Sex Steroid Receptors in Polycystic Ovary Syndrome and Endometriosis: Insights from Laboratory Studies to Clinical Trials

Polycystic ovary syndrome (PCOS) and endometriosis are reproductive disorders that may cause infertility. The pathology of both diseases has been suggested to be associated with sex steroid hormone receptors, including estrogen receptors (ER), progesterone receptors (PRs) and androgen receptors (ARs). Therefore, with this review, we aim to provide an update on the available knowledge of these receptors and how their interactions contribute to the pathogenesis of PCOS and endometriosis. One of the main PCOS-related medical conditions is abnormal folliculo genesis, which is associated with the downregulation of ER and AR expression in the ovaries. In addition, metabolic disorders in PCOS are caused by dysregulation of sex steroid hormone receptor expression. Furthermore, endometriosis is related to the upregulation of ER and the downregulation of PR expression. These receptors may serve as therapeutic targets for the treatment of PCOS-related disorders and endometriosis, considering their pathophysiological roles. Receptor agonists maybe applied to increase the expression of a specific receptor and treat endometriosis or metabolic disorders. In contrast, receptor antagonist functions to reduce receptor expression and can be used to treat endometriosis and induce ovulation. Understanding PCOS and the pathological roles of endometriosis sex steroid receptors is crucial for developing potential therapeutic strategies to treat infertility in both conditions. Therefore, research should be continued to fill the knowledge gap regarding the subject

The spectrum of in vitro maturation in clinical practice: the current insight

In vitro oocyte maturation (IVM) has been used worldwide. Despite the long-term implementation, the uptake of this procedure to complement current in vitro fertilization (IVF) remains low. The main reason is likely due to the non-synchronization of protocol and definition criteria, leading to difficulty in collective proper outcome data worldwide and, thus, lack of understanding of the exact IVM procedure. The review aims to consolidate the current clinical practice of IVM by dissecting relevant publications to be tailored for a current spectrum of clinical practice. Nevertheless, the background theories of oocyte maturation were also explored to provide a comprehensive understanding of the basis of IVM theories. Additional discussion of other potential uses of IVM in the future, such as in ovarian tissue cryopreservation known as OTO-IVM for fertility preservation and among women with diminished ovarian reserve, was also explored. Otherwise, future collaboration among all IVM centers is paramount for better collection of clinical data to provide valid recommendations for IVM in clinical practice, especially in molecular integrity and possible DNA alteration if present for IVM offspring outcome safety purposes

Effects of Dehydroepiandrosterone (DHEA) Supplementation on Ovarian Cumulus Cells following In Vitro Fertilization (IVF)/Intra-Cytoplasmic Sperm Injection (ICSI) Treatment—A Systematic Review

Despite many studies exploring the effects of DHEA supplementation, its application in IVF procedure continues to be a subject of debate owing to the inconsistent findings and the lack of rigorously designed, large-scale, randomized trials. Our review aims to explore the effectiveness of DHEA supplementation in ovarian cumulus cells following IVF/ICSI treatment. We conducted a literature search of Pub-Med, Ovid MEDLINE, and SCOPUS (inception to June 2022) for all relevant articles, including the keywords of “dehydroepiandrosterone/DHEA”, “oocyte”, and “cumulus cells”. From the preliminary search, 69 publications were identified, and following a thorough screening process, seven studies were ultimately incorporated into the final review. Four hundred twenty-four women were enrolled in these studies, with DHEA supplementation being administered exclusively to women exhibiting poor ovarian response/diminished ovarian reserve or belonging to an older age demographic. The intervention in the studies was DHEA 75–90 mg daily for at least 8–12 weeks. The only randomized controlled trial showed no difference in clinical or cumulus cell-related outcomes between the control and treatment groups. However, the remaining six studies (two cohorts, four case-controls) showed significant beneficial effects of DHEA in cumulus cell-related outcomes compared to the group (older age or POR/DOR) without DHEA supplementation. All studies revealed no significant difference in stimulation and pregnancy outcomes. Our review concludes that DHEA supplementation did show beneficial effect on ovarian cumulus cells in improving oocyte quality for women of advanced age or with poor ovarian responders

Infertility and cortisol: a systematic review

Introduction: Stress and infertility form a complex relationship. In line with this, various stress-related biological markers have been investigated in infertility. Methods: This systematic review was performed using PRISMA guidelines (i) to report whether cortisol is highly present in infertile patients compared to fertile control; (ii) to report whether there is any significant difference in the cortisol level in infertile subjects that conceive and those that didn’t at the end of assisted reproduction treatments. Original articles involving human (male and female) as subjects were extracted from four electronic databases, including the list of references from the published papers. Sixteen original full-length articles involving male (4), female (11), and both genders (1) were included. Results: Findings from studies that compared the cortisol level between infertile and fertile subjects indicate that (i) Male: three studies reported elevated cortisol level in infertile patients and one found no significant difference; (ii) Female: four studies reported increased cortisol level in infertile subjects and three studies found no significant difference. Findings from studies that measured the cortisol level from infertile patients that conceived and those that didn’t indicate that (i) Male: one study reported no significant difference; (ii) Female: one study reported elevated cortisol in infertile patients that conceived, whereas two studies reported increased cortisol in infertile patients that was unable to conceive. Five studies found no significant difference between the groups. Discussion: In the present review we only included the cortisol value that was measured prior to stimulation or IVF treatment or during natural or spontaneous cycles, despite this, there are still variations in the sampling period, assessment techniques and patients’ characteristics. Hence, at present, we are still unable to conclude that cortisol is significantly elevated in infertile patients. We warrant future studies to standardize the time of biological sample collection and other limitations that were addressed in the review to negate the unwanted influencing factors

Data_Sheet_2_Probiotics, a promising therapy to reduce the recurrence of bacterial vaginosis in women? a systematic review and meta-analysis of randomized controlled trials.pdf

IntroductionThe evidence for probiotic efficacy in preventing bacterial vaginosis (BV) recurrences among women aged 18 years and above is sparse. We aimed to ascertain the efficacy of probiotics in preventing BV recurrences after at least one menstrual cycle in this population.MethodsWe conducted a systematic literature search using PubMed, MEDLINE (Ovid interface), Web of Science (WoS), Scopus, Embase, ProQuest Dissertations and Theses Global, Cochrane Library databases and registries comprised of Open Science Framework (OSF) preprints registry, the ClinicalTrials.gov (USA), WHO International Clinical Trials Registry Platform (WHO-ICTRP), International Standard RCT Number (ISRCTN) registry, limited to randomized clinical trials (RCTs) in English published between January 2000 and December 2021. The inclusion criteria were trials that administered probiotics to BV-positive women in an experimental arm of at least 20 samples. The usage of probiotics should be preceded with standard antibiotic regimen and followed by a reassessment of BV status after at least a single menstrual cycle. Risk of bias assessment was completed using revised Cochrane risk-of-bias tool for randomized trials (RoB 2). The PROSPERO registration number of the review is CRD42022302044.ResultsFrom 8,162 identified records, we included 10 studies (n = 1,234 participants) for final analysis; 7 trials compared probiotics vs. placebo, whereas 3 trials compared probiotics vs. metronidazole alone. Using random-effects meta-analysis, probiotics were shown to reduce the risk of BV recurrences by 45% compared to either placebo or metronidazole [14.8 vs. 25.5%, RR: 0.55 (95%CI: 0.33, 0.91), p = 0.03, I2 = 45.4% (95%CI: 0, 73.7%)]. Sensitivity analysis revealed the robustness of results upon removal of studies with high risk of bias [RR: 0.54 (95%CI: 0.38, 0.77), p = 0.006] and reporting bias (RR: 0.53, 95%CI: 0.39, 0.74, p = 0.002). Meta-regression demonstrated that the route of administration (pvaginal = 0.67; poral = 0.44), the total dosage of probiotics (p = 0.17), cumulative days of probiotic administration (p = 0.76), and the number of species in probiotic preparation (p = 0.40) were not linked to BV recurrences.InterpretationProbiotics were associated with more than twofold reduction in BV recurrences when BV status was assessed after at least 1-month postintervention. Further high-quality and methodologically standardized RCTs should evaluate probiotic efficacy for BV prevention in a diverse community setting.Systematic review registration[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021290613], identifier [CRD42021290613].</p

Data_Sheet_4_Probiotics, a promising therapy to reduce the recurrence of bacterial vaginosis in women? a systematic review and meta-analysis of randomized controlled trials.docx

IntroductionThe evidence for probiotic efficacy in preventing bacterial vaginosis (BV) recurrences among women aged 18 years and above is sparse. We aimed to ascertain the efficacy of probiotics in preventing BV recurrences after at least one menstrual cycle in this population.MethodsWe conducted a systematic literature search using PubMed, MEDLINE (Ovid interface), Web of Science (WoS), Scopus, Embase, ProQuest Dissertations and Theses Global, Cochrane Library databases and registries comprised of Open Science Framework (OSF) preprints registry, the ClinicalTrials.gov (USA), WHO International Clinical Trials Registry Platform (WHO-ICTRP), International Standard RCT Number (ISRCTN) registry, limited to randomized clinical trials (RCTs) in English published between January 2000 and December 2021. The inclusion criteria were trials that administered probiotics to BV-positive women in an experimental arm of at least 20 samples. The usage of probiotics should be preceded with standard antibiotic regimen and followed by a reassessment of BV status after at least a single menstrual cycle. Risk of bias assessment was completed using revised Cochrane risk-of-bias tool for randomized trials (RoB 2). The PROSPERO registration number of the review is CRD42022302044.ResultsFrom 8,162 identified records, we included 10 studies (n = 1,234 participants) for final analysis; 7 trials compared probiotics vs. placebo, whereas 3 trials compared probiotics vs. metronidazole alone. Using random-effects meta-analysis, probiotics were shown to reduce the risk of BV recurrences by 45% compared to either placebo or metronidazole [14.8 vs. 25.5%, RR: 0.55 (95%CI: 0.33, 0.91), p = 0.03, I2 = 45.4% (95%CI: 0, 73.7%)]. Sensitivity analysis revealed the robustness of results upon removal of studies with high risk of bias [RR: 0.54 (95%CI: 0.38, 0.77), p = 0.006] and reporting bias (RR: 0.53, 95%CI: 0.39, 0.74, p = 0.002). Meta-regression demonstrated that the route of administration (pvaginal = 0.67; poral = 0.44), the total dosage of probiotics (p = 0.17), cumulative days of probiotic administration (p = 0.76), and the number of species in probiotic preparation (p = 0.40) were not linked to BV recurrences.InterpretationProbiotics were associated with more than twofold reduction in BV recurrences when BV status was assessed after at least 1-month postintervention. Further high-quality and methodologically standardized RCTs should evaluate probiotic efficacy for BV prevention in a diverse community setting.Systematic review registration[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021290613], identifier [CRD42021290613].</p

Data_Sheet_3_Probiotics, a promising therapy to reduce the recurrence of bacterial vaginosis in women? a systematic review and meta-analysis of randomized controlled trials.docx

IntroductionThe evidence for probiotic efficacy in preventing bacterial vaginosis (BV) recurrences among women aged 18 years and above is sparse. We aimed to ascertain the efficacy of probiotics in preventing BV recurrences after at least one menstrual cycle in this population.MethodsWe conducted a systematic literature search using PubMed, MEDLINE (Ovid interface), Web of Science (WoS), Scopus, Embase, ProQuest Dissertations and Theses Global, Cochrane Library databases and registries comprised of Open Science Framework (OSF) preprints registry, the ClinicalTrials.gov (USA), WHO International Clinical Trials Registry Platform (WHO-ICTRP), International Standard RCT Number (ISRCTN) registry, limited to randomized clinical trials (RCTs) in English published between January 2000 and December 2021. The inclusion criteria were trials that administered probiotics to BV-positive women in an experimental arm of at least 20 samples. The usage of probiotics should be preceded with standard antibiotic regimen and followed by a reassessment of BV status after at least a single menstrual cycle. Risk of bias assessment was completed using revised Cochrane risk-of-bias tool for randomized trials (RoB 2). The PROSPERO registration number of the review is CRD42022302044.ResultsFrom 8,162 identified records, we included 10 studies (n = 1,234 participants) for final analysis; 7 trials compared probiotics vs. placebo, whereas 3 trials compared probiotics vs. metronidazole alone. Using random-effects meta-analysis, probiotics were shown to reduce the risk of BV recurrences by 45% compared to either placebo or metronidazole [14.8 vs. 25.5%, RR: 0.55 (95%CI: 0.33, 0.91), p = 0.03, I2 = 45.4% (95%CI: 0, 73.7%)]. Sensitivity analysis revealed the robustness of results upon removal of studies with high risk of bias [RR: 0.54 (95%CI: 0.38, 0.77), p = 0.006] and reporting bias (RR: 0.53, 95%CI: 0.39, 0.74, p = 0.002). Meta-regression demonstrated that the route of administration (pvaginal = 0.67; poral = 0.44), the total dosage of probiotics (p = 0.17), cumulative days of probiotic administration (p = 0.76), and the number of species in probiotic preparation (p = 0.40) were not linked to BV recurrences.InterpretationProbiotics were associated with more than twofold reduction in BV recurrences when BV status was assessed after at least 1-month postintervention. Further high-quality and methodologically standardized RCTs should evaluate probiotic efficacy for BV prevention in a diverse community setting.Systematic review registration[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021290613], identifier [CRD42021290613].</p

Data_Sheet_1_Probiotics, a promising therapy to reduce the recurrence of bacterial vaginosis in women? a systematic review and meta-analysis of randomized controlled trials.docx

IntroductionThe evidence for probiotic efficacy in preventing bacterial vaginosis (BV) recurrences among women aged 18 years and above is sparse. We aimed to ascertain the efficacy of probiotics in preventing BV recurrences after at least one menstrual cycle in this population.MethodsWe conducted a systematic literature search using PubMed, MEDLINE (Ovid interface), Web of Science (WoS), Scopus, Embase, ProQuest Dissertations and Theses Global, Cochrane Library databases and registries comprised of Open Science Framework (OSF) preprints registry, the ClinicalTrials.gov (USA), WHO International Clinical Trials Registry Platform (WHO-ICTRP), International Standard RCT Number (ISRCTN) registry, limited to randomized clinical trials (RCTs) in English published between January 2000 and December 2021. The inclusion criteria were trials that administered probiotics to BV-positive women in an experimental arm of at least 20 samples. The usage of probiotics should be preceded with standard antibiotic regimen and followed by a reassessment of BV status after at least a single menstrual cycle. Risk of bias assessment was completed using revised Cochrane risk-of-bias tool for randomized trials (RoB 2). The PROSPERO registration number of the review is CRD42022302044.ResultsFrom 8,162 identified records, we included 10 studies (n = 1,234 participants) for final analysis; 7 trials compared probiotics vs. placebo, whereas 3 trials compared probiotics vs. metronidazole alone. Using random-effects meta-analysis, probiotics were shown to reduce the risk of BV recurrences by 45% compared to either placebo or metronidazole [14.8 vs. 25.5%, RR: 0.55 (95%CI: 0.33, 0.91), p = 0.03, I2 = 45.4% (95%CI: 0, 73.7%)]. Sensitivity analysis revealed the robustness of results upon removal of studies with high risk of bias [RR: 0.54 (95%CI: 0.38, 0.77), p = 0.006] and reporting bias (RR: 0.53, 95%CI: 0.39, 0.74, p = 0.002). Meta-regression demonstrated that the route of administration (pvaginal = 0.67; poral = 0.44), the total dosage of probiotics (p = 0.17), cumulative days of probiotic administration (p = 0.76), and the number of species in probiotic preparation (p = 0.40) were not linked to BV recurrences.InterpretationProbiotics were associated with more than twofold reduction in BV recurrences when BV status was assessed after at least 1-month postintervention. Further high-quality and methodologically standardized RCTs should evaluate probiotic efficacy for BV prevention in a diverse community setting.Systematic review registration[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021290613], identifier [CRD42021290613].</p

Effect of Acupressure at P6 on Nausea and Vomiting in Women with Hyperemesis Gravidarum: A Randomized Controlled Trial

Hyperemesis gravidarum is characterized by severe nausea and vomiting. This study aims to illustrate the efficacy of acupressure at P6 in treating nausea and vomiting in hyperemesis gravidarum. This parallel randomized controlled trial was conducted from 2016&ndash;2017 in a tertiary hospital. Hospitalized women with &le;16 weeks of gestation and moderate to severe nausea and vomiting classified using a modified PUQE score were randomly assigned in a 1:1 ratio to either apply an acupressure wristband at the P6 point three times daily or to receive regular doses of intravenous antiemetics. The primary outcome was differences in modified PUQE scores among the groups. The secondary outcomes were differences in the rate of urine ketone clearance and the frequency of requiring rescue antiemetics. Ninety women were equally randomized into two groups, with no dropout. There was a statistically significant difference in the degrees of nausea and vomiting between the groups at 8, 16, and 24 hours post-admission (p8hours= 0.001, p16hours = 0.006, and p24hours = 0.001). The requirement of antiemetics and the rate of urine ketone clearance between the two groups were also statistically significant, at p = 0.001 and p = 0.02 respectively. There were no side effects in either group. The P6 acupressure was efficacious in alleviating nausea and vomiting among hyperemesis gravidarum women. The trial was retrospectively registered on ClinicalTrials.gov (NCT05175079)