bluuebunny/crossref_metadata_2025 huggingface dataset:
O-081 High variability of molecular isoforms of AMH in follicular fluid and granulosa cells from human small antral follicles
Authors: Mamsen L S , Bøtkjær J A , Kristensen S G , Pors S E , Jeppesen J V , Kumar A , Kalra B , Ernst E , Andersen C Y
Published: August 2021

Study question

Is the composition of AMH isoforms different in follicular fluids (FF) and granulosa cells (GCs) from human small antral follicles?

Summary answer

There is a high viability of AMH isoforms in FFs and GCs. Even between same size follicles from the same women, the isoform composition differs.

What is known already

Anti Müllerian Hormone (AMH) is a member of the TGF-β superfamily produced by follicular granulosa cells (GCs) in women from late gestation to the end of reproductive live. AMH is suggested to inhibit aromatase (i.e. CYP19) expression and thereby decreasing the conversion of androgens to oestrogens in humans, especially in small antral follicles before dominance is achieved and thereby act as a gatekeeper of ovarian steroidogenesis. However, the exact function and processing of AMH in human follicles is still not clarified.

Study design, size, duration

This retrospective study measured AMH isoforms in human FF and GCs from small antral follicles using ELISA, Western blot, and immunofluorescence analysis. A total of 41 female adolescents and women aged 15 to 38 years (mean age: 29.7 years), who underwent ovarian tissue cryopreservation (OTC) at the University Hospital of Copenhagen, Rigshospitalet were included between year 2006 and 2020 included.

Participants/materials, setting, methods

Donated human ovarian medulla tissue were FFs and GCs were obtained in connection with OTC. The following isoforms were evaluated in FFs using ELISA analysis: full-length AMH precursor (proAMH), cleaved associated AMH (AMHN,C), N-terminal pro-region (AMHN), and active C-terminal (AMHC) AMH. Antibodies specific for the N-terminal and the C-terminal AMH were used in both Western blot and immunofluorescence analysis of FFs and GCs.

Main results and the role of chance

A negative correlation between follicle diameter and the mentioned AMH forms were detected. Moreover, Western blot analysis detected various AMH forms in both FFs and GCs, which did not match the above-mentioned consensus forms suggesting an unknown proteolytic processing of AMH. The presence of these new molecular weight isoforms of AMH differs between individual follicles of identical size from the same woman.

Limitations, reasons for caution

The study group is limited and the significance of the variable AMH isoforms compositions between follicles cannot not be clarified from this data.

Wider implications of the findings

Collectively, these data suggest that intrafollicular processing of AMH is complex and variable, and thus, it may be difficult to develop an antibody based AMH assay that detect all AMH isoforms. Furthermore, the variability between follicles suggests that designing a proper standard will be difficult.

Trial registration number

not applicable
O-011 You are what your father ate- epigenetic implications
Authors: Soubry Adelheid
Published: August 2021

An unhealthy life style, obesity and excess of dietary fats or chronic consumption of processed foods create a harmful environment for sperm health. In the current presentation our most recent findings will be presented on male exposures related to an unhealthy life style and the effects measured on clinical sperm and/or embryo parameters in humans. Next, epigenetic implications will be shown from male obesity, “healthy” and “unhealthy” foods and other related determinants (such as advanced age) before conception. Our results lend support for the existence of epigenetic windows of susceptibility in life. If the acquired epigenetic signatures are passed down to the next generation(s) this may affect future health.

Our data are based on human studies, including the Newborn Epigenetics Study (NEST) cohort, The Influence of the Environment on Gametic Epigenetic Reprogramming (TIEGER) study and the Epigenetic Legacy of Paternal Obesity (ELPO) cohort.

In brief, we found that consumption of healthy food items, such as vegetables, fruits and nuts, is positively related to total motile sperm count (TMC), while consumption of fast foods (such as fries) is associated with lower TMC. Frequent consumption of fast foods (incl. pizza and fries) is associated with opposing effects on DNA methylation patterns at the DMRs of imprinted genes (such as IGF2 and MEG3-IG), compared to dietary patterns rich in whole grains and vegetables. These results correspond to our findings in sperm from obese versus non-obese men, and are in line with our earlier findings in children from obese fathers. While this talk will be a compilation and comparison of our research findings, it will also serve as a base for guidance and counselling in infertility.

Our results fit our new concept of the Paternal Origins of Health and Disease (POHaD), where the role of the father has been suggested in disease development of his future offspring. If better understood, tailored dietary changes may positively shape the human sperm epigenetic profile and future programming of offspring health.

Trial registration number

Study funding

Funding source
O-017 Appeased embryo transfer with hypnosis
Authors: Lelaidier D
Published: August 2021

Abstract text

Objective

, We report in this presentation the use for couples undergoing infertility treatment of a new way of accompaniment. Hypnosis associated with learning of self-hypnosis is a solid support to valid an appeased uptake of an infertility program and lower the emotional charge associated with such treatments.

Main

enhance emotional comfort in couples undergoing infertility treatment.

Secondary

patients feelings after results of the attempt (whether failure or success), pregnancy rates.

Contains

During a first meeting family and historical back ground is analyzed as well as medical file and causes for infertility. Then a first specific session is proposed in relation with underlying problems using ericksonian hypnosis. For example sessions using amnesia can be used in patients having had traumatic experiences. Comfort and wellbeing suggestions are used after each hypnosis session.

Two other sessions can be proposed at office, one called “the two chests” first one to pack all past failures and second to collect present or past successes regarding all fields. These successes will be resourceful to refer to. The second session will be to enhance self-confidence using contes.

In order to enhance autonomy patients are given 4 audio sessions prerecorded to home practice.

Three of them are specific to intra uterine insemination or embryo transfer. One is called FIVETE to listen the day before medical procedure, one is called SIMPLE INDUCTION to start just before and throughout the procedure. One to do after procedure at home called DO NOTHING.

Patients are called few weeks after the attempt for debrief and results.
O-033 Where ethics hits the patients needs - Case Germany
Authors: Kordic K
Published: August 2021

Abstract text

The German Embryo Protection Act was passed in 1990 and has never been changed since, other than minor changes in 2011 regarding PGD.

Germany is a country with 83 million inhabitants, where more than 6 million people of reproductive age are facing infertility or difficulties conceiving and delivering a healthy child. Germany also has the oldest and arguably most restrictive law regulating reproductive medicine, especially IVF. By passing a law with such an imposing title and starting the act with a list of prohibitions, 31 years ago German legislators made their intentions very clear: to protect the embryo rather than to help infertile people to become parents using assisted reproductive technology.

Since reproductive medicine has developed tremendously in the last 30 years and since the number of people in need of medical assistance to have a child is constantly growing,Germany now is not only far behind other European countries with its legislation but also seems to be against its patients and citizens in need of the assistance of modern medicine to have children.

How can we change an inappropriate and archaic law? How can we create a modern law which suits patients’ needs without compromising ethics?

How can reproductive medicine in Germany come back on track again and serve the people by evidence based medicine in the first place?I
O-041 Functional sperm diagnostics: The evidence behind commercially available tests
Authors: Hotaling J
Published: August 2021

Abstract text

Despite the fact that the semen analysis has remained the cornerstone of the male infertility evaluation for decades, it has significant limitations. Among them are the inability to completely predict reproductive potential and the inability to analyze the fitness of individual sperm. There remains a real need for novel tests that can determine which interventions for male infertility are the most likely to result in a significant improvement in reproductive potential, to analyze the chance of success or failure with ART and to determine if there exists a sub population of sperm whose use could lead to optimal chances of success with fertility treatments. In this talk we will cover what the limitations of the current semen analysis are, what novel tests are available and delve into the impact of future technologies such as microfluidics, machine learning and others to optimize the diagnostic armamentarium of male fertility assessment. We will also focus on tools that could, potentially, non-invasively image sperm and report reproductive fitness while maintaining viability for ART.

Trial registration number:

Study funding:

Funding source:
O-046 Implantation and beyond, the endometrial perspective
Authors: Aplin J
Published: August 2021

Abstract text

Early pregnancy failures are spread throughout the first few weeks, suggesting that impairment of normal biological processes can occur at sequential stages: epithelial attachment and breaching, early stromal and then decidual invasion, glandular and vascular invasion. Biopsy-based transcriptomics and proteomics have failed to demonstrate a reproducible or interpretable molecular signature for endometrial receptivity, but single cell RNAseq suggests a step change in the epithelial transcriptome in the mid secretory phase, consistent with the appearance of new cell phenotype(s). Previously unseen heterogeneity in both epithelial and stromal cell populations has become evident, but gene signatures have not yet achieved a level of resolution that allows insights clear enough to decode the biology of the receptive state. However, methodology for propagating and recombining endometrial cell populations into 3D engineered tissue models has advanced, so that new mechanistic questions can be asked. Initial acquisition of receptivity to implantation is followed by the development of a supportive environment for embryos that possess the capacity to progress, with maternal cell populations (epithelial, stromal, immune and vascular) acting cooperatively within a remodelling extracellular matrix (ECM). A balance must be achieved in the ECM between breakdown, with opening of hydrated spaces to allow expansion of the embryonic sac while maintaining a substrate for stable physical attachment to allow invasion by extravillous trophoblast. The extent and nature of cellular trafficking to and from the uterus is important before and during early pregnancy. There is evidence that regulation of a resident senescent cell subpopulation by uterine NK cells occurs in concert with ECM remodelling to achieve a functionally supportive environment in the early first trimester. Access of bone marrow-derived cells to vessel walls is regulated by placental-endothelial signalling to initiate remodelling for the increased blood flow to the conceptus that is required in later pregnancy. Thus ‘receptivity’ and ‘supportiveness’ require normal cell proportions and functional phenotypes in multiple endometrial cell populations and their physical environment in order to allow a well-calibrated sequential developmental response in the conceptus.
O-133 Effect of non-surgical treatments on the size of endometrioma: A systematic review and Meta-Analysis
Authors: Mekki S , Hamdan M , Omar S Z , Shunmugam R H
Published: August 2021

Study question

This review aims to determine the effectiveness of medical preparations in the management of endometrioma size

Summary answer

Medical treatment from different groups significantly reduces the endometrioma size, and relives painful symptoms

What is known already

Endometrioma is usually found in more severe stage of endometriosis and likely to be treated surgically. However, surgery of an endometrioma always destroys ovarian tissue and eventually reduces the ovarian reserve.

Study design, size, duration

Systematic review and analysis.The studies included 810 women in the intervention groups and 442 in the control groups

Participants/materials, setting, methods

810 women included in the intervention groups . 442 in the control . All were women with endometrioma; 30-60% had pelvic pain. age was 33.4 years (range 27-39.8).

Four electronic databases search PubMed, Embase, CINAHL Google Scholar from each database inception date until 10 .9. 2019 using the specific search term. randomized and nonrandomized were included. trials comparing different medications for endometiotic cyst medical treatment, without language restriction and in consultation with a search methodologist

Main results and the role of chance

We found 3121studies from the initial search and out of which 3102 were excluded due to they did not fulﬁl the selection criteria, We included 14 studies for the systematic review leaving 4/14 for the meta-analysis. 14 final studies included for the systematic review out of which 6/14 were uncontrolled. The majority of the studies were prospective (10/14), and four were RCTs. 2/4 (n = 395). controlled studies patient treated with a low-dose (OCP) or NET and dienogest +EE compared with patients treated with placebo, the endometrioma size significantly reduced (odds ratio[OR]1.32;95%CI [0.61,2.84],2studies, 255women, I = 0%).2/4 studies included in meta-analysis patients treated with dienogest versus norethendrone or ethinyl estradiol [EE] plus dienogest (SMD - 6.73;95%CI[-16.53, 3.06],2studies,185 women, I = 83%)

Conclusions

Medical treatment from different groups significantly reduces the endometrioma size, and relives painful symptoms.

Limitations, reasons for caution

Despite the nature of the randomized includedstudies, the results of this study are still subjected to confounders relating to clinical and statistical heterogeneity. the studies reported the outcomes differently

Wider implications of the findings

medical treatment can be given the surgery can be avoided, therefore preserve the ovarian tissue. There is limited controlled study to examine the effectiveness of the treatment for endometrioma.

Trial registration number

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O-049 How is AI changing the way we make babies?
Authors: Zaninovic N
Published: August 2021

Abstract text

ART is one of the fastest-growing fields in medicine. Besides the advancements in the hormonal stimulation and treatment regimes, the laboratory aspect of IVF showed emerged development in science and especially technology. The emphasis of future IVF treatments and laboratory procedures is on the non-invasive methods of embryo evaluation and selection. The application of Artificial Intelligence (AI) in daily life prompts us to evaluate this technology in this context. The AI is one of the main candidates to drive future IVF not only in the lab but also in all aspects of the IVF procedures. The benefit of AI technology involves “big data” analysis, objectivity, standardization, and precision. The most advancement of AI application is in the IVF lab where technology can be used as a tool to enhance our ability to select the “best” viable embryo objectively. As a new technology, it is important to evaluate it on the large scale. The AI technology will also enable us to standardize clinical parameters of patient reproductive potential and objectively predict each patient reproductive outcome per cycle. Ultimately, AI will help us to achieve the personalized and precision medicine needed in our field.
O-051 Telenursing within fertility
Authors: Peddie V
Published: August 2021

Abstract text

Aberdeen Fertility Centre provides fertility investigation and treatment across the north east, highlands and islands (Orkney & Shetland) of Scotland, which includes rural and remote communities. Whilst the SARS-Cov-2 pandemic has accelerated the delivery of Tele-fertility Nursing, the National Health Service (NHS) in Grampian, Scotland launched both ‘No Delays’ and ‘Near Me’ platforms in 2019 to keep pace with the digital age and with the intention of improving the quality of patient care.

No Delays (series of video packages and virtual consultations) has revolutionised clinical pathways, providing individualised patient information from investigation to treatment, permitting email ‘prescription’ of digital postcards (personalised package of short videos introducing members of the team and explaining their role) that explain the fertility journey and management plan in detail, from investigation (ie., tubal evaluation), to treatment (ie., ovulation induction or IVF), and self-administration of medicines.

Thereafter, patients receive invitation to virtual ‘Near Me’ consultation which can take place in the comfort of their own home whilst acknowledging flexibility in lifestyle (partner can remotely access consultation from workplace, including overseas).

Electronic patient records (EPR’s) provide immediate access to complete, accurate and up to date clinical patient data, which, together with Electronic Consents compliment the tele-nursing experience through a complete library of consent forms, automatically allocated to patient and partner according to treatment type and personal circumstances: information being provided in video format to meet the requirements for informed consent. Forms are completed online, at home or in the ‘virtual’ clinic via computers, tablets or smartphones, with workflow automation tools allowing for digital signature/s. The complete digital package ensures patients have an early understanding of the process, therefore better prepared for face-to-face appointments and ensuring quality care delivered at point of contact.

The aims and objectives of ‘Tele-fertility Nursing’ were to: (1) reinforce key information routinely provided at consultation which may not always be understood, (2) meet patient need and lifestyle, (3) increase patient choice, (4) save time and money by reducing unnecessary travel (often complicated by adverse weather conditions from rural communities), (5) avoid unnecessary time off work, and (6) reduce environmental impact of attended appointments (health miles and miles not travelled).

Whilst concern remains around the digital interface and nurse/patient relationship, preliminary evaluation of ‘Near Me’ consultations and patient feedback - relative to electronic consent - suggests overall patient satisfaction; the above aims and objectives being met. However, full evaluation of the patient and fertility nurse experience of the ‘digital fertility journey’ is required.
O-057 The impact of diagnosis endometriosis as part of the fertility workup
Authors: Garcia-Velasco J A
Published: August 2021

Abstract text

The impact of diagnosis endometriosis as part of the Fertility workup

Endometriosis is a multifaceted disease that may go from completely asymptomatic to a debilitating condition with severe pelvic pain complicated infertility. In the last few years, how we approach fertility in women with endometriosis has clearly changed, postponing definitive/radical surgery till the patient has completed her family. As a clear association exists with endometriosis and infertility, during the fertility workup it is one of the diseases to investigate, as it may have been missed in previous annual gynecologic checkups. Here we may face two problems: a) the stigma of diagnosis a young women with the label “endometriosis”, as she may be under the pressure of a progressive disease that may or may not affect her quality of life, and b) if the diagnosis of endometriosis is positive, how this may affect the decision making process during the fertility journey.

In this lecture we will discuss the difficulties of early diagnosis of endometriosis, why most of the previous test have failed, and the new opportunity that miRNAs seem to offer. Once endometriosis is diagnosed –early or late stages- how this may affect spontaneous chances of pregnancy, ovarian reserve, oocyte and embryo quality, endometrial receptivity, and last but not least, time to pregnancy. Obviously, the prognosis changes over time, and women’s age will be conditioning most of our decisions. We will try to identify whom to treat, to increase the absolute pregnancy rate, and when to treat, to reduce the time to pregnancy. Finally, we will discuss the opportunity of fertility preservation in this particular subgroup of women. Being aware of the potential damage that endometriosis by itself, or the associated ovarian surgery, may inflict on ovarian reserve make these women more proactive for fertility preservation.
O-062 In vitro maturation of oocytes in connection with ovarian tissue cryopreservation
Authors: De Vos M
Published: August 2021

Abstract text

Discussing fertility preservation (FP) in young cancer patients has become a key component of routine oncological health care. Although ovarian stimulation followed by oocyte cryopreservation has been recommended in cases where two to three weeks are available before the start of chemotherapy, ovarian tissue cryopreservation (OTC) is the preferred option when this timeframe is not available and when the potential gonadotoxic impact of cancer therapy is deemed moderate or severe, or in prepubertal girls. During ovarian tissue processing in the laboratory, cumulus-oocyte complexes can be identified. In vitro maturation and further vitrification of oocytes retrieved in ex vivo from the extracted ovarian tissue (ovarian tissue oocytes in vitro maturation; OTO-IVM) can be attempted to enhance the future reproductive options of the patient. Although the number of reported live births after OTO-IVM are limited, this experimental FP procedure has potential to become a standard appended procedure in conjunction with OTC. In cancer patients with haematological tumours and ovarian invasion, or patients with primary tumours of the ovary, ovarian tissue grafting may be contraindicated because of the risk of reintroducing malignant cells. Utilisation of vitrified oocytes after OTO-IVM may be the only hope for genetic offspring for these patients. Moreover, exogenous hormonal pretreatment is not required and COC can be recovered during ovarian tissue processing in the majority of patients who undergo partial or total unilateral oophorectomy. Nevertheless, maturation rates after OTO-IVM vary and are generally lower compared to IVM of transvaginally harvested IVM oocytes; currently available IVM systems registered for clinical use will have to be adapted to accommodate the in vitro requirements of oocytes derived from extracorporeal ovarian tissue, and follow-up data are needed to assess the success rate and safety of this novel approach.
O-063 PGT-M, for multi-system genetic diseases
Authors: Xu J
Published: August 2021

Abstract text

Reciprocal translocations (RecT) and Robertsonian translocations (RobT) are among the most common chromosomal abnormalities that cause infertility and birth defects. In 2017, the Reproductive Medicine Center of the first affiliated Hospital of Zhengzhou University reported a method named "Mapping Allele with Resolved Carrier Status" (MaReCs), which enables chromosomal ploidy screening and resolution of the translocation carrier status of the same embryo. Meanwhile, the first international healthy baby, where the chromosomal balanced translocation that can be transmitted to offspring was precisely blocked by ''MaReCS, was born in our center''. Roche translocation can also delivery healthy babies. Therefore, MaReCs accurately enables the selection of translocation-free embryos from patients carrying chromosomal translocations.In addition, with regard to the monogenic disorders and relative cases, our center used Karyomapping-SNP and NGS technology for preimplantation genetic diagnosis, completed the first Huntington's disease patient in China and delivered a healthy embryos. NGS/Karyomapping PGD can be used to assist pregnancy for all genetic diseases with clear genetic patterns and pathogenic genes.

Trial registration number:

Study funding:

Funding source:
P-180 Bisphenols are present in culture media used for ART and cell culture
Authors: Vignault C , Togola A , Desmarchais A , Téteau O , Maillard V , Bristeau S , Binet A , Guérif F , Elis S
Published: August 2021

Study question

Do plastic laboratory consumables and cell culture media used in human ART contain bisphenols?

Summary answer

Human embryo development media contained bisphenols close to the nanomolar concentration range while no release of bisphenols by plastic consumables was detected under routine conditions.

What is known already

The deleterious effect of the endocrine disruptor bisphenol A (BPA) on female fertility raised concerns regarding ART outcome. BPA was detected neither in media nor in the majority of plastic consumables used in ART, however it might have already been replaced by its structural analogs, including bisphenol S (BPS).

Study design, size, duration

Seventeen plastic consumables and 18 cell culture and ART media were assessed for the presence of bisphenols.

Participants/materials, setting, methods

Ten different bisphenols (bisphenol A, S, AF, AP, B, C, E, F, P, and Z) were measured using an isotopic dilution according to an on-line solid phase extraction / liquid chromatography/mass spectrometry method.

Main results and the role of chance

While all the plastic consumables of this study did contain bisphenols, none of them did release bisphenols under routine conditions. Moreover, 16 of the 18 cell culture and ART media assessed contained bisphenols, including 8 among the 10 media used in human ART. Five human ART media exhibited bisphenol concentrations higher than 0.8 nM and reached up to 3.2 nM (799 ng/L).

Limitations, reasons for caution

Further studies are required to investigate a greater number of ART media to identify less potentially harmful ones, in terms of bisphenol content.

Wider implications of the findings

As BPS has already been reported to impair oocyte quality at nanomolar concentrations, its presence in ART media, at a similar concentration range, could contribute to a decrease in the ART success rate. Thus far, there has been no regulation of these compounds in the ART context.

Trial registration number

Not applicable
O-189 Male fertility restoration by direct transplantation of human infant testicular cells into infertile recipient mouse testis
Authors: Wang D , Hildorf S , Dong L , Pors S E , Mamsen L S , Hoffmann E R , Cortes D , Thorup J , Andersen C Y
Published: August 2021

Study question

Is colonization of human gonocytes and spermatogonial stem cells (SSCs) directly transplanted to seminiferous tubules of busulfan sterilised mice testis during an 8-week period feasible? 

Summary answer

Gonocytes and SSCs from infant boys can settle on the basal membrane and form germline stem cell colonies in the seminiferous tubules of recipient mice.

What is known already

The neonatal or immature animal provides higher populations of gonocytes and/or SSCs than adults, and the number of transplanted donor SSCs directly affects the colonization rate of the recipient testes. Along with SSC transplantation restoring the recipient’s spermatogenesis, donor gonocyte was also reported to be capable of establishing spermatogenesis in rodents.

Study design, size, duration

Transplantation of human testicular cells including gonocytes and SSCs into seminiferous tubules of infertile recipient mice. We included 10 infant testis biopsies from which single-cell suspension was transplanted individually into the seminiferous tubules of 10 immunodeficient mice. The immunodeficient mouse testes were injected with busulfan to deplete germ cells. Four weeks later, we did the xenotransplantation. Then after eight weeks, we collected all mouse testes to do further analysis.

Participants/materials, setting, methods

Testis biopsies were obtained from cryptorchid boys undergoing orchidopexy. After enzymatic digestion of the testis biopsies, dissociated single-cell suspensions were pre-labeled with a green fluorescent dye. Then the single-cell suspensions were transplanted into seminiferous tubules of the infertile recipient mice. Eight weeks later, the presence of gonocytes and SSCs was determined by immunohistochemistry and whole-mount immunofluorescence.

Main results and the role of chance

Without in vitro propagation, naturally enriched human germline stem cells settled on the basal membrane of seminiferous tubules and survived in the mouse testes at least for two months demonstrating that human gonocytes and SSCs were capable of colonizing the recipient mouse seminiferous tubules.

Limitations, reasons for caution

The study samples were from infant boys with undescended testes that were more likely to contain gonocytes. It was not possible to determine which germ-cell type at transplantation resulted in the detected gonocytes and SSC colonies after xenotransplantation. Transplantation of gonocytes may include the potential risk of stem cell-related malignancy.

Wider implications of the findings

Without in vitro propagation, male germline stem cell-based transplantation could provide a relatively safe therapeutic treatment for prepubertal boys with cryptorchidism and boys diagnosed with cancer. This method could also facilitate clinical translation.

Trial registration number

not applicable
O-200 Frozen embryo transfer: Miscarriage rates depending on the starting day of intramuscular progesterone
Authors: Kalhorpour N , Martin B , Kulski O , Mayenga J M , Grefenstette I , Allart J. Belaisch
Published: August 2021

Study question

Objective was to assess whether adjusting starting day of intramuscular progesterone the day of vaginal supplementation versus day of embryo transfer or later, might affect the outcome of the cycle.

Summary answer

additional injection of intramuscular progesterone the day of progesterone initiation or later, is not likely to be more effective on live birth and miscarriage rates.

What is known already

There is no consensus on the most effective method of endometrium preparation prior to FET. However, many studies report that high serum progesterone concentration during the implantation period is associated with optimal live birth rates. Adjusting progesterone treatment the day of embryo transfer seems to be too late and ineffective for rescuing low progesterone levels and should be done before.

Study design, size, duration

In this single center prospective study from October 2019 to november 2020, 239 patients undergoing hormonal replacement therapy protocol for frozen embryo transfer were randomly divided into two groups: additional injection of intramuscular progesterone the day of progesterone initiation or intramuscular progesterone the day of embryo transfer. We compare these results to our previous protocol beginning intramuscular progesterone day 22 of the treatment.

Participants/materials, setting, methods

Our frozen embryo transfer protocol consists to initiate GnRH agonist the day 1 of the cycle. After 14 days of estrogens, we introduce vaginal progesterone, prior to embryo transfer. Patients in group A received an additional injection of intramuscular progesterone the day of progesterone initiation. The group B received intramuscular progesterone the day of embryo transfer. For both, intramuscular injection of progesterone was followed every 3 days.

Main results and the role of chance

239 patients were enrolled in this study, 125 in the group A and 114 in the group B. The ongoing pregnancy rate in the group A was 26.4 % and miscarriage rate 7.2%, not statistically different from ongoing pregnancy rate and miscarriage rate of women in the group B (22.81 %, p = 0.66/ 6.14%, p = 0.8).

The ongoing pregnancy rate in the group D22 was 24.89 % et miscarriage rate 7.2%, not statistically different from ongoing pregnancy rate of women in the group A and B (p = 0.78 and p = 0.31).

Limitations, reasons for caution

The main limitation of our study is the lack of randomization for the group with additional progesterone IM on day 22. The study is actually followed to enroll more patients in 3 different groups.

Wider implications of the findings

This study tries to determine optimal adaptive management of hormonal replacement treatment for embryo transfer in patients with potential low progesterone values.

Trial registration number

no applicable
O-212 MACS vs TESA for raised sperm DNA fragmentation index – a RCT
Authors: Mantravadi K C , Gedela D R
Published: August 2021

Study question

In Individuals with raised Sperm DNA Fragmentation Index (SDF), will sperm selection by magnetic activated cell sorting (MACS) or surgical retrieval of testicular sperms (TESA) optimize the reproductive outcomes?

Summary answer

Couples with failed implantation raised SDF, TESA /MACS offer similar results. This RCT doesn’t prove superiority or added benefit with any of the above interventions.

What is known already

It is evident that raised SDF negatively affects the reproductive outcomes. Management for raised SDF to optimize reproductive outcomes is still elusive.

Study design, size, duration

This was a Randomized Control Trial (RCT) with prior approval from institutional Ethical Committee and trial registration. Couples undergoing stimulation with raised SDF were randomized to MACS (n = 75) and TESA (n = 75) for sperm selection between April2019 & February2020.

Participants/materials, setting, methods

Couples with history of one failed IVF had SDF testing and SDF>30% were recruited. SDF test done with SCSA method and randomized using software. ICSI was the method of insemination. Extended embryo culture till blastocyst was done and freeze all policy was opted. Two Blastocysts that showed 100% survival were transferred in a Frozen Embryo transfer (FET) cycle. Embryonic and Reproductive outcomes were compared between both groups. Live birth and Miscarriage were the primary outcomes.

Main results and the role of chance

Reproductive Outcomes of MACS Vs TESA were:

Average Blastocyst conversion - 32% Vs 39% (RR 1.22, CI1.00 to 1.50)

Implantation rate (IR) - 50% Vs 35% (RR - 0.71, CI 0.51 to 0.98)

Miscarriage rate (MR) - 5.3% Vs 11% (RR1.6333, CI 0.5227 to 5.1039)

Multiple Pregnancy rate (MPR) - 8% Vs 4%

Live birth Rate (LBR) per Intention to treat (ITT) - 41.3% Vs 44% (RR 0.95, 95% CI 0.72 to 1.26)

LBR per ET cycle - 63% Vs 56% (RR 1.23, 95% CI 0.77 to 1.94)

Our preliminary results suggest that despite greater availability of blastocysts for transfer in the TESA group, no difference in ART outcomes was observed between the groups.

Though the IR was statistically low with TESA, our primary outcomes LBR and MR were comparable.

TESA or MACS seem to offer similar outcomes. Considering the invasiveness with TESA, MACS can be offered for better sperm selection for couples with raised sperm DFI & failed implantation.

Limitations, reasons for caution

Small sample size. TESA is a surgical intervention

Wider implications of the findings

Optimal intervention for management of SDF still needs further research.

Trial registration number

CTRI/2019/07/020140
P-797 A novel method for establishing human embryonic stem cells independent of feeder cells
Authors: Cai B
Published: August 2021

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
O-228 The SSRI antidepressant Sertraline inhibits CatSper calcium channels in human sperm
Authors: Rahban R , Rehfeld A , Schiffer C , Brenker C , Palme D. Louise Egeberg , Wang T , Lorenz J , Almstrup K , Skakkebaek N E , Strünker T , Nef S
Published: August 2021

Study question

Do Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants affect the function of human sperm?

Summary answer

The SSRI-antidepressant Sertraline (e.g. Zoloft) inhibits the sperm-specific Ca2+ channel CatSper and affects human sperm function in vitro.

What is known already

In human sperm, CatSper translates changes of the chemical microenvironment into changes of the intracellular Ca2+ concentration ([Ca2+]i) and swimming behavior. CatSper is promiscuously activated by oviductal ligands, but also by synthetic chemicals that might disturb the fertilization process. It is well known that SSRIs have off-target actions on Ca2+, Na+, and K+ channels in somatic cells. Whether SSRIs affect the activity of CatSper is, however, unknown.

Study design, size, duration

We studied the action of the seven drugs belonging to the most commonly prescribed class of antidepressants, SSRIs, on resting [Ca2+]i and Ca2+ influx via CatSper in human sperm. The SSRI Sertraline was selected for in-depth analysis of its action on steroid-, prostaglandin-, pH-, and voltage-activation of human CatSper. Moreover, the action of Sertraline on sperm acrosomal exocytosis and penetration into viscous media was evaluated.

Participants/materials, setting, methods

The activity of CatSper was investigated in sperm of healthy volunteers, using kinetic Ca2+ fluorimetry and patch-clamp recordings. Acrosomal exocytosis was investigated using Pisum sativum agglutinin (PSA) and image cytometry. Sperm penetration in viscous media was evaluated using the Kremer test.

Main results and the role of chance

Four SSRIs increased [Ca2+]i, two out of which also attenuated ligand-induced Ca2+ influx via CatSper. In contrast, Sertraline decreased [Ca2+]i and almost completely suppressed ligand-induced Ca2+ influx via CatSper. Remarkably, the drug was about four-fold more potent to suppress prostaglandin- versus steroid-induced Ca2+ influx. Sertraline also suppressed alkaline- and voltage-activation of CatSper, indicating that the drug directly inhibits human CatSper. Finally, Sertraline suppressed ligand-induced acrosome reaction and sperm penetration into viscous media.

Limitations, reasons for caution

This is an in vitro study. Future studies have to assess the physiological relevance in vivo.

Wider implications of the findings

The off-target action of Sertraline on CatSper in human sperm might impair the fertilization process. In a research setting, Sertraline may be used to selectively inhibit prostaglandin-induced Ca2+ influx.

Trial registration number

CRU326
O-238 Preterm birth after recurrent pregnancy loss: A systematic review and meta-analysis
Authors: Wu C , Nichols K , Carwana M , Nicholas C , Maratta C
Published: August 2021

Study question

What is the impact of recurrent pregnancy loss on the risk of preterm birth?

Summary answer

Women with RPL were found to be at increased odds of having preterm deliveries (<37 weeks gestation) in their subsequent live pregnancies.

What is known already

Recurrent pregnancy loss (RPL) occurs in up to 5% of all women with miscarriages. The emotional, physical, and financial burden associated with RPL is unequivocal, and over the years, much research has gone into the management of RPL. However, relatively little is known about the perinatal outcomes following RPL. Past research in the area reports conflicting data on the association between RPL and preterm birth (PTB) in a subsequent pregnancy.

Study design, size, duration

A systematic search was performed across thePubMed, EMBASE and Google Scholar databases for relevant studies published up until October 2020. Observational cohort and case-control studies comparing the risk of preterm birth (PTB) among women with and without a history of RPL were included. Effect estimates were pooled using a DerSimonian and Laird random-effects meta-analysis model. Study appraisal was performed using the Newcastle-Ottawa scale.

Participants/materials, setting, methods

We included studies where the study population consisted of women with a history of RPL (defined as 2 or more pregnancy losses), where the comparator group consisted of women without a history of RPL, and where the outcomes assessed included PTB (defined as birth prior to 37 completed weeks gestation). Two reviewers independently extracted data in duplicate. Publication date, population, exposure and outcome data were extracted.

Main results and the role of chance

A total of 12 retrospective observational studies met inclusion criteria, and were included in the systematic review and meta-analysis (N = 37,046 women with a history of RPL). Incidence of PTB among the RPL groups ranged from 5.8% to 19.6%, and from 1.5-14.0% in the non-RPL groups. A pooled OR of 1.59 with 95% CI 1.40-1.80 was observed in our random-effects meta-analysis with an I2 of 84%. Subgroup analyses were completed for the pooled risk of only 2 RPL (pooled odds ratio [OR] 1.35; 95% CI 1.08-1.69; I2=84.7%); ≥2 RPL (pooled OR 1.42; 95% CI 0.91-2.22; I2=68.9%); and ≥3 RPL (pooled OR 1.86; 95% CI 1.51-2.29; I2=79.5%).

Limitations, reasons for caution

Inconsistent adjustment for confounders and significant between-study heterogeneity were noted in this study.

Wider implications of the findings

Despite significant heterogeneity among studies, we found that women with a history of RPL had significantly higher odds of delivering preterm infants in their subsequent pregnancies.

Trial registration number

CRD 224763
P–003 Transposon insertion profiling by sequencing (TIPseq) identifies novel LINE–1 insertions in human sperm
Authors: Berteli T , Wang F , McKerrow W , Navarro P , Fenyo D , Boeke J , Kohlrausch F , Keefe D
Published: August 2021

Study question

Do human sperm contain novel LINE–1 insertions and are they affected by paternal age?

Summary answer

Human sperm contain novel LINE–1 insertions. Their location or number are not affected by paternal age.

What is known already

LINE–1 comprises 17% of the human genome and some LINE–1s are the only autonomous retrotransposons in humans. Retrotransposons influence genomic instability and/or regulation if new retrotransposition events disrupt coding or regulatory regions in the host genome. Demethylation during germ cell development de-represses retrotransposons. Advanced paternal age is associated with genomic instability. Previously we showed that sperm LINE–1 copy number decreases with paternal age. We hypothesize that human sperm exhibit de novo retrotransposition and that sperm from older men contain increased novel LINE–1 insertions.

Study design, size, duration

Cross-sectional case–control study with semen samples collected between February to July 2020.

Participants/materials, setting, methods

Normospermic sperm samples (n = 10; 5 <35 years old and 5 ≥45 years old) obtained from consenting men undergoing IVF at NYU Fertility Center were submitted to a novel method, single cell Transposon Insertion Profiling by Sequencing (scTIPseq) to identify and map LINE–1 insertions in human sperm. TIPseqHunter, a custom bioinformatics pipeline, compared the architecture of sperm LINE–1 to known LINE–1 insertions from the European database of human specific LINE–1 (L1Hs) retrotransposon insertions in humans (euL1db).

Main results and the role of chance

TIPseq identified 17 novel insertions in sperm, 8 from older (≥ 45 years) and 9 in younger men (<35 years). New insertions were mainly intergenic or intronic, including AC007402 (2/10), TMEM163 (2/7), CTTNBP2NL (3/5), AC107023 (3/3), TMC2 (2/19), MacroD2 (2/6), RAB3C (3/4), LINC02664 (1/1), AC079052 (2/3) and AC017091 (4/4). One novel insertion (<35 years old) hits a known regulatory element. Only one sample (≥ 45 years old) did not exhibit any new insertion. The location or number of novel insertions did not differ by paternal age.

Limitations, reasons for caution

The small sample-size and use of normospermic specimens limit interpretation of paternal age effect on LINE–1. Besides, the novel insertions could be polymorphic sites that have low allele frequency and thus have not yet been described.

Wider implications of the findings: This study for the first time reports novel LINE–1 insertions in human sperm, demonstrating that scTIPseq method is a feasible technique, and identifying new contributions to genetic diversity in the human germ line. Further studies are needed to evaluate the impact of these insertions on sperm function.

Trial registration number

Not applicable