Poor Responders Research Articles

GnRH agonist-only trigger, compared to dual trigger, reduces oocyte retrieval rate in high responders without affecting cumulative live birth rate.

This study compared, in high responders undergoing IVF treatment, GnRH agonist-only trigger and dual trigger on oocyte retrieval rate and cumulative live birth rate (LBR). The aim was to determine if the GnRH agonist-only triggers had provided outcomes comparable to dual trigger, while minimizing the risk of ovarian hyperstimulation syndrome (OHSS). A retrospective, matched case-control study was conducted at Taichung Veterans General Hospital, Taiwan, including women who underwent IVF/ICSI between January 1, 2014, and December 31, 2022. Inclusion criteria were: GnRH antagonist protocol and estrogen level >3,000 pg/ml on trigger day. Exclusion criteria were: immune/metabolic diseases, donated oocytes, and mixed stimulation cycles. Propensity score matching was applied to balance age, AMH level, and oocyte number between the GnRH agonist-only and dual trigger groups. Outcomes were analyzed for patients who had complete treatment cycles, focusing on oocyte retrieval rate and cumulative LBR. We analyzed 116 cycles in the agonist-only group, and 232 cycles in the dual trigger group. No inter-group difference was found in their age, BMI, and AMH levels. The dual trigger group had a higher oocyte retrieval rate (93% vs. 80%; p <0.05), while fertilization rates, blastocyst formation rates, and cumulative LBR were comparable. Notably, no OHSS cases had been reported in the GnRH agonist-only group, compared with 7 cases in the dual trigger group. GnRH agonist-only triggers resulted in a lower oocyte retrieval rate compared to dual triggers but did not significantly affect cumulative LBR in high responders. This approach effectively reduces OHSS risk without compromising pregnancy outcomes, making it a preferable option in freeze-all strategies, despite a longer oocyte pick-up duration and a medium cost. GnRH agonist-only trigger, however, may not be suitable for fresh embryo transfers or patients with low serum LH levels on trigger day.

A new decision-support tool in a multi-center randomized trial for personalized, optimized, and simplified fertility treatment in non-PCOS patients.

This study aimed to evaluate the effectiveness of a clinical decision support tool, Opt-IVF, in achieving the following outcomes: reducing the total cumulative dosage of Gonadotropins (Gns) used during controlled ovarian stimulation cycles and reducing the repeated ultrasonograms (USG) for monitoring follicular growth without compromising the number of good quality blastocysts obtained. The study design employed a multi-center randomized trial. The study enrolled 115 women aged 25-45 years undergoing IVF. Among the participants, 55 were randomly assigned to the intervention group (Opt-IVF), and 60 were randomly assigned to the control group. The intervention involved using a clinical decision support tool, Opt-IVF, to guide Gn dosing and trigger dates. The participants in the intervention group required significantly lower cumulative Gn dosage. The intervention group had higher numbers of oocytes retrieved and M2 retrieved than the control group. The number of good-quality blastocysts, the good-quality blastocyst rate, the ovarian sensitivity index (OSI), and the pregnancy rate in the intervention group were significantly higher than in the control group. The utilization of the clinical decision support tool led to several positive outcomes, including eliminating the need for ultrasound exams after day 5, reducing the dosage of Gn required, and yielding significantly higher numbers of high-quality blastocysts and higher pregnancy rates. Thus, Opt-IVF can successfully provide a personalized, optimized, and simplified approach to superovulation. Opt-IVF consistently outperformed the clinical teams in most of the outcomes. Clinical trials registration: ClinicalTrials.gov (ID - NCT05811065). Date of Registration: 15 March 2023. Date of enrollment of the first subject: 20 March 2023. The high cost of IVF is a result of costly drugs, fixed prices for infrastructure, extensive testing required, and labor costs for physicians and other healthcare personnel. Superovulation, which involves the drug-induced release of multiple eggs needed for IVF, accounts for a significant share of these costs. Current approaches to superovulation involve almost daily monitoring of follicle development using ultrasound and/or blood tests. The daily dosage of stimulatory hormones is then prescribed by physicians based on empirical data and clinical experience. However, the dose is not optimized for each patient, and overstimulation complications can occur. The cost of testing and drugs makes this stage very expensive. To overcome the shortcomings of this system, we have developed a decision support tool (Opt-IVF) that can provide a personalized model-optimized dosage profile for each patient. The clinical results show that Opt-IVF optimizes and personalizes dosage, reduces testing, and provides better outcomes for patients.

Economic evaluation of GnRH-agonist long protocol and GnRH-antagonist protocol in IVT/ICSI among the Chinese population: using pharmacoeconomic models

ObjectiveThis paper uses health economics methods to discuss the cost-effectiveness value of long protocol and antagonist protocol for in vitro fertilisation and embryo transfer (ET) in the Chinese population.DesignHealth economic...

Impact of Hysteroscopic Polypectomy on IVF Outcomes in Women with Unexplained Infertility.

Objective: To assess the effect of hysteroscopic polypectomy on the in vitro fertilization (IVF) results in infertile women with at least one prior negative IVF outcome. Methods: This retrospective cohort study included women who had attended the "2nd Department of Obstetrics and Gynecology of the National and Kapodistrian University of Athens" and "Iaso" Maternity Hospital from October 2019 to January 2023 for infertility treatment. The medical records of 345 women aged 18-45 years old without abnormal findings in hysterosalpingography (HSG) and with at least one previous failed IVF procedure were analyzed. The male factor was excluded, as well as a prior hysteroscopic removal of polyps. In 67 women, polyps were suspected during initial two-dimensional ultrasound (2D-US) examination. The final sample of the study comprised 40 patients, in which endometrial polyps were removed by hysteroscopy with the use of resectoscope. All patients underwent ovarian stimulation and IVF in the consecutive cycle using a short GnRh antagonist protocol. Main Results: After hysteroscopic polypectomy, 29 (72.5%) out of 40 patients had a positive pregnancy result: 26 (65%) clinical and 3 (7.5%) biochemical pregnancies were documented. There was a statistically significant difference between the number of clinical pregnancies before and after polypectomy (p < 0.001), as well as between the total number of pregnancies (p < 0.001). Secondary Results: Women with positive outcome were significantly younger and had significantly lower FSH levels (p < 0.007). They also had significantly higher AMH (p < 0.009) and peak estradiol levels (p < 0.013) and yielded more M II oocytes (p < 0.009) and embryos (p < 0.002). Conclusions: Hysteroscopic polypectomy in women with a suspected endometrial polyp using 2D ultrasound and a history of prior failed IVF attempt improves IVF outcomes in terms of the clinical and total number of pregnancies.

Evaluation of ovarian reserve and the assisted reproductive technology (ART) cycles’ outcome as well as the relapse rate within one year after ART in women with multiple sclerosis: a case-control study

ObjectiveTo compare the ovarian reserve and the results of infertility treatment, as well as to investigate the relapse rate in the first year after the assisted reproductive technology (ART) cycle in patients with multiple sclerosis (MS) referred to Royan Institute.Materials and methodsThis retrospective study was carried out to evaluate all women diagnosed with MS and referred to Royan Institute for assessment and treatment of possible infertility between 2011 and 2022. The control group consisted of randomly selected healthy women with tubal factor infertility who were referred for treatment during the same time period and matched in terms of age. A comparison was made between groups in terms of ovarian reserve and infertility treatment outcomes. Additionally, patients with MS who met the criteria were monitored via telephone to evaluate the symptoms, disability and relapse rate both pre- and post-ART.ResultsOver the course of a decade, the database documented a total of 60 cases diagnosed with MS. Upon examination of the records, it was found that in 27 patients only admission was done without any hormonal assessment or infertility treatment cycle and 5 patients proceeded with the intrauterine insemination cycle. Eventually, 28 women with MS underwent the ART cycle and all of them were treated with interferon beta, glatiramer acetate, or some oral disease modifying therapies. No statistically significant difference in terms of the basal levels of luteinizing hormone, follicle-stimulating hormone and anti-Müllerian hormone was found between the MS and control groups (P > 0.05). Two groups were comparable in terms of menstrual status. The study revealed that both groups exhibited similarities in terms of the controlled ovarian stimulation protocol and duration, the dosage of gonadotropin administered, as well as the ovarian response type, clinical pregnancy rate, and live birth rate (P > 0.05). After follow up, only 2 patients (9.5%) reported relapse of symptoms within one year after ART.ConclusionThe ovarian reserve and ovarian stimulation cycle and pregnancy outcomes following the ART cycle in MS patients were similar to the age-matched control group. The relapse rate of multiple sclerosis did not show a significant increase within a year following the ART cycle.

Use of tamoxifene-controlled ovarian hyperstimulation for fertility preservation before breast cancer treatment: A prospective cohort study with a 5-year follow-up

PurposeFertility issues are of great concern for young women undergoing treatment for breast cancer (BC). Fertility preservation (FP) protocols using controlled ovarian stimulation (COS) with letrozole have been widely used with overall good results. However, letrozole cannot be used in every country in this context. This study aimed to assess the efficacy of tamoxifen for COS in women with early BC undergoing FP. MethodsThis multicentric prospective study included patients aged 18–40, diagnosed with stage I, II and III invasive BC, undergoing tamoxifen-COS before adjuvant or neoadjuvant chemotherapy (NAC). The primary endpoint was the efficacy of tamoxifen-COS protocol evaluated by the number of oocytes collected and vitrified. Secondary endpoints included the time interval before chemotherapy, breast cancer (BC) recurrence rates, and reproductive outcomes. ResultsNinety-five patients were included between 2014 and 2017, aged 31.5 ± 4 years on average. 37.9 % received NAC and 62.1 % received adjuvant chemotherapy. FP procedure was successful in 89.5 % of the cycles. The mean number of collected and vitrified oocytes was 12.8 ± 7.9 and 9.8 ± 6.2, respectively. The mean duration of COS was 10.4 ± 1.9 days. Median time before chemotherapy initiation was 3.6 weeks (IQR 3.1; 4.1) for women receiving NAC. Five-year relapse-free and overall survival rates were in-line with those expected in this population. Twenty-one women had spontaneous full-term pregnancies, while 5 underwent IVF cycles with frozen-thawed oocytes, without pregnancy. ConclusionTamoxifen-COS protocols appear to be feasible before adjuvant or NAC treatment in young BC patients and efficient in terms of oocyte yield.

Intratumoral Heterogeneity Assessment of the Extracellular Bone Matrix and Immune Microenvironment in Osteosarcoma Using Digital Imaging to Predict Therapeutic Response

The assessment of chemotherapy response in osteosarcoma (OS) based on the average percentage of viable cells is limited, as it overlooks the spatial heterogeneity of tumor cell response (foci of resistant cells), immune microenvironment, and bone microarchitecture. Despite the resulting positive classification for response to chemotherapy, some patients experience early metastatic recurrence, demonstrating that our conventional tools for evaluating treatment response are insufficient. We studied the interactions between tumor cells, immune cells (lymphocytes, histiocytes, and osteoclasts), and bone extracellular matrix (ECM) in 18 surgical resection samples of OS using multiplex and conventional immunohistochemistry (IHC: CD8, CD163, CD68, and SATB2), combined with multiscale characterization approaches in territories of good and poor response (GRT/PRT) to treatment. GRT and PRT were defined as subregions with <10% and ≥10% of viable tumor cells, respectively. Local correlations between bone ECM porosity and density of immune cells were assessed in these territories. Immune cell density was then correlated to overall patient survival. Two patterns were identified for histiocytes and osteoclasts. In poor responder patients, CD68 osteoclast density exceeded that of CD163 histiocytes but was not related to bone ECM load. Conversely, in good responder patients, CD163 histiocytes were more numerous than CD68 osteoclasts. For both of them, a significant negative local correlation with bone ECM porosity was found (P < .01). Moreover, in PRT, multinucleated osteoclasts were rounded and intermingled with tumor cells, whereas in GRT, they were elongated and found in close contact with bone trabeculae. CD8 levels were always low in metastatic patients, and those initially considered good responders rapidly died from their disease. The specific recruitment of histiocytes and osteoclasts within the bone ECM, and the level of CD8 represent new features of OS response to treatment. The associated prognostic signatures should be integrated into the therapeutic stratification algorithm of patients after surgery.

AB052. A multicenter prospective exploratory phase II study of neoadjuvant bevacizumab for newly diagnosed malignant glioma.

We conducted a multicenter study for neoadjuvant bevacizumab (neoBev) for newly diagnosed glioblastoma (nGB). In this study, median overall survival (mOS) related to radiological response, of which reliability as a prediction of overall survival (OS) was explored. A total of 15 patients with nGB were enrolled, and given ring enhancement and perifocal edema on magnetic resonance imaging (MRI). Two weeks after neoBev, the tumor volumes on T1 weighted image with contrast medium (T1CE) and fluid attenuated inversion recovery (FLAIR) were assessed. Three to four weeks after neoBev, surgery was performed. Clinical outcomes including mOS as well as the safety of neoBev were evaluated. Severe adverse events were observed in two of 15 patients as one postoperative hematoma and one wound infection. The average volume decrease rates on T1CE and FLAIR were -37% and -54%, respectively. The decrease rate on T1CE was not correlated with that on FLAIR. Based on MRI, good (GR) and poor responders (PR) on T1CE were defined as more or less of the average volume reduction rate, respectively. In addition, there was a case with discordance in tumor volume changes between T1CE and FLAIR. And OS in a discordant case was 20.4 months, which was not unfavorable. mOS of GR and PR on T1CE were 19.8 and 12.9 months, respectively. In contrast, mOS of GR and PR on FLAIR were 16.0 and 17.0 months, respectively. Preoperative neoBev was confirmed a safe procedure. mOS in the present cohort was not significantly prolonged. Early tumor volume regression on T1CE but not FLAIR after neoBev therapy has a significant prognostic indicator for mOS in nGB.

Spironolactone use and oocyte maturation in patients undergoing controlled ovarian hyperstimulation.

To evaluate the association between spironolactone use and controlled ovarian hyperstimulation (COH) outcomes. Retrospective study, including patients who underwent COH. Oocyte yield and maturation rates were compared by categories of spironolactone use at the start of their cycle. 402 patients were included. 83 patients continued spironolactone, 44 patients discontinued spironolactone, and 275 matched control patients were spironolactone-naïve. No difference was observed in the number of oocytes retrieved (17 ± 14 vs. 15 ± 13, p = 0.4) or mature oocytes vitrified (15 ± 9.5 vs. 12 ± 11, p = 0.4) in patients who continued spironolactone use and spironolactone naïve patients, respectively. When comparing patients who continued spironolactone use and patients who discontinued spironolactone use, no difference was seen in the number of oocytes retrieved (17 ± 14 vs. 17.5 ± 7.8, p = 0.9) or mature oocytes vitrified (15 ± 9.5 vs. 13.5 ± 6.5, p = 0.5), respectively. There was no observed relationship between total daily spironolactone dose (< 100mg/day, 100mg/day, 150mg/day and > 200 mg/day) and the total number of mature oocytes vitrified (respectively, 14.0 ± 13.0, 16.0 ± 7.8, 14.0 ± 4.5, 11.0 ± 7.0 oocytes, p = 0.4). This is the first study to evaluate the association between spironolactone and oocyte yield and maturation rates during COH cycles. These findings can assist in counseling patients on the implications of continuing spironolactone during COH cycle.

Effect of Interval Between Neoadjuvant Chemotherapy and Surgery on Oncological Outcomes in Poor Responders With Locally Advanced Breast Cancer.

The interval between neoadjuvant chemotherapy (NAC) and surgery for locally advanced breast cancer (LABC) remains controversial. At the same time, the prognostic effect of delayed surgery in patients with poor responses is currently unclear. Data was collected from patients who had poor responses to NAC and underwent modified radical surgery from January 2013 to December 2018. The interval from completion of NAC to surgery was divided into two groups: a longer (greater than four weeks) or shorter (four weeks or less) interval. The associations of these interval groups with overall survival (OS) and recurrence-free survival (RFS) were evaluated by multivariable Cox models adjusting for the existing prognostic factors. Propensity score matching (PSM) was used to minimize election bias. A total of 1,229 patients (mean age, 47.2 ± 8.9 years; median follow-up duration, 32.67 [6.57-52.63] months) were included. The 5-year OS rates were 73.2% and 60.8% in the shorter (n = 171) and longer interval group (n = 1,058), respectively, while the 3-year RFS rates were 80.8% and 71.7%, respectively. In multivariate Cox analysis, the longer interval was associated with an increased risk of mortality (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.01-2.02; p = 0.046) and recurrence (HR, 1.50; 95% CI, 1.12-1.99; p = 0.006). There was an interaction between the molecular subtype and the surgery interval for OS (pinteraction = 0.014) and RFS (pinteraction = 0.027). After PSM, no significant difference in OS (p = 0.180) and RFS (p = 0.069) was observed between the two groups. Among LABC patients with a poor response, those with a longer interval between NAC and surgery had worse OS and RFS. The results indicate that these patients should receive modified radical surgery timely, which may in turn improve their prognosis.

Initiation and outcomes of women pursuing planned fertility preservation

To study cycle outcomes of women who choose to pursue oocyte cryopreservation, using published age-specific oocyte recommendations. Retrospective cohort. Clinic. A total of 5,915 patients seeking planned oocyte cryopreservation, 3,504 ultimately underwent ovarian stimulation with oocyte retrieval and cryopreservation, 425 of this cohort subsequently thawed with intent to use embryo transfer. Planned oocyte cryopreservation. Planned oocyte cryopreservation consultation, fertility preservation cycle(s) and ovarian stimulation outcomes. A total of 5,915 women were seen in the initial consultation for planned fertility preservation (2012-2022). Ethnicity and the highest level of education were significant in predicting who would move forward with oocyte stimulation for fertility preservation. Women who reported working within the law and public policy and in the fields of health and medicine were statistically more likely to proceed with a cycle than those who listed other occupations. Of 3,504 women in the study cohort who underwent ovarian stimulation and egg retrieval, 1,331 (38.0%) achieved the age-based recommended number of oocytes to freeze. Only 57 (4.3%) of these women who met their age-based oocyte goal did so after their initial cryopreservation cycle. There was a significant association between ethnicity and number of cryopreservation cycles, specifically showing that Black or African American women were less likely to complete two or more cycles. Patients whose education background included graduate or professional degrees were more likely to have completed more than one cycle. Self-identified ethnicity was significantly associated with the odds of moving forward with oocyte stimulation for fertility preservation and egg retrieval after initial consultation with ethnic minorities significantly less likely to continue treatment. Of those who undergo egg freezing, most women pursue more than one stimulation and cryopreservation cycle, yet the majority never meet their recommended number to freeze.

Preimplantation genetic testing for aneuploidy is associated with reduced live birth rates in fresh but not frozen donor oocyte in vitro fertilization cycles: an analysis of 18,562 donor cycles reported to Society for Assisted Reproductive Technology Clinic Outcome Reporting System

ObjectiveTo evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on first transfer live birth rate (LBR) and cumulative LBR (CLBR) in donor oocyte IVF cycles. DesignRetrospective cohort study of the SART CORS database. Subjects11,348 fresh and 7,214 frozen-thawed donor oocyte IVF cycles were analyzed. ExposureThe first reported donor stimulation cycle per patient between January 1, 2014 and December 31, 2015, and all linked embryo transfer cycles between January 1, 2014 and December 31, 2016, were included in the study. Main Outcome MeasuresLBR was compared for patients using fresh and frozen-thawed donor oocytes, with or without PGT-A. Logistic regression models were adjusted for age, body mass index, gravidity, infertility etiology, and prior IVF cycles. ResultsAmong patients who had blastocysts available for transfer or PGT-A, use of PGT-A was associated with a decreased first transfer LBR (46.9 vs 53.2%, p <0.001) and CLBR (58.4 vs 66.6%, p <0.001) in fresh oocyte donor cycles compared with no PGT-A. LBR in frozen-thawed oocyte donor cycles with PGT-A were nominally higher than those without PGTA (48.3% vs. 40.5%) but were not statistically significant in multivariable logistic regression models (p=0.14). Early pregnancy loss was not significantly different with and without PGT-A. Multiple gestation, preterm birth, and low birthweight infants were all reduced with addition of PGT-A in fresh donor oocyte cycles, though these outcomes were not significantly different when comparing single embryo transfers in fresh oocyte cycles and also not significantly different among frozen-thawed donor oocyte cycles. ConclusionPGT-A in fresh oocyte donor cycles was associated with decreased LBR and CLBR, while effects on frozen-thawed oocyte donor cycles were clinically negligible. Obstetrical benefits associated with PGT-A in fresh donor cycles appear linked to increased single embryo transfer.

Drug-free in vitro activation and autologous transplantation in infertile women with diminished ovarian reserve: An experimental pilot study.

Poor ovarian response and diminished ovarian reserves (DOR) significantly contribute to female infertility. Previous attempts have been made to enhance follicular growth and improve pregnancy outcomes in these participants. This study aimed to assess the efficacy of the in vitro drug-free activation technique of the ovarian reservation and in vitro fertilization stimulation cycle outcomes in DOR participants. This pilot phase study investigated the impact of in vitro activation (IVA) on ovarian reservation and in vitro fertilization outcome in 10 infertile women with DOR from May to December 2023 at Taleghani Infertility Center, Tehran, Iran. Participants underwent general surgery and laparoscopy, involving the removal of a portion of one ovary, immediate transfer to the laboratory, dissection into small cubes, and subsequent re-implantation into the cases's ovary. The primary outcomes, include the count of retrieved oocytes, the number of oocytes reaching metaphase, and the secondary outcomes were the quantity and the number of embryos transferred, implantation rate, and occurrence of clinical pregnancy. The study revealed a significant increase in the antral follicle count before and after IVA (p = 0.033). Before IVA, the median estradiol level was 93.5 (57.0), which reduced to 79.0 (35.0) after IVA, indicating a statistically significant difference. On average, 2.3 (0.8) oocytes were retrieved, among which 1.5 (0.7) were metaphase II oocytes. The observed pregnancy rate among the 2 cases was 22.2%. The current study suggests that IVA may positively impact follicular growth and pregnancy outcomes among women with DOR.

Impact of Luteinizing Hormone on IVF/ICSI Assisted Reproduction on the Initiation Day of Gonadotropin-releasing Hormone Antagonist Protocol.

The aim of the study was to explore the optimal timing of gonadotropin initiation and the reasonable interval of luteinizing hormone (LH) levels in the gonadotropin-releasing hormone antagonist (GnRH-A) protocol. A retrospective cohort study was conducted to analyze the data concerning the oocyte retrieval cycles from 1,361 cases with the GnRH-A protocol implemented. The ovarian responses (including AMH, AFC) in these patients were divided into the poor ovarian response group (an antral follicle count [AFC] ≤ 6, n = 394), the normal ovarian response group (an AFC > 6 and < 15, n = 570), and the high ovarian response group (an AFC ≥ 15, n = 397), according to the AFC. The patients were sub-grouped according to LH levels on the protocol initiation day, and the clinical outcomes (including dose of Gn initiation, Gn administration days, GnRH-ant administration days, P levels on the HCG day, E2 levels on the HCG day, LH levels on the HCG day, number of embryos transferred, total fertilization rate, embryo implantation rate(%), proportion of 2PN, proportion of good-quality embryos, endometrial thickness on the hCG injection day(mm), moderate to severe OHSS, AFC on the initiation day, proportion of type A endometrium on the hCG injection day, clinical pregnancy rate, biochemical pregnancy rate, early abortion rate, ectopic pregnancy rate) were compared. On the GnRH-A protocol initiation day, among all patients with different ovarian responses, the body mass index (BMI) in those with an LH ≥ 5 IU/L was lower. The differences in pregnancy outcomes between the LH < 5 IU/L group and the LH ≥ 5 IU/L group were not statistically significant across the different ovarian response groups, but the LH < 5 IU/L group had a higher proportion of good-quality embryos (80.3±24.9 vs. 74.8±26.9, P =0.035) than the LH≥5IU/Lgroup in those with poor ovarian response. The total fertilization rate (82.2±18.1 vs 85.4±15.1, P =0.021) and proportion of two pronuclei (2PN) (69.0±20.9 vs 72.7±19.9, P =0.035) were higher in the LH ≥ 5 IU/L group than the LH<5 IU/L group for those with normal ovarian responses. The embryo implantation rate (41.4±41.3 vs 52.6±43.4, P =0.012) was higher in the LH ≥ 5 IU/L group than in the LH<5 IU/L group in those with high ovarian response. The results of the multivariate logistic analysis showed that the age of the female partner, number of embryos transferred, proportion of good-quality embryos, endometrial thickness on the hCG injection day, and moderate- to-severe ovarian hyperstimulation syndrome (OHSS) were independent factors correlated with the outcome of live births (P < 0.05). The LH levels on the gonadotropins (Gn) initiation day in the GnRH-A protocol will not affect pregnancy outcomes.

Utility of interim apparent diffusion coefficient value in predicting treatment response among patients with locally advanced cervical cancer treated with radiotherapy

BackgroundFor locally advanced cervical cancer (LACC), treatment response to radiotherapy (RT) can vary significantly even among those with the same stage classification of International Federation of Gynecology and Obstetrics (FIGO). This study investigated the value of ADC metric for forecasting end-of-treatment outcomes in LACC patients referred for RT. MethodsEighty patients with pathologically confirmed cervical squamous cell carcinoma with (SCC) were included in the research. Abdominal or pelvic MRI scans were conducted at least three times for all participants: before RT, three weeks after beginning of RT and approximately two months after RT was finalized. Calculated apparent diffusion coefficient (ADC) values of the LACC include: pre-ADC, interim-ADC, ΔADC and Δ%ADC. Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1,subjects were calculated and subsequently categorized into good responders group (complete response) and poor responders group (progressive disease, stable disease or partial response). ResultsCompared to good-responders, subjects of poor-responder group showed significantly lower values of interim-ADC, ΔADC, and Δ%ADC (all P < 0.05). To distinguish between good and poor responders, the optimal cutoff values of interim-ADC, ΔADC, and Δ%ADC were determined to be 1.067 × 10−3 mm2/sec, 0.209 × 10−3 mm2/sec, and 30.74 % using the ROC curve, with corresponding sensitivities of 83.78 %, 86.49 %, 75.68 %, and specificities of 88.37 %, 86.49 %, 75.68 %, respectively. Multivariate logistic regression revealed that the baseline tumor diameter and interim-ADC were significant prognostic factors for treatment response with an odds ratio (OR) of 0.105 (95 % confidence interval [95 % CI] 0.018–0.616) for baseline tumor diameter and 42.896 (95 % CI 8.205–224.262) for interim-ADC. ConclusionThe interim-ADC value and baseline tumor diameter surfaced as possible indicative factors for predicting the response to RT in patients with LACC.

Immunoprophylaxis failure and vaccine response in infants born to mothers with chronic hepatitis B infection in Djibouti.

In endemic areas, vertical transmission of hepatitis B virus (HBV) remains a major source of the global reservoir of infected people. Eliminating mother-to-child transmission (MTCT) of HBV is at the heart of World Health Organization's goal of reducing the incidence of HBV in children to less than 0.1% by 2030. Universal screening for hepatitis B during pregnancy and neonatal vaccination are the main preventive measures. To evaluate the efficacy of HBV vaccination combined with one dose of immunoglobulin in children born to hepatitis B surface antigen (HBsAg)-positive mothers in Djibouti city. We conducted a study in a prospective cohort of HBsAg-positive pregnant women and their infants. The study ran from January 2021 to May 2022, and infants were followed up to 7 mo of age. HBV serological markers and viral load in pregnant women were measured using aVidas microparticle enzyme-linked immunosorbent assay (Biomérieux, Paris, France) and the automated Amplix platform (Biosynex, Strasbourg, France). All infants received hepatitis B immunoglobulin and were vaccinated against HBV at birth. These infants were closely monitored to assess their seroprotective response and for failure of immunoprophylaxis. Simple logistic regression was also used to identify risk factors associated with immunoprophylaxis failure and poor vaccine response. All statistical analyses were performed with version 4.0.1 of the R software. Of the 50 pregnant women recruited, the median age was 31 years, ranging from 18 years to 41 years. The MTCT rate in this cohort was 4% (2/50) in HBsAg-positive women and 67% (2/3) in hepatitis B e antigen-positive women with a viral load > 200000 IU/mL. Of the 48 infants who did not fail immunoprophylaxis, 8 (16%) became poor responders (anti-HB < 100 mIU/mL) after HBV vaccination and hepatitis B immunoglobulin, while 40 (84%) infants achieved a good level of seroprotection (anti-HB > 100 mIU/mL). Factors associated with this failure of immunoprophylaxis were maternal HBV DNA levels (> 200000 IU/mL) and hepatitis B e antigen-positive status (odds ratio = 158, 95% confidence interval: 5.05-4958, P < 0.01). Birth weight < 2500 g was associated with a poor immune response to vaccination (odds ratio = 34, 95% confidence interval: 3.01-383.86, P < 0.01). Despite a failure rate of immunoprophylaxis higher than the World Health Organization target, this study showed that the combination of immunoglobulin and HBV vaccine was effective in preventing MTCT of HBV. Therefore, further studies are needed to better understand the challenges associated with immunoprophylaxis failure in infants in Djibouti city.

Using progesterone to follicular index ratio is better correlated with intracytoplasmic sperm injection outcome than using serum progesterone level alone.

to investigate the possibility of using the ratio of serum progesterone level to the number of follicles, according to ovarian response in the day of human chorionic gonadotrophin trigger, as a predictor of cycle outcome. A prospective intervensional study was conducted at Kamal Al-Samarai Hospital for Infertility Treatment and IVF during the period from December 2020 to September 2021. Ninety infertile women underwent intracytoplasmic sperm injection (ICSI) cycles using antagonist protocol. Moreover, once the patient reached triggering criteria, meticulous recording of follicular index together with serum estrogen level and serum progesterone level are measured. Fresh embryo transfer of cleavage stage embryo is done once serum progesterone level was less than 1.5 ng/mL. A follow-up to confirm pregnancy rate and cycle outcome was done. The study showed a positive pregnancy rate of 28.9%. The relationship between progesterone follicular index (Prog/FI) ratio and (ICSI) outcome was highly significant with a p value of 0.001. Additionally, an inverse relationship, as the ratio was lower the pregnancy rate was improved, was documented. The receiver operating characteristic (ROC) curve for progesterone follicular index ratio was 0.711 with a cut off value of 0.0354 ng/mL in addition to a sensitivity of 65.6 and a specificity of 65.4. The serum progesterone level is an independent factor for the prediction of intracytoplasmic sperm injection (ICSI) outcome, whereas the progesterone follicular index ratio can be used as a potential marker for predicting ICSI outcome in fresh embryo transfer.

Effect of electroacupuncture pre-conditioning on the expression rhythm of core clock gene Bmal1 in uterine tissue of controlled hyperstimulation rats.

To observe the effect of electroacupuncture (EA) pre-conditioning on the expression rhythm of clock gene Bmal1 in the uterine tissue of rats with controlled ovarian hyperstimulation(COH), so as to explore its mechanisms underlying improvement of the endometrial receptivity of ovarian superovulation during implantation. Seventy-two female SD rats with typical estrous cycles were randomly divided into normal control, model and EA pre-conditioning (pre-EA) groups, with 24 rats in each group. The COH model was established by giving the rats with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (HCG) by intraperitoneal injection. The rats of the pre-EA group received EA stimulation (1 Hz/5 Hz, a tolerable strength) of "Guanyuan"(CV4) and "Sanyinjiao"(SP6) for 15 min each time, once daily (at 21：00 every day). After successive EA intervention during the first two estrous cycles, the modeling began in the third estrus cycle and the EA intervention was continued till the end of modeling, followed by raising the rats with superovulation induction and male rats undergoing vasoligation in one cage (1∶1). The rats during the estrum in the normal control group or those of the model group at the end of modeling were raised together with the male rats undergoing vasoligation in one cage. On the 5th day (04：00 AM) after raising in one cage, the rats in the three groups were sacrificed in six batches every 4 hours, with 4 rats in each group in each batch. The H.E. staining was used for revealing alterations of the endometrial thickness, number of glands and blood vessels and tissue histology, and ELISA employed to ascertain the contents of estradiol (E2) and progesterone (Pg) in serum. The expression rhythm of core clock gene Bmal1 ［In the present study, Zeitgeber time (ZT) is an artificially set laboratory time, i.e., ZT7 (07：00) is light on and ZT19 (19：00) is light off.］ and the expression of endometrial HoxA10 and leukemia inhibitory factor (LIF) mRNAs were detected by quantitative real-time PCR. The Western blot was employed to detect the expression levels of HoxA10 and LIF proteins. Findings of the clock gene Bmal1 level showed that the expression peak was at ZT12 and the valley value at ZT20 in the normal control group, and that of the peak value was at ZT20 and valley value at ZT12 in the model group, while in the pre-EA group, the peak value was at ZT8, and the valley value at ZT4. The difference of Bmal1 levels among the three groups was most significant at ZT12 (12：00), therefore, the tissue samples were taken at ZT12 in this study for comparison of the levels of different indexes among the 3 groups. Compared with the control group, the endometrial thickness, number of glands and blood vessels, HoxA10 and LIF mRNAs and proteins were significantly down-regulated (P<0.01, P<0.05), and contents of serum E2 and Pg were considerably up-regulated in the model group (P<0.01, P<0.05). Relevant to the model group, the pre-EA group had an apparent increase in the endometrial thickness, number of glands and blood vessels, and expression levels of HoxA10 and LIF mRNAs and proteins (P<0.05, P<0.01), and a marked decrease in the serum Pg (P<0.05). At the ZT12 (12：00 noon), compared with the normal control group, the mRNA level of Bmal1 was significantly decreased in the model group (P<0.01)；and compared with the model group, the level of Bmal1 mRNA was significantly increased in the pre-EA group (P<0.05). In addition, at the node of ZT16, the mRNA level of Bmal1 was significantly decreased in the model group in comparison with the normal control group (P<0.01). EA preconditioning can improve the endometrial receptivity during the implantation window period in rats with COH, which may be related to its functions in regulating the expression of clock gene Bmal1 in the uterine tissue and in correcting the disturbance of clock gene rhythm.

Assessing the developmental competence of oocytes matured following rescue in vitro maturation: a systematic review and meta-analysis.

To assess the developmental competence of oocytes matured following rescue in vitro maturation (IVM). PubMed, EmBASE, and SCOPUS were systematically searched for peer-reviewed original papers using relevant keywords and Medical Subject Heading terms. Study quality was assessed using the Newcastle-Ottawa Scale. Odds ratios with a 95% confidence interval were calculated by applying a random effects model. The primary outcomes were fertilization and blastulation rates. Secondary outcomes included abnormal fertilization, cleavage, euploidy, clinical pregnancy, and live-birth rates. Twenty-four studies were included in the meta-analysis. The oocytes matured following rescue IVM showed significantly reduced fertilization, cleavage, blastulation, and clinical pregnancy rates compared to sibling in vivo-matured oocytes. No significant differences were found for the euploidy and live-birth rates in euploid blastocyst transfer. In poor responders, a reduced fertilization rate was observed using in vitro-matured GV but not with in vitro-matured MI. A reduced cleavage rate in MI matured overnight compared to < 6 incubation hours was found. Our results showed compromised developmental competence in oocytes matured following rescue IVM. However, in poor responders, rescue IVM could maximize the efficiency of the treatment. Notably, our data suggests using in vitro MI matured within 6 incubation hours. CRD42023467232.

Optimizing trigger timing in minimal ovarian stimulation for In Vitro fertilization using machine learning models with random search hyperparameter tuning

Various studies have emphasized the importance of identifying the optimal Trigger Timing (TT) for the trigger shot in In Vitro Fertilization (IVF), which is crucial for the successful maturation and release of oocytes, especially in minimal ovarian stimulation treatments. Despite its significance for the ultimate success of IVF, determining the precise TT remains a complex challenge for physicians due to the involvement of multiple variables. This study aims to enhance TT by developing a machine learning multi-output model that predicts the expected number of retrieved oocytes, mature oocytes (MII), fertilized oocytes (2 PN), and useable blastocysts within a 48-h window after the trigger shot in minimal stimulation cycles. By utilizing this model, physicians can identify patients with possible early, late, or on-time trigger shots. The study found that approximately 27 % of treatments administered the trigger shot on a suboptimal day, but optimizing the TT using the developed Artificial Intelligence (AI) model can potentially increase useable blastocyst production by 46 %. These findings highlight the potential of predictive models as a supplementary tool for optimizing trigger shot timing and improving IVF outcomes, particularly in minimal ovarian stimulation. The experimental results underwent statistical validation, demonstrating the accuracy and performance of the model. Overall, this study emphasizes the value of AI prediction models in enhancing TT and making the IVF process safer and more efficient.