Female Factor Infertility Research Articles

Donor IUI is equally effective for heterosexual couples, single women and lesbians, but autologous IUI does worse.

Are there differences in the clinical outcomes of IUI among different populational groups (heterosexual couples, single women and lesbian couples)? The outcome of donor IUI (D-IUI) is similar in all populational groups and better than that seen with autologous insemination. A vast body of literature on clinical outcome is available for counselling heterosexual couples regarding decisions related to ART. The reproductive potential of single women, lesbian couples and heterosexual couples who need donor semen is assumed to be better, but there is a scarcity of data on their ART performance to actually confirm it. In this retrospective multicentric cohort study, a total of 7228 IUI treatment cycles performed in 3807 patients between January 2013 and December 2016 in 13 private clinics belonging to the same reproductive medicine group in Spain were included. Patients with previous IUI attempts were excluded from the study. Only 1.9% of cycles were lost to follow-up. A total of 5318 D-IUI cycles were performed in three different populational groups: heterosexual couples (D-HC, 1167cycles), single women (SW, 2839cycles) and lesbian couples (LC, 1312), while a total of 1910 autologous IUI cycles were performed in heterosexual couples (A-HC). This last one was considered the control group and was composed of cycles performed in couples with a male partner with sperm parameters equivalent to those requested from donors. In order to identify factors with an impact on clinical outcome, a multivariate logistic regression analysis was performed. Regarding live birth rate (LBR), mixed effect models were employed to control for the fact that different patients were submitted to different numbers of treatments. Parameters that were significant to the primary outcome (LBR) according to the multivariate analysis were the populational group (D-HC, SW, LC and A-HC) to which the patient belonged, female age and a diagnosis of low ovarian reserve. At the age range of good prognosis (≤37years), LBR was similar in all groups that underwent D-IUI (18.8% for D-HC, 16.5% for SW and 17.6% for LC) but was significantly lower in the autologous IUI (A-HC) group (11%). For all these significant findings, the strength of the association was confirmed by P values <0.001. From 38years of age on, no significant differences were observed among the populational groups studied, and for all of them, LBR was below 7% from 40years of age on. To the best of our knowledge, a smoking habit was the only known factor with a potential effect on ART outcome that could not be controlled for, due to the unavailability of this information in a significant percentage of the clinical files studied. Our study was not capable of precisely quantifying the impact of a diagnosis of low ovarian reserve on the LBR of both IUI and D-IUI, due to the number of cycles performed in patients with such diagnosis (n= 231, 3.2% of the total). For the first time, a comparison among D-HC, SW, LC and A-HC was performed in a study with a robust sample size and controlling for potential sources of bias. There is now sound evidence that equivalent clinical outcome is seen in the three groups treated with donor semen (D-HC, SW and LC). Specifically, regarding the comparison between SW and LC, our findings rule out differences in LBR proposed by previous publications, with very similar clinical outcomes within the same age ranges. At age ranges of good prognosis (≤37years), reproductive performance of D-IUI is significantly better than that seen in heterosexual couples undergoing autologous IUI, even when only cases of optimal sperm quality are considered in this last group. This finding is in agreement with the concept that, as a group, A-HC are more prone to have female factor infertility, even when their infertility assessment finds no contraindication to IUI. Age affects all these groups equally, with none of them reaching a 7% LBR after the age of 40years. Our findings will be useful for the counselling of patients from the different populations studied here about ART strategies. None.

Risk of hospitalization for early onset of cardiovascular disease among infertile women: a register-based cohort study.

Is female infertility predictive of a woman's future risk of early cardiovascular disease (CVD)? Female infertility does not seem to be predictive of early CVD during a mean follow-up of 9 years. Associations between infertility and comorbidity have been found in several studies, but data on the association between female infertility and risk of CVD are scarce and inconclusive. In this nationwide cohort study, we included 87 221 women registered in the Danish National IVF register, undergoing medically assisted reproduction (MAR) between 1st of January 1994 and 31st of December 2015. The cohort was followed for incident hospitalization due to CVD in the Danish National Patient Register from enrollment to 31 December 2015. Women with a history of CVD prior to enrollment were excluded. Cox proportional hazard models with age as the underlying time scale were used to estimate hazard ratios (HR) with 95% CI of CVD among women with an infertility diagnosis, compared to women without an infertility diagnosis. All analyses were adjusted for educational attainment. Female infertility and the reason for infertility was diagnosed and registered in the IVF register by specialists in Danish public and private fertility clinics since 1st of January 1994. In our cohort, 53 806 women (61.7%) were diagnosed with female factor infertility, while 33 415 (38.3%) did not have a female factor infertility diagnosis and made up the reference group. A total of 686 (1.3%) infertile women were hospitalized for CVD compared to 250 (0.7%) among women without an infertility diagnosis during a mean follow-up time of 9 years. We found no increased risk of early CVD in our analyses (adjusted HR 0.98, 95% CI: 0.85;1.14). Likewise, analyses stratified by specific infertility diagnosis, showed no risk difference. We were unable to adjust for confounding parameters such as body mass index, cigarette smoking or alcohol consumption. These results may not be generalizable to infertile women who do not seek out fertility treatment, or infertile women with other lifestyle characteristics than Danish women. Diagnosing female infertility or the time of MAR does not seem to be a window of opportunity where early screening for cardiovascular disease risk factors can have a prophylactic potential. This study is part of the ReproUnion collaborative study, co-financed by the European Union, Interreg V ÖKS. None of the authors declare any conflict of interest.

Assisted reproductive technology treatment and risk of ovarian cancer-a nationwide population-based cohort study.

Does hormone stimulation during assisted reproductive technology (ART) treatment increase the risk of ovarian cancer? No increased risk of ovarian cancer was found among ART-treated women, with the exception of ART-treated women with endometriosis. Previous studies on the association between ovarian stimulation during ART and ovarian cancer have shown conflicting results. The risk of ovarian cancer varies according to the cause of infertility, and only a few studies on ART treatment and risk of ovarian cancer have had sufficient data to address this issue. Endometriosis has been linked to an increased risk of ovarian cancer. Women undergoing ART treatment during 1994-2015 were registered in the Danish IVF register. Data were linked with data from the Danish Cancer Register and socio-demographic population registers using an individual person identification number assigned to people residing in Denmark. All women undergoing ART treatment were age-matched with a random sample of the female background population and followed for up to 22years. After relevant exclusions, the population consisted of 58 472 ART-treated women and 625 330 untreated women, all with no previous malignancies. Ovarian cancer risk was assessed using multivariable cox regression analyses with adjustment for educational level, marital status, parity and treatment year. Results are shown as hazard ratios (HRs) with corresponding CIs. In total, 393 (0.06%) women were diagnosed with ovarian cancer during follow-up (mean 9.7years). Women treated with ART had an increased risk of ovarian cancer (HR 1.20, 95% CI 1.10-1.31), which diminished over time. The increased risk was apparent among women with female factor infertility (HR 1.36, 95% CI 1.25-1.48), whereas no female factor infertility was associated with a lower risk (HR 0.87, 95% CI 0.76-1.00). The risk was increased among women with endometriosis (HR 3.78, 95% CI 2.45-5.84), whereas no increased risk was found among ART-treated women with polycystic ovary syndrome, other female causes of infertility and unexplained infertility. The association between ART treatment and ovarian cancer is likely influenced by increased detection due to multiple ultrasound scans during ART treatment. Undergoing ART treatment without the presence of endometriosis was not associated with an increased risk of ovarian cancer, which is reassuring. Whether ART treatment increases the risk of ovarian cancer among women with endometriosis needs further investigation. This work was supported by a PhD grant to D.V. from the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Funding for establishing the Danish National ART-couple II cohort was achieved from Ebba Rosa Hansen Foundation. The funders had no influence on data collection, analyses or results presented. The authors have no conflicts of interest to declare.

Laparoscopic Evaluation of Female Factor in Bangladeshi Infertile Couple

Background: Infertility prevails in good number in our society, causing social disharmony and distress. Laparoscopy is now a very effective tool for diagnosis and evaluation of female infertility.&#x0D; Method: This cross sectional study was conducted in Infertility Unit of Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM) General Hospital, from July, 2012 to June 2014. The aim of the study is to identify common pelvic pathologies of female factor infertility by laparoscopy so that early detection and treatment modalities can be instituted. Total 230 sub fertile patients attending OPD were selected for this study. Patients with DM, HTN, known case of hypothyroidism and male factor infertility was excluded from study. Detailed clinical history of every patient was recorded on a pre-set questionnaire and physical examination was performed. Laparoscopy was scheduled in proliferative phase of menstrual cycle.&#x0D; Results: Among the study subjects, 130 (56.5%) had primary infertility while 100 (43.5%) secondary infertility. On laparoscopy, 64.4% patient had normal sized uterus, 31 % had bulky uterus. Two patients had bicornuate uterus in secondary infertility cases. Uterus was restricted in mobility in 41% of patients due to endometriosis, pelvic inflammatory disease (PID) or previous pelvic surgery. Fibroid uterus was detected in 30(13%) and 10(4.3%) cases of primary and secondary infertility cases respectively. Bilateral tubal blockage was present in 16(6.9%) and 17 (7.4%) cases of primary and secondary infertility respectively. Forty (17.4%) cases of primary infertility were detected as polycystic ovaries (PCO) which was 30(13%) in cases of secondary infertility. Endometriosis was found in total 9(3.9%) patient in both the groups. Pelvic adhesion was found in 22(9.5%) and 21 (9.1%) cases of primary and secondary infertility respectively.&#x0D; Conclusion: Laparoscopy could diagnose a substantial number of portion pelvic pathology. In a developing country like Bangladesh, earlier and justified intervention with laparoscopy can save time and expense of infertility treatment by diagnosing pelvic factor responsible for infertility.&#x0D; Bangladesh J Obstet Gynaecol, 2018; Vol. 33(1) : 29-35

Female Factors related with Infertility and Their Pregnancy Outcome after Intrauterine Insemination: Experience of 790 Cases in Bangladesh

Background: Several female factors are related with the cause of infertility.&#x0D; Objectives: The purpose of the present study was to assess female factors related with infertility and their pregnancy outcome after intrauterine insemination.&#x0D; Methodology: This prospective cohort study was carried out at a private infertility centre (Central Hospital Limited, Dhaka) in Dhaka city of Bangladesh from January 2012 to December 2017 for a period of 6 years. Infertile couples who already had undergone natural cycles of super-ovulation for six months or whose duration of infertility was more than one year were included. Infertile women were evaluated and the causes of infertility were assessed. The follow up was performed to see the pregnancy outcome.&#x0D; Result: A total number of 790 women were recruited. The mean age with standard deviation of study population was 28.94±5.386 years. Among 790 infertile women 12 women were become pregnant after IUI. Among these 12 women female factors of infertility was present in 8(66.7%) cases and the rest 4(33.3%) cases were absent. However, 778 women could not pregnant after IUI and among these 277(35.6%) cases had the presence of female factors and the rest 501(64.4%) cases had absence of female infertility causes. The presence of female factor had 3.62 (95% CI 1.08-12.12) times more risk to become pregnant among the infertile women after IUI (p=0.026). Among 790 infertile women 285(36.1%) women had presence of female infertility factors.&#x0D; Conclusion: In conclusion female factors are significantly related with infertility and their pregnancy outcome after intrauterine insemination.&#x0D; Journal of Current and Advance Medical Research 2019;6(2):87-91

Cognitive Behavior Therapy in Management of Psychosocial Factors in Female Infertility

Cognitive Behavior Therapy in Management of Psychosocial Factors in Female Infertility

Exposure to Fine Particulate Matter and Ovarian Reserve Among Women from a Fertility Clinic.

An increasing number of studies have linked air pollution to decreased fertility. Whether this is due to an effect on ovarian reserve is unknown. Our study included 632 women attending the Massachusetts General Hospital Fertility Center (2004-2015) who had a measured antral follicle count. Validated spatiotemporal models estimated daily particulate matter <2.5 µg/m (PM2.5) (based on residential address) for the 3 months before the antral follicle count. We analyzed associations with Poisson regression. Every 2 µg/m increase in estimated PM2.5 exposure was associated with a -7.2% (95% confidence interval = -10.4%, -3.8%) lower antral follicle count adjusting for age, body mass index, smoking status, and year and season of the count. The association of PM2.5 with antral follicle count was stronger among women with female factor infertility (-16.3% per 2 µg/m). Among women from an infertility clinic, higher PM2.5 exposure was associated with lower ovarian reserve, raising concern that air pollution may accelerate reproductive aging.

Ulmus minor bark hydro-alcoholic extract ameliorates histological parameters and testosterone level in an experimental model of PCOS rats.

Polycystic ovary syndrome (PCOS) is a common and multifactorial disease associated with female factor infertility. Ulmus minor bark (UMB) is one of the medicinal plants used in Persian folklore as a fertility enhancer. In the current study, we aimed to elucidate the effect of UMB hydro-alcoholic extract on histological parameters and testosterone condition in an experimental model of PCOS rats. Thirty female rats were randomly divided into five groups: (1) control, (2) vehicle, (3) PCOS/50 mg [6 mg/kg dehydroepiandrosterone (DHEA) + 50 mg/kg UMB hydro-alcoholic extract], (4) PCOS/150 mg (6 mg/kg DHEA + 150 mg/kg UMB hydro-alcoholic extract), and (5) PCOS (6 mg/kg DHEA). All interventions were performed for 21 days. Afterwards, stereological analysis was done for determination of ovarian volume and follicle number. The serum level of testosterone was measured by ELISA kit. UMB hydro-alcoholic extract improved the total number of the corpus luteum in the treatment groups when compared to the PCOS group (p<0.05). PCOS/150 mg and PCOS/50 mg groups showed significantly lower total number of the primordial, primary, and secondary follicles as well as testosterone level compared to the PCOS group (p<0.05). The total number of antral follicles and volume of ovary did not differ significantly between groups. UMB extract may be an effective and good alternative in improving PCOS histo-logical and testosterone disturbances although further studies are warranted to confirm the safety of UMB plant in human.

Testosterone levels after treatment with urofollitropin in infertile patients with idiopathic mild reduction of testicular volume.

A reduction of testicular volume (TV) represents an important clinical sign, which may hide sperm abnormalities and predispose to hypogonadism. The primary purpose of this study was to evaluate the serum levels of total testosterone after treatment with urofollitropin in selected patients with male infertility and idiopathic mild reduction of testicular volume. In this 1-year-long prospective design, patients with abnormal sperm parameters, mild reduction in TV (8-12 mL) and normal gonadotropin, and total testosterone (TT) serum levels were recruited in this study. Patients treated for 4 months with urofollitropin were included in group A, those treated with intracytoplasmatic sperm injection due to a female-factor infertility were included in group B. Hormone values, sperm parameters, and TV were detected at baseline (T0), after 4 (T1) and 12 months (T2) in group A and at T0 and T2 in group B. Group A (n = 80) showed increased follicle-stimulating hormone (FSH) at T1 and sperm morphology at T1 and T2 compared to T0 (all p < 0.05). Group B (n = 50) had lower TT and higher FSH levels at T2 compared to T0 (all p < 0.05). At T2, TT, VT, total sperm count, progressive motility, total motility, and sperm morphology were higher in group A compared to group B (all p < 0.05). Reduced TV may predispose to infertility and hypogonadism. FSH treatment may improve Sertoli and Leydig cell function and prevent the development of hypogonadism.

The association of female and male infertility with telomere length (Review).

Telomere length (TL) has long been associated with aging, as telomeres serve as protective caps of chromosomes, and are thus deeply involved in the preservation of genome integrity and are vital to cellular functions. Traditionally, a strong link connects aging and infertility in both sexes, with an earlier onset in females. Over the past decade, telomeres have attracted increasing attention due to the role they play in fertility. In this review, we investigated the potential positive or negative association between relative TL and different factors of female and male infertility. A systematic search of the PubMed database was conducted. Out of the 206 studies identified, 45 were reviewed as they fulfilled the criteria of validity and relevance. Following an analysis and a comparison of the study outcomes, several clear trends were observed. The majority of female infertility factors were associated with a shorter TL, with the exception of endometriosis, premature ovarian failure and clear cell carcinoma that were associated with a longer TL and polycystic ovary syndrome (PCOS), which revealed conflicting results among several studies, leading to ambiguous conclusions. Male infertility factors were associated with a shorter TL. Although this review can provide an outline of general trends in the association of TL with infertility factors, further epidemiological and original research studies are required to focus on investigating the basis of these varying lengths of telomeres.

Risk of preterm delivery in singletons conceived by in vitro fertilization

To evaluate the preterm delivery and other obstetrics complications similar in singleton pregnancies achieved through IVF compared to spontaneous pregnancies. Retrospective case-control study included 1663 women with singleton pregnancies following IVF-ICSI (study group) and 3326 women with singleton spontaneous pregnancies (control group) who delivered between January 2015 and January 2018 at the Peking University Third Hospital. The control group matched 1:2 by age, BMI, parity, and gravidity. Maternal outcomes included preterm delivery and complications. There was significantly higher incidence of gestational diabetes, hypertensive disorders, and placenta previa in IVF-ICSI pregnancies versus controls (p < .05). IVF-ICSI resulted in significantly higher rate of preterm birth than in spontaneous pregnancies (p < .05) and the difference remained significant for deliveries that occurred before 28, 32, and 34 weeks gestation (p < .05). Multivariate logistic regression analysis revealed that female-factor infertility, hypertensive disorder, placenta previa, and PROM were significant prognostic factors associated with increased risk of prematurity. IVF-ICSI is associated with increased risk of obstetric complications including preterm delivery in singleton pregnancies. Female-factor infertility is an independent prognostic factor for preterm birth. This information is important for patient counseling and helps to refine the recommendation to optimize maternal health before embarking on fertility treatments.

The transgenerational effects of oocyte mitochondrial supplementation

Many women suffer from either failed fertilisation or their embryos arrest early during development. Autologous mitochondrial supplementation has been proposed as an assisted reproductive technology to overcome these problems. However, its safety remains to be tested in an animal model to determine if there are transgenerational effects. We have supplemented oocytes with autologous populations of mitochondria to generate founders. We mated the female founders and their offspring to produce three generations. We assessed litter size, the ovarian reserve, and weight gain and conducted a full histopathological analysis from each of the three generations. Across the generations, we observed significant increases in litter size and in the number of primordial follicles in the ovary matched by changes in global gene expression patterns for these early-stage oocytes. However, full histopathological analysis revealed that cardiac structure was compromised in first and second generation offspring, which could seriously affect the health of the offspring. Furthermore, the offspring were prone to increased weight gain during early life. Mitochondrial supplementation appears to perturb the regulation of the chromosomal genome resulting in transgenerational phenotypic gains and losses. These data highlight the need for caution when using autologous mitochondrial supplementation to treat female factor infertility.

PO-01-080 Intracytoplasmic Sperm Injection (ICSI) Outcome Using Cryopreserved Testicular Sperm from Non-Obstructive Azoospermic Infertile Men with Varicocele

To study the outcome of ICSI using cryopreserved testicular sperm from infertile men with varicocele-associated non-obstructive azoospermia (NOA). The study included 40 infertile men with NOA who underwent ICSI with cryopreserved testicular sperm. Twenty two patients had clinically palpable varicocele (group 1) and 18 had no detectable abnormality in their genital examination (group2). Diagnosis of varicocele was confirmed by scrotal color Doppler ultrasound. Diagnosis of azoospermia was confirmed by repeated absence of sperms in centrifuged semen pellets. Men with abnormal hormonal profiles, genetic abnormalities or genitourinary anomalies suggestive of obstructive pathology were excluded. Couples with known female factor infertility were excluded. ICSI was done using mature MII oocytes with good morphology. The pronuclear formation was assessed at 17 ± 1 hours following injection. Embryo quality was assessed on day 3 (67 ± 2 hours) and day 5. Positive clinical pregnancy was considered upon finding of gestational sac(s) and fetal pulsation by trans-vaginal US, 15 days after BHCG assessment. Results were presented as mean ± standard deviation (SD) for continuous variables and frequency and percentage (%) for categorical variables. P-value <0.05 was significant.

Compromised global embryonic transcriptome associated with advanced maternal age

PurposeTo investigate the global transcriptome and associated embryonic molecular networks impacted with advanced maternal age (AMA).MethodsBlastocysts derived from donor oocyte IVF cycles with no male factor infertility (< 30 years of age) and AMA blastocysts (≥ 42 years) with no other significant female factor infertility or male factor infertility were collected with informed patient consent. RNA sequencing libraries were prepared using the SMARTer® Ultra® Low Kit (Clontech Laboratories) and sequenced on the Illumina HiSEQ 4000. Bioinformatics included Ingenuity® Pathway Analysis (Qiagen) with ViiA™ 7 qPCR utilized for gene expression validation (Applied Biosystems).ResultsA total of 2688 significant differentially expressed transcripts were identified to distinguish the AMA blastocysts from young, donor controls. 2551 (95%) of these displayed decreased transcription in the blastocysts from older women. Pathway analysis revealed three altered molecular signaling networks known to be critical for embryo and fetal development: CREBBP, ESR1, and SP1. Validation of genes within these networks confirmed the global decreased transcription observed in AMA blastocysts (P < 0.05).ConclusionsA significant, overall decreased global transcriptome was observed in blastocysts from AMA women. The ESR1/SP1/CREBBP pathway, in particular, was found to be a highly significant upstream regulator impacting biological processes that are vital during embryonic patterning and pre-implantation development. These results provide evidence that AMA embryos are compromised on a cell signaling level which can repress the embryo’s ability to proliferate and implant, contributing to a deterioration of reproductive outcomes.

Omega-3 and vitamin E co-supplementation can improve antioxidant markers in obese/overweight women with polycystic ovary syndrome.

Background: Polycystic ovary syndrome is one of the most important factors in female infertility. Oxidative stress is likely to contribute to increased insulin and androgen production in the ovaries, as well as probably impairing follicle production. Aims: This study aims to determine the complementary effects of omega-3 and vitamin E supplements on certain oxidative stress indices in obese and overweight women with polycystic ovary syndrome. Materials and Methods: This double-blind, randomized clinical trial was performed on polycystic ovary syndrome subjects with BMI>25. Patients were randomly allocated into two groups to receive either 2g of omega-3 plus 400IU of vitamin E, or a placebo, for 8 weeks. At the beginning and the end of the study, total antioxidant capacity, glutathione levels, catalase activity, malondialdehyde concentrations, as well as dietary intake and physical activity were evaluated. Statistical analysis was performed using SPSS. Results: 32 patients in the intervention group and 30 patients in the placebo group completed the study. Co-supplementation of omega-3 and vitamin E significantly increased total antioxidant capacity (mg/dl) (1.15±0.93 vs -0.6±0.72; P<0.001), catalase activity (IU/L) (1.19±1.06 vs 0.12±0.36; P<0.001) and glutathione levels (μmol/L) (1.5±1.06 vs 0.23±1.43; P=0.028). Additionally, a significant reduction of malondialdehyde levels (nmol/L) (-0.34±0.32 vs 0.57±2.20; P=0.008) was observed, in comparison with placebo. Conclusion: Co-supplementation with omega-3 and vitamin E had beneficial effect on total antioxidant capacity, malondialdehyde concentrations, glutathione levels and catalase activity.

High-risk human papillomavirus infection in female and subsequent risk of infertility: a population-based cohort study

To study whether infection with high-risk human papillomavirus (HPV), registered both as a single HPV positive test and as HPV persistence, increases the risk of female factor infertility in later reproductive life. Population-based cohort study. Not applicable. A random sample of 11,088 women (20-29years of age at enrollment) tested for cervical HPV at enrollment during 1991-93 and again after 2years. Information on female factor infertility was obtained by linkage to the Danish Infertility Cohort. None. Follow-up for each study participant was the period from the date of enrollment or date of the second visit until diagnosis of female factor infertility (main outcome), conception, death, emigration, disappearance, or end of study period. Data were analyzed by means of a Cox proportional hazards regression model. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between HPV status and female factor infertility after adjustment for potentially confounding factors were determined. After relevant exclusions, 10,595 women were eligible for analysis, 1,861 (17.6%) of whom were high-risk HPV positive at the first visit. There was no association between a positive HPV test at first visit (HR = 0.88; 95% CI, 0.75-1.02) or positivity for the same high-risk HPV type at the first and second visit (persistence; HR = 0.97; 95% CI, 0.66-1.44) and subsequent risk of female factor infertility in reproductive life. We found no association between a high-risk HPV infection and risk of female factor infertility, neither for a single HPV positive test nor for a persistent HPV infection.

Etiology and Risk Factors Associated With Infertility

Objectives: Infertility is one of the important complications in gynecology and the aim of the present study was to investigate the etiology and risk factors associated with infertility in the southern region of Iran. Materials and Methods: This cross-sectional study was conducted in infertility centers of Hormozgan University of Medical Science (HUMS). Totally, 250 infertile couples were included. The variables including socio-demographic characteristics, smoking, body mass index (BMI), and infertility status (e.g., type of fertility, duration, etc.) were assessed by a self-administered and validated questionnaire. Data analysis was carried out using SPSS version 22.0. Results: The most common causes of male and female infertility were varicocele (49.4%) and ovulation disorders (57.5%), respectively. There was a significant association between female factor infertility and level of education, age of women, women’s age at marriage, number of abortions, alcohol consumption, presence of an underlying disease, and BMI (P&lt;0.005). There was also a significant relationship between male factor infertility and men’s job, addiction, smoking, and presence of an underlying disease (P&lt;0.005). Conclusions: Considering various risk factors for infertility, an important step forward can be taken towards reducing the incidence of these risk factors by providing different education classes during pre-marriage, pre-partum, pregnancy and postpartum periods so as to inform couples of controllable risk factors.

The ubiquitin ligase KBTBD8 regulates PKM1 levels via Erk1/2 and Aurora A to ensure oocyte quality.

Tight control of energy metabolism is essential for normal cell function and organism survival. PKM (pyruvate kinase, muscle) isoforms 1 and 2 originate from alternative splicing of PKM pre-mRNA. They are key enzymes in oxidative phosphorylation and aerobic glycolysis, respectively, and are essential for ATP generation. The PKM1:PKM2 expression ratio changes with development and differentiation, and may also vary under metabolic stress and other conditions. Until now, there have been no reports about the function and regulation of PKM isozymes in oocytes. Here, we demonstrate that PKM1 or PKM2 depletion significantly disrupts ATP levels and mitochondrial integrity, and exacerbates free-radical generation and apoptosis in mouse oocytes. We also show that KBTBD8, a female fertility factor in the KBTBD ubiquitin ligase family, selectively regulates PKM1 levels through a signaling cascade that includes Erk1/2 and Aurora A kinases as intermediates. Finally, using RNA sequencing and protein network analysis, we identify several regulatory proteins that may be govern generation of mature PKM1 mRNA. These results suggest KBTBD8 affects PKM1 levels in oocytes via a KBTBD8→Erk1/2→Aurora A axis, and may also affect other essential processes involved in maintaining oocyte quality.

Impact of sperm DNA fragmentation on ICSI outcome and incidence of apoptosis of human pre-implantation embryos obtained from in vitro matured MII oocytes

BackgroundSperm DNA integrity and oocyte quality significantly affect embryo development and survival. The current study evaluated embryo development and quality, as well as the expression level of apoptosis-related genes and microRNAs in embryo derived from in vitro matured MII oocytes according to sperm DNA fragmentation (SDF) level. MethodsThe semen and immature oocytes were collected from 50 ICSI cycles with any recognizable female factor infertility. After ovarian stimulation, germinal vesicle stage (GV) oocytes were collected and incubated in in vitro maturation (IVM) medium for 24 h. Next, reactive oxygen species (ROS) level of media culture was determined. Using by sperm chromatin dispersion (SCD) test, the SDF levels of processed semen were assessed and categorized into SDF ≤ 30% and SDF>30%. Seventy two hours after intracytoplasmic injection, the embryo development and quality score were recorded in the groups I (GV-MII + SDF≤ 30%) and II (GV-MII + SDF> 30%). Also, the apoptosis incidence of embryos at morula stage was evaluated at molecular and cellular levels by quantitative real time PCR and TUNEL staining, respectively. ResultsCleavage rate did not differ between two groups. The quality score of embryos obtained from IVM matured oocytes and high level of SDF was significantly lower than that of low level of SDF (P < 0.05). The embryos from group II had a significant reduction of the expression of BCL-2 compared to group I (P < 0.05). Also, they showed an increase in relative transcription of pro-apoptotic microRNAs; miR 15a and miR 16-1 versus group I (P < 0.05). A rise of TUNEL positive blastomers of embryo was observed at group II versus group I, but it did not reach to significantly level. ConclusionThe IVM oocytes, probably, did not suffice to recover the high level of paternal genomic damage and inhibition of apoptosis pathway beginning.

Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility.

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.