Case Report: Implication of antiangiogenic therapy (bevacizumab) along with dichloroacetate therapy on endometriosis patient seeking infertility treatment

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Current endometriosis medications, which often entail surgical intervention and hormone therapy, are geared around easing discomfort as well as improving fertility. However, alternative approaches targeting angiogenesis have shown promise in managing endometriosis-associated infertility. This case report highlights the implications of combining antiangiogenic therapy (bevacizumab) with dichloroacetate (DCA) therapy in a patient with endometriosis seeking infertility treatment. A 34-year-old woman presented with a five-year history of severe pelvic pain and primary infertility due to stage IV endometriosis. The patient sought other possibilities after repeated unsuccessful attempts using assisted reproductive technology. A revolutionary therapy strategy combining bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, and DCA, a metabolic modulator, has been proposed considering the potential significance of angiogenesis in endometriosis-related infertility. The patient underwent a six-month treatment regimen consisting of intravenous bevacizumab infusions combined with oral DCA administration. The theory behind this combination was to target the metabolic reprogramming typically associated with the disease in addition to altering the abnormal angiogenic signaling pathways that contribute to the pathogenesis of endometriosis. Given the scores on the visual analogue scale, the patient's pelvic pain substantially decreased during the time frame of treatment. Additionally, a notable improvement in ovarian reserve markers was observed, including an increase in anti-Müllerian hormone levels and the number of antral follicles. This case report suggests that the combination of bevacizumab and DCA may have a synergistic effect in managing endometriosis-associated infertility. This form of therapy may provide patients who have failed typical infertility treatment options with an innovative therapeutic approach since it targets both angiogenesis and metabolic changes." } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/12-1169/v1", "name": "Case Report: Implication of antiangiogenic therapy (bevacizumab) along..." } } ] } Home Browse Case Report: Implication of antiangiogenic therapy (bevacizumab) along... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Mehakar S, More A, Dutta S et al. Case Report: Implication of antiangiogenic therapy (bevacizumab) along with dichloroacetate therapy on endometriosis patient seeking infertility treatment [version 1; peer review: 1 approved with reservations] . F1000Research 2023, 12 :1169 ( https://doi.org/10.12688/f1000research.141510.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Case Report Case Report: Implication of antiangiogenic therapy (bevacizumab) along with dichloroacetate therapy on endometriosis patient seeking infertility treatment [version 1; peer review: 1 approved with reservations] Saurabh Mehakar https://orcid.org/0009-0009-5021-9012 1 , Akash More https://orcid.org/0000-0002-9958-1479 1 , Shilpa Dutta https://orcid.org/0000-0003-0759-1133 1 , Ritesh Jadhav https://orcid.org/0009-0001-4772-4204 1 , Namrata Chaudhari 1 , Rukaiya Shaikh https://orcid.org/0009-0009-1504-8692 1 Saurabh Mehakar https://orcid.org/0009-0009-5021-9012 1 , Akash More https://orcid.org/0000-0002-9958-1479 1 , [...] Shilpa Dutta https://orcid.org/0000-0003-0759-1133 1 , Ritesh Jadhav https://orcid.org/0009-0001-4772-4204 1 , Namrata Chaudhari 1 , Rukaiya Shaikh https://orcid.org/0009-0009-1504-8692 1 PUBLISHED 19 Sep 2023 Author details Author details 1 Clinical Embryology, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, 442001, India Saurabh Mehakar Roles: Conceptualization, Data Curation, Formal Analysis, Visualization, Writing – Original Draft Preparation Akash More Roles: Funding Acquisition, Methodology, Project Administration, Supervision, Validation, Writing – Review & Editing Shilpa Dutta Roles: Investigation, Methodology, Project Administration, Supervision, Validation, Visualization, Writing – Review & Editing Ritesh Jadhav Roles: Conceptualization, Project Administration, Validation, Writing – Review & Editing Namrata Chaudhari Roles: Investigation, Supervision, Validation, Writing – Review & Editing Rukaiya Shaikh Roles: Resources, Software, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Datta Meghe Institute of Higher Education and Research collection. Abstract Endometriosis is a pervasive gynecological ailment which usually results in unease and infertility and is signified by an accumulation of endometrial-like tissue outside the uterus. Current endometriosis medications, which often entail surgical intervention and hormone therapy, are geared around easing discomfort as well as improving fertility. However, alternative approaches targeting angiogenesis have shown promise in managing endometriosis-associated infertility. This case report highlights the implications of combining antiangiogenic therapy (bevacizumab) with dichloroacetate (DCA) therapy in a patient with endometriosis seeking infertility treatment. A 34-year-old woman presented with a five-year history of severe pelvic pain and primary infertility due to stage IV endometriosis. The patient sought other possibilities after repeated unsuccessful attempts using assisted reproductive technology. A revolutionary therapy strategy combining bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, and DCA, a metabolic modulator, has been proposed considering the potential significance of angiogenesis in endometriosis-related infertility. The patient underwent a six-month treatment regimen consisting of intravenous bevacizumab infusions combined with oral DCA administration. The theory behind this combination was to target the metabolic reprogramming typically associated with the disease in addition to altering the abnormal angiogenic signaling pathways that contribute to the pathogenesis of endometriosis. Given the scores on the visual analogue scale, the patient's pelvic pain substantially decreased during the time frame of treatment. Additionally, a notable improvement in ovarian reserve markers was observed, including an increase in anti-Müllerian hormone levels and the number of antral follicles. This case report suggests that the combination of bevacizumab and DCA may have a synergistic effect in managing endometriosis-associated infertility. This form of therapy may provide patients who have failed typical infertility treatment options with an innovative therapeutic approach since it targets both angiogenesis and metabolic changes. READ ALL READ LESS Keywords fallopian tube, endometriosis, inflammation Corresponding Author(s) Akash More ( [email protected] ) Close Corresponding author: Akash More Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2023 Mehakar S et al . 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 work is properly cited. How to cite: Mehakar S, More A, Dutta S et al. Case Report: Implication of antiangiogenic therapy (bevacizumab) along with dichloroacetate therapy on endometriosis patient seeking infertility treatment [version 1; peer review: 1 approved with reservations] . F1000Research 2023, 12 :1169 ( https://doi.org/10.12688/f1000research.141510.1 ) First published: 19 Sep 2023, 12 :1169 ( https://doi.org/10.12688/f1000research.141510.1 ) Latest published: 19 Sep 2023, 12 :1169 ( https://doi.org/10.12688/f1000research.141510.1 ) Introduction Endometriosis is characterized by the presence of inflammation and abnormal tissue growth outside the uterus in the female reproductive system. 1 This case study focuses on the management of infertility in a patient with endometriosis as the underlying cause. Endometriosis may culminate in pain and infertility in women who are fertile. Laparoscopy is the gold standard for diagnosing endometriosis, and biopsy in any suspicious lesions is recommended preceded by histological confirmation. The true prevalence of endometriosis in reproductive-aged patients remains unknown due to the difficulties and costs associated with surgical intervention. 2 When endometrial tissue, which typically originates inside the uterus, becomes apparent on the ovaries, fallopian tubes, or the pelvic lining, endometriosis is a consequence. 2 Although numerous hypotheses suggest that a genetic predisposition, hormonal imbalances, immune system problems, and retrograde menstruation—a phenomenon that occurs when menstrual blood flows to the pelvic rather of exiting the body—could be contributing factors, it is not yet understood what exactly causes endometriosis. None of these hypotheses, however, fully explain the development of endometriosis. 3 Pelvic pain, that may fluctuate from mild to severe and occur prior to or throughout menstruation, sexual activity, bowel and urine movements, is the most characteristic symptom of endometriosis. 4 Other common symptoms include infertility or difficulty conceiving, heavy or irregular periods, fatigue, and gastrointestinal issues such as bloating, constipation, or diarrhea. 5 Notwithstanding knowing that there is currently no known treatment for endometriosis, there are an assortment of alternatives to cope with the signs and symptoms of the disease while improving the quality of life of the individuals who have been impacted. These may include pain medications, hormone therapy (such as contraceptives or hormonal intrauterine devices), and, in severe cases, surgical removal of endometrial tissue or repair of any organ damage. 6 Stage 4 endometriosis is a severe form of endometriosis characterized by extensive infiltration and adhesions involving pelvic organs. The condition has significant adverse effects on the quality of life for those who are impacted by it given that it has been associated to debilitating pain, inflammation, and infertility. Despite the fact that stage 4 endometriosis frequently responds to therapy predominantly through surgical intervention, additional methods of treatment are essential, notably for people seeking in vitro fertilisation. Antiangiogenic therapy, such as Bevacizumab, has shown promise in inhibiting the formation of new blood vessels, known as angiogenesis, which is crucial for the growth and progression of endometriotic lesions. In the field of malignancy, bevacizumab, a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF), went through noteworthy research and has proven to be successful in inhibiting tumour angiogenesis. Dichloroacetate (DCA) therapy has gained attention for its potential in targeting metabolic dysregulation in various diseases, including cancer. DCA acts by modulating the activity of pyruvate dehydrogenase kinase, promoting mitochondrial metabolism and potentially reversing the metabolic alterations observed in endometriosis. In particular for patients seeking treatment for infertility, the simultaneous administration of antiangiogenic therapy with Bevacizumab and dichloroacetate therapy has emerged as an innovative approach in the management of stage 4 endometriosis. By targeting both the angiogenic and metabolic components that make up endometriosis, this combination therapy could significantly increase the probability of regaining fertility. This case report explores the implications and outcomes of using the combination therapy of antiangiogenic therapy (Bevacizumab) along with dichloroacetate therapy in the treatment of stage 4 endometriosis patients seeking infertility treatment. Recognising the prospective benefits of this a combination therapy could assist with establish more productive and comprehensive therapeutic strategies for individuals with stage 4 endometriosis-related infertility. Case presentation Patient medical history This case report is based on south Asian patient who is a 34-year-old woman who was nurse by profession who visited our WTTBC (Wardha Test Tube Baby), Wardha, with a medical history of stage IV endometriosis, a severe form of endometriosis characterized by the presence of extensive endometrial tissue outside the uterus. She has also been diagnosed with hypothyroidism, indicating an underactive thyroid gland. Despite these conditions, the male partner’s semen parameters were found to be normal, indicating no significant abnormalities in sperm quality or quantity. There were no notable medical reports in the patient’s family history. It is important to note that the male partner is a non-alcoholic as well as non-smoker, which may have potential implications for their fertility journey. The patient also had history of failed IUI attempt before visiting our center. Clinical findings Based on the preliminary investigation, we decided to perform Ovum pick up cycle on our patient. In assisted reproductive techniques (ART), such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), the ovum pick-up (OPU) cycle is an essential procedure. It involves the retrieval of oocytes from the woman’s ovaries for subsequent fertilization. Once the follicles had reached an optimal size, a trigger injection was administered to induce final maturation of the oocytes within the follicles. Approximately 36 hours after the trigger injection, oocyte retrieval was performed under ultrasound guidance. The retrieved oocytes were then evaluated and prepared for fertilization through ICSI in our case study. During the first ovum pick-up (OPU) procedure, no oocytes were retrieved due to the patient’s chronic condition of stage IV endometriosis. Subsequently, the first OPU cycle was conducted, followed by Gonadotropins releasing hormone. Low dosage can be given for 24 month and high dosage given for 6 month. So we gave high dosage of 6 month to the patient. The route of administration was injectable. High dosage of 10 mg/day. 7 However, the conventional therapy yielded no improvements or discernible outcomes. Notably, in the first OPU cycle, no oocytes were retrieved. Therefore, in the second ovum pick-up (OPU) procedure, a combination therapy involving bevacizumab treatment (antiangiogenic therapy) 10mcg every 2 week in combination with cyclophosphamide and dichloroacetate (DCA) therapy 12.5 and 10.6 mcg twice-daily was administered orally for 3 months. Following the application of this therapeutic regimen during the second OPU cycle, the patient’s oocytes were successfully retrieved. Specifically, two oocytes in the metaphase II (MII) phase were retrieved after the implementation of bevacizumab treatment (antiangiogenic therapy) and dichloroacetate therapy during the second OPU cycle. The process of intracytoplasmic sperm injection (ICSI) was employed to facilitate fertilization of the retrieved oocytes using the male partner’s sperm, thereby enhancing the likelihood of successful conception. To meet the patient’s hormonal needs and prepare the endometrium for embryo transfer, progesterone 200mcg orally and estrogen 1.25 to 2.5mg three times a day orally for 10 days were administered. Subsequently, a high- quality blastocyst was transferred into the patient’s uterus via a transcervical tube. There was no complications faced during the procedure. Follow up Following the embryo transfer procedure, the patient was counselled to take prescribed medications, including progesterone supplementation 200mcg orally for next 14 days, to support the development of the uterine lining and enhance implantation. The patient was closely monitored through periodical follow-up visits to assess her progress. The patient was also advised on lifestyle modifications, including recommendations for a healthy diet, physical activity, and avoidance of potential risks. Ongoing support and guidance were provided to address any concerns or queries during the follow-up period. The patient’s well-being and the progression of the pregnancy were closely monitored to optimize the chances of a successful outcome. Following routine follow-up examinations two weeks later, a positive beta-human chorionic gonadotropin (β-hCG) test confirmed the patient’s pregnancy. The value of β-hCG was reported to be 1245 mIU/mL. Discussion Agustin Gracia et al observed that the endometriosis is cured by this Bevacizumab therapy was very effective therapy. The limitation of this therapy was Agustin Gracia and et al was observed this therapy only in one patient so this therapy required RCT randomized control trial to validate the result. The goals of endometriosis medication include symptom relief, slowing the disease’s course, and enhancing fertility outcomes. The use of prescription or over-the-counter painkillers, hormonal treatments like Gonadotropins releasing hormone. Low dosage was be given for 24 month and high dosage given for 6 month. So we gave high dosage of 6 month to the patient. The route of administration was injectable. High dosage of 10 mg/day. 8 Endometriosis is a chronic and complex condition that significantly affects the lives of women. Its exact cause remains unknown, and the wide range of symptoms and the lack of a definitive diagnostic test contribute to delays in diagnosis. The impact of endometriosis on a woman’s quality of life, fertility, and mental well-being cannot be underestimated. 9 A monoclonal anti-angiogenic antibody that targets the VEGF is bevacizumab. Thus, it may have an effect on neo-angiogenesis, one of the key aspects of endometriosis. With this history in mind, we suggested this treatment as off-label to a patient who had a severe case of endometriosis that had failed to respond to traditional treatments. 10 A monoclonal antibody known as bevacizumab blocks the creation of new blood vessels by specifically targeting the vascular endothelial growth factor (VEGF) protein. It has been largely approved for the therapy of specific tumors, including ovarian, lung, and colorectal cancer. Angiogenesis (creation of new blood vessels) contributes to the onset and development of endometriosis, an abnormal development of endometrial tissue beyond the uterus. Bevacizumab has been studied for its potential to reduce pain and lesion size associated with endometriosis, but more studies are required to determine the drug’s efficacy and safety in this setting. 11 This research states that a high tolerability profile and a favourable impact on managing pain were attained. Importantly, we noticed that the hormone receptor was expressed more strongly in endometriosis cells. Knowing the crucial role performed by hormones in the prevention of cell/proliferation, inflammation, and neovascularization, these results may be of significant therapeutic value. Reverting to standard hormonal therapy in cases of refractoriness could contribute to a cautious approach to the condition. 12 We also noted a favourable tolerance profile with no adverse effects. Bevacizumab should be used cautiously due to its anti-angiogenic activity, however, since it has been associated with intestinal, renal, and cardiovascular adverse reactions. When organizing a second opinion surgery, it’s important to keep in mind that poor wound healing caused by anti-angiogenesis therapy should also be taken into consideration. 13 Finally, our experience suggests that bevacizumab treatment (antiangiogenic therapy) may be impacted by an elevated tissue fibrosis. Less bleeding, but a harder time dissecting implants because to inflammation, should be taken into account. After using bevacizumab treatment (antiangiogenic therapy), endometriosis was significantly cured and improved the chances of fertilization and implantation chances in the patient. Hormonal treatment involving the use of a combined oral contraceptive pill, routine follow-up visits, and conversations about fertility preservation strategies. This case emphasizes the necessity of raising awareness, developing diagnostic methods, and doing additional research to improve the care and quality of life for endometriosis sufferers. 13 Conclusion This case report is the testament of an endoemetrisos patient undergoing infertility treatment at WTTBC wardha who underwent bevacizumab treatment (antiangiogenic therapy) and dichloro acetate therapy for treating her ailment and resulted in significant improvement of the same, which resulted in positive clinical pregnancy. Consent Written informed consent was obtained from the patient and her partner for the publication of their clinical details. Ethical approval Prospective Ethical approval: DMIHER (DU)/IEC/2023/603. Data availability All data underlying the results are available as part of the article and no additional source data are required. References 1. Gardos G, Cole JO: Maintenance antipsychotic therapy: is the cure worse than the disease? Am. J. Psychiatry. 1976 Jan; 133 (1): 32–36. PubMed Abstract | Publisher Full Text 2. Libíková H, Pogády J, Wiedermann V, et al. : Search for herpetic antibodies in the cerebrospinal fluid in senile dementia and mental retardation. Acta Virol. 1975 Nov; 19 (6): 493–495. PubMed Abstract 3. Poole-Wilson PA, Langer GA: Effect of pH on ionic exchange and function in rat and rabbit myocardium. Am. J. Phys. 1975 Sep; 229 (3): 570–581. Publisher Full Text 4. Gardos G, Cole JO: Maintenance antipsychotic therapy: is the cure worse than the disease? Am. J. Psychiatry. 1976 Jan; 133 (1): 32–36. PubMed Abstract | Publisher Full Text 5. Fiddian-Green RG, Silen W: Mechanisms of disposal of acid and alkali in rabbit duodenum. Am. J. Phys. 1975 Dec; 229 (6): 1641–1648. Publisher Full Text 6. Kidder GW, Montgomery CW: Oxygenation of frog gastric mucosa in vitro. Am. J. Phys. 1975 Dec; 229 (6): 1510–1513. Publisher Full Text 7. Behre HM, Kliesch S, Pühse G, et al. : High Loading and Low Maintenance Doses of a Gonadotropin-Releasing Hormone Antagonist Effectively Suppress Serum Luteinizing Hormone, Follicle-Stimulating Hormone, and Testosterone in Normal Men. J. Clin. Endocrinol. Metab. 1997 May; 82 (5): 1403–1408. PubMed Abstract | Publisher Full Text 8. Ehrhart IC, Parker PE, Weidner WJ, et al. : Coronary vascular and myocardial responses to carotid body stimulation in the dog. Am. J. Phys. 1975 Sep; 229 (3): 754–760. Publisher Full Text 9. Share JB: Review of drug treatment for Down’s syndrome persons. Am. J. Ment. Defic. 1976 Jan; 80 (4): 388–393. PubMed Abstract 10. Bouquet De Joliniere J, Fruscalzo A, Khomsi F, et al. : Antiangiogenic Therapy as a New Strategy in the Treatment of Endometriosis? The First Case Report. Front. Surg. 2021 Dec 8; 8 : 791686. Publisher Full Text 11. Taira K, Okazaki S, Akiyoshi K, et al. : Short bevacizumab infusion as an effective and safe treatment for colorectal cancer. Mol. Clin. Oncol. 2022 Jul 27; 17 (3): 139. PubMed Abstract | Publisher Full Text | Free Full Text 12. Kahn T, Bosch J, Levitt MF, et al. : Effect of sodium nitrate loading on electrolyte transport by the renal tubule. Am. J. Phys. 1975 Sep; 229 (3): 746–753. Publisher Full Text 13. Kidder GW, Montgomery CW: Oxygenation of frog gastric mucosa in vitro. Am. J. Phys. 1975 Dec; 229 (6): 1510–1513. Publisher Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 19 Sep 2023 ADD YOUR COMMENT Comment Author details Author details 1 Clinical Embryology, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, 442001, India Saurabh Mehakar Roles: Conceptualization, Data Curation, Formal Analysis, Visualization, Writing – Original Draft Preparation Akash More Roles: Funding Acquisition, Methodology, Project Administration, Supervision, Validation, Writing – Review & Editing Shilpa Dutta Roles: Investigation, Methodology, Project Administration, Supervision, Validation, Visualization, Writing – Review & Editing Ritesh Jadhav Roles: Conceptualization, Project Administration, Validation, Writing – Review & Editing Namrata Chaudhari Roles: Investigation, Supervision, Validation, Writing – Review & Editing Rukaiya Shaikh Roles: Resources, Software, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 19 Sep 2023, 12:1169 https://doi.org/10.12688/f1000research.141510.1 Copyright © 2023 Mehakar S et al . 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 work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Mehakar S, More A, Dutta S et al. Case Report: Implication of antiangiogenic therapy (bevacizumab) along with dichloroacetate therapy on endometriosis patient seeking infertility treatment [version 1; peer review: 1 approved with reservations] . F1000Research 2023, 12 :1169 ( https://doi.org/10.12688/f1000research.141510.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 19 Sep 2023 Views 0 Cite How to cite this report: Leonardi M and Freger S. Reviewer Report For: Case Report: Implication of antiangiogenic therapy (bevacizumab) along with dichloroacetate therapy on endometriosis patient seeking infertility treatment [version 1; peer review: 1 approved with reservations] . F1000Research 2023, 12 :1169 ( https://doi.org/10.5256/f1000research.154963.r208441 ) The direct URL for this report is: https://f1000research.com/articles/12-1169/v1#referee-response-208441 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 23 Oct 2023 Mathew Leonardi , McMaster University, Hamilton, Ontario, Canada Shay Freger , McMaster University, Hamilton, Ontario, Canada Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.154963.r208441 Overall Impression: The authors of the case report titled “ Implication of antiangiogenic therapy (bevacizumab) along with dichloroacetate therapy on endometriosis patient seeking infertility treatment” provided novel evidence of the effectiveness of conjoined treatment using an angiogenic inhibitor and metabolic ... Continue reading READ ALL Overall Impression: The authors of the case report titled “ Implication of antiangiogenic therapy (bevacizumab) along with dichloroacetate therapy on endometriosis patient seeking infertility treatment” provided novel evidence of the effectiveness of conjoined treatment using an angiogenic inhibitor and metabolic modulator in the treatment of endometriosis-associated infertility. The current case report suggests improvement in fertility outcomes and disease upon administration of both interventions. Please see the comments below: Introduction The manuscript has several grammatical errors, particularly in the introduction and discussion sections, which need to be revised. I suggest using a grammar software. Please stay consistent when referring to stages of disease; in some cases, “Stage 4” was used, and in others, “Stage IV.” I would suggest breaking the introduction into four sections: 1) introducing the disease, 2) the pathobiology of endometriosis in the context of angiogenesis and metabolic dysregulation, 3) defining the intervention and their past use in malignancies, and 4) case report hypothesis and objective. Case presentation The authors describe that the patient was diagnosed with Stage IV disease, assuming rASRM was used. How was the patient diagnosed (i.e. imagining, surgically, clinically)? How did the patient present to the clinic? What were the symptoms, and what past treatments were provided? Has the patient had any past surgeries related to endometriosis? Clinical Findings The authors state, "the first OPU cycle was conducted, followed by Gonadotropins releasing hormone. Low dosage can be given for 24 month and high dosage given for 6 month. So we gave high dosage of 6 month to the patient. The route of administration was injectable. High dosage of 10 mg/day. However, the conventional therapy yielded no improvements or discernible outcomes. Notably, in the first OPU cycle, no oocytes were retrieved." - Were the number of follicles counted sonographically in the first OPU cycle? If so, what was the count of visible follicles? Were AMH levels assessed at this time? The authors suggest this treatment be used among those with Stage IV disease, particularly those who are unresponsive to the current conventional treatments. However, patients with stage IV disease typically present with significant adhesions throughout the pelvis, making imaging and oocyte retrieval difficult. For example, the ovaries may be adherent to pivotal structures such as the uterosacral or pelvic side wall, or the rectouterine pouch is commonly obliterated, making it challenging to retrieve eggs altogether. Similarly, what was the follicle and AMH count? Were the patients using any self-management strategies during the cycle period? Did the patient have any adverse reactions to the medication, and if so, what were they? A large contraindication of bevacizumab is pregnancy or the potential of childbearing, as it can readily pass the placental barrier, transmitting it from the mother to the developing fetus. Do you expect bevacizumab to affect the development period, given the half-life negatively? If so, is bevacizumab a feasible treatment in the context of fertility? Discussion The limitations were reported adequately, though they may be elaborated on, particularly the author's comment on fibrosis. The authors state “After using bevacizumab treatment (antiangiogenic therapy), endometriosis was significantly cured and improved the chances of fertilization and implantation chances in the patient.” What do you mean by the endometriosis being cured, followed by treatment? Did the endometriosis disappear? References Please review the references, as some are irrelevant to the field or topic, such as Share JB: Review of drug treatment for Down’s syndrome persons. Am. J. Ment. Defic. 1976 Jan; 80(4): 388–393 Is the background of the case’s history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the case presented with sufficient detail to be useful for other practitioners? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Gynecology, Endometriosis We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however we have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Leonardi M and Freger S. Reviewer Report For: Case Report: Implication of antiangiogenic therapy (bevacizumab) along with dichloroacetate therapy on endometriosis patient seeking infertility treatment [version 1; peer review: 1 approved with reservations] . F1000Research 2023, 12 :1169 ( https://doi.org/10.5256/f1000research.154963.r208441 ) The direct URL for this report is: https://f1000research.com/articles/12-1169/v1#referee-response-208441 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 19 Sep 2023 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 Version 1 19 Sep 23 read Mathew Leonardi , McMaster University, Hamilton, Canada Shay Freger , McMaster University, Hamilton, Canada Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2023 Leonardi M et al. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 23 Oct 2023 | for Version 1 Mathew Leonardi , McMaster University, Hamilton, Ontario, Canada Shay Freger , McMaster University, Hamilton, Ontario, Canada 0 Views copyright © 2023 Leonardi M et al. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Overall Impression: The authors of the case report titled “ Implication of antiangiogenic therapy (bevacizumab) along with dichloroacetate therapy on endometriosis patient seeking infertility treatment” provided novel evidence of the effectiveness of conjoined treatment using an angiogenic inhibitor and metabolic modulator in the treatment of endometriosis-associated infertility. The current case report suggests improvement in fertility outcomes and disease upon administration of both interventions. Please see the comments below: Introduction The manuscript has several grammatical errors, particularly in the introduction and discussion sections, which need to be revised. I suggest using a grammar software. Please stay consistent when referring to stages of disease; in some cases, “Stage 4” was used, and in others, “Stage IV.” I would suggest breaking the introduction into four sections: 1) introducing the disease, 2) the pathobiology of endometriosis in the context of angiogenesis and metabolic dysregulation, 3) defining the intervention and their past use in malignancies, and 4) case report hypothesis and objective. Case presentation The authors describe that the patient was diagnosed with Stage IV disease, assuming rASRM was used. How was the patient diagnosed (i.e. imagining, surgically, clinically)? How did the patient present to the clinic? What were the symptoms, and what past treatments were provided? Has the patient had any past surgeries related to endometriosis? Clinical Findings The authors state, "the first OPU cycle was conducted, followed by Gonadotropins releasing hormone. Low dosage can be given for 24 month and high dosage given for 6 month. So we gave high dosage of 6 month to the patient. The route of administration was injectable. High dosage of 10 mg/day. However, the conventional therapy yielded no improvements or discernible outcomes. Notably, in the first OPU cycle, no oocytes were retrieved." - Were the number of follicles counted sonographically in the first OPU cycle? If so, what was the count of visible follicles? Were AMH levels assessed at this time? The authors suggest this treatment be used among those with Stage IV disease, particularly those who are unresponsive to the current conventional treatments. However, patients with stage IV disease typically present with significant adhesions throughout the pelvis, making imaging and oocyte retrieval difficult. For example, the ovaries may be adherent to pivotal structures such as the uterosacral or pelvic side wall, or the rectouterine pouch is commonly obliterated, making it challenging to retrieve eggs altogether. Similarly, what was the follicle and AMH count? Were the patients using any self-management strategies during the cycle period? Did the patient have any adverse reactions to the medication, and if so, what were they? A large contraindication of bevacizumab is pregnancy or the potential of childbearing, as it can readily pass the placental barrier, transmitting it from the mother to the developing fetus. Do you expect bevacizumab to affect the development period, given the half-life negatively? If so, is bevacizumab a feasible treatment in the context of fertility? Discussion The limitations were reported adequately, though they may be elaborated on, particularly the author's comment on fibrosis. The authors state “After using bevacizumab treatment (antiangiogenic therapy), endometriosis was significantly cured and improved the chances of fertilization and implantation chances in the patient.” What do you mean by the endometriosis being cured, followed by treatment? Did the endometriosis disappear? References Please review the references, as some are irrelevant to the field or topic, such as Share JB: Review of drug treatment for Down’s syndrome persons. Am. J. Ment. Defic. 1976 Jan; 80(4): 388–393 Is the background of the case’s history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the case presented with sufficient detail to be useful for other practitioners? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Gynecology, Endometriosis We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however we have significant reservations, as outlined above. reply Respond to this report Responses (0) Leonardi M and Freger S. Peer Review Report For: Case Report: Implication of antiangiogenic therapy (bevacizumab) along with dichloroacetate therapy on endometriosis patient seeking infertility treatment [version 1; peer review: 1 approved with reservations] . F1000Research 2023, 12 :1169 ( https://doi.org/10.5256/f1000research.154963.r208441) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-1169/v1#referee-response-208441 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. 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