Multiple Miscarriages Research Articles

The Complexity Around Mosaic Embryo Decision Making– A Genetic Counselling Perspective

Background: In recent years there is an evident increase in the interest of transferring mosaic embryos. Our genetic counselling team have reported mosaic results to over 250 patients since the beginning of 2020, and there is an upward trend in patient interest, and willingness to consider transfer. As patients continue to request the transfer of mosaic embryos, and research advances regarding transfer outcomes, it is critical that the genetic/medical professionals who counsel these patients are aware of the complex factors that feed into important decision making. Aim: To explore the genetic counselling perspectives on counselling issues for patients considering transfer of a mosaic embryo, including barriers, commonalities, and themes that impact their decision pathway. Method: Fundamental thematic analysis on genetic counselling consultation notes detailing questions, concerns, motivations, and decision outcomes was utilized for gaining a preliminary perspective. Specific case vignettes help highlight the complexity in these decisions. Results: Depending on the result, patients with PGT-A NGS reported mosaic embryo(s) have the option to consider transfer, retaining, or discarding these embryos. Thematic analysis revealed themes regarding factors that influence decision making. Patients less likely to proceed with embryo transfer: highly risk averse, poor management of uncertainty, perceived limited options, lived experience of unhealthy pregnancy or birth (ie. family/friend), complex reproductive history (ie. multiple miscarriages), and high emotional burden of the decision. Patients more likely to proceed with transfer: extensive fertility journey, high level of information comprehension, encouraging community support, low emotional burden of the decision, and awareness of age-related limitations. Conclusion: Our work highlights potential benefits of a genetic counselling guideline of factors to present/challenge to patients, as each patient has their own journey.

Response to "The History of Uterus Transplantation, Rewritten."

Response to "The History of Uterus Transplantation, Rewritten."

Comparison of Transvaginal and Transabdominal Ultrasound in the Diagnosis of Adnexal Masses

Objective: Our research aims to compare the diagnostic efficacy of transvaginal and transabdominal ultrasonography for detecting adnexal masses. Study Design: A Comparative study Place and Duration: Conducted at Central Park Medical College, Lahore, during from the period August 2021 to January 2022. Methods: This study included 84 women. Once written consent has been obtained, we involve consideration such as aging, gender, menstrual abnormalities (Oligomenorrhea / Menstrual periods), infertility, recurrent multiple miscarriages, series of acts, acne vulgaris, and obesity. The ultrasound data included the location, size, borders, hypoechoic and dilatation of ovary lesions. Group M had 42 patients and underwent for transvaginal ultrasound, whereas group N had transabdominal ultrasound with MRI. Using histological results (positive/negative), frequency of adnexal mass among all cases were compared. SPSS 20.0 analyzed all data. Results: In group M mean parity was 3.5±2.13 and in group N parity was 2.9±4.13. Most common complaint among all cases was infertility and irregular cycle. We found that frequency of adnexal mass in group M was lower than that of group N. It was determined that the specificity, positive predictive value, and negative predictive value of transvaginal sonography were all lower than those of transabdominal sonography. Conclusion: In this study, we came to the conclusion that abdominal ultrasonography combined with MRI was superior in terms of its usefulness and efficacy in identifying adnexal masses with genuine levels of both specificity and sensitivity. Keywords: Accuracy, Transvaginal ultrasonography,Transabdominal ultrasonography, Adnexal Masses, Complications,

Predictors of non-response to successive waves of surveys in the Japan Environment and Children’s Study during the 3-year postpartum period: a longitudinal cohort study

ObjectivesWe examined changes in factors related to non-response to successive waves of the nationwide birth cohort study, the Japan Environment and Children’s Study (JECS), during the first 3 years after...

Frequency Of Uterine Anomalies Associated with Persistent Miscarriages in Pregnancy on Ultrasound

Miscarriages is when an embryo/foetus expires before the tenth week of gestation. It occurs most commonly early during pregnancy. Women who had a miscarriage looked to be more likely to die before the age of 70 than those who had any other pregnancy outcomes. Objective: To determine the frequency of uterine abnormalities related with persistent miscarriages in pregnancy on ultrasound. Methods: It was a cross-sectional study conducted over a period of 4 months from February 2022 to May 2022. A sample size of 70 patients was collected using purposive sampling technique. Data was collected from Memorial Christian Hospital Sialkot. Patients with multiple miscarriages due to uterine abnormalities were included in the current study. Patients with less than two miscarriages, self-induced miscarriages and miscarriages due to foetal anomalies were excluded. Data was analysed using SPSS version 20.0. Results: The study showed that the mean age of affected women experiencing miscarriage is 28.72. The highest rate of miscarriage was found in 38 (54.3%) of females and least in 4 (5.7%). The common cause of miscarriage was fibroids. Out of 70 females, 34 (48.6%) had fibroids, 14 (20%) had cervical incompetence, 9 (12.9%) had uterine adhesions, 6 (8.6%) had abnormal uterine size, 4 (5.7%) had uterine polyp and remaining 3 (4.3%) had congenital anomalies. Conclusion: The study concluded that miscarriages and uterine factors are closely linked. Uterine fibroids have shown the highest percentage of patients that had undergone miscarriage.

P-750 The cost-effectiveness of transvaginal hydrolaparoscopy versus hysterosalpingography in the work-up for subfertility

Abstract Study question Is transvaginal hydrolaparoscopy (THL) cost-effective compared to hysterosalpingography (HSG) in the work-up for subfertility in a population at low-risk for tubal pathology? Summary answer THL is cost-effective compared to HSG in a preselected group of women at low-risk of tubal pathology. What is known already Tubal pathology is a common cause of subfertility and tubal patency testing plays an important part in the work-up of the subfertile couple and the subsequent counseling for fertility treatment. THL is an out-patient procedure. After access through the pouch of Douglas, the tubes and pelvic cavity are directly observed using hydroflotation, whereas HSG is a radiographic evaluation of the uterine cavity and patency of the tubes with injection of contrast medium in the uterine cavity. Both methods are safe and feasible for subfertile women at low-risk of tubal pathology. Study design, size, duration We performed an economic analysis as part of a randomized controlled trial comparing THL and HSG in the work-up for subfertility. Women were eligible if they had an indication for evaluation of tubal patency. Primary outcome was a conception leading to live birth in 24 months. We randomly assigned 300 subfertile women to THL or HSG between May 2013 and October 2016. Participants/materials, setting, methods This study was performed in four Dutch teaching hospitals. The economic evaluation was performed from a health care perspective. Costs were either derived from literature or calculated. The mean costs and outcomes for each treatment group were compared. Costs were combined with effectiveness by calculating ICER, and bootstrap resampling was performed. We generated a cost-effectiveness plane and cost-effectiveness acceptability curves. Main results and the role of chance After 24 months of follow-up there was a 3% difference in live birth rate in favour of the THL group (58.5% in the THL group versus 55.4% in the HSG group (83/142 versus 82/148 difference 3.0% (95% CI: -8.3 – 14.4)). Multiple pregnancy and miscarriage rate were low and did not differ between groups. Ectopic pregnancy occurred in two women in the HSG group and not in the THL group. The mean cost was lower in the THL group, compared to the HSG group (THL group 4,927 EUR versus 5,197 EUR in the HSG group, difference -270 EUR). Although the costs of the diagnostic procedure itself were higher in the THL group (425 EUR versus 289 EUR, difference 136 EUR), the costs for fertility treatments are higher in the HSG group. The base case outcome is that THL costs less and is more effective than HSG, making THL the dominant strategy. The spread of the bootstrap indicates that there is uncertainty regarding the effectiveness of THL over HSG but less uncertainty regarding the cost difference between THL and HSG. Limitations, reasons for caution This trial was conducted in the Netherlands, using price calculations of the Dutch healthcare system in Euro’s. Since prices of fertility treatments and especially ART or fertility enhancing surgery can vary widely worldwide, it is possible that the outcomes of our study are not generalizable to other countries. Wider implications of the findings The findings of our trial suggest that in a preselected group of women with low risk for tubal pathology, a diagnostic strategy starting with THL is cost-effective compared to a diagnostic strategy starting with HSG in the workup for subfertility. Trial registration number NTR3462

Cleavage-stage versus blastocyst-stage embryo transfer in assisted reproductive technology.

Advances in embryo culture media have led to a shift in in vitro fertilisation (IVF) practice from cleavage-stage embryo transfer to blastocyst-stage embryo transfer. The rationale for blastocyst-stage transfer is to improve both uterine and embryonic synchronicity and enable self selection of viable embryos, thus resulting in better live birth rates. To determine whether blastocyst-stage (day 5 to 6) embryo transfer improves the live birth rate (LBR) per fresh transfer, and other associated outcomes, compared with cleavage-stage (day 2 to 3) embryo transfer. We searched the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, CENTRAL, MEDLINE, Embase, PsycINFO, and CINAHL, from inception to October 2021. We also searched registers of ongoing trials and the reference lists of studies retrieved. We included randomised controlled trials (RCTs) which compared the effectiveness of IVF with blastocyst-stage embryo transfer versus IVF with cleavage-stage embryo transfer. We used standard methodological procedures recommended by Cochrane. Our primary outcomes were LBR per fresh transfer and cumulative clinical pregnancy rates (cCPR). Secondary outcomes were clinical pregnancy rate (CPR), multiple pregnancy, high-order multiple pregnancy, miscarriage (all following first embryo transfer), failure to transfer embryos, and whether supernumerary embryos were frozen for transfer at a later date (frozen-thawed embryo transfer). We assessed the overall quality of the evidence for the main comparisons using GRADE methods. We included 32 RCTs (5821 couples or women). The live birth rate following fresh transfer was higher in the blastocyst-stage transfer group (odds ratio (OR) 1.27, 95% confidence interval (CI) 1.06 to 1.51; I2 = 53%; 15 studies, 2219 women; low-quality evidence). This suggests that if 31% of women achieve live birth after fresh cleavage-stage transfer, between 32% and 41% would do so after fresh blastocyst-stage transfer. We are uncertain whether blastocyst-stage transfer improves the cCPR. A post hoc analysis showed that vitrification could increase the cCPR. This is an interesting finding that warrants further investigation when more studies using vitrification are published. The CPR was also higher in the blastocyst-stage transfer group, following fresh transfer (OR 1.25, 95% CI 1.12 to 1.39; I2 = 51%; 32 studies, 5821 women; moderate-quality evidence). This suggests that if 39% of women achieve a clinical pregnancy after fresh cleavage-stage transfer, between 42% and 47% will probably do so after fresh blastocyst-stage transfer. We are uncertain whether blastocyst-stage transfer increases multiple pregnancy (OR 1.05, 95% CI 0.83 to 1.33; I2 = 30%; 19 studies, 3019 women; low-quality evidence) or miscarriage rates (OR 1.12, 95% CI 0.90 to 1.38; I2 = 24%; 22 studies, 4208 women; low-quality evidence). This suggests that if 9% of women have a multiple pregnancy after fresh cleavage-stage transfer, between 8% and 12% would do so after fresh blastocyst-stage transfer. However, a sensitivity analysis restricted only to studies with low or 'some concerns' for risk of bias, in the subgroup of equal number of embryos transferred, showed that blastocyst transfer probably increases the multiple pregnancy rate. Embryo freezing rates (when there are frozen supernumerary embryos for transfer at a later date) were lower in the blastocyst-stage transfer group (OR 0.48, 95% CI 0.40 to 0.57; I2 = 84%; 14 studies, 2292 women; low-quality evidence). This suggests that if 60% of women have embryos frozen after cleavage-stage transfer, between 37% and 46% would do so after blastocyst-stage transfer. Failure to transfer any embryos was higher in the blastocyst transfer group (OR 2.50, 95% CI 1.76 to 3.55; I2 = 36%; 17 studies, 2577 women; moderate-quality evidence). This suggests that if 1% of women have no embryos transferred in planned fresh cleavage-stage transfer, between 2% and 4% probably have no embryos transferred in planned fresh blastocyst-stage transfer. The evidence was of low quality for most outcomes. The main limitations were serious imprecision and serious risk of bias, associated with failure to describe acceptable methods of randomisation. There is low-quality evidence for live birth and moderate-quality evidence for clinical pregnancy that fresh blastocyst-stage transfer is associated with higher rates of both than fresh cleavage-stage transfer. We are uncertain whether blastocyst-stage transfer improves the cCPR derived from fresh and frozen-thawed cycles following a single oocyte retrieval. Although there is a benefit favouring blastocyst-stage transfer in fresh cycles, more evidence is needed to know whether the stage of transfer impacts on cumulative live birth and pregnancy rates. Future RCTs should report rates of live birth, cumulative live birth, and miscarriage. They should also evaluate women with a poor prognosis to enable those undergoing assisted reproductive technology (ART) and service providers to make well-informed decisions on the best treatment option available.

Exposure to multiple trace elements and miscarriage during early pregnancy: A mixtures approach.

Exposure to some conventional trace elements has been found to be associated with miscarriage; however, evidence for combined exposure is inconclusive. Therefore, it is important to explore the joint associations between toxic and essential trace elements and miscarriage. This cross-sectional study measured a wide range of element levels in the whole blood of pregnant women by using inductively coupled plasma mass spectrometry. The associations between individual elements and miscarriage were appraised using logistic regression model. Multi-exposure models, including Bayesian kernel machine regression (BKMR) and weighted quantile sum regression (WQS), were used to explore the mixed exposure to elements. Furthermore, grouped weighted quantile sum (GWQS) considered multiple elements with different magnitudes and directions of associations. In logistic regression, the odds ratios (ORs) with a 95% confidence interval (CI) in the highest quartiles were 5.45 (2.00, 15.91) for barium, 0.28 (0.09, 0.76) for copper, and 0.32 (0.12, 0.83) for rubidium. These exposure-outcome associations were confirmed and supplemented by BKMR, which indicated a positive association for barium and negative associations for copper and rubidium. In WQS, a positive association was found between mixed elements and miscarriage (OR: 1.71; 95% CI: 1.07, 2.78), in which barium (75.7%) was the highest weighted element. The results of GWQS showed that the toxic trace element group dominated by barium was significantly associated with increased ORs (OR: 2.71; 95% CI: 1.74, 4.38). Additionally, a negative association was observed between the essential trace element group and miscarriage (OR: 0.32; 95% CI: 0.18, 0.54), with rubidium contributing the most to the result. As a toxic trace element, barium was positively associated with miscarriage both by individual and multiple evaluations, while essential trace elements, particularly rubidium and copper, exhibited negative associations. Our findings provide significant evidence for exploring the effects of trace elements on miscarriage.

I Got It from My Mamma: Sensitization by Transplacental Transfer of Maternal HLA Antibodies Managed with Manual Exchange Transfusion

<h3>Introduction</h3> During pregnancy antibodies are passed from mother to fetus with many known immunologic benefits. There is no data about the implications of this on pediatric transplant immunology. We report a case of transplacental transfer of maternal Human Leukocyte Antigen (HLA) antibodies affecting cardiac transplant candidacy in an infant with cardiomyopathy. <h3>Case Report</h3> A 3-week-old Amish boy with a homozygous MYBPC3 mutation causing severe cardiomyopathy admitted for refractory heart failure symptoms was referred for heart transplant evaluation. Labs were notable for high levels of high Mean Fluorescence Intensity (MFI) HLA antibodies (Panel of Reactive Antibodies (PRA) Class I: 74%, Class II: 80%) with no known sensitizing events. Maternal history was remarkable for multiple miscarriages raising the question that his HLA antibodies could be a result of maternal HLA sensitization with transplacental antibody transfer versus active antibody production by the child. Subsequent antibody testing of his mother's blood and breast milk revealed nearly identical HLA antibody profiles to that of the patient. Given the patient's prohibitively small size for antibody removal by plasmapheresis, we elected to perform double volume whole blood exchange transfusions with serial monitoring of his HLA antibodies. Considering his severe ventricular dysfunction, exchange transfusions were performed manually via the push pull method over 6 hours. He ultimately underwent 6 exchange transfusions over the course of 7 weeks. Serial antibody testing revealed a progressive decline in all his HLA antibody levels to <3,000 MFI with only mild rebound after each transfusion consistent with tissue redistribution rather than active antibody production. He was successfully transplanted with a negative PRA (Class I: 0%, Class II: 0%) without post-transplant complications. <h3>Summary</h3> We believe this is the first report demonstrating transplacental acquisition of maternal HLA antibodies in an infant successfully removed via serial whole blood exchange transfusions enabling successful cardiac transplantation.

Conventional GnRH antagonist protocols versus long GnRH agonist protocol in IVF/ICSI cycles of polycystic ovary syndrome women: a systematic review and meta-analysis

Gonadotropin-releasing hormone (GnRH) analogues are commonly used in clinical practice to prevent premature luteinizing hormone (LH) surge during In-Vitro Fertilization/ Intra-Cytoplasmic Sperm Injection (IVF/ICSI) cycles. This review aimed to summarize the available evidence comparing the effects of conventional GnRH antagonist protocols, the most commonly used GnRH antagonist protocols, and GnRH agonist protocols on IVF/ICSI outcomes in women with polycystic ovary syndrome (PCOS). A comprehensive electronic search was carried out in Pubmed, Cochrane CENTRAL, Scopus, Web of Science, CINAHL, TRIP, ClinicalTrials.gov and ISRCTN registry from inception until 24 November 2020 without any language or date restrictions. In addition, reference lists of eligible studies and previous meta-analyses were hand-searched to identify relevant studies. Eligible randomized controlled trials were those designed to compare the effects of conventional GnRH antagonist protocols and GnRH agonist protocols on IVF/ICSI outcomes in PCOS subjects. The Cochrane ROB 2.0 tool was used to assess the risk of bias of each study, and the GRADE assessment was used to evaluate the overall quality of evidence. Data synthesis and analyses were done using Review Manager 5.3 with the assistance of Revman Web. A random-effects model was used for all meta-analysis. Dichotomous outcomes were reported as Relative Risk (RR) and continuous outcomes as Weighted Mean Difference (WMD), both with 95% CIs. The primary outcomes were Live birth rate, Ongoing pregnancy rate, and Ovarian hyperstimulation syndrome (OHSS) rate. Other IVF outcomes were considered secondary outcomes. We included ten studies with 1214 randomized PCOS women. Using GnRH antagonist protocols led to a significantly lower OHSS rate (RR = 0.58; 95% CI: [0.44 to 0.77], P = 0.0002), shorter stimulation duration (WMD = − 0.91; 95% CI: [-1.45 to − 0.37] day, P = 0.0009), lower gonadotropin consumption (WMD = − 221.36; 95% CI: [− 332.28 to − 110.45] IU, P < 0.0001), lower E2 levels on hCG day (WMD = − 259.21; 95% CI: [− 485.81 to − 32.60] pg/ml, P = 0.02), thinner endometrial thickness on hCG day (WMD = − 0.73; 95% CI: [− 1.17 to − 0.29] mm, P = 0.001), and lower number of retrieved oocytes (WMD = − 1.82; 95% CI: [− 3.48 to − 0.15] oocytes, P = 0.03). However, no significant differences in live birth rate, ongoing pregnancy rate, clinical pregnancy rate, multiple pregnancy rate, miscarriage rate and cycle cancellation rate were seen between the GnRH antagonist protocols and the long GnRH agonist one. Although more cycles were cancelled due to poor ovarian response in the GnRH antagonist protocol (RR = 4.63; 95% CI: [1.49 to 14.41], P = 0.008), similar rates of cancellation due to risk of OHSS were noticed in both groups. The differences in IVF/ICSI outcomes may arise from the different patterns of gonadotropins suppression that the GnRH analogues exhibit during the early follicular phase of IVF/ICSI cycles and the divergent direct impacts of these analogues on ovaries and endometrial receptivity. The main evidence limitation was Imprecision. Conventional GnRH antagonist protocols represent a safer and more cost-effective treatment choice for PCOS women undergoing IVF/ICSI cycles than the standard long GnRH agonist protocol without compromising the IVF/ICSI clinical outcomes. The study had no sources of financial support and was prospectively registered at PROSPERO (International Prospective Register of Systematic Reviews) under registration number (CRD42021242476).

Contraception after in vitro fertilisation (IVF): a qualitative study of the views of women who have had spontaneous pregnancies after successful IVF

BackgroundThe use of in vitro fertilisation (IVF) has increased rapidly since its inception in 1978. Women seeking IVF have a wide range of subfertility causes including unexplained subfertility. A growing subgroup of women seek treatment for other reasons than fertility problems, for example, women in same sex relationships and single women. This study aims to better understand the contraceptive needs of women after successful IVF pregnancy in order to improve service delivery and prevent unplanned and rapid-repeat pregnancies.MethodsA qualitative study of views of women who have had spontaneous pregnancies after successful IVF. Participants were recruited using purposive and snowballing sampling methods from social media and peer networks. The framework method was used for analysis using NVivo12.ResultsThe sample comprised 21 interviewees from the United Kingdom (UK), having a range of spontaneous pregnancy outcomes, including single and multiple livebirths, miscarriage, ectopic pregnancy and termination of pregnancy. Contraceptive choices were subject to a complex and dynamic interaction of influencing factors including beliefs regarding subfertility, desire for children and views on contraception. None of the women recalled receiving any information or useful counselling about contraception during fertility or maternity care. After IVF pregnancy, most women (n = 16) used no or ineffective contraception. Spontaneous pregnancy was not universally welcomed in this group and inter-pregnancy intervals were often short (n = 16, less than 18 months). Even after subsequent spontaneous pregnancy, use of contraception and the most effective methods remained low. Women held persistent beliefs regarding their subfertility despite subsequent spontaneous pregnancy. They associated aspects of the IVF process with a sense of personal failure, despite an ultimately “successful” outcome of livebirth. These aspects may reinforce their self-belief in subfertility. Other barriers to contraception use in women having IVF included: lack of knowledge of likelihood of spontaneous pregnancy, lack of contraceptive experience and inherent incentives towards shorter inter-pregnancy intervals.ConclusionsThe contraceptive needs of women having IVF pregnancies are real and are being overlooked. Fertility services should take responsibility for providing information on the risks of subsequent spontaneous pregnancy. Maternity and community healthcare professionals must address women’s perceptions of their fertility in order to engage them in contraception counselling.

Power Beyond Sex: A Foucauldian Reading of Lady Macbeth

Shakespeare’s most haunting tragedy, Macbeth, has been regarded as one of his best tragic trios. One of the most significant characters of the play – Lady Macbeth – often realized as the ‘antagonist’ of the play, is portrayed as the impetus and motivational factor behind Macbeth’s brief victory and, apparently, even his ultimum ruinam. With her actions within the course of the play, it becomes a daunting task to justify them without referring to the history of Lady Macbeth. Most of the past studies have focused on her earlier marriage and multiple miscarriages in order to condone her behaviour. The present research essay, however, reviews the play in a deconstructive approach and delves into a deep exploration of the representation of Lady Macbeth in Shakespeare’s renowned tragedy. The study focuses on the influence of normalizing power and gender distinction upon the actions of the characters. It studies the theory of Normalizing Power (as given by Michel Foucault) and views it in the context of how femininity is depicted within Macbeth. It further reinvestigates the patriarchal dominance and looks at the existing power structures that subconsciously affect Lady Macbeth’s motivation, leading to the tragic fall of the characters. By visiting the play from the lens of power and femininity inherent in the subconscious mind of the readers, the research aims to portray Lady Macbeth in a different light, one that is not dominated by supporting ideologies of male dominance or the notion of power in the hands of the phallus.

Does LIN28B gene dysregulation make women more likely to abort?

BackgroundLIN28B plays an important role in early embryonic development, but its role in villous trophoblast implantation and differentiation remains unknown. This study aims to verify the role of LIN28B in trophoblastic villous tissue and cells from women with URSA (unexplained recurrent spontaneous abortion) and artificial termination of pregnancy (negative control, NC).MethodsThe LIN28B gene and its protein expression level were detected with real-time quantitative PCR, Western immunoblotting analysis, and immunocytochemistry. The gene was also overexpressed in chorionic villous cell lines (HTR-8/SVneo and BeWo) to examine its effect on trophoblast function.ResultsThe expression of LIN28B mRNA and protein of URSA villi was lower than that in the NC group. At the cellular level, overexpression of LIN28B enhanced cellular migration, and invasion, and inhibited apoptosis. LIN28B may inhibit apoptosis by promoting Akt phosphorylation and by inhibiting Bad phosphorylation and Bcl-2 expression. In addition, LIN28B inhibited cell fusion and reduced cellular syncytia.ConclusionsLIN28B can inhibit cell invasion and migration in vitro and promote apoptosis and fusion. The low expression of LIN28B in URSA villous trophoblast cells may be one of the causes of abortion. The role of LIN28B in villous trophoblasts needs further study.Lay summaryPropagation of offspring is of great significance to the continuation of the human race. However, continuous pregnancy is more difficult for some women, especially women who have multiple miscarriages. One important contributor is the cessation of development caused by genetic factors of the embryo, but there are still many unknown reasons. We investigated the LIN28B gene which is a possible pathogenic factor in the placenta. We collected 25 cases of abortion in the experimental group (unexplained recurrent abortion group) and 25 in the control group (artificial termination of pregnancy group): on average at 7–8 weeks of pregnancy. We tested the function of lin28b in these samples and verified its function in cell lines. LIN28B plays an important role in maintaining early pregnancy by promoting the invasion of villous cells, inhibiting apoptosis and fusion, and the reduction of LIN28B expression may lead to the occurrence of early miscarriage.

P–753 A randomised controlled trial comparing expectant management versus intrauterine insemination in couples with unexplained subfertility and a poor prognosis for natural conception

Abstract Study question Does 6 months expectant management reduces ongoing pregnancy rates compared to intrauterine insemination with ovarian stimulation (IUI-OS) in couples with unexplained subfertility? Summary answer In couples with unexplained subfertility and a poor prognosis for natural conception, 6 months of expectant management decreases ongoing pregnancy rates as compared to IUI-OS. What is known already In couples with unexplained subfertility and a poor prognosis, IUI-OS is a first line treatment. We have previously shown that in couples with unexplained subfertility and a good prognosis for natural conception (&amp;gt;30% in 12 months), 6 months expectant management does not reduce pregnancy changes. However, in couples with a poor prognosis for natural conception, effectiveness of IUI-OS is uncertain. Study design, size, duration We performed a non-inferiority multicentre randomised controlled trial (RCT) within the infrastructure of the Dutch Consortium for Healthcare Evaluation and Research in Obstetrics and Gynaecology. We studied couples with unexplained subfertility and a poor prognosis for natural conception. The couples were allocated in a 1:1 ratio to six months expectant management or six months IUI-OS with either clomiphene citrate or gonadotrophins. Participants/materials, setting, methods We intended to include 1091 couples. The trial was halted pre-maturely due to slow inclusion after randomisation of 178 couples. The primary outcome was ongoing pregnancy leading to a live birth with multiple pregnancy and miscarriage rate as important secondary outcomes. We calculated relative risks with 95% CI and a corresponding hazard-rate for ongoing-pregnancy-over-time based on intention-to-treat. Main results and the role of chance Between October 2016 and September 2020 92 couples were allocated to expectant management and 86 to IUI-OS. Baseline characteristics were equally distributed. Mean female age was 34 years, median duration of subfertility was 21 months. Within 6 months after randomisation, women allocated to expectant management had a lower ongoing pregnancy rate than women allocated to IUI-OS (12/92 [13.0%] vs 29/86 women [33.7%], risk ratio 0.39 (95%CI 0.21 to 0.71)). There were two ongoing twin pregnancies in the expectant management group versus none in the IUI-OS group. Of 15 clinical pregnancies in the expectant management group three miscarried (20%), of 36 clinical pregnancies in the IUI-OS group seven miscarried (19.4%) (RR 1.03 (95% CI 0.31 to 3.45)). For the outcome ongoing pregnancy, the hazard ratio for expectant management versus IUI-OS was 0.34 (95%CI 0.18 to 0.67). Limitations, reasons for caution Our trial did not reach the planned sample size and therefore the results are limited by the number of participants. As 8 women are still pregnant, in this abstract we report ongoing pregnancy rates. Live birth rates will be presented at the conference. Wider implications of the findings: In couples with unexplained subfertility and a poor prognosis for natural conception, expectant management is inferior to IUI-OS. We advise the basic work-up for subfertility to contain a prognostic assessment, and when subfertility is unexplained and natural fertility prospects are poor IUI-OS should be the preferred treatment. Trial registration number NTR5599

P–743 The fertility paradox: the need for contraception after in vitro fertilisation

Abstract Study question What are a woman’s contraceptive needs after successful in vitro fertilisation (IVF) pregnancy? and how should services respond to help prevent unintended pregnancies? Summary answer Women who have IVF pregnancies require tailored, postnatal contraception counselling. Services must provide evidence-based information about the risks of spontaneous conception to engage them effectively. What is known already Women undergoing IVF are an increasingly heterogeneous group with a wide range of causative subfertility factors. Furthermore, increasingly, women are accessing treatment primarily for reasons other than subfertility. The evidence relating to rates of spontaneous conception post assisted conception varies widely according to population, cause of subfertility, type and outcome of fertility treatment and length of follow-up. A recent large retrospective UK cohort study estimated the treatment-independent live birth rate after IVF live birth over 5 year follow up as 15% [https://doi.org/10.1093/humrep/dez099]. We aim to explore the experiences and views about contraception among this diverse group of women. Study design, size, duration A qualitative study of the views of women who have had spontaneous pregnancies after successful IVF was conducted in September/October 2020. A qualitative approach of in-depth interviews was chosen to allow exploration of individual experiences in an area not much studied previously. The sample consisted of twenty interviewees from around the UK. Participants/materials, setting, methods Purposive and snowballing sampling methods were used with eligible participants recruited from a range of sources including social media and peer networks. The sample included a wide range of spontaneous pregnancy outcomes after successful IVF, including single and multiple livebirths, miscarriage, ectopic pregnancy and termination of pregnancy. The framework method was used for analysis using NVivo12 software. Main results and the role of chance Contraceptive choices were subject to a complex and dynamic interaction of influencing factors including i) beliefs regarding their own subfertility, ii) desire for more children and iii) their views on contraception. After IVF pregnancy, the majority of women (n = 15) used no contraception or ineffective methods (inconsistent condom use or withdrawal) before their next pregnancy with only two women using hormonal methods (progesterone-only pill). Spontaneous pregnancy was not universally welcomed in this group and the inter-pregnancy intervals were often short (n = 15, less than 18 months) or very short (n = 6, less than 12 months). After subsequent spontaneous pregnancy, use of contraception and the most effective (long-acting reversible) methods remained low. Women held persistent beliefs regarding their subfertility despite subsequent spontaneous pregnancy (or pregnancies). Women associated aspects of the IVF process (e.g. need for multiple cycles, low numbers of eggs collected etc.) with a sense of personal failure, despite an ultimately “successful” outcome resulting in livebirth. This may contribute to or reinforce their self-belief in subfertility. Other specific barriers to contraception use, in women having IVF, included lack of knowledge of the likelihood of spontaneous pregnancy, lack of contraceptive experience and inherent incentives towards shorter inter-pregnancy intervals. Limitations, reasons for caution There is potential recall bias with some women recalling experiences associated with IVF treatment more than ten years ago. However our sample included women who were currently pregnant as well as women who were further towards the end of their reproductive life to capture a range of experiences. Wider implications of the findings: The contraceptive needs of women having IVF pregnancies are being overlooked. Fertility services should take responsibility for providing accurate information on the risks of subsequent spontaneous pregnancy in this population. Maternity and community healthcare professionals must address women’s perceptions of their fertility in order to engage them in contraception counselling. Trial registration number N/A

O-130 The influence of vaginal microbiota on frozen blastocyst implantation after transfer: a prospective study through next-generation 16S rRNA sequencing

Abstract Study question A prospective study to investigate the relationship between the composition of vaginal microbiota through next-generation sequencing and the efficacy of single frozen blastocyst transfer in the same cycle. Summary answer Dominant presence of lactobacillus and other lactate producing microbes in the upper vagina was highly correlated with implantation of transferred blastocyst in this pilot study. What is known already Next-generation sequencing of 16S rRNA detected microbes in the uterine cavity and recent studies indicated that dominant presence of Lactobacillus correlated highly with successful implantation of the transferred embryos. Aberrant vaginal microbiota has been known to cause poor obstetrical outcomes, however little is known for its effect on embryo implantation in assisted reproduction. Study design, size, duration A prospective study with 25 female subjects transferring a frozen blastocyst using autologous oocyte, over 14 months period in 2019-2020. Participants/materials, setting, methods 25 female patients without tubal and uterine pathology and no history of multiple miscarriages and implantation failures were recruited with consent at a private ART clinic. Transdermal estrogen was used to prepare endometrium. Upper vaginal fluid was obtained in follicular phase of the the same cycle and analyzed through next-generation sequencing, but the result was reported after pregnancy confirmation. Single frozen blastocyst transfer and standard luteal phase support were performed. Institutional IRB approved the protocol. Main results and the role of chance The mean age was 36.2 y.o.(range 29-41 y.o.), and 14 gestational sacs (implantation rate 56%), and 3 miscarriage (21.4%) were observed. Next-generation sequencing for 16S rRNA revealed average 69.2% presence of Lactobacillus (0-100%) and average 78.0% (0.2-100%) lactate producing microbes (LPM: Lactobacillus, Bifidobacterium, Streptococcus, and Enterococcus) in the vaginal fluid. Using 90% as cut-off, implantation rates were 11/15 (73.3%) and 3/10 (30%) with Lactobacillus dominant and non-dominant, 12/16 (75%) and 2/9 (22.2%) with LPM dominant and non-dominant microbiota, respectively. The difference in each group were not statistically significant. The relative risks for pregnancy were 2.63 (95%CI 1.03-6.67, P=0.04) for Lactobacillus and 3.11 (95%CI 1.24-7.79, P=0.02) for LPM. As for ROC analysis for embryo implantation and dominant microbes, AUC and associated criterion were 0.62 and 90.7% (sensitivity 78.6%, specificity 72.7%) for Lactobacillus, 0.69 and 96.6% (sensitivity 85.7%, specificity 72.7%) for LPM, respectively. The difference of AUC was not significant (P=0.24). Limitations, reasons for caution Despite prospective nature of the study, small sample size limited the analytical power of the study. Aneuploidy screening was not performed to remove confounding factor. Wider implications of the findings Our pilot study revealed possible relationship between vaginal microbiota and embryo implantation. Dominance of Lactobacillus or other lactate producing microbes may be advantageous for successful ART. Sampling vaginal fluid for microbe analysis is less invasive than endometrial sampling and can obtain more abundant RNA with possible higher accuracy of analysis. Trial registration number not applicable

Genetic Testing for Aneuploidy in Patients Who Have Had Multiple Miscarriages: A Review of Current Literature.

Recurrent pregnancy loss (RPL) is an obstetrical complication that affects about 3% of reproductive age couples. Genetic and non-genetic causes of RPL are multiple; however, aneuploidy is the most common obstetrical complication that can explain single and recurrent pregnancy loss (present in about 60% of recognized clinical pregnancies which result in a miscarriage). Parental karyotyping will only be of potential benefit for 2 to 5 percentage of RPL couples who are translocation carriers. Products of conception (POC) karyotype analysis has been used to direct management in RPL and has been shown to be cost-effective, but the technique has many limitations including high culture failure rate and maternal cell contamination. These limitations can be significantly reduced using POC chromosomal microarray (CMA) technology. We believe that POC genetic testing should be performed after the second and subsequent pregnancy loss using CMA. Although the results will not generally alter the course of treatment, the knowledge of the reason for the loss is of great emotional comfort to many patients. In addition, POC CMA performed in conjunction with a regular complete maternal RPL work-up will identify the group of truly unexplained RPL. Thus, only 10% of patients with RPL will complete an evaluation having a euploid loss and an otherwise normal work-up. This group of “truly unexplained RPL” would be ideal for new research trials and therapies. Pre-implantation genetic testing (PGT) technology has improved recently with day 5 trophectoderm biopsy as compared to biopsy on day 3 as well as with the addition of CMA and next-generation sequencing technologies. The most recent studies on PGT-SR (PGT-Structural rearrangement) show improved clinical and live birth rates per pregnancy, as well as decreased miscarriage rate for translocation carriers. PGT-A (PGT-aneuploidy) may have a limited role in RPL in cases with documented recurrent POC aneuploidy.

Prune belly syndrome in Finland – A population-based study on current epidemiology and hospital admissions

Prune belly syndrome (PBS) is a multisystem disease characterized by absent or deficient abdominal musculature with accompanying lax skin, urinary tract abnormalities, and cryptorchidism. Previous studies have estimated a birth prevalence of 1 in 35,000-50,000 live births. We set out to clarify the epidemiology and early hospital admissions of PBS in Finland through a population-based register study. Further, possible maternal risk factors for PBS were analyzed in a case-control setting. The Finnish Register of Congenital Malformations was linked to the Care Register for Health Care, a population-based hospital admission data for PBS patients. Additionally, five matched controls were identified in the Birth Register and maternal risk factors of PBS were studied utilizing data from the Drugs and Pregnancy database. We identified 31 cases of PBS during 1993-2015, 15 of which were live born and 16 elective terminations. The total prevalence was 1 in 44,000 births. Three patients (20%) died during infancy. On average, PBS-patients had 3.2 admissions and 10.6 hospital days per year in Finland during the study period years 1998-2015, 35- and 27-fold compared to children in Finland in general. Multiple miscarriages were significantly associated to PBS in maternal risk factor analyses. The burden of disease is significant in PBS, demonstrated as a high infant mortality rate (20%), multiple hospital admissions, and inpatient care in days. The available variables are limited as a register-based study. We present data on contemporary epidemiology in a population-based study and show that the total prevalence of PBS is 1 in 44,000 in Finland. PBS entails a significant disease burden with admissions and hospital days over 35- and 27-fold compared to the general pediatric population, further aggravated by an infant mortality rate of 20%.

Ovarian Hyperthecosis: Hyperandrogenism in a Post-Menopausal Woman

Introduction: Ovarian Hyperthecosis (OH) is a disorder characterized by severe hyperandrogenism and insulin resistance. It is a rare cause of hyperandrogenism primarily among postmenopausal women. We present a case report about a patient with adrenal incidentalomas and later found to have ovarian hyperthecosis during her evaluation. Case Description: 62-year-old post-menopausal female was referred to the Endocrinology clinic for evaluation of adrenal incidentalomas which were discovered on imaging work-up for hematuria. MRI Abdomen and Pelvis revealed a 17mm right and 14mm left sided adrenal nodules, with signal dropout suggesting benign adenomas. Patient stated she had menopause at age 39 years old, one child, and multiple miscarriages during her reproductive years. Examination revealed BMI of 31.1 kg/m2, moderate hirsutism, and skin tags near the neck. There was no evidence of hyperpigmentation or abdominal striae. Patient had phenotype suggestive of insulin resistance-without diagnosis of diabetes. Results: Laboratory workup revealed normal levels of 24-hour metanephrines, cortisol, renin, aldosterone, and DHEA-S suggesting that the adrenal adenomas were not hyperfunctioning. Further workup revealed: Total Testosterone: 220 [2 - 45 ng/dL]; Free Testosterone 23.8 [0.1 - 6.4 pg/mL]; DHEA-S 43 [12 - 133 mcg/dL]. Prolactin 6.3 [Postmenopausal 2.0-20.0 ng/mL]. A1c 5.4 [<5.7%]. Serum FSH, LH, PRL, and IGF-1 were within normal reference ranges. The patient, with adrenal adenomas, elevated testosterone, and a normal DHEA-S suggested a non-adrenal source. Patient was evaluated by OB/GYN with finding of normal postmenopausal ovaries on transvaginal ultrasonography. Based on a high suspicion for OH, patient underwent hysterectomy with bilateral salpingo-oophorectomy which confirmed pathological diagnosis of Bilateral OH. On follow-up 2 months post-op, Total/Free Testosterone had normalized 36 [2 - 45 ng/dL] and 3 [0.1 - 6.4 pg/mL] respectively). Conclusion: In women presenting with elevated testosterone (>150 ng/dL) and clinical features of hyperandrogenism, proper laboratory and imaging evaluation is imperative to determine the source of excess androgen production. Untreated, OH is associated with increased mortality from type 2 diabetes, cardiovascular disease, and endometrial carcinoma. The diagnosis of OH can be confirmed only by histologic examination of the ovaries. Often, ovarian imaging is negative, therefore, surgical intervention is recommended. Hence, clinicians should rely on the clinical assessment in making management decisions in patients with OH.

Effect of Happiness Counseling on Depression, Anxiety, and Stress in Women with Recurrent Miscarriage

PurposeThis study investigated the effectiveness of a happiness counseling program on depression, anxiety, and stress in pregnant women with a history of recurrent miscarriage.Patients and MethodsA parallel randomized controlled trial research design was used in this study, which was conducted at the high-risk inpatient unit of the Obstetrics and Gynecology Hospital of Cairo University Hospitals in Cairo, Egypt. A total of 60 pregnant women who had previously experienced multiple miscarriages were randomly assigned to intervention and control groups (n=30 each). The tools used for data collection were demographic and obstetric data questionnaires and the 21-item Depression, Anxiety, and Stress Scale (DASS-21). Happiness counseling sessions were conducted for the intervention group. Data for qualitative variables were analyzed with the chi-squared test, and the Student’s t test for paired samples was used to compare mean DASS-21 scores of the intervention and control groups. The Pearson correlation coefficient was used to analyze the association between variables.ResultsThe happiness counseling sessions reduced depression, anxiety, and stress in women with recurrent miscarriage, resulting in lower mean DASS-21 scores for the intervention group compared to the control group.ConclusionThe happiness counseling program had a positive effect on reducing depression, anxiety, and stress in women with recurrent miscarriage. We recommend that this program be used as an effective, low-cost, and noninvasive intervention to improve the mental health and overall wellbeing of women with recurrent miscarriage.