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Recent methodological recommendations suggest the use of the "3-step method," consisting of calendar-based counting, urinary ovulation testing, and serum blood sampling, for the identification of subtle menstrual disturbances (SMDs). However, the use of the 3-step method is not always feasible, so a less demanding combination of calendar-based counting and urinary ovulation testing, that is, the 2-step method, may be a viable alternative. Purpose: To investigate the agreement between the 2- and 3-step methods for the detection of SMDs. Methods: Menstrual cycles (MCs, 98) of 59 athletes were assessed using the 2- and 3-step methods. Regular-length MCs (ie, ≥21 and ≤35 d) were classified as either having no SMD (luteal phase length ≥10 d, midluteal progesterone concentration ≥16 nmol·L−1, and being ovulatory) or having an SMD (eg, short luteal phase [<10 d], inadequate luteal phase [midluteal progesterone concentration <16 nmol·L−1], or being anovulatory). Method agreement was assessed using the McNemar test and Cohen kappa (κ). Results: Substantial agreement was observed between methods (κ =.72; 95% CI,.53–.91), but the 2-step method did not detect all MCs with an SMD, resulting in evidence of systematic bias (χ2 = 5.14; P =.023). The 2-step method detected 61.1% of MCs that had an SMD ([51.4, 70.8]), as verified using the 3-step method, and correctly identified 100% of MCs without an SMD. Conclusions: MCs classified as being disturbed using the 2-step method could be considered valid evidence of SMDs. However, MCs classified without SMDs do not definitively confirm their absence, due to the proven underdetection via the 2-step method. [ABSTRACT FROM AUTHOR]

The menstrual cycle is a loop involving the interplay of different organs and hormones, with the capacity to impact numerous physiological processes, including body temperature and heart rate, which in turn display menstrual rhythms. The advent of wearable devices that can continuously track physiological data opens the possibility of using these prolonged time series of skin temperature data to noninvasively detect the temperature variations that occur in ovulatory menstrual cycles. Here, we show that the menstrual skin temperature variation is better represented by a model of oscillation, the cosinor, than by a biphasic square wave model. We describe how applying a cosinor model to a menstrual cycle of distal skin temperature data can be used to assess whether the data oscillate or not, and in cases of oscillation, rhythm metrics for the cycle, including mesor, amplitude, and acrophase, can be obtained. We apply the method to wearable temperature data collected at a minute resolution each day from 120 female individuals over a menstrual cycle to illustrate how the method can be used to derive and present menstrual cycle characteristics, which can be used in other analyses examining indicators of female health. The cosinor method, frequently used in circadian rhythms studies, can be employed in research to facilitate the assessment of menstrual cycle effects on physiological parameters, and in clinical settings to use the characteristics of the menstrual cycles as health markers or to facilitate menstrual chronotherapy.

Embryo-maternal crosstalk is essential to establish pregnancy, with the equine embryo moving throughout the uterus on days 9-15 (ovulation = day 0) as part of this interaction. We hypothesized that the presence of a mobile embryo induces local changes in the gene expression of the endometrium. On Day 12, the endometrial transcripts were compared among three groups: uterine horn with an embryo (P+, n = 7), without an embryo (P-, n = 7) in pregnant mares, and both uterine horns of nonbred mares (NB, n = 6). We identified 1,101 differentially expressed genes (DEGs) between P+ vs. NB and 1,229 DEGs between P- vs. NB. The genes upregulated in both P+ and P- relative to NB were involved in growth factor pathway and fatty acid activation, while downregulated genes were associated with oxytocin signaling pathway and estrogen receptor signaling. Comparing the transcriptome of P+ to that of P-, we found 59 DEGs, of which 30 genes had a higher expression in P+. These genes are associated with regulating vascular growth factors and the immune system, all known to be essential in early pregnancy. Overall, this study suggests that the mobile embryo influences the endometrial gene expression locally.

Aminergic nuclei in mammals are generally composed of relatively small numbers of cells with broad projection patterns. Despite the gross similarity of many individual neurons, recent transcriptomic, anatomic and behavioral studies suggest previously unsuspected diversity. Smaller clusters of aminergic neurons in the model organism Drosophila melanogaster provide an opportunity to explore the ramifications of neuronal diversity at the level of individual cells. A group of approximately 10 tyraminergic/octopaminergic neurons innervates the female reproductive tract in flies and has been proposed to regulate multiple activities required for fertility. The projection patterns of individual neurons within the cluster are not known and it remains unclear whether they are functionally heterogenous. Using a single cell labeling technique, we show that each region of the reproductive tract is innervated by a distinct subset of tyraminergic/octopaminergic cells. Optogenetic activation of one subset stimulates oviduct contractions, indicating that the cluster as a whole is not required for this activity, and underscoring the potential for functional diversity across individual cells. Using whole cell patch clamp, we show that two adjacent and morphologically similar cells are tonically inhibited, but each responds differently to injection of current or activation of the inhibitory GluCl receptor. GluCl appears to be expressed at relatively low levels in tyraminergic/octopaminergic neurons within the cluster, suggesting that it may regulate their excitability via indirect pathways. Together, our data indicate that specific tyraminergic/octopaminergic cells within a relatively homogenous cluster have heterogenous properties and provide a platform for further studies to determine the function of each cell.

The African claw-toed frog, Xenopus laevis, is a well-established laboratory model for the biology of vertebrate oogenesis, fertilisation, and development at embryonic, larval, and metamorphic stages. For ovulation, X. laevis females are usually injected with chorionic gonadotropin, whereupon they lay typically hundreds to thousands of eggs in a day. After being rested for a minimum of three months, animals are re-used. The literature suggests that adult females can lay much larger numbers of eggs in a short period. Here, we compared the standard single ovulation protocol with a double ovulation protocol, in which females were ovulated, then re-ovulated after seven days and then rested for three months before re-use. We quantified egg number, fertilisation rate (development to cleavage stage), and corticosterone secretion rate as a measure of stress response for the two protocol groups over seven 3-month cycles. We found no differences in egg number-per-ovulation or egg quality between the groups and no long-term changes in any measures over the 21-month trial period. Corticosterone secretion was elevated by ovulation, similarly for the single ovulation as for the first ovulation in the double-ovulation protocol, but more highly for the second ovulation (to a level comparable to that seen following shipment) in the latter. However, both groups exhibited the same baseline secretion rates by the time of the subsequent cycle. Double ovulation is thus transiently more stressful/demanding than single ovulation but within the levels routinely experienced by laboratory X. laevis. Noting that stress hormone corticosterone/cortisol secretion is linked to physiological processes, such as ovulation, that are not necessarily harmful to the individual, we suggest that the benefits of a doubling in egg yield-per-cycle per animal without loss of egg quality or signs of acute or long-term harm may outweigh the relatively modest and transient corticosterone elevation we observed. The double ovulation protocol therefore represents a potential new standard practice for promoting the 3Rs (animal use reduction, refinement and replacement) mission for Xenopus research.

Background: Before pregnancy is recognized, ovulation, fertilization, and implantation must all occur. Physical activity and sedentary behavior may impact pregnancy success by altering each or all of these processes. The aim of this review was to review the association between physical activity and sedentary behavior with spontaneous female and male fertility. Method: PubMed/MEDLINE, Web of Science, CINAHL, SPORTDiscus, and Embase were searched from inception to August 9, 2021. Eligible studies included randomized controlled trials or observational studies, published in English, describing an association between physical activity or sedentary behavior (exposures) and spontaneous fertility (outcome) among women or men. Results: Thirty-four studies from 31 unique populations were included in this review (12 cross-sectional studies, 10 cohort studies, 6 case–control studies, 5 randomized controlled trials, and one case–cohort study). Of the 25 studies among women, the majority identified mixed results (n = 11) or no association (n = 9) between physical activity and female fertility. Seven studies reported on female fertility and sedentary behavior, and 2 found sedentary behavior was associated with decreased female fertility. Of the 11 studies among men, most of the studies (n = 6) found that physical activity was associated with increased male fertility. Two of the studies reported on male fertility and sedentary behavior, and neither identified an association. Conclusions: The association between spontaneous fertility and physical activity in both men and women remains unclear, and the association with sedentary behavior remains largely unexplored. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the superestimulatory and superovulatory responses of cattle treated with corifollitropin-alpha, a long-acting human recombinant FSH (rhFSH). In the first and second experiments, we used Nelore (Bos indicus) heifers previously submitted to follicular wave suppression by active immunization against GnRH. In Experiment 1 (a dose-response study), heifers (n = 20) were randomly allocated into five groups, which received placebo (saline) or a single sc dose of 7.5, 15.0, 22.5 or 30.0 μg rhFSH. The heifers were subjected to daily ovarian scan and blood sampling during 11 days. We observed group, time, and group x time effects (P< 0.0001) for both average follicle size and circulating FSH concentrations, with a strong correlation (R = 0.82, P< 0.0001) between the area under curve (AUC) for both parameters. The peak concentration of FSH 24h after treatment and average follicle size at all timepoints, however, were similar (P> 0.05) between groups 22.5 and 30.0 μg. In Experiment 2, heifers (n = 18) were allocated into three groups, which received (0h) either placebo (control), 25 μg rhFSH or 130 mg pFSH (Folltropin). There was no difference (P> 0.05) in average follicle size at any moment, as well as in intrafollicular E2 at 120h or in plasma P4 seven days later between groups rhFSH and pFSH. In Experiment 3, cycling Nelore heifers (n = 20) were subjected to a wave synchronization protocol and superovulated (day 0) using a standard pFSH protocol (120 mg split in eight decreasing im doses) or with a single sc injection of 20 μg rhFSH. The number of follicles >7 mm on day 4 did not differ (P= 0.4370). Heifers receiving rhFSH had greater average follicle size on day 4 (P= 0.0005), ovulation rate (P< 0.0001), and number of CL (P= 0.0155), as well as a trend towards a greater number of ova (P= 0.07) and viable embryos (P= 0.0590). In Experiment 4, superovulation was induced with a single sc injection of 25 μg rhFSH in Girolando and Nelore cows and heifers (n = 20). None of the embryo yield endpoints differed between the two breeds (P> 0.05). In conclusion, cattle superstimulation and superovulation can be successfully induced with a single dose of a long-acting rhFSH (corifollitropin-alpha). • Cattle respond to superstimulation with corifollitropin-alpha in a dose-dependent manner. • Ovarian superovulation can be induced with 20–25 mcg of corifollitropin-alpha. • Corifollitropin-alpha is detected in circulating serum up to 11 days after treatment. [ABSTRACT FROM AUTHOR]

The bovine embryo production industry has seen significant growth over the past two decades, particularly in the production of in vitro produced embryos. This growth, driven by advancements in cryopreservation, in vitro culture mediums, ovum pick-up (OPU) procedures, ultrasonography devices, and embryo transfer (ET) has been notable. Particularly, ET is crucial for disseminating high genetic merit and amplifying foreign breeds by importing frozen embryos. This retrospective study aimed to assess factors affecting conception per embryo transfer (CPET) in Holstein-Friesian cattle in South Korea from October 2008 to July 2022. We evaluated type of embryo breed, type of embryo production (fresh and frozen; in vitro and in vivo production), recipient conditions including estrus type, corpus luteum quality, parity (nulliparous heifers, primiparous, and multiparous cows), and the daily mean temperature-humidity index (THI) as an index for heat stress. Type of embryo breed and estrus had no significant impact on CPET. However, we observed higher CPET in recipients with good quality corpus luteum, nulliparous heifers, and surrogates receiving fresh in vitro and frozen in vivo embryos. Importantly, CPET was not adversely affected by mild heat stress conditions (up to daily mean THI 76), indicating that using frozen in vivo embryos produced by multiple ovulation embryo transfer and fresh in vitro embryos by OPU-ET can help alleviate the subfertility issues in dairy cattle caused by global warming in Korea. • Recipient parity and corpus luteum were significant determinants of conception per embryo transfer (CPET) in Holstein cattle • The temperature-humidity index, a measure of heat stress, did not significantly affect CPET. • Embryo type significantly influenced CPET, • Selecting recipients by parity and CL quality is crucial for ET success, offering an effective AI alternative in heat-stressed environments. [ABSTRACT FROM AUTHOR]

Two experiments evaluated the effect of different hormonal treatments to synchronize follicle wave emergence on follicle dynamics and pregnancies per AI (P/AI) in estradiol (E2)/progesterone (P4) timed-AI (TAI) protocols in lactating dairy cows. In Experiment 1, lactating, primiparous Holstein cows (n = 36) received a P4 releasing device (Day 0) and were allocated at random to one of the following three treatment groups: Group EB received 2 mg E2 benzoate (EB) intramuscularly (i.m.), Group EB + GnRH received 2 mg EB+20 μg buserelin (GnRH) i.m., or Group EB + P4 received 2 mg EB + 100 mg of injectable P4 (iP4) in oil i.m. All cows received 0.150 mg D-Cloprostenol on Days 7 and 8 followed by P4 device removal, 400 IU eCG and 1 mg ECP on Day 8. Daily ultrasound examinations revealed that although the interval from P4 device removal to ovulation was not affected by treatment, cows that received EB + GnRH had an earlier (P < 0.05) emergence of the new follicular wave (Day 2.6 ± 0.2) than the other two treatment groups (Days 3.5 ± 0.3 and 6.1 ± 0.3, for EB and EB + P4, respectively). In Experiment 2, 808 lactating cows were assigned randomly to the three treatments evaluated in Experiment 1, and all the cows were TAI to determine P/AI. Cows in the EB + GnRH group had greater P/AI (57.4 %, P < 0.01) than those in the EB (44.6 %) or EB + P4 (45.7 %) groups. In conclusion, the administration of GnRH, but not iP4, on the day of insertion of a P4 device improves P/AI in lactating dairy cows synchronized for TAI with an estradiol/P4-based protocol. • The addition of GnRH or injectable P4 to synchronize follicular wave emergence in an estradiol/P4-based protocol for TAI was evaluated in dairy cows. • The combination of EB + GnRH at P4 device insertion synchronized follicle wave emergence and improved P/AI following TAI. • Adding injectable P4 to EB at P4 device insertion did not improve follicle wave synchronization or P/AI compared to EB given alone. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effects of different doses of equine chorionic gonadotropin (eCG; 200 and 300 IU) administered at the end of a fixed-time artificial insemination (FTAI) treatment protocol on ovulation, pregnancy, and twin rates in Bos taurus beef heifers. In addition, pregnancy losses in heifers with singleton and twin pregnancies were determined. A total of 2382 Angus heifers treated with a 6-day estradiol/progesterone-based protocol for FTAI (J-Synch protocol) were randomly allocated to two experimental groups to receive 200 or 300 IU of eCG administered intramuscularly at the time of intravaginal progesterone device removal; FTAI was performed from 60 to 72 h after device removal. The pregnancy rate did not differ (P = 0.89) between the 200 and 300 IU eCG groups. The number of corpus luteum induced by both eCG doses was determined by ultrasonographic examination 14 days after insemination and those treated with 300 IU of eCG had a greater double ovulation rate (P < 0.05). In addition, 300 IU eCG treated heifers had a higher twinning rate on day 30 of gestation (P < 0.05) and parturition (P < 0.05). Pregnancy losses from 30 days of gestation to calving did not differ between heifers treated with 200 and 300 IU of eCG (P = 0.70). However, regardless of the experimental group, heifers bearing twins had greater pregnancy losses than heifers with singletons (P < 0.05). In conclusion, reducing the dose of eCG from 300 to 200 IU under FTAI treatment protocol decreases double ovulation and twinning rates, maintaining a similar pregnancy rate in heifers. Nulliparous cows carrying two fetuses suffer greater pregnancy losses than cows with singletons. • Different doses of eCG were evaluated in a progesterone-based protocol for FTAI. • Reducing from 300 to 200 IU eCG maintained similar P/AI. • Twinning rate was lower with 200 IU eCG. • Those heifers bearing twins, suffer greater pregnancy losses than singletons. [ABSTRACT FROM AUTHOR]

Fetal age in Quarter Horses can be predicted within 2 weeks from 100- to 200- days of gestation using femur length, biparietal diameter (cranium diameter) and eye approximated volume. However, as pregnancy advances, the femur and cranium become too large to be imaged in their entirety using ultrasound and the corresponding biometric parameters can no longer be measured. In this longitudinal study, the proximal phalanx (P1) was evaluated as a novel biometric parameter for late gestation to predict fetal age and bone maturation. Transrectal ultrasound was performed in ten pregnant mares with known ovulation dates, every two weeks from 240- days of gestation until parturition. P1 was imaged in 69 % of the examinations. Inability to image P1 was due to obstructive positioning such as carpal or fetlock flexion, or posterior presentation of the fetus. Advancing fetal age did not affect visibility of P1. P1 length correlated significantly with days of gestation and a correlation equation was established: y = 0.3837x -69.55 where y is the predicted value of P1 length and x is the day of gestation (with day 0 being the day of ovulation). When P1 length was equal to or larger than the width of the ultrasound image (52.5 mm), 90 % of mares (9/10) were above 300- days of gestation. Ossification of the proximal and distal epiphysis of P1 typically appeared between 277- and 303 -days of gestation (mean: 288 days). The proximal epiphysis did not close before parturition whereas the distal one closed between 306- and 333-days of gestation (mean: 320 days). P1 epiphyseal appearance and closure occurred chronologically reflecting bone maturation. Radiographic findings at birth and prenatal ultrasound findings were in agreement, apart from timing of P1 distal epiphyseal closure. In conclusion, P1 length can be used as a new fetal biometric parameter to assess fetal age and growth after 240- days of gestation. The knowledge of P1 bone maturation process in utero as a marker for fetal bone development, may also be valuable in clinical decision-making when considering inducing parturition in the mare. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is oocyte developmental competence associated with changes in granulosa cell (GC) metabolism? SUMMARY ANSWER GC metabolism is regulated by the LH surge, altered by obesity and reproductive aging, and, in women, specific metabolic profiles are associated with failed fertilization versus increased blastocyst development. WHAT IS KNOWN ALREADY The cellular environment in which an oocyte matures is critical to its future developmental competence. Metabolism is emerging as a potentially important factor; however, relative energy production profiles between GCs and cumulus cells and their use of differential substrates under normal in vivo ovulatory conditions are not well understood. STUDY DESIGN, SIZE, DURATION This study identified metabolic and substrate utilization profiles within ovarian cells in response to the LH surge, using mouse models and GCs of women undergoing gonadotropin-induced oocyte aspiration followed by IVF/ICSI. PARTICIPANTS/MATERIALS, SETTING, METHODS To comprehensively assess follicular energy metabolism, we used real-time metabolic analysis (Seahorse XFe96) to map energy metabolism dynamics (mitochondrial respiration, glycolysis, and fatty acid oxidation) in mouse GCs and cumulus–oocyte complexes (COCs) across a detailed time course in the lead up to ovulation. In parallel, the metabolic profile of GCs was measured in a cohort of 85 women undergoing IVF/ICSI (n = 21 with normal ovarian function; n = 64 with ovarian infertility) and correlated with clinical parameters and cycle outcomes. MAIN RESULTS AND THE ROLE OF CHANCE Our study reveals dynamic changes in GC energy metabolism in response to ovulatory LH, with mitochondrial respiration and glycolysis differentially affected by obesity versus aging, in both mice and women. High respiration in GCs is associated with failed fertilization (P  <   0.05) in a subset of women, while glycolytic reserve and mitochondrial ATP production are correlated with on-time development at Day 3 (P  <   0.05) and blastocyst formation (P  <   0.01) respectively. These data provide new insights into the cellular mechanisms of infertility, by uncovering significant associations between metabolism within the ovarian follicle and oocyte developmental competence. LIMITATIONS, REASONS FOR CAUTION A larger prospective study is needed before the metabolic markers that were positively and negatively associated with oocyte quality can be used clinically to predict embryo outcomes. WIDER IMPLICATIONS OF THE FINDINGS This study offers new insights into the importance of GC metabolism for subsequent embryonic development and highlights the potential for therapeutic strategies focused on optimizing mitochondrial metabolism to support embryonic development. STUDY FUNDING/COMPETING INTEREST(S) National Health and Medical Research Council (Australia). The authors have no competing interests. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. The objectives of this prospective cohort study were to characterize associations among genomic merit for fertility with ovarian and endocrine function and the estrous behavior of dairy cows during an entire nonhormonally manipulated estrous cycle. Lactating Holstein cows entering their first (n = 82) or second (n = 37) lactation had ear-notch tissue samples collected for genotyping using a commercial genomic test. Based on genomic predicted transmitting ability values for daughter pregnancy rate (gDPR), cows were classified into high (Hi-Fert; gDPR > 0.6, n = 36), medium (Med-Fert; gDPR −1.3 to 0.6, n = 45), and low fertility (Lo-Fert; gDPR < −1.3, n = 38) groups. At 33 to 39 DIM, cohorts of cows were enrolled in the Presynch-Ovsynch protocol for synchronization of ovulation and initiation of a new estrous cycle. Thereafter, the ovarian function and endocrine dynamics were monitored daily until the next ovulation by transrectal ultrasonography and concentrations of progesterone (P4), estradiol, and FSH. Estrous behavior was monitored with an ear-attached automated estrus detection system that recorded physical activity and rumination time. Overall, we observed an association between fertility group and the ovarian and hormonal phenotype of dairy cows during the estrous cycle. Cows in the Hi-Fert group had greater circulating concentrations of P4 than cows in the Lo-Fert group from d 4 to 13 after induction of ovulation and from day −3 to −1 before the onset of luteolysis. The frequency of atypical estrous cycles was 3-fold greater for cows in the Lo-Fert than the Hi-Fert group. We also observed other modest associations between genomic merit for fertility with the follicular dynamics and estrous behavior. We found several associations between milk yield and parity with ovarian, endocrine, and estrous behavior phenotypes as cows with greater milk yield and in the second lactation were more likely to have unfavorable phenotypes. These results demonstrate that differences in reproductive performance between cows of different genomic merit for fertility classified based on gDPR may be partially associated with circulating concentrations of P4, the incidence of atypical phenotypes during the estrous cycles, and, to a lesser extent, the follicular wave dynamics. The observed physiological and endocrine phenotypes might help explain part of the differences in reproductive performance between cows of superior and inferior genomic merit for fertility. [ABSTRACT FROM AUTHOR]

Derived ornithopods, such as hadrosaurids, show a high occurrence of fossilized lesions and diseases. However, paleopathologies in iguanodontians seem to be less common, considering the rich fossil record of these taxa in Europe, in particular in Belgium, Britain and Spain. Here, we describe an iguanodontian femur discovered in England that exhibits a large overgrowth of its lateral aspect, not previously recognized in any other similar remains. The specimen was scanned with micro‐computed tomography (microCT) and later sectioned in three sites of the overgrowth for histological analysis. The femur belongs to an early adult Iguanodontia indet., based on the presence of a woven parallel fibered complex in the outer cortex and three to four lines of arrested growth. Internal analysis of the dome‐like overgrowth suggests it can be diagnosed as a fracture callus. The injury might have negatively impacted upon the animal's locomotion as the trauma had occurred in the region above the knee, a crucial spot for hindlimb musculature. Finally, a cancellous medullary bone‐like tissue was recognized in the medullary cavity next to the pathological overgrowth. An attempt was made to determine the precise nature of this tissue, as medullary bone is linked with the ovulation period in (avian) dinosaurs, whereas other types of endosteal, medullary bone‐like tissue have previously been recognized in pathological bones. [ABSTRACT FROM AUTHOR]

Background & Objective: Endometrial carcinoma (EC) is one of the most common cancers and the fourth most common cancer affecting females, mostly affecting postmenopausal women. EC originates from the endometrium and is further subdivided into two types that are estrogen dependent; type 1 and type 2 with different gene expression patterns. Materials & Methods: This research was carried out between December 2021 and August 2022 in the Laboratories of the College of Science/Department of Biology and the other local lab and PCR was employed to establish HOXA11 presence. The aims of the study were to reveal the histological alterations in malignant and benign tumors and normal endometrium and to examine the relationship between HOXA11 levels and clinicopathological parameters including stage, grade, muscle and lymph node invasion, and histological type. Results: The mean HOXA11 expression values were compared in cancer, benign, and control endometrial patients' groups. The mean HOXA11 expression level was the lowest in endometrial cancer patients; they had a mean of 0. 24±0. 03, those with benign endometrial tumors had the second lowest with a mean of 0. 94±0. 06, while the control patients had the highest mean expression with 1. 00±0. 07. The comparison of the HOXA11 expression between the endometrial cancer patients and the control group showed a statistically significant difference (P-value >0. 001), thus underlining its diagnostic value. Also, there was a significant difference in the HOXA11 expression means between patients with benign tumors and control patients (P-value = 0. 021). As for HOXA11, the mean expression was relatively lower in the patients with benign endometrial tumors, 0. 94±0. 06 as compared to the control group 1. 00±0. 07. In addition, the mean HOXA11 expression in endometrial cancer patients was 0. 24±0. 03 which was significantly (P-value >0. 001) less than that in benign endometrial tumor patients. Conclusion: These results stress the importance of HOXA11 expression as a diagnostic marker and its possible application in differential diagnosis between endometrial cancer and benign neoplasms and normal tissues. [ABSTRACT FROM AUTHOR]

Background: Accurately predicting ovulation timing is critical for women undergoing natural cycle-frozen embryo transfer. However, the precise predicting of the ovulation timing remains challenging due to the lack of consensus among different clinics regarding the definition of this significant event. Objective: To compare the effectiveness of preovulatory serum progesterone levels (P4) versus luteinizing hormone levels (LH) in predicting ovulation time using two machine learning models. Methods: 771 patients who underwent autologous natural cycle-frozen embryo transfer between January 2015 and February 2022 were recruited. Utilizing variables including follicle diameters, preovulatory serum levels of LH, E2, and P4, two machine learning models were constructed to predict the ovulation time, the importance of the variables in predicting ovulation timing was further ranked. Results: Two machine learning models have the capability to accurately predict the timing of ovulation, specifically within 72, 48, or 24 h. The overall accuracy rates of the validation dataset, as determined by the classification trees and random forest models, were found to be 78.83% and 85.28% respectively. Notably, when predicting ovulation within 24 h, the accuracy rate of P4 ≥ 0.65ng/ml exceeded 92%. Furthermore, it was important to consider LH or E2 levels in conjunction with P4 when assessing ovulation timing in cases where P4<0.65ng/ml. Conclusions: Preovulatory serum P4 levels are better predictors of ovulation timing than LH levels and could be used as an alternative in clinical settings, and the model we developed can be used to pinpoint the day of ovulation. Ongoing research and advancements in technology are anticipated to enhance and refine the ovulation method. [ABSTRACT FROM AUTHOR]

Reproductive strategies of hibernating insectivorous bats and reproduction phenology parameters can vary considerably as they will be influenced by ecological seasonality. While the exact timing of greater mouseeared bat (Myotis myotis) reproduction is described through morphological assessment of dissected embryos, most recent studies have focused only on population or behavioural aspects of reproduction. In our study, non-invasive ultrasound examination and non-lethal blood sampling were used to assess basic reproduction parameters of M. myotis from two nursery colonies over two gestation periods with different weather conditions. We found that ovulation probably occurred before female emergence from the hibernacula between late March and mid-April, triggered by a short period of high ambient temperature lasting at least three days. On the other hand, the estimated date of blastocyst implantation only varied within four days despite weather conditions differing significantly over the two years. Though specific foetal growth velocity did not differ between localities, the date of parturition was influenced by shelter temperature in May (difference between localities) and average ambient temperature in April (difference between years). The progesterone level does not appear to be a suitable indicator of pregnancy stage as it changed significantly during pregnancy and did not correlate with foetus size. The total gestation period (from fertilisation to parturition) varied between 56 and 73 days in our study. [ABSTRACT FROM AUTHOR]

Aminergic nuclei in mammals are generally composed of relatively small numbers of cells with broad projection patterns. Despite the gross similarity of many individual neurons, recent transcriptomic, anatomic and behavioral studies suggest previously unsuspected diversity. Smaller clusters of aminergic neurons in the model organism Drosophila melanogaster provide an opportunity to explore the ramifications of neuronal diversity at the level of individual cells. A group of approximately 10 tyraminergic/octopaminergic neurons innervates the female reproductive tract in flies and has been proposed to regulate multiple activities required for fertility. The projection patterns of individual neurons within the cluster are not known and it remains unclear whether they are functionally heterogenous. Using a single cell labeling technique, we show that each region of the reproductive tract is innervated by a distinct subset of tyraminergic/octopaminergic cells. Optogenetic activation of one subset stimulates oviduct contractions, indicating that the cluster as a whole is not required for this activity, and underscoring the potential for functional diversity across individual cells. Using whole cell patch clamp, we show that two adjacent and morphologically similar cells are tonically inhibited, but each responds differently to injection of current or activation of the inhibitory GluCl receptor. GluCl appears to be expressed at relatively low levels in tyraminergic/octopaminergic neurons within the cluster, suggesting that it may regulate their excitability via indirect pathways. Together, our data indicate that specific tyraminergic/octopaminergic cells within a relatively homogenous cluster have heterogenous properties and provide a platform for further studies to determine the function of each cell. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a chronic inflammatory disease of women during their reproductive years. The relationship between the severity and location of endometriosis and menstruation, ovulation, reproductive function, and mode of delivery remains unclear. Methods: We explored the association between the various phenotypes of endometriosis and menstruation, ovulation, reproductive function, and mode of delivery, using two-sample Mendelian randomization (MR) and summary data on endometriosis stages and locations from the FinnGen consortium and women's menstruation, ovulation, reproductive function, and mode of delivery from OpenGWAS and ReproGen. Inverse-variance weighting was used for the primary MR analysis. In addition, a series of sensitivity analyses, confounding analyses, co-localization analyses, and multivariate MR analyses were performed. Results: MR analysis showed a negative effect of moderate to severe endometriosis on age at last live birth (OR = 0.973, 95% CI: 0.960-0.986) and normal delivery (OR = 0.999, 95% CI: 0.998-1.000; values for endpoint were excluded), ovarian endometriosis on age at last live birth (OR = 0.976, 95% CI: 0.965-0.988) and normal delivery (OR = 0.999, 95% CI: 0.998-1.000; values for endpoint were excluded), and fallopian tubal endometriosis on excessive irregular menstruation (OR = 0.966, 95% CI: 0.942-0.990). Bidirectional MR analysis showed that age at menarche had a negative causal effect on intestinal endometriosis (OR = 0.417, 95% CI: 0.216-0.804). All MR analyses were confirmed by sensitivity analyses, and only the genetic effects of moderate to severe endometriosis on normal delivery and age at last live birth were supported by co-localization evidence. Conclusion: Our findings deepen the understanding of the relationship between various types of endometriosis and menstruation, ovulation, reproductive function, and mode of delivery and clarify the important role of moderate to severe endometriosis. [ABSTRACT FROM AUTHOR]

Batch spawner fishes develop successive clutches of oocytes which allows them to participate in many reproductive cycles during their adult life (iteroparous) and spawn in multiple events within each breeding cycle. Here, ovarian follicular development was morpho‐functionally analyzed in females of the iteroparous batch spawner fish Gymnocorymbus ternetzi. To obtain better insights into the reproductive morpho‐physiology in batch spawners, the objective of this research was to analyze the dynamics of the follicular development, with its hormonal regulation between two active reproduction events. We found that over 16 days, follicles progressed asynchronously to chromatin nucleolus, Primary and Secondary growth stages of oogenesis with progressive secretion of 17β‐estradiol (E2). During the end of secondary growth, the increase in 17α,20β‐dihydroxy‐4‐pregnen‐3‐one (17,20β‐p) was measured relative to the maturation process of the ovarian follicles (e.g., nuclear migration and its rupture during the resumption of meiosis). Interestingly, an additional increase in E2 was observed after fish reproduction, probably related to the recruitment of new batch follicles for secondary growth. We also measured the high values of multiple condition factor post‐reproduction measurements, reflecting more energy invested during the pre‐reproductive process. We also quantified high concentrations of 17,20β‐p, probably related to the recruitment of a new batch of oogonia to meiosis, presumably secreted by post‐ovulatory follicles, after fish reproduction. We finally found that fish without exposure to reproductive stimulus developed a regression phase at day 24, characterized by massive follicle atresia, that allow them to recycle energy and constitutive materials of the follicles invested during oogenesis for another reproductive cycle. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion The use of fertility indicators to predict ovulation has largely been studied for contraceptive purposes, while less so as fertility‐promoting tools.To investigate the association between fertility indicators and fecundability in Danish women trying to conceive.Web‐based preconception cohort study. We analysed data from 11,328 females aged 18–49 years trying to conceive without fertility treatment for ≤6 menstrual cycles, from the Danish SnartGravid.dk and SnartForældre.dk cohorts (2007–2023). Participants reported the use of fertility indicators (counting days since the last menstrual period, cervical fluid monitoring, urinary ovulation testing, feeling ovulation, using a smartphone fertility app and measuring basal body temperature [BBT]). Time to pregnancy was measured in menstrual cycles ascertained by self‐reported pregnancy status. We estimated fecundability ratios (FR) and 95% confidence intervals (CIs) using proportional probabilities regression models adjusted for age, socio‐economic position, health indicators, reproductive history and gynaecological factors.Fertility indicators were used by 63.3% of participants at study entry. Counting days was the most common (46.9%), while measuring BBT was the least (3.0%). Other indicators ranged from 17.0% to 23.6%, with 69.7% using more than one indicator. Compared with non‐use, use of any fertility indicator was associated with greater fecundability (adjusted FR 1.14, 95% CI 1.08, 1.19). Cervical fluid monitoring showed the strongest association (aFR 1.46, 95% CI 1.03, 2.07), followed by urinary ovulation testing (aFR 1.35, 95% CI 1.16, 1.58) and counting days (aFR 1.18, 95% CI 1.09, 1.29). Feeling ovulation and fertility apps were modestly associated with fecundability, while measuring BBT was not associated. Sensitivity analysis restricting to ≤2 cycles of attempt time and two cycles of follow‐up showed an aFR for any indicator use of 1.21 (95% CI 1.13, 1.31).In this Danish preconception cohort, use of fertility indicators was associated with a higher fecundability, varying by type of indicator. [ABSTRACT FROM AUTHOR]

The Booroola fecunditymutation (FecB) in Small Tail Han sheep has been shown to enhance ovulation rates and litter sizes by affecting the hypothalamic-pituitary-gonadal (HPG) axis. Despite the pituitary's role in reproductive regulation, its involvement in FecB-induced ovulation remains understudied. Our study aimed to fill this gap by analyzing pituitary tissues from FecB homozygous (BB) and wildtype (WW) ewes during luteal and follicular phases using tandem mass tag-based protein quantification and the DIABLO framework for proteomic and transcriptomic data integration. Significant differences in 277 proteins were observed across estrus periods, with network analysis highlighting the voltagedependent calcium channel L-type alpha-1C as a key convergence point in oxytocin signaling and GnRH secretion pathways. The DIABLO method revealed a strong correlation (0.98) between proteomic and transcriptomic datasets, indicating a coordinated response in FecB ewes. Notably, higher expression levels of Follicle Stimulating Hormone Subunit Beta (FSHB) and Luteinizing Hormone Subunit Beta (LHB) were found in BB ewes during the follicular phase, potentially due to elevated E2 concentrations. Furthermore, our analysis identified genes related to the Gamma-aminobutyric acid type A receptor family (GABRA2, GABRG1, GABRB1) in the pituitary, with GABRB1 showing higher expression in BB ewes. This suggests a role for GABA in modulating GnRH and gonadotropin feedback loops, potentially contributing to the FecB mutation's effect on ovulation. This study provides novel insights into the pituitary's role in fertility among FecB sheep, identifying GABA as a potential regulatory factor within the HPG axis. The findings also open avenues for discovering new biomarkers in pituitary endocrinology for sheep breeding purposes. [ABSTRACT FROM AUTHOR]

Simple Summary: Chronic stress significantly impacts physical and mental health and has also been shown to affect female reproduction, but the underlying mechanisms are not well understood. Our research focused on the P2X7 receptor, a protein involved in the pathological response under long-term stress. Using mouse models subjected to chronic restraint and cold stress, we observed reduced ovulation rates, a key indicator of reproductive health. We discovered that stress increases the expression of the P2X7 receptor in the ovaries. Treatment with P2X7R inhibitor partially rescued the ovulation rate of the two chronic stress models. This study reveals that managing stress and potentially targeting the P2X7 receptor could help improve reproductive health in women experiencing chronic stress, offering a new approach to treating stress-related reproductive issues. Chronic stress has become a major problem that endangers people's physical and mental health. Studies have shown that chronic stress impairs female reproduction. However, the related mechanism is not fully understood. P2X7 receptor (P2X7R) is involved in a variety of pathological changes induced by chronic stress. Whether P2X7R is involved in the effect of chronic stress on female reproduction has not been studied. In this study, we established a chronic restraint stress mouse model and chronic cold stress mouse model. We found that the number of corpora lutea was significantly reduced in the two chronic stress models. The number of corpora lutea indirectly reflects the ovulation, suggesting that chronic stress influences ovulation. P2X7R expression was significantly increased in ovaries of the two chronic stress models. A superovulation experiment showed that P2X7R inhibitor A-438079 HCL partially rescued the ovulation rate of the two chronic stress models. Further studies showed that activation of P2X7R signaling inhibited the cumulus expansion and promoted the expression of NPPC in granulosa cells, one key negative factor of cumulus expansion. Moreover, sirius red staining showed that the ovarian fibrosis was increased in the two chronic stress models. For the fibrosis-related factors, TGF-β1 was increased and MMP2 was decreased. In vitro studies also showed that activation of P2X7R signaling upregulated the expression of TGF-β1 and downregulated the expression of MMP2 in granulosa cells. In conclusion, P2X7R expression was increased in the ovaries of the chronic restraint-stress and chronic cold-stress mouse models. Activation of P2X7R signaling promoted NPPC expression and cumulus expansion disorder, which contributed to the abnormal ovulation of the chronic stress model. Activation of P2X7R signaling is also associated with the ovarian fibrosis changes in the chronic stress model. [ABSTRACT FROM AUTHOR]

Purpose: To examine the pattern of kisspeptin expression throughout the menstrual cycle in polycystic ovary syndrome (PCOS) patients under the ovulation induction and identify any possible associations with early pregnancy. Materials and methods: A prospective cohort of 80 PCOS women who expressed the desire for fertility was enrolled in this study. All of them received the ovulation induction by using letrozole. Levels of kisspeptin, luteinizing hormone (LH), and estradiol (E2) were measured at three different time points during menstruation. The early pregnancy rate was recorded for the study participants after three ovulation cycles. Results: Kisspeptin levels varied regularly during the menstrual cycle, reaching a peak on the day of hCG injection and decreasing after ovulation. There was no significant correlation between kisspeptin and LH levels. Basal kisspeptin levels decreased after letrozole treatment without a significant difference while LH and E2 levels decreased significantly. PCOS participants who became pregnant early had higher basal kisspeptin levels compared to non-pregnant PCOS patients, which had a significant difference (P = 0.006). And the average basal kisspeptin level in pregnant patients was 2293.0 ± 398.7 pg/ml, with a 95% confidence interval of 1511.5–3074.5 pg/ml. Conclusion: Kisspeptin levels in PCOS women undergoing ovulation induction showed a regular variation, which was similar with the healthy women reported in previous studies. The use of LE may result in PCOS endocrine improvement and fertility achievement. In a certain range, kisspeptin might be a potential predictor for early pregnancy in PCOS patients as people with slightly higher basal kisspeptin levels seemed more likely to be pregnant. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. The initial ovulatory response during synchronization programs is often low in dairy heifers, largely due to follicular dynamics and hormonal dynamics. Specifically, the progesterone (P4) concentration at the time of the first GnRH treatment in a breeding program can influence the LH response, often resulting in a suboptimal ovulatory response. The objective of this study was to determine the effect of the highest label dose 200 μg (100 μg vs. 200 μg) of GnRH (50 μg of gonadorelin hydrochloride per mL; Factrel, Zoetis Inc. Madison, NJ) at the first GnRH of a 6-d CO-Synch plus P4 device program on ovulatory response and pregnancy per AI (P/AI) in first service in Holstein heifers. A total of 1,308 Holstein heifers were randomly allocated at the beginning of a 6-d CO-Synch program at day 0 to receive either i.m. treatment of 100 μg (2CC, n = 655) or 200 μg (4CC, n = 653) of GnRH. Also, at d 0, heifers received an intravaginal insert with 1.38 g of P4 (Eazi-Breed CIDR Cattle Insert, Zoetis Inc.). On day 6, the insert was removed, and i.m. treatment of 25 mg of PGF 2α (12.5 mg of dinoprost tromethamine/mL; Lutalyse HighCon Injection, Zoetis Inc.) was administered. On d 7, a second i.m. treatment of 25 mg of PGF 2α was given, followed on d 9 by concurrent i.m. treatment of 100 μg of GnRH, and timed AI. A subset of 396 heifers had their ovaries scanned to evaluate ovulatory response, and blood samples were collected to measure the serum concentration of P4 at d 0 and d 6 of the study. The P4 concentrations at d 0 were categorized as low (≤3 ng/mL) or high (>3 ng/mL). The ovulatory response was greater for heifers receiving 4CC than 2CC at d 0 (54.7% vs. 42.8%). The ovulatory response was greater for low P4 than high P4 at d 0 (54.3% vs. 37.8%). However, we did not observe an interaction between treatment and P4 concentrations (low P4 2CC = 48.6% vs. high P4 2CC = 30.0%; low P4 4CC = 60.0% vs. high P4 4CC = 45.5%). The receiver operating characteristic curve analysis indicated that P4 concentrations at d 0 treatment could predict the ovulatory response, although the area under the curve was only 0.6. As expected, heifers that ovulated had increased P/AI (no = 55.6% vs. yes = 67.7%); however, we found no effect of treatment on P/AI (2CC = 63.3% vs. 4CC = 59.6%), and no interactions between treatment and ovulation and treatment and P4 (high vs. low) for pregnancy outcomes. In summary, P4 concentration and increasing the dose of GnRH at d 0 positively affected ovulatory response in Holstein heifers. However, there was no interaction between treatment and P4 on ovulation and no subsequent impact of GnRH dose on P/AI. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the effects of administering estradiol (E−17β) at the moment of timed-AI (TAI) on uterine gene expression, estrous expression rate (EER), and pregnancy rate (P/TAI) in Nelore cows with a small dominant follicle (DF) or not showing estrus at TAI. In Experiments 1 and 2 (Exp1, Exp2) cows were submitted to a P4/E−17β-based protocol (day 0) for synchronization of ovulation. On day 7, devices were removed, cows received 1 mg E−17β cypionate and 12.5 mg dinoprost. On day 9, cows with DF < 11.5 mm in diameter were split into different groups. In Exp1 (n = 16/group): Control (no treatment), E−2 (2 mg E−17β) and E−4 (4 mg E−17β). In Exp2: Control (n = 12); E−2 (n = 14); GnRH (0.1 mg gonadorelin acetate, n = 13); and E−2+GnRH (association of GnRH and E−17β, n = 13). Between days 9 and 11, endometrial thickness (ET), time of ovulation detection, and EER were recorded. In Exp1, a uterine cytological sample was collected 4 h after treatment to evaluate the transcript expression of receptors for E−17β (ESR1 and ESR2), oxytocin (OXTR), and P4 (PGR). In Experiment 3 (Exp3), 3829 suckled cows were submitted to a P4/E−17β-based protocol for TAI. On day 9, devices were removed and cows received 1 mg E−17β cypionate and 0.4 mg sodium cloprostenol. On day 11, TAI was performed and cows that did not demonstrate estrus received 0.1 mg gonadorelin acetate, and were allocated into two groups: GnRH (n = 368) and E−2+GnRH (2 mg E−17β; n = 363). In Exp1, plasma E−17β concentrations increased at 4 h after treatment in a dose-dependent manner but reduced at 12 h. The E−17β-treated cows had greater transcript abundance for OXTR and lesser for ESR1 and ESR2, and the ET was reduced 12 h after treatment (P < 0.05). No significant difference (P > 0.1) was observed between the E−17β doses in estrus or ovulation rate. In Exp2, the interval from treatment to ovulation was longer (P < 0.05) in the E−17β group. GnRH-treated cows showed higher ovulation rates (89 vs. 35 %) compared to cows not treated with GnRH, as E−17β-treated cows (P < 0.01) had a lower ovulation rate compared to those not receiving E−17β (44 vs. 78 %). In Exp3, P/TAI was 55 % for cows in estrus. For those not showing estrus, no difference (P > 0.1) in P/TAI was observed between GnRH (34 %) and E−2+GnRH (31 %) groups. Cows with a DF ≥ 11 mm (n = 192) had a greater (P < 0.05) P/TAI (49 %) than those with DF < 11 mm (n = 377; 29 %). In conclusion, E−17β administration in the moment of TAI modulates the mRNA expression of uterine receptors in cows with a small DF but does not impact the P/TAI compared with GnRH treatment in suckled Nelore not showing estrus previous to TAI. • Administration 2 and 4 mg E−17β increase in circulating E−17β in cows with DF < 11 mm. • Administration 2 and 4 mg E−17β reduces ESR1 and ESR2, and increases OXTR expression. • Administration 2 mg E−17β with GnRH at TAI in non-estrus Nelore had no P/TAI impact. • The dominate follicle is larger in cows with fluid present in uterus at TAI moment. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether trigger and oocyte collection at a smaller follicle size decreases the risk of premature ovulation while maintaining the reproductive potential of oocytes in women with a severely diminished ovarian reserve undergoing modified natural‐cycle in‐vitro fertilization. Methods: This was a retrospective cohort study including women who had at least one unsuccessful cycle (due to no response) of conventional ovarian stimulation with a high dosage of gonadotropins and subsequently underwent a modified natural cycle with a solitary growing follicle (i.e. only one follicle > 10 mm at the time of trigger). The association between follicle size at trigger and various cycle outcomes was tested using regression analyses. Results: A total of 160 ovarian stimulation cycles from 110 patients were included in the analysis. Oocyte pick‐up (OPU) was performed in 153 cycles and 7 cycles were canceled due to premature ovulation. Patients who received their trigger at smaller follicle sizes (≤ 15 mm) had significantly lower rates of premature ovulation and thus higher rates of OPU (98.9% vs 90.8%; odds ratio, 9.56 (95% CI, 1.58–182.9); P = 0.039) compared with those who received their trigger at larger follicle sizes (> 15 mm). On multivariable analysis, smaller follicle sizes at trigger (> 10 to 13 mm, > 13 to 15 mm, > 15 mm to 17 mm) were not associated significantly with a lower rate of cumulus–oocyte complex (COC) retrieval, metaphase‐II (MII) oocytes or blastulation when compared to the > 17‐mm group. On sensitivity analysis including only the first cycle of each couple, the maturity rate among those with COC retrieval was highest in follicle sizes > 15 to 17 mm (92.3%) and > 13 to 15 mm (91.7%), followed by > 10 to 13 mm (85.7%) and lowest in the > 17‐mm group (58.8%). During the study period, five euploid blastocysts developed from 48 fertilized MII oocytes with follicle sizes of 12 mm (n = 3), 14 mm (n = 1) and 16 mm (n = 1) at trigger. Of those, four were transferred and resulted in two live births, both of which developed from follicles with a size at trigger of 12 mm. Conclusions: The ideal follicle size for triggering oocyte maturation may be smaller in women with a severely diminished ovarian reserve managed on a modified natural cycle when compared to conventional cut‐offs. The risk of OPU cancellation was significantly higher in women triggered at follicle size > 15 mm and the yield of mature oocytes was not adversely affected in women triggered at follicle size > 13 to 15 mm compared with > 15 to 17 mm. Waiting for follicles to reach sizes > 17mm may be detrimental to achieving optimal outcome. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

This study evaluated the use of the GnRH agonist hormone, deslorelin, to control the follicular population before initiating multiple ovulation and embryo transfer (MOET) treatment. Twenty‐four cross‐bred Santa Inês ewes, aged between 2 and 4 years, were randomly assigned to either a control group (n = 11) or a treated group (n = 13). All ewes received an intravaginal device containing 60 mg of medroxyprogesterone acetate on day 0, and a new device on day 7, which remained in place until day 14. Additionally, the ewes were administered 125 μg of cloprostenol on day 7. The superovulatory treatment involved administering 200 mg of pFSH, divided into eight decreasing doses at 12‐h intervals starting on day 12. On day 14, 300 IU of eCG was administered. In the deslorelin group, three doses of 100 μg of deslorelin were administered starting on day 3 after the insertion of the vaginal device, with subsequent doses given at 72‐h and 144‐h intervals. Natural mating was performed 36 h after the removal of the progesterone implant using males with proven fertility. Embryo collection took place on the 6th day after mating, and the recovered structures were quantified and evaluated for quality and developmental stage. Transrectal ultrasonography was conducted on days 12, 16 and 21 to evaluate the ovaries, specifically to assess the ovarian follicular population and the presence of the corpus luteum. Ewes in the control group had higher embryo recovery rates (p <.01) compared to the treated group (5.2 ± 0.8 vs. 1.1 ± 0.8), with differences observed primarily in the number of morulae. The number of corpus luteum observed during the laparotomy on day 21 was significantly higher (p <.01) in the control group (10.44 vs. 4.5 corpus luteum per ewe). Yet, the treated group had a significantly higher number of follicles (p <.05) on the first day of pFSH application (5.5 vs. 3.0 follicles per ewe). In conclusion, although the inclusion of deslorelin in the superovulation protocol resulted in increased synchronization of oestrus and follicle number, it did not lead to an increase in the number of corpus luteum or harvested embryos. [ABSTRACT FROM AUTHOR]

The nature of the human being, especially that of women, is complex (de Jonge et al., 2019). Various interacting variables, including physiological, biomechanical, physical, psychological, and emotional factors, constitute the nature of women. In this context, across the menstrual cycle (MC) there are fluctuations in the levels of sex hormones such as progesterone, estrogen, follicle-stimulating hormone (FSH), and luteinizing hormone (LH), which is crucial to regulate ovulation and delimiting phases (Romero-Moraleda et al. 2019). This study aimed to compare neuromuscular performance, perceived exertion, and well-being across menstrual cycle (MC), specifically follicular phase (FPh) and luteal phase (LPh) in under-17 players from national soccer team. Thirteen players (age = 15.69 ± 0.48 years) were assessed for mean propulsive velocity (MPV) in the back squat, countermovement jump (CMJ), 10-meter time (T10). Additionally, subjective measures were collected using a well-being questionnaire (WQ) administered before training, wich evaluated muscular pain, mood, stress, sleep, fatigue and overall well-being (the sum of these five factors), as the rating of perceived exertion (RPE) scale after training. Just T10 exhibited only trivial to small differences between phases (p = .040; ES = 0.13), favoring LPh. Both MPV30 and CMJ showed trivial differences between phases. The remaining variables demonstrated unclear differences (p > .05) across the MC phases. Based on the results, it can be inferred that the MC phases had a discernible impact only on T10 in this sample, where participants exhibited superior performance in LPh, albeit with trivial to small effects that may lack clinical significance. Conversely, subjective measures obtained from the WQ and RPE scale indicated unclear differences between phases. [ABSTRACT FROM AUTHOR]

Simple Summary: The goal of this research was to determine if the neurotrophin β-Nerve growth factor is present in the reproductive tract of stallions. This protein has been identified in the semen of camelids and functions to stimulate the release of a hormone from the pituitary of female camelids that is ultimately responsible for the induction of ovulation. β-Nerve growth factor (β-NGF) is a protein produced in the reproductive tract of camelids (camels, llamas, and alpacas) that has been identified as the ovulation inducing factor in seminal plasma. β-NGF from seminal plasma deposited into the reproductive tract of the female camelid acts systemically to stimulate the secretion of luteinizing hormone (LH) from the anterior pituitary, which in turn induces follicle maturation and ovulation. The objectives of the present study were to determine if β-NGF is present in the reproductive tract of the stallion and identify the specific site(s) of production. The hypotheses were that β-NGF would be present in the stallion reproductive tract and would primarily be localized in Sertoli cells of the testes and the prostate gland. Immunohistochemistry on paraffin-embedded paraformaldehyde-fixed tissues was performed using a rabbit polyclonal anti-β-NGF antibody on a total of six male equine reproductive tracts, including a one-day old colt, a one-year-old colt, and four adult stallion tracts. Strong immunostaining was observed in the efferent ducts of the testes and the epithelial cells of the prostate, seminal vesicles, bulbourethral glands, and ampullae. Weaker β-NGF staining was noted in Leydig cells, Sertoli cells, and spermatogonia within the testes and in epithelial cells of the epididymis. In conclusion, immunohistochemistry revealed that β-NGF is present in the stallion reproductive tract, and the protein is primarily present in the efferent ducts of the testes and in all accessory sex glands. [ABSTRACT FROM AUTHOR]

Background and Objectives: Polycystic ovarian syndrome (PCOS) is a widespread endocrine disorder affecting 5–18% of females in their childbearing age. The aim of this study is to assess the efficacy of combining a low dosage of human chorionic gonadotropin (HCG) along with clomiphene citrate (CC) for stimulating ovulation in infertile women diagnosed with CC-resistant PCOS. Materials and Methods: A randomized controlled trial was carried out on 300 infertile CC-resistant PCOS women. All participants were assigned to two groups: the CC-HCG group and the CC-Placebo group. Subjects in the CC-HCG group were given CC (150 mg/day for 5 days starting on the 2nd day of the cycle) and HCG (200 IU/day SC starting on the 7th day of the cycle). Subjects in the CC-Placebo group were given CC and a placebo. The number of ovarian follicles > 18 mm, cycle cancellation rate, endometrial thickness, ovulation rate, clinical pregnancy rate, and occurrence of early ovarian hyper-stimulation syndrome were all outcome variables in the primary research. Results: Data from 138 individuals in the CC-HCG group and 131 participants in the CC-Placebo group were subjected to final analysis. In comparison to the CC-Placebo group, the cycle cancellation rate in the CC-HCG group was considerably lower. The CC-HCG group exhibited a substantial increase in ovarian follicles reaching > 18 mm, endometrial thickness, and ovulation rate. The clinical pregnancy rate was higher in the CC-HCG group (7.2% vs. 2.3%; CC-HCG vs. CC-Placebo). Upon adjusting for BMI and age, the findings of our study revealed that individuals in the CC-HCG group who had serum prolactin levels below 20 (ng/mL), secondary infertility, infertility duration less than 4 years, baseline LH/FSH ratios below 1.5, and serum AMH levels more than 4 (ng/mL) had a higher likelihood of achieving pregnancy. In the CC-Placebo group, there was a greater prediction of clinical pregnancy for those with serum AMH (<4), primary infertility, serum prolactin ≤ 20 (ng/mL), baseline LH/FSH < 1.5, and infertility duration < 4 years. Conclusions: The use of a small dose of HCG along with CC appeared to be an effective treatment in reducing cycle cancelation, improving the clinical pregnancy rate and ovulation rate in CC-resistant PCOS patients. The trial was registered with Clinical Trials.gov, identifier NCT02436226 [ABSTRACT FROM AUTHOR]

Background and Objectives: Fertility tracking apps and devices are now currently available, but urinary hormone levels lack accuracy and sensitivity in timing the start of the 6-day fertile window and the precise 24 h interval of transition from ovulation to the luteal phase. We hypothesized the serum hormones estradiol (E2) and progesterone (P) might be better biomarkers for these major ovulatory cycle events, using appropriate mathematical tools. Materials and Methods: Four women provided daily blood samples for serum E2, P, and LH (luteinizing hormone) levels throughout their entire ovulatory cycles, which were indexed to the first day of dominant follicle (DF) collapse (defined as Day 0) determined by transvaginal sonography; therefore, ovulation occurred in the 24 h interval of Day −1 (last day of maximum diameter DF) to Day 0. For comparison, a MiraTM fertility monitor was used to measure daily morning urinary LH (ULH), estrone-3-glucuronide (E3G), and pregnanediol-3-glucuronide (PDG) levels in three of these cycles. Results: There were more fluctuations in the MiraTM hormone levels compared to the serum levels. Previously described methods, the Fertility Indicator Equation (FIE) and Area Under the Curve (AUC) algorithm, were tested for identifying the start of the fertile window and the ovulation/luteal transition point using the day-specific hormone levels. The FIE with E2 levels predicted the start of the 6-day fertile window on Day −7 (two cycles) and Day −5 (two cycles), whereas no identifying signal was found with E3G. However, both pairs of (E2, P) and (E3G, PDG) levels with the AUC algorithm signaled the Day −1 to Day 0 ovulation/luteal transition interval in all cycles. Conclusions: serum E2 and (E2, P) were better biomarkers for signaling the start of the 6-day fertile window, but both MiraTM and serum hormone levels were successful in timing the [Day −1, Day 0] ovulatory/luteal transition interval. These results can presently be applied to urinary hormone monitors for fertility tracking and have implications for the direction of future fertility tracking technology. [ABSTRACT FROM AUTHOR]

Bone morphogenetic protein 15 (BMP15) is an oocyte‐specific growth factor important for successful female reproduction in mammals. While mutations in BMP15/Bmp15 cause ovulatory deficiency and/or infertility in certain mammalian species, loss of bmp15 in zebrafish, a continuous spawner and the only bmp15 knockout model in fish to date, results in complete arrest of follicle development and later female‐to‐male sex reversal, preventing to examine effects on ovulation/fertilization. Here, we used Atlantic salmon, a seasonal spawner, and generated bmp15 mutants to investigate ovarian development and fertility. Histological and morphometric analyses revealed that in biallelic frameshift (bmp15 fs/fs) mutant ovaries, folliculogenesis started earlier, resulting in an advanced development compared to wild‐type (WT) controls, accompanied by a weaker expression of the (early) oocyte‐specific factor figla. This precocious ovarian development was followed in bmp15 fs/fs females by enhanced follicle atresia during vitellogenic stages. Although genes involved in steroid synthesis and signaling (star, cyp11b, cyp17a1 and esr1) were dramatically higher in late vitellogenic bmp15 fs/fs mutant ovaries, estradiol‐17β plasma levels were lower than in WT counterparts, potentially reflecting compensatory changes at the level of ovarian gene expression. At spawning, bmp15 fs/fs females displayed lower gonado‐somatic index values and reduced oocyte diameter, and the majority (71.4%), showed mature non‐ovulating ovaries with a high degree of atresia. The remaining (28.6%) females spawned eggs but they either could not be fertilized or, upon fertilization, showed severe malformations and embryonic mortality. Our results show that Bmp15 is required for proper follicle recruitment and growth and later ovulatory success in Atlantic salmon, providing an alternative candidate target to induce sterility in farmed salmon. Moreover, since loss of bmp15 in salmon, in contrast to zebrafish, does not result in female‐to‐male sex change, this is the first mutant model in fish allowing further investigations on Bmp15‐mediated functions in the ovulatory period. [ABSTRACT FROM AUTHOR]

Although men's attraction to women's body odour has been suggested to vary over the ovulatory cycle, peaking around the fertile window, we still lack methodologically robust evidence corroborating this effect. Further, the chemical underpinnings of male preference for the odour of ovulating women remain unknown. Here, we combined perceptual and chemical analyses to investigate the axillary odour of naturally cycling women over 10 days, covering the gradual change in fertility across the ovulatory cycle with a focus on fertile days. The fertile state was confirmed by urinary ovulation tests as well as salivary oestradiol and progesterone levels. Men rated the scent of unfamiliar women, resembling a first encounter. We used multivariate analyses to relate variation in both odour ratings and chemical composition to female conception probability, temporal distance to ovulation and ovarian hormone levels. Our results provide no evidence that males prefer the odour of fertile women. Furthermore, the volatile analysis indicated no link between axillary odour composition and current fertility status. Together, our results showed no convincing support for a chemical fertility cue in women's axillary odour, questioning the presence of olfactory fertility information that is recognizable during first encounters in modern humans. [ABSTRACT FROM AUTHOR]

Summary Abdominal ultrasonography is an important diagnostic tool in the evaluation of colic, yet primary care equine veterinary practitioners are often limited by availability and access to low‐frequency (2–5 MHz curvilinear array or sector) abdominal transducers. Use of high‐frequency (5–10 MHz linear array) transrectal transducers has not previously been compared with use of abdominal transducers for transcutaneous abdominal ultrasonography. One recent pilot study established that there was no significant difference in organ detection by the two transducers on the right side of the equine abdomen, but the stomach, liver and kidney on the left side were less likely to be detected using the transrectal transducer in healthy horses. A clinical study found that the transrectal transducer can be used successfully using the FLASH protocol in horses presenting with colic, with high‐quality images that detected abnormalities of the peritoneal fluid, small intestine and large intestine. The transrectal transducer had decreased visualisation of the stomach and left kidney and was less likely to detect pathology surrounding these organs. This is the first series of studies to evaluate use of transrectal transducers in abdominal ultrasonography of the horse, a tool that is readily accessible to the field practitioner. [ABSTRACT FROM AUTHOR]

Objective: To explore the impact of the level of differentiation in aminimum of two follicles with a diameter of ≥18 mm on the outcome of controlled ovarian hyperstimulation on the day of human chorionic gonadotropin (hCG) administration. Methods: Single-center data from January 2018 to December 2021 was retrospectively analyzed for 1,199 patients with fresh embryo transfer for assisted reproduction. The absolute value of the standard deviation of the follicle size of at least 2 follicles ≥18 mm in diameter in both ovaries on the day of hCG was taken as the degree of differentiation of the dominant follicle after ovulation induction, based on the standard deviation response to the degree of dispersion of the data. The degree of follicular differentiation was divided into 3 groups according to the size of the value, and the general clinical conditions, laboratory indexes, and clinical outcomes of the patients in the 3 groups were compared. Results: Among the three groups, the body mass index (BMI) of the ≤1s group was lower than that of the other two groups (P< 0.05), while the follicle-stimulating hormone (FSH) and Anti-Mullerian hormone (AMH) were higher (P< 0.05), and the implantation rate and clinical pregnancy rate were significantly higher than those of the other two groups (P< 0.01). After multifactorial logistic regression to correct for confounding factors, with the ≤1s group as the reference, the implantation rate, hCG-positive rate, clinical pregnancy rate and live birth rate of embryo transfer in the ≥2S group were significantly lower (P< 0.01). The results of curve fitting analysis showed that the live birth rate decreased gradually with the increase of the absolute standard deviation (P=0.0079). Conclusion: Differences in follicle diameters ≥18 mm on the day of hCG injection did not have an impact on embryo quality, but had an impact on pregnancy outcomes. The less the variation in follicle size, the more homogeneous the follicle development and the higher the likelihood of live births. [ABSTRACT FROM AUTHOR]

Introduction: Premature ovarian insufficiency (POI) is one of the causes of female infertility. Unexplained POI is increasingly affecting women in their reproductive years. However, the etiology of POI is diverse and remains elusive. We and others have shown that brain-derived neurotrophic factor (BDNF) plays an important role in adult ovarian function. Here, we report on a novel role of BDNF in the Developmental Origins of POI. Methods: Placental BDNF knockout mice were created using CRISPR/CAS9. Homozygous knockout (cKO(HO)) mice didn't survive, while heterozygous knockout (cKO(HE)) mice did. BDNF reduction in cKO(HE) mice was confirmed via immunohistochemistry and Western blots. Ovaries were collected from cKO(HE) mice at various ages, analyzing ovarian metrics, FSH expression, and litter sizes. In one-month-old mice, oocyte numbers were assessed using super-ovulation, and oocyte gene expression was analyzed with smart RNAseq. Ovaries of P7 mice were studied with SEM, and gene expression was confirmed with RT-qPCR. Alkaline phosphatase staining at E11.5 and immunofluorescence for cyclinD1 assessed germ cell number and cell proliferation. Results: cKO(HE) mice had decreased ovarian function and litter size in adulthood. They were insensitive to ovulation induction drugs manifested by lower oocyte release after superovulation in one-month-old cKO(HE) mice. The transcriptome and SEM results indicate that mitochondria-mediated cell death or aging might occur in cKO(HE) ovaries. Decreased placental BDNF led to diminished primordial germ cell proliferation at E11.5 and ovarian reserve which may underlie POI in adulthood. Conclusion: The current results showed decreased placental BDNF diminished primordial germ cell proliferation in female fetuses during pregnancy and POI in adulthood. Our findings can provide insights into understanding the underlying mechanisms of POI. [ABSTRACT FROM AUTHOR]

Background: Women with polycystic ovary syndrome (PCOS) are usually selected to undergo an ovulation induction regimen or a programmed regimen for endometrial preparation in the frozen-thawed embryo transfer (FET) during their IVF/ICSI treatment. The programmed regimen permits flexible scheduling of embryo transfer but requires long-term usage of exogenous estrogen and higher dosages of luteal support while the letrozole ovulation regimen needs lower dosages of luteal support only. Recently, multiple studies have shown that the letrozole ovulation regimen can improve pregnancy outcomes of FET in women with PCOS compared with the programmed regimen. However, most of these studies are retrospective, and prospective studies are urgently needed the evidence from the perspective study is insufficient. Methods/design: We are undertaking a multicentre, randomized, controlled clinical trial of an endometrial preparation regimen for FET in women with PCOS. The eligible women are randomly assigned to either the letrozole ovulation regimen or the programmed regimen for endometrial preparation. The primary outcome is the clinical pregnancy rate. Discussion: The results of this study will provide evidence for whether the letrozole ovulation regimen for endometrial preparation could improve pregnancy outcomes in PCOS women undergoing FET. Trial registration: Chinese Clinical Trial Registry ChiCTR2200062244. Registered on 31 July 2022. [ABSTRACT FROM AUTHOR]

Abstract\nSHORT CONDENSATIONProgestin-only pills (POPs) have emerged as a crucial contraceptive option for women, particularly those contraindicated to oestrogens. This opinion paper introduces two new indices, the Inhibition Ratio (I.R.) (cyclical and daily) and the Transformation Index (T.I.), to evaluate and compare the efficacy and clinical behaviour of modern POPs. The I.R. quantifies the ratio between the progestin dosage in a POP and the minimum dose required to inhibit ovarian function, providing insights into contraceptive efficacy. The T.I., on the other hand, assesses its clinical impact by considering the ratio between the total progestin dose and the dose required to induce endometrial luteinising changes. Both indices thus offer valuable tools for comparing progestins even at significantly different dosages and regimens, providing information on clinical characteristics and drug effects. The newest formulations of POPs (Desogestrel 28 and Drospirenone 24 + 4) have demonstrated higher I.R. and T.I. in comparison to older versions, indicating significant improvements in contraceptive efficacy and clinical impact with better menstrual cycle control. We believe that using these indices will ensure a more informed and personalised choice of progestin not only for contraceptive purposes but also for therapeutic use in gynaecology. The future goal is to develop other progestins with even more advantageous I.R. and T.I., ensuring the best contraceptive efficacy with fewer side effects, even in women at risk (obese, etc.).The Inhibition Ratio (I.R.) (cyclical and daily) and the Transformation Index (T.I.) are two new proposed indexes to evaluate and compare the efficacy and clinical behaviour of modern and future POPs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Oxidative modification of high-density lipoprotein occurs in patients with polycystic ovary syndrome. However, the relationship between oxidized high-density lipoprotein and ovulation dysfunction and its mechanism are unknown. OBJECTIVE: To investigate the effect and potential mechanism of oxidized high-density lipoprotein on ovarian granulosa cell apoptosis. METHODS: Polycystic ovary syndrome rat model was established, then the high-density lipoprotein was harvested from the rat serum of heart blood. The degree of oxidation of the high-density lipoprotein was detected by high-density lipoprotein inflammation index assay, malondialdehyde assay and lipoprotein agarose gel electrophoresis assay. The normal rat ovarian granulosa cells were isolated and treated with high-density lipoprotein and oxidized high-density lipoprotein isolated from the model rat serum. Cell viability was detected by CCK-8 assay. Cell apoptosis was detected by flow cytometry. The generation of reactive oxygen species was detected by H2DCF-DA staining. The p38 signaling activity was detected by western blot assay. Ovarian granulosa cells were pretreated with reactive oxygen species inhibitors N-acetylcysteine, tetramethylpiperidine (Tempol) and p38 inhibitor SB203580, and then treated with oxidized high-density lipoprotein. Finally, cell apoptosis, reactive oxygen species production and p38 signaling activity were detected. RESULTS AND CONCLUSION: A portion of the high-density lipoprotein from the serum of polycystic ovary syndrome model rats affected oxidative modification. High-density lipoprotein and oxidized high-density lipoprotein isolated from the model rat serum inhibited granulosa cell viability and promoted apoptosis (all P < 0.05). They promoted rat granulosa cell reactive oxygen species production and p38 activation (all P < 0.05). N-acetylcysteine, Tempol and SB203580 reversed oxidized high-density lipoprotein induced granulosa cell apoptosis (all P < 0.05). N-acetylcysteine and Tempol suppressed oxidized high-density lipoprotein-induced p38 activation (all P < 0.05). SB203580 did not have a regulatory effect on reactive oxygen species production (P > 0.05). In summary, polycystic ovary syndrome can promote partial oxidative modification of high-density lipoprotein. The oxidized high-density lipoprotein promotes rat granulosa cell apoptosis by the activation of the reactive oxygen species-initiated p38 signaling pathway. [ABSTRACT FROM AUTHOR]

Purpose: This study estimates the need of IVF/ICSI in Australia as compared to its actual uptake. Methods: We created a model estimating for the annual demand for IVF/ICSI in a hypothetical infertile population, using demographic data from medical literature and Australian government databases. For each category of infertility (tubal, severe male, endometriosis, anovulation and unexplained), our estimated need for IVF/ICSI was compared to the actual IVF/ICSI uptake (ANZARD 2019). The model consisted of three categories depending on couples' cause of infertility, i.e. couples with absolute indications for IVF/ICSI (couples with severe male factor infertility and tubal obstruction); couples with anovulatory infertility (couples with ovulation disorders) and couples with ovulatory infertility (couples suffering from unexplained infertility and endometriosis). The model was applied to each of these categories to determine the number of couples that would require IVF/ICSI treatment after failing to conceive naturally or after following alternative treatment plans. The main outcomes of this study were the estimate of IVF/ICSI cycles and the difference between the estimate and the reported number of IVF/ICSI cycles (2019 ANZARD report). Results: We estimated that approximately 35,300 couples required IVF/ICSI treatment in Australia in 2019, while in 2019 according to ANZARD, 46,000 couples underwent IVF/ICSI. A higher uptake of IVF/ICSI cycles than expected was specifically reported in couples with unexplained infertility, ovulation disorders and endometriosis, while for tubal and severe male infertility uptake seemed adequate. Conclusion: In Australia, there seems to be overservicing of IVF/ICSI, specifically for unexplained, ovulatory and endometriosis-related infertility. [ABSTRACT FROM AUTHOR]

Research question: Can an optimal LH threshold algorithm accurately predict timing of ovulation for natural cycle–intrauterine insemination (NC-IUI)? Design: A retrospective cohort study (2018–2022) including 2467 natural cycles. Ovulation timing for these cycles was determined using a previously developed AI model. Two LH thresholds, low and high, were determined in the LH algorithm. Being below the low threshold meant that ovulation is likely to occur in ≥ 4 days, suggesting another daily blood test. Between the two thresholds meant that ovulation was likely in 2–3 days, suggesting IUI the next day. Above the high threshold meant that ovulation will likely occur tomorrow, suggesting performing IUI on the same day. Results: The optimal LH model with a high threshold of 40 mIU/ml and a low threshold of 11 mIU/ml succeeded in correctly predicting timing for IUI (day − 1, − 2 relative to ovulation) in 75.4% (95%CI 75.3–75.4). In 23.1% (95%CI 23.0–23.2), the algorithm predicted "error," suggesting performing insemination when in fact it would have been performed on a non-optimal day (0 or − 3). A previously described 3-hormone-based (LH, estradiol, progesterone) AI model performed significantly better in all parameters (93.6% success rate, 4.3 "error" rate). Conclusions: An LH threshold model, representing common practice, evaluating all possible high and low LH threshold combinations, was successful in accurately scheduling timing for IUI in only 75% of cases. Integrating all three hormones as performed in the AI model may have an advantage in accurately predicting the optimal time for IUI, over the use of LH only. [ABSTRACT FROM AUTHOR]

BACKGROUND The increasing prevalence of obesity worldwide poses a significant threat to reproductive function owing, in part, to hormonal disturbances caused by negative feedback between excess adiposity and the hypothalamic–pituitary–ovarian axis. Consequently, finding the most appropriate strategies to lose weight and improve ovulation in women with overweight or obesity is a clinically relevant matter that needs to be investigated. A comprehensive comparison of the independent and combined efficacy of lifestyle and/or pharmacological interventions on BMI, ovulation, and hormonal profile in women with overweight or obesity at risk of anovulatory infertility would facilitate improving fertility strategies in this population. OBJECTIVE AND RATIONALE This study aimed to evaluate the comparative efficacy of exercise, diet, and pharmacological interventions on BMI, ovulation, and hormonal profile in reproductive-aged women with overweight or obesity. SEARCH METHODS A systematic review was performed by searching PubMed, Scopus, Web of Science, PsycINFO, and Cochrane Library up to 14 December 2023, for randomized controlled trials assessing the effects of exercise, diet and/or pharmacological interventions (i.e. weight-lowering drugs or ovulation inducers) on BMI, ovulation, and/or hormonal profile in reproductive-aged women with overweight or obesity. We performed frequentist random-effect network meta-analyses and rated the certainty of the evidence. The primary outcomes were BMI and ovulation rate, and the secondary outcomes were serum reproductive hormone levels (gonadotrophins, androgens, or oestrogens). We performed sensitivity analyses, including the studies that only involved women with PCOS. OUTCOMES Among 1190 records screened, 148 full texts were assessed for eligibility resulting in 95 trials (9910 women), of which 53% presented a high or unclear risk of bias. The network meta-analyses revealed that, compared to control: diet combined with weight-lowering drugs (mean difference (MD) −2.61 kg/m2; 95% CI −3.04 to −2.19; τ2 = 0.22) and adding exercise (MD −2.35 kg/m2; 95% CI −2.81 to −1.89; τ2 = 0.22) led to the greatest decrease in BMI; exercise combined with diet and ovulation inducers (risk ratio (RR) 7.15; 95% CI 1.94–26.40; τ2 = 0.07) and exercise combined with diet and weight-lowering drugs (RR 4.80; 95% CI 1.67–13.84; τ2 = 0.07) produced the highest increase in ovulation rate; and exercise combined with diet and weight-lowering drugs was the most effective strategy in reducing testosterone levels (standardized mean difference (SMD) −2.91; 95% CI −4.07 to −1.74; τ2 = 2.25), the third most effective strategy in increasing sex hormone-binding globulin levels (SMD 2.37; 95% CI 0.99–3.76; τ2 = 2.48), and it was coupled with being ranked first in terms of free androgen index reduction (SMD −1.59; 95% CI −3.18 to 0.01; τ2 = 1.91). The surface under the cumulative ranking curve scores suggested that: diet combined with weight-lowering drugs is the strategy most likely (94%) to produce the highest BMI reduction; and exercise combined with diet and ovulation inducers is the strategy most likely (89%) to produce the highest ovulation rate improvement. The sensitivity analyses, which exclusively included studies involving women diagnosed with PCOS, were consistent with the results presented above. WIDER IMPLICATIONS Overall, the findings of this network meta-analysis indicate that the combination of exercise, diet, and pharmacological interventions is effective for weight loss, improving ovulation, and normalizing the androgen levels of women with overweight or obesity. Although higher quality studies are needed, these results support that the optimal treatment strategy for women with overweight or obesity wishing to conceive must consider exercise, diet, and pharmacological interventions during the shared decision-making process. [ABSTRACT FROM AUTHOR]

Secretory cells in the fallopian tube fimbria epithelium (FTE) are regarded as the main cells of origin of ovarian high-grade serous carcinoma (HGSC). Ovulation is the main cause of FTE oncogenesis, which proceeds through a sequence of TP53 mutations, chromosomal instability due to Rb/cyclin E aberration, in situ carcinoma (STIC), and metastasis to the ovary and peritoneum (metastatic HGSC). Previously, we have identified multiple oncogenic activities of the ovulatory follicular fluid (FF), which exerts the full spectrum of transforming activity on FTE cells at different stages of transformation. After ovulation, the FF is transfused into the peritoneal fluid (PF), in which the FTE constantly bathes. We wondered whether PF exerts the same spectrum of oncogenic activities as done by FF and whether these activities are derived from FF. By using a panel of FTE cell lines with p53 mutation (FT282-V), p53/CCNE1 aberrations (FT282-CCNE1), and p53/Rb aberrations plus spontaneous transformation, and peritoneal metastasis (FEXT2), we analyzed the changes of different transformation phenotypes after treating with FF and PF collected before or after ovulation. Similar to effects exhibited by FF, we found that, to a lesser extent, PF promoted anchorage-independent growth (AIG), migration, anoikis resistance, and peritoneal attachment in transforming FTE cells. The more transformed cells were typically more affected. Among the transforming activities exhibited by PF treatment, AIG, Matrigel invasion, and peritoneal attachment growth were higher with luteal-phase PF treatment than with the proliferative-phase PF treatment, suggesting an ovulation source. In contrast, changes in anoikis resistance and migration activities were similar in response to treatment with PF collected before and after ovulation, suggesting an ovulation-independent source. The overall transforming activity of luteal-phase PF was verified in an i.p. co-injection xenograft mouse model. Co-injection of Luc-FEXT2 cells with either FF or luteal-phase PF supported early peritoneal implantation, whereas co-injection with follicular-phase PF did not. This study, for the first time, demonstrates that PF from ovulating women can promote different oncogenic phenotypes in FTE cells at different stages of malignant transformation. Most of these activities, other than anoikis resistance and cell migration, are sourced from ovulation. [ABSTRACT FROM AUTHOR]

Ex vivo follicle growth is an essential tool, enabling interrogation of folliculogenesis, ovulation, and luteinization. Though significant advancements have been made, existing follicle culture strategies can be technically challenging and laborious. In this study, we advanced the field through development of a custom agarose micromold, which enables scaffold-free follicle culture. We established an accessible and economical manufacturing method using 3D printing and silicone molding that generates biocompatible hydrogel molds without the risk of cytotoxicity from leachates. Each mold supports simultaneous culture of multiple multilayer secondary follicles in a single focal plane, allowing for constant timelapse monitoring and automated analysis. Mouse follicles cultured using this novel system exhibit significantly improved growth and ovulation outcomes with comparable survival, oocyte maturation, and hormone production profiles as established three-dimensional encapsulated in vitro follicle growth (eIVFG) systems. Additionally, follicles recapitulated aspects of in vivo ovulation physiology with respect to their architecture and spatial polarization, which has not been observed in eIVFG systems. This system offers simplicity, scalability, integration with morphokinetic analyses of follicle growth and ovulation, and compatibility with existing microphysiological platforms. This culture strategy has implications for fundamental follicle biology, fertility preservation strategies, reproductive toxicology, and contraceptive drug discovery. [ABSTRACT FROM AUTHOR]

Summary: Background: Bone‐derived exosomes are considered nano‐sized extracellular vesicles secreted by the bone marrow stromal cells. Objectives: This study used exosomes derived from bone marrow mesenchymal stem cells to treat chronic endometritis in Arabian mares with follow‐up alterations in haemodynamics, hormonal and histopathological expressions. Methods and study design: Fourteen (n = 14) Arabian mares (aged 13–15 years old) were equally divided into the control group and an endometritis group (chronic type). Exosomes were infused twice 21 days apart at the first and second ovulations. Follow‐up was done ultrasonographically, and samples were taken for histopathology. Blood samples were taken to estimate hormonal levels. Results: Uterine biopsy samples before treatment showed a marked degree of degeneration, while the second exosomal treatment showed regression of fibrous tissue and restoration of healthy endometrial glands with normal epithelium. Uterine body and horns thickness/mm were decreased after treatment at day 0 of the 3rd ovulation compared to day −1 before treatment, the uterine body‐coloured area and total uterine coloured areas/pixels were elevated (p < 0.05) at day 0 of the 3rd ovulation compared to day −1 before treatment. Uterine artery blood parameters (pulsatility index, resistance index, peak systolic and end‐diastolic points) did not change before, during and after treatment, but the blood flow rate was elevated (p < 0.05) on day 0 of the 3rd ovulation compared to day −1 before treatment. Oestradiol level was decreased (p < 0.05), while progesterone level was increased (p < 0.05) on day 0 of the 3rd ovulation compared to day −1 before treatment. Conclusion: Two intrauterine administrations of exosomes restored the normal endometrial appearance after chronic endometritis resulting in the elevation of the conception rate in infertile mares. [ABSTRACT FROM AUTHOR]

Orang-utans are well-known for their vocal flexibility. However, the described vocal repertoire of female orang-utans is relatively limited. This anecdotal report discusses the occurrence of long call-like vocalisations in two zoo-housed Bornean orang-utan females. While Temmy demonstrated these vocalisations in response to playbacks of male long calls, Eloise proactively produced vocalisations during her ovulation before her reproductive senescence. The vocalisations produced by Temmy and Eloise seem to differ in many aspects from known orang-utan calls, although they bear some similarities to male long calls. Thus, the vocal repertoire of female orang-utans may be more extensive than previously thought. We carefully suggest that these calls might indicate proceptivity, while also discussing methodological limitations and theoretical considerations. [ABSTRACT FROM AUTHOR]

Female fecundity is dependent on age and mated status. Young female insects accumulate considerable fat stores to fuel energetically expensive ovary development and egg production. Consequently, younger females are expected to have more stored fat than older females while the latter should have larger eggloads than the former. Mating is expected to increase fecundity because male ejaculates contain fecundity-enhancing substances that stimulate egg development, ovulation and oviposition. We experimentally tested the effect of female age (young versus old) and mated status (virgin versus mated) on fat and eggloads in female Gryllus firmus field crickets (Orthoptera: Gryllidae), in addition to testing the prediction that young or mated females have higher resting metabolic rates (RMR) than old or virgin females because the former should be significantly more engaged in the energetically expensive activity of egg production than the latter. As predicted, we found that young females had more fat and fewer eggs than old females and that fat loads negatively correlated with fecundity across all females. Young females also exhibited higher RMR, as expected if egg production is energetically costly. Contrary to expectation, however, mated status had little effect on fat load, egg production or RMR. That mating had little effect on total egg production (i.e. stored and oviposited eggs) challenges the hypothesis that male fecundity-enhancing substances in the ejaculate stimulate egg production. Our experiment also permitted us to examine the validity of two popular indices of body condition, the scaled mass index (SMI) and residual body mass (R i). Neither index accurately represented the true treatment effects of age and mated status on fat load; however, the SMI reflected true fat content in young, but not old, females. • We tested effects of age and mated status on fat and eggloads in female Gryllus firmus. • Young females had more fat and fewer eggs than old females. • Fat loads were negatively correlated with fecundity across all females. • Young females had a higher resting metabolic rate (RMR) than old females. • Mated status had little effect on fat load, egg production or RMR. [ABSTRACT FROM AUTHOR]

This study evaluated the relationship between CL features assessed by ultrasound (luteal tissue area and blood flow, BF) or rectal palpation (size), uterine tone (UT), plasma progesterone (P4) concentration on Day 7 (D7) and subsequent pregnancy outcomes in bovine embryo recipients. A total of 163 cows and heifers were included in this study. The expected day of ovulation after the synchronization protocol was designated as D0. On D7, ovaries and uterus were examined by ultrasonography and rectal palpation, and subjective scores (1–3 scale) were assigned for CL size, area and BF, and for UT. Blood samples were collected for further P4 analysis. Each embryo recipient then received a grade I frozen–thawed in vivo‐produced blastocyst, which was transferred to the uterine horn ipsilateral to the CL. Pregnancy diagnosis was performed on D35, and the results were retrospectively compared with the assigned scores for CL and UT. We observed a significant (p <.02) interaction between CL size and UT, with a progressive increase in the likelihood of pregnancy for recipients bearing a large CL among those with turgid UT. Ultrasound scoring of the CL using B‐mode and Doppler‐mode did not significantly predict pregnancy rates on D35 (p <.6 and p <.5, respectively). However, logistic regression analysis revealed a trend towards a quadratic effect (p <.08 and p <.06) indicating that the probability of pregnancy varied according to the area of luteal tissue and P4 concentrations, respectively. No significant (p >.05) association was found between the probability of pregnancy and the BF area of the CL. In summary, UT before embryo transfer may reflect successful recipient synchronization. Elevated P4 levels, assessed by CL size, may offset uterine contractility, mitigating adverse effects. Additionally, the CL area may be more important than its vascularization area when evaluating recipients D7 after ovulation. [ABSTRACT FROM AUTHOR]