Impact of elective frozen vs. fresh embryo transfer strategies on cumulative live birth: Do deleterious effects still exist in normal & hyper responders?

Improvements in human IVF have led to increased pregnancy rates but at the expense of increasing twinning rates. Twins are a bad outcome for the offspring, parents and the healthcare system. An obvious solution to this is to transfer only one embryo and freeze the rest for potential further treatment. This study looked at the effect of doing this on the cumulative live birth rate (when the cryopreserved embryos were thawed and transferred). Patients less than 38 years of age presenting for IVF treatment and with more than two embryos suitable for transfer were offered the chance of transferring only one embryo (elective single embryo transfer, eSET) and freezing the rest. Those patients declining a single embryo transfer had two transferred and served as the controls. Patients not achieving a pregnancy returned for a frozen embryo transfer but were not restricted on the number transferred (to a maximum of two). Cumulative live birth rates were recorded over the ensuing two years. Statistical comparisons were made using paired chi-square tests. The live birth rates from the initial fresh transfer was 41% for eSET (41/111) and significantly higher (53%, P<0.05) for the two-embryo transfer group. These differences were eliminated when the frozen embryos were factored in, both groups rising to 61% of patients treated (68 and 172 live births, respectively). The twinning rate was significantly reduced (P<0.01) from 33% in the two-embryo transfer group to 6% (arising from 4 sets of twins in the frozen embryo transfers) in the eSET group. eSET in the fresh embryo transfer cycle does not affect the chances of a live birth and reduces the twinning rate at least fivefold. Currently, 70% of patients under the age of 38 are electing to have eSET.

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The cumulative live birth rate after a freeze-only strategy versus a conventional fresh embryo transfer strategy: a call for more level 1 evidence

BMC Medicine ◽

10.1186/s12916-019-1479-2 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Daimin Wei ◽

Richard S. Legro ◽

Zi-Jiang Chen

Keyword(s):

Embryo Transfer ◽

Live Birth ◽

Birth Rate ◽

Live Birth Rate ◽

Cumulative Live Birth Rate ◽

Fresh Embryo Transfer ◽

Cumulative Live Birth ◽

Strategy Versus ◽

Level 1

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Comparing the cumulative live birth rate of cleavage-stage versus blastocyst-stage embryo transfers between IVF cycles: a study protocol for a multicentre randomised controlled superiority trial (the ToF trial)

BMJ Open ◽

10.1136/bmjopen-2020-042395 ◽

2021 ◽

Vol 11 (1) ◽

pp. e042395

Author(s):

Simone Cornelisse ◽

Liliana Ramos ◽

Brigitte Arends ◽

Janneke J Brink-van der Vlugt ◽

Jan Peter de Bruin ◽

...

Keyword(s):

Embryo Transfer ◽

Live Birth ◽

Birth Rate ◽

Live Birth Rate ◽

Oocyte Retrieval ◽

Blastocyst Stage ◽

Cleavage Stage ◽

Cumulative Live Birth Rate ◽

Cumulative Live Birth ◽

Superiority Trial

IntroductionIn vitro fertilisation (IVF) has evolved as an intervention of choice to help couples with infertility to conceive. In the last decade, a strategy change in the day of embryo transfer has been developed. Many IVF centres choose nowadays to transfer at later stages of embryo development, for example, transferring embryos at blastocyst stage instead of cleavage stage. However, it still is not known which embryo transfer policy in IVF is more efficient in terms of cumulative live birth rate (cLBR), following a fresh and the subsequent frozen–thawed transfers after one oocyte retrieval. Furthermore, studies reporting on obstetric and neonatal outcomes from both transfer policies are limited.Methods and analysisWe have set up a multicentre randomised superiority trial in the Netherlands, named the Three or Fivetrial. We plan to include 1200 women with an indication for IVF with at least four embryos available on day 2 after the oocyte retrieval. Women are randomly allocated to either (1) control group: embryo transfer on day 3 and cryopreservation of supernumerary good-quality embryos on day 3 or 4, or (2) intervention group: embryo transfer on day 5 and cryopreservation of supernumerary good-quality embryos on day 5 or 6. The primary outcome is the cLBR per oocyte retrieval. Secondary outcomes include LBR following fresh transfer, multiple pregnancy rate and time until pregnancy leading a live birth. We will also assess the obstetric and neonatal outcomes, costs and patients’ treatment burden.Ethics and disseminationThe study protocol has been approved by the Central Committee on Research involving Human Subjects in the Netherlands in June 2018 (CCMO NL 64060.000.18). The results of this trial will be submitted for publication in international peer-reviewed and in open access journals.Trial registration numberNetherlands Trial Register (NL 6857).

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Impact of Endometrial Thickness and Volume Compaction on the Live Birth Rate Following Fresh Embryo Transfer of In Vitro Fertilization

Journal of Ultrasound in Medicine ◽

10.1002/jum.15830 ◽

2021 ◽

Author(s):

Mei T. Lam ◽

Hang W. R. Li ◽

Ernest H. Y. Ng

Keyword(s):

In Vitro Fertilization ◽

Embryo Transfer ◽

Live Birth ◽

Birth Rate ◽

Endometrial Thickness ◽

Live Birth Rate ◽

Fresh Embryo Transfer ◽

Vitro Fertilization

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P–590 Women with hypothalamic hypogonadism have lower live birth rates following frozen embryo transfer

Human Reproduction ◽

10.1093/humrep/deab130.589 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

R Heidenberg ◽

A Lanes ◽

E Ginsburg ◽

C Gordon

Keyword(s):

Embryo Transfer ◽

Live Birth ◽

Polycystic Ovary ◽

Frozen Embryo Transfer ◽

Fresh Embryo Transfer ◽

Ovary Syndrome ◽

Birth Rates ◽

Live Birth Rates ◽

Tubal Factor Infertility ◽

Tubal Factor

Abstract Study question How do live birth rates differ in anovulatory women with polycystic ovary syndrome and hypothalamic hypogonadism compared to normo-ovulatory women undergoing fresh or frozen embryo transfer? Summary answer Live birth rates are similar among all groups undergoing fresh embryo transfer but are significantly lower in women with hypothalamic hypogonadism undergoing frozen embryo transfer. What is known already Conflicting data exist regarding pregnancy outcomes in patients with tubal factor infertility versus polycystic ovary syndrome (PCOS). Some studies demonstrate higher pregnancy and live birth rates for women with PCOS undergoing fresh embryo transfer, but other studies demonstrate no difference. Women with PCOS have higher live birth rates than those with tubal factor infertility when undergoing frozen embryo transfer. Fewer data are available regarding IVF outcomes in women with hypothalamic hypogonadism (HH) and tubal factor infertility. Several studies report comparable live birth rates with fresh embryo transfer, but there are no data on frozen embryo transfer outcomes. Study design, size, duration Retrospective cohort study of all fresh and frozen autologous embryo transfers performed for patients with oligo-anovulation (PCOS, n = 380 and HH, n = 39) and normo-ovulation (tubal factor infertility, n = 315) from 1/1/2012 to 6/30/2019. A total of 734 transfers from 653 patients were analyzed. Participants/materials, setting, methods Transfer outcomes, including implantation, miscarriage, clinical pregnancy and live birth rates, were assessed in fresh and frozen embryo transfer cycles. Adjusted relative risks (RR) and 95% confidence intervals (CI) were calculated adjusting for age, BMI, stimulation protocol, number of embryos transferred, embryo quality, endometrial stripe thickness and day of transfer. Poisson regression was used for counts and with an offset for ratios. Generalized estimating equations were used to account for patients contributing multiple cycles. Main results and the role of chance For fresh embryo transfer cycles, live birth rates are similar among patients with tubal factor infertility, PCOS and HH (29.5% vs. 37.9% vs. 35.9%, respectively, aRR 1.15 95% CI: 0.91–1.44 and aRR 1.23 95% CI: 0.81–2.00, respectively). When evaluating frozen embryo transfer cycles, patients with HH have lower live birth rates than patients with tubal factor infertility (26.5% vs. 42.6%, aRR 0.54 95% CI: 0.33–0.88) and patients with PCOS (26.5% vs. 46.7%, aRR 0.55 95% CI: 0.34–0.88). Additionally, patients with HH have higher chemical pregnancy rates and miscarriage rates than patients with tubal factor infertility (26.5% vs. 13.0% and 17.7% vs. 6.5%, respectively, RR 2.71 95% CI: 1.27–5.77 and RR 2.03 95% CI: 1.05–3.80, respectively). Point biserial correlation showed no significant correlation between live birth and endometrial stripe thickness in HH patients undergoing frozen embryo transfer (r = 0.028, p-value 0.876). Limitations, reasons for caution This study is limited by its retrospective nature and the small sample size of women with hypothalamic hypogonadism. Additionally, these data represent outcomes from a single academic center, so generalizability of our findings may be limited. Wider implications of the findings: Lower live birth rates for HH patients undergoing frozen embryo transfer cycles are not correlated with endometrial stripe thickness. This may be due to absent gonadotropin signaling on endometrial receptors. A prospective randomized trial of HH patients to modified natural versus programmed frozen embryo transfer would best support this hypothesis. Trial registration number Not applicable

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Cumulative live birth rate after up to three consecutive embryo transfer cycles in women with poor ovarian response

Clinical and Experimental Reproductive Medicine ◽

10.5653/cerm.2019.03349 ◽

2020 ◽

Vol 47 (2) ◽

pp. 135-139

Author(s):

Se Jeong Kim ◽

Dayong Lee ◽

Seul Ki Kim ◽

Byung Chul Jee ◽

Seok Hyun Kim

Keyword(s):

Embryo Transfer ◽

Live Birth ◽

Birth Rate ◽

Live Birth Rate ◽

Ovarian Response ◽

Rank Test ◽

Poor Ovarian Response ◽

Cumulative Live Birth Rate ◽

Cumulative Live Birth

Objective: In the present study, we aimed to retrospectively evaluate the cumulative live birth rate (LBR) after up to three consecutive embryo transfer (ET) cycles, either fresh or frozen, in women with expected poor ovarian response (ePOR). Methods: We selected 115 women who entered the first <i>in vitro</i> fertilization (IVF) cycle between August 2013 and July 2016. The women were divided into an ePOR group (37 women) and a non-ePOR group (78 women). All women in the ePOR group were ≥40 years old or had serum anti-Müllerian hormone levels of less than 1.1 ng/mL at the time of the first IVF cycle. Live birth outcomes were monitored until December 2017. The cumulative LBR (with both conservative and optimistic estimates) was calculated according to the serial number of ET cycles. Results: After up to three ET cycles, the overall cumulative LBR was significantly lower in the ePOR group than in the non-ePOR group (conservative estimate, 10.8% vs. 44.9%, respectively; optimistic estimate, 14.7% vs. 56.1%, respectively; log-rank test, <i>p</i>=0.003). Conclusion: Women with ePOR exhibited a lower cumulative LBR than women in the non-ePOR group, and this information should be provided to ePOR women during counseling before starting IVF.

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Live Birth Rate of Fresh Embryo Transfer with GnRH Agonist Long Protocol is Higher Than Frozen Embryo Transfer

10.21203/rs.3.rs-70853/v1 ◽

2020 ◽

Author(s):

Xiaoyan Ding ◽

Jingwei Yang ◽

Lan Li ◽

Na Yang ◽

Ling Lan ◽

...

Keyword(s):

Pregnancy Rate ◽

Embryo Transfer ◽

Live Birth ◽

Pregnancy Loss ◽

Birth Rate ◽

Implantation Rate ◽

Live Birth Rate ◽

Clinical Pregnancy ◽

Fresh Embryo Transfer ◽

Long Protocol

Abstract Background: Along with progress in embryo cryopreservation, especially in vitrification has made freeze all strategy more acceptable. Some studies found comparable or higher live birth rate with frozen embryo transfer (FET) than with fresh embryo transfer（ET）in gonadotropin releasing hormone antagonist (GnRH-ant) protocol. But there were no reports about live birth rate differences between fresh ET and FET with gonadotropin releasing hormone agonist (GnRH-a) long protocol. The aim of this study is to analyze whether patients benefit from freeze all strategy in GnRH-a protocol from real-world data.Methods: This is a retrospective cohort study, in which women undergoing fresh ET or FET with GnRH-a long protocol at Chongqing Reproductive and Genetics Institute from January 2016 to December 2018 were evaluated. The primary outcome was live birth rate. The secondary outcomes were implantation rate, clinical pregnancy rate, pregnancy loss and ectopic pregnancy rate.Results: A total of 7,814 patients met inclusion criteria, implementing 5,216 fresh ET cycles and 2,598 FET cycles, respectively. The demographic characteristics of the patients were significantly different between two groups, except BMI. After controlling for a broad range of potential confounders (including age, infertility duration, BMI, AMH, no. of oocytes retrieved and no. of available embryos), multivariate logistic regression analysis demonstrated that there was no significant difference in terms of clinical pregnancy rate, ectopic pregnancy rate and pregnancy loss rate between two groups (all P>0.05). However, the implantation rate and live birth rate of fresh ET group were significantly higher than FET group (P<0.001 and P=0.012, respectively).Conclusion: Compared to FET, fresh ET following GnRH-a long protocol could lead to higher implantation rate and live birth rate in infertile patients underwent in vitro fertilization (IVF). The freeze all strategy should be individualized and made with caution especially with GnRH-a long protocol.

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P–513 Analysis of the extent of dropout-rates by extraction from cumulative live birth rates in IVF/ICSI: systematic review and meta-analysis

Human Reproduction ◽

10.1093/humrep/deab130.512 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

S Vereeck ◽

A Sugihara ◽

D D Neubourg

Keyword(s):

Embryo Transfer ◽

Live Birth ◽

Weighted Average ◽

Dropout Rate ◽

Dropout Rates ◽

Birth Rates ◽

Complete Cycle ◽

Live Birth Rates ◽

Cumulative Live Birth ◽

Icsi Cycle

Abstract Study question The purpose of this systematic review is to calculate dropout-rates of IVF/ICSI treatment by analysing the published cumulative live birth rates of IVF/ICSI treatment. Summary answer One out of three patients stop their treatment after their first IVF/ICSI cycle and dropout-rates tend to increase per consecutive cycle. What is known already Cumulative live birth rates (CLBRs) have created the possibility to present realistic probabilities of having a live birth after IVF/ICSI treatment. However, it is noted that a significant percentage of the patients stop their treatment before having a child (“dropout”). Possible reasons and predicting factors for dropout of treatment are already extensively investigated. However, only a few studies try to report about the incidence of dropout. Publications on CLBRs of large numbers of patients allow the extraction of dropout-rates. These rates will provide insight in the extent of the problem and could be used as a reference for interventional studies. Study design, size, duration Four databases (PubMed, The Cochrane Library, EMBASE, DoKS) were systematically searched from 1992 to December 2020. Search terms referred to “cumulative live birth” AND “ART/IVF/ICSI”. No restrictions were made on the type or language of publication. Studies were included if they reported absolute numbers of patients and live births per consecutive complete IVF/ICSI cycle or per consecutive embryo transfer cycle, starting from the first IVF/ICSI cycle for each patient. Participants/materials, setting, methods Dropout-rates per cycle were calculated in two manners: “intrinsic dropout-rate” with all patients that started the particular IVF/ICSI cycle in the denominator, and “potential dropout-rate” with all patients who did not achieve a live birth after IVF/ICSI (and potentially could have started a consecutive cycle) in the denominator. Dropout-rates were analysed for consecutive complete cycles and consecutive embryo transfer cycles, because these two manners are used in reporting CLBRs, often related to the reimbursement policy. Main results and the role of chance This review included 29 studies and almost 800,000 patients from different countries and registries. Regarding the patients who started their first IVF/ICSI cycle, trying to conceive their first child by IVF/ICSI, intrinsic dropout-rate was 33% (weighted average) after the first complete cycle, meaning they did not return for their second oocyte retrieval cycle. After the first embryo transfer cycle, intrinsic dropout-rate was 27% (weighted average), meaning those patients did not return for their next frozen-thawed embryo transfer cycle or for the next oocyte retrieval cycle. Regarding the patients who did not achieve a live birth after the first complete cycle, potential dropout-rate was 48% (weighted average), and 37% (weighted average) after the first embryo transfer cycle. Both potential and intrinsic dropout-rates for both consecutive complete and embryo transfer cycles tended to increase with cycle number. One study on second IVF/ICSI conceived children showed a potential dropout-rate after the first complete cycle of 29%. From studies on women >40 years of age, the potential dropout-rate after the first complete cycle was 45% (weighted average) and from studies with the uses of testicular sperm extraction, the potential dropout-rate after the first complete cycle was 34% (weighted average). Limitations, reasons for caution Our analysis was hampered by the different ways of reporting on CLBRs (complete cycles versus embryo transfer cycles), informative censoring, patients changing clinics and spontaneous pregnancies. Dropout-rates were potentially overestimated given that spontaneous pregnancies were not taken into account. Wider implications of the findings: The extent of dropout in IVF/ICSI treatment is substantial and has an important impact on its effectiveness. Therefore, it is a challenge for fertility centers to try to keep patients longer on board, by taking into account the patients’ preferences and managing their expectations. Trial registration number PROSPERO Registration number: CRD42020223512

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