Ovarian Disorders Research Articles

ScRNA-seq revealing the molecular atlas of the goat follicular microenvironment over the time course of ovulation

Ovulation is paramount for female animal fertility, necessitating a thorough understanding of its process and molecular underpinnings. This study aimed to delineate the goat ovary temporal dynamics of ovulation. Utilizing single-cell sequencing, we analyzed follicular fluid samples obtained at 0, 6, 12, 18, and 24 h post-hCG administration, identifying 4 cell types and 6 myeloid cell subtypes. We elucidated gene expression and functional changes in granulosa cells over the time course of ovulation. Notably, our study detected and confirmed immune cell infiltration at 6 h post-LH peak. Additionally, we observed significant cellular interactions between granulosa cells and macrophages, with granulosa cells expressing IL1RAP, COL4A1, COL4A2 implicated in immune cell regulation, while macrophages expressed EREG to facilitate oocyte maturation. Collectively, our investigation has established a comprehensive single-cell transcriptome atlas of the ovulating goat ovary for advancing exploration into ovulation mechanisms and developing therapies for ovulatory disorders.

Correlation of Hypothyroidism with Age and Comorbidities Among Women: A Cross-Sectional Study

Background Hypothyroidism, an endocrine disorder caused by thyroid dysfunction found to be more prevalent globally in females than in males. Young females are more prone to subclinical hypothyroidism (SCH). The study aimed to estimate the different types of hypothyroidism based on the clinical profile of thyroid hormone and to detect various comorbidities in correlation with age in women. In female patients with hypothyroidism, there is a significant association between age groups and the type of hypothyroidism (subclinical, clinical, overt), with younger age groups showing a higher prevalence of SCH. Additionally, comorbidities, such as polycystic ovarian disorder (PCOD), are more prevalent in hypothyroidism patients, particularly in those with SCH. Materials and Methods A prospective cross-sectional study executed in a tertiary care hospital for one year with an inclusion of female hypothyroid patients above 18 years of age. An informed written consent form was received from each patient with clarification of the protocol. Results A total of 44.6% women were in the 18–28 years of age group (young females) and 42.8% of women with SCH. PCOD (38.2%) was a predominant comorbid condition among hypothyroidism women. In the age group of 18–28 years, there were significantly more patients 114 (81.4%) with SCH ( p < 0.01) than those with clinical 22 (18.4%) and overt hypothyroidism 10 (14.7%). The hypothyroidism of women with PCOD 95 (67.8%) was significantly ( p < 0.01) more in subclinical than clinical 28 (23.5%) and overt hypothyroidism 2 (2.9%). Conclusion Thyroid dysfunction is uncertain in females, bulges to complications of maternal and fetal outcomes, and is associated with other comorbidities, leading to an increase in the mortality rate. Hypothyroidism is a growing burden for other comorbidities. Pharmaceutical care by healthcare professionals is to be adopted with prompt diagnostic and screening techniques.

Liraglutide improves follicle development in polycystic ovary syndrome by inhibiting CXCL10 secretion

BackgroundAt present, a number of clinical trials have been carried out on GLP-1 receptor agonist liraglutide in the treatment of polycystic ovary syndrome (PCOS). However, the effect of liraglutide on follicle development and its specific mechanism are still unclear.MethodsRNA sequencing was used to explore the molecular characteristics of granulosa cells from patients with PCOS treated with liraglutide. The levels of C-X-C motif chemokine ligand 10 (CXCL10) in follicular fluid were detected by ELISA, the expression levels of ovulation related genes and inflammatory factor genes in follicles and granulosa cells were detected by qPCR and the protein levels of connexin 43 (Cx43), Janus Kinase 2 (JAK2) and phosphorylated JAK2 were detected by Western blot. The mouse ovarian follicles culture system in vitro was used to detect the status of follicle development and ovulation.ResultsIn the present study, we found that liraglutide inhibited the secretion of inflammatory factors in PCOS granulosa cells, among which CXCL10 was the most significant. In addition, CXCL10 was significantly higher in granulosa cells and follicular fluid in PCOS patients than in non-PCOS patients. We applied in vitro follicle culture and other techniques to carry out the mechanism exploration which revealed that CXCL10 disrupted the homeostasis of gap junction protein alpha 1 (GJA1) between oocyte and granulosa cells before physiological ovulation, thus inhibiting follicular development and ovulation. Liraglutide inhibited CXCL10 secretion in PCOS granulosa cells by inhibiting the JAK signaling pathway and can improved dehydroepiandrosterone (DHEA)-induced follicle development disorders, which is reversed by CXCL10 supplementation.ConclusionsThe present study suggests that liraglutide inhibits CXCL10 secretion in granulosa cells through JAK signaling pathway, thereby improving the homeostasis of GJA1 between oocyte and granulosa cells before physiological ovulation and ultimately improving the follicular development and ovulation of PCOS, which provides more supportive evidence for the clinical application of liraglutide in the treatment of ovulatory disorders in PCOS.Trial registrationNot applicable.

Feasibility of acupuncture as an adjunct intervention for ovulatory disorder infertility: A systematic review and meta-analysis.

Acupuncture (AT) is widely used in treatment of ovulatory disorder infertility (ODI), but the safety and efficacy of AT for ODI still lack an evidence-based basis. To evaluate the feasibility and effectiveness of AT as an adjunct intervention for ODI. The Cochrane Library, Embase, PubMed, VIP, China National Knowledge Infrastructure, WanFang Data, and Chinese biomedical literature databases were searched from inception to January 20, 2024. Two reviewers independently selected studies, collected data, and evaluated methodological quality through the Cochrane Risk of Bias tool. Revman 5.4 was used for meta-analysis, and the Grade system was performed to evaluate the level of evidence for the outcomes of the meta-analysis. A total of 20 randomized controlled trials with 1677 ODI patients were included. Compared with the clomiphene citrate (CC) group, the AT plus CC group exhibited significant improvement of the pregnancy rate [relative risk (RR) = 1.68, 95% confidence interval (CI): 1.45-1.95, P < 0.00001, I 2 = 23%], ovulation rate (RR = 1.34, 95%CI: 1.22-1.47, P < 0.00001, I 2 = 32%), serum E2 level [mean difference (MD) = 31.36, 95%CI: 21.83-40.88, P < 0.00001, I 2 = 97%], thickness of endometrium (MD = 1.76, 95%CI: 0.71-2.81, P = 0.001, I 2 = 98%) and decreasing miscarriage rate (RR = 0.25, 95%CI: 0.09-0.65, P = 0.005, I 2 = 0%), serum follicle-stimulating hormone level (MD = -2.10, 95%CI: -3.27 to -0.94, P = 0.0004, I 2 = 99%), serum luteinizing hormone level (MD = -6.94, 95%CI: -9.89 to -4.00, P < 0.00001, I 2 = 100%), and serum progesterone level (MD = -1.66, 95%CI: -2.98 to -0.34, P = 0.01, I 2 = 96%). The AT group had a more favorable effect than CC group for improving pregnancy rate (RR = 1.52, 95%CI: 1.33-1.73, P < 0.00001, I 2 = 0%), thickness of endometrium (MD = 2.48, 95%CI: 2.15-2.81, P < 0.00001, I 2 = 0%) and reducing miscarriage rate (RR = 0.23, 95%CI: 0.13-0.44, P < 0.00001, I 2 = 0%), serum follicle-stimulating hormone level (MD = -0.55, 95%CI: -0.86 to -0.24, P = 0.0005, I 2 = 0%), and serum progesterone level (MD = -0.24, 95%CI: -0.28 to -0.20, P < 0.00001). However, the level of evidence was predominantly assessed as very low to moderate. AT can improve the pregnancy outcomes and sex hormone levels for patients with ODI. However, further studies are needed to confirm these findings.

Zishen Qingre Lishi Huayu Recipe May Ameliorate the Symptoms of PCOS Model Rats via Alleviating Systemic and Ovarian Inflammation.

Zishen Qingre Lishi Huayu recipe (ZQLHR) has shown significant therapeutic effects in treating sex hormone levels and follicular developmental disorders in patients with polycystic ovary syndrome (PCOS). However, little is known about the potential mechanisms of its treatment. Dehydroepiandrosterone and a high-fat diet induced the PCOS model rat. The serum of rats was collected to detect the levels of sex hormones and inflammatory cytokines by enzyme-linked immunosorbent assay, and the ovaries were collected for ovarian histopathology and qPCR assay to detect the levels of inflammatory cytokines in ovarian tissues. Granulosa cells (GCs) were collected for western blot assay to detect of IL-1β, IL-6R, and LOX protein expression levels. ZQLHR could reduce body weight, regulate estrous cycles, and improve serum sex hormone levels, follicular development, and insulin resistance (IR) in PCOS model rats. In addition, ZQLHR treatment improved the levels of inflammatory cytokines in serum and ovary, and regulated the protein expression of IL-6R, IL-1β, and LOX in GCs of PCOS model rats. The results showed that the HOMA-IR index increased with the increasing levels of IL-6, IL-1β, and CRP, and decreased with the increased IL-10. This study reveals that the treatment of endocrine disorders and ovulation disorders in PCOS with ZQLHR may be closely related to the improvement of systemic and ovarian inflammation in PCOS patients, as well as the inhibition of IL-6R, IL-1β, and LOX expression in GCs, which reemphasizes the role of reducing chronic inflammatory states in the treatment of PCOS. Moreover, this study reemphasizes the correlation between multiple inflammatory mediators and IR.

Evaluation of Knowledge and Assessment of Polycystic Ovarian Syndrome (PCOS) Among Healthcare Providers in Medical Institutes of Bahawalpur

Polycystic ovarian syndrome (PCOS) is an endocrine disorder (an imbalance of sex hormones) in which water-filled sacs called cysts form in ovaries. Hormone imbalances in PCOS can lead to problems like irregular periods, troubled ovulation, diabetes, and cardiovascular disorders. PCOS is the main reason for ovulation issues and infertility among females. This study aims to check how many female healthcare providers in the medical institutes of Bahawalpur know about PCOS. In Pakistan, around 52% of reproductive-age women deal with PCOS versus 20–25% in the UK. The study surveyed 341 participants to assess their knowledge. Findings showed that nearly all participants had good knowledge about PCOS (94.4%), and over one-fifth showed possible symptoms (23%). Many of them were undergraduates. The research highlights the need for better education and awareness of PCOS for the general population through these healthcare providers and care to enhance affected women’s quality of life. Based on signs and symptoms, 78 respondents (22.9%) are suspected to have PCOS but are living unknowingly with a low quality of life. They should take medical action as early diagnosis of PCOS is beneficial for improving their quality of life. Hence, community-based awareness programs are needed to address the risk factors, problems, and clinical manifestations for healthcare providers and the general population.

Study of Sonographic Indicators of Ovarian Reserves in Women With WHO-Defined Anovulatory Disorders.

Depending on the age of the wife or female partner, infertility is defined as the inability of a couple to achieve conception after 12 months if the age is ≤35 years and six months if the age is ≥35 years. About half of female infertility is attributed to ovulatory dysfunction, and the rest is either due to tubal and pelvic pathology or problems such as thyroid disease or anatomic abnormalities. Ovulatory disorders are one of the major factors for infertility problems in couples. Ultrasound monitoring of ovarian follicle growth plays a pivotal role in infertility treatment. The total number of small antral follicles in both ovaries is an important predictive parameter of the ovarian induction cycle, whereas ovarian volume is the parameter most easily assessed by ultrasound. The purpose of this study is to analyze the sonographic indicators of infertility (antral follicle count and ovarian volume) in four World Health Organization (WHO)-defined anovulatory groups and compare the same with that of healthy fertile women.

O-220 Ovarify: a deep learning model for automatic calculation of ovarian morphological features in pelvic ultrasonography

Abstract Study question Can a deep learning model accurately characterize ovarian features on pelvic ultrasounds? Summary answer We developed a deep learning model, Ovarify, that can accurately classify and segment ovarian features on pelvic ultrasounds. What is known already Ovarian morphology, as detected using pelvic ultrasonography, is used widely in the assessment of gynecological health. Morphological metrics such as ovarian volume and antral follicle count have known diagnostic and prognostic value for a variety of gynecological outcomes, ranging from risk for ovulatory disorders to likelihood of response to assisted reproductive technologies. However, a lack of standardization in the interpretation of ovarian features, and the time-intensive nature of validated image analysis techniques (such as 2D grid analysis), limits their utility in clinical practice. Deep learning provides an opportunity to overcome these limitations. Study design, size, duration The training dataset for the model comprised 426 3D pelvic ultrasounds obtained using the GE Voluson ultrasound platform, yielding 56,538 individual frames with potential ovarian content. In addition, a similarly collected validation dataset consisted of 95 ultrasounds, yielding 11,304 frames. The held-out test set comprised 107 ultrasounds with 14,767 frames. All frames were manually labeled with the associated 2D ovarian contour, and 163 of the ultrasounds had an associated ovarian volume label. Participants/materials, setting, methods Ovarify consists of two stages: 1) a lightweight classifier that labels ultrasound frames as either positive or negative (having or not having ovarian content) and 2) a subsequent U-Net-inspired segmentation module with an Xception backbone and attention-based decoder that segments the ovary and antral follicles in all frames previously classified as positive. Classification performance was evaluated using F1-score and area under the receiver operating characteristic curve (AUROC). Segmentation performance was evaluated using the Jaccard index. Main results and the role of chance For the classification stage, Ovarify achieved an AUROC of 0.980±0.002 and 0.976±0.004 on the training and validation sets, respectively. On the held-out test set, the model achieved an AUROC of 0.971±0.005. In addition, the model achieved an F1-score of 0.825±0.006, 0.810±0.013, and 0.784±0.014 on the training, validation, and held-out testing sets, respectively. The high AUROC and F1-scores across both seen and unseen datasets support a high-performing classifier. In the segmentation stage, Ovarify reached a median Jaccard index of 0.815±0.004 on the unseen test set when tasked with segmenting the ovary, and a median Jaccard index of 0.657±0.018 on the unseen test set when segmenting antral follicles. High agreement between the ground truth ovary and follicle labels and the predicted segmented regions increases confidence in the downstream morphological analysis. For example, the Pearson correlation coefficient between the Ovarify-calculated ovarian volume and manually-validated ovarian volume was 0.813, indicating that an automatic ovarian volume calculation highly aligns with the ground truth. Ovarify was able to provide predictions in under one minute for the entirety of the held-out test set. Limitations, reasons for caution Ovarify was trained on images generated by the GE Voluson platform and has not been evaluated for generalizability across ultrasound images generated using machines whose output does not match the DICOM format standard. Wider implications of the findings The model developed is relevant for automatically calculating ovarian morphological features from pelvic ultrasounds. This approach has implications in removing user-specific bias and error when calculating biomarkers associated with female reproductive health, including but not limited to ovulatory disorders such as polycystic ovary syndrome (PCOS). Trial registration number not applicable

P-649 Unconventional action of Luteinizing Hormone

Abstract Study question Has Luteinizing Hormone (LH) a role in the activation/survival of follicles of the primary ovarian reserve? Summary answer LH promotes survival and perhaps activation/growth of primordial and primary follicles, proliferation of granulosa cells of secondary follicles, reduces follicle atresia at later growing stages. What is known already In the mammalian ovary, Primordial Follicles (PMFs) constitutes the primary ovarian reserve, which declines over time due to physiological events such as atresia, recruitment, and ovulation. While in the adult, the role of LH in steroidogenesis and ovulation is well established, recent work from our laboratory has shown that under chemotherapeutic treatments, LH supports PMFs survival in prepuberal mouse ovary. Study design, size, duration LH effects on follicle dynamics and some activities of pre-granulosa cells were investigated in vitro and in vivo. In vitroexperiments were performed on PD4 GFP/Kit mice ovarian fragments and on PD8 CD1 mice ovarian somatic cells cultured up to six days in continuous presence of 0.2, 0.5, 1IU LH. In vivo experiments were performed on 9 PD4 and 8 PD28 CD1 mice receiving an intra-peritoneal injection for eight consecutive days of 1-5IU LH. Participants/materials, setting, methods Number and diameters of the GFP stained oocyte were counted in the ovarian fragments. Kit-Ligand and LH-R mRNA expression levels were analyzed by qPCR in pre-granulosa cells. For in vivo experiments, ovarian volume was measured by Micro-Ct and follicle counts were performed on histological sections. Estrous cycle phases were monitored by vaginal smear during the 8 days of treatment. Statistics was performed using Student’s t-test. Main results and the role of chance In fragments of PD4 mouse ovaries cultured in vitro for six days, 1IU LH significantly increased the number of oocytes with a diameter &amp;gt;40 mm (CTRL 17.7% vs LH 36.07%, p &amp;lt; 0,05), suggesting activation of PMFs. Moreover, the hormone increased the expression of mRNA for LHR and KL in the somatic ovarian cells and promoted their proliferation in vitro. The effects of 1IU LH on PD4 females can be summarized as follows: 1. Ovary volume increase (CTRL 0.3 mm3 vs LH 0.36 mm3, p = 0.07), 2. higher percent of PMFs (CTRL 68.227% vs LH 78.29%, p &amp;lt; 0,05) associated with lower percent of primary (CTRL 7.2% vs LH 4.05%, p &amp;lt; 0.04) and growing follicles (CTRL 14.18% vs LH 8.56%, p = 0.1), 3. higher number of granulosa cell layers (&amp;gt; three layers) in secondary follicles (CTRL 42.8% vs LH 54.6%), and 4. lower percent of atretic follicles (CTRL 2.64% vs LH 1.72%, p = 0.1). Similar results were obtained on 28 dpp mice. Morever, we observed that corpora lutea were present only in ovaries of LH-treated females and that all such females were in estrus. Limitations, reasons for caution The study was conducted only in mice. Wider implications of the findings These studies have highlighted new possible roles of LH on follicle classes (primordial/primary) whose development is considered gonadotropin independent. The results, if confirmed in humans, imply that LH might be used as a treatment for patients with ovarian disorders involved the survival/dynamics of the ovarian reserve. Trial registration number NA

O-060 Ovarian rejuvenation - fact or fiction?

Abstract Ovarian aging is a reality and a physiological process which occurs with age resulting in to premature depletion of eggs . POI occurs in approximately 1% of the women who have not reached 40 years of age. The frequency is roughly 4–8% in women experiencing secondary amenorrhea and 10–28% in cases of primary amenorrhea .The prevalence of POI was higher in countries with medium and low human development indexes . . We analysed 1000 infertile patients of less than 40 years . 110 patients had AFC less then 2 and opted for egg donor program . cycle cancellation was due to nonavailability of eggs on OPU was seen in 4% cases in our analysis . Presence of oogonial stem cells (OSCs) in the ovarian cortex , hinting at a possibility of therapeutic stimulation of post-natal folliculogenesis in subfertile women it is postulated that ovarian aging or insufficiency could be reversed if OSCs are provided a healthy environment. Ovarian rejuvenation therapy is a new and innovative approach to enhancing fertility in this group of patients . It is often carried out using platelet-rich plasma (PRP) or stem cell therapy. Ovarian Rejuvenation with Stem cells is also called Autologous Stem Cell Transplant in the Ovary (ASCOT). PRP is having lots of advantages like therapeutic effect, cost effectiveness, ease of isolation and autologous nature. However some drawbacks are also there like inconclusive efficacy and lack of understanding of mechanism of action, lack of RCT /fundamental research . regenerative processes organized by platelet cytokines in somatic cells are poorly understood . PRP infusion may only be an appropriate treatment for select ovarian disorders. perimenopausal women and women deemed to be POR benefitted the most from the treatment, more so than POI and menopausal patients . platelet cytokines are ligands that attach to cell membrane receptors—not the nucleus . no case of tumorogenic activity observed in any clinical context so far . Further reassurance comes from work in other human tissue treated with PRP, where accelerated growth of healthy cells was noted without triggering malignant transformation . 13 registered clinical trials investigating the effect of PRP on ovarian rejuvenation .few of these trials describe the inclusion of appropriate PRP controls. It is only from well-controlled trials, built on detailed mechanistic understanding that we can clarify the platelet-mediated effects of PRP therapy in ovarian rejuvenation and folliculogenesis. The PRP injections into the ovaries are safe, productive, and a natural treatment that may help women with premature ovarian insufficiency to give birth to their own child . Stem cell therapy is attracting attention in the field of regenerative medicine and is advancing rapidly. Many recent studies have applied stem cell therapy to treat reproductive system diseases; however, data are not yet available as to whether this therapy shows enhanced therapeutic effects. It is evident that stem cell therapies have potential in treating POI. Stem cells and their exosomes, including content such as miRNAs, show positive effects in enhancing and restoring various aspects of ovarian function, such as folliculogenesis, the GC apoptosis rate, vascular formation, and genetic stability. Among the 10 clinical trials in the NIH database, only 4 have been completed; the rest are ongoing, recruiting and/or active. Research subjects have been selected by strict standards. Although there are several active ongoing clinical trials for POI using stem cell-based therapeutics, there are restrictions in each country regarding ethical and clinical concerns from the health-care community .Potential of stem cell therapies in treating POI still needs further research and clinical results.

Analysis of determinants of infertility among women at &lt;i&gt;in vitro&lt;/i&gt; fertilization clinic in Surabaya

In social life and global health, infertility is common. History of abdominal surgery, body mass index (BMI), endometriosis, menstrual history, and polycystic ovarian syndrome (PCOS) have not been fully explained as female infertility factors. This study examined infertility causes at ASHA in vitro fertilization Primasatya Husada Citra (PHC) Hospital Surabaya. This quantitative study was cross-sectional. In May-July 2023, 82 childbearing-age women with infertility issues visited the hospital and completed questionnaires. Description and analysis were performed using the Wilcoxon rank test to evaluate menstrual history, BMI, PCOS, endometriosis, and abdominal surgery history in relation to infertility. Infertility was statistically associated with abdominal surgery history (P=0.008), BMI (P=0.000), endometriosis diagnosis (P=0.000), and PCOS (P=0.000). Women with abdominal surgery, endometriosis, and PCOS had significant infertility. Women’s infertility can be caused by ovulation disorders, tubal and pelvic disorders, or uterine disorders, but one-third of cases are unexplained. Infertility treatment may benefit from addressing abdominal surgery history, BMI, endometriosis, and PCOS. Early intervention and targeted care based on these determinants may improve fertility outcomes and reduce unexplained infertility.

Exploring the association of male-factor related infertility with first-trimester anomalies, aneuploidy, and biochemical markers in infertile patients undergoing ART

Background: A higher risk of birth defects in assisted reproductive technologies (ART) pregnancies compared to natural pregnancies has been previously reported. Objective: This retrospective study aimed to explore the association of male-factor related infertility with first-trimester anomalies, aneuploidy, and biochemical markers in infertile patients undergoing ART. Method: The complete medical records of infertile patients referred to the infertility and prenatal centers in Ahvaz, Iran during the past five years were assessed, which included ART-induced pregnancies due to male factors (n=124) and or other infertility causes (n=176). Results: The most common causes of infertility were respectively the male factor (41.3%), ovulation disorders (26%), and unexplained factors (13.3%). A significant correlation was found between the infertility causes and the history underlying systemic diseases and medication history (p&lt;0.05). The serum levels of MoM β‐hCG and PAPP-A were significantly lower in the male factor-related infertilities than non-male factor-related infertilities (p=0.0001). The rate of fetal and placental anomalies was significantly higher in male factor-related infertilities than non-male factor-related infertilities (p=0.03). However, according to the results of multivariable logistic regression, association between the male factor-related infertility and fetal/placental anomalies was not independent of the effects of low levels of MoM β‐hCG and PAPP-A. Conclusion: Causes of infertility, particularly male factor, together with low levels of MoM β‐hCG and PAPP-A, might be associated with the high risk of fetal and placental anomalies in ART pregnancies. However, further large-scale multi-center and prospective investigations are needed to reach more accurate conclusion.

Factors Causing Primary Infertility In Couples Of Reproductive Age: Literature Review

Primary infertility, the inability of couples of reproduvtive age to conceive after 12 months of unprotected sexual intercourse, is a complex health problem with multiple causative factors. This literature review aims to identify and analyze factors associated with primary infertility in couples of reproductive age. The search method was conducted on electronic databases such as PubMed, ScienceDirect, and Google Scholar with the keywords “primary infertility”, “infertility factors”, “reproductive age couples”, and “literature review”. The results of the literature review found that primary infertility can be caused by various factors, both from the man (sperm quality disorders, sexual function, reproductive tract infections, chromosomal abnormalities, varicocele, lifestyle), woman (ovulation disorders, fallopian tubes, endometriosis, uterus, hormonal, lifestyle), and partner (age, lifestyle, environment, stress). These factors can be interrelated and result in primary infertility. It can be concluded that primary infertility is a complex and multifactorial health issue. Understanding these factors is important to help couples achieve pregnancy and improve their quality of life.

Modelling and comparing the use of IVF and ICSI in Australia

PurposeThis study estimates the need of IVF/ICSI in Australia as compared to its actual uptake.MethodsWe created a model estimating for the annual demand for IVF/ICSI in a hypothetical infertile population, using demographic data from medical literature and Australian government databases. For each category of infertility (tubal, severe male, endometriosis, anovulation and unexplained), our estimated need for IVF/ICSI was compared to the actual IVF/ICSI uptake (ANZARD 2019). The model consisted of three categories depending on couples’ cause of infertility, i.e. couples with absolute indications for IVF/ICSI (couples with severe male factor infertility and tubal obstruction); couples with anovulatory infertility (couples with ovulation disorders) and couples with ovulatory infertility (couples suffering from unexplained infertility and endometriosis). The model was applied to each of these categories to determine the number of couples that would require IVF/ICSI treatment after failing to conceive naturally or after following alternative treatment plans. The main outcomes of this study were the estimate of IVF/ICSI cycles and the difference between the estimate and the reported number of IVF/ICSI cycles (2019 ANZARD report).ResultsWe estimated that approximately 35,300 couples required IVF/ICSI treatment in Australia in 2019, while in 2019 according to ANZARD, 46,000 couples underwent IVF/ICSI. A higher uptake of IVF/ICSI cycles than expected was specifically reported in couples with unexplained infertility, ovulation disorders and endometriosis, while for tubal and severe male infertility uptake seemed adequate.ConclusionIn Australia, there seems to be overservicing of IVF/ICSI, specifically for unexplained, ovulatory and endometriosis-related infertility.

Trends in acupuncture for infertility: a scoping review with bibliometric and visual analysis.

Unexplained recurrent implantation failure and the high cost of assisted reproductive techniques for those experiencing infertility have increasingly resulted in the use of acupuncture. However, the trends and research status of acupuncture on infertility resulting in natural conception have not been systematically summarized. This scoping review and knowledge graph analysis aimed to summarize existing clinical studies on acupuncture for infertility that resulted in natural conception. Seven databases, namely, PubMed, Embase, the Cochrane Library, CNKI, VIP, Wanfang Data, and SinoMed, were searched up to August 2023 (updated on 1 April). Two authors independently identified related clinical studies and systematic reviews, and extracted data from included studies on acupuncture for infertility; any discrepancies were resolved by discussion or judged by a third author. A meta-analysis was conducted based on randomized controlled trials (RCTs), and data were synthesized using risk ratios with 95% confidence intervals. Of the 310 articles meeting the inclusion criteria, 274 were primary studies, 7 were systematic reviews, and 29 were case reports. Reported adverse events included mild ovarian irritation and early signs of miscarriage. Out of the 274 primary studies, there were 40 (14.60%) cases of male infertility and 234 (85.40%) cases of female infertility. Current research highlights on acupuncture for infertility focused on female infertility caused by polycystic ovary syndrome, ovulation disorder, and luteinized unruptured follicle syndrome (LUFS), while acupuncture for male infertility was a hotspot in the early research stage. The meta-analysis also suggested that acupuncture was more effective than human chorionic gonadotropin (HCG) [RR = 1.89, 95% CI (1.47, 2.42), 11 RCTs, 662 participants]. Acupuncture combined with HCG was comparable to HCG [RR = 2.33, 95% CI (1.53, 3.55), four RCTs, 259 participants]. Compared with no treatment, acupuncture resulted in a higher pregnancy rate [RR = 22.12, 95% CI (1.39, 353.09), one RCT, 47 participants]. There was no statistical difference between acupuncture combined with HCG plus letrozole and HCG plus letrozole [RR = 1.56, 95% CI (0.84, 2.89), one RCT, 84 participants]. Current research highlights on acupuncture for infertility resulting in natural conception focused on female infertility caused by polycystic ovary syndrome, ovulation disorder, and LUFS, while studies on male infertility and female infertility caused by blockage in the fallopian tube, thin endometrium, and other factors were insufficient. Well-designed confirmatory clinical studies are still needed as the research hypotheses of most studies were unclear.

Oocyte Maturation and miRNAs: Studying a Complicate Interaction to Reveal Possible Biomarkers for Female Infertility.

Cellular metabolism, apoptosis, fertilization, and proliferation of granulosa cells belong to a battery of processes where microRNAs can be detected and associated with infertility. The aim of the present review is to focus on mammalian oocyte maturation events and the association between oocyte growth and miRNA expression. PubMed/Medline, Google Scholar and Scopus databases were searched, and 33 studies were included. Regarding the correlation among miRNA expression and the regulation of granulosa cells and cumulus cells, the most important miRNAs were let-7b, let-7c and miR-21. Additionally, the loss of Dicer, an enzyme involved in miRNA biogenesis, is probably a crucial factor in oogenesis, oocyte maturation and embryogenesis. Furthermore, miRNAs interfere with different cellular mechanisms like apoptosis, steroidogenesis, genome integrity, angiogenesis, antioxidative response and, consequently, oocyte maturation. Hence, it is of major importance to clarify the role and mechanism of each miRNA as understanding its action may develop new tools and establish new diagnostic and treatment approaches for infertility and ovarian disorders.

Etiology and Treatment of Infertility in Tertiary Care Center of Anand, Gujarat, India

This study sought to investigate the etiology and risk factors contributing to infertility, assess the efficacy of fertility-inducing drugs, and analyze the treatment modalities' impact on the quality of life for infertile patients. Spanning a 6-month duration, the research incorporated 50 patients, and risk factors were discerned through a tailored case report form reflecting daily routines and habits. A comparative analysis of Letrozole, Clomiphene citrate, and Metformin was conducted based on existing literature. Predominant causes of female infertility encompassed tubal factors, ovulatory disorders, endometriosis, and unexplained factors. Common risk factors included advanced age, smoking, alcohol consumption, abnormal body weight, and excessive caffeine intake. The study highlighted that while no single risk factor exclusively caused infertility, the presence of multiple factors heightened the likelihood of its development. Clomiphene emerged as the most effective fertility-inducing medication among the three drugs examined. Categories: Obstetrics/Gynecology

Lifestyle changes and Nutrition in Polycystic Ovarian Disorder: A Holistic Review

Polycystic Ovarian Disorder (PCOD) is a prevalent endocrine illness in women of reproductive age which is a reproductive and metabolic disorder. It shows hormonal abnormalities in which there is an excessive production of androgens and that is one of the main causes of infertility, diabetes, irregular menstrual periods, hirsutism, hair loss, obesity and acne. One of the main features of PCOD is the presence of cysts on the ovaries, which can affect their ability to release eggs regularly and Anti-Müllerian hormone (AMH) plays an inhibitory role in follicular development and recruitment, contributing to follicular arrest. AMH inhibitory action on FSH-induced aromatase production likely contributes to hyperandrogenism in PCOD. Some factors which can cause of PCOD such as lack of exercise, skipping breakfast, fast food, unbalanced sleep, obesity, genetic, environmental factors and stress level. Lifestyle and nutrition can affect PCOD development and maintenance in PCOD can be done by lifestyle changes such as diet regulation (in taking of vitamins, antioxidant and Creatine) and exercise, as well as medications to regulate hormones, improve fertility and sleep which play a vital role in PCOD management.

Irisin alleviated the reproductive endocrinal disorders of PCOS mice accompanied by changes in gut microbiota and metabolomic characteristics

IntroductionFolliculogenesis and oligo/anovulation are common pathophysiological characteristics in polycystic ovary syndrome (PCOS) patients, and it is also accompanied by gut microbiota dysbiosis. It is known that physical activity has beneficial effects on improving metabolism and promoting ovulation and menstrual cycle disorder in PCOS patients, and it can also modulate the gastrointestinal microbiota in human beings. However, the mechanism remains vague. Irisin, a novel myokine, plays a positive role in the mediating effects of physical activity.MethodsMice were randomly divided into the control group, PCOS group and PCOS+irisin group. PCOS model was induced by dehydroepiandrosterone (DHEA) and high-fat diet (HFD). The PCOS+irisin group was given irisin 400μg/kg intraperitoneal injection every other day for 21 days. The serum sex hormones were measured by radioimmunoassay. Hematoxylin and Eosin (H&amp;amp;E) Staining and immunohistochemistry (IHC) were conducted on ovarian tissue. The feces microbiota and metabolomic characteristics were collected by 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC–MS).ResultsIn this study, we demonstrated that irisin supplementation alleviated reproductive endocrine disorders of PCOS mice, including estrous cycle disturbance, ovarian polycystic degeneration, and hyperandrogenemia. Irisin also improved the PCOS follicles dysplasia and ovulation disorders, while it had no significant effect on the quality of oocytes. Moreover, irisin could mitigate the decreased bacteria of Odoribacter and the increased bacteria of Eisenbergiella and Dubosiella in PCOS mice model. Moreover, irisin could alleviate the increased fecal metabolites: Methallenestril and PS (22:5(4Z,7Z,10Z,13Z,16Z)/ LTE4).ConclusionThese results suggest that irisin may alleviate the status of PCOS mice model by modulating androgen-induced gut microbiota dysbiosis and fecal metabolites. Hence, our study provided evidence that irisin may be considered as a promising strategy for the treatment of PCOS.

Irregular Cycles, Ovulatory Disorders, and Cardiometabolic Conditions in a US-Based Digital Cohort

Polycystic ovary syndrome (PCOS), characterized by irregular menstrual cycles and hyperandrogenism, is a common ovulatory disorder. Having an irregular cycle is a potential marker for cardiometabolic conditions, but data are limited on whether the associations differ by PCOS status or potential interventions. To evaluate the association of PCOS, time to regularity since menarche (adolescence), and irregular cycles (adulthood) with cardiometabolic conditions. This cross-sectional study used a large, US-based digital cohort of users of the Apple Research application on their iPhone. Eligibility criteria were having ever menstruated, living in the US, being at age of consent of at least 18 years (or 19 years in Alabama and Nebraska or 21 years in Puerto Rico), and being able to communicate in English. Participants were enrolled between November 14, 2019, and December 13, 2022, and completed relevant surveys. Self-reported PCOS diagnosis, prolonged time to regularity (not spontaneously establishing regularity within 5 years of menarche), and irregular cycles. The primary outcome was self-reported cardiometabolic conditions, including obesity, prediabetes, type 1 and 2 diabetes, high cholesterol, hypertension, metabolic syndrome, arrhythmia, congestive heart failure, coronary artery disease, heart attack, heart valve disease, stroke, transient ischemic attack (TIA), deep vein thrombosis, and pulmonary embolism measured using descriptive statistics and logistic regression to estimate prevalence odds ratios (PORs) and 95% CIs. Effect modification by lifestyle factors was also estimated. The study sample (N = 60 789) had a mean (SD) age of 34.5 (11.1) years, with 12.3% having PCOS and 26.3% having prolonged time to regularity. Among a subset of 25 399 participants who completed the hormonal symptoms survey, 25.6% reported irregular cycles. In covariate-adjusted logistic regression models, PCOS was associated with a higher prevalence of all metabolic and several cardiovascular conditions, eg, arrhythmia (POR, 1.37; 95% CI, 1.20-1.55), coronary artery disease (POR, 2.92; 95% CI, 1.95-4.29), heart attack (POR, 1.79; 95% CI, 1.23-2.54), and stroke (POR, 1.66; 95% CI, 1.21-2.24). Among participants without PCOS, prolonged time to regularity was associated with type 2 diabetes (POR, 1.24; 95% CI, 1.05-1.46), hypertension (POR, 1.09; 95% CI, 1.01-1.19), arrhythmia (POR, 1.20; 95% CI, 1.06-1.35), and TIA (POR, 1.33; 95% CI, 1.01-1.73), and having irregular cycles was associated with type 2 diabetes (POR, 1.36; 95% CI, 1.08-1.69), high cholesterol (POR, 1.17; 95% CI, 1.05-1.30), arrhythmia (POR, 1.21; 95% CI, 1.02-1.43), and TIA (POR, 1.56; 95% CI, 1.06-2.26). Some of these associations were modified by high vs low body mass index or low vs high physical activity. These findings suggest that PCOS and irregular cycles may be independent markers for cardiometabolic conditions. Early screening and intervention among individuals with irregular menstrual cycles may be beneficial.