bluuebunny/crossref_metadata_2025 huggingface dataset:
P–184 Assisted hatching does not improve live birth rates, a prospective double-blinded randomized study
Authors: Montalvo V , Masso J , Garcia-Faura A , Marques B , Lopez-Teijon M
Published: August 2021

Study question

Does Assisted hatching (AH) improve success rates when applied to frozen embryo transfers?

Summary answer

AH does not improve implantation, ongoing pregnancy or live birth rates when applied to thawed embryos.

What is known already

Vitrification has been proven to be the most efficient technique to preserve human embryos. However, vitrification has some consequences for the embryos, zona pellucida (ZP) hardening being one of them. Multiple studies suggest the need to apply laser Assisted hatching or ZP thinning to thawed embryos in order to improve success rates. Still, there is not enough evidence to ensure the utility of AH, and considering the great variation in design between studies more evidence is needed.

Study design, size, duration

Study performed from October 2019 and January 2020. Disregarding embryos with natural Hatching and PGT-A. Embryos that, immediately after thawing, were completely expanded (trophectoderm in contact with ZP) were also excluded from the study. We applied a randomization to choose in which embryos we had to perform AH. Neither the gynecologist nor the embryologist performing the embryo transfer knew whether the embryo had AH performed or not.

Participants/materials, setting, methods

353 frozen embryo transfers of one blastocist were considered for the study, 71 excluded for expansion after thawing, 65 excluded because of PGT-A, 103 in which we performed AH (AH+) and 114 without AH (AH-). In the AH+ group we performed laser-AH of 1/3 of the ZP, avoiding to damage the trophectoderm and performing the laser shots as far away to the ICM as possible. We used Chi-square testing to assess the effects of AH.

Main results and the role of chance

We assessed all relevant clinical data parameters. No statistical differences were found in egg age, maternal age, embryo quality, nor endometrial thickness between groups. Implantation and miscarriage rates were equivalent between AH+ group (40.9%; 20.5%) and AH- group (47.4%; 18.5%).

The main outcome of this study was live birth rates. No statistical differences were found between groups (AH-= 38.6%; AH + = 30.1%; p = 03221) proving that making it easier to get out of the ZP does not affect success rates.

Analyzing the data from the excluded embryos we found no improvement on live birth rates when embryos were expanded just after thawing (38.0%; p = 0.457). As expected, PGT-A embryos yielded higher live birth rates (52.3%; p < 0,05)

Limitations, reasons for caution

Preliminary study with a small data set.

Wider implications of the findings: This study suggest that thawed embryos have the capacity to get out of the ZP regardless if AH was performed or not. Having no positive effects, AH seems to be unnecessary in this scenario.

Trial registration number

Not applicable
P–190 Can pregnancy be predicted according to mean infra-red attenuated total reflectance (MIR-ATR) spectrometry of incubation medium of embryos in IVF?: A proof of concept
Authors: Aslih N , Shalom-Paz E , Molenik D , Dekel B Z
Published: August 2021

Study question

Can MIR-ATR spectrometry of embryo incubation medium be used to predict embryo quality and IVF treatment results.

Summary answer

MIR-ATR spectrometry is able to distinguish between good and poor embryo quality and may improve the prediction of pregnancy based on better embryo selection.

What is known already

Infra Red (IR) spectra enable to determine if certain chemical functional components are present in a molecule. Attenuated total reflection (ATR) spectroscopy is a well established, simple and rapid technique for objective classification of biological samples. ATR spectrometry was investigated and confirmed to serve as an additional diagnostic tool in oral and gynecologic cancer. Currently, embryo quality is assessed based on morphokinetics parameters from Time-laps incubator and/or final embryo’s grading

Study design, size, duration

Culture media of 227 embryos on cleavage stage and blastocyst stage were collected and analysed between January 1st, 2018 and December 31st 2020.

Participants/materials, setting, methods

The incubation medium liquid of embryos cultured in Time-lapse incubator were collected after transferring the embryos to their final destination. Infra-Red (IR) absorbance spectra was measured. Nominal resolution was 4 cm–1, wavenumber range was from 600 cm–1 to 5000 cm–1 and each absorbance spectrum was normalized to the height of amide I band at ∼1650cm–1. Machine learning techniques utilized to build discrimination models for the absorbance data. Results were correlated with clinical and pregnancy results.

Main results and the role of chance

This preliminary study demonstrates that ATR spectrometry differs in media of : Day 3 embryos compared to day 5 embryos, top quality compared to poor quality embryos and implanting embryos comparing to non-implanting embryos. We found that MIR-ATR spectrometry might predict pregnancy in accuracy rates of 85%. MIR-ATR spectrometry of incubation medium can be used as an additional tool for selection of embryos for transfer.

Limitations, reasons for caution

Additional study and collection of larger number of culture Media is requested to validate MIR-ATR spectrometry as an additional tool in clinical set up in IVF units and laboratories.

Wider implications of the findings: MIR-ATR spectrometry can be used in the future as an additional tool for selection of embryos and prediction of cycles outcomes.

Trial registration number

NCT03317418
P–199 A case report to suggest that there must be other mutations than PATL2 or TUBB8 to cause oocyte maturation arrest
Authors: Molinari E , Yang M , Hu J , Zhang L , Albertini D F , Barad D H , Gleicher N
Published: August 2021

Study question

What causes our patient’s repeated almost complete oocyte maturation arrest (OMA)?

Summary answer

Since we did not detect PATL2 and TUBB8 mutations, both known to cause OMA, this case was likely caused by mutations in HUS1 and ITGB3

What is known already

OMA has been associated with loss-of-function in key genes, such as PATL2 and TUBB8. Such patients have, however, uniformly have been unable to conceive with IVF

Study design, size, duration

We here report the case of repeatedly presenting patient between 2009 until 2020 (age 30 at 1st and 41 at last visit).

Participants/materials, setting, methods

The couple underwent 7 IVF treatments under several ovarian stimulation protocols at different gonadotropin dosages and in different preparations to try to recruit mature eggs. She conceived in her 2nd IVF cycle in 2009 and delivered uneventfully in 2010. She then conceived spontaneously and delivered a healthy boy in 2014. The couple since then has been attempting another pregnancy. Remarkably, in all IVF cycles all eggs but one arrested at prophase.

Main results and the role of chance

The female demonstrates abnormally high ovarian reserve for age (AMH=5.9 ng/mL in 2019) (mean, 10.6 oocytes). In all cycles, all but one retrieved were immature. In vitro maturation rate for the GV oocytes was 28%. Resultant M2s, however, demonstrated morphological abnormalities, such as giant polar bodies. In vivo M2s, in contrast, were always morphologically unremarkable, and their fertilization rate was 85%. Embryo morphology deteriorated appreciatively with advancing age. Sanger sequencing for TUBB8 and PATL2 genes were unremarkable. Whole genome sequencing of her and her sister (who had no fertility problems) revealed mutations of genes belonging to the integrin family (ITGB3) and DNA repair checkpoint (HUS1), both of which could be determinants in the observed maturation arrest.

Limitations, reasons for caution

A functional study, coupled with imaging of the discarded material, will likely offer further information regarding the mechanisms leading to OMA in this female.

Wider implications of the findings: This case report represents a new phenotype of female infertility, characterized by almost complete maturation arrest which, however, still offers opportunity for pregnancy. Further isolation of underlying mutation(s) may offer additional insights about checkpoints required for the transition of prophase to metaphase in human oocytes.

Trial registration number

NA
P–219 mtDNA content in bovine cumulus cells does not predict oocytés developmental competence
Authors: Martíne. Moro Á , Lamas-Toranzo I , González-Brusi L , Pérez-Gómez A , Bermejo-Álvarez P
Published: August 2021

Study question

Does cumulus cell mtDNA content correlate with oocyte developmental potential in the bovine model?

Summary answer

The relative amount of mtDNA content did not vary significantly in oocytes showing different developmental outcomes following IVF

What is known already

Cumulus cells are closely connected to the oocyte through transzonal projections, serving essential metabolic functions during folliculogenesis. These oocyte-supporting cells are removed and discarded prior to ICSI, thereby constituting an interesting biological material on which to perform molecular analysis aimed to predict oocyte developmental competence. Previous studies have positively associated oocytés mtDNA content with developmental potential in both animal models and women. However, it remains debatable whether mtDNA content in cumulus cells could be used as a proxy to infer oocyte developmental potential.

Study design, size, duration

Bovine cumulus cells were allocated into three groups according to the developmental potential of the oocyte: 1) oocytes developing to blastocysts following IVF (Bl+Cl+), 2) oocytes cleaving following IVF but arresting their development prior to the blastocyst stage (Bl-Cl+), and 3) oocytes not cleaving following IVF (Bl-Cl-). Relative mtDNA content was analysed in 40 samples/group, each composed by the cumulus cells from one cumulus-oocyte complex (COC).

Participants/materials, setting, methods

Bovine cumulus-oocyte complexes were obtained from slaughtered cattle and individually matured in vitro (IVM). Following IVM, cumulus cells were removed by hyaluronidase treatment, pelleted, snap frozen in liquid nitrogen and stored at –80 ºC until analysis. Cumulus-free oocytes were fertilized and cultured in vitro individually and development was recorded for each oocyte. Relative mtDNA abundance was determined by qPCR, amplifying a mtDNA sequence (COX1) and a chromosomal sequence (PPIA). Statistical differences were tested by ANOVA.

Main results and the role of chance

Relative mtDNA abundance did not differ significantly (ANOVA p > 0.05) between the three groups exhibiting different developmental potential (1±0.06 vs. 1.19±0.05 vs. 1.11±0.05, for Bl+Cl+ vs. Bl-Cl+ vs. Bl-Cl-, mean±s.e.m.).

Limitations, reasons for caution

Experiments were conducted in the bovine model. Although bovine folliculogenesis, monoovulatory ovulation and early embryo development exhibit considerable similarities with that of humans, caution should be taken when extrapolating these data to humans.

Wider implications of the findings: The use of molecular markers for oocyte developmental potential in cumulus cells could be used to enhance success rates following single-embryo transfer. Unfortunately, mtDNA in cumulus cells was not found to be a good proxy for oocyte quality.

Trial registration number

Not applicable
P–272 The aneuploid embryo secretome
Authors: Piccolomini M , Garcia C , Turco E L , Massaia I , Orteiro M , Duarte O , Yamakami L , Miyadahira E , Prado F
Published: August 2021

Study question

Does the metabolomic analysis of the embryonic culture medium predict the embryo aneuploidy?

Summary answer

The presence and quantity of some metabolites in the culture medium can select euploid embryos for transfer.

What is known already

Advances in analytical techniques for metabolomics have brought the possibility of better tools for the characterization of molecules. Embryonic metabolism can be used as a good indicator of viability, regardless of the morphology of the blastocysts, since differences were observed in the metabolic activities between the days of embryo development and in the rates of live births.

Study design, size, duration

17 patients had their embryos biopsied between January to July 2019 in a human reproduction laboratory. All cases had PGT-A indication and after the biopsy, the embryos were frozen. The culture medium samples were individually prepared for metabolites extraction according to the Bligh and Dyer protocol. Controlled ovarian stimulation and dose adjustments according to the response of each patient. The metabolomics analysis was performed by mass spectrometry.

Participants/materials, setting, methods

Ovum pick up will be performed 35 hours after r-hCG administration. The embryos were kept in individual 50ul drops until the blastocyst stage. The biopsy was performed in 26 blastocysts. The samples were sent to the 337 metabolites analysis by mass spectrometry. 15 molecules with the highest score on the PLS-Da was submitted the ROC curves to illustrate the power of the metabolic ploidy analysis. Besides, we performed the functional enrichment analysis for each group.

Main results and the role of chance

After the genetic analysis by PGT-a, 10 aneuploid embryos and 16 euploid embryos were found. Comparing the quantitative target metabolomic analysis of the 337 metabolites in the embryo culture medium, we observed the L-Alanine, Cytosine, Guanosine monophosphate, Homocysteine, Hypoxanthine, and Xanthine hiperrepresented in the aneuploid embryos, and the Citrulline, L-Glutamic acid, Kynurenine, L-Leucine, Methionine, Ornithine, L-Phenylalanine, L-Tyrosine, L-Valine were hiperrepresented in the euploid embryos. Through the ROC curve, we can verify AUC = 0.987. This result suggests that the analysis of euploid embryos through the metabolomic analysis of the culture medium is valid to be used as a noninvasive aneuploid diagnostic. The functional enrichment analysis shows the urea cycle and the glycine and serine metabolism as the principal function alter by aneuploid.

Limitations, reasons for caution

Small number of samples and not validate sample group.

Wider implications of the findings: Further studies are needed to validate these findings for the diagnostic of embryo euploidy.

Trial registration number

N/A
P–286 Uterine vascularity in women with previous caesarean section and its potential role in implantation failure: a retrospective cohort study
Authors: Moliner B , Llacer J , Castillo J C , Cirillo P , Fuentes A , Bernabeu A , Bernabeu R
Published: August 2021

Study question

Does a previous Caesarean section affect uterine vascularisation the day of embryo transfer?

Summary answer

3D vascularisation parameters show less uterine irrigation in patients with previous Caesarean section

What is known already

A recent retrospective cohort study demonstrates that previous Caesarean section impairs live birth rates after assisted reproductive treatment (ART) compared to a previous vaginal delivery. Furthermore, it has been hypothesized about the mechanisms by which post-cesarean section niche may diminish clinical pregnancy rates. One of the hypothetical process mentioned has been a distorted contractility of the uterus caused by fibrosis, which can influence in the vascularisation of the endometrium.

Study design, size, duration

We retrospectively studied the uterine contractility and 3D vascularisation parameters in women who had an embryo transfer at the Instituto Bernabeu of Alicante, between 2018 and 2020 with one recurrent implantation failure (at least two good quality blastocysts transferred from egg donation treatment).

Participants/materials, setting, methods

Patients with large myomas (more than 4 cm), adenomyosis or polyp were excluded. In total, 196 patients were assessed on the day of embryo transfer which 12 patients had a previous caesarean section. Uterine contractility was analyzed using 4D ultrasound after 6 minutes of video recording. Vascularisation index and vascularisation flow index were assessed after the endometrial volume definition.

Main results and the role of chance

Baseline characteristics of both groups were comparable. 3D vascularization parameters were significantly lower in women with a previous caesarean section. Vascularization Index (VI) reached 0,8% in caesarean section group (CS group) versus 2,3% (p = 0,038) and vascularization flow index (VFI) was 0,2 in CS group versus 0,8 (p = 0,038) Despite uterine peristalsis showed less contractility in those patients with previous caesarean section (0,8 contractions per minute versus 1,1 contractions per minute), non-statistical differences were demonstrated (p = 0,154)

Limitations, reasons for caution

This study is limited by its retrospective design and the low number of cases.

Wider implications of the findings: The lower 3D vascularisation indexes support a post-Caesarean section vascular-related impaired perfusion as a hypothetical mechanism. Its correlation with a possible impairment in the embryo implantation after fertility treatments warrants further studies.

Trial registration number

Not applicable
P–317 Uterine cavity in patients with repeated implantation failure (RIF) and before the first IVFprogram
Authors: Rybina A , Lokshin V , Askar Y , Valiev R , Karibayeva S
Published: August 2021

Study question

What is the frequency of uterine pathology and histological analysis of chronic endometritis in the RIF group and in patients before the first IVF program?

Summary answer

We report a lower incidence of chronic endometritis in the group of patients just preparing for the first IVF program and higher effectiveness

What is known already

Chronic endometritis (CE) is one of the reasons for implantation failures in IVF cycles. The presence of chronic inflammation in the endometrium changes its susceptibility, resulting in failed implantations and loss of pregnancy. CE diagnostics is rather complicated. Visual examination during hysteroscopy allows one to suspect CE in 20–70%, routine histology - in 10–20%. The new gold standard is immunohistochemistry (IHC).

Study design, size, duration

A continuous study of 2003 hysteroscopies was carried out, conducted in 1944 patients from May 2018 to January 2020. All patients were divided into 2 groups: 1 - 650 patients preparing for IVF for the first time; 2 - 1294 with repeated implantation failures.

Participants/materials, setting, methods

All included patients had diagnostic office hysteroscopy (OH) with biopsy and IHC CD 138, CD 20, and CD 8. We compared the frequency of CE detection by visual examination during hysteroscopy, routine histology and IHC of the two groups, as well as the effectiveness of 1 course of antibiotic therapy with CE.

Main results and the role of chance

In group 1 of women preparing for IVF for the first time, during visual examination by hysteroscopy, CE was detected in 17% (110/650), in group 2 RIF - in 27% (349/1294), p < 0.001. Routine histology also more often detected CE in the RIF group, 42% (543/1294) compared with group 1 - 23% (149/650), p < 0.001. IHC markers of CE were detected in 81.8% (1058/1294) of samples from RIP group than in group 1 - 71.4% (464/650), p < 0.001. At the same time, IHC mild CE was more common in group 1 in 320/650 (49.2%), p < 0.001. In the second group, mild, moderate and severe CE occurred with the same frequency (33.2%, 36.5%, 30.3%, respectively). The frequency of CE detection by IHC in the groups after 1 course of antibiotic therapy with fluoroquinolones was 31.2% (145/464) and 43.2% (457/1058), respectively, p < 0.001. The pregnancy rate (PR) also differed and was the lowest in the RIF group: in group 1 after treatment with CE PR = 42.7% (198/464), in group 2 after treatment with CE PR = 27.2% (288 / 1058), p < 0.05.

Limitations, reasons for caution

The limitations are related to study design. More research is also needed.

Wider implications of the findings: The question of overdiagnosis of CE using IHC remains open. Therefore, well-designed prospective studies or RCTs should be conducted to clarify possible correlations between ChE and poor reproductive outcomes and the effectiveness of endometrial interventions and treatments.

Trial registration number

not avaliable
P–319 Measuring intraobserver and intermethod reliability of endometriotic cyst volumes: a comparison between MRI and 3D transvaginal ultrasound
Authors: Bergwerff J , Schreurs A M F , Lier M C I , Va. Waesberghe J H T M , Va. de. Houwen L E E , Mijatovic V
Published: August 2021

Study question

Are three-dimensional imaging techniques, MRI and three-dimensional transvaginal ultrasound reliable for the volume measurement of endometriotic cysts?

Summary answer

MRI and XI VOCAL 3D-transvaginal ultrasound both provide a very good intraobserver reliability. The imaging techniques are however not advised to be used interchangeably.

What is known already

Two-dimensional transvaginal ultrasound (2D-TVUS) and MRI are commonly used in endometriosis care. However, three-dimensional ultrasound (3D-US) has gained more attention in recent years. The use of 3D-US, more specifically VOCAL and XI VOCAL software has proven to be a reliable tool in the measurement of volumes such as splenic volumes and uterine niche volumes. Up to date, 3D-TVUS has not been evaluated for volume measurements in endometrioma.

Study design, size, duration

A prospective case-control study was performed in an academic endometriosis centre. In total, 23 endometriosis cysts from 16 patients were included.

Participants/materials, setting, methods

Women diagnosed with endometriosis through laparoscopy with histological confirmation presenting with uni- or bilateral endometrioma on TVUS were included in this study. All women had a regular menstrual cycle (28 days ± 3 days). Women were seen for examinations at two time points during one menstrual cycle: on cycle day 2–4 (T0) and cycle day 20–22 (T1). At both time points a 2D and 3D TVUS and an MRI at 1,5T were performed.

Main results and the role of chance

The intraclass correlation for intraobserver reliability is good to very good for all three techniques ranging from the lowest value of 0.953 to the highest of 1.000. MRI has the most narrow limits of agreement (–3.93 to 4.53), followed by XI VOCAL (–5.16 – 5.65) while VOCAL has the widest limits of agreement (–10.22 to 11.39). Intraclass correlations are poor in the comparison of XI VOCAL to MRI, moderate between VOCAL and XI VOCAL, and good for the comparison between VOCAL and MRI. The limits of agreement are widest for XI VOCAL versus MRI (–36.96 –10.54). Similar limits of agreement are found between VOCAL versus XI VOCAL (–7.80 –23.40) as between VOCAL versus MRI (–18.27–8.96).

Limitations, reasons for caution

No absolute volume measurements were obtained during subsequent surgery to compare the imaging data to. This makes it more difficult to determine an acceptable error margin for the 3D imaging techniques used.

Wider implications of the findings: Being able to determine (small) volumetric changes in endometrioma can give more insight into the development and circumstances under which endometrioma grow or decrease in size. For reliable and accurate follow up of endometrioma a single measuring technique must be used as three-dimensional imaging techniques are not interchangeable.

Trial registration number

Trial NL2106 (NTR2223)
P–344 Clarifying tubo-ovarian abscess management: a risk score for predicting antibiotic failure
Authors: Yongue G , Mollier J , Reshmi S , Ibeto L , Ross C , Ayim F , Guha S
Published: August 2021

Study question

Can antibiotic treatment failure of tubo-ovarian abscesses (TOA) be predicted based on clinical features at the time of diagnosis?

Summary answer

We propose a risk score including patient temperature, c-reactive protein and TOA size that could predict which patients are likely to fail parental antibiotic treatment.

What is known already

Current guidance is that the first line management of non-ruptured TOA is with parental antibiotics. However, it is reported that treatment failure rate is 20–30%. Alternative treatment modalities include radiological drainage or laparoscopic/open surgery. In patients who require intervention, outcomes, such as morbidity, length of hospital stay and fertility, are improved when this is performed early rather than later in their hospital admission. However, our current guidance is scant with regards to the decision making for interventional TOA management.

Study design, size, duration

This is a multicentre retrospective cohort study over 81 months (01/01/13- 30/09/19) identifying 214 consecutive patients admitted to hospitals in North-West London with diagnosed TOA. Participants/materials, setting, methods: Demographics, medical history, presenting symptoms, laboratory results, radiological findings, treatments administered, hospital length of stay and follow up data was collected. The patients were chronologically split with the first 150 being used for the development of our risk score. Univariate and bivariate analyses were employed to ascertain statistically significant variables in the failure of parental antibiotic. The remaining 64 patients were used for risk score validation.

Main results and the role of chance

Statistically significant variables were: temperature at admission (median= 37.1 °C vs 38.2 °C, p = 0.0001), C-reactive protein (CRP) at admission (151mg/L vs 243mg/L, p = 0.0001) and size of TOA (6.0cm vs 8.0cm, p = 0.0001). Those requiring intervention, stayed in hospital twice as long as those who did not (4 days vs 8 days, p < 0.001). A scoring system was formulated using the statistically significant variables. A score of ≥ 4 was associated with requiring radiological/surgical intervention (p < 0.001), with sensitivity 69% and specificity 88% (AUC 0.859) when tested on the validation cohort.

Limitations, reasons for caution

Being a retrospective study, which puts the data at risk of information and selection bias. Although there are merits to a multi-centre study, variation in patient management will invariably cause data heterogeneity.

Wider implications of the findings: TOA patients may have their hospital management tailored early according to the postulated tool, alleviating uncertainty in their treatment as well as possibly reducing morbidity and length of hospital stay.

Trial registration number

Not applicable
P–376 S100P in syncytiotrophoblast regulates lipid metabolism during early pregnancy
Authors: Zhou H , Zhu H , Zhang S
Published: August 2021

Study question

Does S100P involve in the regulation of lipid metabolism in trophoblast syncytialization during the early stage of pregnancy?

Summary answer

S100P suppressed lipid droplets overloading in trophoblast syncytialization during the early stage of pregnancy.

What is known already

S100P is a 95-amino acid protein belongs to the large family of S100 calcium-binding proteins and is exclusively expressed in syncytiotrophoblast layer of placenta, enhancing trophoblast cells proliferation, motility and invasion. Recent studies indicated S100P was aberrantly expressed in various malignant tumors, promoting their proliferation, survival, the formation and invasion of vessels, and has a close relationship with their grade malignancy, hormone dependency and the drug-resistance. Syncytialization is trophoblast cells differentiated from cytotrophoblasts fused into multinucleated cell clusters with cell boundaries deficiency.

Study design, size, duration

Tissues were collected from elective first trimester pregnancy terminations of healthy people and patients with recurrent spontaneous abortion. Human trophoblast stem cells (hTSCs) were isolated from Week 6 to Week 8 of fresh placental tissues (n = 8) and use forskolin to induce syncytialization.

Participants/materials, setting, methods

Tissues were collected from elective first trimester surgical pregnancy terminations to determine localization, abundance and function of S100P. The level of S100P protein and gene was measured by Real-time quantitative PCR (RT-qPCR), western blot, ELISA and immunofluorescence in hTSC induced ST(2D)-TSCT. The lipid droplets were assessed by Oil red O stain, BODIPY and electron microscope. Serum S100P concentration in normal and recurrent miscarriage patients were measured by ELISA.

Main results and the role of chance

S100P was exclusively localized in syncytiotrophoblast layer of the placental villous from gestational weeks 6–8 (n = 4); S100p serum concentration was increased markedly as the gestation progressed (n = 40, p < 0.05); the protein abundance of S100P was increased during syncytialization of hTSCs; Lipid droplets increased during syncytialization and knockdown of S100P leads to trophoblast cell death with the overload of lipid droplet; The expression of S100P was down regulated and the amount of lipid droplets apparently accumulated in villus of recurrent miscarriage patients (n = 4).

Limitations, reasons for caution

The role of S100P on placenta lacks the evidence from animal models.

Wider implications of the findings: S100P is an important factor facilitating in trophoblast syncytialization in the first trimester of pregnancy and could be a biomarker of the early pregnancy sustenance.

Trial registration number

Not applicable
P–383 Cytogenetic analysis of products of conception from miscarriages following natural conception and IVF pregnancy: a comparative study
Authors: Kaderbhai F , Kalu E , Chan P
Published: August 2021

Study question

Do cytogenetic results from products of conception from miscarriages differ from patients conceiving by natural conception versus IVF? Summary answer: Cytogenetic results were similar, with no statistical difference from miscarriages following natural conception and assisted conception.

What is known already

Cytogenetic sampling of products of conception (POC) following recurrent miscarriages (RM) are recommended to rule out parental chromosomal rearrangements. The RCOG recommends cytogenetic testing in cases of recurrent miscarriages (3 consecutive miscarriages). However some units routinely request cytogenetic analysis following a single miscarriage following an IVF pregnancy. There is no evidence to support the routine sampling of POCs following assisted conception. Study design, size, duration: Retrospective cohort study of 117 cytogenetic samples, followed up by the outcome of parental karyotyping if applicable. Patients were categorised based on mode of conception into natural conception (NC) with recurrent miscarriages (≥3) or one miscarriage following IVF. Data collected between 2018–2020. Primary Outcome measure: Presence and type of cytogenetic abnormality; individual parental targeted G-band karyotyping result. Participants/materials, setting, methods: A total of 117 cytogenetic results were reviewed, of which 35 were unsuitable for analysis due to contamination (Total n = 79: NC = 60, IVF = 19). Main results and the role of chance: Cytogenetic analysis showed abnormal results in 59% of miscarriages following natural conception and 53% of miscarriages from IVF pregnancy (p = 0.46).

Abnormal cytogenetic results were mainly sporadic. Trisomy 16 was the commonest abnormality in both groups. Others included Trisomy 15, 22, 21, 8, 13, 5, 9, 10, 14, 18, single X (Turner’s), all occurring in the same frequency in both groups. As expected 35 out of 45 abnormal cytogenetic results occurred with a maternal age greater than 35 years.

One couple from the NC group were referred to a geneticist for a Trisomy 9 imbalance. All other parental karyotyping results were normal.

Limitations, reasons for caution

This study contains a small sample size, and would benefit from further data collection to account for a percentage of samples being inadequate for analysis. Wider implications of the findings: Cytogenetic results were similar from miscarriages following natural conception and assisted conception. IVF does not increase the risk of miscarriage from abnormal embryonic karyotype. Routine cytogenetic testing following one miscarriage in patients undergoing IVF is not cost effective.

Trial registration number

Not applicable
P–389 The relationship between serum hormone profiles and missed abortion in humans
Authors: Yang Y , Wu J , Wang X , Yao J , Lao K S , Xu Y , Hu Y , Pan Y , Feng Y , Shi S , Zhang J , Qiao Y , Li Q , Ye D , Wang Y
Published: August 2021

Study question

Are circulating profiles of metabolic-related hormones also associated with the missed abortion (MA) in humans?

Summary answer

Serum levels of fatty acid-binding protein–4 (FABP4) and fibroblast growth factor 21 (FGF21) are positively associated with MA.

What is known already

A cluster of endocrine hormones, including FABP4, FGF21, adiponectin, lipocalin–2 (LCN2), exhibit pleiotropic effects on regulating systematic metabolism. Serum levels of them are associated with gestational obesity and diabetes and affect pregnancy outcomes, however, the relationship between their circulating profiles and MA is under-investigated.

Study design, size, duration

78 patients with MA and 86 healthy pregnant subjects matching on maternal age and body mass index (BMI) were nested from a prospective cohort in the Chinese population.

Participants/materials, setting, methods

Fasting serum samples from all participants were collected to test their serum levels of FGF21, FABP4, adiponectin, and LCN2 by enzyme-linked immunosorbent assay method (ELISA).

Main results and the role of chance

There were no significant differences in circulating profiles of adiponectin and LCN2 between MA patients and healthy pregnant subjects. By contrast, circulating levels of FGF21 and FABP4 were significantly and independently elevated in patients with MA relative to control cases even after adjusting confounding factors (for FGF21: MA: 28.96 ± 2.17 ng/ml; HP: 19.18 ± 1.12 ng/ml, P < 0.001, for FABP4: MA: 152.50 ± 9.31 pg/ml; HP: 90.86 ± 4.14 pg/ml, P < 0.001). Linear regression analysis showed, FGF21 raised every 10 pg/ml contributed to a 24% (95% CI: 15% - 34%) increase in the risk of MA, whereas the OR of FABP4 for the risk of MA was 1.052 (95% CI: 1.022 –1.088). Furthermore, using serum FGF21 level or FABP4 levels discriminated MA from healthy controls with an area under the operating characteristic’s curve (AUROC) of 0.81 (95% CI 0.76–0.92) and 0.70 (95% CI 0.62 - 0.78), respectively.

Limitations, reasons for caution

The study is limited by the sample size. In addition, our results were based-on Chinese population, whether it could be observed in other ethics group remain to be investigated. Meanwhile, the cause-effect relationship between increased serum FGF21 level and MA remains to be explored.

Wider implications of the findings: Our data would suggest that serum levels of FGF21 and FABP4 are associated with MA. Moreover, circulating FGF21 levels may serve as a potential diagnostic biomarker for the recognition of M.

Trial registration number

IRB Ref. No.: KY201913
P–391 Role of subcutaneous granulocyte colony-stimulating factor infusion in thin endometrium
Authors: Banerjee K , Singla B
Published: August 2021

Study question

To assess the role of subcutaneous granulocyte colony-stimulating factor (G-CSF) in thin endometrium cases.

Summary answer

G CSF has beneficial role to improve the endometrium thickness in thin endometrium.

What is known already

Endometrium is very important for embryo implantation and the endometrial thickness is the marker of receptivity of the endometrium.

Study design, size, duration

Study design - Retrospective analysis

Size - 88 infertile females with thin endometrium (< 7 mm) in the age group of 23 to 40 years Duration - one year.

Participants/materials, setting, methods

In the group 1 of 44 females, subcutaneous infusion of G CSF (300 mcg/ml) was added along with other supplements and if lining was not more than 7 mm in 72 hours, then second infusion was given. In the group 2 of 44 females, only estradiol valerate and sildenafil were given.The efficacy of G CSF was evaluated by assessing the endometrium thickness before embryo transfer, pregnancy rates and clinical pregnancy rates.

Main results and the role of chance

There was no difference between the two groups regarding demographic variables, egg reserve, sperm parameters, number of embryos transferred and embryo quality. . The pregnancy rate was 60% (24 out of 40 cases) in the group 1 that was significantly higher than in-group 2 that was 31% (9 out of 29 cases) with p value < 0.0001. The clinical pregnancy rate was also significantly higher in-group 1 (55%) as compared to group 2 (24%) with p value < 0.0001.

Limitations, reasons for caution

Further larger cohort studies are required to explore the subcutaneous role of G CSF in thin endometrium.

Wider implications of the findings: Granulocyte colony-stimulating factor has beneficial role to improve the endometrium thickness in thin endometrium. In most of previous studies, the intrauterine infusion of G CSF was given to improve the uterine lining. This is one of the few studies done that showed subcutaneous role of G CSF in thin endometrium.

Trial registration number

Not applicable
P–396 Preconceptual male and female metabolite profiles are associated with ongoing pregnancy after IVF
Authors: Alrashid K , Goulding N , Taylor A , Lumsden M A , Lawlor D A , Nelson S
Published: August 2021

Study question

In men and women undergoing IVF are preconceptual circulating metabolites associated with ongoing pregnancy rates?

Summary answer

Preconceptual serum histidine levels, in both women and men were associated with ongoing pregnancy. Several amino acids and lipoproteins exhibited possible sex-specific associations.

What is known already

Preconceptual maternal health has been associated with pregnancy outcomes after IVF. The extent to which this is because of pre-existing metabolic factors related to infertility and the role of paternal metabolic health is unclear.

Study design, size, duration

Cohort of 398 women and 325 male partners prospectively recruited between 1 April 2017 and 31 March 2019.

Participants/materials, setting, methods

Women and their male partners intending to undergo assisted conception at a University Hospital, had detailed pre-treatment phenotyping including non-fasting serum lipids, lipoprotein subclasses, and low-molecular weight metabolites (including amino acids, glycolysis and inflammatory markers) (155 metabolites) quantified by NMR spectroscopy. Multivariable linear and logistic regression were used to examine the associations of pre-treatment serum metabolic profiles, with ongoing pregnancy at 20 weeks gestation with adjustment for confounders.

Main results and the role of chance

392 women and 322 men proceeded to IVF treatment, with an overall ongoing pregnancy rate of 47.2% (95% CI 0.42, 0.52) per cycle started and a multiple pregnancy rate of 1.1% (95%CI 0.0, 0.04). In both females and males in confounder adjusted analyses histidine was associated with the chance of ongoing pregnancy, with similar magnitudes in each parent (OR 1.28 (95% CI 1.03, 1.60) per one standard deviation (SD) increase for males and OR 1.26 (95% CI 0.99, 1.60) per one SD increase for females). In females Alanine (OR = 1.31 (1.05, 1.64)), Isoleucine (OR = 1.28 (1.02, 1.61)) and Leucine (OR = 1.24 (0.99, 1.55)) had a positive association with ongoing pregnancy, while in males, pyruvate (OR = 1.30 (1.02,1.66)) exhibited a positive association with ongoing pregnancy. In both parents, associations of lipids, lipoproteins sub-particles and fatty acids with pregnancy were closer to the null.

Limitations, reasons for caution

Suggestive parental differences could be due to chance. Patients were relatively homogenous undertaking their first IVF cycle and the results may not be generalisable to other clinical populations.

Wider implications of the findings: This study provides data on a range of metabolic pathways and their association with ongoing pregnancy following IVF. The identification of potentially relevant clinical effect sizes in both men and women warrants further exploration.

Trial registration number

Not applicable
P–397 Threatened Miscarriage and increase in Perinatal Morbidity
Authors: Pillai R , Tincello D , Potdar N
Published: August 2021

Study question

Are women presenting with bleeding in the first trimester of pregnancy at a higher risk for perinatal complications later in pregnancy?

Summary answer

Women presenting with bleeding in the first trimester of pregnancy are more likely to experience perinatal and neonatal morbidity in pregnancy.

What is known already

Observational studies and a previously reported systematic review showed that women who experienced threatened miscarriage are more likely to have still birth, intra uterine growth restriction (IUGR), low birth weight, pre-eclampsia, placental abruption, placenta previa, preterm labour, preterm prelabour rupture of membrane, neonatal asphyxia and congenital anomalies in pregnancy. However, the evidence has been inconclusive and currently the women who experience threatened miscarriage receive low risk care.

Study design, size, duration

This was a prospective cohort study conducted on 298 women with threatened miscarriage (Cohort A) and 107 asymptomatic women (Cohort B). The women were recruited over a period of 18 months and were followed up for 9 months until delivery.

Participants/materials, setting, methods

Cohort A were women who presented with bleeding in the early pregnancy assessment unit and had a confirmed heartbeat on ultrasound scan between 6 weeks and 11 + 6 weeks of pregnancy and cohort B were women who were asymptomatic and booked with the community midwives as low risk. Both groups of women were followed up prospectively until delivery and data were collected on any perinatal outcomes and complications for both mother and the neonate.

Main results and the role of chance

The analysis showed that women who had bleeding in early pregnancy were more likely to have preterm delivery (RR 95% CI; 2.98 (1.07 – 8.27)); IUGR (unable to calculate the RR, as none of the women who continued their pregnancies beyond 24 weeks of gestation, developed IUGR in the asymptomatic control cohort. Nonetheless, IUGR occurred more frequently in the threatened miscarriage cohort than the asymptomatic cohort (P-value 0.02)); LBW (RR 95% CI; 6.14 (1.49 – 25.19), neonatal asphyxia (unable to calculate the RR, as none of the babies who were born to women in the asymptomatic control cohort develop neonatal asphyxia. Nonetheless, neonatal asphyxia occurred more frequently in the threatened miscarriage cohort than the asymptomatic cohort (P-value 0.02)). Preterm prelabour rupture of membrane was not significant with a P-value of 0.07.

Limitations, reasons for caution

The major limitation of this study was lower sample size and hence due to the rarity of many of the perinatal and neonatal outcomes, we were unable to calculate the relative risk.

Wider implications of the findings: Current study agrees with the existing literature and reaffirms the association of perinatal and neonatal morbidities with threatened miscarriage and this group of women need to be managed as high-risk group antenatally.

Trial registration number

Not applicable
P–497 Anxiety, depression and sexual dysfunction among women with genital diseases
Authors: Libei D , Yin M X C , Chan C H , Li H W R
Published: August 2021

Study question

How is the prevalence of anxiety, depression and sexual dysfunction among Chinese women who is suffering from genital diseases? What is the relationship among their anxiety, depression and sexual dysfunction?

Summary answer

Anxiety, depression and sexual dysfunction symptoms were self-reported by the participants. Besides, their anxiety, depression and sexual dysfunction were inter-correlated.

What is known already

Reduced sexual activity and dysfunctional problems are highly prevalent in females. Approximately 43% of American women reported experiencing sexual problems.

Women who are facing pressure on childbirth, may be more likely to have mental health problems. Some studies have shown that having gynecological disease can lead to anxiety, depression and sexual dysfunction. However, the mental health of females who are suffering from genital diseases has been little studied.

Study design, size, duration

The investigation was carried out from March to November, 2020. Participants were recruited in the Hong Kong University-Shenzhen Hospital, located in Shenzhen, China. 135 patients were approached while 116 agreed to join the survey.

Participants/materials, setting, methods

116 women (35.42±8.19 years old) with a diagnosis of fallopian tube disease, ovarian benign disease or uterine disease voluntarily filled a questionnaire which contains the Female Sexual Function Index–6 Items (FSFI–6) and the Hospital Anxiety and Depression Scale (HADS). Descriptive analysis and stepwise regression were used to present participants’ self-reported anxiety, depression, and sexual dysfunction problems, as well as the relationship among their anxiety, depression, and sexual dysfunction.

Main results and the role of chance

25% of the participants reported anxiety symptoms; 9.5% of the women reported depressive symptoms; while 37.3% reported sexual dysfunction problems. Anxiety (p < 0.001) was significantly associated with depression. Depressive symptom can significantly predict sexual dysfunction (p < 0.05) while anxiety was not associated with sexual dysfunction (p > 0.05). Targeted interventions are needed to improve the mental health status of women with genital diseases in China.

Limitations, reasons for caution

This study can only present mental health status of this population. To better show the odds ratio of mental health problems, a case-control study design is needed. Besides, future qualitative or longitudinal studies are needed to detect the risk factors for the poor mental health of women with genital diseases.

Wider implications of the findings: Reduced sexual activity and dysfunctional problems are highly prevalent in females with genital diseases. Sexuality is an important element in patients’ quality of life. For female patients with genital diseases, we should not only treat their physical symptoms, but also guide and treat patients in mental ways.

Trial registration number

ChiCTR2000031343