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

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