Impaired embryo development potential associated with thyroid autoimmunity in euthyroid infertile women with diminished ovarian reserve.

Purpose: The aim of this study was to evaluate the associations of thyroid autoimmunity (TAI) with the number of oocytes retrieved (NOR), fertilization rate (FR), and embryo quality (EQ) in euthyroid women with infertility and diminished ovarian reserve (DOR). Methods: This retrospective cohort study involved 1,172 euthyroid women aged 20-40 years with infertility and DOR who underwent an oocyte retrieval cycle. TAI was diagnosed in the presence of serum thyroperoxidase antibody (TPOAb) concentrations higher than 34 IU/ml and/or serum thyroglobulin antibody (TgAb) concentrations exceeding 115.0 IU/ml. Among these women, 147 patients with TAI were classified as the TAI-positive group, while 1,025 patients without TAI were classified as the TAI-negative group. Using generalized linear models (GLMs) adjusted for confounding factors, we evaluated the associations of TAI and the serum TPOAb and TgAb concentrations and NOR, FR, and EQ in this study's subjects. The TPOAb and TGAb values were subjected to log10 transformation to reduce skewness. Logistic regression models were used to estimate the effects of TPOAb and TgAb concentrations on the probabilities of achieving a high NOR (≥7) and high FR (>60%). Results: For the whole study population, women with TAI had a significantly lower NOR and poorer EQ than women without TAI (P < 0.001 for both). Interestingly, in the TSH ≤2.5 subgroup, the TAI-positive group also had a significantly lower NOR and poorer EQ than the TAI-negative group (P < 0.001 for both). Furthermore, negative associations were observed between log10(TPOAb) concentrations and NOR and the number of high-quality embryos and available embryos (P < 0.05 for all). The log10(TgAb) concentrations were inversely associated with NOR and the number of high-quality embryos (P < 0.05 for all). In the regression analysis, the log10(TPOAb) concentrations had lower probabilities of achieving a high NOR [adjusted odds ratio (aOR): 0.56; 95% confidence interval (95% CI) 0.37, 0.85; P = 0.007]. Conclusions: TAI and higher TPOAb and TgAb concentrations were shown to be associated with reductions in the NOR and EQ in the study population. Our findings provide further evidence to support systematic screening and treatment for TAI in euthyroid women with infertility and DOR.

Fertility issues in women of childbearing age with spondyloarthritis.

The topic of fertility in women with spondyloarthritis (SpA) has been scarcely investigated to date. Recent systematic reviews and registry studies have brought renewed attention to the plight of women of childbearing age with rheumatic diseases, in particular SpA. Fertility may be impacted by physical impairment, hormonal imbalances and psychological distress. Several studies observed a reduction in anti-Müllerian hormone in women with SpA, reflecting a reduced ovarian reserve (OR). Furthermore, disease activity and the use of certain therapies can alter fertility, and this is reflected in a prolonged time-to-pregnancy (TTP), a validated outcome measure that can evaluate the status of subfertility. The employment of glucocorticoids or non-steroidal anti-inflammatory drugs has also been linked to reduced fertility, whereas the use of biologics, especially tumour necrosis factor inhibitors (TNFi), is not associated with a prolonged TTP. In all women of childbearing age with rheumatic diseases, preconception counselling is paramount, and a referral to a reproductive specialist should be considered in the presence of multiple factors that may influence fertility. A comprehensive evaluation involving a multidisciplinary team of rheumatologists, gynaecologists, and often psychologists is warranted. In this narrative review, we collected the currently available literature focusing on fertility issues in women affected by SpA, providing data on fertility outcomes, hormonal imbalance, and therapeutic concerns.

Association between bedtime and female infertility: a secondary analysis from a cross-sectional study.

Objective: To evaluate the association between bedtime and infertility and to identify the optimal bedtime for women of reproductive age. Methods: We conducted a cross-sectional study using data from 3,903 female participants in the National Health and Nutrition Examination Survey (NHANES) from 2015 to 2020. The effect of bedtime on female infertility was assessed using the binary logistic regression in different models, including crude model and adjusted models. To identify the non-linear correlation between bedtime and infertility, generalized additive models (GAM) were utilized. Subgroup analyses were conducted by age, body mass index (BMI), waist circumference, physical activity total time, marital status, smoking status, drinking status and sleep duration. Results: After adjusting for potential confounders (age, race, sleep duration, waist circumference, marital status, education, BMI, smoking status, drinking status and physical activity total time), a non-linear relationship was observed between bedtime and infertility, with the inflection point at 22:45. To the left side of the inflection point, no significant association was detected. However, to the right of it, bedtime was positively related to the infertility (OR: 1.22; 95% CI: 1.06 to 1.39; P = 0.0049). Subgroup analyses showed that late sleepers with higher BMI were more prone to infertility than those with a lower BMI (BMI: 25-30 kg/m2: OR: 1.26; 95% CI: 1.06 to 1.51; P = 0.0136; BMI ≥ 30 kg/m²: OR: 1.21, 95% CI: 1.09 to 1.34; P = 0.0014). Conclusion: Bedtime was non-linearly associated with infertility, which may provide guidance for sleep behavior in women of childbearing age.

Chronic endometritis - a constantly discussed issue in infertile women.

OBJECTIVE: A review of current knowledge on the pathophysiology, diagnostic and treatment options for chronic endometritis in infertile women. METHODS AND RESULTS: One of the major causes of failed in vitro fertilization (IVF) is undiagnosed intrauterine pathologies, including chronic inflammation of the uterine mucosa - chronic endometritis. However, some authors relativize the negative impact of chronic endometritis on reproductive outcomes. The etiopathogenesis of chronic endometritis is due to qualitative and quantitative changes in the endometrial microbiome with abnormal multiplication of microorganisms naturally occurring in the uterine cavity or vagina. There is no uniform consensus on the most common pathogen causing chronic endometritis. It is characterized by infiltration of plasma cells into the endometrial stroma outside the menstrual cycle, accompanied by hyperaemia and endometrial oedema. Clinical symptoms are very mild or absent. The diagnosis of chronic endometritis is often difficult because there is no specific clinical or laboratory diagnostic method. The following investigative options are commonly used for the diagnosis of chronic endometritis: diagnostic hysteroscopy, histopathological examination of the endometrium including CD 138 immunohistochemistry and culture from the uterine cavity. However, standardised international hysteroscopic and histopathological criteria for accurate diagnosis of chronic endometritis are still lacking. Empirically administered antibiotic therapy improves the success rate of pregnancy and delivery of a viable foetus in infertile patients with proven chronic endometritis. In addition to reviewing the current knowledge of chronic endometritis, this article discusses the importance of hysteroscopy in the diagnostic process. CONCLUSION: Chronic endometritis is often a clinically silent disease with negative impact on reproduction in infertile women. Although there are still many unresolved issues, the introduction of hysteroscopy into the diagnostic process is important for clinical practice; however, hysteroscopy even in combination with histological examination of the endometrium, often does not allow an unequivocal diagnosis of chronic endometritis. Further prospective randomised studies in a selected group of women with proven chronic endometritis and repeated failure to implant proven euploid embryos should refine this knowledge.

Associations between cardiovascular health and female infertility: A national population-based study.

OBJECTIVE: This study investigates the relationship between cardiovascular health (CVH), as quantified by the American Heart Association's Life's Essential 8 (LE8) metric, and female infertility, utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2013-2018. METHODS: We encompassed females aged 20-49 years and above from the NHANES in this cross-sectional analysis. We assessed CVH using the LE8 score, encompassing eight domains: dietary pattern, physical activity, nicotine exposure, sleep duration, body mass index (BMI), lipid profile, fasting blood glucose, and blood pressure levels. Logistic regression models were applied to explore the association between CVH scores and reported infertility, adjusting for potential confounders including age, race/ethnicity, and socioeconomic status. RESULTS: Findings revealed a notable inverse association between CVH scores (per 10 scores) and female infertility [OR = 0.93, 95%CI: 0.90-0.96], Participants with higher CVH levels were 41% less likely to had female infertility compared to those with lower levels [OR = 0.59, 95%CI: 0.41-0.84]. Higher overall CVH scores, particularly in physical activity, BMI, and blood glucose, were associated with lower odds of infertility. This trend remained consistent across various demographic subgroups. CONCLUSION: Our findings underscore the significance of maintaining optimal cardiovascular health, as evidenced by higher LE8 scores, in mitigating the risk of female infertility. These insights advocate for the integration of CVH improvement strategies within the broader framework of reproductive health care, emphasizing the dual benefits of cardiovascular and reproductive health optimization.

Effect of oral glucose tolerance test-based insulin resistance on embryo quality in women with/without polycystic ovary syndrome.

Objective: To explore the effects of insulin resistance (IR) on embryo quality and pregnancy outcomes in women with or without polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Methods: A retrospective cohort study concerning patients with/without PCOS who received gonadotropin-releasing hormone (GnRH)-antagonist protocol for IVF/ICSI from January 2019 to July 2022 was conducted. All the patients included underwent oral glucose tolerance test plus the assessment of insulin release within 6 months before the controlled ovarian stimulation. The Matsuda Index was calculated to diagnose IR. Two populations (PCOS and non-PCOS) were included and each was divided into IR and non-IR groups and analyzed respectively. The primary outcome was the high-quality day 3 embryo rate. Results: A total of 895 patients were included (751 with PCOS and 144 without PCOS). For patients with PCOS, the IR group had a lower high-quality day 3 embryo rate (36.8% vs. 39.7%, p=0.005) and available day 3 embryo rate (67.2% vs. 70.6%, p<0.001). For patients without PCOS, there was no significant difference between the IR and non-IR groups in high-quality day 3 embryo rate (p=0.414) and available day 3 embryo rate (p=0.560). There was no significant difference in blastocyst outcomes and pregnancy outcomes for both populations. Conclusion: Based on the diagnosis by the Matsuda Index, IR may adversely affect the day 3 embryo quality in patients with PCOS but not pregnancy outcomes. In women without PCOS, IR alone seems to have less significant adverse effects on embryo quality than in patients with PCOS. Better-designed studies are still needed to compare the differences statistically between PCOS and non-PCOS populations.

The impact of clomiphene citrate on the endometrium in comparison to gonadotropins in intrauterine insemination cycles: is it thinner and does it matter?

Objective: To determine whether endometrial thickness (EMT) differs between i) clomiphene citrate (CC) and gonadotropin (Gn) utilizing patients as their own controls, and ii) patients who conceived with CC and those who did not. Furthermore, to investigate the association between late-follicular EMT and pregnancy outcomes, in CC and Gn cycles. Methods: Retrospective study. Three sets of analyses were conducted separately for the purpose of this study. In analysis 1, we included all cycles from women who initially underwent CC/IUI (CC1, n=1252), followed by Gn/IUI (Gn1, n=1307), to compare EMT differences between CC/IUI and Gn/IUI, utilizing women as their own controls. In analysis 2, we included all CC/IUI cycles (CC2, n=686) from women who eventually conceived with CC during the same study period, to evaluate EMT differences between patients who conceived with CC (CC2) and those who did not (CC1). In analysis 3, pregnancy outcomes among different EMT quartiles were evaluated in CC/IUI and Gn/IUI cycles, separately, to investigate the potential association between EMT and pregnancy outcomes. Results: In analysis 1, when CC1 was compared to Gn1 cycles, EMT was noted to be significantly thinner [Median (IQR): 6.8 (5.5-8.0) vs. 8.3 (7.0-10.0) mm, p<0.001]. Within-patient, CC1 compared to Gn1 EMT was on average 1.7mm thinner. Generalized linear mixed models, adjusted for confounders, revealed similar results (coefficient: 1.69, 95% CI: 1.52-1.85, CC1 as ref.). In analysis 2, CC1 was compared to CC2 EMT, the former being thinner both before [Median (IQR): 6.8 (5.5-8.0) vs. 7.2 (6.0-8.9) mm, p<0.001] and after adjustment (coefficient: 0.59, 95%CI: 0.34-0.85, CC1 as ref.). In analysis 3, clinical pregnancy rates (CPRs) and ongoing pregnancy rates (OPRs) improved as EMT quartiles increased (Q1 to Q4) among CC cycles (p<0.001, p<0.001, respectively), while no such trend was observed among Gn cycles (p=0.94, p=0.68, respectively). Generalized estimating equations models, adjusted for confounders, suggested that EMT was positively associated with CPR and OPR in CC cycles, but not in Gn cycles. Conclusions: Within-patient, CC generally resulted in thinner EMT compared to Gn. Thinner endometrium was associated with decreased OPR in CC cycles, while no such association was detected in Gn cycles.

Psychological, sociocultural, and coping experiences of women with infertility using traditional healthcare services in Harare urban, Zimbabwe: A qualitative study.

This study focused on the psychological, social, and cultural dimensions of infertility among women with infertility in Harare Urban who have utilised traditional healthcare systems to address their infertility problem. It also emphasises their coping strategies for dealing with the challenges encountered along the infertile journey. This was a qualitative study using a phenomenological approach, focusing on the experiences of five women. Data from the interviews was analysed using a simplified version of Hycner's (1985) five-step explication process. The study produced three main themes: psychological experiences, socio-cultural experiences, and coping experiences, along with seven sub-themes. The results showed that women experienced intense distress, sorrow, and self-blame because of their inability to have children, further compounded by the stigma they faced from their families and communities. Women with infertility are subjected to derogatory labels, social contempt, ridicule, and being undervalued, which leads them to develop coping strategies to endure the adverse encounters. These coping mechanisms can have either positive or negative effects on their overall welfare. The exploration of psychological, socio-cultural factors, and coping mechanisms of women with infertility problems' presents a chance to co-create interventions that empower them.

Cette étude s'est concentrée sur les dimensions psychologiques, sociales et culturelles de l'infertilité chez les femmes infertiles de Harare Urban qui ont utilisé les systèmes de santé traditionnels pour résoudre leur problème d'infertilité. Il met également l'accent sur leurs stratégies d'adaptation pour faire face aux défis rencontrés tout au long du parcours stérile. Il s'agissait d'une étude qualitative utilisant une approche phénoménologique, axée sur les expériences de cinq femmes. Les données des entretiens ont été analysées à l'aide d'une version simplifiée du processus d'explication en cinq étapes de Hycner (1985). L'étude a produit trois thèmes principaux : les expériences psychologiques, les expériences socioculturelles et les expériences d'adaptation, ainsi que sept sous-thèmes. Les résultats ont montré que les femmes éprouvaient une détresse, un chagrin et une culpabilité intenses en raison de leur incapacité à avoir des enfants, encore aggravés par la stigmatisation à laquelle elles étaient confrontées de la part de leur famille et de leur communauté. Les femmes infertiles sont soumises à des étiquettes désobligeantes, au mépris social, au ridicule et à la sous-évaluation, ce qui les amène à développer des stratégies d'adaptation pour supporter les rencontres défavorables. Ces mécanismes d'adaptation peuvent avoir des effets positifs ou négatifs sur leur bien-être global. L'exploration des facteurs psychologiques, socioculturels et des mécanismes d'adaptation des femmes souffrant de problèmes d'infertilité présente une opportunité de co-créer des interventions qui les autonomisent.

Analyzing the infertility burden of polycystic ovarian syndrome in China: A comprehensive age-period-cohort analysis with future burden prediction (1990-2030).

OBJECTIVE: Polycystic ovarian syndrome (PCOS) is a common but complex endocrine disorder widely linked to infertility and miscarriage. This study assessed the correlation between PCOS and infertility. METHODS: Using the latest data from the Global Burden of Disease 2019 database, we conducted an in-depth assessment of the disease burden attributed to PCOS in China. This analysis was performed using the joinpoint regression, age-period-cohort, and autoregressive integrated moving average (ARIMA) models. RESULTS: Between 1990-2019, an upward trend was observed in the age-standardized prevalence of PCOS-related female infertility in China. Joinpoint regression analysis revealed an increasing trend in the age-standardized prevalence of PCOS-related female infertility burden indicators as well as the average annual percentage change and annual percentage change across all age groups in China. In terms of the cohort effect, the period rate ratios associated with the age-standardized prevalence of PCOS-related infertility increased steadily over time. The ARIMA model predicted a relatively swift upward trend in the age-standardized prevalence of PCOS-related infertility in China from 2020-2030. CONCLUSION: The age-standardized prevalence of PCOS-related female infertility in China has increased between 1990-2019. The ARIMA model predicted that the age-standardized prevalence of this disease may continue to increase over the next decade. This study can increase the public's attention, improve women's health awareness, and have a certain significance for reducing female infertility related to PCOS.

Iodine and other factors associated with fertility outcome following oil-soluble contrast medium hysterosalpingography: a prospective cohort study.

Objective: To examine factors associated with fertility following hysterosalpingography (HSG) using an oil-soluble contrast medium (OSCM). Design: In a prospective cohort study on 196 women undergoing OSCM HSG, we showed that iodine excess was almost universal (98%) and mild subclinical hypothyroidism was frequent (38%). Here, we report the analyses of secondary outcomes examining factors associated with the likelihood of pregnancy following the HSG. Setting: Auckland, New Zealand (2019-2021). Sample: 196 women with primary or secondary infertility who underwent OSCM HSG. Methods: Baseline and serial urine iodine concentrations (UIC) and thyroid function tests were measured over six months following the HSG. Pregnancy and treatment with levothyroxine during the study period were documented. Results: Following OSCM HSG, pregnancy rates were 49% in women aged <40 years (77/158) but considerably lower (16%) among those ≥40 years (6/38). Similarly, live birth rates were markedly lower in women ≥40 years (17%; 1/6) versus <40 years (73%; 56/77). 29% of participants were iodine deficient at baseline despite advice recommending iodine fortification. Following HSG, the likelihood of pregnancy in women with moderate iodine deficiency was 64% higher than in women with normal iodine levels (p=0.048). Among women aged <40 years who had subclinical hypothyroidism (n=75), levothyroxine treatment was associated with higher pregnancy rates compared to untreated women [63% (26/48) vs 37% (10/27), respectively; p=0.047]. Conclusion: OSCM HSG was associated with higher pregnancy rates in women ≤40 than in those aged >40 years. Iodine deficiency was relatively common in this cohort, and increased iodine levels from OSCM exposure may contribute to the improved fertility observed with this procedure. Trial registration: This study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR: 12620000738921) https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620000738921.

Vitamin D and Lipid Profiles in Infertile PCOS and Non-PCOS Females.

OBJECTIVE: This research is aimed to explore the relationship between vitamin D and lipid profile in females with PCOS and non-PCOS infertile female subjects. STUDY DESIGN: Comparative descriptive study. Place and Duration of the Study: Department of Biological and Biomedical Sciences, The Aga Khan University, Karachi, Pakistan and Jinnah Postgraduate Medical Centre, Karachi, Pakistan in collaboration with the Australian Concept Infertility Medical Centre, from February 2021 to March 2023. METHODOLOGY: A total of 180 infertile women with 120 PCOS and 60 non-PCOS were enrolled. The lipid profile and BMI of the patients were acquired from desk records, and vitamin D was estimated by enzyme-linked immunosorbent assay (ELISA). Participants were classified according to their vitamin D levels as sufficient (30-100 ng/ml), insufficient (20-29 ng/ml), or deficient (below 20 ng/ml). Median, interquartile range, frequency, and percentages were described. Statistical significance was calculated by Mann-Whitney U and Chi-square tests with p-values of 0.05. RESULTS: Females with PCOS had significantly low vitamin D (p <0.001). Total cholesterol, low-density lipoprotein, very low-density lipoprotein, and triglyceride levels were significantly increased, and high-density lipoprotein cholesterol (HDL) was less in comparison to the non-PCOS group (p <0.001). A significant increase in total cholesterol, triglycerides, low-density lipoproteins, and very low-density lipoproteins was found in the vitamin D deficient subgroup compared with insufficient or sufficient groups (p = 0.05). CONCLUSION: The study provides a link between females with PCOS and abnormalities in lipid profile. Decreased vitamin D levels in females with PCOS were linked with an abnormal lipid profile characterised by rise in cholesterol, triglycerides, and low-density lipoproteins which may lead to metabolic abnormalities. KEY WORDS: Vitamin D, Polycystic ovary syndrome, Metabolic syndrome, Body mass index, Lipid profile.

Follicular Fluid and Blood Monitorization of Infertility Biomarkers in Women with Endometriosis.

Infertility is recognized globally as a social disease and a growing medical condition, posing a significant challenge to modern reproductive health. Endometriosis, the third-most frequent gynecologic disorder, is one of the most common and intricate conditions that can lead to female infertility. Despite extensive research, the etiology, malignant transformation, and biological therapy of endometriosis remain unknown. Blood and follicular fluid are two matrices that have been carefully studied and can provide insights into women's health. These matrices are clinically significant because they contain metabolites closely associated with women's illness stage and reproductive outcomes. Nowadays, the application of metabolomic analysis in biological matrices may be able to predict the outcome of assisted reproductive technologies with greater precision. From a molecular viewpoint on reproductive health, we evaluate and compare the utilization of human follicular fluid and blood as matrices in analysis for diagnostic and assisted reproductive technology (ART) predictors of success for endometriosis patients. In the follicular fluid (FF), plasma, and serum of endometriosis-affected women, researchers identified dysregulations of oxidative stress, upregulation of several immune factors, and aberrations in energy metabolic pathways. The altered signatures negatively correlate with the overall oocyte and embryo quality and fertilization rate.

Effects of obesity on clinical outcomes in diminished ovarian reserve patients undergoing intracytoplasmic sperm injection cycles.

The aim of this study is to evaluate the effects of obesity on clinical outcomes in diminished ovarian reserve (DOR) patients undergoing intracytoplasmic sperm injection cycles. In this retrospective observational cross-sectional study, women admitted to current clinic with DOR undergoing intracytoplasmic sperm injection were divided into 2 groups according to the obesity. Patient age, body mass index, anti-mullerian hormone, baseline follicle stimulating hormone and baseline estradiol levels, antral follicle count, total gonadotropin dose, day of stimulation, number of mature (MII) oocytes, and clinical pregnancy were evaluated. There were no statistically significant differences between groups in terms of age, anti-mullerian hormone, baseline follicle stimulating hormone, baseline estradiol levels, antral follicle count, and clinical pregnancy (P > .05). Total gonadotropin dose, the days of ovarian stimulation were higher and number of MII oocyte were less in the obese group (P < .05). Logistic regression analyses also revealed that the days of ovarian stimulation and number of MII oocyte were significant factors in the study group. ROC curve analysis showed obesity is a negatively affecting factor in DOR patients. Obesity causes more gonadotropin dose longer days of stimulation, and less number of MII oocyte. However clinical pregnancy rate is not negatively affected by obesity according to the current study.

Health-related quality of life and its associated factors among infertile women compared with fertile women in public hospital Addis Ababa, Ethiopia: a comparative cross-sectional study.

BACKGROUND: Infertility can have detrimental physical, psychological, and social effects that significantly impact health-related quality of life. Although the impact of infertility on quality of life is well established, there is a lack of research comparing the quality of life between fertile and infertile women in Ethiopia. METHODS: A hospital-based comparative cross-sectional study was conducted among 287 infertile and 301 fertile women. Participants were selected using systematic random sampling. A structured, validated tool was used to collect data. An independent sample t-test was conducted to determine if there was a difference in the study participants' quality of life domains and the mean total quality of life score. Multiple linear regressions were used to correlate quality of life scores with significant predictor factors for the infertile group. RESULTS: Infertile women had a mean total Herbal of 66.54 ± 10.18, and fertile women (72.68 ± 7.57) were found to be statistically different between the groups. All domains except the physical domain were significantly different between the groups. Duration of marriage (ß = -0.529), number of previous sexual partners (ß = -0.410), total number of working hours per day (ß = -0.345), types of infertility (ß = -0.34), and history of the sexually transmitted disease (ß = -0.277), in decreasing order of effect, were found to be associated with the quality of life of infertile women (R2 = 0.725). CONCLUSIONS: The study found that infertile women had a lower mean HRQoL score compared to fertile women, with all domains except for the physical domain being significantly different between the two groups. This suggests that infertility can have a significant impact on various aspects of a woman's life, including her emotional well-being, social functioning, and psychological health. The factors associated with the quality of life of infertile women were the duration of marriage, the number of previous sexual partners, the total number of working hours per day, the types of infertility, and the history of sexually transmitted diseases, with duration of marriage having the strongest association. These findings highlight the need for healthcare providers to address the psychological and social aspects of infertility.

Effect of aromatase inhibitors for preventing ovarian hyperstimulation syndrome in infertile patients undergoing in vitro fertilization: a systematic review and meta-analysis.

PURPOSE: To summarize the findings of relevant randomized controlled trials (RCTs) and conduct a meta-analysis to investigate the potential effect of aromatase inhibitors on preventing moderate to severe ovarian hyperstimulation syndrome (OHSS) in infertile women undergoing in vitro fertilization (IVF). METHODS: We searched for relevant RCTs in electronic databases, including MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov (from inception to August 2023). In addition, we manually searched the related reviews and reference lists of included studies for further relevant studies. We included RCTs where aromatase inhibitors prescribed either during controlled ovarian stimulation (COS) or in early luteal phase. The meta-analysis was performed using RevMan 5.4.1 software. The primary outcome was the incidence of moderate to severe OHSS. A descriptive analysis was conducted in cases where a meta-analysis was not feasible due to heterogeneity or lack of comparable data. RESULTS: 2858 records were retrieved and 12 RCTs were finally included. Letrozole was administered in the treatment group during COS in seven RCTs, whereas in the early luteal phase in five RCTs. Compared with the control group, the risk of moderate to severe OHSS significantly reduced by 55% in the letrozole group (RR 0.45, 95% CI 0.32 to 0.64, I2 = 0%, 5 RCTs, 494 patients). Moreover, serum estradiol (E2) levels on hCG trigger day significantly decreased with the administration of letrozole during COS (MD -847.23, 95% CI -1398.00 to -296.47, I2 = 93%, 5 RCTs, 374 patients). And serum E2 levels on the 4th, 5th and 7th to 10th day after hCG trigger were also significantly lower than those in the control group when letrozole was administered in the early luteal phase. CONCLUSIONS: Patients with high risk of OHSS probably benefit from letrozole, which has been revealed to reduce the incidence of moderate to severe OHSS by this systematic review. However, the very limited number of participants and the quality of the included studies does not allow to recommend letrozole for the prevention of severe OHSS.

Reproductive outcome after in vitro fertilization in endometriosis - key factors and implications.

Endometriosis is a benign chronic disease with a major impact on a woman's quality of life, mainly due to painful physical symptoms. Endometriosis is also a common cause of infertility caused by low ovarian reserve, distorted pelvic anatomy, and severe local inflammation with a direct negative impact on the quality of oocytes, embryos, and endometrium. We conducted a retrospective study between January 2019 and December 2023, including women with a history of surgery for endometriosis who underwent in vitro fertilization (IVF) to achieve pregnancy. Their reproductive outcome was compared with a group of patients with documented tubal obstruction. The aim of our study was to identify the factors associated with a positive impact on the pregnancy rate, specifically age, anti-Mullerian hormone (AMH), ovarian stimulation protocol, and types of gonadotropins used. We analyzed a group of 175 patients with endometriosis compared with 189 patients with tubal obstruction. The average age was similar between the two groups but with a difference in the average AMH value (1.63 ± 1.09 ng/mL vs. 2.55 ± 1.67 ng/mL). The most utilized ovarian stimulation protocol in both groups was the short gonadotropin-releasing hormone (GnRH) antagonist. The clinical pregnancy rate was 27.2% in the endometriosis group and 54.7% in the tubal obstruction group. Our study revealed that treatment with corifollitropin alfa in the endometriosis group was associated with a higher clinical pregnancy rate. AMH and age proved to be significant independent factors for the reproductive outcome.

Assessing vaginal microbiome through Vaginal Microecology Evaluation System as a predictor for in vitro fertilization outcomes: a retrospective study.

Objective: This study aims to evaluate the effectiveness of the Vaginal Microecology Evaluation System (VMES) in assessing the dynamics of the vaginal microbiome (VM) throughout the process of in vitro fertilization and embryo transfer (IVF-ET). Furthermore, it seeks to explore the potential correlation between distinct types of VM ecology and the success rate of IVF-ET. Methods: This study employed VMES to ascertain the composition of the VM. Data were collected from infertile women who underwent their initial IVF-ET treatment for tubal factor between January 2018 and December 2021. A retrospective analysis of pregnancy outcomes resulting from their fresh embryo transfer was conducted to determine the predictive significance of the vaginal microenvironment. Results: We demonstrate that VMES is able to predict IVF-ET outcomes in patients diagnosed with Bacterial Vaginosis (BV). Notably, a discernible shift in the VM was observed in a decent subset of patients following Controlled Ovarian Stimulation (COS), though this phenomenon was not universal across all participants. Specifically, there was a noteworthy increase in the proportion of patients exhibiting BV and uncharacterized dysbiosis subsequent to COS. Furthermore, our investigation revealed a significant correlation between VM and both the live birth rate and early miscarriage rate. Employing a multivariable logistic regression model, we identified that VM status pre-COS, VM status post-COS, patient age, and the number of embryos transferred emerged as independent predictors of the live birth rate. Conclusion: Our study suggests that, during IVF-ET treatment, the VMES can effectively detect changes in the VM, which are strongly correlated with the pregnancy outcome of IVF-ET procedures.

A differential expression of an identical mutation in CYP17A1 gene in two infertility patients: a case report.

BACKGROUND: 17-Hydroxylase deficiency is the rarest form of congenital adrenal hyperplasia, a disorder that affects steroidogenesis, causing abnormal hormone levels. Studies have shown a clear association between 17-hydroxylase deficiency and primary infertility, but a definite protocol to treat the disorder has not been determined yet. CASE PRESENTATION: Case I presents a 24-year-old Caucasian Israeli-Arab female who experienced 6 years of infertility. Before her initial visit to our clinic, she underwent three laparoscopic ovarian cystectomies, had an unsuccessful in vitro fertilization cycle, and was treated with combined oral contraceptives. Her hormonal profile was tested, and the results led to genetic counseling and the diagnosis of non-classical congenital adrenal hyperplasia. She was treated with estradiol, glucocorticoids, and transdermal testosterone. After hormonal levels were lowered, in vitro fertilization cycles were initiated, and the patient had a spontaneous ovulation. In case II, a 20-year-old Caucasian Israeli-Arab female presented for infertility evaluation owing to her oligomenorrhea. Her vitals and physical examination had normal results. The investigation of her abnormal hormonal profile led her to be referred to genetic testing, where the results showed the same genetic mutation as seen in case I. CONCLUSION: Both cases highlight the distinctiveness of the condition, where an identical mutation in the gene responsible for the same enzyme can bring about diverse phenotypes. Case I offers a potential treatment protocol for this rare disorder.

An insight into the vaginal microbiome of infertile women in Bangladesh using metagenomic approach.

Introduction: The dysbiosis of vaginal microbiota is recognized as a potential underlying factor contributing to infertility in women. This study aimed to compare the vaginal microbiomes of infertile and fertile women to investigate their relationship with infertility. Methods: Metagenomic analysis was conducted on samples from 5 infertile and 5 fertile individuals using both amplicon 16S and metagenomics shotgun sequencing methods. Results and discussion: In the infertile group, the bacterial community was primarily represented by three major bacterial genera: Lactobacillus (79.42%), Gardnerella (12.56%) and Prevotella (3.33%), whereas, the fertile group exhibited a more diverse composition with over 8 major bacterial genera, accompanied by significantly reduced abundance of Lactobacillus (48.79%) and Gardnerella (6.98%). At the species level, higher abundances of L. iners, L. gasseri and G. vaginalis were observed in the infertile group. Regarding the microbiome composition, only one fertile and two infertile subjects exhibited the healthiest Community State Types, CST-1, while CST-3 was observed among two infertile and one fertile subject, and CST-4 in three other fertile and one infertile subject. Overall, alpha diversity metrics indicated greater diversity and lower species richness in the control (fertile) group, while the infertile group displayed the opposite trend. However, beta-diversity analysis did not show distinct clustering of samples associated with any specific group; instead, it demonstrated CST-type specific clustering. Shotgun metagenomics further confirmed the dominance of Firmicutes, with a greater abundance of Lactobacillus species in the infertile group. Specifically, L. iners and G. vaginalis were identified as the most dominant and highly abundant in the infertile group. Fungi were only identified in the control group, dominated by Penicillium citrinum (62.5%). Metagenome-assembled genomes (MAGs) corroborated read-based taxonomic profiling, with the taxon L. johnsonii identified exclusively in disease samples. MAG identities shared by both groups include Shamonda orthobunyavirus, L. crispatus, Human endogenous retrovirus K113, L. iners, and G. vaginalis. Interestingly, the healthy microbiomes sequenced in this study contained two clusters, Penicillium and Staphylococcus haemolyticus, not found in the public dataset. In conclusion, this study suggests that lower species diversity with a higher abundance of L. iners, L. gasseri and G. vaginalis, may contribute to female infertility in our study datasets. However, larger sample sizes are necessary to further evaluate such association.