Comparison of the multiples of the median of serum anti-müllerian hormone and pregnancy outcomes in patients with gestational trophoblastic disease: A case-control study.

INTRODUCTION: Chemotherapy is crucial in treating gestational trophoblastic neoplasia (GTN), but its impact on gonadotoxicity is unclear. MATERIALS AND METHODS: This case-control study included 57 GTN patients and 19 age-matched patients with molar pregnancies (MP) in 2012-2018. Multiples of the median (MoM) of the serum AMH levels were compared between the two groups, and between patients using single-agent and combination chemotherapy, at baseline, 6, 12, and 24 months after treatment. Their pregnancy outcomes were also compared. RESULTS: There was no significant difference in the MoM of serum AMH between GTN and MP groups at all time points. Single-agent chemotherapy did not adversely affect the MoM. However, those receiving combination chemotherapy had lower MoM than those receiving single-agent chemotherapy at all time points. The trend of decline from the baseline was marginally significant in patients with combination chemotherapy, but the drop was only significant at 12 months (Z = -2.69, p = 0.007) but not at 24 months (Z = -1.90; p = 0.058). Multivariable analysis revealed that combination chemotherapy did not affect the MoM. There was no significant difference in the 4-year pregnancy rate and the livebirth rate between the single-agent and combination groups who attempting pregnancy, but it took 1 year longer to achieve the first pregnancy in the combination group compared to the single-agent group (2.88 vs. 1.88 years). CONCLUSION: This study showed combination chemotherapy led to a decreasing trend of MoM of serum AMH especially at 12 months after treatment, but the drop became static at 24 months. Although pregnancy is achievable, thorough counseling is still needed in this group especially those wish to achieve pregnancy 1-2 years after treatment or with other risk factors.

A randomized controlled trial to compare the live birth rate of the first frozen embryo transfer following the progestin-primed ovarian stimulation protocol vs. the antagonist protocol in women with an anticipated high ovarian response.

OBJECTIVE: To compare the live birth rate of the first frozen embryo transfer (FET) after ovarian stimulation by the progestin-primed ovarian stimulation (PPOS) protocol vs. the antagonist protocol in women with an anticipated high ovarian response who were undergoing in vitro fertilization. DESIGN: Randomized controlled trial. SETTING: A tertiary assisted reproduction center. PATIENTS: Women with infertility aged <43 years undergoing the first in vitro fertilization cycle and having antral follicle count of >15. INTERVENTIONS: Medroxyprogesterone 10 mg daily was given from the start of ovarian stimulation until the day of ovulation trigger in the PPOS protocol. In the antagonist protocol, an antagonist 0.25 mg daily was given from the sixth day of ovarian stimulation until the day of ovulation trigger. Blinding was not possible for women or physicians but the biostatistician was blinded to the group assignment. MAIN OUTCOME MEASURE: Live birth rate of the first FET cycle. RESULTS: A total of 784 women were recruited from June 2020 and October 2021 and assigned randomly in a 1:1 ratio into two groups: PPOS group (n = 392) and antagonist group (n = 392). Embryo transfer was either cancelled or postponed in 62 women (62/392, 15.8%) in the PPOS group and 65 (65/392, 16.6%) in the antagonist group because of no transferable embryos or no FET within 6 months after randomization. The two groups were similar in demographic characteristics and the numbers of oocytes obtained or fertilized, cleaving embryos, good-quality embryos at day 3, blastocysts developed, and embryos or blastocysts frozen. There was no statistically significant difference in the live birth rate of the first FET cycle between the PPOS and antagonist groups on the basis of both the intention-to-treat analysis (37.5.0% [147/392] vs. 32.7% [128/392]; relative risk, 1.148 [95% confidence interval, 0.949-1.390]) and per-protocol analysis (44.5% [147/330] vs. 39.1% [128/327]; relative risk, 1.138 [95% confidence interval, 0.950-1.364]). Both groups showed comparable clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy, and cumulative live birth rates. CONCLUSION: The live birth rates of the first FET following the PPOS and antagonist protocols were comparable in women with an anticipated high ovarian response. CLINICAL TRIAL REGISTRATION NUMBER: NCT04414761 (ClinicalTrials.gov).

A construct of adipose-derived mesenchymal stem cells-laden collagen scaffold for fertility restoration by inhibiting fibrosis in a rat model of endometrial injury.

Severe endometrium damage causes pathological conditions such as thin endometrium and intrauterine adhesion, resulting in uterine factor infertility. Mesenchymal stem cell (MSC) therapy is a promising strategy in endometrial repair; yet, exogenous MSCs still raise concerns for safety and ethical issues. Human adipose-derived mesenchymal stem cells (ADMSCs) residing in adipose tissue have high translational potentials due to their autologous origin. To harness the high translation potentials of ADMSC in clinical endometrium regeneration, here we constructed an ADMSCs composited porous scaffold (CS/ADMSC) and evaluated its effectiveness on endometrial regeneration in a rat endometrium-injury model. We found that CS/ADMSC intrauterine implantation (i) promoted endometrial thickness and gland number, (ii) enhanced tissue angiogenesis, (iii) reduced fibrosis and (iv) restored fertility. We ascertained the pro-proliferation, pro-angiogenesis, immunomodulating and anti-fibrotic effects of CS/ADMSC in vitro and revealed that the CS/ADMSC influenced extracellular matrix composition and organization by a transcriptomic analysis. Our results demonstrated the effectiveness of CS/ADMSC for endometrial regeneration and provided solid proof for our future clinical study.

The impact of the embryo banking on the cumulative live birth rate in women with poor ovarian response according to the Bologna criteria.

Purpose: To evaluate the impact of embryo banking on the cumulative live birth rate (CLBR) and the time to live birth (TTLB) in poor ovarian responders (POR) according to the Bologna criteria. Methods: A total of 276 infertile women undergoing IVF with POR were included in this retrospective study. They were divided into two groups with (n = 121) or without (n = 155) embryo banking at the discretion of the attending physicians. A total of 656 and 405 stimulation cycles were started in the two groups respectively during the 24 month follow-up. Results: The biochemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth rate per transfer were comparable between two groups (p > 0.05). The CLBR was significantly lower in the banking group than in the non-banking group (31.4% (38/121) and 43.2% (67/151), p < 0.05). TTLB was significantly longer in the banking group (20.5 months vs. 16.0 months, p < 0.001). In the Kaplan-Meier analysis, the cumulative incidence of live birth was significantly lower in the banking group compared with the non-banking group (Log rank test, chi-square = 21.958, p < 0.001). Conclusions: Embryo banking in women undergoing IVF with POR based on the Bologna criteria reduces CLBR and lengthens TTLB when compared with no embryo banking.

Oral emergency contraception with levonorgestrel plus piroxicam: a randomised double-blind placebo-controlled trial.

BACKGROUND: Levonorgestrel, a standard drug for emergency contraception (EC), is not effective if administered post-ovulation. A cyclo-oxygenase inhibitor could contribute synergistic effects. We investigated whether a single 40 mg oral dose of piroxicam as co-treatment with levonorgestrel improved emergency contraceptive efficacy. METHODS: This was a randomised double-blind placebo-controlled trial carried out in a major community sexual and reproductive health service in Hong Kong. Women who required levonorgestrel EC within 72 h of unprotected sexual intercourse were recruited and block-randomised in a 1:1 ratio to receive a single supervised dose of levonorgestrel 1·5 mg plus either piroxicam 40 mg or placebo orally. Group assignment was concealed in opaque envelopes and masked to the women, clinicians, and investigators. At follow-up 1-2 weeks after the next expected period, the pregnancy status was noted by history or pregnancy test. The primary efficacy outcome was the proportion of pregnancies prevented out of those expected based on an established model. All women randomised to receive the study drug and who completed the follow-up were analysed. The trial was registered with ClinicalTrials.gov, NCT03614494. FINDINGS: 860 women (430 in each group) were recruited between Aug 20, 2018, and Aug 30, 2022. One (0·2%) of 418 efficacy-eligible women in the piroxicam group were pregnant, compared with seven (1·7%) of 418 in the placebo group (odds ratio 0·20 [95% CI 0·02-0·91]; p=0·036). Levonorgestrel plus piroxicam prevented 94·7% of expected pregnancies compared with 63·4% for levonorgestrel plus placebo. We noted no significant difference between the two groups in the proportion of women with advancement or delay of their next period, or in the adverse event profile. INTERPRETATION: Oral piroxicam 40 mg co-administered with levonorgestrel improved efficacy of EC in our study. Piroxicam co-administration could be considered clinically where levonorgestrel EC is the option of choice. FUNDING: None.

Advanced glycation end-products and its soluble receptor are not independent predictors of incident dysglycaemia or metabolic syndrome in women with polycystic ovary syndrome: a prospective observational study.

BACKGROUND: To evaluate the association of serum advanced glycation end-products (AGEs) and its soluble receptor of AGE (sRAGE) levels with dysglycaemia and metabolic syndrome in women with polycystic ovary syndrome (PCOS). METHODS: This was an analysis of a cohort of women with PCOS who were prospectively recruited for a longitudinal observational study on their endocrine and metabolic profile between January 2010 and December 2013. The association of serum AGEs and sRAGE levels with dysglycaemia and metabolic syndrome at the second-year visit (the index visit) and the sixth-year visit (the outcome visit) were determined. Comparisons of continuous variables between groups were made using the Mann-Whitney U-test. Spearman test was used for correlation analysis. Multivariate binary logistic regression analysis was employed to identify the factors independently associated with the outcome events. RESULTS: A total of 329 women were analysed at the index visit. Significantly lower serum levels of sRAGE (both p < 0.001), but no significant difference in AGEs, were observed in those with dysglycaemia or metabolic syndrome. At the outcome visit, those with incident metabolic syndrome had a significantly lower initial serum sRAGE levels (p = 0.008). The association of serum sRAGE with dysglycaemia and metabolic syndrome at the index visit was no longer significant in multivariate logistic regression after controlling for body mass index, free androgen index and homeostatic model assessment for insulin resistance (HOMA-IR). sRAGE was also not significantly associated with incident metabolic syndrome at the outcome visit on multivariate logistic regression. CONCLUSIONS: Serum sRAGE levels are significantly lower in women with PCOS who have dysglycaemia or metabolic syndrome, and in those developing incident metabolic syndrome in four years. However, it does not have a significant independent association with these outcome measures after adjusting for body mass index, free androgen index and HOMA-IR.

Attachment of a trophoblastic spheroid onto endometrial epithelial cells predicts cumulative live birth in women aged 35 and older.

OBJECTIVE: To evaluate the attachment rate of a human embryonic stem cell-derived trophoblastic spheroid onto endometrial epithelial cells in predicting the cumulative live birth rate of an in vitro fertilization (IVF) cycle. DESIGN: A prospective observational study. SETTING: University hospital and research laboratory. PATIENT(S): A total of 240 infertile women from 2017-2021. INTERVENTION(S): Infertile women with regular cycles attending for IVF were recruited. An endometrial aspirate was collected from a natural cycle 1 month before IVF to determine the BAP-EB attachment rate. MAIN OUTCOME MEASURE(S): Cumulative live birth rates from a stimulated cycle and its derived frozen embryo transfer cycles within 6 months of ovarian stimulation were obtained. RESULT(S): The BAP-EB attachment rate in women who attained a cumulative live birth was similar to that in those who did not. When women were stratified by age into <35 years and ≥35 years, the BAP-EB attachment rate was significantly higher only in women aged ≥35 years having a live birth when compared with those in the same age group without a live birth. Receiver operating characteristic curve analysis of BAP-EB attachment rate in predicting cumulative live birth showed the areas under the curve of 0.559 (95% confidence interval [CI], 0.479-0.639), 0.448 (95% CI, 0.310-0.585), and 0.613 (95% CI, 0.517-0.710) for all ages, an age of <35 years, and an age of ≥35 years, respectively. CONCLUSION(S): The BAP-EB attachment rate offers only a very modest prediction of the cumulative live birth rate in women aged ≥35 years undergoing IVF. CLINICAL TRIAL REGISTRATION NUMBER: NCT02713854 (https://clinicaltrials.gov/ct2/show/NCT02713854; Date of registration, March 21, 2016; date of enrollment of the first subject, August 1, 2017).

Non-Coding RNAs as Biomarkers for Embryo Quality and Pregnancy Outcomes: A Systematic Review and Meta-Analysis.

Despite advances in in vitro fertilization (IVF), there is still a lack of non-invasive and reliable biomarkers for selecting embryos with the highest developmental and implantation potential. Recently, small non-coding RNAs (sncRNAs) have been identified in biological fluids, and extracellular sncRNAs are explored as diagnostic biomarkers in the prediction of IVF outcomes. To determine the predictive role of sncRNAs in embryo quality and IVF outcomes, a systematic review and meta-analysis was performed. Articles were retrieved from PubMed, EMBASE, and Web of Science from 1990 to 31 July 2022. Eighteen studies that met the selection criteria were analyzed. In total, 22 and 47 different sncRNAs were found to be dysregulated in follicular fluid (FF) and embryo spent culture medium (SCM), respectively. MiR-663b, miR-454 and miR-320a in FF and miR-20a in SCM showed consistent dysregulation in two different studies. The meta-analysis indicated the potential predictive performance of sncRNAs as non-invasive biomarkers, with a pooled area under curve (AUC) value of 0.81 (95% CI 0.78, 0.844), a sensitivity of 0.79 (95% CI 0.72, 0.85), a specificity of 0.67 (95% CI 0.52, 0.79) and a diagnostic odds ratio (DOR) of 8 (95% CI 5, 12). Significant heterogeneity was identified among studies in sensitivity (I2 = 46.11%) and specificity (I2 = 89.73%). This study demonstrates that sncRNAs may distinguish embryos with higher developmental and implantation potentials. They can be promising non-invasive biomarkers for embryo selection in ART. However, the significant heterogeneity among studies highlights the demand for prospective multicenter studies with optimized methods and adequate sample sizes in the future.

Longitudinal study on sexual function and quality of life in infertile couples undergoing intrauterine insemination.

BACKGROUND: Cross-sectional studies have shown that sexual dysfunction and poor quality of life were prevalent among couples undergoing assisted reproduction at specific time points, but nothing is known about how these outcomes change over the course of their intrauterine insemination (IUI) journey. AIM: We investigated the longitudinal changes in sexual function and quality of life of infertile couples undergoing IUI. METHODS: Sixty-six infertile couples completed an anonymous questionnaire at 3 time points: after IUI counseling (T1), 1 day before IUI (T2), and 2 weeks after IUI (T3). The questionnaire consisted of demographic data, Female Sexual Function Index (FSFI) or International Index of Erectile Function-5, and Fertility Quality of Life (FertiQoL). OUTCOMES: Descriptive statistics, significance testing with the Friedman test, and post hoc analysis with the Wilcoxon signed rank test were used to compare changes in sexual function and quality of life at different time points. RESULTS: Overall, 18 (26.1%), 16 (23.2%), and 12 (17.4%) women and 29 (42.0%), 37 (53.6%), and 31 (44.9%) men were at risk for sexual dysfunction at T1, T2, and T3, respectively. There were significant differences in mean FSFI scores in arousal (3.87, 4.06, 4.10) and orgasm (4.15, 4.24, 4.39) domains at T1, T2, and T3. After post hoc analysis, only the increase in mean orgasm FSFI scores between T1 and T3 was statistically significant. Men's FertiQoL scores remained high during IUI (74.33-75.63 out of 100). Men also scored significantly higher than women on all FertiQoL domains except environment at the 3 time points. Post hoc analysis showed significant improvement in women's FertiQoL domain scores between T1 and T2: mind-body, environment, treatment, and total. Women's FertiQoL score at T2 for the treatment domain was also significantly higher than that at T3. CLINICAL IMPLICATIONS: Men should not be neglected during IUI as their erectile function got worse in the process, with half of the men being affected. Although women's quality of life showed some improvement during IUI, most of their scores were lower than men's. STRENGTHS AND LIMITATIONS: The use of psychometrically validated questionnaires and a longitudinal approach are the major strengths; a small sample size and the lack of a dyadic approach are the major limitations. CONCLUSION: During IUI, women's sexual performance and quality of life improved. The proportion of men having erectile problems was high for this age group, but men's FertiQoL scores remained good and were better than their partners' throughout IUI.

Characteristics of Maternal Mortality Missed by Vital Statistics in Hong Kong, 2000-2019.

Importance: Reducing maternal mortality is a global objective. The maternal mortality ratio (MMR) is low in Hong Kong, China, but there has been no local confidential enquiry into maternal death, and underreporting is likely. Objective: To determine the causes and timing of maternal death in Hong Kong and identify deaths and their causes that were missed by the Hong Kong vital statistics database. Design, Setting, and Participants: This cross-sectional study was conducted among all 8 public maternity hospitals in Hong Kong. Maternal deaths were identified using prespecified search criteria, including a registered delivery episode between 2000 to 2019 and a registered death episode within 365 days after delivery. Cases as reported by the vital statistics were then compared with the deaths found in the hospital-based cohort. Data were analyzed from June to July 2022. Main Outcomes and Measures: The outcomes of interest were maternal mortality, defined as death during pregnancy or within 42 days after ending the pregnancy, and late maternal death, defined as death more than 42 days but less than 1 year after end of the pregnancy. Results: A total of 173 maternal deaths (median [IQR] age at childbirth, 33 [29-36] years) were found, including 74 maternal mortality events (45 direct deaths and 29 indirect deaths) and 99 late maternal deaths. Of 173 maternal deaths, 66 women (38.2%) of individuals had preexisting medical conditions. For maternal mortality, the MMR ranged from 1.63 to 16.78 deaths per 100 000 live births. Suicide was the leading cause of direct death (15 of 45 deaths [33.3%]). Stroke and cancer deaths were the most common causes of indirect death (8 of 29 deaths [27.6%] each). A total of 63 individuals (85.1%) died during the postpartum period. In the theme-based approach analysis, the leading causes of death were suicide (15 of 74 deaths [20.3%]) and hypertensive disorders (10 of 74 deaths [13.5%]). The vital statistics in Hong Kong missed 67 maternal mortality events (90.5%). All suicides and amniotic fluid embolisms, 90.0% of hypertensive disorders, 50.0% of obstetric hemorrhages, and 96.6% of indirect deaths were missed by the vital statistics. The late maternal death ratio ranged from 0 to 16.36 deaths per 100 000 live births. The leading causes of late maternal death were cancer (40 of 99 deaths [40.4%]) and suicide (22 of 99 deaths [22.2%]). Conclusions and Relevance: In this cross-sectional study of maternal mortality in Hong Kong, suicide and hypertensive disorder were the dominant causes of death. The current vital statistics methods were unable to capture most of the maternal mortality events found in this hospital-based cohort. Adding a pregnancy checkbox to death certificates and setting up a confidential enquiry into maternal death could be possible solutions to reveal the hidden deaths.

Endometrial stromal cells from women with repeated implantation failure display impaired invasion towards trophoblastic spheroids.

In brief: Implantation failure can occur even after the transfer of good-quality embryos. This study showed that the migration of human endometrial stromal cells towards embryonic trophoblasts is higher in women with live births in the first in vitro fertilization cycle than those with repeated implantation failure, suggesting that the chemotactic response of stroma cells is associated with successful pregnancy. Abstract: The success rate of in vitro fertilization (IVF) remains limited in some women despite transfers of good-quality embryos in repeated attempts. There is no reliable tool for assessing endometrial receptivity. This study aimed to assess the interaction between decidualized human primary endometrial stromal cells (1°-EnSC) and human embryonic stem cell-derived trophoblastic spheroids (BAP-EB) and to compare the invasion ability of decidualized 1°-EnSC towards BAP-EB between women attaining live birth in the first IVF cycle and those with repeated implantation failure (RIF). The invasion of the decidualized human endometrial cell line (T-HESC) and 1°-EnSC towards BAP-EB was studied. Real-time quantitative PCR and immunocytochemistry were employed to determine the expression of decidualization markers at mRNA and protein levels, respectively. Trophoblast-like BAP-EB-96h, instead of early trophectoderm (TE)-like BAP-EB-48h, facilitated the invasion ability of decidualized T-HESC and decidualized 1°-EnSC. Human chorionic gonadotropin at supra-physiological levels promoted the invasiveness of decidualized 1°-EnSC. The extent of BAP-EB-96h-induced invasion was significantly stronger in decidualized 1°-EnSC from women who had a live birth in the first IVF cycle when compared to those with RIF. While no difference was found in the expression of decidualization markers, PRL and IGFBP1 among two groups of women, significantly lower HLA-B was detected in the non-decidualized and decidualized 1°-EnSC from women with RIF. Collectively, the findings suggested that the invasion of decidualized 1°-EnSC towards trophoblast-like BAP-EB-96h was higher in women who had a live birth in the first IVF cycle than those with RIF.

Trend and causes of maternal death, stillbirth and neonatal death over seven decades in Hong Kong.

Background: Reducing maternal and perinatal mortality is a global objective. Hong Kong is a city with low maternal and perinatal mortality but little is known about the trend and causes of these deaths in this high-income city. We analyzed the maternal death, stillbirth and neonatal death since 1946 in Hong Kong. Methods: Data were extracted from vital statistics, based on the number of registered deaths and births, provided by the Department of Health, the Government of the HKSAR. The annual change rate of mortality was evaluated by regression analysis. Contextual factors were collected to assess the association with mortality. Findings: Between 1946 and 2017, the stillbirth rate (per 1,000 total births) reduced from 21·5 to 2·4; early and late neonatal deaths (per 1,000 live births) reduced from 14·1 and 18·1 to 0·7 and 0·4 in 2017, respectively. The maternal mortality ratio (per 100,000 live births) declined from 125 to 1·8.The causes of maternal and perinatal deaths were available since 1981 and 1980 respectively. The leading causes of death were thromboembolism (37·0%) and obstetric haemorrhage (30·4%) for maternal death; congenital problem (30·1%) and prematurity (29·0%) for neonatal death. No data on causes of stillbirth were available. No specific shift of pattern was observed in the causes of maternal and neonatal death with time. There were no cases of maternal death due to sepsis and only 2 cases (2·2%) of maternal deaths due to indirect cause. Interpretation: The maternal and perinatal death have reduced significantly in Hong Kong and maintained at the lowest level globally. Indirect maternal death and sepsis were unusual causes of maternal deaths. Use of ICD-PM stillbirth classification, setting up a maternal death confidential enquiry and adding pregnancy checkbox could be the next step to identify and categorize hidden burden. Funding: Nil.

High-Throughput In Vitro Screening Identified Nemadipine as a Novel Suppressor of Embryo Implantation.

Current contraceptive methods interfere with folliculogenesis, fertilization, and embryo implantation by physical or hormonal approaches. Although hormonal contraceptive pills are effective in regulating egg formation, they are less effective in preventing embryo implantation. To explore the use of non-hormonal compounds that suppress embryo implantation, we established a high-throughput spheroid-endometrial epithelial cell co-culture assay to screen the Library of Pharmacologically Active Compounds (LOPAC) for compounds that affect trophoblastic spheroid (blastocyst surrogate) attachment onto endometrial epithelial Ishikawa cells. We identified 174 out of 1280 LOPAC that significantly suppressed BeWo spheroid attachment onto endometrial Ishikawa cells. Among the top 20 compounds, we found the one with the lowest cytotoxicity in Ishikawa cells, P11B5, which was later identified as Nemadipine-A. Nemadipine-A at 10 µM also suppressed BeWo spheroid attachment onto endometrial epithelial RL95-2 cells and primary human endometrial epithelial cells (hEECs) isolated from LH +7/8-day endometrial biopsies. Mice at 1.5 days post coitum (dpc) treated with a transcervical injection of 100 µg/kg Nemadipine-A or 500 µg/kg PRI-724 (control, Wnt-inhibitor), but not 10 µg/kg Nemadipine-A, suppressed embryo implantation compared with controls. The transcript expressions of endometrial receptivity markers, integrin αV (ITGAV) and mucin 1 (MUC1), but not ß-catenin (CTNNB1), were significantly decreased at 2.5 dpc in the uterus of treated mice compared with controls. The reduction of embryo implantation by Nemadipine-A was likely mediated through suppressing endometrial receptivity molecules ITGAV and MUC1. Nemadipine-A is a potential novel non-hormonal compound for contraception.

Live birth after letrozole as an adjunct to follicle-stimulating hormone versus follicle-stimulating hormone alone for ovarian stimulation in in vitro fertilisation cycles-study protocol for a randomised controlled trial.

INTRODUCTION: In vitro fertilisation (IVF) is an effective infertility treatment but the live birth rate remains unsatisfactory. Ovarian stimulation by follicle-stimulating hormone (FSH) is routinely used in IVF and the resulting high serum estradiol levels may impair oocyte/embryo quality and endometrial receptivity. Letrozole, an aromatase inhibitor, can reduce serum estradiol levels following ovarian stimulation. We aim to test the hypothesis that co-treatment with letrozole reduces supraphysiological serum estradiol levels and improves endometrial receptivity, leading to a higher live birth rate of IVF. We are conducting a randomised controlled trial (RCT) to evaluate whether letrozole as an adjunct to FSH in IVF is superior to FSH alone in the live birth rate of fresh embryo transfer. METHODS/DESIGN: This is an open-label randomised controlled superiority trial being performed in two assisted reproduction centres in China. Infertile women who have antral follicle count (AFC) before ovarian stimulation or on day 5 of ovarian stimulation ≥15 are randomly allocated in a 1:1 ratio to receive either letrozole and FSH or FSH alone in a GnRH antagonist protocol. Recruited women follow the standard operating procedures of the two centres. The primary outcome is the live birth rate of the fresh embryo transfer. Stimulation parameters, maternal side effects and obstetric and perinatal complications are secondary outcomes. The planned sample size is 900, i.e. 450 per group. DISCUSSION: The present study is the first multicentre randomised study to compare the live birth rate of the fresh embryo transfer following ovarian stimulation by letrozole and FSH versus FSH alone in women with anticipated high ovarian responses. TRIAL REGISTRATION: ClinicalTrials.gov NCT02912988 . Registered on September 23, 2016. This trial protocol is version 2.0.

Sexual function and quality of life in Chinese couples undergoing assisted reproductive treatment: a prospective cohort study.

Couples undergoing assisted reproductive technologies (ART) are prone to sexual dysfunction and lower quality of life (QoL), but whether the incidence of these problems differs with the type of ART is unknown. As such, we conducted this cross-sectional survey to compare the sexual function and QoL of 75 couples undergoing intrauterine insemination (IUI), and 160 couples undergoing in vitro fertilization (IVF). They completed an anonymous questionnaire which included: (i) demographic characteristics; (ii) female sexual function index (FSFI) or (iii) international index of erectile function-5 (IIEF-5); and (iv) fertility QoL questionnaire (FertiQoL). Overall, 22.6% of wives and 39.1% of husbands were at risk for sexual dysfunction, and the risk was similar in IUI and IVF groups. Mean core/treatment/total FertiQoL scores of husbands were higher than wives: 74.98 vs. 68.24/70.02 vs. 65.87/73.52 vs. 67.54 (all p < 0.001). FertiQoL scores were similar in IUI and IVF groups except wives' treatment FertiQoL score was significantly higher in the IUI group (68.93 vs. 64.44; p = 0.009). This study confirms that risks for sexual dysfunction were similar in IUI and IVF couples. Wives undergoing IVF had significantly lower treatment FertiQoL score. In both IUI and IVF groups, husbands' QoL was better than wives' QoL.

Comparison of the ongoing pregnancy rate of in vitro fertilisation following tubal occlusion by microcoil placement versus laparoscopic tubal ligation for hydrosalpinges.

To compare the pregnancy outcomes of in vitro fertilisation (IVF) following tubal occlusion by microcoil placement versus laparoscopic tubal ligation for hydrosalpinges. This was a single centre retrospective study of 127 infertile women aged <43 years with unilateral or bilateral hydrosalpinges on transvaginal ultrasound who underwent either tubal occlusion by the microcoil placement under X-ray control (the microcoil group (n = 60)) or laparoscopic tubal ligation (the ligation group (n = 67)) prior to IVF at the discretion of the attending physicians. In all women, laparoscopy was not considered to be contraindicated due to extensive pelvic adhesions. The pregnancy outcomes of the IVF cycle following the treatment for hydrosalpinges were compared. Both groups had comparable demographic and cycle stimulation characteristics. The positive pregnancy test (43.3% (26/60) vs 64.2% (43/67), p = 0.02, RR = 0.68 (0.48-0.95)), ongoing pregnancy (35.0% (21/60) vs 58.2% (39/67), p = 0.009, RR = 0.60 (0.40-0.89)) and implantation rates (33.3% (34/102) vs 49.5% (56/113), p = 0.016, RR 0.67 (0.48-0.94)) were significantly lower in the microcoil group than those in the ligation group. Both groups had similar miscarriage, multiple pregnancy and ectopic pregnancy rates. A multivariate logistic regression revealed that only the women's age and the treatment method of hydrosalpinx were significant factors in predicting the ongoing pregnancy. A lower ongoing pregnancy rate of IVF was found in women with hydrosalpinges following tubal occlusion by microcoil placement under X-ray when compared with laparoscopic tubal ligation.

Randomized double-blind trial comparing low dose and conventional dose of a modified traditional herbal formula Guizhi Fuling Wan in women with symptomatic uterine fibroids.

ETHNOPHARMACOLOGICAL RELEVANCE: The herbal formula Guizhi Fuling Wan is one common remedy for treating uterine fibroids (UFs) and the relevant symptoms in Traditional Chinese Medicine (TCM). Previous systematic reviews showed that Guizhi Fuling Formula appeared to have additional benefit based on mifepristone treatment in reducing volume of fibroids. AIM OF STUDY: To study the efficacy and safety of the conventional dose of a modified herbal formula Guizhi Fuling Wan in patients with symptomatic uterine fibroids in comparison with a sub-effective dose control. MATERIALS AND METHODS: This randomized double-blind, dosage-controlled trial was carried out in an outpatient clinic of traditional Chinese medicine in Hong Kong. Women with symptomatic uterine fibroids diagnosed according to the WHO International Classification of Diseases (ICD-10) were recruited and randomly assigned to one of two groups that received modified Guizhi Fuling Wan at either a low dose or the conventional dose on a daily basis for 16 weeks. This study was quality controlled by a data safety monitoring board. The primary outcome was the symptom severity as measured with the Uterine Fibroid Symptom-Quality of Life questionnaire. The secondary outcomes included quality of life, menstrual bleeding (measured on a pictorial blood loss assessment chart), pain severity (measured on the 6-point behavioral rating scale), change in Chinese medicine syndrome score, fibroid volume (measured by magnetic resonance imaging), hemoglobin level, and hormone levels. RESULTS: Seventy-eight women were recruited for this study. Between-groups comparison showed no significant difference at the endpoint for all outcomes except for the Chinese medicine syndrome score; however, at the endpoint, within-group comparison showed significant improvement in both groups relative to baseline in symptom severity, functional influence of pelvic pain, Chinese medicine syndrome score, and fibroid volume and uterus condition on magnetic resonance imaging (p < 0.05).The low-dose group yielded greater endpoint improvement in the Chinese medicine syndrome score than the conventional-dose group (p=0.024). No serious adverse events related to the intervention were noted. CONCLUSION: Both low-dose and conventional-dose preparations significantly ameliorated uterine fibroid-related symptoms and fibroid volume, although no significant difference was found between the low-dose and conventional-dose groups. The herbal formula GuizhiFuling Wan is safe in women with uterine fibroids.

Acceptability of different mechanisms of action of contraception in women: a questionnaire survey.

BACKGROUND: The mechanism of action of a contraceptive method is an importantg consideration in a woman's choice of contraception. For the development of new methods of contraception it is important to understand the acceptability of different contraceptive mechanisms within a population. METHODS: We recruited women attending contraceptive, termination of pregnancy or postnatal care services in Hong Kong for a questionnaire survey on their acceptability of the different ways in which contraceptive methods prevent pregnancy. Univariable and multivariable analyses were used to establish factors which may predict acceptability of the mechanism of action. RESULTS: A total of 1448 women completed the survey. The acceptability of contraceptive methods that act by preventing fertilisation ranked highest (78%), followed by those that inhibit ovulation (52%), disrupt implantation (43%) and dislodge an implanted embryo (30%). A history of termination of pregnancy was associated with greater acceptance of all posited contraceptive mechanisms. There was a very low degree of agreement between the declared acceptance of the various contraceptive mechanisms and the ever use of a method with the respective mechanism of action (Cohen's kappa coefficient range 0.017-0.162). CONCLUSIONS: In this population the acceptability of contraceptive methods that act by preventing fertilisation ranked highest, followed by those that inhibit ovulation, disrupt implantation and dislodge an implanted embryo. Women who had ever had a termination of pregnancy were more likely to accept all the posited contraceptive mechanisms.

A randomized controlled study of acupuncture for pain relief during first trimester surgical termination of pregnancy performed under local analgesia.

BACKGROUND: Acupuncture reduces pain levels in many painful conditions. This study compared pain levels during surgical termination of first trimester pregnancy by suction evacuation (SE) under local analgesia with and without the use of acupuncture. METHODS: In all, 60 nulliparous women undergoing SE before 10 weeks of gestation were randomly assigned into one of the following three groups in a 1:1:1 ratio according to a computer-generated randomization list. In the control group, women received oral diazepam 5 mg and intramuscular (i.m.) injection of pethidine 30 and 15 min, respectively, prior to SE. In the acupuncture group, women received acupuncture 10 min before SE until the end of SE while oral diazepam 5 mg and i.m. injection of normal saline were given. In the combined group, women received acupuncture in addition to the drugs in the control group. Data from 52 participants were analysed. Pain scores during and after SE, post-operative side-effects and satisfaction levels were compared. RESULTS: The three groups had similar baseline characteristics. The median pain levels during SE differed significantly between the control, acupuncture, and combined groups (80, 50 and 66 mm, respectively, p = 0.03). Pain levels during SE in the acupuncture and combined groups were significantly lower than that of the control group. However, the anxiety scores did not differ between the three groups after SE (p = 0.86). CONCLUSION: Acupuncture can provide additional benefit in terms of pain relief in women undergoing first trimester termination of pregnancy by SE under local analgesia.

The Prevalence and Factors Associated With Anxiety-Like and Depression-Like Behaviors in Women With Polycystic Ovary Syndrome.

Increasing evidence shows that polycystic ovary syndrome (PCOS) patients are particularly vulnerable to anxiety/depression-like behaviors. This study sought to determine the prevalence of anxiety/depression-like behaviors among women with PCOS and to identify factors associated with these behaviors. This study was a secondary analysis of three studies performed on Chinese women who were aged 18 to 40 and diagnosed with PCOS according to the modified Rotterdam criteria. We obtained 802 useable responses for the self-rating anxiety scale and 798 responses for the self-rating depression scale. The prevalence of anxiety-like and depression-like behaviors among women with PCOS was 26.1% (209/802) and 52.0% (415/798), respectively. Anxiety-like behaviors were associated with age, body image-related factors (including body mass index and waist-to-hip ratio), and hyperandrogenism-related factors (including free androgen index and hirsutism). Depression-like behaviors were associated with age, body image-related factors, hyperandrogenism-related factors, and metabolic factors (including fasting insulin, fasting plasma glucose, and homeostatic model assessment of insulin resistance). Body image-related factors and hyperandrogenism-related factors were related to both anxiety-like behaviors and depression-like behaviors in both infertile and fertile PCOS patients.