bluuebunny/crossref_metadata_2025 huggingface dataset:
P-769 fertility treatments and the risk for long-term respiratory morbidity of the offspring; a sibling analysis
Authors: Lavi T , Pariente G , Sheiner E , Gutvirtz G , Zeadna A , Steiner N , Wainstock T
Published: June 2023

Study question

Is the risk of long-term respiratory morbidity increased among children born following fertility treatments (in-vitro fertilization and ovulation induction)? Sibling analysis to maximize confounder control.

Summary answer

Fertility treatments do not appear to be an independent risk factor for long-term respiratory morbidity of the offspring up to 18 years of age.

What is known already

Studies have found an association between fertility treatments and long-term respiratory morbidity of the offspring, specifically obstructive sleep apnea (OSA).

Study design, size, duration

A retrospective population-based cohort analysis was performed, including all sibling deliveries occurring between 1991 and 2021 at a tertiary medical center. Offspring were followed-up until the age of 18 years.

Participants/materials, setting, methods

The study population included 10,691 siblings of women who had at least one spontaneous pregnancy and at least one pregnancy following fertility treatments. A Kaplan–Meier survival curve was used to compare the cumulative respiratory morbidity incidence, and a multivariable Cox survival hazards regression model was used to control for confounders.

Main results and the role of chance

There were 5,869 siblings (54.9%) conceived following fertility treatment and 4,822 spontaneously conceived siblings (45.1%). Using a univariable analysis, respiratory morbidity was higher among siblings born following fertility treatments as compared with those conceived spontaneously (9.6% vs. 8.4%; p = 0.023), in particular, OSA (2.6% vs. 1.8%; p = 0.005). However, using a Kaplan-Meier survival curve, being born following fertility treatments did not have a higher cumulative incidence rate of long-term respiratory morbidity (Log-Rank, p = 0.339). Likewise, when using a Cox regression model, controlling for confounders such as maternal age, diabetes mellitus, preterm delivery, and hypertensive disorders, the association between being born following fertility treatments was no longer associated with long-term respiratory morbidity (adjusted HR = 1.0, 95% CI 0.88-1.14, p = 0.957).

Limitations, reasons for caution

This retrospective cohort study can only provide evidence of association but not causation. Also, our study results are hospital-based diagnoses of respiratory morbidity which most likely represent acute and severe disease.

Wider implications of the findings

In this large retrospective cohort study of siblings, we showed that, in contrary to current literary findings, and after matching for siblings, fertility treatments are not associated with long-term respiratory morbidity of the offspring. These findings raise questions about the existence of certain maternal predispositions that may associate the two.

Trial registration number

Not applicable
P-770 Risk factors for placenta accreta spectrum among pregnant women conceived with assisted reproductive technology
Authors: Li C , Li T , Wu Y T , Huang H F
Published: June 2023

Study question

What are the risk factors for placenta accreta spectrum (PAS) among women conceived with assisted reproductive technology (ART)?

Summary answer

The risk of PAS was associated with elevated estradiol and progesterone levels during COH, and HRT protocol, and abnormal endometrial thickness when preforming FET.

What is known already

Increasing evidence suggests an association between ART and PAS. Some studies have reported a high rate of diagnosis of PAS after embryo transfer compared to those with spontaneous conception. Despite this, little is known about the detailed risk factors for PAS during the procedures of ART.

Study design, size, duration

This retrospective case-control study included 1541 pregnant women with live birth conceived ART between 2013 and 2019 in a university hospital.

Participants/materials, setting, methods

Pregnant women were categorized into case and control group according to the postpartum diagnosis of PAS. The associations between PAS and ART procedures were estimated using multivariate logistic regression, and represented as adjusted odds ratio (aOR) and 95% confidential interval (CI).

Main results and the role of chance

Among all pregnant women in this study, 118 were delivered with PAS, and 1423 were delivered without PAS. During the procedures of COH and oocytes retrieval, elevated levels of estradiol (aOR=1.03, 95% CI: 1.01-1.06) and progesterone (aOR=1.02, 95% CI: 1.00-1.04) were found to be associated with the risk of PAS. The number of oocytes retrieved over 10 were also found to have an association with PAS (aOR=1.58, 95% CI: 1.05-2.37). Additionally, FET was another risk factor forPAS (aOR=1.93, 95% CI: 1.06-3.51). Among pregnant women with FET, preparing the endometrium using HRT protocol increased the risk of PAS (aOR=2.46, 95% CI: 1.57-3.84). Notably, PAS was also found to have an association with abnormal endometrial thickness after preparing the endometrium, whether too thin (<7mm: aOR=15.90, 95% CI: 4.42-57.21) or too thick (>14mm: aOR=6.56, 95% CI: 1.84-23.45).

Limitations, reasons for caution

As a hospital-based study, several confounders related to medical procedures have been taken into consideration. However, it is not possible to rule out unknown confounders.

Wider implications of the findings

Caution is warranted when preforming COH, and endometrial preparation before FET due to the increased risk of PAS after deliveries.

Trial registration number

NA
O-092 Does embryo biosensing really determine endometrial fate decisions at implantation?
Authors: Brosens J
Published: June 2023

Implantation depends on bi-directional communication between the blastocyst and endometrium. Encoded in this communication is information on maternal and embryonic fitness, which in turn can lead to the activation of species-specific reproductive suppression mechanisms. For example, blastocysts in over 130 mammals, although not humans, respond to the presence or absence of specific endocrine or endometrial cues by entering or exiting diapause, a state of suspended animation that leads to postponement of implantation. By contrast, embryo biosensing and selection depend on the endometrium first receiving and decoding fitness information from the conceptus and then either promoting implantation or initiating rapid tissue breakdown, thus limiting maternal investment into a failing pregnancy. Importantly, embryo selection relies on physiological mechanisms that sense deleterious (internal/external) cues, which is fundamentally different from reproductive failure caused by disease or trauma. Nevertheless, physiological embryo selection is easily conflated with pathology. For example, repeated implantation failure of low-fitness IVF embryos can lead to the diagnosis of ‘recurrent implantation failure’, an ill-defined clinical label, which often spurs uninformative investigations and ineffective ad-hoc treatments. On the other hand, pathological relaxation of embryo selection at implantation causes early pregnancy loss, with the frequency of affected cycles determining the age-independent recurrence risk of miscarriage. In this presentation, I will elaborate on the cellular mechanisms that control embryo biosensing and selection, highlight the clinical consequences, and discuss emerging strategies for pre-pregnancy optimisation of the endometrium.

Trial registration number

XXXX
O-108 C-section scar defect: Hysteroscopic vs laparoscopic repair
Authors: Mashiach R , Burke Y Z
Published: June 2023

Objective: To present a systematic review of the literature on the hysteroscopic and laparoscopic repair of cesarean scar niche and offer an evidence-based approach to the treatment of cesarean scar niche.

Data sources: A thorough search of the PubMed/Medline, Embase, and Cochrane databases was performed. (PROSPERO registration number CRD42020190668).

Methods of study selection: Studies from the last 20 years that addressed cesarean scar niche repair were collected. Both authors screened for study eligibility and extracted data. All prospective and retrospective studies of more than ten women were included.

Tabulation and integration: The initial search identified 666 articles [PRISMA flow chart]. We excluded duplicates, case reports, reviews, video articles, and technique articles. We also excluded studies describing only laparotomy or vaginal repair as these were not of the scope of this review.

A total of 31 articles met the inclusion criteria, 21 for hysteroscopic resection and 13 for laparoscopic or combined repair (4 articles tested both modalities and appear in both tables).

Results: For abnormal uterine bleeding (AUB), hysteroscopic remodeling relieved symptoms in 60%-100% of cases and laparoscopy in 78%-94%. Secondary infertility was not evaluated in all studies. We found that after hysteroscopic and laparoscopic treatment, 46%-100% and 37.5%-90% of those who wished to conceive became pregnant following the procedure, respectively.

Pain and dysmenorrhea seem to be uncommon. All studies that tested improvement of pain had less than ten women. However, it would appear that between 66% and 100% of women who complain of pain or dysmenorrhea will note a marked improvement to full resolution.

Conclusion: cesarean scar niche or cesarean scar defect is usually asymptomatic. For symptomatic women, a repair is a valid option. For those with RMT (Residual Myometrial thickness) >2-3 mm, hysteroscopic remodeling is the modality of choice with an improvement in AUB, secondary infertility, and pain. For women with a RMT <2-3 mm, laparoscopic repair with simultaneous hysteroscopic guidance shows similar results. Since available data is limited, no cutoff for the correct choice between hysteroscopy or laparoscopy can be concluded. We recommend 2.5 mm as the cutoff value based on common practice and expert opinion, although no significance between hysteroscopic and laparoscopic treatment was shown.
O-109 Avoiding the C-section scar defect
Authors: Kalem Z , Namli Kalem M
Published: June 2023

The cesarean scar defect was first described in 1961 by Poidevin et al. Cesarean delivery is one of the most common surgeries today, and millions of women give birth this way every year. The prevalence of cesarean scar defect is increasing due to increasing cesarean section rates. The cesarean scar defect is called by different names in the literatüre, such as isthmocele, niche, diverticulum, dehiscence of the cesarean scar. It was discovered that the prevalence of isthmocele varied widely. Using contrast-enhanced sonohysterography, the prevalence in a random group of women with a history of CS was between 56% and 84%, whereas the incidence in pelvic ultrasonography fluctuates between 6% and 36%.

The most common gynecological problems that may occur due to isthmocele are menstrual spotting, dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. The likelihood of scar pregnancy, placentation abnormalities, and uterine rupture increases with subsequent pregnancies. Both hysteroscopic and laparoscopic isthmocele repair techniques are highly effective. Therefore, precautions against isthmocele during cesarean delivery should be made more transparent.

The development of isthmocele is influenced by the timing of the cesarean section (during pre/early or advanced labor), the position of the uterine incision (its distance or proximity to the internal os of the cervix), and the opening and closing (suturation) method of the uterine incision. Once more, both gestational diabetes and being overweight might be viewed as independent risk factors.

Understanding the risk factors for isthmocele development will aid in the development of preventative measures. The two most crucial elements in the formation of isthmocele, according to our knowledge of the literature, are the site of the uterine incision and the suture methods. In this presentation, we will discuss ways to prevent the development of isthmocele.
O-167  The good egg: on the onset of transcription in mouse and human embryos
Authors: Perry A
Published: June 2023

At the moment of union in fertilisation, sperm and oocyte are transcriptionally silent, but little is understood about how transcription initiates in the newly-formed embryo. In this talk, I shall suggest why this fundamental process has remained arcane for so long, and how my lab has sought to unlock its secrets in mouse and human embryos. By combining micromanipulation and single-cell RNA-sequencing, we have revealed a programme of embryonic transcription initiation beginning within four hours of fertilisation in the mouse. The talk will outline our efforts to characterise this initiating transcription, and its conservation in human one-cell embryos. Transcribed genes predict regulation by oncogenic factors, including c-Myc, whose features will be detailed, together with a model suggesting predictive parallels between the onset of embryogenesis and cancer.

Trial registration number

XXXX
O-168 The dark shadow of historical eugenics on reproductive technologies and practices
Authors: Cavaliere G
Published: June 2023

Eugenics is often referred to in discussions on the ethics of reproductive technologies. References to the word “eugenics” are often used to draw distinctions between ethically permissible and impermissible technologies, and permissible and impermissible uses of these technologies. While historians have long argued that 20th century eugenics cannot be reduced to a uniform set of practices, references to eugenics in discussions on the ethics of reproductive technologies have proven difficult to eradicate. Some authors stress the similarities between past eugenics and present reproductive technologies (what I define here as “the continuity view”) to condemn these technologies. Others focus instead on the differences between past and present (what I define here as “the discontinuity view”) to defend reproductive technologies.

In this talk, I canvass the meanings and uses of the word “eugenics” in relation to the permissibility of reproductive technologies and argue that disagreement concerning the value and ethical standing of these technologies originates in divergent views of condemnable and justifiable features of the past. Moreover, I suggest focusing on the reproductive preferences of those accessing fertility treatment as a starting point for any analysis concerning the permissibility of novel reproductive technologies.

Trial registration number

XXXX
O-171 Psychological support: the light in the darkness of my infertility journey
Authors: Dumont S
Published: June 2023

Sandrine Dumont shares her own personal patient experience : « my infertility journey started at the age of 32, when I was finally diagnosed with endometriosis after years of pain. I went through one year of natural but monitored baby trials, 4 artificial inseminations, a break-up with my then partner, and 3 IVF with my new partner : these 3 IVF took place during a short period of 5 months. First IVF was in a public hospital, who kicked us out after first IVF failed. Other two IVF took place in a private hospital in Paris, who incidentally diagnosed PCOS : both IVF were also unsuccessful. I was physically and psychologically exhausted, and then decided to take a break from fertility treatments. We expected information and guidance from both fertility centers to help us through this. It never came.

During all these years, we’ve been appalled with how very few information we were given from all the medical staff. We were never prepared for failure at all. We felt treated badly, even in a rude and sometimes brutal way, by some professionals. Patient care was almost inexistent. We felt like a mere number on a list, not worth being explained anything or just answered our legitimate and simple questions about our own case. We were left alone with our doubts and questions: how could we make an enlightened decision as whether to continue treatments or not, with no information to nurture this decision ?

It seemed an endless dark tunnel with no exit. Then came guilt, loneliness and depression. I searched for external psychological support to help us get through this: this was not easy, since psychological weakness was something to be very ashamed of at the time, in French society. Psychological support turned out to be the light in our darkness. I found a psychiatrist to whom I went weekly for almost two years. This is what it took to heal : accepting failure, accepting my own limits to what I was ready to endure to try to be a mother, accepting to be different from what is expected of a woman in our traditional French society. This therapy was a lifesaver. There also came the association Collectif Bamp, thanks to whom I met a two women in the same situation as me. Knowing I was not alone just changed everything : it was the first day of the rest of my life.

Today, 10 years later, I am now an active member of Bamp association : I try to be there for patients as Bamp was there for me. I share my experience, so people don’t feel alone. I advocate pyschological support and real patient care.
O-173 Cellular and developmental damage from oocyte cryopreservation
Authors: Comizzoli P
Published: June 2023

Compared to somatic or sperm cells, mammalian oocytes are much more sensitive to cryopreservation mainly because of the large volume, cytoskeleton, and presence of the zona pellucida. Connections with the surrounding cumulus cells also are challenging to preserve in immature oocytes. Besides the genetic and epigenetic information enclosed in the nucleus, oocytes contain organelles and cytoplasmic factors that are necessary for the early embryo development. Therefore, exposure to cryoprotectant and freezing temperatures can easily damage the oocyte’s complex cellular structure and developmental competence, which leads to poor success in fertilization, lower embryo quality, and reduced pregnancy rates. Using the domestic cat as a model, our laboratory has studied damages in cumulus-oocyte complexes (immature oocytes) occurring at each step of the cryopreservation process. Specifically, this included the impact of cryoprotectants on microtubules, the effect of osmotic changes on the overall structures, as well as sensitivity of the nuclear chromatin and epigenetic patterns to freezing temperatures. Based on those findings, it has been possible to design mitigating solutions like customized ultra-rapid freezing or vitrification protocols, Laser-warming methods, or post-warming reanimations. New horizons have also been explored to move away from issues and limitations related to cryopreservation. Approaches like storage of oocytes for the long-term at non-freezing temperatures are currently being developed based on encouraging data generated in preliminary studies. For instance, incorporation of trehalose into the oocyte followed by microwave-assisted dehydration can allow to remove enough water while creating a protective trehalose glass compatible with survival and storage at non-freezing temperatures. Interestingly, transcriptomic and proteomic studies have already shown that stresses and damages induced by dehydration versus cryopreservation are different and may be easier to overcome.
O-204 Treatment of unexplained infertility: IUI for all?
Authors: Bhattacharya S
Published: June 2023

Study question

What is the recommended management for couples presenting with unexplained infertility, based on the best available evidence in the literature?

Summary answer

The ESHRE Guideline on Unexplained infertility makes 19 recommendations on treatment of couples with unexplained infertility.

What is known already?

Unexplained infertility (UI) is diagnosed in the absence of any abnormalities of the female and/or male reproductive systems after “standard” investigations. The management of UI is traditionally empirical. The efficacy, safety, costs, and risks of treatment options have not been subjected to robust evaluation.

Study design, size, duration

The guideline was developed according to the structured methodology for the development of ESHRE guidelines. Following formulation of key questions by a group of experts, literature searches and assessments were undertaken. Papers written in English and published up until 24 October 2022 were included. Prior to publication, the guidelines were reviewed by independent international reviewers.

Participants/materials, setting, methods

Based on the available evidence, recommendations were formulated and discussed until consensus was reached within the guideline group. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline group and the ESHRE Executive Committee.

Main results and the role of chance

This guideline aims to help clinicians provide the best care for couples with unexplained infertility. The first-line treatment for couples with unexplained infertility was deemed to be intra-uterine insemination (IUI) in combination with ovarian stimulation. This lecture will focus on the rationale behind this recommendation and the place of additional and alternative options for the treatment of unexplained infertility.

The guideline has been in stakeholder review and is prepared for submission in 2023.

Limitations, reasons for caution

Most interventions in couples with unexplained infertility have not been subjected to robust evaluation. For a large proportion of these treatments, evidence was very limited and of very low quality. More evidence is required, and the results of future studies may require the current recommendations to be revised.

Wider implications of the findings

The guideline provides clinicians with clear advice on best practices in the care of couples with unexplained infertility, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in the field.

Study funding/competing interest(s)

The guideline was developed by ESHRE which funded the guideline meetings, the literature searches and dissemination. The guideline group members did not receive any financial incentives; all work was provided voluntarily.
O-243 Personalized pregnancy odds estimation can be obtained using AI embryo evaluation and individual patient characteristics
Authors: Seidman D , Maor R , Tauber Y , Amar Y , Gilboa D
Published: June 2023

Study question

Can EMATM (AIVF, Israel) artificial intelligence (AI) platform provide personalized success estimates based on the patient’s metadata and embryonic development?

Summary answer

Individual patients can be given an accurate estimation of their chances for a clinical pregnancy using AI-based embryo evaluation and patient metadata.

What is known already: AI models for embryo evaluation are trained on diverse datasets using data from multiple clinics and from patients with varying ages and clinical history. Precision medicine can be attained by AI models that provide individual patients with personalized success rates per embryo transfer based on their characteristics.

Study design, size, duration

A large dataset (9,812 embryos) from 3 geographically diverse IVF Clinics (Israel, Spain, USA) with known clinical pregnancy (fetal heartbeat) and patient characteristics obtained from Electronic Medical Records (EMR) were used to evaluate the importance of individual features contributing to pregnancy.

Participants/materials, setting, methods

Machine learning models were trained to predict clinical pregnancy on a large training and feature set which combines AI scores (EMATM, AIVF) with additional information obtained from EMR systems and intrinsic features that can be derived from the embryo cohort. The importance of each one of the features for the prediction ability of the models was evaluated.

Main results and the role of chance

AI embryo score, maternal age and cohort features were found to be the major contributing factors for the prediction models, thus improving the accuracy of the estimates for pregnancy probability. Significant contributing factors were: cohort size, number of viable embryos, patient age, number of past treatments, BMI and EMA score. The AUC of the AI embryo score model was 0.7, when factoring in the patient metadata and the cohort features, the AUC of the combined model was 0.75.

Limitations, reasons for caution

This study is limited by its retrospective design. A prospective study is needed to validate the results.

Wider implications of the findings

This study validates the use of AI-based scores for embryo evaluation, for relative grading of the embryos within the cohort, and also to estimate the true pregnancy odds of each embryo based on individual patient features. This can provide a superior decision support tool for doctors, embryologists, and patients.

Trial registration number

not applicable
O-249 Calcium directly influences pituitary function through the Calcium Sensing Receptor (CaSR)
Authors: Poulsen N N , Hjerresen J , Juel Mortensen L , Sørensen K , Juul A , Blomberg Jensen M
Published: June 2023

Study question

Does calcium have a direct effect on pituitary function through CaSR?

Summary answer

CaSR is important for Hypothalamus-pituitary-gonadal (HPG) axis signaling, and lack of CaSR in the anterior pituitary leads to smaller reproductive organs in female mice.

What is known already

In a randomized clinical trial, prepubertal children were given calcium supplementation or placebo and girls in the intervention group went into puberty 5 months earlier than the placebo group. This effect was not detected in the boys who participated. CaSR is the main receptor for systemic calcium homeostasis, and its presence has been established in the anterior pituitary.

Study design, size, duration

We performed a mouse study comparing knock-out mice with a deletion of the CaSR in the anterior pituitary to wildtype mice. 13/13 female and 6/13 male knock-out/controls mice were included in the study.

Participants/materials, setting, methods

Female and male knock-out and control mice were sacrificed at 8 weeks. We obtained blood samples and reproductive organs was dissected, weighted and stored at -80 °C or stored in formalin before being paraffin embedded.

Main results and the role of chance

Female reproductive organs showed significantly lower weight when comparing CaSR knock-out to control mice. This includes ovary weight (3.7 mg vs. 6.4 mg; p = 0.0004) and uterus weight (27.9 mg vs. 67.0 mg; p = 0.0008). The weight difference was still significant after correcting for total body weight (organ weight/total body weight%): (0.02176 vs. 0,03534; p = 0.0035 and 0.1788 vs. 0.3826; p = 0.0023 respectively).

We did not observe a significant difference in male reproductive organs, nor any difference in pituitary weight in either sex.

Limitations, reasons for caution

The difference in reproductive organ weights is interesting, but it is also an early finding. Further analysis of the collected organs and blood samples will be conducted to further investigate the phenotype of the mouse model. We are also looking into correcting weight differences for estrous cycle effects.

Wider implications of the findings

If CaSR proves to be important for the regulation of the HPG-axis, it has a clinical perspective since CaSR can be modulated by the drug Cinacalcet, an allosteric agonist of CaSR, already on the market where it is used to treat kidney patients.

Trial registration number

Not applicable
O-280 Reading between the lines: Evaluating the clinical benefit of laboratory interventions from published studies
Authors: Wilkinson J
Published: June 2023

Embryologists rely on both randomised and non-randomised studies evaluating the effectiveness and safety of interventions. However, many of these studies contain subtle but critical methodological limitations, which are not identified by peer reviewers. Embryologists must therefore be critical consumers of the published literature. In this talk, I will highlight some common, serious methodological flaws occurring in studies of embryological interventions, and will give intuitive explanations of both the problems and the impact they may have on study results. This includes methods of analysing randomised controlled trials which nullify the benefits conferred by randomisation, and flawed methods of identifying study groups in observational studies which prevent any meaningful evaluation of an intervention's benefit. I will discuss underappreciated methodological challenges in studies evaluating artificial intelligence algorithms for embryo selection, which limit their usefulness, and will outline superior approaches to evaluate these interventions.
P-003 Obstructive azoospermia; MESA should be employed as the method for sperm retrieval, not TESE
Authors: Hibi H , Sonohara M , Sugie M , Fukunaga N , Asada Y
Published: June 2023

Study question

TESE is widely used for obstructive azoospermia (OA) as a surgical method for sperm retrieval, but is it benefiting the patient?

Summary answer

Since MESA-ICSI has a very good fertilization rate, clinical pregnancy rate and delivery rate, MESA should be employed for the OA subjects, not TESE.

What is known already

TESE and micro-TESE are technically simple, and widely used as a sperm retrieval surgery because they do not require microsurgical skills. Some review articles have shown no significant differences in the rates of cleavage, good-quality embryos, implantation, clinical pregnancy between ICSI with epididymal sperm or testicular sperm. Clinical usefulness of MESA is still controversial according to previous reports.

Study design, size, duration

We studied 110 patients diagnosed with OA and treated with MESA at the Asada Ladies Clinic between April 2004 and December 2021.

Participants/materials, setting, methods

The MESA was performed using a micropipette with a micropuncture technique under operative microscope. When no sperm were present or motility was not observed, additional punctures to the epididymal tubule were performed. Aspirated samples were transferred into modified human tubal fluid and sent to the in vitro fertilization (IVF) laboratory for cryopreservation.

Main results and the role of chance

Motile sperm were recovered in all cases (110 cases). Of these, ICSI using frozen thawed sperm was performed in 101 cases. The rate of normal fertilization rate was 76%. Of the 399 embryo transfer (ET) cycles, 168 had a clinical pregnancy (41% per ET). Of the 101 patients who underwent ART, 94 (93% per case) had clinical pregnancies resulting in 90 (89.1%) deliveries. It should be emphasized that since MESA does not involve incision of the testes, there are fewer postoperative peritoneal irritation symptoms and no concerns about postoperative testicular atrophy or low testosterone levels. Some review articles showed no significant differences in the rates of cleavage, good-quality embryo, implantation, clinical pregnancy between ICSI with epididymal sperm or testicular sperm. Although clinical usefulness of MESA is still controversial, if the ART results of MESA-ICSI and TESE-ICSI are the same, MESA should be performed as it is less invasive on the patient and reduces the burden on the embryologist who have to process the TESE tissue.

Limitations, reasons for caution

Some authors have reported that since MESA specimens contain DNA fragmentated sperm when compared with specimen of TESE, subsequent ICSI results in poorer fertilization and pregnancy rates. We did not evaluate sperm DNA fragmentation.

Wider implications of the findings

A large quantity of uncontaminated sperm can be retrieved using MESA which is less invasive for the patient, and there is no need for special processing before cryopreservation. Additionally, it can reduce the laboratory workload.

Trial registration number

not applicable
P-012 Time, risk & motion study of an integrated artificial intelligence robotic system for semen analysis
Authors: Hill K , Alvarez M , Mora F , Thomas D , Tozer A , Viñals Gonzalez X
Published: June 2023

Study question

Can integration of a robotic system for semen analysis reduce operational failure modes and eliminate risk in the IVF laboratory?

Summary answer

A robotic system for semen analysis reduces operational failure modes and eliminates severe risks including those associated with reduced patient experience and increased patient stress.

What is known already

Recently, the ever-evolving field of IVF has experienced a rise in innovations to boost laboratory performance. Considering the lack of robust evidence in some of them, decisions on implementation are often based on opinion and product cost. Currently, an approach to assess risk, time and effectiveness has not been fully described. IVF is not error-free (Sakkas et al., 2018), hence all new technology coming into the laboratory ought to reduce risk of errors happening.

Study design, size, duration

Failure mode effects analysis (FMEA) was carried out on the workflow integration into an IVF centre (>500 cycles per annum) to evaluate the possible procedural risks of manual semen analysis compared to a digitalised pathway. Possible sources of error were identified, and the Risk Priority Number (RPN), a product of likelihood, severity and detection of incidence was associated with each risk, as previously described by Rienzi et al., 2015.

Participants/materials, setting, methods

Using a systematic decision-making approach to quantify the value of incorporating the use of a robotic system (Mojo AISA) for semen analysis.

Main results and the role of chance

Five process phases were identified for conventional specimen analysis. There were eight associated process steps and 29 failure modes, among which 13 risks were given a moderate (RPN 15-50, i.e. data entry errors, incorrect count and sperm classification) and three were severe RPNs (RPN>50), resulting in reduction in efficacy of treatment. Protocol using the robotic system resulted in a reduction of process phases to four and failure modes to 16, with four moderate and none severe RPNs. Implementation of the robotic system improved workflow by optimising time in motion for the IVF specialist and further reducing active time by at least 30%.

Limitations, reasons for caution

FMEA is a proactive method to identify potential incidents and help to develop strategies to mitigate risks. Ultimately, this forms part of a scheme for responsible development. The likelihood of incidences and time analysis were estimated based on clinical experience. Risks inherent to sample handling remained present.

Wider implications of the findings

The robotic system has the potential to eliminate risks that exist when manually inputting data to electronic medical records, whilst offering support to IVF specialists.

Trial registration number

not applicable
P-017 Validation of origami microscope “Foldscope” as a preliminary screening tool for male infertility
Authors: Errazuriz J , Carlos C , Alvaro S M , Isabel F , Pablo S , Patricio G , Patricio D
Published: June 2023

Study question

Is there a concordance between the new optical microscope based on origami (Foldscope) with a traditional microscope for semen analysis as a screening method?

Summary answer

There is a 91% direct concordance between the foldscope and a traditional microscope as screening for initial approximation to male infertility.

What is known already

Semen analysis is a key element on men fertility evaluation. In order to obtain a semen sample, patients have to assist to a fertility clinic where the sample is analyzed. However, due to either time or distance problems, many patients cannot attend to fertility clinics. On the other hand, Foldscope is an origami-based microscope that can provide over 2000x magnification, and it can be attached to a smartphone and take photos and videos, which can be sent to fertility specialists for analysis. This technology might provide important information about semen status, especially in areas with limited fertility care access.

Study design, size, duration

A retrospective observational study was carried out, we included semen samples obtained by masturbation from volunteers were analyzed for count, concentration, and motility from patients who were undergoing a fertility study between November 2021 and November 2022 in Clínica Alemana, Santiago, Chile.

Participants/materials, setting, methods

A total of 188 human semen samples were evaluated by a single embryologist under a standard microscope and later used the same sample to make a cell phone video with Foldscope. This information was randomized and the videos were subsequently analyzed by the same embryologist blindly. Finally, the matching of the results was carried out.

Main results and the role of chance

Moderate and significant positive correlation for concentration calculated as > or < 15 million/ml between Conventional Microscopy and Foldscope (correlation coefficient= 0.67, p < 0.005) Sperm motility for progressives A+B recorded with Foldscope demonstrated a significant correlation with the traditional microscope results (correlation coefficient = 0.69, p < 0.005). Finally, the concordance for the sperm count between both methods was 91%, with a kappa index of 0.66 (p < 0.0001).

Limitations, reasons for caution

One of the most important limitations of semen analysis by foldscope is that it must be interpreted by an embryologist, which means that the images must be sent to a specialized center.

Wider implications of the findings

In countries with few economic resources and not many options to for reproductive medicine centers, the use of the foldscope microscope as a screening as an initial approximation to male fertility allows a quick and economical immediate referral to men with reproductive problems.

Trial registration number

not applicable
P-024 Effect of microsurgical varicocelectomy on fertility potential in patients with low sperm vitality
Authors: Mahdi M , Majzoub A , Arafa M , Elbardisi H , Khalafalla K , Alsaid S , Al Malki A
Published: June 2023

Study question

Does microsurgical varicocelectomy improve semen parameters and fertility potential in patients with low sperm vitality?

Summary answer

Micro surgical varicocelectomy in patients with low sperm vitality is beneficial as it results in significant improvement in sperm count and progressive motility.

What is known already

Low sperm vitality (Necrozoospermia) indicates the presence of higher percentage of necrotic/ dead sperm in the ejaculate which can impair fertility potential. Varicocele induced testicular hyperthermia is among the most common causes of impaired semen quality, including necrozoosprmia. While many studies confirmed the beneficial effect of varicocelectomy on different semen parameters, very few have evaluated its role on sperm vitality in particular.

Study design, size, duration

A retrospective study of 1521 patients who underwent microsurgical sub inguinal varicocelectomy in our center from 2011–2021.

A total of 115 patients with clinical varicocele and low sperm vitality (<58%) were included.

Participants/materials, setting, methods

The exclusion criteria were history of genitourinary tract infection, exposure to heat, drugs or toxic compounds, hormonal disturbances or prior infertility related treatments. Patients demographics, and clinical data were collected, in addition to the pre- and post-operative Semen analysis (WHO 5th edition), sperm DNA fragmentation (Halosperm) and hormonal profile (estradiol, FSH, LH, Prolactin, Testosterone). Spearman’s correlations and Wilcoxon Signed Ranked Test were used for data analysis.

Main results and the role of chance

Mean age was 34.9±7.6 years. Varicocelectomy was done on left side in 75 patients and bilateral in 40 patients.

Sperm vitality was significantly negatively correlated with sperm DNA fragmentation (-0.618, p = 0.000) and abnormal sperm morphology (-0.435, p = 0.000, while it was significantly positively correlated with total motility (0.674, p = 0.000) & progressive motility (0.272, p = 0.003).

The median (IQR) sperm vitality pre-operatively was 41% (30-50) and the level increased post-operatively to 54% (31-63). There was a significant improvement in post-operative sperm count, progressive motility as well as LH and FSH levels. Improvements were also noted in total motility, normal morphology and sperm DNA fragmentation however the result didn’t reach statistical significance.

Limitations, reasons for caution

The main limitation is the retrospective design of the study and it did not evaluate the pregnancy outcomes.

Wider implications of the findings

Improvement in semen parameters by microsurgical varicocelectomy in patients with low sperm vitality is important as it may change the management plan for patients and extend their fertility options to natural conception or intrauterine insemination instead of only intracytoplasmic sperm injection.

Trial registration number

not applicable
P-028 Loss of the m6A methyltransferase METTL5 impairs spermiogenesis and male fertility
Authors: Chen H , Zhang M , Lin S , Xu W
Published: June 2023

Study question

Whether and how METTL5 regulates germ cell development during spermatogenesis.

Summary answer

METTL5 is required for spermiogenesis. Loss of METTL5 resulted in teratozoospermia and male infertility via reduced translation of acrosome and flagellum formation proteins.

What is known already

The roles of m6A modifications on mRNA in spermatogenesis have been extensively studied. It was reported that METTL5 knockout mice showed the brain development defect and sterility of 16-week male mice. However, the detailed mechanism of METTL5 affecting male fertility remains elusive.

Study design, size, duration

Mettl5 KO mice were kindly gifted from Prof. Shuibin Lin of The First Affiliated Hospital of Sun Yat-sen University. Heterozygotes of Mettl5 mice were used to generate Mettl5 homozygous knockout mice. The phenotype of KO mice was assessed. Ribosomal sequencing, proteomics analysis and further validation of protein translation were performed to explore the mechanism.

Participants/materials, setting, methods

Fertility assessment, sperm parameter analyses, sperm nuclear morphology analysis, Transmission electron microscopy (TEM), tissue Collection and histological analysis, protein extraction and western blot analysis, immunofluorescence studies, cDNA synthesis and qRT-PCR, in vitro fertilization (IVF) were used in this study.

Main results and the role of chance

Here we reported that methyltransferase-like 5 (METTL5) is involved in spermiogenesis as a methyltransferase mediating m6A modification on rRNA. Mettl5 knockout mice were infertile with teratozoospermia. The acrosome in the sperm head was absent with reduced sperm motility. Furthermore, the fertilization ability of sperm in the IVF experiment failed. Mechanistically, the level of rRNA m6A modification was significantly decreased in the testes of Mettl5 KO mice. The translational efficiency and protein levels of acrosome and flagellum formation proteins such as FSIP2, ODF2, GK2, PGK2, and AKAP4 were significantly reduced when METTL5 was depleted.

Limitations, reasons for caution

The METTL5 mutation in the patient with teratozoospermia was not examined in the present study

Wider implications of the findings

The rRNA m6A modification is also involved in regulating spermatogenesis by METTL5. This study highlights the critical role of rRNA epigenetic modifications during spermatogenesis and provides novel theoretical explanations for the m6A modifications.

Trial registration number

Not applicable
P-035 Effect of Varicocelectomy on normal semen in patients undergoing the procedure for indications other than fertility: evidence needed for counseling
Authors: Khalafalla K , Mahdi M , Majzoub A , Elbardisi H , AlSaid S , Arafa M
Published: June 2023

Study question

Does microsurgical varicocelectomy impact normal semen parameters in fertile patients undergoing the procedure for indications other than infertility?

Summary answer

Micro surgical varicocelectomy does not alter the fertility potential of men with normal semen.

What is known already

Varicocele repair results in improvement in semen parameters and fertility potential in sub fertile patients with clinical varicocele. However, the procedure is also offered to patients with indications other than infertility including testicular pain, testicular size affection, or before army recruitment. Queries about the effect of varicocelectomy on fertility potential in this patient population have been raised but unfortunately not strongly backed by literature.

Study design, size, duration

A retrospective study of 1521 patients who underwent microsurgical sub inguinal varicocelectomy in our center from 2011–2021.

Participants/materials, setting, methods

A total of 435 patients with normal semen parameters and underwent varicocelectomy for indications other than infertility were included. Exclusion criteria were patients with infertility, abnormal semen parameters, and prior varicocelectomy. Patient demographics, clinical and laboratory data were collected. Semen analysis (WHO 5th edition), sperm DNA fragmentation (Halosperm) & hormonal assay were performed pre-operative and up to 6 months post-operative. Data were compared using Wilcoxon Signed Ranked Test. A p value <0.05 was considered significant.

Main results and the role of chance

The mean age was 32.8±7.7 years. Varicocelectomy was performed on left side in 373 patients and bilateral in 62 patients. The majority of the study population had grade III varicocele on the left side. There were no statistically significant changes in semen volume, concentration, total & progressive motility, sperm DNA fragmentation, and hormonal profile after 6 months post varicocelectomy in comparison to initial baseline parameters (table 1). Only a statistically significant improvement in morphology was observed.

Limitations, reasons for caution

The main limitation is the retrospective design of the study. Long-term effect and conception rate were not evaluated.

Wider implications of the findings

Results of this work are beneficial during preoperative counseling of patients with normal semen undergoing varicocelectomy for non-fertility indications. Patients can be reassured that the procedure would not affect their fertility potentials negatively.

Trial registration number

not applicable