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To report utilization, effectiveness, and safety of assisted reproductive technologies in 2015 and 2016. A retrospective, cross-sectional survey of 3,103 assisted reproductive technology clinics in 74 countries in 2015 and 3,249 clinics in 79 countries in 2016 that submitted cycle and pregnancy outcome data through national and regional registries. Seventy-nine countries and >3,000 assisted reproductive technology clinics. Patients undergoing assisted reproductive technology procedures. Assisted reproductive technology. Outcomes on country, regional, and global levels. Reported for 2015: 2,358,239 cycles with 548,652 infants born; for 2016: 2,807,963 cycles with 647,188 infants born. Estimated in 2015, ≥2,683,677 cycles resulted in >675,134 infants; in 2016, ≥3,100,448 cycles resulted in ≥723,026 infants. Reported cycles represent approximately 80% of global utilization. In 2015 and 2016, 27.6% and 27.8%, respectively, of women undergoing fresh autologous treatment cycles were aged ≥40 years. Frozen-thawed embryo transfer (ET) cycles accounted for 47.0% and 51.9%, respectively, of all ETs in 2015 and 2016. Oocyte donation cycles accounted for 6.7% and 7.1% of all ETs in 2015 and 2016. Intracytoplasmic sperm injection was performed in 57.7% and 56.4% of autologous aspiration cycles in 2015 and 2016, respectively. The cumulative delivery rate per aspiration cycle for fresh and frozen-thawed ET was 32.4% in 2015 and 33.1% in 2016, respectively. The average number of transferred embryos was 1.70 in 2015 and 1.69 in 2016. The proportion of single ETs in fresh autologous cycles increased from 42.1% in 2015 to 44.0% in 2016. The twin delivery rate decreased from 16.0% in 2015 to 14.7% in 2016, and the triplet rate decreased from 0.6% in 2015 to 0.4% in 2016. The proportion of single ETs in frozen-thawed ET autologous treatment cycles was 62.2% in 2015 and 64.2% in 2016, with twin and triplet rates of 10.1% and 0.3% in 2015 and 10.0% and 0.2% in 2016, respectively. Utilization of assisted reproductive technology treatment and births per cycle increased from 2015 to 2016, although multiple births were reduced. An increasing proportion of frozen-thawed ET cycles, continuing wide variation in use of intracytoplasmic sperm injection, and an increase in single ET rates are reported. [ABSTRACT FROM AUTHOR]

To evaluate in vitro fertilization (IVF) and perinatal outcomes of donor egg and autologous cycles in patients with advanced reproductive age after undergoing single frozen euploid embryo transfer. A multicenter, retrospective, cohort study. University-affiliated and private IVF centers. Patients aged 39–46 years who underwent IVF with intracytoplasmic sperm injection and preimplantation genetic testing for aneuploidy using whole-chromosome sequencing with donor (n = 278) or autologous (n = 278) oocytes between October 2017 and October 2021. Single frozen euploid embryo transfer with donor or autologous euploid embryo. The main outcome measure was the live birth rate (LBR) after the first embryo transfer, calculated per embryo transfer. The secondary outcomes included the implantation rate, ectopic pregnancy rate, miscarriage rate, and gestational age and birth weight at the time of delivery. Patients using donor or autologous oocytes had a similar likelihood of implantation (57.91% [51.87–63.78] vs. 57.19% [51.15–63.09]) and LBR (41.01% [95% confidence interval {CI}, 35.17–47.04] vs. 42.45% [95% CI, 36.56–48.49]). Furthermore, there were no significant differences in the ectopic pregnancy rate (0.72% [0.09–2.57] vs. 0.36% [0.01–1.99]), miscarriage rate (16.19% [12.06–21.05] vs. 14.39% [95% CI, 10.48–19.08]), gestational age (38.50 [38.08–38.92] vs. 39.16 [38.25–40.07] weeks), or birth weight of infants (2,982.25 [2,606.69–3,357.81] vs. 3,128.24 [2,962.30–3,294.17] kg). The univariate analysis showed no association between advanced maternal age and the LBR (relative risk, 1.03 [95% CI, 0.84–1.25]). Multivariate analysis using putative confounders for embryo competency found no associations with LBR (adjusted relative risk, 1.22 [95% CI, 0.75–1.98]). Patients with euploid blastocysts derived from donor or autologous oocytes did not reveal statistically significant differences in the LBR, implantation rate, ectopic pregnancy rate, miscarriage rate, duration of gestation, or infant birth weight. These findings suggest that age-related reproductive decline and/or poor IVF outcomes associated with women with advanced reproductive age undergoing IVF are heavily driven by embryonic aneuploidy. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Can pregnancy outcomes following fresh elective single embryo transfer (eSET) in gonadotropin-releasing hormone (GnRH) antagonist protocols increase using a gonadotropin (Gn) step-down approach with cessation of GnRH antagonist on the day of hCG administration (hCG day) in patients with normal ovarian response? SUMMARY ANSWER The modified GnRH antagonist protocol using the Gn step-down approach and cessation of GnRH antagonist on the hCG day is effective in improving live birth rates (LBRs) per fresh eSET cycle. WHAT IS KNOWN ALREADY Currently, there is no consensus on optimal GnRH antagonist regimens. Studies have shown that fresh GnRH antagonist cycles result in poorer pregnancy outcomes than the long GnRH agonist (GnRHa) protocol. Endometrial receptivity is a key factor that contributes to this phenomenon. STUDY DESIGN, SIZE, DURATION An open label randomized controlled trial (RCT) was performed between November 2021 and August 2022. There were 546 patients allocated to either the modified GnRH antagonist or the conventional antagonist protocol at a 1:1 ratio. PARTICIPANTS/MATERIALS, SETTING, METHODS Both IVF and ICSI cycles were included, and the sperm samples used were either fresh or frozen from the partner, or from frozen donor ejaculates. The primary outcome was the LBRs per fresh SET cycle. Secondary outcomes included rates of implantation, clinical and ongoing pregnancy, miscarriage, and ovarian hyperstimulation syndrome (OHSS), as well as clinical outcomes of ovarian stimulation. MAIN RESULTS AND THE ROLE OF CHANCE Baseline demographic features were not significantly different between the two ovarian stimulation groups. However, in the intention-to-treat (ITT) population, the LBRs in the modified antagonist group were significantly higher than in the conventional group (38.1% [104/273] vs. 27.5% [75/273], relative risk 1.39 [95% CI, 1.09–1.77], P  =   0.008). Using a per-protocol (PP) analysis which included all the patients who received an embryo transfer, the LBRs in the modified antagonist group were also significantly higher than in the conventional group (48.6% [103/212] vs. 36.8% [74/201], relative risk 1.32 [95% CI, 1.05–1.66], P  =   0.016). The modified antagonist group achieved significantly higher implantation rates, and clinical and ongoing pregnancy rates than the conventional group in both the ITT and PP analyses (P  <   0.05). The two groups did not show significant differences between the number of oocytes retrieved or mature oocytes, two-pronuclear zygote (2PN) rates, the number of embryos obtained, blastocyst progression and good-quality embryo rates, early miscarriage rates, or OHSS incidence rates (P  >   0.05). LIMITATIONS, REASONS FOR CAUTION A limitation of our study was that the subjects were not blinded to the treatment allocation in the RCT trial. Only women under 40 years of age who had a good prognosis were included in the analysis. Therefore, use of the modified antagonist protocol in older patients with a low ovarian reserve remains to be investigated. In addition, the sample size for Day 5 elective SET was small, so larger trials will be required to strengthen these findings. WIDER IMPLICATIONS OF THE FINDINGS The modified GnRH antagonist protocol using the Gn step-down approach and cessation of GnRH antagonist on hCG day improved the LBRs per fresh eSET cycle in normal responders. STUDY FUNDING/COMPETING INTEREST(S) This project was funded by grant 2022YFC2702503 from the National Key Research & Development Program of China and grant 2021140 from the Beijing Health Promotion Association. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER The RCT was registered in the Chinese Clinical Trial Registry; Study Number: ChiCTR2100053453. TRIAL REGISTRATION DATE 21 November 2021. DATE OF FIRST PATIENT'S ENROLLMENT 23 November 2021 [ABSTRACT FROM AUTHOR]

STUDY QUESTION Which clinical and embryological factors should be considered to apply double embryo transfer (DET) instead of elective single embryo transfer (eSET)? SUMMARY ANSWER No clinical or embryological factor per se justifies a recommendation of DET instead of eSET in IVF/ICSI. WHAT IS KNOWN ALREADY DET is correlated with a higher rate of multiple pregnancy, leading to a subsequent increase in complications for both mother and babies. These complications include preterm birth, low birthweight, and other perinatal adverse outcomes. To mitigate the risks associated with multiple pregnancy, eSET is recommended by international and national professional organizations as the preferred approach in ART. STUDY DESIGN, SIZE, DURATION The guideline was developed according to the structured methodology for development and update of ESHRE guidelines. Literature searches were performed in PUBMED/MEDLINE and Cochrane databases, and relevant papers published up to May 2023, written in English, were included. Live birth rate, cumulative live birth rate, and multiple pregnancy rate were considered as critical outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS Based on the collected evidence, recommendations were discussed until a consensus was reached within the Guideline Development Group (GDG). A stakeholder review was organized after the guideline draft was finalized. The final version was approved by the GDG and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE The guideline provides 35 recommendations on the medical and non-medical risks associated with multiple pregnancies and on the clinical and embryological factors to be considered when deciding on the number of embryos to transfer. These recommendations include 25 evidence-based recommendations, of which 24 were formulated as strong recommendations and one as conditional, and 10 good practice points. Of the evidence-based recommendations, seven (28%) were supported by moderate-quality evidence. The remaining recommendations were supported by low (three recommendations; 12%), or very low-quality evidence (15 recommendations; 60%). Owing to the lack of evidence-based research, the guideline also clearly mentions recommendations for future studies. LIMITATIONS, REASONS FOR CAUTION The guideline assessed different factors one by one based on existing evidence. However, in real life, clinicians' decisions are based on several prognostic factors related to each patient's case. Furthermore, the evidence from randomized controlled trials is too scarce to formulate high-quality evidence-based recommendations. WIDER IMPLICATIONS OF THE FINDINGS The guideline provides health professionals with clear advice on best practice in the decision-making process during IVF/ICSI, based on the best evidence currently available, and recommendations on relevant information that should be communicated to patients. 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 and funded by ESHRE, covering expenses associated with the guideline meetings, the literature searches, and the dissemination of the guideline. The guideline group members did not receive payment. DPB declared receiving honoraria for lectures from Merck, Ferring, and Gedeon Richter. She is a member of ESHRE EXCO, and the Mediterranean Society for reproductive medicine and the president of the Croatian Society for Gynaecological Endocrinology and Reproductive Medicine. CDG is the past Chair of the ESHRE EIM Consortium and a paid deputy member of the Editorial board of Human Reproduction. IR declared receiving reimbursement from ESHRE and EDCD for attending meetings. She holds an unpaid leadership role in OBBCSSR, ECDC Sohonet, and AER. KAR-W declared receiving grants for clinical researchers and funding provision to the institution from the Swedish Cancer Society (200170F), the Senior Clinical Investigator Award, Radiumhemmets Forskningsfonder (Dnr: 201313), Stockholm County Council FoU (FoUI-953912) and Karolinska Institutet (Dnr 2020-01963), NovoNordisk, Merck and Ferring Pharmaceuticals. She received consulting fees from the Swedish Ministry of Health and Welfare. She received honoraria from Roche, Pfizer, and Organon for chairmanship and lectures. She received support from Organon for attending meetings. She participated in advisory boards for Merck, Nordic countries, and Ferring. She declared receiving time-lapse equipment and grants with payment to institution for pre-clinical research from Merck pharmaceuticals and from Ferring. SS-R received research funding from Roche Diagnostics, Organon/MSD, Theramex, and Gedeo-Richter. He received consulting fees from Organon/MSD, Ferring Pharmaceuticals, and Merck Serono. He declared receiving honoraria for lectures from Ferring Pharmaceuticals, Besins, Organon/MSD, Theramex, and Gedeon Richter. He received support for attending Gedeon Richter meetings and participated in the Data Safety Monitoring Board of the T-TRANSPORT trial. He is the Deputy of ESHRE SQART special interest group. He holds stock options in IVI Lisboa and received equipment and other services from Roche Diagnostics and Ferring Pharmaceuticals. KT declared receiving payment for honoraria for giving lectures from Merck Serono and Organon. She is member of the safety advisory board of EDQM. She holds a leadership role in the ICCBBA board of directors. ZV received reimbursement from ESHRE for attending meetings. She also received research grants from ESHRE and Juhani Aaltonen Foundation. She is the coordinator of EHSRE SQART special interest group. The other authors have no conflicts of interest to declare. DISCLAIMER This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose (full disclaimer available at https://www.eshre.eu/Guidelines-and-Legal). [ABSTRACT FROM AUTHOR]

To prospectively examine the association between adenomyosis type, location, and severity with reproductive outcomes in patients undergoing single embryo transfer (SET) with embryos derived from donor oocytes. A prospective observational cohort study. University-affiliated in vitro fertilization center. Patients with infertility with (n = 114) and without (n = 114) adenomyosis who received their first donor oocyte transfer between January 2019 and January 2023 were included in this study. Adenomyosis was confirmed with the presence of at least one direct feature visualized by 2- or 3-dimensional transvaginal ultrasound and classified according to type (diffuse or focal), localization (inner or outer myometrium and/or junctional zone [JZ]), and uterine extension (mild, moderate, or severe). After an artificial or natural endometrial preparation cycle, patients underwent SET in the blastocyst stage. The primary outcome was the implantation rate. The secondary outcomes were the clinical pregnancy, live birth, and miscarriage rates after SET. The presence of adenomyosis did not significantly affect the implantation, clinical pregnancy, or live birth rates. However, women with adenomyosis had a significantly higher miscarriage rate than those without adenomyosis (35.4% vs. 18.1%, respectively). The multivariate analysis assessed possible risk factors for each clinical outcome considered in the study and showed that adenomyosis affected the risk of miscarriage. Specifically, transvaginal sonography detection of adenomyosis in the JZ was associated with over threefold higher relative risk of miscarriage (relative risk [RR], 3.28; 95% confidence interval [CI], 1.38–7.78). Conversely, adenomyosis features detected exclusively in the outer myometrium were associated with a higher ongoing pregnancy rate (RR, 0.30; 95% CI, 0.13–0.72). Diffuse adenomyosis in the JZ and severe adenomyosis increased the relative risk of miscarriage two-fold (RR, 2.29; 95% CI, 1.22–4.30 and RR, 2.20; 95% CI, 1.19–4.04, respectively). This study demonstrated that although adenomyosis did not significantly reduce the odds of implantation, the direct signs of adenomyosis in the JZ and disease severity are significant risk factors for miscarriage in patients receiving donor oocyte transfers. This study highlights the importance of thorough ultrasound examination and detailed adenomyosis classification in the assessment and management of patients with infertility. [ABSTRACT FROM AUTHOR]

Background: The present evidence is deficient for the trade-offs between the pros and cons of single blastocyst transfer (SBT) versus double blastocyst transfer (DBT) in frozen-thawed embryo transfer cycles for women in advanced reproductive age, especially in the second cycle. The current study aimed to investigate the impact of transferred blastocyst numbers on pregnancy outcomes in the first and second embryo transfer for women ≥ 35 years. Methods: This was a retrospective cohort study including 1284 frozen-thawed blastocyst transfer (FBT) cycles from two reproductive centers. We analyzed the pregnancy outcomes after SBT and DBT in the first and second FBT cycles. Moreover, stratified analysis was conducted by maternal age. Results: In the first FBT cycle, the LBR was higher in the DBT group than that in the SBT group [52.3% vs. 33.9%; adjusted odds ratio (aOR), 1.65; 95% confidence interval (CI), 1.26–2.15, P < 0.001]. However, the LBR of the DBT group showed no remarkable difference compared with that of the SBT group in the second cycle of FBT (44.3% vs. 33.3%; aOR, 1.30; 95% CI, 0.81–2.08; P = 0.271). Furthermore, stratified analysis by age showed a higher LBR for the DBT group than the SBT group in patients aged 38–42 years (43.1% vs. 33.9%; aOR, 2.27; 95% CI, 1.05–4.90; P = 0.036). Conclusions: The present study demonstrated that the SBT regimen is a better choice for both, the first and second frozen-thawed embryo transfer cycles, for women aged 35–37 years. Additionally, the DBT regimen is still recommended to achieve a high LBR in women aged 38–42 years in the second FBT cycle. These findings may be beneficial for deciding the embryo transfer regimens in women of advanced reproductive age. [ABSTRACT FROM AUTHOR]

Background: Several studies have demonstrated that iDAScore is more accurate in predicting pregnancy outcomes in cycles without preimplantation genetic testing for aneuploidy (PGT-A) compared to KIDScore and the Gardner criteria. However, the effectiveness of iDAScore in cycles with PGT-A has not been thoroughly investigated. Therefore, this study aims to assess the association between artificial intelligence (AI)-based iDAScore (version 1.0) and pregnancy outcomes in single-embryo transfer (SET) cycles with PGT-A. Methods: This retrospective study was approved by the Institutional Review Board of Chung Sun Medical University, Taichung, Taiwan. Patients undergoing SET cycles (n = 482) following PGT-A at a single reproductive center between January 2017 and June 2021. The blastocyst morphology and morphokinetics of all embryos were evaluated using a time-lapse system. The blastocysts were ranked based on the scores generated by iDAScore, which were defined as AI scores, or by KIDScore D5 (version 3.2) following the manufacturer's protocols. A single blastocyst without aneuploidy was transferred after examining the embryonic ploidy status using a next-generation sequencing-based PGT-A platform. Logistic regression analysis with generalized estimating equations was conducted to assess whether AI scores are associated with the probability of live birth (LB) while considering confounding factors. Results: Logistic regression analysis revealed that AI score was significantly associated with LB probability (adjusted odds ratio [OR] = 2.037, 95% confidence interval [CI]: 1.632–2.542) when pulsatility index (PI) level and types of chromosomal abnormalities were controlled. Blastocysts were divided into quartiles in accordance with their AI score (group 1: 3.0–7.8; group 2: 7.9–8.6; group 3: 8.7–8.9; and group 4: 9.0–9.5). Group 1 had a lower LB rate (34.6% vs. 59.8–72.3%) and a higher rate of pregnancy loss (26% vs. 4.7–8.9%) compared with the other groups (p < 0.05). The receiver operating characteristic curve analysis verified that the iDAScore had a significant but limited ability to predict LB (area under the curve [AUC] = 0.64); this ability was significantly weaker than that of the combination of iDAScore, type of chromosomal abnormalities, and PI level (AUC = 0.67). In the comparison of the LB groups with the non-LB groups, the AI scores were significantly lower in the non-LB groups, both for euploid (median: 8.6 vs. 8.8) and mosaic (median: 8.0 vs. 8.6) SETs. Conclusions: Although its predictive ability can be further enhanced, the AI score was significantly associated with LB probability in SET cycles. Euploid or mosaic blastocysts with low AI scores (≤ 7.8) were associated with a lower LB rate, indicating the potential of this annotation-free AI system as a decision-support tool for deselecting embryos with poor pregnancy outcomes following PGT-A. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of hatching status on predicting pregnancy outcomes in single vitrified‐warmed blastocyst transfer (SVBT) by objectively subdividing pre‐implantation blastocysts according to hatching status. Methods: This retrospective study included 817 SVBT cycles performed between January 2016 and December 2017. Transferred embryos were categorized according to their hatching status as follows: group I (n = 147), non‐hatching blastocysts; group II (n = 484), hatching blastocysts; and group III (n = 186), completely hatched blastocysts. Hatching blastocysts (group II) were then classified based on the ratio of the blastocystic diameter outside and inside the zona pellucida into early (n = 185), mid‐ (n = 103), and late (n = 196) hatching stages. Implantation rate (IR), clinical pregnancy rate (CPR), live birth rate (LBR), multiple pregnancy rate (MPR), miscarriage rate, and neonatal outcomes were evaluated. Results: For groups I, II, and III, respectively, the results were as follows: IR (28.6%, 43.6%, and 53.8%; P < 0.001), CPR (27.9%, 42.8%, and 53.2%; P < 0.001), and LBR (23.1%, 32.0%, and 42.5%; P < 0.001). Group III had better IR, CPR, and LBR. Among hatching blastocysts, late‐hatching blastocysts had the highest IR (33.5%, 46.6%, and 51.5% for early, mid‐, and late hatching, respectively; P = 0.002) and CPR (33.0%, 45.6%, and 50.5%; P = 0.002), with a tendency for a higher rate of LBR. Neonatal outcomes were not influenced by the hatching status. Conclusion: Advanced hatching status is positively associated with a higher rate of clinical pregnancy and live birth with no negative effects on neonatal outcomes. Additionally, the quantitative classification of hatching status was found to be predictive of pregnancy outcomes. Synopsis: Hatching status in single vitrified‐warmed blastocyst transfer improved clinical pregnancy and live birth rates compared with the expanded state of the blastocyst. [ABSTRACT FROM AUTHOR]

To investigate whether morphokinetic parameters differ between male and female embryos in IVF embryos resulting in live births, a retrospective cohort study was undertaken. Files of all live births resulting from a single embryo transfer (SET) cultured in time-lapse incubators between 2013 and 2019 in two tertiary care centres were reviewed. The study group consisted of 187 SETs resulted in 187 live births, of which 100 were females (53.5%) and 87 were males (46.5%). Embryo selection for transfer was based on the known implantation data (KID) score provided by the Embryoscope and morphological assessment by experienced embryologists. Neonatal sex was confirmed through live birth documentation. Morphokinetic parameters and day 3 and day 5 KID scores of male and female embryos were compared. Maternal baseline and treatment characteristics were similar between groups. Morphokinetic time-lapse parameters of male and female embryos including: pronuclei fading; cleavage timings (t2-t9); second and third cell cycle durations; synchrony of the second and third cleavages; late morphokinetic parameters and KID scores did not differ between groups. In conclusion, time-lapse morphokinetic parameters and embryo selection methods do not seem to differ between male and female embryos, and their utilization does not bias towards any neonatal sex. [ABSTRACT FROM AUTHOR]

Didelphic uterus are caused by Müllerian tube fusion failure that eventually form two uterine cavities, which is one of the rarest uterine malformations. Women with Müllerian anomalies may increase the incidence of perinatal complications and adverse outcomes of pregnancy. If Müllerian anomalies are found during pregnancy, the type of abnormality should be identified promptly, the impact on the mother and fetus should be assessed, and the frequency of prenatal care should be appropriately increased. Ovarian pregnancy as a rare ectopic gestation is often difficult to diagnose before surgery. Ovarian pregnancy seemingly has no logical relationship with the didelphic uterus. The high risk factors of ovarian pregnancy may include intrauterine device, assisted reproductive technology (ART) and intrauterine surgery history. A case of ovarian pregnancy in a woman with didelphic uterus after ART was reviewed, and the possible causes of ovarian pregnancy were summarized and analyzed. Single embryo transfer should be considered as the best transplantation strategy for those patients with didelphic uterus. Women of childbearing age should undergo a thorough pelvic examination before ART in order to make early diagnosis and proper management of congenital uterine abnormalities. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of shrinkage blastocyst transfer on embryo implantation and clinical outcome. Methods The clinical data of patients with the apperance of shrinkage (the blastocyst shrinkage group) by time-lapse imaging during blastocyst culture in this center from January 2019 to April 2021 were retrospectively analyzed, and the pregnancy outcome after single blastocyst transplantation in freeze-thaw cycle was compared with that of the control group (patients without blastocyst shrinkage). Results The implantation rate (45.07%) and clinical pregnancy rate (45.07%) in the blastocyst shrinkage group were significantly lower than those of the the control group (59.93%,59.93%), and the differences were statistically significant (P＜0.05). The live birth rate (40.85%) in the blastocyst shrinkage group was lower than that of the control group (50.68%), and the abortion rate was similar to that of the control group (9.38%,13.71%), with no statistically significant difference (P＞0.05). Conclusion Blastocyst collapse is an important factor affecting embryo implantation rate and clinical pregnancy rate. [ABSTRACT FROM AUTHOR]

This article details the case report of an infertile couple for more than two years. The patient has an obstetrical history of three pregnancies with two living children and her partner has no significant medical or surgical history. The first medical assessments are strictly normal. However, the semen analysis of the patient shows a severe oligoasthenoteratospermia. A pre in vitro fertilization assessment is then started. Eleven oocytes are collected from the oocyte retrieval. Ten of them are fertilized by the intracytoplasmic sperm injection (ICSI) technique. Six embryos will be obtained and frozen in L3 stage. The patient undergoes a single embryo transfer which will result in a monozygotic dichorionic-diamniotic twin pregnancy. Fertility enhancing treatments increase the prevalence of monozygotic dichorionic-diamniotic twin pregnancies compared with natural conception. This case report will allow us to approach the rare cases of monozygotic dichorionic-diamniotic twin pregnancies and to identify the factors which could explain this gap between the prevalences. [ABSTRACT FROM AUTHOR]

Women with polycystic ovary syndrome make up the vast majority of patients with anovulatory infertility. The commonly accepted treatment guidelines recommend ovulation induction for timed intercourse as the first-line treatment. After a 2-year treatment period, the cumulative pregnancy rates with a singleton live-born baby reached 71% and 78% in two prospective studies. Despite aiming for monofollicular growth, multifollicular responses with subsequent multiple/higher order multiple pregnancies are a dreaded risk associated with ovarian induction. However, the lengthy treatment, the increase of maternal age and the psychological effects of 'obligatory intercourse' are also factors challenging the concept of ovarian induction as the first treatment approach in anovulatory infertility. Nowadays, individualized IVF treatment with cycle segmentation, freeze-all strategies and single-embryo transfers in frozen embryo transfer cycles dramatically reduces the risk of multiple pregnancies, and a cumulative pregnancy rate of 83% can be achieved over three complete cycles, thereby reducing exposure to fertility medication and time to pregnancy. Although on first sight ovarian induction might present the easier and less costly approach, efficient and individualized IVF treatments with low complication rates and the chance of preventing multiple pregnancies challenge this concept, and it seems that the time has come to abandon ovarian induction in anovulatory infertility. [ABSTRACT FROM AUTHOR]

To investigate the effect on the pregnancy rate of transfer of a good-quality embryo (GQE) and a poor-quality embryo (PQE) in comparison with a single GQE transfer. Systematic review and meta-analysis. Not applicable. Infertility patients undergoing in vitro fertilization/intracytoplasmic sperm injection- embryo transfer. Three major electronic databases (PubMed, Embase, and Cochrane Library) for studies those compared single GQE transfer to double embryo transfer of a GQE + PQE were searched. The Newcastle–Ottawa Quality Assessment Scale was used to evaluate the study quality. Random-effect meta-analysis was performed on all data for an overall analysis, followed by a subgroup analysis (fresh cleavage-stage embryos, fresh blastocysts, frozen-thawed blastocysts, and the same assessment criteria for blastocyst quality). The primary outcome was clinical pregnancy rate (CPR). A total of 17 studies with 17,612 cycles for GQE transfer and 6,431 cycles for GQE + PQE transfer were included in the meta-analysis. No significant differences were found in CPR (relative risk [RR] = 1.02; 95% confidence interval [CI], 0.91 – 1.14) and live birth rate (RR = 0.96; 95% CI, 0.87 – 1.07) between GQE + PQE and GQE transfers. However, the transfer of GQE + PQE increased multiple pregnancy rate (RR = 0.14; 95% CI, 0.09–0.20) and multiple birth rate (RR = 0.08; 95% CI, 0.06 – 0.12), when compared with the patients undergoing a single GQE transfer. Subgroup analyses by type of embryo for transfer and assessment criteria for embryo quality showed similar trends. Double embryo transfer with GQE + PQE does not result in increased or decreased CPR and live birth rate when compared with a single GQE transfer but leads to a higher multiple pregnancy rate and multiple birth rate. Prospero CRD42022296681 (https://www.crd.york.ac.uk/prospero/display%5frecord.php?RecordID=296681) registered on January 7, 2022. [ABSTRACT FROM AUTHOR]

• Stable IVF outcomes can be achieved for women aged 45+ years using donor eggs. • Single-embryo transfer minimizes twin pregnancies and optimizes safety. • Cumulative live birth rates remain over 50% for very advanced maternal age. • These results are from a nationwide Taiwan IVF registry analysis of advanced maternal age. Does very advanced maternal age (VAMA; age ≥45 years) influence obstetric outcomes among women using donor oocytes in IVF? This retrospective cohort study analysed data from a nationwide IVF registry in Taiwan, focusing on IVF cycles involving women aged 45 years and older using donated oocytes between 2007 and 2016. The study assessed cumulative live birth rates (CLBR) and secondary outcomes such as clinical pregnancy, miscarriage, live birth and twin pregnancy rates, alongside perinatal outcomes such as Caesarean section rates, pre-eclampsia, gestational diabetes and birthweight. The study included 1226 embryo transfer cycles from 745 women, with a stable live birth rate of about 40% across the study period. The CLBR was slightly lower in women aged 50 years and older (54.2%) compared with those aged 45–46 years (58.0%), but these differences were not statistically significant (P = 0.647). Secondary outcomes and perinatal outcomes did not significantly differ across age groups. Regression analysis suggested a non-significant trend towards a decrease in live birth rate and birthweight with increasing maternal age. The study also found that single-embryo transfer (SET) minimized the risk of twin pregnancies without significantly affecting live birth rates. IVF with donor oocytes remains a viable option for women of VAMA, with consistent live birth rates across age groups. However, the study underscores the importance of elective SET to reduce the risk of twin pregnancies and associated adverse outcomes. Further research is needed to explore the impact of other factors such as paternal age and embryo development stage on IVF success in this population. [ABSTRACT FROM AUTHOR]

Purpose: Specific serum beta human chorionic gonadotropin (β-hCG) parameters that can predict live birth after an embryo transfer have yet to be defined. Methods: We performed a retrospective cohort study of 1,028 patients with a detectable β-hCG who underwent a single embryo transfer between 2002 and 2019 at a large academic center. Two β-hCG parameters were examined in relation to live birth: 1) "doubling" defined as β-hCG doubling over 48 h and 2) "reaching 100" defined as a β-hCG ≥ 100 mIU/mL by 15 days after oocyte retrieval (AOR). Results: One thousand three hundred forty cycles involving a single embryo were analyzed. Two thirds were frozen embryos and 86% were blastocyst transfers. Preimplantation genetic testing was performed in almost 30% of cycles. When β-hCG levels "doubled," a live birth occurred in 80.7% of cycles and when β-hCG levels "reached 100" by 15 days AOR, live birth occurred in 81.6% of cycles. When β-hCG levels both doubled and reached 100 by 15 days, AOR 85.4% cycles resulted in live birth. A multiple logistic regression model to control for patient and cycle level factors revealed a live birth odds ratio (OR) of 8.0 (95% CI 5.7–11.1) when β-hCG "doubled" and an OR of 21.2 (95% CI 14.3–31.5) when β-hCG "reached 100." When both these latter parameters were met, the OR was 12.5 (95% CI 8.9–17.8). Conclusion: β-hCG parameters of "doubling" and "reaching 100" by 15 days AOR are robust predictors of live birth and can aid in patient counseling regarding pregnancy outcomes soon after single embryo transfer. [ABSTRACT FROM AUTHOR]

Does the COVID-19 vaccination affect endometrial receptivity after single euploid embryo transfer, measured by sustained implantation rate? A retrospective cohort study analysing two groups of single euploid embryo transfers using own oocytes: one historical cohort of 3272 transfers 1 year before the pandemic; and one comprising 890 transfers in women previously vaccinated with mRNA vaccines against severe acute respiratory syndrome coronavirus 2. The main outcomes were clinical pregnancy rate (CPR) and sustained implantation rate (SIR) per embryo transfer. These outcomes were compared between non-vaccinated and vaccinated women, and women who had received one and two doses. Lastly, vaccinated women were divided into quartiles according to the time from last dose to embryo transfer. Similar CPR and SIR were found between non-vaccinated and vaccinated women, and the odds ratio for both outcomes was not statistically significant after being controlled for potential confounders (OR 0.937, 95% CI 0.695 to 1.265 and OR 0.910, 95% CI 0.648 to 1.227 respectively). Within the vaccinated group, women who had received one or two doses also had similar outcomes. In addition, no differences were found according to the time interval from vaccination to embryo transfer. The administration of mRNA vaccines against COVID-19 had no effect on endometrial receptivity and embryo implantation, regardless of the number of doses and time interval from vaccination to embryo transfer. The potential negative effect of the vaccine on endometrial receptivity and reproductive outcomes is reassuring for patients in the process of undergoing assisted reproductive treatment. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of ectopic pregnancy is up to four times higher after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) than in spontaneous pregnancies, and the risk of ectopic pregnancy is increased by tubal factor infertility and the transfer of multiple embryos. However, the effect of embryo quality on the probability of ectopic pregnancy has not been investigated until now and it is not clear whether ovarian stimulation parameters affect the incidence of ectopic pregnancy. Material and Methods: An historical cohort study of 15 006 clinical pregnancies (diagnosed by ultrasound at 6–8 gestational weeks) after non‐donor IVF/ICSI with fresh embryo transfer (n = 8952) or frozen–thawed embryo transfer (n = 6054). Treatments were performed during 2000–2017 in Finland. A total of 9207 (61.4%) single and 5799 (38.6%) double embryo transfers of no more than one top‐quality embryo were evaluated. We analyzed the effects of multiple factors on ectopic pregnancy by logistic regression, including type of cycle (fresh vs frozen embryo transfer), female age, number and quality of embryos transferred, tubal factor infertility and factors of ovarian response to gonadotropin stimulation. Results: Ectopic pregnancy was observed in 2.3% of cycles. There was no significant difference in ectopic pregnancy rate after fresh embryo transfer and frozen embryo transfer (2.2% vs 2.4%, p = 0.3). The ectopic pregnancy rate was lower in cycles with top‐quality embryo transfer (1.9%) than of those where only non‐top quality embryos were transferred (2.7%, p < 0.0001). Tubal factor infertility was diagnosed more often in ectopic pregnancy than in intrauterine pregnancies (21.2% vs 11.0%, p < 0.0001). Logistic regression revealed lower odds for ectopic pregnancy after a top‐quality embryo transfer than after transfer of a non‐top quality embryo (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.56–0.92, p = 0.007). Transfer of two vs one embryo (OR 1.35, 95% CI 1.05–1.70, p = 0.02) and tubal factor infertility (OR 2.21, 95% CI 1.68–2.91, p < 0.0001) significantly increased the risk of ectopic pregnancy. Conclusions: Transfer of non‐top quality embryos is associated with a higher rate of ectopic pregnancy. This is particularly important to keep in mind in treatments with only non‐top embryos available even in the absence of tubal factor infertility. To minimize the risk of ectopic pregnancy, the number of embryos transferred should be as low as possible. [ABSTRACT FROM AUTHOR]

Reflecting the current trends, the utilization of frozen-thawed transfer cycles has been steadily increasing worldwide; outcome predictors of these cycles are therefore a major research goal. Our aim was to investigate whether the outcome of a fresh single blastocyst transfer (SBT) can serve as a prognostic factor for the subsequent vitrified–warmed SBT originating from the same cohort. A retrospective cohort study was performed at a single unit. Non-donor fresh cycles were analyzed as predictors of the following vitrified–warmed cycle. Only SBTs were included. Cycles designated to a freeze-all policy and cycles involving pre-implantation genetic analysis were excluded. A total of 1127 vitrified–warmed single blastocyst cycles were included. The indications for artificial reproductive technologies were comparable across the study groups. Vitrified–warmed cycles following a live birth outcome in the fresh cycle were more likely to result in a clinical pregnancy than those following a fresh cycle, which failed to reach a live birth. The same trend was observed for live birth rate following vitrified–warmed transfer in the fresh cycle. After correcting for possible confounders, age and embryo quality were significantly correlated with the chance for a live birth, but the previous fresh cycle did not affect the results. We therefore conclude that after adjustment for age, embryo quality and number of previous oocyte retrieval cycles, the fresh cycle outcome was not a significant influential factor for the following vitrified–warmed cycle. [ABSTRACT FROM AUTHOR]

Study Question: Can use of a commercially available time-lapse algorithm for Day 5 blastocyst selection improve pregnancy rates compared with morphology alone?Summary Answer: The use of a time-lapse selection model to choose blastocysts for fresh single embryo transfer on Day 5 did not improve ongoing pregnancy rate compared to morphology alone.What Is Known Already: Evidence from time-lapse monitoring suggests correlations between timing of key developmental events and embryo viability. No good quality evidence exists to support improved pregnancy rates following time-lapse selection.Study Design, Size, Duration: A prospective multicenter randomized controlled trial including 776 randomized patients was performed between 2018 and 2021. Patients with at least two good quality blastocysts on Day 5 were allocated by a computer randomization program in a proportion of 1:1 into either the control group, whereby single blastocysts were selected for transfer by morphology alone, or the intervention group whereby final selection was decided by a commercially available time-lapse model. The embryologists at the time of blastocyst morphological scoring were blinded to which study group the patients would be randomized, and the physician and patients were blind to which group they were allocated until after the primary outcome was known. The primary outcome was number of ongoing pregnancies in the two groups.Participants/materials, Setting, Methods: From 10 Nordic IVF clinics, 776 patients with a minimum of two good quality blastocysts on Day 5 (D5) were randomized into one of the two study groups. A commercial time-lapse model decided the final selection of blastocysts for 387 patients in the intervention (time-lapse) group, and blastocysts with the highest morphological score were transferred for 389 patients in the control group. Only single embryo transfers in fresh cycles were performed.Main Results and the Role Of Chance: In the full analysis set, the ongoing pregnancy rate for the time-lapse group was 47.4% (175/369) and 48.1% (181/376) in the control group. No statistically significant difference was found between the two groups: mean difference -0.7% (95% CI -8.2, 6.7, P = 0.90). Pregnancy rate (60.2% versus 59.0%, mean difference 1.1%, 95% CI -6.2, 8.4, P = 0.81) and early pregnancy loss (21.2% versus 18.5%, mean difference 2.7%, 95% CI -5.2, 10.6, P = 0.55) were the same for the time-lapse and the control group. Subgroup analyses showed that patient and treatment characteristics did not significantly affect the commercial time-lapse model D5 performance. In the time-lapse group, the choice of best blastocyst changed on 42% of occasions (154/369, 95% CI 36.9, 47.2) after the algorithm was applied, and this rate was similar for most treatment clinics.Limitations, Reasons For Caution: During 2020, the patient recruitment rate slowed down at participating clinics owing to coronavirus disease-19 restrictions, so the target sample size was not achieved as planned and it was decided to stop the trial prematurely. The study only investigated embryo selection at the blastocyst stage on D5 in fresh IVF transfer cycles. In addition, only blastocysts of good morphological quality were considered for transfer, limiting the number of embryos for selection in both groups: also, it could be argued that this manual preselection of blastocysts limits the theoretical selection power of time-lapse, as well as restricting the results mainly to a good prognosis patient group. Most patients were aimed for blastocyst stage transfer when a minimum of five zygotes were available for extended culture. Finally, the primary clinical outcome evaluated was pregnancy to only 6-8 weeks.Wider Implications Of the Findings: The study suggests that time-lapse selection with a commercially available time-lapse model does not increase chance of ongoing pregnancy after single blastocyst transfer on Day 5 compared to morphology alone.Study Funding/competing Interest(s): The study was financed by a grant from the Swedish state under the ALF-agreement between the Swedish government and the county councils (ALFGBG-723141). Vitrolife supported the study with embryo culture dishes and culture media. During the study period, T.H. changed his employment from Livio AB to Vitrolife AB. All other authors have no conflicts of interests to disclose.Trial Registration Number: ClinicalTrials.gov registration number NCT03445923.Trial Registration Date: 26 February 2018.Date Of First Patient’s Enrolment: 11 June 2018. [ABSTRACT FROM AUTHOR]

Background: Embryo quality may affect birth weight among neonates born through assisted reproductive technology. There are very limited studies assessing the adverse effect of transferring a poor-quality embryo with a good-quality one on neonatal outcomes. Objective: The aim of this study was to evaluate the effect of double embryo transfer (DET) with one good-quality embryo (GQE) plus a poor-quality one on the birth weight of newborns conceived by in vitro fertilization in both fresh and frozen-thawed embryo transfer cycles. Materials and Methods: This study was conducted at Yazd Reproductive Sciences Institute, Yazd, Iran. A total of 626 women were classified into three groups according to the embryo quality: single embryo transfer with a GQE (group A); DET using two GQEs (group B); and DET using one good-quality and one poor-quality embryo (group C). The primary outcome was singleton birth weight which was compared between the three groups among fresh and frozen-embryo transfer cycles. A comparative analysis was also performed regarding the effect of vitrification procedures on neonatal birth weight within each of the three embryo quality-based groups. Results: The mean birth weight and the rate of preterm birth were similar between the three groups (p = 0.45 and 0.32, respectively). There were also no significant differences found in the vitrification comparative analysis between and within the groups with regard to birth weight. Conclusion: Our results showed that a poor-quality embryo did not have a significant influence on a good-quality one regarding neonatal birth weight when transferred together. [ABSTRACT FROM AUTHOR]

Background: Evidence referring to the trade-offs between the benefits and risks of single embryo transfer (SET) versus double embryo transfer (DET) following assisted reproduction technology are insufficient, especially for those women with a defined embryo quality or advanced age. Methods: A systematic review and meta-analysis was conducted according to PRISMA guidelines. PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov were searched based on established search strategy from inception through February 2021. Pre-specified primary outcomes were live birth rate (LBR) and multiple pregnancy rate (MPR). Odds ratio (OR) with 95% confidence interval (CI) were pooled by a random-effects model using R version 4.1.0. Results: Eighty-five studies (14 randomized controlled trials and 71 observational studies) were eligible. Compared with DET, SET decreased the probability of a live birth (OR = 0.78, 95% CI: 0.71–0.85, P < 0.001, n = 62), and lowered the rate of multiple pregnancy (0.05, 0.04–0.06, P < 0.001, n = 45). In the sub-analyses of age stratification, both the differences of LBR (0.87, 0.54–1.40, P = 0.565, n = 4) and MPR (0.34, 0.06–2.03, P = 0.236, n = 3) between SET and DET groups became insignificant in patients aged ≥40 years. No significant difference in LBR for single GQE versus two embryos of mixed quality [GQE + PQE (non-good quality embryo)] (0.99, 0.77–1.27, P = 0.915, n = 8), nor any difference of MPR in single PQE versus two PQEs (0.23, 0.04–1.49, P = 0.123, n = 6). Moreover, women who conceived through SET were associated with lower risks of poor outcomes, including cesarean section (0.64, 0.43-0.94), antepartum haemorrhage (0.35, 0.15-0.82), preterm birth (0.25, 0.21-0.30), low birth weight (0.20, 0.16-0.25), Apgar1 < 7 rate (0.12, 0.02-0.93) or neonatal intensive care unit admission (0.30, 0.14-0.66) than those following DET. Conclusions: In women aged < 40 years or if any GQE is available, SET should be incorporated into clinical practice. While in the absence of GQEs, DET may be preferable. However, for elderly women aged ≥40 years, current evidence is not enough to recommend an appropriate number of embryo transfer. The findings need to be further confirmed. [ABSTRACT FROM AUTHOR]

Purpose: Assisted reproductive technology (ART) has an impact on secondary sex ratio (SSR), which is seemed to be elevated after blastocyst transfer (BT) but decreased following ICSI procedure. We aim to assess whether the higher SSR associated with BT could be influenced by fertilization method used. Methods: All consecutive IVF/ICSI cycles (fresh and frozen) involving single embryo transfer (SET) resulting in a live birth between 2015 and 2019 were retrospective analyzed. Logistic regression was used to model the effect on the SSR of maternal and specific ART characteristics. Results: Six thousand nine hundred twenty-two women were included with the crude SSR of 54.8%. The impact of BT on SSR is influenced by the fertilization method used. After adjustment for potential confounders, the SSR in the ICSI BT group was significantly higher when compared to ICSI cleavage-stage embryo SET (aOR 1.24; 95% CI 1.10–1.40, P < 0.001). However, this effect was not detected among SBT with IVF treatment (aOR 1.04; 95% CI 0.97–1.12, P = 0.260). Assessing blastocyst morphological parameters, high trophectoderm quality was significantly associated with elevated SSR (aOR 1.76, 95% CI 1.34–2.31 [A vs. C], and aOR 1.28, 95% CI 1.14–1.44 [B vs. C]). No significant difference was shown in expansion, inner cell mass, or days of blastocyst formation between male and female blastocysts. Conclusions: The impact of BT on SSR could be influenced by the fertilization method used. The higher SSR was observed after BT with ICSI procedures but not with IVF. Interpretation of the findings is limited by the potential for selection and confounding bias. [ABSTRACT FROM AUTHOR]

Purpose: To analyze whether the morphokinetics algorithm based on data from day 5 blastocyst transfer (KIDScoreD5 version 3) can predict the pregnancy rate of both day 5 and day 6 blastocyst transfers. Methods: The relationship between KIDScoreD5 and clinical pregnancy rate was evaluated using the Cochran–Armitage test and receiver‐operating characteristic (ROC) curve analysis. Results: A positive correlation was observed between the KIDScoreD5 value and clinical pregnancy rate for both day 5 (p = 0.0003) and day 6 blastocysts (p = 0.0019) using the Cochrane–Armitage test. ROC curve analysis showed that the area under the curve (AUC) of KIDScoreD5 for clinical pregnancy was 0.627 (0.575–0.677, p < 0.0001) for day 5 blastocysts and 0.685 (0.571–0.780, p = 0.0009) for day 6 blastocysts. The combined analysis of both day 5 and day 6 blastocysts also showed an AUC of 0.680 (0.636–0.720, p < 0.0001), suggesting that it is possible to select embryos that are more likely to result in pregnancy. Conclusions: KIDScoreD5 could predict pregnancy not only in day 5 blastocysts but also in day 6 blastocysts. When both day 5 and day 6 blastocysts are vitrified, embryo selection by KIDScoreD5 is possible with a high prediction ability of pregnancy.The morphokinetics algorithm (KIDScoreD5) was able to predict pregnancy not only in day 5 blastocyst transfer but also in day 6 blastocysts. ROC curve analysis showed that the area under the curve (AUC) of KIDScoreD5 for clinical pregnancy was 0.627 (0.575‐0.677, p < 0.0001) for day 5 blastocysts and 0.685 (0.571‐0.780, p = 0.0009) for day 6 blastocysts. The combined analysis of both day 5 and day 6 blastocysts also showed an AUC of 0.680 (0.636‐0.720, p < 0.0001), suggesting that it is possible to select embryos that are more likely to lead to pregnancy. [ABSTRACT FROM AUTHOR]

Objectives: To compare the available evidence of the effectiveness of single blastocyst stage transfer against the effectiveness of single cleavage stage embryo transfer.Study Design: A systematic research based on Pubmed, Embase and the Cochrane Library was performed until May 2, 2020 to identify all relevant studies. The Cochrane Collaboration's Review Manager (RevMan) 5.0.2 software was used for statistical analysis.Results: Five randomized controlled trials (RCTs) were included in analysis, involving 1784 patients in total, who were divided into 2 groups, which were the single blastocyst stage transfer (SBT) group of 932, and the single cleavage stage transfer (SCT) group of 852. Our meta-analysis concluded that SBT group had a significantly higher clinical pregnancy rate (RR 1.26; 95%CI: 1.14-1.39), ongoing pregnancy rate (RR 1.19; 95%CI: 1.05-1.35) and delivery rate (RR 1.4; 95%CI: 1.13-1.75) than SCT group during the fresh transfer. While miscarriage rate (RR 0.93; 95% CI: 0.66-1.33), multiple pregnancy rate (RR, 1.12; 95% CI, 0.51-2.45) and ectopic pregnancy rate (RR, 0.5; 95% CI: 0.13-1.90) between two groups showed no significant difference. However, the SCT group contained notably more cryopreserved embryos than the SBT group. (RR -0.68, 95% CI: -0.95 to -0.41).Conclusions: Our results indicate that single blastocyst stage transfer is associated with higher ongoing pregnancy rate and delivery rate comparing to single cleavage stage transfer in the clinical practice. Due to the low quality of the evidence of the primary outcomes, other higher-quality lager RCTs are necessary before a fully informed decision is made. [ABSTRACT FROM AUTHOR]

Heterotopic pregnancy (HP) is a rare but life‐threatening disease. We report a rare case of HP that occurred after single embryo transfer (SET) with spontaneous natural pregnancy possibly due to sexual intercourse (SI) during assisted reproductive technology treatment and reviewed previous reports. A 39‐year‐old woman at 7 weeks 5 days' gestation with anti‐sperm antibody who underwent a single frozen–thawed embryo transfer in her natural cycle presented with lower abdominal pain and vaginal bleeding. She had several SIs before the day of SET. A viable intrauterine fetus and an extrauterine mass at the right adnexa were detected on transvaginal ultrasonography. An emergent laparoscopic surgery showed a swollen right fallopian tube, and right salpingectomy was performed. Unfortunately, intrauterine fetal death was diagnosed at 19 weeks' gestation. In conclusion, the possibility of HP should be considered in patients with SIs around the day of SET. [ABSTRACT FROM AUTHOR]

Objective: To compare outcomes transferring one or two embryos in autologous frozen oocyte cycles. Material and Methods: A retrospective cohort study conducted at an academic fertility center between January 2012 and December 2018. One-hundred and fourteen patients underwent frozen oocyte transfers; 67 single embryo transfer (SET) and 47 double embryo transfer (DET). No subjects had more than two embryos transferred. Data were analyzed using t-test and chi-squared testing. Multivariate logistic regression was used to control for confounding effects. Power analysis suggested an 82% power with alpha of 5% and effect size of 27%. Results: Regarding the embryo stage, 72% were cleavage embryos and 28% were blastocyst embryos. Among those who had cleavage stage embryos, 48.8% underwent SET and 51.2% underwent DET. In the blastocyst embryos group these proportions were 84.4% and 15.6%, respectively. There were no difference in pregnancy rate for SET (40.3%) vs DET (36.2%) (p=0.78). Additionally, the live birth rate did not differ between SET and DET (28.4 vs 19.1%, respectively, p=0.26). The multivariate multilevel analysis provided adjusted odds ratios (95% confidence interval) of: 1.85 (0.46-7.44) for pregnancy; 0.497 (0.05-4.86) for clinical pregnancy; and 0.82 (0.11-6.29) for live birth when comparing SET and DET. Multiple pregnancy rates were significantly lower in the SET (0%), compared with DET group (44.4%) (p<0.002). Conclusion: SET results in excellent live birth outcomes in autologous frozen oocyte cycles. However DET results in significantly increased rates of multiple pregnancies. This suggests that SET is a viable option in autologous frozen oocyte cycles. [ABSTRACT FROM AUTHOR]

Objectives: Pregnancies and births following assisted reproductive treatment (ART) are related to an increased risk for adverse perinatal outcomes. The aim of this retrospective cohort study at a University Hospital with a tertiary perinatal center was the combined risk analysis of singleton and twin pregnancies after ART in comparison to spontaneously conceived pregnancies.Study Design: Maternal and fetal risks were analyzed in subgroups after spontaneous conception (N = 14,233) and ART (N = 785) during the 6-year study period from 2014 to 2019. Odds ratios for perinatal risks between the groups were calculated and adjusted for maternal age and gestational week at birth using a matched control analysis. Subgroups of preterm delivery were compared.Results: The overall maternofetal risks after ART are higher than after spontaneous conception. Maternal risks after ART are mainly related to higher maternal age (p < 0.001). Preterm delivery and neonatal complications are more frequent in twins than in singletons (p < 0.001), but no statistically significant differences were seen in comparison in the subgroup of twins due to conception. Higher maternal age and body mass index did not increase the risk of preterm birth in twin pregnancies.Conclusions: Maternal risks in pregnancies after ART are mainly influenced by maternal age. The strongest risk factor in ART pregnancies is a multiple pregnancy. Every 5th pregnancy after ART was a twin pregnancy with higher risks for preterm delivery, maternal hospitalization and adverse neonatal outcome (p < 0.001). Advanced maternal age in ART cannot be altered, but twin pregnancies can be actively avoided using the single embryo transfer strategy. [ABSTRACT FROM AUTHOR]

Study Question: Are the decreasing multiple birth rates after ART associated with a simultaneous drop in the incidence of cerebral palsy (CP) in ART children over time?Summary Answer: The relative odds of CP in ART children have declined in the Nordic countries over the past two decades concurrently with declining multiple birth rates.What Is Known Already: In the Nordic countries, the rate of twin pregnancies after ART has decreased from 30% in the early 1990s to 4-13% in 2014, following the implementation of elective single embryo transfer (SET). Consequently, preterm birth rates have declined substantially in ART pregnancies. However, whether the risk of CP, a known consequence of preterm birth, has decreased correspondingly is still unknown.Study Design, Size, Duration: Retrospective register-based cohort study based on data on all singletons, twins, and higher-order multiples born in Denmark (birth year 1994-2010), Finland (1990-2010), and Sweden (1990-2014), corresponding to 111 844 ART children and 4 679 351 spontaneously conceived children.Participants/material, Setting, Methods: Data were obtained from a large Nordic cohort of children born after ART and spontaneous conception initiated by the Committee of Nordic ART and Safety-CoNARTaS. The CoNARTaS cohort was established by cross-linking national register data using the unique personal identification number, allocated to every citizen in the Nordic countries. Data from the National Medical Birth Registers, where information on maternal, obstetric, and perinatal outcomes is recorded, were cross-linked to data from the National ART- and Patients Registers to obtain information on fertility treatments and CP diagnoses. Relative risks of CP for ART compared to spontaneous conception were estimated as odds ratios from multivariate logistic regression analyses across all birth years, as well as for the following birth year categories: 1990-1993, 1994-1998, 1999-2002, 2003-2006, 2007-2010, and 2011-2014. Analyses were made for all children and for singletons and twins, separately.Main Results and the Role Of Chance: The main outcome measure was the relative odds of CP in different time periods for ART versus spontaneously conceived children. CP was diagnosed in 661 ART children and 16 478 spontaneously conceived children born between 1990 and 2014. In 1990-1993, the relative odds of CP were substantially higher in all ART children (adjusted odds ratio (aOR) 2.76 (95% CI 2.03-3.67)) compared with all spontaneously conceived children, while in 2011-2014, it was only moderately higher (aOR 1.39 (95% CI 1.01-1.87)). In singletons, the higher relative odds of CP in ART children diminished over time from 1990 to 1993 (aOR 2.02 (95% CI 1.22-3.14)) to 2003-2006 (aOR 1.18 (95% CI 0.91-1. 49)) and was not significantly increased for birth cohorts 2007-2010 and 2011-2014. For ART twins versus spontaneously conceived twins, the relative odds of CP was not statistically significantly increased throughout the study period.Limitations, Reasons For Caution: The main limitation of the study was a shorter follow-up time and younger age at first CP diagnosis for ART children compared with spontaneously conceived children. However, analyses ensuring a minimum of bias from differences in age at CP diagnosis and follow-up time confirmed the results, hence, we do not consider this to cause substantial bias.Wider Implications Of the Findings: A SET policy in ART treatments has the potential to reduce the increased risk of cerebral palsy in the ART population due to lower rates of multiple deliveries. At a time with high survival rates of frozen/thawed embryos, this study provides a strong argument against the continued use of multiple embryo transfer in most ART settings. Larger cohort studies including also the number of gestational sacs in early pregnancy will be preferable to show an effect of vanishing twins on the risk of CP in the ART population.Study Funding/competing Interest(s): The study was financed by grants from NordForsk (grant number 71450), Elsass Foundation (19-3-0444), the ALF-agreement (ALFGBG 70940), and The Research Fund of Rigshospitalet, Copenhagen University Hospital. There are no conflicts of interest to declare.Trial Registration Number: ISRCTN11780826. [ABSTRACT FROM AUTHOR]

Background: The KIDScore™ Day 5 (KS-D5) model, version 3, is a general morphokinetic prediction model (Vitrolife, Sweden) for fetal heartbeat prediction after embryo transfer that was developed based on a large data set that included implantation results from a range of clinics with different patient populations, culture conditions and clinical practices. However, there was no study to comparing their pregnancy and live birth prediction ability among different maternal age. The aim of this study is to analyze the performance of KS-D5 in predicting pregnancy and live birth in various maternal age groups after single vitrified-warmed blastocyst transfer (SVBT). Methods: A total of 2486 single vitrified-warmed blastocyst transfer (SVBT) cycles were analyzed retrospectively. Confirmed fetal heartbeat positive (FHB+) and live birth (LB+) rates were stratified by Society for Assisted Reproductive Technology (SART) maternal age criteria (< 35, 35–37, 38–40, 41–42 and ≥ 43 years of age). Within each age group, the performance of the prediction model was calculated using the AUC, and the results were compared across the age groups. Results: In all age groups, the FHB+ rates decreased as the KIDScore decreased (P < 0.05). Conversely, the AUCs increased as the maternal age increased. The AUC of the < 35 age group (0.589) was significantly lower than the AUCs of the 41–42 age group (0.673) and the ≥43 age group (0.737), respectively (P < 0.05). In all age groups, the LB+ rates decreased as the KIDScore decreased (P < 0.05). Conversely, the AUCs increased as the maternal age increased. The AUC of the ≥43 age group (0.768) was significantly higher than the AUCs of other age groups (P < 0.05; < 35 age group = 0.596, 35–37 age group = 0.640, 38–40 age group = 0.646, 41–42 age group = 0.679). Conclusions: In the present study, we determined that the KIDScore model worked well for prediction of pregnancy and live birth outcomes in advanced age patients. [ABSTRACT FROM AUTHOR]

Objective: To compare gestational age, birth weight (BW), and live birth rates in gestational carriers (GC) after the transfer of 1 or 2 frozen embryo(s) with or without preimplantation genetic testing for aneuploidy (PGT-A), with the understanding that several social and economic factors may motivate intended parents to request the transfer of 2 embryos and/or PGT-A when using a GC.Design: Retrospective cohort study SETTING: An assisted reproductive technology practice.Patient(s): All frozen blastocyst transfers with GCs from 2009-2018.Intervention(s): One or 2 embryo frozen embryo transfers with and without PGT-A.Main Outcome Measure(s): Live birth, preterm birth, and low BW.Results: A total of 583 frozen embryo transfer cycles with vitrified high-grade blastocysts (grade BB or higher) to GCs were analyzed. Although the live birth rate was significantly greater in frozen embryo transfers with 2 embryos, after single embryo transfer (SET), the mean gestational age and BW of live births were statistically significantly greater than those of double embryo transfer (DET). The rate of multiple births was 1.9% for SET compared to 20.0% for DET per transfer. Only 3.8% of live births from SET experienced low BW and 0.6% had very low or extremely low BW. By comparison, 12.5% of DET live births were low BW and 5% were very low BW. After SET, 13.4% of live births were preterm, compared with 40% in DET. The analysis also included a total of 194 transfers with PGT-A compared to 389 cycles without. Overall, live births per transfer were not significantly different between these latter 2 subgroups.Conclusion: Frozen embryo transfer cycles in GCs with DET were associated with more preterm births and lower birth weights compared with those of SET. Intended parents and GCs should be counseled that DET is associated with greater risks of adverse pregnancy and perinatal outcomes, which mitigates higher live birth rates. The use of PGT-A did not appear to improve the live birth rate. [ABSTRACT FROM AUTHOR]

The process of selecting a good quality embryo to improve the pregnancy outcomes is very important. The aim of our study was to elaborate the embryo selection process in a single vitrified-warmed blastocyst transfer (VBT) cycle by analyzing pre-vitrified and post-warmed blastocyst morphological factors to improve pregnancy outcomes. In this retrospective cohort study, we performed 329 single VBT cycles. The pre-vitrified and post-warmed morphological factors of all blastocysts were analyzed. Logistic regression analysis was conducted to select the independent morphological factor associated with ongoing pregnancy. The expansion of blastocoel (mid blastocoel; aOR 2.27, 95% CI.0.80–6.42, p = 0.12, expanded blastocoel; aOR 3.15, 95% CI.1.18–8.44, p = 0.02) in a pre-vitrified blastocyst and the grade of inner cell mass (ICM) (grade B; aOR 0.47, 95% CI.0.27–0.83, p = 0.01, grade C; aOR 0.22, 95% CI 0.09–0.56 p < 0.01) in post-warmed blastocysts significantly predicted the ongoing pregnancy. After fertilization, the embryo developed as a blastocyst on day 5 (day 5) showed a higher ongoing pregnancy than that on day 6 (day 6) (aOR 0.50, 95% CI.0.26–0.94, p = 0.03). The results suggest that while selecting a vitrified-warmed blastocyst in a single VBT cycle, the day 5 vitrified blastocyst should be considered, and a higher expansion grade in the pre-vitrified blastocyst should be selected. Our study has shown that post-warmed ICM grade tends to be a predictive indicator for the selection of the best blastocyst and allows for successful pregnancy, with ongoing pregnancy in a single blastocyst transfer. [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate the reproductive outcomes of patients with previous cesarean section (CS) undergoing single-embryo transfer (SET). A total of 5479 patients previously underwent CS or vaginal delivery (VD) were included. The patients with previous CS included single/double cleavage (SCT/DCT), single/double blastocyst stage embryo transfer (SBT/DBT). The comparison of reproductive outcomes between CS and VD, SET, and double-embryo transfer of CS was conducted. The main outcome measures included clinical pregnancy rate (CPR), multiple pregnancy rate (MPR), live birth rate (LBR), and cumulative live birth rate (CLBR). There were no differences in CPR and LBR between patients previously underwent CS and VD, and the preterm birth rate of multiple births in patients underwent CS were significantly higher than underwent VD. As for patients underwent CS, the CPR, MPR, and LBR were lower in patients treated with SCT than DCT in IVF/ICSI cycles. The CPR and LBR of patients treated with SCT were not statistically different compared with DCT and SBT when patients' age were younger than 35 years in FET cycles, and the MPR of patients treated with SCT was lower. The CPR and LBR of patients treated with SCT were lower than DCT/SBT when patients' age were 35 years or older in FET cycles. The CPR, LBR, and CLBR of patients treated with SBT were not lower than DCT in IVF/ICSI-ET, FET, and complete cycles, but the MPR was lower. Reducing the number of embryos transferred should be considered seriously for CS. SCT under the 35 years of FET cycles is feasible. SBT is an effective strategy to reduce MPR of IVF/ICSI, FET, and complete cycles regardless of overall or age stratification. [ABSTRACT FROM AUTHOR]

Purpose: To assess the impact of additional embryo transfer (ET) on pregnancy in young women, we used a natural-experiment approach. Patients and Methods: The design was based on the national policy of South Korea limiting the number of embryos transferred in vitro fertilization (IVF):≦2 embryos on day 2– 4 or one on day 5– 6 for patients aged < 35, with one extra embryo allowed for patients aged ≥ 35. Using the data from 1909 ET cycles of 1287 women aged ≥ 34 and ≤ 35, we calculated adjusted risk ratios (RRs) for pregnancy. Results: Half of cycles were undertaken by women aged 35, and additional ET was performed in 68.7% of them. Intrauterine pregnancy (45.2% vs 51.3%) and multiple gestation (30.5% vs 6.9%) were more common in women aged 35 than in those aged 34. The RR for intrauterine pregnancy was 1.34 (95% confidence interval: 1.12– 1.59) when comparing double ET to single ET in frozen day 5– 6 cycles. Conclusion: We observed no evidence of a higher probability of pregnancy with additional ET in fresh or frozen day 3– 4 ET, or in fresh day 5– 6 ET of women aged 35. Additional ET may not increase the successful pregnancy rate in the 35-year-old group, unless it is a frozen day 5– 6 ET cycle. [ABSTRACT FROM AUTHOR]

Background: Non-invasive oocyte quality scoring, based on cumulus gene expression analysis, in combination with morphology scoring, can increase the clinical pregnancy (CPR) and live birth rates (LBR) in Day 3 eSET (elective single embryo transfer) ICSI patients. This was first investigated in a pilot study and is now confirmed in a large patient cohort of 633 patients. It was investigated whether CPR, LBR and time-to-pregnancy could be improved by analyzing the gene expression profile of three predictive genes in the cumulus cells, compared to patients with morphology-based embryo selection only. Methods: A large interventional, non-randomized, assessor-blinded cohort study with 633 ICSI patients was conducted in a tertiary fertility center. Non-PCOS patients, 22–39 years old, with good ovarian reserve, were stimulated with HP-hMG using a GnRH antagonist protocol and planned for fresh Day 3 eSET. The cumulus cells from individually denuded oocytes were ranked by a lab-developed cumulus cell test: qRT-PCR for three predictive genes (CAMK1D, EFNB2 and SASH1) and two control genes (UBC, B2M). The embryo selected for transfer was highest ranked from the pool of morphologically transferable Day 3 embryos. Patients in the control (n = 520) and experimental arm (n = 113) were compared for clinical pregnancy and live birth, using a weighted generalized linear model, and time-to-pregnancy using Kaplan-Meier curves. Results: The CPR was 61% in the experimental arm (n = 113) vs 29% in the control arm (n = 520, p < 0.0001). The LBR in the experimental arm (50%) was significantly higher than in the control arm (27%,p < 0.0001). Time-to-pregnancy was significantly shortened by 3 transfer cycles independent of the number of embryos available on Day 3 (Kaplan-Meier, p < 0.0001). Cumulus cell tested patients < 35 years (n = 65) or ≥ 35 years (n = 48) had a CPR of 62 and 60% respectively (ns). For cumulus cell tested patients with 2, 3–4, or > 4 transferable embryos, the CPR was 66, 52, and 67% (ns) respectively, and thus independent of the number of transferable embryos on Day 3. Conclusions: This study provides further evidence of the clinical usefulness of the non-invasive cumulus cell test over time in a larger patient cohort. Trial registration: Clinicaltrials.gov, NCT03659786/NCT02962466 (Registered 6Sep2018/11Nov2016, retrospectively registered. [ABSTRACT FROM AUTHOR]

As women age, the increasing rate of aneuploidy lead to an augmentation in the incidence of clinical miscarriages. It was anticipated that biochemical pregnancy rates would also rise with maternal age. However, no study has previously evaluated the effect of maternal age on biochemical pregnancy rates. A retrospective cohort study of 2177 subjects who underwent single embryo transfer (SET) as part of a fresh or thawed IVF cycle were recruited from 2008 through 2012, resulting in 952 pregnancies. Data was stratified for age and compared using analysis of variance (continuous data) and chi-squared tests (categorical data). The likelihood of a clinical miscarriage increased with age (p <.001). Surprisingly, advancing age had no effect on the biochemical pregnancy loss rate (p =.72) (Age 21–30 y: 10.7%, Age 31–35 y:9.8%, Age 36–40y:11.5%, Age 41–42 y:13.6%). Biochemical pregnancy loss rate did not increase as a function of age in women 21 to 42 years of age. [ABSTRACT FROM AUTHOR]

Study Question: Does publicly funded assisted reproductive technology result in improved maternal and infant outcomes?Summary Answer: Publicly funded ART in Quebec was associated with reduced risks of preeclampsia, cesarean delivery, preterm birth, low birth weight and other adverse outcomes.What Is Known Already: Publicly funded ART programs that provide free access to single embryo transfer are known to decrease the rate of multiple pregnancy, but the impact on other pregnancy outcomes is unknown.Study Design, Size, Duration: We conducted a pre- and post-comparison study of 597 416 pregnancies conceived between July 2008 and September 2015 in Quebec, Canada, a region where public funding of ART began in August 2010.Participants/materials, Setting, Methods: We included all pregnant women who conceived by ART (n = 14 309) or spontaneously (n = 583 107) and delivered a live or stillborn infant in hospitals of Quebec. The main exposure measure was conception before versus during the publicly funded ART program. Outcomes included measures of maternal and infant morbidity and mortality. We estimated risk ratios (RR) and 95% confidence intervals for the association of publicly funded ART with maternal and infant outcomes using log-binomial regression models adjusted for maternal characteristics.Main Results and the Role Of Chance: In this study, 2638 pregnancies were conceived by ART before, and 11 671 were conceived by ART, during public funding. Compared with no public funding, ART funding was associated with reduced risks of severe maternal morbidity (RR 0.64, 95% CI 0.50-0.83), preeclampsia (RR 0.55, 95% CI 0.44-0.68), cesarean delivery (RR 0.83, 95% CI 0.77-0.89), preterm birth (RR 0.67, 95% CI 0.60-0.75), low birth weight (RR 0.63, 95% CI 0.55-0.72), severe neonatal morbidity (RR 0.75, 95% CI 0.57-0.99) and neonatal intensive care unit admission (RR 0.65, 95% CI 0.53-0.78). When multiple pregnancies were excluded, ART funding continued to be associated with a lower risk of preeclampsia (RR 0.61, 95% CI 0.48-0.79) and preterm birth (RR 0.85, 95% CI 0.73-0.99). However, ART funding was associated with increased risk of gestational diabetes.Limitations, Reasons For Caution: We had no information on the type of ART, number of in-vitro fertilization cycles or number of embryos transferred. We lacked data on body mass index, ethnicity and smoking and cannot rule out residual confounding.Wider Implication Of the Findings: Our findings suggest that publicly funded ART programs that encourage single embryo transfer may have substantial benefits for a range of maternal and infant outcomes, beyond prevention of multiple births.Study Funding/competing Interest(s): This study was supported by grant 6D02363004 from the Public Health Agency of Canada. N.A. acknowledges a career award from the Fonds de recherche du Québec-Santé (34695). The authors declare no competing interests.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

This study reports the results of a 2-year long IVF programme ('One by One') in which all patients (median age 40 years; range 27–45 years) were offered preimplantation genetic testing for aneuploidy (PGT-A) and had all blastocysts vitrified (freeze-only), followed later by single vitrified-warmed blastocyst transfer (vSET) in managed cycles. Between January 2016 and December 2017, a total of 155 patients started 222 treatment cycles and 99 (45%) cycles resulted in one or more vitrified blastocysts (untested or with normal copy number for all chromosomes) available for transfer. Seventeen patients (11%) aged ≤35 years opted out of PGT-A. Over this period, 85 vSETs in 74 patients resulted in an implantation rate of 80% (68/85) and a singleton clinical pregnancy rate of 66% (56/85). Cumulative live birth rates will not be known for 1–2 years. Nevertheless, these high success rates with vSET confirm larger studies using selected patients and are likely to deliver similar, if not higher, live birth rates per cycle started than rates typically reported in national registries with conventional IVF and transfer of one or more fresh and/or frozen embryos. [ABSTRACT FROM AUTHOR]

In vitro fertilization can be considered as causative factor of increasing rate of multiple pregnancies. Analysis of factors contributing to reduction in the percentage of multiple pregnancies may contribute to overall improvement of ART results. We compared annual reports from The Australian and New Zealand Assisted Reproduction Database and US National Summary Reports presented by The Centers for Disease Control and Prevention. The aim of this study was to analyze results of ART outcomes in two countries presenting opposite approach to ART, particularly to number of transferred embryos and number of eSETs (elective single embryo transfers). We found significant increase in total number of initiated cycles and transfers with significant shift toward frozen cycles and transfers in both countries. Percentage of eSET increased while average number of embryos transferred per one transfer decreased significantly in both countries without significant difference between countries. We also noticed significant decrease in the rate of multiple pregnancies and percentage of pregnancies resulting in triplets in Australia with New Zealand. Decreasing number of multiple pregnancies and higher percentage of transfers and pregnancies resulting in singleton live birth are the changes in ART politics found in our analysis. United States of America have more significant changes toward eSET, although Australia and New Zealand have significantly higher percentage of eSET from the beginning of analysis. [ABSTRACT FROM AUTHOR]

Do uterine size parameters measured by baseline transvaginal ultrasound predict live birth after single embryo transfer (SET) of a high-quality blastocyst? Retrospective cohort study including women undergoing their first SET between August 2010 and March 2014 at a large university hospital reproductive centre. The effects of baseline uterine dimensions on live birth rate (LBR) were analysed while controlling for confounding effects. A total of 437 nulliparous and 70 parous women were included. The nulliparous group had lower body mass index (BMI) (24.4 ± 5.1 versus 25.9 ± 4.5 kg/m2; P = 0.015) and a higher number of fibroids (0.4 ± 1.0 versus 0.2 ± 0.5; P = 0.005) than the parous group. While controlling for confounding effects, none of the uterine parameters appeared to be a significant predictor of LBR among nulliparous and parous women (P > 0.05 in all cases). A subsequent analysis of endometrial length was done, whereby the endometrial lengths were divided into quartiles (20.0–32.2 mm; 32.3–36.5 mm; 36.6–40.0 mm; 40.1–54.0 mm). After controlling for confounders, the shortest quartile in the nulliparous group had a significantly lower LBR (P = 0.02) than the other groups. Receiver operating characteristic curves suggested that endometrial cavity length and cervical length did not aid clinically. Uterine parameters do not have a clinically useful impact on LBR after SET of a blastocyst in infertile women. The use of baseline endometrial length to predict live birth is no better than chance, while cervical length only predicts failure to live birth. [ABSTRACT FROM AUTHOR]

In the early years of in vitro fertilization, overall pregnancy rates were low, and it was considered necessary to transfer more than one embryo to increase the chances of pregnancy. It was not until advances in assisted reproductive technologies resulting in increased pregnancy rates that the concept of transferring just one embryo was considered possible. A consequence of improvements in implantation rates was also an increase in multiple pregnancies when more than one embryo was transferred. Although some countries have reduced the number of embryos transferred, international data show that in many parts of the world high twin and higher order multiple pregnancy rates still exist. Even in developed countries these problems persist depending on clinical practice, funding of health services, and patient demands. Perinatal and other outcomes are significantly worse with twins compared with singleton pregnancies and there is an urgent need to reduce multiple pregnancy rates to at least 10%. This has been achieved in several countries and clinics by introducing single embryo transfer but there are many barriers to the introduction of this technique in most clinics worldwide. We discuss the background to the high multiple rate in assisted reproduction and the factors that contribute to its persistence even in excellent clinics and in high-quality health services. Practices that may promote single embryo transfer are discussed. [ABSTRACT FROM AUTHOR]

Background and objectives: Most of previous studies are comparing the perinatal outcome on singleton babies. There has been no study evaluating the possible effect of singleton embryo transfer on the perinatal outcomes in initial singleton pregnancy resulting from fresh embryo transfer. The purpose of our study is to access the effect of embryo transfer number on obstetric and perinatal risks in order to examine the role of single embryo transfer on perinatal outcomes on initial singleton pregnancy. Materials and methods: This study is a retrospective cohort study and analyzed 6439 fresh embryo transfer women. 1647 initial singleton pregnancy patients were divided into one of the following three groups according to the embryo transfer number: group A (n = 94): single embryo transfer (SET); group B (n = 1321): double embryo transfer (DET); group C (n = 262): triple embryo transfer (TET). The miscarriage rate and the ectopic pregnancy rate was compared between group A and group B, group C. 1273 live birth patients were divided into three groups too. The obstetrics outcomes and perinatal outcomes between group A and group B, group C. Results: There were 94 singleton pregnancy patients in unselective single embryo transfer. Comparing with double embryo transfer, the early miscarriage rate was higher, but late miscarriage rate, ectopic rate, and live birth rate were comparable between two groups. The obstetrics outcomes were comparable between single embryo transfer and other two groups. Although there was no significant difference between group A and other two groups, preterm birth rate, extremely preterm birth rate, low-birth weight rate and very low-birth weight rate increased with the increase of embryo transfer number. The mean delivery weight was highest in singleton babies in single embryo transfer group. It is higher in group A comparing with group B (3440.4 versus 3320.7 g) and comparing with group C (3440.4 versus 3277.4 g). Conclusions: Single embryo transfer was associated with a better perinatal outcome such as preterm birth and low-birth weight in a singleton pregnancy. The mean birth weight was significantly higher in single embryo transfer group too. Single embryo transfer is a reasonable option to reach the goal of in vitro-fertilization – a healthy singleton neonate. [ABSTRACT FROM AUTHOR]

Research question: Do live birth rates (LBRs) differ in frozen cycles of women who received single versus double embryo transfer? Design: Retrospective cohort study including women who underwent their first frozen embryo transfer (FET) in a tertiary referral University Hospital between 2009–2014. Results: 3601 patients were included in the analysis with 1936 (53.8%) having a single embryo transfer (SET) and 1665 (46.2%) having a double embryo transfer (DET). Overall, 657/3601 (18.24%) had a live birth. LBR were similar between SET and DET either for cleavage [100/757 (13.1%) versus 153/1032 (14.8%), p =.33] or blastocyst stage FET [256/1179 (21.7%) versus 148/633 (23.4%), p =.4). Ongoing pregnancy rates were comparable between DET and SET [316/1665 (18.9%) versus 359/1936 (18.5%)]. Multiple delivery rates were significantly higher in women with DET compared to SET [53/316 (16.7%) versus 7/359 (1.9%), p <.001]. Multivariate logistic regression analysis allowing adjustment for relevant confounders showed that the number of embryos transferred in the frozen cycle was not related to LBR. Conclusions: This is the largest study providing evidence that both SET and DET may result in similar LBR, albeit multiple pregnancy rates are significantly lower in case of SET. Therefore, SET should be the main strategy in women undergoing FET. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated the potential viability of embryos with low mosaicism level (< 50%) by comparing the clinical outcomes of single mosaic versus euploid blastocyst transfer. In addition, the live birth outcomes for various types of mosaicism with respect to abnormalities in chromosome structure and content were analyzed. Methods: This study included patients who underwent in vitro fertilization with preimplantation genetic testing for aneuploidy (PGT-A). The PGT-A cycles performed through next-generation sequencing with single euploid or mosaic embryo transfers were included. We collected 299 frozen single embryo transfer cycles—216 single euploid and 83 mosaic—between July 2016 and July 2018. This study analyzed clinical outcomes, including fetal karyotyping by using amniocentesis, gestational age at delivery, and live birth weight after single mosaic embryo transfer. Results: The average birth weight of infants in the euploid and mosaic blastocyst transfer groups was 3146.2 and 2997.7 g, respectively. The karyotyping results of prenatal diagnosis in all pregnant women were normal. Our study indicated that mosaic embryos can develop into euploid healthy infants with various levels or types of mosaicism. No significant difference was observed between infants from euploid and mosaic blastocyst transfers. Conclusion: If patients have no euploid embryos, mosaic embryos can be transferred as they have potential for implantation and development into euploid healthy infants. This study is invaluable for counseling clinical results after single mosaic embryo transfers. [ABSTRACT FROM AUTHOR]

Objective: To assess whether receiving information about twin pregnancy in the form of oral presentation given by a physician could affect the acceptance of single embryo transfer (SET) by couples undergoing IVF. Study design: Prospective interventional study. Setting: University hospital IVF unit. Patients: One hundred and forty patients (70 couples) undergoing IVF. Interventions: A questionnaire to measure patients' emotions about twin pregnancy was administered to IVF patients just before and immediately after attending a slide presentation in which the risks of twin pregnancy were explained. Patients scored (1 to 6) ten adjectives linked either to positive or negative emotions; scores before and after presentation were compared. The patients' preference between double embryo transfer (DET) and SET was also registered before and after the presentation. Results: The presentation about twin pregnancy caused a significant (p < 0.001) shift of the score distribution toward lower values for positive adjectives referred to twin pregnancy and higher values for negative adjectives. Information impacted similarly on women and men. Despite the relevant change in the emotional attitude, after presentation, 45.7% of women and 48.6% of men were still favorable to DET, whereas 24.3% of women and 37.1% of men preferred SET. Conclusions: Oral information on the risks of twin pregnancy can affect the emotional attitude of patients toward twin pregnancy, but the wish of getting pregnant after fresh embryo transfer overcomes all rational consideration, and the majority of patients still prefer DET. [ABSTRACT FROM AUTHOR]

In IVF/ICSI programs, after receiving the information about the success results of single embryo transfer (SET) vs double embryo transfer (DET) and the risks of multiple pregnancy, a significant number of patients opt for SET. Up to date, no comparable studies have been published in oocyte recipients. The aim of this study was to evaluate if the counseling provided to oocyte recipients influence their decision on the number of embryos to be transferred. Fifty-five recipients expressed their preference and the relevance for the decision-making process that they attribute to certain factors through an anonymous questionnaire completed pre and post-counseling. Before counseling, 32 out of 55 recipients preferred DET, 13 preferred SET and 10 were undecided. From the 32 recipients who preferred DET, 16 (50%) maintained their preference after counseling, 13 (40.6%) changed their decision to SET and 3 (9.4%) changed to undecided (McNemar's test: p <.05). After counseling, the patients attached less importance to the probability of pregnancy and more importance to maternal and perinatal risks (p <.05). We conclude that after counseling, a significant number of recipients changed their preferences from DET to SET. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to assess whether the outcomes from IVF-preimplantation genetic testing (IVF-PGT) cycles for single gene defects (SGD) (PGT-M) differ between a privately funded period (PRP) and publicly funded period (PUP). Methods: A retrospective cohort study was conducted in a North-American single tertiary center. The PRP (March 1998 to July 2010) comprised 56 PGT-M cycles from 58 IVF cycles in 38 couples, and the PUP (August 2010 to May 2015) comprised 59 PGT-M cycles from 87 IVF cycles in 38 couples. One PGT-M cycle is defined as one biopsy procedure from one or serial IVF cycles. A p-value of 0.05 was considered statistically significant. Results: The clinical pregnancy rates (CPR) per PGT-M cycle were 30.4% and 52.5% in each period, respectively (p=0.021). The live birth rates (LBR) per PGT-M cycle were 21.5% versus 40.9% in each period, respectively (p=0.037). A sub-analysis within the PUP comparing 39 PGT-M cycles from 39 IVF cycles with 20 PGTM cycles from 49 IVF cycles yielded CPRs per PGT-M cycle of 64.1% and 30.0% and LBRs per PGT-M cycle of 53.8% and 15.0%, in each group, respectively (p< 0.05 for both). Conclusion: The transition from private to public funding and a single embryo transfer (ET) guideline has little impact on embryological and clinical outcomes of PGT-M cycles, and results in lower rates of multiple pregnancies. However, these two systems may serve different populations. [ABSTRACT FROM AUTHOR]

Study Question: Which is the most suitable clinical strategy in egg donation IVF cycles conducted with imported donated vitrified oocytes?Summary Answer: The importation, and allocation, of at least eight vitrified eggs per couple during an egg donation cycle is associated with a high cumulative live birth delivery rate per cycle, as well as the confident adoption of a single blastocyst transfer strategy to minimize the risk of multiple pregnancies.What Is Known Already: IVF using donor eggs is commonly used worldwide to treat women who are unable to conceive with their own oocytes. In 2014, the Constitutional Court (n.162/2014) gave permission for gamete donation to be allowed for ART in Italy. Initially recommended as a therapeutic approach for premature ovarian insufficiency, the use of donated oocytes has become more and more common. In countries such as Italy, fresh oocyte donation is theoretically possible, but practically impossible due to the lack of donors. In fact, the Italian law does not allow reimbursement to the young women, who can only voluntarily donate their eggs. Therefore, Italian IVF centers have established several collaborations with international oocyte cryo-banks. The most popular workflow involves the importation of donated oocytes that have been vitrified. However, recent evidence has questioned the overall efficacy of such an approach. This is because detrimental effects arising from oocyte vitrification and warming might reduce the number of eggs available for insemination, with a consequential reduction in the achievable live birth rate per cycle.Study Design, Size, Duration: This was a longitudinal cohort study, conducted between October 2015 and December 2018 at two private IVF centers. Overall, 273 couples were treated (mean maternal age: 42.5 ± 3.5 years, range: 31-50 years; mean donor age: 25.7 ± 4.2, 20-35 years) with oocytes purchased from three different Spanish egg banks.Participants/materials, Setting, Methods: We performed an overall analysis, as well as several sub-analyses clustering the data according to the year of treatment (2015-2016, 2017 or 2018), the number of warmed (6, 7, 8 or 9) and surviving oocytes (≤4, 5, 6, 7, 8 or 9) and the cycle strategy adopted (cleavage stage embryo transfer and vitrification, cleavage stage embryo transfer and blastocyst vitrification, blastocyst stage embryo transfer and vitrification). This study aimed to create a workflow to maximize IVF efficacy, efficiency, and safety, during egg donation cycles with imported vitrified oocytes. The primary outcome was the cumulative live birth delivery rate among completed cycles (i.e. cycles where at least a delivery of a live birth was achieved, or no embryo was produced/left to transfer). All cycles, along with their embryological, obstetric and neonatal outcomes, were registered and inspected.Main Results and the Role Of Chance: The survival rate after warming was 86 ± 16%. When 6, 7, 8 and 9 oocytes were warmed, 94, 100, 72 and 70% of cycles were completed, resulting in 35, 44, 69 and 59% cumulative live birth delivery rates per completed cycle, respectively. When ≤4, 5, 6, 7, 8 and 9 oocytes survived, 98, 94, 85, 84, 66 and 68% of cycles were completed, resulting in 16, 46, 50, 61, 76 and 60% cumulative live birth delivery rates per completed cycle, respectively. When correcting for donor age, and oocyte bank, in a multivariate logistic regression analysis, warming eight to nine oocytes resulted in an odds ratio (OR) of 2.5 (95% CI: 1.07-6.03, P = 0.03) for the cumulative live birth delivery rate per completed cycle with respect to six to seven oocytes. Similarly, when seven to nine oocytes survived warming, the OR was 2.7 (95% CI: 1.28-5.71, P < 0.01) with respect to ≤6 oocytes. When cleavage stage embryos were transferred, a single embryo transfer strategy was adopted in 17% of cases (N = 28/162); the live birth delivery rate per transfer was 26% (n = 43/162), but among the pregnancies to term, 28% involved twins (n = 12/43). Conversely, when blastocysts were transferred, a single embryo transfer strategy was adopted in 96% of cases (n = 224/234) with a 30% live birth delivery rate per transfer (N = 70/234), and the pregnancies to term were all singleton (n = 70/70). During the study period, 125 babies were born from 113 patients. When comparing the obstetric outcomes for the cleavage and blastocyst stage transfer strategies, the only significant difference was the prevalence of low birthweight: 34 versus 5%, respectively (P < 0.01). However, several significant differences were identified when comparing singleton with twin pregnancies; in fact, the latter resulted in a generally lower birthweight (mean ± SD: 3048 ± 566 g versus 2271 ± 247 g, P < 0.01), a significantly shorter gestation (38 ± 2 versus 36 ± 2 weeks, P < 0.01), solely Caesarean sections (72 versus 100%, P = 0.02), a higher prevalence of low birthweight (8 versus 86%, P < 0.01), small newborns for gestational age (24 versus 57%, P = 0.02) and preterm births (25 versus 86%, P < 0.01).Limitations, Reasons For Caution: This retrospective study should now be confirmed across several IVF centers and with a greater sample size in order to improve the accuracy of the sub-analyses.Wider Implications Of the Findings: Single blastocyst transfer is the most suitable approach to achieve high success rates per procedure, thereby also limiting the obstetric complications that arise from twin pregnancies in oocyte donation programs. In this regard, the larger the cohort of imported donated vitrified oocytes, the more efficient the management of each cycle.Study Funding/competing Interest(s): None.Trial Registration Number: None. [ABSTRACT FROM AUTHOR]

A belief exists that transferring multiple embryos can improve pregnancy rates. However, this concept is flawed. Multiple factors affect outcomes when transferring embryos, endometrial receptivity, and rates of aneuploidy among them. In this article, we will discuss how factors can affect outcomes at IVF that are independent of the number of embryos transferred. It is important to understand the role of accessory factors on pregnancy rates to be able to counsel patients as per the number of embryos that should be transferred. An understanding of this concept will also lead to a realistic understanding of how multiple embryo transfers may result in better cumulative pregnancy rates than a single transfer of multiple embryos. Finally, we will present a SWOT analysis diagram to help guide clinical decision-making. [ABSTRACT FROM AUTHOR]

Purpose: The rate of embryonic aneuploidy increases with increasing female age and is the primary cause of lower pregnancy and live birth rates (LBR) in older reproductive age women. This retrospective cohort study evaluates single euploid embryo transfers to determine whether an age-related decline in reproductive efficiency persists. Methods: A total of 8175 non-donor single embryo transfers (SET) after pre-implantation testing for aneuploidy (PGT-A) and cryopreservation were included. These were divided into five groups by patient age: < 35 years old (n = 3789 embryos transferred), 35–37 (n = 2200), 38–40 (n = 1624), 41–42 (n = 319), and > 42 (n = 243). Implantation rate (IR), clinical pregnancy rate (CPR), and LBR were calculated for each group as a percentage of embryos transferred and compared. CPR was also analyzed as a percentage of implanted pregnancies, and LBR as a percentage of clinical pregnancies, to determine when age has the greatest impact. These results were then adjusted for confounding variables via a multivariate logistic regression model. Results: Implantation rates negatively correlated with age. After adjusting for confounders, women 38 years or older had a significantly lower IR than those under 35 (OR 0.85, 95%CI 0.73–0.99 for 38–40 years old; 0.69, 0.53–0.91 for 41–42, and 0.69, 0.51–0.94 for > 42). These differences are also apparent in CPR and LBR. The rates of progression to clinical pregnancy and live birth did not differ significantly by age group. Other factors observed to affect IR independently were anti-Müllerian hormone (AMH), day of embryo transfer, and embryo morphology. Conclusion: While selection of euploid embryos may be effective in overcoming a significant proportion of the age-related decline in reproductive efficiency, a decrease in IR, CPR, and LBR persists even when analyzing only euploid embryo transfers. The observed impact of aging is, therefore, independent of ploidy, as well as of other variables that affect reproductive efficiency. These results indicate that factors other than aneuploidy contribute to reproductive senescence. [ABSTRACT FROM AUTHOR]