Introduction: To report the progress of the human living uterus transplant research project in Singapore.
Material and methods: The uterus transplant research project began in 2012 with a collaboration between the Swedish and Singapore teams. Ethics approval was obtained from the SingHealth Centralised Institutional Review Board, the SingHealth Transplant and the Singapore General Hospital Biomedical Ethics Committee to perform 5 uterus transplant procedures in a collaborative multi-site research study at the Singapore General Hospital. Regulatory approval was obtained from the Ministry of Health, Singapore. A suitable recipient-donor pair was identified. The living donor was the perimenopausal mother-in-law of the recipient who had Mayer-Rokitansky-Kuster-Hauser syndrome. They underwent the requisite matching process as well as robust medical, psychiatric and psychosocial assessments. The recipient then underwent in vitro fertilization (IVF) treatment resulting in 6 frozen blastocysts. Preparations were made for the transplant surgery on 25 November 2023 in Singapore General Hospital, aided by the 3 Uterus transplant experts from the Swedish Team, for whom temporary registration was granted by the Singapore Medical Council.
Results: This first uterus transplant procedure involved an operative time of 10 h and 30 min for the donor. The synchronized recipient surgery lasted 6 h and 20 min. Surgery was by midline laparotomy in both the living donor and recipient. The total warm ischemic time of the graft was 45 min, and the cold ischemic time was 1 h 45 min (total ischemic time 2 h 30 min). The patient's first menstruation occurred 38 days after the uterus transplant procedure. Cytomegalovirus infection was detected 6 weeks postoperatively for which she was aggressively treated. Serial cervical biopsies showed no rejection and Doppler ultrasound of the transplanted uterus showed good uterine blood flow.
Conclusions: To date the Living Donor Uterus Transplant Research Project in Singapore has progressed with a uterus transplant surgery involving a living donor performed by a multidisciplinary team. The recipient had a menstrual period 38 days postoperatively. Further study of the outcomes from this procedure will inform the safety and efficacy of uterus transplant in the Singapore context.
Introduction: Graft optimization is a necessity in order to develop uterus transplantation from brain-dead donors, as a complement to living donors, as these grafts are rare and the last organs retrieved in multiple organ donation. The aim of this study was to assess the feasibility and interest of hypothermic machine perfusion (HMP) in uterus transplantation using a porcine model; secondary outcomes were the evaluation of the graft's tolerance to a prolonged cold ischaemia time and to find new biomarkers of uterus viability.
Material and methods: Fifteen uterus allotransplantations were performed in a porcine model, after 18 h of cold ischaemia, divided in three groups: Static cold storage in a HTK solution, HMP (with the VitaSmart (™) machine Bridge to Life Ltd.) with a UW-MP solution, and static cold storage in a UW solution. The main outcome was macroscopic: uterine arteries pulsatility, recoloration, and bleeding at the cut. Secondary outcomes were histological analyses (Zitkute and inflammation scores), caspase3 immunohistochemistry and plasmatic dosage of biomarkers.
Results: 14/15 allotransplantations were performed according to the protocol and met the criteria of macroscopic vitality. Grafts treated with HMP (MP did not show significantly more tissue) damage than the recipient's uterus, contrary to grafts in static cold storage, independently of the solution used. This difference disappeared one and 3 h after uterus transplantation. Plasma dosages before and after uterus transplantation did not allow to identify a new biomarker of uterus viability.
Conclusions: HMP is feasible in a porcine model, without inflicting damage on the grafts during cold ischaemia time. Grafts exposed to HMP seemed to better endure reperfusion phenomena, but this advantage did not last over time.
Introduction: Intrauterine devices (IUDs) are highly effective contraceptives. Despite their effectiveness, pregnancies can occur during IUD use, and the management of such cases, particularly when the pregnancy is desired, remains controversial.
Material and methods: We conducted a systematic review and meta-analysis to evaluate outcomes in women who unintentionally conceived while using IUDs and chose to continue their pregnancies. We searched PubMed, Embase, and Cochrane databases to identify studies comparing women who removed their IUD after pregnancy discovery to those who retained it. The primary outcomes assessed were miscarriage, bleeding during pregnancy, and preterm delivery. Secondary outcomes included cesarean delivery, chorioamnionitis, congenital malformations, intrauterine growth restriction, preterm premature rupture of membranes, and stillbirth. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for the binary outcomes using random-effects models to account for variability across studies. The certainty of evidence was measured using the Grading of Recommendations Assessment, Development, and Evaluation approach.
Results: From 3719 records, 4 cohorts were included. Among the 693 pregnant women analyzed, 402 had their IUD removed, while 291 retained the device. The analysis focused on copper IUDs, with most studies reporting removal during the first trimester and after ultrasound evaluation, although gaps in standardized reporting practices and removal methods were noted. Significant benefits were observed for the IUD-removed group, including reduced incidences of bleeding during gestation (OR 0.42; 95% CI 0.24 to 0.73; p < 0.01. Moderate certainty of evidence), and miscarriage (OR 0.29; 95% CI 0.17 to 0.48; p < 0.01. Moderate certainty of evidence). There was no significant difference in preterm delivery rates (OR 0.78; 95% CI 0.34 to 1.76; p = 0.55).
Conclusions: This meta-analysis, based on data from cohort studies with moderate certainty of evidence, indicates that removing an IUD after pregnancy diagnosis may reduce the odds of miscarriage and bleeding during gestation. However, further high-quality research is needed to evaluate outcomes in pregnancies associated with hormonal IUDs, as well as critical factors such as gestational age at diagnosis, timing of IUD removal, and the position of the gestational sac relative to the device.
Introduction: Ectopic pregnancy (EP) is a serious clinical gynecological emergency. Patients with EP history are at higher risk of EP resulting from IVF/ICSI (IVF-EP). Besides, studies have suggested that previous EP treatments may affect the incidence of IVF-EP. However, this result does not consider possible confounding factors due to the number of previous EP. Therefore, we assessed the impact of salpingectomy on the risk and characteristics of IVF-EP in patients with different previous spontaneous EP.
Material and methods: This retrospective cohort study included 43 647 patients receiving their first IVF/ICSI treatments at our center from January 2013 to June 2022. Cohorts were assigned according to the number of previous spontaneous EP by propensity score matching. After propensity score matching, there were 3252 participants in the no previous EP history cohort (NEP cohort), 3252 in the one EP history cohort (One-EP cohort), and 1571 in the 2 or more EP history cohort (> = 2 EP cohort). To assess the effect of previous salpingectomy on IVF-EP, One-EP cohort and > =2 EP cohort were divided into three subcohorts separately, according to their tubal statuses.
Results: The IVF-EP rate was significantly higher in patients with EP history (NEP cohort: 1.3% vs. One-EP cohort: 2.2% vs. >=2 EP cohort: 2.0%, p = 0.023). In subcohort analysis, patients with different tubal statuses presented no statistical differences in IVF-EP rate (both in One-EP cohort and > =2 EP cohort). Considering the interaction between tubal status and number of previous EP, binary logistic regression was performed and it was demonstrated that bilateral salpingectomy might reduce the risk of IVF-EP in patients with recurrent EP history but increase the risk of non-tubal IVF-EP, while the history of spontaneous EP increased both IVF-EP and non-tubal IVF-EP rate.
Conclusions: Previous EP history was associated with a higher risk of IVF-EP and non-tubal IVF-EP. Salpingectomy reduced the overall risk of IVF-EP in patients with EP history, while bilateral salpingectomy increased the risk of non-tubal IVF-EP.
Introduction: Raising the temperature of abdominal wall endometriosis lesions contributes to an effective ablation; however, providing sufficient protection to the surrounding tissues remains a challenge. In this study, we aimed to combine ultrasound and single-port laparoscopic images to not only achieve complete ablation of abdominal wall endometriosis lesions but also protect surrounding tissues from damage. The adverse events and complications were Common Terminology Criteria for Adverse Events grade 1 or Society of Interventional Radiology classification grade A.
Material and methods: This historical study included 30 patients with abdominal wall endometriosis who underwent ultrasound and single-port laparoscopic-guided microwave ablation at the Ultrasonography and Gynecology Department of the Wuhan Central Hospital between October 2017 and February 2022. Ultrasonography and magnetic resonance imaging were used to evaluate the number, size, and depth of the lesions. Pain levels were assessed using a visual analog scale. Subsequently, ultrasound and single-port laparoscopic-guided microwave ablation of the lesions was performed, and patients were followed up to monitor the lesion volume and pain.
Results: One patient experienced an intra-abdominal wall burn that was detected by single-port laparoscopy, and ablation was stopped immediately. No other complications were recorded. Following surgery, the lesion volume decreased and was lower than the preoperative lesion volume at 1 year postoperatively (1.6 ± 1.3 vs. 4.0 ± 3.6 cm3; p < 0.05). Visual analog scale scores revealed that, compared with preoperative levels, pain was reduced significantly at all postoperative time points (p < 0.01). The recurrence rate was 16.7% (5/30).
Conclusions: The addition of single-port laparoscopy to ultrasound-guided microwave ablation may allow greater protection of the surrounding tissues, particularly in cases involving deep lesions, and may, therefore, represent a promising clinical treatment strategy.
Introduction: Recurrent pregnancy loss (RPL), defined as two or more consecutive pregnancy losses before 24 weeks of gestation, affects up to 1%-2% of couples. Aim of this retrospective cohort study was to report the main causes and pregnancy outcomes of a cohort of women with RPL and the efficacy of a personalized work-up and treatment in terms of live birth rate.
Material and methods: Women with primary (pRPL) and secondary (sRPL) RPL underwent a complete work-up and personalized therapeutic management. Data related to clinical findings and subsequent pregnancy outcomes were collected. A retrospective comparison between clinical findings and pregnancy outcomes of pRPL versus sRPL was performed by Mann-Whitney U or Chi-square test.
Results: Main findings after diagnostic work-up in pRPL (n = 157) versus sRPL (n = 138) couples were hormonal and metabolic factors (75% vs. 90%, p < 0.01), autoimmunity (52% vs. 59%, p = 0.2), acquired uterine/endometrial factors (43% vs. 34%, p = 0.2), vaginal and/or cervical infections (19% vs. 49%; p < 0.0001), congenital Mullerian anomalies (15% vs. 9%; p = 0.1), inherited thrombophilias (13% vs. 21%; p = 0.1), female karyotype abnormalities (2% vs. 2%; p = 0.9), sperm infections (27% vs. 22%; p = 0.1), abnormal semen analysis (17% vs. 14%; p = 0.1), male karyotype abnormalities (2% vs. 0%; p = 0.1). Higher pregnancy and fetal loss rate was observed in pRPL compared with sRPL (85% vs. 56%, p < 0.0001and 9% vs. 0%, p < 0.01, respectively). Higher live birth rate was found in pRLP versus sRPL women (76% vs. 56%, p < 0.001). Increased live birth rate was observed among pRPL women aged <40 years (OR 2.76; CI 1.36-5.64, p < 0.01) and/or with an AMH >1 ng/mL (OR 3.96; CI 1.34-12.52, p < 0.05). Among sRPL women, the age < 40 years was significantly associated to higher live birth rate (OR 3.23; 1.55-6.94, p < 0.01).
Conclusions: RPL is a heterogeneous multifactorial syndrome. A customized management can lead to a good pregnancy outcome in more than a half of cases. Age <40 and AMH >1 ng/mL are the major positive predictors of live birth rate in RPL women.
Introduction: To compare the effectiveness and safety of Manchester procedure versus vaginal hysterectomy in the treatment of mid-compartment prolapse in women.
Material and methods: We searched PubMed, Web of Science, Google Scholar, and the Cochrane Library for randomized controlled trials (RCTs), prospective, or retrospective studies comparing the Manchester procedure and vaginal hysterectomy up to July 2024. Primary outcomes included anatomical recurrence, subjective recurrence, overall complication rate, and reoperation. Secondary outcomes included estimated blood loss, operative time, and relevant subgroup analyses. This study has been registered in PROSPERO with the registration number CRD42024575874.
Results: A total of 11 783 cases from 1 RCT, 1 prospective study, and 9 retrospective studies were included. For the primary outcomes, the Manchester procedure demonstrated significantly lower subjective recurrence rates (risk ratio [RR] = 0.85; 95% confidence interval [CI]: 0.73-0.98; I2 = 0%; p = 0.03) and reoperation rates (RR = 0.62; 95% CI: 0.43-0.89; I2 = 64%; p = 0.009) compared with vaginal hysterectomy, with no significant difference in anatomical recurrence rates (RR = 0.84; 95% CI: 0.58-1.21; I2 = 54%; p = 0.34) and overall complication rates (RR = 0.89; 95% CI: 0.79-1.00; I2 = 0%; p = 0.06) between the two groups. Secondary outcomes indicated that the Manchester procedure had a significantly shorter operative time and less estimated blood loss (p < 0.05). Subgroup analysis indicated that the Manchester procedure was associated with lower short-term (1-3 years) subjective recurrence rates (RR = 0.87; 95% CI: 0.78-0.98; I2 = 0%; p = 0.02) and reoperation rates (RR = 0.71; 95% CI: 0.55-0.92; I2 = 0%; p = 0.008). No significant differences were found between the two groups in terms of short-term anatomical recurrence rates or in mid- to long-term (>3 years) subjective recurrence rates, anatomical recurrence rates, and reoperation rates (p > 0.05).
Conclusions: Overall, the rates of anatomical recurrence and overall complications for Manchester procedure and vaginal hysterectomy are similar. Manchester procedure appears to have a lower subjective recurrence and reoperation rate in the short term, but this advantage was not observed in mid- to long-term follow-up. Further high-quality prospective studies are needed to confirm these findings.
Uterus transplantation (UTx) has emerged from clinical trials and is expected to become the standard of care for uterine factor infertility. Uterus transplant candidates historically have had to meet strict eligibility criteria to participate in clinical trials. Continued application of psychologic selection criteria from clinical trial may hinder the expansion of UTx. UTx candidates come with unique mental health challenges, having a higher incidence of mental health problems than the general population. We posit in this commentary that broadening psychological inclusion criterion and provision of mental health support will enhance access to UTx. At the University of Alabama at Birmingham (UAB), candidates are not required to mention mental health comorbidities at initial screening. Regardless of their mental health comorbidity status, all recipients at the UAB have had a successful uterus transplant. Outcome of a live birth has also not been affected. Perioperative mental health challenges are successfully managed with a support of psychologists and psychiatrists.
Introduction: Overall childbirth experience scores are used both in research and in clinical settings. Since it is still not fully understood what assessment of childbirth experience on a single-item numeric rating scale or visual analog scale represents, the aim of this study was to explore women's reasoning and thoughts when rating overall childbirth experience numerically.
Material and methods: A qualitative interview study of 26 women was conducted using a think-aloud technique at a university referral hospital in Sweden. A manifest qualitative content analysis was performed to generate categories and sub-categories representing how women decided which single value should represent their experience of giving birth.
Results: Two main categories emerged from the analysis. The first, Strategies for choosing a number, reflects variations in how the women approached the rating scale itself and includes five sub-categories, each relating to a different strategy: (1) Comparison, (2) Start from the maximum value, (3) Start from the middle, (4) Weigh certain experiences more heavily, and (5) A means to an end. The second category, Specific factors considered in the rating, includes four sub-categories, representing groups of factors contributing to the final childbirth experience score: (1) The time period, (2) Events linked to strong emotions, (3) Perceived support, and (4) Previous expectations. What the women included in their overall childbirth experience was hence translated into a number, using strategies from the first category and factors from the second category.
Conclusions: The considerable variations in how women approach the rating scale, and what they include in the assessment of overall childbirth experience, suggest that not only the childbirth experience itself but also the reasoning when evaluating it, is multifaceted. A standardized phrasing of the question and a clear purpose for the evaluation is warranted to strengthen the validity of the measurement. When used clinically for identifying women in need of support after childbirth, the rating should be followed by a conversation about the experience of giving birth, independent of the value chosen.
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