Assisted Reproduction Treatment Research Articles

Nurturing Hope: Reproductive Outcomes with Sinosomatics Following Unsuccessful IVF Attempts.

For women who have experienced failed attempts at in vitro fertilization (IVF) and face medical issues leading to infertility, the renewed effort to seek fertility treatment, coupled with decreasing likelihood of success, can exert substantial emotional and physical strains. Consequently, many couples opt to discontinue treatment before attaining pregnancy. The objective of this study was to evaluate the reproductive outcomes in patients with unsuccessful prior IVF attempts who received a complementary treatment designed to alleviate emotional distress and burden. A retrospective analysis of data from infertile patients who initiated the complementary intervention at a private clinic between January 2014 and December 2016 was conducted. Information on diagnosis, history of infertility, prior assisted reproductive technologies treatments, mode of conception, and pregnancy outcomes were retrieved. The data of 133 patients with a history of one or more unsuccessful IVF treatments were analyzed. Patients had an average age of 36.7 years (± 4.4 SD) and had been experiencing infertility for an average of 4.6 years (± 2.7 SD). The two main causes of their infertility were endometriosis (36.1%, 48 patients) and diminished egg quality (31.6%, 42 patients). By May 2020, a significant proportion of the patients, 81.2% (108 patients), had achieved pregnancy, leading to 94 live births, which represents a 70.7% success rate. These pregnancies mostly resulted from natural-cycle IVF (35.1%), donor cycles (23.4%), and conventional IVF (21.3%). The dropout rate was comparatively low at 23.3%. The median time from the start of complementary treatment to delivery was 18 months, with a range of 12 to 28 months. This study highlights the potential value of complementary treatment approaches in conjunction with standard medical care for women who have experienced unsuccessful IVF treatments in the past and thus face a reduced chance of motherhood. The reported 71% live birth rate is notably high, indicating that the inclusion of complementary treatments may provide women with past IVF failures a tangible opportunity for achieving successful pregnancy and childbirth. However, these findings need to be confirmed through randomized controlled studies.

Compatibility of Family Planning and Surgical Training in Switzerland

Abstract Background Surgeons undertake a long training and have stressful work schedules during optimal childbearing age. Training and career plans can entice young surgeons to renounce part-time work and delay pregnancy, risking pregnancy complications and infertility. Aims This survey study aims to determine the prevalence and constraints of part-time work and family planning among young surgeons in Switzerland. Methods An anonymous, voluntary survey was distributed to young board-certified surgeons. It queried work schedules and desire for part-time work as well as history of pregnancies and use of assisted reproductive treatment. Results A total of 375 surgeons participated, 308 were included (157 female, 151 male). There were no differences in current age (male median 37 (IQR 5), female 37 (6), p=0.93), median age at medical school graduation (male 26 (2), female 26 (2), p=0.90), and mean time to board certification (male 8.3 (SD 2.4), female 8.2 (SD 2.7), p=0.61). Female surgeons had a higher rate of part-time employment (38% vs 19%, p=0.0002). More male surgeons had children compared to their female counterparts (70% vs 45%, p<0.0001). Female surgeons were older (median 35 (IQR 4.5)) than male surgeons (median 33.5 (IQR 3.25), p=0.0002) and female partners of male surgeons (median 32 (IQR 3), p<0.0001) at birth of their first child. Female surgeons more frequently desired further children (71% vs 38%, p<0.0001) and delayed pregnancy due to training (74% vs 22%, p<0.0001). Female surgeons had longer time to conceive (>12 months 24% vs 10%, p=0.014), lower spontaneous pregnancy rates (82% vs 93%, p=0.029) and higher rates of assisted reproductive treatment (14% vs 4%, p=0.0089). Female surgeons more frequently perceived their gender as a negative career influence (67% vs 5%, p<0.0001). Conclusion Whilst part-time work and family planning are challenging for surgeons of both genders, female surgeons face striking inequities when trying to consolidate family planning with their profession.

Association between the length of in vitro embryo culture, mode of ART, and the initial endogenous hCG rise in ongoing singleton pregnancies.

Is there an association between the length of in vitro culture, mode of ART and the initial endogenous hCG rise, in cycles with a foetal heartbeat after single embryo transfer (ET) and implantation? Both the length of in vitro culture and the mode of ART have an impact on the initial endogenous rise in hCG in singleton pregnancies. Different factors have been identified to alter the kinetics of hCG in pregnancies. Current studies show conflicting results regarding the kinetics of hCG after different types of ART (fresh vs frozen ET (FET)), the inclusion or not of preimplantation genetic testing (PGT), and the length of time in in vitro culture. This was a multicentre cohort study, using prospectively collected data derived from 4938 women (5524 treatment cycles) undergoing IUI (cycles, n = 608) or ART (cycles, n = 4916) treatments, resulting a in singleton ongoing pregnancy verified by first-trimester ultrasound scan. Data were collected from the Danish Medical Data Centre, used by the three participating Danish public fertility clinics at Copenhagen University hospitals: Herlev Hospital, Hvidovre Hospital, and Rigshospitalet, from January 2014 to December 2021. The fresh ET cycles included cleavage-stage (2 or 3 days in vitro) and blastocyst (5 days in vitro) transfers. FET cycles included cleavage-stage (3 days in vitro before cryopreservation) or blastocyst (5 or 6 days in vitro before cryopreservation) transfers. The IUI cycles represented no time in vitro. To attain a comparable interval for serum-hCG (s-hCG), the ovulation induction time was identical: 35-37 h before oocyte retrieval or IUI. The conception day was considered as: the insemination day for pregnancies conceived after IUI, the oocyte retrieval day for fresh ET, or the transfer day minus 3 or 5 as appropriate for FET of Day 3 or 5 embryos. Multiple linear regression analysis was used, including days post-conception for the hCG measurement as a covariate, and was adjusted for the women's age, the cause of infertility, and the centre. For FET, a sensitivity analysis was used to adjust for endometrial preparation. The study totally includes 5524 cycles: 2395 FET cycles, 2521 fresh ET cycles, and 608 IUI cycles. Regarding the length of in vitro culture, with IUI as reference (for no time in in vitro culture), we found a significantly lower s-hCG in pregnancies achieved after fresh ET (cleavage-stage ET or blastocyst transfer). S-hCG was 18% (95% CI: 13-23%, P < 0.001) lower after fresh cleavage-stage ET, and 23% (95% CI: 18-28%, P < 0.001) lower after fresh blastocyst transfer compared to IUI. In FET cycles, s-hCG was significantly higher after blastocyst transfers compared to cleavage-stage FET, respectively, 26% (95% CI: 13-40%, P < 0.001) higher when cryopreserved on in vitro Day 5, and 14% (95% CI: 2-26%, P = 0.02) higher when cryopreserved on in vitro Day 6 as compared to Day 3. Regarding the ART treatment type, s-hCG after FET blastocyst transfer (Day 5 blastocysts) cycles was significantly higher, 33% (95% CI: 27-45%, P < 0.001), compared to fresh ET (Day 5 blastocyst), while there was no difference between cleavage-stage FET (Days 2 + 3) and fresh ET (Days 2 + 3). S-hCG was 12% (95% CI: 4-19%, 0.005) lower in PGT FET (Day 5 blastocysts) cycles as compared to FET cycles without PGT (Day 5 blastocysts). The retrospective design is a limitation which introduces the risk of possible bias and confounders such as embryo score, parity, and ovarian stimulation. This study elucidates how practices in medically assisted reproduction treatment are associated with the hCG kinetics, underlining a potential impact of in vitro culture length and mode of ART on the very early embryo development and implantation. The study provides clinicians knowledge that the type of ART used may be relevant to take into account when evaluating s-hCG for the prognosis of the pregnancy. No funding was received for this study. AP has received consulting fees, research grants, or honoraria from the following companies: Preglem, Novo Nordisk, Ferring Pharmaceuticals, Gedeon Richter, Cryos, Merck A/S, and Organon. AZ has received grants and honoraria from Gedeon Richter. NLF has received grants from Gedeon Richter, Merck A/S, and Cryos. MLG has received honoraria fees or research grants from Gedeon Richter, Merck A/S, and Cooper Surgical. CB has received honoraria from Merck A/S. MB has received research grants and honoraria from IBSA. MPR, KM, and PVS all report no conflicts of interest. The study was registered and approved by the Danish Protection Agency, Capital Region, Denmark (Journal-nr.: 21019857). No approval was required from the regional ethics committee according to Danish law.

The cultural representations and symbolizations emerging from Italian psychologists working in multidisciplinary assisted reproduction teams: A linguistic analysis with the emotional text mining.

This study aims to explore the perspectives of Italian psychologists who work in assisted reproductive treatment (ART) centres regarding their roles within multidisciplinary teams. Twenty-eight psychologists were interviewed, recorded and their transcribed text was analysed using emotional text mining. The analysis revealed four clusters representing the psychologists' cultural symbolizations of their works: 'Clinical Practice with the patient', 'Placing Psychology within the Treatment', 'Psychologist's Loneliness' and; 'Collusion with Medicine'. The symbolic representations emerging clearly highlighted a lack of integration of psychology within the medical field. Psychologists expressed emotional and practical difficulties in trying to integrate their role, including a desire to provide psychological assistance, feelings of loneliness and concerns about jeopardizing their professional opportunities, which are intertwined with the medical field. Present findings underscore the importance of integrating psychology within ART centres and multidisciplinary teams and of establishing operational guidelines for psychologists. These steps are crucial for reaching integration of psychologists within the medical setting.

Infertility psychological distress in women undergoing assisted reproductive treatment: A grounded theory study.

While there exists an ample body of research in international contexts focused on the characterization and quantification of infertility psychological distress, the level of scholarly scrutiny directed towards this phenomenon within the context of China remains scant. To investigate the formation and developmental processes of psychological distress associated with infertility and infertility treatment among women within the Chinese cultural context and to construct a theoretical framework that elucidates this phenomenon. Qualitative approach with grounded theory methodology. This study was conducted within the reproductive medicine department of a tertiary-level hospital located in central China from May to August 2023. Twenty-seven women who experienced infertility and underwent assisted reproductive treatment (ART) were interviewed. The interview sessions spanned durations ranging from 20 min to 1 h and 35 min. Data analysis included open coding, axial coding and selective coding. The study is reported using the COREQ checklist. The infertility psychological distress experienced by women undergoing ART is a socially constructed phenomenon influenced by a dynamic interplay of forces that construct and conciliate it. The formation and progression of infertility psychological distress are rooted in the process of self-construction. A Middle-Ranged Theory titled 'self-reconstruction under the dome of infertility and infertility treatment' (SUDIT theory) was developed to explain this phenomenon. Within this framework, infertility psychological distress manifests across three distinct phases under the gambling ofthe constructive force and conciliative force: (1) distress of disrupting the former self; (2) distress linked to the struggling present self; and (3) the renewed-self harmonized with distress. It is imperative for healthcare professionals and policymakers to acknowledge the socially constructed nature of infertility psychological distress, and proactively implement measures aimed at ameliorating it. No patient or public contribution.

The reproductive journeys of French women over 40 seeking assisted reproductive technology treatments in Spain

Fertility decline is a complex phenomenon resulting from converging social and cultural changes that are governed through politics. As it has been discussed in many studies, the European's low fertility rate goes hand in hand with the trend of maternity postponement. Although in many European countries over the last decades reproduction is envisaged as an individual choice that can be made at older ages, having a child after a certain age can be impossible -either “naturally” or using assisted reproductive technology-depending on the medical and legislative possibilities and limits of the country in which people live. In the extremely diverse European reproscape, reproductive legislations have forced but also allowed many people to seek reproductive treatments outside their home countries.Spain is a leading destination in Europe for cross border reproductive travel and, of the foreigners it receives, the French are the largest group. Despite having a history of strong pro-natalist policies, France has been one of the strictest European countries regarding access to medically assisted procreation. Until 2022, only heterosexual couples in which women were under 43 years of age could access treatments. Despite the recent opening of access to “all women”, including single women and same-sex female couples, women over 43 years of age were once again excluded from the new legal framework and therefore remain condemned to travel abroad to access reproductive treatments. In this article, we analyze the experience of French women over 40 who cross the Spanish border to access reproductive treatments in order to fulfill their desire to have children. Through ethnographic data emerging from six years of participant observation and in-depth interviews with 15 women, we explore why they remain excluded from the French system of reproductive governance and the obstacles they face during their reproductive journey.

Consumption of hookahs, e-cigarettes, and classic cigarettes and the impact on medically assisted reproduction treatment

Smoking of classic cigarettes has been well-established as a health risk factor, including cardiovascular, neurological, and pulmonary diseases. Adverse effects on human reproduction have also been shown. Smokers are assumed to have a significantly lower chance of pregnancy, however, the impact of smoking on medically assisted reproduction (MAR) treatment outcomes is controversial. Moreover, smoking habits have changed during the last decades since e-cigarettes and hookahs, or water pipes, have become very popular, yet little is known regarding vaping or hookah-smoking patients undergoing MAR treatments. This prospective study aimed to examine the presence of benzo[a]pyrene, nicotine, and its main metabolite, cotinine, in human follicular fluid (FF) in non-smoking, smoking, and vaping/hookah-smoking patients and to evaluate the impact on female fertility. Human FF samples were collected from 320 women subjected to intracytoplasmic sperm injection (ICSI) cycles due to male subfertility. Gas chromatography combined with mass spectrometry was used to analyse the presence of benzo[a]pyrene, nicotine, and cotinine. A questionnaire was provided to assess patient consumption behaviour and to identify (1) non-smoking patients, (2) patients who consumed cigarettes, and (3) patients with exclusive consumption of e-cigarettes or hookahs. Data were analysed using linear and logistic regression, Fisher’s exact test, and the Mann–Whitney U Test. Nicotine was present in 22 (6.8%) and cotinine in 65 (20.3%) of the 320 samples. The nicotine and cotinine concentrations per sample ranged from 0 to 26.3 ng/ml and 0–363.0 ng/ml, respectively. Benzo[a]pyrene was not detectable in any of the samples analysed. Nicotine and cotinine were also present in the FF of patients with exclusive consumption of e-cigarettes or hookahs. The clinical pregnancy rate, fertilization and maturation rates, and number of oocytes per oocyte pick-up were not statistically significantly different between non-smoking, smoking, or vaping/hookah-smoking patients. Smoking and the accumulation of smoking toxins in the FF have no impact on the outcome of MAR treatments—neither the clinical pregnancy rate, maturation and fertilization rates, nor the number of retrieved oocytes were affected. For the first time, nicotine and cotinine were quantified in the FF of patients exclusively vaping e-cigarettes or smoking hookahs. Since vaping liquids and hookah tobaccos contain potentially harmful substances, other adverse effects cannot be excluded.Trial registration ClinicalTrials.gov Identifier: NCT03414567.

The impact and inflammatory characteristics of SARS-CoV-2 infection during ovarian stimulation on the outcomes of assisted reproductive treatment.

Despite the global prevalence of coronavirus disease 2019 (COVID-19), limited research has been conducted on the effects of SARS-CoV-2 infection on human reproduction. The aims of this study were to investigate the impact of SARS-CoV-2 infection during controlled ovarian stimulation (COS) on the outcomes of assisted reproductive treatment (ART) and the cytokine status of patients. This retrospective cohort study included 202 couples who received ART treatment, 101 couples infected with SARS-CoV-2 during COS and 101 matched uninfected couples. The parameters of ovarian stimulation and pregnancy outcomes were compared between the two groups. The All-Human Inflammation Array Q3 kit was utilized to measure cytokine levels in both blood and follicular fluid. No difference was found in the number of good-quality embryos (3.3 ± 3.1 vs. 3.0 ± 2.2, P = 0.553) between the infected and uninfected groups. Among couples who received fresh embryo transfers, no difference was observed in clinical pregnancy rate (53.3% vs. 51.5%, P = 0.907). The rates of fertilization, implantation, miscarriage, ectopic pregnancy and live birth were also comparable between the two groups. After adjustments were made for confounders, regression models indicated that the quality of embryos (B = 0.16, P = 0.605) and clinical pregnancy rate (P = 0.206) remained unaffected by SARS-CoV-2 infection. The serum levels of MCP-1, TIMP-1, I-309, TNF-RI and TNF-RII were increased, while that of eotaxin-2 was decreased in COVID-19 patients. No significant difference was found in the levels of cytokines in follicular fluid between the two groups. Asymptomatic or mild COVID-19 during COS had no adverse effects on ART outcomes. Although mild inflammation was present in the serum, it was not detected in the follicular fluid of these patients. The subsequent immune response needs further investigation.

Follicular fluid-derived exosomal LncRNA LIPE-AS1 modulates steroid metabolism and survival of granulosa cells leading to oocyte maturation arrest in polycystic ovary syndrome.

Women who are of reproductive age can suffer from polycystic ovary syndrome (PCOS), an endocrine disorder. Anovulatory infertility is mostly caused by aberrant follicular development, which is seen in PCOS patients. Due to the dysfunction of reproductive and endocrine function in PCOS patients, assisted reproduction treatment is one of the main means to obtain clinical pregnancy for PCOS patients. Long non-coding RNA (lncRNA) as a group of functional RNA molecules have been found to participate in the regulation of oocyte function, hormone metabolism, and proliferation and apoptosis of granulosa cells. In this study, we investigated the role of lncRNAs in follicular fluid-derived exosomes and the underlying mechanism of lncRNA LIPE-AS1. We used RNA sequencing to analyze the lncRNA profiles of follicular fluid-derived exosomes in PCOS patients and controls. RT-qPCR was performed to detect the expression levels of these lncRNAs in control (n = 30) and PCOS (n = 30) FF exosome samples. Furthermore, we validated the performance of lncRNA LIPE-AS1 in oocyte maturation by in vitro maturation (IVM) experiments in mouse and steroid metabolism in granulosa cells. We found 501 lncRNAs were exclusively expressed in the control group and another 273 lncRNAs were found to be specifically expressed in the PCOS group. LncRNA LIPE-AS1, highly expressed in PCOS exosomes, was related to a poor oocyte maturation and embryo development in PCOS patients. Reduced number of MII oocytes were observed in the LIPE-AS1 group by in vitro maturation (IVM) experiments in mouse. LIPE-AS1 was also shown to modulate steroid metabolism and granulosa cell proliferation and apoptosis by LIPE-AS1/miR-4306/LHCGR axis. These findings suggested that the increased expression of LIPE-AS1, facilitated by follicular fluid exosomes, had a significant impact on both oocyte maturation and embryo development. We demonstrated the ceRNA mechanism involving LIPE-AS1, miR-4306, and LHCGR as a regulator of hormone production and metabolism. These findings indicate that LIPE-AS1 is essential in PCOS oocyte maturation and revealed a ceRNA network of LIPE-AS1 and provided new information on abnormal steroid metabolism and oocyte development in PCOS.

APOE-E4 allele as a potential marker for implantation failure: A comparison between fertile women, ART success and RIF patients.

Apolipoprotein E (APOE) is the most important precursor for the production of steroid hormones and is also involved in regulating the function of steroid hormones, hence playing a significant role in reproductive processes. So, APOE gene expression may be correlated with the implantation process. This study tries to make a better clarification of the correlation between APOE gene polymorphisms and recurrent implantation failure (RIF), where we compared the frequency of APOE polymorphisms in RIF patients, assisted reproductive treatment (ART) success cases and fertile women. In all, 100 women with successful ART who got pregnant (fetal heart rate positive) in their first or second cycle of invitro fertilization or intracytoplasmic sperm injection, 100 infertile RIF cases, and 100 normal fertile control cases with at least one live birth were included in present study. Following DNA extraction, genotypes were determined through polymerase chain reaction-restriction fragment length polymorphism method using HhaI restriction enzyme. Finally, statistical analysis was performed by chi-squared (χ2) test in SPSS software (P < 0.05). The RIF group showed significantly higher frequency for E3/E4 genotype (29%) compared with the other two control groups (fertile = 15%, ART success [ART+] = 13%) (P = 0.007). There was also a significantly higher frequency of the E4 allele in the RIF group (14.5%) compared with both of the control groups (fertile = 7.5%, ART+ = 6.5%) (P = 0.018). APOE4 is correlated with recurrent failure in the process of embryo implantation and, accordingly, it may potentially be considered a possible risk factor to the implantation process. The presence of E4 can be proposed as a predictive indicator in determining the results of assisted reproductive techniques.

Is infertility more common among patients with multiple sclerosis? Implications to assisted reproductive techniques utilization

Research QuestionTo evaluate whether fertility is affected, and the usage of assisted reproductive treatment (ART), among women with multiple sclerosis (MS). DesignData regarding MS and ART usage among patients with multiple sclerosis was extracted from the Israeli HMO - Clalit Health Service database. Data regarding diagnosis and treatment of MS, cause of infertility and fertility treatments usage were collected for all female MS patients aged 18-45 between the years 2005-2020. Each MS patient was matched by age 1:10 with reference women from the general population. The prevalence of infertility was compared between the two groups. Univariate and multivariate statistical tests were used to analyze the association between MS and fertility treatments including in vitro fertilization (IVF) and controlled ovarian hyperstimulation (COH). ResultsDuring the study period, 1309 MS patients were compared to 13,090 controls from the general population matched for age. Mean age was 29 (±7.8 SD) years old. The overall prevalence of infertility was 15.4% (202/1309) among MS patients, similar to the general population 16.3% (2129/13090) p=0.939. The prevalence of both IVF and COH were similar among MS patients and matched controls from the general population (8.1% vs 7.2% p=0.427, 13.8% vs 14.3% p=0.624 accordingly). ConclusionsOur results show similar rate of infertility and fertility treatments among MS patients and the general population. The results of this study provide reassurance that fertility among women with MS do not differ from the general women population, and indicate no excessive assisted reproductive technology utilization.

Deleterious variant in FAM71D cause male infertility with asthenoteratospermia.

Asthenoteratospermia is a significant cause of male infertility. FAM71D (Family with sequence similarity 71, member D), as a novel protein exclusively expressed in the testis, has been found to be associated with sperm motility. However, the association of FAM71D mutation with male infertility has yet to be examined. Here, we conducted whole-exome sequencing and identified a homozygous missense mutation c.440G > A (p. Arg147Gln) of FAM71D in an asthenoteratospermia-affected man from a consanguineous family. The FAM71D variant is extremely rare in human population genome databases and predicted to be deleterious by multiple bioinformatics tools. Semen analysis indicated decreased sperm motility and obvious morphological abnormalities in sperm cells from the FAM71D-deficient man. Immunofluorescence assays revealed that the identified FAM71D mutation had an important influence on the assembly of sperm structure-related proteins. Furthermore, intra-cytoplasmic sperm injection (ICSI) treatment performed on the infertile man with FAM71D variant achieved a satisfactory outcome. Overall, our study identified FAM71D as a novel causative gene for male infertility with asthenoteratospermia, for which ICSI treatment may be suggested to acquire good prognosis. All these findings will provide effective guidance for genetic counselling and assisted reproduction treatments of asthenoteratospermia-affected subjects.

Deciphering the role of PGRMC2 in the human endometrium during the menstrual cycle and in vitro decidualization using an in vitro approach.

What is the human endometrial non-classical progesterone receptor (PGR) membrane component 2 (PGRMC2) expression pattern throughout the menstrual cycle and what role does it play during decidualization? Endometrial PGRMC2 expression fluctuates during the human menstrual cycle and is abundantly expressed in human endometrial stromal cells (hEnSCs) during in vitro decidualization, process where PGRMC2 is involved in embryo implantation-related pathways. The endometrial response to progesterone is mediated by the classical and non-classical PGRs. We previously demonstrated that PGR membrane component 1 (PGRMC1) is critical for endometrial function, embryo implantation, and future placentation, however, the role(s) of PGRMC2, which is structurally similar to PGRMC1, have not been studied in the human endometrium. This prospective study comprehensively evaluated the endometrial expression of PGRMC2 throughout the human menstrual cycle and during in vitro decidualization of hEnSCs (isolated from 77 endometrial biopsies that were collected from 66 oocyte donors), using immunohistochemistry, RT-qPCR, western blot, transcriptomic, and proteomic analyses. In addition, functional analysis was carried out to validate the implication of PGRMC2 in hEnSCs during embryo invasion using an in vitro outgrowth model. In vitro decidualization of hEnSCs was induced using co-treatment with cAMP and medroxyprogesterone 17-acetate progestin, and evaluated by measuring prolactin by ELISA and F-actin immunostaining. RT-qPCR was employed to compare expression with other PGRs. To reveal the function of PGRMC2 during the decidualization process, we specifically knocked down PGRMC2 with siRNAs and performed RNA-seq and quantitative proteomics techniques (SWATH-MS). The common differentially expressed genes (DEGs) and proteins (DEPs) were considered for downstream functional enrichment analysis. Finally, to verify its implication in the trophoblast invasion, an outgrowth model was carried out where hEnSCs with silenced PGRMC2 were co-cultured with human trophoblastic spheroids (JEG-3) following in vitro decidualization. In contrast to PGRMC1 and classical PGRs, endometrial PGRMC2 gene expression was significantly lower during the late- versus mid-secretory phase (P < 0.05). Accordingly, the elevated PGRMC2 protein abundance observed in the endometrial epithelial glands throughout the menstrual cycle dropped in the late secretory phase, when abundance decreased in all endometrial compartments. Nevertheless, PGRMC2 protein increased during the mid-secretory phase in stromal and glandular cells, and PGRMC2 mRNA (P < 0.0001) and protein (P < 0.001) levels were significantly enhanced in the membranes/organelles of decidualized hEnSCs, compared to non-decidualized hEnSCs. Notably, PGRMC1 and PGRMC2 mRNA were significantly more abundant than classical PGRs throughout menstrual cycle phases and in decidualized and non-decidualized hEnSCs (P < 0.05). RNA-seq and proteomics data revealed 4687 DEGs and 28 DEPs, respectively, in decidualized hEnSCs after PGRMC2 silencing. While functional enrichment analysis showed that the 2420 upregulated genes were mainly associated with endoplasmic reticulum function, vesicular transport, morphogenesis, angiogenesis, cell migration, and cell adhesion, the 2267 downregulated genes were associated with aerobic respiration and protein biosynthesis. The protein enrichment analysis showed that 4 upregulated and 24 downregulated proteins were related to aerobic respiration, cellular response, metabolism, localization of endoplasmic reticulum proteins, and ribonucleoside biosynthesis routes. Finally, PGRMC2 knockdown significantly compromised the ability of the decidualized hEnSCs to support trophoblast expansion in an outgrowth model (P < 0.05). Transcriptomic data are available via NCBI's Gene Expression Omnibus (GEO) under GEO Series accession number GSE251843 and proteomic data via ProteomeXchange with identifier PXD048494. The functional analyses were limited by the discrete number of human endometrial biopsies. A larger sample size is required to further investigate the potential role(s) of PGRMC2 during embryo implantation and maintenance of pregnancy. Further, the results obtained in the present work should be taken with caution, as the use of a pure primary endometrial stromal population differentiated in vitro does not fully represent the heterogeneity of the endometrium in vivo, nor the paracrine communications occurring between the distinct endometrial cell types. The repression of endometrial PGRMC2 during the late- versus mid-secretory phase, together with its overexpression during decidualization and multiple implications with embryo implantation not only highlighted the unknown roles of PGRMC2 in female reproduction but also the potential to exploit PGRMC2 signaling pathways to improve assisted reproduction treatments in the future. This research was funded by Instituto de Salud Carlos III (ISCIII) granted to F.D. (PI20/00405 and PI23/00860), co-funded by the European Union. Y.M.-L. was supported by a predoctoral research grant from Generalitat Valenciana (ACIF/2019/262). R.G.-M. was supported by Generalitat Valenciana (CIAPOT/2022/15). P.d.C. was supported by a predoctoral grant for training in research into health (PFIS FI20/00086) from the Instituto de Salud Carlos III. I.D.-H. was supported by the Spanish Ministry of Science, Innovation and Universities (FPU18/01550). A.P. was supported by the Instituto de Salud Carlos III (PFIS FI18/00009). This research was also supported by IVI Foundation-RMA Global (1911-FIVI-103-FD). The authors declare no conflict of interest.

Time to childbirth and assisted reproductive treatment in women with congenital heart disease

ObjectiveTo investigate the time to first childbirth and to compare the prevalence of assisted reproductive treatment (ART) in women with congenital heart disease (CHD) compared with women without CHD.MethodsAll women...

Obstetric outcomes of nulliparous women with pelvic pain undergoing fertility treatment

Research QuestionTo evaluate the association between pelvic pain disorders and primary caesarean delivery for patients undergoing assisted reproductive technology treatment. DesignRetrospective cohort study of nulliparous patients with singleton pregnancies who underwent assisted reproductive technology treatment and achieved a live birth from 2012-2020. Cases included patients with prior diagnoses of pelvic pain disorders. A 3:1 ratio propensity score matched population of patients without pelvic pain was included as Controls. Comparative statistics were performed using chi-square and students t-test. A multivariate regression analysis was conducted to evaluate the association between pelvic pain patients and mode of delivery. Results174 pelvic pain patients were compared to 575 controls. Pelvic pain patients reported a significantly longer duration of infertility (18.9±20 months vs. 14.0±14 months, p=0.003) compared to controls. Pelvic pain patients had a significantly higher rate of anxiety disorders (115±21.9 vs. 55±31.6, p= 0.009) and use of anxiolytics at embryo transfer (17±3.2 vs. 12±6.9, p=0.03). Pelvic pain patients had a higher rate of primary caesarean delivery compared with controls (59.7% vs. 49.1%, p=0.01). After adjusting for multiple variables, there was a significant association between pelvic pain patients and increased odds of primary caesarean delivery (aOR = 1.48, CI 95%; 1.02-2.1). ConclusionPelvic pain patients have significantly greater odds of primary caesarean delivery when compared to patients without pelvic pain history. The infertility outpatient setting may be uniquely positioned to identify patients at risk for undergoing primary caesarean delivery and could facilitate earlier intervention for pelvic floor physical therapy during the preconception and antepartum periods.

A sonographic endometrial thickness

BackgroundThe prevalence of placenta accreta spectrum (PAS), a potentially life-threatening condition, has exhibited a significant global rise in recent decades. Effective screening methods and early identification strategies for PAS could enable early treatment and improved outcomes. Endometrial thickness (EMT) plays a crucial role in successful embryo implantation and favorable pregnancy outcomes. Extensive research has been conducted on the impact of EMT on assisted reproductive technology cycles, specifically in terms of pregnancy rates, live birth rates, and pregnancy loss rates. However, limited knowledge exists regarding the influence of EMT on PAS. ObjectiveThis study aims to evaluate association between pre-implantation EMT and the occurrence of PAS in women undergoing assisted reproductive technology cycles. Study DesignA total of 4637 women who had not undergone prior caesarean section, conceived by in vitro fertilization or intracytoplasmic sperm injection embryo transfer treatment and subsequently delivered at the Third Affiliated Hospital of Guangzhou Medical University between January 2008 to December 2020 were included in this study. To explore the relationship between EMT and PAS, we employed smooth curve fitting, threshold effect, and saturation effect analysis. Multivariate logistic regression analysis was performed to evaluate the independent association between EMT and PAS while adjusting for potential confounding factors. Propensity score matching (PSM) was performed to reduce the influence of bias and unmeasured confounders. Furthermore, we employed causal mediation effect analysis to investigate the mediating role of EMT in the relationship between gravidity and ovarian stimulation protocol and the occurrence of PAS. ResultsAmong the 4637 women included in this study, pregnancies with PAS (159, 3.4%) had significantly thinner EMT (non-PAS 10.08±2.04 vs PAS 8.88±2.21 mm，P<0.001) during the last ultrasound before embryo transfer. By smooth curve fitting, the saturated effect was found on EMT and PAS, with an inflection point at 10.9mm. Then the EMT was divided into four groups: ≤7mm, >7 to≤10.9mm, >10.9 to≤13mm, >13mm, and the absolute rates of PAS in each group was 11.91%, 3.73%, 1.35%, and 2.54%, respectively. When compared to women with an EMT ranging from between 10.9-13mm, the odds of PAS increased from adjusted odds ratio (aOR) of 2.27 (95% CI, 1.33-3.86) for EMT ranging from 7-10.9mm to aOR of 7.15 (95% CI, 3.73-13.71) for EMT <7mm after adjusting for potential confounding factors. Placenta previa remained as an independent risk factor for PAS (aOR, 11.80; 95% CI, 7.65-18.19). Moreover, EMT <7mm was still an independent risk factor for PAS (aOR, 3.91; 95% CI, 1.57-9.73) in the matched cohort after PSM. Causal mediation analysis revealed that approximately 63.9% of the total effect of gravidity and 18.6% of the total effect of ovarian stimulation protocol on PAS were mediated by the EMT. ConclusionsThe findings from our study indicate that thin EMT is an independent risk factor for PAS in women without prior caesarean section undergoing assisted reproductive technology treatment. The clinical significance of this risk factor is slightly lower than placenta previa. Furthermore, our results demonstrate that EMT plays a significant mediating role in the relationship between gravida or ovarian stimulation protocol and PAS.

Matrix for understanding perinatal psychic processes mediated by assisted reproductive technology

This writing is the product of more than fifteen years of clinical work with patients who attend to medically assisted reproduction treatments, including our own clinical cases and those of other colleagues. Some of them compiled in the book “Wishes, children, technologies”, others developed in writings of my authorship in recent years. This clinical material has allowed me to develop a matrix of understanding of the psychological processes that women undergo throughout reproductive treatments, which includes a series of losses that are added to the psychic processing that occurs in natural pregnancies. This general matrix serves as a compass to guide us around some common elements that usually appear in reproductive treatments that last years. Having an ethical horizon of promotion and protection of the right to mental health of women facing reproductive treatments, we propose an interdisciplinary approach to medically assisted reproduction processes with a privileged heeding to singularity

Prevalence of adenomyosis features in women scheduled for assisted reproductive treatment, using the Morphological Uterus Sonographic Assessment group definitions.

Studies that use standardized ultrasonographic criteria to diagnose adenomyosis in subfertile women are needed. These would improve the understanding of the disease burden and enable further studies on its impact on fertility and assisted reproductive treatment (ART) outcome. The aim of this study was to determine the prevalence of different features of adenomyosis in women scheduled for their first ART, diagnosed at two (2D) and three-dimensional (3D) transvaginal ultrasonography (TVUS) using the revised Morphological Uterus Sonographic Assessment (MUSA) group definitions. This was a prospective, observational cross-sectional study of subfertile women aged 25 to ≤39 years, that were referred to a university hospital for their first ART between December 2018 and May 2021. Of 1224 eligible women, 1160 women fulfilled the inclusion criteria and consented to participate in the study. All women underwent a systematic 2D and 3D TVUS examination. The primary outcome was the presence of direct and indirect features of adenomyosis, as proposed by the MUSA group. Secondary outcomes were to describe the ultrasonographic characteristics of the different features, as well as any difference in the diagnostics at 2D or 3D TVUS and any association with clinical characteristics such as endometriosis. At least one direct or indirect feature of adenomyosis was observed in 272 (23.4%, 95% confidence interval [CI] 21.0-25.9) women. Direct features that are pathognomonic for the disease were observed in 111 (9.6%, 95% CI, 7.9-11.3) women. Direct features were visible only at 3D TVUS in 56 (4.8%, 95% CI 3.6-6.1) women, that is, 56/111 (50.5%) of women with at least one direct adenomyosis feature. Direct features were more common in women with endometriosis (OR 2.8, 95% CI 1.8-4.3). We found than one in 10 women scheduled for ART had direct features of adenomyosis at ultrasound examination. The present study suggests that the use of 3D TVUS is an important complement to 2D in the diagnostics of adenomyosis. Our results may further improve the counseling of women scheduled for ART and enables future studies on the impact of different features of adenomyosis on subfertility, ART results and obstetric outcomes.

Intrauterine autologous platelet-rich plasma treatment in women with at least two implantation failures: A retrospective cohort study.

Finding the most effective way to improve implantation rate in women who are receiving assisted reproductive technology treatment is still a challenge. This study aimed to assess the pregnancy outcomes of intrauterine platelet-rich plasma (PRP) therapy in women with a history of at least 2 implantation failures. In this retrospective cohort study, data of 852 women who were candidates for frozen-thawed embryo transfer was extracted from their medical records from April 2017 to September 2021 at Yazd Reproductive Sciences Institute, Yazd, Iran. Of these, 432 received intrauterine PRP treatment 48 hr before transfer (PRP group), and the results of the pregnancy outcomes compared with 420 of the control group who did not receive the treatment before transfer. Pregnancy outcomes, including chemical, clinical, ongoing pregnancy, and live birth rate were statistically significant in the PRP group (p 0.001). However, when categorized according to the implantation history, this significant improvement in all 4 was only seen in women with at least 2 prior implantation failures. In women with a history of only one implantation failure, PRP therapy significantly improved the ongoing pregnancy and live birth rate (19.5%, p = 0.04). Also, in women who received donor eggs and had repeated implantation failure, PRP improved pregnancy outcomes clinically but not statistically (p = 0.15). PRP seems to be effective in improving the pregnancy rate in women with a history of 2 or more implantation failures and also shows an increase in the live birth rate in women with only one implantation failure.

Association of fat distribution differences in infertile women with assisted reproductive outcomes: A prospective cohort study.

To investigate the impacts of fat distribution on assisted reproductive outcomes in infertile women. The study randomly recruited 576 infertile women who underwent assisted reproductive technology treatment at the Reproductive Medicine Center of the First Affiliated Hospital of Anhui Medical University between July and October 2022. Questionnaires and body composition measurements were administered to assess baseline information and fat distribution. The numbers of oocytes, zygotes presenting with two pronuclei (2PN), and available embryos were tracked at the end of the cycle. Multifactorial logistic regression models and restricted cubic spline (RCS) curve models were used to explore the relationships between fat distribution and reproductive outcomes while controlling for confounding factors. The study found that the participants had a mean age of 30.82 years. The analysis showed that there was a significant difference between the amount of leg body fat mass (LBFM) and the distribution of reproductive outcomes. However, there was no significant correlation between the level of visceral fat and reproductive outcomes. After taking confounding factors into account, the multifactorial regression analysis showed that the total body fat mass and the number of oocytes (odds ratio (OR) 0.92, 95% confidence interval (CI) 0.84-0.99), 2PN (OR 0.92, 95% CI 0.84-0.99), and embryos available for transfer (OR 0.90, 95% CI 0.82-0.99) were negatively correlated. RCS modeling revealed a linear dose-response relationship between LBFM and assisted reproductive outcomes. Fat distribution varies among infertile women, and higher amounts of fat are associated with poorer assisted reproductive outcomes.