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This review article explores the possibility of developing an integrated approach to the management of the different needs of endometrial cancer (EC) patients seeking to become pregnant. Life preservation of the woman, health preservation of the baby, a precocious and—as much as possible—minimally invasive characterization of the health and fertility parameters of the patient, together with the concerns regarding the obstetric, neonatal, and adult health risks of the children conceived via assisted reproductive techniques (ART) are all essential aspects of the problem to be taken into consideration, yet the possibility to harmonize such needs through a concerted and integrated approach is still very challenging. This review aims to illustrate the main features of EC and how it affects the normal physiology of pre-menopausal women. We also focus on the prospect of a miR-based, molecular evaluation of patient health status, including both EC early diagnosis and staging and, similarly, the receptivity of the woman, discussing the possible evaluation of both aspects using a single specific panel of circulating miRs in the patient, thus allowing a relatively fast, non-invasive testing with a significantly reduced margin of error. Finally, the ethical and legal/regulatory aspects of such innovative techniques require not only a risk-benefit analysis; respect for patient autonomy and equitable health care access allocation are fundamental issues as well.

Background The optimal duration of ovarian stimulation in GnRH antagonist protocols remains insufficiently explored, despite its potential impact on oocyte quality, embryo development, and endometrial receptivity. Identifying an optimal stimulation window may improve success rates in assisted reproductive technologies (ART) while minimizing unnecessary hormonal exposure. The aim of the study was to evaluate if the duration of ovarian stimulation in GnRH antagonist IVF/ICSI protocols influence cumulative ongoing pregnancy rates (COPR). Methods This retrospective single-centre study analyzed 1456 IVF/ICSI cycles conducted between 2019 and 2023 in women with normal ovarian reserve using an antagonist protocol. Stimulation duration was classified into three categories: ≤ 8 days, 9–13 days (reference), and ≥ 14 days corresponding to the ≤ 5th, 5th–95th, and ≥ 95th percentiles, respectively. Clinical, biological, and embryological outcomes were compared across groups using the Kruskal–Wallis test. Logistic regression was applied to identify independent predictors of cumulative ongoing pregnancy and pregnancy outcomes. Results A total of 1456 cycles were included in the study. At least one embryo was obtained in 95.2% of cycles, with 69.5% proceeding to fresh transfer. Cumulative ongoing pregnancy was assessed for 1339 cycles, among which 36.4% resulted in an ongoing pregnancy. Stimulation duration did not significantly influence COPR: ≤ 8 days (OR = 1.04, 95% CI 0.78–1.39), 9–13 days (reference), ≥ 14 days (OR = 0.84, 95% CI 0.64–1.11). Multivariate analysis identified younger age and higher AMH as independent predictors of COPR. Conclusions In women with normal ovarian reserve undergoing IVF/ICSI with a GnRH antagonist protocol, the duration of ovarian stimulation does not significantly impact cumulative pregnancy outcomes. These findings support a personalized approach to trigger timing based on ovarian response independent of stimulation length.

Background Women with uterine adenomyosis seeking assisted reproduction have been associated with compromised endometrial receptivity to embryo implantation. To understand the mechanisms involved in this process, we aimed to compare endometrial transcriptome profiles during the window of implantation (WOI) between women with and without adenomyosis. Methods We obtained endometrial biopsies LH-timed to the WOI from women with sonographic features of adenomyosis (n=10) and controls (n=10). Isolated RNA samples were subjected to RNA sequencing (RNA-seq) by the Illumina NovaSeq 6000 platform and endometrial receptivity classification with a molecular tool for menstrual cycle phase dating (beREADY®, CCHT). The program language R and Bioconductor packages were applied to analyse RNA-seq data in the setting of the result of accurate endometrial dating. To suggest robust candidate pathways, the identified differentially expressed genes (DEGs) associated with the adenomyosis group in the receptive phase were further integrated with 151, 173 and 42 extracted genes from published studies that were related to endometrial receptivity in healthy uterus, endometriosis and adenomyosis, respectively. Enrichment analyses were performed using Cytoscape ClueGO and CluePedia apps. Results Out of 20 endometrial samples, 2 were dated to the early receptive phase, 13 to the receptive phase and 5 to the late receptive phase. Comparison of the transcriptomics data from all 20 samples provided 909 DEGs (p<0.05; nonsignificant after adjusted p value) in the adenomyosis group but only 4 enriched pathways (Bonferroni p value < 0.05). The analysis of 13 samples only dated to the receptive phase provided suggestive 382 DEGs (p<0.05; nonsignificant after adjusted p value) in the adenomyosis group, leading to 33 enriched pathways (Bonferroni p value < 0.05). These included pathways were already associated with endometrial biology, such as “Expression of interferon (IFN)-induced genes” and “Response to IFN-alpha”. Data integration revealed pathways indicating a unique effect of adenomyosis on endometrial molecular organization (e.g., “Expression of IFN-induced genes”) and its interference with endometrial receptivity establishment (e.g., “Extracellular matrix organization” and “Tumour necrosis factor production”). Conclusions Accurate endometrial dating and RNA-seq analysis resulted in the identification of altered response to IFN signalling as the most promising candidate of impaired uterine receptivity in adenomyosis.

Male infertility stands as a significant global concern, contributing to nearly 50% of infertility cases and affecting approximately 7% of the male population. Mounting evidence identifies environmental degradation is a major, modifiable driver. Numerous environmental contaminants, including air pollution, heavy metals, endocrine-disrupting chemicals (EDCs), microplastics, pharmaceutical contaminants, and climate change linked to deteriorating semen quality. These environmental toxins can decrease spermatogenesis and overall sperm function by triggering oxidative stress, hormonal imbalance, inflammation, and epigenetic alterations. This review highlights the increasing necessity of incorporating environmental exposure data (eco-profiles) into routine semen analysis. An integrated framework is outlined in which AI algorithms analyze multi-omics biomarkers, ranging from genomics to metabolomics, together with environmental metrics. These combined data are used to predict individual fertility risk and to guide personalized treatment strategies, particularly in the context of assisted reproductive technologies. Future studies are essential to find trustworthy biomarkers and elucidate the molecular processes that connect environmental contaminants to male infertility. As environmental toxicants intensify, the comprehensive toxicological studies are in need to enhance curative approaches and preventative strategies that ultimately aim at safeguarding male fertility.

Background: Infertility affects 8–12% of couples globally, with causes including hormonal and structural abnormalities. Letrozole, an aromatase inhibitor, is commonly used for ovulation induction, but its role in various assisted reproductive technologies (ARTs) and across different subgroups of infertile women remains unclear. Objective: This scoping review aimed to map the existing evidence on the use of letrozole in assisted reproductive cycles, focusing on reproductive outcomes and its application across different patient populations. Methods: A scoping review was conducted following the PRISMA-ScR guidelines. Twelve studies—including randomized controlled trials and retrospective cohorts—were identified through a structured search strategy. Studies comparing letrozole alone or in combination with gonadotropins/clomiphene to other stimulation protocols were included. Data were charted across multiple outcomes including oocyte yield, implantation, pregnancy, miscarriage, and live birth rates. Results: Evidence suggests that letrozole-based protocols may enhance oocyte yield and improve reproductive outcomes in certain settings. The highest implantation rate (57%) was observed in natural cycles, while the letrozole-only group showed the highest clinical pregnancy (50.57%) and live birth rates (45.58%). Combination protocols achieved the highest ongoing pregnancy rate (58.3%), with the lowest miscarriage rate (14.86%) in the letrozole-only group. Conclusions: Letrozole appears to be a versatile agent in ART, especially for patients requiring reduced gonadotropin doses or estradiol modulation. This scoping review highlights the need for further research to clarify its optimal use across different infertility subgroups and ART modalities.

Background This study compared the effectiveness of cabergoline and hydroxychloroquine in preventing ovarian hyperstimulation syndrome (OHSS) in patients with polycystic ovary syndrome (PCOS) undergoing controlled ovarian stimulation. Materials and methods This double-blind, parallel, and randomized clinical trial was performed from April to June 2024. Forty-two patients with PCOS who were candidates for assisted reproductive techniques were randomized into two groups. The first group received 0.5 mg of cabergoline, and the second group received 400 mg of hydroxychloroquine for 8 days. Then, ultrasounds were conducted on days 3 and 5 after oocyte retrieval to assess for OHSS. Results Three and five days after oocyte retrieval, laboratory findings, and clinical outcomes were similar between the cabergoline and hydroxychloroquine groups. Key laboratory parameters, including hemoglobin, hematocrit, sodium, potassium, blood urea nitrogen, and creatinine, did not show significant differences between the groups. On day three, OHSS incidence didn’t have a significant difference between the hydroxychloroquine and cabergoline groups, both for the mild (31.58% vs. 42.86%) and moderate (15.79% vs. 9.52%) groups. Mild cases were observed in one of the patients in both groups 5 days after pickup ( p  = 0.942). No patients in the cabergoline group required hospitalization or treatment, compared to one in the hydroxychloroquine group ( p  = 0.127). Conclusion The incidence of OHSS was similar between cabergoline and hydroxychloroquine, with no significant differences observed in laboratory parameters or clinical outcomes after oocyte retrieval. However, given the study’s sample size, further research is needed before these findings can be generalized to a larger population. Clinical trial number http://www.irct.ir ; Registration number: IRCT20240305061171N1; Registration date: 2024 June 29.

Background: It is estimated that in women at reproductive age, the risk of polycystic ovary syndrome (PCOS) is about 5–21%. In PCOS cases with ovulation dysfunction, assisted reproductive techniques (ART) are useful for infertility treatment. Objective: This study aimed to evaluate the ART outcome in infertile PCOS women based on different testosterone levels. Finally, the relationships between testosterone in different levels and reproductive parameters including endocrine status, the response of ovaries, and pregnancy outcomes were assessed. Methods: In this retrospective study, 352 infertile PCOS women were examined. The women were categorised into five groups according to their testosterone levels: A = T < 0.4, B = 0.4 < T > 0.6, C = 0.6 < T > 0.8, D = 0.8 < T > 1.0 and E = T > 1.0 ng/dL. All study cases were in similar hyper-stimulation protocol and finally, hormonal profile and ART outcomes were compared between testosterone levels. P value ≤ 0.05 was statistically significant. Results: In testosterone levels >1.0, the levels of anti-mullerian hormone (AMH) and luteinising hormone (LH) were higher than in other testosterone level groups. AMH (P = 0.05) and LH (P = 0.001) levels showed significant differences. No correlation was present between testosterone levels and ART outcomes, including stimulation duration, endometrial thickness, oocyte numbers, numbers of matured oocytes, number of obtained embryos, fertilisation rate, implantation rate clinical pregnancy and abortion rate. Conclusions: Serum testosterone levels did not show any correlation with pregnancy outcomes in ART cycles of PCOS. However, basal testosterone levels are a good predictor for ovarian reserve and ovarian response. Consequently, we suggest that some prospective studies must be designed to approve the role of testosterone in the prediction of the outcome of pregnancy in ART cycles.

IntroductionObesity has a derogatory effect on female reproductive health. Obesity contributes to difficulty in natural conception, increased risk of pregnancy-associated complications, miscarriages, congenital anomalies, and also the long-term negative impact on both mother and the child.ObjectivesOur study aimed to analyze and assess the reproductive health-associated outcomes of females who underwent bariatric surgery.MethodsWe performed a retrospective analysis from a prospectively collected database from June 2013 to June2016. Out of 71 females studied, 45 patients (63.5%) had completed 3 years of follow-up. The data were collected from inpatient and outpatient records. Patients were studied under three groups (A, patients with polycystic ovarian disease (PCOD) symptoms; B, patients with primary infertility; and C, patients who conceived after bariatric surgery that were included in groups A and B).ResultsOut of 45 patients studied, 40 patients underwent laparoscopic sleeve gastrectomy (LSG), four patients underwent laparoscopic Roux-en-Y gastric bypass (RYGB), and one patient underwent laparoscopic adjustable gastric banding (LAGB). The mean BMI of the patients was 43.64 ± 6.8 kg/m2. PCOD symptoms improved symptomatically (p = 0.001) after surgery in the group. Seven (43.75%) primary infertility patients conceived after surgery. Three (42.9%) patients conceived naturally while 4 (57.1%) conceived with ART in group B. Out of total population of 45 in group C, percentages of patients who delivered baby with short gestational age (SGA), low birth weight (LBW), normal vaginal deliveries (NVD), and maternal anemia were 63.15%,47.3%,73.4%, and26.3%, respectively.ConclusionObesity is closely associated with primary infertility and PCOD. Menstrual abnormalities associated with PCOD significantly improve after bariatric surgery with significant improvement in fertility along with maternal outcomes.

Abstract Background: It is estimated that in women at reproductive age, the risk of polycystic ovary syndrome (PCOS) is about 5-21%. In PCOS cases with ovulation dysfunction, assisted reproductive techniques (ART) are useful for infertility treatment. Objective: This study aimed to evaluate the ART outcome in infertile PCOS women based on different testosterone levels. Finally, the relationships between testosterone in different levels and reproductive parameters including endocrine status, the response of ovaries, and pregnancy outcomes were assessed. Methods: In this retrospective study, 352 infertile PCOS women were examined. The women were categorised into five groups according to their testosterone levels: A = T < 0.4, B = 0.4 < T > 0.6, C = 0.6 < T > 0.8, D = 0.8 < T > 1.0 and E = T > 1.0 ng/dL. All study cases were in similar hyper-stimulation protocol and finally, hormonal profile and ART outcomes were compared between testosterone levels. P value ≤ 0.05 was statistically significant. Results: In testosterone levels >1.0, the levels of anti-mullerian hormone (AMH) and luteinising hormone (LH) were higher than in other testosterone level groups. AMH (P = 0.05) and LH (P = 0.001) levels showed significant differences. No correlation was present between testosterone levels and ART outcomes, including stimulation duration, endometrial thickness, oocyte numbers, numbers of matured oocytes, number of obtained embryos, fertilisation rate, implantation rate clinical pregnancy and abortion rate. Conclusions: Serum testosterone levels did not show any correlation with pregnancy outcomes in ART cycles of PCOS. However, basal testosterone levels are a good predictor for ovarian reserve and ovarian response. Consequently, we suggest that some prospective studies must be designed to approve the role of testosterone in the prediction of the outcome of pregnancy in ART cycles.

Abstract In this study, we aimed to investigate the efficacy of FSH treatment in idiopathic patients who are candidates for ART (assisted reproductive techniques) 2 oligosoospermic, 10 oligoasthenosoospermic, 11 oligoteratosoospermic and 38 oligoasthenoteratosoospermic, 61 patients received FSH treatment. 45 patients were selected as control groups. All patients received 150 iü FSH 3 times a week for 2 months. In 2 patients at the time of treatment and in 1 patient after treatment, totally in 3 patients pregnancy occurred spontaneously. The remaining 58 patients went to IUI (intrauterine insemination) and ICSI (intracytoplasmic sperm injection) at GATA Obstetrics and Gynecology Department IVF Unit. In all patients, after FSH treatment, sperm parameters have been improved. These improvements are significant in sperm count and morphology. After FSH treatment in 15 of 61 patients occurred pregnancy 3 of which were spontaneous. In 12 patients pregnancy occurred by ART. Only 1 pregnancy occurred in severe oligosoospermic patients and this resulted with abortion. In the groups which pregnancy occurred or not, sperm parameters improved. In control group, 7 pregnancies occurred with ART and 2 of which resulted with abortion. When compared the pregnancy rate between the patients who received treatment or did not, the results were meaningful. FSH treatment increases sperm count and morphology. According to our results, FSH treatment may be useful in fertilizing effect of sperm and increasing rates by ART. Our results also show that ART success rates are lower in patients who have poor sperm parameters.