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Animal Reproduction Science Oct 2023The objective of this study was to compare the reproductive performance of lactating dairy cows submitted to first AI after combination of estrus detection and fixed...
Comparison of three reproductive management strategies for lactating dairy cows using combination of estrus detection or ovulation synchronization and Fixed-Timed Artificial Insemination.
The objective of this study was to compare the reproductive performance of lactating dairy cows submitted to first AI after combination of estrus detection and fixed timed AI (FTAI) and FTAI only. Cows were randomly assigned to receive AI at detected estrus between 50 and 70 d in milk (DIM), if not detected in estrus, were enrolled in either Ovsynch (ED-Ov, n = 485) or PRIDsynch (ED-PR, n = 505) protocols; or received FTAI at 80 DIM after Double-Ovsynch protocol (DO, n = 501). Cows were body condition scored (BCS) at calving and at 43 DIM; and evaluated for postpartum disorders within 7 d postpartum; clinical mastitis, lameness and bovine respiratory disease were recorded until first AI. Ovarian cyclicity was monitored at 43 and 50 DIM, and at 70 and 77 DIM. Pregnancy diagnoses (PD) were performed at 32 and 63 d after AI. Overall prevalence of postpartum anovulation was 7.8%. Pregnancy per AI (P/AI) did not differ between reproductive strategies at 32 d PD (ED-Ov = 43.2%; ED-PR = 41.7%; DO= 45.3%). Primiparous cows had greater P/AI than multiparous cows (53.7% vs 36.8%). Cows on farm 1 had lower P/AI compared with their counterparts on farm 2 (42.1% vs 45.4%). Cows with BCS > 2.5 at 43 DIM had greater P/AI compared with cows with BCS ≤ 2.5 (44.5% vs 34.7%). Similar P/AI for cow's receiving AI at detected estrus and FTAI, low prevalence of disease anovulation may have contributed to the similar performance of ED-Ov, ED-PR and DO.
PubMed: 37717491
DOI: 10.1016/j.anireprosci.2023.107331 -
Trials Sep 2023Polycystic ovary syndrome (PCOS) is the most prevalent, chronic endocrine-metabolic disorder of adolescents and young women (AYAs), affecting 5-10% of AYAs worldwide....
SPIOMET4HEALTH-efficacy, tolerability and safety of lifestyle intervention plus a fixed dose combination of spironolactone, pioglitazone and metformin (SPIOMET) for adolescent girls and young women with polycystic ovary syndrome: study protocol for a multicentre, randomised, double-blind,...
BACKGROUND
Polycystic ovary syndrome (PCOS) is the most prevalent, chronic endocrine-metabolic disorder of adolescents and young women (AYAs), affecting 5-10% of AYAs worldwide. There is no approved pharmacological therapy for PCOS. Standard off-label treatment with oral contraceptives (OCs) reverts neither the underlying pathophysiology nor the associated co-morbidities. Pilot studies have generated new insights into the pathogenesis of PCOS, leading to the development of a new treatment consisting of a fixed, low-dose combination of two so-called insulin sensitisers [pioglitazone (PIO), metformin (MET)] and one mixed anti-androgen and anti-mineralocorticoid also acting as an activator of brown adipose tissue [spironolactone (SPI)], within a single tablet (SPIOMET). The present trial will evaluate the efficacy, tolerability and safety of SPIOMET, on top of lifestyle measures, for the treatment of PCOS in AYAs.
METHODS
In this multicentre, randomised, double-blind, placebo-controlled, four-arm, parallel-group, phase II clinical trial, AYAs with PCOS will be recruited from 7 clinical centres across Europe. Intention is to randomise a total of 364 eligible patients into four arms (1:1:1:1): Placebo, PIO, SPI + PIO (SPIO) and SPI + PIO + MET (SPIOMET). Active treatment over 12 months will consist of lifestyle guidance plus the ingestion of one tablet daily (at dinner time); post-treatment follow-up will span 6 months. Primary endpoint is on- and post-treatment ovulation rate. Secondary endpoints are clinical features (hirsutism, menstrual regularity); endocrine-metabolic variables (androgens, lipids, insulin, inflammatory markers); epigenetic markers; imaging data (carotid intima-media thickness, body composition, abdominal fat partitioning, hepatic fat); safety profile; adherence, tolerability and acceptability of the medication; and quality of life in the study participants. Superiority (in this order) of SPIOMET, SPIO and PIO will be tested over placebo, and if present, subsequently the superiority of SPIOMET versus PIO, and if still present, finally versus SPIO.
DISCUSSION
The present study will be the first to evaluate-in a randomised, double-blind, placebo-controlled way-the efficacy, tolerability and safety of SPIOMET treatment for early PCOS, on top of a lifestyle intervention.
TRIAL REGISTRATION
EudraCT 2021-003177-58. Registered on 22 December 2021. https://www.clinicaltrialsregister.eu/ctr-search/search?query=%092021-003177-58 .
Topics: Adolescent; Female; Humans; Carotid Intima-Media Thickness; Clinical Trials, Phase II as Topic; Insulin; Life Style; Metformin; Multicenter Studies as Topic; Pioglitazone; Polycystic Ovary Syndrome; Quality of Life; Randomized Controlled Trials as Topic; Spironolactone; Young Adult
PubMed: 37715279
DOI: 10.1186/s13063-023-07593-6 -
International Journal of Molecular... Aug 2023Polycystic ovary syndrome (PCOS) is a complex, but relatively common endocrine disorder associated with chronic anovulation, hyperandrogenism, and micro-polycystic... (Review)
Review
Polycystic ovary syndrome (PCOS) is a complex, but relatively common endocrine disorder associated with chronic anovulation, hyperandrogenism, and micro-polycystic ovaries. In addition to reduced fertility, people with PCOS have a higher risk of obesity, insulin resistance, and metabolic disease, all comorbidities that are associated with mitochondrial dysfunction. This review summarizes human and animal data that report mitochondrial dysfunction and metabolic dysregulation in PCOS to better understand how mitochondria impact reproductive organ pathophysiology. This in-depth review considers all the elements regulating mitochondrial quantity and quality, from mitochondrial biogenesis under the transcriptional regulation of both the nuclear and mitochondrial genome to the ultrastructural and functional complexes that regulate cellular metabolism and reactive oxygen species production, as well as the dynamics that regulate subcellular interactions that are key to mitochondrial quality control. When any of these mitochondrial functions are disrupted, the energetic equilibrium within the cell changes, cell processes can fail, and cell death can occur. If this process is ongoing, it affects tissue and organ function, causing disease. The objective of this review is to consolidate and classify a broad number of PCOS studies to understand how various mitochondrial processes impact reproductive organs, including the ovary (oocytes and granulosa cells), uterus, placenta, and circulation, causing reproductive pathophysiology. A secondary objective is to uncover the potential role of mitochondria in the transgenerational transmission of PCOS and metabolic disorders.
Topics: Animals; Female; Pregnancy; Humans; Polycystic Ovary Syndrome; Fertility; Cell Death; Genitalia
PubMed: 37685928
DOI: 10.3390/ijms241713123 -
Diagnostics (Basel, Switzerland) Aug 2023We aimed to investigate the association between kidney stones and polycystic ovarian syndrome (PCOS).
BACKGROUND
We aimed to investigate the association between kidney stones and polycystic ovarian syndrome (PCOS).
MATERIALS AND METHODS
In a cross-sectional study, data from the Tehran Lipid and Glucose Study (TLGS) were used to investigate the risk of kidney stones in women with Polycystic Ovary Syndrome (PCOS). Four distinct phenotypes of PCOS, as defined by the Rotterdam criteria, were examined in a sample of 520 women and compared to a control group of 1638 eumenorrheic non-hirsute healthy women. Univariate and multivariable logistic regression models were employed for analysis. The four PCOS phenotypes were classified as follows: Phenotype A, characterized by the presence of all three PCOS features (anovulation (OA), hyperandrogenism (HA), and polycystic ovarian morphology on ultrasound (PCOM)); Phenotype B, characterized by the presence of anovulation and hyperandrogenism; Phenotype C, characterized by the presence of hyperandrogenism and polycystic ovarian morphology on ultrasound; and Phenotype D, characterized by the presence of anovulation and polycystic ovarian morphology on ultrasound.
RESULTS
The prevalence of a history of kidney stones was found to be significantly higher in women with Polycystic Ovary Syndrome (PCOS) compared to healthy controls (12.5% vs. 7.7%, = 0.001). This increased prevalence was observed across all PCOS phenotypes ( < 0.001). After adjusting for potential risk factors, including age, family history of kidney stones, waist-to-height ratio, total cholesterol, and low-density lipoprotein, the odds ratio for kidney stones in women with PCOS was found to be 1.59 [95% CI: 1.12-2.25, = 0.01], indicating a 59% increase in risk compared to healthy women. Women with PCOS Phenotype A [OR: 1.97, 95% CI: 1.09-3.55, = 0.02] and Phenotype D [OR: 3.03, 95% CI: 1.24-7.41, = 0.01] were found to be at a higher risk for kidney stones.
CONCLUSION
Women with Polycystic Ovary Syndrome (PCOS), particularly those exhibiting menstrual irregularities and polycystic ovarian morphology on ultrasound (PCOM), have been found to be two to three times more likely to develop kidney stones. This increased prevalence should be taken into consideration when providing preventive care and counseling to these individuals.
PubMed: 37685351
DOI: 10.3390/diagnostics13172814 -
Cureus Aug 2023Background Infertility is a public health issue with a significant impact on the well-being of affected couples. Aim This paper aims to detect the determinants of...
Background Infertility is a public health issue with a significant impact on the well-being of affected couples. Aim This paper aims to detect the determinants of pregnancy and their outcome after assisted reproductive therapy (ART) in a sample of Palestinian society. Methods A retrospective observational study was carried out at Razan Medical Center for Infertility. Subjects were assigned into twelve categories based on the type of infertility (primary versus secondary), the cause of infertility, and the treatment modality. Age at marriage, age at presentation, duration of infertility, in addition to regularity of menstruation, were also studied. Biochemical pregnancy was considered the endpoint for the purpose of the analysis. Results We reviewed the files of 459 subjects diagnosed with infertility. 79.74% had primary infertility while 20.26% had secondary. 28.85% were found to be infertile due to anovulation, 2.86% due to endometriosis, 16.74% attributed to male factor, and 3.3% had tubal damage. 13.43% of cases were multifactorial while 34.80% were idiopathic. Four biochemical markers were assessed in our study: thyroid-stimulating hormone (TSH) (=2.32±2.46), luteinizing hormone (=6.71±4.90), follicle-stimulating hormone (FSH) (=6.59±6.11), and human prolactin (=41.88±6.50). The menstrual cycle was regular in 70.58% of subjects, in contrast to 29.41% with irregular cycles. The female mean age at presentation was 22.76±5.58, while their mean age of marriage was 22.76±4. The mean duration of infertility was 3.97±6.87 years. Patients were treated via three modalities - ovarian stimulation (2.2%), intrauterine insemination (29.58%), and intracytoplasmic sperm injection (68.21%) - with a success rate of 51.85%. Of the studied factors, only diagnosis, follicle-stimulating hormone, and treatment modality had a significant impact on the outcome, with values of 0.040, 0.003, and <.0.001, respectively. Conclusions There is a strong relationship between diagnosis prior to intervention, level of FSH, and treatment modality and successful outcome of ART.
PubMed: 37674937
DOI: 10.7759/cureus.43011 -
Medicine Sep 2023This study aimed to determine whether serum mid-luteal progesterone (MLP) levels measured in the current treatment cycles of infertile women undergoing controlled...
This study aimed to determine whether serum mid-luteal progesterone (MLP) levels measured in the current treatment cycles of infertile women undergoing controlled ovarian hyperstimulation and intrauterine insemination following the sequential use of clomiphene citrate and gonadotropin may predict pregnancy. A total of 107 consecutive anovulatory women were included in this prospective cohort study. Patients with other causes of infertility were also excluded from the study. None of the patients received progesterone treatment for luteal phase support. The data recorded for each woman included age, body mass index, infertility type and duration, basal hormone levels, and previous and current cycle characteristics with MLP levels. Ovulation was confirmed using MLP and sonographic evaluation in all patients. An MLP level of > 3 ng/mL was regarded as a sign of ovulation. After treatment, the patients were divided into 2 groups according to the presence or absence of pregnancy, and the obtained data were compared between the groups. There were no significant differences in age, body mass index, or basal hormone levels between the 2 groups (all P > .05). However, the duration of infertility was significantly shorter in the pregnancy group (P = .003). The anovulation rate in this cohort was 18.7% (n = 20). A total of 15 (14%) were examined. MLP levels were 25.1 ± 13.8 ng/mL and 18.3 ± 14.5 ng/mL in the pregnant and nonpregnant groups, respectively (P:.089). Based on the receiver operating characteristic curve analysis, it was determined that there was no predictive value of the mid-luteal phase progesterone level for pregnancy in patients in whom ovulation was detected. Mid-luteal serum progesterone levels did not predict pregnancy in infertile women who underwent controlled ovarian hyperstimulation with sequential clomiphene citrate plus gonadotropin treatment and intrauterine insemination.
Topics: Pregnancy; Humans; Female; Progesterone; Infertility, Female; Prospective Studies; Clomiphene; Gonadotropins; Insemination
PubMed: 37657005
DOI: 10.1097/MD.0000000000034754 -
Phytomedicine : International Journal... Nov 2023Polycystic ovary syndrome (PCOS) leads to persistent anovulation, hyperandrogenism, insulin resistance, and polycystic ovary, and is mainly characterized by menstrual...
The efficacy and mechanism of Angelica sinensis (Oliv.) Diels root aqueous extract based on RNA sequencing and 16S rDNA sequencing in alleviating polycystic ovary syndrome.
BACKGROUND
Polycystic ovary syndrome (PCOS) leads to persistent anovulation, hyperandrogenism, insulin resistance, and polycystic ovary, and is mainly characterized by menstrual disorders, and reproductive dysfunction. Angelica sinensis (Oliv.) Diels root has been used in many classical formulas of traditional Chinese medicine, and is commonly used to treat various gynecological diseases.
PURPOSE
To investigate the protective effect of water extract of A. sinensis root (WEA) on PCOS rats, and the mechanism by RNA sequencing, and 16S rDNA sequencing.
METHODS
The PCOS rat model was established by letrozole combined with high-fat diet (gavage; 2 months), and treated with WEA (gavage; 2 g/kg, 4 g/kg or 8 g/kg; 1 month). To evaluate the therapeutic effect of WEA on PCOS rats, vaginal smear, hematoxylin-eosin staining, and biochemical indicators detection were performed. The rat ovarian tissue was analyzed by RNA sequencing, and the results were verified by qRT-PCR, and Western blot. 16S rDNA sequencing was used to analyze the gut microbiota of rats.
RESULTS
The results of the vaginal smear, and hematoxylin-eosin staining showed that WEA improved estrous cycle disorder, and ovarian tissue lesions. WEA (4 g/kg or 8 g/kg; 1 months) alleviated hormone disorders, insulin resistance, and dyslipidemia. RNA sequencing showed that WEA intervention significantly changed the expressions of 2756 genes, which were enriched in phosphatidylinositol3-kinase/phosphorylated protein kinase B (PI3K/AKT), peroxisome proliferator-activated receptor (PPAR), mitogen-activated protein kinase (MAPK), AMP-activated protein kinase (AMPK), and insulin signaling pathways. 16S rDNA sequencing found that WEA increased the species diversity of gut microbiota, and regulated the abundance of some microbiota (genus level: Dubosiella, Bifidobacterium, Coriobacteriaceae (UCG-002), and Treponema; species level: Bifidobacterium animalis, Lactobacillus murinus, and Lactobacillus johnsonii).
CONCLUSION
WEA regulated hormone, and glycolipid metabolism disorders, thereby relieving the PCOS induced by letrozole combined with high-fat diet. The mechanism was related to the regulation of PI3K/AKT, PPAR, MAPK, AMPK, and insulin signaling pathways in ovarian tissues, and the maintenance of gut microbiota homeostasis. Clarifying the efficacy and mechanism of WEA in alleviating PCOS based on RNA sequencing and 16S rDNA sequencing will guide the more reasonable clinical use of WEA.
Topics: Female; Humans; Animals; Rats; Polycystic Ovary Syndrome; Angelica sinensis; AMP-Activated Protein Kinases; Eosine Yellowish-(YS); Hematoxylin; Insulin Resistance; Letrozole; Peroxisome Proliferator-Activated Receptors; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; DNA, Ribosomal; Sequence Analysis, RNA; Insulins
PubMed: 37639812
DOI: 10.1016/j.phymed.2023.155013 -
Bone Reports Dec 2023Whether polycystic ovary syndrome (PCOS) affects bone health during a woman's lifespan remains controversial. An androgenized rodent model replicated many metabolic and...
BACKGROUND
Whether polycystic ovary syndrome (PCOS) affects bone health during a woman's lifespan remains controversial. An androgenized rodent model replicated many metabolic and reproductive features of women with PCOS, and we aimed to use it to investigate the impact of androgens on microarchitecture (by micro-CT), bone mechanical strength, bone formation and resorption markers in rats with intact ovaries (SHAM) who underwent oophorectomy.
METHODS
Wistar rats ( were employed for the experiments in this study. The protocol of androgenization consisted of the application of 1.25 mg s.c. testosterone propionate beteween days 2-5 of life, while the controls received the same amount of corn oil s.c. as previously established. Androgenized SHAM rats exhibited chronic anovulation identified by vaginal cytology and a reduction in the proportion of corpus luteum in the ovary in comparison to control SHAM rats. The realization of the ovariectomy or SHAM procedure occurred on Day 100 of life. All groups (n = 8) were followed-up for 180 days to address the study endpoints.
RESULTS
Micro-CT from androgenized female rats (SHAM) showed a divergence between the trabecular and cortical bone profiles. Compared to SHAM controls, these rats had an increase in trabecular bone mass with a diminution in bone resorption C-terminal telopeptide of type 1 collagen (CTX) (p < 0.05), a concomitant decrease in cortical area and thickness in the femur, and a reduction in the strength of the femur on the mechanical test (p < 0.01).
CONCLUSIONS
Our results suggest that a reduction in the cortical thickness and cortical area observed in PCOS model rats was associated with a reduced strength of the femur, despite increased trabecular formation. Ovariectomy in the androgenized OVX group limited the progression rate of cortical bone loss, resulting in bone resistance and cortical thickness comparable to those observed in the control OVX group.
PubMed: 37637757
DOI: 10.1016/j.bonr.2023.101710 -
Cureus Jul 2023Background Ovulatory disruption is the primary reversible cause of infertility, which affects 12-24% of couples. The FDA's first-line recommendation for ovulation...
Background Ovulatory disruption is the primary reversible cause of infertility, which affects 12-24% of couples. The FDA's first-line recommendation for ovulation induction in such cases is clomiphene citrate. Serial ultrasonography can be used to evaluate follicular development. Methodology The current study is a two-year prospective cohort study conducted at a tertiary care centre. One hundred patients with either primary or secondary infertility and no pelvic pathology were involved in the study and split into two groups: Group I included ovulatory women whose infertility was caused by a factor other than ovulatory disorder, and Group II comprised anovulatory women. Folliculometry was performed using transvaginal sonography; Group I had a spontaneous cycle, whereas Group II received clomiphene citrate (CC) to induce ovulation. The ovulation rate, pregnancy rate, multiple pregnancy rate, and rate of ovarian hyperstimulation (OHSS) were all studied. Results Seventy-two percent of the patients had primary infertility, and most appeared after 3-6 years of infertility. 62% of the patients were between the ages of 21 and 30 years. 50% of cases had ovulatory dysfunction, and polycystic ovarian disease (PCOD) was the most frequent cause of anovulation (24%). The leading follicular diameter was substantially bigger (22-26 mm) in the CC-triggered cycle compared to the spontaneous cycle (16-21 mm). In both spontaneous and induced cycles, the endometrial thickness displayed a linear development pattern during the pre-ovulatory phase and plateaued during the luteal phase. With CC, there was a 68% ovulation rate, a 32% pregnancy rate, a 12.5% multiple pregnancy rate, and a 2% incidence of OHSS. Conclusion Clomiphene citrate increases the rate of ovulation and pregnancy in females having ovulatory disorders.
PubMed: 37605698
DOI: 10.7759/cureus.42234 -
Cureus Jul 2023Background and objectives Polycystic ovary syndrome (PCOS) is a prominent cause of anovulation. Thus, this study aimed to compare the pregnancy rates of women with PCOS...
Background and objectives Polycystic ovary syndrome (PCOS) is a prominent cause of anovulation. Thus, this study aimed to compare the pregnancy rates of women with PCOS treated with letrozole (LE) or clomiphene citrate (CC) at King Abdulaziz University Hospital. Patients and methods A retrospective record review was conducted from April 2021 to August 2022 to review 1370 records of women with PCOS from January 2015 to December 2021. Sixty-one patients were included in this analysis. Chi-square tests and independent sample t-tests were used to analyze various associations. Statistical significance was set at < 0.05. Results Letrozole was associated with a higher pregnancy rate (41.7%) than CC (32.0%). However, this relationship was not statistically significant ( = .619). Furthermore, patients treated with letrozole required fewer cycles to achieve pregnancy (two cycles compared to three cycles). The different age groups and body mass indexes did not affect the pregnancy rate in either group. Conclusion No significant difference was found between CC and LE in ovulation induction and outcome among PCOS patients. Studies with larger sample sizes and multiple centers should be conducted in Saudi Arabia to obtain more conclusive results, which will eventually lead to changes in guidelines for anovulation treatment in women with PCOS.
PubMed: 37605693
DOI: 10.7759/cureus.42257