Mammalian oocytes store proteins for the early embryo on cytoplasmic lattices.

Mammalian oocytes are filled with poorly understood structures called cytoplasmic lattices. First discovered in the 1960s and speculated to correspond to mammalian yolk, ribosomal arrays, or intermediate filaments, their function has remained enigmatic to date. Here, we show that cytoplasmic lattices are sites where oocytes store essential proteins for early embryonic development. Using super-resolution light microscopy and cryoelectron tomography, we show that cytoplasmic lattices are composed of filaments with a high surface area, which contain PADI6 and subcortical maternal complex proteins. The lattices associate with many proteins critical for embryonic development, including proteins that control epigenetic reprogramming of the preimplantation embryo. Loss of cytoplasmic lattices by knocking out PADI6 or the subcortical maternal complex prevents the accumulation of these proteins and results in early embryonic arrest. Our work suggests that cytoplasmic lattices enrich maternally provided proteins to prevent their premature degradation and cellular activity, thereby enabling early mammalian development.

PATL2 regulates mRNA homeostasis in oocytes by interacting with EIF4E and CPEB1.

The accumulation and storage of maternal mRNA is crucial for oocyte maturation and embryonic development. PATL2 is an oocyte-specific RNA-binding protein, and previous studies have confirmed that PATL2 mutation in humans and knockout mice cause oocyte maturation arrest or embryonic development arrest, respectively. However, the physiological function of PATL2 in the process of oocyte maturation and embryonic development is largely unknown. Here, we report that PATL2 is highly expressed in growing oocytes and couples with EIF4E and CPEB1 to regulate maternal mRNA expression in immature oocytes. The germinal vesicle oocytes from Patl2-/- mice exhibit decreasing maternal mRNA expression and reduced levels of protein synthesis. We further confirmed that PATL2 phosphorylation occurs in the oocyte maturation process and identified the S279 phosphorylation site using phosphoproteomics. We found that the S279D mutation decreased the protein level of PATL2 and led to subfertility in Palt2S279D knock-in mice. Our work reveals the previously unrecognized role of PATL2 in regulating the maternal transcriptome and shows that phosphorylation of PATL2 leads to the regulation of PATL2 protein levels via ubiquitin-mediated proteasomal degradation in oocytes.

Oocytes orchestrate protein prenylation for mitochondrial function through selective inactivation of cholesterol biosynthesis in murine species.

Emerging research and clinical evidence suggest that the metabolic activity of oocytes may play a pivotal role in reproductive anomalies. However, the intrinsic mechanisms governing oocyte development regulated by metabolic enzymes remain largely unknown. Our investigation demonstrates that geranylgeranyl diphosphate synthase1 (Ggps1), the crucial enzyme in the mevalonate pathway responsible for synthesizing isoprenoid metabolite geranylgeranyl pyrophosphate from farnesyl pyrophosphate, is essential for oocyte maturation in mice. Our findings reveal that the deletion of Ggps1 that prevents protein prenylation in fully grown oocytes leads to subfertility and offspring metabolic defects without affecting follicle development. Oocytes that lack Ggps1 exhibit disrupted mitochondrial homeostasis and the mitochondrial defects arising from oocytes are inherited by the fetal offspring. Mechanistically, the excessive farnesylation of mitochondrial ribosome protein, Dap3, and decreased levels of small G proteins mediate the mitochondrial dysfunction induced by Ggps1 deficiency. Additionally, a significant reduction in Ggps1 levels in oocytes is accompanied by offspring defects when females are exposed to a high-cholesterol diet. Collectively, this study establishes that mevalonate pathway-protein prenylation is vital for mitochondrial function in oocyte maturation and provides evidence that the disrupted protein prenylation resulting from an imbalance between farnesyl pyrophosphate and geranylgeranyl pyrophosphate is the major mechanism underlying impairment of oocyte quality induced by high cholesterol.

Assisted reproductive technology use and outcomes in childhood cancer survivors.

BACKGROUND: Treatment exposures for childhood cancer reduce ovarian reserve. However, the success of assisted reproductive technology (ART) among female survivors is not well established. METHODS: Five-year survivors of childhood cancer in the Childhood Cancer Survivor Study were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System, which captures national ART outcomes. The authors assessed the live birth rate, the relative risk (RR) with 95% confidence intervals (95% CIs), and associations with treatment exposure using generalized estimating equations to account for multiple ovarian stimulations per individual. Siblings from a random sample of survivors were recruited to serve as a comparison group. RESULTS: Among 9885 female survivors, 137 (1.4%; median age at diagnosis, 10 years [range, 0-20 years]; median years of follow-up after age 18 years, 11 years [range, 2-11 years]) underwent 224 ovarian stimulations using autologous or donor eggs and/or gestational carriers (157 autologous ovarian stimulation cycles, 67 donor ovarian stimulation cycles). In siblings, 33 (1.4%) underwent 51 autologous or donor ovarian stimulations. Of those who used embryos from autologous eggs without using gestational carriers, 97 survivors underwent 155 stimulations, resulting in 49 live births, for a 31.6% chance of live birth per ovarian stimulation (vs. 38.3% for siblings; p = .39) and a 43.9% chance of live birth per transfer (vs. 50.0%; p = .33). Prior treatment with cranial radiation therapy (RR, 0.44; 95% CI, 0.20-0.97) and pelvic radiation therapy (RR, 0.33; 95% CI, 0.15-0.73) resulted in a reduced chance of live birth compared with siblings. The likelihood of live birth after ART treatment in survivors was not affected by alkylator exposure (cyclophosphamide-equivalent dose, ≥8000 mg/m2 vs. none; RR, 1.04; 95% CI, 0.52-2.05). CONCLUSIONS: Childhood cancer survivors are as likely to undergo treatment using ART as sibling controls. The success of ART treatment was not reduced after alkylator exposure. The results from the current study provide needed guidance on the use of ART in this population.

Oocyte-specific EXOC5 expression is required for mouse oogenesis and folliculogenesis.

EXOC5 is a crucial component of a large multi-subunit tethering complex, the exocyst complex, that is required for fusion of secretory vesicles with the plasma membrane. Exoc5 deleted mice die as early embryos. Therefore, to determine the role of EXOC5 in follicular and oocyte development, it was necessary to produce a conditional knockout (cKO), Zp3-Exoc5-cKO, in which Exoc5 was deleted only in oocytes. The first wave of folliculogenesis appeared histologically normal and progressed to the antral stage. However, after IVF with normal sperm, oocytes collected from the first wave (superovulated 21-day-old cKO mice) were shown to be developmentally incompetent. Adult follicular waves did not progress beyond the secondary follicle stage where they underwent apoptosis. Female cKO mice were infertile. Overall, these data suggest that the first wave of folliculogenesis is less sensitive to oocyte-specific loss of Exoc5, but the resulting gametes have reduced developmental competence. In contrast, subsequent waves of folliculogenesis require oocyte-specific Exoc5 for development past the preantral follicle stage. The Zp3-Exoc5-cKO mouse provides a model for disrupting folliculogenesis that also enables the separation between the first and subsequent waves of folliculogenesis.

Use of levothyroxine for euthyroid, thyroid antibody positive women with infertility: Analyses of aggregate data from a survey of European thyroid specialists (Treatment of Hypothyroidism in Europe by Specialists: An International Survey).

OBJECTIVES: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients. DESIGN: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb. RESULTS: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%-83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7-0.9) and respondents >60 years (OR: 0.7; 0.6-0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0-1.9], "daily" [OR: 1.8; CI: 1.3-2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3-1.9) were most likely to consider LT4. CONCLUSIONS: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment.

Connecting the dots: the role of fatigue in female infertility.

Fatigue, an increasingly acknowledged symptom in various chronic diseases, has garnered heightened attention, during the medical era of bio-psycho-social model. Its persistence not only significantly compromises an individual's quality of life but also correlates with chronic organ damage. Surprisingly, the intricate relationship between fatigue and female reproductive health, specifically infertility, remains largely unexplored. Our exploration into the existing body of evidence establishes a compelling link between fatigue with uterine and ovarian diseases, as well as conditions associated with infertility, such as rheumatism. This observation suggests a potentially pivotal role of fatigue in influencing overall female fertility. Furthermore, we propose a hypothetical mechanism elucidating the impact of fatigue on infertility from multiple perspectives, postulating that neuroendocrine, neurotransmitter, inflammatory immune, and mitochondrial dysfunction resulting from fatigue and its co-factors may further contribute to endocrine disorders, menstrual irregularities, and sexual dysfunction, ultimately leading to infertility. In addition to providing this comprehensive theoretical framework, we summarize anti-fatigue strategies and accentuate current knowledge gaps. By doing so, our aim is to offer novel insights, stimulate further research, and advance our understanding of the crucial interplay between fatigue and female reproductive health.

A critical systematic review and meta-analyses of risk factors for fertility problems in a globalized world.

Globally, fertility awareness efforts include well-established risk factors for fertility problems. Risks disproportionately affecting women in the Global South, however, are neglected. To address this gap, we conducted a systematic review and meta-analyses of relevant risk factors to examine the association between risk factors and fertility problems. MEDLINE, Embase, Cochrane Library, regional databases and key organizational websites were used. Three authors screened and extracted data independently. Studies assessing exposure to risk (clinical, community-based samples) were included, and studies without control groups were excluded. Outcome of interest was fertility problems, e.g. inability to achieve pregnancy, live birth, neonatal death depending on study. The Newcastle-Ottawa Scale was used to assess study quality. A total of 3843 studies were identified, and 62 were included (58 in meta-analyses; n = 111,977). Results revealed the following: a ninefold risk of inability to become pregnant in genital tuberculosis (OR 8.91, 95% CI 1.89 to 42.12); an almost threefold risk in human immunodeficiency virus (OR 2.93, 95% CI 1.95 to 4.42) and bacterial vaginosis (OR 2.81, 95% CI 1.85 to 4.27); a twofold risk of tubal-factor infertility in female genital mutilation/cutting-Type II/III (OR 2.06, 95% CI 1.03 to 4.15); and postnatal mortality in consanguinity (stillbirth, OR 1.28, 95% CI 1.04 to 1.57; neonatal death, OR 1.57, 95% CI 1.22 to 2.02). It seems that risk factors affected reproductive processes through multiple pathways. Health promotion encompassing relevant health indicators could enhance prevention and early detection of fertility problems in the Global South and disproportionately affected populations. The multifactorial risk profile reinforces the need to place fertility within global health initiatives.

Effect of radiation on serum anti-Müllerian hormone during hysterosalpingography in female infertility.

RESEARCH QUESTION: Does radiation exposure during hysterosalpingography (HSG) negatively affect serum anti-Müllerian hormone (AMH) levels in infertile women? DESIGN: Prospective cohort study conducted at Songklanagarind Hospital, Thailand, between April 2021 and May 2023. Thirty-two infertile women and 34 control participants were enrolled. Serum AMH levels were assessed in the infertile group at baseline before the HSG procedure and at 1 and 3 months after the procedure. Control participants, who self-reported no medical conditions, underwent the same AMH level assessments. Changes in serum AMH levels were compared. RESULTS: Infertile women had a mean age of 32.4 ± 3.8 years, body mass index of 21.2 ± 2.0 kg/m2 and baseline mean AMH level of 3.66 ng/ml (95% CI 3.00 to 4.32), which did not significantly differ from the control group. One month after HSG, mean AMH level significantly declined (0.33 ng/ml, 95% CI -0.65 to -0.01; P = 0.045) in the infertile group. The change in serum AMH levels between baseline and 1 month was significantly different in the HSG group compared with controls (-0.33 ng/ml, 95% CI -0.65 to -0.01 versus 0.36 ng/ml, 95% CI 0.06 to 0.67; P = 0.002). Changes in serum AMH levels from baseline to 3 months did not differ between the two groups. CONCLUSIONS: One month after the HSG, infertile women experienced a significant decrease in serum AMH levels compared with controls. The change in serum AMH levels between baseline and 3 months after HSG did not significantly differ from that of the control group.

Association between visceral adipose tissue area and infertility: a cross-sectional analysis.

RESEARCH QUESTION: Is intra-abdominal fat obesity associated with infertility? DESIGN: This study analysed data from the 2013-2018 National Health and Nutrition Examination Survey, with a total of 3013 women enrolled. The participants were divided into two groups: infertility and non-infertility. Differences between the two groups were analysed using a weighted Student's t-test or Mann-Whitney U-test for continuous variables, or a weighted chi-squared test for categorical data. Visceral adipose tissue area (VATA) was assessed by dual-energy X-ray absorptiometry. The independent association between infertility and log VATA was assessed by weighted multivariate logistic regression models. Subgroup analyses were performed to assess the strength of the results. Interaction tests were used to examine whether covariates interacted with log VATA to influence infertility. RESULTS: Log VATA was significantly higher in the infertility group compared with the non-infertility group (P < 0.001). After adjustment for potential confounders, the results of multivariate logistic regression analysis revealed that an increase in log VATA was associated with increased prevalence of female infertility (OR = 2.453, 95% CI 1.278-4.792). Subgroup analyses showed this association in individuals aged <35 years (P = 0.002), Mexican-Americans (P = 0.033), non-hypertensive individuals (P = 0.013) and non-diabetic individuals (P = 0.003). CONCLUSIONS: An enlarged VATA is associated with increased risk of infertility. The direct effect of VATA on female infertility needs to be clarified further to provide a basis for future prevention and treatment of female infertility.

Revitalizing female fertility: platelet-rich plasma - hype or hope?

Platelet-rich plasma (PRP) has gained popularity as an experimental tool in regenerative medicine, with potential applications in reproductive medicine. This review will assess the existing literature on the role of PRP in female fertility enhancement, focusing on ovarian rejuvenation and increased endometrial thickness. PRP is being explored as a treatment for recurrent implantation failure, primary ovarian insufficiency and poor ovarian response. While the influence of PRP on endometrial thickness and implantation success is postulated, its effectiveness remains the subject of debate due to protocol variability and unclear patient selection criteria. This narrative review includes 36 articles published before December 2022, and highlights the lack of comprehensive molecular studies examining the impact of PRP on reproductive capacity. This review underscores the importance of standardizing PRP preparation protocols in reproductive medicine. However, challenges persist, and there is a need for well-planned randomized controlled trials and a deeper understanding of the patient population that would gain the greatest benefit from PRP treatment. Clarifying these aspects is crucial to improve outcomes for low-prognosis patients undergoing assisted reproductive technology.

Therapeutic effects of curculigoside on cyclophosphamide-induced premature ovarian failure in mice.

OBJECTIVE: The main purpose of this study was to elucidate the anti-apoptotic effects of curculigoside (CUR) on ovarian granulosa cells (GCs) in a mouse model of cyclophosphamide (CTX)-induced premature ovarian failure (POF). METHOD: Intraperitoneal injection of CTX (100 mg/kg body weight) induced POF in mice. Thirty-six female mice were divided into six groups: blank group; POF model group; low-dose CUR group; medium-dose CUR group; high-dose CUR group; and estradiol benzoate group. Mice were orally administered for 28 consecutive days. Twenty-four hours after the completion of treatment, mice were weighed and euthanized, and blood was collected from the eyeball under anesthesia. The ovaries were surgically separated and weighed, and the ovarian index was calculated. Hematoxylin-eosin (HE) staining was used to observe follicular development and corpus luteum morphology in the ovaries. Serum levels of follicle stimulating hormone (FSH), anti-Müllerian hormone (AMH) and estradiol (E2) were measured. Superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) content and malondialdehyde (MDA) levels in ovarian tissue were determined. The GC apoptosis level was measured. Western blotting was used to detect protein expression levels of Beclin-1, LC3, P62, AKT, p-AKT, mTOR and p-mTOR in the ovaries. RESULTS: The results showed that CUR can improve body weight and ovarian index; promote follicular development and reduce follicular atresia; improve FSH, AMH and E2 levels; downregulate MDA levels and restore antioxidant enzyme activity; inhibit the autophagy level; activate the AKT/mTOR signaling pathway; and alleviate GC apoptosis. CONCLUSION: CUR improves POF by activating the AKT/mTOR signaling pathway, inhibiting autophagy and alleviating GC apoptosis.

Gene mutations impede oocyte maturation, fertilization, and early embryonic development.

Reproductive diseases are a long-standing problem and have become more common in the world. Currently, 15% of the world's population suffers from infertility, and half of them are women. Maturation of oocytes, successful fertilization, and high-quality embryos are prerequisites for pregnancy. With the development of assisted reproductive technology and advanced genetic assays, we have found that infertility in many young female patients is caused by mutations in various developmental regulators. These pathogenic factors may result in impediment of oocyte maturation, failure of fertilization or early embryonic development arrest. In this review, we categorize these clinically-identified, mutated genetic factors by their molecular characteristics: nuclear factors (PALT2, TRIP13, WEE2, TBPL2, REC114, MEI1 and CDC20), cytoplasmic factors (TLE6, PADI6, NLRP2/5, FBXO43, MOS and BTG4), a factor unique to primates (TUBB8), cell membrane factor (PANX1), and zona pellucida factors (ZP1-3). We compared discrepancies observed in phenotypes between human and mouse models to provide clues for clinical diagnosis and treatment of related reproductive diseases.

The causal relationship of female infertility and psychiatric disorders in the European population: a bidirectional two-sample Mendelian randomization study.

BACKGROUND: Infertility affects many couples globally, causing physical, emotional, and financial burdens. While observational studies suggest a link between psychiatric disorders and female infertility, causal relationships remain uncertain. Mendelian randomization analysis, using genome-wide association studies data, minimizes confounding factors and reverse causation, providing valuable insights into causal associations. METHODS: We conducted Mendelian randomization analysis to explore the potential causal relationship between female infertility and psychiatric disorders. Genome-wide association studies summary data for female infertility (112,105 individuals of European ancestry, comprising 11,442 cases and 100,663 controls), depression (807,553 individuals of European ancestry, comprising 246,363 cases and 561,190 controls), anxiety (21,763 individuals of European ancestry, comprising 7,016 cases and 14,745 controls), bipolar disorder (51,710 individuals of European ancestry, comprising 20,352 cases and 31,358 controls), and eating disorders (72,517 individuals of European ancestry, comprising 16,992 cases and 55,525 controls) were utilized. Instrumental variables were selected based on significant single nucleotide polymorphisms associated with each phenotype. We assessed instrumental variable strength, examined confounding factors, and employed inverse variance weighting, weighted median, and MR-Egger approaches for analysis. RESULTS: Our analysis included 85 single nucleotide polymorphisms for female infertility and 62 single nucleotide polymorphisms for psychiatric disorders. Results suggest a potential causal relationship between depression and female infertility, with both inverse variance weighting and weighted median methods showing increased infertility risk in depressed patients. Evidence is weak regarding bipolar disorder not increasing female infertility risk. We found no evidence supporting causal links between anxiety, eating disorders, and female infertility. Similarly, no causal relationship was found between female infertility and psychiatric disorders in the opposite direction. Sensitivity analyses and tests for heterogeneity and polymorphism supported result robustness. CONCLUSIONS: This analysis provides evidence for a potential causal relationship between depression and female infertility. Addressing depression in infertile women may improve fertility outcomes. Further research is needed to explore underlying mechanisms and potential interventions for improving fertility outcomes in women with psychiatric disorders.

Combined impact of sleep and obesity on female infertility in the NHANES 2017-2020.

BACKGROUND: Sleep health and obesity may affect the risk of female infertility. However, few studies focused on the interaction of obesity and sleep health on the female infertility risk. This study aimed to evaluate the combined impact of trouble sleeping / sleep duration and overweight/obesity/ abdominal obesity on the risk of female infertility. METHODS: The data for this cross-sectional study was obtained from National Health and Nutritional Examination Survey, which provided information on trouble sleeping, sleep duration, overweight/obesity, abdominal obesity, and confounding factors. Adopted weighted univariate and multivariate logistic regression models to explore the relationship between trouble sleeping, sleep duration, overweight/obesity, abdominal obesity, and the risk of infertility, respectively, and the combined effect of trouble sleeping and overweight/obesity, trouble sleeping and abdominal obesity, sleep duration and overweight/obesity, sleep duration and abdominal obesity, on the female infertility risk. RESULTS: This study included a total of 1,577 women, and 191 were diagnosed with infertility. Women with infertility had a higher proportion of people with overweight/obesity, abdominal obesity, sleep duration ≤ 7 h and trouble sleeping than those with non-infertility. The result indicated that trouble sleeping [odds ratio (OR) = 2.25, 95% confidence intervals (CI): 1.49-3.39], sleep duration ≤ 7 h (OR = 1.59, 95% CI: 1.03-2.48), and the combined impact of abdominal obesity and trouble sleeping (OR = 2.18, 95% CI: 1.28-3.72), abdominal obesity and sleep duration ≤ 7 h (OR = 2.00, 95% CI: 1.17-3.40), overweight/obesity and trouble sleeping (OR = 2.29, 95% CI: 1.24-4.26), and overweight/obesity and sleep duration ≤ 7 h (OR = 1.88, 95% CI: 1.01-3.49) were associated with increased odds of infertility, respectively. CONCLUSION: There was combined effects of trouble sleeping/sleep duration ≤ 7 h and overweight/obesity/ abdominal obesity on increased odds of female infertility.

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.

Cadmium as an ovarian toxicant: A review.

Cadmium (Cd) is a ubiquitous heavy metal toxicant with no biological function in the human body. Considerably, because of its long biological half-life and very low excretion rate, Cd is inclined to accumulate and cause deleterious effects on various body organs (e.g., liver, kidney, and ovary) in humans and animals. Ovaries are the most vulnerable targets of Cd toxicity. Cd has been shown to induce oxidative stress, follicular atresia, hormonal imbalance, and impairment of oocyte growth and development. Moreover, Cd toxicity has been associated with increasing incidences of menstrual disorders, pregnancy loss, preterm births, delayed puberty, and female infertility. Therefore, it is crucial to understand how Cd poisoning impacts specific ovarian processes for the development of preventive interventions to enhance female fertility. The current review attempts to collate the recent findings on Cd-induced oxidative stress, follicular apoptosis, steroid synthesis inhibition, and teratogenic toxicity, along with their possible mechanisms in the ovarian tissue of different animal species. Additionally, the review also summarizes the studies related to the use of many antioxidants, medicinal herbs, and other compounds as remedial approaches for managing Cd-induced ovarian toxicity.

RAD51 and Infertility: A Review and Case-Control Study.

RAD51 is a highly conserved recombinase involved in the strand invasion/exchange of double-stranded DNA by homologous single-stranded DNA during homologous recombination repair. Although a majority of existing literature associates RAD51 with the pathogenesis of various types of cancer, recent reports indicate a role of RAD51 in maintenance of fertility. The present study reviews the role of RAD51 and its interacting proteins in spermatogenesis/oogenesis and additionally reports the findings from the molecular genetic screening of RAD51 135 G > C polymorphism in infertile cases and controls. Fifty-nine articles from PubMed and Google Scholar related to the reproductive role of RAD51 were reviewed. For case-control study, the PCR-RFLP method was used to screen the RAD51 135 G > C polymorphism in 201 infertile cases (100 males, 101 females) and 201 age- and gender-matched healthy controls (100 males, 101 females) from Punjab, North-West India. The review of literature shows that RAD51 is indispensable for spermatogenesis and oogenesis in animal models. Reports on the role of RAD51 in human fertility are limited, however it is involved in the pathogenesis of infertility in both males and females. Molecular genetic analyses in the infertile cases and healthy controls showed no statistically significant difference in the genotypic and allelic frequencies for RAD51 135 G > C polymorphism, even after segregation of the cases by type of infertility (primary/secondary). Therefore, the present study concluded that the RAD51 135 G > C polymorphism was neither associated with male nor female infertility in North-West Indians. This is the first report on RAD51 135 G > C polymorphism and infertility.

Live birth derived from a markedly large polar body oocyte: a rare case report.

Oocytes with excessively large first polar bodies (PB1) often occur in assisted reproductive procedures. Many times these oocytes are discarded without insemination and, as a result, the application of this portion of oocytes has scarcely been reported to date. Few studies have examined large PB1 oocytes in infertile women and have virtually entirely studied genetic variations for large PB1 oocyte abnormalities. Here, we describe an unusual case of a live birth from a remarkably large PB1 oocyte in a frozen embryo transfer (FET) cycle. This is the first instance of a successful live birth resulting from a PB1 oocyte with an extremely large polar body measuring 80 µM × 40 µM in size. The large PB1 oocyte was performed by an early rescue intracytoplasmic sperm injection (r-ICSI) and was formed into a blastocyst on day 5. Following FET, a healthy boy baby weighing 3100 g was finally delivered by caesarean section at 37 weeks and 5 days after conception. Additionally, there were no complications throughout the antenatal period or the perinatal phase of this following full-term delivery. In this study, it is revealed for the first time that a huge PB1 oocyte can be fertilized, resulting in the growth of a blastocyst, a subsequent pregnancy, and a live birth. This new information prompts us to reconsider the use of large PB1 oocytes. More insightful talks should be given attention to prevent the waste of embryos because not all oocytes with aberrant morphology are unavailable.

Miracles of science: Birth after uterus transplantation.

AIM: The concept of regaining childbearing ability via uterus transplantation (UTx) motivates many infertile women to pursue giving birth to their own children. This article provides insight into maternal and neonatal outcomes of the procedure globally and facilitates quality of care in related medical fields. METHODS: The authors searched ISI Web of Science, MEDLINE, non-PubMed-indexed journals, and common search engines to identify peer-review publications and unpublished sources in scientific reference databases. RESULTS: The feasibility of the procedure has been proven with 46 healthy children in 88 procedures so far. Success relies upon dedicated teamwork involving transplantation surgery, obstetrics and reproductive medicine, neonatology, pediatrics, psychology, and bioethics. However, challenges exist owing to donor, recipient, and fetus. Fetal growth in genetically foreign uterine allograft with altered feto-maternal interface and vascular anatomy, immunosuppressive exposure, lack of graft innervation leading to "unable-to-feel" uterine contractions and conception via assisted reproductive technology create notable risks during pregnancy. Significant portion of women are complicated by at least one or more obstetric problems. Preeclampsia, gestational hypertension and diabetes mellitus, elevated kidney indices, and preterm delivery are common complications. CONCLUSIONS: UTx has short- and long-term satisfying outcome. Advancements in the post-transplant management would undoubtedly lead this experimental procedure into mainstream clinical practice in the near future. However, both women and children of UTx need special consideration due to prematurity-related neonatal problems and the long-term effects of transplant pregnancy. Notable health risks for the recipient and fetus should be discussed with potential candidates for UTx.