Intrauterine adhesion in ultrasound-guided manual vacuum aspiration (USG-MVA) versus electric vacuum aspiration (EVA): a randomised controlled trial.

BACKGROUND: Intrauterine adhesion (IUA) can arise as a potential complication following uterine surgery, as the surgical procedure may damage the endometrial stratum basalis. The objective of this study was to assess and compare the occurrence of IUA in women who underwent ultrasound-guided manual vacuum aspiration (USG-MVA) versus electric vacuum aspiration (EVA) for managing first-trimester miscarriage. METHODS: This was a prospective, single-centre, randomised controlled trial conducted at a university-affiliated tertiary hospital. Chinese women aged 18 years and above who had a delayed or incomplete miscarriage of ≤ 12 weeks of gestation were recruited in the Department of Obstetrics and Gynaecology at the Prince of Wales. Recruited participants received either USG-MVA or EVA for the management of their miscarriage and were invited for a hysteroscopic assessment to evaluate the incidence of IUA between 6 and 20 weeks after the surgery. Patients were contacted by phone at 6 months to assess their menstrual and reproductive outcomes. RESULTS: 303 patients underwent USG-MVA or EVA, of whom 152 were randomised to 'USG-MVA' and 151 patients to the 'EVA' group. Out of the USG-MVA group, 126 patients returned and completed the hysteroscopic assessment, while in the EVA group, 125 patients did the same. The incidence of intrauterine adhesion (IUA) was 19.0% (24/126) in the USG-MVA group and 32.0% (40/125) in the EVA group, showing a significant difference (p < 0.02) between the two groups. No significant difference in the menstrual outcomes at 6 months postoperatively between the two groups but more patients had miscarriages in the EVA group with IUA. CONCLUSIONS: IUAs are a possible complication of USG-MVA. However, USG-MVA is associated with a lower incidence of IUA postoperatively at 6-20 weeks. USG-MVA is a feasible, effective, and safe alternative surgical treatment with less IUA for the management of first-trimester miscarriage. TRIAL REGISTRATION: The study was registered with the Centre for Clinical Research and Biostatics- Clinical Trials Registry (CCRBCTR), which is a partner registry of the WHO Primary Registry-Chinese Clinical Trials Registry (ChiCTR) (Unique Trial Number: ChiCTR1900023198 with the first trial registration date on 16/05/2019).

Incidence of intrauterine adhesion after ultrasound-guided manual vacuum aspiration (USG-MVA) for first-trimester miscarriages: a prospective cohort study.

PURPOSE: Ultrasound-guided manual vacuum aspiration (USG-MVA) is a feasible and effective outpatient treatment to treat early pregnancy loss. METHODS: This was a prospective observational study at a university-affiliated hospital. All women undergoing either a USG-MVA or electric vacuum aspiration (EVA) were invited to return 3-6 months later for follow-up at which women completed a questionnaire to document their post-evacuation menstrual and reproductive history, and underwent a hysteroscopy if they were not pregnant. The severity of intrauterine adhesion (IUA), if present, was graded (Stage I-III) according to the American fertility society classification. RESULTS: A total of 292 women had a hysteroscopy after their initial surgical evacuation, USG-MVA 169(57.9%) versus EVA 123(42.1%). Women undergoing EVA as opposed to a USG-MVA had a 12.9% higher incidence of IUA (24.1% vs. 37.0%, p = 0.042) equivalent to 1.84 times higher risk (95% CI 1.01-3.34; p = 0.048). Women having EVA continued to show an increased but not statistically significant trend towards an increased risk of IUA after adjusting for the type of miscarriage (aOR = 1.3; 95% CI 0.66-2.50; p = 0.46). CONCLUSION: There were no significant differences in their reproductive outcomes and fewer women post-USG-MVA complained of hypomenorrhea. IUA may still occur in women undergoing USG-MVA but it is lower than the rate in women undergoing EVA. Clinical trials registry The trial was registered with the Centre for Clinical Research and Biostatistics - Clinical Trials Registry (CCRBCTR), a partner registry of the WHO Primary Registry-Chinese Clinical Trials Registry (ChiCTR) with a Unique Trial Number: CUHK_CCRB00541 on 22 Dec 2016.

Mate-pair genome sequencing reveals structural variants for idiopathic male infertility.

Currently, routine genetic investigation for male infertility includes karyotyping analysis and PCR for Y chromosomal microdeletions to provide prognostic information such as sperm retrieval success rate. However, over 85% of male infertility remain idiopathic. We assessed 101 male patients with primary infertility in a retrospective cohort analysis who have previously received negative results from standard-of-care tests. Mate-pair genome sequencing (large-insert size library), an alternative long-DNA sequencing method, was performed to detect clinically significant structural variants (SVs) and copy-number neutral absence of heterozygosity (AOH). Candidate SVs were filtered against our in-house cohort of 1077 fertile men. Genes disrupted by potentially clinically significant variants were correlated with single-cell gene expression profiles of human fetal and postnatal testicular developmental lineages and adult germ cells. Follow-up studies were conducted for each patient with clinically relevant finding(s). Molecular diagnoses were made in 11.1% (7/63) of patients with non-obstructive azoospermia and 13.2% (5/38) of patients with severe oligozoospermia. Among them, 12 clinically significant SVs were identified in 12 cases, including five known syndromes, one inversion, and six SVs with direct disruption of genes by intragenic rearrangements or complex insertions. Importantly, a genetic defect related to intracytoplasmic sperm injection (ICSI) failure was identified in a patient with non-obstructive azoospermia, illustrating the additional value of an etiologic diagnosis in addition to determining sperm retrieval rate. Our study reveals a landscape of various genomic variants in 101 males with idiopathic infertility, not only advancing understanding of the underlying mechanisms of male infertility, but also impacting clinical management.

Ultrasound-guided Manual Vacuum Aspiration is an optimal method for obtaining products of conception from early pregnancy loss for cytogenetic testing.

OBJECTIVE: The culture failure rate of conventional karyotyping in products of conception evacuated from early pregnancy loss by traditional electrical vacuum aspiration and/or dilation & curettage remains high. We aim to determine whether obtaining products of conception from early pregnancy loss via another evacuation approach, ultrasound-guided manual vacuum aspiration, could decrease the culture failure rate of karyotyping. METHODS: For patients with early pregnancy loss, ultrasound-guided manual vacuum aspiration (Case group) and traditional electrical vacuum aspiration and/or dilation & curettage (Control group) were applied as surgical methods for pregnancy loss management respectively. The evacuated products of conception were subjected to cytogenetic karyotyping analysis. The primary outcome was the culture failure rate of karyotyping. Secondary outcomes included the chromosomal abnormality spectrum, maternal cell contamination, and complications from the manual vacuum aspiration procedure. RESULTS: For the case group, 132 products of conception were genetically analyzed by conventional karyotyping. The culture failure rate was significantly lower than that of the control cohort (2.3% vs 7.4%, p = 0.027). 65.2% of cases were abnormal within the detection scope of karyotyping. The euploid female to male ratio was 0.82 (18:22), suggesting a lower likelihood of maternal cell contamination. The efficacy in achieving complete evacuation was 99.6%. There were no significant complications from the procedure. CONCLUSION: Ultrasound-guided manual vacuum aspiration approach significantly decreased the culture failure rate of karyotyping and decreased maternal cell contamination tendency, enabling a high and accurate cytogenetic diagnosis. It is especially crucial when the cytogenetic analysis is required in the early pregnancy loss clinics.

Hyoscine butylbromide in pain reduction associated with ultrasound-guided manual vacuum aspiration: a randomized placebo-controlled trial.

RESEARCH QUESTION: What is the effect of adding an anti-spasmodic drug to an existing ultrasound-guided manual vacuum aspiration (USG-MVA) protocol to alleviate immediate post-procedure abdominal cramping pain in women treated for early pregnancy loss? DESIGN: Double-blind, placebo-controlled, randomized controlled trial conducted between February 2018 and January 2020. Participants were assigned to receive a 1-ml intravenous injection containing 20-mg hyoscine butylbromide (HBB) (n=55) or saline (n =56) as a control immediately before USG-MVA. Primary outcome was reduced abdominal pain after adding a 20-mg dose of HBB to the current pain control regimen. Secondary outcomes were vaginal pain, complications and side-effects, women's pre- and post-procedure psychological state, physiological stress (saliva alpha-amylase) and procedure pain control satisfaction. Two-way mixed ANOVA was used to evaluate the main effects and interactions. RESULTS: VAS abdominal pain scores in the HBB group were 16% lower immediately after and 21% lower 2 h after surgery (not statistically significant). Two-way ANOVA indicated that time (F[1108] = 83.41, P < 0.001) was the only significant main effect for reduced abdominal pain after the procedure and vaginal pain score (F[1108] = 180.1, P < 0.0001) but not drug received. No adverse events were reported. No significant difference was found for psychological state, physiological stress and procedure pain control satisfaction between the two groups. CONCLUSIONS: Anti-spasmodic drugs can help to reduce abdominal cramping pain associated with USG-MVA; HBB produced an insignificant decrease in abdominal pain score. Further studies with longer acting or larger doses of anti-spasmodic drugs are warranted.

Ovarian reserve and recurrence 1 year post-operatively after using haemostatic sealant and bipolar diathermy for haemostasis during laparoscopic ovarian cystectomy.

RESEARCH QUESTION: Is there a difference in the ovarian reserve 1 year post-operatively in those who used a haemostatic sealant or bipolar diathermy for haemostasis during laparoscopic ovarian cystectomy for ovarian endometriomas? DESIGN: This was an extended follow-up observational study of a previous randomized controlled trial where women aged 18 to 40 years with 3-8 cm unilateral or bilateral endometriomas were randomized to receive haemostasis by a haemostatic sealant or bipolar diathermy following ovarian cystectomy. The primary outcome was the ovarian reserve as assessed by antral follicle count (AFC) 1 year post-operatively. Secondary outcomes included the recurrence rate of ovarian endometrioma, the change in anti-Müllerian hormone (AMH) and FSH concentrations, and reproductive outcomes. RESULTS: The significant increase in AFC at 3 months after initial surgery (P = 0.025) in the haemostatic sealant group compared with the diathermy group was sustained at 1 year (P = 0.024) but there was no difference in AMH or FSH concentrations between the groups throughout the follow-up period. The recurrence rate in the FloSeal group was 7.7% (n = 3/39) compared with 22.2% (n = 8/36) in the diathermy group (P = 0.060). The recurrence rate in women who had bilateral lesions was significantly higher than those with unilateral lesions (risk ratio 5.33, interquartile range 1.55-18.38). No difference in reproductive outcomes was found between the two groups. CONCLUSIONS: Applying haemostatic sealant after laparoscopic cystectomy of ovarian endometriomas produces a significantly greater improvement in AFC, which was apparent at 3-month follow-up, and was sustained at 1-year follow-up without compromising the recurrence rate.

Endometrium imaging using real-time rotational optical coherence tomography imaging system: A pilot, prospective and ex-vivo study.

This study aimed to evaluate a novel real-time rotational optical coherence tomography (OCT) imaging system (OCTIS) with a fiber-optic probe to look at endometrium and to correlate the OCTIS images with standard histology. OCT could obtain real-time images resembling histological examination. With recent development of customized probes, it allows OCT to be used in the field of gynecology.This is a pilot, prospective, ex-vivo and observational study. Women underwent hysterectomy for various gynecological conditions were recruited and OCTIS images were obtained from endometrium of 15 fresh uterus specimens immediately after hysterectomy. The excised uterus was cut open and OCTIS imaging was obtained. The scanned region of endometrium was excised for histological examination and OCTIS images were precisely compared to corresponding histological images and ultrasound images. Blinded qualitative analysis on OCTIS images was performed by 2 assessors to determine inter-rating reliability on the histopathological diagnosis.Epithelium, glands, cysts, and stroma of endometrium were clearly seen by the OCTIS. Different phases of menstrual cycle of normal endometrium could be differentiated and pathological condition such as hyperplastic and dysplasic endometrium, which corresponded well with histological findings, could be identified. The inter-rater reliability between assessors on overall OCTIS endometrium and neoplastic OCTIS endometrium was moderate (Kendall τb of 0.58) and substantial (Kendall τb of 0.76), respectively.OCTIS can provide real-time, high-resolution and rotational imaging modality to view endometrial structure with high consistency with histological examination and satisfactory agreement between observers. It has a great potential to be developed in the clinical use of endometrial assessment for gynecological applications.

A double-blinded, randomized placebo-controlled trial on the effect of traditional Chinese medicine formula Wuzi Yanzong pill on improving semen qualities in men with suboptimal parameters.

BACKGROUND: In Hong Kong, one of six couples is affected by subfertility problems. Male infertility contributes to half of the infertility cases. In male infertility, there is no effective treatment for patients with idiopathic infertility/poor semen parameters. Recent meta-analysis results suggest that a traditional Chinese medicine (TCM) formula - Wuzi Yanzong pill - showed a curative effect on male fertility. However, the heterogeneity of the studies could not draw a definitive conclusion on the therapeutic effect of this formula. The aim of this study is to conduct a well-designed randomized controlled trial to investigate the effect of TCM formula Wuzi Yanzong pill on improving semen qualities in men with suboptimal parameters. METHODS: This study is a double-blinded, randomized placebo-controlled trial conducted in a public hospital in Hong Kong. Participants will be randomized, using computer-generated random numbers, with a 1:1 ratio to either the Wuzi Yanzong pill formula group or the placebo group. Both groups will be administered the drugs for 12 weeks. Participants will have a total of four visits for their semen and blood assessments for a 6-month period, and we will follow up for another 6 months to record their conception outcome. The primary outcome is to compare the total motile sperm count, natural conception rate, and pregnancy outcome to those under placebo treatment. Secondary objectives are sperm functions and assisted reproductive technology outcome. DISCUSSION: To date, there are no studies using the disclosed Wuzi Yanzong formula or double-blinded, randomized trials. The Wuzi Yanzong TCM formula may provide a good clinical solution for subfertile males for which contemporary western medicine has no cure. Therefore, a well-designed randomized trial for evaluating the effect of Wuzi Yanzong TCM formula is urgently needed. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR-INR-17010790 . Registered on 27 February 2017. Centre for Clinical Research and Biostatistics - Clinical Trials Registry, CUHK_CCRB00548 . Registered on 27 February 2017.

Endometrial microbiota in infertile women with and without chronic endometritis as diagnosed using a quantitative and reference range-based method.

OBJECTIVE: To systematically compare the endometrial microbiota in infertile women with and without chronic endometritis (CE), as diagnosed by a quantitative and reference range-based method. DESIGN: Case-control observational study. SETTING: University-affiliated hospital. PATIENT(S): One hundred and thirty infertile women. INTERVENTION(S): Endometrial biopsy and fluid (uterine lavage, UL) collected precisely 7 days after LH surge, with plasma cell density (PCD) determined based on Syndecan-1 (CD138)-positive cells in the entire biopsy section and culture-independent massively parallel sequencing of the 16S ribosomal RNA gene performed on both the CE and non-CE endometrial fluid samples. MAIN OUTCOME MEASURE(S): Relative abundance of bacterial taxa. RESULT(S): Chronic endometritis was diagnosed if the PCD was above the 95th percentile (>5.15 cells per 10 mm2) of the reference range in fertile control subjects. With this stringent diagnostic criterion, 12 women (9%) were diagnosed with CE. Sequencing was successfully performed on all endometrial samples obtained by UL) (CE, n = 12; non-CE, n = 118). The median relative abundance of Lactobacillus was 1.89% and 80.7% in the CE and non-CE microbiotas, respectively. Lactobacillus crispatus was less abundant in the CE microbiota (fold-change, range: 2.10-2.30). Eighteen non-Lactobacillus taxa including Dialister, Bifidobacterium, Prevotella, Gardnerella, and Anaerococcus were more abundant in the CE microbiota (fold-change, 2.10-18.9). Of these, Anaerococcus and Gardnerella were negatively correlated in relative abundance with Lactobacillus (SparCC correlation magnitude, range: 0.142-0.177). CONCLUSION(S): Chronic endometritis was associated with a statistically significantly higher abundance of 18 bacterial taxa in the endometrial cavity. CLINICAL TRIALS REGISTRY NUMBER: ChiCTR-IOC-16007882.

A comparison of uterine natural killer cell density in the peri-implantation period between natural cycles and hormone replacement therapy cycles.

PROBLEM: A reference range for uterine natural killer (uNK) cell density in the peri-implantation period has recently been established in natural cycles. However, it is uncertain whether the results can be applied to hormonal replacement therapy (HRT) cycles, used increasingly in frozen-thaw embryo replacement cycles and which is known to be capable of supporting implantation. METHOD OF STUDY: A total of 183 women from two IVF centers participated in this study, including 75 women in natural cycles and 108 women in HRT cycles. All endometrial biopsies were collected precisely on the putative day of embryo implantation, namely 7 days after LH surge (LH+7) of the natural cycles or 5 days after initiation of progesterone (P+5) of the HRT cycles. Endometrial sections were immunostained for CD56 for uNK cells. Cell counting was performed by a standardized protocol, and results were expressed as percentage of positive uNK cells/total stromal cells. RESULTS: There was no significant difference (P > 0.05) in uNK cell density between natural cycles (median 2.28%, range 0.99%-4.78%) and HRT cycles (median 2.55%, range 0.69%-5.02%) in women undergoing IVF-ET treatment on the putative day of blastocyst transfer. Using reference range from 1.2% to 4.5% for uNK cell density, there was no significant difference (P > 0.05) in high uNK cell density proportion between natural cycles (8%, 6/75) and HRT cycles (10.2%, 11/108). CONCLUSION: The results indicated that the reference range for uNK cell density derived from natural cycles may apply to HRT cycles.

Endometrial Vascularization Characterized by Optical Coherence Tomography and Immunohistochemistry in Women Undergoing In Vitro Fertilization-Embryo Transfer Treatment.

BACKGROUND AND OBJECTIVE: Endometrial angiogenesis is a prerequisite for successful pregnancy. Optical coherence tomography (OCT) is a non-invasive physically optical imaging technique widely used in ophthalmology and cardiology. However, there is no study using OCT to evaluate endometrium. The aim of this study was to use OCT and traditionally histological methods to investigate endometrial vascularization in women undergoing in vitro fertilization-embryo transfer (IVF-ET) treatment and to determine the association with the pregnancy outcome. METHODS: A total of 47 women were included in this study. OCT was used to assess endometrial vascularization by determining the high signal areas precisely on the seventh day after luteinizing hormone surge in non-conception natural cycles. Endometrial biopsies were obtained following OCT and immunohistochemistry was used to determine micro vessel and expression of vascular endothelial growth factor-A (VEGF-A) in the luminal epithelium, glandular epithelium and stroma, separately. Micro vessel counting was performed and the result was expressed as micro vessel density (MVD). A semi-quantitative H-score was used to determine the staining intensity of VEGF-A. RESULTS: In women who successfully conceived after embryo transfer, the proportion of extensive high signal area in the uterine body detected by OCT (80%, 8/10), MVD (median number of micro vessels/mm² of 10, range 4⁻17) and stromal expression of VEGF-A (median H-score of 189, range 72⁻395) were found to be significantly higher than those of women who did not conceive after embryo transfer in the subsequent IVF-ET treatment (OCT: 30%, 3/10; MVD: median number of micro vessels/mm² of 7, range 4⁻10; VEGF-A: median H-score of 125, range 86⁻299, respectively). In addition, a significantly higher stromal expression of VEGF-A (median H-score of 196, range 84⁻395) and MVD (median number of micro vessels/mm2 of 9, range 5⁻16) was found in women with extensive high signal area in uterine body, compared to those with focal or no high signal area (stromal VEGF-A: median H-score of 135, range 92⁻302; MVD: number of micro vessels/mm2 of 6, range 4-11). CONCLUSIONS: Both immunohistochemistry and OCT demonstrated significant difference in vascularization of the peri-implantation endometrium between subjects who did and did not conceive after IVF-ET treatment. Our findings also suggest OCT appears to be a promising non-invasive or minimally invasive alternative to study endometrial vascularity in women with reproductive failure.

Pelvic floor muscle training improves quality of life of women with urinary incontinence: a prospective study.

BACKGROUND: Women suffering from urinary incontinence have impaired quality of life (QoL). Pelvic floor muscle training (PFMT) has been recommended to be the first-line treatment for them. AIMS: This study evaluated the role of (PFMT) in women with urinary incontinence. MATERIALS AND METHODS: All women suffering from urinary incontinence without pelvic organ prolapse who attended the urogynaecology unit of a university hospital from January 2009 to June 2010 were recruited. Urinary symptoms and impact on QoL were assessed using the Chinese validated Urogenital Distress Inventory short form (UDI-6) and Incontinence Impact Questionnaire short form (IIQ-7) before and after PFMT. Urodynamic studies (UDS) were used to differentiate the diagnoses of urinary incontinence. RESULTS: Three hundred and seventy-two women, aged 52.3 ± 10.8 years and practised PFMT for 9.9 ± 7.3 months, completed the study. Over 65% recorded improvement in both UDI-6 and IIQ-7. Stratified for urodynamic diagnosis, stress incontinence group and those who had no UDS abnormality had significant improvement in their urinary symptoms and QoL after PFMT. UDI-6 and IIQ-7 also improved significantly after PFMT in groups where the clinical presentation was stress incontinence, overactive bladder symptoms or mixed urinary incontinence. Age was not associated with a significant difference in the response to PFMT. CONCLUSIONS: Pelvic floor muscle training appears to be an effective first-line intervention for improving urinary symptoms and QoL of women presenting with urinary incontinence. Future studies on long-term effectiveness and cost-effectiveness are also required.