bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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 &lt; 0.001) was significantly associated with depression. Depressive symptom can significantly predict sexual dysfunction (p &lt; 0.05) while anxiety was not associated with sexual dysfunction (p &gt; 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
P–539 The use of expanded carrier screening of gamete donors
Authors: Payne M , Skytte A B , Harper J 
Published: August 2021

Abstract

Study question
What are the sperm and egg donor rejection rates after expanded carrier screening (ECS)?

Summary answer
Using an ECS panel looking at 46/47 genes, 17.6% of donors were rejected.

What is known already
The use of ECS is becoming commonplace in assisted reproductive technology, including testing of egg and sperm donors. Most national guidelines recommend rejection of donors if they are carriers of a genetic disease. If the use of ECS increases, there will be a decline in the number of donors available.

Study design, size, duration
A review of the current preconception ECS panels available to donors was carried out through an online search. The genetic testing results of donors from Cryos International were analysed to determine how many were rejected on the basis of the ECS.

Participants/materials, setting, methods
Data on gamete donors and their carrier status was provided by Cryos International, who screen donors using their own bespoke ECS panel. The ECS panels identified through the review were compared to the Cryos International panel and data.

Main results and the role of chance
A total of 16 companies and 42 associated ECS panels were reviewed. There were a total of 2673 unique disorders covered by the panels examined, with a mean of 329 disorders screened. None of these disorders were common to all panels. Cryos International screen 46 disorders in males and 47 in females. From 883 candidate donors, 17.6% (155/883) were rejected based on their ECS result. Carriers of alpha-thalassaemia represented the largest proportion of those rejected (19.4%, 30/155), then spinal muscular atrophy (15.5%, 24/155) and cystic fibrosis (14.8%, 23/155).

Limitations, reasons for caution
Panel information was found on company web sites and may not have been accurate.
Wider implications of the findings: This study highlights the need for consistent EU regulations and guidelines which allow genetic matching of gamete donors to recipients, preventing the need to reject donors who are known carriers. A larger ECS panel would be most beneficial, however, this would not be viable without matching of donors and recipients.

Trial registration number
Not applicable
P–559 Proof of principle for Extended Carrier Screening (ECS) in medically assisted reproduction: First 33 cases of genetic matching for donors and recipients
Authors: Shaikly V , Sage K , Callum P 
Published: August 2021

Abstract

Study question
Does implementation of ECS to reduce reproductive risk when using a donor with a known carrier status serves as a wider model for ART patients.

Summary answer
ECS should be routinely offered to ART patients using their own or donor gametes to reduce risk of having a child with a recessive condition.

What is known already
Responsible implementation of ECS in assisted reproduction is required as commercial offerings increase and become more accessible; ESHRE ethical guidelines are shortly to be published after consideration of stakeholder reviews. Increasingly ECS is included in donor screening, rejecting potential donors for a known carrier status will reduce donor gamete availability. Clinics should consider potential match yield in carrier panels to develop tools and specialist support to deliver and guide patients to help make informed decisions for ECS.

Study design, size, duration
Retrospective evaluation of ECS results for the first 33 patients who undertook counter screening in the clinic setting from April 2020 to December 2020 before using a donor with known carrier status. The findings would serve as proof of concept for wider application.

Participants/materials, setting, methods
Patients had opted to undertake ECS after discussion of risk estimates, family history review and personal options.Testing was commissioned between two ECS providers for international donor banks using panels of 283+ genes. Incidence of carrier match, the number of variants reported, and their clinical significance were reviewed. Main results and the role of chance: Of the 33 co-carrier tests, one carrier match for a patient and potential donor was identified. 41%, 26%, 9% and 3% of patients were carriers of 1, 2, 3 and 4 pathogenic variants respectively in 30 different genes. In 21% of patients, no pathogenic variants were reported. Of the variants identified as incidental findings, six were actionable and eligible for cascade screening to the wider family. This included Cystic Fibrosis, Sickle cell and Thalassemia. A variant for Familial hypercholesterolemia had preventative value. An incidental finding of a fragile X pre-mutation allowed for PGT-M as part of planned treatment

Limitations, reasons for caution
Findings from this first cohort of 33 tests may not represent the general population, follow up evaluation as participant numbers increase is required.
Wider implications of the findings: Implementation of guidelines is required to ensure consistency of methodology and availability of transparent information for ECS to ART patients. Incidental findings may be of value to the patient and wider family.

Trial registration number
Not applicable
P–568 Homozygous Pathogenic Variants in ACTL9 Cause Fertilization Failure and Male Infertility in Human and Mouse
Authors: Dai J , Zhang T , Guo J , Zhou Q , Gu Y , Zhang J , Hu L , Zong Y , Song J , Zhang S , Dai C , Gong F , Lu G , Zheng W , Lin G 
Published: August 2021

Abstract

Study question
What are the other male factors that cause total fertilization failure (TFF) excepting for variants in PLCZ1?

Summary answer
Homozygous variants in ACTL9 (actin like 9) cause abnormal localization of PLCζ in a loosened perinuclear theca (PT) structure and leads to TFF.

What is known already
In previous studies, investigators have reported that the female factors in TFF after intracytoplasmic sperm injection (ICSI) include pathogenic variants in WEE2, TLE6, and TUBB8, whereas for male factors, pathogenic variants in PLCZ1 were reported to be the primary cause of TFF, which account for approximately 30% of couples with male factors in TFF excluding globozoospermia. Most recently, it was reported that pathogenic variants in ACTL7A led to reduced expression and abnormal localization of PLCζ, thereby identifying this genetic variant as a potential cause of TFF.

Study design, size, duration
Fifty-four infertile couples with TFF or poor fertilization (fertilization rate of &lt; 20%) at the Reproductive and Genetic Hospital of CITIC-Xiangya during January 2014 to June 2020 were recruited into this study.

Participants/materials, setting, methods
Male factors were identified in (MOAT). WES analysis was used to analyze the genetic factors of individuals with male factors. Sperm morphological study was conducted by H&E staining and TEM. Immunostaining of PLCζ was used to analyze the status of sperm-borne activation factor. A knock-in mouse model was generated by CRISPER-Cas9 technology. Sperm from homozygous Actl9 variant mice were analyzed by TEM and ICSI. ICSI with AOA was performed in couples with ACTL9 variants.

Main results and the role of chance
A total of 54 couples with TFF or poor fertilization were screened, with 21 couples determined to have a male infertility factor by MOAT. Whole-exome sequencing of these 21 male individuals identified three homozygous pathogenic variants in ACTL9 in three individuals. ACTL9 variations led to abnormal ultrastructure of the PT, with PLCζ absent in the head and present in the neck of the mutant sperm, which contributed to failed normal calcium oscillations in oocytes and subsequent TFF. The key roles of ACTL9 in the PT structure and TFF after ICSI were further confirmed in Actl9-mutated mouse model. Furthermore, assisted oocyte activation by calcium ionophore exposure successfully overcame TFF and achieved live births in a couple with an ACTL9 variant.

Limitations, reasons for caution
The mechanism of how ACTL9 regulate PLCζ remains unknown.
Wider implications of the findings: It provided a genetic marker and a therapeutic option for individuals who have undergone ICSI without successful fertilization.

Trial registration number
not applioable
P–599 random antral follicle count, performed at any day of the menstrual cycle, demonstrates the same predictive value for ovarian response in in vitro fertilization cycles
Authors: Razafintsalama M , Bah M , Amand G , Vienet-Lègue L , Pietin-Vialle C , Bry-Gauillard H , Pinto M , Pasquier M , Jung C , Levaillant J M , Massin N 
Published: August 2021

Abstract

Study question
Does antral follicle count (AFC) retains its predictive value for ovarian response to stimulation for in vitro fertilization (IVF) throughout the whole menstrual cycle?

Summary answer
AFC is strongly correlated to anti-mullerian hormone (AMH) and highly predictive of good ovarian response whatever the day of cycle the ultrasound is performed.

What is known already
Usually performed in the early follicular phase (at day 2–3 of the menstrual cycle), AFC and AMH are the most accurate markers of ovarian reserve. They are routinely used to predict ovarian response to ovarian stimulation for IVF and eventually to individualize the gonadotropin starting dose.

Study design, size, duration
Retrospective cohort study performed between January, 2017 and December, 2019.

Participants/materials, setting, methods
410 consecutive women aged 20 to 42 years were included. Random AFC (r-AFC) was performed during the fertility workup whatever the day of their menstrual cycle was: early follicular phase i.e. day 1 to day 6 (eFP-AFC), mid follicular phase i.e. day 7 to 12 (mFP-AFC) and luteal phase i.e. day 13 or after (LP-AFC). A second AFC was performed before the start of the stimulation (SD1-AFC). AMH was measured in the early follicular phase.

Main results and the role of chance
Random AFC (r-AFC) was correlated to AMH (r = 0.692; p &lt; 0.001), SD1-AFC (r = 0.756; p &lt; 0.001) and number of oocytes retrieved (r = 0.491; p &lt; 0.001). When regarding AFC depending on the cycle day group, the correlation with AMH was significantly higher for the LP-AFC, (LP-AFC) (r = 0.853) than for the eFP-AFC (r = 0.657; p &lt; 0.001) and for the mFP-AFC (r = 0.668). The correlation with SD1-AFC was similar regardless of the time of performance of r-AFC (r = 0.739, 0.783, 0.733, respectively for eFP, mFP and LP-AFC). Moreover, the ROC analysis showed the same predictive value for good ovarian response (more than 6 oocytes retrieved) for the eFP-AFC, mFP-AFC and LP-AFC (AUC 0.73, 0.75 and 0.84 respectively) as well as for AMH and SD1-AFC (AUC 0.74 and 0.74, respectively).

Limitations, reasons for caution
This is a retrospective analysis, however data were prospectively collected and the method for ultrasound acquisition of AFC was standardized.
Wider implications of the findings: The absence of significant variation of AFC across the menstrual cycle allows to its random performance. Ultrasound performed besides early follicular phase discloses informations on ovaries, the uterus and the endometrium. It is more comfortable and convenient for women and physicians by limiting targeted appointment during menstruation and reiterated examination.

Trial registration number
Not applicable
P–602 Pregnancy outcomes of progestin primed ovarian stimulation protocol, GnRH antagonist protocol and GnRH agonist protocol for young patients undergoing PGT-M
Authors: Li Y , Zhao W , Liang X 
Published: August 2021

Abstract

Study question
To investigate the pregnancy outcomes of progestin primed ovarian stimulation protocol, GnRH antagonist protocol and GnRH agonist protocol for young patients undergoing preimplantation genetic testing for monogenic gene diseases.

Summary answer
PPOS protocol could reduce the normal chromosome formation and further development potential of embryos, suggesting that the PPOS protocol should be used cautiously.

What is known already
GnRH antagonist protocol (GnRHant) and GnRH agonist protocol (GnRHa) have been used in clinic for many years as routine regimens, and their ovarian stimulation effects and pregnancy outcomes have been confirmed by a large number of literatures. As a new protocol in recent years, the reports of pregnancy outcomes of progestin primed ovarian stimulation protocol (PPOS) are inconsistent.

Study design, size, duration
This retrospective cohort study was performed in a reproduction center from a tertiary hospital between September 2018 and November 2020 which included 147 young patients (&lt;35 year old) undergoing preimplantation genetic testing for monogenic gene diseases (PGT-M) after stimulated by progestin primed ovarian stimulation protocol (n = 44), GnRH antagonist protocol (n = 60) or GnRH agonist protocol (n = 43).

Participants/materials, setting, methods
This study included 147 young patients (&lt;35 year old) undergoing preimplantation genetic testing for monogenic gene diseases (PGT-M) after stimulated by progestin primed ovarian stimulation protocol (PPOS, n = 44), GnRH antagonist protocol (GnRHant, n = 60) or GnRH agonist protocol (GnRHa, n = 43). The primary outcomes were normal karyotype embryo rate and live birth rate. The embryological and clinical outcomes were measured.

Main results and the role of chance
Basic characteristics such as infertility duration, age, and body mass index (BMI) were comparable in study groups. No significant difference was found in the number oocytes retrieved or viable embryos between the groups.
Normal karyotype embryo rate of PPOS protocol was significantly lower than GnRHant and GnRHa protocol (57.6% for PPOS vs 76.0% for GnRHant vs 67.3% for GnRHa).
No significant difference were found in chemical pregnancy rate (77.3% for PPOS vs 73.3% for GnRHant vs 74.4% for GnRHa) or clinical pregnancy rate (69.8% for PPOS vs 71.7% for GnRHant vs 72.5% for GnRHa). While live birth rate of PPOS protocol was significantly lower than GnRHant and GnRHa protocol ( 45.5% for PPOS vs 58.3% for GnRHant vs 72.2% for GnRHa).

Limitations, reasons for caution
This is a preliminary study which needs to be further confirmed by large-scale clinical studies.
Wider implications of the findings: Although this is a preliminary study which needs to be further confirmed by large-scale clinical studies, the current results suggest that the application of PPOS should be cautious.

Trial registration number
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