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STUDY QUESTION Is preconception depression associated with time to pregnancy (TTP) and infertility? SUMMARY ANSWER Couples with preconception depression needed a longer time to become pregnant and exhibited an increased risk of infertility. WHAT IS KNOWN ALREADY Preconception depression in women contributes to impaired fertility in clinical populations. However, evidence from the general population—especially based on couples—is relatively scant. STUDY DESIGN, SIZE, DURATION A couple-based prospective preconception cohort study was performed in 16 premarital examination centers between April 2019 and June 2021. The final analysis included 16 521 couples who tried to conceive for ≤6 months at enrollment. Patients with infertility were defined as those with a TTP ≥12 months and those who conceived through ART. PARTICIPANTS/MATERIALS, SETTING, METHODS Couples' depression was assessed using the Patient Health Questionnaire-9 at baseline. Reproductive outcomes were obtained via telephone at 6 and 12 months after enrollment. Fertility odds ratios (FORs) and infertility risk ratios (RRs) in different preconception depression groups were analyzed using the Cox proportional-hazard models and logistic regression, respectively. MAIN RESULTS AND THE ROLE OF CHANCE Of the 16 521 couples analyzed, 10 834 (65.6%) and 746 (4.5%) couples achieved pregnancy within the first 6 months and between the 6th and 12th months, respectively. The median (P25, P75) TTP was 3.0 (2.0, 6.0) months. The infertility rate was 13.01%. After adjusting for potential confounders, in the individual-specific analyses, we found that preconception depression in women was significantly related to reduced odds of fertility (FOR = 0.947, 95% CI: 0.908–0.988), and preconception depression in either men or women was associated with an increased risk of infertility (women: RR = 1.212, 95% CI: 1.076–1.366; men: RR = 1.214, 95% CI: 1.068–1.381); in the couple-based analyses, we found that—compared to couples where neither partner had depression—the couples where both partners had depression exhibited reduced fertility (adjusted FOR = 0.904, 95% CI: 0.838–0.975). The risk of infertility in the group where only the woman had depression and both partners had depression increased by 17.8% (RR = 1.178, 95% CI: 1.026–1.353) and 46.9% (RR = 1.469, 95% CI: 1.203–1.793), respectively. LIMITATIONS, REASONS FOR CAUTION Reporting and recall bias were unavoidable in this large epidemiological study. Some residual confounding factors—such as the use of anti-depressants and other medications, sexual habits, and prior depressive and anxiety symptoms—remain unaddressed. We used a cut-off score of 5 to define depression, which is lower than prior studies. Finally, we assessed depression only at baseline, therefore we could not detect effects of temporal changes in depression on fertility. WIDER IMPLICATIONS OF THE FINDINGS This couple-based study indicated that preconception depression in individuals and couples negatively impacts couples' fertility. Early detection and intervention of depression to improve fertility should focus on both sexes. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by grants from the National Natural Science Foundation of China (No. 82273638) and the National Key Research and Development Program of China (No. 2018YFC1004201). All authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

The corona of the glans clitoris is a clinically important yet poorly understood anatomical structure. There has been longstanding confusion regarding the prevalence of the corona of the glans clitoris and, moreover, its very existence. Therefore, this anatomical study assesses the prevalence of the corona of the glans clitoris and the gross anatomy of the proximal glans clitoris. Anatomy was assessed in 104 female donor bodies ranging in age from 50 to 102 years with an average age-at-death of 78.1±10.9 years (mean±SD). All clitorises (100%; 104:104 dorsums and 100%; 208:208 sides) were found to have a well-defined clitoral corona. Three of 104 (2.9%) coronas possessed grossly visible, outward-projecting, bluntly rounded papillae. Some donors possessed a coronopreputial frenulum. Clitoropreputial adhesions were common and associated with clitoral pearls. Clitoral pearls were identified in 37.8% (14:37) of unembalmed donors and observed to create clitoral craters, structural deformations in the surface of the corona and glans. The results of this study suggest that the corona of the glans clitoris is a ubiquitous anatomical structure. The clitoral coronal papillae and coronopreputial frenulum are novel, previously undescribed, anatomical structures. This study identifies that the corona of the glans clitoris is prone to pathological processes such as clitoral pearl formation and clitoral deformation. In addition to novel anatomical findings, the results of this study call attention to the need for life-long clitoral examinations. Furthermore, the corona of the glans clitoris should be regularly included in anatomical texts and accurately depicted in anatomical illustrations. [ABSTRACT FROM AUTHOR]

Hyperandrogenism is a clinical state consequent to excess androgen production by the ovary, adrenals, or increased peripheral conversion of androgens. The varied manifestations of hyperandrogenism include seborrhea, acne, infertility, hirsutism, or overt virilization of which adult female acne, hirsutism, and female pattern hair loss are of clinical relevance to dermatologists. We limited our narrative review to literature published during period from 1 January 1985 to Dec 2022 and searched PubMed/MEDLINE, Web of Science (WOS), Scopus, and Embase databases with main search keywords were 'Hyperandrogenism,' 'Female,' 'Biochemical,' 'Dermatological', and 'Dermatology.' We detail the common etiological causes, nuances in interpretation of biochemical tests and imaging tools, followed by an algorithmic approach which can help avoid extensive tests and diagnose the common causes of hyperandrogenism. Based on current data, total testosterone, sex hormone binding globulin, DHEAS, prolactin, free androgen index, and peripheral androgenic metabolites like 3-alpha diol and androsterone glucuronide are ideal tests though not all are required in all patients. Abnormalities in these biochemical investigations may require radiological examination for further clarification. Total testosterone levels can help delineate broadly the varied causes of hyperandrogenism. Serum AMH could be used for defining PCOM in adults. [ABSTRACT FROM AUTHOR]

BACKGROUND Estrogens regulate disparate female physiological processes, thus ensuring reproduction. Altered estrogen levels and signaling have been associated with increased risks of pregnancy failure and complications, including hypertensive disorders and low birthweight babies. However, the role of estrogens in the periconceptional period and early pregnancy is still understudied. OBJECTIVE AND RATIONALE This review aims to summarize the current evidence on the role of maternal estrogens during the periconceptional period and the first trimester of pregnancies conceived naturally and following ART. Detailed molecular mechanisms and related clinical impacts are extensively described. SEARCH METHODS Data for this narrative review were independently identified by seven researchers on Pubmed and Embase databases. The following keywords were selected: 'estrogens' OR 'estrogen level(s)' OR 'serum estradiol' OR 'estradiol/estrogen concentration', AND 'early pregnancy' OR 'first trimester of pregnancy' OR 'preconceptional period' OR 'ART' OR 'In Vitro Fertilization (IVF)' OR 'Embryo Transfer' OR 'Frozen Embryo Transfer' OR 'oocyte donation' OR 'egg donation' OR 'miscarriage' OR 'pregnancy outcome' OR 'endometrium'. OUTCOMES During the periconceptional period (defined here as the critical time window starting 1 month before conception), estrogens play a crucial role in endometrial receptivity, through the activation of paracrine/autocrine signaling. A derailed estrogenic milieu within this period seems to be detrimental both in natural and ART-conceived pregnancies. Low estrogen levels are associated with non-conception cycles in natural pregnancies. On the other hand, excessive supraphysiologic estrogen concentrations at time of the LH peak correlate with lower live birth rates and higher risks of pregnancy complications. In early pregnancy, estrogen plays a massive role in placentation mainly by modulating angiogenic factor expression—and in the development of an immune-tolerant uterine micro-environment by remodeling the function of uterine natural killer and T-helper cells. Lower estrogen levels are thought to trigger abnormal placentation in naturally conceived pregnancies, whereas an estrogen excess seems to worsen pregnancy development and outcomes. WIDER IMPLICATIONS Most current evidence available endorses a relation between periconceptional and first trimester estrogen levels and pregnancy outcomes, further depicting an optimal concentration range to optimize pregnancy success. However, how estrogens co-operate with other factors in order to maintain a fine balance between local tolerance towards the developing fetus and immune responses to pathogens remains elusive. Further studies are highly warranted, also aiming to identify the determinants of estrogen response and biomarkers for personalized estrogen administration regimens in ART. [ABSTRACT FROM AUTHOR]

Estetrol (E4) is the most recently described natural estrogen. It is produced by the human fetal liver during pregnancy and its physiological function remains unclear. E4 is the estrogenic component of a recently approved combined oral contraceptive. It is also in development for use as menopausal hormone therapy. In the context of these developments, the pharmacological activity of E4, alone or in combination with a progestin, has been extensively characterized in preclinical models as well as in clinical studies in women of reproductive age and postmenopausal women. Despite the clinical benefits, the use of oral estrogens for contraception or menopause is also associated with unwanted effects, such as an increased risk of breast cancer and thromboembolic events, due to their impact on non-target tissues. Preclinical and clinical data for E4 point to a tissue-specific activity and a more selective pharmacological profile compared with other estrogens, including a low impact on the liver and hemostasis balance. This review summarizes the characterization of the pharmacological properties of E4 as well as recent advances made in the understanding of the molecular mechanisms of action driving its activity. How the unique mode of action and the different metabolism of E4 might support its favorable benefit–risk ratio is also discussed. [ABSTRACT FROM AUTHOR]

Copyright of Firat Tip Dergisi is the property of Firat University, Faculty of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Postmenopausal hyperandrogenism is a condition caused by relative or absolute androgen excess originating from the ovaries and/or the adrenal glands. Hirsutism, in other words, increased terminal hair growth in androgen-dependent areas of the body, is considered the most effective measure of hyperandrogenism in women. Other symptoms can be acne and androgenic alopecia or the development of virilization, including clitoromegaly. Postmenopausal hyperandrogenism may also be associated with metabolic disorders such as abdominal obesity, insulin resistance, and type 2 diabetes. Mild hyperandrogenic symptoms can be due to relative androgen excess associated with menopausal transition or polycystic ovary syndrome, which is likely the most common cause of postmenopausal hyperandrogenism. Virilizing symptoms, on the other hand, can be caused by ovarian hyperthecosis or an androgen-producing ovarian or adrenal tumor that could be malignant. Determination of serum testosterone, preferably by tandem mass spectrometry, is the first step in the endocrine evaluation, providing important information on the degree of androgen excess. Testosterone >5 nmol/L is associated with virilization and requires prompt investigation to rule out an androgen-producing tumor in the first instance. To localize the source of androgen excess, imaging techniques are used, such as transvaginal ultrasound or magnetic resonance imaging (MRI) for the ovaries and computed tomography and MRI for the adrenals. Bilateral oophorectomy or surgical removal of an adrenal tumor is the main curative treatment and will ultimately lead to a histopathological diagnosis. Mild to moderate symptoms of androgen excess are treated with antiandrogen therapy or specific endocrine therapy depending on diagnosis. This review summarizes the most relevant causes of hyperandrogenism in postmenopausal women and suggests principles for clinical investigation and treatment. [ABSTRACT FROM AUTHOR]

Amphiregulin (AREG) is an epidermal growth factor (EGF)-like growth factor that binds exclusively to the EGF receptor (EGFR). Treatment with luteinizing hormone (LH) and/or human chorionic gonadotropin dramatically induces the expression of AREG in the granulosa cells of the preovulatory follicle. In addition, AREG is the most abundant EGFR ligand in human follicular fluid. Therefore, AREG is considered a predominant propagator that mediates LH surge-regulated ovarian functions in an autocrine and/or paracrine manner. In addition to the well-characterized stimulatory effect of LH on AREG expression, recent studies discovered that several local factors and epigenetic modifications participate in the regulation of ovarian AREG expression. Moreover, aberrant expression of AREG has recently been reported to contribute to the pathogenesis of several ovarian diseases, such as ovarian hyperstimulation syndrome, polycystic ovary syndrome, and epithelial ovarian cancer. Furthermore, increasing evidence has elucidated new applications of AREG in assisted reproductive technology. Collectively, these studies highlight the importance of AREG in female reproductive health and disease. Understanding the normal and pathological roles of AREG and elucidating the molecular and cellular mechanisms of AREG regulation of ovarian functions will inform innovative approaches for fertility regulation and the prevention and treatment of ovarian diseases. Therefore, this review summarizes the functional roles of AREG in ovarian function and disease. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) and major depression (MD) are frequent diseases with a significant impact on the quality of life, and epidemiological studies show a correlation between early depressive episodes and AD. Although apparently different, they nonetheless maintain significant similarities, such as the common genetic substrate, involvement of similar structures, and a number of common pathogenetic hypotheses. This in-depth literature review aims at highlighting possible linkages between the two diseases: A chronic inflammatory process that selectively alters the blood-brain barrier in certain regions can be hypothesized. [ABSTRACT FROM AUTHOR]

Background: Reinke crystals are structures pathognomonic for Leydig cells, which have the important function of testosterone production and are vital for male reproductive health. These crystalline inclusions are thought to be of protein origin; however, the molecular composition has not yet been resolved. Objectives: This review summarizes all available information regarding Reinke crystal's characteristics and aims to produce a comprehensive guide for research on this topic as well as to determine and discuss potential Reinke‐protein candidates. Methods: Pubmed was thoroughly searched for all publications regarding Reinke crystals and 137 publications were identified. All publications were surveyed and all relevant information was included in the review. Results: Along with the cytoplasm, structures that resemble Reinke crystals were also observed in the nucleus, suggesting that their formation depends only on protein concentration. Variations in tissue processing protocols could impact Reinke crystal microscopic visualization, which is an important factor in diagnosing Leydig cell disorders such as Leydig cell tumors. Reinke crystals appear to be hallmarks of normally differentiated, adult, Leydig or Leydig‐like cells in humans, while some abnormal and nonhuman Leydig cells contain Reinke‐like paracrystalline inclusions or crystalloids. Conclusions: These characteristics point to some differentially expressed proteins, which could be involved in Reinke crystal formation. Differential Reinke crystal and paracrystalline inclusion presence could also be due to small changes in protein structure or the cell environment. Further research is needed to solve the ongoing mystery of the Reinke crystal, which would enhance our knowledge of Leydig cell contribution in the pathogenesis of various male reproductive disorders and improve their diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Summary: The production of high-quality embryos in the laboratory and a successful pregnancy are closely related to the condition and contents of oocyte and embryo culture media. In this study, we investigated the effects of embryonic stem cell-conditioned medium (ESCCM) and embryonic stem cells growth medium (ESCGM) compared with potassium-enriched simplex optimized medium (KSOM) on preimplantation embryo development stages during natural or in vitro fertilization (IVF). Birth rate of pups was measured. To obtain mature oocytes, and 2-cell and 8-cell embryos, human chorionic gonadotropin (HCG) was injected 48 h after i.p. injection of 5 units of pregnant mare serum gonadotropin. Mature oocytes were obtained from non-mated female mice 14 h after HCG injection. To obtain 2-cell and 8-cell embryos, mated female mice, 1 day and 3 days, respectively, after HCG injection, were used. Mature oocytes were fertilized in HTF medium. Embryos obtained from natural or in vitro fertilization were cultured in experimental media, ESCCM and ESCGM, or KSOM as the control culture medium. Embryos that developed to the blastocyst stage were transferred to the uteri of pseudopregnant mice and effects of the experimental media on embryo viability were determined. ESCCM and ESCGM could not pass the embryo after the 2-cell stage, but they were suitable for the development of the embryo from the 8-cell stage to the blastocyst. It can be concluded that the embryo has various requirements at different stages of development. [ABSTRACT FROM AUTHOR]

Sertoli-Leydig cell tumours (SLCTs) represent a rare cause of hyperandrogenic state. SLCTs are sex cord ovarian neoplasms, accounting for <0.2% of all ovarian tumours. Most of the sex cord-stromal tumours have a benign clinical course, with 10%–20% of them at risk of aggressive course. We report a case of a woman in her 30s who presented with androgenic alopecia, virilisation and secondary amenorrhoea. The evaluation revealed an extremely high testosterone level. Imaging for the localisation of source of excess testosterone with contrast-enhanced CT of the abdomen revealed a right ovarian mass. Hence, a diagnosis of testosterone-secreting ovarian tumour was considered. The patient underwent right salphingo-oophorectomy, and histopathology was reported as Sertoli cell tumour. Postoperatively, there was normalisation of serum testosterone levels with decrease in virilisation and resumption of spontaneous menstrual cycles. The patient conceived spontaneously after 2 months of surgery. [ABSTRACT FROM AUTHOR]

Background: The clitoris is the primary somatosensory organ of female sexual response. Knowledge of its neural anatomy and related landmarks is essential for safe genital surgery.Objectives: The aim of this study was to describe the distal course of the dorsal nerves of the clitoris and associated structures.Methods: Clitorises of 10 fresh cadavers were dissected. Measurements of the dorsal nerves, suspensory ligament, clitoral body, clitoral hood, and clitoral glans were obtained. The course of the dorsal nerves was examined.Results: The dorsal nerves of the clitoris were larger than expected, ranging from 2.0 to 3.2 mm in diameter, on average, along their course in the clitoral body. In 9 of 10 specimens, the dorsal nerves could be traced to within 6 mm of the glans. They traveled deep to a superficial clitoral fascia but superficial to the tunica albuginea, were variably located between 10 and 2 o'clock, and were separated by the deep suspensory ligament (DSL) of the clitoris. The mean length of the descending clitoral body, from the angle to the base of the glans, was 37.0 mm. The mean distance from the pubic rim to the DSL was 37.7 mm.Conclusions: The clitoral body is substantial in length, mostly lying superficially under the clitoral hood and mons pubis. The dorsal nerves of the clitoris are large and superficial, terminating at or near the base of the clitoral glans. Knowledge of this anatomy is critical prior to performing surgery near the clitoris. [ABSTRACT FROM AUTHOR]

Vaginal lubricants are commonly used by couples trying-to-conceive. However, most vaginal lubricants are sperm toxic and therefore should not be used by couples trying-to-conceive. Despite this, lubricant sperm toxicity is insufficiently reported and guidance for healthcare professionals (HCPs) is absent. In this study, lubricant-related practices of fertility-based HCPs in Scotland were sampled via an online survey. Lubricants identified as being utilised in the fertility setting were subsequently incubated with prepared sperm samples to establish effects on sperm motility. HCP recommendations (n = 32) on lubricant use were varied although knowledge related to sperm toxicity was generally poor. HCPs infrequently asked about lubricant use and were unaware of guidance in this area. Aquagel, the only prescribed lubricant identified in this study, reduced sperm progressive motility to 49% of control after 10 minutes, even at concentrations as low as 5%. Vitality testing suggested the deterioration in progressive motility with Aquagel was not as a result of cell death. Conversely, Pré Vaginal Lubricant, a ‘sperm-safe’ lubricant, did not significantly affect any markers of sperm function assessed. Development of clinical guidance in this area is recommended to ensure HCPs deliver informed advice as lubricant use in couples trying-to-conceive may inadvertently contribute to delay in conception. [ABSTRACT FROM AUTHOR]

Aim: Recently, it is widely recognized that positivity for anti‐phospholipid antibodies is a causative factor for a range of reproductive failures. Anti‐cardiolipin beta2 glycoprotein I antibody (anti‐CL‐beta2‐GPI) is a representative anti‐phospholipid antibody, which strongly correlates with the development of thrombotic events and diversity of adverse pregnancies. In this series, we aimed to elucidate effective treatment for patients with recurrent fetal losses positive for anti‐CL‐beta2‐GPI using Japanese‐modified Chinese herbal medicine. Methods: Twenty‐one patients with recurrent fetal losses who were positive for anti‐CL‐beta2‐GPI were treated with the Japanese‐modified Chinese herbal medicine, Sairei‐to (Chai‐ling‐tang), and low‐dose aspirin with or without adrenal corticosteroid hormone. Of the 21 patients, the value of anti‐CL‐beta2‐GPI ranged from 1.9 to 3.4 in 10 patients, and it was over 3.5 in 11 patients. Results: Of the 21 patients treated with the current protocol, the pregnancy successfully continued in 17 patients (success rate: 81.0%). Of the four patients who showed repeated abortion, chromosome abnormality of chorionic villi was observed in two; thus, the success rate would be 89.5% (17 of 19 cases) on excluding these cases from the evaluation. Conclusion: The efficacy of the current treatment adopting the modified Japanese version of the Chinese herbal medicine Sairei‐to for patients with recurrent fetal losses positive for anti‐CL‐beta2‐GPI was indicated. [ABSTRACT FROM AUTHOR]

Objective: To assess the extent to which lubricant use during intercourse is associated with time to pregnancy (TTP). Design: Prospective cohort study. Setting: Denmark and North America. Population: A total of 6467 women aged 18–49 years who were not using contraception or fertility treatment. Methods: We pooled data from two continuing prospective cohort studies of pregnancy planners in Denmark (2011–2017) and North America (2013–2017). Female participants completed bimonthly questionnaires for 12 months or until they reported pregnancy. After restricting the study to women without a history of infertility who had been trying to conceive for six or fewer cycles at enrollment, 6467 women were retained for analysis. Self‐reported lubricant use was categorised as water‐based/not pH balanced, water‐based/pH balanced 'fertility friendly', silicone‐based, oil‐based, or a combination of these. We used proportional probability models to calculate fecundability ratios (FRs) and 95% confidence intervals (95% CIs) for the association between lubricant use and fecundability, after adjusting for cohort and sociodemographic and lifestyle factors. Main outcome measure: Fecundability. Results: At baseline, 17.5% of participants reported the use of lubricants, most commonly water‐based/not pH balanced (11.4%). Compared with non‐use of lubricants, FRs were 1.02 (95% CI 0.93–1.11) for water‐based/not pH‐balanced lubricant use, 1.01 (95% CI 0.86–1.18) for water‐based/pH balanced 'fertility friendly' lubricant use, 1.23 (95% CI 0.94–1.61) for oil‐based lubricant use, and 1.27 (95% CI 0.93–1.73) for silicone‐based lubricant use. Associations between oil‐based lubricant use and fecundability were inconsistent across subgroups of study cohort, age, parity, and intercourse frequency. Conclusions: Lubricant use was not associated with reduced fecundability in the preconception cohorts of pregnancy planners studied. Lubricant use during intercourse was not associated with time to pregnancy in a study of pregnancy planners. Lubricant use during intercourse was not associated with time to pregnancy in a study of pregnancy planners. [ABSTRACT FROM AUTHOR]

Summary: The high miscarriage rates that result following transfer of embryos derived from in vitro maturation (IVM) of oocytes necessitate improvements in the processes involved. This study aimed to improve the quality of in vitro matured oocytes using granulosa cell conditioned medium (GCCM) as the culture medium. In this work, germinal vesicle (GV)-stage oocytes from NMRI mice were collected and cultured using three types of culture medium: Base medium (BM) (control), 50% granulosa cell conditioned medium (GCCM50) and 100% GCCM (GCCM100). After IVM, the mitochondria activity potential and viability of metaphase II (MII) oocytes were evaluated by JC-1 and trypan blue staining, respectively. Maturational gene expression levels of CyclinB1 , Cdk1 and Gdf9 in the control, GCCM50 and GCCM100 samples were analyzed using real-time polymerase chain reaction (PCR). The viability rate of in vitro matured oocytes was highest in the GCCM50 group. JC-1 staining showed that GCCM50 enhances mitochondrial activity more than the other groups (P < 0.05). Gene expression levels of Cdk1 and Gdf9 were higher in the group with GCCM50 treatment, than in the control and GCCM100 groups (P < 0.05), while the expression level of CyclinB1 did not differ among the groups. The results indicated that a 50% concentration of GCCM in combination with BM components enhanced MII and viability rates and mitochondria activity of mouse immature oocytes. [ABSTRACT FROM AUTHOR]

Summary: Parabens are used as antimicrobial preservative agent in many commercial products including cosmetics and pharmaceuticals. Weak oestrogenic and antiandrogenic activities have been attributed to parabens in in vitro and in vivo studies. In this study, human spermatozoa were exposed to different concentrations of an equimolar paraben mixture containing methyl, ethyl, propyl and butylparaben as well as to methylparaben alone at a concentration that is typical of commercially available vaginal lubricants. The induction of oxidative stress and DNA damage was then assessed at different time points. Our results demonstrate that the paraben mixture was capable of stimulating the generation of mitochondrial and cytosolic reactive oxygen species (ROS), inhibiting sperm motility and viability in a dose‐dependent manner. The ability of individual parabens to activate ROS generation and induce oxidative DNA damage was related to alkyl chain length. At the concentration used clinically, methylparaben inhibited sperm motility after both 2 and 5 h exposure (p < 0.05) and affected cell viability (p < 0.01) while augmenting ROS production and oxidative DNA damage. However, DNA fragmentation was not evident following methylparaben exposure. Based on these results, we conclude that, at the concentrations used in commercially available formulations, parabens may impair sperm motility, enhance the generation of mitochondrial ROS and stimulate the formation of oxidative DNA adducts. Taken together, these data underline the potential cytotoxic and genotoxic impact of such compounds in a clinical setting. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Obstetrics & Gynecology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: We have identified a non‐steroidal selective androgen receptor modulator (SARM), termed LY305, that is bioavailable through a transdermal route of administration while highly cleared via hepatic metabolism to limit parent compound exposure in the liver. Selection of this compound and its transdermal formulation was based on the optimization of skin absorption properties using both in vitro and in vivo skin models that supported PBPK modeling for human PK predictions. This molecule is an agonist in perineal muscle while being a weak partial agonist in the androgenic tissues such as prostate. When LY305 was tested in animal models of skeletal atrophy it restored the skeletal muscle mass through accelerated repair. In a bone fracture model, LY305 remained osteoprotective in the regenerating tissue and void of deleterious effects. Finally, in a small cohort of healthy volunteers, we assessed the safety and tolerability of LY305 when administered transdermally. LY305 showed a dose‐dependent increase in serum exposure and was well tolerated with minimal adverse effects. Notably, there were no statistically significant changes to hematocrit or HDL after 4‐week treatment period. Collectively, LY305 represents a first of its kind de novo development of a non‐steroidal transdermal SARM with unique properties which could find clinical utility in hypogonadal men. [ABSTRACT FROM AUTHOR]

Background: The LH surge induces great physiological changes within the preovulatory follicle, which culminate in the ovulation of a mature oocyte that is capable of supporting embryo and foetal development. However, unlike mural granulosa cells, the oocyte and its surrounding cumulus cells are not directly responsive to LH, indicating that the LH signal is mediated by secondary factors produced by the granulosa cells. The mechanisms by which the oocyte senses the ovulatory LH signal and hence prepares for ovulation has been a subject of considerable controversy for the past four decades. Within the last 15 years several significant insights have been made into the molecular mechanisms orchestrating oocyte development, maturation and ovulation. These findings centre on the epidermal growth factor (EGF) pathway and the role it plays in the complex signalling network that finely regulates oocyte maturation and ovulation.Objective and Rationale: This review outlines the role of the EGF network during oocyte development and regulation of the ovulatory cascade, and in particular focuses on the effect of the EGF network on oocyte developmental competence. Application of this new knowledge to advances in ART is examined.Search Methods: The PubMed database was used to search for peer-reviewed original and review articles concerning the EGF network. Publications offering a comprehensive description of the role of the EGF network in follicle and oocyte development were used.Outcomes: It is now clear that acute upregulation of the EGF network is an essential component of the ovulatory cascade as it transmits the LH signal from the periphery of the follicle to the cumulus-oocyte complex (COC). More recent findings have elucidated new roles for the EGF network in the regulation of oocyte development. EGF signalling downregulates the somatic signal 3'5'-cyclic guanine monophosphate that suppresses oocyte meiotic maturation and simultaneously provides meiotic inducing signals. The EGF network also controls translation of maternal transcripts in the quiescent oocyte, a process that is integral to oocyte competence. As a means of restricting the ovulatory signal to the Graffian follicle, most COCs in the ovary are unresponsive to EGF-ligands. Recent studies have revealed that development of a functional EGF signalling network in cumulus cells requires dual endocrine (FSH) and oocyte paracrine cues (growth differentiation factor 9 and bone morphogenetic protein 15), and this occurs progressively in COCs during the last stages of folliculogenesis. Hence, a new concept to emerge is that cumulus cell acquisition of EGF receptor responsiveness represents a developmental hallmark in folliculogenesis, analogous to FSH-induction of LH receptor signalling in mural granulosa cells. Likewise, this event represents a major milestone in the oocyte's developmental progression and acquisition of developmental competence. It is now clear that EGF signalling is perturbed in COCs matured in vitro. This has inspired novel concepts in IVM systems to ameliorate this perturbation, resulting in improved oocyte developmental competence.Wider Implications: An oocyte of high quality is imperative for fertility. Elucidating the fundamental molecular and cellular mechanims by which the EGF network regulates oocyte maturation and ovulation can be expected to open new opportunities in ART. This knowledge has already led to advances in oocyte IVM in animal models. Translation of such advances into a clinical setting should increase the efficacy of IVM, making it a viable treatment option for a wide range of patients, thereby simplifying fertility treatment and bringing substantial cost and health benefits. [ABSTRACT FROM AUTHOR]

Several lines of evidence showed that apoptosis rate of cumulus cells in oocytes derived by assisted reproductive technologies could be used as an indicator of fertilizing gamete quality. Aim of the study was to investigate the effects of three different ovarian stimulation protocols on the biological and clinical outcome in hyporesponder patients. Collected data showed a higher significant rate of DNA fragmentation index (DFI) in U group (patients treated with Highly Purified human Menopausal Gonadotrophin) than in P group (treated with recombinant human Follicle Stimulating Hormone (r-hFSH) combined with recombinant human Luteinizing Hormone (r-hLH)). Both groups R (treated with r-hFSH alone) and P showed a significant increase in collected and fertilized oocytes number, embryo quality number. This study showed that combined r-hFSH/r-hLH therapy could represent the best pharmacological strategy for controlled ovarian stimulation and suggests to use DFI as a biomarker of ovarian function in hyporesponder patients. [ABSTRACT FROM AUTHOR]

This contribution summarizes the pivotal role of the ovarian renin–angiotensin system (OVRAS) in ovarian physiology and disease, with particular emphasis on human clinical implications and established translational applications. The presence of a complete OVRAS in all studied species has been known for decades. The OVRAS has major effects on follicle development/atresia and ovulation and steroid hormone secretion, that is, it is necessary for normal reproduction. It is well established that OVRAS activity is regulated by gonadotropins and depends on activation of proteases in the area of growing follicles. Angiotensin and angiotensin receptors are widely distributed in the ovarian follicle, preovulatory theca and granulosa cells, and postovulatory mural granulosa-lutein cells and regulate steroidogenesis. Molecular blockade of the OVRAS inhibits oocyte maturation and ovulation. Pathologically abnormal OVRAS function has been associated with infertility, polycystic ovarian syndrome (PCOS), ovarian hyperstimulation syndrome (OHSS), and ovarian cancer. Both hyperandrogenism in PCOS and third space fluid accumulation in OHSS have been convincingly linked to overexpression of renin and angiotensin. Blockade of angiotensin receptors is under study for the treatment of gynecologic cancer, OHSS, and PCOS. However, a full understanding of the OVRAS and translational applications is lacking. In part, this is due to the discovery in recent years of previously unknown renin–angiotensin system (RAS) components and novel functions of “classical” RAS components that remain to be integrated into translational studies; newer, more specific agents to block RAS components are available only now for such research and treatment. The need for further studies is evident. [ABSTRACT FROM AUTHOR]

Aim: Clitoral size references are useful for diagnosing genital abnormalities. Despite the fact that examining the genitalia is an important aspect of newborn evaluation, few studies have been carried out to determine normal clitoral size in newborn infants. The aim of this study was to establish reference values for clitoral size in Nigerian newborn girls and to compare them with references from other ethnic populations.Methods: A total of 244 healthy newborn girls delivered at 28-43 weeks gestation were enrolled in the study, and clitoral lengths and widths were measured at <72 hours.Results: The mean clitoral length was 7.7 mm with a standard deviation of ±1.37 mm, while the mean clitoral width was 4.40 ± 0.89 mm. The clitoral length was significantly longer than those reported for Caucasian (4.00 ± 1.24 mm), Korean (3.82 ± 1.47), Turkish (4.93 ± 1.61) and Japanese (4.30 ± 1.10) babies.Conclusion: The present results make it possible to evaluate clitoral size in Nigerian newborn baby girls in an objective way, to identify genital abnormalities and endocrine disorders. Based on this study, a clitoral length of more than 10 mm would be considered clitoromegaly in a newborn girl in Nigeria. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Accurate and comprehensive measurements of the external genitalia in female adults are of great significance in surgery designs and for aesthetic evaluation in genital plastic surgeries. The authors carried out a 319-case study and provided baseline data and morphometric reference for plastic surgery involving the genital deformity caused by trauma or burns and male-to-female transsexual operations. Methods: Our study design recruited 319 women referred to the out-patient clinic from August 2010 to August 2013. From each individual we measured 16 parameters and assessed the significance of variations in age, height, weight, BMI, and marital status (as a proxy for parity). We tried to establish a female external genitalia database of the population presenting for cosmetic surgery and define the general proportions of female genitalia in Chinese adults from the data we obtained. Results: A wide range of values was noted in female genital measurements especially in labia minora parameters. Four parameters, including clitoral prepuce length, clitoris to urethra, labial length, and perineal body length had a proportional relationship to some extent. The position of the clitoris and urethral orifice was found to be regular in female adults. Compared with unmarried women, perineal body length decreased ( P = 0.048), while the apex to perineum (bilateral) and labial length increased ( P = 0.005, 0.006, <0.0001) in those who were married. Several parameters were statistically significantly associated with age, height, weight, BMI, and marital status. Conclusions: We presented an external genitalia database of Chinese female adults asking for cosmetic surgery. Although the ranges of genital measurements vary, there is a proportional relationship in female genital appearance, which should be heeded in surgical designs and genital aesthetic evaluation. [ABSTRACT FROM AUTHOR]

Aims To investigate the immunohistochemical properties of the sex cord cells of gonadoblastoma and Sertoli cell nodule with intratubular germ cell neoplasia unclassified ( IGCNU) as a means of objective distinction and to provide insight into the pathogenesis. Methods and results Immunohistochemical stains for SOX9, Fox L2 and SF-1 were performed on 10 gonadoblastomas (all phenotypical females) and 14 Sertoli cell nodules with IGCNU in normal phenotypical males with coexisting germ cell tumours. The sex cord cells of gonadoblastomas showed strong, diffuse Fox L2 and SF-1 positivity and focal weak to moderate SOX9 reactivity, whereas those of Sertoli cell nodules with IGCNU were uniformly, strongly positive for SOX9 and SF-1, while negative for Fox L2. Conclusions Coexpression of SOX9 and Fox L2 in the sex cord cells of gonadoblastomas provides evidence that these morphologically ambiguous sex cord cells are incompletely differentiated. The strong, diffuse SOX9 and SF-1 positivity and absence of Fox L2 reactivity in the Sertoli cell nodules with IGNCU support full Sertoli cell differentiation of the sex cord cells and distinguish them from gonadoblastomas. Deficient SOX9 expression in gonadoblastoma supports a current model of pathogenesis where immature germ cells, in the absence of well-formed Sertoli cells, retain a fetal phenotype and susceptibility to malignant transformation. [ABSTRACT FROM AUTHOR]

Introduction: A large proportion of women around the world suffer from chronic diseases including mental health diseases. In the United States alone, over 12% of women of reproductive age suffer from a chronic medical condition, especially diabetes and hypertension. Chronic diseases significantly increase the odds for poor maternal and newborn outcomes in pregnant women. Methods: A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for preventing and managing chronic diseases and promoting psychological health on maternal, newborn and child health outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture. Results: Maternal prepregnancy diabetic care is a significant intervention that reduces the occurrence of congenital malformations by 70% (95% Confidence Interval (CI): 59-78%) and perinatal mortality by 69% (95% CI: 47-81%). Furthermore, preconception management of epilepsy and phenylketonuria are essential and can optimize maternal, fetal and neonatal outcomes if given before conception. Ideally changes in antiepileptic drug therapy should be made at least 6 months before planned conception. Interventions specifically targeting women of reproductive age suffering from a psychiatric condition show that group-counseling and interventions leading to empowerment of women have reported non-significant reduction in depression (economic skill building: Mean Difference (MD) -7.53; 95% CI: -17.24, 2.18; counseling: MD-2.92; 95% CI: -13.17, 7.33). Conclusion: While prevention and management of the chronic diseases like diabetes and hypertension, through counseling, and other dietary and pharmacological intervention, is important, delivering solutions to prevent and respond to women’s psychological health problems are urgently needed to combat this leading cause of morbidity. [ABSTRACT FROM AUTHOR]

Background Although highly controversial, the treatment of obesity with exogenous human chorionic gonadotropin ( HCG) remains popular in the USA. We report the case of a patient whose first manic episode was associated with the use of HCG for weight loss. Case report A 32-year-old female patient was admitted to our psychiatric inpatient unit due to a two-week history of manic symptoms. She had no previous history of manic or hypomanic episodes and had completed a 45-day course of sublingual HCG for weight loss immediately prior to the onset of the manic episode. The patient was treated with lithium carbonate and aripiprazole, and progressed with improvement in the symptoms. Conclusion While it is not possible to definitively link the HCG use to the development of mania, available evidence suggests that HCG may have a contributing role in triggering manic symptomatology. [ABSTRACT FROM AUTHOR]

Different culture system conditions can affect cleavage, zygote genome activation, embryo development, and viability. The purpose of the present study was to compare a monoculture synthetic oviductal fluid medium with modified sequential G1/G2 media and also to investigate the effect of epidermal growth factor (EGF) on bovine embryo development. Oocytes were aspirated from 2- to 6-mm ovarian follicles and matured in maturation media. After in vitro fertilization of matured oocytes, presumptive zygotes were cultured in test media with or without additional exogenous EGF. Results indicated that EGF significantly increased blastocyst formation but not cleavage rate in both media. There was no significant difference between the sequential and the monoculture media. [ABSTRACT FROM AUTHOR]

Purpose: Only 30 % of IVF cycles result in a pregnancy, so that multiple embryos need to be replaced, per treatment cycle, to increase pregnancy rates, resulting in a multiple gestation rate of 25 %. The use of new markers in the gamete selection, could reduce the number of the oocytes to be fertilized and embryos to be produced, but the tools to evidence the gamete competence remain unavailable and more studies are needed to identify bio-markers to select the best oocyte and sperm to produce embryos with higher implantation potentiality. Methods: To define oocyte competence, the apoptosis of the surrounding cumulus cells and the oxygen consumption rates for individual oocytes before fertilization seems to provide a non-invasive marker of oocyte competence and hence a quantitative assessment of the reproductive potential for the oocyte. The chromatin integrity seems to be used also as biological marker of sperm competence, together with the morphological evaluation of large vacuoles in the head. Results: The apoptosis rate of cumulus cells lower than 25 % and an higher oxygen consumption could be an evidence of an overall metabolic activity, related to a better fertilization ability and embryo cleavage quality. The apoptosis rate of the sperm chromatin, evaluated by direct Tunel in situ analysis, seems to be, also for the male gamete, a marker of competence and implantation potentiality, in particular when it is lower than 20 %. The evaluation of the presence of large vacuoles in the sperm head prior to perform ICSI seems to increase the implantation rate, but it is not associated to chromatin integrity. Conclusions: The biological concept of competence appears unrelated to any morphological parameters, so that it is necessary to investigate new molecular markers in the gamete selection. Apoptosis of cumulus cells in the oocytes and spermatozoa, revealing the presence of large vacuoles, could help to determine the competence of the gamete to be fertilize. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosis (SLE) commonly affects women of child bearing-age, and advances in treatment have resulted in an increasing number of women with renal involvement becoming pregnant. Knowledge of the relationship of the condition with respect to fertility and pregnancy is important for all clinicians involved in the care of women with lupus nephritis because they have complicated pregnancies. Presentation of lupus nephritis can range from mild asymptomatic proteinuria to rapidly progressive renal failure and may occur before, during, or after pregnancy. The timing of diagnosis may influence pregnancy outcome. Pregnancy may also affect the course of lupus nephritis. All pregnancies in women with lupus nephritis should be planned, preferably after more than six-months of quiescent disease. Predictors of poor obstetric outcome include active disease at conception or early pregnancy, baseline poor renal function with Creatinine >100 μmol/L, proteinuria >0.5 g/24 hours, presence of concurrent antiphospholipid syndrome and hypertension. In this review the most recent studies of pregnancies in women with lupus nephritis are discussed and a practical approach to managing women prepregnancy, during pregnancy and post-partum is described [ABSTRACT FROM PUBLISHER]

BACKGROUND Human cloned blastocysts generated from oocytes following in vitro maturation (IVM) are a potential resource for embryonic stem cells (ESC) with homologous immune systems. The purpose of this study was to evaluate the effects of multiple growth factors [epidermal growth factor (EGF), brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1)] on human oocyte maturation, early embryo development, blastocyst formation and ESC line generation. METHODS Patients (n= 344) undergoing IVF owing to male factor infertility were enrolled in this study. Metaphase II oocytes were separated into four grades based on their morphology. Spindle assembly from IVM oocytes with or without growth factor treatment was assessed by immunostaining. Piezo-assisted micromanipulation technology was used to produce fertilized (ICSI) and cloned [(somatic cell nuclear transfer (SCNT)] embryos. Embryos received four different growth factor treatments; embryo development rates from pronuclear to blastocyst stage and embryo grading (for quality) at the 8-cell stage were analyzed. The presence of receptors on human cumulus cells and IVM oocytes was assessed by immunofluorescence. The blastocysts generated from fertilized and cloned embryos were used for ESC derivation. RESULTS The combination of EGF, BDNF and IGF-1 can effectively increase oocyte maturation rate in vitro, and significantly improve the oocyte quality in terms of morphology and normal spindle levels (P< 0.05). Also, the developmental competence of fertilized oocytes to 8-cell and blastocyst stages was improved by the addition of growth factors (P< 0.05). However, there were no significant differences among the four groups in 8-cell grading. Blastocyst formation in cloned embryos cultured with the three growth factors was higher than the control group (23.1 versus 4.3%, P< 0.05). Receptors for the three growth factors were present in cumulus cells and IVM oocytes, and four human ESC lines were derived from fertilized blastocysts but none from cloned blastocysts. CONCLUSION This study demonstrated that EGF, BDNF and IGF-1 can improve oocyte maturation rate and quality in vitro, and consequently increase early embryo development and blastocyst formation, which is very beneficial in improving the reprogramming efficiency of SCNT. The present study has identified a valuable culture system for IVM and cloned human embryos, potentially using these embryos to derive human therapeutic ESC. [ABSTRACT FROM AUTHOR]

Summary Chlamydia trachomatis is an important bacterial cause of infertility. In men, the recommended specimen for diagnosing chlamydial infection is urine, with little or no emphasis placed on testing semen. A systematic review of the literature was conducted to search for studies in which men undergoing investigations for infertility produced both samples of urine and semen that were tested concurrently for C. trachomatis. An analysis of these studies was then performed. From 322 papers identified from the US National Library of Medicine PubMed database, 14 were selected for a detailed review and 11 were analysed further. Overall, the size of the study groups was only modest and differences between the studies included variation in geography and test methodology, especially whether commercial testing systems had been used. There was also a lack of consistency with regard to including men with azoospermia. Patients were typically 30-35 years old and the median duration of infertility was about 4 years. Of those patients positive for C. trachomatis in the 11 studies, 56% could be detected in both semen and urine, 20% only in urine and 23% only in semen. Deficiencies in existing studies would not allow for a meta-analysis, emphasizing the need for further research in this area for which a number of recommendations are made. [ABSTRACT FROM AUTHOR]

In most mammals, oocyte maturation is the final process of oogenesis, from the prophase of the first meiosis (germinal vesicle stage) to the metaphase of the second meiosis (MII), during which the oocyte acquires fertilizable competence as well as post-fertilization development competence. The nuclear and cytoplasmic maturation processes occur in synchrony but independently. Cytoplasmic maturation entails biochemical and structural changes in the cytoplasm, which give rise to oocytes capable of being fertilized and developing into embryos. Herein we review the literature and results from our own experiments on the structural and molecular events regulating cytoplasmic maturation in oocytes, concentrating on (1) the appropriate reorganization of active mitochondria and the endoplasmic reticulum, a structural and functional feature of cytoplasmic maturation, and (2) factors involved in regulatory mechanisms such as cumulus cell-oocyte gap junctional signaling, cumulus cell-oocyte bidirectional paracrine signaling, and the complex interactions of these signaling processes and follicular fluid constituents in the follicle environment. [ABSTRACT FROM AUTHOR]

BACKGROUND In vitro maturation (IVM) of oocytes is a promising technique to reduce the costs and avert the side effects of gonadotrophin stimulation for IVF. The pregnancy rates from oocytes matured in vitro are still lower than those of in vivo stimulation cycles, indicating that optimization of IVM remains a challenge. Recently, it was demonstrated that LH exerts its action on ovulation, at least in part, through stimulation of the production of the epidermal growth factor family members amphiregulin (Areg) and epiregulin (Ereg) in pre-ovulatory follicles, and they, in turn, serve as paracrine mediators of LH. We aimed to investigate the effect of supplementation of the medium with Areg and Ereg on the maturation rate of immature oocytes. METHODS A total of 105 sibling human germinal vesicle (GV) oocytes obtained after gonadotrophin stimulation were cultured in a complex defined medium either with or without supplemented recombinant human Areg (75 ng/ml) and Ereg (75 ng/ml) for 24 h. RESULTS Significantly more oocytes reached the metaphase II stage at 24 h in media supplemented with Areg and Ereg (75.5 versus 36.5%, P < 0.001). In vitro matured oocytes retrieved from the two subgroups had no statistically significant difference in fertilization and cleavage rates or morphology scores. Overall, a significantly higher number of Day 2 (52.8 versus 26.9% P < 0.01) and Day 3 (45.2 versus 23%, P < 0.05) embryos originated from GV oocytes cultured in the Areg- and Ereg-enriched medium. CONCLUSIONS Supplementation of the maturation medium with Areg and Ereg improves the maturation of human GV oocytes in vitro. [ABSTRACT FROM AUTHOR]

BACKGROUND Polycystic ovary syndrome (PCOS) is a common metabolic dysfunction and heterogeneous endocrine disorder in women of reproductive age. Although patients with PCOS are typically characterized by increased numbers of oocytes retrieved during IVF, they are often of poor quality, leading to lower fertilization, cleavage and implantation rates, and a higher miscarriage rate. METHODS For this review, we searched the database MEDLINE (1950 to January 2010) and Google for all full texts and/or abstract articles published in English with content related to oocyte maturation and embryo developmental competence. RESULTS The search showed that alteration of many factors may directly or indirectly impair the competence of maturating oocytes through endocrine and local paracrine/autocrine actions, resulting in a lower pregnancy rate in patients with PCOS. The extra-ovarian factors identified included gonadotrophins, hyperandrogenemia and hyperinsulinemia, although intra-ovarian factors included members of the epidermal, fibroblast, insulin-like and neurotrophin families of growth factors, as well as the cytokines. CONCLUSIONS Any abnormality in the extra- and/or intra-ovarian factors may negatively affect the granulosa cell–oocyte interaction, oocyte maturation and potential embryonic developmental competence, contributing to unsuccessful outcomes for patients with PCOS who are undergoing assisted reproduction. [ABSTRACT FROM AUTHOR]

Background: The LH surge promotes ovulation via activation of multiple signaling networks in the ovarian follicle. Studies in animal models have shown the importance of LH-induced activation of the epidermal growth factor (EGF)signaling network in critical peri-ovulatory events. We investigated the biological significance of regulatory mechanisms mediated by EGF-like growth factors during LH stimulation in humans.Methods: We characterized the EGF signaling network in mature human ovarian follicles using in vivo and in vitro approaches. Amphiregulin (AREG) levels were measured in 119 follicular fluid (FF) samples from IVF/ICSI patients. Biological activity of human FF was assessed using in vitro oocyte maturation, cumulus expansion and cell mitogenic assays.Results: AREG is the most abundant EGF-like growth factor accumulating in the FF of mature follicles of hCG-stimulated patients. No AREG was detected before the LH surge or before hCG stimulation of granulosa cells in vitro, demonstrating that the accumulation of AREG requires gonadotrophin stimulation. Epiregulin and betacellulin mRNA were detected in both human mural and cumulus granulosa cells, although at significantly lower levels than AREG. FF from stimulated follicles causes cumulus expansion and oocyte maturation in a reconstitution assay. Immunodepletion of AREG abolishes the ability of FF to stimulate expansion (P < 0.0001) and oocyte maturation (P < 0.05), confirming the biological activity of AREG. Conversely, mitogenic activity of FF remained after depletion of AREG, indicating that other mitogens accumulate in FF. FF from follicles yielding an immature germinal vesicle oocyte or from an oocyte that develops into an aberrant embryo contains lower AREG levels than that from follicles yielding a healthy oocyte (P = 0.008).Conclusions: EGF-like growth factors play a role in critical peri-ovulatory events in humans, and AREG accumulation is a useful marker of gonadotrophin stimulation and oocyte competence. [ABSTRACT FROM AUTHOR]

Background: This is the first study of the effect of epidermal growth factor (EGF) on marmoset monkey oocytes matured in vitro. Methods: We have evaluated the effects of 10 ng/ml EGF in combination with 1 or 10 IU/ml of gonadotrophins (FSH/hCG 1:1 ratio) during in vitro maturation (IVM) of marmoset oocytes. Immature cumulus-oocyte complexes (COCs) were retrieved from ovarian antral follicles of unprimed monkeys. COCs from six animals (n= 268) used in this study were randomly distributed among four experimental groups: (A) 1 FSH +1 hCG; (B) 10 FSH +10 hCG; (C) 1 FSH +1 hCG + EGF; and (D) 10 FSH +10 hCG + EGF (where 1 and 10 are concentrations, IU/ml). After IVM, oocytes were fertilized in vitro and embryos were allowed to progress up to 87-88 h. Results: the highest rate of total and radial cumulus expansion was observed in Group A, with the lowest in Group B (P < 0.05). Neither maturation nor fertilization rate were affected by gonadotrophin concentration or presence of EGF. Addition of EGF increased degeneration and decreased first cleavage rate, which was significantly lower in Group C than Group A (P < 0.005). Interestingly, in the EGF groups some embryos cleaved faster than without EGF. Conclusions: The effects of EGF are highly dependent on concentration of gonadotrophins present in IVM medium. EGF has a negative effect on oocytes in the presence of low gonadotrophins, but contrastingly partially protects oocytes from the negative effects of high gonadotrophins. We propose that these observed negative effects of EGF may suggest use of an inappropriate dose of growth factor. [ABSTRACT FROM AUTHOR]