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

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

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.