Exploring the knowledge, attitudes, and perceptions of women of reproductive age towards fertility and elective oocyte cryopreservation for age-related fertility decline in the UK: a cross-sectional survey.

STUDY QUESTION: What are the knowledge, perceptions and attitudes towards fertility and elective oocyte cryopreservation (OC) for age-related fertility decline (ARFD) in women in the UK? SUMMARY ANSWER: Awareness of OC for ARFD has reportedly improved compared to studies carried out almost a decade ago, but inconsistencies in knowledge remain regarding the rate of miscarriage amongst specific age groups, the financial costs and optimal age to undergo OC for ARFD. WHAT IS KNOWN ALREADY: The age of first-time motherhood has increased amongst western societies, with many women of reproductive age underestimating the impact of age on fertility. Further understanding of women's awareness of their fertility, the options available to preserve it and the barriers for seeking treatment earlier are required in order to prevent the risk of involuntary childlessness. STUDY DESIGN, SIZE, DURATION: A hyperlink to a cross-sectional survey was posted on social media (Instagram) between 25 February 2021 and 11 March 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women from the general population aged 18-50 years were invited to complete the survey. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 5482 women fulfilled the inclusion criteria and completed the survey. The mean age of participants was 35.0 years (SD 10.25; range 16-52). Three quarters (74.1%; n = 4055) disagreed or strongly disagreed they felt well informed regarding the options available to preserve their fertility, in case of a health-related problem or ARFD. The majority overestimated the risk of miscarriage in women aged ≥30 years old, with 14.5% correctly answering 20%, but underestimated the risks in women ≥40, as 20.1% correctly answered 40-50%. Three quarters (73.2%; n = 4007) reported an awareness of OC for ARFD and 65.8% (n = 3605) reported that they would consider undergoing the procedure. The number of women who considered OC for ARFD across age groups were as follows: 18-25 (8.3%; n = 300), 26-30 (35.8%; n = 1289), 31-35 (45.9%; n = 1654), 36-40 (9.6%; n = 347), 41-45 (0.3%; n = 13), and 46-50 (0.1%; n = 2). The majority of women (81.3%; n = 4443) underestimated the cost of a single cycle of OC for ARFD (<£5000). Furthermore, 10.4% (n = 566) believed a single cycle would be adequate enough to retrieve sufficient oocytes for cryopreservation. Approximately 11.0% (n = 599) believed OC for ARFD may pose significant health risks and affect future fertility. Less than half agreed or strongly agreed that the lack of awareness regarding OC for ARFD has impacted the likelihood of pursuing this method of fertility preservation further (41.4%; n = 2259). LIMITATIONS, REASONS FOR CAUTION: Results from cross-sectional studies are limited as interpretations made are merely associations and not of causal relationships. The online nature of participant recruitment is subject to selection bias, considering women with access to social media are often from higher socioeconomic and education backgrounds, thus limiting generalizability of the findings. WIDER IMPLICATIONS OF THE FINDINGS: Further education regarding the financial costs and optimal age to undergo elective OC to increase the chances of successful livebirth are required. Clinicians should encourage earlier fertility counselling to ensure that OC is deemed a preventative measure of ARFD, rather than an ultimate recourse to saving declining fertility. STUDY FUNDING/COMPETING INTEREST(S): No funding was required for this article. There are no conflicts of interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Uterine Transplantation: Scientific Impact Paper No. 65 April 2021.

A uterine transplant, or womb transplant, provides a potential treatment for women who cannot become pregnant or carry a pregnancy because they do not have a womb, or have a womb that is unable to maintain a pregnancy. This is estimated to affect one in 500 women. Options for those who wish to start a family include adoption and surrogacy, but these are associated with legal, cultural, ethical and religious implications that may not be appropriate for some women and their families. A womb transplant is undertaken when the woman is ready to start a family, and is removed following the completion of their family. Womb transplants have been performed all over the world, with more than 70 procedures carried out so far. At least 23 babies have been born as a result, demonstrating that womb transplants can work. While the procedure offers a different option to adoption and surrogacy, it is associated with significant risks, including multiple major surgeries and the need to take medications that help to dampen the immune system to prevent rejection of the womb. To date there has been a 30% risk of a transplant being unsuccessful. Although the number of transplants to date is still relatively small, the number being performed globally is growing, providing an opportunity to learn from the experience gained so far. This paper looks at the issues that have been encountered, which may arise at each step of the process, and proposes a framework for the future. However, long term follow-up of cases will be essential to draw reliable conclusions about any overall benefits of this procedure.

Potential importance of supplementation with zinc for autism spectrum disorder.

Zinc is an essential micronutrient for cellular proliferation and subsequent body and brain development. Zinc deficiency is becoming a major public health issue equally in under-developed and developed countries. The lack of sufficient zinc, whether related to environmental or internal factors, is an important environmental stressor that is eligible to become elucidated as a contributing factor for the pathogenesis of autism spectrum disorder (ASD). The aim of this manuscript is to briefly overview available data regarding the relationship of zinc deficiency with the development of ASD and to relate these data with currently known pathogenetic mechanisms of this disorder namely brain growth disturbances and neuropeptides secretion. Zinc deficiency impacts brain connectivity and growth and alters adequate neurotransmission. In addition, zinc deficiency may indirectly act on the brain by disturbing the immune system and by altering the normal gut-brain connection. Zinc seems to be important for the social effect of neuropeptides. Zinc supplementation in pregnant women and newborn children with the aim of preventing ASD needs further consideration.

The vaginal microbiome in uterine transplantation.

Women with congenital absolute uterine factor infertility (AUFI) often need vaginal restoration to optimise sexual function. Given their lack of procreative ability, little consideration has previously been given to the resultant vaginal microbiome (VM). Uterine transplantation (UTx) now offers the opportunity to restore these women's reproductive potential. The structure of the VM is associated with clinical and reproductive implications that are intricately intertwined with the process of UTx. Consideration of how vaginal restoration methods impact VM is now warranted and assessment of the VM in future UTx procedures is essential to understand the interrelation of the VM and clinical and reproductive outcomes. TWEETABLE ABSTRACT: The vaginal microbiome has numerous implications for clinical and reproductive outcomes in the context of uterine transplantation.

Human uterine transplantation: a review of outcomes from the first 45 cases.

Uterine transplantation restores reproductive anatomy in women with absolute uterine factor infertility and allows the opportunity to conceive, experience gestation, and acquire motherhood. The number of cases being performed is increasing exponentially, with detailed outcomes from 45 cases, including nine live births, now available. In light of the data presented herein, including detailed surgical, immunosuppressive and obstetric outcomes, the feasibility of uterine transplantation is now difficult to refute. However, it is associated with significant risk with more than one-quarter of grafts removed because of complications, and one in ten donors suffering complications requiring surgical repair. TWEETABLE ABSTRACT: Uterine transplantation is feasible in women with uterine factor infertility, but is associated with significant risk of complication.

Radiological predictors of cytoreductive outcomes in patients with advanced ovarian cancer.

OBJECTIVE: To assess site of disease on preoperative computed tomography (CT) to predict surgical debulking in patients with ovarian cancer. DESIGN: Two-phase retrospective cohort study. SETTING: West London Gynaecological Cancer Centre, UK. POPULATION: Women with stage 3 or 4, ovarian, fallopian or primary peritoneal cancer undergoing cytoreductive surgery. METHODS: Preoperative CT images were reviewed by experienced radiologists to assess the presence or absence of disease at predetermined sites. Multivariable stepwise logistic regression models determined sites of disease which were significantly associated with surgical outcomes in the test (n = 111) and validation (n = 70) sets. MAIN OUTCOME MEASURES: Sensitivity and specificity of CT in predicting surgical outcome. RESULTS: Stepwise logistic regression identified that the presence of lung metastasis, pleural effusion, deposits on the large-bowel mesentery and small-bowel mesentery, and infrarenal para-aortic nodes were associated with debulking status. Logistic regression determined a surgical predictive score which was able to significantly predict suboptimal debulking (n = 94, P = 0.0001) with an area under the curve (AUC) of 0.749 (95% confidence interval [95% CI]: 0.652, 0.846) and a sensitivity of 69.2%, specificity of 71.4%, positive predictive value of 75.0% and negative predictive value of 65.2%. These results remained significant in a recent validation set. There was a significant difference in residual disease volume in the test and validation sets (P < 0.001) in keeping with improved optimal debulking rates. CONCLUSIONS: The presence of disease at some sites on preoperative CT scan is significantly associated with suboptimal debulking and may be an indication for a change in surgical planning.

Supporting the wider use of laparoscopy in the treatment of ovarian masses.

Patients with ovarian masses which have a moderate risk of malignancy are frequently treated by open laparotomy, despite the Royal College of Obstetricians and Gynaecologists (RCOG) guidance indicating that laparoscopic oophorectomy may be performed in selected cases. The reluctance to perform laparoscopic surgery in these cases is normally due to the perception that survival is affected if the mass is subsequently diagnosed as being malignant, the risk of rupture impacting on FIGO stage and the need for additional staging surgery. However, there is no good evidence to support these views. Preoperative diagnosis of ovarian masses is limited and thus a significant number of patients are subjected to open surgery, where they may have benefitted from the advantages of laparoscopic surgery. We argue that in the absence of a definitive preoperative test, there are advantages to the laparoscopic approach in patients who have a moderate risk of malignancy and further high level evidence should be encouraged in this field.

Prospective evaluation of the IOTA logistic regression model LR2 for the diagnosis of ovarian cancer.

OBJECTIVES: To assess the accuracy of the IOTA logistic regression model LR2 for the diagnosis of ovarian cancer. METHODS: This was a prospective single-center study of women with an ultrasound diagnosis of an adnexal tumor. They were all examined by a single Level-II ultrasound operator, who had received training in the systematic examination of ovarian tumors in accordance with the IOTA guidelines. In all women the likelihood of the adnexal lesion being malignant was calculated using the IOTA LR2 model. All women underwent surgery within 120 days of ultrasound examination and the ultrasound findings were compared with operative findings and the final histological diagnosis. RESULTS: One hundred and twenty-four women were included in the final analysis. The mean age was 53.2 (range, 20-91) years and 61/124 (49.2%) women were postmenopausal. 66/124 (53.2%) women had malignant lesions on postoperative histological examination. The IOTA LR2 model had a sensitivity of 97.0% (95% CI, 89.5-99.6%) and a specificity of 69.0% (95% CI, 55.5-80.5%). The area under the receiver-operating characteristics curve was 0.93 (SE, 0.022; 95% CI, 0.89-0.97), which was not significantly different from 0.92 (SE, 0.018) reported in the original study (P > 0.05). CONCLUSION: When evaluated prospectively, the accuracy of the IOTA LR2 model was similar to that reported in the original study.

Expert opinion: Stepwise ultrasound assessment of suspected placenta accreta spectrum using 2D, Doppler and 3D imaging.

Placenta Accreta Spectrum (PAS) describes a spectrum of conditions ranging from 'sticky' placenta to placenta accreta, increta and percreta-each describing progressively deeper invasion into the uterus. It is a major contributor to maternal and perinatal morbidity particularly where clinical facilities are not immediately available. Hence accurate diagnosis is important in determining timing and place of delivery, and logistical arrangements of the clinical team and specialties. Although many different ultrasound features have been described, their relationship to the final operative diagnosis remains variably described. Ultrasound manufactures have developed new imaging techniques particularly in relation to Doppler and 3D processing techniques. We describe a standardized imaging approach employing new ultrasound modalities matched to the attributes unique to invasive placenta. The '3V' system describes the stages of placental invasion: namely low-flow Doppler techniques to delineate the vascular anatomy of the placenta and delineating its interface with the myometrium, and 3D 'context preserving' post processing technologies defining the placental interface with maternal structures (vesicular invasion and visceral extension). Used together with well characterized 2D imaging signs, we describe pictorially by reference to clinical cases how this standardized methodology allows new insights into the ultrasound diagnosis of PAS.

Value of transvaginal ultrasound in assessing severity of pelvic endometriosis.

OBJECTIVE: The objective of this study was to examine the ability of preoperative transvaginal ultrasound (TVS) scanning to assess the severity of pelvic endometriosis. METHODS: Consecutive women with clinically suspected or proven pelvic endometriosis, who were booked for laparoscopy, were invited to join the study. The severity of endometriosis was assessed preoperatively using TVS and the findings were compared with the results obtained by laparoscopy using the American Society for Reproductive Medicine (ASRM) classification. RESULTS: In total, 201 women had preoperative TVS and laparoscopies. Of these, no endometriosis was found at laparoscopy for 62/201 (30.8%; 95% CI, 24.8-37.5), whereas 33/201 (16.4%; 95% CI, 11.9-22.2) had minimal endometriosis, 31/201 (15.4%; 95% CI, 11.1-21.1) had mild endometriosis, 27/201 (13.4%; 95% CI, 9.4-18.8) had moderate endometriosis and 48/201 (23.9%; 95% CI, 18.5-30.2) had severe endometriosis. The sensitivity and specificity of the TVS diagnosis of severe pelvic endometriosis were 0.85 (95% CI, 0.716-0.934) and 0.98 (95% CI, 0.939-0.994), respectively, and the positive and negative likelihood ratios were 43.5 (95% CI, 14.1-134) and 0.15 (95% CI, 0.075-0.295), respectively. Overall, there was a good level of agreement between ultrasound and laparoscopy in identifying absent, minimal, mild, moderate and severe disease (quadratic weighted kappa = 0.786). The mean ASRM score difference between TVS and laparoscopy in assessing severity of endometriosis was -2.398 (95% CI, -4.685 to -0.1112) and the limits of agreement were -34.62 (95% CI, -38.54 to -30.709) to 29.83 (95% CI, 25.91-33.74). CONCLUSIONS: TVS is a good test for assessing the severity of pelvic endometriosis. TVS is particularly accurate in detecting severe disease, which could facilitate more effective triaging of women for appropriate surgical care.

Expectant management of ultrasonically diagnosed ovarian dermoid cysts: is it possible to predict outcome?

OBJECTIVE: The aim of this study was to assess the natural history of ultrasonically diagnosed ovarian dermoid cysts in a large group of women who were managed expectantly, and to assess the factors that were associated with failure of expectant management. METHODS: Our database was searched for dermoid cysts diagnosed on ultrasonography by a single expert operator between 2001 and 2007 in this retrospective study. In women who opted for expectant management, demographic data including age, gravidity and parity were recorded. Indications for scan, site of cysts, dimensions and the outcomes of expectant management were also recorded. RESULTS: Two hundred and eighty-nine women were diagnosed with a total of 323 dermoid cysts by a single expert ultrasound operator. 93/289 (32.2%; 95% CI, 26.8-37.6%) women with 105/323 (32.5%; 95% CI, 27.4-37.6%) ovarian dermoid cysts were managed expectantly for longer than 3 months. The mean age at diagnosis was 33.8 (range, 13-79) years and the median duration of follow up was 12.6 (interquartile range, 7.6-29.3) months. The mean growth rate of dermoid cysts during follow up was 1.67 mm/year. There were no demographic or morphological features that could be used to predict the growth rate of dermoid cysts. After a period of expectant management, 24/93 (25.8%; 95% CI, 16.9-34.7%) women had surgical intervention. The risk of surgical intervention was significantly increased in younger women, those of parity > or = 2 and in women with bilateral cysts or larger-diameter cysts, and reduced in women with a past history of ovarian cyst. CONCLUSIONS: The success rate of expectant management of dermoid cysts is high and this approach should be considered as a viable alternative to surgical management.