Search

Introduction: Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disturbance that affects many women worldwide and is characterized by chronic anovulation, hyperandrogenism, and ovarian dysfunction. Placenta-derived mesenchymal stem cells (PDMSCs) are derived from the placenta and have advantages over other sources of MSCs in terms of availability, safety, and immunomodulation. Materials and methods: In this experimental study, twenty female Wistar rats were assigned to four groups (n = 5) including control, sham, PCOS, and PCOS+PDMSCs groups. Then, PCOS was induced in the rats through administering letrozole for 21 days. PDMSCs (1 × 106 cells) were injected through the tail vein. Fourteen days after the cell infusion, evaluation was performed on the number of healthy follicles, corpus luteum, and cystic follicles as well as the levels of testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), fasting blood glucose, fasting insulin, and insulin resistance. Moreover, the serum levels of cholesterol, triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were measured. Liver function was also determined by the evaluation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Results: The number of corpus luteum and primordial, primary, secondary, and antral follicles was significantly elevated in the PCOS+PDMSCs group compared to the PCOS group. However, the number of cystic follicles significantly decreased in the PCOS+PDMSCs group. The LH and testosterone levels also decreased significantly, while FSH levels increased significantly in the PCOS+PDMSCs group. The levels of fasting blood glucose, fasting insulin, and insulin resistance notably decreased in the PCOS+PDMSCs group. Moreover, the lipid profile improved in the PCOS+PDMSCs group along with a significant decrease of cholesterol, LDL, and TG and an increase in HDL. The PCOS+PDMSCs group exhibited marked decreases in the AST and ALT levels as well. Conclusion: The results of this study suggest that PDMSCs are a potential treatment option for PCOS because they can effectively restore folliculogenesis and correct hormonal imbalances, lipid profiles and liver dysfunction in a rat model of PCOS. However, further research is needed to establish the safety and effectiveness of PDMSCs for treating PCOS. [ABSTRACT FROM AUTHOR]

Simple Summary: Gonadal teratomas are tumours that can be benign or malignant and affect the gonads, specifically the ovaries in women and the testicles in men. They are predominantly young tumours that affect children and adolescents; therefore, early diagnosis is essential to apply the most suitable therapy to preserve fertility. In this article, based on articles found in the literature, we analysed the past, present and future of gonadal teratomas, starting from the description of the possible causes, the distinction between benign and malignant, and consequent diversification of the diagnostic and, therefore, therapeutic procedure. Furthermore, we concluded on the importance of a team that involves various specialists, including the pathologist, for the correct diagnosis and therapy to guarantee the best possible quality of life for the patient. Teratomas are neoplasms arising from germ cells and encompass tissues derived from two or more embryonic germ layers, including ectoderm, mesoderm, and endoderm. These tumours typically localize along the midline or in paramedian positions and can manifest as gonadal (20%) or extragonadal (80%) entities. Although gonadal teratomas are uncommon, they represent the predominant type of gonadal tumour in the paediatric population. They comprise approximately 20–25% of all ovarian tumours in females and about 3–5% of all testicular tumours in males. Ovarian teratomas exhibit a higher incidence in early childhood and adolescence, whereas testicular teratomas are more prevalent during the first three months of life and between the ages of 15 and 19. While the majority of paediatric gonadal teratomas are benign, malignant or mixed variants may also arise, necessitating more aggressive therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic reverse submucosal dissection (LRSD) is a standardised surgical technique for removal of rectosigmoid endometriosis which optimises the anatomical dissection plane for excision of endometriotic nodules. Aim: This cohort study assesses the outcomes of the first cohort of women treated by LRSD, for deeply infiltrating rectosigmoid endometriosis. Materials and Methods: Primary outcomes assessed were complication rate as defined by the Clavien–Dindo system, and completion of the planned LRSD. Secondary outcomes include mucosal breach, specimen margin involvement, length of hospital admission, and a comparison of pre‐operative and post‐operative pain, bowel function and quality of life surveys. These included the Endometriosis Health Profile Questionnaire (EHP‐30), the Knowles‐Eccersley‐Scott Symptom Questionnaire (KESS) and the Wexner scale. Results: Of 19 patients treated, one required a segmental resection. The median length of hospital admission was two days (range 1–5) and no post‐operative complications occurred. Median pain visual analogue scales (scale 0–10) were higher prior to surgery (dysmenorrhoea 9.0, dyspareunia 7.5, dyschezia 9.0, pelvic pain 6.0) compared to post‐surgical median scores (dysmenorrhoea 5.0, dyspareunia 4.0, dyschezia 2.0, pelvic pain 4.0) at a median of six months (range 4–32). Quality of life studies suggested improvement following surgery with pre‐operative median EHP‐30 and KESS scores (EHP‐30: 85 (5–106), KESS score 9 (0–20)) higher than post‐operative scores (EHP‐30: 48.5 (0–80), KESS score: 3 (0–19)). Conclusion: This series highlights the feasibility of LRSD with low associated morbidity as a progression of partial thickness discoid excision (rectal shaving) for the treatment of rectosigmoid deep infiltrating endometriosis. [ABSTRACT FROM AUTHOR]

Some failures in ovary function, like folliculogenesis and oogenesis, can give rise to various infertility-associated problems, including polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI). PCOS influences 8 to 20% of women; while POI occurs in at least 1% of all women. Regrettably, the current therapies for these diseases have not sufficiently been effective, and finding a suitable strategy is still a puzzle. One of the helpful strategies for managing and treating these disorders is understanding the contributing pathogenesis and mechanisms. Recently, it has been declared that abnormal expression of microRNAs (miRNAs), as a subset of non-coding RNAs, is involved in the pathogenesis of reproductive diseases. Among the miRNAs, the roles of miRNA-21 in the pathogenesis of PCOS and POI have been highlighted in some documents; hence, the purpose of this mini-review was to summarize the evidences in conjunction with the functions of this miRNA and other effective microRNAs in the normal or abnormal functions of the ovary (i.e., PCOS and POI) with a mechanistic insight. [ABSTRACT FROM AUTHOR]

The term "ovarian insufficiency" describes the decline of ovarian function resulting in fertility loss and the marked decrease of ovarian steroid hormone production. From a clinical standpoint, ovarian insufficiency presents in three different settings. The first is natural menopause at midlife occurring at the average age of 51 years. The second arises after surgical oophorectomy owing to disease or elective cancer prophylaxis. Finally, primary or premature ovarian insufficiency is characterized by menopause occurring before age 40, often of undetermined etiology, but at times linked with genetic mutations, autoimmune syndromes, metabolic conditions, iatrogenic etiologies, and toxic exposures. Each clinical situation presents unique concerns and management challenges. The majority of women with intact ovaries who live to age 51 experience natural menopause, with early menopause <45 years. In the United States, surgical menopause with bilateral oophorectomy occurs in ∼600,000 women per year. The timing and specific clinical indication for oophorectomy alters management. Primary ovarian insufficiency occurs in 1% of women, although recent estimates suggest the prevalence may be increasing. Symptoms of ovarian insufficiency include hot flashes or vasomotor symptoms, mood disorders, sleep disruption, and vaginal/urinary symptoms. Health concerns include bone, cardiovascular, and cognitive health. Management of symptoms and preventive strategies varies depending upon the age, clinical situation, and specific health concerns of each individual. Treatment options for symptom relief include cognitive behavior therapy and hypnosis, nonhormonal prescription therapies, and hormone therapy. Tailoring the therapeutic approach over time in response to age, emerging medical issues, and patient desires constitutes individualized care. [ABSTRACT FROM AUTHOR]

The optimal strategy for stimulation of young women with a low ovarian reserve is still a challenging issue because the physio-pathogeny of this disorder is often unknown. As androgen production by the ovary plays a crucial role in folliculogenesis, it was tempting to speculate that subtle perturbations in ovarian steroidogenesis might participate to the low responsiveness to gonadotrophins. Indeed, in vitro analysis of human luteinized granulosa cells has recently provided evidence for some enzymatic deficits in steroidogenesis and altered response to gonadotrophins. Therefore, improving androgen environment of women classified in Poseidon Group 3 should be considered. In this clinical situation, the potential benefit of androgen supplementation or stimulation of theca cells by LH-activity products are respectively discussed. [ABSTRACT FROM AUTHOR]

Objective: It has been reported in many studies that Growth Differentiation Factor-15 (GDF-15) has an important role in physiological or pathological processes. This study was aimed to investigate the role of GDF-15 in infertility and its treatment outcomes. Material and Method: According to their ovarian reserve characteristics, 88 infertile women were divided into three groups: normal ovarian reserve (NOR) (n= 42), diminished ovarian reserve (DOR) (n= 22), and polycystic ovary syndrome (PCOS) (n= 24). Serum estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Mullerian hormone (AMH), and GDF-15 levels were measured in their serum. The antagonist protocol patients' total oocyte, meiosis II (MII) oocytes, embryo count, and clinical pregnancy rates were documented and compared. Results: In terms of serum GDF-15 concentrations, there was no statistically significant difference among the mean values of the three study groups. The mean FSH level at baseline was substantially higher in the DOR group compared to the PCOS group (p=0.006*). The median serum AMH levels of all three groups were found to be statistically different (p=<0.001*). When the groups were compared in terms of averages of total oocytes, MII oocytes, and embryos, it was observed that the NOR group and the PCOS group both had higher values than the AOR group (p=0.001*). Conclusion: In our study, a significant and strong relationship was found between serum GDF-15 level and the number of embryos formed as a result of in-vitro fertilization (IVF) treatment. Thereby, serum GDF-15 level may be considered to be a biomarker for predicting IVF clinical outcomes. [ABSTRACT FROM AUTHOR]

Ovarian cells, including oocytes, granulosa/cumulus cells, theca cells, and stromal cells, contain abundant mitochondria, which play indispensable roles in the processes of ovarian follicle development. Ovarian function is closely controlled by mitochondrial proteostasis and mitostasis. While mitochondrial proteostasis and mitostasis are disturbed by several factors, leading to dysfunction of ovarian function and initiating the mitochondrial unfolded protein response (UPRmt) and mitophagy to maintain or recover ovarian function and mitochondrial function, clear interactions between the 2 pathways in the ovary have not been fully elucidated. Here, we comprehensively summarize the molecular networks or regulatory mechanisms behind further mitochondrial research in the ovary. This review provides novel insights into the interactions between the UPRmt and mitophagy in ovarian functions. [ABSTRACT FROM AUTHOR]

Ovarian response to stimulation mainly determines the length of stimulation. However, there is no clarity in the literature regarding the optimal duration required to achieve oocyte maturity in patients with the poor ovarian response (POR) defined by Bologna criteria. Therefore, a total of 267 cycles that fulfilled the inclusion criteria were selected retrospectively. Group A constitute of patients with a stimulation period < 9 d (n = 70); and group B included patients with a stimulation period ≥ 9 d (n = 133). The results showed that antral follicle count (5.72 ± 1.82 vs. 5.10 ± 1.78, p = 0.023), serum oestradiol level on hCG day (1286.88 ± 778.18 pg/mL vs. 820.14 ± 479.04 pg/mL, p = 0.001), and total gonadotropin dose used (2949.53 ± 727.92 IU vs 2020.94 ± 415.17 IU, p = 0.0001) were higher in group B when compared to group A. Although the number of total (5.47 ± 3.32 vs 3.86 ± 2.15, p = 0.0001) and mature oocytes retrieved (4.34 ± 2.88 vs 2.84 ± 1.67, p = 0.0001) were higher in group B, no significant difference was observed in the pregnancy rates between groups (25.6 vs 15.7%, p > 0.05). In conclusion, no deleterious effect of a shorter duration of stimulation on cycle outcome was seen in patients with POR. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis is a common immune disease with early symptoms of joint swelling, morning stiffness, pain, and swelling. It could develop into a joint deformity as the disease progresses, resulting in the loss of normal joint function and seriously affecting the patient's quality of life. Methotrexate is the "anchor drug" for rheumatoid arthritis treatment, which has an immunosuppressive effect and could effectively prevent the abnormal activation of B cells in vivo, inhibit the abnormal generation of cytokines, and relieve related symptoms. However, in some cases, methotrexate alone is not ideal and often needs to be combined with other drugs like xianlinggubao capsules. This study has provided an experimental basis for the combined efficacy of methotrexate and xianlinggubao capsules for female patients with moderate to severe rheumatoid arthritis and their impact on ovarian function. [ABSTRACT FROM AUTHOR]

Primary fallopian tube carcinoma is a very rare gynecological malignancy and poses a challenge in diagnosis preoperatively. We are reporting a rare case of bilateral primary fallopian tube carcinoma in a 48-year-old lady with classical symptoms. These symptoms are seen in less than 15% of cases. The differential diagnosis for bilateral fallopian tube cancer includes secondary malignancies arising from endometrial, ovarian and gastrointestinal cancers. Although the prognosis is poor. Early diagnosis, optimum cytoreduction and adjuvant chemotherapy are important to improve survival in such patients [ABSTRACT FROM AUTHOR]

The optimal strategy for stimulation of young women with a low ovarian reserve is still a challenging issue because the physio-pathogeny of this disorder is often unknown. As androgen production by the ovary plays a crucial role in folliculogenesis, it was tempting to speculate that subtle perturbations in ovarian steroidogenesis might participate to the low responsiveness to gonadotrophins. Indeed, in vitro analysis of human luteinized granulosa cells has recently provided evidence for some enzymatic deficits in steroidogenesis and altered response to gonadotrophins. Therefore, improving androgen environment of women classified in Poseidon Group 3 should be considered. In this clinical situation, the potential benefit of androgen supplementation or stimulation of theca cells by LH-activity products are respectively discussed.

Aim: Despite the remarkable progress made in reproductive medical technology in recent years, there has been no improvement in overall pregnancy and birth rates for the rising number of infertile patients. This is thought to be due to the increase in intractable infertility with ovarian dysfunction, as the desired age of pregnancy has increased for women. The aim of this article is to review preclinical studies that used laboratory animals and other tools to examine the effectiveness of diverse supplement ingredients on age‐related ovarian dysfunction as well as recent human clinical trials using supplement ingredients. Method: We summarized the articles discussing the effectiveness of supplement ingredients on infertility treatment in advanced‐aged women by searching PubMed, Cochrane, EMBASE, and Google Scholar databases until December 2022. Results: Supplements are relatively inexpensive and convenient for patients, as they can be purchased at the will of the individual and from among multiple options. Although supplements have been demonstrated to have certain effects in animal studies, evidence of their effectiveness in humans is either lacking or insufficient for reaching a definite conclusion. This may be due to the lack of standardized diagnostic criteria for ovarian dysfunction and poor responders, unclear optimal dosages and duration of supplement intake, and well‐designed randomized clinical trials. Conclusion: Additional lines of evidence on the effectiveness of supplements in patients with ovarian dysfunction at an older age need to be accumulated in the future. [ABSTRACT FROM AUTHOR]

Purpose: We examined the effects of aerobic exercise and detraining on adiponectin, resistin, tumor necrosis factor alpha (TNF-α), white blood cell, and pubertal signs (uterine length, ovarian volume, luteinizing hormone [LH], and follicle-stimulating hormone [FSH]) in girls with central precocious puberty (CPP). Methods: Thirty girls with CPP (7–9 yr old) were randomly divided into CPP and CPP + Exercise (EX) groups. Fifteen healthy age-matched girls without precocious puberty participated for comparison with CPP. Subjects in the CPP + EX group attended 12 wk of aerobic exercise protocol three sessions a week. In the baseline, after completing the exercise protocol and after 4 wk of detraining, all the parameters were measured. In the CPP and healthy groups, all the parameters were measured in all three stages. To measure adiponectin, resistin, and TNF-α, the ELISA method was used. LH and FSH were measured by electrochemiluminescence immunoassay. White blood cell counts were analyzed by an automated blood cell counter. Repeated-measures ANOVA was used to analyze the results. Results: CPP girls have lower adiponectin (P = 0.01) and higher TNF-α levels (P = 0.001) than healthy girls. In the CPP + EX group, after 12 wk, body weight and fat mass decreased, and adiponectin increased significantly (P = 0.02). Resistin (P = 0.02), TNF-α (P = 0.02), neutrophils (P = 0.01), and signs of puberty significantly (P < 0.05) decreased. After detraining, no significant change was observed except TNF-α, which increased significantly (P = 0.03). In the CPP group, no significant change was observed in any of the parameters; only LH (P = 0.0001) and uterine length and ovarian volume (P = 0.003, P = 0.001) decreased after 12 and 16 wk, respectively. Conclusions: Aerobic exercise can have a positive effect on the state of inflammation and pubertal signs. Positive effects remain after 4 wk of detraining. [ABSTRACT FROM AUTHOR]

Estrogen signaling exerts a decisive role in female sex determination and differentiation in chicken and fish. Aromatase encoded by Cyp19a1 is the key enzyme that catalyzes the conversion of androgen to estrogen. Correlative analyses implicate the potential involvement of aromatase in reptilian sexual development, however, the direct genetic evidence is lacking. Herein, we found that Cyp19a1 exhibited temperature-dependent sexually dimorphic expression, and located in the medullary somatic cells in early female embryos of the red-eared slider turtle (Trachemys scripta elegans), before the gonad is distinct. To determine the functional role of Cyp19a1 in turtle ovarian determination, we established loss- and gain-of-function models through in ovo lentivirus-mediated genetic manipulation. At female-producing temperature, inhibition of aromatase or knockdown of Cyp19a1 in turtle embryos resulted in female-to-male sex reversal, with the formation of a testis-like structure and a male distribution pattern of germ cells, as well as ectopic expression of malespecific markers (SOX9 and AMH) and disappearance of ovarian regulator FOXL2. On the contrary, overexpression of Cyp19a1 at male-producing temperature led to male-to-female sex reversal. In conclusion, our results suggest that Cyp19a1 is both necessary and sufficient for ovarian determination in the red-eared slider turtle, establishing causality and a direct genetic link between aromatase and reptilian sex determination and differentiation. [ABSTRACT FROM AUTHOR]

Several studies and research papers have been published to elucidate and understand the mechanism of the coronavirus disease 2019 (COVID-19) pandemic and its long-term effects on the human body. COVID-19 affects a number of organs, including the female reproductive system. However, less attention has been given to the effects of COVID-19 on the female reproductive system due to their low morbidity. The results of studies investigating the relationship between COVID-19 infection and ovarian function in women of reproductive age have shown the harmless involvement of COVID-19 infection. Several studies have reported the involvement of COVID-19 infection in oocyte quality, ovarian function, and dysfunctions in the uterine endometrium and the menstrual cycle. The findings of these studies indicate that COVID-19 infection negatively affects the follicular microenvironment and dysregulate ovarian function. Although the COVID-19 pandemic and female reproductive health have been studied in humans and animals, very few studies have examined how COVID-19 affects the female reproductive system. The objective of this review is to summarize the current literature and categorize the effects of COVID-19 on the female reproductive system, including the ovaries, uterus, and hormonal profiles. The effects on oocyte maturation, oxidative stress, which causes chromosomal instability and apoptosis in ovaries, in vitro fertilization cycle, high-quality embryos, premature ovarian insufficiency, ovarian vein thrombosis, hypercoagulable state, women's menstrual cycle, the hypothalamus-pituitary-ovary axis, and sex hormones, including estrogen, progesterone, and the anti- Müllerian hormone, are discussed in particular. [ABSTRACT FROM AUTHOR]

Premature ovarian failure (POF) is characterized by hormonal disorders, amenorrhea, and premature loss of fertility potential in women of reproductive age. Several studies have been conducted on the effectiveness of traditional Chinese medicine (TCM) in treating POF. TCM relied primarily on apoptosis, immunity, and aging to treat POF based on the studies of domestic and foreign literature. Zuogui pills inhibited mitochondrial-dependent apoptosis in the treatment of POF. Huyang Yangkun formula regulated the downstream of the Bcl-2 family to resist apoptosis through the aquaporin-1 protein. Modified Bazhen decoction regulated apoptosis in POF by regulating X-linked inhibitors of apoptosis protein. Bushen Tianjing recipe was effective in treating POF by promoting angiogenesis and preventing apoptosis. As for immunity, Bushen Jianpi prescription and Er-Xian decoction cured autoimmunity POF models and increased follicular development-related protein expression. Bushen Huoxue Tang improved ovarian function and reduced ovarian inflammation by regulating the Nrf2/Keap1 signaling pathway and T lymphocytes. Taohong Siwu decoction promoted the proliferation and differentiation of granulosa cells of POF mice by regulating the TGF-β1/Smads signaling pathway. In addition, ginsenoside Rg1 and Jiajian Guisheng formula treated POF by regulating cell aging-related mechanisms. Si Wu Tang treated POF by activating the angiogenesis-related proteins. The goal of this review is to serve as a reference for in-depth research into the treatment of POF with TCM and provide inspiration for new diagnostic methods and treatment options. [ABSTRACT FROM AUTHOR]

Objective. To explore the diagnostic value of serum anti-Mullerian hormone (AMH) for patients with premature ovarian insufficiency (POI) and premature ovarian failure (POF). Methods. Totally, 125 women with menstrual disorder treated in the Obstetrics and Gynecology Department of Ningbo Women & Children Hospital between January 2020 and December 2021 were enrolled. Among them, based on the follicle-stimulating hormone (FSH) level, 54 patients (25 IU / L < FSH ≤ 40 IU / L) were assigned to the POI group, and 71 patients (FSH > 40 IU / L) were assigned to the POF group. In addition, 72 individuals who went physical examination in the hospital and showed normal menstrual cycle were selected as the control (CON) group. Serum AMH in each group was quantified via enzyme-linked immunosorbent assay (ELISA) and Beckman Coulter Access active immunoassay analyzer, and the levels of serum neutral hormones [luteinizing hormone (LH), FSH, as well as estradiol (E2)] in each group were detected through the electrochemiluminescence method. The difference between AMH level acquired by the latest automatic method and that acquired by the traditional manual ELISA was compared, and the correlation of serum AMH with sex hormones was analyzed. In addition, receiver-operating characteristic (ROC) curves were drawn for determining the diagnostic value of serum AHM for POI ad POF. Results. Beckman Coulter Access quantified AMH more accurately and fastly (Beckman Coulter Access: 35 minutes; manual quantification: 3-4 hours) and was more sensitive than ELISA, with a requirement to less serum. The levels of serum AMH and E2 in the POF group were 0.04 ± 0.10 ng/mL and 35.16 ± 53.06 ng/mL, respectively, which were notably lower than those in the POI group ((0.69 ± 1.46) ng/mL and (3.96 ± 2.82) ng/mL) and CON group ((76.31 ± 97.84) ng/mL and (113.19 ± 114.84) ng/mL). The LH and FSH levels in the POF group were 37.86 ± 19.44 IU/L and 75.05 ± 35.31 IU/L, which were higher than those in POI group ((22.66 ± 26.15) IU/L and (11.30 ± 17.05) IU/L) and the CON group ((29.81 ± 4.45) IU/L and (6.78 ± 3.45) IU/L) (P < 0.05). The POI group showed a notably lower serum AMH level and notably higher LH and FSH levels than the CON group (P < 0.05), and the POI group was similar to the CON group in the E2 level (P > 0.05). Serum AMH showed a positive correlation with E2 (r = 0.291 , P < 0.05) and a negative association with both FSH (r = − 0.476 , P < 0.05) and LH (r = − 0.143 , P < 0.1). The optimal cut-off value of serum AMH in predicting POI was 0.83 ng/mL, and the corresponding sensitivity and specificity were 95.8% and 85.2%. The optimal cut-off of serum AMH in predicting POF was 0.075 ng/mL, and the corresponding sensitivity and specificity were 81.7% and 94.4%. The area under ROC curve (AUC) of serum AMH + FSH in the diagnosis of POF was close to 1. Conclusion. Beckman Coulter Access AMH test is the latest automatic electrochemiluminescence sandwich immunoassay, with higher sensitivity and reproducibility than traditional manual ELISA and with ability to produce repeatable results. With the decline of ovarian function, the serum AMH of POI patients decreases gradually, and the serum AMH of POF patients decreases obviously, so serum AMH level has great value in predicting POI and POF and can be used as a sensitive index for early diagnosis of the two. Serum AMH combined with FSH can lift the diagnostic efficiency of POF. [ABSTRACT FROM AUTHOR]

Ovarian aging leads to menopause, loss of fertility and other disorders in multiple organs, which brings great distress to women. For ethical reasons, it is impossible to use humans as direct study subjects for aging research. Therefore, biomedical researchers have employed different non-human organisms to study ovarian aging, including worms, fruit flies, fishes, amphibians, birds, mice, rats, cavies, rabbits, pigs, sheep, cows, horses, monkeys, and apes. Because each of these model organisms has its own features, multiple factors, such as size, anatomical structure, cost, ease of operation, fertility, generation time, lifespan, and gene heredity, should be carefully considered when selecting a model system to study ovarian aging. An appropriate model organism would help researchers explore the risk factors and elucidate molecular mechanisms underlying declined ovarian functions, which might be conducive to preventing or delaying the ovarian aging process. This article will offer an overview on several currently available and commonly used model organisms for ovarian aging research by comparing their pros and cons. In doing so, we hope to provide useful information for ovarian aging researchers. [ABSTRACT FROM AUTHOR]

Cancer during childhood and adolescence remains a major public health issue, affecting a significant portion of this age group. Although newer anti-cancer treatments have improved survival rates, this comes at a cost in terms of gonadotoxic effects. As a result, the preservation of fertility is important. Ovarian tissue cryopreservation, one of the newest methods, has some advantages, especially for prepubertal patients: no need for ovarian stimulation, thus, no further risk for estrogen-sensitive cancer types, and preservation of more and better-quality primordial follicles of the ovarian cortex. The most frequent indications include treatment with alkylating agents, ovarian-focused radiotherapy, leukemias, lymphomas, brain and neurological tumors, as well as Turner syndrome and benign hemoglobinopathies. An expected survival exceeding 5 years, the absence of systematic disease and an overall risk of premature ovarian insufficiency over 50% are among the criteria that need to be fulfilled in order for a patient to undertake this method. Orthotopic transplantation is more frequently used, since it can allow both live birth and the recovery of endocrine function. Reimplantation of malignant cells is always a major risk and should always be taken into consideration. Histological analysis, as well as immunohistochemical and molecular methods, are needed in order to improve the search for malignant cells before transplantation. Ovarian tissue cryopreservation appears to be a method with specific benefits, indications and risks which can be an important tool in terms of preserving fertility in younger women. [ABSTRACT FROM AUTHOR]

Study Question: Does luteal phase estrogen valerate pretreatment improve oocyte yield and clinical outcomes in patients with low ovarian response during ovarian stimulation with the antagonist protocol?Summary Answer: Pretreatment with oral estrogen valerate from Day 7 after ovulation to Day 2 of the next menstrual cycle did not increase oocyte yield in patients with a low ovarian response compared to no pretreatment.What Is Known Already: Previous studies showed that patients with a normal ovarian response can obtain better clinical outcomes after pretreatment with estrogen in the antagonist protocol. For patients with advanced age and low ovarian response, it remains unclear if estrogen valerate pretreatment with the antagonist protocol yields more oocytes and improves pregnancy outcomes.Study Design, Size, Duration: This non-blinded randomized controlled trial (RCT) was conducted between November 2017 and March 2021. Participants were 552 women with low response who requested IVF treatment. The primary endpoint was comparison of the total number of retrieved oocytes between the two groups. The secondary endpoints were the total number of retrieved metaphase II (MII) oocytes, duration and total dosage of recombinant FSH (rFSH), good-quality embryo rate and clinical pregnancy rate.Participants/materials, Setting, Methods: The study was conducted at a reproductive center. The RCT enrolled 552 infertile women with a low ovarian response (according to the Bologna criteria) who were undergoing IVF. In the study group, on Day 7 after ovulation patients were administered oral estrogen valerate (2 mg twice a day) until Day 2 of their next menstruation. Ovary stimulation was performed using rFSH, and a GnRH antagonist (0.25 mg/day) was started when a dominant follicle had a mean diameter ≥13 mm.Main Results and the Role Of Chance: No significant difference was observed in the number (mean [SD]) of oocytes retrieved from the estrogen valerate pretreatment and control group (3.2 [2.8] versus 3.4 [2.6], respectively). The treatment difference was -0.18 (95% CI -0.67, 0.32, P = 0.49). No significant differences were observed in the number of MII oocytes (2.9 [2.5] versus 3.1 [2.4], mean difference -0.23, 95% CI (-0.69, 0.23), P = 0.16) and good-quality embryos (1.0 [1.3] versus 1.20 [1.6], mean difference -0.23, 95% CI (-0.50, 0.04), P = 0.19) between the two groups. The duration of rFSH treatment was significantly longer in the estrogen valerate pretreatment group than in the control group (10.3 [2.2] versus 8.6 [2.1] days, mean difference 1.7, 95% CI (1.3, 2.2), P = 0.00), and the total rFSH dosage was significantly higher in the estrogen valerate pretreatment group than in the control group (3081 [680] versus 2548 [649] IU, mean difference 553.7, 95% CI (405.8, 661.6), P = 0.00). The clinical pregnancy rate in the pretreatment group (19.3% [23/119]) was not significantly different from that in the control group (28.7% [43/150]). The mean difference was -0.09, 95% CI (-0.20, 0.01), P = 0.08.Limitations, Reasons For Caution: The major limitation was the high dropout rate of patients. Some patients did not return to the hospital for treatment because of predicted low success rates and for economic reasons. In addition, it is possible that the fixed dose of 300 IU rFSH was not sufficient to see differences in oocyte yield between the groups.Wider Implications Of the Findings: Estrogen valerate pretreatment with an antagonist protocol did not increase oocyte yield in patients with low ovarian response. Similar to the number of retrieved oocytes, there was no significant difference in clinical pregnancy rate between estrogen pretreatment group and control group. More research is needed on whether patients with low ovarian response need pretreatment and which pretreatment is more appropriate.Study Funding/competing Interest(s): This study was supported in part by a research grant from the Investigator-Initiated Studies Program of MSD (China) Holding Co., Ltd. and Organon (Shanghai) Pharmaceutical Technology Co., Ltd. (Grant number: IIS 56284). The authors declare that they have no competing interests regarding authorship or publication of this study.Trial Registration Number: ClinicalTrials.gov NCT03300518.Trial Registration Date: 28 September 2017.Date Of First Patient’s Enrolment: 15 November 2017. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effect of different oral dosages of levonorgestrel (LNG) on ovarian activity and to identify the lowest dosage at which no ovulation occurred. Secondary objectives were to assess return of ovulation after stopping treatment, bleeding pattern, pharmacokinetic (PK) parameters and safety and tolerability.Study Design: A parallel-group study with adaptive design was performed in 90 healthy women with proven ovulatory cycles. Investigated dosages were LNG 0.095, 0.115 and 0.135 mg per day. Measurements of follicular growth and estradiol (E2) and progesterone concentrations were performed every 3 (±1) days during a 56-day treatment and a post-treatment period. Follicle-stimulating hormone and luteinizing hormone concentrations and multiple-dose PK parameters were determined during treatment.Results: Two normal ovulations occurred in the LNG 0.095 mg group, none in the higher dose groups. Most subjects had active follicle-like structures without ovulation (Hoogland-Skouby scores 4). Ovarian activity was more suppressed in the highest dose group than in the other groups. Mean E2 concentrations were 241, 219 and 180 pmol/L during treatment with 0.095, 0.115 and 0.135 mg per day, respectively. PK results showed dose-proportionality. Most subjects ovulated during the post-treatment period.Conclusion: LNG 0.115 mg per day was the lowest effective dosage for consistent ovulation inhibition. All investigated dosages were safe and well-tolerated, and mean E2 concentrations were sufficient for prevention of hypoestrogenic side effects.Implications: Marketed progestogen-only pills (POP) containing 0.03 mg LNG do not consistently inhibit ovulation. Increasing the dosage to 0.115 mg or 0.135 mg per day, resulting in consistent ovulation inhibition, may improve the contraceptive efficacy of the LNG-POP. [ABSTRACT FROM AUTHOR]

Background: As the number of cancer survivors has increased with advancements in cancer treatment, fertility preservation has become a treatment goal. Ovarian tissue cryopreservation (OTC) and transplantation (OTT) has made great progress over the past few decades. It has become the treatment of choice for fertility preservation in adolescents or patients in urgent need of chemotherapy. However, it is considered to be experimental compared with oocyte or embryo cryopreservation in some countries. Nevertheless, OTC and OTT is regarded as the more ideal method for fertility preservation in that it can also restore hormonal functions. Current Concepts: Currently, over 200 live births have been reported worldwide after OTC and OTT, proving the excellence of the technology. However, before its application in clinical settings, some challenges, including cryoinjury, ischemic injury, and cancer cell reimplantation, should be overcome. For cryoinjury, studies are underway on protocol improvement with the addition of agents such as antifreeze protein during cryopreservation. For ischemic injury, various agents have been studied to promote angiogenesis or revascularization. Furthermore, studies are underway on artificial ovary or xenotransplantation for fertility preservation in an effort to avoid cancer cell metastasis. Discussion and Conclusion: OTC and OTT is a clinically applicable option for fertility preservation. To set OTC and OTT as an established method for fertility preservation, further research is necessary to overcome the current challenges. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the influence of different transcutaneous electrical acupoint stimulation (TEAS) modes on ovarian responses and pregnancy outcomes in patients with infertility undergoing in vitro fertilization and embryo transfer (IVF-ET). Methods: Two hundred infertility patients undergoing IVF-ET were divided randomly into experimental groups (TEAS groups: E-I, E-II, E-III, and E-IV, 40 cases each group) and a control group (mock TEAS group, 40 patients) using the random number method. The patients in the experimental groups received TEAS treatment of 20, 30, 40 and 50 mA for the E-I, E-II, E-III and E-IV groups, respectively. The control group received a treatment of 5 mA. TEAS was applied at acupoints of Guanyuan (RN 4), Zhongji (RN 3), Sanyinjiao (SP 6), Zigong (EX-CA 1), and Taixi (KI 13), once a day for 30 min each time for a treatment period of 10–13 d. Treatment effect was assessed using the following indicators: endometrial thickness on the 6th day of gonadotropin treatment (GN6 day), endometrial thickness on the day on chorionic gonadotropin administration (HCG day), number of ovarian follicles on HCG day, number of ova captured, amount of estrogen required for each harvested ova, number of mature ova divided by the total number of ova, percentage of high-quality embryos, and clinical pregnancy. Results: Endometrial thickness in the experimental groups on the HCG day was significantly better than that of the control group after TEAS stimulation (P=0.01). TEAS exhibited a greater impact on the number of ova captured (P=0.003). However, the effect of TEAS stimulation on the high-quality embryo rate and clinical pregnancy in patients was not statistically significant (P>0.05). Conclusions: TEAS is an effective method in improving the ovarian state. When the stimulus intensity was at 40 mA and above, it could be helpful to improve the patient's endometrial condition and endometrial receptivity and to retrieve more oocytes. (Trial registration No. ChiCTR-TRC-11001780) [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the performance of ovarian response prediction index (ORPI) in predicting ovarian response and livebirth of women undergoing their first in-vitro fertilisation (IVF) cycle. This is a retrospective analysis of 285 women from 2013 to 2016. The outcome measures were area (AUC) under the receiver-operator characteristic (ROC) curves for prediction of excessive and poor response, livebirth in the fresh cycle and cumulative livebirth. The ORPI was significantly correlated with the oocyte number. For prediction of excessive response, AUC for ORPI was comparable to AMH and significantly higher than AFC and female age. At a cut-off of 0.42, ORPI has a sensitivity and specificity of 84% and 77% respectively for prediction of excessive response. For prediction of poor response, AUC for ORPI was significantly higher than AFC, AMH and female age. At a cut-off of 0.12, ORPI has a sensitivity of 69% and specificity of 89% respectively for prediction of poor response. For prediction of livebirth, AUCs of ORPI were not significantly different from AFC and female age. Therefore, ORPI is not a good predictor of livebirth. Its prediction of excessive and poor ovarian response is comparable to that of serum AMH. [ABSTRACT FROM AUTHOR]

Pretreatment medications/manipulations are offered to patients with poor ovarian response, aiming to prevent the occurrence of a spontaneous luteinizing hormone surge, increase the number of preantral and antral follicles, synchronize follicular development, and increase oocytes' yield and quality, with the consequent improvement in cycle outcome. Although early small human studies were encouraging, interpretation of the studies is compromised by variations in the type, dose, combination and duration of the pretreatment medications. Whether these measures would serve as valuable tools in the armamentarium for treating patients with poor ovarian response requires further, large prospective studies that should validate the specific mode/combination of pretreatment measures and identify, before initiating ovarian stimulation, the specific characteristics of women who might benefit from the specific regimen. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether ovarian fragmentation for follicular activation (OFFA) improves ovarian reserve markers and in vitro fertilization (IVF) outcomes in women with poor ovarian response (POR).Design: Randomized, controlled trial, with parallel assignment.Setting: University hospital.Patient(s): Thirty-four women with POR according to the European Society of Human Reproduction and Embryology criteria.Intervention(s): Women with POR were randomly allocated to receive ovarian fragmentation in 1 ovary or to no intervention (control group). Ovarian reserve markers were followed at 2-week intervals for 6 months. In vitro fertilization cycles were initiated when the antral follicle count (AFC) doubled or at the end of follow-up.Main Outcome Measure(s): The primary outcome was the number of metaphase II (MII) oocytes obtained. Antral follicle count, antimüllerian hormone level, and reproductive outcomes were recorded as secondary outcomes. Exploratory outcomes included surgical results and analysis of protein and gene expression.Result(s): Ovarian fragmentation for follicular activation resulted in an increase in AFC in the intervention ovary compared with the control ovary and an increase in total AFC in the OFFA group compared with controls. Serum antimüllerian hormone and follicle-stimulating-hormone levels did not improve in the OFFA group throughout the follow-up period. Fifteen patients from each arm underwent IVF. In the control group, 33 MII oocytes were retrieved and 18 embryo transfers were performed, with a 20% pregnancy rate and an 18.7% live birth rate per cycle. In the OFFA group, 23 MII oocytes were retrieved and 11 embryo transfers were performed, with a 13.3% pregnancy rate and a 6.7% live birth rate per cycle. Reproductive outcomes did not significantly differ between the groups. Hippo pathway inhibition was confirmed by an 18.8% reduction in the phospho-YAP/YAP (Yes-associated protein 1) ratio and BIRC and CCN overexpression after fragmentation.Conclusion(s): Ovarian fragmentation for follicular activation in women with POR resulted in an increase in AFC but did not modify IVF outcomes when compared with controls.Clinical Trial Registration Number: NCT02354963. [ABSTRACT FROM AUTHOR]

Growing evidence showed that the gut microbiota was associated with premature ovarian failure (POF). Many clinical types of research had shown that electroacupuncture was effective in the treatment of POF. However, there was little research on regulating the gut microbiome of POF mice by electroacupuncture. Therefore, this study attempted to verify whether electroacupuncture could regulate the gut microbiome in POF mice. POF mice were established by being injected intraperitoneally with cisplatin (2 mg/kg) for 2 weeks. Guanyuan (CV4) and Sanyinjiao (SP6) were selected in the electroacupuncture-at-the-acupoints group (EA group). Nonacupoints around CV4 and SP6 were selected in the electroacupuncture-at-the-nonacupoints group (EN group). The EA group and EN group were treated for 3 weeks. The ovarian function was evaluated by histopathological and molecular assays. Meanwhile, the gut microbiome of all mice was detected by 16S rDNA sequencing. The results showed that EA could restore the estrous cycle and reduce the number of atresia follicles in POF mice. The levels of serum follicle-stimulating hormone and luteinizing hormone were decreased by EA. As well, the levels of serum estradiol, anti-Mullerian hormone, and β-glucuronidase were increased by EA. The relative expressions of PI3K, AKT, and mTOR were increased to promote the proliferation of ovarian cells in the EA group. According to the results of 16S rDNA sequencing, the abundance and diversity of the gut microbiome could be regulated by EA. The relative abundance of beneficial bacteria was increased by EA. The KEGG pathway analysis showed that the gut microbiome associated with the estrogen signaling pathway, oocyte maturation, and PI3K-AKT signaling pathway was regulated by EA. [ABSTRACT FROM AUTHOR]

Copyright of Reproductive Health of Woman is the property of Professional-Event Publishing House 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.)

Histological analysis was carried out on ovarian development in the picnic seabream, Acanthopagrus berda (Forsskål 1775) caught in the estuarine waters of Calicut, Kerala, India from January to December 2016. Four developmental phases of oocyte development were identified viz., oogonia proliferation and transformation into the primary oocyte, primary growth phase, secondary growth phase and maturation phase and these are similar to those described for other species. The reproductive development process begins in a very young ovary with the formation of oogonia, the cells originally derived from special primordial germ cells formed early in the embryonic development; their multiplication and differentiation are followed by the release of mature oocytes. Oocyte development stages observed in A. berda were chromatin nucleolus, early perinucleolar, late perinucleolar, lipid vesicle stage I oocyte, lipid vesicle stage II oocyte, primary yolk granule stage, secondary yolk granule stage, tertiary yolk granule stage, hydrated oocyte and atretic oocyte. The oocytes entered the maturation phase when they attained the maximum size of 459.6±71.83 µm. Histological examination of the mature ovaries showed the presence of all the different oocyte stages in the ovary of A. berda with an asynchronous mode of ovarian development shortly before spawning, indicating that the species is a multiple spawner. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between ambient temperature and antral follicle count (AFC), a standard measure of ovarian reserve.Design: Prospective cohort study.Setting: Fertility center at an academic hospital in the northeastern United States.Patient(s): 631 women attending the Massachusetts General Hospital Fertility Center (2005-2015) who participated in the Environment and Reproductive Health Study.Intervention(s): Daily temperature at the women's residential address was estimated for the 90 days before their antral follicle scan using a spatially refined gridded climate data set. We evaluated the associations between temperature and AFC using Poisson regression with robust standard errors, adjusting for relative humidity, fine particulate matter exposure, age, education, smoking status, year and month of AFC, and diagnosis of diminished ovarian reserve and ovulation disorders.Main Outcome Measure(s): Antral follicle count as measured with transvaginal ultrasonography.Result(s): A 1°C increase in average maximum temperature during the 90 days before ovarian reserve testing was associated with a -1.6% (95% confidence interval [CI], -2.8, -0.4) lower AFC. Associations remained negative, but were attenuated, for average maximum temperature exposure in the 30 days (-0.9%, 95% CI, -1.8, 0.1) and 14 days (-0.8%, 95% CI, -1.6, 0.0) before AFC. The negative association between average maximum temperature and AFC was stronger in November through June than during the summer months, suggesting that timing of heat exposure and acclimatization to heat may be important factors to consider in future research.Conclusion(s): Exposure to higher temperatures was associated with lower ovarian reserve. These results raise concern that rising ambient temperatures worldwide may result in accelerated reproductive aging among women. [ABSTRACT FROM AUTHOR]

Objective. To explore the effect of Wenjing Decoction and Tiaobu Chongren acupuncture and moxibustion therapy on serum sex hormones and ovarian function recovery in premature ovarian failure (POF) patients with deficiency-cold syndrome. Methods. From February 2018 to October 2019, 119 POI patients with deficiency-cold syndrome who met the selection criteria were randomly divided into the control group (n = 59) and the observation group (n = 60). The control group was treated with hormone replacement therapy, and the observation group was treated with Wenjing Decoction and Tiaobu Chongren acupuncture and moxibustion therapy on the basis of the control group. Both groups were treated continuously for 3 months. After treatment, the clinical efficacy of the two groups was compared, the Chinese medicine syndrome score, serum estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-mullerian hormone (AMH) and bilateral antral follicle count (AFC), mean ovarian volume, and endometrial thickness of the two groups before and after treatment were compared. Result. The effective rate of the observation group (93.10%) was higher than that of the control group (77.59%) (P < 0.05). After treatment, the index scores of traditional Chinese medicine syndromes in two groups were lower than before (P < 0.05), and the observation group was lower than the control group (P < 0.05). The serum E2 and AMH levels in the two groups increased, while FSH and LH levels decreased compared with before treatment, and the observation group improved significantly compared with the control group (P < 0.05). The bilateral AFC, mean ovarian volume, and endometrial thickness of the two groups increased compared with before treatment, and the observation group was higher than the control group (P < 0.05). Conclusion. On the basis of hormone replacement therapy, the combination of Wenjing Decoction and Tiaobu Chongren acupuncture and moxibustion therapy is effective in treating POF patients with deficiency-cold syndrome, which can effectively regulate their serum sex hormone levels and promote the recovery of ovarian function. [ABSTRACT FROM AUTHOR]

The mammalian female is born with a limited ovarian reserve of primordial follicles. These primordial follicles are slowly activated throughout the reproductive lifecycle, thereby determining lifecycle length. Once primordial follicles are exhausted, women undergo menopause, which is associated with several metabolic perturbations and a higher mortality risk. Long before exhaustion of the reserve, females experience severe declines in fertility and health. As such, significant efforts have been made to unravel the mechanisms that promote ovarian aging and insufficiency. In this review, we explain how long-living murine models can provide insights in the regulation of ovarian aging. There is now overwhelming evidence that most life-span-extending strategies, and long-living mutant models simultaneously delay ovarian aging. Therefore, it appears that the same mechanisms that regulate somatic aging may also be modulating ovarian aging and germ cell exhaustion. We explore several potential contributing mechanisms including insulin resistance, inflammation, and DNA damage-all of which are hallmarks of cellular aging throughout the body including the ovary. These findings are in alignment with the disposable soma theory of aging, which dictates a trade-off between growth, reproduction, and DNA repair. Therefore, delaying ovarian aging will not only increase the fertility window of middle age females, but may also actively prevent menopausal-related decline in systemic health parameters, compressing the period of morbidity in mid-to-late life in females. [ABSTRACT FROM AUTHOR]

Increases in delayed childbearing worldwide have elicited the need for a better understanding of the biological underpinnings and implications of age-related infertility. In women 35 years and older the incidences of infertility, aneuploidy, and birth defects dramatically increase. These outcomes are a result of age-related declines in both ovarian reserve and oocyte quality. In addition to waning reproductive function, the decline in estrogen secretion at menopause contributes to multisystem aging and the initiation of frailty. Both reproductive and hormonal ovarian function are limited by the primordial follicle pool, which is established in utero and declines irreversibly until menopause. Because ovarian function is dependent on the primordial follicle pool, an understanding of the mechanisms that regulate follicular growth and maintenance of the primordial follicle pool is critical for the development of interventions to prolong the reproductive life span. Multiple pathways related to aging and nutrient-sensing converge in the mammalian ovary to regulate quiescence or activation of primordial follicles. The PI3K/PTEN/AKT/FOXO3 and associated TSC/mTOR pathways are central to the regulation of the primordial follicle pool; however, aging-associated systems such as the insulin-like growth factor-1/growth hormone pathway, and transsulfuration/hydrogen sulfide pathways may also play a role. Additionally, sirtuins aid in maintaining developmental metabolic competence and chromosomal integrity of the oocyte. Here we review the pathways that regulate ovarian reserve and oocyte quality, and discuss geroscience interventions that leverage our understanding of these pathways to promote reproductive longevity. [ABSTRACT FROM AUTHOR]

Adding ovarian function suppression (OFS) after chemotherapy improves survival in young women with moderate- and high-risk breast cancer. Assessment of ovarian function restoration after chemotherapy becomes critical for subsequent endocrine treatment and addressing fertility issues. In the adding OFS after chemotherapy trial, patients who resumed ovarian function up to 2 years after chemotherapy were randomised to receive either 5 years of tamoxifen or adding 2 years of OFS with tamoxifen. Ovarian function was evaluated from enrolment to randomisation, and patients who did not randomise because of amenorrhoea for 2 years received tamoxifen and were followed up for 5 years. Prospectively collected consecutive hormone levels (proportion of patients with premenopausal follicle-stimulating hormone [FSH] levels <30 mIU/mL and oestradiol [E2] levels ≥40 pg/mL) and history of menstruation were available for 1067 patients with breast cancer. Over 5 years of tamoxifen treatment, 69% of patients resumed menstruation and 98% and 74% of patients satisfied predefined ovarian function restoration as per serum FSH and E2 levels, respectively. Menstruation was restored in 91% of patients younger than 35 years at baseline, but in only 33% of 45-year-old patients over 5 years. Among these patients, 41% experienced menstruation restoration within 2 years after chemotherapy and 28% slowly restored menstruation after 2–5 years. Younger age (<35 years) at baseline, anthracycline without taxanes and ≤90 days of chemotherapy were predictors of menstruation restoration. During 5 years of tamoxifen treatment after chemotherapy, two-thirds of the patients experienced menstruation restoration, especially patients younger than 35 years. Young age, Adriamycin without taxanes and short duration of chemotherapy appeared to have a positive effect on ovarian reserves in the long term. ClinicalTrials.gov identifier: NCT00912548. • Over 5 years after chemotherapy, 69% resumed menstruation, especially under 35. • Two-thirds experienced menstruation restoration within 2 years after chemotherapy. • Young age, adriamycine without taxane had a positive effect on ovarian reserves. [ABSTRACT FROM AUTHOR]

This study was conducted on goats with the purpose to evaluate the ovarian reserve before females submit to the ova retrieval for intracytoplasmic sperm injection (ICSI). The study was conducted at the college of veterinary medicine -- the University of Baghdad and Middle East Labs - Baghdad (2019-2020). The study included thirty female goats (does) within the age of puberty and sexual maturity. The animals were divided into two groups: group I (< 4 years old), and group II (> 4 years old). A blood sample (6 ml) was collected from each animal through the jugular vein (before slaughter) in tubes containing anticoagulants and then sent to the laboratory for estimation of antimullerian hormone (AMH). The study showed significant increases in the level of AMH (4.02 ± 0.17) of the group I (< 4 years old) comparative with (2.22 ± 0.54) to the group II (> 4 years old) at the (<0.01), and this result relation with the number of oocytes obtained from ovarian samples of animals after slaughtering, it was found that the number and quality of oocytes increased in the group I (29 oocytes from a 15ovarian samples, compared with group II (16 oocytes from 15ovarian samples. This result explains the decrease in the ovarian reservoir of follicles with an increase in the age in the doe as a result of the decrease in the level of AMH in the serum, which is considered an indicator for knowing the ovarian reservoir from the follicles and determining the productive age of the ovaries. According to the results of this study, the decrease in the level of AMH in the serum is an indication of a decrease in the number of follicles on the surface of the ovaries, which negatively affects the fertility and productivity of the goats or may affect the fertilization rate and the number of fertilized embryos. The AMH test is considered one of the important tests that must be taken before oocyte collection to reduce the effort and costs involved in conducting any assisted reproduction technique that requires collecting the oocytes from the donor. [ABSTRACT FROM AUTHOR]

Objective: To investigate mechanisms of primordial follicle (PMF) loss in vivo in human ovaries shortly after alkylating agent (AA) chemotherapy.Design: Cohort study.Setting: Tertiary university medical center.Patient(s): Ninety-six women aged 15-39 years who underwent ovarian tissue cryopreservation for fertility preservation.Intervention(s): Fresh ovarian tissue samples were harvested from women treated with AA (n = 24) or non-AA (n = 24) chemotherapy <6 months after treatment and age-matched untreated women (n = 48).Main Outcome Measure(s): Differential follicle counts, time from chemotherapy exposure, immunostaining for apoptosis (cleaved caspase-3) and FOXO3A on tissue harvested within ultrashort time intervals (4-12 days), collagen (Sirius red) and neovascularization (CD34).Result(s): AA-treated ovaries had significant loss of PMFs, and significant increase in absolute numbers of growing follicles compared with untreated control ovaries. The number of growing follicles was inversely correlated with time from chemotherapy. Representative staining for FOXO3A observed decreased nuclear localization in PMF oocytes in AA-treated ovaries removed within the ultrashort time interval compared with untreated ovaries. Neither significant loss of PMFs, increase in growing follicles, nor decrease in nuclear FOXO3A were observed in non-AA-treated ovaries. No increased expression of cleaved caspase-3 was seen in PMFs within the ultrashort time interval after AA or non-AA chemotherapy. Significant stromal fibrosis and neovascularization were observed in AA-treated ovaries only after follicle loss had already occurred (4-6 months).Conclusion(s): Follicle activation occurs in vivo in ovaries of patients treated with AA, indicating a pathologic mechanism which may contribute to chemotherapy-induced follicle loss. [ABSTRACT FROM AUTHOR]

Background: Complementary remedies such as the Chinese herb 'Sheng Ma' (Black cohosh; Actaea racemosa 'AR') are being sought to overcome the shortcomings of conventional hormonal and surgical therapies developed for the treatment of polycystic ovary syndrome (PCOS). However, AR-induced hepatotoxicity necessitates a cautionary warning to be labeled on its products as recommended by the United States Pharmacopeia, where four out of seven hepatotoxic cases in Sweden were possibly associated with black cohosh products. Methods: We investigated the effects, safety, and molecular targets of black cohosh ethanolic extract and/or vitamin C on ovarian functionality and oxidative response in hyperandrogenism-induced PCOS rats. A well-established rat model using oral letrozole, daily, for 21 days was employed. The rats then received the AR extract with and without vitamin C for 28 days. The hormonal evaluation, antioxidant status, histopathological examination, immunohistochemical analysis, cell proliferation, and the expression ratio of the aromatase (Cyp19α1) gene were evaluated. Additionally, holistic profiling of the AR arsenal of secondary metabolites was performed using ultra-high-performance liquid chromatography (UHPLC) coupled with quadrupole high-resolution time of flight mass spectrometry (QTOF-MS). Results: Beneficial effects were exerted by AR in PCOS rats as antioxidant status, hormonal profile, lipid profile, glucose level, liver functions, and the induced Ki-67 expression in the granulosa, theca cell layers and interstitial stromal cells were all improved. Notably, the combination of AR with vitamin C was not only more effective in reversing the dysregulated levels of testosterone, luteinizing hormone, and mRNA level of Cyp19α1 gene in the PCOS rat, but also safer. The combination regulated both ovarian and hepatic malondialdehyde (MDA) and glutathione (GSH) levels with histological improvement observed in the liver and ovaries. In addition, the untargeted metabolomic profiling enabled the identification of 61 metabolites allocated in five major chemical classes. Conclusion: This study demonstrated the benefit of the combinatorial effects of AR and vitamin C in mitigating the reproductive and metabolic disorders associated with PCOS with the elimination of AR hepatotoxic risk. [ABSTRACT FROM AUTHOR]

Objective: To determine whether follicle flushing during oocyte retrieval improves live birth or secondary outcomes in assisted reproductive technology (ART).Design: Systematic review and meta-analysis.Setting: Not applicable.Patient(s): Women undergoing ART using autologous gametes.Intervention(s): A systematic search of PubMed, EMBASE, Cochrane Database, and Web of Science for randomized controlled trials comparing follicle flushing to direct aspiration during oocyte retrieval published in English between 1989 to 2020.Main Outcome Measure(s): Live birth as primary outcome, and clinical and ongoing pregnancy, total and mature metaphase II (MII) oocytes retrieved, and operating time as secondary outcomes.Result(s): Eleven studies were included totaling 1,178 cases. No difference in live birth was demonstrated between follicle flushing and direct aspiration. Clinical pregnancy and ongoing pregnancy were not improved with flushing. Total oocyte and MII yield were lower with flushing compared with direct aspiration. Procedure time was increased with flushing by 2 minutes in poor responders and 9 minutes in normal responders. Other sensitivity analyses did not demonstrate any changes, except the difference in MII yield was no longer statistically significant.Conclusion(s): Follicle flushing during oocyte retrieval increases procedure time and does not improve live birth or secondary ART outcomes. Randomized data do not support the use of follicle flushing as an intervention in ART. [ABSTRACT FROM AUTHOR]

Objective: To identify the optimal lead follicle size for hCG trigger in clomiphene citrate (CC)-intrauterine insemination (IUI) cycles.Design: Retrospective cohort study.Setting: University-affiliated center.Patient(s): Patients <40 years of age with ovulatory dysfunction or unexplained infertility undergoing their first CC-IUI cycle.Intervention(s): Ovulation induction, hCG trigger, and IUI.Main Outcome Measure(s): Clinical pregnancy rate (CPR) was the primary outcome and was plotted against lead follicle size in increments of 1 mm. Odds ratios with 95% confidence intervals for associations between lead follicle size and CPR were calculated from a multivariable logistic regression model. A receiver operating characteristic (ROC) curve was generated for CPR as a function of lead follicle size.Result(s): 1,676 cycles were included. The overall CPR was 13.8% (232/1,676). There was no difference in baseline demographics or ovulation induction parameters of patients who did or did not conceive. The odds of clinical pregnancy were 2.3 and 2.2 times higher with lead follicle sizes of 21.1-22.0 mm and >22.0 mm, respectively, compared with the referent category of 19.1-20.0 mm. Lead follicle size was an independent predictor of CPR, even after accounting for confounders. A lead follicle size of 22.1 mm corresponded to a sensitivity and specificity of 80.1% and 90.4% for clinical pregnancy, respectively, with an area under the ROC curve of 0.89.Conclusion(s): hCG administration at a lead follicle size of 21.1-22.0 mm is associated with higher odds of clinical pregnancy in patients undergoing their first CC-IUI cycles for ovulatory dysfunction or unexplained infertility. [ABSTRACT FROM AUTHOR]

Bushen Huoxue recipe (BSHXR) is a widely used prescription medicine for treating gynecological diseases. We have previously found that BSHXR can improve the pregnancy outcome of controlled ovarian hyperstimulation (COH) mice by modulating the abnormal high level of progesterone. While the pharmacological mechanism of such therapeutic effect is not clear. We aimed to investigate the effects of BSHXR on the ovarian steroidogenesis and luteal function in mice undergoing COH. A COH mouse model was established via an intraperitoneal injection of 0.4 IU/g pregnant mare serum gonadotropin (PMSG) and 1 IU/g human chorionic gonadotropin (HCG). The histological features of ovaries were observed using hematoxylin-eosin staining. The expression levels of FSHR, LHCGR, and key molecules in ovarian steroidogenesis, including CYP11A1, CYP17A1, CYP19A1, HSD3B1, and StAR, were examined via immunohistochemical staining, western blotting, and RT-qPCR. CD31, VEGFA, and FGF2 levels were assessed to evaluate ovarian vascularization. The protein and mRNA levels of ovarian ERK1/2, p-ERK1/2, MEK1/2, and p-MEK1/2 were also detected using western blotting, RT-qPCR, or immunofluorescence staining. COH mice had a significantly increased volume and weight of the ovary and number of corpora lutea. In particular, COH exhibited a long-term influence on ovarian FSHR and LHCGR expression, disrupting the levels of CYP11A1, HSD3B1, and CYP17A1, causing poorer luteal angiogenesis. Compared with normal mice, the expression levels of ovarian VEGFA and FGF2 in COH mice were considerably lower on Day 1 after PMSG. On concomitant HCG treatment, both VEGFA and FGF2 expression surged dramatically on ED1 and then declined on ED4 and ED8. Moreover, the expression pattern of MEK1/2-ERK1/2 was almost consistent with that of VEGFA and FGF2. After treatment, BSHXR increased ovarian LHCGR, FSHR, CYP11A1, HSD3B1, and CYP17A1 levels, boosted luteal vascularization, and restored MEK1/2-ERK1/2 signaling in COH mice. BSHXR restored the abnormally high progesterone level by regulating the CYP11A1 and HSD3B1 expression as well as promoted luteal angiogenesis, which was related with LHCGR-MEK1/2-ERK1/2-VEGFA/FGF2 signaling pathway in the ovary. This effect prevented the fluctuation of sex hormones in COH mice and benefited the outcome of pregnancy. BSHXR restored the abnormally high progesterone level by regulating the CYP11A1 and HSD3B1 expression as well as promoted luteal angiogenesis, which was related with LHCGR-MEK1/2-ERK1/2-VEGFA/FGF2 signaling pathway in the ovary. [Display omitted] • BSHXR restores the abnormally high progesterone level in COH mice. • BSHXR modulates the expression level of key molecules in ovarian steroidogenesis. • BSHXR promotes the LHCGR-MEK1/2-ERK1/2-VEGFA/FGF2 signaling pathway in luteal angiogenesis. [ABSTRACT FROM AUTHOR]

Ovary development is an important determinant of the procreative capacity of female animals. Here, we performed genome-wide sequencing of long non-coding RNAs (lncRNAs) and mRNAs on ovaries of 1, 3 and 8 months old Hu sheep to assess their expression profiles and roles in ovarian development. We identified 37,309 lncRNAs, 45,404 messenger RNAs (mRNAs) and 330 novel micro RNAs (miRNAs) from the transcriptomic analysis. Six thousand, seven hundred and sixteen (6716) mRNAs and 1972 lncRNAs were significantly and differentially expressed in ovaries of 1 month and 3 months old Hu sheep (H1 vs H3). These mRNAs and target genes of lncRNAs were primarily enriched in the TGF-β and PI3K-Akt signalling pathways which are closely associated with ovarian follicular development and steroid hormone biosynthesis regulation. We identified MSTRG.162061.1, MSTRG.222844.7, MSTRG.335777.1, MSTRG.334059.16, MSTRG.188947.6 and MSTRG.24344.3 as vital genes in ovary development by regulating CTNNB1, CCNA2, CDK2, CDC20, CDK1 and EGFR expressions. A total of 2903 mRNAs and 636 lncRNAs were differentially expressed in 3 and 8 months old ovaries of Hu sheep (H3 vs H8); and were predominantly enriched in PI3K-Akt, progesterone-mediated oocyte maturation, estrogen metabolism, ovulation from the ovarian follicle and oogenesis pathways. These lncRNAs were also found to regulate FGF7, PRLR, PTK2, AMH and INHBA expressions during follicular development. Our result indicates the identified genes participate in the development of the final stages of follicles and ovary development in Hu sheep. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether epigenetic profiles of mural granulosa cells (MGC) and leukocytes from women with diminished ovarian reserve (DOR) differ from those of women with normal or high ovarian reserve.Design: Prospectively collected material from a multicenter cohort of women undergoing fertility treatment.Setting: Private and university-based facilities for clinical services and research.Patient(s): One hundred and nineteen women of various ages and ovarian reserve status (antimüllerian hormone level) who provided blood samples and MGC.Intervention(s): None.Main Outcome Measure(s): Measures of epigenetic aging rates from whole-genome methylation array data: DNA methylation variability, age acceleration, DNA methylation telomere length estimator (DNAmTL), and accumulation of epimutations.Result(s): Comparison of DOR or high ovarian reserve samples to controls (normal ovarian reserve) showed differential methylation variability between DOR and normal samples at 4,199 CpGs in MGC, and 447 between high and normal (false-discovery rate < 0.05). Variable sites in MGC from DOR were enriched in regions marked with the repressive histone modification H3K27me3, and also included genes involved in folliculogenesis, such as insulin growth factor 2 (IGF2) and antimüllerian hormone (AMH). Regardless of ovarian reserve, very few signals were detected in leukocytes, and no overlaps with those in MGC were found. Furthermore, we found a higher number of epimutations in MGC from women with DOR (Kruskal-Wallis test, difference in mean = 3,485).Conclusion(s): The somatic cells of human ovarian follicles have a distinctive epigenetic profile in women with DOR. A high frequency of epimutations suggests premature aging. Ovarian reserve status was not reflected in the leukocyte epigenetic profile. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of acupuncture on ovary morphology and function in dehydroepiandrosterone (DHEA)-induced polycystic ovary syndrome (PCOS) model rats. Methods: A total of 40 adult female Wistar rats were randomly allocated to 4 groups by a random number table, including control, model, metformin and acupuncture groups, 10 rats in each group. PCOS rat model was developed by injecting with DHEA (6 mg/100 g body weight) in 0.2 mL of oil subcutaneously. Electrical stimulation (2 Hz, 3 mA) was applied to Guanyuan (CV 4), Zigong (EX-CA1) and Qihai (CV 6) acupoints for 30 min daily in the acupuncture group, and metformin (200 mg/kg) was given to rats in the metformin group, both once per day for 21 consecutive days, and rats in the normal group was fed with normal saline and fed regularly. After 21 days of administration, the rat blood samples were collected for detecting the reproductive hormonal levels [luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), progesterone (P), testosterone (T)] and inflammatory factors (visfatin, IL-6) analysis. Ovary tissue was used for histopathological analysis. Results: Compared with the model group, rats in the acupuncture and metformin groups were significantly lower in weight gain, FSH, LH and T levels, and E2 and P levels significantly increased (alll P<0.05). Meanwhile, LH and FSH levels were significantly decreased, and P, T and E2 levels significantly increased in the acupuncture group, compared with the metformin group (P<0.05). Compared with the model group, IL-6 and visfatin levels were significantly decreased in the acupuncture and metformin groups (P<0.05). There were no significant differences in IL-6 and visfatin levels between the acupuncture and metformin groups (P>0.05). Ovarian diameter in the acupuncture and metformin groups were smaller than the model group (P<0.05). However, there were no significant differences in ovarian diameters between the acupuncture and metformin groups (P>0.05). Conclusion: Acupuncture might improve ovary morphology and its function in DHEA-induced PCOS model rats. [ABSTRACT FROM AUTHOR]

Purpose: Photon radiation therapy (x-ray radiation therapy [XRT] and gamma-ray radiation therapy [GRT]) of tumors close to ovaries causes reproductive and endocrine sequelae due to ovarian primordial follicle depletion. Given its finite range, proton radiation therapy (PRT) can preserve ovarian function when ovaries are positioned distal to the spread-out Bragg peak (SOBP) in tumors of the abdominopelvic region. This study compared anti-Müllerian hormone (AMH) levels (a biomarker of ovarian function) and primordial follicle survival after in vivo mouse pelvic GRT versus PRT.Methods and Materials: One hundred twenty-four female prepubertal mice received sham, GRT, or PRT with ovaries positioned at various depth with respect to the proton SOBP, with single doses of 1.8 or 0.2 Gy. AMH was measured at baseline, 1, 3, and 8 weeks after treatment, and the total number of surviving primordial follicles was counted. Multivariable linear mixed-effects modeling was used to assess the relationship between radiation therapy modality and dose on AMH and primordial follicle survival.Results: For ovaries beyond the SOBP, ovarian function (P = .5) and ovarian primordial follicle (OPF; P = 1.0) were spared relative to sham controls. For ovaries in the SOBP plateau, ovarian function and primordial follicle reserve 8 weeks after treatment were reduced for all groups: 1.8 Gy GRT (βAMH = -4.9 ng/mL; βOPF = -728.2/animal), 1.8 Gy (relative biological effectiveness [RBE] = 1.1) PRT (βAMH = -5.1 ng/mL; βOPF = -728.2/animal), 0.2 Gy GRT (βAMH = -2.5 ng/mL; βOPF = -595.1/animal), and 0.2 Gy (RBE = 1.1) PRT (βAMH = -3.0 ng/mL; βOPF = -555.4/animal) relative to sham controls (all differences P < .001).Conclusions: This study uses an animal model to demonstrate the safety of proton therapy in sparing fertility. Ovaries positioned beyond the SOBP during PRT maintain ovarian reserve, suggesting that a proton beam has no energy and exit dose beyond SOBP. This study proposes that proton therapy is much safer than photon radiation therapy to protect ovarian follicles with the same dose, and it supports further testing of proton therapy for abdominopelvic tumors in young women. [ABSTRACT FROM AUTHOR]