Hum Reprod Research Articles

Natural Proliferative Phase Frozen Embryo Transfer—A New Approach Which May Facilitate Scheduling Without Hindering Pregnancy Outcomes

(Abstracted from Hum Reprod 2024;39(5):1089–1097 Frozen embryo transfer (FET) use is increasing worldwide due to continuous cryopreservation technique improvements, reassuring safety data, and a growing list of indications. Different FET protocols include artificial (AC) and natural cycle (NC), and further exploration of the efficacy and safety of these protocols is of utmost importance.

Does Recurrent Implantation Failure Exist? Prevalence and Outcomes of Five Consecutive Euploid Blastocyst Transfers in 123 987 Patients

(Abstracted from Hum Reprod 2024;39(5):974–980 Recurrent implant failure (RIF) has been defined as repeated failed implantations following multiple embryo transfers. A landmark paper on RIF reported the cumulative sustained implantation and live birth rates achieved with 3 consecutive single euploid blastocyst transfers and found a similar live birth rate across the first 3 consecutive transfers with a “true” unexplained RIF rate of <5% in the in vitro fertilization population.

P-118 Behavior of the second polar body and its relationship to subsequent embryonic development, embryo ploidy status and viability in human embryos

Abstract Study question Can the behavior of the second polar body (PBII) be an indicator of embryo viability? Summary answer The behavior of PBII was shown to possibly reflect the viability of human embryos depending on the type of its behavior. What is known already Lately, time-lapse incubators have become widely available. Using time-lapse imaging, second polar bodies (PBII) can be observed from the time of extrusion to the first cleavage, exhibiting a variety of behaviors such as morphologically static, moving like an amoeba, shrinking, fragmenting and ruffling (Shimura et al, Hum Reprod:38,Suppl_1,2023). Although the ploidy and morphology of the first polar body have been variously reported to reflect the quality of embryos after fertilization, there are few studies on PBII, which is thought to directly reflect the state of oocyte after sperm entry, and its relationship to the subsequent embryonic development and embryo viability. Study design, size, duration Retrospective study involving 282 ICSI zygotes derived from 69 ART treatment cycles from January to August 2019. Zygotes were classified into two groups according to the type of PBII behaviors (Group1: static, Group2: others), and developmental outcome was compared (Study1). The relationship between the type of PBII behaviors and ploidy in 64 biopsied blastocysts from 11 cycles in which one or more euploid embryos were obtained between August 2021 and October 2023 was examined (Study2). Participants/materials, setting, methods Time-lapse imaging was performed in EmbryoScope® or Geri®. Study1: Zygotes with morphologically static PBII (n = 70) and PBII showing various behaviors (n = 212) were classified into Group1 and Group2, respectively. The rates of irregular division, good quality embryos, and the time from the PBII extrusion and pronuclear breakdown to the first cleavage were compared between groups. Study2: Biopsied blastocysts were classified according to the type of PBII behavior, and the euploid rates were examined. Main results and the role of chance Study1: The incidence of irregular divisions at the first cleavage was 21.4% (n = 15/70) in Group1 and 28.3% (n = 60/212) in Group2. Good quality embryos at the early cleavage stage were cryopreserved/transferred on Day-2/3 according to our clinic policy, and only those that were not cryopreserved or freshly transferred on Day-2/3 were extendedly cultured up to Day-7. Of those, the rate of good quality blastocysts was 32.4% (n = 12/37) in Group1 and 22.5% (n = 32/142) in Group2. Meanwhile, the rate of good quality embryos at the early cleavage stage was significantly higher in Group1 than in Group2 [P < 0.001; 58.6% (n = 41/70) in Group1, 35.4% (n = 75/212) in Group2]. The utilization rate for cryopreservation and embryo transfer was also significantly higher in Group1 than in Group2 [P < 0.05; 64.3% (n = 45/70) in Group1, 48.1% (n = 102/212) in Group2]. The time elapsed from the pronuclear breakdown to the first cleavage was significantly longer for Group2 than for Group1 [P < 0.05; 2.57 ± 0.42h in Group1, 3.07 ± 1.90h in Group2]. Study2: There were 20 euploid embryos in embryos with PBII showing static, amoebic and shrinking behavior (37.0%; n = 20/54), whereas there were no euploid embryos in embryos with ruffling and fragmenting PBII (0%, n = 0/10) (P < 0.05). Limitations, reasons for caution Categorizing PBII behavior is difficult and requires some proficiency because it varies widely including time-based changes. For the conventional IVF-derived embryos examined in Study2, time-lapse imaging was mostly started after PBII extrusion to allow sufficient insemination time. Wider implications of the findings This study showed that good quality embryos tended to have morphologically static PBII, and that euploid embryos were absent in embryos with PBII showing certain types of behavior. The behavior of PBII may be a new indicator for embryo assessment, but further clarification is needed for clinical use. Trial registration number not applicable

Multidisciplinary surgical management of severe posterior compartment endometriosis

BackgroundEndometriosis is a chronic, inflammatory, and hormone-dependent disease that affects approximately 10% of women in reproductive age. Endometriosis is categorized into different types, as superficial, deep, and ovarian endometriosis. When deep endometriosis occurs, the sigmoid and rectum are often affected (Becker et al. in Hum Reprod Open, 2022, https://doi.org/10.1093/hropen/hoac009). In the following article, we aim to demonstrate stepwise surgery for stage IV endometriosis involving the anterior rectosigmoid.MethodsWe present the case of a 26-year-old obese (BMI 35.87) woman with severe posterior pelvic compartment endometriosis, persistent abdominal pain, and constipation. On preoperative MRI of the pelvis, a 13 cm conglomerate incorporating both ovaries (kissing ovaries), uterine serosa, and the anterior rectosigmoid was observed (Fig. 1). Accordingly, interdisciplinary laparoscopic surgery with a gynecologist and colorectal surgeon was planned.ResultsThe total laparoscopic approach is demonstrated step by step in the video.ConclusionsDeep endometriosis is a rare condition. When involvement of other organs (e.g., the bowel) is suspected, preoperative endometriosis-specific imaging should be performed for optimal surgical planning. Experienced endometriosis multidisciplinary surgical teams can provide specialized and high-quality care for patients suffering from this debilitating disease (Luna Russo et al. in Minerva Ginecol, 2020, https://doi.org/10.23736/S0026-4784.20.04544-X).

Development of a Single-Visit Protocol for the Management of Pregnancy of Unknown Location Following In Vitro Fertilization: A Retrospective Study

(Abstracted from Hum Reprod 2024;39(3):509–515) Pregnancy of unknown location (PUL) refers to a positive pregnancy test that cannot be visualized on transvaginal ultrasound. No medical intervention should be initiated without a clear diagnosis in PUL, despite the term “pregnancy of unknown location” often being used synonymously with suspected ectopic pregnancy.

Time to Pregnancy and Life Expectancy: A Cohort Study of 18 796 Pregnant Couples

(Abstracted from Hum Reprod 2024;39(3):595–603) It is hypothesized that the well-evidenced global decline in reproductive health may, together with behavioral factors, be contributing to the world’s declining fertility and to a soon-expected decreasing global population. Time to pregnancy (TTP), defined as the time to success to conceive under unprotected intercourse, is a commonly used population measure of fecundity, defined as an individual’s capacity to reproduce irrespective of pregnancy intentions.

Serum Progesterone Is Lower in Ovarian Stimulation With Highly Purified HMG Compared to Recombinant FSH Owing to a Different Regulation of Follicular Steroidogenesis: A Randomized Controlled Trial

(Abstracted from Hum Reprod 2024;39:393–402 Serum progesterone levels following ovarian stimulation (OS) are associated with the cycle result in terms of ongoing pregnancy and live birth rate, with levels above a certain threshold associated with poorer results. An increase in progesterone is positively associated with the ovarian response and the FSH dose administered during OS; however, this mechanism is not well understood.

Recommendations From the 2023 International Evidence-Based Guideline for the Assessment and Management of Polycystic Ovary Syndrome

(Abstracted from Hum Reprod 2023;38(9):1655–1679) Polycystic ovary syndrome (PCOS) has a prevalence of 10% to 13%, making it the most common endocrinopathy affecting reproductive-aged women. The etiology of PCOS is complex, and its presentation is heterogeneous with reproductive, metabolic, and psychological features.

Association of Infertility With Type and Timing of Menopause: A Prospective Cohort Study

(Abstracted from Hum Reprod 2023;38(9):1843–1852) Up to 25% of women experience infertility in their lifetime, with a variety of possible causes including dysfunction in the endocrine system, immune system, or reproductive anatomic structures. Research has found that infertility is associated with propensity for poor health outcomes later in life, including reproductive cancer, cardiovascular disease, stroke, and diabetes mellitus.

OR20-02 Trans-Ethnic Analysis Of PCOS Subtype Genomewide Association Signals Reveals 3 Shared Subtype-Specific Loci

Abstract Disclosure: K. Brewer: None. R. Sisk: None. H. Lee: None. L.M. Moolhuijsen: None. K. van der Ham: None. Y. Louwers: None. J.A. Visser: None. M. Dapas: None. S. Franks: None. J.S. Laven: None. C. Li: None. A.E. Dunaif: None. The phenotypic variation observed in PCOS is suggestive of underlying genetic heterogeneity, but a recent meta-analysis of European ancestry (EA) PCOS cases found that the genetic architecture of PCOS defined by NIH and Rotterdam diagnostic criteria was similar, suggesting that these criteria do not identify biologically distinct disease phenotypes. Using Hierarchical Clustering (HC) in EA NIH PCOS cases, we have identified discrete, stable PCOS subtypes, which we called reproductive and metabolic (Dapas. PLoS Med, 2020); cases that did not cluster were designated as “background”. These subtypes appeared to capture biologically meaningful differences because they were associated with distinct genomewide significant loci. We were unable to replicate 4 of 6 loci since the lead SNPs were neither genotyped nor imputed on the array used for replication, the Metabochip custom array for cardiometabolic traits with additional PCOS-relevant SNPs. Here, we report an updated EA genomewide association study (GWAS) meta-analysis with additional EA NIH PCOS cases, and a trans-ethnic meta-analysis including a Korean ancestry (KA) NIH PCOS cohort (Lee. Hum Reprod, 2015). HC was applied to cases in both cohorts to identify PCOS subtypes. The EA discovery cohort, 620 cases and 2951 controls, was genotyped with the Illumina OmniExpress array. The replication EA cohort, 371 cases and 926 controls, was genotyped with the Metabochip. The KA cohort, 417 cases and 926 controls, was genotyped with the HumanOmni1-Quad v1 array. The imputation of previously reported genotype data was updated using the larger, more deeply sequenced TOPMed (R2) imputation panel. Nine loci were genomewide significant in the EA meta-analysis: 5 novel loci (reproductive subtype); 2 loci (metabolic subtype), including c9orf3; 2 loci (background subtype), including FSHB/ARL14P. Five of 6 other lead SNPs in the original analysis remained nominally significant. Three loci were significant in the trans-ethnic meta-analysis: a novel locus on chr 3, EPHA6, a receptor tyrosine kinase that binds promiscuously GPI-anchored ephrin-A family ligands (rs140766105, p=1.08 x 10-8, reproductive subtype); a previously identified GWAS locus on chr 9, c9orf3 (AOPEP), an aminopeptidase that catalyzes the hydrolysis of amino acid residues from the N-terminus of peptides (rs10761370, p=4.12 x 10-9, metabolic subtype); a previously identified GWAS locus on chr 11, FSHB/ARL14P, FSHB encodes the β-subunit of FSH and is associated with general fertility status, (rs10835649, 1.23 x 10-11, background subtype). We have replicated the 9 distinct subtype loci in the EA meta-analysis providing orthogonal (independent) validation suggesting these subtypes have distinct genetic architecture. For the first time, a trans-ethnic meta-analysis demonstrates that 3 subtype-specific loci play a role in PCOS pathogenesis across diverse populations. Presentation Date: Saturday, June 17, 2023

Twin anemia polycythemia sequence in discordant dichorionic twins.

A 23-year-old primiparous woman with spontaneous dichorionic pregnancy was diagnosed by early ultrasonography. She developed hypertensive disorder of pregnancy at 27 weeks of gestation. At 29 weeks and 3 days of gestation, she was transferred to our perinatal center due to increasing discrepancy between the fetal weights (fetus A 1203 g, fetus B 989 g). Notably, polyhydramnios-oligohydramnios sequence was not observed. An emergency cesarean section was performed at 31 weeks 1 day of gestation because of elevated liver enzyme levels. Two male neonates were delivered with birth weights of 1413 and 1098 g, respectively. At birth, twin A was peripherally cyanotic with hemoglobin of 26.4 g/dL and a reticulocyte count of 4.1%. He was treated using partial exchange transfusion for polycythemia. Twin B was pale with hemoglobin of 7.8 g/dL and a reticulocyte count of 20.5%; thus, an emergent red blood cell transfusion was performed for anemia. Based on their hematological values, the twins were diagnosed with twin anemia polycythemia sequence (TAPS). A marked difference in the coloration of the maternal surface was observed in the two placentas on a macroscopic examination (Fig. 1); however, no vascular anastomosis was detected during dye studies. Microscopic histopathology revealed two amniotic layers and two chorionic layers, which confirmed dichorionicity. Recent literature reviews reported that twin-to-twin transfusion syndrome (TTTS) or TAPS occurs in dichorionic twin placentas with evidence of vascular anastomoses, although it is extremely rare.1Kanagaretnam D. Nayyar R. Zen M. Twin anemia polycythemia sequence in dichorionic diamniotic twins: a case report and review of the literature.Clin Case Rep. 2021; 9e04184Crossref Scopus (1) Google Scholar, 2Lanna M. Faiola S. Casati D. Rustico M.A. Twin-twin transfusion syndrome in dichorionic twin pregnancy: rare but not impossible.Ultrasound Obstet Gynecol. 2019; 54: 412-418Crossref Scopus (2) Google Scholar, 3Zilliox M. Koch A. Farve R. Sananes N. Unusual twin anemia-polycythemia sequence in a dichorionic diamniotic pregnancy.J Gynecol Obstet Hum Reprod. 2019; 48: 359-361Crossref Scopus (4) Google Scholar Miniscule anastomoses undetectable by a dye study may have been present in our dichorionic twins. Prenatal diagnosis, close monitoring, appropriate early delivery, and postnatal management are necessary to improve the outcomes of TTTS and TAPS. Thus, this report highlights the importance of prenatal recognition and postnatal confirmation of TTTS or TAPS, regardless of chorionicity. S.H. and S.I. drafted the initial manuscript. S.H., S.I. and S.T. treated the patient, and contributed to the acquisition of clinical data and imaging. M.Y. performed pathological evaluation. S. Y. supervised the manuscript. All authors approved the final manuscript. The authors have no conflicts of interest to declare. We thank the patient's parents for their kind cooperation. We also thank Dr. Chizen Tarui, Department of Neonatology, and Dr. Tomoko Kibara and Megumi Kaneko, Department of Obstetrics, in Hyogo Prefectural Kobe Children's Hospital for their support.

P-144 An artificial intelligence algorithm demonstrates optimal performance for evaluating embryo genetic status at 120 hours post-fertilization

Abstract Study question What is the effect of time-point on performance of a non-invasive artificial intelligence (AI) algorithm for evaluating embryo genetic status? Summary answer While predictive ability was maintained across different time-points on day 5, optimal performance for ranking and selecting euploid embryos was observed at 120 hours post-fertilization. What is known already Studies have shown that it is possible to develop computer vision-based AI algorithms capable of predicting embryo ploidy status using single images of blastocyst-stage embryos. The genetic status of embryos is linked to morphokinetic development, with aneuploidy generally resulting in earlier arrest. Given the dynamic nature of embryo development, it might be expected that the time-point selected for analysis could influence AI performance. The key questions remaining to be answered are to what extent is AI analysis affected by expansion grade, and what does this mean for selection of a time-point for evaluation? Study design, size, duration 2,683 images of day 5 blastocyst-stage embryos with matched ploidy outcomes from pre-implantation genetic testing for aneuploidies (PGT-A) were provided by 10 IVF clinics in the USA, Australia, Malaysia, and India. A subset of 182 embryos had images provided at 110, 115, and 120 hour time points (GERI and EmbryoScope time lapse systems). Participants/materials, setting, methods Images were analysed by a previously developed AI algorithm which evaluates the likelihood of an embryo being euploid according to PGT-A (Diakiw et al, 2022. Hum Reprod, Jul 30;37(8):1746-1759). Evaluation was performed on embryos of each expansion grade, and at three time-points on day 5. Correlations were assessed using Chi-squared test for trend, with pair-wise comparisons conducted using Student’s t-test. Performance was evaluated using ROC-AUC, and a simulated cohort ranking analysis method. Main results and the role of chance AI scores positively correlated with expansion grade, and expansion grade likewise correlated with an increasing proportion of euploid embryos. AI scores also increased over time on day 5, consistent with continued embryo expansion. Scores for grade 4 (expanded) embryos increased more than for grade 5 (hatching) embryos (+2.2-fold and +0.8-fold, respectively), indicative of continued expansion becoming limited at later stages. Despite the valid association of AI scores with expansion grade, results showed the AI could predict euploidy even amongst embryos of the same expansion grade (ROC-AUC ranging from 0.61−0.69). While predictive ability was maintained at each time-point on day 5, ROC-AUC values were highest at 120 hours (0.64, 0.64, and 0.68 for 110, 115, and 120 hours, respectively). Simulated cohort ranking analyses also showed that the AI performed best at 120 hours, selecting a euploid embryo as the top-ranked embryo in 77.1% of patient cohorts (71.4%, 75.1%, and 77.1% for 110, 115, and 120 hours, respectively). These results suggest that regardless of expansion grade, all embryos should be assessed at the same time-point on day 5, preferably closer to the 120 hour time-point. Limitations, reasons for caution The time-point analyses were conducted on a relatively small dataset, and therefore findings should be validated on a larger dataset including embryos of other expansion grades. The analysis was limited to day 5 post-fertilization, however it would be interesting to extend the study to embryos on day 6 also. Wider implications of the findings These results suggest that the AI is providing additional information regarding embryo genetic status, over and above that provided by known morphological parameters. The dynamic nature of AI score related to expansion is of interest as it relates to the optimal time-point for conducting analyses for selection of euploid embryos. Trial registration number Not applicable

O-285 The 6th edition of the WHO manual for the examination and processing of human semen: How should it affect our practice?

Abstract The WHO laboratory manual (World Health Organization 2021) has widened the scope of semen examination from primarily a prognostic tool for Medically Assisted Reproduction (MAR) by indicating the importance of evaluating men with possible disorders in male reproductive functions. Practical instructions for basic examination have been clarified and focused to measures of sperm production and motility as judged from sperm number, motility (vitality if poor motility) and sperm morphology. In addition to the recommendations by the WHO, an international standard based on the same laboratory science as the WHO manual has been published (International Organization for Standardization 2021) to facilitate for laboratories to provide reliable results of semen examination. Each ejaculate must be handled with great care before analysis begins. Time and temperature between sample collection and start of assessments is crucial. To reduce assessment variability, it is essential to ascertain that the examined aliquots are representative for the entire ejaculate and that the number of observations is sufficient to reduce the risk for significant influence of random factors. The former is handled both by aliquot volume (at least 50 µL for sperm concentration) and replicate assessment and comparison that the two assessments don’t differ too much. Regarding number of observations, 400 sperm counted in sperm concentration and in sperm motility assessments is required to reduce this source of errors to ± 10%. For assessment of sperm morphology and vitality a minimum number of observations is 200 spermatozoa. To achieve acceptable performance, thorough in-house training is necessary. There are protocols how to set up and run such schemes (Mortimer 1994, 1994). Basic medical laboratory standards also require that the laboratory regularly performs internal quality control to monitor that inter- and intra-personal variability is under control. Each laboratory should also participate in an external scheme for quality assessment (EQA) (International Organization for Standardization 2012). For the proper interpretation of semen examination results reference limits are important. However, the reference limits suggested by the WHO (World Health Organization 2021) come from a very mixed group of men and should therefore not be mistaken for true limits between fertility and infertility. The new WHO manual therefore argues for development of decision limits (when is it reasonable to act?) that are much more important than limits from a mixed population. It has been argued that semen examination must be better standardized (Björndahl et al. 2016), but the compliance has been almost non-existent (Vasconcelos et al. 2022) leading to even stronger appeals for stronger improvement of basic laboratory investigations of male reproductive functions (Björndahl et al. 2022) References Björndahl L, Barratt CL, Mortimer D, and Jouannet P. ‘How to count sperm properly': checklist for acceptability of studies based on human semen analysis. Hum Reprod 2016: 31; 227-232. Björndahl L, Barratt CLR, Mortimer D, Agarwal A, Aitken RJ, Alvarez JG, Aneck-Hahn N, Arver S, Baldi E, Bassas L, et al. Standards in semen examination: publishing reproducible and reliable data based on high-quality methodology. Hum Reprod 2022. International Organization for Standardization. ISO 15189:2012 Medical Laboratories – Requirements for Quality and Competence 2012. Geneva. International Organization for Standardization. ISO 23162:2021 Basic semen examination — Specification and test methods 2021. ISO, Geneva. Mortimer D. Laboratory standards in routine clinical andrology. Reproductive Medicine Review 1994: 3; 97-111. Mortimer D. Practical Laboratory Andrology 1994. Oxford University Press, Oxford. Vasconcelos AL, Campbell MJ, Barratt CLR, and Gellatly SA. Do studies published in two leading reproduction journals between 2011 and 2020 demonstrate that they followed WHO5 recommendations for basic semen analysis? Hum Reprod 2022. World Health Organization. WHO laboratory manual for the examination and processing of human semen. 6th edn, 2021. World Health Organization, Geneva.

O-050 The impact of embryo biopsy on obstetric and neonatal outcomes

Abstract Background Preimplantation genetic testing of embryos (PGT) was performed first in 1990 to prevent the transmission of X-linked disease. Since then, the technique has improved to include couples who are both carriers of the same autosomal recessive disorder, to those with balanced translocations having recurrent pregnancy loss, and to women with advanced maternal age who are at higher risk for having aneuploid embryos. Originally, PGT involved biopsy of the polar body or of one blastomere of a cleavage stage embryo for diagnosis. The contemporary practice of PGT involves the culture of embryos to the blastocyst stage (5-7 days after fertilization), with biopsy of several trophectoderm cells that would become the placenta, transport of biopsy tissue off-site for genetic analysis, and cryopreservation of blastocysts until biopsy results are available. A single euploid embryo is then transferred into the uterus as a frozen embryo transfer. Objective We sought to determine if removal of these cells for preimplantation genetic testing was associated with adverse obstetrical or neonatal outcomes after frozen-thawed single embryo transfer compared to frozen-thawed single embryo transfer without biopsy. Further, we review other studies of contemporary practice of PGT to draw conclusions about the safety of the practice. Study design We linked assisted reproductive technology surveillance data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System to birth certificates and maternal and neonatal hospitalization discharge diagnoses in Massachusetts, USA, from 2014-2017, considering singleton births after frozen-thawed single embryo transfer. We compared outcomes of cycles having embryo biopsy (n = 585) to those having no biopsy (n = 2,191), adjusting for mother’s age, race, education, parity, body mass index, birth year, insurance, and all infertility diagnoses (Sites CK et al, Am J Obstet Gynecol 2021;225:285.e1-7). Results With no biopsy used as the reference, we found no differences between no biopsy and biopsy groups with respect to preeclampsia, pregnancy-induced hypertension, placental disorders (placental abruption, placenta previa, placenta accreta, placenta increta, and placenta percreta), preterm birth, low birthweight, cesarean delivery, gestational diabetes mellitus, or maternal or infant length of stay after delivery. Comparing our outcomes to 4 other studies of contemporary PGT practice of frozen-thawed embryo transfers (Zhang WY Fertil Steril 2019, Li M Am J Obstet Gynecol 2020, Makhijani R Hum Reprod 2021, He H Fertil Steril 2019), our data are consistent with no effect of biopsy on low birth weight, pregnancy-induced hypertension, gestational diabetes, placenta previa, and placenta accreta. A slight decrease in preterm delivery (RR 1.10, CI 1.02-1.18), slight reduction in cesarean section (RR 0.90, CI 0.82-0.99), and increase in intrauterine growth restriction (RR 1.21, CI 1.06-1.38) are reported with biopsy in a systematic review (Hou W, Fertil Steril 2021). The increase in risk for intrauterine growth restriction with biopsy was influenced by one study (Li M Am J Obstet Gynecol 2020). Conclusion Embryo biopsy of trophectoderm cells for PGT in contemporary practice appears to be safe generally with respect to maternal and neonatal outcomes. There is no clear increase in diagnoses related to placentation (preeclampsia, pregnancy-induced hypertension, placental disorders, preterm birth, low birthweight), cesarean delivery, gestational diabetes mellitus, or maternal or infant length of stay after delivery. Further study of a possible increase in intrauterine growth restriction with biopsy is indicated.

P-457 A biosimilar FSH is a cost-effective option for women undergoing IVF/ICSI treatment in France

Abstract Study question Is Bemfola® a cost-effective treatment option compared to Gonal-f® for women undergoing IVF/ICSI treatment in France based on real-world evidence? Summary answer Bemfola® is a cost-effective treatment option, based on real-world evidence, demonstrating lower gonadotropin costs per live-birth following one ovarian stimulation cycle compared to Gonal-f®. What is known already Since Bemfola®’s first launch in 2015, real-world data has been collected in France, comparing it with the originator Gonal-f®, in the REOLA study (Barriere P, et al., J Gynecol Obstet Hum Reprod. 2023;52:102510). This study demonstrated comparable clinical outcomes according to follicle stimulating hormones (FSH) starting dose between the two FSH, in terms of oocytes retrieved, cumulative live-birth rate (CLBR), and total FSH dose per cycle. Previous health economic studies comparing the cost-effectiveness of Bemfola® against Gonal-f® utilise clinical trial data and therefore leave ambiguity over the cost-effectiveness as the results may not reflect what happens in clinical practice. Study design, size, duration We developed a decision-tree cost-effectiveness model with a one-year time horizon based on the gonadotropin costs and CLBR per ovarian stimulation for Bemfola® and Gonal-f®. The output was gonadotropin cost per live-birth following one ovarian stimulation cycle. CLBR per ovarian stimulation data were taken from the REOLA real-world study while acquisition costs were taken from publicly available databases in France. Model structure and methodology were based on previous publications and validated by clinical experts. Participants/materials, setting, methods The model used clinical data from REOLA, a non-interventional, retrospective, real-world study conducted in 17 French Assisted Reproductive Technology (ART) centres including data from 2,319 Bemfola® and 4,287 Gonal-f® ovarian stimulation cycles for IVF/ICSI grouped according to starting dose. Data was collected for ovarian stimulations between the dates of 01/01/16 and 28/02/17 and CLBR included a follow-up to live-birth of all pregnancies following both fresh and frozen embryo transfer within 12 months of oocyte retrieval. Main results and the role of chance The REOLA study data utilised within the model comparing Bemfola® vs Gonal-f® grouped according to FSH starting dose (< 150 IU, 150 - 224 IU, 225 −299 IU and ≥ 300 IU) are the median total FSH used - 1100 IU, 1500 IU, 2250 IU and 3300 IU vs 1008 IU, 1500 IU, 2250 IU and 3300 IU, and the CLBR - 30.5%, 25.4%, 21.4% and 12.3% vs 27.0%, 27.3%, 19.6% and 12.0%, respectively. The gonadotropin cost per live-birth for Bemfola® was €2,302.12 compared to €2,856.26 per live-birth for Gonal-f®, saving €554.15 per live-birth. The main reasons for this cost saving was the lower acquisition costs of Bemfola® of €489.01 compared with Gonal-f® costs of €597.36 on average per ovarian stimulation. As this analysis is based on real world data as opposed to results from clinical studies it can be used to estimate potential gonadotrophin cost savings in clinical practice in France. With 27,861 babies born annually in France using ART it can be estimated that if all had been born following Gonal-f® usage then a change to all being born following Bemfola® usage could result in savings sufficient to fund gonadotrophins for an additional 31,572 ovarian stimulation cycles. Limitations, reasons for caution The model assumed equal distribution of Bemfola® and Gonal-f® across the starting dose categories and have assumed that the number of fresh and frozen cycles required following ovarian stimulation would be equivalent irrespective of the gonadotropin used. Wider implications of the findings Bemfola® is cost-effective compared to Gonal-f® for IVF/ICSI treatment which would potentially enable more women to be treated with the same healthcare budget for the French health system. This might apply for other countries where Bemfola® is available and benefit from lower acquisition costs than Gonal-f®. Trial registration number not applicable

Zero or 18

Zero or 18

Abbreviating exposure of oocytes to sperm during IVF is associated with reduced fertilisation rates and an increased proportion of unfertilised mature oocytes as assessed 16-18 hours after insemination

Background and Aim: A systematic review and meta-analysis on abbreviated co-incubation times has shown that as little as one hour's exposure of oocytes to sperm improves clinical pregnancy rates without compromising fertilisation rates (Zhang et al 2013, Hum Reprod Update, 19(6), 685-695). The aim of this retrospective cohort study was to compare fertilisation events after abbreviated and extended co-incubation protocols.

Stromal Cell Senescence Contributes to Impaired Endometrial Decidualization and Defective Interaction With Trophoblast Cells

(Abstracted from Hum Reprod 2022;37:1505–1524) The term senescence refers to the cellular state wherein cells preserve viability and metabolic activity while ceasing proliferation. Senescence-associated secretory phenotype (SASP) secretions produced by senescent cells have been shown to facilitate tumor development and play a positive role in cancer progression.

Where Are We in Understanding the Natural History of Polycystic Ovary Syndrome? A Systematic Review of Longitudinal Cohort Studies

(Abstracted from Hum Reprod 2022;37:1255–1273) Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder affecting 5% to 15% of reproductive aged women worldwide. Traditionally, PCOS has been diagnosed based on the presence of 2 of 3 features, including radiologically confirmed polycystic ovaries, oligo/amenorrhea, and hyperandrogenism.

Sperm Selection With Hyaluronic Acid Improved Live Birth Outcomes Among Older Couples and Was Connected to Sperm DNA Quality, Potentially Affecting All Treatment Outcomes

(Abstracted from Hum Reprod 2022;37:1106–1125) With intracytoplasmic sperm injection (ICSI), many natural barriers that would normally prevent the entry of abnormal sperm are lost, increasing the importance of sperm DNA integrity for successful in vitro fertilization. There is currently no consensus on the optimal assay for measuring sperm DNA quality (DNAq), defined as any structural aspect of sperm chromatin that can compromise function if disrupted.