Reprod. Med., Volume 7, Issue 1 (March 2026) – 16 articles

Background/Objectives: Women’s health has historically lagged behind other medical specialties in transformative innovation, despite significant technological advances in adjacent fields. In this collection of papers, we examine the current state of innovation in women’s health and maternal–fetal medicine, identify barriers to transformation, and propose strategies for accelerating breakthrough developments. This paper presents an overview of multiple forces and their often-competing relationships that influence the environment in which advances in multiple areas of healthcare have had to navigate to enter mainstream practice. An understanding of these forces is essential to explain why some new technologies are readily deployed into clinical practice while others take many years to be adopted. Understanding the entire “echo-system” around any specific technology provides a much fuller understanding of how any individual advance can make its way into actual utilization. Methods: We synthesized current literature on innovation in women’s health, analyzing technological advances in artificial intelligence, precision medicine, non-invasive diagnostics, and surgical robotics. We examined patterns of innovation adoption and barriers to implementation across multiple domains. Results: Several key areas presented in this paper and the following show promise for transformative change: artificial intelligence (AI)-driven diagnostics achieving expert-level performance in prenatal screening, precision medicine approaches transforming genetic disease management, and non-invasive monitoring technologies revolutionizing maternal–fetal care. However, systemic barriers including regulatory complexity, liability concerns, and institutional inertia continue to limit widespread adoption of numerous breakthrough technologies. Conclusions: The convergence of multiple technological advances, particularly artificial intelligence and precision medicine, positions women’s health for unprecedented transformation. Success requires fostering innovation-ready environments, embracing systems-awareness approaches, and maintaining focus on human-centered care while leveraging technological capabilities with continual feedback and course corrections. Full article

Background: Oocyte cryopreservation has emerged as a viable fertility preservation method, gaining popularity among women delaying motherhood for non-medical reasons. This study examines the awareness, perceptions, and social factors influencing young women’s decisions regarding elective oocyte cryopreservation (EOC), intending to identify key demographic and psychosocial determinants. Methods: A cross-sectional study was conducted using an online survey distributed via digital platforms between November 2024 and February 2025. A structured questionnaire comprising 31 multiple-choice questions assessed participants’ sociodemographic characteristics, reproductive health history, lifestyle factors, and perceptions of fertility and EOC. Statistical analyses included Chi-square tests, t-tests, and binary logistic regression to identify factors associated with willingness to undergo EOC. Results: A total of 390 women (mean age 22.57 ± 1.41 years) participated. Awareness of oocyte cryopreservation was remarkably high (93.1%). Significant predictors for the intention to undergo EOC included higher educational attainment (Master’s level) (OR = 4.27, 95% CI: 1.10–16.48) and living in a student dormitory (OR = 15.39, 95% CI: 4.86–48.71). Conversely, living with a partner showed a non-significant downward trend in interest (OR = 0.07, 95% CI: 0.01–1.43). Psychological factors, specifically anxiety about future fertility (OR = 0.23, 95% CI: 0.08–0.62 for moderate vs. high anxiety) and a strong desire for future parenthood (OR = 21.75, 95% CI: 1.45–32.99), also emerged as primary drivers of women’s reproductive decisions. Conclusions: Despite high awareness, the willingness to undergo elective oocyte cryopreservation remains limited. Targeted fertility education and supportive policies are needed to address misconceptions, financial barriers, and psychological concerns influencing reproductive decision-making. Further research should explore longitudinal trends in women’s attitudes toward EOC. Full article

Pregnancy (HP), defined as the coexistence of intrauterine and ectopic gestations, is a rare condition, especially in spontaneous conception, but it is a life-threatening obstetric emergency when rupture occurs, with a reported maternal mortality rate of 0.03%. Diagnosis is often delayed because confirmation of an intrauterine pregnancy can mask clinical signs of a concurrent ectopic gestation. Early recognition and prompt surgical intervention are therefore critical to maternal safety and preservation of intrauterine viability. This case highlights the diagnostic challenges and successful management of a spontaneous ruptured heterotopic pregnancy. Case presentation: A 34-year-old Middle Eastern woman, gravida 4, with a spontaneous conception, presented with sudden severe lower abdominal pain and signs of acute hemoperitoneum (hypotension, tachycardia, and marked peritoneal signs). Transvaginal ultrasound demonstrated a viable intrauterine pregnancy at 9 weeks 4 days gestation, together with a ruptured left tubal ectopic pregnancy of similar gestational age. The patient underwent urgent laparoscopic left salpingectomy with evacuation of approximately 1200 mL of intraperitoneal blood and clots. Postoperatively, she developed significant anemia (hemoglobin drop from 11.2 g/dL on admission to 6.5 g/dL) requiring transfusion of four units of packed red blood cells. Serial ultrasonographic follow-up confirmed ongoing viability of the intrauterine pregnancy, which ultimately resulted in a live birth at term. Progressive resolution of the postoperative pelvic hematoma was also noted. Conclusions: Ruptured heterotopic pregnancy remains a diagnostic and therapeutic challenge. This case, along with a synthesis of the contemporary literature, demonstrates that a high clinical index of suspicion, timely ultrasound diagnosis, and immediate minimally invasive surgical management are paramount. Furthermore, rigorous postoperative monitoring and resuscitation, including targeted transfusion, are essential to achieve maternal stabilization while allowing continuation of a viable intrauterine pregnancy, with reported live birth rates exceeding 70% following timely intervention. Full article

Background/Objectives: Primary dysmenorrhea is a common menstrual condition that significantly affects women’s daily functioning and quality of life. Although physiotherapy has been shown to reduce menstrual pain, the awareness of these methods in Saudi Arabia remains unclear. This study aimed to assess women’s awareness and experiences of physiotherapy methods for managing primary dysmenorrhea in Saudi Arabia. Methods: A cross-sectional online survey was conducted among women living in SA between 16 and 28 February 2024. The questionnaire collected information on six sections including on sociodemographic characteristics, menstrual history and pain severity, work-related impact, pain-management practices, healthcare utilisation, and awareness and use of physiotherapy modalities. Convenience sampling was employed, and participation was voluntary and anonymous. Descriptive data analysis was performed using SPSS software. Results: A total of 431 women participated; most were Saudis (91.9%) and aged 18–24 years (43.2%). Primary dysmenorrhea was reported by 86.5% of participants. More than half (58%) had used at least one physiotherapy-related method, mainly heat, massage, or exercise, and 55.2% considered these methods effective. However, most relied on basic home strategies rather than structured physiotherapy interventions. Additionally, 60.8% expressed willingness to use physiotherapy in the future. Conclusions: Despite the frequent use of simple home-based methods, structured physiotherapy interventions remain underutilised. Increasing public education, improving access to physiotherapy services, and integrating self-management guidance and telerehabilitation into women’s health programmes may enhance menstrual pain management and overall quality of life. Full article

Background/Objectives: Dichorionic triamniotic (DCTA) triplet pregnancies are associated with increased rates of placenta-specific complications primarily attributed to vascular anastomoses in the monochorionic (MC) pair. Selective fetal reduction to twins (of one of the MC pair) is a complex and not a widely available procedure. Multifetal reduction (MFR) to singleton pregnancy can reduce adverse pregnancy outcomes but is controversial due to medico-legal and socio-ethical issues. The aim of this study is to identify the rate of miscarriage < 24 weeks or preterm birth < 34 weeks following MFR to singleton pregnancy in DCTA triplets and compare the results with expectant management. Methods: This systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the Prospective Register of Systematic Reviews System (ID: CRD42023422585). Results: Overall, from 21 citations of relevance, 6 studies with a total of 548 DCTA triplet pregnancies fulfilled the inclusion/exclusion criteria. In comparison with expectant management (n = 336), meta-analysis demonstrated that MFR to singleton pregnancy (n = 212) was associated with a lower rate (9.4% vs. 48.5%) of preterm birth (RR = 0.19, 95%CI 0.07–0.51), whereas the rate of miscarriage (14.6% vs. 9.2%) did not significantly increase (RR = 1.53, 95%CI 0.91–2.55). Conclusions: In DCTA triplet pregnancies, MFR to singleton pregnancy was associated with a reduced preterm birth rate and not associated with an increased miscarriage rate. Given the fact that the MC pair is reduced only to lower the rate of preterm birth, appropriate counselling and justification are important. In the absence of randomized controlled trials, data from systematic reviews are the best available evidence for counseling on the different management options. Full article

Background/Objectives: Geographical differences exist in the clinical presentation of polycystic ovary syndrome (PCOS). The degree to which ovarian morphology contributes to this variability is unknown. Methods: This study compared ovarian ultrasound features between women with PCOS residing in two geographical regions (India and the United States) using stored de-identified ultrasound scans from 331 women with PCOS. Sonographic markers of interest included follicle number per ovary (FNPO), follicle number per cross-section (FNPS), ovarian volume (OV), ovarian area (OA), stromal area (SA), and stromal-to-ovarian area ratio (S/A). Results: Most participants in both regions met the accepted criteria for polycystic ovarian morphology (India 87% vs. U.S. 83%). The U.S.-based group had a higher prevalence of follicle excess (41% in U.S. vs. 29% in India; p = 0.037), whereas the prevalence of ovarian enlargement was similar across groups (India 37% vs. U.S. 31%, p = 0.252). FNPS was higher in the U.S.-based group (p = 0.046), while the India-based group had higher OV (p = 0.010). SA and S/A did not differ between groups, albeit OA was slightly larger in women with PCOS from India (p = 0.022). Associations between ovarian morphology and menstrual cycle length (ρ = 0.16–0.25), hirsutism score (ρ = 0.19–0.23), and total testosterone (ρ = −0.33–0.42) were noted in both groups (p < 0.05). Conclusions: Some variation in ovarian morphology may exist across geographic regions. However, the degree of variability is unlikely to warrant regional definitions for polycystic ovarian morphology at this time. Full article

Background/Objectives: Precocious puberty (PP), defined as the onset of secondary sexual characteristics before 8 years in girls and 9 years in boys, is associated with psychosocial distress, compromised adult height, and long-term metabolic risk. Early identification remains challenging, as current diagnostic approaches are largely reactive and rely on invasive or resource-intensive testing. This narrative review examines how artificial intelligence (AI) can support earlier risk prediction and detection of PP through integration of clinical, hormonal, imaging, lifestyle, and environmental data. Methods: A narrative literature review was conducted using PubMed, Scopus, Embase, Web of Science, and Google Scholar to identify relevant studies published between 2005 and 2025. Eligible studies included original research and high-quality reviews that examined AI-based approaches, such as machine learning and deep learning, in pediatric endocrinology, particularly for the prediction or diagnosis of central or peripheral precocious puberty. Studies incorporating clinical, hormonal, radiological, lifestyle, environmental, or multi-omics data relevant to AI modeling were included. Results: AI models, including XGBoost, random forest, convolutional neural networks, and regression-based approaches, have demonstrated potential utility in predicting central precocious puberty using hormonal, imaging, and growth data. Reported applications include automated bone age assessment, lifestyle and dietary risk stratification, and exploratory use of wearable-derived behavioral data. However, progress is limited by small pediatric datasets, population bias, limited interpretability, and unresolved ethical challenges related to privacy, consent, and equity. Conclusions: Artificial intelligence represents a promising decision-support approach for earlier, non-invasive, and individualized risk assessment in precocious puberty. Future progress will depend on the integration of longitudinal, multimodal data, the development of ethical models, and interdisciplinary collaboration among pediatric endocrinologists, data scientists, and public health stakeholders. Full article

Background/Objectives: Infertility is a major public health concern, affecting one in six individuals worldwide and nearly one-quarter of couples in France. While a male, female, or combined factor can be identified in approximately 75% of cases, infertility remains unexplained in 10–25%. Genital tract infections account for roughly 15% of male infertility cases and are often asymptomatic, being detected incidentally during routine evaluation prior to assisted reproductive technology (ART). Emerging evidence suggests that the seminal microbiota may contribute to sperm quality and male reproductive health. This systematic review aims to evaluate whether specific microbial profiles are associated with alterations in semen parameters. Methods: A comprehensive literature search was conducted in PubMed and ScienceDirect, yielding 165 and 1418 records, respectively. In the end, 20 articles were included in this systematic review. Results: Men with normal semen parameters commonly exhibited a higher abundance of Lactobacillus and Bifidobacterium, whereas Prevotella was more frequently observed in individuals with impaired semen quality. Several taxa—such as Gardnerella, Corynebacterium, and Staphylococcus spp.—were detected in both normal and altered semen profiles, suggesting that their impact on sperm quality may depend on reaching a pathogenic threshold. Conclusions: Current evidence supports an association between seminal microbiota composition and sperm quality. However, the heterogeneity of available studies and the lack of standardized methodologies limit the ability to draw firm conclusions. Further well-designed studies are required to clarify causal relationships and to determine the clinical relevance of seminal microbiota assessment in male infertility. Full article

Background/Objectives: Dynein axonemal heavy chain (DNAH) genes, including DNAH6, are implicated in male infertility, particularly multiple morphological abnormalities of the spermatozoa flagellum (MMAF). However, an underlying mechanism is unclear. Methods: This in silico study analyzed 19 previously reported DNAH6 mutations to elucidate their effects on the structural, mechanical, and microstructural aspects and axonemal assembly of flagellum and how these changes impact reproductive health, correlating with pathogenicity scores, ATP binding capacity, and protein interactions. Results: DNAH mutations were associated with CDGP (52.63%), male infertility (36.84%), and primary ovarian insufficiency (10.53%). MMAF-linked mutations exhibited higher SNAP2 scores (57.25 ± 5.68 vs. −32.58 ± 44.85, p = 0.002), reduced ATP binding affinity (−6.27 ± 4.20 vs. −8.92 ± 0.23 kcal/mol, p = 0.05), and smaller catalytic cavity size (17,646 ± 13,005 vs. 27190 ± 3485 ų, p = 0.04). These mutations showed reduced DNAH6-CLIP4 binding affinity (−303.90 ± 5.23 vs. −313.60 ± 4.28 kcal/mol, p = 0.002). Literature-based semen analysis revealed correlations between Phred scores and absent flagella (r = 0.952, p = 0.012) and inverse correlations between ATP binding capacity and absent flagella (r = −0.902, p = 0.036) or irregular width (r = −0.949, p = 0.014). A mathematical model of ATP binding kinetics predicted reduced flagellar motility in MMAF mutants due to impaired dynein function. Ultrastructural analyses indicated that high pathogenicity scores and reduced ATP binding correlate with absent inner dynein arms and radial spokes, while impaired DNAH6-CLIP4 interactions disrupt axonemal assembly. Conclusions: In silico analyses, integrated with microstructural, axonemal, and mathematical modeling data, demonstrate that DNAH6 mutations cause MMAF by impairing ATP binding, protein interactions, and axonemal assembly, leading to severe flagellar dysfunction and thereby negatively affecting reproductive health. Full article

Background: Following gonadotropin-releasing hormone (GnRH) agonist trigger and “freeze all” in order to prevent ovarian hyper-stimulation syndrome (OHSS), patients are usually anxious to continue immediately with a frozen embryo transfer (FET). Currently, the preferred FET protocol in based on natural or induced ovulation. Objectives: Do ovarian stimulation and GnRH-a, used to trigger final oocyte maturation, affect the reproductive axis in the next natural cycle? Design: An observational case series of 100 subsequent in vitro fertilization (IVF) patients to whom GnRH-a (Triptorelin 0.2 mg) was given for final oocyte maturation in the context of ovarian hyper-stimulation syndrome prevention, followed by embryos “freeze all”. Methods: In the next natural cycle, patients were followed to detect a dominant follicle (≥17 mm), at which time ovulation was triggered with human chorionic gonadotropin (hCG, 250 µg), and FET was scheduled according to embryo’s age on freezing day. Results: Whereas natural ovulation according to pre-IVF treatment was predicted to be on cycle day 14, the actual hCG-scheduled ovulation in our patients was on day 21. In eight patients, follicular activity was not detected after 15–28 days; therefore, the natural cycle frozen embryo transfer approach was abandoned. Conclusions: Ovarian stimulation and GnRH-a used to trigger final oocyte maturation in IVF patients inhibits the reproductive axis for days. Therefore, natural ovulation in the subsequent cycle may be deferred for about one week relative to the patient’s pre-IVF menstrual cycle pattern. This may help schedule clinic visits to optimize monitoring efficiency. Full article

Background/Objectives: Preterm birth remains a major cause of neonatal morbidity and mortality, particularly in multiple pregnancies and in cases of cervical shortening. While cervical cerclage is established in singleton pregnancies, its efficacy in multiple gestations remains uncertain. This study compares pregnancy and neonatal outcomes following second-trimester cerclage in singleton and multiple pregnancies with a short cervix. Methods: In this retrospective cohort study, 96 women underwent second-trimester cerclage at a tertiary perinatal center between 2020 and 2024. All had a cervical length ≤ 25 mm or prolapsed membranes without infection or premature rupture. Primary outcomes included term delivery rate, gestational age, mode of delivery, and neonatal outcomes; secondary outcomes comprised surgical complications and rehospitalization, defined as the need for renewed inpatient care due to threatened preterm labor or procedure-related complications. Results: In total, 79 singleton and 17 multiple pregnancies were analyzed. Term delivery occurred more often in singletons (54%) than multiples (18%, p = 0.006). Mean gestational age at birth was 258 ± 25 days in singletons versus 228 ± 28 days in multiples (p < 0.001). Birth weight was significantly lower in multiples (1985 g vs. 2943 g; p < 0.001), and neonatal infections were more frequent (53% vs. 26%; p = 0.008). Caesarean delivery was more common in multiples (82% vs. 33%; p < 0.001). Apart from increased postoperative contractions in multiples (24% vs. 5%; p = 0.031), complication rates and rehospitalization (27% vs. 29%; p = 0.8) were similar. Conclusions: Second-trimester cerclage is less effective in preventing preterm birth in multiple pregnancies compared to singleton pregnancies; however, it appears to be associated with a stabilizing clinical course and may facilitate outpatient management in selected high-risk cases. These findings support individualized counseling and shared decision-making, particularly in multifetal gestations. Full article

Obstructive sleep apnea (OSA) is a highly prevalent disorder with far-reaching systemic consequences. While its cardiometabolic and neurocognitive impacts are well established, growing evidence highlights OSA as a contributor to infertility in both men and women. The pathophysiological mechanisms include intermittent hypoxia, oxidative stress, systemic inflammation, and endocrine disruption, all of which can impair spermatogenesis, reduce semen quality, alter gonadal hormone secretion, and compromise ovarian function. Clinical studies consistently demonstrate associations between OSA and impaired semen parameters, reduced testosterone, and erectile dysfunction in men. In women, OSA is frequently observed in those with polycystic ovary syndrome, is associated with ovulatory dysfunction, and negatively affects in vitro fertilization outcomes, pregnancy rates, and miscarriage risk. Despite these findings, infertility is not systematically included in global burden estimates of OSA, leading to the underestimation of its true health and socioeconomic impact. Therapeutic strategies such as weight loss, continuous positive airway pressure, and integrative approaches show promise, though robust evidence from randomized trials is still lacking. Integrating sleep health into reproductive medicine may provide a cost-effective and equitable pathway to improve fertility outcomes worldwide. Full article

Background: Retained products of conception (RPOC) after term delivery are uncommon but may lead to persistent abnormal uterine bleeding and other complications. Hysteroscopic removal is considered the optimal management strategy, and technological advances have increasingly enabled operative procedures to be performed safely in an office setting. Clinical case: We report the case of a 43-year-old woman who presented with intermittent spotting four months after spontaneous vaginal delivery. Transvaginal ultrasound revealed a small, avascular hyperechoic intrauterine lesion consistent with retained amniochorionic tissue. She underwent office hysteroscopic removal using a 16 Fr bipolar mini-resectoscope under nitrous oxide (N₂O) buccal–nasal analgesia. The procedure was performed using a vaginoscopic, no-touch approach without speculum, tenaculum, or cervical dilation. Complete resection was achieved in a seven-minute procedure, with a postoperative pain score of 2/10 on the VAS and no complications. At 30-day follow-up, the patient was asymptomatic, and an ultrasound confirmed complete resolution. Conclusion: This case demonstrates that retained amniochorionic tissue can be safely and effectively treated in a fully ambulatory setting using mini-resectoscopic technology and N₂O analgesia. The combination of minimally invasive instruments, patient-centered procedural strategies, and well-tolerated analgesia supports the growing role of office operative hysteroscopy for selected complex intrauterine conditions. Full article

The success of embryo implantation and pregnancy depends on a complex interaction between the trophoblast and the endometrial environment, where endometrial receptivity plays a crucial role in this process. Assisted reproductive technologies (ARTs) are essential in overcoming biological barriers and enabling implantation in women with fertility issues. However, one of the main challenges in ART is ensuring that the endometrium is receptive at the time of implantation. Therefore, identifying endometrial receptivity biomarkers is essential to optimize ART treatments, improving success rates. A comprehensive literature review was conducted by searching peer-reviewed articles published in PubMed, Scopus, and Web of Science databases. The search included studies focusing on molecular and cellular mechanisms underlying endometrial receptivity in both natural and stimulated cycles. Various experimental methods, including proteomic and microRNA studies, have identified key biomarkers involved in endometrial receptivity, such as adhesion molecules, growth factors, and others. However, ovarian stimulation in fertility treatments can alter endometrial receptivity, making approaches like frozen embryo transfer necessary. Despite advancements, many questions persist regarding the endometrial receptivity and implantation mechanisms in both natural and stimulated cycles. This article reviews the main molecules involved in endometrial receptivity in natural and stimulated cycles, highlighting their potential role as biomarkers for embryo implantation. Full article

Background/Objectives: Menstrual blood, a periodic uterine discharge, represents a non-invasive source for an indication of the functional status of the endometrium. While menstrual blood-derived stem cells have been extensively characterized and menstrual blood is considered a diagnostic material for the analysis of gynecologic pathology in research studies, it is not routinely used in clinical settings. To develop novel noninvasive diagnostic tools for endometrial status assessment, we aimed to characterize the morphological and molecular markers of menstrual blood. Methods: Menstrual blood samples were obtained from healthy volunteers and characterized macroscopically and microscopically using smears (May-Grunwald-Giemsa staining), confocal microscopy, and imaging flow cytometry (cluster of differentiation [CD]90, CD45, fibrin). Clot dissociation was performed to analyze the cellular composition of clots. Results: We morphologically characterized menstrual blood cells and identified three uterine-derived cells and cell cluster types (endometrial stromal, endometrial epithelial, and vaginal epithelial). Additionally, we confirmed the specificity of CD90 for endometrial stromal cell populations, which were separately characterized in the supernatant and menstrual blood clots using light and confocal microscopy, and we analyzed the composition of the menstrual blood supernatant and dissociated clots using imaging flow cytometry. Conclusions: The results of this study may serve as a foundation for the development of new non-invasive diagnostic tools for endometrial pathology for the potential support or replacement of highly invasive procedures, such as diagnostic dilation and curettage. Full article