Ovarian Morphology in Non-Hirsute, Normo-Androgenic, Eumenorrheic Premenopausal Women from a Multi-Ethnic Unselected Siberian Population.

Polycystic ovary syndrome (PCOS) is a highly prevalent disorder in women, and its diagnosis rests on three principal features: ovulatory/menstrual dysfunction, clinical and/or biochemical hyperandrogenism, and polycystic ovarian morphology (PCOM). Currently, data on age- and ethnicity-dependent features of PCOM remain insufficient. We aimed to estimate ethnicity- and age-dependent differences in ovarian volume (OV) and follicle number per ovary (FNPO) in a healthy, medically unbiased population of Caucasian and Asian premenopausal women, who participated in the cross-sectional Eastern Siberia PCOS epidemiology and phenotype (ESPEP) study (ClinicalTrials.gov ID: NCT05194384) in 2016-2019. The study population consisted of 408 non-hirsute, normo-androgenic, eumenorrheic premenopausal women aged 18-44 years. All participants underwent a uniform evaluation including a review of their medical history and a physical examination, blood sampling, and pelvic ultrasonography. The statistical analysis included non-parametric tests and the estimation of the upper normal limits (UNLs) by 98th percentiles for OV and FNPO. In the total study population, the upper OV percentiles did not differ by ethnicity or age group. By contrast, the UNL of FNPO was higher in Caucasian women than in Asian women, and women aged <35 years demonstrated a higher UNL of FNPO compared to older women. In summary, these data suggest that the estimation of FNPO, but not OV, should take into account the ethnicity and age of the individual in estimating the presence of PCOM.

Growth hormone therapy is associated with improved uterine dimensions in girls with Turner syndrome prior to oestrogen replacement.

BACKGROUND: Adult women with Turner syndrome (TS) have high rates of miscarriage, presumably due to the abnormal size and shape of the uterus. There is a paucity of data regarding the determinants of uterine volume (UtVol) in young girls with TS before the initiation of oestrogen replacement therapy (ERT). METHODS: We performed a cross-sectional study on premenarchal girls with TS, aged 5-15 years, pubertal stage B1-B3, not having received ERT (n = 73) and 50 age-matched healthy controls. Anthropometric parameters and a history of growth hormone (GH) therapy (≥1 year) were noted. Uterine length (UtL), UtVol, and mean-ovarian-volume (MOV) standard-deviation scores (SDS) were determined from transabdominal ultrasonography data. RESULTS: Girls with TS had lower median UtVol-SDS (-1.07 vs. 0.86; p < .001), UtL-SDS (-3.72 vs. -0.41; p < .001) and MOV-SDS (-5.53 vs. 1.96; p < .001) compared to age-matched controls. Among TS girls, recipients of GH (n = 38) had higher UtVol-SDS (-0.63 vs. -1.39; p = .0001), UtL-SDS (-1.73 vs. -6.49; p < .0001) but similar MOV-SDS compared to nonrecipients (n = 35). Those with normal uterine volume for age (NUVA, n = 29) had earlier initiation (7.8 vs. 9.3 years; p = .03) and a longer duration of GH (3.71 vs. 2.14 years; p = .002) than those with low UtVol for age (n = 44). UtVol-SDS correlated with duration of GH (ρ = 0.411, p = .01) and negatively with age at GH initiation (ρ = -0.479, p = .003). In a model adjusted for pubertal status, karyotype and height-SDS, GH use could independently predict having NUVA (odds ratio: 5.09, confidence interval: 1.63-15.94, p = .005). CONCLUSION: GH therapy has a stimulatory effect on uterine dimensions in pre-and peripubertal girls with TS. Earlier initiation and longer duration of GH is important in TS girls before ERT.

The effect of subclinical hypothyroidism on ovarian volume in prepubertal girls.

OBJECTIVE: Enlargement and cystic changes in ovaries of patients with long-standing overt hypothyroidism have been described in numerous case reports. However, there are limited data about the effect of subclinical hypothyroidism (SH) on ovarian volume. The aim of the study is to evaluate the relationship between serum thyroid stimulating hormone (TSH) level and ovarian volume in prepubertal girls with SH. METHODS: Patients who were aged between 6 and 10 years and diagnosed with SH and age-matched healthy euthyroid controls were enrolled in the study. All subjects were prepubertal. RESULTS: Thirty-five children with SH (mean age; 7.6±1.0 years) and 50 euthyroid healthy girls (mean age; 7.7±1.2 years) were enrolled in the study. TSH and LH levels and both ovarian volumes were significantly higher in SH group than controls (p<0.05). In addition, TSH was positively correlated with ovarian volumes and LH in patients with SH (p<0.05). CONCLUSION: The results of this study showed that ovarian volumes of prepubertal girls with SH were significantly greater than those with normal thyroid function. Although ovarian enlargement and cyst formation is well recognized in long-standing overt hypothyroidism, it has been shown for the 1st time in patients with SH.

Ovarian volume partially explains associations of phthalate biomarkers with anti-Müllerian hormone and estradiol in midlife women.

BACKGROUND/OBJECTIVES: Women are ubiquitously exposed to endocrine disruptors, including phthalates. Ovarian follicles undergoing folliculogenesis (indirectly measured by ovarian volume) produce anti-Müllerian hormone (AMH) and estradiol (E2). We evaluated associations of phthalates with ovarian volume to assess whether this explained prior positive associations of phthalates with AMH and E2. METHODS: Women ages 45-54 years (n = 614) had transvaginal ultrasounds of right/left ovaries to calculate mean ovarian volume. Women provided up-to-four urine and blood samples for quantifying AMH (first serum sample), E2 (all serum samples), and nine phthalate metabolites (from pooled urine, representing six parent phthalates). Multivariable linear or logistic regression models (for individual phthalate biomarkers), as well as weighted quantile sum (WQS) regression (for mixture analyses) evaluated associations of phthalate biomarkers with ovarian volume. Using cross-sectional mediation analysis, we assessed whether associations of phthalates with ovarian volume partially explained those of phthalates with AMH or E2. RESULTS: Most women were non-Hispanic White (68%) and pre-menopausal (67%) with higher urinary phthalate metabolite concentrations than U.S. women. In single-pollutant models, 10% increases in mono(3-carboxypropyl) phthalate (MCPP) and monobenzyl phthalate (MBzP) were associated with 0.44% (95% CI: -0.02%, 0.91%) and 0.62% (95% CI: 0.02%, 1.23%) larger ovarian volumes, respectively. As a cumulative mixture, 10% increases in the phthalate mixture were associated with 2.89% larger ovarian volume (95%CI: 0.27, 5.59) with MCPP (35%) and MBzP (41%) identified as major contributors. Higher ovarian volume due to a 10% increase in MBzP (indirect effect OR: 1.004; 95% CI: 1.00, 1.01) explained 16% of the positive association between MBzP and higher AMH, whereas higher ovarian volume due to a 10% increase in MCPP (indirect effect %Δ: 0.11; 95% CI: -0.01, 0.22) explained 23% of the positive association between MCPP and E2. CONCLUSION: In this cross-sectional study, phthalates were associated with increased ovarian volume, with implications for midlife hormone production.

Diagnostic Performance of Ovarian Morphology on Ultrasonography across Anovulatory Conditions-Impact of Body Mass Index.

The study objectives were to determine whether ovarian morphology can distinguish between women with regular menstrual cycles, normo-androgenic anovulation (NA-Anov), and PCOS and whether body mass index (BMI)-specific thresholds improved diagnostic potential. Women with PCOS (biochemical and/or clinical hyperandrogenism and irregular cycles; N = 66), NA-Anov (irregular cycles without clinical and/or biochemical hyperandrogenism; N = 64), or regular cycles (controls; cycles every 21-35 days in the absence of clinical or biochemical hyperandrogenism; N = 51) were evaluated. Participants underwent a reproductive history, physical exam, transvaginal ultrasound, and a fasting blood sample. Linear regression analyses were used to assess the impact of BMI on ovarian morphology across groups. The diagnostic performance of ovarian morphology for anovulatory conditions, and by BMI (lean: <25 kg/m2; overweight: ≥25 kg/m2), was tested using Receiver Operating Characteristic (ROC) curves. Follicle number per ovary (FNPO) and ovarian volume (OV), but not follicle number per cross-section (FNPS), increased across controls, NA-Anov, and PCOS. Overall, FNPO had the best diagnostic performance for PCOS versus controls (AUCROC = 0.815) and NA-Anov and controls (AUCROC = 0.704), and OV to differentiate between PCOS and NA-Anov (AUCROC = 0.698). In lean women, FNPO best differentiated between PCOS and controls (AUCROC = 0.843) and PCOS versus NA-Anov (AUCROC = 0.710). FNPS better distinguished between NA-Anov and controls (AUCROC = 0.687), although diagnostic performance was lower than when thresholds were generated using all participants. In women with overweight and obesity, OV persisted as the best diagnostic feature across all analyses (PCOS versus control, AUCROC = 0.885; PCOS versus NA-Anov, AUCROC = 0.673; NA-Anov versus controls, AUCROC = 0.754). Ovarian morphology holds diagnostic potential to distinguish between NA-Anov and PCOS, with marginal differences in diagnostic potential when participants were stratified by BMI suggesting that follicle number may provide better diagnostic performance in lean women and ovarian size in those with overweight.

Analysis of the effect of hashimoto's thyroiditis and insulin resistance on ovarian volume in patients with polycystic ovary syndrome.

OBJECTIVE: In this study, patients were divided into two groups. Patients with polycystic ovary syndrome (PCOS) and patients with polycystic ovary syndrome + Hashimoto's Thyroid (PCOS + HT). The effect of insulin resistance on ovarian volume in patients divided into two groups and the change in ovarian volume with the addition of HT to PCOS will be investigated. MATERIAL AND METHODS: 46 PCOS patients and 46 PCOS patients diagnosed with HT were included in this study. A detailed medical history was taken from all participants. Polycystic ovary image was evaluated as below or above 10 ml and antral follicles were counted by transvaginal ultrasound. Insulin resistance of the patients was evaluated according to the fasting insulin (HOMA) index. RESULTS: Insulin resistance was found to be associated with fasting insulin, HOMA index, body mass index and right ovarian volume in patients diagnosed with PCOS. Among the patients diagnosed with PCOS + HT, insulin resistance was found to be significantly correlated with fasting insulin, HOMA index, (BMI), (SHBG) and left ovarian volume. An increase in right ovarian volume was found in 37.5% of patients with PCOS without insulin resistance and in 76.3% of patients with insulin resistance. An increase in left ovarian volume was found in 35.7% of patients without insulin resistance diagnosed with PCOS + HT and in 68.8% of patients with insulin resistance. CONCLUSIONS: This study shows that ovarian volume should be evaluated in every PCOS patient in order to predict insulin resistance, which causes long-term metabolic diseases, and that all PCOS patients with increased ovarian volume should be investigated for insulin resistance. In addition, it has been observed that insulin resistance affects left ovarian volume in patients with PCOS + HT, whereas insulin resistance affects the volume of the right ovary more in patients with PCOS. At least one ovary has been found to be affected by long-term metabolic diseases. While there was a greater increase in ovarian volume with the addition of insulin resistance, no significant change was observed in the number of patients with increased ovarian volume (PCOS-58, PCOS + HT-57) with the addition of HT finding.

Diagnostic values of MRI indexes for polycystic ovary syndrome.

BACKGROUND: Magnetic resonance imaging (MRI) is a useful non-invasive modality for observation of ovarian morphologic characteristics. Few studies have focused on the value of MRI-derived indexes in reproductive-aged women with polycystic ovary syndrome (PCOS). PURPOSE: To assess the diagnostic value of MRI in women with PCOS. MATERIAL AND METHODS: This prospective case-control study included 85 women with PCOS and 50 controls who underwent pelvic MRI during 2017-2019. Ovarian volume (OV), follicle count (FC; counts of follicles sizing 2-3, 4-6, 7-9, 2-9 mm, respectively), follicular peripheral distribution, absence of a dominant follicle and stromal to total area ratio (S:A) were determined with MRI. The diagnostic value (sensitivity, specificity, area under the receiver operating characteristic curve [AUC]) of OV, FC2-9, and follicular peripheral distribution for PCOS were assessed. RESULTS: The AUCs were 0.94 for OV, 0.96 for FC2-9, and 0.78 for follicular peripheral distribution. The optimal threshold to detect PCOS was 8.5 mL for OV (sensitivity 78%; specificity 96%) and 26 for FC2-9 (sensitivity 85%; specificity 98%). Sensitivity and specificity were 73% and 82% for follicular peripheral distribution, respectively. Reproducibility was perfect for OV (ICC = 0.96) and absence of a dominant follicle (k = 0.85), substantial for FC2-9 (ICC = 0.79) and S:A (ICC = 0.69), and moderate for follicular peripheral distribution (k = 0.56). CONCLUSION: Detected by MRI, OV >8.5 mL or FC2-9 >26 are accurate for diagnosing PCOS.

The physiological sonographic features of the ovary in healthy subjects: a joint systematic review and meta-analysis by the Italian Society of Gynecology and Obstetrics (SIGO) and the Italian Society of Endocrinology (SIE).

PURPOSE: There is a lack of uniformity in the definition of normal ovary ultrasound parameters. Our aim was to summarize and meta-analyze the evidence on the topic. Full-text English articles published through December 31, 2020 were retrieved via MEDLINE and Embase. Data available for meta-analysis included: ovarian follicular count, ovarian volume, and ovarian Pulsatility Index (PI) assessed by Doppler ultrasound. METHODS: Cohort, cross-sectional, prospective studies with a single or double arm were considered eligible. Interventional studies were included when providing baseline data. Both studies on pre- and post-menopausal women were screened; however, data on menopausal women were not sufficient to perform a meta-analysis. Studies on pre-pubertal girls were considered separately. Eighty-one papers were included in the meta-analysis. RESULTS: The mean ovarian volume was 6.11 [5.81-6.42] ml in healthy women in reproductive age (5.81-6.42) and 1.67 ml [1.02-2.32] in pre-pubertal girls. In reproductive age, the mean follicular count was 8.04 [7.26-8.82] when calculated in the whole ovary and 5.88 [5.20-6.56] in an ovarian section, and the mean ovarian PI was 1.86 [1.35-2.37]. Age and the frequency of the transducers partly modulated these values. In particular, the 25-30-year group showed the higher mean follicular count (9.27 [7.71-10.82]), followed by a progressive age-related reduction (5.67 [2.23-9.12] in fertile women > 35 years). A significant difference in follicular count was also found according to the transducer's upper MHz limit. CONCLUSION: Our findings provide a significant input to improve the interpretation and diagnostic accuracy of ovarian ultrasound parameters in different physiological and pathological settings.

Ovarian volume, not follicle count, is independently associated with androgens in patients with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is diagnosed based on chronic anovulation, androgen excess (clinical and/or biochemical), and polycystic ovaries in ultrasound. The aim of the present study was to evaluate which parameters in the transvaginal ultrasound (TVUS) of ovaries could be better associated with concurrent hormonal imbalance in the women with PCOS. METHODS: Using a cross-sectional design, this study focused on 61 subjects (18-40 years) with PCOS. Patients were recruited at three academic hospitals during the 2017-2019 period. PCOS was defined according to the Rotterdam criteria. The association of ovarian morphology with hormonal and metabolic feature was investigated using linear regression models, adjusted for a set of possible confounding variables including age, mensuration status and body mass index (BMI). RESULTS: The mean volume of both ovaries was positively associated with the total testosterone level (ß = 0.025, P value < 0.001), free androgen index (ß = 0.041, P value < 0.001) and luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio (ß = 0.032, P value = 0.004), even after adjustments made for age, mensuration status and BMI (fully-adjusted model). In contrast, in the fully-adjusted model, antral follicle count (AFC), follicle number per ovary (FNPO), ovarian area, stromal area, and ratio of stromal area to ovarian area (S/A) were not associated with androgen levels and LH/FSH ratio. In addition, after full adjustments, ovarian volume, AFC, FNPO, ovarian area, stromal area and S/A were not associated with insulin resistance, which was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR). CONCLUSION: Increased ovarian volume is, thus, highly predictive of hyperandrogenemia and high LH/FSH ratio in PCOS patients.

Ovarian volume as an independent marker for metabolic dysfunction in women with suspected androgen excess.

Objective: To determine whether ovarian volume (OV) alone is an independent marker for metabolic dysfunction in women with suspected androgen excess. Design: Retrospective cohort study. Setting: Tertiary academic reproductive endocrinology clinic. Patients: Women aged ≥21 years recruited/referred for symptoms related to androgen excess. Interventions: Transvaginal ovarian ultrasound, physical and medical evaluation, 2-hour 75-g oral glucose tolerance test (oGTT), and blood sampling. Main Outcome Measures: Prevalence of hyperandrogenism and metabolic dysfunction. Results: This study included 666 women, of whom 412 (61.9%) and 254 had OVs of >10 and ≤10 mL, respectively. An OV of >10 mL was associated with a higher prevalence of hirsutism (65.1% vs. 51.5%) than an OV of ≤10 mL. Polycystic ovary syndrome by the National Institutes of Health 1990 criteria was found in 67.3% and 51.4% of women with OVs of >10 and ≤10 mL, respectively. Metabolic parameters, including body mass index, waist circumference, and 1-hour insulin levels during the oGTT (odds ratio, 1.98; 95% confidence interval, 1.18-3.31), were significantly higher in women with an OV of >10 mL than in those with an OV of ≤10 mL. An OV of ≤10 mL had a 76.3% negative predictive value for hyperinsulinemia at 1 hour. Conclusions: In women with suspected androgen excess, an OV of >10 mL in at least 1 ovary is not associated with metabolic syndrome but is associated with younger age; an increased body mass index and waist circumference; a higher prevalence of hirsutism, oligoovulation, and polycystic ovary syndrome; and a higher 60-minute insulin level during the oGTT. Overall, an increased OV appears to be a good marker for hyperinsulinemia and hyperandrogenism in women suspected of having an androgen excess disorder.

Anti-Mullerian Hormone as a Marker of Ovarian Reserve and Function.

BACKGROUND: Ovarian reserve tests are required to screen women with a diminished ovarian reserve so that women who are more likely to exhibit poor response to ovarian stimulation and a lower likelihood of becoming pregnant with treatment can be identified. AIM AND OBJECTIVES: This study aimed to determine whether serum anti-Mullerian hormone (AMH) level is a better predictor of ovarian reserve and function than other biochemical tests for ovarian reserve. The primary objective of this study was to find out the correlations of day 3 serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, inhibin B, AMH, ovarian volume, and antral follicle count (AFC) with advancing age; and a secondary objective was to find out the correlations between day 3 serum AMH, LH, FSH, estradiol, and inhibin B levels with AFC. METHODS: This was a prospective, single-center, observational study. A total of 100 infertile women who attended the Gynecology outpatient department over a period of two years and met the inclusion criteria were included in the study. History, clinical examination, routine investigations, hysterosalpingography for tubal patency, estimation of day 3 serum AMH, LH, FSH, estradiol and inhibin B, measurement of ovarian volume, and AFC were done. Correlations of different parameters with advancing age and with AFC were found using Spearman's rho correlations. p-value < 0.05 was considered significant. RESULTS: The maximum infertile women were in the age group of 21-30 years (58 of 100). Serum AMH showed the strongest negative correlation (r=-0.931) with age, followed by AFC (r=-0.884), ovarian volume (r=-0.876), and inhibin B (r=-0.878), whereas serum LH, FSH, and estradiol showed a positive correlation (r=0.589, 0.408, and 0.638 respectively). Serum AMH also showed a strong positive correlation (r=0.972) with AFC followed by ovarian volume (r=0.919) and inhibin B (r=0.769), whereas serum LH, FSH, and estradiol showed a negative correlation (r=-0.504, -0.663, and -0.543 respectively) with AFC.  Conclusion: Among all the different tests of ovarian reserve, serum AMH was the most reliable indicator of reproductive aging and decline in the ovarian pool as well as very closely related to AFC, which is one of the best predictors of ovarian reserve.

Value of ultrasonography parameters in diagnosing polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrinopathy among women of reproductive age associated with hyperandrogenism, oligo-amenorrhea, and infertility. Symptoms and their severity vary among the individuals. If the manifestation is mild, PCOS may remain undiagnosed. In more severe cases, it results in a spectrum of symptoms of metabolic syndrome, insulin resistance, and cardiovascular diseases. The diagnosis is established after a physical examination and evaluating the patient's hormonal profile. In addition to these required methods, ultrasonographic assessment of the patient's ovaries is another non-invasive, cheap, and time-saving tool, making the examination more profound and leading to the correct diagnosis. Specific ultrasonographic parameters are used to tell the healthy and polycystic ovaries apart: the ovarian volume (OV), ovarian follicle count, follicle distribution pattern, ovarian stromal echogenicity, and the resistance and pulsatility indices assessed using the Doppler function. This review evaluated the selected articles and ascertained the ultrasonographic parameters that accurately predict PCOS. This systematic review showed that the most valuable ultrasonographic parameters in diagnosing PCOS are the OV and follicle number per ovary.

Ovarian follicle count by magnetic resonance imaging is greater in adolescents and young adults with polycystic ovary syndrome than in controls.

Objective: To use magnetic resonance imaging (MRI) to quantify the follicle number per ovary (FNPO) using biplanar measurements and determine the ovarian volume (OV) using three-dimensional measurements in adolescents and young adults with polycystic ovary syndrome (PCOS) and controls and compare the differences between these groups; to examine the relationships between FNPO and OV and metabolic markers associated with PCOS; to compare OV obtained by use of MRI and ultrasound between young patients with PCOS and controls. Design: Cross-sectional study. Setting: Outpatient within a major medical center in New York City. Patients: Adolescent girls and young women aged 13-25 years with PCOS (n = 16) and body mass index-, age-, and ethnicity-comparable control subjects (n = 15). Interventions: None. Main Outcome Measures: The OV and FNPO by use of MRI, OV by use of transabdominal pelvic ultrasound, anthropometric measurements, and biochemical and hormonal evaluation. Results: The FNPO was higher in participants with PCOS (23.7 ± 4.6 follicles) than in controls (15.2 ± 4 follicles) when adjusted for menstrual age. The OV by use of ultrasound was higher in participants with PCOS (11.7 ± 5.6 mL) than in controls (8.1 ± 3.4 mL); however, OV by use of MRI did not differ between the groups. The OV by use of MRI and ultrasound correlated in participants with PCOS (r = 0.62) but not in controls. Conclusions: Our results are in line with prior studies showing that FNPO may be a more sensitive measure of polycystic ovary morphology than OV. The results of this study support the use of ovarian k, a promising diagnostic tool for PCOS, in young patients.

Predictive performance of peritoneal fluid in the pouch of Douglas measured five days after oocyte pick-up in predicting severe late-onset OHSS: A secondary analysis of a randomized trial.

OBJECTIVES: To investigate if the amount of peritoneal fluid (PF) in the Pouch of Douglas at oocyte pick-up (OPU) or OPU + 5 days predict severe late-onset ovarian hyperstimulation syndrome (OHSS) in women undergoing ovarian stimulation for assisted reproductive technology (ART). STUDY DESIGN: A secondary analysis of a dual-centre RCT on 1050 women referred for their first ART treatment in two public fertility clinics in Denmark and randomized 1:1 to GnRH-antagonist or GnRH-agonist protocol. All women from the two arms who were examined on day of OPU and OPU + 5 days were included in this study (n = 940). The ability of PF in the pouch of Douglas to predict severe late-onset OHSS was assessed by multivariate logistic regression analyses and receiver operator characteristics (ROC) curve analyses and compared with other known predictors of OHSS. The final models were cross-validated by the leave-one-out method to assess the models' generalizability. RESULTS: A total of 28 (3%) women developed severe late-onset OHSS. PF in the pouch of Douglas measured on OPU + 5 days predicted severe late-onset OHSS. The optimal cut-off value was 17.5 mm at OPU + 5 days with a 61% sensitivity and 71% specificity (Area under the curve = 0.70 95% CI 0.61-0.80). PF on the day of OPU was not predictive of late on-set OHSS as the adjusted multivariate logistic regression analyses showed insignificant results. CONCLUSION: Although PF in the pouch of Douglas could predict late-onset severe OHSS, the low sensitivity underlines that it is not useful as a sole marker to decide whether to perform blastocyst transfer or to use a freeze-all strategy.

Effect of risk-reducing salpingo-oophorectomy on sex steroid hormone serum levels among postmenopausal women: an NRG Oncology/Gynecologic Oncology Group study.

BACKGROUND: Risk-reducing salpingo-oophorectomy is an effective ovarian cancer risk reduction strategy. However, bilateral oophorectomy has also been associated with increased long-term nonneoplastic sequelae, effects suggested to be mediated through reductions in systemic sex steroid hormone levels. Currently, it is unclear whether the postmenopausal ovary contributes to the systemic hormonal milieu or whether postmenopausal ovarian volume or other factors, such as body mass index and age, affect systemic hormone levels. OBJECTIVE: We examined the impact of oophorectomy on sex steroid hormone levels in postmenopausal women. Furthermore, we explored how well ovarian volume measured by transvaginal ultrasound correlated with direct ovarian measures obtained during surgical pathology evaluation and investigated the association between hormone levels and ovarian volumes. STUDY DESIGN: Postmenopausal women who underwent risk-reducing salpingo-oophorectomy (180 cases) or ovarian cancer screening (38 controls) enrolled in an international, prospective study of risk-reducing salpingo-oophorectomy and risk of ovarian cancer algorithm-based screening among women at increased risk of ovarian cancer (Gynecologic Oncology Group-0199) were included in this analysis. Controls were frequency matched to the cases on age at menopause, age at study entry, and time interval between blood draws. Ovarian volume was calculated using measurements obtained from transvaginal ultrasound in both cases and controls and measurements recorded in surgical pathology reports from cases. Serum hormone levels of testosterone, androstenedione, androstenediol, dihydrotestosterone, androsterone, dehydroepiandrosterone, estrone, estradiol, and sex hormone-binding globulin were measured at baseline and follow-up. Spearman correlation coefficients were used to compare ovarian volumes as measured on transvaginal ultrasound and pathology examinations. Correlations between ovarian volumes by transvaginal ultrasound and measured hormone levels were examined using linear regression models. All models were adjusted for age. Paired t tests were performed to evaluate individual differences in hormone levels before and after risk-reducing salpingo-oophorectomy. RESULTS: Ovarian volumes measured by transvaginal ultrasound were only moderately correlated with those reported on pathology reports (Spearman rho [ρ]=0.42). The median time interval between risk-reducing salpingo-oophorectomy and follow-up for the cases was 13.3 months (range, 6.0-19.3), and the median time interval between baseline and follow-up for the controls was 12.7 months (range, 8.7-13.4). Sex steroid levels decreased with age but were not correlated with transvaginal ultrasound ovarian volume, body mass index, or time since menopause. Estradiol levels were significantly lower after risk-reducing salpingo-oophorectomy (percentage change, -61.9 post-risk-reducing salpingo-oophorectomy vs +15.2 in controls; P=.02), but no significant differences were seen for the other hormones. CONCLUSION: Ovarian volumes measured by transvaginal ultrasound were moderately correlated with volumes directly measured on pathology specimens and were not correlated with sex steroid hormone levels in postmenopausal women. Estradiol was the only hormone that declined significantly after risk-reducing salpingo-oophorectomy. Thus, it remains unclear whether the limited post-risk-reducing salpingo-oophorectomy changes in sex steroid hormones among postmenopausal women impact long-term adverse outcomes.

Is there a Relationship between Serum IGF-1 and Thyroid Nodule, Thyroid or Ovarian Volume in Polycystic Ovarian Syndrome?

CONTEXT: Studies investigating the association between serum IGF-1, and thyroid nodule, ovarian or thyroid volume in polycystic ovarian syndrome (PCOS) are limited. OBJECTIVE: We aimed to analyze the association between serum IGF-1 level, and ovarian or thyroid volume, or thyroid nodule in PCOS. DESIGN: The study was performed between June 2017 and August 2019 as prospective design. SUBJECTS AND METHODS: Adult females with new-onset PCOS were included. The patients having comorbid illness, or using medication were excluded. Basic tests, thyroid and ovarian sonography were performed. The patients were grouped according to thyroid nodule(absent/present) and ovarian volume (<10mL/≥10mL). We planned to find a positive association between IGF-1, and thyroid nodule, thyroid or ovarian volume in PCOS. RESULTS: Of total 118 patients, 11(9%) had thyroid nodule. The patients with thyroid nodule had a higher ovarian volume (p=0.006). No correlation was found between GH or IGF-1, and thyroid or ovarian volume. IGF-1 was not a predictor for thyroid nodule or higher ovarian volume. Thyroid nodule was a significant predictor for higher ovarian volume. CONCLUSION: Our study is the first to analyze the association between IGF-1 and thyroid nodule in PCOS. We found that thyroid nodule was associated with thyroid and ovarian volume, but IGF-1 was not associated with thyroid nodule, thyroid or ovarian volume.

A Cross-Sectional Study on Potential Ovarian Volume and Related Factors in Women with Polycystic Ovary Syndrome from Infertile Couples.

PURPOSE: This study was designed to explore the value of ovarian volume (OV) measured by transvaginal ultrasound and its relationship with anthropometry and serum hormonal levels in a polycystic ovary syndrome (PCOS) population. PATIENTS AND METHODS: A total of 119 women with PCOS from infertile couples were recruited in this cross-sectional study. On days 2-4 of the menstrual cycle, transvaginal ultrasound examinations were performed, and hormonal profiles were measured. PCOS diagnosis was based on the Rotterdam 2003 criteria and classified into four phenotype groups. The PCOS group (study group) and the non-PCOS group (control group) were compared. RESULTS: The mean age of the participants was 32.66±4.10 years compared to 33.99±4.78 years in 273 cases (69.6%) without PCOS. The mean OV was statistically larger in the PCOS group than in the non-PCOS group (7.65±3.23 mL vs 6.08±3.67 mL, p < 0.001) and positively correlated with serum anti-Mullerian (AMH) and luteinizing hormone (LH) levels (r=0.30; p < 0.001 and r=0.23; p < 0.001, respectively), and weakly and inversely correlated with age (-0.182, p < 0.001). The area under the receiver operating characteristic (ROC) curve of OV in the diagnosis of PCOS was 0.613 (0.557-0.670, 95% CI). CONCLUSION: The enlarged OV is remarkable in women with PCOS and is related to AMH and LH concentrations. Although the diagnostic potential of PCOS is substantially low, OV alone may contribute to predicting the severity of PCOS and better performance for the diagnosis of PCOS phenotypes.

Uterine and ovarian parameters in healthy North Indian girls from 5 to 16 years by ultrasonography.

INTRODUCTION: Knowledge of uterine and ovarian growth patterns during early age and puberty helps in investigating disorders of pubertal development i.e. precocious puberty, premature thelarche, or pubarche. There is a paucity of data for uterine and ovarian parameters. Aim of the study: The aim of this study is to present normative data for Uterine length, Mean ovarian volume (MOV), and fundo cervical ratio (FCR) from 5 to 16 years in healthy girls from north India and to correlate these parameters with age, weight, height, and pubertal Tanner staging. MATERIAL AND METHODS: A cross-sectional observational study was performed on 130 healthy girls age 5 to 16 years. Age, anthropometric parameters were measured and the pubertal stage was categorized using Tanner staging. All subjects underwent pelvic ultrasonography for the measurement of uterine and ovarian parameters. RESULTS: Normative data of uterine length, MOV, and FCR were presented as mean, SD, median, and 95% confidence interval as per age and Tanner stage. A progressive increase in uterine length, MOV & FCR was observed with increasing age, weight, height, and Tanner stage (p < 0.001). A sudden significant increment in uterine length and MOV was observed between the age of 11-12 and 12-13 years (p < 0.001). Uterine length of < 4 cm, MOV < 2 cm3 and FCR < 1 were specific to identify pre-pubertal girls. CONCLUSIONS: Normative data of uterine and ovarian parameters generated in our study by ultrasonography would be useful for screening girls with abnormalities of pubertal development.

Evaluation of safety, feasibility and efficacy of intra-ovarian transplantation of autologous adipose derived mesenchymal stromal cells in idiopathic premature ovarian failure patients: non-randomized clinical trial, phase I, first in human.

BACKGROUND: Premature ovarian failure (POF) is characterized by the loss of ovarian activity before the age of 40 years. Stem cell therapy has the capability to create a regenerative microenvironment and is a proposed treatment for POF-related infertility due to the presence of renewal folliculogenesis and germ cells in the adult ovaries. In this study, we assessed the safety, feasibility, efficacy and dose adjustment of autologous adipose-derived stromal cells (ADSCs) and their ability to improve ovarian function in POF patients. METHODS: This study was a non-randomized clinical trial, phase I. Nine women with a definitive diagnosis of POF were divided into three groups (n = 3 per group) that received either 5 × 106, 10 × 106, or 15 × 106 autologous ADSCs suspension transplanted in the one ovary. Participants were followed-up at 24 h after the transplantation, and at 1 and 2 weeks, and 1, 2, 3, 6, and 12 months after the transplantation. The primary objective was to evaluate the safety of ADSCs transplantation. Secondary objectives included the effects of ADSCs transplantation on the resumption of menstruation, hormones level (Follicle-stimulating hormone (FSH) and anti-Müllerian hormone), ovarian function (Antral follicle count and ovary volume by ultrasonography evaluation) as well as dose escalation. RESULTS: Participants had not shown any early-onset possible side effects and secondary complications during follow-up. The menstruation resumption was observed in four patients which established for several months. In the 15 × 106 group, two POF patients had a return of menstruation second months after the intervention. Two other POF patients in 5 × 106 and 10 × 106 cell groups reported menstruation resumption at 1 month after the intervention. We observed decreased serum FSH levels of less than 25 IU/l in four patients. In two patients in 5 × 106 and 10 × 106 cell groups, serum FSH showed an inconsistent decline during a 1 year follow up after ADSCs transplantation. The ovarian volume, AMH, and AFC were variable during the follow-up and no significant differences between cell groups (p > 0.05). CONCLUSIONS: We showed the intra-ovarian embedding of ADSCs is safe and feasible and is associated with an inconsistent decline in serum FSH. This should be further investigated with a large RCT. TRIAL REGISTRATION: NCT02603744 , Registered 13 November 2015 - Retrospectively registered, http://www.Clinicaltrials.gov.

Correlation of Serum Anti-Mullerian Hormone (AMH) Level on Ovarian Volume in Women with Endometrioma.

BACKGROUND: The correlation between endometrioma and serum Anti-mullerian hormone (AMH) level is a benchmark in determining the prognosis and management of endometrioma. Endometrioma causes a decrease in ovarian reserve due to tissue damage that affects the formation of serum AMH. Serum AMH levels in daily practice are useful as a tool to determine ovarian reserve, markers for diagnosis and prognosis in infertility and reproductive abnormalities. The purpose of this study was to determine the relationship of serum AMH level in women with endometrioma and their correlation to ovarian volume. METHODS: This research was an analytical observational study with a cross-sectional design in women of reproductive age who were diagnosed with endometrioma within the period of August 2019-March 2020 at Hasan Sadikin Hospital, Bandung. Forty-four women who met the inclusion and exclusion criteria were then divided into endometrioma (n=22) and control (n=22) groups. In both groups, transvaginal ultrasound examination was performed to measure the volume of the ovary, then a laboratory examination of serum AMH level was carried out. RESULTS: Serum AMH levels in the endometrioma group were significantly lower than those in the control group (P<0.001). Serum AMH level did not differ significantly based on laterality of the observation group (P=1.000). There was a negative correlation between serum AMH level and the volume of ovarian endometrioma, although not statistically significant (r=-0.332; P=0.066). CONCLUSION: There was a correlation between serum AMH level and endometrioma. Serum AMH levels were significantly lower in the endometrioma group but were not influenced by their laterality. We found a negative correlation between serum AMH level and ovarian volume containing endometrioma, but not statistically significant.