Reproductive Medicine

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.

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.

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.