Cellular senescence in the pathogenesis of ovarian dysfunction.

The follicular microenvironment is crucial for normal ovarian function, and intra-ovarian factors, in coordination with gonadotropins, contribute to its regulation. Recent research has revealed that the accumulation of senescent cells worsens the adverse environment of various tissues and plays critical roles in chronological aging and various pathological conditions. Cellular senescence involves cell-cycle arrest, a senescence-associated secretory phenotype (SASP), macromolecular damage, and dysmetabolism. In this review, I summarize the latest knowledge regarding the role of cellular senescence in pathological conditions in the ovary, in the context of reproduction. Specifically, cellular senescence is known to impair follicular and oocyte health in cisplatin- and cyclophosphamide-induced primary ovarian insufficiency and to contribute to the pathogenesis of polycystic ovary syndrome (PCOS). In addition, cellular senescence is induced during the decline in ovarian reserve that is associated with chronological aging, endometriosis, psychological stress, and obesity, but it remains unclear whether it plays a causative role in these conditions. Finally, I discuss the potential for use of cellular senescence as a novel therapeutic target. The modification of SASP using a senomorphic and/or the elimination of senescent cells using a senolytic represent promising therapeutic strategies. Further elucidation of the role of cellular senescence in the effects of various insults on ovarian reserve, including chronological aging, as well as in pathogenesis of ovarian pathologies, including PCOS, may facilitate a new era of reproductive medicine.

[Ovulatory disorders under "common therapeutic principle for different diseases": essence of "Tiangui" and relationship with ovulation disorders].

The essence of the "common therapeutic principle for different diseases"(Yibing Tongzhi in Chinese for short) is the disease-syndrome combination, which is the classic mode of understanding and treating diseases in traditional Chinese medicine(TCM). This study holds the view that Yibing Tongzhi is the optimal treatment mode of ovulation disorders since ovulation disorders have the common pathogenesis, i.e., "kidney-Tiangui(reproduction-stimulating essence)-Chongren(thoroughfare and conception vessels)-uterus axis" disorder. Kidney is an important basis of the reproductive axis, where kidney essence, kidney yang, and kidney Qi are the key substances and driving forces promoting the operation of the reproductive axis. Chongren is an important transmission path. "Tiangui", the upstream substance related to the heart, brain and kidney with a connecting effect, plays a key role in the ovulation mechanism and is a representative of the reproductive axis function. There are four common Tiangui abnormalities in ovulatory disorders, including hypomenorrhea, yin and yang deficiency, abnormal exuberance of extreme yin, and abnormal phase. The dynamic changes of "Tiangui" can induce different diseases, such as polycystic ovary syndrome and hyperprolactinemia, which ultimately lead to anovulatory infertility. Therefore, with "Tiangui" as the entry point, it is the treatment trend for ovulatory disorders under Yibing Tongzhi.

Endoplasmic reticulum stress: a key regulator of the follicular microenvironment in the ovary.

Intra-ovarian local factors regulate the follicular microenvironment in coordination with gonadotrophins, thus playing a crucial role in ovarian physiology as well as pathological states such as polycystic ovary syndrome (PCOS). One recently recognized local factor is endoplasmic reticulum (ER) stress, which involves the accumulation of unfolded or misfolded proteins in the ER related to various physiological and pathological conditions that increase the demand for protein folding or attenuate the protein-folding capacity of the organelle. ER stress results in activation of several signal transduction cascades, collectively termed the unfolded protein response (UPR), which affect a wide variety of cellular functions. Recent studies have revealed diverse roles of ER stress in physiological and pathological conditions in the ovary. In this review, we summarize the most current knowledge of the regulatory roles of ER stress in the ovary, in the context of reproduction. The physiological roles of ER stress and the UPR in the ovary remain largely undetermined. On the contrary, activation of ER stress is known to impair follicular and oocyte health in various pathological conditions; moreover, ER stress also contributes to the pathogenesis of several ovarian diseases, including PCOS. Finally, we discuss the potential of ER stress as a novel therapeutic target. Inhibition of ER stress or UPR activation, by treatment with existing chemical chaperones, lifestyle intervention, or the development of small molecules that target the UPR, represents a promising therapeutic strategy.

Ovarian reserve and recurrence 1 year post-operatively after using haemostatic sealant and bipolar diathermy for haemostasis during laparoscopic ovarian cystectomy.

RESEARCH QUESTION: Is there a difference in the ovarian reserve 1 year post-operatively in those who used a haemostatic sealant or bipolar diathermy for haemostasis during laparoscopic ovarian cystectomy for ovarian endometriomas? DESIGN: This was an extended follow-up observational study of a previous randomized controlled trial where women aged 18 to 40 years with 3-8 cm unilateral or bilateral endometriomas were randomized to receive haemostasis by a haemostatic sealant or bipolar diathermy following ovarian cystectomy. The primary outcome was the ovarian reserve as assessed by antral follicle count (AFC) 1 year post-operatively. Secondary outcomes included the recurrence rate of ovarian endometrioma, the change in anti-Müllerian hormone (AMH) and FSH concentrations, and reproductive outcomes. RESULTS: The significant increase in AFC at 3 months after initial surgery (P = 0.025) in the haemostatic sealant group compared with the diathermy group was sustained at 1 year (P = 0.024) but there was no difference in AMH or FSH concentrations between the groups throughout the follow-up period. The recurrence rate in the FloSeal group was 7.7% (n = 3/39) compared with 22.2% (n = 8/36) in the diathermy group (P = 0.060). The recurrence rate in women who had bilateral lesions was significantly higher than those with unilateral lesions (risk ratio 5.33, interquartile range 1.55-18.38). No difference in reproductive outcomes was found between the two groups. CONCLUSIONS: Applying haemostatic sealant after laparoscopic cystectomy of ovarian endometriomas produces a significantly greater improvement in AFC, which was apparent at 3-month follow-up, and was sustained at 1-year follow-up without compromising the recurrence rate.

Estradiol/nomegestrol acetate as a first-line and rescue therapy for the treatment of ovarian and deep infiltrating endometriosis.

PURPOSE: Estradiol valerate/nomegestrol acetate (E2V/NOMAC) is a new combined oral contraceptive with a good tolerability profile and low drop-out rates, which was shown to improve menstrual-related symptoms. This study aims to evaluate its effectiveness in the control of symptoms and progression of disease in women with ovarian endomestriomas and deep infiltrating endometriosis (DIE). METHODS: This was a retrospective cohort study on 39 women with pelvic endometriosis treated with E2V/NOMAC. We assessed for each patient, at the beginning of treatment and after 6 months, the painful symptoms, through a global VAS (Visual Analogue Scale) index and the size of the greatest ovarian and/or deep infiltrating endometriotic lesions. RESULTS: After 6 months of treatment, a significant reduction was observed for the global VAS score for pain symptoms and for the mean size of ovarian endometriomas, whereas DIE lesions did not present significant changes in mean size. CONCLUSIONS: E2/NOMAC was effective in reducing pain symptoms associated with pelvic endometriosis and the size of ovarian endometriomas, whereas DIE lesions remained stable. This therapy could provide good results in the control of symptoms and disease progression in women with pelvic endometriosis.

Relationship between Cyst Fluid Concentrations of Iron and Severity of Dysmenorrhea in Patients with Ovarian Endometrioma.

OBJECTIVES AND DESIGN: Endometriosis-related pain can be caused by anatomical distortions as well as environmental factors such as inflammation and oxidative stress. The aim of this study is to investigate the relationship between the severity of dysmenorrhea in patients with ovarian endometrioma (OMA) and cyst fluid (CF) concentrations of irons, including total iron, heme iron, and free iron. METHOD: Eighty-three patients who were histologically diagnosed with OMA were enrolled in the Department of Gynecology, Nara Medical University Hospital, between 2013 and 2019. The patients were divided into 4 groups according to the severity of dysmenorrhea: no pain, mild, moderate, and severe. Iron concentration was measured by the inductively coupled plasma optical emission spectrometry method. RESULTS: There were no significant differences among the 4 groups in variables such as age at diagnosis, preoperative CA125, preoperative CA19-9, cyst size, and tumor laterality (unilateral or bilateral). There was a positive correlation between the severity of dysmenorrhea and total iron (p < 0.001) and heme iron (p = 0.016) concentrations. Multiple regression analyses revealed that the CF concentration of total iron (hazard ratio 18.75, 95% confidence interval: 2.26-155.35, p = 0.007) was a significant independent variable associated with the severity of dysmenorrhea. A receiver operating characteristic curve analysis showed that a total iron exceeding 290.8 mg/L was associated with severe dysmenorrhea with a sensitivity of 90.9% and a specificity of 65.7%. LIMITATIONS: This study excluded patients with adenomyosis, superficial endometriosis, or deep endometriosis, resulting in a smaller number of cases. Iron levels could not be compared to the endometriosis stage using the r-ASRM score. CONCLUSIONS: There is no clear evidence that iron predicts the severity of endometriosis-related pain. However, iron may be closely associated with dysmenorrhea.

Retinol-binding protein 4 (RBP4) and high sensitivity C-reactive protein (hs-CRP) levels in patients with diminished ovarian reserve (DOR): a cross-sectional study.

BACKGROUND: Antioxidant/oxidant imbalance has been reported to be related to diminished ovarian reserve (DOR). Vitamin A (retinol), a kind of antioxidant, plays a role in restoring ovarian oxidative damage, while C-reactive protein (CRP) is the classical marker of oxidative stress and has recently been identified as an independent variable that is associated with low anti-Mullerian hormone (AMH) levels in young women with DOR. Additionally, retinol binding protein 4 (RBP4) can be considered a substitute for retinol in healthy, nonobese women. The study aim was to determine the relationship between serum RBP4, high sensitivity C-reactive protein (hs-CRP) concentrations and ovarian reserve in nonobese DOR patients. METHODS: This study included 24 DOR women and 48 normal ovarian reserve (NOR) women from the reproductive medical center of Renmin Hospital of Wuhan University. The serum RBP4 and high-sensitivity CRP (hs-CRP) levels were measured with ELISA kits. RESULTS: RBP4 levels (20,648.36 ± 5475.16 ng/ml vs 23,986.48 ± 5995.64 ng/ml, p = 0.025) were decreased, and hs-CRP levels (695.08 ± 1090.19 ng/ml vs 364.32 ± 786.29 ng/ml, p = 0.012) were increased in the DOR group. Serum RBP4 was positively related to AMH (Pearson r = 0.518, p = 0.000), while hs-CRP was negatively correlated with AMH (Spearman r = - 0.345, p = 0.005). after adjustments were made for the covariables, multiple line regression analysis showed that positive association between RBP4 and AMH still existed (ß = 0.450, p < 0.001). CONCLUSION: Decreased serum RBP4 levels and increased serum hs-CRP were observed in DOR patients in our study, and the strong correlation between RBP4 and AMH supports the notion that oxidative stress plays a role in DOR, and that appropriate levels of antioxidant vitamin A may be protective against ovarian reserve dysfunction.

Do ovarian endometriomas affect ovarian response to ovarian stimulation for IVF/ICSI?

RESEARCH QUESTION: Does the presence of ovarian endometriomas affect ovarian response to ovarian stimulation after adjusting for age and ovarian reserve markers? DESIGN: This retrospective cross-sectional study compared the ovarian response between patients with ovarian endometriomas and women with other infertility factors undergoing their first ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI). An age-specific nomogram model for the number of oocytes retrieved was built for both groups, and ovarian response was compared after adjusting for age, gonadotrophin dose, anti-Mullerian hormone (AMH) concentration and antral follicle count (AFC). RESULTS: A total of 923 patients were included: 101 women with at least one ovarian endometrioma, and 822 patients with other infertility factors. Comparisons of the nomograms for the number of oocytes retrieved demonstrated that response was significantly lower for women with endometrioma when the results were adjusted for age the z-score for the number of oocytes retrieved (-0.49 ± 0.71 versus -0.20 ± 0.86; 95% confidence interval [CI] -0.47 to -0.12) and also after adjustment for the total dose of gonadotrophins and AMH values (z-score mean difference -0.338; 95% CI -0.54, -0.14). When the z-score was adjusted for gonadotrophin dose and AFC, the number of oocytes retrieved was comparable between the two groups (z-score mean difference -0.038; 95% CI -0.34 to 0.27). CONCLUSIONS: Ovarian response after ovarian stimulation for IVF/ICSI in women with endometriomas is significantly lower than in controls after adjusting for age, gonadotrophin dose and AMH. Dose and protocol selection for ovarian stimulation in patients with endometrioma should be based on AFC rather than AMH, as the latter may be overestimated.

Medical treatment of ovarian endometriomas: a prospective evaluation of the effect of dienogest on ovarian reserve, cyst diameter, and associated pain.

The aim of the present study was to evaluate the effect of medical treatment of ovarian endometriomas on cyst diameter, associated pain, and ovarian reserve as measured with antral follicle count (AFC) and anti-Mullerian hormone (AMH). In this prospective study, 32 patients with unilateral endometrioma associated with pelvic pain, underwent 6-month medical treatment with dienogest. Before treatment, and at the end of 6 months of treatment, patients underwent evaluation of endometrioma diameter and AFC at transvaginal ultrasonography, measurement of AMH, and evaluation of associated pain. Mean cyst diameter was 4.0 ± 1.3 cm at baseline, and 2.4 ± 1.2 cm after 6 months of treatment (p < .0001), for a reduction in diameter of 40% and a reduction in volume of 79%. Mean visual analog scale score at enrollment was 6.3 ± 2.0, with a significant improvement at 6 months (0.9 ± 1.0, p < .0001). AFC for the affected ovary improved from 4.2 ± 2.8 at baseline, to 8.6 ± 4.2 cm after 6 months (+105%; p < .0001). AMH did not change significantly from baseline (3.40 ± 2.32 ng/mL) to end of treatment (2.80 ± 1.90 ng/mL, -18%, p = .27). Medical treatment with dienogest significantly reduces endometrioma diameter and associated pain, whereas the ovarian reserve appears to be preserved, with a significant improvement of AFC and no significant change in AMH.

Is dienogest the best medical treatment for ovarian endometriomas? Results of a multicentric case control study.

Ovarian endometriomas are common manifestations of endometriosis. Surgical excision has been shown to potentially decrease ovarian reserves. In this prospective study, we included 81 patients with ovarian endometriosis. 40 were treated with 2 mg of dienogest daily (DNG) and 41 were treated with cyclic oral estro-progestins (ethinyl estradiol 30 mcg [EE] plus dienogest 2 mg) (DNG + EE). Aim of the study was the effect of the treatment on the size of the endometriotic cysts. Further, in the symptomatic patients, follow-up included an evaluation of chronic pain before and during treatment. Both treatments were able to significantly decrease the pain in symptomatic patients with no statistical differences. The mean visual analog scale score at enrollment was 65 ± 14 and 70 ± 18, and there was significant improvement (19 ± 15, p < .001, DNG; 18 ± 12, p < .001, DNG + EE). The size of the endometrioma cysts were significantly reduced in the DNG group. The mean cyst diameter was 52 ± 22 mm at baseline and 32 ± 12 mm after six months of treatment (p < .001), yielding a 75% volume reduction in DNG group. The decrease in the size of endometrioma cysts observed in the women treated with only progestin could be noteworthy, as it may reduce the negative impacts on the affected ovary and avoid surgery.

Hyperprolactinemic African elephant (Loxodonta africana) females exhibit elevated dopamine, oxytocin and serotonin concentrations compared to normal cycling and noncycling, low prolactin elephants†.

Many zoo elephants do not cycle normally, and for African elephants, it is often associated with hyperprolactinemia. Dopamine agonists successfully treat hyperprolactinemia-induced ovarian dysfunction in women, but not elephants. The objective of this study was to determine how longitudinal dopamine, serotonin, and oxytocin patterns in African elephants are related to ovarian cycle function. We hypothesized that dopamine concentrations are decreased, while oxytocin and serotonin are increased in non-cycling, hyperprolactinemic African elephants. Weekly urine and serum samples were collected for eight consecutive months from 28 female African elephants. Females were categorized as follows: (1) non-cycling with average prolactin concentrations of 15 ng/ml or greater (HIGH; n = 7); (2) non-cycling with average prolactin concentrations below 15 ng/ml (LOW; n = 13); and (3) cycling with normal progestagen and prolactin patterns (CYCLING; n = 8). Both oxytocin and serotonin were elevated in hyperprolactinemic elephants. Thus, we propose that stimulatory factors may play a role in the observed hyperprolactinemia in this species. Interestingly, rather than being reduced as hypothesized, urinary dopamine was elevated in hyperprolactinemic elephants compared to CYCLING and LOW prolactin groups. Despite its apparent lack of regulatory control over prolactin, this new evidence suggests that dopamine synthesis and secretion are not impaired in these elephants, and perhaps are augmented.

Do young women with unexplained infertility show manifestations of decreased ovarian reserve?

PURPOSE: To investigate whether unexplained infertility at a young age demonstrates manifestations of decreased ovarian reserve. METHODS: A total of 100 women were divided into two equally sized groups. The study group comprised women aged ≤ 37 years diagnosed with unexplained infertility, and the control group included age-matched women with either mechanical factor or severe male factor infertility. RESULTS: Both groups were comparable in their basic characteristics. Overall, women with unexplained infertility presented with inferior ovarian reserve results set against women of the control group. The number of ≥ 14-mm follicles on the day of hCG administration was significantly lower in the study compared with the control group (7.0 ± 4.5 vs. 10.4 ± 4.1 follicles, respectively, P < 0.001). Likewise, basal serum FSH was higher in the study compared with the control group (8.4 ± 5.5 vs. 6.4 ± 1.7 IU/L, respectively, P = 0.015), while antral follicle count was lower (10.9 ± 6.6 vs. 16.2 ± 6.6 follicles, respectively, P < 0.001). Furthermore, women with unexplained infertility required a higher total dose of FSH for ovarian stimulation (2,923 ± 1,701 vs. 2,196 ± 941 IU/L, respectively, P = 0.010), but exhibited a lower number of retrieved oocytes (9.3 ± 6.3 vs. 15.6 ± 7.9 oocytes, respectively, P < 0.001), alongside a lower number of achieved embryos (5.3 ± 4.0 vs. 8.0 ± 4.7 embryos, respectively, P = 0.002). Interestingly, the cumulative clinical pregnancy rate was not significantly different between the two groups (44% vs. 58%, respectively, P = 0.163). CONCLUSIONS: Young women ≤ 37 years of age with unexplained infertility have clear manifestations of sub-optimal ovarian reserve set against controls. Our findings suggest that unexplained infertility at a young age may be a risk factor for developing poor ovarian response, specifically as a quantitative, rather than a qualitative, risk factor.

Relationships between intensity, duration, cumulative dose, and timing of smoking with age at menopause: A pooled analysis of individual data from 17 observational studies.

BACKGROUND: Cigarette smoking is associated with earlier menopause, but the impact of being a former smoker and any dose-response relationships on the degree of smoking and age at menopause have been less clear. If the toxic impact of cigarette smoking on ovarian function is irreversible, we hypothesized that even former smokers might experience earlier menopause, and variations in intensity, duration, cumulative dose, and age at start/quit of smoking might have varying impacts on the risk of experiencing earlier menopause. METHODS AND FINDINGS: A total of 207,231 and 27,580 postmenopausal women were included in the cross-sectional and prospective analyses, respectively. They were from 17 studies in 7 countries (Australia, Denmark, France, Japan, Sweden, United Kingdom, United States) that contributed data to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on smoking status, cigarettes smoked per day (intensity), smoking duration, pack-years (cumulative dose), age started, and years since quitting smoking was collected at baseline. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CIs) for the associations between each smoking measure and categorised age at menopause (<40 (premature), 40-44 (early), 45-49, 50-51 (reference), and ≥52 years). The association with current and former smokers was analysed separately. Sensitivity analyses and two-step meta-analyses were also conducted to test the results. The Bayesian information criterion (BIC) was used to compare the fit of the models of smoking measures. Overall, 1.9% and 7.3% of women experienced premature and early menopause, respectively. Compared with never smokers, current smokers had around twice the risk of experiencing premature (RRR 2.05; 95% CI 1.73-2.44) (p < 0.001) and early menopause (1.80; 1.66-1.95) (p < 0.001). The corresponding RRRs in former smokers were attenuated to 1.13 (1.04-1.23; p = 0.006) and 1.15 (1.05-1.27; p = 0.005). In both current and former smokers, dose-response relationships were observed, i.e., higher intensity, longer duration, higher cumulative dose, earlier age at start smoking, and shorter time since quitting smoking were significantly associated with higher risk of premature and early menopause, as well as earlier menopause at 45-49 years. Duration of smoking was a strong predictor of age at natural menopause. Among current smokers with duration of 15-20 years, the risk was markedly higher for premature (15.58; 11.29-19.86; p < 0.001) and early (6.55; 5.04-8.52; p < 0.001) menopause. Also, current smokers with 11-15 pack-years had over 4-fold (4.35; 2.78-5.92; p < 0.001) and 3-fold (3.01; 2.15-4.21; p < 0.001) risk of premature and early menopause, respectively. Smokers who had quit smoking for more than 10 years had similar risk as never smokers (1.04; 0.98-1.10; p = 0.176). A limitation of the study is the measurement errors that may have arisen due to recall bias. CONCLUSIONS: The probability of earlier menopause is positively associated with intensity, duration, cumulative dose, and earlier initiation of smoking. Smoking duration is a much stronger predictor of premature and early menopause than others. Our findings highlight the clear benefits for women of early smoking cessation to lower their excess risk of earlier menopause.

Pretreatment with coenzyme Q10 improves ovarian response and embryo quality in low-prognosis young women with decreased ovarian reserve: a randomized controlled trial.

BACKGROUND: Management of women with reduced ovarian reserve or poor ovarian response (POR) to stimulation is one of the major challenges in reproductive medicine. The primary causes of POR remain elusive and oxidative stress was proposed as one of the important contributors. It has been suggested that focus on the specific subpopulations within heterogeneous group of poor responders could assist in evaluating optimal management strategies for these patients. This study investigated the effect of anti-oxidant treatment with coenzyme Q10 (CoQ10) on ovarian response and embryo quality in young low-prognosis patients with POR. METHODS: This prospective, randomized controlled study included 186 consecutive patients with POR stratified according to the POSEIDON classification group 3 (age < 35, poor ovarian reserve parameters). The participants were randomized to the CoQ10 pre-treatment for 60 days preceding IVF-ICSI cycle or no pre-treatment. The number of high quality embryos was a primary outcome measure. RESULTS: A total of 169 participants were evaluated (76 treated with CoQ10 and 93 controls); 17 women were excluded due to low compliance with CoQ10 administration. The baseline demographic and clinical characteristics were comparable between the groups. CoQ10 pretreatment resulted in significantly lower gonadotrophin requirements and higher peak E2 levels. Women in CoQ10 group had increased number of retrieved oocytes (4, IQR 2-5), higher fertilization rate (67.49%) and more high-quality embryos (1, IQR 0-2); p < 0.05. Significantly less women treated with CoQ10 had cancelled embryo transfer because of poor embryo development than controls (8.33% vs. 22.89%, p = 0.04) and more women from treatment group had available cryopreserved embryos (18.42% vs. 4.3%, p = 0.012). The clinical pregnancy and live birth rates per embryo transfer and per one complete stimulation cycle tended to be higher in CoQ10 group but did not achieve statistical significance. CONCLUSION: Pretreatment with CoQ10 improves ovarian response to stimulation and embryological parameters in young women with poor ovarian reserve in IVF-ICSI cycles. Further work is required to determine whether there is an effect on clinical treatment endpoints.

Pelvic floor muscle assessment on three- and four-dimensional transperineal ultrasound in women with ovarian endometriosis with or without retroperitoneal infiltration: a step towards complete functional assessment.

OBJECTIVES: Previous studies comparing women with deep infiltrating endometriosis (DIE) and healthy controls have underlined an association between pelvic floor muscle (PFM) hypertonic dysfunction and deep lesions. The aim of this study was to compare the morphometry of PFM in women affected by ovarian endometriosis with DIE vs those without DIE in order to assess the impact of retroperitoneal infiltration by the disease on PFM function. METHODS: This was a prospective study conducted between March 2015 and December 2016 on symptomatic women with a clinical and sonographic diagnosis of ovarian endometriosis with or without DIE, scheduled for laparoscopic surgery. We excluded patients with current or previous pregnancy, previous surgery for deep endometriosis, other causes of chronic pelvic pain or congenital or acquired abnormalities of pelvic floor anatomy. Three- and four-dimensional transperineal ultrasound was performed to evaluate PFM morphometry and assess levator hiatal area (LHA) and diameters at rest, during PFM contraction and during Valsalva maneuver. All volumes were analyzed offline by an investigator blinded to the clinical data. RESULTS: One hundred and fourteen patients with ovarian endometriosis were enrolled in the study, 75 with DIE and 39 without DIE. The diagnosis of endometriosis was confirmed by histological examination in all patients. Compared with women without DIE, women with DIE showed a smaller LHA at rest, during contraction and during Valsalva maneuver (P = 0.03, P = 0.03 and P = 0.02, respectively) and a smaller reduction in LHA during PFM contraction (P = 0.04). CONCLUSIONS: Women with ovarian endometriosis who were affected by DIE showed smaller hiatal dimensions than did women without DIE. Considering that PFM dysfunction in patients with DIE could cause pain symptoms and pelvic organ dysfunction, transperineal ultrasound could allow a more complete functional assessment and tailored therapy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Fertility, IVF and reproductive genetics.

PURPOSE OF REVIEW: Telomere attrition and dysfunction has become a well established pathway involved in organismal aging, not only because it imposes a limitation to cell division and therefore, tissue regeneration but also because telomere homeostasis influences other pathways involved in aging. However, the implication of telomere biology in ovarian aging and fertility is barely starting to be unveiled. RECENT FINDINGS: During the last years, mounting evidence in favor of the relationship between the accumulation of short telomeres and ovarian senescence has emerged. Telomere attrition and the loss of telomerase activity in ovarian cell types is a common characteristic of female infertility. SUMMARY: Recent findings regarding telomere attrition in the ovary open the possibility of both, finding new molecular biomarkers related to telomere homeostasis that make possible the early detection of ovarian dysfunction before the ovarian reserve has vanished, and the search of new therapies to preserve or set up ovarian cell types so that new and better quality oocytes can be generated in aged ovaries to improve IVF outcomes.

Egg Quality and Pregnancy Outcome in Young Infertile Women with Diminished Ovarian Reserve.

BACKGROUND This study investigated the quality and quantity of eggs and embryos as well as the clinical pregnancy outcome in young infertile women with diminished ovarian reserve (DOR) after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). MATERIAL AND METHODS We retrospectively reviewed records of 4285 infertile women and divided them into 3 groups according to age and ovarian reserve: young women with normal ovarian reserve (n=1695), young women with DOR (n=1121), and older women with DOR (n=1469). RESULTS In young women with DOR, the proportion of high-quality embryos was significantly higher than in older women with DOR and lower than in young women with normal ovarian reserve (P<0.01). The proportions of ovulation cancellation, ovulation without egg acquisition, and ovulation without available embryos in young women with DOR were significantly higher than in young women with normal ovarian reserve. The rates of biochemical pregnancy, clinical pregnancy, and embryo implantation in young women with DOR were significantly higher than in older women with DOR, and lower than in young women with normal ovarian reserve. The miscarriage rate was 19.17% in young women with DOR, significantly lower than in older women with DOR (33.90%), and higher than in young women with normal ovarian reserve. CONCLUSIONS Young women with DOR have ovarian hypo-response and low numbers of acquired eggs and embryos, but the possibilities of high-quality embryo and good clinical pregnancy are higher once eggs are acquired. The indications to IVF/ICSI can be widened and active treatments should be administered for these women.

Effect of Pregnancy on the Management and Outcomes of Ovarian Torsion: A Population-Based Matched Cohort Study.

STUDY OBJECTIVE: To compare the treatment and surgical outcomes of ovarian torsion in pregnant and nonpregnant women. DESIGN: A population-based matched cohort study (Canadian Task Force classification II.1). SETTING: The United States Health Care Cost and Utilization Project Nationwide Inpatient Sample from 2003 to 2011. PATIENTS: All cases of ovarian torsion among pregnant women and nonpregnant women with ovarian torsion (matched by age in a ratio of 1:1). INTERVENTIONS: Outcomes of interest included the type of treatment received for ovarian torsion and the complications of surgery. MEASUREMENTS AND MAIN RESULTS: There were 1366 women diagnosed with ovarian torsion among 8 532 163 pregnant women for an incidence of 1.6 in 10 000. Surgery was the predominant treatment, with laparotomy being more commonly performed on pregnant women versus nonpregnant women (57.0% vs 51.0%; odds ratio = 1.28; 95% confidence interval, 1.08-1.51; p < .01). Overall conservative management was less likely performed; however, it was more common among pregnant women versus nonpregnant women (odds ratio = 1.85; 95% confidence interval, 1.44-2.37; p < .01). In general, adverse events were uncommon in both groups although ovarian infarction was more commonly reported among nonpregnant women. CONCLUSION: The diagnosis of ovarian torsion in pregnancy is rare. Compared with nonpregnant women, laparotomy and conservative management are more common among pregnant women. Treatment of ovarian torsion in pregnancy has comparable outcomes with treatment in nonpregnant women.

Diagnosis of Ovarian Torsion: Is It Time to Forget About Doppler?

OBJECTIVE: Accuracy of ultrasound in diagnosis of ovarian torsion remains controversial, with some studies reporting correct diagnosis in only 23% to 66% of cases. Normal Doppler flow does not necessarily exclude an ovarian torsion; in fact, it may lead to missing the diagnosis and has been show to delay management. The objective of our study was to assess sensitivity and specificity of ultrasound diagnosis of ovarian torsion and to analyze the factors contributing to correct and incorrect diagnosis. METHODS: All women presenting with abdominal pain and admitted for urgent/emergent surgery to the gynaecology service at a major teaching hospital between September 2010 and August 2015 were reviewed. Of those, 55 cases of surgically proven ovarian torsion and 48 control cases were selected. Ultrasound reports were reviewed and analyzed. RESULTS: Sixty-one percent of right ovarian torsion case and 27% of left ovarian torsion cases had normal Doppler flow. Presence of ovarian cysts was significantly associated with torsion. Sensitivity of ultrasound was 70% and specificity was 87%. CONCLUSION: While ultrasound can be used to support a diagnosis of ovarian torsion, it is a clinical diagnosis that requires integration of many factors, especially patient presentation and exclusion of other non-gynaecological pathologies. Doppler flow is not a useful variable to diagnose or exclude ovarian torsion and we recommend it should not be used to exclude a diagnosis of ovarian torsion.

[ON THE ISSUE OF AUTOIMMUNE OVARY DAMAGE DURING PUBERTY].

The aim of the study was to ascertain the influence of AІТ on the formation of autoimmune damage to ovaries by determining the connections between the levels of AOAB, ATPO, gonadotropic and sex hormone levels, and the functional state of the ovaries and thyroid gland. 198 girls age 10-18 were studied: 166 with AIT (AIT+ Group), и 32- without AIT (the AIT- Group). A defined difference between TTH. and ATPO, was revealed, which is explained by the presence of thyroid pathology in the AIT+ Group. Prolactin levels and ovarian volume were notably higher, while Progesterone levels were lower in the AIT+ Group. No discernable differences among levels of AOAB, sex hormones, Estrogen, Testosterone or antral follicules were observed. A direct correlation was revealed between AOAB levels and the girls' age both in the AIT+ and AIT- groups. AOAB data was divided into three tertials in order to study links with various hormonal homeostasis. Analysis of data obtained showed numerous correlative links between ATPO, AOAB, gonadotropins, sex hormones, TTH and ovarian volume in all tertials of both the AIT+ and AIT- groups; correlative links were found, too, between AOAB and ATPO in the III tertial groups AIT+ and AIT-. In adolescents with AIT disbalance occurs at all levels of hormonal homeostasis as well as in ovarian structure. Such changes and the presence of ATPO and AOAB may be associated with emerging autoimmune ovary damage.