triggering also resulted in increased numbers of MII oocytes [ 7 , 8 ]. However, due to inadequate corpus luteum formation, GnRH-a triggering is known to be associated with luteal phase deficiencies. Progesterone support and endometrial stabilization cannot be provided which may result in poor implantation rates and early pregnancy losses in fresh embryo transfers [ 7 , 9 – 11 ]. In a systematic review, it was demonstrated that administration of GnRH-a as a single triggering agent had negative effects on implantation rates, ongoing pregnancy rates, and live birth rates [ 12 ]. Adding hCG or estradiol and progesterone combinations to the treatment are some of the preventive measures that have been tried over the past years to solve this problem. Freezing all embryos and postponing embryo transfers are some of the common approaches in GnRH-a triggered cycles. A study conducted by Griffin, in 2012, about the effects of GnRH-a triggering of high-responder patients, in contrast, showed a positive relationship of GnRH-a triggering with ongoing pregnancy rates and live birth rates [ 13 ]. Schachter et al. also proved a similar positive relationship between GnRH-a triggering and ongoing pregnancy rates in the normoresponder group [ 14 ]. Dual triggering was associated with a considerably higher number of retrieved oocytes, mature oocytes, pregnancy rate, and live birth rate than the standard hCG trigger, according to the current meta-analysis[ 15 ]. Our aim in this study was to apply both hCG and dual triggering to poor responder patients in their consecutive COH cycles to compare the oocyte counts, MII oocytes and MII/total oocyte ratios obtained after each triggering method. Previous studies compared the effects of hCG and dual triggering in consecutive cycles of different patient populations. However, retrieved oocytes and MII/total oocyte counts of the patients with poor ovarian response were compared for the first time. Although some publications demonstrate the increased total oocyte counts and MII oocyte rates after dual triggering in different patient groups; we found that the triggering method did not significantly affect the results in patients with poor ovarian reponse. Some studies in the past demonstrated the different effects of GnRH-a triggering on implantation rates, ongoing pregnancy rates and live birth rates of different patient groups; namely high responders and normoresponders. In our study, we were not able to demonstrate the rates of implantation, ongoing pregnancies and live births of poor responder patients who were triggered with GnRH-a since we wanted to prevent the undesired effects of GnRH-a triggering on luteal phase and endometrial receptivity. The major limitation of the study is that it was conducted with a small number of the cases. Our results should be confirmed in further large scale studies comparing the effects of two protocols on fertilization rates, embryo quality and ICF outcomes. Conclusion This study aimed to investigate the impact of different triggering methods, hCG and dual triggering, on poor responder patients undergoing in vitro fertilization (IVF) cycles. While previous research has explored the effects of dual triggering in various patient populations, this study provides a unique perspective by focusing on patients with poor ovarian reponse. The results demonstrated that the choice of triggering method, whether hCG or dual triggering, did not significantly influence neither the retrieved oocyte count nor maturation in this specific group of patients. The findings of the current study emphasize the complexity of IVF treatment and the need for tailored approaches to trigger methods based on individual patient characteristics. While the present investigation adds valuable insights to the field, further research is needed to comprehensively address the multifaceted aspects of triggering methods and their influence on diverse patient cohorts undergoing IVF. Declarations Conflict of Interest Statement The authors have no relevant financial or non-financial interests to disclose. Authors Contribution The planning and conduct of the study have been made by Melis Gokce Kocer Yazici, M.D . Clinical examinations were performed by Melis Gokce Kocer Yazici, Gulcin Ozkara , Mert Yesiladali, Ece Gumusoglu Caglar, Oya Alagoz and Erkut Attar. Gulcin Ozkara, Melis Gokce Kocer Yazici, have contributed to the statistical analysis, interpretation of data, writing and revising processes. Ethical Compliance This study was approved by Yeditepe University Ethics Committee (approval number: 202202180). Funding There was no financial or non-financial support for this study. Conflict of interests The authors declare no competing interest. References Ovarian hyperstimulation syndrome (2008) Fertil Steril 90(5 Suppl): p. S188-93. https://doi.org/10.1016/j.fertnstert.2008.08.034 Delvigne, A. and S. Rozenberg (2002) Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review. Hum Reprod Update 8(6): p. 559-77. https://doi.org/10.1093/humupd/8.6.559 Griffin, D., et al. (2014) Dual trigger with gonadotropin-releasing hormone agonist and standard dose human chorionic gonadotropin to improve oocyte maturity rates. Fertil Steril 102(2): p. 405-9. https://doi.org/10.1016/j.fertnstert.2014.04.028 Lin, M.H., et al. (2013) Dual trigger with combination of gonadotropin-releasing hormone agonist and human chorionic gonadotropin significantly improves the live-birth rate for normal responders in GnRH-antagonist cycles. Fertil Steril 100(5): p. 1296-302. https://doi.org/10.1016/j.fertnstert.2013.07.1976 Ferraretti, A.P., et al. (2011) ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod 26(7): p. 1616-24. https://doi.org/10.1093/humrep/der092 Gonen, Y., et al. (1990) Use of gonadotropin-releasing hormone agonist to trigger follicular maturation for in vitro fertilization. J Clin Endocrinol Metab 71(4): p. 918-22. https://doi.org/10.1210/jcem-71-4-918 Humaidan, P., et al. (2005) GnRH agonist (buserelin) or hCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study. Hum Reprod 20(5): p. 1213-20. https://doi.org/10.1093/humrep/deh765 Imoedemhe, D.A., et al. (1991) Stimulation of endogenous surge of luteinizing hormone with gonadotropin-releasing hormone analog after ovarian stimulation for in vitro fertilization. Fertil Steril 55(2): p. 328-32. https://doi.org/10.1016/S0015-0282(16)54125-9 Kolibianakis, E.M., B. Tarlatzis, and P. Devroey (2005) GnRH antagonists in IVF. Reprod Biomed Online 10(6): p. 705-12. hptts://doi.org/10.1016/s1472-6483(10)61113-3 Humaidan, P., et al. (2013) GnRHa trigger and individualized luteal phase hCG support according to ovarian response to stimulation: two prospective randomized controlled multi-centre studies in IVF patients. Hum Reprod 28(9): p. 2511-21. https://doi.org/10.1093/humrep/det249 Griesinger, G., et al. (2007) Triggering of final oocyte maturation with gonadotropin-releasing hormone agonist or human chorionic gonadotropin. Live birth after frozen-thawed embryo replacement cycles. Fertil Steril 88(3): p. 616-21. https://doi.org/10.1016/j.fertnstert.2006.12.006 Youssef, M.A., et al. (2011) Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist assisted reproductive technology cycles. Cochrane Database Syst Rev (1): p. Cd008046. https://doi.org/10.1002/14651858.CD008046.pub3 Griffin, D., et al.(2012) Dual trigger of oocyte maturation with gonadotropin-releasing hormone agonist and low-dose human chorionic gonadotropin to optimize live birth rates in high responders. Fertil Steril 97(6): p. 1316-20. https://doi.org/10.1016/j.fertnstert.2012.03.015 Schachter, M., et al. (2008) Can pregnancy rate be improved in gonadotropin-releasing hormone (GnRH) antagonist cycles by administering GnRH agonist before oocyte retrieval? A prospective, randomized study. Fertil Steril 90(4): p. 1087-93. https://doi.org/10.1016/j.fertnstert.2007.07.1316 Hsia, L.-H., et al. (2023) Dual trigger improves the pregnancy rate in fresh in vitro fertilization (IVF) cycles compared with the human chorionic gonadotropin (hCG) trigger: a systematic review and meta-analysis of randomized trials. Journal of Assisted Reproduction and Genetics 40(9): p. 2063-2077. https://doi.org/10.1007/s10815-023-02888-8 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3357308","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":236914810,"identity":"1925bee8-d465-4a2a-96c5-8a09156c4941","order_by":0,"name":"MELIS GOKCE KOCER YAZICI","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA80lEQVRIiWNgGAWjYFAC5oYDQNIAzP4AxGzsBLUwIrQwzgBpYSZCCwNMCzMPmCSgQbe9sfHgD4ZaY372w8c+2/zaJs/HzMD44WMObi1mZw42HOZhOG4m2ZOWPDu377ZhGzMDs+TMbXi03EhsOMzAcMzG4AaPMXNuz21GoBY2Zl58Wu4/bAA6DKSF/zOzZc9te8JabgBDjIehxgxoCzMzw4/biYS1nAE6jMfggDHQL8aMvQ23k9uYGZvx++X44cMff1TUGfazH37M8OPPbdv57c0HP3zEowUCDA5DaMY2MNlASD0I1EHpP8QoHgWjYBSMgpEGAJJbUeSZDW1bAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-2327-9123","institution":"Yeditepe University School of Medicine: Yeditepe Universitesi Tip Fakultesi","correspondingAuthor":true,"prefix":"","firstName":"MELIS","middleName":"GOKCE KOCER","lastName":"YAZICI","suffix":""},{"id":236914811,"identity":"13ceca3f-b437-4951-9208-bea40076de35","order_by":1,"name":"Gulcin Ozkara","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Gulcin","middleName":"","lastName":"Ozkara","suffix":""},{"id":236914812,"identity":"254fbe14-da72-46ce-9727-b9764d5bde0a","order_by":2,"name":"Mert Yesiladali","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Mert","middleName":"","lastName":"Yesiladali","suffix":""},{"id":236914813,"identity":"2b3b5250-badd-4b5f-8c48-7fe26e278c06","order_by":3,"name":"Ece Gumusoglu Caglar","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Ece","middleName":"Gumusoglu","lastName":"Caglar","suffix":""},{"id":236914814,"identity":"b5c0efae-20e6-4380-9d32-9710ea8e1ade","order_by":4,"name":"Oya Algoz","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Oya","middleName":"","lastName":"Algoz","suffix":""},{"id":236914815,"identity":"46bb3f68-d675-4fd3-bb83-e8733ea0ab96","order_by":5,"name":"Erkut Attar","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Erkut","middleName":"","lastName":"Attar","suffix":""}],"badges":[],"createdAt":"2023-09-15 05:19:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3357308/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3357308/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":48417560,"identity":"a2903042-b5d4-4cf0-9ba7-5006ea995098","added_by":"auto","created_at":"2023-12-18 21:37:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":275757,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3357308/v1/51d95274-6e90-4987-8da8-dce82d68f34a.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eComparing the results of human chorionic gonadotropin and dual triggering protocols in consecutive IVF cycles of women with poor ovarian response: A retrospective case-control study.\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFor many years, human chorionic gonadotropin (hCG) has been widely used in IVF treatments to stimulate oocyte maturation and ovulation triggering by mimicking reproductive physiology and influencing the natural luteinizing hormone (LH) surge. Luteotropic effects of hCG, with its long half-life, results in an intrauterine environment that is optimal for pregnancy. The extended half-life of hCG is, however, a key contributor to the increased risk of ovarian hyperstimulation syndrome (OHSS) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Different medical approaches have been tried to prevent OHSS in oocyte pick up (OPU) cycles but no effective treatment method has been proven. To lower the incidence of OHSS, Shapiro et al. put forward the administration of low-dose hCG and GnRH-a on the same day of oocyte retrieval, so called dual triggering. Shortly after, it was shown that patients with a history of recurrent empty follicles and immature oocyte rates achieved better results after dual triggering in terms of mature oocytes (metaphase II, MII). In another study, Griffin et al. observed that by dual triggering, more mature oocytes were retrieved from the patients who had more than 25% of immature oocytes in their previous OPU cycles [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStudies until today aimed to investigate the effects of dual triggering to prevent OHSS in patients who have high, normal or low responses to controlled ovarian hyperstimulation (COH). By means of those studies, the effect of dual triggering on oocyte maturation has been brought to light. While investigating the live birth rates in patients who had normal response to dual triggering, Lin et al. found a statistically significant increase in the total number of oocytes and the number of mature (metaphase II, MII) oocytes retrieved [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Recently, the first prospective, double-blinded, randomized controlled study on normal responders to dual triggering (n: 155) demonstrated the increase in oocytes per follicle, MII oocytes and total oocyte counts, with no reported cases of OHSS (14). But the effects of different triggering methods on the same poor responder patients\u0026rsquo; oocytes have not been evaluated and compared before. Our aim in this study is to apply two different triggering methods in consecutive COH cycles to poor responder patients and compare the oocyte counts, MII oocytes and MII/total oocyte ratios obtained after each COH cycle.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient Selection\u003c/h2\u003e \u003cp\u003eA total of 54 patients that had two consecutive treatment cycles were included into this single-centered, retrospective cohort study that was conducted at Yeditepe University Hospitals, Istanbul, Turkey, between 2014 and 2021. All patients were diagnosed with poor ovarian reponse according to the Bologna Criteria(2011)(Meeting 2 of 3: 1- Advanced maternal age (\u0026gt;\u0026thinsp;40 years) or any other risk factor for poor ovarian response (POR); 2- \u0026le; 3 oocyte retrieval in a previous traditional stimulation protocols; 3- Antral follicle count (AFC)\u0026thinsp;\u0026le;\u0026thinsp;5\u0026ndash;7 or anti-M\u0026uuml;llerian hormone (AMH)\u0026thinsp;\u0026lt;\u0026thinsp;0.5\u0026ndash;1.1 ng/ml)[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Patients who had not meeting the above given criteria, and identified a genetic mutation regarding the oocyte maturation or had more than two years between those consecutive treatment cycles were excluded from the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eTreatment Protocol\u003c/h2\u003e \u003cp\u003ePatients were evaluated ultrasonographically on the 2nd or 3rd day of their menstrual cycle. COH was initiated to patients who did not have any contraindications for treatment. Appropriate dosage was determined according to the patients\u0026rsquo; individual characteristics. Recombinant follicle stimulating hormone (rFSH) (GONAL-f, Merck-Serono) and/or human menopausal gonadotropin (HMG) (Merional, IBSA) were/was used for ovarian hyperstimulation.\u003c/p\u003e \u003cp\u003ePatients who were scheduled for flexible GnRH-a protocol for pituitary suppression were evaluated ultrasonographically on the 5th or 6th days of their menstrual cycles. GnRH-a (Cetrotide, Merck-Serono or Orgalutran, MSD) was administered if at least one follicle was \u0026ge;\u0026thinsp;14 mm. Ultrasonography was performed at regular intervals to follow up the follicular developments. When at least two dominant follicles of 17 mm\u0026rsquo;s were observed; standard hCG (Pregnyl 10.000 IU, Merck or Ovitrelle 500 mcg, Merck) or dual triggering was planned. Dual triggering was accomplished by the simultaneous injections of hCG (Pregnyl 10.000 IU, Merck or Ovitrelle 500 mcg, Merck) and GnRH-a (Gonapeptyl 0.2 mg, Ferring). OPU was performed 36\u0026ndash;38 hours after ovulation triggering.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using IBM Statistical Package for the Social Sciences (SPSS) Software Version 25. Non-parametric Wilcoxon signed ranks test was used for the comparisons of two different triggering protocols. P value of \u0026lt;\u0026thinsp;0.05 was considered as statistically significant. Primary outcome was the effect of dual triggering on oocyte maturation; hence on mature oocyte counts.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eDemographic and clinical characteristics of the patients were given in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. Vast majority of patients had 77.8% (n\u0026thinsp;=\u0026thinsp;42) primary infertility and remaining ones had secondary infertility 22.2% (n\u0026thinsp;=\u0026thinsp;12). Other concomitant pathologies to diminished ovarian reserve were 44.4% (n\u0026thinsp;=\u0026thinsp;24) advanced maternal age, 3.7% endometrioma, 3.7% absolute tubal factor. Although a statistically significant difference was observed between the ages of patients in their consecutive IVF cycles (dual vs hCG triggering), it did not have a clinical significance (38.80\u0026thinsp;\u0026plusmn;\u0026thinsp;3.72 vs 38.17\u0026thinsp;\u0026plusmn;\u0026thinsp;3.75, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, respectively). Anti mullerian hormone (AMH) (ng/ml) levels and body mass indexes (BMI) (kg/m\u003csup\u003e2\u003c/sup\u003e) were found similar between dual and hCG triggering groups (AMH: 0.4565\u0026thinsp;\u0026plusmn;\u0026thinsp;0.30 vs 0.4561\u0026thinsp;\u0026plusmn;\u0026thinsp;0.30, BMI: 29.86\u0026thinsp;\u0026plusmn;\u0026thinsp;3.76 vs 29.24\u0026thinsp;\u0026plusmn;\u0026thinsp;4.23, respectively). Basal FSH and estradiol (E2) levels were not statistically significant between two treatment groups (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Total gonadotropin doses were higher in dual triggering group than hCG triggering group (3955.56\u0026thinsp;\u0026plusmn;\u0026thinsp;963.78 vs 3619.81\u0026thinsp;\u0026plusmn;\u0026thinsp;911.27, p\u0026thinsp;=\u0026thinsp;0.011), however, stimulation days were similar (10.24\u0026thinsp;\u0026plusmn;\u0026thinsp;1.45 vs 9.98\u0026thinsp;\u0026plusmn;\u0026thinsp;1.18, respectively). No statistically significant difference was found between the dual triggering protocol and hCG protocol in different assisted reproductive technology (ART) cycles of the same patients in terms of total retrieved oocytes (Dual: 3.72\u0026thinsp;\u0026plusmn;\u0026thinsp;2.96 vs hCG: 3.61\u0026thinsp;\u0026plusmn;\u0026thinsp;2.13, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05, respectively) (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDemographic and clinical characteristics of patients\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e(n: 54)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDual Triggering\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ehCG Triggering\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e38.17\u0026thinsp;\u0026plusmn;\u0026thinsp;3.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e38.17\u0026thinsp;\u0026plusmn;\u0026thinsp;3.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAMH (ng/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBody Mass Index (BMI) (kg/m\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29.86\u0026thinsp;\u0026plusmn;\u0026thinsp;3.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29.24\u0026thinsp;\u0026plusmn;\u0026thinsp;4.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBasal FSH (mIU/mL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.74\u0026thinsp;\u0026plusmn;\u0026thinsp;4.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.71\u0026thinsp;\u0026plusmn;\u0026thinsp;3.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBasal E2 (pg/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e36.76\u0026thinsp;\u0026plusmn;\u0026thinsp;17.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e43.06\u0026thinsp;\u0026plusmn;\u0026thinsp;19.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Gonadotropin dose (Units)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3955.56\u0026thinsp;\u0026plusmn;\u0026thinsp;963.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3619.81\u0026thinsp;\u0026plusmn;\u0026thinsp;911.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.011\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of stimulation (days)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.24\u0026thinsp;\u0026plusmn;\u0026thinsp;1.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.98\u0026thinsp;\u0026plusmn;\u0026thinsp;1.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal retrieved oocytes (n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.72\u0026thinsp;\u0026plusmn;\u0026thinsp;2.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.61\u0026thinsp;\u0026plusmn;\u0026thinsp;2.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMII oocyte (n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.88\u0026thinsp;\u0026plusmn;\u0026thinsp;2.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.94\u0026thinsp;\u0026plusmn;\u0026thinsp;1.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eValues were given as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD). AMH, anti-mullerian hormone; BMI, body mass index; FSH, follicle-stimulating hormone; E2, estradiol hormone; MII, metaphase II; NS, statistically non-significant; n, number. Bold values are statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eGnRH analogs have shown promise in reducing the risk of ovarian hyperstimulation syndrome (OHSS) associated with hCG triggering. The concept of dual triggering, combining GnRH-a and hCG, has gained attention for its potential to enhance IVF outcomes, especially in cases of poor ovarian response. While previous studies have indicated positive effects of dual triggering on oocyte maturation and overall IVF success, the current study underscores that such benefits might not extend uniformly to patients with poor ovarian response.\u003c/p\u003e \u003cp\u003eAs the landscape of IVF continues to evolve, further investigation is warranted to fully understand the nuances of triggering methods in different patient populations. By shedding light on the specific circumstances of poor responder patients, this study contributes to the broader dialogue surrounding IVF protocols and optimization of outcomes. However, it is important to note that this study focused solely on oocyte-related outcomes, and the potential impact on implantation, ongoing pregnancies, and live birth rates warrants additional exploration, especially considering the potential effects of GnRH-a triggering on luteal phase support and endometrial receptivity.\u003c/p\u003e \u003cp\u003eGonen et al. demonstrated the physiological effects of GnRH-a\u0026rsquo;s on follicle maturation and oocyte triggering [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Since LH surge occurred within natural limits, the risk of OHSS was shown to be lower with GnRH-a triggering. Later studies demonstrated that endogenous LH surge and the following increase in FSH due to GnRH-a triggering also resulted in increased numbers of MII oocytes [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, due to inadequate corpus luteum formation, GnRH-a triggering is known to be associated with luteal phase deficiencies. Progesterone support and endometrial stabilization cannot be provided which may result in poor implantation rates and early pregnancy losses in fresh embryo transfers [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In a systematic review, it was demonstrated that administration of GnRH-a as a single triggering agent had negative effects on implantation rates, ongoing pregnancy rates, and live birth rates [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Adding hCG or estradiol and progesterone combinations to the treatment are some of the preventive measures that have been tried over the past years to solve this problem. Freezing all embryos and postponing embryo transfers are some of the common approaches in GnRH-a triggered cycles. A study conducted by Griffin, in 2012, about the effects of GnRH-a triggering of high-responder patients, in contrast, showed a positive relationship of GnRH-a triggering with ongoing pregnancy rates and live birth rates [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Schachter et al. also proved a similar positive relationship between GnRH-a triggering and ongoing pregnancy rates in the normoresponder group [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Dual triggering was associated with a considerably higher number of retrieved oocytes, mature oocytes, pregnancy rate, and live birth rate than the standard hCG trigger, according to the current meta-analysis[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur aim in this study was to apply both hCG and dual triggering to poor responder patients in their consecutive COH cycles to compare the oocyte counts, MII oocytes and MII/total oocyte ratios obtained after each triggering method. Previous studies compared the effects of hCG and dual triggering in consecutive cycles of different patient populations. However, retrieved oocytes and MII/total oocyte counts of the patients with poor ovarian response were compared for the first time. Although some publications demonstrate the increased total oocyte counts and MII oocyte rates after dual triggering in different patient groups; we found that the triggering method did not significantly affect the results in patients with poor ovarian reponse.\u003c/p\u003e \u003cp\u003eSome studies in the past demonstrated the different effects of GnRH-a triggering on implantation rates, ongoing pregnancy rates and live birth rates of different patient groups; namely high responders and normoresponders. In our study, we were not able to demonstrate the rates of implantation, ongoing pregnancies and live births of poor responder patients who were triggered with GnRH-a since we wanted to prevent the undesired effects of GnRH-a triggering on luteal phase and endometrial receptivity.\u003c/p\u003e \u003cp\u003eThe major limitation of the study is that it was conducted with a small number of the cases. Our results should be confirmed in further large scale studies comparing the effects of two protocols on fertilization rates, embryo quality and ICF outcomes.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study aimed to investigate the impact of different triggering methods, hCG and dual triggering, on poor responder patients undergoing in vitro fertilization (IVF) cycles. While previous research has explored the effects of dual triggering in various patient populations, this study provides a unique perspective by focusing on patients with poor ovarian reponse. The results demonstrated that the choice of triggering method, whether hCG or dual triggering, did not significantly influence neither the retrieved oocyte count nor maturation in this specific group of patients. The findings of the current study emphasize the complexity of IVF treatment and the need for tailored approaches to trigger methods based on individual patient characteristics. While the present investigation adds valuable insights to the field, further research is needed to comprehensively address the multifaceted aspects of triggering methods and their influence on diverse patient cohorts undergoing IVF.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of Interest Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe planning and conduct of the study have been made by Melis Gokce Kocer Yazici, M.D . Clinical examinations were performed by Melis Gokce Kocer Yazici, Gulcin Ozkara , Mert Yesiladali, Ece Gumusoglu Caglar, Oya Alagoz and Erkut Attar. Gulcin Ozkara, Melis Gokce Kocer Yazici, have contributed to the statistical analysis, interpretation of data, writing and revising processes.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Compliance\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by Yeditepe University Ethics Committee (approval number: 202202180).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere was no financial or non-financial support for this study.\u003c/p\u003e\n\u003ch3\u003eConflict of interests\u003c/h3\u003e\n\u003cp\u003eThe authors declare no competing interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eOvarian hyperstimulation syndrome (2008) Fertil Steril 90(5 Suppl): p. S188-93. https://doi.org/10.1016/j.fertnstert.2008.08.034\u003c/li\u003e\n \u003cli\u003eDelvigne, A. and S. Rozenberg (2002) Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review. Hum Reprod Update 8(6): p. 559-77. https://doi.org/10.1093/humupd/8.6.559\u003c/li\u003e\n \u003cli\u003eGriffin, D., et al. (2014) Dual trigger with gonadotropin-releasing hormone agonist and standard dose human chorionic gonadotropin to improve oocyte maturity rates. Fertil Steril 102(2): p. 405-9. https://doi.org/10.1016/j.fertnstert.2014.04.028\u003c/li\u003e\n \u003cli\u003eLin, M.H., et al. (2013) Dual trigger with combination of gonadotropin-releasing hormone agonist and human chorionic gonadotropin significantly improves the live-birth rate for normal responders in GnRH-antagonist cycles. Fertil Steril 100(5): p. 1296-302. https://doi.org/10.1016/j.fertnstert.2013.07.1976\u003c/li\u003e\n \u003cli\u003eFerraretti, A.P., et al. (2011) ESHRE consensus on the definition of \u0026apos;poor response\u0026apos; to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod 26(7): p. 1616-24. https://doi.org/10.1093/humrep/der092\u003c/li\u003e\n \u003cli\u003eGonen, Y., et al. (1990) Use of gonadotropin-releasing hormone agonist to trigger follicular maturation for in vitro fertilization. J Clin Endocrinol Metab 71(4): p. 918-22. https://doi.org/10.1210/jcem-71-4-918\u003c/li\u003e\n \u003cli\u003eHumaidan, P., et al. (2005) GnRH agonist (buserelin) or hCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study. Hum Reprod 20(5): p. 1213-20. https://doi.org/10.1093/humrep/deh765\u003c/li\u003e\n \u003cli\u003eImoedemhe, D.A., et al. (1991) Stimulation of endogenous surge of luteinizing hormone with gonadotropin-releasing hormone analog after ovarian stimulation for in vitro fertilization. Fertil Steril 55(2): p. 328-32. https://doi.org/10.1016/S0015-0282(16)54125-9\u003c/li\u003e\n \u003cli\u003eKolibianakis, E.M., B. Tarlatzis, and P. Devroey (2005) GnRH antagonists in IVF. Reprod Biomed Online 10(6): p. 705-12. hptts://doi.org/10.1016/s1472-6483(10)61113-3\u003c/li\u003e\n \u003cli\u003eHumaidan, P., et al. (2013) GnRHa trigger and individualized luteal phase hCG support according to ovarian response to stimulation: two prospective randomized controlled multi-centre studies in IVF patients. Hum Reprod 28(9): p. 2511-21. https://doi.org/10.1093/humrep/det249\u003c/li\u003e\n \u003cli\u003eGriesinger, G., et al. (2007) Triggering of final oocyte maturation with gonadotropin-releasing hormone agonist or human chorionic gonadotropin. Live birth after frozen-thawed embryo replacement cycles. Fertil Steril 88(3): p. 616-21. https://doi.org/10.1016/j.fertnstert.2006.12.006\u003c/li\u003e\n \u003cli\u003eYoussef, M.A., et al. (2011) Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist assisted reproductive technology cycles. Cochrane Database Syst Rev (1): p. Cd008046. https://doi.org/10.1002/14651858.CD008046.pub3\u003c/li\u003e\n \u003cli\u003eGriffin, D., et al.(2012) Dual trigger of oocyte maturation with gonadotropin-releasing hormone agonist and low-dose human chorionic gonadotropin to optimize live birth rates in high responders. Fertil Steril 97(6): p. 1316-20. https://doi.org/10.1016/j.fertnstert.2012.03.015\u003c/li\u003e\n \u003cli\u003eSchachter, M., et al. (2008) Can pregnancy rate be improved in gonadotropin-releasing hormone (GnRH) antagonist cycles by administering GnRH agonist before oocyte retrieval? A prospective, randomized study. Fertil Steril 90(4): p. 1087-93. https://doi.org/10.1016/j.fertnstert.2007.07.1316\u003c/li\u003e\n \u003cli\u003eHsia, L.-H., et al. (2023) Dual trigger improves the pregnancy rate in fresh in vitro fertilization (IVF) cycles compared with the human chorionic gonadotropin (hCG) trigger: a systematic review and meta-analysis of randomized trials. Journal of Assisted Reproduction and Genetics 40(9): p. 2063-2077. https://doi.org/10.1007/s10815-023-02888-8\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Poor ovarian response, dual triggering, IVF, oocyte maturation, MII/total oocyte ratio","lastPublishedDoi":"10.21203/rs.3.rs-3357308/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3357308/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBolus administration of GnRH analogs mimics physiological ovulation and adding GnRH-a to hCG (“dual triggering”) to induce final oocyte maturation stimulates the luteinizing hormone surge which improves IVF outcomes by decreasing immature oocyte rates. Effects of dual triggering on oocytes have been investigated in previous studies. However, retrieved oocytes in consecutive hCG and dual triggering cycles of poor responder(POR) patients has not been studied yet. In this study, we aimed to examine the retrieved/mature oocyte counts after administering hCG and dual triggering to POR patients in their consecutive IVF cycles.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 54 patients with two consecutive cycles within two years were included into this single-centered, retrospective cohort study that was conducted at Yeditepe University Hospitals, Istanbul, Turkey, between 2014 and 2021. All patients were diagnosed with POR according to the Bologna Criteria (2011). Dual vs hCG triggering protocols were compared using Wilcoxon test in terms of oocyte count and maturation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAlthough a statistically significant difference was observed between the ages of patients in their consecutive IVF cycles, it did not have a clinical significance (38.80±3.72 vs 38.17±3.75, p\u0026lt;0.001). Anti mullerian hormone levels and body mass indexes, basal follicle stimulating hormone and estradiol levels were similar between two cycles (p\u0026gt;0.05). No statistically significant difference was found in terms of total and mature oocytes between two protocols.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe results demonstrated that the choice of triggering method, whether hCG or dual triggering, did not significantly influence neither the retrieved oocyte count nor maturation in POR patients.\u003c/p\u003e","manuscriptTitle":"Comparing the results of human chorionic gonadotropin and dual triggering protocols in consecutive IVF cycles of women with poor ovarian response: A retrospective case-control study.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-10-04 06:21:13","doi":"10.21203/rs.3.rs-3357308/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a714ee99-66f7-47be-963a-1fdef138e728","owner":[],"postedDate":"October 4th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-12-18T21:28:57+00:00","versionOfRecord":[],"versionCreatedAt":"2023-10-04 06:21:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3357308","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3357308","identity":"rs-3357308","version":["v1"]},"buildId":"J0_U0BvcaRcwD8yVFaRlm","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}