Improvement of early miscarriage rates in women with adenomyosis via oxytocin receptor antagonist during frozen embryo transfer-a propensity score-matched study.

BACKGROUND: Dysfunctional uterine peristalsis seems to play a pivotal role in hindering embryo implantation among women diagnosed with adenomyosis. This research aims to investigate whether administering an oxytocin receptor antagonist during a frozen embryo transfer (FET) cycle using a hormone replacement therapy (HRT) protocol can enhance in vitro fertilization (IVF) outcomes for infertile women affected by adenomyosis. METHODS: Between January 2018 and June 2022, our reproductive center conducted IVF-FET HRT cycles for infertile women diagnosed with adenomyosis. Propensity score matching was employed to select matched subjects between the two groups in a 1:1 ratio. Following this, 168 women received an oxytocin receptor antagonist during FET, constituting the study group, while the matched 168 women underwent FET without this antagonist, forming the control group. We conducted comparative analyses of baseline and cycle characteristics between the two groups, along with additional subgroup analyses. RESULTS: The study group exhibited notably lower rates of early miscarriage compared to the control group, although there were no significant differences in clinical pregnancy rates, ongoing pregnancy rates, and live birth rates between the two groups. Multivariate analysis revealed a negative correlation between the use of oxytocin receptor antagonists and early miscarriage rates in women with adenomyosis. Subgroup analyses, categorized by age, infertility types, and embryo transfer day, showed a substantial decrease in early miscarriage rates within specific subgroups: women aged ≥ 37 years, those with secondary infertility, and individuals undergoing day 3 embryo transfers in the study group compared to the control group. Furthermore, subgroup analysis based on adenomyosis types indicated significantly higher clinical pregnancy rates, ongoing pregnancy rates and live birth rates in the study group compared to the control group among women with diffuse adenomyosis. CONCLUSIONS: Administering an oxytocin receptor antagonist during FET may reduce the early miscarriage rates in women with adenomyosis.

Intravascular Laser Blood Irradiation (ILIB) Enhances Antioxidant Activity and Energy Metabolism in Aging Ovaries.

BACKGROUND: Ovarian aging is characterized by the accumulation of free radicals, leading to tissue damage and affecting reproductive health. Intravascular laser irradiation of blood (ILIB, using a low-energy He-Ne laser) is known for its efficacy in treating vascular-related diseases by reducing free radicals and inflammation. However, its impact on ovarian aging remains unexplored. This study aimed to investigate the effects of ILIB on oxidative stress and energy metabolism in aging ovaries. METHODS: Genetic analysis was conducted on 75 infertile patients with aging ovaries, divided into ILIB-treated and control (CTRL) groups. Patients underwent two courses of laser treatment, and clinical parameters were evaluated. Cumulus cells were collected for the genetic analysis of oxeiptosis, glycolysis, and the tricarboxylic acid (TCA) cycle. RESULTS: The analysis of gene expression patterns revealed intriguing findings in ILIB-treated patients compared to the untreated group. Notably, ILIB treatment resulted in significant upregulation of oxeiptosis-related genes AIFM1 and NRF2, suggesting a potential protective effect against oxidative stress-induced cell death. Furthermore, ILIB treatment led to a downregulation of glycolysis-associated gene hexokinase 2 (HK2), indicating a shift away from anaerobic metabolism, along with an increase in PDHA levels, indicative of enhanced mitochondrial function. Consistent with these changes, ILIB-treated patients exhibited elevated expression of the key TCA cycle genes citrate synthase (CS), succinate dehydrogenase complex subunit A (SDHA), and fumarate hydratase (FH), signifying improved energy metabolism. CONCLUSION: The findings from this study underscore the potential of ILIB as a therapeutic strategy for mitigating ovarian aging. By targeting oxidative stress and enhancing energy metabolism, ILIB holds promise for preserving ovarian function and reproductive health in aging individuals. Further research is warranted to elucidate the underlying mechanisms and optimize the application of ILIB in clinical settings, with the ultimate goal of improving fertility outcomes in women experiencing age-related ovarian decline.

Additional single dose GnRH agonist during luteal phase support may improve live birth rate in GnRHa-HRT frozen-thawed embryo transfer cycle: a retrospective cohort study.

BACKGROUND: GnRH agonist (GnRHa) has been reported to have direct effects and functional roles in the endometrium and embryos. Several meta-analyses have shown that GnRHa administration in the luteal phase improved the live birth rate or pregnancy rate in both fresh and frozen embryo transfer (FET) cycles. The aim of this study was to investigate whether luteal GnRHa administration could also improve in vitro fertilization (IVF) outcomes in patients undergoing hormone replacement therapy (HRT) cycles with GnRHa suppression. METHODS: The retrospective cohort study included a total of 350 patients undergoing GnRHa-HRT FET cycles. The study group included 179 patients receiving an additional single dose of GnRHa in the luteal phase following embryo transfer. A total of 171 patients in the control group did not receive luteal GnRHa. The baseline and cycle characteristics and reproductive outcomes were compared between the two groups. RESULTS: Baseline and cycle characteristics were similar between the two groups, except lower AMH levels were found in the luteal GnRHa group than in the control group. The luteal GnRHa group had a significantly higher ongoing pregnancy rate and live birth rate than the control group. The multivariate analysis revealed that luteal GnRHa administration was positively associated with ongoing pregnancy (OR 2.04, 95% CI 1.20-3.47, P = 0.008) and live birth (OR 2.03, 95% CI 1.20-3.45, P = 0.009). When the subgroup of patients with recurrent implantation failure was analyzed, the multivariate analysis also showed that luteal GnRHa administration had beneficial effects on ongoing pregnancy (OR 4.55, 95% CI 1.69-12.30, P = 0.003) and live birth (OR 4.30, 95% CI 1.59-11.65, P = 0.004). CONCLUSIONS: Our data suggest that the addition of one luteal dose of GnRHa may improve the live birth rate in patients undergoing the GnRHa-HRT protocol.

The Molecular Regulation in the Pathophysiology in Ovarian Aging.

The female reproductive system is of great significance to women's health. Aging of the female reproductive system occurs approximately 10 years prior to the natural age-associated functional decline of other organ systems. With an increase in life expectancy worldwide, reproductive aging has gradually become a key health issue among women. Therefore, an adequate understanding of the causes and molecular mechanisms of ovarian aging is essential towards the inhibition of age-related diseases and the promotion of health and longevity in women. In general, women begin to experience a decline in ovarian function around the age of 35 years, which is mainly manifested as a decrease in the number of ovarian follicles and the quality of oocytes. Studies have revealed the occurrence of mitochondrial dysfunction, reduced DNA repair, epigenetic changes, and metabolic alterations in the cells within the ovaries as age increases. In the present work, we reviewed the possible factors of aging-induced ovarian insufficiency based on its clinical diagnosis and performed an in-depth investigation of the relevant molecular mechanisms and potential targets to provide novel approaches for the effective improvement of ovarian function in older women.

Dual-trigger improves the outcomes of in vitro fertilization cycles in older patients with diminished ovarian reserve: A retrospective cohort study.

BACKGROUND: Dual-trigger for final oocyte maturation has been applied on the women with poor ovarian response or diminished ovarian reserve. However, the results were controversial. The Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) stratification is a set of newly established criteria for low prognosis patients. The aim of this study was to examine the effectiveness of dual-trigger for final oocyte maturation on the in vitro fertilization (IVF) outcomes of patients who fulfill the POSEIDON group 4 criteria. METHODS: This retrospective cohort study investigated 384 cycles fulfilling the POSEIDON group 4 criteria. The patients underwent IVF treatment using the gonadotropin-releasing hormone (GnRH) antagonist protocol. The study group contained 194 cycles that received dual-trigger (human chorionic gonadotropin [hCG] plus GnRH-agonist) for final oocyte maturation. The control group included 114 cycles where final oocyte maturation was performed with only hCG. Baseline characteristics and cycle parameters, as well as IVF outcomes of both groups were compared. RESULTS: Baseline characteristics were similar between the dual trigger group and the control group. In terms of IVF outcomes, the dual trigger group demonstrated significantly higher number of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day-3 embryos, and top-quality day-3 embryos. A statistically significant improvement in clinical pregnancy rate and live birth rate was also observed in the dual trigger group. CONCLUSIONS: Our data suggests that dual trigger for final oocyte maturation might improve clinical pregnancy rates and live birth rates of IVF cycles in patients fulfilling the POSEIDON group 4 criteria.

Dehydroepiandrosterone Supplementation Improves the Outcomes of in vitro Fertilization Cycles in Older Patients With Diminished Ovarian Reserve.

Background: Dehydroepiandrosterone (DHEA) supplementation has been reported to have beneficial effects on the in vitro fertilization (IVF) outcomes of patients with poor ovarian response or diminished ovarian reserve. The Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) stratification is a set of newly established criteria for low prognosis patients. The aim of this study was to examine the potential effects of DHEA supplementation on the IVF outcomes of patients who fulfill the POSEIDON group 4 criteria. Methods: This retrospective cohort study investigated 297 cycles that fulfilled the POSEIDON group 4 criteria and underwent IVF treatment using the gonadotropin-releasing hormone antagonist protocol. The study group contained 159 cycles that received DHEA (30 mg three times per day) daily for 12 weeks before their IVF cycles. The control group included 138 cycles that underwent IVF cycles but did not receive DHEA. The baseline characteristics and cycle parameters as well as the IVF outcomes of both groups were compared. Results: In terms of baseline characteristics, more previous IVF attempts and lower AMH levels were found in the study group than in the control group. Regarding IVF outcomes, patients in the study group had significantly higher follicular oocyte index and higher numbers of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day 3 embryos and top-quality day 3 embryos than those in the control group. Besides, a higher cumulative pregnancy rate and lower cancellation rate were observed in the study group than in the control group although clinical pregnancy rate, live birth rate, and cumulative live birth rate did not differ between the two groups. Whether patients are aged ≤ 40 years or aged > 40, higher numbers of oocytes and embryos were observed in the study group than in the control group. In patients aged > 40, cumulative pregnancy rate was significantly higher in the study group than in the control group. Conclusions: Our data suggest that DHEA supplementation might increase both oocyte and embryo yields, as well as cumulative pregnancy rates, in patients fulfilling the POSEIDON group 4 criteria.

MicroRNA in Ovarian Cancer: Biology, Pathogenesis, and Therapeutic Opportunities.

Ovarian cancer comprises one of the three major malignant tumor types in the female reproductive system. The mortality rate of this cancer is the highest among all gynecological tumors, with ovarian cancer metastasis constituting an important cause of death. Therefore, markers for disease prediction and prognosis are highly desirable for early diagnosis as well as for helping optimize and personalize treatment. Recently, microRNAs (miRNAs), which consist of short-sequence RNAs that do not encode a protein, have emerged as new biomarkers in the clinical diagnosis and treatment of ovarian cancer. By pairing with bases specific to the target messenger RNA (mRNA), miRNAs cause degradation of the target mRNA or inhibit its translation, thereby regulating various cellular processes including cell proliferation and adhesion. Increasing numbers of studies have shown that miRNA expression abnormality plays an important role in the development of ovarian cancer. In this review, we discuss the mechanisms of miRNA action, current research regarding their role in the suppression or promotion of ovarian cancer, and their use as markers for diagnosis of prognosis or as therapeutic targets for this disease. Finally, we present future perspectives regarding the clinical management of ovarian cancer and the role for miRNAs therein.

Trends in the incidence of thymoma, thymic carcinoma, and thymic neuroendocrine tumor in the United States.

This study aimed to identify the trends in the incidence of thymic cancer, i.e., thymoma, thymic carcinoma, and thymic neuroendocrine tumor, in the United States. Data from the United States Cancer Statistics (USCS) database (2001-2015) and those from the Surveillance, Epidemiology, and End Results (SEER) database (SEER 9 [1973-2015], SEER 13 [1992-2015], and SEER 18 [2000-2015]) were used in this study. All incidences were per 100,000 population at risk. The trends in incidence were described as annual percent change (APC) using the Joinpoint regression program. Data from the USCS (2001-2015) database showed an increase in thymic cancer diagnosis with an APC of 4.89% from 2001 to 2006, which is mainly attributed to the significant increase in the incidence of thymoma and thymic carcinoma particularly in women. The incidence of thymic cancer did not increase from 2006 to 2015, which may be attributed to the increase in the diagnosis of thymic carcinoma from 2004 to 2015, with a concomitant decrease in thymoma from 2008 to 2015. Before declining, the age-specific incidence of thymic cancer peaked at ages 70-74 years, with a peak incidence at 1.06 per 100,000 population, and decreased in older age groups. The incidence of thymic cancer was higher in men than in women. Asian/Pacific Islanders had the highest incidence of thymoma, followed by black and then white people. The incidence of thymic carcinoma increased from 2004 to 2015, with a concomitant decrease in thymoma from 2008 to 2015. Asian/Pacific Islanders had the highest incidence of thymoma than other races.

Dehydroepiandrosterone Ameliorates Abnormal Mitochondrial Dynamics and Mitophagy of Cumulus Cells in Poor Ovarian Responders.

Mitochondrial dysfunction is related to reproductive decline in humans, with consequences for in vitro fertilization (IVF). We assessed whether dehydroepiandrosterone (DHEA) could regulate mitochondrial homeostasis and mitophagy of cumulus cells (CCs) in poor ovarian responders (PORs). A total of 66 women who underwent IVF treatment at the Reproductive Medicine Center of Kaohsiung Veterans General Hospital were included in this study. Twenty-eight normal ovarian responders (NOR) and 38 PORs were enrolled. PORs were assigned to receive DHEA supplementation (n = 19) or not (n = 19) before IVF cycles. DHEA prevents mitochondrial dysfunction by decreasing the activation of DNM1L and MFF, and increasing MFN1 expression. Downregulation of PINK1 and PRKN occurred after DHEA treatment, along with increased lysosome formation. DHEA not only promoted mitochondrial mass but also improved mitochondrial homeostasis and dynamics in the CCs of POR. We also observed effects of alterations in mRNAs known to regulate mitochondrial dynamics and mitophagy in the CCs of POR. DHEA may prevent mitochondrial dysfunction through regulating mitochondrial homeostasis and mitophagy.

Dehydroepiandrosterone (DHEA) supplementation improves in vitro fertilization outcomes of poor ovarian responders, especially in women with low serum concentration of DHEA-S: a retrospective cohort study.

BACKGROUND: Dehydroepiandrosterone (DHEA) is now widely used as an adjuvant for in vitro fertilization (IVF) cycles in poor ovarian responders (PORs). Several studies showed that DHEA supplementation could improve IVF outcomes of PORs. However, most of the PORs do not respond to DHEA clinically. Therefore, the aim of this study is to confirm the beneficial effects of DHEA on IVF outcomes of PORs and to investigate which subgroups of PORs can best benefit from DHEA supplementation. METHODS: This retrospective cohort study was performed between January 2015 and December 2017. A total of 151 PORs who fulfilled the Bologna criteria and underwent IVF cycles with the gonadotropin-releasing hormone antagonist protocol were identified. The study group (n = 67) received 90 mg of DHEA daily for an average of 3 months before the IVF cycles. The control group (n = 84) underwent the IVF cycles without DHEA pretreatment. The basic and cycle characteristics and IVF outcomes between the two groups were compared using independent t-tests, Chi-Square tests and binary logistic regression. RESULTS: The study and control groups did not show significant differences in terms of basic characteristics. The study group demonstrated a significantly greater number of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day 3 embryos and top-quality embryos at day 3 and a higher clinical pregnancy rate, ongoing pregnancy rate and live birth rate than those measures in the control group. The multivariate analysis revealed that DHEA supplementation was positively associated with clinical pregnancy rate (OR = 4.93, 95% CI 1.68-14.43, p = 0.004). Additionally, in the study group, the multivariate analysis showed that serum dehydroepiandrosterone-sulfate (DHEA-S) levels < 180 µg/dl were significantly associated with a rate of retrieved oocytes > 3 (OR = 5.92, 95% CI 1.48-23.26, p = 0.012). CONCLUSIONS: DHEA supplementation improves IVF outcomes of PORs. In PORs with DHEA pretreatment, women with lower DHEA-S level may have greater possibility of attaining more than 3 oocytes.

Hypertensive disorders of pregnancy and future heart failure risk: A nationwide population-based retrospective cohort study.

OBJECTIVE: To assess whether hypertensive disorders of pregnancy (HDP) increased the risk of subsequent heart failure (HF) and identify possible risk factors. STUDY DESIGN: A nationwide population-based retrospective cohort study. MAIN OUTCOME MEASURES: Incidence of heart failure. RESULTS: Among the 23.3 million individuals registered in the National Health Insurance Research Database in Taiwan, 29,186 patients with HDP and 116,744 matched controls were identified. The overall incidence of HF was greater in the HDP group than it was in the control group (9.83 vs. 1.67 per 10,000 person-years), with a significant incidence rate ratio (IRR = 5.88, 95% confidence interval [CI] 5.84-5.92, p < 0.0001). When stratified by age, parity, gestational age, gestational number, and follow-up years, the IRR for subsequent HF remained significantly higher in the HDP group in all stratifications. Additionally, the Kaplan-Meier analysis indicated that the cumulative incidence rate of HF was higher in the HDP group than it was in the control group. The Cox proportional-hazard model analysis showed that in addition to HDP, single parity, preterm and hypertension were independent risk factors for developing HF. Moreover, HF was more likely to develop within 5 years post-partum. Among patients with a history of HDP, the Cox proportional-hazard model showed that severe forms of HDP and increased HDP occurrences were independently associated with the subsequent development of HF. CONCLUSIONS: Patients who have experienced HDP presented an increased risk for developing HF later in life. Moreover, among individuals with a history of HDP, those with severe forms of HDP or recurrent HDP displayed an increased subsequent risk of HF.

Luteal Phase Ovarian Stimulation May Improve Oocyte Retrieval and Oocyte Quality in Poor Ovarian Responders Undergoing In Vitro Fertilization: Preliminary Results from a Single-Center Prospective Pilot Study.

INTRODUCTION: Luteal phase ovarian stimulation (LPOS) has been proven a feasible protocol for infertile patients. High progesterone level in the luteal phase could physiologically inhibit premature luteinizing hormone surge, from which poor ovarian responders (PORs) could obtain benefits. Therefore, we aimed to compare clinical outcomes between LPOS and follicular phase ovarian stimulation (FPOS) protocol in PORs undergoing in vitro fertilization (IVF). METHODS: This prospective pilot study was performed at one tertiary center from January 2016 to October 2017. A total of 60 PORs who met Bologna criteria and undergoing IVF were enrolled. Thirty PORs were allocated to the LPOS group and 30 PORs were allocated to the FPOS group. Basic characteristics, cycle characteristics, and pregnancy outcomes were compared between the two groups. RESULTS: The length of stimulation was significantly longer in the LPOS group than in the FPOS group. The numbers of retrieved oocytes, metaphase II oocytes, fertilized oocytes, and day-3 embryos were significantly higher in the LPOS group than in the FPOS group. Conversely, we could not find any significant difference for clinical pregnancy rate, ongoing pregnancy rate, abortion rate, and cancellation rate. The multivariate analysis showed that only LPOS (p = 0.007) was significantly associated the possibility to retrieve three or more oocytes, whereas basal follicle-stimulating hormone (FSH) < 8 IU/l (p = 0.103) and antral follicle count (AFC) ≥ 3 (p = 0.143) did not significantly affect this event. CONCLUSION: LPOS allows improved oocyte retrieval and oocyte quality in PORs with respect to FPOS, despite comparable pregnancy outcomes. LPOS may be considered a feasible option for oocytes accumulation in PORs. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03238833.