bluuebunny/crossref_metadata_2025_split huggingface dataset:
P–598 Further evidence for a functional hormonal adrenal-ovarian axis affecting female infertility
Authors: Benor A , Molinari E , Barad D H , Gleicher N 
Published: August 2021

Abstract

Study question
How does here presented case offer further evidence for existence of a functional hormonal adrenal-ovarian axis?

Summary answer
This is the first case of iatrogenic Cushing syndrome leading to severe adrenal and ovarian insufficiency, as evidenced by undetectable estrogen and low androgen levels.

What is known already
Animal models and human data have convincingly demonstrated that hypo-androgenism affects follicle recruitment and growth, especially at small growing follicle stages, in most severe cases even mimicking primary ovarian insufficiency (POI). In milder forms, hypoandrogenism reduces follicle number, egg numbers as well as egg quality, unless reconstituted in timely fashion before IVF cycle start.

Study design, size, duration
We here report a 34-year-old G1P1, who presented for a second opinion with a diagnosis of secondary “unexplained” infertility after two IVF cycles at another fertility center.

Participants/materials, setting, methods
Since our center considers a diagnosis of “unexplained” infertility as subjective, the patient underwent a thorough diagnostic evaluation. She was using oral contraceptive pills for one week at the time her laboratory results were drawn. Main results and the role of chance: Her free (FT) and total testosterone (TT) (0.4 pg/ml and 5.0 ng/dL, respectively), DHEA and DHEAS (103.0 ng/dL and 92.0 µg/dL, respectively) were low and her estradiol was undetectable (&lt;25 pg/mL), reflecting significant adrenal as well as ovarian suppression. Morning ACTH was undetectable at &lt; 5 pg/mL but cortisol was abnormally elevated (17.7mcg/dL), leading to diagnoses of secondary adrenal insufficiency as well as secondary ovarian insufficiency (SOI) due to adrenal hypo-androgenism from lack of ACTH production. She, in addition, revealed a positive ANA titer (1:160). Because of eczema, she for over a year had been on a super-potent topical steroid ointment. Upon termination of this steroid, adrenal as well as ovarian function, as evidenced by her hormonal values, normalized.

Limitations, reasons for caution
This is the first case in the literature where iatrogenic-induced insufficiency of adrenal androgen production resulted in secondary ovarian insufficiency (SOI), characterized by undetectable estradiol, reversible by withdrawal of topical steroid treatment.
Wider implications of the findings: This case offers further evidence that the traditional hypothalamic-pituitary-ovarian axis (HPAA) extends downstream to ovaries (HPAOA), reaffirming the ability of adrenals to control ovarian function.

Trial registration number
n/a
P–600 Ovarian function following intraovarian injection of autologous platelet rich plasma (APRP) in women with low functional ovarian reserve
Authors: Barad D , Darmon S K , Benor A , Gleicher N 
Published: August 2021

Abstract

Study question
Does exposure of ovaries to autologous growth factors in platelet rich plasma (APRP) affect the pituitary ovarian axis?

Summary answer
Within 60 days after injection, growing follicle numbers and estrogen levels increased, though FSH did not change, with effects most pronounced in still menstruating women.

What is known already
APRP is extracted from a patient’s autologous blood and delivers growth factors. It is widely used in several medical specialties and has in infertility practice been reported to increase folicle/egg numbers if injected into ovaries and improve endometrial thickness/implantation if used for perfusion of the endometrium.

Study design, size, duration
Prospective observational cohort study of women with low functional ovarian reserve, followed for 60 days after subcortical injection of ovaries.

Participants/materials, setting, methods
44 women with prior poor response to ovulation induction, FSH &gt; 12 mIU/mL and AMH &lt; 1.0 ng/mL. APRP was prepared using Regen Lab PRP Kit which is approved by the US-FDA. 1.0–1.5 ml of PRP was injected into the cortex of each ovary divided among 7 to 10 injection sites. Participants were followed every three days with monitoring for estradiol, FSH and follicle growth for the first two weeks after PRP and then weekly.

Main results and the role of chance
21/43 patients still regularly menstruated (subgroup A, age 43.9 ± 5.1 years); 23/43 (subgroup B, age 42.6 ± 6.2 years) were amenorrheic for a median of 6 months. In A, AMH, FSH and estradiol were 0.18 ± 0.20 ng/mL, 37.5 ± 47.6 mIU/mL, and 100.2 ± 73.4 pg/mL, while in B they were 0.06 ± 0.11 ng/mL, 73.0 ± 44.8 mIU/mL and 66.7 ± 57.6 pg/mL. Following APRP, A-patients demonstrated increased estradiol to 211 ± 193.7 pg/mL (P = 0.029) while B-patients only demonstrated a trend to 98.1 ± 86.5 (P = 0.09). Among A patients, 14/21 (66.7%) entered IVF cycles and 5/21 (23.8%) reached retrieval. So-far 1 patients established an ongoing clinical pregnancy. Among B patients 8/23 (34.8%) entered IVF cycles and only 2/23 (8.7%) reached retrieval and none achieved pregnancy.

Limitations, reasons for caution
This observational study was only carried out to estimate possible effects of APRP treatments. Based on these observations, we are now conducting a randomized controlled trial, limited to cycling women under age 45 years [registration # NCT04278313].
Wider implications of the findings: PRP appears to have limited ability to affect ovarian reserve of older, and especially amenorrheic women. It may, however, exert more favorable effects on still menstruating women. Promotion of APRP treatment as “ovarian rejuvenation,” however, appears to be an inappropriate choice of words.

Trial registration number
N/A
P–645 Abnormal thyroid hormone levels are associated with biochemical primary ovarian insufficiency and low ovarian reserve: a cross-sectional study
Authors: Feng C 
Published: August 2021

Abstract

Study question
To address whether there was a correlation between thyroid parameters and primary ovarian insufficiency.

Summary answer
Thyroid dysfunction was related with bPOI and LOR.

What is known already
In our daily clinical work, there seems to be a link between thyroid disease and POI. A recent study reported that subclinical hypothyroidism was associated with lower ovarian reserve during later reproductive age. Animal studies demonstrated that thyroid hormones played important roles in ovarian functions, and both maternal hypothyroidism and hyperthyroidism were related with reduced primordial, primary and secondary follicle number in rats. However, others reported that thyroid autoimmunity (TAI) and hypothyroidism were not associated with DOR. In all, accumulative animal and epidemiological studies indicated the connection between thyroid function and ovarian reserve, but the results were still inconsistent.

Study design, size, duration
This is a cross-sectional study with consecutive women performed ovarian reserve assessment and thyroid test in the Second Hospital of Zhejiang University School of Medicine from April 2016 to March 2019. A total of 2109 women were included, with 111 with bPOI and 1771 without bPOI. To exclude the influence of age the participants were categorized into low ovarian reserve (LOR) and non-LOR groups based on age-specific AMH, including 78 LOR and 2031 non-LOR.

Participants/materials, setting, methods
At the outpatient, a doctor carried out an interview, recorded age, body mass index (BMI), past history, and current treatment, and made a diagnosis. Serum AMH, FSH, TPOAb, TgAb, Tg, TT3, FT3, TT4, FT4, and TSH levels were measured with electrochemiluminescence method.

Main results and the role of chance
TT3, FT3, FT4 was significantly positively correlated with serum AMH level. Further logistic regression analysis found that abnormal TT3, FT3 and TT4 levels were related to increased risks of bPOI and LOR. Chi-square analysis also proved that the incidence of abnormal TT3, FT3 and TT4 increased significantly in women with bPOI or LOR. The incidence of bPOI and LOR increased significantly in women with 2 or 3 abnormal thyroid hormones. The above analyses demonstrate in multiple aspects that thyroid dysfunction is related with decreased ovarian reserve.

Limitations, reasons for caution
Since this is a retrospective cross-sectional study, we only got the correlation between factors, and we could not achieve causal relationship. Further prospective cohort or randomized controlled trial (RCT) studies are required to make the results more robust.
Wider implications of the findings: The present study demonstrated that thyroid dysfunction was related with bPOI and LOR. It might be thyroid hormones, not TSH or thyroid antibodies, played the major role in ovarian reserve impairment. The treatment of euthyroxine may improve the ovarian reserve function.

Trial registration number
Not applicable
P–647 How do migraine attacks change during puberty?
Authors: Boettcher B , Kyprianou A , Wildt L , Lechner C , Kößler M , Neururer S , Bettina T , Matthias B , Rostasy K , Rauchenzauner M 
Published: August 2021

Abstract

Study question
How do the stage of puberty and the menstrual cycle influence characteristics of migraine?

Summary answer
During puberty, the frequency of migraine attacks increases, especially during the follicular phase. The pattern of migraine changes to a typical adult pattern of migraine.

What is known already
Up to puberty, headaches are as common in girls as in boys. After the onset of puberty migraine is more prevalent in adolescent girls suggesting an association with sex hormones. Attacks of menstrual migraine are characterized by a longer duration, tend to be more severe, and are less responsive to acute medication compared to migraine attacks which are independent from the menstrual cycle phase.

Study design, size, duration
For this prospective cohort study 47 girls were recruited from two Departments of Pediatrics and Adolescent Medicine between 01/2016 and 12/2018.

Participants/materials, setting, methods
Girls between 7 and 18 years old, diagnosed with migraine without aura according to the “International Classification of Headache Disorders II” diagnostic criteria, took part. Three groups (pre-, peri-, and postpubertal) were formed according to the Tanner stage and the onset of a regular menstruation. Girls kept a daily headache and menstrual cycle diary over 8 weeks. Ovulatory cycles were analyzed by weekly progesterone saliva tests.

Main results and the role of chance
Three groups according to Tanner stage and onset of regular menstruation were compared: pre- (n = 16), peri- (n = 19) and post-pubertal (n = 12) girls. A significant difference in migraine frequency was found between pre- and post- pubertal girls (p = 0.005). Headache characteristics did not differ significantly between the three groups. Interestingly, a higher frequency of attacks in follicular phase occurred compared to luteal phase (p = 0.030).

Limitations, reasons for caution
Repeated blood sampling would have been a more reliable technique compared to saliva assays. The sample size is small.
Wider implications of the findings: During puberty, the number of migraine attacks but not the specific headache characteristics changes in adolescent girls which should be taken into consideration regarding the management of these patients.

Trial registration number
AN2013–0027
P–658 Lovastatin promotes the expression of LDL receptor and enhances E2 production in the cumulus cells
Authors: Kim Y J , Choi K H , Kang K Y , Park E A , Kim Y S , Kim M J , Kim H O , Koong M K , Kim Y S , Yoon T K , Ko J J , Lee J H 
Published: August 2021

Abstract

Study question
Lovastatin enhanced E2 productive ratios in the cumulus cells through promoted expression of Low-density lipoprotein receptor (LDLR).

Summary answer
Lovastatin up-regulated gene expression of LDLR in the CCs. And the high expression of LDLR promoted E2 productive ratios from CCs.

What is known already
We already reported that the up-regulation of LDLR correlated with clinical pregnancy. Therefore, we found lovastatin as an up-regulator of LDLR expression of clinical pregnancy.

Study design, size, duration
This is an expended study of LDLR to enhance steroidogenesis regarding the effect of lovastatin in the CCs. The collection of human cumulus cells was approved by the Institutional Research and Ethical Committees of CHA University (approval number: 1044308–201611-BR–027–04) from January to December 2019. The CCs were collected from 12 patients with normal ovarian response after oocyte denudation for ICSI.

Participants/materials, setting, methods
We studied whether lovastatin has up-regulated LDLR expression in human CCs. Cumulus cells were collected from patients with young (∼ 36) and old aged patients (37 ∼). After culturing human CCs, they were treated lovastatin for one day. The concentration of E2 in culture medium was measured using Chemiluminescence immunoassay. The mRNA isolated from CCs was analyzed gene expression level through real time-PCR.

Main results and the role of chance
The concentration of E2 was significantly increased in the culture medium treated with lovastatin. The CCs treated with lovastatin increased the expression of LDLR and StAR which are components of the steroidogenesis pathway.

Limitations, reasons for caution
We have found that the role of lovastatin promotes the E2 production by increasing the ldlr gene of CCs. Therefore, further investigations aimed at lovastatin effect on human oocytes embryo whether enhanced quality of oocytes or not.
Wider implications of the findings: Previous data show that high activation of LDLR and StAR was associated with embryo quality and clinical pregnancy in infertile women. Our data suggest that lovastatin is stimulated LDLR expression to enhanced pregnancy ratios of IVF patients.

Trial registration number
none
P–791 Comparison of the live birth rate after single embryo transfer in fresh versus frozen cycle: no evidence to support routine freeze-all strategy
Authors: Toikkanen R , Terho A , Pelkonen S , Martikainen H 
Published: August 2021

Abstract

Study question
Is the treatment outcome compromised after superovulation for fresh IVF/ICSI in comparison to frozen cycle with spontaneous ovulation and luteal support with progesterone?

Summary answer
Live birth rate (LBR) is dependent on embryo quality both in the fresh and frozen cycles with no sign of harmful effect of the superovulation.

What is known already
Freeze-all strategy has been advocated in recent years based on the assumption that luteal phase after superovulation is not optimal for embryo implantation. The effects of variable hormonal treatments, given in association with ART, on the endometrium, are still largely unknown. Therefore, more data is needed in order to optimize the treatment policies.

Study design, size, duration
This is an observational retrospective single-center cohort study. Data were collected from Oulu University Hospital’s ART-database including a total of 5647 single embryo transfer cycles from years 1995–2020. Patients stimulated with long agonist protocol for IVF/ICSI and day 2–3 transfer were included. Frozen embryo transfer was performed in a natural cycle with an ovulation test used for timing of transfer. Luteal support with progesterone was given for two weeks in all cycles.

Participants/materials, setting, methods
There were 3053 IVF/ICSI fresh cycles (2237 top and 816 N-top) and 2594 frozen cycles (806 top and 1788 N-top). The main outcome measure was LBR compared between fresh and frozen cycles when either a top or a N-top embryo was transferred. As a secondary outcome, clinical pregnancy rate was investigated. Data on the age and body mass index (BMI) of the patients was available. Student’s T-test was used to compare continuous variables.

Main results and the role of chance
The groups did not differ regarding the age and BMI of the patients. After the transfer of a top quality embryo the clinical pregnancy rate (35.4 vs. 30.8%; p &lt; 0.05) and LBR (29.4 vs. 25.5%; p not significant) was slightly higher in the fresh cycle. After the transfer of a N-top quality embryo the clinical pregnancy rate (19.9 vs. 19.4%) and LBR (15.9 vs. 15.4%) were similar both in the fresh and frozen cycles.

Limitations, reasons for caution
This study only represents cleavage stage embryo transfers, and all FETs were performed in a natural cycle. In a retrospective study there may also be residual confounding that could not be excluded.
Wider implications of the findings: This study provides further evidence that treatment outcome regarding LBR is not affected by superovulation therapy. Hence, the use of freeze-all strategy is warranted only in cases with a risk of ovarian hyperstimulation syndrome.

Trial registration number
Not applicable
P–794 Prevalence of positivity for SARS-CoV–2 RNA in follicular fluid in infertile patients
Authors: Porcu E , Cipriani L , Dirodi M , Calza N , Ciotti P M , Tranquillo M L , Notarangelo L , Zuffa S , Labriola F S , Vocale C , Damiano G 
Published: August 2021

Abstract

Study question
Is Sars-Cov–2 present in the follicular fluid of infertile patients?

Summary answer
In the experience of the Infertility and IVF Unit, University Of Bologna, Italy, RNA of SARS-Cov–2 was not detected in the follicular fluid.

What is known already
Data on the risk of virus presence in reproductive cells and transmissibility in IVF procedures are very limited. In literature only one study reports the detection of SARS-Cov–2 viral RNA in oocytes of PCR positive women. Research of RNA in follicular fluid could be a marker able to indicate whether to continue IVF treatments in the case of swab-positive patients.

Study design, size, duration
Prospective study performed at Infertility and IVF Unit, Sant’Orsola University Hospital, University of Bologna, Italy, from March 2020 to January 2021. 451 IVF cycles were performed on 902 patients. In addition 59 cycles of oocyte cryopreservation were also performed to fertility preservation in oncological patients. In all positive swab patients was analyzed the follicular fluid for RNA virus detection.

Participants/materials, setting, methods
961 patients underwent telephone triage before going to the IVF Center to identify subjects with suspected or confirmed infection. Body temperature was measured on all patients before entering the IVF Center.
All patients were subjected to real-time analysis (RT PCR) of pharyngeal swab samples 48 hours before transvaginal ultrasound-guided oocyte retrieval.
In case of positive swab, PCR was performed on follicular fluid.

Main results and the role of chance
In our population of infertile patients the incidence of SARS COV–2 infection positivity was 0.4% (4/961).
No IVF treatments were suspended. The oocytes of the 4 women with positive swab were cryopreserved using closed devices stored in a special dedicated cryogenic container. No viral RNA was detected in the follicular fluid.

Limitations, reasons for caution
there are no limitations to the study.
Wider implications of the findings: The absence of SARS-COV–2 RNA in the follicular fluid is a reassuring result in the storage and future use of oocytes.

Trial registration number
Not applicable
P–797 A novel method for establishing human embryonic stem cells independent of feeder cells
Authors: Cai B 
Published: August 2021

Abstract

Study question
Is there a efficient establishing method of human embryonic stem cells directly from the human blastocysts independent of feeder cells?

Summary answer
We established a novel method of generating human embryonic stem cells directly from human blastocysts independent of feeder layer cells.

What is known already
Establishing embryonic stem cells lines mainly needed to coculture ICM clumps with feeder cells (like mouse or human fibroblasts) ,this brought in potential heterogeneous pollution.Although there had be some reports about generating human ESCs independent of feeder cells,but the efficiency was low and conditioned medium were unstable and also had the biological contamination.

Study design, size, duration
We used ten day5/6 donated human blastocysts from our reproductive center ,most of them were genetically diseased embryos with abnormal PGT diagnosis.After establishing ESCs procedure , all the cell lines were identified with pluripotency and differentiation potential tests.The success rate of system was calculated and compared with the conventional methods.

Participants/materials, setting, methods
In brief, ICM clumps were separated mechanically by using a micromanipulation system,and then transferred to a 30ul mTESR plus culture media drop pretreated with the geltrex (1:100 dilution) matrix and oxygen concentration was 5%. When cells attached and migrated,we also used laser to destroy the remaining trophoblast cells.About 10 days,the typical ES clone can be mechanically passaged and cells can be cultured in normal oxygen concentrations after passage 2. .

Main results and the role of chance
Using this method we had successfully established nine embryonic stem cell lines from donated human blastocysts ,the success rate was 90% (9/10). Each cell lines had passed the evaluation test of embryonic stem cell. When compared with the conventional feeder cells dependent method,our novol methods not only eliminated the pollution from heterogeneous cells,but also had higher success rate (90% vs 25%).

Limitations, reasons for caution
Due to the scarcity of donated human blastocysts, this experiment was a single-center experiment with small samples.
Wider implications of the findings: We speculated that the batch differences of culture dishes, matrix and culture medium might affect the establish efficiency , and how to carry out a high level of quality control work might be the key factor to keep the system stable.

Trial registration number
basic research
P2T2: Protein Panoramic annoTation Tool for the interpretation of protein coding genetic variants
Authors: DeVoe Elias , Oliver Gavin R , Zenka Roman , Blackburn Patrick R , Cousin Margot A , Boczek Nicole J , Kocher Jean-Pierre A , Urrutia Raul , Klee Eric W , Zimmermann Michael T 
Published: August 2021

Abstract

Motivation
Genomic data are prevalent, leading to frequent encounters with uninterpreted variants or mutations with unknown mechanisms of effect. Researchers must manually aggregate data from multiple sources and across related proteins, mentally translating effects between the genome and proteome, to attempt to understand mechanisms.

Materials and methods
P2T2 presents diverse data and annotation types in a unified protein-centric view, facilitating the interpretation of coding variants and hypothesis generation. Information from primary sequence, domain, motif, and structural levels are presented and also organized into the first Paralog Annotation Analysis across the human proteome.

Results
Our tool assists research efforts to interpret genomic variation by aggregating diverse, relevant, and proteome-wide information into a unified interactive web-based interface. Additionally, we provide a REST API enabling automated data queries, or repurposing data for other studies.

Conclusion
The unified protein-centric interface presented in P2T2 will help researchers interpret novel variants identified through next-generation sequencing. Code and server link available at github.com/GenomicInterpretation/p2t2.