Social determinants of health that impact the time to diagnosis and treatment of infertility in Taiwan.

BACKGROUND/PURPOSE: Taiwan is one of the countries with the lowest birth rate in the world. We investigated factors associated with the time to diagnosis and treatment of infertility in Taiwan. METHODS: The study was conducted through an online questionnaire in December 2021. The questionnaire was adapted from a previously published multinational survey, and culture-specific questions were added. 91 infertile patients and 89 partners of patients in Taiwan, aged 20- to 45- year-old, were included. RESULTS: The average duration before diagnosis was 2.9 years, followed by 1.5 years before treatment. Older age at marriage (p = 0.0024), higher education level (P = 0.0001), and a higher gender equality score (p = 0.0031) were associated with earlier diagnosis. Conversely, folk therapy use was linked to later diagnosis (p < 0.0001) and treatment (p < 0.0001). Notably, in the female (p = 0.039) and patient (p = 0.0377) subgroups, a higher gender equality score was associated with a shorter duration of folk therapy. Subjectively, the most frequent factor influencing treatment decision was affordability or lack thereof. The government subsidy for in vitro fertilization led to increased treatment willingness for 46.3% of respondents, and 47.3% reported more likely to pursue earlier treatment. CONCLUSIONS: This study highlights the influence of education, gender equality, folk therapy, and government subsidy on fertility care decisions. To improve the timeliness of infertility healthcare in Taiwan, potential strategies include promoting education, fostering gender equality, providing financial support, and raising awareness on the association between folk therapy and delayed medical care.

The Current Trend of Fertility Preservation in Patients with Cervical Cancer.

Although the incidence of most cancers increases with age, a considerable number of patients receive a diagnosis of cancer during their reproductive years. Young women wishing to get pregnant after cancer treatment should be provided consultation for fertility preservation and possible options. In patients with cervical cancer, hysterectomy is often inevitable because the uterus is located too close to the cervix. For young patients with cervical cancer who desire to get pregnant and whose lesion is confined to the cervix, sparing the uterus and, partially, the cervix should be prioritized as much as possible, while simultaneously ensuring favorable oncologic outcomes. In this review, we explore how to choose an adequate fertility-preserving procedure to achieve a balance between favorable oncologic outcomes and fertility and management during pregnancy after a radical trachelectomy in women with early-stage cervical cancer. For patients who require hysterectomy or radiation, evaluation of the ovarian condition and laparoscopic ovarian transposition followed by the use of artificial reproduction techniques and pregnancy by surrogacy should be discussed as options to achieve a successful pregnancy.

A direct healthcare cost analysis of recombinant LH versus hMG supplementation on FSH during controlled ovarian hyperstimulation in the GnRH-antagonist protocol.

PURPOSE: We have previously published a retrospective matched-case control study comparing the effect of recombinant LH (r-hLH) versus highly purified human menopausal gonadotropin (hMG) supplementation on the follicle-stimulating hormone (FSH) during controlled ovarian hyperstimulation (COH) in the GnRH-antagonist protocol. The result from that study showed that the cumulative live birth rate (CLBR) was significantly higher in the r-hLH group (53% vs. 64%, p = 0.02). In this study, we aim to do a cost analysis between these two groups based on our previous study. METHODS: The analysis consisted of 425 IVF and ICSI cycles in our previous study. There were 259 cycles in the r-hFSH + hMG group and 166 cycles in the r-hFSH + r-hLH group. The total cost related to the treatment of each patient was recorded. Probabilistic sensitivity analysis (PSA) and a cost-effectiveness acceptability curve (CEAC) were performed and created. RESULTS: The total treatment cost per patient was significantly higher in the r-hFSH + r-hLH group than in the r-hFSH + hMG group ($4550 ± 798.86 vs. $4290 ± 734.6, p = 0.003). However, the mean cost per live birth in the r-hFSH + hMG group was higher at $8052, vs. $7059 in the r-hFSH + r-hLH group. The CEAC showed that treatment with hFSH + r-hLH proved to be more cost-effective than treatment with r-hFSH + hMG. Willingness-to-pay was evident when considering a hypothetical threshold of $18,513, with the r-hFSH + r-hLH group exhibiting a 99% probability of being considered cost-effective. CONCLUSION: The cost analysis showed that recombinant LH is more cost-effective than hMG supplementation on r-hFSH during COH in the GnRH-antagonist protocol.

Dinoprostone tablet versus continuous vaginal insert (Propess®) for elective induction in low-risk nulliparous women at term.

OBJECTIVE: To evaluate the efficacy and safety of dinoprostone tablet and continuous vaginal insert (Propess®) in low-risk nulliparous women at term with insufficient cervical ripening receiving elective induction. MATERIALS AND METHODS: A retrospective study was conducted between March 2020 and February 2022 and included 230 women who underwent elective induction with dinoprostone tablet or vaginal insert. The primary endpoint was failure of induction. Secondary endpoints included time to vaginal delivery, vaginal delivery rate, as well as maternal and neonatal complications and adverse outcomes. RESULTS: No statistically significant differences were found between the two groups regarding the main outcome measures; however, the high responders had a significant higher proportion of hyperstimulation and non-reassuring fetal status. The high responder in the Propess group was statistically significant younger (31.68 ± 4.73 vs. 33.82 ± 4.39, p = 0.027), while they had a significantly lower BMI at delivery time of the tablet group (24.49 ± 2.24 vs. 27.42 ± 4.32, p = 0.024). Factors associated with success of vaginal delivery within 24 h (p = 0.015, OR = 0.9, 95%CI = 0.82-0.98) and the Cesarean section (p < 0.001, OR = 1.17, 95%CI = 1.08-1.27) was BMI at delivery time. CONCLUSION: Slow-release vaginal insert and dinoprostone tablet had similar efficacy and safety for elective induction in low risk nulliparous women at term. Women with younger maternal age or lower BMI at delivery time may have a better response to dinoprostone and had a significantly higher proportion of hyperstimulation and non-reassuring fetal status.

Modified Vaginal Mesh Procedure with DynaMesh®-PR4 for the Treatment of Anterior/Apical Vaginal Prolapse.

(1) Background: Treating female pelvic organ prolapse (POP) is challenging. Surgical meshes have been used in transvaginal surgeries since the 1990s, but complications such as mesh exposure and infection have been reported. Polyvinylidene fluoride (PVDF) mesh, known for its stability and non-reactive properties, has shown promise in urogynecological surgeries. (2) Methods: A retrospective analysis was conducted on 27 patients who underwent a modified PVDF vaginal mesh repair procedure using DynaMesh®-PR4 and combined trans-obturator and sacrospinous fixation techniques. Additional surgeries were performed as needed. (3) Results: The mean operation time was 56.7 min, and the mean blood loss was 66.7 mL. The average hospitalization period was 4.2 days with Foley catheter removal after 2 days. Patients experienced lower pain scores from the day of the operation to the following day. Postoperative follow-up revealed that 85.2% of patients achieved anatomic success, with 14.8% experiencing recurrent stage II cystocele. No recurrence of apical prolapse was observed. Complications were rare, with one case (3.7%) of asymptomatic mesh protrusion. (4) Conclusions: The modified vaginal mesh procedure using DynaMesh®-PR4 showed favorable outcomes with a short operation time, low recurrence rate, rare complications, and improved functional outcomes. This surgical option could be considered for anterior and apical pelvic organ prolapse in women.

Can HPV Test on Random Urine Replace Self-HPV Test on Vaginal Self-Samples or Clinician-Collected Cervical Samples?

Objective: This study investigated whether random urine (RU) samples can be used to accurately identify human papillomavirus (HPV) and whether these samples can replace self-collected vaginal samples in HPV tests. Methods: A total of 167 patients with abnormal Pap smears were recruited. The patients provided self-collected vaginal and RU samples for HPV testing. Clinicians obtained cervical samples from the patients. Colposcopy examination and cervical biopsy were performed. Hybrid Capture II (HC II) and Cervista tests were used to detect HPV in the RU samples. Results: The results of tests on clinician-collected cervical samples were used as the benchmark. The sensitivities of the Cervista tests on vaginal samples and the HC II and Cervista tests on RU samples were 75.00%, 49.07%, and 44.44%, respectively. After we adjusted the HPV detection cutoff value for urine samples based on values in the receiver operating characteristic curve, the sensitivities of the HC II and Cervista tests increased to 63.89% and 58.33%, respectively. In 167 patients, 59 had cervix biopsies showing CIN2 or worse (CIN2+). For CIN2+, the sensitivity was 47.5% and 50.8% in the HC II and Cervista tests on RU samples, respectively. Conclusion: HPV tests on RU samples had approximately 60% sensitivity to HPV tests on clinician-collected cervical samples after the cutoff values were adjusted. For CIN2+, the sensitivity was only approximately 50%. Further studies and improvements in urine-based HPV testing are needed to establish it as a more convenient and accessible method for detecting HPV and cervical dysplasia in patients.

Comparison of clinical outcome between day 5 and day 6 single blastocyst transfers in cycles undergoing preimplantation genetic testing for aneuploidy.

OBJECTIVE: In vitro fertilization (IVF) treatment has gradually adopted the practice of culturing embryos until the blastocyst stage on the D5 or D6 as the standard approach. PGT-A is commonly used in vitro fertilization (IVF). This study aimed to evaluate the clinical outcomes of frozen embryo transfers (FETs) using single blastocyst transfers (SBTs) on the fifth (D5) or sixth (D6) day of development in cycles that underwent preimplantation genetic testing for aneuploidy (PGT-A). MATERIALS AND METHODS: The patients who had at least one euploid or mosaic blastocyst of good quality determined by PGT-A results and received single embryo transfer (SET) cycles were included in the study. In this study, the live birth rate (LBR) and neonatal outcomes were compared after the transfer of single biopsied D5 and D6 blastocysts in frozen embryo transfer (FET) cycles. RESULTS: A total of 527 frozen-thawed blastocyst transfer (FET) cycles (8449 biopsied embryos were analyzed). No significant difference in the implantation rate (IR), clinical pregnancy rate (CPR), and live birth rate (LBR) between the transfers of D5 and D6 blastocysts. Birth weight was the only perinatal outcome that showed a significant difference between the D5 and D6 groups. CONCLUSION: The study confirmed that the transfer of a single euploid or mosaic blastocyst, regardless of whether it was on the fifth (D5) or sixth (D6) day of development, can lead to promising clinical results.

Impact of adenomyosis and endometriosis on IVF/ICSI pregnancy outcome in patients undergoing gonadotropin-releasing hormone agonist treatment and frozen embryo transfer.

Although numerous studies have attempted to establish the relationship between adenomyosis and infertility, no consensus has emerged. Our aim was to investigate whether adenomyosis and endometriosis affected IVF outcomes in our patients. This was a retrospective study of 1720 patients from January 2016 to December 2019. In total, 1389 cycles were included: 229 cycles in the endometriosis group (group E), 89 cycles in the adenomyosis group (group A), 69 cycles in the endometriosis and adenomyosis group (group EA), and 1002 cycles in the control group (group C). Most patients in groups A and EA received GnRH agonist treatment before FET. The 1st FET live birth rates (LBR) were 39.3%, 32.1%, 25% and 48.1% in groups E, A, EA, and C. The miscarriage rates were 19.9%, 34.7%, 39%, and 17.6%. The per retrieval cycle cumulative live birth rates (cLBRs) in patients < 38 y/o were 56.4%, 58.1%, 44.8%, and 63%. The per retrieval cycle cLBRs in patients ≥ 38 y/o were 25%, 9.8%, 17.2%, and 29.5%. Among groups A and EA, LBRs were 25.58% and 18.89% in patients with a ≥ sevenfold decrease and a < sevenfold decrease in CA-125 level, respectively, after GnRH agonist treatment. Endometriosis was not associated with a poorer pregnancy outcome. Patients with adenomyosis with/without endometriosis had higher miscarriage rates, lower LBRs, and lower cLBRs, especially in patients aged ≥ 38 years, even after GnRH agonist treatment before FET cycles. Patients who have a greater than sevenfold decrease in CA-125 level after GnRH agonist treatment might have better clinical pregnancy outcomes.

Presence of endometrioma decreased blastocyst formation rate but not impair Assisted Reproductive Technology (ART) outcome.

PURPOSE: This study aims to assess the impact of endometrioma on patients who undergo ART treatment due to endometriosis. METHODS: A retrospective study was conducted on women ≤ 40 years of age who underwent ART treatment at an academic medical center between January 2014 and December 2020. Two-hundred-and-eight women had received IVF/ICSI treatment due to endometriosis and there were 89 patients presence of endometrioma. Patients were further divided into primary endometrioma, recurrent endometrioma and those having received cystectomy for endometrioma prior to IVF/ICSI. The control group included 624 infertile women without endometriosis. RESULTS: In the endometrioma subgroup (B) the blastocyst formation rate was significantly lower when compared with the endometriosis (A) and control groups (C). The cumulative live birth rates (CLBRs) (60.5% versus 49.4% versus 56.9%, p = 0.194 in A versus B, p = 0.406 in A versus C, p = 0.878 in B versus C) were comparable. Multiple logistic regression analysis revealed that female age, total FSH dose and blastocyst formation rate were the significant variables in predicting CLBR (OR 0.89, CI 0.80-0.99, p < 0.025, OR 0.68 CI 0.53-0.88, p = 0.003 and OR 30.04, CI 9.93-90.9, p < 0.001, respectively). The CLBRs were comparable at 47.1%, 60% and 57.9% in the primary endometrioma, s/p cystectomy and recurrent endometrioma group. CONCLUSION: Although the blastocyst formation rate was lower in the endometrioma group, CLBR was not worse than those who were in the endometriosis or control group. Cystectomy for endometrioma did not alter IVF/ICSI outcomes if the ovarian reserve was comparable. Recurrent endometrioma did not worsen IVF/ICSI outcomes than primary endometrioma.

Improved Progression-Free Survival Associated with Tumor-Infiltrating Lymphocytes in High-Grade Endometrial Cancer.

Tumor-infiltrating lymphocytes (TILs) have emerged as a prognostic marker in endometrial cancer (EC). However, the role of TILs in EC with distinct histology grades and molecular types (such as mismatch repair [MMR] deficiency) has not yet been made clear. We retrospectively included 237 patients with primary EC who underwent a standard staging operation of laparoscopic or laparotomy total hysterectomy and bilateral salpingo-oophorectomy for analyses. An independent pathologist who was blind to the study patients' information reviewed the pathologic slides to assess TILs according to the method introduced by the International Immuno-Oncology Biomarkers Working Group in 2017. The outcomes of interest included both progression-free survival (PFS) and overall survival (OS). The Kaplan-Meier method was used to determine the curves of PFS and OS according to TILs, and also in the relevant subgroups (low-grade vs. high-grade, MMR-proficient vs. MMR-deficient). After a median follow-up duration of 1.82 years, 18 patients had experienced either disease progression or death. Overall, TILs (+) were not associated with PFS or OS. We did observe, however, that TILs (+) were associated with a better PFS (p = 0.045) in patients with high-grade EC, but not in those with low-grade tumors (p = 0.733). The effect of TILs on PFS was not observed in patients with MMR-proficient (p = 0.347) or MMR-deficient (p = 0.168) EC. TILs were associated with a better PFS in patients with high-grade EC. Our results suggest that TILs may be a potential prognostic marker in these patients.

Development of a Predictive Model for Optimization of Embryo Transfer Timing Using Blood-Based microRNA Expression Profile.

MicroRNAs (miRNAs) can regulate the expression of genes involved in the establishment of the window of implantation (WOI) in the endometrium. Recent studies indicated that cell-free miRNAs in uterine fluid and blood samples could act as alternative and non-invasive sample types for endometrial receptivity analysis. In this study, we attempt to systematically evaluate whether the expression levels of cell-free microRNAs in blood samples could be used as non-invasive biomarkers for assessing endometrial receptivity status. We profiled the miRNA expression levels of 111 blood samples using next-generation sequencing to establish a predictive model for the assessment of endometrial receptivity status. This model was validated with an independent dataset (n = 73). The overall accuracy is 95.9%. Specifically, we achieved accuracies of 95.9%, 95.9%, and 100.0% for the pre-receptive group, the receptive group, and the post-respective group, respectively. Additionally, we identified a set of differentially expressed miRNAs between different endometrial receptivity statuses using the following criteria: p-value < 0.05 and fold change greater than 1.5 or less than -1.5. In conclusion, the expression levels of cell-free miRNAs in blood samples can be utilized in a non-invasive manner to distinguish different endometrial receptivity statuses.

Corrigendum: A retrospective, matched case-control study of recombinant LH versus hMG supplementation on FSH during controlled ovarian hyperstimulation in the GnRH-antagonist protocol.

[This corrects the article DOI: 10.3389/fendo.2022.931756.].

Automatic ovarian tumors recognition system based on ensemble convolutional neural network with ultrasound imaging.

BACKGROUND: Upon the discovery of ovarian cysts, obstetricians, gynecologists, and ultrasound examiners must address the common clinical challenge of distinguishing between benign and malignant ovarian tumors. Numerous types of ovarian tumors exist, many of which exhibit similar characteristics that increase the ambiguity in clinical diagnosis. Using deep learning technology, we aimed to develop a method that rapidly and accurately assists the different diagnosis of ovarian tumors in ultrasound images. METHODS: Based on deep learning method, we used ten well-known convolutional neural network models (e.g., Alexnet, GoogleNet, and ResNet) for training of transfer learning. To ensure method stability and robustness, we repeated the random sampling of the training and validation data ten times. The mean of the ten test results was set as the final assessment data. After the training process was completed, the three models with the highest ratio of calculation accuracy to time required for classification were used for ensemble learning pertaining. Finally, the interpretation results of the ensemble classifier were used as the final results. We also applied ensemble gradient-weighted class activation mapping (Grad-CAM) technology to visualize the decision-making results of the models. RESULTS: The highest mean accuracy, mean sensitivity, and mean specificity of ten single CNN models were 90.51 ± 4.36%, 89.77 ± 4.16%, and 92.00 ± 5.95%, respectively. The mean accuracy, mean sensitivity, and mean specificity of the ensemble classifier method were 92.15 ± 2.84%, 91.37 ± 3.60%, and 92.92 ± 4.00%, respectively. The performance of the ensemble classifier is better than that of a single classifier in three evaluation metrics. Moreover, the standard deviation is also better which means the ensemble classifier is more stable and robust. CONCLUSION: From the comprehensive perspective of data quantity, data diversity, robustness of validation strategy, and overall accuracy, the proposed method outperformed the methods used in previous studies. In future studies, we will continue to increase the number of authenticated images and apply our proposed method in clinical settings to increase its robustness and reliability.

A retrospective, matched case-control study of recombinant LH versus hMG supplementation on FSH during controlled ovarian hyperstimulation in the GnRH-antagonist protocol.

Background: The role of luteinizing hormone (LH) in controlled ovarian hyperstimulation (COH) requires more evidence for its efficacy. Several studies compared recombinant human LH (r-hLH) or human menopausal gonadotropin (hMG) in combination with recombinant human follicle-stimulating hormone (r-hFSH) but lack the results with GnRH-antagonist protocol and in Asians. Methods: This is a retrospective, single-center study inspecting women receiving GnRH antagonist protocol and r-hFSH+hMG or r-hFSH+r-hLH regimen for over five days for COH in the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle in Taiwan from 2013 to 2018. The outcomes of IVF/ICSI cycles were analyzed after propensity score matching between the two groups. A subgroup analysis was conducted in cycles in which women underwent their first embryo transfer (ET), including fresh ET and frozen ET (FET). Results: With a total of 503 cycles, the results revealed that the r-hFSH+r-hLH group performed better in terms of numbers of oocytes retrieved (r-hFSH+hMG vs. r-hFSH+r-hLH, 11.7 vs. 13.7, p=0.014), mature oocytes (8.7 vs. 10.9, p=0.001), and fertilized oocytes (8.3 vs. 9.8, p=0.022), while other outcomes were comparable. The analysis of first ET cycles also showed similar trends. Although the implantation rate (39% vs. 43%, p=0.37), pregnancy rate (52% vs. 53%, p=0.90), and live birth rate (39% vs. 45%, p=0.19) were not significantly different, the miscarriage rate was higher in the r-hFSH+hMG group than the r-hFSH+r-hLH group (26% vs. 15%, p<0.05) in first ET cycles. The cumulative pregnancy rate was significantly higher in the r-hFSH+r-hLH group (53% vs. 64%, p=0.02). No significant difference in rates of ovarian hyperstimulation syndrome (OHSS) was observed. Conclusion: The results support the hypothesis that the treatment of r-hLH+r-hFSH improves COH clinical outcomes in the IVF/ICSI cycle.

Changes in Cystoscopic Findings after Intravesical Hyaluronic Acid Instillation Therapy in Patients with Interstitial Cystitis.

(1) Background: Limited data showed changes in glomerulation in the bladder mucosa of patients with interstitial cystitis (IC) after intravesical hyaluronic acid (HA) bladder infusion. We aimed to investigate the above changes. (2) Methods: Medical records of IC patients were reviewed retrospectively, from January 2010 to October 2019. Patients who had received repeated cystoscopy after intravesical HA treatment were enrolled. The associations of multiple parameters, including the ages, symptoms, initial glomerulation stage, HA doses, and the interval period of repeated cystoscopy between the glomerulation change in the repeated cystoscopy were analyzed. (3) Results: Among the 35 patients, 9 cases (25.7%) showed better glomerulation grades in the repeated cystoscope (Group 1), 20 cases (57.1%) showed the same grades (Group 2), and 6 cases showed worse grades (Group 3). No difference was seen in the initial grades or treatment course among the three groups. The interval periods from the initial to the repeated cystoscopy of Group 1 were longer than Group 2 and Group 3 (p = 0.031). Group 3 presents an elder age trend than the other two groups. (4) Conclusion: Intravesical HA repaired bladder glomerulation in a small group of patients with IC. Prolonged treatment has potential benefits, while older age is possibly a negative factor. However, no strong correlation was found between the initial glomerulation grades or changes in glomerulation grades with clinical symptoms.

Case Report: Myomatous erythrocytosis syndrome presenting as rapid growth of an extra-uterine mass.

Objective: To report a case of myomatous erythrocytosis syndrome (MES) with an extra-uterine manifestation. Case report: A 43-year-old woman presented with progressive abdominal distension and rapid enlargement of a pelvic mass. Upon survey, a high-level of hemoglobin (19.0 g/dl) was documented. The initial impression was an ovarian malignancy, but uterine sarcoma could not be ruled out because of its rapid growth. However, during exploratory laparotomy, the pelvic mass was found to be a 31 cm broad ligament leiomyoma; which is extremely rare for its size and location. The specimen was further studied immunohistochemically, which revealed excessive expressions of erythropoietin and erythropoietin receptors in addition to the diffusely matured blood vessels in the myoma tissue. The patient's hemoglobin level resumed to normal three months post-surgery. The diagnosis of MES was confirmed both clinically and histologically. Conclusion: A correct preoperative diagnosis is challenging when MES manifests as an extrauterine mass. The coexistence of MES should be considered in the management of all leiomyoma with polycythemia, regardless of locations.

Real-World Efficacy of Bevacizumab in Patients With Recurrent Epithelial Ovarian Cancer.

Background: Bevacizumab in combination with chemotherapy prolonged the progression-free survival (PFS) of patients with recurrent epithelial ovarian cancer (EOC) in large-scale randomized controlled trials. However, real-world data for the use of bevacizumab in Asian patients with EOC is lacking. This study investigated the efficacy of adding bevacizumab to chemotherapy and compared it with that of chemotherapy alone in patients with recurrent EOC using real-world data from an Asian population. Method: We conducted a retrospective cohort study using data from a tertiary medical center in central Taiwan. Patients who had EOC with first relapse between 2011 and 2019 were enrolled. Patients' medical histories, medication treatment, and relevant information were collected. The outcomes were PFS and overall survival (OS). The Kaplan-Meier plot was used to generate a survival curve for OS and PFS. Cox proportional hazard analysis was used to determine the associations of Bevacizumab treatment with OS and PFS with adjustment of relevant variables. Subgroup analyses were conducted to determine if there was a significant variation in the aforementioned associations. Results: After a median follow-up of 23 months, 67% of patients in the Bevacizumab group and 81% of patients in the non-Bevacizumab group had disease progression or death. There was no significant between-group difference in OS (p = 0.475). The median duration of PFS was 18.9 and 9.6 months, respectively, favoring those who were treated with Bevacizumab. After multivariate adjustment, treatment with Bevacizumab was associated with a lower risk of disease progression (hazard ratio 0.33, 95% CI 0.13-0.85, p = 0.021). The improvement in PFS was consistent in the subgroups of different histological types, different disease stages at diagnosis, different treatment-free intervals, those undergoing or not undergoing secondary cytoreductive surgery, diverse chemotherapy regimens. Conclusion: Our findings provided crucial insights into the efficacy of bevacizumab for the treatment of recurrent EOC in the real-world setting.

Contamination of ART culture Media-The role of semen and strategies for prevention.

OBJECTIVE: Microbial contamination of ART culture media is rare but serious. We examined our own experience and conducted a review of the literature with a view to preventing its occurrence and recurrence. CASE REPORT: A total of 12 cases were recorded during January 2006 to March 2019. The contaminations were caused by semen and were shown to be bacteria that were resistant to the prophylactic antibiotics used in the medium. After the procedures were cancelled due to contaminations, nine husbands received antibiotic treatment, while nine couples changed over to the ICSI program. Eventually, eight couples concluded the study with live birth deliveries, and there was no recurrence of contamination. CONCLUSION: ART laboratories should preserve all sperm suspension samples until embryo transfer has been completed for the purpose of checking whether contamination has occurred. In addition to antibiotic treatment, implementation of the ICSI procedure during the next ART cycle has already been proven to be effective. In the future, the zona-removal technique may be considered as another potential option.

Integration of genome-wide association study and expression quantitative trait locus mapping for identification of endometriosis-associated genes.

To determine whether genetic predisposition to endometriosis varies depending on ethnicity and in association with expression quantitative trait loci (eQTL) in a Taiwanese population. We conducted a genome-wide association study (GWAS) and replicated it in 259 individuals with laparoscopy-confirmed stage III or IV endometriosis (cases) and 171 women without endometriosis (controls). Their genomic DNA was extracted from blood and evaluated by the GWAS of Taiwan Biobank Array. Novel genetic variants that predispose individuals to endometriosis were identified using GWAS and replication, including rs10739199 (P = 6.75 × 10-5) and rs2025392 (P = 8.01 × 10-5) at chromosome 9, rs1998998 (P = 6.5 × 10-6) at chromosome 14, and rs6576560 (P = 9.7 × 10-6) at chromosome 15. After imputation, strong signals were exhibited by rs10822312 (P = 1.80 × 10-7) at chromosome 10, rs58991632 (P = 1.92 × 10-6) and rs2273422 (P = 2.42 × 10-6) at chromosome 20, and rs12566078 (P = 2.5 × 10-6) at chromosome 1. We used the Genotype-Tissue Expression (GTEx) database to observe eQTL. Among these SNPs, the cis-eQTL rs13126673 of inturned planar cell polarity protein (INTU) showed significant association with INTU expression (P = 5.1 × 10-33). Moreover, the eQTL analysis was performed on endometriotic tissues from women with endometriosis. The expression of INTU in 78 endometriotic tissue of women with endometriosis is associated with rs13126673 genotype (P = 0.034). To our knowledge, this is the first GWAS to link endometriosis and eQTL in a Taiwanese population.

Cost-effectiveness of freeze-all policy - A retrospective study based upon the outcome of cumulative live births.

OBJECT: We have previously reported that cumulative live birth rates (CLBRs) are higher in the freeze-all group compared with controls (64.3% vs. 45.8%, p = 0.001). Here, we aim to determine if the freeze-all policy is more cost-effective than fresh embryo transfer followed by frozen-thawed embryo transfer (FET). MATERIALS AND METHODS: The analysis consisted of 704 ART (Assisted reproductive technology) cycles, which included in IVF (In vitro fertilisation) and ICSI (Intra Cytoplasmic Sperm Injection) cycles performed in Taichung Veterans General Hospital, Taiwan between January 2012 and June 2014. The freeze-all group involved 84 patients and the fresh Group 625 patients. Patients were followed up until all embryos obtained from a single controlled ovarian hyper-stimulation cycle were used up, or a live birth had been achieved. The total cost related to treatment of each patient was recorded. The incremental cost-effectiveness ratio (ICER) was based on the incremental cost per couple and the incremental live birth rate of the freeze-all strategy compared with the fresh ET strategy. Probabilistic sensitivity analysis (PSA) and a cost-effectiveness acceptability curve (CEAC) were performed. RESULTS: The total treatment cost per patient was significantly higher for the freeze-all group than in the fresh group (USD 3419.93 ± 638.13 vs. $2920.59 ± 711.08 p < 0.001). However, the total treatment cost per live birth in the freeze-all group was US $5319.89, vs. US $6382.42 in the fresh group. CEAC show that the freeze-all policy was a cost-effective treatment at a threshold of US $2703.57 for one additional live birth. Considering the Willingness-to-pay threshold per live birth, the probability was 60.1% at the threshold of US $2896.5, with the freeze-all group being more cost-effective than the fresh-ET group; or 90.1% at the threshold of $4183.8. CONCLUSION: The freeze-all policy is a cost-effective treatment, as long as the additional cost of US $2703.57 per additional live birth is financially acceptable for the subjects.