Ovarian Volume Research Articles

The Impact of Gestational Diabetes Mellitus on Minipuberty in Girls

Minipuberty is the second phase of physiological activation of the reproductive axis, playing a role in the postnatal development of sexual organs. The course of female minipuberty was found to be affected by low maternal vitamin D status and hypothyroidism during pregnancy. The aim of the current study was to assess the hormonal profile and the size of sexual organs in daughters of mothers with gestational diabetes mellitus. The study included three matched groups of infant girls: daughters of healthy women without metabolic disorders during pregnancy (group 1), daughters of women with poorly controlled gestational diabetes mellitus (group 2), and daughters of women with gestational diabetes mellitus adequately controlled during pregnancy (group 3). Urinary levels of gonadotropins, salivary levels of estradiol, testosterone, DHEA-S and progesterone, ovarian volume, uterine length and breast diameter were measured from postnatal month 1 to postnatal month 18. Concentrations of FSH, LH and estradiol were higher, while concentration of progesterone was lower in group 2 than in the remaining groups. There were no between-group differences in concentrations of testosterone and DHEA-S. Levels of LH, FSH, estradiol and progesterone correlated with maternal whole-blood levels of glycated hemoglobin. Group 2 was also characterized by the longest detection periods for LH and estradiol. Ovarian volume, uterine length and breast diameter were greater in group 1 than in the remaining two groups. Over the entire observation period, there were no differences in hormone levels and sizes of the sexual organs between groups 1 and 3. The obtained results suggest that poorly controlled, but not well controlled, gestational diabetes mellitus affects the course of female minipuberty.

Type 1 diabetes mellitus; ovarian reserve; anti-Müllerian hormone; ovarian function

BACKGROUND: Prolonged course of diabetes mellitus often leads to the development of vascular complications, insufficiency of ovarian function. The occurrence of diabetes mellitus in women before pregnancy (pregestational diabetes mellitus) it can have various adverse consequences for the mother, fetus, child and the course of pregnancy. Pregnancy planning in women with pregestational diabetes significantly improves the outcomes of pregnancy and childbirth. AIM: The aim of this study was to analyze gonadotropic and ovarian function parameters in patients with type 1 diabetes mellitus depending on the age of onset, duration and compensation level of the disease. MATERIALS AND METHODS: The patients included into this clinical prospective study were divided into two groups. The main group consisted of 216 patients with type 1 diabetes mellitus aged 18 to 39 years (mean age: 27.1 ± 3.1 years). The control group consisted of 30 healthy women of reproductive age. Chemiluminescent immunoassay was used to determine blood serum levels of anti-Müllerian hormone, follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, testosterone, free testosterone, and sex hormone-binding globulin from day 2 to day 5 of the menstrual cycle. Serum progesterone levels were measured on days 20–23 of the menstrual cycle for three consecutive cycles. Glycated hemoglobin levels were also studied in the blood serum of patients with type 1 diabetes mellitus. All the patients underwent pelvic ultrasound examination to assess the cohort of antral follicles and ovarian volume. RESULTS: The average age of menarche in patients with type 1 diabetes mellitus who developed the disease at the age of under 10 years was 14.2 ± 1.2 years. This was higher than in the group of girls with the onset of the disease over the age of 10 years (13.5 ± 1.2 years) and in women of the control group (11.9 ± 1.1 years). When assessing the ovarian reserve in patients with type 1 diabetes mellitus, we found a decrease in anti-Müllerian hormone level and antral follicle count in the group of women with disease onset at the age of under 10 years. We did not find differences in the ovarian reserve parameters in patients depending on disease duration. Normogonadotropic normoprolactinemic ovarian insufficiency was detected in 154 (71.3%) of 216 patients, while the rest 62 (28.7%) women had an ovulatory menstrual cycle. In patients with anovulation, luteal phase deficiency and ovulatory menstrual cycle, we found no differences between the age of development of type 1 diabetes mellitus, its duration, glycated hemoglobin levels, total daily insulin dose and insulin dose per kilogram of body mass. In patients receiving intensive insulin therapy with continuous subcutaneous insulin infusion, glycated hemoglobin level was lower than in those receiving multiple dose insulin injection therapy. CONCLUSIONS: The average age of menarche in patients with type 1 diabetes mellitus is higher than in healthy women. The ovarian reserve parameters in patients with early onset of the disease, before 10 years of age, are lower than in patients who developed type 1 diabetes mellitus after 10 years of age. Duration of pregnancy planning period depends on compensation level of the disease and lasts from six to 12 months. This requires the doctor and patient to prepare for the implementation of reproductive tasks as early as possible, especially in patients whose disease onset occurred in pre-pubertal period.

7770 Damage of Ovarian Vasculature by Chemotherapies induces Ovarian Dysfunction in Mice

Abstract Disclosure: W. So: None. R. Dong: None. Y. Luan: None. A. Abazarikia: None. S. Kim: None. Background: Chemotherapy demonstrates efficacy to destroying cancer cells; however, it can inadvertently impact normal healthy cells, leading to irreversible side effects, particularly affecting the ovaries in female patients. Female cancer survivors encounter endocrine dysfunction and infertility due to ovarian damage caused by gonadotoxic cancer therapies. The ovary, a vital organ responsible for producing oocytes and endocrine hormones, faces significant challenges following such treatment. A study with premenopausal breast cancer patients reported a significant reduction in ovarian blood flow and volume immediately following chemotherapy. The preservation of ovarian function depends on the ovarian vasculature in supporting the development and maintenance of ovarian follicles. Despite its importance, the relationship between ovarian vasculature and follicle following chemotherapy has not been studied. Results: To investigate the direct impacts of chemotherapy, ovaries from postnatal 5 CD-1 mice were subjected to testing with three chemotherapeutic agents: cisplatin (CDDP), cyclophosphamide (CPA), and doxorubicin (DOXO). The expression of CD31/PECAM-1 (platelet endothelial adhesion molecule) exhibited a significant decrase after 96 hours of culture with 4-HC, an active metabolite of CPA. This reduction implies that ovarian vasculature was also compromised when chemotherapy eliminated immature follicles. In order to evaluate the influence of vascular endothelial growth factor (VEGF) in safeguarding both vasculature and ovarian follicles, ovaries were co-cultured with VEGF165 or VEGF165b in combination with chemotherapy. Interestingly, pre-treatment with VEGF165 before 4-HC led to an increased expression of CD31 in the cortex area, while VEGF165b further diminished CD31 expression compared to treatment with 4-HC alone. Additionally, adolescent CD-1 mice were intraperitoneally injected with CDDP, CPA, or DOXO, and ovaries were harvested one week after injection. Ovaries treated with chemotherapeutic agents exhibited a reduction in ovary weight and decreased CD31 expression compared to control mice. Conclusions: We propose that these chemotherapeutic agents not only induced the loss of ovarian follicles but also affected ovarian vasculature in mice. This suggests a potential decrease in folliculogenesis within the ovary, coupled with the depletion of ovarian reserve, as the delivery of nutrients and oxygen to growing ovarian follicles may be compromised. VEGF165 may play a beneficial role in maintaining ovarian function by safeguarding ovarian vasculature following chemotherapy. Understanding these intricate dynamics is essential for developing strategies to mitigate the negative impact of cancer therapies on reproductive health in female cancer survivors, particularly in preserving endocrine function and reproductive lifespan. Presentation: 6/2/2024

7238 A rare cause of primary ovarian failure in an adolescent due to a genetic mutation in mitochondrial poly-A-polymerase (mTPAP) mRNA

Abstract Disclosure: J. Epstein: None. S. Veera: None. J. Pappas: None. B.C. Shah: None. Primary ovarian insufficiency (POI) is a dysfunction or loss of ovarian follicles with associated amenorrhea. While most causes are idiopathic, approximately 15% of POI cases are due to single gene or chromosomal abnormalities, such as X chromosome abnormalities. Many of these nuclear genes encode for proteins that function within the mitochondria. Mitochondrial disorders affect tissues with high energy demand, such as the neurological, skeletal, cardiac, and endocrine systems. Furthermore, mature ovaries have a relatively higher concentration of mitochondria, which play a role in cellular respiration along with steroidogenesis. Mutations that disrupt these pathways can therefore lead to ovarian dysfunction. We present a case of a 17-year-old female with concern for primary amenorrhea. She underwent pubarche at age 12 years and thelarche at 14 years, with slowed progression. Height Z score was -1.61 and weight Z score was -0.41. Lab work at presentation was significant for LH 18.6 IU/L (N 2.4-12.6 IU/L), FSH 43.9 IU/L (N 1.1-9.6 IU/L), low estradiol <2.5 pg/mL (N 30-100 pg/mL), low total testosterone 8.3 ng/dL (N 15-31 ng/dL), unremarkable HbA1C, cortisol, thyroid levels, and a 46 XX karyotype. Pelvic ultrasound showed small ovarian volumes with a 1.9 cc right ovary, 1.5 cc left ovary consistent with lack of hormonal stimulation, and uterus length of 4.9 cm (N > 4 cm) consistent with early hormonal stimulation. She was started on transdermal estrogen replacement. Past medical history included stable pericardial effusion, episodes of supraventricular tachycardia, pre-cataracts, speech delays, mild learning disabilities, spastic diplegia, progressive gait abnormalities, ligamentous laxity, and recurrent patellar dislocations requiring multiple orthopedic limb surgeries. Family history was significant for parental consanguinity as first cousins. As the etiology of the POI remained unknown, genetic testing was completed. Whole exome sequencing (WES) revealed a homozygous pathogenic variant in the MTPAP gene: p.(Leu495Arg) (CTG>CGG): c.1484 T>G in exon 9 on chromosome 10p11.23. MTPAP, also known as SPAX4, TENT6, or PAPD1, is a nuclear-encoded polymerase involved in synthesizing the 3’ poly(A) tail of mitochondrial transcripts as well as in mRNA degradation. She was diagnosed with autosomal recessive MTPAP-related neurodevelopmental and movement disorder. Monogenic disorders affecting mitochondrial function are rare causes of POI. A high index of suspicion should be raised when a constellation of neurological, musculoskeletal, and cardiac problems co-exist. WES can be a very useful tool for uncovering rare genetic disorders. Further studies are needed to clarify details of organ specific mitochondrial dysfunction and possible therapeutics in individuals affected with MTPAP-related neurodevelopmental and movement disorders. Presentation: 6/1/2024

The Sonographic Characteristics of Isolated Fallopian Tube Torsion

ObjectiveIsolated fallopian tube torsion (IFTT) presents a challenging preoperative diagnosis. This study investigated the specific sonographic characteristics of IFTT and compared them to the characteristics of ovarian and adnexal torsion. DesignRetrospective cohort study. SettingTertiary level gynecological ultrasound unit.: 225 women operated for suspected isolated ovarian, fallopian tube or adnexal torsion (ovary and tube) were included. InterventionsElectronic medical records of patients diagnosed with torsion at our ultrasound unit from 2001 to 2018 were retrieved. Inclusion criteria were women operated for suspicion of isolated ovarian, fallopian tube or adnexal torsion (involving both ovary and tube), with a preoperative sonogram performed in our tertiary level gynecologic ultrasound unit. Patients operated after a sonographic examination in the emergency department were excluded. MeasurementsPatients were divided into 4 groups according to their laparoscopic diagnosis: IFTT, ovarian torsion, adnexal torsion or no torsion.The sonographic characteristics of the groups were compared and the diagnosis was confirmed according to laparoscopy findings. Main resultsIFTT was reported in 28/225 (12.4%) cases. Ovarian volume was significantly lower in IFTT (29.2 ± 44 cm3) compared to ovarian torsion (111 ± 143 cm3, p=.037). There were fewer cases of ovarian edema in IFTT compared to ovarian torsion (12/22 (54.5%) vs. 54/63 (85.7%) respectively, p=.001). IFTT was associated with paraovarian cyst significantly more often than with ovarian torsion (13/24 (54.2%) vs. 4/75 (5.3%), respectively; p=.003). There was no difference between whirlpool sign and location in all forms of torsion. The sensitivity, specificity, Positive predictive value and Negative predictive value for IFTT were 88.4%, 83.3%, 95.8% and 62% respectively. ConclusionIFTT has distinct sonographic characteristics, including normal ipsilateral ovary, paraovarian cyst, and whirlpool sign. Awareness of these features may improve the diagnosis of IFTT and promote faster and more efficient treatment. Further studies are needed to establish these characteristics.

Exposure to ambient particulate matter and ovarian reserve impairment among reproductive age women in China

Ovarian aging, characterized by a decline in ovarian reserve, is a critical concern in female reproductive health. However, the evidence linking ambient air pollution exposure with ovarian reserve impairment remains limited. We aimed to estimate the association between exposure to fine particulate matter (PM2.5) and respirable particulate matter (PM10) and key indicators of ovarian reserve, including antral follicle count (AFC), ovarian volume (OV), anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), estradiol (E2), luteinizing hormone (LH), FSH/LH ratio, and inhibin B (INHB). The cohort consisted of women attending an infertility clinic at the Tongji Reproductive and Environmental (TREE) study between 2018 and 2020. We used multivariate linear and Poisson regression models to estimate the association between PM2.5 and PM10 exposure and these ovarian reserve indicators. Our results showed that PM2.5 and PM10 exposure were associated with a reduction in AFC and an increase in E2 levels, highlighting the adverse effects of ambient air pollution on ovarian reserve. Our findings have important public health implications, emphasizing the urgent need for interventions to safeguard female reproductive health and reduce exposure to ambient air pollution.

Effect of Choline Inositol and Metformin Combination Versus Metformin Alone on Ovarian Activities in PCOS Iraqi Women: A Cross Sectional Study

Abstract: Polycystic ovary syndrome (PCOS) is a predominant endocrine sickness disturbing females. It is marked via unequal menstrual cycles, hyper-androgenism, and polycystic ovarian morphology. Furthermore, PCOS is linked to several health issues, including insulin resistance and metabolic syndrome. PCOS management encompasses a range of strategies and treatments. Medications acting on hormones, including insulin sensitizers such as inositol and metformin, are commonly used to treat PCOS symptoms. Also choline is other potential therapies that could improve reproductive health. It has been suggested to be beneficial in various aspects of fertility, including endocrine disorders like polycystic ovarian syndrome (PCOS). Aim of the study: The current study aims to determine the effect of choline inositol and metformin combination versus metformin alone on ovarian. Materials and methods: This study was performed at the Maternity and Paediatrics Teaching Hospital in ALdiwaniyah Province, Iraq. The study involved a total of (150) patients at (18- <40) years. A gynecologist uses Rotterdam criteria and ultrasound ovarian morphology in the selection of PCOS patients. The study consisted of several groups: G1 is a thirty women had received oral Metformin 500 mg bid during meal for last three months and served as metformin group. G2 is a thirty women had received choline inositol supplement 500/500 mg per- oral twice daily for last three months and served as the choline inositol supplement group. G3 is a thirty women had received choline inositol and metformin combination, they received with the same above dose for last three months and served as the choline inositol and metformin combination group . G4 is a thirty women who have not received any treatment for PCOS and served as new diagnosis PCOS group. Finally G5 is a thirty healthy women control group (control group). Characteristics included body mass index, type of period (regular, irregular ,amenorrhea ) were evaluated for all the participants. Furthermore, follicle and ovary volume were measured for all women .Additionally, serum hormonal levels [prolactin, (FSH), (LH), (TSH)], test were done. Results: There was no important alteration in the mean age, TSH and prolactin among the five groups. The results showed that metformin had significantly lowered in BMI but the addition choline inositol to metformin showed more significantly lowering in BMI but new PCOS group had higher significant BMI than other groups followed by choline inositol group. Rate of amenorrhea and rate of cycle irregularity stayed considerably upper in metformin grouping paralleled to choline inositol and choline inositol + metformin combination groups but this rate was more significantly higher in new PCOS compared to other groups. Metformin had significantly higher LH level compared to other groups but choline inositol + metformin and choline inositol groups had significantly lower LH level and there were no significance in the mean of LH between Choline inositol + metformin and choline inositol groups. Moreover, choline inositol + metformin group showed more significant FSH normal followed by metformin and new PCOS then by choline inositol and lastly control group. Choline inositol followed by metformin showed a significance in the mean of follicle and ovary volume but when adding choline inositol to metformin it showed more significant improvement in follicle and ovary volume ,so positive pregnancy was only seen in choline inositol + metformin as compared to other groups.

Effects of Coenzyme Q10 Combined With Metformin on Ovarian Function Compared to Metformin Alone in Iraqi PCOS Patients

Background: Data about the response of ovary function in women with polycystic ovary syndrome (PCOS) to metformin treatment are controversial and the use of metformin in women with this syndrome combined with CoQ10 has never been assessed previously using the current study design. Research objective: to figure out the effect of Co Q10 and metformin combination in contrast to monotherapy using metformin on ovary activity in PCOS Patients and methods: The present study included 150 patients with an age range of 20 to less than 35 years. Patients were categorized into five groups: CoQ10 groups who were treated using 10 mg per-oral (bid), metformin group (positive control group) and they received metformin as 500 mg per-oral (bid), combination groups who received both agents with similar doses as above, newly diagnosed group who received no treatment and finally newly diagnosed PCOS. Each group included 30 women. Pediatrics and Maternity Teaching Hospital in Adiwaniyah Province (Iraq) was the location of sample collection. Beginning of study was at September the 21st 2023 and extended to March 31st 2024. Data about age and body mass index were included in the study. Ultrasound assessment of ovarian volume and antral follicle volume was carried out before and after treatment.Results: Comparison of mean ovary volume among research cohorts is shown in table 2. Statistically notable variance was reported in average ovary volume across research cohorts (p < 0.001). Mean ovary volume was highest in newly diagnosed PCOS group and it was lowest in negative control group and combination group. The volume was comparable in CoQ10 group and metformin group; however, combination group had significantly lower mean ovary volume in comparison with either treatment approach alone (p < 0.05). Statistically notable variance was reported in average follicle volume across study cohorts (p < 0.001). Average follicle volume was lowest in newly diagnosed PCOS group and it was highest in negative control group. The volume was comparable in CoQ10 group and metformin group; however, combination group had significantly higher mean follicle volume in comparison with either treatment approach alone (p < 0.05). Conclusion: Both treatment approaches using metformin alone or CoQ10 alone produces significant improvement in ovary volume and antral follicle volume in women with PCOS; however, combination of both agents resulted in more significant improvement.

Clinical and diagnostic evidence of benign endometrial pathology in postmenopausal patients

The objective: to study clinical and diagnostic features of the benign endometrial conditions in the postmenopausal women.Materials and method. 64 postmenopausal patients with various severity of postmenopausal vaginal bleeding were examined. All patients underwent clinical, radiological, laboratory and histological examinations, reproductive history data and body mass index indicators were evaluated. Of them 33 persons were diagnosed with complex endometrial hyperplasia without atypia, 16 women – endometrial polyp and 15 women – hyperplasia with atypia. Routine gynecological examination including abdominal and pelvic examination following transvaginal ultrasound examination for the determination of the uterine and ovarian volume as well, as the endometrial thickness were conducted. Patients included in the study underwent computer tomography and magnetic resonance imaging as indicated. All patients with endometrial pathology underwent endometrial biopsy by standard dilatation and curettage or Pipelle-biopsy with histological examination of the obtained material. The concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEA-S), estradiol, estrone, progesterone, prolactin, and testosterone were determined in blood serum.Results. It was confirmed that in 87,5% of cases endometrial hyperplasia manifested with vaginal bleeding. Endometrial thickness in examined persons ranged from 14.1±1.6 mm in patients with atypical endometrial hyperplasia to 21.3±4.8 mm in patients with complex endometrial hyperplasia without atypia. The study of blood levels of hormones found that postmenopausal patients with endometrial hyperplasia have lower FSH concentration, LH/FSH ratio, estradiol, testosterone levels, with significantly high values of prolactin, DHEA-S and estrone. During the postmenopausal period, hyperplasia was developed in 10% of cases by the presence of bleeding, and 86.2% of cases by the presence of blood spotting. Conclusions. The study suggests that high body mass index, numerous artificial abortions, high blood levels of estrone, DHEA-S and prolactin as well as increased thickness of endometrium influence the frequency of endometrial hyperplasia in postmenopausal women.

Ovarian and Uterine Morphology in Minipuberty: Associations with Reproductive Hormones. A COPANA Study of 302 girls.

Female minipuberty is characterized by complex dynamics of circulating reproductive hormones, while the relationship between ovarian and uterine morphology and reproductive hormones remains to be elucidated. To investigate the association between reproductive hormones and ovarian as well as uterine morphology by transabdominal ultrasound (TAUS) at minipuberty. Secondary analysis from The Copenhagen Analgesic Study (COPANA) (ClinicalTrials.gov NCT04369222). Healthy infant girls (n=302, age 3.4 months (0.4) mean (±SD): mamma tissue diameter (mm), n=300. TAUS: uterine volume (n=230), endometrial thickness (n=255), ovarian volume, antral follicle count (total/2-4mm/≥5mm) (n=203).Blood samples (n=269/302=89%): AMH, FSH, LH, inhibin B (immunoassays), progesterone (PROG), androstenedione (Adione), testosterone (T), estrone (E1), estradiol (E2) (LC/MS-MS).Statistics: Pearson/Spearman´s correlation coefficient (parametric/non-parametric data). Total follicle count correlated positively with ovarian volume (r= 0.606, p<0.001), AMH (r=0.378, p<0.001), inhibin B (r=0.251, p<0.001), and negatively with FSH concentrations (r=-0.327, p<0.001). Larger follicles (≥5mm) correlated positively with AMH (r=0.264, p<0.001), inhibin B (0.230, p=0.002), E1 (r=0.209, p=0.004), E2 (r=0.269, p<0.001), PROG (r=0.160, p=0.031) and T (r=0.210, p=0.004) and negatively with FSH (r=-0.183, p=0.015). Circulating E1 and E2 levels correlated with the size of estrogen-responsive tissue sizes: E2 vs. uterine volume (r=0.134, p=0.054), E2 vs. endometrial thickness (r=0.155, p=0.020), E1 and E2 vs. mammary tissue diameter (r=0.213 and r=0.198, respectively, both p < 0.001). Correlations between reproductive hormones and the number of antral follicles suggest that negative feedback in the female HPG axis is established during minipuberty, with ovarian activity promoting uterine and glandular breast tissue growth We provide normative data of infant ovarian- and uterine morphology directly implementable to a clinical setting.

Can ultrasound elastography be useful in the diagnosis of poor ovarian response?

This study aims to compare the elastographic properties of the ovaries of patients with poor ovarian response (POR) with healthy controls by using real-time ultrasound tissue elastography and to investigate the predictive value of ovarian strain ratio (OSR) in the diagnosis of POR. A cross-sectional study was conducted among infertility patients. OSR measurements of 46 women diagnosed with POR and 41 healthy controls with male infertility were performed by real-time ultrasound tissue elastography. Ovarian volume, OSR, antral follicle count (AFC), age, body mass index (BMI), anti-mullerian hormone (AMH), follicle stimulating hormone (FSH), and estradiol (E2) values, were compared between the groups. A receiver operating characteristic curve was used to compare the sensitivity and specificity of OSR, AFC, AMH, FSH, and E2 for POR diagnosis. Patients with POR were significantly older, had a lower duration of infertility, lower AMH, higher FSH, higher E2, lower AFC and ovarian volume (p < 0.01, p = 0.02, p < 0.01, p < 0.01, p < 0.01, p < 0.01, p < 0.01, respectively). The mean OSR of both ovaries was similar between the groups. For the diagnosis of POR, the sensitivity and specificity for AMH were 97.5% and 100%, for AFC were 86.7% and 97.6%; for FSH were 66.7% and 80.5%, for E2 were 53.3% and 90.2%, respectively. The significant independent predictors of the POR were AMH, AFC, and FSH, with no additional significant contribution from OSR. However, considering the relationship between POR and ovarian fibrosis, it is recommended to investigate this issue in more comprehensive studies.

Mechanism study of YangJing ZhongYu decoction on regulating mitochondrial dynamics of ovarian granular cells and improving diminished ovarian reserve

ObjectiveDiminished ovarian reserve (DOR) encompasses both reproductive and endocrine disorders, resulting in a decline in female fertility. This paper explored the mechanism of Yangjing Zhongyu Decoction (YJZYD) regulating mitochondrial dynamics of ovarian granulosa cells (GCs) to improve DOR.MethodsDOR patients were treated with YJZYD, with ovarian volume (OV), antral follicle count (AFC), and endometrial thickness (EMT) detected. C57BL/6 female mice were treated by cyclophosphamide (Cy) intraperitoneal injection and YJZYD solution daily gavage, with serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels determined. Ovarian GCs (KGN) were interfered with 4-Hydroperoxy-Cyclophosphamide (4-HC) and treated with the MAPK/ERK pathway inhibitor or activator.ResultsDOR patients showed increased levels of serum AMH, E2, OV, AFC and EMT, while reduced FSH and LH levels after YJZYD treatment. After Cy induction, DOR mice exhibited irregular estrous cycles, diminished serum AMH and E2 levels, elevated FSH and LH levels, reduced follicle number and atresia follicle number, disorderly arranged GCs, and severe interstitial fibrosis. After 4-HC treatment, KGN proliferation and Bcl-2, MFN1, and MFN2 were suppressed, while apoptotic rate, Bax, Cleaved-caspase-3, and p-Drp1 (Ser616) levels, and mitochondrial fission and quantity increased. YJZYD promoted 4-HC-treated KGN proliferation, boosted mitochondrial fusion, and inhibited apoptosis and mitochondrial fission via the MAPK/ERK pathway.ConclusionYJZYD promoted ovarian GC proliferation and mitochondrial fusion, suppressed cell apoptosis and mitochondrial fission, and effectively improved DOR in mice by activating the MAPK/ERK pathway, providing a theoretical basis for the clinical application value of YJZYD in DOR treatment.

How Frequently Is Ultrasound Required to Diagnose Polycystic Ovary Syndrome in a Clinical Population?

Background: Polycystic ovary syndrome (PCOS) is a common endocrine condition, affecting up to 20% of reproductive aged women worldwide. Polycystic ovarian morphology (PCOM) may be present, but is not required for diagnosis. Our study seeks to evaluate the utility of ultrasound in diagnosing or excluding PCOS by 2023 International Guidelines Criteria. Materials and Methods: Subjects were patients seen in a tertiary care referral clinic in whom other causes of hyperandrogenism (HA) were ruled out. All underwent complete history, physical, modified Ferriman Gallwey scoring, and serum androgen testing; followed by transvaginal ultrasound (TVUS) to assess ovarian morphology if indicated. PCOM was identified as antral follicle count ≥20 and/or ovarian volume >10 mL in at least one ovary. After clinical classification, PCOS was diagnosed by at least two of three: biochemical/clinical HA, ovulatory dysfunction (OD), and PCOM. Statistics were calculated using Fisher's exact test and chi-square. Results: In total, 454 subjects were included. 299 were classified as group A/B and did not require TVUS for diagnosis. Of 82 subjects with HA alone, 50 (61.0%) were classified as group C after demonstrating PCOM. Fifty-five subjects had OD alone, 37 (67.3%) of which were classified as group D based on PCOM. In total, 137/454, or 30.2% of subjects required TVUS for diagnosis or exclusion of PCOS. Conclusions: TVUS was necessary in less than one-third of subjects, primarily identifying PCOS groups C or D. Selective use of ovarian ultrasonography may reduce the costs and complexity of epidemiological and clinical studies for PCOS.

Ovarian Insufficiency in Adolescent Females with Transfusion-Dependent β-Thalassemia: Pituitary versus Ovarian Iron Overload

Introduction: Females with transfusion-dependent β-thalassemia (TDT) display menstrual irregularities and subfertility at certain points in their lives, even if well-chelated, representing a significant physical and psychological burden. Little is known about the effects of pituitary and ovarian iron contents on ovarian reserve and function. Hence, this study aimed to assess ovarian reserve and pituitary-gonadal axis function in adolescent females with TDT and correlate them with pituitary and ovarian volume, pituitary iron load, and serum ferritin. Methods: Fifty adolescent females with TDT were compared to 50 age-matched healthy females. Age of diagnosis of TDT, transfusion index, type of chelation therapy, age at menarche, and Tanner breast stage were assessed. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), and ferritin were measured. Magnetic resonance imaging (MRI) pituitary iron content R2* and T2* were measured, and 3-D transabdominal ovarian ultrasound performed. Results: The mean age of the studied females with TDT was 14.54 ± 2.24 years. Ovarian insufficiency was found in 20 of them (40%). Compared to controls, adolescent females with TDT had significantly delayed age of menarche, AMH, FSH, LH, antral follicle count (AFC), and ovarian volume. Upon comparing those with ovarian insufficiency and those without, adolescents with TDT having ovarian insufficiency had significantly higher serum ferritin and pituitary MRI-R2* than those without insufficiency. Multivariate-logistic regression showed that pituitary MRI-R2* was the most significant independent variable associated with ovarian insufficiency among adolescent females with TDT. Conclusion: Adolescent females with TDT have decreased ovarian reserve, AFC, and gonadotropins that are correlated with serum ferritin, pituitary iron load, and ovarian volume. Hence, regular ovarian reserve assessment should be implemented as a part of endocrinological follow-up of females with TDT advising procedures to preserve fertility to those who are likely to have ovarian insufficiency.

Potential of AKNA as a Predictive Biomarker for Ovarian Cancer and Its Relationship to Tumor Grading.

Ovarian cancer exhibits a significant prevalence and incidence on a global scale. Low-grade or high-grade epithelial-type ovarian cancer can be classified by using the dualistic model. Inflammation has been associated with AKNA protein by cancer researchers. The potential of AKNA as a cancer biomarker is supported by its significance and association with ovarian carcinoma. Uninvestigated is this enormous potential. This study examines the correlation between AKNA expression in low-grade and high-grade ovarian tumors and its utility as a predictive biomarker for ovarian cancer. This study examined a total of thirty-one samples, which were classified into three groups: cyst, low-grade, and high-grade ovarian carcinoma. The departmental archive was accessed for the following information: age, tumor size, nuclear grade, mitosis, ovary volume, implant tumor status, lymph vascular invasion status, lymph node metastasis, and tumor-infiltrating lymphocyte. The expression of AKNA was determined using IHC staining. The information was collected and analyzed via analysis of variance. The AKNA H-score shows the mean difference between all three groups (P < 0.001). Cysts had the highest AKNA expression, followed by low-grade and high-grade ovarian carcinoma. Higher-grade ovarian cancer expressed less AKNA compared to cysts or low-grade forms of the disease. This considerable difference suggests that AKNA might predict ovarian cancer tumor grade.

Fundamentals to Diagnosing Polycystic Ovary Syndrome in Adolescents: A Critical Literature Review

Background: Because of this prevalence and frequent association with various comorbidites, the diagnosis of polycystic ovary syndrome (PCOS) must be performed as early as possible. Despite conflicting findings, many studies have been published on adolescents with a diagnosis of polycystic ovary syndrome. Methods: The Google Scholar and PubMed data bases were searched for publications in the English language reporting on PCOS diagnosis in adolescents. Results: A comprehensive analysis of data regarding the overlay of physiological ripening of menstrual cycle characteristics, androgen levels, and ovary aspects during puberty with the established criteria to diagnose PCOS in adults revealed that are liable diagnosis of PCOS in adolescence is possibleas soon as 2-3 years postmenarche. Persistant menstrual cycle intervals shorter than 21 days or longer than 45 days, total testosterone levels &amp;gt;1.9-2.0 nmol/l and ovary volume &amp;gt;10cm&amp;lt;sup&amp;gt;3 &amp;lt;/sup&amp;gt;after 15-16 years of age can be used to diagnose PCOS. Conclusion: When combined, any persistent deviation of physiological parameters in adolescents as a criterion to diagnose PCOS in adults allows a certain diagnosis of PCOS in adolescents.

Efficacy and safety of cangfu daotan decoction as an adjuvant treatment of Diane-35 for polycystic ovary syndrome: A systematic review and meta-analysis

ObjectiveCangfu Daotan decoction is a classic traditional Chinese medicine formula that has been found to be beneficial for treating polycystic ovarian syndrome (PCOS) in animal models. This systematic review aimed to assess the efficacy and safety of Cangfu Daotan decoction as an adjuvant treatment to Diane-35 for PCOS in humans. MethodsSeven electronic databases were searched up to June 22, 2024, to identify randomized controlled trials (RCTs) that evaluated Cangfu Daotan decoction combined with Diane-35 versus Diane-35 alone for the treatment of PCOS. The effects of individual RCTs were combined via meta-analysis and were measured as relative risks (RRs) or weighted mean differences (WMDs). ResultsTwenty-five RCTs with a moderate to high risk of bias were included, involving 1845 patients with PCOS. Meta-analyses indicated that compared with Diane-35 alone, the combination of Diane-35 and Cangfu Daotan decoction significantly improved the response rate (RR 1.19, 95 % confidence interval [CI] 1.14 to 1.24), pregnancy rate (RR 1.57, 95 % CI 1.18 to 2.09), ovulation rate (RR 1.22, 95 % CI 1.11 to 1.35), and ovarian volume (WMD -1.43 cm3, 95 % CI -2.46 to −0.39). Cangfu Daotan decoction also significantly reduced the luteinizing hormone (LH) level, LH:FSH ratio, testosterone level, prolactin level, body mass index (BMI) and hirsutism and acne scores but had no significant effect on the follicle-stimulating hormone (FSH) level. All adverse events were mild and not related to Cangfu Daotan decoction treatment. ConclusionsThe findings suggest that Cangfu Daotan decoction, as an adjuvant therapy to Diane-35 for the treatment of PCOS, can reduce multiple sex hormone levels and BMI, relieve hyperandrogenism signs, and ultimately improve pregnancy outcomes, with good safety. The effect of Cangfu Daotan decoction on FSH remains uncertain. Due to limitations of risk of bias and heterogeneity, the quality of evidence was rated as moderate to very low.

Anti-Müllerian hormone and fertility in women after childhood cancer treatment: Association with current infertility risk classifications.

To identify childhood cancer survivors (CCSs) at risk of premature ovarian insufficiency (POI) and impaired fertility is important given its impact on quality of life. The aim of this study was to assess ovarian markers and fertility outcomes in adult female CCSs. We used the Swedish and the PanCareLIFE classifications for infertility risk grouping. 167 CCSs, at median age 34.6 years (19.3-57.8) with a median follow-up time of 25.4 years (11.6-41.3), and 164 healthy matched controls were included in this cross-sectional study. We assessed anti-Müllerian hormone (AMH) levels, antral follicle count (AFC), ovarian volume (OV), and fertility outcomes. Based on gonadotoxic treatments given, CCSs were categorized into infertility risk groups. The median levels of AMH, AFC and OV were lower in CCSs (1.9 vs. 2.1 ng/ml, 12.0 vs. 13.0, 6.8 vs. 8.0 cm3) compared with controls, although statistically significant only for OV (p = 0.021). AMH levels in CCSs <40 years were lower for those classified as high-risk (p = 0.034) and very high-risk (p<0.001) for infertility, based on the Swedish risk classification. Similarly, AFC was reduced in the high-risk (p<0.001) and the very high-risk groups (p = 0.003). CCSs of all ages showed a trend towards impaired fertility, especially in the very high-risk group. POI was diagnosed in 22/167 CCSs, of whom 14 were in the high- and very high-risk groups. The results according to the PanCareLIFE classification were similar. Both the Swedish and the PanCareLIFE infertility risk classifications are reliable tools for identifying those at risk of reduced ovarian markers and fertility, as well as POI. We recommend fertility preservation counselling for patients receiving highly gonadotoxic treatments (i.e., Cyclophosphamide Equivalent Dose ≥6 g/m2, radiotherapy exposure to ovaries or stem cell transplantation) with follow-up at a young reproductive age due to the risk of a shortened reproductive window.

Efficacy analysis of letrozole combined with gonadotropin-releasing hormone antagonists in patients with high risk of ovarian hyperstimulation syndrome undergoing total embryo freezing

Objective: To investigate the clinical efficacy of letrozole combined with gonadotropin-releasing hormone antagonists (GnRH-ant) in patients at high risk of ovarian hyperstimulation syndrome (OHSS) who underwent total embryo freezing after oocyte retrieval. Methods: A retrospective analysis was conducted on 348 female patients who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) at the Reproductive and Genetic Hospital of the First Affiliated Hospital of Zhengzhou University between January and July 2023. Due to their high risk of OHSS, these patients canceled fresh embryo transfer and opted for total embryo freezing. Based on patients' preferences, those who received GnRH-ant and letrozole after oocyte retrieval were categorized as the intervention group (164 cases), while those who did not receive these medications were categorized as the control group (184 cases). The first luteal phase after oocyte retrieval, OHSS grading, ovarian volume, and estradiol (E2) levels were evaluated in both groups. A multivariate logistic regression model was used to analyze factors related to moderate-to-severe OHSS among patients at high risk of OHSS who underwent total embryo freezing after oocyte retrieval. Results: The age of the intervention and control groups was (29.3±3.8) and (29.4±4.1) years, respectively (P=0.821). The duration of the first luteal phase post-oocyte retrieval was shorter in the intervention group [(7.16±1.39) days] compared to that in the control group [(13.88±2.11) days] (P<0.001). The incidences of mild, moderate, and severe OHSS in the intervention group were 75.0% (123 cases), 23.8% (39 cases), and 1.2% (2 cases), respectively, whereas in the control group they were 12.5% (23 cases), 60.9% (112 cases), and 26.6% (49 cases) (P<0.001). E2 levels on the 2nd and 6th days after oocyte retrieval [M(Q1,Q3)] in the intervention group were 1 520.0 (1 213.8, 1 884.8) and 108.5 (45.6, 218.0) ng/L, respectively, which were statistically significantly lower than those in the control group [1 666.0 (508.8, 1 702.0) ng/L] and [1 761.0 (826.0, 2 546.5) ng/L] (P<0.001). The abdominal cavity effusion in the intervention group [M(Q1,Q3)] were 19.5 (0, 30) and 0 mm, statistically significantly less than those in the control group [46.0 (0, 61.0) mm] and [54.5 (0, 69.5) mm] (P<0.001). On the 6th day after oocyte retrieval, the bilateral ovarian volumes in the intervention group were smaller than those in the control group (P<0.001). Multivariate logistic regression analysis indicated that no combined treatment with letrozole and GnRH-ant was a risk factor of moderate to severe OHSS. The risk of developing moderate to severe OHSS in the control group was 35.312 times higher than that in the intervention group (OR=35.312, 95%CI: 17.488-71.300). Conclusions: The administration of letrozole combined with GnRH-ant post-oocyte retrieval in patients at high risk of OHSS can prevent the occurrence of moderate-to-severe OHSS, shorten the first luteal phase, accelerate the reduction of serum E2 levels, and promote the recovery of ovarian volume and absorption of abdominal fluid.

The additional value of ultrasound markers in the diagnosis of polycystic ovary syndrome

ObjectiveTo study the value of current definitions for follicle number per ovary and ovarian volume in the diagnosis of polycystic ovary syndrome (PCOS). DesignCross-sectional study. SubjectsWomen diagnosed with PCOS after standardized screening were eligible for inclusion in the PCOS group. Women without PCOS who underwent the same screening, had regular menstrual cycles, normal hormonal values, and no other endocrine pathology were eligible for inclusion. Exposure: -Main Outcome measuresFollicle number per ovary and ovarian volume in women with PCOS, stratified by age. Linear regression models to investigate the influence of BMI on follicle number per ovary and ovarian volume. Differences of follicle number per ovary and ovarian volume between the PCOS phenotypes and the additional value of ovarian volume compared to follicle number per ovary. ResultsA total of 2492 women (16 – 50 years) with PCOS and 152 women without PCOS were included. Most women with PCOS up to age 35 exhibit a follicle number per ovary ≥ 20 (87.8 – 100%) (using an ultrasound transducer ≥ 8 MHz) or ≥ 12 (95.1 – 98.6%) (using a transducer < 8 MHz), followed by a decline in follicle number per ovary above the age of 35. Median ovarian volume was below the 10 mL cut-off in every age group, for both ultrasound transducers. Follicle number per ovary and ovarian volume was higher in women with PCOS compared to women without PCOS in every age category. In our cohort, 13/2297 women with PCOS (0.6%) would not have received the diagnosis if ovarian volume was not considered as a marker for polycystic ovarian morphology. For both ultrasound transducers, women with phenotype A (ovulatory dysfunction + hyperandrogenism + polycystic ovarian morphology) exhibited the highest follicle number per ovary and ovarian volume, followed by phenotype D (ovulatory dysfunction + polycystic ovarian morphology), then phenotype C (hyperandrogenism + polycystic ovarian morphology), and then phenotype B (ovulatory dysfunction + hyperandrogenism) (all p-values < 0.001 after adjusting for age). No clinically significant correlation between BMI and follicle number per ovary or ovarian volume was observed. ConclusionCriteria to define follicle number per ovary should be established per age category, as follicle number per ovary decreases with age. Ovarian volume shows a less clear decline with age and has a lower discriminative power, and therefore could be excluded from the diagnostic criteria. follicle number per ovary does not need to be stratified by BMI.