Frozen Embryo Research Articles

Perinatal outcomes in children born after fresh or frozen embryo transfer using donated oocytes.

Do children born after vitrified-thawed embryo transfers (ETs) using donated oocytes have worse perinatal outcomes when compared with fresh ET? No significant difference in birthweight and prematurity rates between fresh or frozen embryo transfers (FETs) in newborns after oocyte donation was found. Autologous singletons born after fresh ET have been previously associated with higher rates of preterm birth and low birthweight, while FETs seem to confer a higher risk of hypertensive disorders during pregnancy and macrosomia. However, studies comparing these outcomes using autologous oocytes are unable to adequately disentangle the putative detrimental consequences of embryo vitrification from the possible effects that ovarian stimulation and endometrial preparation may have on endometrial receptivity prior to ET. The oocyte donation model is, for this reason, a more appropriate setting to study these hypotheses; however so far, the information available regarding neonatal outcomes in this patient population is limited to either small and/or heterogeneous studies. We performed a multicentre retrospective cohort study including 5848 singletons born between 2009 and February 2020 following oocyte donation and single blastocyst transfer, subdivided according to whether a fresh ET or FET was performed. We also performed two additional sensitivity analyses, subgrouping the sample according to the type of endometrial preparation (natural versus artificial) and whether the donated oocytes had previously been vitrified or not. Patients with a first singleton livebirth after single blastocyst transfer were compared using multivariable regression analysis to account for potential confounding factors. The primary outcome was birthweight. Secondary outcomes were birthweight z-scores and percentiles, small/large for gestational age, gestational age at delivery, gender, prematurity (<37 weeks and <32 weeks), neonatal morbidity (Apgar scores and need for neonatal intensive care) and maternal morbidity (gestational hypertensive disorders, gestational diabetes and caesarean delivery). There was no significant difference between the fresh ET and FET groups in terms of mean birthweight (3215 g versus 3200 g) and birthweight z-scores (0.03 versus 0.1), in both the unadjusted and confounder-adjusted models. However, artificial endometrial preparation was associated with a higher birthweight (3220 g versus 3105 g) and birthweight z-scores (0.06 versus -0.13) when compared with a transfer in a natural cycle. Although a 1-day statistically significant difference in gestational age at birth (275 versus 274 days) was detected, premature birth rates (<37 weeks) did not vary significantly between groups (9.9% and 11.2% for fresh ET and FET, respectively). No other statistically significant differences were found in the remaining neonatal and maternal outcomes studies between the fresh ET and FET groups. This study is limited by its retrospective design and lack of information regarding congenital malformations. Moreover, the sample selection criteria that were used may limit the generalizability of our results. Perinatal outcomes did not seem to be affected significantly by the embryo vitrification process in an oocyte donation model. Hence, other factors may contribute to the hindered perinatal outcomes described in ART, particularly the potential effect that ovarian stimulation and endometrial preparation may have on endometrial receptivity. No specific funding was obtained for this study. All authors have no conflicts to declare. N/A.

The Effects of City Lockdown Policy on Frozen Embryo Transfer Outcome during COVID-19 Epidemic in Hubei Province, China.

Objective To evaluate whether there is a difference in clinical pregnancy rate and live birth rate between the corresponding period in 2019 and COVID-19 city lockdown period in 2020 in frozen embryo transfer (FET). Methods In one single in vitro fertilization (IVF) center (Shiyan, Hubei province, China), a retrospective cohort analysis was conducted, with a sample size of 59 patients in the lockdown period (2020.1.23-2020.2.23, 2020 group) and 34 patients in the corresponding 2019 period (2019.1.23-2019.2.23, 2019 group). Implantation, biochemical and clinical pregnancy, miscarriage, and live birth rates were all measured. Results Age, basal serum follicle-stimulating hormone (FSH), basal serum luteinizing hormone (LH), basal serum E2, and serum total T were all comparable between the two groups. On the day of progesterone administration, endometrial thickness was similar (8.5 ± 1.3 vs. 8.2 ± 1.4, P = 0.356). The number of transferred blastocysts was not significantly different. The two groups had similar clinical pregnancy rate (61.8% vs. 61.0%, P > 0.05) and live birth rate (47.1% vs. 49.2%, P > 0.05), which did not significantly differ. Nonetheless, there was a significant difference in the cancelled cycle rate between the two groups (0% vs. 28.0%, P = 0.043). Conclusions Lockdown period FET versus corresponding period FET outcome did not show any significant difference in terms of pregnancy rate and live birth rate between two groups of patients. Although there was no significant difference, in the 2020 group, the live birth rate was higher compared with that in the 2019 group. There was a significant difference in the rate of cancelled cycles due to the seal off control. In summary, artificial endometrial preparation is an appropriate protocol for special periods.

Obstetric Outcomes and Successful Reduction of Twin Pregnancies Achieved by In Vitro Fertilization

The use of in vitro fertilization methods around the world is constantly increasing. In some developed countries, up to 5% of newborns are as a result of pregnancies after IVF procedures. In vitro fertilization as one of the main and widespread methods for treatment of infertility is the main reason for the high frequency of multiple pregnancies, which, in many countries, is still too high. Most of the multiple pregnancies are in fact twin pregnancies. Twin pregnancies, regardless of how they are achieved, are associated with large number of complications compared with singleton ones. More often these pregnancies can lead to maternal complications and adverse pregnancy outcomes. Maternal complications include development of preeclampsia, gestational diabetes, placenta previa, placental abruption, premature rupture of membranes, antepartum and postpartum hemorrhage, and delivery by cesarean sections. Adverse pregnancy outcomes mostly include preterm birth (PTB), low birth weight (LBW), small for gestational age newborn (SGA), intrauterine growth restriction (IUGR), neonatal respiratory distress syndrome (RDS), and admission to neonatal intensive care unit (NICU). A number of studies have found differences in the course of twin pregnancies according to their mode of occurrence – spontaneous or after IVF. Some of them have found that twin pregnancies after IVF are associated with poorer obstetric and perinatal outcomes, others do not find such a difference, and there are even studies that find a better outcome in IVF twin pregnancies. Twin pregnancy is a common occurrence after IVF procedure, because multiple-embryo transfer is commonly regarded as an effective strategy to improve the likelihood of a successful pregnancy. Understanding the risks of these pregnancies should be a strong motive for the transfer of fewer embryos during IVF procedures. The most effective way to do this is to transfer a single-embryo into the uterus in cases, where this is justified and the chances of getting pregnant are high. An important element in achieving this goal is the use of methods for vitrification of embryos, which leads to a sufficiently high rate of clinical pregnancies after freezing of embryos obtained by IVF and their subsequent transfer after thawing in case of failure of fresh ET.

Effect of previous Chlamydia Trachomatis infection on the outcomes of ivf/icsi treatment: a retrospective study

BackgroundThe impact of Chlamydia trachomatis infection (CT) on the outcomes of In-Vitro Fertilization / Intracytoplasmic sperm injection (IVF/ICSI) has been controversial.MethodsA total of 431 infertility women aged 20–38 years with or without Chlamydia trachomatis infection before fresh/ frozen embryo transfer were included to investigate the effect of cured CT infection. The infected group was divided into two subgroups for ≤3 months and > 3 months according to the different intervals between Chlamydia trachomatis positive testing and embryo transfer. The effect of chlamydia infection and the intervals between infection and embryo transfer on pregnancy outcomes was analyzed with correction for potential confounders within a multivariable model.ResultsOur results revealed that implantation rate was significantly lower and the premature rupture of membranes (PROM) was higher in women with CT infection than non-infection. The multivariate logistic regression analysis adjusting for baseline characteristics showed no significant difference in live birth rate between neither two groups nor two subgroups.ConclusionsThe study suggests that previous Chlamydia trachomatis infection would lead to high risk of PROM. The intervals between infection and embryo transfer would not impact the pregnancy outcomes of IVF/ICSI.

Regulation of endometrial NF-κB expression in patients with PCOS undergoing total embryo freezing

Background: To investigate Nuclear Factor kappa B (NF-κB) expression pattern in the endometrial samples taken on the day of egg collection in women with polycystic ovarian syndrome (PCOS)scheduled for total embryo freezing due to the risk of ovarian hyperstimulation syndrome (OHSS). Methods: Forty women with PCOS scheduled for total embryo freezing due to the risk of ovarian hyperstimulation syndrome were included in the study. Twenty-five infertile women who decided to freeze all of their embryos for any reason other than PCOS were utilized as the control group. Endometrial sampling was performed from all patients in both groups immediately following the egg collection. Five fertile women with at least two children constituted the second control group. Endometrial sampling was performed from fertile patients during the mid-luteal phase. After immunohistochemical staining of endometrial samples with NF-κB/p65, the intensity of endometrial NF-κB/p65 expression was measured utilizing the H-score method. Results: NF-κB/p65 immunoreactivity was detected in both luminal and glandular endometrial cells from all samples. The mean H-score of endometrial NF-κB/p65 expression in the PCOS group was significantly increased compared to age and Body mass index (BMI) matched control group and fertile controls. NF-κB/p65 immunoreactivity of the control and fertile groups were found to be similar. There was no statistically significant difference in the mean H-score of endometrial NF-κB/p65 expression between the control and fertile groups. A positive and significant correlation was found between H-score values of NF-κB and E2 (estradiol), endometrial thickness, total oocyte count and total follicle stimulating hormone (rFSH) dose on human chorionic gonadotropin (hCG) day. Similarly, a strong positive correlation was found between serum testosterone, insulin levels, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) values and NF-κB values. In addition to progesterone values on hCG day, no significant correlation was found between other parameters and NF-κB. Conclusions: Increased endometrial NF-κB/p65 expression may contribute to the diminished reproductive potential of women with PCOS undergoing total embryo freezing.

Live birth rate following a euploid blastocyst transfer is not affected by double vitrification and warming at cleavage or blastocyst stage.

To compare reproductive outcomes following a euploid embryo transfer, between those embryos vitrified-warmed twice to those vitrified-warmed once. We retrospectively analysed 694 single euploid frozen embryo transfer cycles following preimplantation genetic testing for aneuploidy (PGT-A). For cycles in group 1 (N = 451), embryos were biopsied for PGT-A at blastocyst stage and vitrified. For cycles in group 2 (N = 146), embryos were vitrified at blastocyst stage, before being warmed and biopsied for PGT-A and vitrified again. For cycles in group 3 (N = 97), embryos were vitrified on day-3, before being warmed, cultured to day-5 and biopsied for PGT-A and re-vitrified. The pregnancy, clinical pregnancy and livebirth rate in group 2 were not statistically different to group 1 (pregnancy rate, adjusted OR 1.09, 95% CI 0.62-1.91; clinical pregnancy, aOR 0.89, 95% CI 0.58-1.37; live birth rate, aOR 0.85, 95% CI 0.56-1.28). There was also no significant difference between group 3 and group 1, with similar pregnancy rate (aOR 1.22, 95% CI 0.74-1.99), clinical pregnancy rate (aOR 1.21, 95% CI 0.75-1.96) and live birth rate (aOR 1.15, 95% CI, 0.73-1.80). There was no significant difference in miscarriage rates between all three groups. The age at the oocyte collection, embryo quality and day of biopsy were associated with pregnancy, clinical pregnancy and live birth rate. This study suggests that vitrifying and warming embryos twice at blastocyst or at cleavage and then blastocyst stage, can lead to similar reproductive outcomes to embryos vitrified-warmed once, after a single euploid embryo transfer.

The Impact of Maternal Age on Chromosomal Aneuploidy, Blastocyst Quality, and Pregnancy Outcomes During Intracytoplasmic Sperm Injection Cycles

Background &amp; Objective: Assisted reproduction techniques and preimplantation genetic testing (PGT) for aneuploidies help infertile couples achieve a healthy live birth. The objective of this study was to investigate if there is a correlation between chromosomal aneuploidy and maternal age. Materials &amp; Methods: We used 277 embryos with 6-8 cells and graded A derived from intracytoplasmic sperm injection cycles. There were two subgroups: fresh-PGT cycles (n = 38) and Frozen Embryo Transfer (FET) cycles (n = 38). The PGT cycles results were evaluated by fluorescence in situ hybridization and polymerase chain reaction assays. Couples (n = 76) with PGT on the third day were classified into four maternal age groups: ≤35 years (n = 35), 36-40 years (n = 24), 41-45 years (n = 11), and ≥46 years (n = 6). The rate of aneuploidy, blastocyst quality, and pregnancy was assessed in FET and fresh-PGT cycle. Results: Aneuploidy rate in 13, 18, 21, X, and Y chromosomes in FET and fresh-PGT cycles are not significantly related to maternal age (p = 0.1). Significant differences were found in a decreased chemical pregnancy (p = 0.001), clinical pregnancy (p = 0.001), ongoing pregnancy (p = 0.001), and live birth rate (p = 0.001) among both groups. Decreased blastocyst rate increased maternal age in fresh PGT and FET PGT (p = 0.02). Early and clinical pregnancy loss was not related significantly to maternal age. Conclusion: After evaluating cycle characteristics, an association was found between maternal age and declined pregnancy outcomes in embryos. There was a significant relationship between increasing female age with decreasing blastocyst rate.

Artificial Wombs, Frozen Embryos, and Parenthood: Will Ectogenesis Redistribute Gendered Responsibility for Gestation?

Artificial Wombs, Frozen Embryos, and Parenthood: Will Ectogenesis Redistribute Gendered Responsibility for Gestation?

Elective freezing of embryos versus fresh embryo transfer in IVF: a multicentre randomized controlled trial in the UK (E-Freeze).

Elective freezing of embryos versus fresh embryo transfer in IVF: a multicentre randomized controlled trial in the UK (E-Freeze).

Comparison of pregnancy rates following fresh and frozen embryo transfer in women undergoing assisted reproductive techniques.

Freezing embryos is the best way to increase fertility for women with ovarian hyper-stimulation syndrome and women at risk for ovarian dysfunction. Due to the importance of freezing and pregnancy embryos, the present study was conducted to compare the fertility rate and the affecting factors following fresh embryos and frozen embryos in women treated with assisted reproductive techniques. In this study, 250 infertile women and IVF/ICSI candidates were studied. Embryos were used in fresh or frozen groups for transfer to the uterus. The expression of the caspase-3 gene was also examined for further evaluation. Data analysis was performed using SPSS 16 software, Chi-square, independent t-test, and Kruskal-Wallis tests. Out of 250 infertile women, 96 (38.4%) became pregnant, of which 54 were in the fresh embryo group and 42 were in the frozen embryo group, which was not statistically significant (P=0.32). Infertility causes, number of embryonic cells and grading of transferred embryos, delivery complications, embryo implantation methods, number of produced embryos after delivery, and endometrial thickness were not significantly different between the two groups (P=0.53). The difference between the mean number of transferred embryos in the two groups was significant (P<0.05), which was no longer significant after excluding non-pregnant women, and in comparing with only pregnant women (P=0.36). The result of caspase-3 gene expression showed that there was significant differences between fresh embryos, healthy thawed frozen embryos, and destroyed thawed frozen embryos. But these results were totally different from the results of the Pregnancy rate section. Therefore, it is inferred that although caspase-3 genes are expressed in frozen embryos after thawing and are ready to destroy the embryo, there are probably a number of involved factors that prevent the activity of caspase-3 and do not allow the apoptotic process to occur. What these factors are and how they prevent this process needs further study.

Dydrogesterone supplementation in addition to routine micronized progesterone administration for luteal support in cycles triggered with lone GnRH agonist results in an acceptable pregnancy rate and avoids the need to freeze embryos.

Ovarian hyperstimulation syndrome (OHSS) is reduced when using antagonist cycle with gonadotrophin releasing hormone (GnRH) agonist trigger before ovum pick up. This trigger induces short luteinizing hormone (LH) and follicle stimulating hormone (FSH) peaks, resulting in an inadequate luteal phase and a reduced implantation rate. We assessed whether the luteal phase can be rescued by supplementing with oral dydrogesterone (duphaston) in antagonist cycles after a lone GnRH agonist trigger. A retrospective cohort study. The study group (N.=123) included women who underwent IVF. Patients received a GnRH-antagonist with a lone GnRH-agonist trigger due to imminent OHSS. The control group (N.=374) included patients who underwent a standard antagonist protocol with a dual trigger of a GnRH-agonist and human chorionic gonadotrophin (hCG). All the patients were treated with micronized progesterone (utrogestan) for luteal phase support. Study patients were given duphaston in addition. The fertilization rate was comparable between the two groups. The mean number of embryos transferred, the clinical pregnancy rate and the take-home baby rate were comparable between groups (1.5±0.6 vs. 1.5±0.5 and 46.3% vs. 41.2%, and 66.7% vs. 87.7%, respectively). No OHSS event was reported in either group. This study was the first to evaluate outcomes of duphaston supplementation for luteal support in an antagonist cycle with lone GnRH agonist trigger. The functionality of the luteal phase of those cycles could be restored by adding duphaston. This approach was found to be safe and prevented the need to postpone embryo transfer in case of pending OHSS.

RasH2 mouse: reproducibility and stability of carcinogenicity due to a standardized production and monitoring system.

The rasH2 mouse was developed as a model for carcinogenicity studies in regulatory science. Its phenotype is stable during high-volume production and over successive generations. To produce rasH2 mice, three strains of mice (C57BL/6J-TgrasH2, C57BL/6J, and BALB/cByJ) were maintained individually. Since the homozygous c-HRAS genotype is lethal, hemizygous transgenic mice were maintained by crossing with inbred C57BL/6J mice. After breeding, male B6-transgenic mice were mated with female BALB/cByJ mice to obtain transgenic mice. Pups that were rasH2-Tg (tg/wt) or rasH2-Wt (wt/wt) were confirmed by genotyping. Frozen embryos were preserved by the Central Institute for Experimental Animals (CIEA) and sent to two facilities, CLEA Japan and Taconic Biosciences, where the mice were produced. Production colonies are created in both facilities and supplied to customers worldwide. To prevent genetic drift, the colonies were renewed for up to 10 generations, and renewals were carried out four times every five years from 2005 to 2021. To ensure the uniformity and maintenance of the phenotype of rasH2 mice, the carcinogen susceptibilities were monitored in every renewal of colonies by CIEA based on a standard protocol of the short-term carcinogenicity study using the positive control compound N-methyl-N-nitrosourea (MNU). Furthermore, simple carcinogenicity monitoring targeting the forestomach, the organ most sensitive to MNU, was performed approximately once a year. Based on the optimally designed production and monitoring systems, the quality of rasH2 mice with reproducibility and stability of carcinogenicity is maintained and supplied globally.

Are ICSI results affected by months and seasons? A retrospective cohort study of fresh and frozen cycles

In present study, we aimed to investigate the effect of seasonal variation on ICSI results both in fresh and frozen embryo transfer cycles. Between January 2007 and December 2019, a total of 4039 ICSI cycles (3227 fresh and 812 frozen ET) which resulted in embryo transfer were included in the study. We found no significant difference in the pregnancy outcome among different seasons and months. The best results were obtained for spring (41.0%) and the least for winter (37.1%) in fresh cycles and the best for spring (42.5%) and the least for winter (29.7%) in FET cycles. In monthly distribution, the best results were obtained for September (57.0%) and the least for November (24.1%) in fresh cycles and the best for October (49.3%) and the least for December (20.2%) in FET cycles. Our study did not show any significant influence of the months or seasons on clinical pregnancy rates in either fresh and frozen embryo transfers. However, the difference among months in frozen cycles was notable although it did not reach statistical significance. It can be suggested that the strict control of reproductive hormones especially in fresh cycles as well as the standardized laboratory temperature minimize the influence of seasonal effect on ICSI outcome.

The Impact of Embryo Storage Time on Pregnancy and Perinatal Outcomes and the Time Limit of Vitrification: A Retrospective Cohort Study.

BackgroundThe technique of embryo cryopreservation has been increasingly applied in clinical settings. However, there has been a concern about the safety and efficacy of long-term freezing of embryos. Therefore, the aim of this study was to evaluate whether storage time of vitrification had any effects on pregnancy as well as perinatal outcomes, further, to explore the appropriate time limit of vitrification.MethodsThe study included women who underwent at least one frozen-thawed cycle with single embryo transfer between January 1st, 2016 and September 30th, 2019. Patients were assigned into 3 groups according to the storage time (<3 months, 3-12 months and >12 months) to evaluate the impact of embryo storage time on pregnancy and perinatal outcomes. To further investigate the time limit of vitrification, propensity score matching was used to compare the primary outcomes of patients with storage time of 1-3 years, 3-5 years, and >5 years to those stored for ≤1 year.ResultsA total of 9806 frozen-thawed embryo transfer cycles were included in our study. After adjustment for confounding variables, no significant differences were found in pregnancy outcomes among groups. However, postponement of transfer increased the risks of large for gestational age and placenta previa. In addition, after propensity score matching, 171 cycles with storage time >5 years were matched with those ≤1 year, both the clinical pregnancy rate and live birth rate decreased significantly when the storage time exceeded 5 years.ConclusionsThe duration of vitrification did not significantly affect the pregnancy outcomes within 5 years period. However, the clinical pregnancy rate and live birth rate both decreased significantly when the duration of vitrification exceeded 5 years. It is worth noting that the conclusion was drawn from a small sample study after propensity score matching and should be treated with caution. In addition, the cycles were from different time periods, which could have an impact on the results.

Natural vs. programmed cycles for frozen embryo transfer: study protocol for an investigator-initiated, randomized, controlled, multicenter clinical trial

BackgroundRandomized trials of assisted reproductive technology (ART) have been designed for outcomes of clinical pregnancy or live birth and have not been powered for obstetric outcomes such as preeclampsia, critical for maternal and fetal health. ART increasingly involves frozen embryo transfer (FET). Although there are advantages of FET, multiple studies have shown that risk of preeclampsia is increased with FET compared with fresh embryo transfer, and the reason for this difference is not clear. NatPro will compare the proportion of preeclampsia between two commonly used protocols for FET,modified natural and programmed cycle.MethodsIn this two-arm, parallel-group, multi-center randomized trial, NatPro will randomize 788 women to either modified natural or programmed FET and follow them for up to three FET cycles. Primary outcome will be the proportion of preeclampsia in women with a viable pregnancy assigned to a modified natural cycle FET (corpus luteum present) protocol compared to the proportion of preeclampsia in pregnant women assigned to a programmed FET (corpus luteum absent) protocol. Secondary outcomes will compare the proportion of live births and the proportion of preeclampsia with severe features between the protocols.ConclusionThis study has a potential significant impact on millions of women who pursue ART to build their families. NatPro is designed to provide clinically relevant guidance to inform patients and clinicians regarding maternal risk with programmed and modified natural cycle FET protocols. This study will also provide accurate point estimates regarding the likelihood of live birth with programmed and modified natural cycle FET.Trial registrationClinicalTrials.govNCT04551807. Registered on September 16, 2020

Assessing couples' preferences for fresh or frozen embryo transfer: a discrete choice experiment.

What are couples' preferences for fresh embryo transfer versus freezing of all embryos followed by frozen embryo transfer and the associated clinical outcomes that may differentiate them? Couples' preferences are driven by anticipated chances of live birth, miscarriage, neonatal complications, and costs but not by the differences in the treatment process (including delay of embryo transfer linked to frozen embryo transfer and risk of ovarian hyperstimulation syndrome (OHSS) associated with fresh embryo transfer). A policy of freezing all embryos followed by transfer of frozen embryos results in livebirth rates which are similar to or higher than those following the transfer of fresh embryos while reducing the risk of OHSS and small for gestational age babies: it can, however, increase the risk of pre-eclampsia and large for gestational age offspring. Hence, the controversy continues over whether to do fresh embryo transfer or freeze all embryos followed by frozen embryo transfer. We used a discrete choice experiment (DCE) technique to survey infertile couples between August 2018 and January 2019. We asked IVF naïve couples attending a tertiary referral centre to independently complete a questionnaire with nine hypothetical choice tasks between fresh and frozen embryo transfer. The alternatives varied across the choice occurrences on several attributes including efficacy (live birth rate), safety (miscarriage rate, neonatal complication rate), and cost of treatment. We assumed that a freeze-all strategy prolonged treatment but reduced the risk of OHSS. An error components mixed logit model was used to estimate the relative value (utility) that couples placed on the alternative treatment approaches and the attributes used to describe them. Willingness to pay and marginal rates of substitution between the non-cost attributes were calculated. A total of 360 individual questionnaires were given to 180 couples who fulfilled the inclusion criteria, of which 212 were completed and returned Our study population included 3 same sex couples (2 females and 1 male) and 101 heterosexual couples. Four questionnaires were filled by one partner only. The response rate was 58.8%. Couples preferred both fresh and frozen embryo transfer (odds ratio 27.93 and 28.06, respectively) compared with no IVF treatment, with no strong preference for fresh over frozen. Couples strongly preferred any IVF technique that offered an increase in live birth rates by 5% (P = 0.006) and 15% (P < 0.0001), reduced miscarriage by 18% (P < 0.0001) and diminished neonatal complications by 10% (P < 0.0001). Respondents were willing to pay an additional £2451 (95% CI 604 - 4299) and £761 (95% CI 5056-9265) for a 5 and 15% increase in the chance of live birth, respectively, regardless of whether this involved fresh or frozen embryos. They required compensation of £5230 (95% CI 3320 - 7141) and £13 245 (95% CI 10 110-16 380) to accept a 10 and 25% increase in the risk of neonatal complications, respectively (P < 0.001). Results indicated that couples would be willing to accept a 1.26% (95% CI 1.001 - 1.706) reduction in the live birth rate for a 1% reduction in the risk of neonatal complications per live birth. Older couples appeared to place less emphasis on the risk of neonatal complications than younger couples. DCEs can elicit intentions which may not reflect actual behaviour. The external validity of this study is limited by the fact that it was conducted in a single centre with generous public funding for IVF. We cannot rule out the potential for selection or responder bias. If a strategy of freeze all was to be implemented it would appear to be acceptable to patients, if either success rates can be improved or neonatal complications reduced. Live birth rates, neonatal complication rates, miscarriage rates, and cost are more likely to drive their preferences than a slight delay in the treatment process. The results of this study have important implications for future economic evaluations of IVF, as they suggest that the appropriate balance needs to be struck between success and safety. A holistic approach incorporating patient preferences for expected clinical outcomes and risks should be taken into consideration for individualized care. No external funding was sought for this study. A.M. is the chief investigator of the randomized controlled trial 'Freeze all'. S.B. is an Editor in Chief of Human Reproduction Open. The other co-authors have no conflicts of interest to declare. Graham Scotland reports non-financial support from Merck KGaA, Darmstadt, Germany, outside the submitted work. N/A.

Prolonged Cryopreservation Negatively Affects Embryo Transfer Outcomes Following the Elective Freeze-All Strategy: A Multicenter Retrospective Study.

BackgroundWith the development of embryo freezing and warming technology, frozen-thawed embryo transfer (FET) has been widely utilized. However, studies investigating the association between cryopreservation duration and FET outcomes are limited and controversial, and previous studies did not conduct stratification analyses based on demographic or clinical characteristics.MethodsThis multicenter retrospective study included 17,826 women who underwent their first FET following the freeze-all strategy during the period from January 2014 to December 2018. Duration of cryopreservation was categorized into five groups: 3–8 weeks, 8–12 weeks, 12–26 weeks, 26–52 weeks, and >52 weeks. Modified Poisson regression and multivariate logistic regression were used to assess the association between cryostorage time of vitrified embryos and transfer outcomes. Moreover, further stratification analyses were performed according to variables with p <0.05 in multivariate models.ResultsIn this large multicenter study, we observed that storage duration was inversely associated with the possibility of pregnancy and live birth (p <0.001), but not with the risk of ectopic pregnancy and miscarriage. Stratification analyses based on maternal age, the number of oocytes retrieved, and condition of embryo transferred indicated that the inverse correlation was significant in the subpopulation with characteristics: (1) less than 40 years old, (2) more than 3 oocytes retrieved, and (3) only high-quality blastocysts transferred.ConclusionThe results of this large, multicenter, retrospective study suggested that prolonged cryopreservation was inversely associated with the probability of pregnancy and live birth. Therefore, for patients who adopt a freeze-all strategy, early FET might achieve a better outcome.

Outcomes of embryo transfers performed by Reproductive Endocrinology and Infertility fellows vs. faculty: an 11-year retrospective review

To compare the clinical pregnancy rate (CPR) and live birth rate (LBR) of embryo transfer episodes (ETEs) performed by Reproductive Endocrinology and Infertility fellows vs. those of ETEs performed by faculty physicians. Retrospective cohort analysis. Academic reproductive endocrinology and infertility practice. In total, 3,073 ETEs for 1,488 unique patients were performed by fellows or faculty physicians between January 2009 and January2020. None. Clinical pregnancy rate and LBR. Fifteen fellows performed 1,225 (39.9%) of 3,073 ETEs after completing 30 mock transfers. On comparing outcomes among fellowship years (FY1, FY2, and FY3), CPR (44.1% vs. 43.2% vs. 45.7%, respectively, P = .83) and LBR (39.1% vs. 38.1% vs. 38.4%, respectively, P = .97) were not significantly different. Fellowship year 1 fellows' initial 30 ETEs vs. all the remaining FY1 ETEs had a significantly higher CPR (48.1% vs. 40.5%, respectively, P = .030) and LBR (45.4% vs. 34.3%, respectively, P = .001). There were no significant differences between faculty versus fellow ETEs in terms of CPR (43.0% vs. 45.0%, respectively, P = .30) or LBR (37.3% vs. 39.8%, respectively, P = .16), even after adjusting for patient age, body mass index, primary infertility diagnosis, autologous vs. donor oocyte, fresh vs. frozen embryo, number of embryos transferred, type of transfer catheter, and year of transfer (P = .32 for CPR, P = .22 for LBR). Appropriately trained FY1 fellows had success rates maintained throughout all FYs. There were no significant differences in clinical outcomes between fellow- and faculty-performed transfers. These data demonstrated that allowing fellows to perform live embryo transfers is not detrimental to clinical outcomes.

CHOOSING NOT TO USE: EXAMINING THE REASONS BEHIND DISCARDING VITRIFIED EGGS

Objective: To assess the reasons why patients discard previously vitrified eggs and determine overall outcomes. Materials and Methods: All women who discarded their cryopreserved eggs after having undergone egg vitrification from 2008-2021 at a large assisted reproductive center were analyzed. Demographics such as age at vitrification and disposal, total number of eggs and outcome from vitrification were collected. The reason for disposal was also analyzed through review of disposal request forms. Statistical analysis was performed using ANOVA, with p<0.05 considered statistically significant. Results: We analyzed 124 patients who underwent autologous egg vitrification and later requested to discard their eggs;17 were onco-fertility preservation. 48 patients (39% of those discarding) eventually became pregnant and therefore requested discard. 13 (10%) had natural conception and the remainder (29%) used fertility treatment. 27 patients (22%) discarded based on personal preference, 14 (11%) discarded their eggs because of worsening cancer, and 3 (2.4%) had eggs discarded because of death. 8 patients (6.4%) discarded due to storage costs and 7 (5.6%) discarded due to low yield from retrieval. Ten (8.0%) patients underwent embryo freezing and discarded their previously-frozen eggs;7 (5.6%) patients discarded due to concern from the physician about the quality of the eggs. The average age at freezing and at discard, length of time and total number of eggs frozen varied significantly based on stated reason for discard (p<0.05) (TABLE). Those undergoing fertility preservation were youngest at freeze. Cancer patients stored their eggs the longest and froze the most eggs overall. Interestingly, 32 (26%) of the discards were requested after the COVID-19 pandemic began. Conclusions: This study provides insight into reasons women choose not to use their vitrified eggs. From our exploratory analysis, women who require fertility preservation for cancer are less likely to discard their eggs. Future, larger studies, including survey studies, are needed to further elucidate factors influencing utilization vs. discard of vitrified eggs. Impact Statement: This study will help guide clinical decision making for fertility preservation through oocyte storage. [Formula presented]

Fertility preservation among young breast cancer patients: A single-center experience in China

ObjectiveThis study aims to investigate the status of fertility preservation (FP) in young breast cancer patients. Materials and methodsA clinical database of six women with breast cancer who wished to undergo FP before starting chemotherapy were analyzed between January 2018 and December 2019 in our hospital. Among the six women, three were unmarried and three were married. ResultsThree patients chose oocyte preservation and obtained 23, 7, and 17 MII oocytes, respectively. One patient chose embryo freezing, and three embryos were frozen. Fertility preservation failed for two patients, one of whom had premature ovulation, while the other patient abandoned egg retrieval on the human chorionic gonadotropin (HCG) day. ConclusionThe present results indicate that oocyte and embryo cryopreservation are effective optional methods for young breast cancer patients. However, a lack of knowledge, the urgency of cancer treatment, and financial constraints are causes for a low access rate regarding this process.