Vitrification alters growth differentiation factor 9 and follicle-stimulating hormone receptor expression in human cumulus-mural granulosa cells.

Objective: Ovarian tissue vitrification is widely utilized for fertility preservation in prepubertal and adolescent female patients with cancer. The current literature includes reports of successful pregnancy and live birth following autografting. However, the effects of the vitrification process on cumulus-mural granulosa cells (C-mGCs)-somatic cells in ovarian tissue crucial for oocyte maturation and early embryonic development-remain unclear. This study was conducted to explore the impact of vitrification on the cellular function of C-mGCs by quantifying the expression of growth differentiation factor 9 (GDF-9), bone morphogenetic protein 15 (BMP-15), follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), connexin 37, survivin, and caspase 3. Methods: Mature and immature C-mGCs were obtained from 38 women with polycystic ovary syndrome who participated in an in vitro fertilization program. The C-mGCs were then divided into two groups: fresh and vitrified. The expression levels of target genes were assessed using real-time quantitative polymerase chain reaction. Results: After vitrification, GDF-9 expression was significantly decreased among both mature and immature C-mGCs, with 0.2- and 0.1-fold changes, respectively (p<0.01). Similarly, FSHR expression in the mature and immature groups was reduced by 0.1- and 0.02-fold, respectively, following vitrification (p<0.01). The expression levels of the other genes, including BMP-15, LHR, connexin 37, survivin, and caspase 3, remained similar across the examined groups (p>0.05). Conclusion: Vitrification may compromise oocyte maturation through reduced GDF-9 and FSHR expression in C-mGCs after warming.

Twelve Hours Post-Injection Serum Human Chorionic Gonadotropin and Body Mass Index Predicts In Vitro Fertilization Oocyte Maturation Rate: A Cross-Sectional Study.

BACKGROUND: In vitro fertilization (IVF) remains a main treatment for infertility cases. Post-injection human chorionic gonadotropin (hCG) level is an essential factor in determining oocyte maturation rate in IVF. This study aimed to determine the relationship between 12 hours post-injection serum hCG level and oocyte maturation rate among IVF participants. MATERIALS AND METHODS: A cross-sectional study on IVF participants was done at a tertiary hospital in Indonesia from January 2020 to December 2021. Subjects were injected with 250 µg of recombinant-hCG (r-hCG) subcutaneously. Twelve hours post-injection serum hCG levels and oocyte maturation rate data were retrieved and analyzed accordingly. RESULTS: Twenty-eight subjects were recruited into the study. Higher 12 hours post-injection serum hCG was related to oocyte maturation rate (P=0.046). The cut-off point of 12 hours post-injection serum hCG to predict better oocyte maturation rate was 90.15 mIU/mL (sensitivity 68.2%, specificity 83.3%). Oocyte maturation rate may be predicted using body mass index (BMI) and 12 hours post-injection serum hCG. CONCLUSION: Higher 12 hours post-injection serum hCG was associated with a higher oocyte maturation rate in IVF subjects.

Menstrual cycle changes and mental health states of women hospitalized due to COVID-19.

PURPOSE: Many studies have evaluated the impact of the COVID-19 pandemic on women's mental health and menstrual changes. However, most of these studies only included nonhospitalized COVID-19 patients, while information on hospitalized women is very limited. Thus, this study aimed to examine the mental health status and menstrual changes in hospitalized female COVID-19 patients. METHODS: A survey was administered to female COVID-19 patients in the isolation ward of a national referral hospital in Indonesia between January and August 2021, and the women were followed up 3 months after discharge. The survey evaluated menstrual patterns and mental health using the Self Reporting Questionnaire-29 (SRQ-29). RESULTS: The study enrolled 158 female patients. There was an increase in patients who had a cycle length of > 32 or < 24 days, and significant increases in menstrual irregularity and heavy menstrual bleeding were noted. Overall, 37.3% of the patients reported a change in menstrual pattern after infection with COVID-19. Based on SRQ-29 scores, 32.3% of the women had neurotic symptoms, 12.7% had psychotic symptoms, and 38.0% had symptoms of posttraumatic stress disorder. Patients with symptoms of mental health disorders were twice as likely to report a menstrual change (OR 2.17, 95% CI 1.12-4.22; p = 0.021). CONCLUSION: Menstrual changes and increased symptoms of mental health disorders occur in hospitalized female COVID-19 patients. The length of isolation was the key factor affecting overall menstrual changes and mental health in hospitalized female COVID-19 patients.

Potential Use of Immature Oocyte to Improve Fertility Preservation Outcome: A Narrative Review.

Fertility preservation through gamete vitrification has become one of the critical strategies to secure a childbearing potential in patients who are diagnosed with cancer or risks of infertility. Preserving the gametes would prevent the deleterious effects of cancer drugs or radiotherapy exposure on the quality of the gametes. Furthermore, in vitro fertilisation of vitrified mature human oocytes has lately demonstrated promising results that are reflected in the increased survival rate of thawed oocytes and the resultant clinical pregnancy rate. However, limitations in the cryopreservation of mature oocytes of cancer patients persist. Ovarian stimulation protocols which comprise administering gonadotrophin-releasing hormones could aggravate cancer or delay essential cancer therapy. Considering such circumstances, vitrification of immature oocytes would become a rational option. While the vitrification procedure of mature oocytes has been established, the vitrification of immature oocytes remains controversial due to a low post-thaw in vitro maturation and fertilisation rate. Apparent cryoinjuries to the immature oocytes post thawing or warming have been observed in both human and animal model oocytes. An alternative strategy was therefore proposed to improve the effectiveness of utilising immature oocytes for fertility preservation by conducting the in vitro oocyte maturation process first before vitrification. This method has prevailed, especially in oncofertility patients. Although the success rate of the clinical outcomes remains low, this approach, in conjugation with proper counselling, might provide oncofertility patients with an opportunity to preserve their reproductive potential.

IVF outcome with a high level of AMH: a focus on PCOS versus non-PCOS.

BACKGROUND: The purpose of this research was to investigate whether high AMH levels in PCOS patients resulted in different IVF outcomes compared to those in non-PCOS patients. METHODS: A retrospective cohort study was conducted involving 238 women undergoing IVF who had AMH levels > 4 ng/ml. Participants were divided into two groups: PCOS and non-PCOS. RESULTS: The median AMH level was significantly higher in the PCOS group (7.59 ± 4.61 ng/ml vs. 5.91 ± 2.22 ng/ml, p < 0.001). The PCOS group required less gonadotropin but yielded more oocytes after stimulation. Significantly more participants from the PCOS group (41.5% [n = 39]) developed a hyperresponse to ovarian stimulation compared to the non-PCOS group (26.4% [n = 38]) (OR = 1.978, 95% CI 1.138-3.488; p = 0.015). CONCLUSION: There were significant differences in terms of total doses of gonadotropin and the number of oocytes retrieved in the PCOS and non-PCOS groups. Women with PCOS and high AMH levels have a higher risk of hyperresponse after ovarian stimulation than women without PCOS.

Lean Management Improves the Process Efficiency of Controlled Ovarian Stimulation Monitoring in IVF Treatment.

Background: Evaluation of patients' experiences and satisfaction is vital for assessing the quality of healthcare service, including in fertility clinics. One promising concept that has recently been widely used to increase efficiency and service quality in hospitals is the lean concept. Lean is a form of philosophy that focuses on reducing waste of a process and continuous improvement so that consumers receive greater value. This study aims to identify waste and improve efficiency using lean management methods in the controlled ovarian stimulation (COS) monitoring process during in vitro fertilization (IVF) treatment in a fertility clinic. Methods: This study used an action research approach by observing the total service time of monitoring ovarian stimulation in IVF patients (n = 40). The identified waste and solutions were then compiled for use in a focus group discussion (FGD). From the FGD, a priority plan was obtained for the implementation of lean management. This study uses the PDCA cycle for improvement. Results: Three priority solutions were chosen, which are as follows: (1) evaluating ovarian stimulation via USG only; (2) allocating more time during doctor's counselling; and (3) increasing counselling time by nurses in the injection room. The total patient wait time was reduced to 6 hours 32 minutes over the three visits, 13 hours 35 minutes decrease from before the intervention. In addition, the value-added ratio (VAR) was increased from 9% to 22% after the intervention. Conclusion: This research provides theoretical and practical contributions for the lean management principles in IVF treatment. The findings of this study will contribute to the pursuit of knowledge and dissemination of lean principles in the management of healthcare, including IVF clinics.

Chronic Pelvic Pain in Women with Endometriosis is Associated with Psychiatric Disorder and Quality of Life Deterioration.

BACKGROUND: Endometriosis is a condition associated with pelvic pain, infertility, and possibly with decreased quality of life as well as psychiatric disorder. The purpose of our study was to evaluate the association between pain characteristic, psychiatric disorder, and quality of life in women with endometriosis. METHODS: A cross-sectional study was done involving 160 women with medical diagnosis of endometriosis. Pain intensity was evaluated using Visual Analog Scale (VAS), Quality of Life with Endometriosis Health Profile (EHP-30), and psychologic condition with Mini International Neuropsychiatric Interview International Classification of Diseases (Mini-ICD). RESULTS: VAS and psychiatric disorder were associated with higher EHP-30 score (ß = 9.3 (95% CI: 7.15-11.45; p < 0.001 and ß = 28.51 (95% CI: 20.06-36.05; p < 0.001), respectively) and hence, lower quality of life. The strongest correlation between VAS and EHP-30 was in pain (r=0.586; p<0.001) and 'control and powerlessness' (r = 0.583; p < 0.001). VAS was also higher in subjects with depression (49.5 (25.4-77.8) vs 34.4 (6.1-74.6); p < 0.001). CONCLUSION: We conclude that severe endometriosis-related pain and the presence of psychiatric disorder were associated with lower quality of life. Comprehensive management of endometriosis is crucial to improve patients' quality of life.

Potential of Mesenchymal Stem Cells and Their Secretomes in Decreasing Inflammation Markers in Polycystic Ovary Syndrome Treatment: A Systematic Review.

Background: Polycystic ovary syndrome (PCOS) is a chronic disorder and is one of the most common endocrine disorders in women of a reproductive age. The prevalence of PCOS is growing globally; 52% of women in Southeast Asia alone suffer from this disorder. This disorder is caused by chronic hyperandrogenism, which hinders folliculogenesis. There is also a close relationship between hyperandrogenism and hyperinsulinemia/insulin resistance (IR), and it is estimated that 40-80% of PCOS patients suffer from insulin resistance (IR). Mesenchymal stem cells (MSCs) and their secretomes have been shown to alleviate PCOS symptoms by decreasing IR and androgen secretion by reducing inflammation. This study aimed to systematically review the literature to study the reported potential of MSCs and their secretomes in decreasing inflammation markers in PCOS treatment. Methods: A systematic literature search was performed on EMBASE, PubMed (MEDLINE), and the Cochrane Library with the terms insulin-resistant PCOS, mesenchymal stem cells, and secretome or conditioned medium as the search keywords. A total of 317 articles were reviewed. Four articles were identified as relevant for this systematic review. Results: The results of this study supported the use of mesenchymal stem cells and their secretions in decreasing inflammatory markers in the treatment of polycystic ovary syndrome. Conclusions: This review provided evidence that treatment with mesenchymal stem cells and their secretomes has the potential to treat PCOS due to its ability to downregulate androgen levels and increase insulin sensitivity, which thereby lowers the level of proinflammatory factors.

Increased Levels of CD107a and Intracellular Cytokines in IL-2 Stimulated PBMCs from Endometriosis Patients.

It has been postulated that the immune system is impaired in individuals with endometriosis, with attention directed to natural killer (NK) cells. Specifically, it has been hypothesized that altered numbers of peripheral NK cells in blood are associated with the presence of endometriotic lesions. This study aimed to evaluate the level of the peripheral NK cell surface marker CD107a in endometriosis in the presence of IL-2 stimulation. Peripheral blood mononuclear cells (PBMCs) were obtained from 7 women with endometriosis and 7 women without endometriosis. The PBMCs were divided into two groups and either treated with recombinant IL-2 or left untreated. The cytotoxic activity of the PBMCs toward target cells (K562) was evaluated. Then, both groups were cocultured for 4 days. The expressions of CD107a, TNF-α, and IFN-γ were determined using flow cytometry analysis. There was no difference in the expression of CD107a prior to IL-2 stimulation in PBMCs from women with endometriosis compared to those from women without endometriosis. However, we observed upregulation of the expression of the surface marker CD107a after treatment in the endometriosis group. In addition, there was a significant difference in CD107a expression in the endometriosis group before versus after stimulation with IL-2 (p < 0.01). We also found no difference in the production of TNF-α and IFN-γ before versus after treatment with IL-2 in either groups. The levels of CD107a were significantly enhanced in peripheral blood taken from women with endometriosis after treatment with IL-2.

Oocyte Competence Biomarkers Associated With Oocyte Maturation: A Review.

Oocyte developmental competence is one of the determining factors that influence the outcomes of an IVF cycle regarding the ability of a female gamete to reach maturation, be fertilized, and uphold an embryonic development up until the blastocyst stage. The current approach of assessing the competency of an oocyte is confined to an ambiguous and subjective oocyte morphological evaluation. Over the years, a myriad of biomarkers in the cumulus-oocyte-complex has been identified that could potentially function as molecular predictors for IVF program prognosis. This review aims to describe the predictive significance of several cumulus-oocyte complex (COC) biomarkers in evaluating oocyte developmental competence. A total of eight acclaimed cumulus biomarkers are examined in the study. RT-PCR and microarray analysis were extensively used to assess the significance of these biomarkers in foreseeing oocyte developmental competence. Notably, these biomarkers regulate vital processes associated with oocyte maturation and were found to be differentially expressed in COC encapsulating oocytes of different maturity. The biomarkers were reviewed according to the respective oocyte maturation events namely: nuclear maturation, apoptosis, and extracellular matrix remodeling, and steroid metabolism. Although substantial in vitro evidence was presented to justify the potential use of cumulus biomarkers in predicting oocyte competency and IVF outcomes, the feasibility of assessing these biomarkers as an add-on prognostic procedure in IVF is still restricted due to study challenges.

Impact of IVF on the Timing and Symptoms of Menopause.

BACKGROUND: Age-related loss of female fertility is characterized by a decline in both the quantity and quality of ovarian follicles. Symptoms of ovarian stimulation, which is part of the process of in vitro fertilization (IVF), vary among women. This study was conducted to analyze the differences in menopausal timing and symptoms in women who had undergone IVF compared to those who had natural pregnancies. METHODOLOGY: In this cross-sectional study, menopausal women were categorized into two groups: those who had undergone IVF (n = 50) and those who had not (n = 50). Clinical data were obtained from the participants' medical records, and patient interviews were conducted using the menopause rating scale (MRS) questionnaires. RESULTS: The IVF had no significant impact on psychological or somatic symptoms in either group (p>0.05). However, it affected urogenital symptoms (p<0.05). Additionally, there was a significant difference in the age of onset of menopause between the groups (p<0.05). CONCLUSION: There is a significant correlation between IVF treatment, urogenital symptoms in menopause, and the age of onset of menopause.

mRNA expression and DNA methylation level of the MMP-2 gene in peritoneal endometriosis.

OBJECTIVE: Endometriosis is a multifactorial disease that affects 10% of women of childbearing age. Its development is known to be related to the MMP-2 gene. Specifically, the expression of MMP-2 is increase in endometriosis. The aim of this study was to evaluate the correlation between mRNA expression and DNA methylation levels of the MMP-2 gene in peritoneal endometriosis. METHODS: This study used a cross-sectional design. The samples included peritoneal endometriosis tissue from women with endometriosis and normal endometrial tissue from women without endometriosis. Twenty samples of each type were taken, and the women were 20-45 years of age. Peritoneal endometriosis tissue was acquired using the laparoscopic technique, while normal endometrial tissue was taken with the microcuretase technique. The mRNA expression of the MMP-2 gene was analysed with qRT-PCR, and the level of DNA methylation of the MMP-2 gene was analysed with a methylation-specific PCR method. RESULTS: The mRNA expression of MMP-2 gene in peritoneal endometriosis tissue was increased, and there were significant differences between peritoneal endometriosis tissue and normal endometrial tissue. The MMP-2 gene was hypermethylated, but there was no significant difference (p = 0.596) between peritoneal endometriosis tissue and endometrial tissue in terms of methylation. This study did not show a significant correlation between mRNA expression and DNA methylation levels of the MMP-2 gene (p = 0.769, r = 0.070). CONCLUSIONS: The increase in MMP-2 gene expression in peritoneal endometriosis tissue is likely not only due to hypermethylation; there are other factors that might play a role.

Expression of E-Cadherin in Pig-Tailed Monkey (Macaca nemestrina) Endometrium after Controlled Ovarian Hyperstimulation.

An increase of steroid hormones in controlled ovarian hyperstimulation (COH) procedures is reducing the success rate in assisted reproductive technology (ART), and this includes the pregnancy rate and/or implantation rate. Research has found that the decrease in the success rate occurred due to the decreased expression of the protein that is needed to prepare the endometrium so that the embryo could attach. The aim of the study was to analyse the changes in E-chaderin expression due to COH and its relations with increased level of steroid hormones as one of the proteins in the endometrium. There were 13 samples of stored biological tissue from Macaca nemestrina endometrial tissue; came from one group of natural cycles as the control group (n = 4) and three groups of stimulated cycles. The first stimulated cycle group was injected by a 30 IU dose of rFSH (n = 2). The second stimulated cycle group was injected by a 50 IU dose of rFSH (n = 4). The third stimulated cycle group was injected by a 70 IU dose of rFSH (n = 3). The expression of E-cadherin was measured by the immunohistochemistry (IHC) technique. Estradiol (E2) and progesterone (P4) levels were assessed using ELISA and have already been done. The IHC staining expression of E-cadherin was found in the cytoplasm of glandular epithelium. Immunostaining measurement used the H_SCORE. We found that the expression of E-cadherin within the group was not significantly different (p value: 0.178). Similarly, both the correlation between the estradiol level with E-cadherin and the correlation between the progesterone level with E-cadherin were not significantly different (p value: 0.872 and p value: 0.836). The conclusion is that the level of E-Cadherin expression in the endometrium that were taken in themiddle secretion phase not affected by the dose regimen that given. In addition, the level of expression is not influenced by the increase of serum E2 and P4 levels.

Impact of Serum Human Chorionic Gonadotropin and Luteinizing Hormone Receptor Expression to Oocyte Maturation Rate: A Study of Controlled Ovarian Stimulation.

BACKGROUND: Few studies have assessed the impact of serum human chorionic gonadotropin (hCG) levels before oocyte retrieval and luteinizing hormone receptor (LHR) mRNA expression. AIMS: The objective was to assess the correlations between serum hCG levels at 12-h posttrigger granulosa cell LHR mRNA expression during the in vitro fertilization (IVF) cycle with oocyte maturation rate and to determine the cutoff level of serum hCG at 12-h posttrigger. SETTINGS AND DESIGN: A cross-sectional was conducted for this study at the IVF center of Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia. MATERIALS AND METHODS: Recombinant follicle-stimulating hormone was used on day 2 of the menstrual cycle with multiple doses of a gonadotropin-releasing hormone antagonist. Recombinant hCG was used to trigger ovulation. At 12-h posttrigger, hCG serum levels were measured using an enzyme-linked immunosorbent assay. STATISTICAL ANALYSIS: Pearson's correlation coefficient was used to evaluate the correlation between oocyte maturation rates, serum hCG levels, and LHR mRNA levels. Cutoff values were determined using a receiver operating characteristic (ROC) curve. RESULTS: Serum hCG levels were positively correlated (r = 0.467;P < 0.01), and LHR mRNA expression was weakly correlated (r = 0.073; P = 0.701) with oocyte maturation. The cutoff of serum hCG for a high maturation rate was 77 mIU/mL, with an area under the ROC curve of 0.765 (95% confidence interval: 0.598-0.939) andP < 0.001. CONCLUSION: Oocyte maturation is correlated with serum hCG levels with 77 mIU/mL as the cutoff point for oocyte retrieval.

Correlation between luteinizing hormone receptor gene expression in human granulosa cells with oocyte quality in poor responder patients undergoing in vitro fertilization: A cross-sectional study.

Background: This study was performed to evaluate the role of luteinizing hormone (LH) and granulosa cell LH receptor (LH-R) in poor responder patients who underwent controlled ovarian stimulation. Expression levels of LH-R mRNA in granulosa cells was investigated and compared with oocyte morphology, oocyte maturity and fertilization rate.  Methods: Granulosa cells were obtained from 30 patients who underwent in vitro fertilization (IVF) at Dr. Cipto Mangunkusumo Hospital, Jakarta. The patients were divided into two groups: group I (n=10) poor responders; and group II (n=20) non-poor responders. After the extraction of total RNA from granulosa cells, semi-quantitative RT-PCR was performed and the amount of LH-R mRNA was quantified. The relative values were calculated as the ratio of LH-R mRNA and actin beta mRNA. Statistical analysis was performed using Mann-Whitney test and Spearman correlation.  Results: The relative value of LH-R mRNA was higher in group I compared with group II (27.37[0.00-28939.37] vs 0.00[0.00-7196.12]). Oocyte maturity (r=0.267) and morphology (r=0.267) in group I consistently showed a positive correlation with LH-R mRNA; in group II a negative correlation with LH-R mRNA was shown for oocyte maturity (r= -0.552) and morphology (r= -0.164). Group I had a positive correlation between LH-R expression with fertilization rate (r=0.430), and group II showed a negative correlation (r=-0.340).  Conclusions: The expression of LH-R mRNA has a positive correlation with oocyte quality in poor responder patients and a negative correlation in non-poor responders. Our study suggests an optimal expression of LH- R mRNA in granulosa cells during controlled ovarian stimulation to obtain good quality oocytes.

Triglycerides, independent of Ferriman Gallwey Score, is a main determinant of free testosterone index in PCOS.

Background: Polycystic Ovarian Syndrome (PCOS) is the most common endocrinopathy in women of reproductive age, affecting 5-20% of women worldwide. Hyperandrogenism, as the primary characteristic of PCOS, is not always present in every patient. The hyperandrogenic phenotype of PCOS patients is influenced by both hormonal and metabolic dysfunctions. Therefore, this study aims to determine the correlation between hormone profile, lipid profile, and clinical profile with free testosterone index in subjects with PCOS. Methods: This prospective cross-sectional study was conducted in the Dr. Cipto Mangunkusumo General Hospital between July 2014 and December 2016. The study involved 76 women with PCOS, who were classified into 2 subgroups: 39 subjects in the hyperandrogenism group and 37 subjects in the non-hyperandrogenism group. Each subject underwent physical examination, blood sample collection, and USG examination. Bivariate analysis was done using independent t-tests and Mann Whitney U-tests, while multivariate analysis was done using logistic regression. Results: Triglyceride and testosterone level showed weak (r = 0.232, p = 0.044) and moderate (r = 0.460, p ¡ 0.001) positive correlation with FTI, while SHBG level showed moderate negative correlation (r = -0.483, p ¡ 0.001). Triglyceride was also found to be determinant of hyperandrogenism condition in PCOS patient (OR 0.02, 95% CI 0.00-0.04, p = 0.013). However, there was no significant difference observed between FGS and hyperandrogenism (p = 0.43). Conclusions: Triglycerides, testosterone, and SHBG were associated with hyperandrogenism in PCOS patients, while FGS showed no such association.

Anti-Mullerian hormone levels in female cancer patients of reproductive age in Indonesia: A cross-sectional study.

Background: Efforts in reproductive preservation for cancer patients have become one of the important aspects of cancer management. In fact, decline in reproductive function is known to occur after exposure to anti-cancer treatments. Measuring anti-Müllerian hormone (AMH) levels is known to be the best parameter in predicting ovarian reserves, which indicates reproductive function. In total, 68% of cancer survivors of reproductive age who underwent anti-cancer treatments suffer from infertility. Meanwhile, ovarian reserves also decrease with increasing age. There is ongoing debate on whether the ovarian reserves of cancer patients could be reduced long before exposure to anti-cancer therapy. Therefore, it is important to know whether ovarian reserves in cancer patients decrease before or after anti-cancer therapy. This can help predict the reproductive function in such cases and the effectiveness of ovarian preservation efforts. Methods: A cross-sectional study was conducted, comparing the AMH levels of 44 female cancer patients of reproductive age before cancer therapy, to 44 non-cancer patients of reproductive age (age matched) . The AMH was determined from blood.The biological ages from both groups were adjusted using the Indonesian Kalkulator of Oocytes. Results: The median age in both groups was 28 years old. The AMH levels in the blood of the cancer group were found to be significantly lower in contrast to those in the non-cancer group (1.11 [0.08-4.65] ng/ml vs. 3.99 [1.19- 8.7]; p- value <0.001). Therefore, the biological age in the cancer group was 10 years older than that of the non-cancer group, indicating that ovarian aging occurs earlier in cancer patients. Conclusions: AMH levels of cancer patients of reproductive age were already reduced before cancer therapy, given an older biological age, in contrast to that of the non-cancer patients. Proper counseling and implementation of fertility-preserving methods is highly recommended in this group of patients.