Startseite Reproductive outcomes in women with BRCA 1/2 germline mutations: A retrospective observational study and literature review
Artikel Open Access

Reproductive outcomes in women with BRCA 1/2 germline mutations: A retrospective observational study and literature review

  • Miriam Dellino , Antonio D’Amato , Gaia Battista , Gennaro Cormio , Antonella Vimercati , Vera Loizzi , Antonio Simone Laganà , Gianluca Raffaello Damiani , Alessandro Favilli , Sandro Gerli , Daniele La Forgia , Antonella Daniele , Vittorio Agrifoglio , Ettore Cicinelli , Amerigo Vitagliano und Andrea Etrusco EMAIL logo
Veröffentlicht/Copyright: 20. August 2024
Artikel downloaden (PDF)
Open Medicine
Aus der Zeitschrift Open Medicine Band 19 Heft 1

Abstract

Objective

To evaluate the reproductive outcomes of patients bearing BRCA-1 and BRCA-2 mutations.

Methods

In this retrospective observational cohort study, we assessed data from BRCA-1 and BRCA-2 carriers, analyzing demographics, oncological history, and reproductive outcomes. Statistical analysis compared BRCA-1 and BRCA-2 carriers. A thorough review of the literature was carried out.

Results

Fifty-eight patients were included. BRCA-1 and BRCA-2 mutations were equally distributed. Eighty-nine pregnancies occurred in our series, hesitated in 73 live births and 19 miscarriages. Mean age at first and last pregnancy was 27.8 ± 4.8 and 31.6 ± 4.8 years old. Thirty-nine patients have had at least one live birth (67.2%). Mean number of live births was 1.9 ± 0.6. Live birth rate (LBR) was 81.1% and miscarriage rate was 32.8%. Spontaneous fertility was unaltered, as evidenced by high LBR. Subgroup analysis revealed no significant differences between BRCA-1 and BRCA-2 carriers.

Conclusions

Our results shows that spontaneous reproductive outcomes in BRCA-mutated patients are reassuring. Despite evidence indicating a decrease in ovarian reserve among BRCA patients, this factor seems to not impact spontaneous fertility negatively. Further research is needed, and individuals with BRCA mutations should consider early family planning and fertility preservation in case of partner absence.

Graphical abstract

Despite evidence indicating a decrease in ovarian reserve among BRCA patients, this factor seems to not impact their spontaneous fertility negatively.

Keywords: BRCA mutations; reproductive outcomes; fertility preservation; breast cancer; ovarian cancer

1 Introduction

Approximately 5–10% of ovarian cancer (OC) and breast cancer (BC) are associated with inherited pathological variants in genes that increase susceptibility to cancer [1]. In a minority proportion, other types of female genital cancers may also be associated with BRCA mutations [2–4].

The most common pathogenetic variants involve the BRCA-1 and BRCA-2 genes and are estimated to affect between 1/300 and 1/800 individuals in the general population [5]. These genes have vital functions in the repair of double-stranded breaks (DSB) through the homologous recombination repair process [6]. The dysregulation of one of these genes is responsible for genomic instability, resulting in an increased risk of cancer [7].

Carriers of BRCA-1 and BRCA-2 mutations have a cumulative lifetime risk of developing BC and OC of up to 72–69% for BC and 44–17% for OC, respectively [8]. These types of oncogenic mutations in BRCA genes can occur as germline or somatic mutations. Germline mutations are responsible for BRCA-1 and BRCA-2-associated hereditary breast and ovarian cancer and follow autosomal dominant inheritance. Somatic mutations, on the other hand, characterize cases of “BRCAness” or “BRCA-like” and are not subject to vertical transmission [9,10].

Regarding OC, the vast majority of BRCA mutations are germline, while somatic mutations are observed in around 5–7% of cases [11]. On the other hand, approximately 1–5% of all individuals diagnosed with BC possess a germline mutation in either the BRCA-1 or BRCA-2 genes [12,13], while somatic mutations are found at about half the prevalence of germline mutations [14,15]. The type of mutation is not the only determining aspect when assessing cancer risk in offspring inheriting the BRCA-1 or BRCA-2 pathogenic variant. In fact, multiple factors come into play, including the penetrance of the pathogenic variant, as well as the gender and age of the individual carrying the variant [16].

According to the guidelines of the National Comprehensive Cancer Network, it is recommended that women who carry BRCA mutations consider undergoing risk-reducing salpingo-oophorectomy (RRSO) either between the ages of 35 and 40 or after completing childbearing [17]. Regarding individuals with BRCA-2 mutations, it might be reasonable to postpone RRSO until they reach the ages of 40–45, taking into account the later onset of OC in this group [17]. In a recent study involving 3,517 women who received BRCA testing, the average age at diagnosis of OC was 51.3 years for BRCA-1 and 58.3 years for BRCA-2 [18]. Evidence from multiple studies suggests that RRSO is linked to a reduction in the occurrence of OC and BC, together with a significant decrease in overall mortality rates [19,20]. Several studies have shown that carriers of the BRCA-1 mutation might experience impaired fertility and reproductive potential. In vitro, oocyte-specific knockdown of key genes involved in DSB repair (BRCA-1, ATM, MRE11, Rad51, but not BRCA-2) resulted in an increase in DNA breaks, eventually leading to lower primordial follicle counts and reduced survival, both in human and murine cells [21].

Alongside ovarian aging, the mutations could also be responsible for an increased rate of aneuploidy, since BRCA-1 and ATM are implicated in meiotic spindle assembly and cohesion between sister chromatids [22,23]. During oocyte cryopreservation cycles, BRCA-mutated patients had worse results in terms of retrieved oocytes compared to BRCA-negative ones [24]. Finally, Porcu et al. demonstrated that BRCA-1 patients exhibited significantly lower levels of anti-Müllerian hormone (AMH) compared to BC patients without BRCA mutation and control women, concluding that BRCA-1 patients could have a higher risk of developing premature ovarian insufficiency (POI), together with a lower ovarian reserve [25]. In the same publication, BRCA-2 patients did not show the same decrease [25].

Recently, thanks to technological advances and increased awareness among practitioners, patients are diagnosed with the mutation earlier than in the past. Considering this, at the time of diagnosis, healthy carriers of BRCA are usually young and have to face different decisions on issues related to contraception, fertility, and pregnancy. Indeed, individuals carrying BRCA-1 or BRCA-2 mutations face unique challenges when making decisions regarding family planning, including concerns about pregnancy outcomes and long-term health implications [26].

To date, little information exists about the relationship between BRCA mutations and spontaneous fertility. Thus, the objective of the study is to evaluate the spontaneous reproductive outcome in a cohort of women carrying BRCA1/2 germline mutations.

2 Methods

2.1 Study design

This is a retrospective observational cohort study. The authorization of the ethics committee was not necessary because the data have been collected in a prospective manner on an anonymous database. The study did not mean any modifications in clinical practice for patients included.

Furthermore, a comprehensive literature search was conducted on the following databases: PubMed/MEDLINE, SCOPUS, The Cochrane Library, Science Direct, and Web of Science. All the relevant studies published till September 2023 were screened using relevant search terms as appropriate. Additional articles that met the inclusion criteria were identified by searching through the reference lists of the included articles. Articles that were not written in English or did not focus specifically on the topic were excluded.

The search was conducted independently by two reviewers, and further supervised by a third, reliable member of the research group. Any discrepancies were resolved by discussion. Data were extracted and summarized using a narrative synthesis approach.

2.2 Inclusion criteria

We included all patients diagnosed with germline mutations of BRCA-1 or BRCA-2 who were followed at the gynecological and obstetric clinic of the University Hospital of Bari, Italy from 2000 to 2023 for whom information about their reproductive history was available.

All patients who had other concurrent genetic mutations, a history of oncological treatments unrelated to the mutations of interest in the study, were excluded.

2.3 Data collection

Between the years 2000 and 2023, data belonging to women of reproductive age diagnosed with BRCA mutations at the University Hospital of Bari were retrospectively gathered.

Women carrying the mutation undergo annual routine monitoring at the oncological gynecology outpatient of our unit. During the visits, reproductive aspects were also investigated, with data collection conducted anonymously during the appointments. Various aspects such as patient demographics, clinical presentation, oncology marker levels, surgical procedures (and eventual risk-reducing surgery performed), histological examination, survival rates, and reproductive outcomes were extracted from hospital records.

The cancer history of each patient has been carefully collected, as well as the obstetrical medical history: for each patient, either data regarding previous cancers – in particular OC and BC; eventual previous or current chemotherapy; age at mastectomy or at RRSO; and number of pregnancies, miscarriages, live births were gathered.

Data regarding age at first and at last pregnancy, eventual surgery before or after pregnancy, number of spontaneous births and cesarean sections, and eventual complications during or after pregnancy were also thoroughly examined.

2.4 Statistical analysis

Statistical analysis was conducted using SPSS Statistics (v.22). Continuous variables were reported as mean ± standard deviation, while categorical variables were presented as frequencies (absolute) and percentages (%).

We compared the baseline characteristics and reproductive outcomes of patients with BRCA-1 and BRCA-2 mutations using the Student’s t-test for normally distributed continuous variables, and contingency tables with the chi-square test or Fisher’s exact test for categorical variables as appropriate. A p-value less than 0.05 was considered statistically significant.

  1. Ethical approval: All procedures performed in this research were conducted in accordance with the 2013 Helsinki Declaration. Patients were informed about the protection of their data under the Privacy Act, and their written authorization was obtained specifically for the utilization of personal information only for scientific purposes.

  2. Informed consent: Each patient was provided with a descriptive study form. Informed consent was obtained from all individuals who agreed to be part of the study.

3 Results

3.1 Included patients

Applying our inclusion and exclusion criteria, 58 patients were included in the present study, 29 of them carrying the BRCA-1 mutation (50%) and 29 bearing BRCA-2 mutation (50%).

Mean age of the patients was 41.8 ± 7.9 years old as on January 2023. Mean age at menarche was 12.15 ± 1.4 years old. Thirty-seven patients underwent RRSO (63.8%), while 21 have not yet decided to undergo surgery (36.2%). Four out of 58 patients decided to undergo risk-reducing mastectomy (RRM) (6.9%). Mean age at RRSO was 42.2 ± 4.1 years, while mean age at RRM was 36.5 ± 5.0 years. Twenty-five out of 58 subsequently developed BC and underwent radical mastectomy (43.1%). Of these, 20 BC (80%) occurred before RRSO. Two patients (8%) underwent simultaneously radical mastectomy and RRSO after being diagnosed with BC (patient 1 at the age of 41, BRCA-2 mutated and patient 2 at the age of 45, BRCA-1 mutated). Finally, three patients (12%) underwent radical mastectomy for BC, while they did not undergo RRSO yet. No BC occurred after RRSO in our cohort. Among the 25 patients who underwent radical mastectomy for BC, 14 occurred among BRCA-1 patients (56%) and 11 (44%) in BRCA-2 patients. The difference is not statistically significant. Since these were all adjuvant bilateral RRSOs, the average time between BC diagnosis and the RRSO was 66.8 ± 83.6 months. On the other hand, only one patient developed OC, and thus underwent subsequent debulking surgery and adjuvant chemotherapy (1.7%).

At the last follow-up visit, all patients were confirmed to be alive. No patient has taken or is currently taking hormonal replacement therapy (HRT) after RRSO. Additional data regarding patients’ medical background and surgery can be consulted in Table 1.

Table 1

Patients’ characteristics and data regarding demographics, medical background, surgery they have undergone

Patient characteristics Data
No. of patients 58
BRCA-1 carriers 50% (29/58)
BRCA-2 carriers 50% (29/58)
Mean age, years (range) 41.8 ± 7.9 (19–50)

  1. BRCA-1

 43.4 ± 5.9

  1. BRCA-2

 40.8 ± 9.3
Mean age at menarche, years (range) 12.15 ± 1.4 (9–16)

  1. BRCA-1

 12.2 ± 1.6

  1. BRCA-2

 12.16 ± 1.3
Patients with history of RRSO (percentage) 63.8% (37/58)

  1. BRCA-1

 54.1% (20/37)

  1. BRCA-2

 45.9% (17/37)
Mean age at RRSO, years (range) 42.2 ± 4.1 (31–50)

  1. BRCA-1

 42.2 ± 4.5

  1. BRCA-2

 42.2 ± 3.7
Mean time from RRSO, months from today (range) 43.1 ± 23.4 (3–84)

  1. BRCA-1

 44.4 ± 3.2

  1. BRCA-2

 45.9 ± 25.5
Patients not undergoing RRSO (percentage) 36.2% (21/58)

  1. BRCA-1

 47.6% (10/21)

  1. BRCA-2

 52.4% (11/21)
Patients undergoing RRM (percentage) 6.9% (4/58)

  1. BRCA-1

 50% (2/4)

  1. BRCA-2

 50% (2/4)
Mean age at RRM, years (range) 37.25 ± 4.9 (31–43)

  1. BRCA-1

 33.5 ± 5.0

  1. BRCA-2

 40.5 ± 3.5
Subsequent BC with radical mastectomy (percentage) 43.1% (25/58)

  1. BRCA-1

 56% (14/25)

  1. BRCA-2

 44% (11/25)
Mean time from mastectomy, months from today (range) 90.7 ± 71.2 (3–300)

  1. BRCA-1

 99.8 ± 78.2

  1. BRCA-2

 99.2 ± 77.7
Subsequent OC (percentage) 1.7% (1/58)

  1. BRCA-1

 100% (1/1)

  1. BRCA-2

 0
Adjuvant chemotherapy (percentage) 1.7% (1/58)

  1. BRCA-1

 100% (1/1)

  1. BRCA-2

 0
Survival rate (percentage) 100% (58/58)
HRT 0 (0/58)

RRSO = risk-reducing salpingo-oophorectomy; RRM = risk-reducing mastectomy; BC = breast cancer; OC = ovarian cancer; HRT = hormonal replacement therapy.

3.2 Reproductive outcomes

Eighty-nine pregnancies occurred in our series, hesitated in 73 live births (67 from singleton pregnancies and 6 from twin pregnancies) and 19 miscarriages. Mean age at first and last pregnancy was 27.8 ± 4.8 and 31.6 ± 4.8 years for BRCA-1 and BRCA-2, respectively.

Thirty-nine patients have had at least one live birth (67.2%). The mean number of live births was 1.9 ± 0.6. Live birth rate (LBR) was 81.1% and miscarriage rate was 32.8%. Among the deliveries 43 occurred naturally (58.9%) and 30 via cesarean sections (41.1%).

No pregnancy occurred after RRSO. All pregnancies were reported spontaneous, and no patient reported having used assisted reproductive techniques (ARTs) to conceive.

Eleven patients developed complications of pregnancy (15.7%). Among these, one patient developed gestational cholestasis (1.4%), two patients fetal macrosomia (2.9%), one patient preeclampsia (1.4%), one patient anemia in pregnancy (1.4%), one patient fetal growth restriction (FGR) (1.4%), one patient placenta previa (1.4%), and one patient gestational diabetes (1.4%).

Data regarding obstetric outcomes and complications of the patients are summarized in Table 2.

Table 2

Summary of obstetric outcomes and complications of pregnancy of the patients

Obstetric outcomes Data
Overall pregnancies, no. 89
Spontaneous pregnancies 100% (89/89)
ARTs pregnancies 0% (0/89)
Singleton pregnancies 75.3% (67/89)
Twin pregnancies 3.4% (3/89)
Live births, no. 73
Miscarriages, no. 19
Primiparous 17.2% (10/58)
Multiparous 50% (29/58)
Nulliparous 31% (18/58)
Mean age at first pregnancy, years (range) 27.8 ± 4.8 (17–36)
Mean age at last pregnancy, years (range) 31.6 ± 4.8 (18–40)
Mean number of live births (range) 1.9 ± 0.6 (1–3)
LBR 81.1%
Miscarriage rate 32.8%
Natural deliveries 58.9% (43/73)
Cesarean sections 41.1% (30/73)
Twin pregnancy 4.1% (3/73)
Obstetric complications Data (%)
Obstetric complications 15.7% (11/70)
Fetal macrosomia 2.9% (2/70)
Gestational cholestasis 1.4% (1/70)
Preeclampsia 1.4% (1/70)
Anemia in pregnancy 1.4% (1/70)
FGR 1.4% (1/70)
Placenta previa 1.4% (1/70)
Gestational diabetes 1.4% (1/70)

ARTs = assisted reproductive techniques.

Obstetric complications are reported for the number of ongoing pregnancies, excluding the number of miscarriages.

3.3 Subgroup analysis

Subgroup analysis was conducted to investigate potential differences in various reproductive and demographic variables among patients with BRCA-1 and BRCA-2 mutations (Tables 3 and 4).

Table 3

Summary of BRCA-1 germline mutations and their functional implications in our cohort of patients

BRCA-1 mutation Genomic mutation Protein mutation Functional impact No. of patients
c.5329dupC; p.Gln1777ProfsTer74 c.5329dupC p.Gln1777ProfsTer74 Frameshift, premature termination (Ter74) 10.3% (3/29)
c.1687C > T; p.Gln563Ter; rs80356898 c.1687C > T p.Gln563Ter Premature termination (Ter) 6.9% (2/29)
c.5266dupC; p.Gln1756Profs*74 c.5266dupC p.Gln1756Profs*74 Frameshift, premature termination (Ter74) 20.7% (6/29)
NM_007294.4:c.5266dup; p.Gln1756ProfsTer74 NM_007294.4:c.5266dup p.Gln1756ProfsTer74 Frameshift, premature termination (Ter74) 3.4% (1/29)
c.5266dupC c.5266dupC — Frameshift, premature termination (Ter) 10.3% (3/29)
CNV CNV — CNV 3.4% (1/29)
VUS of intron 5: c.301 + 7G > A c.301 + 7G > A — VUS 3.4% (1/29)
c.65T > C; p.Leu22Ser c.65T > C p.Leu22Ser Missense (Leu22Ser) 10.3% (3/29)
c.4484G > T; p.Arg1495Met c.4484G > T p.Arg1495Met Missense (Arg1495Met) 3.4% (1/29)
c.190T > C; p.Cys64Arg c.190T > C p.Cys64Arg Missense (Cys64Arg) 3.4% (1/29)
c.798_799delTT; p.Ser267Lysfs (rs80357724) c.798_799delTT p.Ser267Lysfs Frameshift, premature termination (Terfs) 3.4% (1/29)
c.3228_3229delAG; p.Gly1077fs c.3228_3229delAG p.Gly1077fs Frameshift, premature termination (Ter) 3.4% (1/29)
No data — — — 17.2% (5/29)

VUS = variant of uncertain significance; CNV = copy number variation.

Mutations in the BRCA-1 and BRCA-2 genes were analyzed, with subsequent classification based on genomic and protein-level alterations.

Table 4

Summary of BRCA-2 germline mutations and their functional implications in our cohort of patients

BRCA-2 mutation Genomic mutation Protein mutation Functional impact No. of patients
c.1813dupA (p.Ile605Asnfs*11) c.1813dupA p.Ile605Asnfs*11 Frameshift, premature termination (Ter11) 3.4% (1/29)
c.1448_1451dupCAGT; p.Lys485Serfs*30 c.1448_1451dupCAGT p.Lys485Serfs*30 Frameshift, premature termination (Ter30) 13.8% (4/29)
c.3029_3039delGAACAGCTTCA; p.Arg1010Lysfs*2 c.3029_3039delGAACAGCTTCA p.Arg1010Lysfs*2 Frameshift, premature termination (Ter2) 6.9% (2/29)
c.6486_6489delACAA, p.Lys2162Asn*5 c.6486_6489delACAA p.Lys2162Asn*5 Frameshift, premature termination (Ter5) 3.4% (1/29)
c.1796_1800del; p.(Ser599*). C.5200G > A; p.(Glu1734Lys) c.1796_1800del; c.5200G > A p.Ser599*; p.Glu1734Lys Frameshift, premature termination (Ter), Missense (Glu1734Lys) 6.9% (2/29)
c.5796_5797delTA; p.His1932Glnfs*12 c.5796_5797delTA p.His1932Glnfs*12 Frameshift, premature termination (Ter12) 10.3% (3/29)
c.859G > A (V211I) c.859G > A p.Val211Ile Missense (Val211Ile) 3.4% (1/29)
c.2049_2050delTC; p.Gln684Glyfs*3 c.2049_2050delTC p.Gln684Glyfs*3 Frameshift, premature termination (Ter3) 3.4% (1/29)
c.1976_1800delCT; p.Ser599fs1 c.1976_1800delCT p.Ser599fs1 Frameshift, premature termination (Terfs*1) 13.8% (4/29)
c.2151T > A; p.Cys717Ter (rs876660512) c.2151T > A p.Cys717Ter Premature termination (Ter) 3.4% (1/29)
c.2151T > C; p.Cys717X of exon 11 c.2151T > C — Premature termination (Ter) 3.4% (1/29)
c.9097dupA; p.(Thr3033Asnfs*11) c.9097dupA p.Thr3033Asnfs*11 Frameshift, premature termination (Ter11) 3.4% (1/29)
c.2045_2046delTC; p.Gln684GlyfsTer3 c.2045_2046delTC p.Gln684GlyfsTer3 Frameshift, premature termination (Ter3) 3.4% (1/29)
p.Ser599* — p.Ser599* Premature termination (Ter) 3.4% (1/29)
VUS c.91T > G; p.Trp31Gly in heterozygosis c.91T > G p.Trp31Gly VUS 3.4% (1/29)
c.6131G > C; p.Gly2044Ala c.6131G > C p.Gly2044Ala Missense (Gly2044Ala) 3.4% (1/29)
c.6468_6469delTC; p.Gln2157IlefsTer18 c.6468_6469delTC p.Gln2157IlefsTer18 Frameshift, premature termination (Ter18) 3.4% (1/29)
No data — — — 6.9% (2/29)

VUS = variant of uncertain significance.

Specifically, we examined age, age at menarche, age at mastectomy, pregnancies, full-term births, preterm births, miscarriages, live births, age at first pregnancy, age at last pregnancy, number of spontaneous births, and number of cesarean sections. For each of these variables, we performed independent sample t-tests to compare the means between the two subgroups, considering both cases with presumed equal variances and those with non-presumed equal variances.

The results, as shown in Table 5, indicate that there were no statistically significant differences in these variables between the two subgroups.

Table 5

Results of independent samples t-tests for reproductive and demographic parameters among BRCA-1 and BRCA-2 patients

Statistical test No. of cases (N) Assumption of equal variances Significance (two-tailed) Mean difference Standard error of difference
Age BRCA-1: n = 29 Assume equal variances 0.162 2.9138 2.0579
BRCA-2: n = 29 Do not assume equal variances 0.167 2.9138 2.0737
Age at menarche BRCA-1: n = 29 Assume equal variances 0.861 0.105 0.591
BRCA-2: n = 29 Do not assume equal variances 0.871 0.105 0.634
Age at mastectomy BRCA-1: n = 15 Assume equal variances 0.587 −0.857 1.560
BRCA-2: n = 14 Do not assume equal variances 0.587 −0.857 1.558
Pregnancies BRCA-1: n = 29 Assume equal variances 0.482 −0.258 0.365
BRCA-2: n = 27 Do not assume equal variances 0.490 −0.258 0.371
Full-term births BRCA-1: n = 29 Assume equal variances 0.842 0.054 0.269
BRCA-2: n = 27 Do not assume equal variances 0.843 0.054 0.270
Preterm births BRCA-1: n = 29 Assume equal variances 0.520 −0.040 0.061
BRCA-2: n = 27 Do not assume equal variances 0.525 −0.040 0.062
Miscarriages BRCA-1: n = 29 Assume equal variances 0.239 −0.203 0.171
BRCA-2: n = 27 Do not assume equal variances 0.246 −0.203 0.173
Live births BRCA-1: n = 29 Assume equal variances 0.754 0.086 0.272
BRCA-2: n = 27 Do not assume equal variances 0.755 0.086 0.273
Age at first pregnancy BRCA-1: n = 28 Assume equal variances 0.779 1.071 3.792
BRCA-2: n = 26 Do not assume equal variances 0.779 1.071 3.793
Age at last pregnancy BRCA-1: n = 28 Assume equal variances 0.932 0.365 4.271
BRCA-2: n = 26 Do not assume equal variances 0.932 0.365 4.279
Number of spontaneous births BRCA-1: n = 29 Assume equal variances 0.391 −0.234 0.270
BRCA-2: n = 27 Do not assume equal variances 0.398 −0.234 0.274
Number of cesarean sections BRCA-1: n = 28 Assume equal variances 0.460 0.164 0.220
BRCA-2: n = 27 Do not assume equal variances 0.459 0.164 0.220

The significance level (two-tailed) indicates the p-value for each test. Mean differences and standard errors of differences are also provided. The tests assume equal variances in one set of data and do not assume equal variances in the other.

The lack of statistically significant differences suggests that the assumption of equal variances does not significantly impact the results for these reproductive and demographic variables.

4 Discussion

Healthy individuals and cancer patients who are carriers of germline pathogenic variants in BRCA-1/2 genes face multiple reproductive challenges that require appropriate counseling and expertise. As previously mentioned, most of the available preclinical evidence suggests that BRCA mutations could directly accelerate ovarian aging, reducing ovarian reserve both quantitatively and qualitatively [27,28].

On the other hand, our study, although on a small sample, shows that the spontaneous reproductive outcomes in BRCA-mutated patients are reassuring. The average number of children in this cohort 1.9 ± 0.6, and at least one live birth occurred in 67.2% of the patients. Only one case of infertility was certified, and the patient underwent IVF without success. The rest of the women did not attempt to have children. These data are consistent with those in the general population and with other studies in the same population [29,30]. Furthermore, the mean age at the first pregnancy in our cohort was 27.8 ± 4.8, which is lower than the Italian national average calculated in 2021, as well as the average number of children per woman being higher than 1.25, which is the latest Italian average [31]. It might be concluded, then, that while there may be a lower ovarian reserve in BRCA carriers compared to the general population according to the current evidence, this factor does not appear to negatively affect spontaneous fertility. Probably, the reduction in ovarian reserve is not reflected in fertility impairment if patients bearing BRCA mutations conceive at a younger age.

Provocatively, some have even discussed the possibility of heightened fertility in these women, countering the mutation’s impact, as if aiming to maximize reproductive potential within a narrower reproductive window [32]. Moreover, regarding spontaneous conception, our limited dataset would show that women carrying the mutation exhibit a higher average number of offspring compared to non-affected ones. This result appears in line with studies with greater statistical power [32].

Another major concern among carriers of pathogenic BRCA-1/2 variants is the potential higher risk of premature ovarian failure (POI) [33]. In our series we have not observed any case of POI.

How do we counsel a patient with a known BRCA germline mutation about fertility then? While in the past we have been addressing these women at the time of cancer diagnosis, their offspring will already be genetically mapped. This represents a significant aspect of the topic. While the current goal is primarily on mapping these patients, soon the role of the practitioner will shift toward counseling individuals who are already aware of their mutation from childhood, or even before birth.

At present, more emphasis should be given on advising women, from a reproductive perspective, to plan their families early in life. In cases of partner absence, cryopreserving their oocytes at a young age may be necessary, potentially requiring multiple controlled ovarian stimulation (COS) cycles, as their ovarian reserve diminishes more rapidly than in other women [25]. A timely execution and a greater consideration of prophylactic procedures should be considered mandatory in these patients. Should this be the way forward, every strategy aimed at preserving the best quality oocytes possible must be implemented [34,35].

If early-stage ovarian malignancy is detected, patients can be referred for fertility-sparing treatments. However, as with other fertility-sparing treatments for gynecologic malignancies [36–38], which, thanks to new technologies applicable to surgery [39,40], are increasingly effective, these patients should also be referred for radical surgery once the desire for offspring is satisfied. To date, it would also seem that fertility or endocrine function preservation techniques such as preservation of ovarian tissue and its subsequent re-implantation would not be recommended for patients with BRCA mutations [41].

As discussed earlier, BRCA1 and 2 are known to be involved in the DNA repair mechanism, through ATM-mediated regulation of DSB repair [6,7]. DBS DNA repair mechanisms play an important role in ovarian aging. A decrease in their efficiency causes not only an accelerated apoptotic loss of follicles with lethal mutations, but also an increase in meiotic errors and a reduced quality of oocytes, with an increase in the number of aneuploidies [22]. There is preclinical evidence that transgenic mice with defective BRCA genes have a reduced ovarian response to stimulation and decreased reproductive potential [21].

AMH levels are considered a quantitative marker of ovarian reserve, although not predictive of the possibility of spontaneous pregnancy [42]. In some studies, AMH levels were significantly lower in women carrying pathogenic variants in BRCA-1 or BRCA-2 or both genes [43], while other studies have reported no significant differences with controls [44,45].

Clinical studies describing a decrease in oocyte quality in human carriers of pathogenic BRCA variants (i.e., an increase in aneuploidies) are still lacking, while age at natural menopause among BRCA carriers is difficult to ascertain, due to various types of selection bias, different control groups, and small study population [46].

An additional problem related to the shortened window of reproductive opportunities is the recommendation of RRSO at a young age [5]. In our series, no patient has gone through menopause yet. 37/58 underwent RRSO (63.8%), while 21/58 did not undergo risk-reducing surgery yet (36.2%). In the first group, mean age at RRSO was 42.1 years for BRCA-1 and 42.3 for BRCA-2. Mean time from RRSO was 43.1 months from today. Although salpingectomy with delayed oophorectomy has been suggested as an option to preserve ovarian function, this strategy is not the gold standard and should not be recommended [47].

There are limited data on fertility outcomes in patients with BRCA-mutated BC. Oktay et al. first described in 2010 reduced ovarian response and lower oocyte count for fertility preservation in patients with BRCA-mutated cancer [48]. Since then, some other studies have found a worse quantitative response to COS in this cohort [48], while others reported no difference with non-mutated BC patients [49]. Similarly, some studies have reported lower levels of AMH at BC diagnosis in BRCA-mutated patients [21], while others did not report a significant difference [49]. Given these different problems, healthy carriers should be advised not to delay pregnancy beyond 35 years of age [50].

In addition, several studies have investigated the effect of parity on BC risk in healthy carriers of pathogenic BRCA variants [51]. About this topic, our study shows that most patients were diagnosed with BC after having at least one live birth (21/25 – 84%). A large prospective study showed that women with pathogenic BRCA-1 variants who had two, three, four, or more full-term pregnancies were at 21, 30, and 50% decreased risk of BC compared to women with a single full-term pregnancy [51]. In contrast, women with pathogenic BRCA-2 variants with multiple pregnancies had a significantly higher risk of developing BC [51]. However, this topic remains controversial due to the differences reported in carriers of pathogenic variants BRCA-1 and BRCA-2 and the different effects of pregnancy on the risk of BC according to age even in the general population not carrying BRCA mutations. In addition, it must also be considered that in the general population, healthy women have a transient increased risk of BC after pregnancy and the increased risk is greater for women with a family history of BC and for women with a pregnancy in old age [52]. This increased risk was attributed to the growth-promoting effect of the endocrinological environment of pregnancy on existing pre-malignant or malignant BC lesions that occur more frequently in later life [52]. In addition, differences between BRCA-1 and BRCA-2 carriers have been found in the literature in relation to the effect of breastfeeding on BC risk. In carriers of pathogenic variants BRCA-1, breastfeeding for at least 1 year reduces the risk of BC (OR = 0.68; 95% CI from 0.52 to 0.91; P = 0.008), while no effect has been described for healthy BRCA2 carriers [53].

Therefore, the timing of bilateral RRM in healthy BRCA carriers remains a matter of debate. On the one hand, breast removal before pregnancy constantly reduces the risk of subsequent BC and the need for careful monitoring during pregnancy and lactation.

On the other hand, many women highly appreciate the benefits of breastfeeding their babies and are reluctant to undergo surgery before pregnancy. For the considerations mentioned above, it is clear that the counseling of young carriers of BRCA pathogenic variants seeking pregnancy is complex and should consider risk estimates based on family history, age, and breast density, but also personal values on reproductive choices, which remain extremely sensitive and personal [26].

The woman chooses to keep the breast and postpone bilateral RRM, careful monitoring with breast ultrasound during pregnancy and with breast ultrasound and mammography during lactation should be planned. In addition, none of our patients had pregnancy after BC. In this group of patients, current data show that subsequent pregnancy does not increase BC-related events [54]. In BC patients requiring 5–10 years of adjuvant endocrine therapy (ET) including BRCA carriers, an international clinical trial, which recently completed target accumulation, is evaluating the safety and feasibility of temporary interruption of ET after at least 18 months, in order to enable pregnancy [55].

In addition, a large international study has recently shown that, regardless of receptor status and particularly for carriers of pathogenic BRCA-1 variants, pregnancy after BC appears to be safe without negative consequences on maternal prognosis or fetal outcomes [56]. Although this study included a significant number of patients, it had some limitations including short-term follow-up (∼4 years follow-up from pregnancy) and limited power to detect differences particularly in BRCA-2 carriers [56]. Moreover, the retrospective nature of this and other studies represents an important limitation that does not allow definitive and strong conclusions to be drawn. Another data to be considered is represented by the high BC rate (43.1%) in our cohort. This parameter is likely attributed to the fact that more than half of the patients received their BRCA diagnosis following a BC diagnosis.

The main limitations of our study were the small sample size and the retrospective design. The main strengths of this study include the long follow-up period, the rigorous sample selection, and its originality.

In conclusion, spontaneous fertility remained unaffected in our cohort of women with BRCA germline variants. These findings are promising and hold significant implications for counseling young patients with BRCA mutations. While there is considerable interest in this field, the absence of large prospective studies on these subjects underscores the necessity for further research endeavors. Moreover, misconceptions persist among healthcare professionals and patients, often resulting in fragmented and suboptimal care.

Since the reproductive window may be narrower compared to the general population, individuals carrying BRCA germline variants should be encouraged to complete their family planning at a younger age and undergo comprehensive breast follow-up examinations during pregnancy and breastfeeding if they choose to retain their breasts. Nevertheless, for patients with BRCA-mutated BC, subsequent pregnancies after receiving appropriate treatment and follow-up do not seem to increase the risk of BC recurrence and should not be discouraged.

# These authors contributed equally to this work (co-first).

## These authors contributed equally to this work (co-last).

Acknowledgement

Not applicable.

  1. Funding information: This study was not funded.

  2. Author contributions: M.D., A.D’a. A.V., and A.E.: study design and project development; G.B., G.C., A.V., V.L., V.A., A.Dan., E.C., and G.R.D.: data collection; A.S.L. A.F. S.G., and D.L.F.: data analysis; A.V. and A.E.: manuscript writing; M.D. and A.D’a. manuscript editing and final approval. All the authors conform the International Committee of Medical Journal Editors criteria for authorship, contributed to the intellectual content of the study and gave approval for the final version of the article. The authors alone are responsible for the content and writing of the article.

  3. Conflict of interest: Dr Antonio Simone Laganà and Andrea Etrusco serve as Editors in Open Medicine but it did not affect the peer-review process. The authors have no proprietary, financial, professional, or other personal interest of any nature in any product, service, or company.

  4. Data availability statement: All data generated or analyzed during this study are included in this published article.

References

[1] Evans O, Gaba F, Manchanda R. Population-based genetic testing for women’s cancer prevention. Best Pract Res Clin Obstet Gynaecol. 2020 May;65:139–53.10.1016/j.bpobgyn.2020.02.007Suche in Google Scholar PubMed

[2] Yousif HMA, Mohammed RAA. Alteration of BRCA-1 tumor suppressor gene expression in serous and mucinous ovarian neoplasms in the benign-borderline-malignant pathway. Curr Probl Cancer. 2019 Aug;43(4):377–85.10.1016/j.currproblcancer.2018.10.003Suche in Google Scholar PubMed

[3] Pecorino B, Laganà AS, Mereu L, Ferrara M, Carrara G, Etrusco A, et al. Evaluation of borderline ovarian tumor recurrence rate after surgery with or without fertility-sparing approach: results of a retrospective analysis. Healthcare (Basel). 2023 Jul;11(13):1922.10.3390/healthcare11131922Suche in Google Scholar PubMed PubMed Central

[4] Matanes E, Volodarsky-Perel A, Eisenberg N, Rottenstreich M, Yasmeen A, Mitric C, et al. Endometrial cancer in germline BRCA mutation carriers: a systematic review and meta-analysis. J Minim Invasive Gynecol. 2021 May;28(5):947–56.10.1016/j.jmig.2020.11.023Suche in Google Scholar PubMed

[5] Paluch-Shimon S, Cardoso F, Sessa C, Balmana J, Cardoso MJ, Gilbert F, et al. Prevention and screening in BRCA mutation carriers and other breast/ovarian hereditary cancer syndromes: ESMO Clinical Practice Guidelines for cancer prevention and screening. Ann Oncol. 2016 Sep;27(suppl 5):v103–10.10.1093/annonc/mdw327Suche in Google Scholar PubMed

[6] O’Donovan PJ, Livingston DM. BRCA1 and BRCA2: breast/ovarian cancer susceptibility gene products and participants in DNA double-strand break repair. Carcinogenesis. 2010 Jun;31(6):961–7.10.1093/carcin/bgq069Suche in Google Scholar PubMed

[7] Honrado E, Benítez J, Palacios J. The molecular pathology of hereditary breast cancer: genetic testing and therapeutic implications. Mod Pathol. 2005 Oct;18(10):1305–20.10.1038/modpathol.3800453Suche in Google Scholar PubMed

[8] Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA. 2017 Jun;317(23):2402–16.Suche in Google Scholar

[9] Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011 Jun;474(7353):609–15.10.1038/nature10166Suche in Google Scholar PubMed PubMed Central

[10] Turner N, Tutt A, Ashworth A. Hallmarks of ‘BRCAness’ in sporadic cancers. Nat Rev Cancer. 2004 Oct;4(10):814–9.10.1038/nrc1457Suche in Google Scholar PubMed

[11] Moschetta M, George A, Kaye SB, Banerjee S. BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer. Ann Oncol. 2016 Aug;27(8):1449–55.10.1093/annonc/mdw142Suche in Google Scholar PubMed

[12] John EM, Miron A, Gong G, Phipps AI, Felberg A, Li FP, et al. Prevalence of pathogenic BRCA1 mutation carriers in 5 US racial/ethnic groups. JAMA. 2007 Dec;298(24):2869–76.10.1001/jama.298.24.2869Suche in Google Scholar PubMed

[13] Malone KE, Daling JR, Doody DR, Hsu L, Bernstein L, Coates RJ, et al. Prevalence and predictors of BRCA1 and BRCA2 mutations in a population-based study of breast cancer in white and black American women ages 35 to 64 years. Cancer Res. 2006 Aug;66(16):8297–308.10.1158/0008-5472.CAN-06-0503Suche in Google Scholar PubMed

[14] Loboda AP, Adonin LS, Zvereva SD, Guschin DY, Korneenko TV, Telegina AV, et al. BRCA mutations – the Achilles heel of breast, ovarian and other epithelial cancers. Int J Mol Sci. 2023 Mar;24(5):4982.10.3390/ijms24054982Suche in Google Scholar PubMed PubMed Central

[15] Winter C, Nilsson MP, Olsson E, George AM, Chen Y, Kvist A, et al. Targeted sequencing of BRCA1 and BRCA2 across a large unselected breast cancer cohort suggests that one-third of mutations are somatic. Ann Oncol. 2016 Aug;27(8):1532–8.10.1093/annonc/mdw209Suche in Google Scholar PubMed PubMed Central

[16] Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Kwan E, et al. Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet. 2001 Mar;68(3):700–10.10.1086/318787Suche in Google Scholar PubMed PubMed Central

[17] Daly MB, Pal T, Berry MP, Buys SS, Dickson P, Domchek SM, et al. Genetic/familial high-risk assessment: breast, ovarian, and pancreatic, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2021 Jan;19(1):77–102.Suche in Google Scholar

[18] Sekine M, Enomoto T, Arai M, Den H, Nomura H, Ikeuchi T, et al. Differences in age at diagnosis of ovarian cancer for each BRCA mutation type in Japan: optimal timing to carry out risk-reducing salpingo-oophorectomy. J Gynecol Oncol. 2022 Mar;33(4):e46.10.3802/jgo.2022.33.e46Suche in Google Scholar PubMed PubMed Central

[19] Eleje GU, Eke AC, Ezebialu IU, Ikechebelu JI, Ugwu EO, Okonkwo OO. Risk-reducing bilateral salpingo-oophorectomy in women with BRCA1 or BRCA2 mutations. Cochrane Database Syst Rev. 2018 Aug;8(8):CD012464.10.1002/14651858.CD012464.pub2Suche in Google Scholar PubMed PubMed Central

[20] Marchetti C, De Felice F, Palaia I, Perniola G, Musella A, Musio D, et al. Risk-reducing salpingo-oophorectomy: a meta-analysis on impact on ovarian cancer risk and all cause mortality in BRCA 1 and BRCA 2 mutation carriers. BMC Womens Health. 2014 Dec;14:150.10.1186/s12905-014-0150-5Suche in Google Scholar PubMed PubMed Central

[21] Titus S, Li F, Stobezki R, Akula K, Unsal E, Jeong K, et al. Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans. Sci Transl Med. 2013 Feb;5(172):172ra21.10.1126/scitranslmed.3004925Suche in Google Scholar PubMed PubMed Central

[22] Turan V, Oktay K. BRCA-related ATM-mediated DNA double-strand break repair and ovarian aging. Hum Reprod Update. 2020 Jan;26(1):43–57.10.1093/humupd/dmz043Suche in Google Scholar PubMed PubMed Central

[23] Oktay K, Turan V, Titus S, Stobezki R, Liu L. BRCA mutations, DNA repair deficiency, and ovarian aging. Biol Reprod. 2015 Sep;93(3):67.10.1095/biolreprod.115.132290Suche in Google Scholar PubMed PubMed Central

[24] Lambertini M, Goldrat O, Ferreira AR, Dechene J, Azim Jr HA, Desir J, et al. Reproductive potential and performance of fertility preservation strategies in BRCA-mutated breast cancer patients. Ann Oncol. 2018 Jan;29(1):237–43.10.1093/annonc/mdx639Suche in Google Scholar PubMed

[25] Porcu E, Cillo GM, Cipriani L, Sacilotto F, Notarangelo L, Damiano G, et al. Impact of BRCA1 and BRCA2 mutations on ovarian reserve and fertility preservation outcomes in young women with breast cancer. J Assist Reprod Genet. 2020 Mar;37(3):709–15.10.1007/s10815-019-01658-9Suche in Google Scholar PubMed PubMed Central

[26] Buonomo B, Massarotti C, Dellino M, Anserini P, Ferrari A, Campanella M, et al. Reproductive issues in carriers of germline pathogenic variants in the BRCA1/2 genes: an expert meeting. BMC Med. 2021 Sep;19(1):205.10.1186/s12916-021-02081-7Suche in Google Scholar PubMed PubMed Central

[27] Wang ET, Pisarska MD, Bresee C, Chen YDI, Lester J, Afshar Y, et al. BRCA1 germline mutations may be associated with reduced ovarian reserve. Fertil Steril. 2014 Dec;102(6):1723–8.10.1016/j.fertnstert.2014.08.014Suche in Google Scholar PubMed PubMed Central

[28] Giordano S, Garrett-Mayer E, Mittal N, Smith K, Shulman L, Passaglia C, et al. Association of BRCA1 mutations with impaired ovarian reserve: connection between infertility and breast/ovarian cancer risk. J Adolesc Young Adult Oncol. 2016 Dec;5(4):337–43.10.1089/jayao.2016.0009Suche in Google Scholar PubMed PubMed Central

[29] Statistics | Eurostat [Internet]. [cited 2023 Aug 21]. Available from: https://ec.europa.eu/eurostat/databrowser/view/demo_find/default/table?lang=en.Suche in Google Scholar

[30] Kufel-Grabowska J, Podolak A, Maliszewski D, Bartoszkiewicz M, Ramlau R, Lukaszuk K. Fertility counseling in BRCA1/2-mutated women with breast cancer and healthy individuals. J Clin Med. 2022 Jan;11(14):3996.10.3390/jcm11143996Suche in Google Scholar PubMed PubMed Central

[31] Istituto Nazionale di Statistica [ISTAT]; 2021. Report Natalità 2021. https://www.istat.it/it/files/2022/12/report-natalita-2021.pdf.Suche in Google Scholar

[32] Kwiatkowski F, Arbre M, Bidet Y, Laquet C, Uhrhammer N, Bignon YJ. BRCA mutations increase fertility in families at hereditary breast/ovarian cancer risk. Plos One. 2015 Jun;10(6):e0127363.10.1371/journal.pone.0127363Suche in Google Scholar PubMed PubMed Central

[33] Zhang X, Niu J, Che T, Zhu Y, Zhang H, Qu J. Fertility preservation in BRCA mutation carriers – efficacy and safety issues: a review. Reprod Biol Endocrinol. 2020 Feb;18(1):11.10.1186/s12958-019-0561-0Suche in Google Scholar PubMed PubMed Central

[34] Etrusco A, Laganà AS, Chiantera V, Buzzaccarini G, Unfer V. Myo-inositol in assisted reproductive technology from bench to bedside. Trends Endocrinol Metab. 2024 Jan;35(1):74–83.10.1016/j.tem.2023.09.005Suche in Google Scholar PubMed

[35] Dragotto J, Buzzaccarini G, Etrusco A, Laganà AS, Venezia R, Terzic S, et al. Effects of low luteinizing hormone serum levels on oocyte retrieval, fertilization rate, and embryo quality during controlled ovarian stimulation: results from a prospective cohort analysis. Gynecol Obstet Invest. 2024;89(1):50–8.10.1159/000534860Suche in Google Scholar PubMed

[36] Gullo G, Etrusco A, Cucinella G, Perino A, Chiantera V, Laganà AS, et al. Fertility-sparing approach in women affected by stage I and low-grade endometrial carcinoma: an updated overview. Int J Mol Sci. 2021 Oct;22(21):11825.10.3390/ijms222111825Suche in Google Scholar PubMed PubMed Central

[37] Etrusco A, Laganà AS, Chiantera V, Mikuš M, Arsalan HM, d’Amati A, et al. Reproductive and oncologic outcomes in young women with stage IA and grade 2 endometrial carcinoma undergoing fertility-sparing treatment: a systematic review. Biomolecules. 2024 Mar;14(3):306.10.3390/biom14030306Suche in Google Scholar PubMed PubMed Central

[38] D’Amato A, Riemma G, Agrifoglio V, Chiantera V, Laganà AS, Mikuš M, et al. Reproductive outcomes in young women with early-stage cervical cancer greater than 2 cm undergoing fertility-sparing treatment: a systematic review. Medicina (Kaunas). 2024 Apr;60(4):608.10.3390/medicina60040608Suche in Google Scholar PubMed PubMed Central

[39] Etrusco A, Buzzaccarini G, Laganà AS, Chiantera V, Vitale SG, Angioni S, et al. Use of diode laser in hysteroscopy for the management of intrauterine pathology: a systematic review. Diagnostics (Basel). 2024 Feb 2;14(3):327.10.3390/diagnostics14030327Suche in Google Scholar PubMed PubMed Central

[40] Etrusco A, Laganà AS, Chiantera V, Gerli S, Carugno J, Sorrentino F, et al. Efficacy, safety, and feasibility of the treatment of intrauterine pathologies with the mini-resectoscope: a systematic review. Int J Gynaecol Obstet. 2024;166(2):527–37.10.1002/ijgo.15393Suche in Google Scholar PubMed

[41] Gullo G, Etrusco A, Cucinella G, Basile G, Fabio M, Perino A, et al. Ovarian tissue cryopreservation and transplantation in menopause: new perspective of therapy in postmenopausal women and the importance of ethical and legal frameworks. Eur Rev Med Pharmacol Sci. 2022 Dec;26(24):9107–16.Suche in Google Scholar

[42] Streuli I, de Mouzon J, Paccolat C, Chapron C, Petignat P, Irion OP, et al. AMH concentration is not related to effective time to pregnancy in women who conceive naturally. Reprod Biomed Online. 2014 Feb;28(2):216–24.10.1016/j.rbmo.2013.10.007Suche in Google Scholar PubMed

[43] Ben-Aharon I, Levi M, Margel D, Yerushalmi R, Rizel S, Perry S, et al. Premature ovarian aging in BRCA carriers: a prototype of systemic precocious aging? Oncotarget. 2018 Mar 23;9(22):15931–41.10.18632/oncotarget.24638Suche in Google Scholar PubMed PubMed Central

[44] van Tilborg TC, Derks-Smeets IAP, Bos AME, Oosterwijk JC, van Golde RJ, de Die-Smulders CE, et al. Serum AMH levels in healthy women from BRCA1/2 mutated families: are they reduced? Hum Reprod. 2016 Nov;31(11):2651–9.10.1093/humrep/dew242Suche in Google Scholar PubMed

[45] Michaelson-Cohen R, Mor P, Srebnik N, Beller U, Levy-Lahad E, Eldar-Geva T. BRCA mutation carriers do not have compromised ovarian reserve. Int J Gynecol Cancer. 2014 Feb;24(2):233–7.10.1097/IGC.0000000000000058Suche in Google Scholar PubMed

[46] Finch A, Valentini A, Greenblatt E, Lynch HT, Ghadirian P, Armel S, et al. Frequency of premature menopause in women who carry a BRCA1 or BRCA2 mutation. Fertil Steril. 2013 May;99(6):1724–8.10.1016/j.fertnstert.2013.01.109Suche in Google Scholar PubMed

[47] Tomao F, Di Pinto A, Sassu CM, Bardhi E, Di Donato V, Muzii L, et al. Fertility preservation in ovarian tumours. Ecancermedicalscience. 2018;12:885.10.3332/ecancer.2018.885Suche in Google Scholar PubMed PubMed Central

[48] Oktay K, Kim JY, Barad D, Babayev SN. Association of BRCA1 mutations with occult primary ovarian insufficiency: a possible explanation for the link between infertility and breast/ovarian cancer risks. JCO. 2010 Jan;28(2):240–4.10.1200/JCO.2009.24.2057Suche in Google Scholar PubMed PubMed Central

[49] Son KA, Lee DY, Choi D. Association of BRCA mutations and anti-müllerian hormone level in young breast cancer patients. Front Endocrinol. 2019;10. [cited 2023 Jul 27]. https://www.frontiersin.org/articles/10.3389/fendo.2019.00235.10.3389/fendo.2019.00235Suche in Google Scholar PubMed PubMed Central

[50] Daum H, Peretz T, Laufer N. BRCA mutations and reproduction. Fertil Steril. 2018 Jan;109(1):33–8.10.1016/j.fertnstert.2017.12.004Suche in Google Scholar PubMed

[51] Terry MB, Liao Y, Kast K, Antoniou AC, McDonald JA, Mooij TM, et al. The influence of number and timing of pregnancies on breast cancer risk for women with BRCA1 or BRCA2 mutations. JNCI Cancer Spectr. 2018 Oct;2(4):pky078.Suche in Google Scholar

[52] Albrektsen G, Heuch I, Thoresen S, Kvåle G. Clinical stage of breast cancer by parity, age at birth, and time since birth: a progressive effect of pregnancy hormones? Cancer Epidemiol Biomarkers Prev. 2006 Jan;15(1):65–9.10.1158/1055-9965.EPI-05-0634Suche in Google Scholar PubMed

[53] Kotsopoulos J, Lubinski J, Salmena L, Lynch HT, Kim-Sing C, Foulkes WD, et al. Breastfeeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res. 2012;14(2):R42.10.1186/bcr3138Suche in Google Scholar PubMed PubMed Central

[54] Lambertini M, Blondeaux E, Bruzzone M, Perachino M, Anderson RA, de Azambuja E, et al. Pregnancy after breast cancer: a systematic review and meta-analysis. JCO. 2021 Oct;39(29):3293–305.10.1200/JCO.21.00535Suche in Google Scholar PubMed

[55] Azim HA, Ameye L, Paesmans M, Lambertini M. Reply to S. A. Narod et al. JCO. 2020 Dec;38(36):4352–4.10.1200/JCO.20.02850Suche in Google Scholar PubMed

[56] Lambertini M, Ameye L, Hamy AS, Zingarello A, Poorvu PD, Carrasco E, et al. Pregnancy after breast cancer in patients with germline BRCA mutations. JCO. 2020 Sep;38(26):3012–23.10.1200/JCO.19.02399Suche in Google Scholar PubMed

Received: 2024-03-21
Revised: 2024-05-23
Accepted: 2024-06-27
Published Online: 2024-08-20

© 2024 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Artikel in diesem Heft

  1. Research Articles
  2. EDNRB inhibits the growth and migration of prostate cancer cells by activating the cGMP-PKG pathway
  3. STK11 (LKB1) mutation suppresses ferroptosis in lung adenocarcinoma by facilitating monounsaturated fatty acid synthesis
  4. Association of SOX6 gene polymorphisms with Kashin-Beck disease risk in the Chinese Han population
  5. The pyroptosis-related signature predicts prognosis and influences the tumor immune microenvironment in dedifferentiated liposarcoma
  6. METTL3 attenuates ferroptosis sensitivity in lung cancer via modulating TFRC
  7. Identification and validation of molecular subtypes and prognostic signature for stage I and stage II gastric cancer based on neutrophil extracellular traps
  8. Novel lumbar plexus block versus femoral nerve block for analgesia and motor recovery after total knee arthroplasty
  9. Correlation between ABCB1 and OLIG2 polymorphisms and the severity and prognosis of patients with cerebral infarction
  10. Study on the radiotherapy effect and serum neutral granulocyte lymphocyte ratio and inflammatory factor expression of nasopharyngeal carcinoma
  11. Transcriptome analysis of effects of Tecrl deficiency on cardiometabolic and calcium regulation in cardiac tissue
  12. Aflatoxin B1 induces infertility, fetal deformities, and potential therapies
  13. Serum levels of HMW adiponectin and its receptors are associated with cytokine levels and clinical characteristics in chronic obstructive pulmonary disease
  14. METTL3-mediated methylation of CYP2C19 mRNA may aggravate clopidogrel resistance in ischemic stroke patients
  15. Understand how machine learning impact lung cancer research from 2010 to 2021: A bibliometric analysis
  16. Pressure ulcers in German hospitals: Analysis of reimbursement and length of stay
  17. Metformin plus L-carnitine enhances brown/beige adipose tissue activity via Nrf2/HO-1 signaling to reduce lipid accumulation and inflammation in murine obesity
  18. Downregulation of carbonic anhydrase IX expression in mouse xenograft nasopharyngeal carcinoma model via doxorubicin nanobubble combined with ultrasound
  19. Feasibility of 3-dimensional printed models in simulated training and teaching of transcatheter aortic valve replacement
  20. miR-335-3p improves type II diabetes mellitus by IGF-1 regulating macrophage polarization
  21. The analyses of human MCPH1 DNA repair machinery and genetic variations
  22. Activation of Piezo1 increases the sensitivity of breast cancer to hyperthermia therapy
  23. Comprehensive analysis based on the disulfidptosis-related genes identifies hub genes and immune infiltration for pancreatic adenocarcinoma
  24. Changes of serum CA125 and PGE2 before and after high-intensity focused ultrasound combined with GnRH-a in treatment of patients with adenomyosis
  25. The clinical value of the hepatic venous pressure gradient in patients undergoing hepatic resection for hepatocellular carcinoma with or without liver cirrhosis
  26. Development and validation of a novel model to predict pulmonary embolism in cardiology suspected patients: A 10-year retrospective analysis
  27. Downregulation of lncRNA XLOC_032768 in diabetic patients predicts the occurrence of diabetic nephropathy
  28. Circ_0051428 targeting miR-885-3p/MMP2 axis enhances the malignancy of cervical cancer
  29. Effectiveness of ginkgo diterpene lactone meglumine on cognitive function in patients with acute ischemic stroke
  30. The construction of a novel prognostic prediction model for glioma based on GWAS-identified prognostic-related risk loci
  31. Evaluating the impact of childhood BMI on the risk of coronavirus disease 2019: A Mendelian randomization study
  32. Lactate dehydrogenase to albumin ratio is associated with in-hospital mortality in patients with acute heart failure: Data from the MIMIC-III database
  33. CD36-mediated podocyte lipotoxicity promotes foot process effacement
  34. Efficacy of etonogestrel subcutaneous implants versus the levonorgestrel-releasing intrauterine system in the conservative treatment of adenomyosis
  35. FLRT2 mediates chondrogenesis of nasal septal cartilage and mandibular condyle cartilage
  36. Challenges in treating primary immune thrombocytopenia patients undergoing COVID-19 vaccination: A retrospective study
  37. Let-7 family regulates HaCaT cell proliferation and apoptosis via the ΔNp63/PI3K/AKT pathway
  38. Phospholipid transfer protein ameliorates sepsis-induced cardiac dysfunction through NLRP3 inflammasome inhibition
  39. Postoperative cognitive dysfunction in elderly patients with colorectal cancer: A randomized controlled study comparing goal-directed and conventional fluid therapy
  40. Long-pulsed ultrasound-mediated microbubble thrombolysis in a rat model of microvascular obstruction
  41. High SEC61A1 expression predicts poor outcome of acute myeloid leukemia
  42. Comparison of polymerase chain reaction and next-generation sequencing with conventional urine culture for the diagnosis of urinary tract infections: A meta-analysis
  43. Secreted frizzled-related protein 5 protects against renal fibrosis by inhibiting Wnt/β-catenin pathway
  44. Pan-cancer and single-cell analysis of actin cytoskeleton genes related to disulfidptosis
  45. Overexpression of miR-532-5p restrains oxidative stress response of chondrocytes in nontraumatic osteonecrosis of the femoral head by inhibiting ABL1
  46. Autologous liver transplantation for unresectable hepatobiliary malignancies in enhanced recovery after surgery model
  47. Clinical analysis of incomplete rupture of the uterus secondary to previous cesarean section
  48. Abnormal sleep duration is associated with sarcopenia in older Chinese people: A large retrospective cross-sectional study
  49. No genetic causality between obesity and benign paroxysmal vertigo: A two-sample Mendelian randomization study
  50. Identification and validation of autophagy-related genes in SSc
  51. Long non-coding RNA SRA1 suppresses radiotherapy resistance in esophageal squamous cell carcinoma by modulating glycolytic reprogramming
  52. Evaluation of quality of life in patients with schizophrenia: An inpatient social welfare institution-based cross-sectional study
  53. The possible role of oxidative stress marker glutathione in the assessment of cognitive impairment in multiple sclerosis
  54. Compilation of a self-management assessment scale for postoperative patients with aortic dissection
  55. Left atrial appendage closure in conjunction with radiofrequency ablation: Effects on left atrial functioning in patients with paroxysmal atrial fibrillation
  56. Effect of anterior femoral cortical notch grade on postoperative function and complications during TKA surgery: A multicenter, retrospective study
  57. Clinical characteristics and assessment of risk factors in patients with influenza A-induced severe pneumonia after the prevalence of SARS-CoV-2
  58. Analgesia nociception index is an indicator of laparoscopic trocar insertion-induced transient nociceptive stimuli
  59. High STAT4 expression correlates with poor prognosis in acute myeloid leukemia and facilitates disease progression by upregulating VEGFA expression
  60. Factors influencing cardiovascular system-related post-COVID-19 sequelae: A single-center cohort study
  61. HOXD10 regulates intestinal permeability and inhibits inflammation of dextran sulfate sodium-induced ulcerative colitis through the inactivation of the Rho/ROCK/MMPs axis
  62. Mesenchymal stem cell-derived exosomal miR-26a induces ferroptosis, suppresses hepatic stellate cell activation, and ameliorates liver fibrosis by modulating SLC7A11
  63. Endovascular thrombectomy versus intravenous thrombolysis for primary distal, medium vessel occlusion in acute ischemic stroke
  64. ANO6 (TMEM16F) inhibits gastrointestinal stromal tumor growth and induces ferroptosis
  65. Prognostic value of EIF5A2 in solid tumors: A meta-analysis and bioinformatics analysis
  66. The role of enhanced expression of Cx43 in patients with ulcerative colitis
  67. Choosing a COVID-19 vaccination site might be driven by anxiety and body vigilance
  68. Role of ICAM-1 in triple-negative breast cancer
  69. Cost-effectiveness of ambroxol in the treatment of Gaucher disease type 2
  70. HLA-DRB5 promotes immune thrombocytopenia via activating CD8+ T cells
  71. Efficacy and factors of myofascial release therapy combined with electrical and magnetic stimulation in the treatment of chronic pelvic pain syndrome
  72. Efficacy of tacrolimus monotherapy in primary membranous nephropathy
  73. Mechanisms of Tripterygium wilfordii Hook F on treating rheumatoid arthritis explored by network pharmacology analysis and molecular docking
  74. FBXO45 levels regulated ferroptosis renal tubular epithelial cells in a model of diabetic nephropathy by PLK1
  75. Optimizing anesthesia strategies to NSCLC patients in VATS procedures: Insights from drug requirements and patient recovery patterns
  76. Alpha-lipoic acid upregulates the PPARγ/NRF2/GPX4 signal pathway to inhibit ferroptosis in the pathogenesis of unexplained recurrent pregnancy loss
  77. Correlation between fat-soluble vitamin levels and inflammatory factors in paediatric community-acquired pneumonia: A prospective study
  78. CD1d affects the proliferation, migration, and apoptosis of human papillary thyroid carcinoma TPC-1 cells via regulating MAPK/NF-κB signaling pathway
  79. miR-let-7a inhibits sympathetic nerve remodeling after myocardial infarction by downregulating the expression of nerve growth factor
  80. Immune response analysis of solid organ transplantation recipients inoculated with inactivated COVID-19 vaccine: A retrospective analysis
  81. The H2Valdien derivatives regulate the epithelial–mesenchymal transition of hepatoma carcinoma cells through the Hedgehog signaling pathway
  82. Clinical efficacy of dexamethasone combined with isoniazid in the treatment of tuberculous meningitis and its effect on peripheral blood T cell subsets
  83. Comparison of short-segment and long-segment fixation in treatment of degenerative scoliosis and analysis of factors associated with adjacent spondylolisthesis
  84. Lycopene inhibits pyroptosis of endothelial progenitor cells induced by ox-LDL through the AMPK/mTOR/NLRP3 pathway
  85. Methylation regulation for FUNDC1 stability in childhood leukemia was up-regulated and facilitates metastasis and reduces ferroptosis of leukemia through mitochondrial damage by FBXL2
  86. Correlation of single-fiber electromyography studies and functional status in patients with amyotrophic lateral sclerosis
  87. Risk factors of postoperative airway obstruction complications in children with oral floor mass
  88. Expression levels and clinical significance of serum miR-19a/CCL20 in patients with acute cerebral infarction
  89. Physical activity and mental health trends in Korean adolescents: Analyzing the impact of the COVID-19 pandemic from 2018 to 2022
  90. Evaluating anemia in HIV-infected patients using chest CT
  91. Ponticulus posticus and skeletal malocclusion: A pilot study in a Southern Italian pre-orthodontic court
  92. Causal association of circulating immune cells and lymphoma: A Mendelian randomization study
  93. Assessment of the renal function and fibrosis indexes of conventional western medicine with Chinese medicine for dredging collaterals on treating renal fibrosis: A systematic review and meta-analysis
  94. Comprehensive landscape of integrator complex subunits and their association with prognosis and tumor microenvironment in gastric cancer
  95. New target-HMGCR inhibitors for the treatment of primary sclerosing cholangitis: A drug Mendelian randomization study
  96. Population pharmacokinetics of meropenem in critically ill patients
  97. Comparison of the ability of newly inflammatory markers to predict complicated appendicitis
  98. Comparative morphology of the cruciate ligaments: A radiological study
  99. Immune landscape of hepatocellular carcinoma: The central role of TP53-inducible glycolysis and apoptosis regulator
  100. Serum SIRT3 levels in epilepsy patients and its association with clinical outcomes and severity: A prospective observational study
  101. SHP-1 mediates cigarette smoke extract-induced epithelial–mesenchymal transformation and inflammation in 16HBE cells
  102. Acute hyper-hypoxia accelerates the development of depression in mice via the IL-6/PGC1α/MFN2 signaling pathway
  103. The GJB3 correlates with the prognosis, immune cell infiltration, and therapeutic responses in lung adenocarcinoma
  104. Physical fitness and blood parameters outcomes of breast cancer survivor in a low-intensity circuit resistance exercise program
  105. Exploring anesthetic-induced gene expression changes and immune cell dynamics in atrial tissue post-coronary artery bypass graft surgery
  106. Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism
  107. Analysis of the risk factors of the radiation-induced encephalopathy in nasopharyngeal carcinoma: A retrospective cohort study
  108. Reproductive outcomes in women with BRCA 1/2 germline mutations: A retrospective observational study and literature review
  109. Evaluation of upper airway ultrasonographic measurements in predicting difficult intubation: A cross-section of the Turkish population
  110. Prognostic and diagnostic value of circulating IGFBP2 in pancreatic cancer
  111. Postural stability after operative reconstruction of the AFTL in chronic ankle instability comparing three different surgical techniques
  112. Research trends related to emergence agitation in the post-anaesthesia care unit from 2001 to 2023: A bibliometric analysis
  113. Frequency and clinicopathological correlation of gastrointestinal polyps: A six-year single center experience
  114. ACSL4 mediates inflammatory bowel disease and contributes to LPS-induced intestinal epithelial cell dysfunction by activating ferroptosis and inflammation
  115. Affibody-based molecular probe 99mTc-(HE)3ZHER2:V2 for non-invasive HER2 detection in ovarian and breast cancer xenografts
  116. Effectiveness of nutritional support for clinical outcomes in gastric cancer patients: A meta-analysis of randomized controlled trials
  117. The relationship between IFN-γ, IL-10, IL-6 cytokines, and severity of the condition with serum zinc and Fe in children infected with Mycoplasma pneumoniae
  118. Paraquat disrupts the blood–brain barrier by increasing IL-6 expression and oxidative stress through the activation of PI3K/AKT signaling pathway
  119. Sleep quality associate with the increased prevalence of cognitive impairment in coronary artery disease patients: A retrospective case–control study
  120. Dioscin protects against chronic prostatitis through the TLR4/NF-κB pathway
  121. Association of polymorphisms in FBN1, MYH11, and TGF-β signaling-related genes with susceptibility of sporadic thoracic aortic aneurysm and dissection in the Zhejiang Han population
  122. Application value of multi-parameter magnetic resonance image-transrectal ultrasound cognitive fusion in prostate biopsy
  123. Laboratory variables‐based artificial neural network models for predicting fatty liver disease: A retrospective study
  124. Decreased BIRC5-206 promotes epithelial–mesenchymal transition in nasopharyngeal carcinoma through sponging miR-145-5p
  125. Sepsis induces the cardiomyocyte apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway
  126. Assessment of iron metabolism and iron deficiency in incident patients on incident continuous ambulatory peritoneal dialysis
  127. Tibial periosteum flap combined with autologous bone grafting in the treatment of Gustilo-IIIB/IIIC open tibial fractures
  128. The application of intravenous general anesthesia under nasopharyngeal airway assisted ventilation undergoing ureteroscopic holmium laser lithotripsy: A prospective, single-center, controlled trial
  129. Long intergenic noncoding RNA for IGF2BP2 stability suppresses gastric cancer cell apoptosis by inhibiting the maturation of microRNA-34a
  130. Role of FOXM1 and AURKB in regulating keratinocyte function in psoriasis
  131. Parental control attitudes over their pre-school children’s diet
  132. The role of auto-HSCT in extranodal natural killer/T cell lymphoma
  133. Significance of negative cervical cytology and positive HPV in the diagnosis of cervical lesions by colposcopy
  134. Echinacoside inhibits PASMCs calcium overload to prevent hypoxic pulmonary artery remodeling by regulating TRPC1/4/6 and calmodulin
  135. ADAR1 plays a protective role in proximal tubular cells under high glucose conditions by attenuating the PI3K/AKT/mTOR signaling pathway
  136. The risk of cancer among insulin glargine users in Lithuania: A retrospective population-based study
  137. The unusual location of primary hydatid cyst: A case series study
  138. Intraoperative changes in electrophysiological monitoring can be used to predict clinical outcomes in patients with spinal cavernous malformation
  139. Obesity and risk of placenta accreta spectrum: A meta-analysis
  140. Shikonin alleviates asthma phenotypes in mice via an airway epithelial STAT3-dependent mechanism
  141. NSUN6 and HTR7 disturbed the stability of carotid atherosclerotic plaques by regulating the immune responses of macrophages
  142. The effect of COVID-19 lockdown on admission rates in Maternity Hospital
  143. Temporal muscle thickness is not a prognostic predictor in patients with high-grade glioma, an experience at two centers in China
  144. Luteolin alleviates cerebral ischemia/reperfusion injury by regulating cell pyroptosis
  145. Therapeutic role of respiratory exercise in patients with tuberculous pleurisy
  146. Effects of CFTR-ENaC on spinal cord edema after spinal cord injury
  147. Irisin-regulated lncRNAs and their potential regulatory functions in chondrogenic differentiation of human mesenchymal stem cells
  148. DMD mutations in pediatric patients with phenotypes of Duchenne/Becker muscular dystrophy
  149. Combination of C-reactive protein and fibrinogen-to-albumin ratio as a novel predictor of all-cause mortality in heart failure patients
  150. Significant role and the underly mechanism of cullin-1 in chronic obstructive pulmonary disease
  151. Ferroptosis-related prognostic model of mantle cell lymphoma
  152. Observation of choking reaction and other related indexes in elderly painless fiberoptic bronchoscopy with transnasal high-flow humidification oxygen therapy
  153. A bibliometric analysis of Prader-Willi syndrome from 2002 to 2022
  154. The causal effects of childhood sunburn occasions on melanoma: A univariable and multivariable Mendelian randomization study
  155. Oxidative stress regulates glycogen synthase kinase-3 in lymphocytes of diabetes mellitus patients complicated with cerebral infarction
  156. Role of COX6C and NDUFB3 in septic shock and stroke
  157. Trends in disease burden of type 2 diabetes, stroke, and hypertensive heart disease attributable to high BMI in China: 1990–2019
  158. Purinergic P2X7 receptor mediates hyperoxia-induced injury in pulmonary microvascular endothelial cells via NLRP3-mediated pyroptotic pathway
  159. Investigating the role of oviductal mucosa–endometrial co-culture in modulating factors relevant to embryo implantation
  160. Analgesic effect of external oblique intercostal block in laparoscopic cholecystectomy: A retrospective study
  161. Elevated serum miR-142-5p correlates with ischemic lesions and both NSE and S100β in ischemic stroke patients
  162. Correlation between the mechanism of arteriopathy in IgA nephropathy and blood stasis syndrome: A cohort study
  163. Risk factors for progressive kyphosis after percutaneous kyphoplasty in osteoporotic vertebral compression fracture
  164. Predictive role of neuron-specific enolase and S100-β in early neurological deterioration and unfavorable prognosis in patients with ischemic stroke
  165. The potential risk factors of postoperative cognitive dysfunction for endovascular therapy in acute ischemic stroke with general anesthesia
  166. Fluoxetine inhibited RANKL-induced osteoclastic differentiation in vitro
  167. Detection of serum FOXM1 and IGF2 in patients with ARDS and their correlation with disease and prognosis
  168. Rhein promotes skin wound healing by activating the PI3K/AKT signaling pathway
  169. Differences in mortality risk by levels of physical activity among persons with disabilities in South Korea
  170. Review Articles
  171. Cutaneous signs of selected cardiovascular disorders: A narrative review
  172. XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis
  173. A narrative review on adverse drug reactions of COVID-19 treatments on the kidney
  174. Emerging role and function of SPDL1 in human health and diseases
  175. Adverse reactions of piperacillin: A literature review of case reports
  176. Molecular mechanism and intervention measures of microvascular complications in diabetes
  177. Regulation of mesenchymal stem cell differentiation by autophagy
  178. Molecular landscape of borderline ovarian tumours: A systematic review
  179. Advances in synthetic lethality modalities for glioblastoma multiforme
  180. Investigating hormesis, aging, and neurodegeneration: From bench to clinics
  181. Frankincense: A neuronutrient to approach Parkinson’s disease treatment
  182. Sox9: A potential regulator of cancer stem cells in osteosarcoma
  183. Early detection of cardiovascular risk markers through non-invasive ultrasound methodologies in periodontitis patients
  184. Advanced neuroimaging and criminal interrogation in lie detection
  185. Maternal factors for neural tube defects in offspring: An umbrella review
  186. The chemoprotective hormetic effects of rosmarinic acid
  187. CBD’s potential impact on Parkinson’s disease: An updated overview
  188. Progress in cytokine research for ARDS: A comprehensive review
  189. Utilizing reactive oxygen species-scavenging nanoparticles for targeting oxidative stress in the treatment of ischemic stroke: A review
  190. NRXN1-related disorders, attempt to better define clinical assessment
  191. Lidocaine infusion for the treatment of complex regional pain syndrome: Case series and literature review
  192. Trends and future directions of autophagy in osteosarcoma: A bibliometric analysis
  193. Iron in ventricular remodeling and aneurysms post-myocardial infarction
  194. Case Reports
  195. Sirolimus potentiated angioedema: A case report and review of the literature
  196. Identification of mixed anaerobic infections after inguinal hernia repair based on metagenomic next-generation sequencing: A case report
  197. Successful treatment with bortezomib in combination with dexamethasone in a middle-aged male with idiopathic multicentric Castleman’s disease: A case report
  198. Complete heart block associated with hepatitis A infection in a female child with fatal outcome
  199. Elevation of D-dimer in eosinophilic gastrointestinal diseases in the absence of venous thrombosis: A case series and literature review
  200. Four years of natural progressive course: A rare case report of juvenile Xp11.2 translocations renal cell carcinoma with TFE3 gene fusion
  201. Advancing prenatal diagnosis: Echocardiographic detection of Scimitar syndrome in China – A case series
  202. Outcomes and complications of hemodialysis in patients with renal cancer following bilateral nephrectomy
  203. Anti-HMGCR myopathy mimicking facioscapulohumeral muscular dystrophy
  204. Recurrent opportunistic infections in a HIV-negative patient with combined C6 and NFKB1 mutations: A case report, pedigree analysis, and literature review
  205. Letter to the Editor
  206. Letter to the Editor: Total parenteral nutrition-induced Wernicke’s encephalopathy after oncologic gastrointestinal surgery
  207. Erratum
  208. Erratum to “Bladder-embedded ectopic intrauterine device with calculus”
  209. Retraction
  210. Retraction of “XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis”
  211. Corrigendum
  212. Corrigendum to “Investigating hormesis, aging, and neurodegeneration: From bench to clinics”
  213. Corrigendum to “Frankincense: A neuronutrient to approach Parkinson’s disease treatment”
  214. Special Issue The evolving saga of RNAs from bench to bedside - Part II
  215. Machine-learning-based prediction of a diagnostic model using autophagy-related genes based on RNA sequencing for patients with papillary thyroid carcinoma
  216. Unlocking the future of hepatocellular carcinoma treatment: A comprehensive analysis of disulfidptosis-related lncRNAs for prognosis and drug screening
  217. Elevated mRNA level indicates FSIP1 promotes EMT and gastric cancer progression by regulating fibroblasts in tumor microenvironment
  218. Special Issue Advancements in oncology: bridging clinical and experimental research - Part I
  219. Ultrasound-guided transperineal vs transrectal prostate biopsy: A meta-analysis of diagnostic accuracy and complication rates
  220. Assessment of diagnostic value of unilateral systematic biopsy combined with targeted biopsy in detecting clinically significant prostate cancer
  221. SENP7 inhibits glioblastoma metastasis and invasion by dissociating SUMO2/3 binding to specific target proteins
  222. MARK1 suppress malignant progression of hepatocellular carcinoma and improves sorafenib resistance through negatively regulating POTEE
  223. Analysis of postoperative complications in bladder cancer patients
  224. Carboplatin combined with arsenic trioxide versus carboplatin combined with docetaxel treatment for LACC: A randomized, open-label, phase II clinical study
  225. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part I
  226. Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma
  227. Identification of signatures associated with microsatellite instability and immune characteristics to predict the prognostic risk of colon cancer
  228. Single-cell analysis identified key macrophage subpopulations associated with atherosclerosis
https://doi.org/10.1515/med-2024-9999
Schlagwörter für diesen Artikel
BRCA mutations; reproductive outcomes; fertility preservation; breast cancer; ovarian cancer
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Research Articles
  2. EDNRB inhibits the growth and migration of prostate cancer cells by activating the cGMP-PKG pathway
  3. STK11 (LKB1) mutation suppresses ferroptosis in lung adenocarcinoma by facilitating monounsaturated fatty acid synthesis
  4. Association of SOX6 gene polymorphisms with Kashin-Beck disease risk in the Chinese Han population
  5. The pyroptosis-related signature predicts prognosis and influences the tumor immune microenvironment in dedifferentiated liposarcoma
  6. METTL3 attenuates ferroptosis sensitivity in lung cancer via modulating TFRC
  7. Identification and validation of molecular subtypes and prognostic signature for stage I and stage II gastric cancer based on neutrophil extracellular traps
  8. Novel lumbar plexus block versus femoral nerve block for analgesia and motor recovery after total knee arthroplasty
  9. Correlation between ABCB1 and OLIG2 polymorphisms and the severity and prognosis of patients with cerebral infarction
  10. Study on the radiotherapy effect and serum neutral granulocyte lymphocyte ratio and inflammatory factor expression of nasopharyngeal carcinoma
  11. Transcriptome analysis of effects of Tecrl deficiency on cardiometabolic and calcium regulation in cardiac tissue
  12. Aflatoxin B1 induces infertility, fetal deformities, and potential therapies
  13. Serum levels of HMW adiponectin and its receptors are associated with cytokine levels and clinical characteristics in chronic obstructive pulmonary disease
  14. METTL3-mediated methylation of CYP2C19 mRNA may aggravate clopidogrel resistance in ischemic stroke patients
  15. Understand how machine learning impact lung cancer research from 2010 to 2021: A bibliometric analysis
  16. Pressure ulcers in German hospitals: Analysis of reimbursement and length of stay
  17. Metformin plus L-carnitine enhances brown/beige adipose tissue activity via Nrf2/HO-1 signaling to reduce lipid accumulation and inflammation in murine obesity
  18. Downregulation of carbonic anhydrase IX expression in mouse xenograft nasopharyngeal carcinoma model via doxorubicin nanobubble combined with ultrasound
  19. Feasibility of 3-dimensional printed models in simulated training and teaching of transcatheter aortic valve replacement
  20. miR-335-3p improves type II diabetes mellitus by IGF-1 regulating macrophage polarization
  21. The analyses of human MCPH1 DNA repair machinery and genetic variations
  22. Activation of Piezo1 increases the sensitivity of breast cancer to hyperthermia therapy
  23. Comprehensive analysis based on the disulfidptosis-related genes identifies hub genes and immune infiltration for pancreatic adenocarcinoma
  24. Changes of serum CA125 and PGE2 before and after high-intensity focused ultrasound combined with GnRH-a in treatment of patients with adenomyosis
  25. The clinical value of the hepatic venous pressure gradient in patients undergoing hepatic resection for hepatocellular carcinoma with or without liver cirrhosis
  26. Development and validation of a novel model to predict pulmonary embolism in cardiology suspected patients: A 10-year retrospective analysis
  27. Downregulation of lncRNA XLOC_032768 in diabetic patients predicts the occurrence of diabetic nephropathy
  28. Circ_0051428 targeting miR-885-3p/MMP2 axis enhances the malignancy of cervical cancer
  29. Effectiveness of ginkgo diterpene lactone meglumine on cognitive function in patients with acute ischemic stroke
  30. The construction of a novel prognostic prediction model for glioma based on GWAS-identified prognostic-related risk loci
  31. Evaluating the impact of childhood BMI on the risk of coronavirus disease 2019: A Mendelian randomization study
  32. Lactate dehydrogenase to albumin ratio is associated with in-hospital mortality in patients with acute heart failure: Data from the MIMIC-III database
  33. CD36-mediated podocyte lipotoxicity promotes foot process effacement
  34. Efficacy of etonogestrel subcutaneous implants versus the levonorgestrel-releasing intrauterine system in the conservative treatment of adenomyosis
  35. FLRT2 mediates chondrogenesis of nasal septal cartilage and mandibular condyle cartilage
  36. Challenges in treating primary immune thrombocytopenia patients undergoing COVID-19 vaccination: A retrospective study
  37. Let-7 family regulates HaCaT cell proliferation and apoptosis via the ΔNp63/PI3K/AKT pathway
  38. Phospholipid transfer protein ameliorates sepsis-induced cardiac dysfunction through NLRP3 inflammasome inhibition
  39. Postoperative cognitive dysfunction in elderly patients with colorectal cancer: A randomized controlled study comparing goal-directed and conventional fluid therapy
  40. Long-pulsed ultrasound-mediated microbubble thrombolysis in a rat model of microvascular obstruction
  41. High SEC61A1 expression predicts poor outcome of acute myeloid leukemia
  42. Comparison of polymerase chain reaction and next-generation sequencing with conventional urine culture for the diagnosis of urinary tract infections: A meta-analysis
  43. Secreted frizzled-related protein 5 protects against renal fibrosis by inhibiting Wnt/β-catenin pathway
  44. Pan-cancer and single-cell analysis of actin cytoskeleton genes related to disulfidptosis
  45. Overexpression of miR-532-5p restrains oxidative stress response of chondrocytes in nontraumatic osteonecrosis of the femoral head by inhibiting ABL1
  46. Autologous liver transplantation for unresectable hepatobiliary malignancies in enhanced recovery after surgery model
  47. Clinical analysis of incomplete rupture of the uterus secondary to previous cesarean section
  48. Abnormal sleep duration is associated with sarcopenia in older Chinese people: A large retrospective cross-sectional study
  49. No genetic causality between obesity and benign paroxysmal vertigo: A two-sample Mendelian randomization study
  50. Identification and validation of autophagy-related genes in SSc
  51. Long non-coding RNA SRA1 suppresses radiotherapy resistance in esophageal squamous cell carcinoma by modulating glycolytic reprogramming
  52. Evaluation of quality of life in patients with schizophrenia: An inpatient social welfare institution-based cross-sectional study
  53. The possible role of oxidative stress marker glutathione in the assessment of cognitive impairment in multiple sclerosis
  54. Compilation of a self-management assessment scale for postoperative patients with aortic dissection
  55. Left atrial appendage closure in conjunction with radiofrequency ablation: Effects on left atrial functioning in patients with paroxysmal atrial fibrillation
  56. Effect of anterior femoral cortical notch grade on postoperative function and complications during TKA surgery: A multicenter, retrospective study
  57. Clinical characteristics and assessment of risk factors in patients with influenza A-induced severe pneumonia after the prevalence of SARS-CoV-2
  58. Analgesia nociception index is an indicator of laparoscopic trocar insertion-induced transient nociceptive stimuli
  59. High STAT4 expression correlates with poor prognosis in acute myeloid leukemia and facilitates disease progression by upregulating VEGFA expression
  60. Factors influencing cardiovascular system-related post-COVID-19 sequelae: A single-center cohort study
  61. HOXD10 regulates intestinal permeability and inhibits inflammation of dextran sulfate sodium-induced ulcerative colitis through the inactivation of the Rho/ROCK/MMPs axis
  62. Mesenchymal stem cell-derived exosomal miR-26a induces ferroptosis, suppresses hepatic stellate cell activation, and ameliorates liver fibrosis by modulating SLC7A11
  63. Endovascular thrombectomy versus intravenous thrombolysis for primary distal, medium vessel occlusion in acute ischemic stroke
  64. ANO6 (TMEM16F) inhibits gastrointestinal stromal tumor growth and induces ferroptosis
  65. Prognostic value of EIF5A2 in solid tumors: A meta-analysis and bioinformatics analysis
  66. The role of enhanced expression of Cx43 in patients with ulcerative colitis
  67. Choosing a COVID-19 vaccination site might be driven by anxiety and body vigilance
  68. Role of ICAM-1 in triple-negative breast cancer
  69. Cost-effectiveness of ambroxol in the treatment of Gaucher disease type 2
  70. HLA-DRB5 promotes immune thrombocytopenia via activating CD8+ T cells
  71. Efficacy and factors of myofascial release therapy combined with electrical and magnetic stimulation in the treatment of chronic pelvic pain syndrome
  72. Efficacy of tacrolimus monotherapy in primary membranous nephropathy
  73. Mechanisms of Tripterygium wilfordii Hook F on treating rheumatoid arthritis explored by network pharmacology analysis and molecular docking
  74. FBXO45 levels regulated ferroptosis renal tubular epithelial cells in a model of diabetic nephropathy by PLK1
  75. Optimizing anesthesia strategies to NSCLC patients in VATS procedures: Insights from drug requirements and patient recovery patterns
  76. Alpha-lipoic acid upregulates the PPARγ/NRF2/GPX4 signal pathway to inhibit ferroptosis in the pathogenesis of unexplained recurrent pregnancy loss
  77. Correlation between fat-soluble vitamin levels and inflammatory factors in paediatric community-acquired pneumonia: A prospective study
  78. CD1d affects the proliferation, migration, and apoptosis of human papillary thyroid carcinoma TPC-1 cells via regulating MAPK/NF-κB signaling pathway
  79. miR-let-7a inhibits sympathetic nerve remodeling after myocardial infarction by downregulating the expression of nerve growth factor
  80. Immune response analysis of solid organ transplantation recipients inoculated with inactivated COVID-19 vaccine: A retrospective analysis
  81. The H2Valdien derivatives regulate the epithelial–mesenchymal transition of hepatoma carcinoma cells through the Hedgehog signaling pathway
  82. Clinical efficacy of dexamethasone combined with isoniazid in the treatment of tuberculous meningitis and its effect on peripheral blood T cell subsets
  83. Comparison of short-segment and long-segment fixation in treatment of degenerative scoliosis and analysis of factors associated with adjacent spondylolisthesis
  84. Lycopene inhibits pyroptosis of endothelial progenitor cells induced by ox-LDL through the AMPK/mTOR/NLRP3 pathway
  85. Methylation regulation for FUNDC1 stability in childhood leukemia was up-regulated and facilitates metastasis and reduces ferroptosis of leukemia through mitochondrial damage by FBXL2
  86. Correlation of single-fiber electromyography studies and functional status in patients with amyotrophic lateral sclerosis
  87. Risk factors of postoperative airway obstruction complications in children with oral floor mass
  88. Expression levels and clinical significance of serum miR-19a/CCL20 in patients with acute cerebral infarction
  89. Physical activity and mental health trends in Korean adolescents: Analyzing the impact of the COVID-19 pandemic from 2018 to 2022
  90. Evaluating anemia in HIV-infected patients using chest CT
  91. Ponticulus posticus and skeletal malocclusion: A pilot study in a Southern Italian pre-orthodontic court
  92. Causal association of circulating immune cells and lymphoma: A Mendelian randomization study
  93. Assessment of the renal function and fibrosis indexes of conventional western medicine with Chinese medicine for dredging collaterals on treating renal fibrosis: A systematic review and meta-analysis
  94. Comprehensive landscape of integrator complex subunits and their association with prognosis and tumor microenvironment in gastric cancer
  95. New target-HMGCR inhibitors for the treatment of primary sclerosing cholangitis: A drug Mendelian randomization study
  96. Population pharmacokinetics of meropenem in critically ill patients
  97. Comparison of the ability of newly inflammatory markers to predict complicated appendicitis
  98. Comparative morphology of the cruciate ligaments: A radiological study
  99. Immune landscape of hepatocellular carcinoma: The central role of TP53-inducible glycolysis and apoptosis regulator
  100. Serum SIRT3 levels in epilepsy patients and its association with clinical outcomes and severity: A prospective observational study
  101. SHP-1 mediates cigarette smoke extract-induced epithelial–mesenchymal transformation and inflammation in 16HBE cells
  102. Acute hyper-hypoxia accelerates the development of depression in mice via the IL-6/PGC1α/MFN2 signaling pathway
  103. The GJB3 correlates with the prognosis, immune cell infiltration, and therapeutic responses in lung adenocarcinoma
  104. Physical fitness and blood parameters outcomes of breast cancer survivor in a low-intensity circuit resistance exercise program
  105. Exploring anesthetic-induced gene expression changes and immune cell dynamics in atrial tissue post-coronary artery bypass graft surgery
  106. Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism
  107. Analysis of the risk factors of the radiation-induced encephalopathy in nasopharyngeal carcinoma: A retrospective cohort study
  108. Reproductive outcomes in women with BRCA 1/2 germline mutations: A retrospective observational study and literature review
  109. Evaluation of upper airway ultrasonographic measurements in predicting difficult intubation: A cross-section of the Turkish population
  110. Prognostic and diagnostic value of circulating IGFBP2 in pancreatic cancer
  111. Postural stability after operative reconstruction of the AFTL in chronic ankle instability comparing three different surgical techniques
  112. Research trends related to emergence agitation in the post-anaesthesia care unit from 2001 to 2023: A bibliometric analysis
  113. Frequency and clinicopathological correlation of gastrointestinal polyps: A six-year single center experience
  114. ACSL4 mediates inflammatory bowel disease and contributes to LPS-induced intestinal epithelial cell dysfunction by activating ferroptosis and inflammation
  115. Affibody-based molecular probe 99mTc-(HE)3ZHER2:V2 for non-invasive HER2 detection in ovarian and breast cancer xenografts
  116. Effectiveness of nutritional support for clinical outcomes in gastric cancer patients: A meta-analysis of randomized controlled trials
  117. The relationship between IFN-γ, IL-10, IL-6 cytokines, and severity of the condition with serum zinc and Fe in children infected with Mycoplasma pneumoniae
  118. Paraquat disrupts the blood–brain barrier by increasing IL-6 expression and oxidative stress through the activation of PI3K/AKT signaling pathway
  119. Sleep quality associate with the increased prevalence of cognitive impairment in coronary artery disease patients: A retrospective case–control study
  120. Dioscin protects against chronic prostatitis through the TLR4/NF-κB pathway
  121. Association of polymorphisms in FBN1, MYH11, and TGF-β signaling-related genes with susceptibility of sporadic thoracic aortic aneurysm and dissection in the Zhejiang Han population
  122. Application value of multi-parameter magnetic resonance image-transrectal ultrasound cognitive fusion in prostate biopsy
  123. Laboratory variables‐based artificial neural network models for predicting fatty liver disease: A retrospective study
  124. Decreased BIRC5-206 promotes epithelial–mesenchymal transition in nasopharyngeal carcinoma through sponging miR-145-5p
  125. Sepsis induces the cardiomyocyte apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway
  126. Assessment of iron metabolism and iron deficiency in incident patients on incident continuous ambulatory peritoneal dialysis
  127. Tibial periosteum flap combined with autologous bone grafting in the treatment of Gustilo-IIIB/IIIC open tibial fractures
  128. The application of intravenous general anesthesia under nasopharyngeal airway assisted ventilation undergoing ureteroscopic holmium laser lithotripsy: A prospective, single-center, controlled trial
  129. Long intergenic noncoding RNA for IGF2BP2 stability suppresses gastric cancer cell apoptosis by inhibiting the maturation of microRNA-34a
  130. Role of FOXM1 and AURKB in regulating keratinocyte function in psoriasis
  131. Parental control attitudes over their pre-school children’s diet
  132. The role of auto-HSCT in extranodal natural killer/T cell lymphoma
  133. Significance of negative cervical cytology and positive HPV in the diagnosis of cervical lesions by colposcopy
  134. Echinacoside inhibits PASMCs calcium overload to prevent hypoxic pulmonary artery remodeling by regulating TRPC1/4/6 and calmodulin
  135. ADAR1 plays a protective role in proximal tubular cells under high glucose conditions by attenuating the PI3K/AKT/mTOR signaling pathway
  136. The risk of cancer among insulin glargine users in Lithuania: A retrospective population-based study
  137. The unusual location of primary hydatid cyst: A case series study
  138. Intraoperative changes in electrophysiological monitoring can be used to predict clinical outcomes in patients with spinal cavernous malformation
  139. Obesity and risk of placenta accreta spectrum: A meta-analysis
  140. Shikonin alleviates asthma phenotypes in mice via an airway epithelial STAT3-dependent mechanism
  141. NSUN6 and HTR7 disturbed the stability of carotid atherosclerotic plaques by regulating the immune responses of macrophages
  142. The effect of COVID-19 lockdown on admission rates in Maternity Hospital
  143. Temporal muscle thickness is not a prognostic predictor in patients with high-grade glioma, an experience at two centers in China
  144. Luteolin alleviates cerebral ischemia/reperfusion injury by regulating cell pyroptosis
  145. Therapeutic role of respiratory exercise in patients with tuberculous pleurisy
  146. Effects of CFTR-ENaC on spinal cord edema after spinal cord injury
  147. Irisin-regulated lncRNAs and their potential regulatory functions in chondrogenic differentiation of human mesenchymal stem cells
  148. DMD mutations in pediatric patients with phenotypes of Duchenne/Becker muscular dystrophy
  149. Combination of C-reactive protein and fibrinogen-to-albumin ratio as a novel predictor of all-cause mortality in heart failure patients
  150. Significant role and the underly mechanism of cullin-1 in chronic obstructive pulmonary disease
  151. Ferroptosis-related prognostic model of mantle cell lymphoma
  152. Observation of choking reaction and other related indexes in elderly painless fiberoptic bronchoscopy with transnasal high-flow humidification oxygen therapy
  153. A bibliometric analysis of Prader-Willi syndrome from 2002 to 2022
  154. The causal effects of childhood sunburn occasions on melanoma: A univariable and multivariable Mendelian randomization study
  155. Oxidative stress regulates glycogen synthase kinase-3 in lymphocytes of diabetes mellitus patients complicated with cerebral infarction
  156. Role of COX6C and NDUFB3 in septic shock and stroke
  157. Trends in disease burden of type 2 diabetes, stroke, and hypertensive heart disease attributable to high BMI in China: 1990–2019
  158. Purinergic P2X7 receptor mediates hyperoxia-induced injury in pulmonary microvascular endothelial cells via NLRP3-mediated pyroptotic pathway
  159. Investigating the role of oviductal mucosa–endometrial co-culture in modulating factors relevant to embryo implantation
  160. Analgesic effect of external oblique intercostal block in laparoscopic cholecystectomy: A retrospective study
  161. Elevated serum miR-142-5p correlates with ischemic lesions and both NSE and S100β in ischemic stroke patients
  162. Correlation between the mechanism of arteriopathy in IgA nephropathy and blood stasis syndrome: A cohort study
  163. Risk factors for progressive kyphosis after percutaneous kyphoplasty in osteoporotic vertebral compression fracture
  164. Predictive role of neuron-specific enolase and S100-β in early neurological deterioration and unfavorable prognosis in patients with ischemic stroke
  165. The potential risk factors of postoperative cognitive dysfunction for endovascular therapy in acute ischemic stroke with general anesthesia
  166. Fluoxetine inhibited RANKL-induced osteoclastic differentiation in vitro
  167. Detection of serum FOXM1 and IGF2 in patients with ARDS and their correlation with disease and prognosis
  168. Rhein promotes skin wound healing by activating the PI3K/AKT signaling pathway
  169. Differences in mortality risk by levels of physical activity among persons with disabilities in South Korea
  170. Review Articles
  171. Cutaneous signs of selected cardiovascular disorders: A narrative review
  172. XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis
  173. A narrative review on adverse drug reactions of COVID-19 treatments on the kidney
  174. Emerging role and function of SPDL1 in human health and diseases
  175. Adverse reactions of piperacillin: A literature review of case reports
  176. Molecular mechanism and intervention measures of microvascular complications in diabetes
  177. Regulation of mesenchymal stem cell differentiation by autophagy
  178. Molecular landscape of borderline ovarian tumours: A systematic review
  179. Advances in synthetic lethality modalities for glioblastoma multiforme
  180. Investigating hormesis, aging, and neurodegeneration: From bench to clinics
  181. Frankincense: A neuronutrient to approach Parkinson’s disease treatment
  182. Sox9: A potential regulator of cancer stem cells in osteosarcoma
  183. Early detection of cardiovascular risk markers through non-invasive ultrasound methodologies in periodontitis patients
  184. Advanced neuroimaging and criminal interrogation in lie detection
  185. Maternal factors for neural tube defects in offspring: An umbrella review
  186. The chemoprotective hormetic effects of rosmarinic acid
  187. CBD’s potential impact on Parkinson’s disease: An updated overview
  188. Progress in cytokine research for ARDS: A comprehensive review
  189. Utilizing reactive oxygen species-scavenging nanoparticles for targeting oxidative stress in the treatment of ischemic stroke: A review
  190. NRXN1-related disorders, attempt to better define clinical assessment
  191. Lidocaine infusion for the treatment of complex regional pain syndrome: Case series and literature review
  192. Trends and future directions of autophagy in osteosarcoma: A bibliometric analysis
  193. Iron in ventricular remodeling and aneurysms post-myocardial infarction
  194. Case Reports
  195. Sirolimus potentiated angioedema: A case report and review of the literature
  196. Identification of mixed anaerobic infections after inguinal hernia repair based on metagenomic next-generation sequencing: A case report
  197. Successful treatment with bortezomib in combination with dexamethasone in a middle-aged male with idiopathic multicentric Castleman’s disease: A case report
  198. Complete heart block associated with hepatitis A infection in a female child with fatal outcome
  199. Elevation of D-dimer in eosinophilic gastrointestinal diseases in the absence of venous thrombosis: A case series and literature review
  200. Four years of natural progressive course: A rare case report of juvenile Xp11.2 translocations renal cell carcinoma with TFE3 gene fusion
  201. Advancing prenatal diagnosis: Echocardiographic detection of Scimitar syndrome in China – A case series
  202. Outcomes and complications of hemodialysis in patients with renal cancer following bilateral nephrectomy
  203. Anti-HMGCR myopathy mimicking facioscapulohumeral muscular dystrophy
  204. Recurrent opportunistic infections in a HIV-negative patient with combined C6 and NFKB1 mutations: A case report, pedigree analysis, and literature review
  205. Letter to the Editor
  206. Letter to the Editor: Total parenteral nutrition-induced Wernicke’s encephalopathy after oncologic gastrointestinal surgery
  207. Erratum
  208. Erratum to “Bladder-embedded ectopic intrauterine device with calculus”
  209. Retraction
  210. Retraction of “XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis”
  211. Corrigendum
  212. Corrigendum to “Investigating hormesis, aging, and neurodegeneration: From bench to clinics”
  213. Corrigendum to “Frankincense: A neuronutrient to approach Parkinson’s disease treatment”
  214. Special Issue The evolving saga of RNAs from bench to bedside - Part II
  215. Machine-learning-based prediction of a diagnostic model using autophagy-related genes based on RNA sequencing for patients with papillary thyroid carcinoma
  216. Unlocking the future of hepatocellular carcinoma treatment: A comprehensive analysis of disulfidptosis-related lncRNAs for prognosis and drug screening
  217. Elevated mRNA level indicates FSIP1 promotes EMT and gastric cancer progression by regulating fibroblasts in tumor microenvironment
  218. Special Issue Advancements in oncology: bridging clinical and experimental research - Part I
  219. Ultrasound-guided transperineal vs transrectal prostate biopsy: A meta-analysis of diagnostic accuracy and complication rates
  220. Assessment of diagnostic value of unilateral systematic biopsy combined with targeted biopsy in detecting clinically significant prostate cancer
  221. SENP7 inhibits glioblastoma metastasis and invasion by dissociating SUMO2/3 binding to specific target proteins
  222. MARK1 suppress malignant progression of hepatocellular carcinoma and improves sorafenib resistance through negatively regulating POTEE
  223. Analysis of postoperative complications in bladder cancer patients
  224. Carboplatin combined with arsenic trioxide versus carboplatin combined with docetaxel treatment for LACC: A randomized, open-label, phase II clinical study
  225. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part I
  226. Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma
  227. Identification of signatures associated with microsatellite instability and immune characteristics to predict the prognostic risk of colon cancer
  228. Single-cell analysis identified key macrophage subpopulations associated with atherosclerosis
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2025 De Gruyter Brill
Heruntergeladen am 5.11.2025 von https://www.degruyterbrill.com/document/doi/10.1515/med-2024-9999/html?lang=de
Button zum nach oben scrollen