Female Infertility Research Articles

Effect of Letrozole and Clomiphene Citrate versus Letrozole Alone for Ovulation Induction in Women with Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome (PCOS) is a common endocrinopathy characterized by oligo-ovulation or anovulation signs of androgen excess and multiple small ovarian cysts. It is thought to be one of the leading causes of female sub-fertility. It has been estimated that PCOS affects 5-10% of females in reproductive age. In this study, we used combination of letrozole and clomiphene vs letrozole alone in ovulation induction in infertile PCOS women. Objective: The objective of the study was to compare the effectiveness of the combination of letrozole and clomiphene citrate and letrozole alone in ovulation induction in infertile women with PCOS. Methods: Randomized controlled trial conducted in the Department of Reproductive Endocrinology and Infertility, Bangabandhu Sheikh Mujib Medical University, Dhaka, from July 2020 to June 2021. A total of 50 women 18-40 years of age with a diagnosis of infertility and PCOS as defined by the Rotterdam criteria and no other known cause of infertility were included in this study. Participants were randomly assigned into two groups by using a computer-generated random table to either 5 mg letrozole alone or the combination of 2.5 mg letrozole and 50 mg CC daily on cycle days 3-7 for two treatment cycle. Statistical analysis was performed by the SPSS program for Windows, version 22.0. Main outcome measured by number & size of mature follicles, endometrial thickness, day 21 serum progesterone & ovulation rate in both groups. The secondary outcome includes pregnancy rate and complication of both treatment arms. Results: Regarding demographic criteria, there was no significant difference between two groups. In the current study, clinical characteristics, laboratory parameters and cycle characteristics were also comparable to both groups and showed no significant difference. Dominant follicles were found 24(52.2%) in group A (CC+Letrozole) and 29(63.0%) in group B (Letrozole Alone) without any significant difference. Mono follicular development was found 18(75.0%) in group A and 24(82.8%) in group B which was not statistically significant. Endometrial thickness and serum progesterone level at 1st and 2nd cycle were not statistically significant between two groups (p>0.05). Ovulation rate was higher in group B than group A (76.0% vs 72.0%) with absolute difference 4.0 and relative ratio 0.95. Pregnancy rate was also higher in group B than group A (24.0% vs 16.0%) with absolute difference 8.0 and relative ratio 0.67. Ovulation and pregnancy rate were not statistically significant between two groups. Regarding side effects, no significant difference was found between two groups. Conclusion: Although it was not statistically significant, ovulation and pregnancy rate was a little higher in alone letrozole group than combined group. The results of this preliminary study suggested that letrozole may have a better role as a first-line treatment for anovulatory patients with PCOS.

Fertility Preservation in Pediatric Age: Future Perspective among Andrological Diseases.

Male infertility is a condition that has always been less studied and known than female infertility. Male infertility is increasingly present and increasingly diagnosed. Although several causes are known, to date about 40% of the causes are considered idiopathic. The worldwide denasality can only be slowed if awareness campaigns are implemented on all the diseases that can alter fertile potential, especially in young adolescents. Male infertility is, in addition, associated with several medical conditions. In particular, the association between infertility and testicular cancer, cardiovascular disease, autoimmune diseases, and genetic diseases is well known. For this reason, fertility preservation should not be proposed or be only oncological in nature, as there are several diagnosable pediatric pathologies that are associated with altered fertile potential to whose patients we could offer a gamete preservation pathway. In this paper we propose our experience on fertility preservation in pediatric andrological diseases.

The potential influence of follicle diameter on natural cycle in vitro fertilization among women with diminished ovarian reserve: a retrospective cohort study

BackgroundNatural cycle- in vitro fertilization (NC-IVF) is particularly recommended for women with decreased ovarian reserve (DOR) or poor response to controlled ovarian hyperstimulation. In these cases, it can be challenging to determine the optimal timing for a trigger, and follicles of varying sizes are typically obtained. The influence of follicular size on IVF outcomes in women with DOR remains uncertain. This study aims to investigate the association between different follicular sizes and NC-IVF outcomes in women with DOR.MethodsA retrospective cohort study involving 477 NC-IVF cycles from 2015 to 2021 was conducted at one of the largest reproductive medical centers in China. Follicular growth was monitored using transvaginal ultrasonography, and the follicles were categorized into three groups based on their diameters:12–15 mm; 16–17 mm and ≥ 18 mm. Laboratory outcomes were evaluated, including the number of canceled cycles, number of oocytes retrieved, 2PN fertilization, embryo and good-quality embryo, fresh embryo transfers, and frozen embryo. Additionally, clinical outcomes, such as the rates of biochemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth, were investigated and compared among the different follicular size groups.ResultsA total of 68 cycles with follicles sizes of 12-15 mm, 171 cycles with follicles sizes of 16-17 mm, and 236 cycles with follicles sizes ≥ 18 mm were included in this study. The basic characteristics, including female age, male age, infertility duration, infertility type, and parity, were comparable among the groups. The rate of cycle cancellation in the 12–15 mm group (27.9%) was higher compared to the other two groups. The 2PN fertilization rate for follicles with a diameter of 16-17 mm (75.0%) was higher than that of follicles with a diameter of 12-15 mm (61.3%) and ≥ 18 mm (56.6%) (P = 0.031). Other clinical outcomes, such as the number of oocytes retrieved, good-quality embryos, fresh embryo transfers, and frozen embryos, did not show significant differences between groups. Further analysis revealed no significant difference in the rates of clinical pregnancy, ongoing pregnancy, and live birth rate among the three groups.ConclusionsThis study indicates that in women with DOR undergoing NC-IVF, if a premature LH surge occurs and small follicles are retrieved, these follicles can still be used in subsequent treatment and provide a comparable chance of clinical pregnancy to normal-sized follicles. These findings have important implications for guiding NC-IVF treatment in patients with severe DOR.Trial registration numberN/A.

Loss of the adaptor protein Sh3bgrl initiates ovarian fibrosis in zebrafish.

Ovarian fibrosis is a reproduction obstacle leading to female infertility in vertebrates, but the cause underlying the cellular events is unclear. Here, we found that the small adaptor protein SH3-domain-binding glutamate-rich protein like (Sh3bgrl) plays an important role in female reproduction in zebrafish. Two sh3bgrl mutant alleles that result in sh3bgrl depletion contributes to female spawning inability. Comparative transcriptome analysis revealed that sh3bgrl knockout mechanistically causes the upregulation of genes associated with extracellular matrix (ECM) and fiber generation in the zebrafish ovary. Consequently, extra ECM or fibers accumulate and are deposited in the ovary, resulting in eventual spawning inability. Our findings thus provide insights into understanding the underlying mechanism of infertility by ovarian fibrosis and provide a novel and valuable model to study female reproduction abnormality.

HEALTH CARE SEEKING AND INFERTILITY-A CROSS SECTIONAL COMPARATIVE STUDY AMONGST FEMALES OF DYAL VILLAGE LAHORE

Background: Female infertility ends up in long term health implications especially in Pakistan where combined family system and social set-up pressurizes the newly married couple for child bearing. But proper diagnosis and effective management is only possible through health care seeking.
 Objective: To assess the actual magnitude of different types of infertility and its associated health care seeking amongst females of Dyal Village Lahore. Methodology: This cross sectional comparative study was conducted in rural female population of Dyal Village Lahore. The sample size was118 and data collection was done through Simple Random Sampling. Data was gathered using Personal Self-Concept Questionnaire containing information related to socio demographic, economic, female medical, family , gynecological and Health Care seeking history. Results: Out of 118 only 42 (35.59%) had Primary infertility. only 24.58% had Menorrhagia, 40.68% had Oligomenorrhea and 22.88% experienced Dysmenorrhea. Only 7% reported male factor. Majority females had ovulatory problems 38.3 % and 11.8 % with tubal blockage 9.7 % reported uterine problems. Only 68(57.63%) visited hospitals, 67 (56.78%) seeked medical treatment and 48(40.68) had both medical and surgical interventions. Surprisingly 29(24.58%) had received Instrumentation and medication by Dai and 10 (8.47) had medication following relatives advice. Study has also shown a significant relation with higher educational and economical status. Conclusion: The higher Primary infertility levels and trends of seeking health care services other than professional experts especially from Dai is alarming. Future research study can be focused for determining the predictors of such health care services for infertility. Key Words: Infertility, Primary Infertility, Secondary infertility and Health Care Seeking,

Identification of nonfunctional PABPC1L causing oocyte maturation abnormalities and early embryonic arrest in female primary infertility.

Oocyte maturation arrest, fertilization failure, and early embryonic arrest are important causes of female infertility, whereas the genetic events that contribute to these processes are largely unknown. Loss-of-function of PABPC1L in mice has been suggested to cause female infertility involved in the absence of mature oocytes or embryos in vivo or in vitro. However, the role of PABPC1L in human female reproduction remains largely elusive. In this study, we identified a homozygous missense mutation (c.536G>A, p.R179Q) and a compound heterozygous mutation (c.793C>T, p.R265W; c.1201C>T, p.Q401*) in PABPC1L in two unrelated infertile females characterized by recurrent oocyte maturation abnormalities and early embryonic arrest. These variants resulted in nonfunctional PABPC1L protein and were associated with impaired chromatin configuration and transcriptional silencing in GV oocytes. Moreover, the binding capacity of mutant PABPC1L to mRNAs related to oocyte maturation and early embryonic development was decreased significantly. Our findings revealed novel PABPC1L mutations causing oocyte maturation abnormalities and early embryonic arrest, confirming the essential role of PABPC1L in human female fertility.

The association between cervical HPV and female fertility

Objective: Genital human papillomavirus (HPV) infection is the most common sexually transmitted viral infection worldwide with a prevalence of 10-12% in the female population in the reproductive age; few studies addressed the effect of HPV infection on fertility. It is aimed to investigate the presence of HPV infection in infertile women in the present study.
 
 Materials and methods: In this retrospective cross-sectional study; the outpatient infertility clinic records between July 2020 and January 2023, were evaluated. Infertility examination and evaluation were performed following the guidelines. Infertile female individuals and control group’s HPV results were analyzed.
 
 Results: 234 infertile and 340 non-infertile females were included in the study, HPV positivity was found %11.5 for all infertile women. No significant relationship was found between and HPV (p=0.850).
 
 Conclusion: No significant association was found between female infertility and HPV. Still HPV may play a role in infertility with different genotypes. Further studies should include HPV genotypes.

Antifouling and Injectable Granular Hydrogel for the Prevention of Postoperative Intrauterine Adhesion.

Postoperative intrauterine adhesion (IUA), caused by endometrial basal layer injury, is one of the main causes of female infertility. The excessive deposition of fibrin as well as fibroblast is considered the root cause of IUA. However, few clinical strategies are effective in preventing extracellular matrix (ECM) deposition at endometrial wounds that include protein and cell deposits. Herein, the injectable granular poly(N-(2-hydroxyethyl) acrylamide) (PHEAA) hydrogel (granular PHEAA gel), which presents excellent antifouling properties and remarkably prevents protein and cell adhesions, is used to prevent postoperative IUA. The granular PHEAA gel with a jammed network structure exhibits outstanding injectability and superior stability. Compared with the IUA group, the granular PHEAA gel can promote regeneration of the endometrium while reducing the area of endometrial fibrosis. Immunohistochemical staining experiments indicate that the granular PHEAA gel can improve the proliferation of the endometrium, promote vascularization, and enhance anti-inflammatory effect in IUA rats. And the granular PHEAA gel can effectively slow down the fibrosis of uterine tissue. Importantly, the number of embryos is significantly increased after injecting granular PHEAA gel, inferring that there is an obvious reproductive function recovery of injured endometrium.

Mediating effects of DNA methylation in the association between sleep quality and infertility among women of childbearing age

BackgroundThis study aims to investigate the association between sleep quality and infertility among women and to explore the mediating effects of DNA methylation in this association.MethodsThis study is a population-based case–control study. The relationship between sleep quality and infertility was investigated in women with anovulatory infertility (n = 43) and healthy controls (n = 43). Genome-wide DNA methylation was profiled from peripheral blood samples using the Illumina Infinium Human Methylation 850k BeadChip. Differentially methylated CpGs between cases and controls were identified using the ChAMP R package. The mediating effect of DNA methylation between sleep quality and infertility among women was investigated using the Bayesian estimation method provided by the R package “mediation”.ResultsThe survey included 86 women of reproductive age, with 43 participants each in the case and control groups. The average age of the women was 27.6 ± 2.8 years (case group: 27.8 ± 3.0 years, control group: 27.4 ± 2.7 years). A total of 262 differentially methylated CpGs corresponding to 185 genes were identified. Difficulty falling asleep was a risk factor for infertility in women (OR = 3.69, 95%CI = 1.14, 11.99), and a causal mediation effect of DNA methylation CpGs was found. The mediating effect coefficient for cg08298632 was 0.10 (95%CI = 0.01–0.22), and the proportion of the total effect mediated by this methylation site increased to 64.3%.ConclusionThese results suggest that DNA methylation CpGs (cg08298632) play a significant role in the relationship between difficulty falling asleep and infertility in females. These findings contribute to our understanding of the underlying mechanisms that connect difficulty falling asleep and infertility in women. Further studies are necessary to fully understand the biological significance and potential therapeutic applications of these findings. The identified DNA methylation sites provide new and valuable insights and potential targets for future studies aiming to prevent and treat female infertility.

Genetic Insights into Intestinal Microbiota and Risk of Infertility: A Mendelian Randomization Study.

The interaction between intestinal microbiota and infertility is less researched. This study was performed to investigate the causal association between gut microbiota and infertility. In this two-sample Mendelian randomization (MR) study, genetic variants of intestinal microbiota were obtained from the MiBioGen consortium, which included 18,340 individuals. Inverse variance weighting (IVW), MR-Egger, weighted median, maximum likelihood, MR Robust adjusted profile score, MR Pleiotropy residual sum, and outlier (MR-PRESSO) methods were used to explore the causal links between intestinal microbiota and infertility. The MR-Egger intercept term and the global test from the MR-PRESSO estimator were used to assess the horizontal pleiotropy. The Cochran Q test was applied to evaluate the heterogeneity of instrumental variables (IVs). As indicated by the IVW estimator, significantly protective effects of the Family XIII AD3011 group (OR = 0.87) and Ruminococcaceae NK4A214 group (OR = 0.85) were identified for female fertility, while Betaproteobacteria (OR = 1.18), Burkholderiales (OR = 1.18), Candidatus Soleaferrea (OR = 1.12), and Lentisphaerae (OR = 1.11) showed adverse effects on female fertility. Meanwhile, Bacteroidaceae (OR = 0.57), Bacteroides (OR = 0.57), and Ruminococcaceae NK4A214 group (OR = 0.61) revealed protective effects on male fertility, and a causal association between Anaerotruncus (OR = 1.81) and male infertility was detected. The effect sizes and directions remained consistent in the other five methods except for Candidatus Soleaferrea. No heterogeneity or pleiotropy were identified by Cochran's Q test, MR-Egger, and global test (all p > 0.05). This two-sample MR study revealed that genetically proxied intestinal microbiota had potentially causal effects on infertility. In all, the Ruminococcaceae NK4A214 group displayed protective effects against both male and female infertility. Further investigations are needed to establish the biological mechanisms linking gut microbiota and infertility.

Can follicular fluid 8-oxo-2'-deoxyguanosine predict the clinical outcomes in ICSI cycle among couples with normospermia male?

Oxidative stress (OS) occurs when excess free radicals damage the DNA. Moreover, 8-oxo-2'-deoxyguanosine (8-OHdG) is a well-known biomarker for OS linked to cellular damage and gene instability. However, its role in female subfertility has not been properly assessed. We aimed to examine the level of OS represented by 8-OHdG based on the cause of subfertility and to test its correlation with reproductive hormones, intracytoplasmic sperm injection (ICSI) parameters, and outcomes. A cross-sectional study examined 108 subfertile couples with endometriosis, polycystic ovary syndrome (PCOS), tubal factors, and unexplained infertility undergoing ICSI treatment with two different stimulation programs. We included couples whose partners had normal sperm parameters. Levels of follicular fluid (FF) 8-OHdG were correlated with the causes of subfertility and fertilization rates and compared between pregnant and non-pregnant cases. Based on the causes of subfertility, FF 8-OHdG was the highest among endometriosis cases, followed by PCOS cases. Furthermore, FF 8-OHdG was higher in non-pregnant (2.37±0.75 ng/mL) vs. pregnant (1.58±0.39 ng/mL), P<0.001. A two-way analysis of variance showed that only subfertility affected ICSI outcomes, whereas the stimulation program did not. FF 8-OHdG correlated positively with female age and inversely with estradiol and good-quality embryos. The receiver operating characteristic estimated 8-OHdG cutoff value of 1.8 ng/mL predicted clinical pregnancies with 86.7% sensitivity and 74.4% specificity (P<0.001). Higher FF 8-OHdG levels negatively impacted ICSI outcomes. FF 8-OHdG discriminated between cases of clinical pregnancy with good specificity and sensitivity. Because OS can be measured and treated, this opens up a therapeutic and prognostic avenue for improving ICSI outcomes.

Transcriptomic Profiling of Reproductive Age Marmoset Monkey Ovaries.

The decline in ovarian reserve and the aging of the ovaries is a significant concern for women, particularly in the context of delayed reproduction. However, there are ethical limitations and challenges associated with conducting long-term studies to understand and manipulate the mechanisms that regulate ovarian aging in human. The marmoset monkey offers several advantages as a reproductive model, including a shorter gestation period and similar reproductive physiology to that of human. Additionally, they have a relatively long lifespan compared to other mammals, making them suitable for long-term studies. In this study, we focused on analyzing the structural characteristics of the marmoset ovary and studying the mRNA expression of 244 genes associated with ovarian aging. We obtained ovaries from marmosets at three different reproductive stages: pre-pubertal (1.5 months), reproductive (82 months), and menopausal (106 months) ovaries. The structural analyses revealed the presence of numerous mitochondria and lipid droplets in the marmoset ovaries. Many of the genes expressed in the ovaries were involved in multicellular organism development and transcriptional regulation. Additionally, we identified the expression of protein-binding genes. Within the expressed genes, VEGFA and MMP9 were found to be critical for regulating ovarian reserve. An intriguing finding of the study was the strong correlation between genes associated with female infertility and genes related to fibrosis and wound healing. The authors suggest that this correlation might be a result of the repeated rupture and subsequent healing processes occurring in the ovary due to the menstrual cycle, potentially leading to the indirect onset of fibrosis. The expression profile of ovarian aging-related gene set in the marmoset monkey ovaries highlight the need for further studies to explore the relationship between fibrosis, wound healing, and ovarian aging.

Chorionic villi-derived nanofibers enhanced mesenchymal stem cell extracellular vesicle secretion and bioactivity for endometrium regeneration toward intrauterine adhesion treatment

Intrauterine adhesion (IUA) is one of the main causes of female infertility. Extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs), are consisted of a complete lipid bilayer structure, rich in multiple factors and miRNAs related to tissue regeneration, which are the main effective paracrine components of MSCs to treat IUA. However, the poor secretion and bioactivity of EVs leading to the unexpected therapeutic efficacy of MSC-EVs, have been obstacles to their widespread use in clinical practice. Here, we developed human chorionic villi (CV)-derived nanofibers that mimic the tissue-specific ECM microenvironment of CV-derived MSCs, maintain the stemness of MSCs for a long time, and are rich in apolipoproteins, HSP90, ANXA1-A6, etc., which can enhance EV secretion and bioactivity. Then, the CV-nanofiber bionic culture system for mesenchymal stem cells was constructed to achieve large-scale cultivation of MSCs for continuous collection of high-concentration EVs enrichment supernatant. Additionally, EVs obtained by this system were encapsulated with CV-nanofibers to form EVs-ECM aggregate, which can effectively promote endometrium regeneration toward supporting fetal development and live births. Our study provides a new idea for enhancing EV secretion and bioactivity, and a cell-free therapy for treating IUA by EVs, thus promoting the potential of clinical application.

Atypical manifestation of celiac disease in carriers of HLA mutant gene

Annotation. Celiac disease is an autoimmune disease, which is manifested by enteropathy of the small intestine and is caused by the consumption of gluten-containing foods. According to statistics, the number of patients suffering from this disease has increased by 7.5% recently, which may be due to epigenetic factors and improvements in diagnostic methods of gluten intolerance. Human Leukocyte Antigen (HLA) gene plays a major role in the pathophysiological development of celiac disease. The function of HLA is an autoimmune response to endogenous and exogenous proteins. The pathogenesis of organ damage is based on an autoimmune reaction that occurs as a result of the entry of gliadin – the main component of gluten – into the organism. The influence of circulating immune complexes (CIC) leads to the appearance of typical and numerous atypical manifestations of the disease. This, in turn, significantly complicates the diagnosis and prescription of the correct treatment, which can ensure the restoration of the structure of the affected organs and improve the quality of life for patients. Atypical manifestations of gluten enteropathy are diverse, including chronic fatigue syndrome, damage to joints, bones, liver, male and female infertility, thyroid gland dysfunction, dermatitis, and tooth enamel structure disorders. Taking into account the importance of this issue, we conducted a systematic review and analysis of sources related to this question. The search was conducted in the scientometric databases PubMed, Google Scholar, Web of Science, Scopus, mostly over the last three years. In particular, it was found that screening for the specific HLA gene in first-degree relatives of patients with gluten enteropathy allows for an explanation of the exact etiology of possible atypical symptoms - manifestations of celiac disease, and subsequently prescribing a gluten-free diet that leads to the involution of the negative impact of the immune system on target organs. Moreover, this screening will be useful for identifying risk groups because manifestations of celiac disease could be in different ages and have different symptoms.

A heterozygous ZP2 mutation causes zona pellucida defects and female infertility in mouse and human

The zona pellucida (ZP) is an extracellular glycoprotein matrix surrounding mammalian oocytes. Recently, numerous mutations in genes encoding ZP proteins have been shown to be possibly related to oocyte abnormality and female infertility; few reports have confirmed the functions of these mutations in living animal models. Here, we identified a novel heterozygous missense mutation (NM_001376231.1:c.1616C>T, p.Thr539Met) in ZP2 from a primary infertile female. We showed that the mutation reduced ZP2 expression and impeded ZP2 secretion in cell lines. Furthermore, we constructed the mouse model with the mutation (Zp2T541M) using CRISPR-Cas9. Zp2WT/T541M female mice had normal fertility though generated oocytes with the thin ZP, whereas Zp2T541M female mice were completely infertile due to degeneration of oocytes without ZP. Additionally, ZP deletion impaired folliculogenesis and caused female infertility in Zp2T541M mice. Our study not only expands the spectrum of ZP2 mutation sites but also, more importantly, increases the understanding of pathogenic mechanisms of ZP2 mutations.

LncRNA AOC4P impacts the differentiation of macrophages and T-lymphocyte by regulating the NF-κB pathways of KGN cells: Potential pathogenesis of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disease, which is an important cause of female infertility worldwide. PCOS patients are in a state of chronic low-grade inflammation, and immune imbalance is considered as a potential cause of its pathogenesis. The expression of AOC4P in PCOS and normal ovarian granulosa cells (GCs) was detected by real-time quantitative PCR. KGN cells were induced by dihydrotestosterone at 500ng/mL to construct the PCOS model. After lentivirus-infected, KGN cells were constructed with AOC4P overexpression cell lines, the proliferation and apoptosis levels of KGN cells in AOC4P and NC groups were detected. Human monocyte cell line (THP-1)-derived macrophages and peripheral blood mononuclear cells (PBMC) were co-cultured with KGN cells for 48h, respectively, and the differentiation of macrophages and CD4+ T cells were detected by flow cytometry. Decreased AOC4P expression was found in PCOS patients. After constructing the PCOS cell model, we observed that overexpression of AOC4P promoted KGN cell proliferation and inhibited apoptosis. After co-culture with AOC4P overexpressed KGN cells, M1 macrophages decreased, M2 macrophages increased, T helper cells type 1 (Th1)/Th2 ratio increased, and regulatory T cell (Treg) cells increased. Finally, we found that AOC4P inhibited the activation of the nuclear factor κ B (NF-κB) pathway in KGN cells. In this study, we found that AOC4P regulated the NF-κB signaling pathway by inhibiting the phosphorylation of P65, thereby affecting the proliferation and apoptosis of GCs, altering the differentiation of macrophages and T cells, thus contributing to the pathogenesis of PCOS.

Familial Mediterranean fever: perspective on female fertility and disease course in pregnancy from a multicenter nationwide network.

The aim of this study was to analyze the pregnancy process, especially the Familial Mediterranean fever (FMF) disease course and attack types during pregnancy, and to examine the relationship between disease-related factors and female infertility in FMF patients. The study, which was planned in a multicenter national network, included 643 female patients. 435 female patients who had regular sexual intercourse were questioned in terms of infertility. Pregnancy and delivery history, FMF disease severity and course during pregnancy were evaluated. The relationship between demographic and clinical findings, disease severity, genetic analysis results and infertility was investigated. 401 patients had at least 1 pregnancy and 34 patients were diagnosed with infertility. 154 patients had an attack during pregnancy. 61.6% of them reported that attacks during pregnancy were similar to those when they were not pregnant. The most common attack symptoms were fever, fatigue and abdominal pain-peritonitis (96%, 87%, and 83%, respectively) in the pregnancy period. The disease-onset age, disease activity score, gene mutation analyses, and regular colchicine use (> 90%) were similar between the fertile and infertile groups, while the frequency of previous appendectomy and alcohol consumption rates were higher in individuals with infertility. Our results indicated no significant change in the frequency and severity of attacks during pregnancy. The low rate of infertility (7.8%) in our patients was noted. It has been suggested that the risk of FMF-related infertility may not be as high as thought in patients who are followed up regularly and received colchicine.

Depression score mediate the association between a body shape index and infertility in overweight and obesity females, NHANES 2013–2018

BackgroundOverweight and obese females demonstrate a significantly increased risk of anovulatory infertility. This study aims to investigate whether depression score could mediate the association between a body shape index (ABSI) and infertility, especially in overweight and obese population.MethodsWe included 5431 adult female Americans from the National Health and Nutrition Examination Survey (NHANES, 2013–2018) database. ABSI manifested the body shape using waist circumference, weight, and height. Infertility or fertility status was defined by interviewing female participants aged ≥ 18 through the reproductive health questionnaires. Depression symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9) with total scores between 0 and 27. To investigate the association of infertility with ABSI and other individual components, survey-weighted multivariable logistic regression was performed. Mediation analysis of PHQ-9 score was conducted to disentangle the pathways that link ABSI to infertility among the NHANES participants.Results596 (10.97%) females were categorized with having infertility among 5431 participants. Participants with infertility showed higher ABSI and PHQ-9 score, appearing greater population proportion with depression symptoms. In the multivariable logistic regression model, ABSI (adjusted odds ratio = 0.14, 95% CI: 0.04 to 0.50) and PHQ-9 (adjusted odds ratio = 1.04, 95% CI: 1.01 to 1.07) were positively associated with infertility. PHQ-9 score was estimated to mediate 0.2% (P = 0.03) of the link between ABSI and infertility in all individuals, but to mediate 13.5% (P < 0.01) of the ABSI-infertility association in overweight and obese adult females.ConclusionThe association between ABSI and infertility seems to be mediated by depression symptoms scored by PHQ-9, especially in those adult females with overweigh and obesity. Future studies should be implemented to further explore this mediator in ABSI-infertility link.

The Application of Different Lasers in Treatment of Male and Female Infertility: A Review

The Application of Different Lasers in Treatment of Male and Female Infertility: A Review

Kisspeptin decreases the adverse effects of human ovarian vitrification by regulating ROS-related apoptotic occurrences.

Kisspeptin is characterized as a neuropeptide with a pivotal function in female and male infertility, and its antioxidant properties have been demonstrated. In this study, the effects of kisspeptin on the improvement of the vitrification and thawing results of human ovarian tissues were investigated. In this work, 12 ovaries from patients who underwent hysterectomy were collected laparoscopically, and then 32 samples from each of their tissues were taken. Haematoxylin and eosin (H&E) staining was performed to check the normality of the ovarian tissue and, subsequently, the samples were allocated randomly into four groups, including: (1) fresh (control), (2) vitrification, (3) vitrified + 1 μM kisspeptin, and (4) vitrified + 10 μM kisspeptin groups. After vitrification, thawing, and tissue culture processes, H&E staining for tissue quality assessment, terminal deoxynucleotidyl transferase dUTP nick end labelling assay for apoptosis evaluation, and malondialdehyde (MDA), superoxide dismutase (SOD), and ferric reducing ability of plasma tests for oxidative stress appraisal were carried out. Our histological results showed incoherency of ovarian tissue morphology in the vitrification group compared with other groups. Other findings implicated increased apoptosis rate and MDA concentration and reduced SOD activity and total antioxidant capacity (TAC) in the vitrification group compared with the control group (P < 0.05). Moreover, decreased apoptosis rate and MDA concentration, and increased TAC and SOD function were observed in the vitrification with kisspeptin groups (1 μM and 10 μM) compared with the vitrified group (P < 0.05). Our reports express that kisspeptin is an effective agent to overcome the negative effects of vitrification by regulating reactive oxygen species-related apoptotic processes.