Chronic endometritis - a constantly discussed issue in infertile women.

OBJECTIVE: A review of current knowledge on the pathophysiology, diagnostic and treatment options for chronic endometritis in infertile women. METHODS AND RESULTS: One of the major causes of failed in vitro fertilization (IVF) is undiagnosed intrauterine pathologies, including chronic inflammation of the uterine mucosa - chronic endometritis. However, some authors relativize the negative impact of chronic endometritis on reproductive outcomes. The etiopathogenesis of chronic endometritis is due to qualitative and quantitative changes in the endometrial microbiome with abnormal multiplication of microorganisms naturally occurring in the uterine cavity or vagina. There is no uniform consensus on the most common pathogen causing chronic endometritis. It is characterized by infiltration of plasma cells into the endometrial stroma outside the menstrual cycle, accompanied by hyperaemia and endometrial oedema. Clinical symptoms are very mild or absent. The diagnosis of chronic endometritis is often difficult because there is no specific clinical or laboratory diagnostic method. The following investigative options are commonly used for the diagnosis of chronic endometritis: diagnostic hysteroscopy, histopathological examination of the endometrium including CD 138 immunohistochemistry and culture from the uterine cavity. However, standardised international hysteroscopic and histopathological criteria for accurate diagnosis of chronic endometritis are still lacking. Empirically administered antibiotic therapy improves the success rate of pregnancy and delivery of a viable foetus in infertile patients with proven chronic endometritis. In addition to reviewing the current knowledge of chronic endometritis, this article discusses the importance of hysteroscopy in the diagnostic process. CONCLUSION: Chronic endometritis is often a clinically silent disease with negative impact on reproduction in infertile women. Although there are still many unresolved issues, the introduction of hysteroscopy into the diagnostic process is important for clinical practice; however, hysteroscopy even in combination with histological examination of the endometrium, often does not allow an unequivocal diagnosis of chronic endometritis. Further prospective randomised studies in a selected group of women with proven chronic endometritis and repeated failure to implant proven euploid embryos should refine this knowledge.

A Real-World Safety Profile in Neurological, Skin, and Sexual Disorders of Anti-Seizure Medications Using the Pharmacovigilance Database of the Korea Adverse Event Reporting System (KAERS).

(1) Background: The utilization of high-quality evidence regarding the safety of anti-seizure medications (ASMs) is constrained by the absence of standardized reporting. This study aims to examine the safety profile of ASMs using real-world data. (2) Methods: The data were collected from the Korea Adverse Event Reporting System Database (KAERS-DB) between 2012 and 2021. In total, 46,963 adverse drug reaction (ADR)-drug pairs were analyzed. (3) Results: At the system organ class level, the most frequently reported classes for sodium channel blockers (SCBs) were skin (37.9%), neurological (16.7%), and psychiatric disorders (9.7%). For non-SCBs, these were neurological (31.2%), gastrointestinal (22.0%), and psychiatric disorders (18.2%). The most common ADRs induced by SCBs were rash (17.8%), pruritus (8.2%), and dizziness (6.7%). Non-SCBs were associated with dizziness (23.7%), somnolence (13.0%), and nausea (6.3%). Rash, pruritus, and urticaria occurred, on average, two days later with SCBs compared to non-SCBs. Sexual/reproductive disorders were reported at a frequency of 0.23%. SCBs were reported as the cause more frequently than non-SCBs (59.8% vs. 40.2%, Fisher's exact test, p < 0.0001). (4) Conclusions: Based on real-world data, the safety profiles of ASMs were identified. The ADRs induced by SCBs exhibited different patterns when compared to those induced by non-SCBs.

Nurturing Hope: Reproductive Outcomes with Sinosomatics following Unsuccessful in vitro Fertilization Attempts.

INTRODUCTION: For women who have experienced failed attempts at in vitro fertilization (IVF) and face medical issues, leading to infertility, the renewed effort to seek fertility treatment, coupled with decreasing likelihood of success, can exert substantial emotional and physical strains. Consequently, many couples opt to discontinue treatment before attaining pregnancy. The objective of this study was to evaluate the reproductive outcomes in patients with unsuccessful prior IVF attempts who received a complementary treatment designed to alleviate emotional distress and burden. PATIENTS AND METHODS: A retrospective analysis of data from infertile patients who initiated the complementary intervention at a private clinic between January 2014 and December 2016 was conducted. Information on diagnosis, history of infertility, prior assisted reproductive technology treatments, mode of conception, and pregnancy outcomes were retrieved. RESULTS: The data of 133 patients with a history of one or more unsuccessful IVF treatments were analyzed. Patients had an average age of 36.7 years (±4.4 SD) and had been experiencing infertility for an average of 4.6 years (±2.7 SD). The two main causes of their infertility were endometriosis (36.1%, 48 patients) and diminished egg quality (31.6%, 42 patients). By May 2020, a significant proportion of the patients, 81.2% (108 patients), had achieved pregnancy, leading to 94 live births, which represents a 70.7% success rate. These pregnancies mostly resulted from natural cycle IVF (35.1%), donor cycles (23.4%), and conventional IVF (21.3%). The dropout rate was comparatively low at 23.3%. The median time from the start of complementary treatment to delivery was 18 months, with a range of 12-28 months. CONCLUSIONS: This study highlights the potential value of complementary treatment approaches in conjunction with standard medical care for women who have experienced unsuccessful IVF treatments in the past and thus face a reduced chance of motherhood. The reported 71% live birth rate is notably high, indicating that the inclusion of complementary treatments may provide women with past IVF failures a tangible opportunity for achieving successful pregnancy and childbirth. However, these findings need to be confirmed through randomized controlled studies.

Reproductive outcome after laparoscopic ovarian cystectomy using barbed sutures versus conventional smooth sutures: A retrospective cohort study.

OBJECTIVE: To investigate the effects of barbed and conventional sutures on reproductive outcomes and ovarian reserve after laparoscopic treatment for benign non-endometrioma ovarian cysts. METHODS: This retrospective study was conducted at an affiliated women's hospital between May 2017 and December 2019. Patients with benign non-endometriotic ovarian cysts undergoing laparoscopic cystectomy were included. RESULTS: Patients received barbed sutures (221 patients) or conventional smooth sutures (203 patients) intraoperatively. The two groups had comparable baseline characteristics. The surgical duration and ovarian suturing time were significantly shorter in the barbed suture group than in the conventional smooth suture group (P < 0.001 and P = 0.002, respectively). The rate of postoperative hemoglobin decline and serum anti-Müllerian hormone decline were similar between the two groups (P > 0.05). A total of 316 (74.53%) patients experienced at least one pregnancy postoperatively: 170 (76.92%) and 146 (71.92%) patients in the barbed suture and conventional smooth suture groups, respectively (χ2 = 1.395, P = 0.238). Multivariate Poisson regression demonstrated that barbed sutures had no significant effect on the overall postoperative pregnancy rate (adjusted incidence rate ratio, 1.10; 95% confidence interval, 0.93-1.36; P = 0.382). CONCLUSION: In patients with benign non-endometriotic ovarian cysts undergoing laparoscopic ovarian cystectomy, barbed sutures had a reproductive outcome similar to that of conventional smooth sutures while providing higher surgical efficiency without adverse effects on the postoperative ovarian reserve. Barbed sutures are probably a viable option to conventional smooth sutures.

Fertility preservation in adult male patients with cancer: a systematic review and meta-analysis.

STUDY QUESTION: Does sperm cryopreservation serve as a feasible and effective method for preserving fertility in adult male patients with cancer? SUMMARY ANSWER: Sperm cryopreservation is an effective fertility preservation method and may benefit patients with cancer. WHAT IS KNOWN ALREADY: Sperm cryopreservation is the only way to efficiently preserve male fertility. It is an important procedure in ART. Recently, due to remarkable advances in cancer treatment, an increasing number of studies have reported the outcomes of sperm cryopreservation in patients with cancer. STUDY DESIGN SIZE DURATION: We conducted an extensive literature search for relevant studies published through to 31 December 2021, in the following databases: CENTRAL, CNKI, Cochrane Systematic Reviews, EMBASE, MEDLINE, PUBMED, and Web of Science. The search terms used were '(cryopreservation OR freeze OR freezing OR banking OR cryostorage OR storage) AND (sperm OR semen OR spermatozoon) AND (cancer OR tumor OR malignancy OR neoplasm)'. PARTICIPANTS/MATERIALS SETTING METHODS: We included all studies that reported offering or attempting to cryopreserve sperm before or during cancer treatment in male patients considered at risk of treatment-related fertility impairment. We evaluated the eligibility of all data in each study. The major exclusion criteria were as follows: non-cancer patients; pediatric and adolescent cancer patients; not reporting the use of cryopreserved sperm; use of fresh semen for ART; not reporting the number of patients with cancer offered sperm cryopreservation or attempting to do so before or during treatment; using an experimental fertility preservation technique such as preservation of testicular tissue or spermatogonial stem cells; duplicate data; abstracts, case report, comments, reviews, or editorials; insufficient data reported. The quality of the included studies was assessed using the Newcastle-Ottawa scale and the Methodological Index for Non-Randomized Studies. MAIN RESULTS AND THE ROLE OF CHANCE: This meta-analysis included 69 non-randomized studies, with 32 234 patients referred for sperm analysis and 23 178 patients cryopreserving at least one sperm sample. The pooled failed-to-cryopreserve rate was 10% (95% CI, 8-12%), and the sperm disposal and sperm use rates were 23% (95% CI, 16-30%) and 9% (95% CI, 8-10%), respectively. The pregnancy, miscarriage, and delivery rates were 28% (95% CI, 22-33%), 13% (95% CI, 10-17%), and 20% (95% CI, 15-25%), respectively. Subgroup analysis showed higher pregnancy and delivery rates, as well as a lower failed-to-cryopreserve rate, in recent studies compared to those released a decade ago. The studies from Asia reported higher sperm disposal and pregnancy rates than in other continents. Our analysis showed clinical pregnancy rates per cycle of 34% (27-41%), 24% (14-35%), and 9% (5-15%) and delivery rates per cycle of 23% (17-30%), 18% (11-26%), and 5% (1-9%) for ICSI, IVF, and IUI, respectively. LIMITATIONS REASONS FOR CAUTION: As with all meta-analyses, some limitations should be considered. The first limitation of our study is that the data span 36 years. During this time, the World Health Organization has revised its sperm analysis standards, and other important changes have been made. There is also a limitation in that the outcome does not analyze the correlation between the type of cancer and sperm quality. Many of the earlier studies were limited by small sample sizes and a lack of control groups. Furthermore, almost all studies did not consider the severity of the disease, which could potentially have a substantial impact on the results. Consequently, further research should evaluate the effect of the type of cancer and, in particular, the severity of the condition on sperm quality in order to draw more precise conclusions. Similarly, it is inappropriate that most studies failed to differentiate between patients with different types of tumors and instead drew generalized conclusions that are presumed to apply to all patients with cancer. In the present analysis, we did not have in-depth information on patients' disease, and although extensive efforts were made to conduct a thorough systematic review and meta-analysis of the outcomes for patients with various types of tumors, the results must be acknowledged as being subject to bias. However, the use of average results obtained in each study, without the patient-level data, might also represent a source of bias. WIDER IMPLICATIONS OF THE FINDINGS: Sperm cryopreservation is an effective fertility preservation method and may benefit patients with cancer. The observed utilization rate of frozen sperm at 9% may underestimate the actual usage, as the short follow-up period is inadequate for obtaining comprehensive data on the use of frozen sperm in young cancer survivors. ART plays an important role in fertility preservation and the achievement of pregnancy, with this meta-analysis showing that ICSI delivers better clinical outcomes than IVF or IUI in patients with cancer undergoing fertility preservation. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Natural Science Foundation of China (grant no. 82001634, 81960550), and the China Postdoctoral Science Foundation (2019M661521). There are no competing interests to declare. REGISTRATION NUMBER: CRID 42022314460.

To transfer or not to transfer: the dilemma of mosaic embryos - a narrative review.

A frequent finding after preimplantation genetic diagnostic testing for aneuploidies using next-generation sequencing is an embryo that is putatively mosaic. The prevalence of this outcome remains unclear and varies with technical and external factors. Mosaic embryos can be classified by the percentage of cells affected, type of chromosome involvement (whole or segmental), number of affected chromosomes or affected cell type (inner mass cell, trophectoderm or both). The origin of mosaicism seems to be intrinsic as a post-zygotic mitotic error, but some external factors can play a role. As experience has increased with the transfer of mosaic embryos, clinical practice has gradually become more flexible in recent years. Nevertheless, clinical results show lower implantation, pregnancy and clinical pregnancy rates and higher miscarriage rates with mosaic embryo transfer when compared with the transfer of euploid embryos. Prenatal diagnosis is highly recommended after the transfer of mosaic embryos. This narrative review is intended to serve as reference material for practitioners in reproductive medicine who must manage a mosaic embryo result after preimplantation genetic testing for aneuploidies.

Reproductive outcomes in couples with recurrent pregnancy loss after embryonic chromosomal microarray analysis.

BACKGROUND: Chromosomal microarray analysis (CMA) has been widely applied to explore the genetic etiology in recurrent pregnancy loss (RPL). However, the reproductive prognosis in RPL couples with different types of chromosomally abnormal miscarriage remains unclear. OBJECTIVES: The main purpose of this study was to evaluate the reproductive prognosis among RPL couples after genetic testing in products of conception (POCs) by CMA. STUDY DESIGN: In this retrospective study, 1101 RPL couples referred for genetic testing in POCs by CMA. A total of 830 couples who met the inclusion criteria were followed up for at least 24 months after the index miscarriage. The rates of live birth and adverse pregnancy events in subsequent pregnancy and cumulative pregnancies were examined. RESULTS: For couples with three or more miscarriage, compared with those with chromosomally normal miscarriage, a significantly higher subsequent live birth rate was found in couples with chromosomally abnormal miscarriage (66.9% vs 71.6%, P = .040). However, differences in cumulative live birth rate among couples with chromosomally abnormal miscarriage and normal miscarriage were nonsignificant (82.7% vs 80.2%, P = .131). Women with advanced maternal age showed a significant decrease in the live birth rate (P < 0.01) and an increase in the miscarriage rate (P < 0.01) than those aged < 35 years old, regardless of whether the miscarriage was chromosomally normal or abnormal. RPL couples with chromosomally normal miscarriage showed a significant decrease in live birth rates in subsequent pregnancy and cumulative pregnancies, when they had experienced a large number of previous miscarriages; however, no significant difference was observed in those with chromosomally abnormal miscarriage. CONCLUSION: For women with three or more previous miscarriages, RPL couples with chromosomally normal miscarriage manifested a poorer reproductive prognosis than those with chromosomally abnormal miscarriage in subsequent pregnancy, while the cumulative live birth rate was similar. Advanced maternal age was a predictor of adverse pregnancy events, regardless of embryonic chromosomal results. Furthermore, among RPL women with large numbers of previous miscarriages, the supportive care and counselling regarding individual risk is necessary for those with chromosomally normal miscarriage.

Oncological and reproductive outcomes of conization combined with pelvic node evaluation in patients with early-stage cervical cancer: a systematic review and meta-analysis.

Objective: This study aims to preliminarily assess the oncological and reproductive outcomes of fertility preservation treatment using conization combined with pelvic node evaluation in young patients with early-stage cervical cancer (ECC) through meta-analysis. Methods: In this meta-analysis, we analyzed studies published in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials. gov that appeared in our search from inception to 0 7/02/2023. Results: There were 17 relevant studies with a total of 620 patients included, of which 444 patients received conization combined with pelvic node evaluation. The combined pregnancy rate was 45.4% (95% CI: 0.34-0.57), the combined live birth rate was 33.9% (95% CI: 0.26-0.42), the combined miscarriage rate was 4.8% (95% CI: 0.02-0.092), the combined preterm delivery rate was 5.1% (95% CI: 0.02-0.092), and the combined recurrence rate was 1.9% (95% CI: 0.006-0.035), which did not significantly differ from that of patients who received radical surgery (OR: 0.689, 95% CI: 0.506-0.938). Conclusion: Cervical conization combined with pelvic lymph node evaluation for fertility preservation in young ECC patients can achieve oncological outcomes similar to radical surgery while improving pregnancy success rates and preserving postoperative fertility. In summary, fertility preservation treatment using cervical conization combined with pelvic lymph node evaluation may be considered as a viable option for young ECC patients with strong fertility preservation desire, resulting in better pregnancy and live birth outcomes. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier PROSPERO (CRD42023423432).

Blastocyst quality and reproductive and perinatal outcomes: a multinational multicentre observational study.

STUDY QUESTION: Does the transfer of single low-grade blastocysts result in acceptable reproductive and perinatal outcomes compared to the transfer of single good-grade blastocysts? SUMMARY ANSWER: The transfer of single low-grade blastocysts resulted in a reduced live birth rate of around 30% (14% for very low-grade blastocysts) compared to 44% for single good-grade blastocysts, but does not lead to more adverse perinatal outcomes. WHAT IS KNOWN ALREADY: It is known that low-grade blastocysts can result in live births. However, the current studies are limited by relatively small sample sizes and single-centre designs. Furthermore, evidence on perinatal outcomes after transferring low-grade blastocysts is limited. STUDY DESIGN, SIZE, DURATION: We conducted a multi-centre, multi-national retrospective cohort study of 10 018 women undergoing 10 964 single blastocyst transfer cycles between 2009 and 2020 from 14 clinics across Australia, China, and New Zealand. PARTICIPANTS/MATERIALS, SETTING, METHODS: Blastocysts were graded individually based on assessment of the morphology and development of the inner cell mass (ICM) and trophectoderm (TE), and were grouped into three quality categories: good- (AB, AB, or BA), moderate- (BB), and low-grade (grade C for ICM or TE) blastocysts. CC blastocysts were individually grouped as very low-grade blastocysts. Logistic regression with generalized estimating equation was used to analyse the association between blastocyst quality and live birth as well as other reproductive outcomes. Binomial, multinomial logistic, or linear regression was used to investigate the association between blastocyst quality and perinatal outcomes. Odds ratio (OR), adjusted OR (aOR), adjusted regression coefficient, and their 95% CIs are presented. Statistical significance was set at P < 0.05. MAIN RESULTS AND THE ROLE OF CHANCE: There were 4386 good-grade blastocysts, 3735 moderate-grade blastocysts, and 2843 low-grade blastocysts were included in the analysis, for which the live birth rates were 44.4%, 38.6%, and 30.2%, respectively. Compared to good-grade blastocysts, the live birth rate of low-grade blastocysts was significantly lower (aOR of 0.48 (0.41-0.55)). Very low-grade blastocysts were associated with an even lower live birth rate (aOR 0.30 (0.18-0.52)) and their absolute live birth rate was 13.7%. There were 4132 singleton live births included in the analysis of perinatal outcomes. Compared with good-grade blastocysts, low-grade blastocysts had comparable preterm birth rates (<37 weeks, aOR 1.00 (0.65-1.54)), birthweight Z-scores (adjusted regression coefficient 0.02 (0.09-0.14)), and rates of very low birth weight (<1500 g, aOR 0.84 (0.22-3.25)), low birth weight (1500-2500 g, aOR 0.96 (0.56-1.65)), high birth weight (>4500 g, aOR 0.93 (0.37-2.32)), small for gestational age (aOR 1.63 (0.91-2.93)), and large for gestational age (aOR 1.28 (0.97-1.70)). LIMITATIONS, REASONS FOR CAUTION: Due to the nature of the retrospective design, residual confounding could not be excluded. In addition, the number of events for some perinatal outcomes was small. Between-operator and between-laboratory variations in blastocyst assessment were difficult to control. WIDER IMPLICATIONS OF THE FINDINGS: Patients undergoing IVF should be informed that low-grade blastocysts result in a lower live birth rate, however they do not increase the risk of adverse perinatal outcomes. Further research should focus on the criteria for embryos that should not be transferred and on the follow-up of long-term outcomes of offspring. STUDY FUNDING/COMPETING INTEREST(S): H.Z. is supported by a Monash Research Scholarship. B.W.J.M. is supported by a NHMRC Investigator grant (GNT1176437). R.W. is supported by an NHMRC Emerging Leadership Investigator grant (2009767). B.W.J.M. reports consultancy, travel support, and research funding from Merck. The other authors do not have competing interests to disclose. TRIAL REGISTRATION NUMBER: N/A.

Dataset for miRNA expression analysis in the peripheral white blood cells of beef heifers at weaning.

Subfertility in beef heifers leads to a substantial economic loss for producers and beef industry. To overcome this problem, producers require an efficient system to discriminate beef heifers with varying reproductive potential as early as possible. MicroRNAs are short non-coding RNAs that post-transcriptionally regulate gene expression. Herein, we profiled the miRNAs in peripheral white blood cells (PWBC) of beef heifers at weaning to investigate the differences in the beef heifers with varying reproductive outcomes. Blood samples from Angus-Simmental crossbred heifers were collected at weaning. The blood was processed to extract the PWBC pellet and was stored at -80 °C until further processing. After the synchronization of estrus and breeding protocol (artificial insemination (AI) followed by natural bull service) and pregnancy diagnosis, the heifers were categorized as fertile (pregnant to AI) or subfertile (not pregnant to AI or bull exposure). Total RNA was extracted from PWBC collected at the time of weaning from the fertile and subfertile heifers. After quality assessment, the total RNA was used to prepare libraries. The quality-checked libraries (n = 14; 7 samples per fertile and subfertile group) were pooled and sequenced (single-end 50 bp) using a NextSeq 500 platform. The raw sequence reads were analyzed using a bioinformatics workflow utilizing FastQC and MultiQC for quality control, Cutadapt for adapter trimming, miRDeep2 for alignment, and DESeq2 for differential expression analysis. The raw and normalized miRNA counts were deposited and made publicly available on the gene expression omnibus database (GEO; GSE225854). This is the first dataset investigating the miRNA expression level in PWBC at weaning in beef heifers to predict the future reproductive outcome. The results from the data presented here are reported in the research article titled "miRNA expression profiles of peripheral white blood cells from beef heifers with varying reproductive potential" [1].

The time interval between laparoscopic tubal ligation and frozen-thawed embryo transfer does not affect the reproductive outcomes.

BACKGROUND: Hydrosalpinx may decrease implantation and pregnancy rates after embryo transfer. Laparoscopic tubal ligation after embryo freeze and before frozen-thawed embryo transfer (FET) is effective at improving reproductive outcomes for hydrosalpinx patients. This study is to find out the optimal interval between laparoscopic tubal ligation and FET. METHODS: We retrospectively analyzed 259 infertile women who performed laparoscopic tubal ligation for embryo freeze and FET. Participants were divided into three groups, based on the interval between laparoscopic tubal ligation and FET. Group I: <30 days; Group II: 31- 60 days; Group III: >60 days. Outcomes of cleavage-stage and blastocyst-stage embryo FET were analyzed respectively. RESULTS: There was no significant difference in clinical pregnancy rate, live birth rate, implantation rate, biochemical pregnancy rate, ectopic pregnancy rate, miscarriage rate and preterm birth rate among the three groups, in both cleavage-stage and blastocyst-stage embryo FET cycles. In cleavage-stage embryo FET cycle, singleton gestational age was significantly younger in group III (38.11 ± 2.28 weeks) compared with group I (39.29 ± 1.06 weeks, P = 0.001) and group II (38.96 ± 1.05, P = 0.026). Singleton birth weight was significantly heavier in group II (3.65 ± 0.32 Kg) compared with group I (3.38 ± 0.29 Kg, P = 0.001) and group III (3.35 ± 0.60 Kg, P = 0.004). Twin birth weight was significantly heavier in group III (2.72 ± 0.43 Kg) compared to group I (2.23 ± 0.67 Kg, P = 0.002). In blastocyst-stage embryo FET cycles, twin gestational age was significantly younger in group II (34.07 ± 3.18 weeks) compared with group I (35.56 ± 2.27 weeks, P = 0.049) and group III (36.50 ± 1.47 weeks, P = 0.005). Twin birth weight was significantly heavier in group III (2.71 ± 0.39 Kg) compared to group II (2.39 ± 0.67 Kg, P = 0.009). CONCLUSIONS: The duration of the interval between laparoscopic tubal ligation and FET does not affect the reproductive outcomes; however, it may affect the neonate outcomes to some extent.

Reproductive outcomes of oocyte donation in patients with uterine Müllerian anomalies.

OBJECTIVE: To evaluate live-birth rates per embryo transfer in patients with uterine Müllerian anomalies (UMAs). Secondary objectives were to compare reproductive outcomes between the normal uterus group, the different UMA types, and UMA subgroups with and without required surgery. DESIGN: This retrospective study compared two cohorts, one with UMAs and other with normal uteri of our oocyte donation program at 12 Instituto Valenciano De Infertilidad/Reproductive Medicine Associates University affiliated clinics from January 2000 to 2020. The oocyte donation reduces confounding because of differences in embryo quality. The primary outcome was the live-birth rate per embryo transfer. Secondary outcomes included the rates of implantation, clinical pregnancy, miscarriage, and ongoing pregnancy. We calculated odds ratios with 95% confidence intervals. PATIENTS: Infertile women undergoing oocyte donation with UMAs. INTERVENTION: None. MAIN OUTCOME MEASURES: The rates of implantation, clinical pregnancy, miscarriage, ongoing pregnancy, and live birth. RESULTS: We analyzed 58,337 cycles of oocyte donation: 57,869 patients had no uterine malformation, and 468 women had UMAs. Compared with patients with normal uteri, patients with UMAs had lower rates of live births (36.67% [32.84-40.65] vs. 38.1% [95% confidence intervals {CI}: 37.82-38.42]) and ongoing pregnancy (39.74% [35.93-43.66] vs. 41.5% [41.24-41.83]). The miscarriage rate was higher in patients with UMAs (19.5% [16.55-22.85] vs. 16.6% [16.47-16.92]). Specifically, patients with a unicornuate uterus (n=29) had lower rates of implantation (24.07% [13.49-37.64] vs. 42.85% [95% CI: 42.6-43.09]), pregnancy (41.86% [27.01-57.87] vs. 59.51% [59.22-59.81]), ongoing pregnancy (16.67% [6.97-31.36] vs. 41.54% [41.24-41.83]), and live births (16.67% [6.97-31.36] vs. 38.12% [37.83-38.42]). In addition, patients with a partial septate uterus (n=91) had a higher miscarriage rate (26.50% [18.44-34.89] vs. 16.7% [16.47-16.92]). Compared with the normal uterus group, the live-birth rates were lower in the UMA without surgery group (33.09% [27.59-38.96] vs. 38.12% [37.83-38.42]). CONCLUSION: Among patients who received embryos derived from donated oocytes, live birth and ongoing pregnancy rates were lower in patients with UMAs compared with patients with normal uteri. A higher miscarriage rate was found in patients with UMAs. Patients with a unicornuate uterus had worse reproductive outcomes. Our results show that the uterus is less competent in patients with UMAs. TRIAL REGISTRATION: This study was registered at clinicaltrial.gov (NCT04571671).

Androgen and inhibin B levels during ovarian stimulation before and after 8 weeks of low-dose hCG priming in women with low ovarian reserve.

STUDY QUESTION: Does 8 weeks of daily low-dose hCG administration affect androgen or inhibin B levels in serum and/or follicular fluid (FF) during the subsequent IVF/ICSI cycle in women with low ovarian reserve? SUMMARY ANSWER: Androgen levels in serum and FF, and inhibin B levels in serum, decreased following 8 weeks of hCG administration. WHAT IS KNOWN ALREADY: Recently, we showed that 8 weeks of low-dose hCG priming, in between two IVF/ICSI treatments in women with poor ovarian responder (anti-Müllerian hormone (AMH) <6.29 pmol/l), resulted in more follicles of 2-5 mm and less of 6-10-mm diameter at the start of stimulation and more retrieved oocytes at oocyte retrieval. The duration of stimulation and total FSH consumption was increased in the IVF/ICSI cycle after priming. Hypothetically, hCG priming stimulates intraovarian androgen synthesis causing upregulation of FSH receptors (FSHR) on granulosa cells. It was therefore unexpected that antral follicles were smaller and the stimulation time longer after hCG priming. This might indicate a different mechanism of action than previously suggested. STUDY DESIGN, SIZE, DURATION: Blood samples were drawn on stimulation day 1, stimulation days 5-6, trigger day, day of oocyte retrieval, and oocyte retrieval + 5 days in the IVF/ICSI cycles before and after hCG priming (the control and study cycles, respectively). FF was collected from the first aspirated follicle on both sides during oocyte retrieval in both cycles. The study was conducted as a prospective, paired, non-blinded, single-center study conducted between January 2021 and July 2021 at a tertiary care center. The 20 participants underwent two identical IVF/ICSI treatments: a control cycle including elective freezing of all blastocysts and a study cycle with fresh blastocyst transfer. The control and study cycles were separated by 8 weeks (two menstrual cycles) of hCG priming by daily injections of 260 IU recombinant hCG. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 18-40 years with cycle lengths of 23-35 days and AMH <6.29 pmol/l were included. Control and study IVF/ICSI cycles were performed in a fixed GnRH-antagonist protocol. MAIN RESULTS AND THE ROLE OF CHANCE: Inhibin B was lower on stimulation day 1 after hCG priming (P = 0.05). Dehydroepiandrosterone sulfate (DHEAS) was significantly lower on stimulation day 1 (P = 0.03), and DHEAS and androstenedione were significantly lower on stimulation days 5-6 after priming (P = 0.02 and P = 0.02) The testosterone level in FF was significantly lower in the study cycle (P = 0.008), while the concentrations of inhibin B and androstenedione in the FF did not differ between the study and control cycles. A lower serum inhibin B in the study cycle corresponds with the antral follicles being significantly smaller after priming, and this probably led to a longer stimulation time in the study cycle. This contradicts the theory that hCG priming increases the intraovarian androgen level, which in turn causes more FSHR on developing (antral up to preovulatory) follicles. However, based on this study, we cannot rule out that an increased intra-follicular androgen level was present at initiation of the ovarian stimulation, without elevating the androgen level in serum and that an increased androgen level may have rescued some small antral follicles that would have otherwise undergone atresia by the end of the previous menstrual cycle. We retrieved significantly more oocytes in the Study cycle, and the production of estradiol per follicle ≥10-mm diameter on trigger day was comparable in the study and control cycles, suggesting that the rescued follicles were competent in terms of producing oocytes and steroid hormones. LIMITATIONS, REASONS FOR CAUTION: The sample size was small, and the study was not randomized. Our study design did not allow for the measurement and comparison of androgen levels or FSHR expression in small antral follicles before and immediately after the hCG-priming period. WIDER IMPLICATIONS OF THE FINDINGS: The results make us question the mechanism of action behind hCG priming prior to IVF. It is important to design a study with the puncture of small antral follicles before and immediately after priming to investigate the proposed hypothesis. Improved cycle outcomes, i.e. more retrieved oocytes, must be confirmed in a larger, preferably randomized study. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by an unrestricted grant from Gedeon Richter awarded to the institution. A.P. reports personal consulting fees from PregLem SA, Novo Nordisk A/S, Ferring Pharmaceuticals A/S, Gedeon Richter Nordics AB, Cryos International, and Merck A/S outside the submitted work and payment or honoraria for lectures from Gedeon Richter Nordics AB, Ferring Pharmaceuticals A/S, Merck A/S, and Theramex and Organon & Co and payment for participation in an advisory board for Preglem. Grants to the institution have been provided by Gedeon Richter Nordics AB, Ferring Pharmaceuticals A/S, and Merck A/S, and equipment and travel support has been given to the institution by Gedeon Richter Nordics AB. The remaining authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04643925.

Upgrading Treatment and Molecular Diagnosis in Endometrial Cancer-Driving New Tools for Endometrial Preservation?

One emerging problem for onco-gynecologists is the incidence of premenopausal patients under 40 years of age diagnosed with stage I Endometrial Cancer (EC) who want to preserve their fertility. Our review aims to define a primary risk assessment that can help fertility experts and onco-gynecologists tailor personalized treatment and fertility-preserving strategies for fertile patients wishing to have children. We confirm that risk factors such as myometrial invasion and The International Federation of Gynecology and Obstetrics (FIGO) staging should be integrated into the novel molecular classification provided by The Cancer Genome Atlas (TCGA). We also corroborate the influence of classical risk factors such as obesity, Polycystic ovarian syndrome (PCOS), and diabetes mellitus to assess fertility outcomes. The fertility preservation options are inadequately discussed with women with a diagnosis of gynecological cancer. A multidisciplinary team of gynecologists, oncologists, and fertility specialists could increase patient satisfaction and improve fertility outcomes. The incidence and death rates of endometrial cancer are rising globally. International guidelines recommend radical hysterectomy and bilateral salpingo-oophorectomy as the standard of care for this cancer; however, fertility-sparing alternatives should be tailored to motivated women of reproductive age, establishing an appropriate cost-benefit balance between childbearing desire and cancer risk. New molecular classifications such as that of TCGA provide a robust supplementary risk assessment tool that can tailor the treatment options to the patient's needs, curtail over- and under-treatment, and contribute to the spread of fertility-preserving strategies.

Comparative analysis of the clinical efficacy and reproductive outcomes of the hysteroscopic tissue removal system (MyoSure) and hysteroscopic electroresection in the treatment of benign intrauterine lesions.

OBJECTIVE: To compare and analyze the clinical efficacy and reproductive outcomes of the hysteroscopic tissue removal system (MyoSure) and hysteroscopic electroresection in the treatment of benign intrauterine lesions in women of reproductive age. METHODS: This is a retrospective study of patients with benign intrauterine lesions treated with MyoSure or hysteroscopic electroresection. The primary outcomes were operative time and resection completeness, and reproductive outcomes were followed up and compared. Secondary outcomes included perioperative adverse events and postoperative adhesions seen during second-look hysteroscopy. Data analysis was performed using χ2 and Fisher tests for qualitative variables and Student t-test for quantitative variables. RESULTS: The operative times of patients with type 0 or I myoma, endometrial polyps, or retained products of conception in the MyoSure group were shorter than those in the electroresection group but were not significantly different for patients with type II myomas. The complete resection rate was lower in the MyoSure group than in the electroresection group. The degree of decrease in the American Fertility Society score of intrauterine adhesion in the MyoSure group was significantly higher (2.90 ± 1.29 points vs 1.31 ± 0.89 points, P = 0.025). The time to pregnancy and the pregnancy rate were higher in the MyoSure group (13.14 ± 7.85 months vs 16.26 ± 8.22 months, P = 0.040; 65.12% vs 54.55%, P = 0.045), but there was no significant difference in the term live birth rate, premature birth rate, or abortion rate between the two groups. CONCLUSION: MyoSure has advantages of a shortened operative time and improvement in reproductive outcomes such as pregnancy rate. However, for type II myomas, MyoSure has limitations, and a comprehensive evaluation before the procedure is required.

Pregnancy Outcomes after Uterus-sparing Operative Treatment for Adenomyosis: A Systematic Review and Meta-analysis.

OBJECTIVE: A meta-analysis was conducted to evaluate the overall pregnancy outcomes after uterus-sparing operative treatment in patients with adenomyosis (AD). DATA SOURCES: We searched PubMed, Web of Science, Cochrane Library, and Embase for literature from January 2000 to January 2022. METHODS OF STUDY SELECTION: We included all studies reporting reproductive outcomes of uterine-sparing surgery for patients with AD with fertility requirements. Surgical treatment was classified as complete excision or incomplete removal of AD and nonexcisional techniques for induction of necrosis in AD. The latter included physically removing the tissue where pathology is present or disrupting the blood flow to the affected area, involving high-intensity focused ultrasound, microwave ablation, radiofrequency ablation, and uterine artery embolization. Two independent researchers performed study selection according to the screening criteria. TABULATION, INTEGRATION, AND RESULTS: A total of 13 studies with 1319 patients with AD were included in this study, comprising 795 women wishing fertility. Pooled estimates of pregnancy, miscarriage, and live-birth rates after excisional treatment for women attempting to conceive were 40% (95% confidence interval [CI], 29-52), 21% (95% CI, 16-27), and 70% (95% CI, 64-76), respectively, and corresponding rates after nonexcisional treatment were 51% (95% CI, 42-60), 22% (95% CI, 13-34), and 71% (95% CI, 57-83), respectively. The differences were not statistically significant. CONCLUSION: Excisional treatment could be a treatment consideration for patients with symptomatic AD and infertility for several years or repeated failure of assisted reproductive technology. Nonexcisional techniques may be considered probably for AD-related infertility.

Eight weeks of androgen priming by daily low-dose hCG injections before ICSI treatment in women with low ovarian reserve.

STUDY QUESTION: Does 8 weeks of continuous low-dose hCG administration increase the proportion of antral follicles that reach the preovulatory state during ovarian stimulation (OS) in women with low ovarian reserve? SUMMARY ANSWER: The proportion of antral follicles (2-10 mm) that reached the preovulatory state did not increase. WHAT IS KNOWN ALREADY: The administration of androgens prior to OS might upregulate FSH receptor (FSHR) expression on granulosa cells, making follicles more responsive to exogenous FSH stimulation during OS. LH and hCG stimulate the local follicular androgen synthesis in theca cells and may be used as an endogenous androgen priming method. Exogenous priming by testosterone and dehydroepiandrosterone (DHEA) have been shown to increase the number of retrieved oocytes and live birth rate but the studies are small, and their use is associated with side effects. STUDY DESIGN, SIZE, DURATION: A prospective, paired, non-blinded single-center study including 20 women serving as their own controls conducted between January 2021 and July 2021 at The University Hospital Copenhagen Rigshospitalet, Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants underwent two identical consecutive IVF/ICSI treatments, a Control cycle and a Study cycle, separated by ∼8 weeks (two menstrual cycles) of daily injections of 260 IU recombinant hCG (rhCG). A freeze-all strategy was applied in the Control cycle. Both IVF/ICSI cycles were performed in a fixed GnRH antagonist protocol using a daily dose of 300 IU recombinant FSH (rFSH) and GnRH antagonist 0.25 mg from stimulation days 5-6. MAIN RESULTS AND THE ROLE OF CHANCE: Follicular output rate, defined as the number of follicles >16 mm on hCG trigger day divided by the antral follicle count (2-10 mm) at baseline, did not increase after 8 weeks of hCG priming (P = 0.8). The mean number of oocytes retrieved was significantly higher after the hCG priming being 4.7 (2.8) vs 3.2 (1.7) in the Study and Control cycle, respectively (P = 0.01). The duration of stimulation was longer in the Study versus the Control cycle (P = 0.05), despite the use of identical hCG trigger criterion and similar diameters of the three biggest follicles on hCG trigger day in the two cycles (P = 0.9). LIMITATIONS, REASONS FOR CAUTION: The sample size was small, and the number of oocytes retrieved was not the primary endpoint. Larger studies are needed to confirm this finding. WIDER IMPLICATIONS OF THE FINDINGS: Long-term, low-dose rhCG administration may increase the number of oocytes retrieved during IVF/ICSI in women with low ovarian reserve, but more research is needed before firm conclusions can be drawn. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by an unrestricted grant from Gedeon Richter. A.P. reports personal consulting fees from PregLem SA, Novo Nordisk A/S, Ferring Pharmaceuticals A/S, Gedeon Richter Nordics AB, Cryos International, and Merck A/S outside the submitted work and payment or honoraria for lectures from Gedeon Richter Nordics AB, Ferring Pharmaceuticals A/S, Merck A/S, and Theramex and Organon & Co. Grants to the institution have been provided by Gedeon Richter Nordics AB, Ferring Pharmaceuticals A/S, and Merck A/S and receipt of equipment by the institution from Gedeon Richter Nordics AB is reported. The remaining authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04643925.

Short-Term and Long-Term Outcomes of Fetal Ventriculomegaly beyond Gestational 37 Weeks: A Retrospective Cohort Study.

Birth defects have brought about major public health problems, and studying the clinical outcomes of the most common prenatal central nervous system abnormality, namely, fetal ventriculomegaly (VM), is helpful for improving reproductive health and fertility quality. This is a retrospective cohort study from 2011 to 2020 in the West China Second University Hospital, Sichuan University, aiming to evaluate the short-term and long-term outcomes of VM over 37 weeks' gestation to exclude the influence of preterm birth. The study analyzed data from 401 term pregnancies, with 179 VM and 222 controls. From the short-term outcomes, the rate of the neonatal intensive care unit (NICU) admission under the VM group (10.06%) was comparatively higher than the control (0.45%), but Apgar scores between both groups at 1 min, 5 min and 10 min were not significantly different. From the long-term outcomes, there were more infants with abnormal neurodevelopment under the VM group than control (14.53% vs. 2.25%, p < 0.001). In addition, NICU admission (p = 0.006), peak width of lateral ventricles (p = 0.030) and postnatal cranial ultrasound suggestive with VM (p = 0.002) were related to infants' long-term outcomes. NICU admission during the perinatal period was an independent risk factor for the adverse long-term outcomes (OR = 3.561, 95% CI 1.029-12.320, p = 0.045). In conclusion, VM impairs short-term and long-term outcomes of term infants. Short-term outcome, especially NICU admission, could predict their adverse long-term outcomes.

The Impact of Chronic Endometritis on Infertility: Prevalence, Reproductive Outcomes, and the Role of Hysteroscopy as a Screening Tool.

OBJECTIVES: The objective of this study was to examine the prevalence of chronic endometritis (CE) in infertile women, its impact on reproductive outcomes, and the accuracy of hysteroscopy as a screening tool for CE. DESIGN: This was a prospective observational study. PARTICIPANTS: Participants involved in this study were 514 asymptomatic patients with infertility. SETTING: The review was conducted in a tertiary care center. METHODS: The participants underwent a hysteroscopy and endometrial biopsy (EMB). Antibiotics were given for cases of CE. We investigated the prevalence of CE in patients starting assisted reproductive technologies (ART) as a primary outcome. Secondary outcomes were the clinical pregnancy rate (CPR) in the ART cycle after hysteroscopy, EMB, and antibiotic treatment in cases of CE; the cumulative CPR in the subsequent 2 years after hysteroscopy and EMB; the sensitivity and specificity of hysteroscopy as a screening tool compared to EMB as the "gold standard" for diagnosing CE. RESULTS: CE was identified in 2.8% of patients starting ART (11/393). CPRs did not differ significantly between patients with CE and the entire cohort of patients without CE in the subsequent ART cycle (OR: 0.43; 95% CI: 0.09-2.02) or in the 2 years after EMB (OR: 0.56; 95% CI: 0.16-1.97). In a matched control comparison (with matching for age, basal FSH, and cause of infertility), CPR in patients with CE did not differ in the subsequent ART cycle (OR: 0.39; 95% CI: 0.09-1.61); however, their CPR in the 2 years after EMB was significantly lower (OR: 0.22; 95% CI: 0.13-0.38). The sensitivity and specificity of hysteroscopy as a screening tool for diagnosing CE were 8.3% and 90.1%, respectively. LIMITATIONS: Due to our cohort's low CE prevalence, we could not detect significant differences in CPRs. CONCLUSION: CE is rare in our studied population of asymptomatic patients starting ART. Hysteroscopy cannot replace EMB for diagnosing CE.

Evaluation of clinical and subclinical endometritis impacts on the reproductive performance and milk production of dairy cows in Brazilian herds.

Clinical endometritis (CE) and subclinical endometritis (SE) are two of the main uterine diseases in dairy cows during the puerperium period that can directly affect milk production and fertility in dairy herds. The first objective of this study was to investigate the effects of the CE and SE on the subsequent reproductive performance and milk production of dairy cows in Brazilian herds, and the second objective was to evaluate the reproductive performance and milk production of dairy cows according to the positive or negative isolation of bacteria in the uterine environment. A total of 279 lactating Holstein dairy cows (28-33 days in milk) from six commercial farms were studied. These were classified into three groups: healthy cows (without CE and SE, n = 161), cows with CE (vaginal discharge score = 3 and ≥18% PMNL, n = 83) and cows with SE (absence of signs of CE and >18% PMNL, n = 35). According to the presence of bacteria isolated from the uterine environment, the animals were classified as healthy cows (n = 161), CE cows with positive (n = 68) and negative (n = 15) bacterial isolation; and SE cows with positive (n = 21) and negative (n = 14) bacterial isolation. Cows with CE (20.5%) and SE (31.4%) had a lower (p < .05) conception rate at first AI than healthy cows (47.8%). Furthermore, both cows with CE (3.1) and SE (2.8) needed more service to become pregnant than healthy cows (1.7) and more days to be pregnant (50.3 days in CE and 43.1 days in SE than healthy group; p < .001). Cows with CE (23.8 kg) and SE (23.7 kg) produced less milk than healthy cows on the day of sampling (28.2 kg); however, milk production during 305 DIM of cows with CE and SE was not impaired when compared to healthy cows. The logistic regression showed that parity, body condition score, 305 days milk production, last calving (eutocia or dystocia), twin birth and stillbirth were not associated with the incidence of CE and SE. In addition, we highlight that cows with CE and SE, but with negative bacteria isolation, did not have reproductive performance and milk production impaired during the postpartum period. These results support that the use of antibiotics would not be beneficial in these cows, contributing to the strategic and rational use of antibiotic therapy on dairy farms.