Ovarian Carcinoma Initially-presented as Cerebral Metastasis: Epidemiology, Pathology, and Outcomes

Abstract

Background:

An initial presentation of ovarian carcinoma with brain metastasis has been reported in the literature in a limited number of cases, as ovarian cancer rarely metastasizes to the brain.

Objective:

This study aims to a) Systematically review the literature to identify studies on ovarian carcinoma presenting initially as cerebral metastasis and b) to investigate cases of ovarian carcinoma that were initially presented with cerebral metastasis.

Methods:

A PRISMA-guided systematic review was conducted, coupled with a retrospective study at the King Abdullah University Hospital from 2005 to 2020. Two hundred sixty-three ovarian carcinoma cases were analyzed for the presence of brain metastasis, out of which 25 were positive for brain metastasis, and seven of them presented initially with neurological symptoms. Demographics, clinical features, histopathology, and treatments were identified.

Results:

Eight out of 215 studies conducted between 1999 and 2024 satisfied the criteria for ovarian cancer initially manifesting with neurological symptoms. In the retrospective analysis, 85% and 71% of patients, with a mean age of 41, exhibited headache and impaired vision. Serous cancer manifested in 58%, with solitary brain lesions observed in 71%; surgical intervention yielded improved outcomes. Multimodal treatments involving craniotomy, radiation, and chemotherapy resulted in a median survival of 18.7 months. Fertility drugs utilization was recorded in 57%, indicating a possible association with aggressive illness.

Conclusion:

This study illustrates that ovarian cancer presenting as brain metastases at its initial presentation is rare and should be considered in younger women with fertility drugs usage. Long-term risks of fertility drugs should be assessed as use increases. Multimodal therapy improves survival and results.

1. BACKGROUND

Ovarian carcinoma is the leading cause of gynecological cancer-related deaths in women, with epithelial ovarian cancer (EOC) being the most common type [1]. Rare types include germ cell tumors, such as choriocarcinoma. Brain metastasis from ovarian carcinoma is scarce, with an estimated incidence of 1.3%, ranging from 0.5% to 6.1% [2, 3]. Typically resulting from hematogenous spread, it often appears late in the natural course of ovarian cancer, primarily in stages III and IV, and with histologically high grades [4]. The management and outcome of patients with ovarian carcinoma will be vividly affected by cerebral metastases [5]. About one-third of ovarian carcinoma cases have been reported to exhibit distant metastases at their first presentation, primarily affecting extra-cranial organs rather than intracranial spaces [5, 6]. However, recent advances in the early detection, diagnosis, and management of cerebral metastases along with improvements in surgical techniques, potent cytotoxic chemotherapy, and new effective radiotherapy methods have prolonged life expectancy [5, 6]. Unfortunately, despite the application of a multimodal treatment, the prognosis for certain tumors remains poor [5] . Increased survival in ovarian cancer patients may contribute to a higher incidence of brain metastasis due to improved treatment modalities, including chemotherapy, which has limited blood-brain barrier penetration [5-7]. Knowledge of various metastatic mechanisms, including genetic factors consistently shown such as mutations in the BRCA1 and BRCA2 genes, become valuable for building targeted therapies and improvements in patient outcomes [8, 9].

According to the Jordanian Cancer Registry, ovarian cancer represents 3% of the yearly diagnosed cases in the country [10]. The significance of investigating cases of ovarian carcinoma that initially present with cerebral metastasis is underscored by the need for improved diagnostic and therapeutic strategies tailored to this unique presentation. Ovarian carcinoma is increasingly developing in both Jordan and the entire world, some present with cerebral metastasis. Therefore, this study is the first of its kind in Jordan and the region aimed to (1) Systematically review the literature to identify studies on ovarian carcinoma presenting initially as cerebral metastasis and (2) to investigate cases of ovarian carcinoma that were initially presented with cerebral metastasis.

2. OBJECTIVE

This study aims to (1) Systematically review the literature to identify studies on ovarian carcinoma presenting initially as cerebral metastasis and (2) to investigate cases of ovarian carcinoma that were initially presented with cerebral metastasis.

3. MATERIAL AND METHODS

Study Design

This was a retrospective observational study conducted at King Abdullah University Hospital (KAUH), a tertiary referral center in Jordan, aimed at ascertaining the rare presentation of ovarian carcinoma, which presented initially with brain metastases by analyzing medical records from December 2005 to December 2020.

Population and Sample size

The study population comprised all patients diagnosed with ovarian cancer at KAUH over the 15-year period. Of the 263 cases of ovarian cancer screened, brain metastases were detected in 25 patients, accounting for approximately 9.5%. Seven of these fulfilled the inclusive criteria laid out specifically, which amounts to 2.7% of the total ovarian cancer cases.

Inclusion and Exclusion Criteria

The inclusion criteria targeted female patients without a prior ovarian cancer diagnosis, presenting with signs and symptoms of increased intracranial pressure such as headache, nausea, and neurological deficits; metastatic lesions in the brain as shown by CT/MRI studies; presence of ovarian mass seen on imaging studies; histopathological diagnosis of ovarian carcinoma as the primary malignancy; and no other systemic metastases. Exclusion criteria included ovarian cancer previously diagnosed, brain metastases from other gynecological malignancies, and secondary ovarian carcinoma from other primary sites.

Ethical Considerations

The study was approved by the Institutional Review Board (IRB) of Jordan University of Science and Technology and King Abdullah University Hospital (Approval No. 12/105/2017).

Systematic Review

We conducted a systematic review, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to identify studies related to ovarian carcinoma that were presented initially as cerebral metastasis. Review of all the literature between 1999 and 2024, searching PubMed, Google Scholar, and Scopus using specific keywords including "ovarian carcinoma" AND "brain metastasis" AND "initial presentation", For this study, we included those case reports, systematic review, letter to editor, series and retrospective reviews which presented clinical, histological, or therapeutic data.

4. RESULTS

Systematic Review

We conducted a systematic review adhering to PRISMA guidelines, as shown in Figure 1, to identify studies on ovarian carcinoma initially presenting as cerebral metastasis. Of 215 records identified through database searches, 178 were excluded based on title and abstract screening. Twenty-nine were excluded from the 37 reviewed full-text articles that included one study retraction was detected, and two others showed brain metastases due to ovarian cancer but not an initial manifestation, so that eight studies met the criteria.

Figure 1. PRISMA of Ovarian Carcinoma Initially Presenting as Cerebral Metastasis.

The eight reviewed studies provide some insight into clinical features, histological variability, and therapeutic modalities undertaken for ovarian carcinoma presenting as a brain metastasis as its initial manifestation, as displayed in Table 1. Matsunami, Imai [11]and Alafaci, Caffo [12] documented a rare case where brain metastasis was the initial presentation; highlighting diagnostic and therapeutic challenges. Imai, Ichigo [13] conducted a systematic review for the evidence available on brain metastasis presenting as a first manifestation of ovarian/fallopian tube carcinomas. Furthermore, Qudsieh, Mm [14] conducted retrospective review of four cases in which the first presenting sign was brain metastasis; discussed some of the diagnostic challenges. Barbarawi, Smith [5] investigated a case of ovarian carcinoma with multicerebral and leptomeningeal metastases presenting for the first time with cerebral manifestations.

Table 1. Studies Included in the Systematic Review on Ovarian Carcinoma Initially Presenting as Cerebral Metastasis (1999–2024).

Study	Year	Authors	Title	Study Type	Key Findings
	1999	Matsunami, K., Imai, A., Tamaya, T., Takagi, H., & Noda, K.[11]	Brain metastasis as first manifestation of ovarian cancer	Case Report	Documented a rare case where brain metastasis was the initial presentation; highlighted diagnostic challenges.
	2005	Mohammed Al Barbarawi, Sarah F. Smith, Suhair Qudsieh, Lali H. S. Sekhon [5]	Multiple cerebral and leptomeningeal metastases from ovarian carcinoma: unusual early presentation	Case Report	First case report of ovarian carcinoma presenting as multicerebral and leptomeningeal metastases in a 41-year-old female presenting for the first time with symptoms of headache, vomiting, and confusion over a one-week period.
	2008	Bakar, B., & TEKKÖK, İ. H [15]	Primary undifferentiated ovarian carcinoma diagnosed by its metastasis to brain: an unusual case report	Case Report	A 56-year-old female patient presented with headache and visual disturbance who later underwent cranial MRI and abdominal ultrasound
	2011	Alafaci, C., Caffo, M., Caruso, G., Barresi, V., Cutugno, M., Salpietro, F. M., & Tomasello, F.[12]	Brain metastases as first clinical manifestation of ovarian carcinoma	Letter to editor including case report	Describe a rare case of brain metastases characterized by the diagnosis of brain metastases that preceded the diagnosis of ovarian carcinoma
	2018	Imai, A., Ichigo, S., Takagi, H., Kawabata, I., & Matsunami, K [13]	Cerebral Metastases as First Clinical Manifestation of Ovarian/Fallopian Tube Carcinoma	Systematic review	Reviewed evidence on brain metastases as the initial presentation; emphasized rarity and poor prognosis.
	2019	Qudsieh ,S1., Al-Barbarawi, MM., and Bany Amer, N3 [14]	Unusual Early Cerebral Metastasis of Ovarian Carcinoma as Initial Presentation	Retrospective Review	Retrospective review of four cases with brain metastases as the first sign; highlighted diagnostic challenges.
	2023	CABITZA, Eleonora, et al.[16]	Cerebellar metastasis of ovarian cancer: a case report	Case Report	A case of a 47-year-old Caucasian woman, BRCA wild type, with ovarian cancer presenting with single cerebellar metastasis.
	2024	Jourdan, A., Zaidi, S. M. A., Iftikhar, H., & Ahmed, S.[17]	Pituitary metastasis from high-grade serous ovarian carcinoma presenting as hyponatremia	Case Report	Rare pituitary metastasis as the initial presentation; highlighted endocrine dysfunction and diagnostic complexity.

Furthermore, Bakar and TEKKÖK [15] reported a 56-year-old female patient who had a history of migraine since middle age who presented with headache and visual disturbance, who later underwent cranial MRI and abdominal ultrasound .Cabitza [16] described a case of a 47-year-old Caucasian woman, BRCA wild type, with ovarian cancer presenting with single cerebellar metastasis, which emphasized various differentials in both the imaging and histological diagnosis. While Jourdan, Zaidi [17] discussed rare pituitary metastasis who presented with hyponatremia as the initial presentation; highlighted endocrine dysfunction and diagnostic complexity. Collectively, these studies indicate the difficulty in diagnosis, variability of clinical presentations, and need for a multidisciplinary approach to the management in these rare conditions.

Retrospective results

Out of 263 ovarian cancer patients treated at KAUH from December 2005 to December 2020, 25 patients had brain metastasis with an incidence of 9.5%. Only seven cases presented initially with symptoms of raised intracranial pressure, corresponding to an incidence of 2.7% among ovarian carcinoma cases. The study group included seven female patients, aged 25 to 57 years (median age of 41), exhibiting symptoms suggestive of raised intracranial pressure such as nocturnal headache, blurred vision, and unsteady gait. None initially presented gynecological complaints. Retrospective analysis showed that four of these patients had a history of infertility and fertility treatment. The patients’ demographics were reviewed and analyzed in Table 2, and where the cases will be referred to.

Table 2. Detailed individual characteristics of patients with brain metastasis from ovarian carcinoma (N=7). WBRT: Whole Brain Radiation Therapy; V-P shunt: Ventriculoperitoneal shunt.

Case Rank (Based on age)		1	2	3	4	5	6	7
Age at diagnosis (years)		57	45	45	42	39	37	25
Presenting symptoms		Headache Behavioral changes	Headache Vomiting Blurred vision	Unsteady gait	Headache Blurred vision	Headache Vomiting Blurred vision Weakness	Headache Blurred vision Unsteady gait	Headache Vomiting Blurred vision weakness
Histopathology		Serous High grade	Serous High grade, papillary	Serous High grade	Mucinous High grade	Mucinous High grade	Serous High grade, papillary	Non-gestational Choriocarcinoma (NGCC)
Fertility drug use		No	Yes	No	Yes	Yes	Yes	No
Site of the lesion		Cerebellum	Cerebrum	Cerebellum	Cerebrum	Cerebrum	Cerebellum	Cerebrum
Number of lesions		Solitary	Multiple	Solitary	Solitary	Solitary	Multiple	Solitary
Treatment modalities	Craniotomy for resection of brain lesion	Craniotomy	Only V-P Shunt	Craniotomy	Craniotomy	Craniotomy	Craniotomy + V-P Shunt	Craniotomy
	Radiotherapy	WBRT	WBRT	WBRT	WBRT	WBRT	WBRT	No
	Chemotherapy	Taxol/Carb	Taxol/Carb	Taxol/Carb	Taxol/Carb	Taxol/Carb	Taxol/Carb	Methotrexate
	Laparotomy for resection of ovarian carcinoma	Yes	No	Yes	Yes	Yes	Yes	No
Tumor marker		CA 125 178 U/ml	CA125 280 U/ml	CA125 161 U/ml	CA 125 154 U/ml	CA125 112 U/ml	CA125 295 U/ml	B-hCG 40,000 mIU/ml
Survival (months)		38	18	23	14	24	12	2

Brain CT and/or MRI scans revealed intracranial enhancing lesions in various locations, causing mass effect and strongly indicating a secondary tumor (Figure 2). Subsequently, all cases underwent comprehensive investigations including bone scans, CT scans of the chest, abdomen, and pelvis, positron emission tomography (PET), and tumor markers. A pelvic mass, size varied between 3x3 cm and 10x12 cm, suggestive of ovarian cancer, was detected on pelvic CT scan, with no evidence of other systemic involvement in the remainder of the work-up (Figure 3). Furthermore, the histopathological examination of both cerebral and ovarian lesions confirmed the presence of similar malignant features (Figure 4).

Figure 2. Brain MRI: (2A) axial T1WI’s pre contrast, (2B) axial T1WI’s post contrast, (2C) Coronal T1WI’s pre contrast, (2D) coronal T1WI’s post contrast. Demonstrates predominantly cystic infratentorial left cerebellar lesion (red star) which shows ring enhancement as well as small transmural nodule enhancement (red arrow) post gadolinium intravenous contrast.

Figure 3. Pelvis CT (axial slice in venous phase): large predominantly cystic pelvic mass lesion mainly in the left adnexa (blue arrow) with posterior extension.

Figure 4. Histopathology (high power 10X magnification Hematoxylin and Eosin histopathology): a view of serous adenocarcinoma, figure 3 a: from cerebellar excision of the tumor and figure 3b: from ovarian tumor. the histopathology shows similar architectural features of both lesions.

Six patients (Cases 1-6) were diagnosed with epithelial ovarian carcinoma (EOC): four with high-grade serous carcinoma (Cases 1-3, 6) and two with high-grade mucinous carcinoma (Cases 4 and 5). The seventh patient had non-gestational ovarian choriocarcinoma (NGOC). Tumor biomarkers were elevated in all cases; the CA-125 level was increased (>35 U/mL) in all EOC cases, averaging 197 U/mL at the time of brain metastasis diagnosis, while β-human chorionic gonadotropin (βhCG) was significantly elevated in the NGOC case, reaching 40,000 mIU/ml.

Once diagnosed, all patients received multimodal treatment targeting both early brain metastases and primary ovarian carcinoma. Treatment included surgical resection of cerebral and ovarian tumors, whole brain radiation (WBRT), and adjuvant chemotherapy. All cases were managed initially by neurosurgeons for central nervous system metastases. Six patients underwent craniotomy for total resection of brain lesions within 2 weeks after diagnosis, including the choriocarcinoma case (Case 7). Case 2, with multiple brain lesions and hydrocephalus, underwent only a ventriculoperitoneal (VP) shunt. Case 6 also required a VP shunt for persistent hydrocephalus due to cerebellar metastasis. Approximately two to three weeks after craniotomy or VP shunt, all epithelial ovarian carcinoma (EOC) cases underwent whole brain radiation therapy (WBRT) at 21 grays over three weeks.

Approximately 8-10 weeks after diagnosis, five patients (Cases 1, 3–6) achieved sufficient neurological stability to be referred to gynecologic oncology for resection of their primary ovarian tumors. The surgical procedure involved total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO), appendectomy, omentectomy, and pelvic lymph node dissection. Two cases (Cases 2 and 7) did not undergo resection of primary ovarian tumor: Case 2, with multiple brain lesions and compromised neurological condition, was deemed unfit for ovarian debulking surgery, while Case 7, with NGOC, experienced a rapid decline in her condition post-craniotomy and passed away within two months of diagnosis.

All patients received adjuvant chemotherapy. Cases 1 and 3–6 completed five cycles of Paclitaxel (Taxol) and Carboplatin, while Case 2 received four cycles. For the NGOC case (Case 7), Methotrexate was initiated at a dose of 50 mg/m² via intramuscular injection; however, the patient’s condition deteriorated rapidly, precluding further treatment. (Table 3).

Table 3. Characteristics of brain metastasis from ovarian carcinoma (N=7).

Characteristic		Number of cases (Percentage)
Symptoms	Headache	6(85%)
	Blurred vision	5(71%)
	Vomiting	3(42%)
	Unsteady gait	2(28%)
	Weakness	2(28%)
	Behavioral changes	1(14%)
Site of metastasis	Supra-tentorial	4(58%)
	Infra-tentorial	3(42%)
Site of metastasis	Cerebrum	3(42%)
	Cerebellum	3(42%)
	Cerebral and leptomeninges	1(14%)
Number of metastatic brain lesions	Single	5(71%)
	Multiple	2(28%)
Histologic type	Serous	4(58%)
	Mucinous	2(28%)
	Non- gestational choriocarcinoma	1(14%)
Treatment modality	Surgical resection of brain metastasis	6(85%)
	Ventriculoperitoneal Shunt	2(28%)
	Combined chemotherapy and/or radiotherapy	7(100%)
	Surgical resection of primary ovarian carcinoma	5(71%)

Furthermore, four patients had previously received multiple courses of ovulation-stimulating drugs for infertility treatment. Two of them received over 10 courses of clomiphene citrate, while the other two patients received gonadotropins, across 4-6 cycles of in vitro fertilization (IVF) or intrauterine insemination (IUI). Additionally, no family history of malignancy was recorded. Corticosteroids and antiepileptic medications were also part of the brain metastasis treatment protocol. Regular follow-up showed survival times varied, averaging 18.7 months, ranging from 2 to 38 months.

5. DISCUSSION

The aim of this study was to investigate cases of ovarian carcinoma that were initially presented with cerebral metastasis, and we also reviewed the literature to identify studies on ovarian carcinoma presenting initially as cerebral metastasis. In this section, we discussed the results of the systematic review with other related studies, comparing them to the findings of the retrospective study. The findings from the current study reveal critical insights into the individual characteristics of patients, their clinical presentations, treatment modalities, and outcomes.

Sociodemographic Factors

The data indicates that the age at diagnosis among the seven cases ranged between 25 and 57 years, the median age of patients was 41 years, which is younger than the classical mean age range of 59-62 years for ovarian cancer. Literature of the brain metastases from ovarian carcinoma, reported the median age ranged from 44 to 60 years [2, 6] that is consistent with findings from other studies [5, 11, 12, 14]. This study is also in agreement with the literature, which has stipulated that younger women could have more aggressive ovarian cancer capable of leading to atypical manifestations of a metastatic pattern, including the involvement of the brain and lowering the survival rate [18, 19].

In this study, fertility drug use was noted in four out of seven cases, 57%, thus possibly relating to the aggressive behavior of ovarian carcinoma, especially in histologic subtypes like high-grade serous, 58%, and mucinous carcinoma, 28%. This aligns with findings from Imai, Ichigo [13] and Hasegawa, Yoshihama [20]which propose that hormonal stimulation may affect tumor growth and metastasis.

Notably, in this cohort, patients with a history of fertility drug use often presented with solitary lesions, 71%, though multiple lesions were seen in 28%, perhaps reflecting different metastatic behaviors influenced by hormonal factors. For instance, women who received treatment with gonadotropins or clomiphene citrate (CC) experienced a rise in the incidence of ovarian cancer. Gonadotropins play an important role in the development of ovarian cancer, with 40% of cases of epithelial ovarian cancer having receptors for gonadotropin[21]. Due to an increase in the number of women using fertility drugs, much attention has to be focused on the long-term health effects of such drugs [22].

Neurological Presentations, Histopathological Subtypes, and Lesion Patterns in Brain Metastases

The most common presenting symptoms in our cohort were headache (85%) and blurred vision (71%), consistent with other study findings [5, 11-13, 15] that emphasized these symptoms as primary indicators of intracranial involvement in ovarian carcinoma. About 80% of the patients had FIGO stage III or IV when first diagnosed with (EOC)[23, 24]. In contrast, our study cases presented advanced-stage IV high-grade (G3) carcinomas, which negatively impacted prognosis despite being younger and having higher functional status at diagnosis.

The histopathological examination revealed that most of the cases were high-grade serous carcinoma, this finding is consistent with previous studies that have shown high-grade serous carcinoma is frequently associated with advanced disease and a higher likelihood of metastasis [25]. Elevated tumor markers, such as β-hCG in NGCC, highlight the unique diagnostic challenges presented by rarer subtypes, as emphasized by Hasegawa, Yoshihama [20].

Cerebellar involvement was observed in 43% of cases in our cohort, correlating with findings by Piermattei, Santoro [26] on the predilection of certain histologic subtypes for posterior fossa involvement. Most patients had solitary lesions (71%), with better surgical outcomes as observed by Cabitza [16], whereas multiple lesions (29%) were associated with reduced survival, aligning with the conclusions of Qudsieh, Mm [14]. Metastases were more frequently located in the supra-tentorial region (58%), with equal involvement of the cerebrum and cerebellum (42% each) in our cohort, that is congruent with Bakar and TEKKÖK [15] findings in their case report study.

The presence of the cerebral and leptomeningeal involvement present in 14% also aligns with Hasegawa, Yoshihama [20], who reported leptomeningeal dissemination as a challenging and aggressive feature of metastatic ovarian cancer. Solitary lesions were predominant (71%), correlating with better outcomes after surgical resection, as discussed by Piermattei, Santoro [26]. Conversely, multiple lesions (28%) and rare sites, such as the pituitary, as described by Jourdan, Zaidi [17] indicate more aggressive disease and poorer prognosis.

The data underlines that solitary lesions and serous histology, combined with aggressive surgical and multimodal therapies, provide the best results. On the other hand, plural lesions or rare histologic subtypes, like NGCC, often predict worse outcomes, as mentioned by Piermattei, Santoro [26]and Hasegawa, Yoshihama [20].

Impact of Multimodal Treatment Approaches on Survival

In our cohort, craniotomy was performed in six out of seven patients, confirming its critical contribution to the improvement of neurological symptoms and prolongation of survival as emphasized by Matsunami, Imai [11],Barbarawi, Smith [5] ,Bakar and TEKKÖK [15] ,Alafaci, Caffo [12] and Cabitza [16].The only patient who received just a ventriculoperitoneal shunt exemplifies the diversity of the clinical situations. Radiotherapy, primarily Whole-Brain Radiation Therapy (WBRT), was administered to six patients in the cohort. Its universal use among cases receiving radiotherapy highlights its integral role in multimodal therapy, as emphasized by Proskuriakova, Aryal [25]. Chemotherapy regimens predominantly included Taxol/Carboplatin, except in the NGCC case, which Methotrexate was used, consistent with the recommendations for this subtype by Imai, Ichigo [13]. Survival varied between 2 and 38 months among our cohort; with poor survival which also observed by Qudsieh, Mm [14]. Despite using a multimodal approach, life expectancy is shortened when the central nervous system is involved [5]. However, the median survival rate is variable, ranging from five to seventeen months [27], which is consistent with our results, 18.7 months.

In the current study, surgical resection of brain metastases was performed in 85% of cases, demonstrating its role in symptom management and disease control. Ventriculoperitoneal shunting was required in 28% of cases, addressing complications like hydrocephalus, as discussed by Stopa, Cuoco [28].Combined chemotherapy and/or radiotherapy were used for all the current study cohort, that is consistent with the multimodal approaches emphasized by and Piermattei et al. (2020). Surgical resection of the primary ovarian carcinoma was performed in 71% of cases, underscoring its role in overall disease management and alignment with best practices outlined by Qudsieh et al. (2019).

6. CONCLUSION

Ovarian carcinoma is one of the common malignancies in females but rarely metastasizes to the brain. In young females presenting with brain metastases, an ovarian origin should be considered in the differential diagnosis, especially in those who have been exposed to fertility medications, since exposure to hormonal therapy might be a factor in carcinogenesis. Management is effective with multimodal therapy and close follow-up for the optimization of prognosis, improvement in quality of life, and reduction in long-term disability. This study highlights the potential link between fertility drugs and aggressive ovarian carcinoma and points to the need for larger studies to explore this relationship. Along with the advancement in assisted reproductive technology, administration of fertility medications has increased ever since, and its long-term health consequences must be kept under close follow-up amongst women. Understanding the potential risks with these medications is crucial to inform healthcare guidance and the safety of the patient population.

Limitations of the study

The small sample size of seven cases reflects the rarity of brain metastases in ovarian carcinoma but limits generalizability and advanced statistical analysis. Additionally, findings are constrained by single-center data and regional variations in healthcare access and treatment protocols.

Institutional Review Board Statement:

This study has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendment. This re-search has obtained ethical approval from Research and Ethics Committee, at Jordan University of Science and Technology with a reference number of 12/105/2017. We confirm that the privacy of the participants was saved, and the data was anonymized and maintained with confidentiality.

Informed Consent Statement:

The need for consent was waived by our institutional review board due to the retrospective nature of the study.

Data Availability Statement:

The original contributions presented in this study are included in the tables. Further inquiries can be directed to the corresponding author.

Author’s Contribution:

The all authors were involved in all steps of preparation of this article. Final proofreading was made by the first author.

Conflicts of interest:

There are no conflicts of interest.

Financial support and sponsorship:

None.