There is no evidence that the time from egg retrieval to embryo transfer affects live birth rates in a freeze-all strategy. Lattes K,Checa M A,Vassena R,Brassesco M,Vernaeve V Human reproduction (Oxford, England) STUDY QUESTION:Does the time from ovum pick-up (OPU) to frozen embryo transfer (FET) affect reproductive outcomes in a freeze-all strategy? SUMMARY ANSWER:Our study did not detect statistically significant differences between first and subsequent cycles, clinically relevant differences are not ruled out and further and larger studies are required. WHAT IS KNOWN ALREADY:Following controlled ovarian hyperstimulation (COH) delaying FET until the endometrium has returned to an optimal pre-stimulation state may have a significant emotional impact on patients, which adds to the stress and anxiety accompanying a standard IVF cycle. Currently there is no agreement on the best time to perform a FET after a freeze-all cycle in order to maximize reproductive outcomes for the patient. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study of 512 freeze-all cycles, performed between January 2012 and December 2014. COH was performed by either a GnRH antagonist (n = 397) or a long GnRH agonist protocol (n = 115). Ovulation was triggered using either a GnRH agonist (n = 258) or hCG (n = 254). Endometrial preparation was performed in an artificial cycle by either oral (n = 238) or transdermal (n = 274) oestrogen. Differences were considered significant if P < 0.05. PARTICIPANTS/MATERIALS, SETTING, METHODS:Reproductive outcomes between FETs which took place either within the first menstrual cycle following OPU (Cycle 1; n = 263) or afterwards (Cycle ≥2; n = 249) were compared. Student's t-test for independent samples, Mann-Whitney U-test and Chi-square analysis were used where appropriate. A multivariable logistic regression analysis was performed adjusting for maternal age, drug used for ovulation trigger, number of retrieved oocytes, number of embryos obtained, day of embryonic development at transfer, number of embryos transferred and type of endometrial preparation. Differences were considered significant if P < 0.05. MAIN RESULTS AND THE ROLE OF CHANCE:Live birth rate (LBR) was significantly higher in FET performed during Cycle 1 vs Cycle ≥2 (37.6% vs 27.3%, respectively; P = 0.01) before adjusting for confounding factors. We found no difference for biochemical pregnancy (49.8% vs 43.8%; P = 0.17), clinical pregnancy (44.1% vs 36.1%; P = 0.07) or pregnancy loss (11.8% vs 16.1%; P = 0.16). A multivariable analysis found no impact of timing of elective FET on LBR (odds ratio, OR 0.73; 95% CI 0.49-1.08). The impact remained not significant after adjusting for number of retrieved oocytes, drug used for ovulation trigger (hCG vs GnRH agonist) and reason for cryopreservation. The factors that significantly affected LBR were: maternal age in both age categories (women between 35 and 40 years vs women below 35 years, OR 0.63, 95% CI 0.4-0.95; and women over 40 years vs women below 35 years, OR 0.34, 95% CI 0.2-0.7), day of embryonic development at transfer (day +4 vs +3; OR 1.7, 95% CI 1.1-2.8) and number of transferred embryos (OR 2.2, 95% CI 1.4-3.3) and oestrogen used for endometrial preparation (transdermal vs oral; OR 0.62, 95% CI 0.4-0.9). LIMITATIONS REASONS FOR CAUTION:The main limitation of our study is its retrospective nature. Although we adjusted our statistical analysis for a number of known and suspected confounders, we cannot exclude the possibility of residual confounding factors. WIDER IMPLICATIONS OF THE FINDINGS:According to our results, clinicians might not need to wait more than one menstrual cycle before performing FET. This allows us to reduce unnecessary delays in FET, without compromising reproductive outcomes. STUDY FUNDING/COMPETING INTERESTS:No funding was sought for this study. Authors declare no competing interests. TRIAL REGISTRATION NUMBER:NA. 10.1093/humrep/dew306

Storage time does not influence pregnancy and neonatal outcomes for first single vitrified high-quality blastocyst transfer cycle. Reproductive biomedicine online RESEARCH QUESTION:Does blastocyst storage time have an impact on pregnancy and neonatal outcomes following the first single vitrified/warmed high-quality blastocyst transfer cycle for young women? DESIGN:Retrospective cohort study in a university-affiliated reproductive medical centre. RESULTS:A total of 2938 patients undergoing their first frozen embryo transfer (FET) cycle with a single high-quality blastocyst (Day 5: 3BB and above; Day 6: 4BB and above) transferred were divided into five groups: Group A with storage time ≤3 months (n = 1621), Group B with storage time of 4-6 months (n = 657), Group C with storage time of 7-12 months (n = 225), Group D with storage time of 13-24 months (n = 104), and Group E with storage time of 25-98 months (n = 331). After adjusting for confounding factors by multivariate logistic regression, there were no significant differences in live birth rate [Group A as reference; Group B: adjusted odds ratio (aOR) 0.954 (95% CI 0.791- 1.151); Group C: aOR 0.905 (95% CI 0.674-1.214); Group D: aOR 0.727 (95% CI 0.474-1.114); Group E: aOR 1.185 (955 CI 0.873-1.608)], β-human-chorionic-gonadotropin-positive rate, clinical pregnancy rate and miscarriage rate between Group A and the other groups. Among all singletons born after FET, there were no significant differences with regards to gestational age, preterm birth, birthweight, low birthweight, high birthweight and macrosomia. CONCLUSION:Long-term cryostorage of human vitrified high-quality blastocysts does not affect pregnancy or neonatal outcomes. 10.1016/j.rbmo.2023.06.009

Conservation of DNA Methylation Programming Between Mouse and Human Gametes and Preimplantation Embryos. White Carlee R,MacDonald William A,Mann Mellissa R W Biology of reproduction In mice, assisted reproductive technologies (ARTs) applied during gametogenesis and preimplantation development can result in disruption of genomic imprinting. In humans, these technologies and/or subfertility have been linked to perturbations in genomic imprinting. To understand how ARTs and infertility affect DNA methylation, it is important to understand DNA methylation dynamics and the role of regulatory factors at these critical stages. Recent genome studies performed using mouse and human gametes and preimplantation embryos have shed light onto these processes. Here, we comprehensively review the current state of knowledge regarding global and imprinted DNA methylation programming in the mouse and human. Available data highlight striking similarities in mouse and human DNA methylation dynamics during gamete and preimplantation development. Just as fascinating, these studies have revealed sex-, gene-, and allele-specific differences in DNA methylation programming, warranting future investigation to untangle the complex regulation of DNA methylation dynamics during gamete and preimplantation development. 10.1095/biolreprod.116.140319

Interval between IVF stimulation cycle and frozen embryo transfer: Is there a benefit to a delay between cycles? Higgins Chloe,Healey Martin,Jatkar Sameer,Vollenhoven Beverley The Australian & New Zealand journal of obstetrics & gynaecology BACKGROUND:There is currently limited evidence available regarding ideal timing for frozen embryo transfer (FET). Demonstrating that delaying FETs has few clinical benefits would allow patients to proceed with FET at their earliest convenience. AIMS:To examine whether the time interval between stimulation cycle and subsequent FET affects pregnancy and live birth rates. MATERIALS AND METHODS:This retrospective cohort study, based in a multi-site private in vitro fertilisation (IVF) clinic categorised women into two groups: those having FET cycles administered within 25-35 days or 50-70 days of IVF stimulation cycle and embryo freeze. Outcomes measured were clinical pregnancy and live birth rates. RESULTS:When comparing the patients who have had a 25-35 days gap between embryo freeze and FET, to the matched patients who had a 50-70 days gap, the statistically significant results showed an adjusted odds ratio for live birth of 1.31 (1.02-1.67). The adjusted odds ratio for clinical pregnancy in matched case : control analysis was not statistically significant at 1.22 (0.97-1.53). CONCLUSION:A gap of 25-35 days between embryo freeze and FET was associated with improved live birth rates compared to a gap of 50-70 days. 10.1111/ajo.12696