Cross-sectional study to assess the psychological morbidity of women facing possible miscarriage.

INTRODUCTION: Threatened miscarriage is a common complication of pregnancy. This study aimed to assess psychological morbidity in women with threatened miscarriage, with the goal of identifying early interventions for women at risk of anxiety or depression. METHODS: Women in their first trimester attending an Early Pregnancy Assessment Clinic were recruited between July 2013 and June 2015. They were asked to complete the 12-item General Health Questionnaire (GHQ-12), the Beck Depression Inventory (BDI), Spielberger's State Anxiety Inventory State form (STAI-S), the Fatigue Scale-14 (FS-14), and the Profile of Mood States (POMS) before consultation. They were also asked to rate anxiety levels before and after consultation using a visual analogue scale (VAS). RESULTS: In total, 1390 women completed the study. The mean ± standard deviation of GHQ-12 (bi-modal) and GHQ-12 (Likert) scores were 4.04 ± 3.17 and 15.19 ± 5.30, respectively. Among these women, 48.4% had a GHQ-12 (bi-modal) score ≥4 and 76.7% had a GHQ-12 (Likert) score >12, indicating distress. The mean ± standard deviation of BDI, STAI-S, and FS-14 scores were 9.35 ± 7.19, 53.81 ± 10.95, and 2.40 ± 0.51, respectively. The VAS score significantly decreased after consultation (P<0.001). Compared with women without a history of miscarriage, women with a previous miscarriage had higher GHQ-12, BDI, and POMS scores (except for fatigue-inertia and vigour-activity subscales). A higher bleeding score was strongly positively correlated with GHQ-12 (Likert) score. There were weak correlations between pain score and the GHQ-12 (bi-modal) ≥4, BDI >12, and POMS scores (except for confusion-bewilderment subscale which showed a strong positive correlation). CONCLUSION: Women with threatened miscarriage experience a considerable psychological burden, emphasising the importance of early recognition for timely management.

Five-year retrospective review of ultrasound-guided manual vacuum aspiration for first-trimester miscarriage.

INTRODUCTION: Manual vacuum aspiration is increasingly accepted as an alternative to medical or surgical evacuation of the uterus after first-trimester miscarriage. This study aimed to assess the efficacy of ultrasound-guided manual vacuum aspiration (USG-MVA) in the management of first-trimester miscarriage. METHODS: This retrospective analysis included adult women with first-trimester miscarriage who underwent USG-MVA in Hong Kong between July 2015 and February 2021. The primary outcome was the efficacy of USG-MVA in terms of complete evacuation of the uterus, without the need for further medical or surgical intervention. Secondary outcomes included tolerance of the entire procedure, the success rate of karyotyping using chorionic villi, and procedural safety (ie, any clinically significant complications). RESULTS: In total, 331 patients were scheduled to undergo USG-MVA for first-trimester miscarriage or incomplete miscarriage. The procedure was completed in 314 patients and well-tolerated in all of those patients. The complete evacuation rate was 94.6% (297/314), which is similar to the rate (98.1%) achieved by conventional surgical evacuation in a previous randomised controlled trial in our unit. There were no major complications. Samples from 95.2% of patients were suitable for karyotyping, which is considerably higher than the rate of suitable samples (82.9%) obtained via conventional surgical evacuation in our previous randomised controlled trial. CONCLUSION: Ultrasound-guided manual vacuum aspiration is a safe and effective method to manage first-trimester miscarriage. Although it currently is not extensively used in Hong Kong, its broader clinical application could avoid general anaesthesia and shorten hospital stay.

Implementation of ovarian tissue cryopreservation in Hong Kong.

INTRODUCTION: Worldwide, >130 babies have been born from ovarian tissue cryopreservation (OTC) and ovarian tissue transplantation (OTT). Ovarian tissue cryopreservation can improve quality of life among young female cancer survivors. Here, we assessed the feasibility of OTC and subsequent OTT in Hong Kong via xenografts in nude mice. METHODS: This pilot study was conducted in a university-affiliated tertiary hospital. Fifty-two ovarian tissues were collected from 12 patients aged 29 to 41 years during ovarian surgery, then engrafted into 34 nude mice. The efficacies of slow freezing and vitrification were directly compared. In Phase I, non-ovariectomised nude mice underwent ovarian tissue engraftment. In Phase II, ovariectomised nude mice underwent ovarian tissue engraftment, followed by gonadotrophin administration to promote folliculogenesis. Ovarian tissue viability was assessed by gross anatomical, histological, and immunohistochemical examinations before and after OTC. Follicular density and morphological integrity were also assessed. RESULTS: After OTC and OTT, grafted ovarian tissues remained viable in nude mice. Primordial follicles were observed in thawed and grafted ovarian tissues, indicating that the cryopreservation and transplantation protocols were both effective. The results were unaffected by gonadotrophin stimulation. CONCLUSION: This study demonstrated the feasibility of OTC in Hong Kong as well as primordial follicle viability after OTC and OTT in nude mice. Ovarian tissue cryopreservation is ideal for patients who cannot undergo the ovarian stimulation necessary for oocyte or embryo freezing as well as prepubertal girls (all ineligible for oocyte freezing). Our findings support the clinical implementation of OTC and subsequent OTT in Hong Kong.

Prediction of spontaneous preterm birth and preterm prelabor rupture of membranes using maternal factors, obstetric history and biomarkers of placental function at 11-13 weeks.

OBJECTIVES: To determine whether first-trimester biomarkers of placental function can be used to screen for spontaneous preterm birth (sPTB), and to develop prediction models using maternal factors, obstetric history and biomarkers of placental function at 11-13 weeks for the calculation of patient-specific risk for sPTB. METHODS: This was a retrospective secondary analysis of data derived from a prospective cohort study on first-trimester screening for pre-eclampsia in singleton pregnancies attending for routine Down syndrome screening at 11 + 0 to 13 + 6 weeks' gestation at a tertiary obstetric unit between December 2016 and September 2019. A split-sample internal validation method was used to explore and develop prediction models for all sPTB at < 37 weeks and for PTB at < 37 weeks after preterm prelabor rupture of membranes (PPROM) using maternal risk factors, uterine artery Doppler indices, serum placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A) and ß-human chorionic gonadotropin (ß-hCG). Screening performance was assessed using receiver-operating-characteristics (ROC)-curve analysis, with calculation of the areas under the ROC curves (AUCs). RESULTS: A total of 9298 singleton pregnancies were included in this study. sPTB at < 37 weeks occurred in 362 (3.89%) cases, including 231 (2.48%) cases of PPROM. sPTB at < 34 weeks occurred in 87 (0.94%) cases, including 39 (0.42%) cases of PPROM. Identified maternal risk factors for sPTB at < 37 weeks included chronic hypertension, conception using in-vitro fertilization and history of PTB. Maternal risk factors for PPROM at < 37 weeks included conception using in-vitro fertilization and history of PTB. Median PlGF multiples of the median (MoM) and PAPP-A MoM were significantly reduced in women with sPTB at < 37 weeks, as well as in those who had PPROM, compared to those who delivered at term. Screening by a combination of maternal risk factors, PAPP-A and PlGF achieved better performance in predicting sPTB at < 37 weeks (AUC, 0.630 vs 0.555; detection rate (DR), 24.8% vs 16.6% at a false-positive rate (FPR) of 10%; P ≤ 0.0001) and PPROM at < 37 weeks (AUC, 0.643 vs 0.558; DR, 28.1% vs 17.0% at a FPR of 10%; P ≤ 0.0001) than using maternal risk factors alone. Both models were successfully applied to the internal validation dataset, with AUCs of 0.628 and 0.650, respectively. CONCLUSIONS: We demonstrated that low levels of maternal serum PAPP-A and PlGF in the first trimester are associated with increased risks of sPTB and PPROM at < 37 weeks. However, further research is needed to identify additional biomarkers to improve the screening performance of the combined model that includes maternal risk factors, PAPP-A and PlGF before clinical application. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Potential effects of COVID-19 on reproductive systems and fertility; assisted reproductive technology guidelines and considerations: a review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) employs the angiotensin-converting enzyme 2 (ACE2) receptor in the renin-angiotensin system for viral entry. The ACE2 receptor is present in both female and male reproductive systems, and reports of multi-organ involvement have led to uncertainty regarding its effects on the reproductive system and fertility. We review the existing literature regarding the function of ACE2 and the renin-angiotensin system in the female and male reproductive systems to postulate the possible implications of SARS-CoV-2 regarding fertility. Because of the presence of ACE2 in the ovaries, SARS-CoV-2 infection may disrupt ovarian function and hence oocyte quality. Higher expression of ACE2 in the endometrium with age and during the secretory phase raises concern about increased susceptibility to infection during periods of high ACE2 expression. The possibility of vertical transmission and the presence of ACE2 in the placenta and during pregnancy are also discussed. The presence of SARS-CoV-2 RNA in semen is controversial, but impaired semen quality has been found in men with moderate coronavirus disease 2019 infection. Evidence of orchitis and hormonal changes seen in male coronavirus disease 2019 infection may lead to infertility. The implications of these effects on assisted reproductive technology (ART) outcomes are also explored. The ART guidelines from different fertility societies for the management of patients treated with ART are provided. The importance of prioritising 'time-sensitive' patients for ART, counselling patients about the uncertainty and risks of ART, and pregnancy during the pandemic is discussed. Recommendations are also provided for infection control and safe regulation of ART centres and laboratories.

Expanded carrier screening using next-generation sequencing of 123 Hong Kong Chinese families: a pilot study.

INTRODUCTION: To determine the carrier frequency and common mutations of Mendelian variants in Chinese couples using next-generation sequencing (NGS). METHODS: Preconception expanded carrier testing using NGS was offered to women who attended the subfertility clinic. The test was then offered to the partners of women who had positive screening results. Carrier frequency was calculated, and the results of the NGS panel were compared with those of a target panel. RESULTS: One hundred twenty-three women and 20 of their partners were screened. Overall, 84 (58.7%) individuals were identified to be carriers of at least one disease, and 68 (47.6%) were carriers after excluding thalassaemias. The most common diseases found were GJB2-related DFNB1 nonsyndromic hearing loss and deafness (1 in 4), alpha-thalassaemia (1 in 7), beta-thalassaemia (1 in 14), 21-hydroxylase deficient congenital adrenal hyperplasia (1 in 13), Pendred's syndrome (1 in 36), Krabbe's disease (1 in 48), and spinal muscular atrophy (1 in 48). Of the 43 identified variants, 29 (67.4%) were not included in the American College of Medical Genetics and Genomics or American College of Obstetrics and Gynecology guidelines. Excluding three couples with alpha-thalassaemia, six at-risk couples were identified. CONCLUSION: The carrier frequency of the investigated members of the Chinese population was 58.7% overall and 47.6% after excluding thalassaemias. This frequency is higher than previously reported. Expanded carrier screening using NGS should be provided to Chinese people to improve the detection rate of carrier status and allow optimal pregnancy planning.

Treatment of patients with Mayer-Rokitansky- Küster-Hauser syndrome in a tertiary hospital.

INTRODUCTION: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is an uncommon congenital malformation characterised by agenesis or hypoplasia of the vagina and uterus. Here, we describe the treatment of patients with MRKH syndrome in a tertiary hospital. METHODS: This retrospective study included patients with MRKH syndrome attending the Paediatric and Adolescent Gynaecology Clinic in a tertiary hospital. Their clinical manifestations, examinations, and methods for neovagina creation were recorded. Among patients who underwent vaginal dilation (VD), therapy duration, vaginal width and length at baseline and after VD, complications, and sexual activity and dyspareunia outcomes were evaluated. RESULTS: Forty nine patients with MRKH syndrome were identified. Their mean age at presentation was 17.9 years; 69.4% and 24.5% of patients presented for primary amenorrhoea treatment and vaginoplasty, respectively. Forty eight patients had normal renal imaging findings and 46 XX karyotypes. Seventeen (34.7%) patients underwent VD as first-line therapy; three did not complete the therapy. Two had surgical vaginoplasty, whereas five achieved adequate vaginal length by sexual intercourse alone; 25 had not yet requested VD. The mean duration of VD was 16±10.2 (range, 4-35) weeks. The widths and lengths of the vagina at baseline and after VD were 1.1±0.28 cm and 1.3±0.7 cm, and 3.1±0.5 cm and 6.9±0.9 cm, respectively. The overall success rate of VD was 92.3%. Vaginal spotting was the most common complication (21%); only one patient reported dyspareunia. CONCLUSIONS: Mayer-Rokitansky-Küster-Hauser syndrome is an uncommon condition that requires multidisciplinary specialist care. Vaginal dilation is an effective first-line approach for neovagina creation.

Preservation of fertility in premenopausal patients with breast cancer.

INTRODUCTION: Cancer survivorship is increasingly important with advances in cancer therapeutics. Minimisation of treatment-related morbidity is an area that requires attention. This situation is most pressing in premenopausal patients with breast cancer, in whom advances in hormonal and targeted therapies have improved mortality rates. However, treatment-related infertility is still poorly addressed, and in East Asia, there is limited discussion regarding management of treatment-related infertility. METHODS: A search of the literature was conducted using PubMed, Google Scholar, and Science Direct using the terms "breast cancer", "fertility preservation", "oocyte and embryonic cryopreservation", "GnRH-a co-administration", "ovarian tissue cryopreservation and transplantation", "Japan", "China", "Korea", and 'Singapore". Only studies published in English from 1980-2019 were included. The focus of the review was on identifying the current fertility preservation methods available to premenopausal women with breast cancer and the barriers that impede access. RESULTS: Fertility preservation options include GnRH-a co-administration to minimise treatment-associated infertility, oocyte and embryonic cryopreservation, and emerging treatments such as ovarian tissue cryopreservation and transplantation. In East Asia, the uptake of fertility preservation options has been limited despite it being a major patient concern. A lack of awareness of fertility preservation treatments hinders discussion between patients and clinicians about fertility preservation. CONCLUSION: Despite progress in fertility preservation technologies, their impact for patients will be minimal if there is a lack of awareness/use of the technology. This review aims to raise awareness of such technologies among clinicians, enabling discussion between patients and clinicians about fertility preservation options.

Awareness of fertility preservation among Chinese medical students.

INTRODUCTION: The fertility preservation (FP) services offered in Hong Kong are underutilised. There have been no previous studies on Chinese medical students to investigate the underlying reasons for this underutilisation in terms of awareness, knowledge, and attitudes towards FP and age-related fertility. METHODS: This was a cross-sectional survey among Chinese medical students in Hong Kong. RESULTS: The majority of participants (77.8%) were not familiar with any clinics or specialists who provide FP services. The vast majority (88.1%) underestimated female infertility at age 45 years, and 89.8% overestimated the age of male fertility decline. The students' FP knowledge was mainly acquired from electronic media (58.4%) and medical school (57.6%). Medical students showed overwhelming support towards FP for medical reasons (97.9%) but had mixed responses about FP for elective reasons related to career development in women (58.8%). Of the participants, 80.2% agreed that the government should subsidise FP services for patients with medical reasons. CONCLUSION: This study highlights the limited awareness and knowledge of FP among Chinese medical students. There is a strong worldwide need to increase education about and exposure to FP in the medical curriculum and improve medical students' knowledge.

External validation of a simple scoring system to predict pregnancy viability in women presenting to an early pregnancy assessment clinic.

INTRODUCTION: A scoring system combining clinical history and simple ultrasound parameters was developed to predict early pregnancy viability beyond the first trimester. The scoring system has not yet been externally validated. This study aimed to externally validate this scoring system to predict ongoing pregnancy viability beyond the first trimester. METHODS: This prospective observational cohort study enrolled women with singleton intrauterine pregnancies before 12 weeks of gestation. Women underwent examination and ultrasound scan to assess gestational sac size, yolk sac size, and fetal pulsation status. A pregnancy-specific viability score was derived in accordance with the Bottomley score. Pregnancy outcomes at 13 to 16 weeks were documented. Receiver-operating characteristic curve analysis was used to assess the discriminatory performance of the scoring system. RESULTS: In total, 1508 women were enrolled; 1271 were eligible for analysis. After adjustment for covariates, miscarriage (13%) was significantly associated with age ≥35 years (odds ratio [OR]=1.99, 95% confidence interval [CI]: 1.19-3.34), higher bleeding score (OR=2.34, 95% CI: 1.25-4.38), gestational age (OR=1.17, 95% CI: 1.13-1.22), absence of yolk sac (OR=4.73, 95% CI: 2.11-10.62), absence of fetal heart pulsation (OR=3.57, 95% CI: 1.87-6.84), mean yolk sac size (OR=1.25, 95% CI: 1.06-1.47), and fetal size (OR=0.82, 95% CI: 0.77-0.88). The area under the receiver operating characteristic curve was 0.91 (95% CI: 0.89-0.93). Viability score of ≥1 corresponded to a >90% probability of viable pregnancy. CONCLUSIONS: The scoring system was easy to use. A score of ≥1 could be used to counsel women who have a high likelihood of viable pregnancy beyond the first trimester.

Uterine Fibroid Symptom and Health-related Quality of Life Questionnaire: a Chinese translation and validation study.

INTRODUCTION: The Uterine Fibroid Symptom and Health-related Quality of Life (UFS-QOL) questionnaire is a validated tool in English language to assess treatment outcomes for women with fibroids. We performed a Chinese (traditional) translation and cultural adaptation of it and evaluated its reliability, validity, and responsiveness. METHODS: Overall, 223 Chinese women aged ≥18 years with uterine fibroids self-administered the UFS-QOL, Short-Form Health Survey-12, pictorial blood loss assessment chart (PBAC), and a visual analogue scale (VAS) on fibroid-related symptom severity. Demographics and haemoglobin levels were recorded; physical examination and ultrasound for size of fibroids were performed. Half of the women were followed up 6 months later for responsiveness. RESULTS: Cronbach's alpha coefficients ranged from 0.706 to 0.937, demonstrating high internal reliability. The intra-class correlation coefficients to measure test-retest reliability implied excellent stability of symptom scores (0.819, P<0.001), health-related quality of life scores (0.897, P<0.001), and all subscales (range 0.721-0.870, P<0.001). Convergent validity was demonstrated by positive correlations between the findings of various symptom severity assessment tools (PBAC, VAS on fibroid-related symptoms severity) and the symptom severity domain of Chinese UFS-QOL. In addition, there were positive correlations between health-related quality of life scores of Chinese UFS-QOL and the corresponding subscales of the Short-Form Health Survey-12. Responsiveness was shown by reduction of symptom severity scores and improvement of health-related quality of life scores after treatment. CONCLUSIONS: The Chinese version of the UFS-QOL is valid, reliable, and responsive to changes after treatment.

Prevalence of obstetric anal sphincter injury following vaginal delivery in primiparous women: a retrospective analysis.

INTRODUCTION: Obstetric anal sphincter injuries (OASIS) may be underdetected in primiparous women. This study evaluated the prevalence of OASIS in primiparous women after normal vaginal delivery or instrumental delivery using endoanal ultrasound (US) during postnatal follow-up. METHODS: This study retrospectively analysed endoanal US data collected during postnatal follow-up (6-12 months after vaginal delivery) at a tertiary hospital in Hong Kong. Offline analysis to determine the prevalence of OASIS was performed by two researchers who were blinded to the clinical diagnosis. Symptoms of faecal and flatal incontinence were assessed with the Pelvic Floor Distress Inventory. RESULTS: Of 542 women included in the study, 205 had normal vaginal delivery and 337 had instrumental delivery. The prevalence of OASIS detected by endoanal US was 7.8% (95% confidence interval [CI]=4.1%-11.5%) in the normal vaginal delivery group and 5.6% (95% CI=3.1%-8.1%) in the instrumental delivery group. Overall, 82.9% of women with OASIS on endoanal US did not show clinical signs of OASIS. Birth weight was significantly higher in the OASIS group (P=0.012). At 6 to 12 months after delivery, 5.5% of women reported faecal incontinence and 17.9% reported flatal incontinence, but OASIS was not associated with these symptoms. CONCLUSIONS: Additional training for midwives and doctors may improve OASIS detection.