Single Embryo Transfer Policy Research Articles

P-781 Managing a change of provider bank in a vitrified oocyte donation program

Abstract Study question Does a change in provider bank affect the outcomes of a vitrified oocyte donation program and require laboratory and clinical adjustments? Summary answer In a vitrified oocyte donation program, a change in the provider bank does not affect patients’ outcomes nor require laboratory or clinical adjustments. What is known already Imported vitrified oocyte donation programs are a valuable strategy to provide oocyte donation treatments in settings were donor availability is low or absent. Little is known about how to a change in the provider oocyte bank should be managed in terms of laboratory or clinical adjustments in order not to jeopardize patients’ outcomes. Study design, size, duration Longitudinal cohort study conducted in a Tertiary IVF Center (Centro Scienze Natalità, IRCCS Ospedale San Raffaele, Milan, Italy) between September 2019 and October 2023. Participants/materials, setting, methods All couples undergoing their first imported vitrified oocyte donation cycle were included (n = 235). Oocytes (6 to 9 per cycle) were purchased from one bank (Bank A, Spain, EU) until December 2022 and then from a different bank (Bank B, Spain, EU) from January to October 2023. Single blastocyst-stage embryo transfer policy was adopted in all patients and the cumulative outcomes of patients treated with oocytes purchased from Bank A and Bank B were compared. Main results and the role of chance The number of provided oocytes was higher in Bank B compared to Bank A (8.0 ± 0.8 vs 6.5 ± 0.7, Mean ± SD, p < 0.01). Oocyte survival rates at thawing (87.2 ± 17.2 vs 91.2 ± 16.1 %, Mean ± SD), fertilization rates (75.7 ± 20.8 vs 78.4 ± 28.7, Mean ± SD) and blastulation rates (49.0 ± 28.0 vs 54.5 ± 27.5, Mean ± SD) were stable between Bank A and Bank B respectively, resulting in a higher number of blastocysts available for transfer in cycles performed with oocytes from Bank B compared to Bank A (3.5 ± 2.0 vs 2.4 ± 1.5, Mean ± SD, p < 0.01). Cumulative outcomes showed an improvement in cycles performed with Bank B compared to Bank A (implantation rates 73.8 % vs 62.6 %, ongoing pregnancy rates 69.8 % vs 56.3 %), despite not reaching a statistically significant difference. On multivariate logistic regression, the number of blastocysts available for transfer (OR 2.1, 1.7 -2.7 95% CI, p < 0.01) but not the Bank providing the vitrified oocytes (OR 0.99, 0.40 – 2.43) resulted as significant predictor of ongoing pregnancy. Limitations, reasons for caution Longer follow-up might strengthen our results, as several cycles performed with Bank B are still ongoing and cumulative live-birth rates cannot be currently calculated. In addition, the two banks used are located in the same country. Whether these results also apply to banks located in different settings needs further investigation. Wider implications of the findings Our results reassure about the possibility to manage a vitrified oocyte donation program using oocytes from different banks without jeopardizing patients’ outcomes and without the need for laboratory and clinical adjustments. Trial registration number not applicable

The Fischer protocol for assisted reproductive technology treatment: Real-world data experience comparing elective single versus double embryo transfer with or without comprehensive chromosome screening.

High rates of multiple implantation after assisted reproductive technology (ART) treatment represent one of the major problems for both mothers and their fetuses. Given the availability of techniques intended to identify embryos with the highest chance for development to term, such as comprehensive chromosome screening (CCS) and blastocyst transfer, the decision on the number of embryos to transfer deserves careful consideration. This report presents real-life data from two clinics using the Fischer protocol for cycle programming in patients undergoing ART. Our data indicate that ovarian stimulation using the Fischer protocol provides consistent and optimal ART outcomes in centers following strict quality management standards. However, high multiple implantation rates were observed in fresh and frozen transfer cycles after transferring two embryos - even in patients aged over 39 years. The live birth rates after CCS were superior to those using untested embryos. These findings were held for the three age groups irrespective of the CCS culture day (D1=PN stages, or D5=blastocysts). Our results support a single embryo transfer policy, particularly in women under 34 years of age with favorable conditions during ART treatment, i.e., a high number of available fertilized oocytes.

Twinning in ART: Single embryo transfer policy.

It is more than thirty years that perinatologists and healthcare personnel aim to reduce the morbidity associated with multiple pregnancy. In many cases, these complications stem from pregnancies achieved through artificial reproductive technologies (ART). Although dramatic measures have been taken to control those risks by increasing the proportion of single embryo transfers, the multiple pregnancy rate still remains relatively high among patient conceived through ART, carrying risks to both mothers and newborns, and is coupled with the related economic burden associated with prematurity. The aim of this review is to provide the current evidence regarding single embryo transfer to assist decision-makers and to promote patient knowledge toward an elective policy to reduce the risk of twinning. Single embryo transfer may aid in the further reduction of multiple pregnancy and, in most cases, will maintain patient autonomy and right of choice.

O-290 Cumulative live birth rates in a freeze-all and fresh transfer strategy after one complete ART cycle in ovulatory women

Abstract Study question Is the cumulative live birth rate(CLBR) similar following a freeze-all and fresh transfer strategy including nearly all subsequent frozen-thaw cycles from the same oocyte retrieval? Summary answer The chance of at least one live birth after use off all fresh and frozen blastocysts is similar following a freeze-all and fresh transfer strategy What is known already Traditionally, ART success rates have been reported as pregnancies per fresh cycle or per embryo transfer. Advancements such as blastocyst culture and vitrification have enhanced survival and improved live birth rates. This facilitates single blastocyst transfer, a steadily increasing use of vitrified-warmed transfers, and a growing implementation of elective freeze-all cycles worldwide. Hence CLBRs, defined as the proportion of deliveries with at least one live birth following the use of all fresh and frozen embryos derived from one ovarian stimulation cycle, constitutes a better measure of IVF treatment success providing an all-inclusive success rate for ART. Study design, size, duration CLBR was a secondary outcome in a multicentre randomised trial with allocation 1:1 to (A) Freeze-all strategy involving GnRH agonist trigger and single vitrified-warmed blastocyst transfer in consecutive modified-natural FET cycles or (B) Fresh transfer strategy with hCG trigger and fresh single blastocyst transfer followed by consecutive single blastocyst FET cycles. The minimum follow-up time from the start of ovarian stimulation was 2 years. Participants/materials, setting, methods 460 women initiating their 1.,2. or 3. ART cycle at eight different clinics in Denmark, Sweden and Spain. The GnRH antagonist protocol and modified-natural frozen-thaw cycles with single blastocyst transfer were applied. Cumulative live birth was defined as at least one live birth per woman after all fresh and/or frozen cycles from a single ovarian stimulation. Women were followed until the first live birth. Analyses were performed according to the ITT principle. Main results and the role of chance Baseline and treatment-related characteristics were similar between the two groups and a similar proportion of women had additional frozen-thawed embryo transfers following the initial fresh or frozen transfer. Combining all fresh and/or frozen transfers from the included oocyte retrieval with a minimum of 2-years of follow-up, the cumulative live birth rate was 42.6% (95/223) in the freeze-all group versus 41.7% (96/230) in the fresh transfer strategy group (risk ratio (RR): 1.0; 95%CI 0.87-1.19, P = 0.93). The median (IQR) time to first pregnancy was 106.0 (80.5-156.5) versus 29.0 (27.0-113.5) days in the Freeze all and Fresh transfer group, respectively. Of all subsequent frozen transfers, a total of 34/103 (33%) cycles resulted in a live birth in the freeze all group compared with 29/108 (26.9%) in the fresh transfer group (risk ratio (RR): 1.09; 95% CI 0.91-1.3; P = 0.41). Finally, a total of three (1.3%) and eight (3.5%) blastocysts in the freeze all and fresh transfer strategy group respectively, did not survive the freezing thawing process (p = 0.24). The number of women with unused cryopreserved embryos at the end of the 2-year follow-up period was four (0.9%) in the freeze all and seven (1.6%) in the fresh transfer group. Limitations, reasons for caution The primary RCT outcome was ongoing pregnancy rate following two treatment strategies within the ART regimen hence two different ovulation trigger modalities were applied, introducing a risk of bias. Furthermore, despite a 2-year follow-up few women (2.4%) still had cryopreserved embryos and no live birth at the end of follow-up. Wider implications of the findings Advancements of embryo culture and freezing-thawing techniques facilitate an elective single embryo transfer policy. CLBRs provide an all-inclusive success rate for ART. A freeze-all strategy can be used as an alternative to a fresh transfer strategy in women at risk of OHSS as CLBRs are similar. Trial registration number NCT02746562

The Maternal-Neonatal Outcomes of Twin Pregnancies with Preeclampsia and Their Association with Assisted Reproductive Technology: A Retrospective Study.

Objective: This study aimed to investigate the maternal–neonatal outcomes of twin pregnancies of mothers with preeclampsia and their association with assisted reproductive technology (ART). Methods: A retrospective study on the clinical and maternal–neonatal outcome data of 698 women with twin pregnancies who delivered in our hospital from December 2013 to September 2021 was conducted. Continuous variables were analyzed using a Student’s t-test or Wilcoxon rank-sum test. Categorical variables were analyzed using the Chi-square test. The risk factors of twin pregnancies with preeclampsia were analyzed by logistic regression. Results: The rate of twin pregnancy complicated by preeclampsia was 17.62% (123/698). Logistic regression analysis showed that ART increased the risk of preeclampsia in twin pregnancies (AOR: 1.868, 95% CI: 1.187–2.941). Mothers with preeclampsia carrying twins conceived with ART had a higher rate of delivery at gestational week < 34 (29.9% vs. 12.5%) and asphyxia of the neonate at 5 min after delivery (13.4% vs. 1.8%) than those with preeclampsia conceived without ART (p < 0.05). Conclusions: ART increases the risk of preeclampsia in twin pregnancies and the rate of adverse maternal–neonatal outcomes for twin pregnancies with preeclampsia. The policy of single embryo transfer is a method to reduce the adverse pregnancy outcomes of ART.

The effect of hyaluronic acid in embryo transfer media in donor oocyte cycles and autologous oocyte cycles: a systematic review and meta-analysis.

Does the addition of hyaluronic acid (HA) to embryo transfer medium improve pregnancy outcomes in both autologous and oocyte donation IVF cycles? The best available evidence indicates that the addition of HA to embryo transfer medium is clinically beneficial in cycles with autologous oocytes. There is a known clinical benefit of HA addition to embryo transfer media but it is not known if HA affects donor and autologous oocyte cycles differently. A systematic review with meta-analysis was performed. The Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL via Cochrane Register of Studies Online (CRSO), MEDLINE, Embase and PsycINFO electronic databases (until 8 January 2020) were searched for randomized controlled trials (RCTs) examining the effect of HA in embryo transfer medium on pregnancy outcomes. RCTs with separate donor and autologous oocyte data that compared embryo transfer medium with functional HA concentrations (0.5 mg/ml) to those containing no or low HA concentrations (0.125 mg/ml) were included. Two review authors independently selected trials for inclusion, extracted data and assessed the included studies using the Cochrane risk of bias assessment tool. Pooled risk ratios and 95% CIs were calculated. A summary of findings table was generated using Grading of Recommendations, Assessment, Development and Evaluation criteria. Judgements about evidence quality were justified and incorporated into the reported results for each outcome. Fifteen studies, totalling 4686 participants, were analysed. In autologous oocyte cycles, live birth increased from 32% to 39% when embryo transfer media contained functional HA concentrations (risk ratio (RR) 1.22, 95% CI 1.11-1.34; nine studies, 3215 participants, I2 = 39%, moderate-quality evidence (number needed to treat (NNT) 14). HA-enriched media increased clinical pregnancy and multiple pregnancy rates by 5% and 8%, respectively (RR 1.11, 95% CI 1.04-1.18; 13 studies, 4014 participants, I2 = 0%, moderate-quality evidence, NNT 21) and (RR 1.49, 95% CI 1.27-1.76; 5 studies, 2400 participants, I2 = 21%, moderate-quality evidence, number needed to harm 13). Conversely, in donor oocyte cycles, HA addition showed little effect on live birth and clinical pregnancy (RR 1.12 95% CI 0.86-1.44; two studies, 317 participants, I2 = 50%, low-quality evidence) and (RR 1.06, 95% CI 0.97-1.28; three studies, 351 participants, I2 = 23%, low-quality evidence). There was insufficient available information on multiple pregnancy in donor oocyte cycles and on total adverse effects in both groups to draw conclusions. There were limited studies with separate data on donor oocyte cycles and limited information on oocyte quality. Additionally, one-third of the included studies did not include the main outcome, live birth rate. There is a moderate level of evidence to suggest that functional HA concentration in embryo transfer medium increases clinical pregnancy, live birth and multiple pregnancy rates in IVF cycles using autologous oocytes. This effect was not seen in donor oocyte cycles, indicating either intrinsic differences between donor and autologous oocytes or lack of statistical power. The combination of HA addition to transfer media in cycles using autologous oocytes and a single embryo transfer policy might yield the best combination, with higher clinical pregnancy and live birth rates without increasing the chance of multiple pregnancies. No financial assistance was received. The authors have no competing interests. N/A.

Why does mode of conception affect early breastfeeding outcomes? A retrospective cohort study.

IntroductionIt is uncertain whether Assisted Reproductive Technology (ART) is associated with an increased risk of poor breastfeeding outcomes and what could be possible mechanisms. This study aimed to examine the effect of mode of conception on breastfeeding outcomes during the first two months postpartum and identify the potential mediating pathways for this relationship.MethodsA retrospective cohort study was conducted in a sample of 3,565 women with live births. Participants were classified by mode of conception as follows: fertile women who conceived naturally (fertile women; n = 2,857), women with infertility who conceived naturally (sub-fertile women; n = 483), and women with infertility who conceived through ART (women with infertility; n = 310). The infant-feeding patterns were assessed with four-time points before two months postpartum. Binary and multinomial logistic regression and causal mediation analyses were performed.ResultsThe rates of breastfeeding initiation and discontinuation across modes of conception were similar. However, infertile and sub-fertile women had 37% (95% CI 1.02, 1.83) and 56% (95% CI 1.06, 2.27) increased risks of introducing formula before the first week postpartum, respectively, and 35% (95% CI 1.01, 1.82) and 52% (95% CI 1.04, 2.24) higher risks of exclusive breastfeeding for less than one week, respectively, compared to fertile women. The relationships were mainly mediated through multiple gestation and admission to neonatal/pediatric intensive care units (NICU/PICU; proportions of mediation were over 50%). The effects of mode of conception on breastfeeding outcomes became not significant in cases of singleton birth.ConclusionsSub-fertile women and women with infertility intended to breastfeed but experienced higher perinatal risks in the early postpartum period. Multiple gestation and admission to NICU/PICU forced them to introduce formula earlier than preferred, thus leading to a shorter duration of exclusive breastfeeding. Single embryo transfer policy and breastfeeding support in NICU/PICU could help those women achieve positive early breastfeeding outcomes.

P–696 The duration of estrogen treatment prior to frozen-blastocyst transfer does not impact live birth rate

Abstract Study question Does the prolonged duration of oestrogen treatment prior to frozen-blastocyst transfer (FET) affect live birth rate? Summary answer Variation in the duration of estrogen treatment prior to frozen-blastocyst transfer does not impact live birth rate. What is known already With improvements in cryopreservation techniques and fertility preservation, single embryo transfer policy and the increase in freeze-all cycles, frozen blastocyst transfer (FET) has strongly risen over the last years. Artificial endometrial preparation (AEP) is often used prior to FET. The endometrium is prepared by a sequentially treatment of estrogen and progesterone in order to synchronize endometrium and the embryo development. Whether the duration of progesterone administration before FET is well established, the optimal estrogen treatment duration remains controversial. Study design, size, duration All consecutive frozen thawed autologous blastocyst transfer cycles conducted between January 1, 2012 and July 1, 2019 in our University IVF center were included in this retrospective cohort study. We included 2235 single blastocyst FET cycles prepared with hormonal replacement therapy using oral E2 and vaginal progesterone administration in 1376 patients aged from 18 to 43 years. Participants/materials, setting, methods Patient’s characteristics, stimulation characteristics, FET cycles characteristics and cycles outcomes were anonymously recorded and analyzed. Univariate and multivariate analysis were performed. At first, each FET cycle was analyzed individually and secondly taking into account that some of the patients had undergone several FET, the model considered the number of implanting attempts for each woman. Main results and the role of chance We found no significant difference in the mean duration of estradiol administration before frozen embryo transfer between the group live birth versus non-live birth (27.0 ± 5.4 days versus 26.6 ± 5.0 days ; p=0.11). Endometrial thickness was not significantly different between the 2 groups (8.3 ± 1.7 mm versus 8,2 ± 1,7 mm ; p = 0.21). When the duration of estradiol exposure was analyzed in weeks, we observed no difference for the £ 21 days group (OR = 0.97 ; IC 0.64–1.47 ; p = 0.88), 29–35 days group (OR = 0.89 ; IC 0.68–1.16 ; p = 0.37) and &amp;gt; 35 days group (OR = 0.75 ; IC 0.50–1.15 ; p = 0.10) compared to the reference group (22–28 days). After multivariate analysis, the duration of estradiol treatment before frozen embryo transfer did not affect live birth. Limitations, reasons for caution The relatively limited numbers of cycles with more than 35 days or less than 21 days as well as the retrospective design of the study are significant limitations. Wider implications of the findings: Variation in the duration of estradiol supplementation before progesterone initiation does not impact FET outcomes. We therefore can be reassuring with our patients when E2 treatments need to be extended, allowing flexibility in scheduling the day of transfer. Trial registration number Not applicable

P–724 The association between use of assisted reproductive techniques and childhood asthma: a Swedish nationwide register-based cohort study

Abstract Study question Are the previously reported greater risks of childhood asthma in children conceived by assisted reproductive techniques due to the intervention or unmeasured parental confounding? Summary answer After accounting for both measured and unmeasured parental factors we found no indication that the use of assisted reproductive techniques increases children’s risk of asthma. What is known already Several earlier studies have reported a higher risk of childhood asthma among children conceived by ART. However, only one previous study has attempted a sibling comparison to account for infertility as well as parental background factors, and their findings need to be replicated. Little is thus known on what underlies the higher risk of childhood asthma. Study design, size, duration In this nationwide register-based cohort, we identified all 1,671,532 live births between 1997 and 2013 in the Swedish Medical Birth Register (MBR) and followed them to the end of 2018. Participants/materials, setting, methods Infertility and ART use were ascertained from IVF clinic reporting, clinical diagnosis, and maternal self-report during the first antenatal visit. Childhood asthma was identified from diagnosis in hospitalization and outpatient specialist care records, and dispensations of asthma medication. Cox proportional hazard regression was used to estimate the association of ART and asthma in the population, in children of couples with known infertility, and in a sample of siblings conceived with and without ART (differentially exposed). Main results and the role of chance Of the 1,671,532 live births in the cohort, 11.7% were born to couples with known infertility, and 3.5% were conceived with ART. Compared with all other children, children conceived by ART had a small, elevated risk of asthma (adjusted hazard ratio (aHR)=1.14, 95% Confidence interval (CI) 1.11 to 1.16). When the comparison was restricted to children of couples with known infertility the difference in risk was even smaller (aHR=1.07, 95% CI 1.05 to 1.10), and in the comparison of siblings conceived with and without ART no difference in risk was seen (aHR=0.98, 95% CI 0.86 to 1.13). Among children conceived with ART, those in which intra-cytoplasmic sperm injection (ICSI) had been used had a slightly lower risk of asthma (aHR=0.93, 95% CI 0.90 to 0.97), and no difference in risk was seen between use of fresh and frozen-thawed embryo transfer. Limitations, reasons for caution Sibling comparison is sensitive to potential misclassification, unmeasured confounding and carryover effects, so should be interpreted with this in mind. Differences in treatment implementation across time and settings could affect the ability to extrapolate the conclusions to another clinical context (where e.g., single-embryo transfer policy is not implemented). Wider implications of the findings: This study found a modestly elevated risk of asthma in children conceived with ART to be largely explained by confounding from parental background factors. There were further no indications of adverse influence from increasingly utilized ART procedures such as ICSI or embryo-freezing, with respect to asthma in childhood. Trial registration number Not applicable

Multiple Gestations and Assisted Reproductive Technologies: Qualitative Study of the Discourse of Health Professionals in Spain.

Multiple gestations have become an increasing phenomenon that has impacted public health globally, largely due to the application of assisted reproductive technologies. The objective of this work was to find out the discourse that the health professionals involved in its follow-up have in our context. For this, a qualitative methodology was chosen, with semi-structured interviews recorded in audio, prior authorisation, and transcribed verbatim. It was based on a script designed for this purpose, with the following analysis categories: the current trend of multiple gestations, impact, and follow-up. The content analysis was based on the experiences, knowledge, and perceptions of the professionals interviewed. Professionals stated that the current socioeconomic and legal context hinders a single embryo transfer policy that decreases multiple gestation rates. They emphasised the importance of the psychic impact of such gestations on the couple, on the mother in particular, as well as the economic effect on families, health, and society in general. They expressed the need to create specific protocols to assist these gestations. Midwives, in particular, demanded that the health administration recognise and support the differentiated care they perform with this type of gestation. Work on specific models is needed to adequately size the impact of multiple gestations, as well as to generate social health policies that lead to co-responsible reconciliation measures that favour women having one pregnancy at a time.

Embryo Glue: The Use of Hyaluronan in Embryo Transfer Media.

EmbryoGlue is available to patients at many in vitro fertilization clinics, usually at an additional cost. The efficacy of hyaluronan-enriched transfer medium (HETM) is supported by moderate quality evidence that indicates a significant improvement in clinical outcomes such as live birth rates for patients, including poorer prognosis women (i.e., maternal age factor [>35 years] and recurrent implantation failure). An increased multiple pregnancy rate has been reported with the use of HETM; therefore, a single embryo transfer policy should be considered in conjunction with the use of EmbryoGlue. There is no evidence to suggest that HETM has any detrimental impact, and therefore the use of HETM in clinics may be justified for a specific demographic of patients. Further robust evidence, in the form of meta-analyses or large-scale randomized controlled trials, is needed to build a sufficient consensus regarding the benefit of hyaluronan supplementation in embryo transfer media.

Association between ambient air pollution and pregnancy outcomes in patients undergoing in vitro fertilization in Shanghai, China: A retrospective cohort study

BackgroundThe effects of ambient air pollutants on adverse pregnancy outcomes have been reported. However, studies about air pollutants exposure and pregnancy outcomes in patients undergoing IVF were limited and inconclusive. To date Shanghai has been the only city in China to implement a compulsory single embryo transfer policy for all patients undergoing their first embryo transfer procedure effective from January 2019. We aimed to investigate the associations between exposure to ambient air pollutants and biochemical pregnancy and live births, and to identify potential vulnerability characteristics of patients undergoing IVF in Shanghai, China. MethodsA retrospective cohort study was conducted on 2766 infertile patients aged ≤ 45 years who underwent first fresh or frozen-thawed cleavage stage embryo transfer in the Shanghai First Maternity and Infant Hospital during April 2016 and December 2019. Daily average ambient levels of six air pollutants (PM2.5, PM10, NO2, SO2, CO and O3 max-8h) were obtained from fixed air monitors located in closest proximity to patients’ residences. The cumulative average level was calculated during three different exposure periods (period1: three months before oocyte retrieval to serum hCG test; period 2: from serum hCG test to live birth outcome; period 3: from three months before oocyte retrieval to live birth). Multiple logistic regression model was performed to investigate associations between exposure to ambient air pollutants and pregnancy outcomes. Stratified analyses were conducted to explore the potential effects modifier. ResultsThe biochemical pregnancy rate and live birth rate were 54.2% and 36.4%, respectively. The ambient NO2 exposure was significantly associated with a 14% lower pregnancy rate during period 1 (aOR = 0.86, 95%CI: 0.75–0.99). The ambient PM10 was related to significantly increased risk of lowering live birth rate among the patients during period 3 [aOR = 0.88(0.79–0.99)]. Stratified analysis showed that ambient PM10 was also significantly associated with a reduced pregnancy rate (aOR = 0.82, 95% CI: 0.69–0.97) in patients who underwent single embryo transfer during period 1. Subjects who underwent single embryo transfer also had a decreased likelihood of a live birth when exposed to ambient SO2 and O3 during period 3 [aOR = 0.74(0.57–0.95), and 0.92 (0.83–0.98), respectively]. Moreover, O3 exposure was associated with decreased live birth rates in patients living in non-urban areas. Sensitivity analyses indicated robust negative association between PM10 exposure and live birth outcomes. ConclusionsOur study suggested that exposure to ambient air pollutants, in particular NO2 and PM10, was associated with an increased risk of lower rates of pregnancy and live birth respectively in patients undergoing IVF. Stratified analyses indicated that ambient SO2 and O3 levels were related to adverse pregnancy outcomes in some subgroups of IVF patients in this study. Notably, patients who underwent single embryo transfer were more susceptible to ambient air pollution exposure. Thus, prospective cohort studies are needed to investigate the underlying mechanisms and the susceptibility windows for women undergoing IVF treatment.

Clinical outcomes after single-versus double-embryo transfers in women with adenomyosis: a retrospective study.

Adenomyosis affects the outcomes of spontaneous fertility and assisted reproductive technology. The single blastocyst embryo transfer (SBT) policy is an effective strategy known to minimize the risk of multiple pregnancy for non-adenomyosis women. However, little is known about its applicability to women with adenomyosis. The purpose of this study is to compare pregnancy outcomes between SBT, double-blastocyst embryo transfer (DBT), single-cleavage-stage embryo transfer (SET) and double-cleavage-stage embryo transfer (DET) in the frozen-thawed embryo transfer cycles among adenomyosis patients. This retrospective study was conducted in all frozen-thawed autologous embryo transfer cycles. 393 frozen-thawed embryo transfer cycles performed in adenomyosis patients were enrolled. The major clinical outcomes were implantation rate (IR), clinical pregnancy rate (CPR), miscarriage rate (MR), multiple pregnancy rate (MPR) and live birth rate (LBR). The SBT and DBT groups achieved higher IR (P < 0.001), CPR (P = 0.017), LBR (P = 0.040) and lower MR (P = 0.020) than the SET and DET groups. But the SBT and DBT groups achieved similar CPR and LBR. The SBT and SET groups achieved lower MPR (P < 0.001) than the DBT and DET groups. The average birth weight (BW) of SBT groups was higher than the DBT and DET groups (P = 0.016). When compared with SBT group, low-birth-weight infants were significantly higher with DBT and DET. When performing frozen-thawed embryo transfer cycles among adenomyosis patients, the SBT group has similar IR, CPR, MR, LBR but lower MPR compared to the DBT group. Therefore, SBT might be offered as standard practice.

The Evolution of the Cryopreservation Techniques in Reproductive Medicine—Exploring the Character of the Vitrified State Intra- and Extracellularly to Better Understand Cell Survival after Cryopreservation

Nowadays, cryopreservation of gametes and embryos is a fundamental, integral, and indispensable part of infertility treatment or fertility preservation. Cryopreservation is not only needed for the policy of single embryo transfer and cryopreservation of surplus embryos, but for deferring embryo transfer in the case of ovarian hyperstimulation syndrome, uterine pathologies, and suboptimal endometrium built-up or when preimplantation genetic testing is needed. Several current strategies in assisted reproduction technology (ART) would be inconceivable without highly efficient cryopreservation protocols. Nevertheless, cryopreservation hampered for a long time, especially in terms of low survival rates after freezing and thawing. Only the technical progress during the last decades, namely, in regard to the implementation and advancement of vitrification, leveraged its application, and thus, even allows the cryopreservation of human oocytes—a process that is far from being easy. This review aims to provide a deeper insight into the physical processes of cryopreservation and to explore the character of the vitrified state in the extra and intracellular milieu in order to demonstrate that the common denominator to all cryopreservation procedures is the establishment of an intracellular amorphous condition that hinders the likelihood of crystallization.

The role of frozen–thawed embryo replacement cycles in assisted conception

Key content Recent years have seen a dramatic rise in the number of frozen–thawed embryo replacement (FER) cycles. Improved embryo cryopreservation techniques have resulted in outcomes for FER that are similar to fresh embryo transfer. FER maximises the cumulative live‐birth rate of a fresh in vitro fertilisation (IVF) cycle by using excess embryos and encourages a policy of single embryo transfer; this has contributed to a fall in the multiple pregnancy rate associated with IVF. Freezing all suitable embryos in a fresh cycle reduces the risk of ovarian hyperstimulation syndrome. The endometrium is prepared for FER by a natural or medicated protocol; the optimum method is unknown. Learning objectives To appreciate the importance of FER in IVF practice. To understand the current debate surrounding fresh versus frozen IVF. To understand the indications for, and methods of, embryo cryopreservation. To understand the commonly used methods of endometrial preparation for FER. To be able to date an FER pregnancy. Ethical issues Funding from the National Health Service (NHS) for embryo storage and FER varies widely across the UK; where funding is limited, this can result in viable embryos being discarded. When an embryo is created by a couple, the consent of both partners is required before transferring the embryo.

A massive embryo morphokinetics comparison system is able to select embryos with high implantation potential enhancing single embryo transfer policy

A massive embryo morphokinetics comparison system is able to select embryos with high implantation potential enhancing single embryo transfer policy

18. EUPLOID BLASTOCYSTS IMPLANT IRRESPECTIVE OF THEIR MORPHOLOGY AFTER PREIMPLANTATION GENETIC TESTING-ANEUPLOIDY USING NEXT GENERATION SEQUENCING

Introduction In the context of IVF, it has become imperative to emphasize on embryo evaluation in order to maximise assisted conception outcome while minimising the risk of multiple pregnancy. Despite the exponential rise in knowledge and understanding of the dynamic process of embryo development in the laboratory, the classical evaluation methods based on morphology are still considered as the gold standard methods to classify and select embryos. Morphology assessment helps embryologists to detect dysmorphic or arrested embryos but chromosomal abnormalities can still be only identified by preimplantation genetic testing for aneuploidies (PGT-A). It remains controversial the strength of morphology as a tool to ensure replacement of euploid blastocysts. The present research aims to corroborate whether blastocyst morphology, using a modified Gardner and Cornell's group scoring system, correlates with ploidy status of embryos analysed with next generation sequencing (NGS). We also wanted to ascertain whether biopsy of poor quality embryo yield a euploid embryo to transfer and thus result in a favourable outcome. This is the first data set describing the correlation between blastocyst morphology and embryo ploidy status using NGS and clinical outcomes. Materials and Methods 296 patients underwent PGT-A. Of 1,549 blastocysts, 1,410 blastocysts had a conclusive result after PGT-A and were included for analysis. An elective single embryo transfer (eSET) policy was followed in a frozen embryo replacement cycle. A total of 179 euploid blastocysts were thawed and transferred. Clinical outcomes were categorised in four different embryo quality groups: excellent, good, average and poor. Results Euploidy rates were 19/36 (52.7%, 95% CI 37-68), 199/470 (42.3%, 95% 38-47), 156/676 (23.0%, 95% CI 20-26) and 39/228 (17.1%, 95% CI 13-23) in the excellent, good, average and poor quality blastocyst groups, respectively. Fitted logistic regression analysis taking into account the following co-variables; female age, embryo chromosomal status, and day of blastocyst development/biopsy showed that good (OR 0.6; 95% CI 0.4-0.8;p=0.001), average (OR 0.5; 95% CI 0.4-0.7; p=0.001) and poor (OR 0.2;95% CI 0.1-0.5; p=0.005) morphology with excellent morphology being the reference group was predictive of the comprehensive chromosome testing result. A logistic regression analysis was also performed on clinical outcomes taking into account for the effect of blastocyst morphology and day of blastocyst development/biopsy. None of the parameters were shown to be significant suggesting morphology irrespective of the embryo quality category and day of blastocyst development/biopsy do not reduce the competence of euploid embryos (p>0.05). Conclusions After euploid eSET, implantation rate was 80-86%; live birth rate per embryo transfer was 60-73% and clinical miscarriage rate was found to be less than 10% and were not significanlty affected by the embryo morphology category. These results are concordant with those reported when using array compartive genomic hybridization and highlights the competence of poor quality euploid embryos.

The health of children conceived by ART: 'the chicken or the egg?'

Worldwide, more than 7 million children have now been born after ART: these delivery rates are steadily rising and now comprise 2-6% of births in the European countries. To achieve higher pregnancy rates, the transfer of two or more embryos was previously the gold standard in ART. However, recently the practise has moved towards a single embryo transfer policy to avoid multiple births. The positive consequences of the declining multiple birth rates after ART are decreasing perinatal risks and overall improved health for the ART progeny. In this review we summarize the risks for short- and long-term health in ART singletons and discuss if the increased health risks are associated with intrinsic maternal or paternal factors related to subfertility or to the ART treatments per se. Although the risks are modest, singletons born after ART are more likely to have adverse perinatal outcomes compared to spontaneously conceived (SC) singletons dependent on the ART method. Fresh embryo transfer is associated with a higher risk of small for gestational age babies (SGA), low birthweight and preterm birth (PTB), while frozen embryo transfer is associated with large-for-gestational age babies and pre-eclampsia. ICSI may be associated with a higher risk of birth defects and transferral of the poor semen quality to male progeny, while oocyte donation is associated with increased risk of SGA and pre-eclampsia. Concerning long-term health risks, the current evidence is limited but suggests an increased risk of altered blood pressure and cardiovascular function in ART children. The data that are available for malignancies seem reassuring, while results on neurodevelopmental health are more equivocal with a possible association between ART and cerebral palsy. The laboratory techniques used in ART may also play a role, as different embryo culture media give rise to different birthweights and growth patterns in children, while culture to blastocyst stage is associated with PTB. In addition, children born after ART have altered epigenetic profiles, and these alterations may be one of the key areas to explore to improve our understanding of adverse child outcomes after ART. A major challenge for research into adverse perinatal outcomes is the difficulty in separating the contribution of infertility per se from the ART treatment (i.e. 'the chicken or the egg'?). Choosing and having access to the appropriate control groups for the ART children in order to eliminate the influence of subfertility per se (thereby exploring the pure association between ART and child outcomes) is in itself challenging. However, studies including children of subfertile couples or of couples treated with milder fertility treatments, such as IUI, as controls show that perinatal risks in these cohorts are lower than for ART children but still higher than for SC indicating that both subfertility and ART influence the future outcome. Sibling studies, where a mother gave birth to both an ART and a SC child, support this theory as ART singletons had slightly poorer outcomes. The conclusion we can reach from the well designed studies aimed at disentangling the influence on child health of parental and ART factors is that both the chicken and the egg matter.

Increased incidence of obstetric and perinatal complications in pregnancies achieved using donor oocytes and single embryo transfer in young and healthy women. A prospective hospital-based matched cohort study

In this single-center matched-cohort study, women who underwent IVF/ICSI with donor oocytes between 2007 and 2014 (n = 259) were compared to women undergoing autologous cycles during the same time period (n = 515). The matching (1:2) took into consideration the women’s age, type of treatment (IVF/ICSI), and year of embryo transfer. All women were healthy and below 40 years of age at the time of IVF/ICSI, and the treatments were performed using a strict policy of single embryo transfer. Multiple logistic regression analysis, adjusted for body mass index (BMI), smoking, and parity, showed a four times increased risk of gestational hypertensive disorders (adjusted odds ratio, AOR 4.25; 95% confidence interval (CI), 2.61–6.92) and pre-eclampsia (AOR 3.99; 95% CI 2.27–7.00) in pregnancies achieved with donor oocytes. There was also a higher rate of cesarean section in women who gave birth after oocyte donation (AOR 1.69; 95% CI 1.22–2.35) and a higher risk of postpartum hemorrhage >1000 mL (AOR 1.59; 95% CI, 1.11–2.27). After further adjustment for preeclampsia in the logistic regression analysis, no additional increased perinatal risks were found. The incidence of preterm delivery, low weight at birth, need of neonatal intensive care, Apgar scores, and incidence of perinatal death were also similar between the groups.

Elective Single Embryo Transfer in the Setting of Funded In Vitro Fertilization: Two Years' Experience in an Ontario Hospital-Based Fertility Clinic.

The objective of this study was to assess data from a fertility clinic and identify differences in patient and cycle characteristics, clinical pregnancy rates, and multiple gestation rates before and after fertility treatment funding and a policy of elective single embryo transfer were instituted by the Ontario government to reduce multiple gestations arising from fertility treatment. This study was a retrospective database review of clinic and embryology laboratory data for all patients undergoing in vitro fertilization (IVF) and intracytoplasmatic sperm injection (ICSI) cycles over a 4-year period. The investigators compared IVF and ICSI cycles before funding, from January 1, 2014 to December 31, 2015, with cycles after funding, from January 1, 2016 to December 31, 2017. The number of cycles performed over a 2-year period increased from 554 to 853, of which 76.2% were funded. Patient age, body mass index, and parity were similar before and after funding. Fewer patients receiving funded IVF or ICSI had had a previous cycle. Cycle cancellation rates were similar before and after funding; however, there were fewer embryo transfers per cycle start after funding (80.3% vs. 72.2%, P = 0.001). The clinical pregnancy rate was similar before and after funding (37.8% vs. 32.5%, P = 0.09), whereas the multiple gestation rate was significantly lower (13.1% vs. 3.5%, P = 0.001). Since the government of Ontario began funding IVF and ICSI cycles, more patients are accessing treatment, many for the first time. The clinical pregnancy rate was maintained, whereas multiple gestations were significantly reduced. These findings support the benefit of single embryo transfer in the context of funded IVF and ICSI and demonstrate the importance of government-funded assisted reproductive technology.