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Introduction: Endometriosis (EM) is a widely recognized disorder in gynecological endocrinology. Although hormonal therapies are frequently employed for EM, their side effects and outcome limitations underscore the need to explore the genetic basis and potential drug targets for developing innovative therapeutic approaches. This study aimed to identify both cerebrospinal fluid (CSF) and plasma protein markers as promising therapeutic targets for EM. Methods: We utilized Mendelian randomization (MR) analysis to explore potential disease-causing proteins, utilizing genetic datasets from genome-wide association studies (GWAS) and protein quantitative trait loci (pQTL) analyses. We applied a range of validation techniques, including reverse causality detection, phenotype scanning, Bayesian co-localization (BC) analysis, and external validations to substantiate our findings. Additionally, we conducted a protein-protein interaction (PPI) network as well as functional enrichment analyses to unveil potential associations among target proteins. Results: MR analysis revealed that a decrease of one standard deviation (SD) in plasma R-Spondin 3 (RSPO3) level had a protective effect on EM (OR = 1.0029; 95% confidence interval (95% CI): 1.0015–1.0043; P = 3.2567e-05; Bonferroni P < 5.63 × 10−5). BC analysis showed that RSPO3 shared the same genetic variant with EM (coloc.abf-PPH4 = 0.874). External validation further supported this causal association. Galectin-3 (LGALS3; OR = 0.9906; 95% CI: 0.9835–0.9977; P = 0.0101), carboxypeptidase E (CPE; OR = 1.0147; 95% CI: 1.0009–1.0287; P = 0.0366), and alpha-(1,3)-fucosyltransferase 5 (FUT5; OR = 1.0053; 95% CI: 1.0013–1.0093; P = 0.002) were detected as potential targets for EM in CSF. PPI analysis showed that fibronectin (FN1) had the highest combined score. Furthermore, several EM-linked proteins were involved in the glycan degradation pathway. Discussion: In conclusion, this comprehensive study offers valuable insights into potential drug targets for EM, with RSPO3 emerging as a promising candidate. Additionally, mechanistic roles of FN1, glycan degradation pathway, LGALS3, CPE, and FUT5 in EM warrant further investigation. [ABSTRACT FROM AUTHOR]

Recurrent implantation failure (RIF) is a common issue in frozen-thawed embryo transfer (FET). Prior to transfer, uterine endometrial receptivity of FET patients can be assessed using multimodal transvaginal ultrasound indicators to predict the success rate of the current FET cycle. Endometrial blood flow is a crucial element in evaluating endometrial receptivity. MV-FLOW™ is an advanced two-dimensional superb microvascular imaging technology that can detect and display blood flow in micro-vessels. The data for this study were obtained from an ongoing cross-sectional study comprising 323 RIF patients and 323 first implantation (FI) patients, who underwent transvaginal ultrasound before FET. We collected basic clinical data and multimodal ultrasound data from these patients as predictive features, with clinical pregnancy as the predictive label, for model training. Based on the above, this study aims to establish and validate a clinical prediction model for FET outcomes using support vector classification (SVC) algorithms, based on MV-FLOW™ and multidimensional transvaginal ultrasound imaging features. The objective is to determine the predictive role of multimodal transvaginal ultrasound in embryo transfer outcomes and provide evidence for the clinical application of MV-FLOW™. Trial registration:Trial Registration: ChiCTR2400086401. [ABSTRACT FROM AUTHOR]

Obesity, a global epidemic, is linked to adverse reproductive outcomes, including infertility and ovulation dysfunction. The cafeteria diet (CAF) serves as an animal model mirroring Western diet habit. Coenzyme Q10 (CoQ10), known for enhancing reproductive outcomes in various pathologies, is not fully understood for its effects on obesity treatment. Here, obesity was modeled using CAF-fed rats to assess CoQ10's impact on metabolic and ovarian disruptions caused by obesity. Wistar rats were divided into control (standard diet) and obese (CAF diet) groups. After 75 days, half of each group received oral CoQ10 (5 mg/kg) for 13 days, while the rest received a vehicle. Animals were euthanized during the estrus phase, and blood and ovaries were collected for analysis. CAF caused increased body weight gain (p < 0.01) associated with hyperglycemia, hypertriglyceridemia, and hypercholesterolemia (p < 0.05). Moreover, it caused a reduction in the number of AMH + follicles (p < 0.001), increasing follicular atresia (p < 0.05) and serum estradiol levels (p < 0.05). Obesity also altered the estrous cycle and reduced the ovulation rate (p < 0.05). CoQ10 administration showed beneficial effects on all ovarian disruptions but had no effect on the metabolic alterations induced by obesity. In summary, CoQ10 could be an additional treatment for obesity-related infertility in patients with normal metabolic profiles. While CoQ10 does not affect metabolic parameters influenced by obesity, crucial for reproductive issues and offspring health, it is recommended as part of a treatment plan that includes a balanced diet and increased physical activity for obese individuals with metabolic alterations seeking pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To clarify whether intrauterine adhesions (IUAs) affect endometrial receptivity (ER) on the day of ovulation and to compare patients with mild and moderate-severe adhesions. Methods: This prospective cohort study included 592 infertile women with IUAs who underwent frozen-thawed embryo transfer (FET). Patients were divided into groups with or without IUAs; and pregnant and nonpregnant populations based on whether a clinical pregnancy was achieved. The ultrasound ER parameters on the ovulation day were compared. Patients with IUAs were then divided into mild or moderate-severe IUA subgroups according to IUA degree. Results: The proportions of patients with Type B plus Type C endometrial morphology (94% vs. 75%, P<0.001), an endometrial thickness≥8mm (97% vs. 81%, P<0.001), an endometrial volume≥2ml (94% vs. 67%, P<0.001), a frequency of endometrial peristalsis≥2 times/min (84% vs. 53%, P<0.001), low subendometrial volume (11.54 ± 2.94 vs. 9.57 ± 2.35, P<0.001) and subendometrial vascularization flow index (VFI) values (2.70 ± 3.10 vs. 2.23 ± 2.23, P=0.033) and a low live birth rate (65% vs. 56%, P=0.039) were significantly higher in the group without IUAs than in the group with IUAs. The group with moderate-severe IUAs had lower proportion of patients with an endometrial thickness≥8mm (73% vs. 89%, P=0.008) and an endometrial volume ≥2ml (58% vs. 78%, P=0.005), a lower frequency of endometrial peristalsis≥2 times/min (42% vs. 65%, P=0.003), and low subendometrial volume (9.22 ± 2.29 vs. 9.97 ± 2.36, P=0.023) and subendometrial flow index (FI) (31.48 ± 3.64 vs. 33.43 ± 4.17, P=0.002) values than the group with mild IUAs; a high antral follicle count (AFC), basal follicle-stimulating hormone (FSH), and anti-Müllerian hormone (AMH) levels and an endometrial thickness≥8mm were independent predictors of clinical pregnancy. Conclusion: IUAs can affect ER on the ovulation day and the live birth rate during natural cycles. Moderate-severe IUAs have a greater impact on ER than mild adhesions do; however, if these adhesions are treated properly, they do not have adverse effects on the clinical pregnancy rate. A high AFC, basal FSH and AMH levels and an endometrial thickness ≥8 mm were found to be independent predictors of clinical pregnancy. [ABSTRACT FROM AUTHOR]

Objectives: Hormone replacement therapy (HRT) frozen embryo transfer (FET) cycles are common in assisted reproductive techniques. As the corpus luteum is absent in these cycles, luteal phase support is provided by administering progesterone (P4) through transvaginal, parenteral, or oral routes. Low serum levels of P4 (below 9-10 ng/mL) on the day before embryo transfer (ET) have been associated with unfavorable cycle outcomes. The aim of this study is to investigate whether individualizing luteal support through rescue protocols in patients with low serum P4 levels improves pregnancy outcomes in HRT-FET cycles. Material and method: This retrospective, single-center cohort analysis includes 1257 cycles involving 942 patients undergoing HRT-FET. Starting in 2019, we have assessed P4 levels before ET day and adjusted MVP doses when P4 levels were <10 ng/mL. In 2021, subcutaneous (SC) P4 was routinely added alongside MVP, with SC doses increased if P4 levels were <10 ng/mL. In this study, Groups 1 and 2 received MVP for luteal support, while Groups 3 and 4 received additional SC progesterone. For patients with P levels below the cut-off level (10 ng/mL) in Groups 2 and 4, the P dose was doubled through a rescue protocol. Results: In the MVP and MVP plus SC groups, 15.8% and 8.9% of the cycles had P4 levels <10 ng/mL, respectively. Ongoing pregnancy rates (OPR) and clinical pregnancy rates (CPR) did not differ between study groups. Regression analysis with a mixed model revealed that age, endometrial thickness, and estradiol levels were confounding factors as well as independent predictors of ongoing pregnancy rates (p<0.05). Pairwise regression analysis revealed no significant differences in pregnancy rates between the groups (p>0.05). Conclusion: Individualizing luteal phase support based on serum P4 levels on the day of ET in FET cycles with HRT may enhance pregnancy outcomes by either doubling the vaginal dose or increasing the SC dose during MVP plus SC administration. The implemented rescue protocol allowed patients with low progesterone levels to achieve pregnancy outcomes similar to those with higher progesterone levels. [ABSTRACT FROM AUTHOR]

Ovarian stimulation (OS) is a crucial component of clinical IVF treatment that strongly influences outcomes. As such, it is useful to understand the indicators for successful OS during IVF. As OS leads to multiple follicular recruitment, it can be quantified as number of oocytes retrieved. Optimal OS should help to maximize the number of oocytes, thus improving preclinical laboratory outcomes. Optimal preclinical outcomes should ultimately lead to clinical outcomes with maximal efficacy, safety, and cost-effectiveness. To help guide successful OS, this review details prognostic factors and appropriate endpoints for an optimal OS at each stage of the IVF cycle. [ABSTRACT FROM AUTHOR]

Background: Increased backfat thickness of sows in early gestation is negative to reproductive performance. Endometrial receptivity is an important determinant of reproductive success, but it is unclear whether the effect of sow backfat thickness on litter size is associated with endometrial receptivity and whether melatonin treatment may have benefits. The present study seeks to answer these questions through in vitro and in vivo investigations. Results: Excessive lipid deposition and lower melatonin levels in the uterus are detrimental to endometrial receptivity and embryo implantation in high backfat thickness sows. In cells treated with melatonin, the MT2/PI3K/LIF axis played a role in reducing lipid accumulation in porcine endometrial epithelium cells and improved endometrial receptivity. Furthermore, we found a reduction of lipids in the uterus after eight weeks of intraperitoneal administration of melatonin to HFD mice. Notably, melatonin treatment caused a significant reduction in the deposition of endometrial collagen, an increase in the number of glands, and repair of the pinopode structure, ultimately improving endometrial receptivity, promoting embryo implantation, and increasing the number of litter size of mice. Conclusions: Collectively, the finding reveals the harmful effects of high backfat thickness sows on embryo implantation and highlight the role of melatonin and the MT2/PI3K/LIF axis in improving endometrial receptivity by enhancing metabolism and reducing the levels of uterine lipids in obese animals. [ABSTRACT FROM AUTHOR]

This study evaluates the effects of double cryopreservation and re-biopsy on embryo viability and clinical outcomes. Studies of interest were selected from an initial cohort of 1027 potentially relevant records retrieved. PubMed was systematically searched for peer-reviewed original papers identified by keywords and medical subject heading terms. Moreover, we elaborated the evidence tables for double cryopreservation and re-biopsy separately. Data were systematically extracted, focusing on live birth, survival, clinical pregnancy, and miscarriage rates. For each study, we identified absolute numbers (numerator and denominator) related to clinical outcomes. Finally, for each outcome, we calculated the percentage change between the control and study groups. Among studies on double cryopreservation, 13 out of 22 reported no effect on clinical outcomes, suggesting contradictory results. Similarly, findings on re-biopsy were controversial, with seven out of 12 studies showing negative effects on survival and clinical outcomes, while five reported no impact. In our analysis of the evidence tables, we observed a reduction in live birth rates of 22.2% and 39.3% in blastocysts undergoing double vitrification and re-biopsy, respectively. These findings suggest that repeated micromanipulations can impair embryo competence. Therefore, double cryopreservation and re-biopsy should be limited in the selected cases without other options by consulting patients about the possible harmful effects., Competing Interests: Declarations. Competing interests: E.P. reported grants and personal fees from MSD; grants from Ferring, IBSA, TEVA, and Gedeon Richter; and grants and personal fees from Merck. The other authors declare no conflict of interest. Attestation statement: Data regarding any of the subjects in the study has not been previously published unless specified., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Poor ovarian response (POR) significantly impacts the success of assisted reproductive technology (ART), and growth hormone (GH) has been proposed as an adjuvant treatment to improve outcomes in POR patients undergoing in vitro fertilization (IVF). A systematic review and meta-analysis were conducted to evaluate the effectiveness of GH in enhancing pregnancy outcomes, registering a protocol on PROSPERO and searching multiple databases up to September 2023. Twelve systematic reviews/meta-analysis and 20 randomized controlled trials (RCTs) involving 1984 patients were included. Quality assessment was performed using AMSTAR 2, GRADE, and RoB tools. The meta-analysis revealed that GH significantly increased live birth rates [OR=1.80, 95% CI (1.22, 2.64)] and clinical pregnancy rates [OR=1.92, 95% CI (1.51, 2.43)] compared to the control group. Subgroup analysis indicated that administering 5-10 IU/d of GH combined with a long protocol during the middle and late follicular stages maximized these benefits. Despite these promising findings, most outcome indicators exhibited low-quality evidence, highlighting the need for improved research standards to ensure solid evidence supports treatment strategies for POR, thereby promoting reliable application of GH in IVF treatments., Competing Interests: Declarations. Conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

PGT-A, what's it for? Considering the increase in fetal aneuploidies with a woman's age and the high number of miscarriages associated with fetal karyotype anomalies, the concept of selecting IVF embryos based on their karyotype in order to transfer only euploid embryos and eliminate aneuploid ones was proposed. Preimplantation genetic testing for aneuploidy (PGT-A) was then established, nearly 30 years ago, with the expectation that the transfer of euploid embryos would lead to a significant improvement in medically assisted reproduction (MAR) outcomes. PGT-A, what's wrong? Despite the practice and widespread use, PGT-A has not consistently proven its effectiveness. The clinical value of PGT-A remains controversial. The initial studies reported an increase in MAR outcomes. However, these studies used embryo transfer as the reference point. More recent studies, which use intention-to-treat as the reference point, show, at best, slight improvements and, at worst, a reduction in the considered IVF outcomes. In this article, we attempt to answer two key questions: "What is it for?" and "What's wrong with PGT-A?". We also explore some of the ethical issues raised by these conclusions. Ultimately, we suggest that PGT-A should no longer be offered to infertile couples., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: We aimed to evaluate if ovarian stimulation with individualized dosing of recombinant follicle-stimulating hormone (rec-FSH) with follitropin delta compared with standard gonadotropin dosing reduce occurrence of follicular asynchrony in women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF)., Methods: Matched case-control study analyzed occurrence of follicular growth asynchrony during ovarian stimulation and IVF outcomes in women with PCOS. Follicular growth was considered to be asynchronous when one or two leading follicles were at least 4 mm larger in diameter than the rest of the cohort on day 5 and 9 of stimulation. Analysis encompassed 44 women stimulated with individualized rec-FSH dosing, and 88 women treated with standard dosing. The patients were matched in terms of age, Anti-Müllerian hormone levels and body weight., Results: Early and late follicular asynchrony were present less frequently in individualized dosing compared to standard dosing group (4.5% vs 17%, p = 0.04 and 2.3% vs 37.5%, p < 0.001, on stimulation day 5 and 9, respectively). Multivariate logistic regression on follicular asynchrony revealed that individualized dosing significantly decreases the occurrence and chances for late follicular asynchrony (Odds Ratio 0.28, p < 0.001). Shorter duration of stimulation (9.6 vs 10.4 days, p = 0.001), lower total gonadotropin dose (1118 vs 1940 IU, p < 0.001), higher number of metaphase II oocytes (7.1 + 4.3 vs 5.4 ± 3.0, p = 0.001), good quality embryos (3.8 vs 2.0, p < 0.001), and implantation rates (31.0 vs 23.4, p = 0.04) were observed in the individualized dosing group., Conclusion: Individualized rec-FSH dosing reduces asynchronous follicular growth and improves ovarian stimulation efficiency in women with PCOS undergoing IVF., Competing Interests: Declarations. Ethics approval: This study was approved by the Institutional review board (decision No.05006-2022-16004). Competing interests: Milan Perovic was a speaker for MERCK, FERRING Pharmaceuticals, Alkaloid and Laboratoire INNOTECH International. Stefan Dugalic was a speaker for Pharmazeutische Fabrik Montavit and Zdravlje Leskovac. Other authors have no conflicts of interest to declare., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The study aimed to evaluate the effect of fertitonex containing L-carnitine L-tartrate together with other micronutrients on different semen parameters in idiopathic male infertility as well as male reproductive hormones., Methods: 100 randomized infertile patients were recruited from July 2023 to February 2024. They were randomized into two groups. Group (A) received fertitonex twice daily for the first 3 months. Group (B) received placebo twice daily for the first 3 months. Crossover was done after 1 month wash-out period for additional 3 months., Results: Group (A) who started fertitonex first showed significant improvement in sperms concentration and motility and progressive motility as well as significant reduction in abnormal forms after 3 months from beginning the study (p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). Interestingly, these improvements continued for additional 3 months after placebo intake (p < 0.001, p 0.005, p < 0.001, p < 0.001, respectively). Group (B) who started placebo first showed significant improvement in sperms concentration and motility and progressive motility as well as significant reduction in abnormal forms after 6 months from beginning the study (p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). LH level was significantly higher among group (A) compared to group (B) at baseline and 3 months and 6 months (p value 0.02, 0.032. 0.024, respectively)., Conclusion: We finally concluded that fertitonex is an effective, tolerable and safe drug that can be used for treating idiopathic male infertility., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Ethical approval: All procedures performed were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the local ethical committee. Informed consent: Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Aim: In developed nations, women have increasingly deferred childbearing, leading to a rise in demand for infertility treatments and the widespread use of assisted reproductive technologies. However, despite advancements in in vitro fertilization (IVF), live birth rates among women over 40 remain suboptimal. Mitochondrial dysfunction is widely recognized as a key factor in the processes driving the age-related deterioration in both the quantity and quality of oocytes. We aim to summarize current insights into ovarian aging, with a particular focus on pathways that impair mitochondrial function, and explore directions for future research., Methods: Electronic databases were searched for articles published up to June 30, 2024., Results: Ongoing ovulation, luteolysis, and menstruation trigger exogenous reactive oxygen species (ROS)-mediated oxidative stress that damages mitochondrial DNA. This, in turn, reduces nuclear gene expression, compromises mitochondrial oxidative phosphorylation, and diminishes adenosine 5' triphosphate production. Persistent endogenous ROS further exacerbate mitochondrial DNA damage and aneuploidy, ultimately causing irreversible chromosomal abnormalities, leading to oocyte aging., Conclusions: We have delineated the pathway from oxidative stress to ovarian aging. Early detection and management of ovarian aging present challenges and opportunities to enhance IVF treatment strategies., (© 2024 Japan Society of Obstetrics and Gynecology.)

Hysteroscopic surgery requires a balance of continuous controlled irrigation and aspiration to distend the endometrial cavity to a degree that provides the clear and stable visual environment necessary for diagnostic and therapeutic procedures. Whereas the preferred distending solution should be isotonic and isonatremic, radiofrequency (RF) electrosurgery with monopolar instrumentation can only be performed with non-ionic (hyponatremic) solutions. Absorption of as little as 500 mL and certainly more than 1000 mL of non-ionic solutions can result in fluid overload and/or dilutional hyponatremia with potentially serious adverse effects under certain conditions and patient characteristics. Both hysteroscopic RF electrosurgery with bipolar instrumentation and electro-mechanical morcellation and aspiration systems use isotonic and isonatremic solutions. Depending on the clinical context, absorption of more than 1500 mL of isonatremic solutions can also result in serious adverse effects. Automated fluid management systems are preferred and recommended, and surgeons should aim to maintain the maximum allowable intravasation of distending media below 1000 and 1500 mL for non-ionic and ionic fluids, respectively., (© 2024 International Federation of Gynecology and Obstetrics.)

Objective: To compare the effectiveness and cost of in-vitro fertilization (IVF) with or without preimplantation genetic testing for aneuploidy (PGT-A) when only one or two blastocysts are obtained., Methods: A dataset was gathered from 1829 patients including 368 non-PGT-A and 1461 PGT-A cycles with one or two blastocysts obtained, between April 2013 and July 2022. Patients were matched 1:1 by propensity-score matching for maternal age, number of metaphase-II oocytes inseminated and number of blastocysts obtained, achieving a database of 242 patients per group. The non-PGT-A and PGT-A groups were compared for differences in live birth rate (LBR) per embryo transfer (ET), cumulative LBR per patient, miscarriage rate (MR) per clinical pregnancy, number of days between oocyte retrieval and conclusion of the IVF cycle (primary outcome), mean expenses incurred at the clinic and incremental cost-effectiveness ratio (ICER)., Results: More than twice as many ETs were conducted in the non-PGT-A group compared with the PGT-A group, yet the cumulative LBR per patient was similar between groups (23.6% (95% CI, 18.5-29.5%) vs 27.3% (95% CI, 21.9-33.4%)). This outcome was achieved with a higher LBR per ET (16.2% (95% CI, 12.6-20.5%) vs 41.5% (95% CI, 33.9-49.4%)) and lower MR per clinical pregnancy (30.1% (95% CI, 21.8-42.6%) vs 13.9% (95% CI, 7.5-24.0%)) in the PGT-A group. The MR per patient was also lower in the PGT-A group (9.5% (95% CI, 6.2-14.1%) vs 4.5% (95% CI, 2.4-8.2%)). The mean duration between oocyte retrieval and IVF cycle conclusion was 131 (95% CI, 113-150) days in the non-PGT-A group vs 74 (95% CI, 61-87) days in the PGT-A group (P < 0.001; power = 99.8%). The ICER of PGT-A for the months saved between oocyte retrieval and conclusion of the IVF cycle was €499 overall, ranging between €170 and €2065 according to the number of blastocysts obtained and/or maternal age. The ICER of PGT-A for prevented miscarriages was €18 968, decreasing to €3525 when calculated among patients aged ≥ 35 years with two blastocysts obtained., Conclusions: When conducted in expert IVF clinics for patients indicated for the procedure, PGT-A is clinically valuable even when only one or two blastocysts are obtained. PGT-A reduces the number of ETs and miscarriages while the cumulative LBR per patient remains unaffected, and allows these outcomes to be achieved in a shorter timeframe. The ICER of PGT-A vs non PGT-A decreased as maternal age increased. © 2024 International Society of Ultrasound in Obstetrics and Gynecology., (© 2024 International Society of Ultrasound in Obstetrics and Gynecology.)