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Biomarker Insights 2024Polycystic ovary syndrome (PCOS) is a common endocrinological condition affecting women of reproductive age, associated with insulin resistance and obesity. PCOS...
BACKGROUND
Polycystic ovary syndrome (PCOS) is a common endocrinological condition affecting women of reproductive age, associated with insulin resistance and obesity. PCOS pathogenesis is complex and multifactorial, involving genetic and environmental factors.
OBJECTIVES
This study aimed to determine and compare genotype and allele frequencies of single nucleotide polymorphisms (SNPs) in the apolipoprotein A5 (; rs662799) and perilipin 1 (; rs894160, rs1052700 and rs6496589) genes in Western Saudi women to investigate their association with PCOS and its clinical characteristics.
DESIGN AND METHODS
This was a case-control study conducted on women with ( = 104) and without ( = 87) PCOS. The SNPs were genotyped using TaqMan genotyping assays.
RESULTS
Significant and direct associations were detected between PCOS susceptibility and SNP rs662799 and SNP rs894160 ( < .001). For SNP rs662799, women with the A allele were more likely to have PCOS (relative risk [RR] = 1.348, odds ratio [OR] = 2.313, < .001) and hypertriglyceridaemia (OR = 17.0, = .5) than women with the G allele. For SNP rs894160, women with the T allele were more likely to have PCOS than women with the C allele (RR = 8.043, OR = 7.427, < .001). For SNP rs1052700, women with the TT genotype were more likely to have hyperandrogenism (OR = 29.75, = .02) and an irregular period (OR = 0.07, = .040) than women with the AT genotype.
CONCLUSION
We identified novel alleles and genotypes contributing to the genetic risk of PCOS in the Western Saudi population.
PubMed: 38887365
DOI: 10.1177/11772719241258585 -
Research Square Jun 2024In women, shorter telomeres have been reported to be associated with conditions such as endometriosis and polycystic ovary syndrome, whereas other studies have reported...
In women, shorter telomeres have been reported to be associated with conditions such as endometriosis and polycystic ovary syndrome, whereas other studies have reported the opposite. In men, studies mostly report associations between shorter telomeres and sperm quality. To our knowledge, no studies have thus far investigated the associations between TL and fecundability or the use of ART. This study is based on the Norwegian Mother, Father, and Child Cohort (MoBa) Study and uses data from the Medical Birth Registry of Norway (MBRN). We included women (24,645 with genotype data and 1,054 with TL measurements) and men (18,339 with genotype data and 965 with TL measurements) participating between 1998 and 2008. We investigated the associations between leukocyte TL and fecundability, infertility, and the use of ART. We also repeated the analyses using instrumental variables for TL, including genetic risk scores for TL and genetically predicted TL. Approximately 11% of couples had experienced infertility and 4% had used ART. TL was not associated with fecundability among women (fecundability ratio [FR], 0.98; 95% confidence interval [CI], 0.92-1.04) or men (FR, 0.99; CI, 0.93-1.06), nor with infertility among women (odds ratio [OR], 1.03; CI, 0.85-1.24) or men (OR, 1.05; CI, 0.87-1.28). We observed an increased likelihood of using ART with increasing TL among men (OR, 1.22; CI, 1.03-1.46), but not among women (OR, 1.10; CI, 0.92-1.31). No significant associations were observed using the instrumental variables. Our results indicate that TL is a poor biomarker of fecundability, infertility and use of ART in MoBa. Additional studies are required to replicate the association observed between TL and ART in men.
PubMed: 38883734
DOI: 10.21203/rs.3.rs-4430021/v1 -
Frontiers in Cell and Developmental... 2024Polycystic ovary syndrome (PCOS) is characterized by excess androgens, ovulatory dysfunction, and polycystic ovaries. The mechanisms underlying ovulatory and metabolic...
Polycystic ovary syndrome (PCOS) is characterized by excess androgens, ovulatory dysfunction, and polycystic ovaries. The mechanisms underlying ovulatory and metabolic disorders in PCOS remain elusive, hampering therapeutic development. Enhanced metabolic health correlates with increased microbiota gene content and microbial diversity. We aimed to explore the impact of gut microbiota and serum steroids on PCOS regulation associated with androgen excess. The fecal samples of patients with hyperandrogenic PCOS ( = 14) and control group with PCOS ( = 14) were analyzed by 16S rRNA gene sequencing. The peripheral venous blood of all subjects was collected to detect serum hormones. The association between gut microbiota and serum hormones was analyzed with the R language. Our findings reveal that the hyperandrogenic PCOS group exhibits lower richness and diversity of gut microbiota compared to the control group. Characteristic genera in PCOS patients with hyperandrogenism include , and . Five hormones, including 5β-androsterone, deoxycorticosterone, corticosterone, 11-dehydrocorticosterone, and cortexolone, emerge as potential serum biomarkers for identifying patients with hyperandrogenic-PCOS (HA-PCOS). Furthermore, a lower vitamin D3 level may act as a susceptibility factor, suggesting that vitamin D3 supplementation could serve as a potential intervention for PCOS with hyperandrogenism. Specific fecal microbiota and serum steroids may be used as characteristic markers for clinical diagnosis of hyperandrogenic-PCOS. This research enhances our understanding of the intricate interplay among hormones, gut microbiota, and hyperandrogenemia in patients with PCOS.
PubMed: 38872933
DOI: 10.3389/fcell.2024.1384233 -
Frontiers in Endocrinology 2024Polycystic ovary syndrome (PCOS) and thyroid disorders have both been linked to adverse pregnancy and neonatal outcomes. Even small variations in thyroid function within... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Polycystic ovary syndrome (PCOS) and thyroid disorders have both been linked to adverse pregnancy and neonatal outcomes. Even small variations in thyroid function within the normal range may influence fetal growth. Our aim was to investigate whether maternal thyroid function is associated with newborn anthropometrics in PCOS and explore the potential modifying effect of metformin.
METHODS
analyses of two RCTs in which pregnant women with PCOS were randomized to metformin or placebo, from first trimester to delivery. Maternal serum levels of thyroid stimulating hormone (TSH) and free thyroxine (fT4) were measured at gestational weeks (gw) 5-12, 19, 32 and 36 in 309 singleton pregnancies. The mean z-scores of birthweight, birth length, and head circumference were estimated in the offspring. Associations of maternal thyroid parameters with offspring anthropometrics and the outcomes large for gestational age (LGA) and small for gestational age (SGA) were studied using linear and logistic regression models, with adjustment for body mass index (BMI) when relevant.
RESULTS
Maternal fT4 at baseline was negatively associated with birth length (b= -0.09, p=0.048). Furthermore, ΔfT4 during pregnancy correlated positively to z-score of both birth weight and length (b=0.10, p=0.017 and b=0.10, p=0.047 respectively), independently of treatment group. TSH at baseline and gw19 was inversely associated with LGA (OR 0.47, p=0.012 and OR 0.58, p=0.042), while ΔTSH was positively associated with LGA (OR 1.99, p=0.023). There were inverse associations between TSH at baseline and SGA (OR 0.32, p=0.005) and between ΔfT4 and SGA (OR 0.59, p=0.005) in the metformin group only. There were no associations between maternal thyroid function and head circumference of the newborns.
CONCLUSION
In women with PCOS, a higher maternal fT4 in early pregnancy and a greater decrease in fT4 during pregnancy was associated with a lower offspring birthweight and shorter birth length. Higher TSH by mid-gestation and smaller increase in TSH during pregnancy was associated with less risk of LGA. Subclinical variations in maternal thyroid function might play a role for birth anthropometrics of PCOS offspring.
Topics: Humans; Female; Polycystic Ovary Syndrome; Pregnancy; Adult; Infant, Newborn; Birth Weight; Metformin; Thyrotropin; Thyroid Gland; Thyroid Function Tests; Pregnancy Complications; Thyroxine; Infant, Small for Gestational Age; Pregnancy Outcome; Anthropometry; Hypoglycemic Agents; Male
PubMed: 38868742
DOI: 10.3389/fendo.2024.1388473 -
International Journal of Reproductive... Mar 2023Some medical conditions, including polycystic ovarian syndrome (PCOs), may lead to infertility. In PCOs, hormonal imbalance is significant. Antioxidants such as natural...
The effect of aqueous extract of orchid root on the structure of ovary and hypothalamic-pituitary-gonadal hormones in polycystic ovary syndrome rat model: An experimental study.
BACKGROUND
Some medical conditions, including polycystic ovarian syndrome (PCOs), may lead to infertility. In PCOs, hormonal imbalance is significant. Antioxidants such as natural antioxidants have many health benefits, including positive effects on hormone production.
OBJECTIVE
Since herbal medicines are more acceptable to people, the present study was designed to evaluate the effect of an aqueous extract of orchid (SA), with antioxidative effects, on the structure of the ovary and the hypothalamic-pituitary-gonadal axis hormones and free testosterone in PCOs rats.
MATERIALS AND METHODS
In this experimental study, 64 healthy female Wistar rats (180-200 gr) were randomly divided into 60 and 89 day control groups, PCOs, and 4 PCOs + SA groups that received 40, 80, 160, and 320 mg/kg of SA. Serum levels of gonadotropin-releasing hormone, estrogen, progesterone, testosterone, follicle-stimulating hormone, and luteinizing hormone were measured. In addition, the ovaries were extracted and examined histologically.
RESULTS
The amount of primordial, primary, secondary, and Graafian follicles and serum levels of follicle-stimulating hormone and progesterone hormones decreased in PCOs groups, while atretic follicles and the serum levels of gonadotropin-releasing hormone, luteinizing hormone, estrogen, and free testosterone were increased. SA at different doses regulated hormonal and histological imbalances caused by PCOs, and 320 mg/kg was the most effective.
CONCLUSION
The aqueous extract of orchids root can have a positive effect on the improvement of polycystic ovary syndrome. This effect can be achieved by regulating the level of sex hormones and correcting follicular abnormalities in the ovarian tissue.
PubMed: 38868447
DOI: 10.18502/ijrm.v22i3.16164 -
International Journal of Reproductive... Mar 2023Recently, letrozole has been used to prevent moderate to severe ovarian hyperstimulation syndrome (OHSS) in assisted reproductive technology cycles due to its...
BACKGROUND
Recently, letrozole has been used to prevent moderate to severe ovarian hyperstimulation syndrome (OHSS) in assisted reproductive technology cycles due to its estrogen-reducing and androgen-increasing effects on the ovaries, affecting granulosa cells, and reducing vascular endothelial growth factor production.
OBJECTIVE
This study aimed to investigate the impact of letrozole consumption in preventing OHSS in infertile women with polycystic ovarian syndrome undergoing in vitro fertilization.
MATERIALS AND METHODS
In this cross-sectional study, among 1743 medical records of infertile women who were scheduled for oocyte retrieval at Research and Clinical Center for Infertility, Yazd, Iran. Data of 343 women with polycystic ovarian syndrome diagnosis and at risk of OHSS was extracted from March 2022-2023. The stimulation was carried out using a flexible gonadotropin releasing hormone (GnRH) antagonist protocol. Women were divided into 2 groups based on whether they received letrozole or not. In the letrozole group, 2.5 mg letrozole twice daily was continued from the trigger day, while in the control group, women did not receive letrozole. The parameters of OHSS severity, hospitalization rates, and the need for albumin prescription were analyzed.
RESULTS
89 women in the letrozole and 254 women in the control group were examined. There was no statistically significant difference between groups in terms of age and body mass index; however, anti-Mullerian hormone was significantly higher than control group (7.53 4.61 vs. 5.47 3.63, p 0.001). The parameters of OHSS severity, hospitalization rates, and the need for albumin prescription showed no significant differences between the groups.
CONCLUSION
Recent study indicates that incorporating letrozole into the treatment of GnRH antagonists and cabergoline does not reduce the OHSS severity.
PubMed: 38868444
DOI: 10.18502/ijrm.v22i3.16165 -
Journal of the Turkish German... Jun 2024To compare in-vitro fertilization (IVF) outcomes in polycystic ovary syndrome (PCOS) patients treated with follicle stimulating hormone (FSH) alone or FSH and...
OBJECTIVE
To compare in-vitro fertilization (IVF) outcomes in polycystic ovary syndrome (PCOS) patients treated with follicle stimulating hormone (FSH) alone or FSH and luteinizing hormone (LH), under freeze-all gonadotropin-releasing hormone (GnRH) antagonist protocols.
MATERIAL AND METHODS
This retrospective study at a university center included PCOS patients, who underwent freeze-all GnRH antagonist IVF cycles between January 2013 and December 2019. They were divided into FSH-only and FSH + LH groups, focusing on pregnancy and live birth rates.
RESULTS
The study included 82 patients: 43 received FSH + LH and 39 FSH only. Baseline characteristics were similar, except for higher thyroid stimulating hormone levels in the FSH-only group. The FSH + LH group required a lower mean ± standard deviation total dose of FSH (1271.5±376.7 vs. 1407.2±645.3 IU, p=0.02), had a shorter mean cycle length (7.3±3.4 vs. 8.3±1.6 days, p=0.004), and had a higher mean number of follicles stimulated (36.9±15.9 vs. 35.9±9.7, p=0.008) compared to the FSH-only group. No significant differences in pregnancy and live birth rates were noted at first transfer, but the cumulative live birth rate was significantly higher in the FSH-only group [30 of 39 (76.9%) vs. 24 of 43 (55.8%), p=0.044].
CONCLUSION
LH supplementation in PCOS patients undergoing GnRH antagonist IVF protocols may impair cumulative live birth rates, despite lowering FSH requirement and reducing IVF cycle length. These results highlight the complex role of LH in IVF outcomes for PCOS patients, suggesting a need for further large studies to fully understand the impact of LH in such treatments.
PubMed: 38867686
DOI: 10.4274/jtgga.galenos.2024.2023-12-9 -
Scientific Reports Jun 2024Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women that is associated with an increased risk of anxiety and depression and with a lower... (Clinical Trial)
Clinical Trial
Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women that is associated with an increased risk of anxiety and depression and with a lower health-related quality of life (HRQoL). PCOS is closely associated with obesity, which per se can lead to symptoms of anxiety and depression and lower HRQoL. The first-line treatment for PCOS is weight loss through lifestyle intervention, which has been shown to improve all symptoms of the syndrome. The aim of this study was to investigate symptoms of anxiety and depression and HRQoL in women with severe obesity (BMI ≥ 35) with and without PCOS, and to evaluate the effect of a one-year structured weight loss intervention. A total of 246 women with severe obesity (PCOS n = 63, non-PCOS n = 183) were included. The comprehensive psychopathological rating scale self-rating scale for affective symptoms (CPRS-S-A) and the short form-36 (SF-36) were used to assess symptoms of anxiety and depression and HRQoL. In total 72 women of the 246 women with severe obesity completed a one-year weight loss programme and were followed up and compared with baseline data. In women with severe obesity, there were no differences in symptoms of anxiety and depression and HRQoL between women with and without PCOS at baseline. Clinically relevant anxiety symptoms were present in 71.3% (PCOS) and 65.6% (non-PCOS), and depression symptoms were present in 56.4% (PCOS) and 52.2% (non-PCOS). Significant weight loss improved physical HRQoL in all women, but reduced symptoms of anxiety and depression only in women without PCOS. There were no differences when comparing the changes between the groups. Women with severe obesity are severely affected by symptoms of anxiety and depression, independent of PCOS. Weight loss improved symptoms of anxiety and depression in women without PCOS, but there were no differences between groups in change from baseline to follow-up.Trial registration number: Clinical trial.gov: NCT01319162, March 18, 2011. Date of registration and enrolment of the first subject September 2011.
Topics: Adult; Female; Humans; Anxiety; Depression; Obesity, Morbid; Polycystic Ovary Syndrome; Quality of Life; Weight Loss; Weight Reduction Programs
PubMed: 38866860
DOI: 10.1038/s41598-024-63166-w -
Endocrine Journal Jun 2024In the early 2000s, metastin, an endogenous ligand for G protein-coupled receptor 54 (GPR54), was discovered in human placental extracts. In 2003, GPR54 receptor...
In the early 2000s, metastin, an endogenous ligand for G protein-coupled receptor 54 (GPR54), was discovered in human placental extracts. In 2003, GPR54 receptor mutations were found in a family with congenital hypogonadotropic hypogonadism. Metastin was subsequently renamed kisspeptin after its coding gene, Kiss1. Since then, studies in mice and other animals have revealed that kisspeptin is located at the apex of the hypothalamic-pituitary-gonadal axis and regulates reproductive functions by modulating gonadotropin-releasing hormone (GnRH). In rodents, kisspeptin (Kiss1) neurons localize to two regions, the hypothalamic arcuate nucleus (ARC) and the anteroventral periventricular nucleus (AVPV). ARC Kiss1 neurons co-express neurokinin B (NKB) and dynorphin and are thus termed KNDy neurons. Kiss1 neurons in humans are concentrated in the infundibular nucleus (equivalent to the ARC), with few Kiss1 neurons localized to the preoptic area (equivalent to the AVPV), and the mechanisms underlying GnRH surge secretion in humans are poorly understood. However, peripheral administration of kisspeptin to humans promotes gonadotropin secretion, and administration of kisspeptin to patients with hypothalamic amenorrhea or congenital hypogonadotropic hypogonadism restores the pulsatile secretion of GnRH/luteinizing hormone. Thus, kisspeptin undoubtedly plays an important role in reproductive function in humans. Studies are currently underway to develop kisspeptin receptor agonists or antagonists for clinical application. Modification of KNDy neurons by NKB agonists/antagonists is also being attempted to develop therapeutic agents for various menstrual abnormalities, including polycystic ovary syndrome and menopausal hot flashes. Here, we review the role of kisspeptin in humans and its clinical applications.
PubMed: 38866494
DOI: 10.1507/endocrj.EJ24-0006 -
Frontiers in Endocrinology 2024Ovarian stimulation (OS) for fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in women with PCOS often results in multiple follicular development, yet some...
BACKGROUND
Ovarian stimulation (OS) for fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in women with PCOS often results in multiple follicular development, yet some individuals experience poor or suboptimal responses. Limited data exist regarding the impact of poor/suboptimal ovarian response on pregnancy outcomes in women with PCOS.
OBJECTIVES
The aim of this study was to evaluate whether the live birth rate (LBR) per fresh embryo transfer and cumulative live birth rate (CLBR) per aspiration cycle differ in women with PCOS defined by the Patient-Oriented Strategy Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria.
METHODS
A retrospective study involving 2,377 women with PCOS who underwent their first IVF/ICSI cycle at Sun Yat-sen Memorial Hospital from January 2011 to December 2020 was used. Patients were categorized into four groups based on age, antral follicle count, and the number of oocytes retrieved, according to the POSEIDON criteria. The LBR and CLBR were compared among these groups. Logistic regression analysis was performed to assess whether the POSEIDON criteria served as independent risk factors and identify factors associated with POSEIDON.
RESULTS
For patients <35 years old, there was no significant difference in the clinical pregnancy rate between POSEIDON and non-POSEIDON patients, whereas POSEIDON patients exhibited lower rates of implantation and live birth. POSEIDON Group 1a displayed lower rates of implantation, clinical pregnancy, and live birth. However, no significant differences were observed in the rates of clinical pregnancy and live birth between POSEIDON Group 1b and non-POSEIDON groups. For patients ≥35 years old, there were no significant differences in the rates of implantation, clinical pregnancy, and live birth between POSEIDON and non-POSEIDON patients. CLBRs were significantly lower in POSEIDON Groups 1 and 2, compared with the non-POSEIDON groups. The levels of body mass index (BMI), follicle-stimulating hormone (FSH), and antral follicle count (AFC) were associated with POSEIDON hypo-response. POSEIDON was found to be associated with lower CLBR, but not LBR per fresh embryo transfer.
CONCLUSIONS
In patients with PCOS, an unexpected suboptimal response can achieve a fair LBR per fresh embryo transfer. However, CLBR per aspirated cycle in POSEIDON patients was lower than that of normal responders. BMI, basal FSH level, and AFC were independent factors associated with POSEIDON. Our study provides data for decision-making in women with PCOS after an unexpected poor/suboptimal response to OS.
Topics: Humans; Female; Retrospective Studies; Adult; Polycystic Ovary Syndrome; Pregnancy; Embryo Transfer; Birth Rate; Live Birth; Ovulation Induction; Fertilization in Vitro; Pregnancy Rate; Sperm Injections, Intracytoplasmic; Pregnancy Outcome; Infertility, Female
PubMed: 38863934
DOI: 10.3389/fendo.2024.1348771