Reproductive biomedicine online最新文献

Research question

Does the NOD-like receptor protein 3 (NLRP3) inflammasome have an effect in adenomyosis?

Design

Fresh-frozen endometrial tissues and paraffin specimens were obtained from endometrial tissues from patients with adenomyosis and controls. Western blot, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were applied to assess expression of the NLRP3 inflammasome components. Primary eutopic endometrial stromal cells were isolated from the uteri of patients with adenomyosis. After NLRP3 was knocked down using small interfering RNA, proliferation, invasion and epithelial–mesenchymal transition (EMT) were evaluated using EdU, CCK8, transwell assays and western blot. Importantly, a mouse model of adenomyosis was established to evaluate the effects of the NLRP3 inhibitor MCC950 on the formation of adenomyosis.

Results

Expression of the NLRP3 inflammasome components was elevated in the ectopic or eutopic endometrium of patients with adenomyosis. NLRP3 knockdown inhibited migration, invasion and EMT in endometrial cells and primary endometrial cells (P < 0.0001). MCC950, which blocks the NLRP3 inflammasome, reduced migration and invasion of endometrial cells (P < 0.01) and primary endometrial cells (P < 0.0001) considerably. Importantly, in the mouse model of adenomyosis, MCC950 had a mitigating effect on the severity of adenomyosis (P < 0.01).

Conclusions

NLRP3 was found to enhance migration, invasion and EMT of human endometrial cells in adenomyosis. Notably, the NLRP3 inhibitor MCC950 reduced migration and invasion of endometrial cells effectively. Furthermore, in the mouse model of adenomyosis, MCC950 exhibited a therapeutic effect by alleviating the severity of adenomyosis.

The discovery of DNA in blastocoel fluid (BF-DNA) generated new perspectives in the potential development of simpler and safer alternative non-invasive tests in reproductive genetics. Short DNA fragments of apoptotic origin, together with specific expression patterns of pro- and anti-apoptotic genes in the blastocoel fluid of euploid and aneuploid embryos, suggest a self-correction mechanism to preferentially eliminate aneuploid cells, and purge defective and non-viable cells. The correlation of blastocoel fluid content with the genetic status of the whole embryo, and therefore its potential use in minimally invasive preimplantation genetic testing (miPGT), or as an indicator of embryo potential, remains uncertain and needs to be determined. The limited amount and compromised integrity of BF-DNA, with likely apoptotic origination, constrains its amplification, leading to low concordance and reproducibility rates for both aneuploidy screening and monogenic testing. While embryo genotyping constitutes a more ambitious goal, the presence of analysable DNA after amplification in blastocoel fluid may be used as a clinical biomarker of embryo competency to select the most viable embryo(s) for transfer, and potentially improve the implantation rate. Although blastocentesis remains a promising area for future research, several technical and methodological limitations are currently constraining its consideration for clinical practice.

Research question

Does frozen embryo transfer (FET) increase the risk of allergic diseases in offspring?

Design

This study followed up 653 singleton children: 166 born through FET and 487 born through natural conception. Demographic characteristics, perinatal information and allergic diseases of children and their parents were collected through clinical medical systems and questionnaires. Among these 653 children, allergen-specific immunoglobulin E (IgE) testing was performed using peripheral blood samples collected from 207 children: 145 in the FET group and 62 in the natural conception group. The prevalence of allergic diseases and positive rates of allergen-specific IgE testing were compared between the two groups with adjustments for confounding factors.

Results

The prevalence of food allergy was significantly higher in children born through FET compared with children born through natural conception (adjusted OR = 3.154, 95% CI 1.895–5.250; P < 0.001). In addition, positive rates of food allergen sensitization were higher in children in the FET group compared with children in the natural conception group (adjusted OR = 5.769, 95% CI 2.859–11.751, P < 0.001). Children in the FET group had a higher positive sensitization rate to at least one allergen compared with children in the natural conception group (adjusted OR = 3.127, 95% CI 1.640–5.961, P < 0.001). No association was observed between FET and other allergic diseases, including asthma (P = 0.136), atopic dermatitis (P = 0.130) and allergic rhinitis (P = 0.922). Allergen sensitization IgE testing indicated no differences between the two groups in terms of positive sensitization rates of other common allergens, including animal and insect allergens (P = 0.627), inhaled outdoor allergens (P = 0.915) and inhaled outdoor allergens (P = 0.544).

Conclusion

This study suggests that children born through FET have increased risk of developing food allergy in early childhood.

Research question

Do different timings of progesterone administration for day 5 and day 6 blastocysts affect the live birth rate (LBR) of artificial frozen embryo transfer (FET) cycles?

Design

This retrospective cohort study included 1362 patients who underwent artificial FET cycles. The effects of 6 and 7 days of progesterone administration prior to blastocyst transfer on clinical outcomes were compared in day 5 and day 6 blastocysts. Univariable and multivariable regression analyses were undertaken.

Results

In all patients, LBR was comparable between the two groups (51.8% versus 47.9%, P = 0.165). For day 6 blastocysts, after adjusting for confounders, the 7-day progesterone regimen resulted in a significantly higher LBR (44.8% versus 36.4%, P = 0.039, adjusted OR = 1.494, 95% CI 1.060–2.106) and lower pregnancy loss rate (15.4% versus 25.2%, P = 0.031, adjusted OR = 0.472, 95% CI 0.260–0.856) compared with the 6-day progesterone regimen. For day 5 blastocysts, there were no significant differences in pregnancy outcomes between the two regimens, but the rate of low birthweight was higher with the 7-day progesterone regimen than with the 6-day progesterone regimen (13.9% versus 6.7%, P = 0.032).

Conclusions

In all blastocyst analyses, no difference in LBR was found between the 6- and 7-day progesterone regimens in artificial FET cycles. For day 6 blastocysts, LBR was significantly higher with the 7-day progesterone regimen than with the 6-day progesterone regimen, whereas for day 5 blastocysts, pregnancy outcomes were comparable between the two regimens.

Research question

What is the profile of women in the USA who become surrogates, and what is their power of decision and motivations?

Design

This quantitative study was performed with 231 participants in the USA, given the country's long history of surrogacy, to help clarify the profile of women who become surrogates, their power of decision and motivations.

Results

Descriptive and multivariate cluster analyses showed that women who become surrogates earn above the average income for their state of residency, have a high level of education, have health insurance, are employed, and decide to become a surrogate for prosocial/altruistic reasons.

Conclusions

In contrast to the premise of both radical feminism and ultra-conservative Catholicism, this study found that altruism and empathy are the primary motivations for participating in surrogacy processes, and that a woman's decision to become a surrogate is not motivated by social conditioning relating to poverty or social status.

There has been a huge increase in the development of new e-health initiatives, including interventions supporting the interaction between patients and healthcare professionals – the clinical encounter. This interaction can influence clinical decision making during a patient's workup or treatment process. This scoping review was designed (i) to display the current landscape of web-based interventions to support the clinical encounter, and (ii) to critically appraise their composition. A literature search of different electronic databases was conducted. The study interventions were required to be for infertile patients and internet based, including the clinical encounter. The selected studies were systematically appraised. Twenty-eight studies were included and divided into four categories: online platform (10 studies), telemonitoring (3 studies), teleconsulting (8 studies) and artificial intelligence (7 studies). The online platform and teleconsulting categories focused most on patient-reported outcomes, with positive results. The other categories focused on development and validation. In conclusion, this review shows a broad landscape of web-based interventions in the clinical encounter, for healthcare professionals and fertility patients. The teleconsulting and the online platform categories have the most ‘ready-to-use’ interventions. However, the actual implementation of the interventions was evaluated in only four studies, suggesting challenges with implementation research and the need for standardized implementation protocols.

Research question

What is the relationship between antral follicle count (AFC) and chronological age, and what are the expected values for AFC?

Design

This was a retrospective cohort study at a specialist gynaecological ultrasound centre in London, UK. Women presenting to a gynaecology diagnostic unit for investigation of symptoms or routine check-up, and undergoing transvaginal ultrasound (TVUS) examinations, between 1 January 2017 and 22 September 2022 were included in this study.

Results

In total, 8821 TVUS records from 7573 patients were analysed. The relationship between AFC and age was estimated to develop an AFC nomogram independent of the stage in the menstrual cycle. AFC corresponding to the 10^th, 25^th, 50^th, 75^th and 90^th centiles for each patient and age group were calculated. Both nomogram and condition-specific populations displayed a Gaussian relationship between AFC and age. For the nomogram population (scans n = 4256, patients n = 3821), a peak median AFC of 30 was observed between 21–23 years of age. The AFC distribution of the group with previous ovarian cystectomy (scans n = 534, patients n = 443) was found to be significantly different compared with the nomogram population (P < 0.0001). However, the same did not hold true for those on hormonal contraception (scans n = 566, patients n = 534) (P = 0.43).

Conclusions

An AFC nomogram reporting median and interquartile values for AFC by chronological age across the reproductive years was developed. This is a useful tool for providing counselling for those undergoing ovarian reserve assessments, and can be taken any time in the menstrual cycle, including in women on hormonal contraceptives or who have undergone previous ovarian cystectomy.

Research question

Design

Results

Conclusions

Studies report interaction difficulties between patients with polycystic ovary syndrome (PCOS) and healthcare professionals (HCP). This systematic review and qualitative evidence synthesis aimed to collate and synthesize the existing peer-reviewed literature investigating challenges for people with PCOS when interacting with HCP. Medline, PsycInfo, EMBASE, All EBM and CINAHL were searched from 1990 to September 2022. Study risk of bias (RoB) was performed and all textual data relevant to challenging interactions between patients with PCOS and HCP were extracted and analysed using thematic synthesis. Of the 6353 studies identified, 28 were included. Two were appraised as high, four as moderate and 22 as low RoB. Four analytic themes were derived illustrating that interactions were challenging when: (i) medical information (PCOS, its management) was not shared in the best way; (ii) information provision and deliberation opportunities were insufficient to achieve outcomes that mattered to patients; (iii) interactions prompted but did not support patient activation; and (iv) health system-level barriers (e.g. policies and guidelines) were present or made worse by HCP behaviour. Future research should examine methods for the implementation and evaluation of established frameworks for sharing medical information and supporting patient agency in the context of PCOS care.

Research question

What are the perspectives of preimplantation genetic testing (PGT) patients in Belgium on the ethics of PGT for polygenic risk scoring (PGT-P)?

Design

In-depth interviews (18 in total, 10 couples, 8 women, n = 28) were performed with patients who had undergone treatment with PGT for monogenic/single-gene defects (PGT-M) or chromosomal structural rearrangements (PGT-SR) between 2017 and 2019 in Belgium. Participants were asked about their own experiences with PGT-M/SR and about their viewpoints on PGT-P, including their own interest and their ideas on its desirability, scope and consequences. Inductive content analysis was used to analyse the interviews.

Results

Participants stated that their experiences with PGT-M/SR had been physically, psychologically and practically difficult. Most participants stated that, partly because of these difficulties, they did not see the added value of knowing the risk scores of embryos via PGT-P. Many participants worried that PGT-P could lead to additional anxieties, responsibilities and complex choices in reproduction and parenthood. They argued that not everything should be controlled and felt that PGT-P, especially non-medical and broad screening, was going too far. With regards to the clinical implementation of PGT-P, participants in general preferred PGT-P to be limited to people with a serious polygenic family history and wanted embryo selection decisions to be made by healthcare professionals.

Conclusions

This study shows that individuals with experience of PGT-M/SR saw PGT-P as different from PGT-M/SR. They had various ethical concerns with regards to PGT-P, especially regarding broadly offering PGT-P. These stakeholder viewpoints need to be considered regarding potential PGT-P implementation and guidelines.