OBJECTIVES:This retrospective study compares pregnancy outcomes in polycystic ovary syndrome (PCOS) patients across different controlled ovarian stimulation (COS) protocols-specifically GnRH antagonist and GnRH agonist cycles-combined with various frozen embryo transfer(FET) preparation methods, such as hormone replacement therapy (HRT) and ovulatory cycles. Despite the known variations in COS and FET protocols, the optimal combination for improving pregnancy outcomes in this population remains unclear. METHODS:We analyzed the first FET cycles of 2510 patients with PCOS at our center between January 2017 and September 2024. Baseline characteristics and pregnancy outcomes were compared using the Kruskal‒Wallis test, the chi-square (χ²) statistic, the Bonferroni correction for multiple comparisons, and inverse probability of treatment weighting (IPTW) adjustment. RESULTS:After IPTW adjustment, no significant differences were observed in live birth rates or other key reproductive outcomes among the four protocol combinations (all P > 0.05). Exploratory analyses revealed nonsignificant trends, suggesting two patterns: 1) GnRH agonist (vs. antagonist) COS protocols were associated with lower point estimates for the risks of preterm PROM and HDP; 2) ovulation (vs. HRT) cycles for FET preparation were similarly associated with lower point estimates for these risks. CONCLUSIONS:For PCOS patients, live birth success is equivalent regardless of COS/FET protocol combination, supporting flexible treatment personalization. Clinical decision-making involves a critical trade-off: GnRH agonist protocols and ovulation FET cycles may be associated with a trend toward lower obstetric morbidity, potentially linked to the promotion of a more physiological ovulatory milieu. This balance between immediate iatrogenic risk and long-term pregnancy health warrants further study.
OBJECTIVE:To compare the efficacy of different COH protocols on pregnancy outcomes in adenomyosis patients. STUDY DESIGN:A real-world retrospective cohort study analyzed 1486 IVF-ET cycles in adenomyosis patients who received COH regimens between 2018 and 2021. Pregnancy outcomes were compared among patients under different COH protocols. RESULTS:The short-acting long protocol achieved the highest live birth (47.92%) and cumulative clinical pregnancy (68.84%) rates. The antagonist protocol showed lower fresh-cycle pregnancy (36.63% vs. 52.10%, p = 0.036), live birth (21.78% vs. 36.55%, p = 0.009), and cumulative clinical pregnancy rates (39.31% vs. 53.29%, p < 0.001) compared to the long/ultra-long protocol. Multivariable logistic regression confirmed that the COH protocol was an independent predictor of both clinical pregnancy (Wald χ² = 8.127, p = 0.043) and cumulative clinical pregnancy (Wald χ² = 40.344, p < 0.001). In patients <35 years with a normal ovarian reserve (anti-Müllerian hormone ≥ 1.2 ng/mL), live birth rates and cumulative clinical pregnancy rates were similar between the antagonist protocol and long/ultra-long protocols (27.59% vs. 44.94%, p = 0.098; 63.83% vs. 63.87%, p = 0.995), with significantly less gonadotropin used in the antagonist protocol. CONCLUSIONS:In adenomyosis patients, the long/ultra-long provided better fresh-cycle outcomes. While the antagonist protocol had lower overall pregnancy rates, it preserved cumulative pregnancy rates in young patients with normal ovarian reserves and reduced gonadotropin exposure.
Background Intra-abdominal hemorrhage (IAH) is a rare but potentially life-threatening complication of ultrasound-guided transvanginal oocyte pick up (OPU). Despite the widespread use of OPU in assisted reproductive technology, minor hemorrhages may remain undetected without vigilant monitoring, potentially escalating to severe bleeding. This study aims to elucidate the clinical characteristics, risk factors, and management outcomes of IAH following OPU. Methods A retrospective analysis was conducted on 25 hospitalized patients who developed IAH within 7 days post-OPU at a university-affiliated hospital between 2010 and 2021. Data on demographics, clinical presentations, laboratory findings, treatment modalities, and reproductive outcomes were systematically reviewed. Results The incidence of IAH was 0.05% (95% CI, 0.03%–0.07%). Symptoms typically manifested within 12 hours post-OPU, with abdominal pain and distension being most common. Hemoglobin (Hb) and hematocrit (Hct) reductions averaged 26.50±13.32 mg/dL and 7.70±3.66%, respectively. Seventeen patients were managed conservatively, while 8 required surgical intervention. Notably, 52% of patients achieved live births, with no adverse pregnancy outcomes linked to IAH. Conclusion IAH is a rare but life-threatening OPU complication. Extended postoperative monitoring is critical for early diagnosis, with conservative management as the first-line approach.
Objective: To analyze the pregnancy outcomes of patients presenting with infertility solely due to diminished ovarian reserve (DOR) and treated by assisted reproductive technology (ART), including artificial insemination by husband (AIH) and in vitro fertilization (IVF).Methods: This was a retrospective study of subfertile patients due to DOR attending the Center for Reproductive Medicine in Guangzhou, China, between January 2010 and October 2015. Patients were assigned into either the AIH or IVF group. Within each group, these patients were further subgrouped based on their serum basal follicle-stimulating hormone (bFSH) level (10 <= bFSH <= 12IU/L and bFSH > 12IU/L) and age (20-30, 31-35, 36-40, and 41-45 years). The live birth rates were compared among these groups and subgroups. Results: A total of 1,003 patients with a median age of 38.91 (21-45) years were enrolled in the study. The live birth rate following AIH was 5.61% (25/446), which was significantly lower than that following IVF (25.13%; 140/557). In the subgroup analysis, the cumulative live birth rates in AIH group were significantly lower than those in the IVF groups (in the 10-12 IU/L bFSH subgroup, 13.74% vs. 41.13% (P<0.05) for patients aged <= 35 years, and 4.82% vs. 19.77% (P<0.05) for patients aged >35 years; in the >12 IU/L bFSH subgroup, 9.52% vs. 29.91% (P<0.05) for patients aged <= 35 years, and 5.71% vs. 20.55% (P<0.05) for patients aged >35 years). Longitudinal analysis showed that majority of live births, in AIH or IVF groups, were achieved in the first two cycles.Conclusions: In subfertile women with DOR, live birth rates following AIH were significantly lower than IVF, especially for the aged women. Considering the low efficacy of AIH and that majority of live births were achieved in the first two cycles, we suggest no more than two AIH treatment attempts for the aged women with DOR.
Background There was inconsistency in optimal endometrial preparation protocol for frozen-thawed embryo transfer (FET) in patients with endometriosis. We conducted this study to investigate the effect of different endometrial preparation protocols on the pregnancy outcomes in patients with endometriosis undergoing FET cycles, and determine the optimal number of GnRHa injections in GnRHa-HRT protocols. Method(s) This was a retrospective cohort analysis of women with endometriosis who underwent FET cycles at a single university-based center. This study retrospectively analyzed 2048 FET cycles in our center from 2011 to 2020. According to the endometrial preparation protocols, patients were divided into 4 groups: gonadotropin releasing hormone agonist-hormone replacement therapy(GnRHa-HRT), hormone replacement therapy(HRT), ovulation induction(OI), and natural cycle(NC). In the GnRHa-HRT group, patients were further divided into 3 groups: one injection of GnRHa, two injections of GnRHa, and three or more injections of GnRHa. The primary outcome was the clinical pregnancy rate. Propensity score matching was used to adjust for potential non-similarities among the groups. Multivariate logistic regression analysis was performed to figure out the risk factors for pregnancy outcomes. Result(s) There were no statistical differences in pregnancy outcomes among the four endometrial preparation protocols in FET cycles with endometriosis patients, the results retained after propensity score matching(PSM). And in endometriosis patients complicated with adenomyosis, the results remained similar. In patients with GnRHa-HRT protocol, there were no differences in clinical pregnancy rate and live birth rate with different numbers of GnRHa injections, the early miscarriage rate were 18% in the two injections of GnRHa group and 6.5% in the one injection of GnRHa group(P = 0.017). Multifactorial logistic regression analysis showed that two injections of GnRHa before FET was associated with increased early miscarriage rate compared with one injection of GnRHa[adjusted OR (95% CI): 3.116(1.079–8.998),p = 0.036]. Conclusion(s) The four kinds of endometrial preparation protocols for FET, GnRHa-HRT, HRT, OI and NC had similar pregnancy outcomes in patients with endometriosis. In endometriosis patients complicated with adenomyosis, the results remained similar. In patients with endometriosis undergoing GnRHa-HRT protocol for FET, more injections of GnRHa had no more advantages in pregnancy outcomes, on the contrary, it might increase the early miscarriage rate.
Endometriosis (EMS) is a common disease in women of reproductive age. EMS may cause pain, infertility and mass. Because EMS affects the entire reproductive period of patients, it is easy to relapse, and difficult to cure. Therefore, a long-term management plan for patients with EMS should be formulated, including medical treatment, surgical treatment, and assisted reproductive technology. Fertility needs are one of the main needs of women with EMS of reproductive age. Therefore, long-term follow-up management is needed for women with EMS of reproductive age. The main purpose of treatment and consultation is to treat the pain caused by EMS and reduce the recurrence and progression of EMS, and give fertility guidance to patients when appropriate, and give appropriate treatment when patients are diagnosed with infertility. This article reviewed the long-term management of EMS patients of reproductive age.
Advances in genetic testing field have contributed to the boom in carrier screening technology. Expanded carrier screening can effectively identify more high-risk couples than traditional guideline-based carrier screening. The introduction of extended carrier screening has increased the number of referrals for preimplantation genetic testing (PGT) for monogenic disease and enriched the types of disease diagnosed. Expanded carrier screening combined with PGT technology is changing the clinical strategy of genetic risk assessment and preventing birth defects by accurately identifying reproductive risk information and rationalizing fertility planning.
Accumulating evidence has demonstrated that aberrant miRNAs contribute to cervical cancer (CC) development and progression. However, the roles of various miRNAs in CC remain to be determined. In the present study, we confirmed that a decreased miR-1297 expression was present in CC tissues and cell lines. Our clinical analysis revealed that the downregulated miR-1297 expression was significantly correlated with poor prognostic features including lymph node metastasis and lymphovascular space invasion. Moreover, we confirmed that miR-1297 was a novel independent prognostic marker for predicting the 5-year survival of CC patients. The ectopic overexpression of miR-1297 inhibited cell migration, invasion and EMT progression, while downregulated miR-1297 reversed these effects. In addition, miR-1297 regulated AEG-1 by directly binding to its 3'-UTR. In clinical samples of CC, miR-1297 was inversely correlated with AEG-1, which was upregulated in CC. Alteration of AEG-1 expression at least partially abolished the migration, invasion and EMT progression effects of miR-1297 on CC cells. In conclusion, our results indicated that miR-1297 functioned as a tumor suppressor gene in regulating the EMT and metastasis of CC via targeting of AEG-1, and may represent a novel potential therapeutic target and prognostic marker for CC.
Background The impact of Chlamydia trachomatis infection (CT) on the outcomes of In-Vitro Fertilization / Intracytoplasmic sperm injection (IVF/ICSI) has been controversial. Methods A total of 431 infertility women aged 20–38 years with or without Chlamydia trachomatis infection before fresh/ frozen embryo transfer were included to investigate the effect of cured CT infection. The infected group was divided into two subgroups for ≤3 months and > 3 months according to the different intervals between Chlamydia trachomatis positive testing and embryo transfer. The effect of chlamydia infection and the intervals between infection and embryo transfer on pregnancy outcomes was analyzed with correction for potential confounders within a multivariable model. Results Our results revealed that implantation rate was significantly lower and the premature rupture of membranes (PROM) was higher in women with CT infection than non-infection. The multivariate logistic regression analysis adjusting for baseline characteristics showed no significant difference in live birth rate between neither two groups nor two subgroups. Conclusions The study suggests that previous Chlamydia trachomatis infection would lead to high risk of PROM. The intervals between infection and embryo transfer would not impact the pregnancy outcomes of IVF/ICSI.
Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the immunohistochemical data shown in Fig. 4C and the cell migration assay data shown in Fig. 3B and D and Fig. 7B and D were strikingly similar to data that had appeared in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 38: 3121‑3129, 2017; DOI: 10.3892/or.2017.5979].
Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disease among women, but its etiology remains unknown. In recent years, many circular RNAs (circRNAs) have been confirmed to be related to the development of PCOS. The role and mechanism of circRNA in the development of PCOS need to be further explored. Methods: In the present study, we used the circRNA chip to detect the difference in the expression of circRNA in the granulosa cells of PCOS patients and controls. Five upregulated circRNAs were then selected for quantitative reverse transcription polymerase chain reaction (qRT-PCR) verification, and circRHBG was found to be upregulated in PCOS. Subsequently, Cell Counting Kit-8 assay and EdU assay were used to observe the effect of circRHBG on the proliferation of KGN and SVOG cells. Furthermore, the pairwise binding relationship between circRHBG/miR515-5 and miR515-5p/SLC7A11 was verified by luciferase reporter assay. The interaction between circRHBG and SLC7A11 was detected with qRT-PCR and Western blot. Results: CircRNA high-throughput chips and qRT-PCR verified that circRHBG was significantly upregulated in granular cells of PCOS patients. Knockdown of circRHBG inhibits KGN and SVOG cell proliferation. Luciferase reporter assays and Ago2-RIP detection showed that circRHBG competes with SLC7A11 to bind to miR-515-5p. Subsequent experiments verified knockdown of circRHBG promotes ferroptosis in PCOS. Conclusions: circRHBG inhibits ferroptosis in PCOS cells through the circRHBG/miR-515-5p/ SLC7A11 axis in PCOS, which may provide new diagnostic molecular markers and therapeutic targets for PCOS.
Objective: To investigate the therapeutic effect of antibiotic treatment on pregnancy outcomes in the following frozen-thawed embryo transfer cycles of infertile women. Design: Retrospective study. Setting: University assisted reproduction unit. Patient(s): A total of 640 women were included. Among them, the number of CD138+ cells per high-power field (CD138+/HPF) in the endometrium at the first evaluation was 0 in 88 women; 315 women had 1-4 CD138+/HPF and the remaining 237 had >5 CD138+/ HPF. Finally, 26 of 237 women had persistent chronic endometritis (PCE) diagnosed. Intervention(s): Hysteroscopy and endometrial biopsy were performed in the proliferative phase. After antibiotic treatment, endometrial biopsy samples were collected again. Main Outcome Measure(s): Live birth rate. Result(s): No significant difference in pregnancy outcomes was found between women with CD138+/HPF = 0 and those with CD138+/HPF 1-4. The cure rate was 89.0% in women with CD138+/HPF >5 after treatment. The implantation rate (51.6% vs. 32.3%, relative risk [RR] 2.23, 95% confidence interval [CI] 1.07-4.66), clinical pregnancy rate (65.7% vs. 42.3%, RR 2.62, 95% CI 1.17-5.86), live birth rate (52.1% vs. 30.7%, RR 2.45, 95% CI 1.04-5.76), and cumulative live birth rate (64.2% vs. 38.5%, RR 2.88, 95% CI 1.27-6.51) were all significantly higher in women with CD138+/HPF <4 than in women with PCE. Conclusion(s): CD138+/HPF <4 in the endometrium had no negative impact on pregnancy outcomes. Antibiotic treatment was an effective way to improve the reproductive outcomes of women with CD138+/HPF >5. PCE was associated with poorer pregnancy outcomes. (Fertil Sterile 2021;116:413-21. (c) 2021 by American Society for Reproductive Medicine.)
Aim This retrospective study aimed to evaluate the predictive value of serum cancer antigen 125 (CA125) levels before hormone replacement therapy on pregnancy outcomes in women with adenomyosis undergoing frozen embryo transfer. Methods A total of 509 women with adenomyosis were screened and 84 patients receiving a total of 114 cycles of frozen embryo transfer were included, based on the inclusion and exclusion criteria. Patients were divided into two groups based on their CA125 levels (≤ or >35 IU/mL) before hormone replacement therapy. The basic characteristics and main outcomes of the two groups were compared. Receiver operating characteristic curve and subgroup analyses were also conducted. Results There were no significant differences in clinical outcomes of frozen embryo transfer cycles in patients with different serum CA125 levels before hormone replacement therapy. Receiver operating characteristic curve analysis demonstrated that CA125 levels before hormone replacement therapy were not predictive of clinical pregnancy outcomes. Conclusions Serum CA125 levels before hormone replacement therapy are not associated with the clinical outcomes of frozen embryo transfer among women with adenomyosis.
Androgens have been reported to be associated with female fertility. The mean serum testosterone concentration in the patients with endometriosis was reported to be significantly lower than that without endometriosis. Our study was designed to investigate the influence of basal serum testosterone levels on the clinical outcome of in vitro fertilization (IVF) in the patients with III‐IV stage endometriosis.
We aimed to explore the clinical effects of the endometrial preparation protocol for frozen-thawed embryo transfer (FET) in women with endometrial polyps. This retrospective study was performed at the Reproductive Medicine Centre of the First Affiliated Hospital of Sun Yat-sen University between January 2015 and May 2018 involving women diagnosed with endometrial polyps by hysteroscopy. The freeze-all strategy was performed in controlled ovarian stimulation cycles followed by FET cycles. Endometrial preparation protocols included: (i) gonadotropin-releasing hormone agonist-hormone replacement therapy (GnRHa-HRT); (ii) hormone replacement therapy (HRT); (iii) natural cycle (NC); and (iv) ovulation induction (OI). Recurrence rate of polyps and clinical results were compared among the four groups. If polyp recurrence was found in ultrasound scans during the FET cycles, the embryo transfers were cancelled. The recurrence rate of polyps was lower in the GnRHa-HRT protocol [2.13% (2/94)] than in the other three protocols [6.15% (26/423), 6.7% (28/418), and 4% (1/25) in the HRT, NC, and OI, respectively; p = 0.038], showing statistically significant difference. Pregnancy, early pregnancy loss, and live birth rates among the four protocols were similar (p = 0.922, p = 0.171, and p = 0.072, respectively). The GnRHa-HRT protocol used for FET in women with endometrial polyps could reduce the recurrence rate of the polyps. In addition, we found that it did not decrease pregnancy or live birth rates.
Vitrification is widely used in assisted reproductive technologies. However, the nervous system of vitrification offspring is of concern, and research on this is lacking. Vitrification-born mice (vitrification group), conventional in vitro fertilization-embryo transfer pregnancy-born mice (IVF group), and natural pregnancy-born mice (control group) were used to study the effects of vitrification of mouse embryos on protein levels in the brain of offspring. Proteins differentially expressed among the three groups were analyzed using proteomic methods, including two-dimensional electrophoresis, mass spectrometry, and bioinformatics analysis. Immunohistochemistry was used to verify the expression of differentially expressed proteins, such as Actb and Actg1, in each group. Twenty differentially expressed proteins in the brain tissue were identified using two-dimensional protein electrophoresis and mass spectrometry. Bioinformatics analysis revealed that these proteins were related to the development of anatomical structure, signal transduction, transport, cell differentiation, and stress response (biological processes) and the binding of molecules in vivo (molecular functions). The Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the differentially expressed proteins were involved in 54 pathways, including phagosome, metabolic pathway, apoptosis, and cysteine and methionine metabolism. Thus, embryo vitrification may cause some changes in the mouse brain at the protein level, necessitating further safety assessment.
There is disputable on the role of nitrilase-like 2 (NIT2) in cancer. Its expression and its relationship with clinicopathological features in tongue squamous cell carcinoma (TSCC) are not yet clear. The purpose of this study is to investigate the expression of NIT2 in TSCC and its correlation with clinicopathological characteristics in TSCC patients. Through proteomic identification, we found that the protein NIT2 was related to the development of TSCC. q-PCR, western blot and immunohistochemistry techniques were applied to detect the expression of NIT2 in TSCC. The relationship between the expression of NIT2 and clinicopathological features was analyzed by Chi square tests. The results showed the expression of NIT2 in TSCC was significantly higher than that in normal tongue tissues ( p < 0.05). Univariate and multivariate analysis showed that the positive expression of NIT2 and N classification were associated with decreased disease-free survival rate (DFS) and overall survival (OS) ( p < 0.05). The results suggested that NIT2 is overexpressed in TSCC and NIT2 may be a potential therapeutic target for TSCC.
Aim To evaluate whether using multiple displacement amplification (MDA) as the first step can increase the diagnostic efficiency of preimplantation genetic testing for monogenic disease (PGT-M) for beta-thalassemia. Methods This is a retrospective cohort study. All included patients underwent PGT-M cycles (n = 307) for beta-thalassemia in our center from January 2014 to February 2018. We divided the patients into two groups based on two different detection methods. For the polymerase chain reaction (PCR) group (n = 115), multiplex nested PCR+ reverse dot blot analysis was performed directly after cell lysis. For the MDA group (n = 192), the whole genomes of single cells were directly amplified using MDA and then examined by singleplex PCR + reverse dot blot for beta-thalassemia. Results A total of 2315 embryos were tested. The overall diagnostic efficiency of the MDA group was significantly higher than that of the PCR group (96.99% vs 88.15%, P < 0.001). The percentage of embryos available for transfer was significantly higher in the MDA group than in the PCR group (74.28% vs 64.98%, P < 0.001). Furthermore, the carrier embryo rate of the MDA group was significantly higher than that of the PCR group (50.11% vs 35.95%, P < 0.001). Conclusion This study indicates that MDA, as the first step in PGT-M for beta-thalassemia, can increase diagnostic efficiency.
To evaluate the relationship between serum β-human chorionic gonadotropin (HCG) levels and early pregnancy outcomes in women who became pregnant using assisted reproductive technologies (ARTs). In this study, we retrospectively analyzed 523 pregnancies after ART use, with respect to the early clinical outcomes based on the serum β-HCG levels. The significance of using serum β-HCG levels to predict outcomes in early pregnancy was evaluated by the receiver operating characteristic (ROC) curve and cutoff values of serum β-HCG. We found that elevated serum β-HCG levels resulted in decreased biochemical pregnancy rates, increased multiple rates, and decreased ongoing and ectopic pregnancy rates. The cutoff values of serum β-HCG levels for the prediction of biochemical pregnancy were 213.15 IU/L, 986.65 IU/L, and 2206.5 IU/L for singletons, multiples, and twins or triplets, respectively. The serum β-HCG level 14 or 12 days after D3 or D5 embryo transfer (conducted 3 or 5 days after oocyte retrieval), respectively, predicts biochemical/clinical pregnancy and singleton/multiple pregnancy with robust sensitivity and specificity.