Beyond black-box models: explainable AI for embryo ploidy prediction and patient-centric consultation.

PURPOSE: To determine if an explainable artificial intelligence (XAI) model enhances the accuracy and transparency of predicting embryo ploidy status based on embryonic characteristics and clinical data. METHODS: This retrospective study utilized a dataset of 1908 blastocyst embryos. The dataset includes ploidy status, morphokinetic features, morphology grades, and 11 clinical variables. Six machine learning (ML) models including Random Forest (RF), Linear Discriminant Analysis (LDA), Logistic Regression (LR), Support Vector Machine (SVM), AdaBoost (ADA), and Light Gradient-Boosting Machine (LGBM) were trained to predict ploidy status probabilities across three distinct datasets: high-grade embryos (HGE, n = 1107), low-grade embryos (LGE, n = 364), and all-grade embryos (AGE, n = 1471). The model's performance was interpreted using XAI, including SHapley Additive exPlanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME) techniques. RESULTS: The mean maternal age was 38.5 ± 3.85 years. The Random Forest (RF) model exhibited superior performance compared to the other five ML models, achieving an accuracy of 0.749 and an AUC of 0.808 for AGE. In the external test set, the RF model achieved an accuracy of 0.714 and an AUC of 0.750 (95% CI, 0.702-0.796). SHAP's feature impact analysis highlighted that maternal age, paternal age, time to blastocyst (tB), and day 5 morphology grade significantly impacted the predictive model. In addition, LIME offered specific case-ploidy prediction probabilities, revealing the model's assigned values for each variable within a finite range. CONCLUSION: The model highlights the potential of using XAI algorithms to enhance ploidy prediction, optimize embryo selection as patient-centric consultation, and provides reliability and transparent insights into the decision-making process.

Targeted anti-apoptosis activity for ovarian protection against chemotherapy-induced ovarian gonadotoxicity.

Chemotherapy damages the reproductive system by enhancing apoptosis, and evidence suggests that targeted anti-apoptotic therapy may preserve fertility in patients receiving chemotherapy. To investigate the protective effect of sphingosine-1-phosphate (S1P) on chemotherapeutic agent-induced ovarian gonadotoxicity, busulfan-treated female mice were pre-treated with low (0.5 mM) and high (2.0 mM) doses of S1P or vehicle 1 h before busulfan injection. In the S1P groups, each mouse was injected with low-dose S1P in one ovary and high-dose S1P in the contralateral ovary. Four weeks later, the ovaries were removed for histological and biochemical examinations. Caspase 3 immunoreactivity was greater in mice treated with busulfan compared with mice pre-treated with S1P, in which more primordial follicles were observed (P < 0.05). The mRNA level of anti-Müllerian hormone was higher in mice pre-treated with S1P than those that received busulfan only, indicating a better ovarian function in mice pre-treated with S1P. No difference was observed in the levels of growth differentiation factor-9 among all groups. In conclusion, S1P protects primordial follicles from chemotherapy-induced gonadotoxicity, and may partially preserve ovarian function.

Successful pregnancy with in vitro fertilization after vaginal radical trachelectomy and pelvic lymphadenectomy in stage IB1 cervical cancer.

OBJECTIVE: To present a case of successful pregnancy after undergoing vaginal radical trachelectomy (VRT) and pelvic lymph node dissection (PLND) for early-stage cervical cancer. CASE REPORT: A 37-year-old female patient has been diagnosed with stage IB1 cervical cancer and underwent VRT and PLND. Two years after the surgery, the patient successfully conceived and delivered a healthy baby through a cesarean section. CONCLUSION: This case report demonstrates that pregnancy after VRT and PLND for stage IB1 cervical cancer is possible and can result in a successful outcome. This report provides valuable information for patients and physicians who are considering these surgical options.

Fetal demise by umbilical cord around abdomen and stricture.

Umbilical cord abnormalities are accepted as conditions associated with intrauterine fetal demise (IUFD), and umbilical cord stricture is most frequently encountered. In addition, although cord entanglement with multiple loops rarely increases the perinatal mortality, it is associated with a significant increase in variable kind of morbidity such as growth restriction. We describe a 27-year-old woman, with a missed abortion history at about 10 weeks' gestation in her first pregnancy, who presented to our outpatient department at 34 4/7 weeks of gestation due to decreased fetal activity during the preceding week. No fetal heart activity and blood flow had been detected by ultrasonography and pulsed-wave Doppler. A demised fetus with umbilical cord stricture and three loops around abdomen was delivered and was weighted 1,830 g that was below the tenth percentile for the gestational age. Either umbilical cord stricture or entanglement around the body can affect the development of the fetus and even be lethal. The former might play a more important role in this case. Their etiology and the sequence of the events are still undetermined, and additional evaluation such as autopsy and further research may be needed. In addition, counsel and frequent fetal surveillance should be done in patients with previous IUFD attributed to cord stricture during next pregnancy because of undetermined risk of recurrence.

A bioinspired hyperthermic macrophage-based polypyrrole-polyethylenimine (Ppy-PEI) nanocomplex carrier to prevent and disrupt thrombotic fibrin clots.

Fibrinolytic treatments for venous or arterial thrombotic syndromes using systemic administration of thrombolytics, such as streptokinase, can induce life-threatening bleeding complications. In this study, we offer the first proof of concept for a targeted photothermal fibrin clot prevention and reduction technology using macrophages loaded with polypyrrole-polyethylenimine nanocomplexes (Ppy-PEI NCs) and subjected to near-infrared radiation (NIR). We first show that the developed Ppy-PEI NCs could be taken up by defensive macrophages in vitro through endocytosis. The Ppy-PEI NCs generated local hyperthermia upon NIR treatment, which appeared to produce reactive oxygen species in Ppy-PEI NC-loaded macrophages. Preliminary evidence of efficacy as an antithrombotic tool is provided, in vitro, using fibrinogen-converted fibrin clots, and in vivo, in a rat femoral vascular thrombosis model generated by exposure to ferric chloride substance. The in vivo biocompatibility, photothermal behavior, biodistribution, and histological observation of cellular interactions with the Ppy-PEI NCs in the rat model provide rationale in support of further preclinical studies. This Ppy-PEI NC/NIR-based method, which uses a unique macrophage-guided targeting approach to prevent and lyse fibrin clots, may potentially overcome some of the disadvantages of current thrombolytic treatments. STATEMENT OF SIGNIFICANCE: Fibrinolytic treatments for venous or arterial thrombotic syndromes using systemic administration of thrombolytics, such as streptokinase, can induce life-threatening bleeding complications. In this study, we offer the first proof of concept for a targeted photothermal fibrin clot reduction technology using macrophages loaded with polypyrrole-polyethylenimine nanocomplexes (Ppy-PEI NCs) and subjected to near-infrared radiation (NIR). We first show that the developed Ppy-PEI NCs can be taken up by defensive macrophages in vitro through endocytosis. The Ppy-PEI NCs generated local hyperthermia upon NIR treatment, which appeared to produce reactive oxygen species in Ppy-PEI NC-loaded macrophages. Preliminary evidence of efficacy as an antithrombotic tool is provided, in vitro, using fibrinogen-converted fibrin clots, and in vivo, in a rat femoral vascular thrombosis model generated by exposure to ferric chloride substance. The in vivo biocompatibility, photothermal behavior, biodistribution, and histological observation of cellular interactions with the Ppy-PEI NCs in the rat model provide rationale in support of further preclinical studies. This Ppy-PEI NC/NIR-based method, which uses a unique macrophage-guided targeting approach to disintegrate fibrin clots, may potentially overcome some of the disadvantages of current thrombolytic treatments.

Pregnancy following robot-assisted laparoscopic partial cystectomy and gonadotropin-releasing hormone agonist treatment within three months in an infertile woman with bladder endometriosis.

OBJECTIVE: To report an infertility case of deep-infiltrating bladder endometriosis conceiving following robot-assisted surgery and modified gonadotropin-releasing hormone agonist (GnRHa) treatment. CASE REPORT: A 33 year-old infertile female presenting with dysmenorrhea was found to have a bladder mass by pelvic ultrasound. Cystoscopy revealed a protruding tumor from the posterior bladder wall, and endometriosis was highly suspected. Robot-assisted laparoscopic partial cystectomy was performed for the deep-infiltrating bladder endometriosis. With postoperative half-dose GnRHa treatment and timed intercourse, she got pregnant within 3 months. CONCLUSION: Robot-assisted complete resection of deep-infiltrating endometriosis and bladder repair immediately followed by GnRHa therapy and medical assistance improves reproductive outcomes efficiently in women with endometriosis-associated infertility.

In vivo fate mapping of cryopreserved murine ovarian grafts.

BACKGROUND: Cryopreservation of ovarian tissue has been suggested as an alternative to restore fertility for ovarian failure before chemotherapy. METHODS: Ovaries of donor FVB/N-Tg (PolII-Luc) Ltc transgenic mice (n = 5) were cryopreserved and transplanted to the back muscles of recipient FVB/NJNarl wild-type mice that had undergone bilateral oophorectomy. We evaluated the fate of cryopreserved murine ovarian grafts by in vivo bioluminescent imaging (BLI), AMH mRNA expression and follicle counts. RESULTS: There were significantly stronger BLI signals in the fresh ovaries than in the frozen-thawed ones. The number of primordial follicles was significantly lower in frozen-thawed ovaries at 10 days after transplantation (P < 0.001). The AMH mRNA expression was significantly lower in the frozen-thawed ovaries (P < 0.001), showing that unavoidable harm occurs after transplantation. CONCLUSIONS: Ovarian cryopreservation by slow freezing compromises ovarian reserve by cryoinjury and ischemia, evident at an early stage after transplantation.

Antiapoptotic agent sphingosine-1-phosphate protects vitrified murine ovarian grafts.

Significant follicle loss from frozen ovarian grafts is unavoidable. The authors evaluated the protective effects of the antiapoptotic agent sphingosine-1-phosphate (S1P) on vitrified ovarian grafts. Three-week-old sexually immature female FVB mice were divided into 4 groups, fresh, control without S1P, 0.5 mmol/L S1P, and 2 mmol/L S1P. The ovaries were pretreated with S1P for 1 hour and then cryopreserved by modified vitrification. The frozen-thawed ovaries were autotransplanted under the back muscles of mice for 10 days. Expression of apoptosis-related genes encoding caspase 3 and c-Myc was analyzed in the vitrified ovaries and 10 days after transplantation using real-time quantitative polymerase chain reaction. To quantify the ovarian reserve, anti-Müllerian hormone (AMH) levels and follicles were measured in the 10-day vitrified ovarian grafts. Caspase 3 and c-Myc messenger RNA did not differ significantly in the 4 groups after vitrification but was significantly upregulated in the control group after transplantation. The AMH levels and primordial follicle pool were significantly higher in the S1P-treated groups than in the control group but lower than that in the fresh group. The S1P protects vitrified ovarian grafts from ischemic reperfusion injury rather than from vitrification-associated process.

Robotic surgery in complicated gynecologic diseases: experience of Tri-Service General Hospital in Taiwan.

OBJECTIVE: Minimally invasive surgery has been the trend in various specialties and continues to evolve as new technology develops. The development of robotic surgery in gynecology remains in its infancy. The present study reports the first descriptive series of robotic surgery in complicated gynecologic diseases in Taiwan. MATERIALS AND METHODS: From March 2009 to February 2011, the records of patients undergoing robotic surgery using the da Vinci Surgical System were reviewed for patient demographics, indications, operative time, hospital stay, conversion to laparotomy, and complications. RESULTS: Sixty cases were reviewed in the present study. Forty-nine patients had benign gynecologic diseases, and 11 patients had malignancies. These robot-assisted laparoscopic procedures include nine hysterectomy, 15 subtotal hysterectomy, 13 myomectomy, eight staging operation, two radical hysterectomy, five ovarian cystectomy, one bilateral salpingo-oophorectomy and myomectomy, two resections of deep pelvic endometriosis, one pelvic adhesiolysis, three sacrocolpopexy and one tuboplasty. Thirty-three patients had prior pelvic surgery, and one had a history of pelvic radiotherapy. Adhesiolysis was necessary in 38 patients to complete the whole operation. Robotic myomectomy was easily accomplished in patients with huge uterus or multiple myomas. The suturing of myometrium or cervical stump after ligation of the uterine arteries minimized the blood loss. In addition, it was much easier to dissect severe pelvic adhesions. The dissection of para-aortic lymph nodes can be easily accomplished. All these surgeries were performed smoothly without ureteral, bladder or bowel injury. CONCLUSION: The present analyses include various complicated gynecologic conditions, which make the estimation of the effectiveness of robotic surgery in each situation individually not appropriate. However, our experiences do show that robotic surgery is feasible and safe for patients with complicated gynecologic diseases.

Protective effect of a gonadotropin-releasing hormone analogue on chemotherapeutic agent-induced ovarian gonadotoxicity: a mouse model.

OBJECTIVE: To demonstrate the protective effect of triptorelin, a GnRH analogue, on chemotherapy-induced ovarian gonadotoxicity. STUDY DESIGN: Twenty-four sexually mature, virgin, female FVB/NJNarl mice were divided into four groups: busulfan (B); low-dose triptorelin plus busulfan (T(L)+B); high-dose triptorelin plus busulfan (T(H)+B); and control. Mice in the T(L)+B and T(H)+B groups were injected with 3.8 and 38 mg/kg of triptorelin subcutaneously, respectively. Four weeks later, mice in the B, T(L)+B, and T(H)+B groups were injected with busulfan intraperitoneally at a dose of 36 mg/kg. Histologic examinations were performed 4 weeks later. RESULTS: Obvious destruction of ovarian structure and significant depletion of primordial, primary, and secondary follicles were demonstrated in the B group compared with the control group, affirming the gonadotoxicity of busulfan. In the T(L)+B group, a greater number of larger primordial and primary follicles were enumerated compared with the B group; however, statistical significance was not achieved. In the T(H)+B group, the number of primordial and primary follicles was significantly greater than in the B group, and the ovarian tissue in the T(H)+B group was spared, demonstrating the effect of triptorelin pre-treatment on ovarian protection. CONCLUSION: Our results have demonstrated a dose-dependent protective effect against gonadotoxic chemotherapy of a GnRH analogue on ovarian reserve, thus suggesting a novel application of GnRH analogues in fertility preservation.