bluuebunny/crossref_metadata_2025_split huggingface dataset:
O-148 Sperm Aminopeptidase N as a predictive biomarker of blastocyst development and embryo viability
Authors: Subiran N , Urizar-Arenaza I , Muñoa-Hoyos I , Irazusta J , Larreategui Z , Garrido N , Gianzo M 
Published: August 2021

Abstract

Study question
To evaluate human sperm APN as a prognostic factor for determining high-quality embryos.

Summary answer
The human sperm APN has the potential to become new molecular prognostic biomarker for having high-quality and viable embryos.

What is known already
Prognosis and diagnosis of male fertility is one of the major concerns in reproductive medicine. Approximately 30%-40% of men with otherwise normal fertility parameters are still unable to achieve pregnancy. The predictive clinical value of a semen analysis to identify fertile or infertile males is limited; therefore, new sperm diagnostic or prognostic methodologies are urgently required. Sperm Aminopeptidase N (APN) may be a relevant molecular marker due to its high concentration in sperm cells and its role in sperm physiology, such as motility, acrosome reaction, and embryo development.

Study design, size, duration
A prospective study that involves a total of 81 couples and 611 embryos who underwent oocyte-donation cycles at the Clínica IVI Bilbao (Spain) between September 2014 and July 2015.

Participants/materials, setting, methods
This study was set in an assisted reproduction unit and in an academic research laboratory. All semen samples were examined and classified following WHO guidelines. Spermatozoa were isolated from semen on discontinuous colloidal silica gradient (45%-90%) technique. Embryo quality and development were determined according to the Spanish Association of Reproduction Biology Studies (ASEBIR) criteria. Flow cytometry analyses of quantitative and semi-quantitative sperm human APN levels.

Main results and the role of chance
The obtained results proved that the most evolved and viable blastocysts were associated with low sperm APN levels. Expanding, expanded, hatching/hatched and viable blastocysts come from semen samples which showed lower APN levels than early blastocysts, blocked and non viable blastocyst. The cumulative probability of having more evolved blastyocysts increased 1.38-fold at day 5 and 1.98-fold at day 6 of embryo development as well as the likelihood of having viable embryo increased 1.48-fold when semen samples with low APN levels are used during the ICSI technique.

Limitations, reasons for caution
Data obtained from a single Fertility Clinic. A multi-centrum study will be required.

Wider implications of the findings
The human sperm APN has the potential to become new molecular prognostic biomarker for having high-quality embryos that could help to diagnose male infertility, especially when seminal parameters are close to the threshold values.

Trial registration number
Not applicable
O-158 The effect of circadian rhythm disruption due to constant light on ovarian and oocyte aging through possible relationship between PER2 and mTOR signaling pathway
Authors: Bora G , Onel T , Yildirim E , Yaba A 
Published: August 2021

Abstract

Study question
Does circadian rhythm disruption by constant light affect the ovarian morphology and function, and cause ovarian and oocyte aging through possible relationship between PER2 and mTOR?

Summary answer
We demonstrated that circadian rhythm disruption by light may cause ovarian and oocyte aging.

What is known already
Circadian rhythm regulates multiple physiological processes and PER2 is one of the core circadian rhythm components. Changes in light conditions may cause circadian rhythm disruptions. Light exposure at night may cause attenuation in PER2 mRNA and protein levels. Circadian rhythm disruptions are thought to be associated with reproductive diseases. mTOR signaling pathway functions in folliculogenesis and oocyte maturation in ovary. Also, it is associated with ovarian and oocyte aging.

Study design, size, duration
A total of 32 female Balb/c mice which enter estrous cycle were used in the study. Mice were randomly assigned to one of two groups as 12:12h L:D and 12:12h L:L. During the experiment, 12:12h L:D (control group) was housed in a 12:12h light:dark cycle and 12:12h L:L (experiment group) was housed in a constant light conditions 12:12h light:light for 1 week.

Participants/materials, setting, methods
We housed 12:12h L:D group in standard lightening conditions and 12:12h L:L group in constant light for one week. We performed food intake and body weight change analysis. We evaluated ovarian morphology, follicle counting analysis. We evaluated ZP3 and nitrotyrosine (NTY) expression for oocyte aging markers. We performed western blot for PER2, mTOR, p-mTOR, p70 S6K, p-p70 S6K, and Caspase-3 protein levels.

Main results and the role of chance
We demonstrated that circadian rhythm disruption caused alteration in their food intake and decrease in primordial follicle numbers and increase in atretic follicles (p &lt; 0.05). It caused increase in oxidative stress and decrease in ZP3 expression in oocytes (p &lt; 0.05). We showed decreased protein levels of PER2, mTOR, p-mTOR and p70 S6K (p &lt; 0.05).

Limitations, reasons for caution
The explanation of molecular mechanism underlying the relationship between circadian rhythm disruptions by light and ovarian function may lead the usage of circadian rhythm-based or light-based therapies currently using to treat some diseases on female reproductive system related diseases.

Wider implications of the findings
We conclude that constant light may reduce follicle reserve, cause follicles to go rapidly atresia and disrupt the oocyte quality, thus it may be a risk factor for female reproductive diseases such as premature ovarian insufficiency and early menopause.

Trial registration number
not applicable
O-058 The impact of endometriosis on fertility treatment
Authors: Somigliana E 
Published: August 2021

Abstract
Abstract text
Endometriosis can affect natural fertility by distorting pelvic anatomy and by causing local pelvic inflammation that affects the quality of the oocytes, the function of the tubes and the sperm capacity to fertilize. Two approaches can be foreseen, either removing the disease with the aim of restoring normality (surgery) or overcoming the disease by retrieving oocytes in the ovary and allowing their fertilization in in vitro conditions (IVF). Both therapeutic approaches seem rational and wise. However, despite this apparently simple clinical scenario, management of endometriosis-related infertility has engendered long-lasting and burning debates over the last two decades and, to date, no consensus has been reached. Robust scientific evidence is scant, actually limited to the demonstration that laparoscopy modestly increases the chance of natural conception.
In this debate, it is noteworthy that chances of pregnancy do not represent the unique stake. Other factors can play a role and deserves consideration. Considering the choice of fertility treatment, he most relevant are the following: 1) the impact of ovarian endometriomas and their removal on ovarian responsiveness, 2) the impact of endometriomas and endometriosis in general on oocytes quality, 3) the additional risks of oocytes retrieval in the presence of endometriosis (infections in particular) 4) the detrimental effects of endometriosis-related hydrosalpinx, 5) the impact of endometriosis on uterine motility and endometrial receptivity, 5) the confounding effect of endometriosis-associated adenomyosis. Unfortunately, for the vast majority of these concerns, evidence is not definite and physicians have to take decisions based on their clinical commonsense.
O-060 Ethical implications of the direct to consumer genetic testing. What should donors and recipients know?
Authors: Frith L 
Published: August 2021

Abstract
Abstract text
The growth in the use of direct-to-consumer-genetic testing (DTCGT) is having a major impact on sperm, egg and embryo donor conception (hereafter donor conception). DTCGT services include family history sites, e.g. Ancestry.com, and medical testing sites, e.g.23andme. Despite the many different motivations people have for using these services, it is now easier to search and find donor relatives, with donor-conceived people, recipients of donor gametes and embryos, and donors all using these services to make hitherto unlikely connections. Some individuals have found large numbers of donor-siblings, while donors have been traced by their adult donor offspring. DTCGT can also reveal unexpected origins with the numbers of people finding out they are donor-conceived through DTCGT rapidly increasing. For example, one woman discovered she was donor conceived after using 23andme to assess her risk of breast cancer, an eventuality she had never anticipated when she decided to take that test.
The increasing use of DTCGT has led to claims that donor anonymity is dead and we are entering a new era where the possibilities of finding our genetic relatives and extended family have dramatically expanded. These developments will produce new landscapes where different systems collide and interact, creating new ways of locating and finding donor relatives. In the UK for example, information on genetic relations, donors and donor siblings, is located within two very different systems: ‘official’ regulatory systems, such as central registers of information held by government bodies such as the Human Fertilisation and Embryology Authority’s (HFEA) registers; and emerging digital online systems, of DTCGT.
This paper will explore how these new developments interact with existing ways of finding out information about donor relatives and consider the ethical and legal issues and challenges for fertility practice.
O-176 Secondary ovarian insufficiency (SOI) - a new infertility diagnosis
Authors: Gleicher N , Darmon S K , Albertini D F , Barad D H 
Published: August 2021

Abstract

Study question
Can, in contrast to primary ovarian insufficiency (POI), ovarian insufficiency also be caused as a secondary event (SOI)?

Summary answer
Adrenal hypo-androgenism, caused by insufficiency in androgen production by the zona reticularis, may mimic POI in clinical presentation.

What is known already
A variety of small and large animal models have, especially at small growing follicle stages, conclusively demonstrated the dependence of normal follicle maturation on adequate testosterone levels, a process mediated via the androgen receptor on granulosa cells. Increasing clinical evidence, moreover, has demonstrated clinical improvements in oocyte numbers and oocyte quality following androgen supplementation at these stages in hypo-androgenic women with premature ovarian aging (POA). Whether adrenal hypo-androgenism in extreme cases can, however, also lead to complete ovarian insufficiency mimicking POI, is unknown.

Study design, size, duration
Based on FSH levels &gt;40.0 mIU/mL and amenorrhea, we searched our center’s electronic research data bank for patients who between 2016-2018 presented with a diagnosis of presumed POI.

Participants/materials, setting, methods
Among 78 POIs, 13 demonstrated low DHEAS (&lt; 100 ug/dL), i.e., adrenal hypo-androgenism, 6 rejected egg donation and received DHEA (Fertinatal®, 25mg TID, Fertility Nutraceuticals, LLC, New York, N.Y., USA) and Coq10 (Ovoenergen®, 333mg TID,same ­manufacturer) before stimulation with 450IU FSH and 150 IU hMG (different ­manufacturers). All women were &lt; age 41, demonstrated menopausal FSH (&gt;40.0 mIU/mL), undetectable AMH, amenorrhea, &gt; prior cycle cancellation, elevated SHBG, low total testosterone and low DHEAS (high DHEA/DHEAS).

Main results and the role of chance
Out of the 6 patients so stimulated, 5 demonstrated follicular responses following DHEA supplementation and 2/6 conceived spontaneously and delivered healthy offspring. One of these two is currently in treatment for another child.

Limitations, reasons for caution
To better understand adrenal control of ovaries via androgen production, further elucidation of endocrine signaling between adrenals and ovaries is required, including detection of unknown, though increasingly likely, feedback loops, considering that adrenals and ovaries share a primordium.

Wider implications of the findings
We confirmed existence of SOI due to adrenal hypoandrogenism, defined its phenotype, demonstrating that some patients with alleged POI actually exhibit SOI. Better pregnancy chances with adrenal SOI than POI, reemphasize the importance of correct differential diagnoses to avoid premature referrals of women into third-party egg donations

Trial registration number
N/A
O-068 Training of clinicians: How to do it and how to best evaluate it
Authors: Feki A , Tatjana M , Roy F 
Published: August 2021

Abstract
Training of clinicians: How to do it and how to best evaluate it?
Anis Feki, Tatjana Motrenko, Roy Farquharson
Many countries within Europe and EU do not have a specific national agency that provides the necessary structure or governance for appropriate training in Reproductive Medicine (RM). Therefore, The European Society of Human Reproduction and Embryology (ESHRE) has been the responsible agency for accreditation of RM training alongside its sister organization, the European Board and College of Obstetrics and Gynaecology (EBCOG). Both of these organizations are ultimately responsible to and approved by the Union of European Medical Specialties (UEMS), which represents the European Union (EU) governing body for medical practitioners’ education.
The Reproductive Medicine subspecialist is a specialist in basic obstetrics and gynecology who has undergone theoretical and practical training in the medical and surgical management of infertility, including assisted reproductive techniques (ART). In general, the comprehensive management of these problems includes both diagnostic and therapeutic procedures allied to continuous audit of outcome.
The global aim is to improve the care of patients with disorders of reproductive function. To reach this target, both ESHRE and EBCOG put in place a program that starts with accreditation of training centers in obstetrics and gynecology and more specifically, specialist training centers in reproductive medicine. Fellows must have a structured program of a minimum of 2 years after completing their basic obstetrics and gynecology syllabus and/or obtaining EFOG European Fellow of Obstetrics and Gynecology) diploma for non-European basic training. When a training fellow in RM has completed their logbook, the fellow will finish by assessing an individual’s knowledge and skills by passing an exit-training exam called the EFRM (ESHRE-EBCOG Fellow in Reproductive Medicine) diploma.
The success of and the need for such certification has led ESHRE to structure the training also for reproductive surgeons, embryologists, as well as nurses and midwives. In addition, several countries within the EU already have a national compulsory specialist accreditation system for RM training.
Recent proposals by the EU Commission to build European reference networks across all specialties, including RM may require the recognition of ESHRE/EBCOG–accreditation as an appropriate entry point for consideration of diagnostic and other interventions. Encouraging subspecialists and centers to apply for training accreditation may well prove to be an increasingly attractive option as educational needs across Europe become integrated and formalized through UEMS. ESHRE holds the view that accredited centers/subspecialists for training are beacons of excellence that often go hand in hand with high-quality research.
O-199 Proof of concept: implantation window must be wider than proposed. Report of seven twins after asynchronous double embryo transfer
Authors: Vega A. Gosálvez , Mazaira M. Rodriguez , Fernandez N. Martin , Nuñez M. Iglesias , Brandt M , Juan L. Vidal , Vargas P. Pastor , Rodriguez Z. Gonzalez , Bermudez S. Corral , Seivane R. García-Abadillo , Abbad R. Sainz de la Cuesta 
Published: August 2021

Abstract

Study question
Can simultaneous transfer of two embryos that were cryopreserved at different stages (D3 and Blastocyst) be appropriate to enhance success in women with more than three failed embryo transfers?

Summary answer
Double asynchronous embryo transfer offered excellent results in RIF. Unexpectedly high twin rate suggests that embryo-endometrium synchrony is overemphasized. Implantation window must be wider.

What is known already
Transcriptomic signature of the endometrium has been investigated in the last few years trying to understand the best moment for embryo implantation. Nevertheless, the optimal period has not been well established yet in humans. Simultaneous transfer of two human embryos at different developmental stages (D3 and Blastocyst) on Day 4 was proposed to help couples who have had RIF.

Study design, size, duration
Observational case-control study. From April 2016 to January 2021, we offered double asynchronous embryo transfer only after Recurrent Implantation Failure (RIF). Two requirements were necessary: 1) Double embryo transfer was acceptable by the couple due to poor reproductive outcome. 2) Availability of two embryos cryopreserved at different stage (D3 and Blastocyst). Results were compared with good prognosis patients (all patients under 35 years in that period who had elected to transfer two day 3 cryopreserved embryos).

Participants/materials, setting, methods
Forty-five patients accepted to participate in the study. Results were compared with all patients (237) under 35 years where two D3 thawed embryos were transferred. All cases received same protocol (oral estradiol 6mg/d or vaginal estradiol 4mg/d until ultrasound showed endometrial growth) LH, P4 and E2 were monitored in all patients to detect spontaneous LH surge. All cases received transvaginal micronized progesterone 800 mg/d. Embryo transfers were ultrasound guided and Wallace Embryosure catheter was employed.

Main results and the role of chance

Limitations, reasons for caution
Multiple pregnancy rate was unacceptably high. Therefore, it should not be suggested for good prognosis couples where single embryo transfer is clearly advidsed. Our main limitation was the combination of D3 embryos with blastocysts. The retrospective design make the results to be considered as a proof of concept.

Wider implications of the findings
Double asynchronic embryo transfer can offer new insights in the understanding of human implantation. The concept of implantation window is clearly challenged. Aiming to the center of the window is fine, but we still dońt know how wide is that center.

Trial registration number
not applicable
P–010 Timing of TESE does not affect laboratory outcomes
Authors: Goktas C , Basar M , Fetahovic M , Spahovic H , Goktas E , Goktolga U 
Published: August 2021

Abstract

Study question
What is the outcome of intracytoplasmic sperm injection (ICSI) using testicular spermatozoa obtained on the day of oocyte pick-up (OPU) or the day before OPU.

Summary answer
Testicular spermatozoa were obtaining the one day before OPU does not affect fertilization rate, top quality embryo on day 3, and blastocyst utilization rate.

What is known already
Usually, TESE is performed just before OPU. OPU is generally cancelled if no sperm is retrieved. The use of fresh testicular spermatozoa, obtained the day before OPU could offer the couple and the caring team both medical and practical advantages. The benefits of this approach, however, has not been evaluated in detail. An uncontrolled preliminary study has revealed that regular fertilization and pregnancy rates could be achieved with sperm extraction performed one day before OPU.

Study design, size, duration
This was a single-center retrospective study in Bahceci BIH IVF center. Sixty-six patients suffering from azoospermia from January 2015 to December 2020 were evaluated. TESE was performed either on the OPU day (43 patients; group A) or one day before OPU (23 patients; group B).

Participants/materials, setting, methods
In this study, primary outcomes were motile spermatozoa at ICSI, fertilization, top quality embryo on day 3, and blastocyst utilization rate. Statistical analyses were performed with chi-squared tests.

Main results and the role of chance
There is no statistical difference fertilization rate (72.3% vs. 72.2, p &gt; 0.05), top quality embryo rate on day 3 (58.3% vs 58.3%, p &gt; 0.05) and blast utilization rate (43.98% vs 49.58%, p &gt; 0.05) between group A and B, respectively.

Limitations, reasons for caution
The retrospective nature of this study may not eliminate potential bias. On the contrary, the strength of our study is that all procedures were performed by the same operators, so there are no operator-dependent differences. More research is needed to prove our findings.
Wider implications of the findings: TESE procedure can be performed one day before OPU without compromising success.

Trial registration number
1
P–020 AZFc partial microdeletions of the Y chromosome is associated with severe oligozoospermia among Iranian men
Authors: AzarAfshar Z , Sadigh. Gilani M A , Ghaheri A , Zamanian M R 
Published: August 2021

Abstract

Study question
Are AZFc partial deletions correlated with severe oligozoospermia in Iranian men? Can we consider them as risk factors for infertility?

Summary answer
The frequency of total partial AZFc microdeletions was significantly higher in the oligozoospermia group compared to control group (8% vs. 3%, P = 0.028).

What is known already
Among many factors affecting male infertility, the second most common genetic factor is Y chromosome microdeletion. Some studies on partial AZFc microdeletions (especially on three major types; gr/gr, b1/b3 and b2/b3) have associated them with impaired spermatogenesis (azoospermia and oligozoospermia) in infertile men from different ethnicities. This finding is attributed to differences in alterations in pattern of DAZ/CDY1 copy numbers as spermatogenesis related genes.

Study design, size, duration
200 oligozoospermic (sperm count &lt;5 mil./mL) and 200 fertile men were included as case and control groups, respectively. Individuals with karyotype abnormalities, complete microdeletions in AZF regions, infections, hypogonadism, history of chemotherapy and radiation, cryptorchidism or history of orchiopexy were not included. The study was approved by the Royan Institute Ethics Committee. Written informed consents were obtained from each participant.

Participants/materials, setting, methods
Total DNA from peripheral blood was used to amplify six sequence-tagged sites (STS) markers through multiplex PCR to detect AZFc partial deletions according to previous studies. Patterns of deletion in DAZ and CDY1 copies were determined through PCR- RFLP.

Main results and the role of chance
The frequency of AZFc partial microdeletions was 8% in oligozoospermic men (16/200) which was significantly higher compared to 3% in control group (6/200) (P = 0.028). Hence, partial deletions may be considered as a risk factor for the male infertility in Iranian population. Also, gr/gr showed a higher frequency in oligozoospermic group (4%) compared to controls (1.5%) (P = 0.126). The combination of DAZ1/2+CDY1b was the most observed deletion pattern in 8 oligozoospermic men with gr/gr deletion (75%), while among 3 controls with gr/gr, DAZ3/4+CDY1a (2 out of 3) and DAZ3/4+CDY1b (1 out of 3) were detected. Therefore, DAZ1/2+CDY1b can be correlated to oligozoospermia.

Limitations, reasons for caution
In order to achieve stronger statistical results, a larger sample size is of more help.
Wider implications of the findings: Risk of vertical transmission to male offspring and expansion in the size of deletions should be considered when providing ART services to infertile men. Genetic counseling is suggested in oligozoospermic men.

Trial registration number
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