Transfer of Fresh Versus Frozen Embryos in Ovulatory Women

Shi, Yuhua; Sun, Yun; Hao, Cuifang; Zhang, Heping; Wei, Daimin; Zhang, Yunshan; Zhu, Yimin; Deng, Xiaohui; Qi, Xiujuan; Li, Hong; Ma, Xiang; Ren, Haiqin; Wang, Yaqin; Zhang, Dan; Wang, Bo; Li, Fenghua; Wu, Qiongfang; Wang, Ze; Bai, Haiyan; Li, Yuan; Zhou, Yi; Sun, Minmin; Lu, Hong; Li, Jing; Zhang, Lin; Chen, Xiaoli; Sun, Xiaoxi; Legro, Richard S.; Chen, Zi‐Jiang

doi:10.1097/ogx.0000000000000546

Cited by 28 publications

(33 citation statements)

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“…The primary endpoint for this analysis was non-inferiority of LBR when comparing euploid vs mosaic embryos. Assuming a LBR of 45% for uniformly euploid embryos vs 42.5% for moderate or low degree mosaics 16 , assuming a 1:1 sampling ratio for the two groups, and a planning non-inferiority margin of 7.5% 17,18 , we calculated that 421 embryos per group would guarantee a power of at least 90% for a significance level fixed at 5%. This sample size was also >90% powered to claim non-inferiority in the miscarriage rate between control and test group with a margin of 2%, assuming a 10% rate for uniformly euploid embryos and 15% for moderate/low mosaics.…”

Section: Resultsmentioning

confidence: 99%

A prospective double-blinded non-selection trial of reproductive outcomes and chromosomal normalcy of newborns derived from putative low/moderate-degree mosaic IVF embryos

Capalbo

Poli

Rienzi

et al. 2021

Preprint

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Background Next generation sequencing (NGS) has increased detection sensitivity of intermediate chromosome copy number variations (CNV) consistent with chromosomal mosaicism. Recently, this methodology has found application in preimplantation genetic testing (PGT) of trophectoderm (TE) biopsies collected from IVF-generated human embryos. As a consequence, the detection rate of intermediate CNV states in IVF embryos has drastically increased, posing questions about the accuracy in identifying genuine mosaicism in highly heterogeneous biological specimens. The association between analytical values consistent with mosaicism and the reproductive potential of the embryo, as well as newborn's chromosomal normalcy, have not yet been thoroughly determined. Methods We conducted a multicentre, double-blinded, non-selection trial including 1,190 patients undergoing in a total of 1,337 IVF with preimplantation genetic testing for aneuploidies (PGT-A) treatment cycles. NGS was performed on clinical TE biopsies collected from blastocyst-stage embryos. All embryos were reported as euploid if all autosomes had a chromosomal copy number value below the threshold of 50% abnormal cells per sample. After embryo transfer, three comparative classes were analysed: uniformly euploid profiles (<20% aneuploid cells), putative low-degree mosaicism (20%-30% aneuploid cells) or putative moderate-degree mosaicism (30%-50% aneuploid cells). Primary outcome measure was live birth rate (LBR) per transfer and newborn's karyotype. Results LBR after transfer of uniformly euploid embryos, low-degree, and moderate-degree mosaic embryos were 43.4% (95% C.I. 38.9 - 47.9), 42.9% (95% C.I. 37.1 - 48.9) and 42% (95% C.I. 33.4 - 50.9), respectively. No difference was detected for this primary outcome between euploid and mosaic low/moderate categories (OR= 0.96; 95% CI 0.743 to 1.263; P=0.816). The non-inferiority endpoint was met as the confidence interval for the difference fell below the planned 7.5% margin (95% C.I. -5.7 - 7.3). Likewise, no statistically significant difference was observed comparing moderate versus low degree mosaic embryos (P=0.92). Neonatal karyotypes were also similar and no instances of mosaicism or uniparental disomies (UPDs) were detected in babies born following putative low or moderate-degree mosaic embryo transfer. Should the embryos with low or moderate-degree mosaic TE biopsies had been classified as chromosomally abnormal and thus discarded for clinical use, LBR per cycle would have decreased by 36% without any clinical benefit. Conclusions This prospective non-selection trial provides substantial evidence that reporting and/or not transferring embryos with low/moderate-degree mosaicism for whole chromosomes have no clinical utility. Moreover, dismissing these embryos from clinical use has the counterproductive effect of reducing overall embryo availability, thus reducing the chance of successful outcome derived from an IVF treatment without any clinical benefit. (Funded by Igenomix; ClinicalTrials.gov number, NCT03673592)

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Section: Resultsmentioning

confidence: 99%

A prospective double-blinded non-selection trial of reproductive outcomes and chromosomal normalcy of newborns derived from putative low/moderate-degree mosaic IVF embryos

Capalbo

Poli

Rienzi

et al. 2021

Preprint

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“…Frozen embryo was conducted when fresh embryo transfer was unsuccessful. A study of 2157 women in a multicenter randomized trial demonstrated that the risk of moderate or severe ovarian hyperstimulation syndrome was lower among patients who underwent the FET in comparison with fresh embryo transfer 18 . Evidences suggested that embryos were frozen in a fresh IVF cycle, then were thawed and transferred into uterus in the proper condition might improve the pregnancy rates 19‐21 .…”

Section: Discussionmentioning

confidence: 99%

“…A study of 2157 women in a multicenter randomized trial demonstrated that the risk of moderate or severe ovarian hyperstimulation syndrome was lower among patients who underwent the FET in comparison with fresh embryo transfer. 18 Evidences suggested that embryos were frozen in a fresh IVF cycle, then were thawed and transferred into uterus in the proper condition might improve the pregnancy rates. [19][20][21] Furthermore, the occurrence of pregnancies after FET can lead to fewer complications such as lower rates of antepartum hemorrhage, and better neonatal outcomes including higher birth weight and lower risk of perinatal death.…”

Section: Multivariable Logistic Analysis Of Livebirth Ratesmentioning

confidence: 99%

Roles of estradiol levels on the day of human chorionic gonadotrophin administration in the live birth of patients with frozen embryo transfer

Chen

Cai

Liu

et al. 2020

Clinical Laboratory Analysis

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Background Estradiol (E2) is an important hormone in women. Changes of serum E2 levels may affect the endometrial receptivity for embryo implantation and thus affect pregnancy outcomes. This study was to assess the association between serum E2 levels on the day of human chorionic gonadotrophin (HCG) administration and live‐birth rates in patients with frozen embryo transfer (FET). Methods Totally 2071 women receiving long protocols of long‐acting gonadotropin‐releasing hormone (GnRH) agonists were enrolled. According to the E2 levels on the day of HCG administration, these patients were divided into four groups: 676 cases of E2 ≤ 3051 pg/mL in Q1 group, 676 cases of 3051 pg/mL < E2 ≤ 4558 pg/mL in Q2 group, 675 cases of 4558 pg/mL < E2 ≤ 6718 pg/mL in Q3 group, and 674 cases of E2 > 6718 pg/mL in Q4 group. The clinical indicators including female age, body mass index (BMI), duration of infertility, infertility styles, treatment protocols, hormone levels, total antral follicle count, endometrial thickness, top‐level embryos, and live‐birth rates were analyzed, and multivariable logistic model was conducted to select significant variables. Results Significant differences were observed for the female age (OR = 0.965, 95% CI: 0.946‐0.985, P < .001), total antral follicle counts (OR = 1.025, 95% CI: 1.008‐1.043, P = .004), transferring what day of embryos (OR = 1.242, 95% CI: 1.137‐1.356, P < .001), endometrial thickness (OR = 1.058, 95% CI: 1.004‐1.115, P = .035), top‐level embryos (OR = 1.416, 95% CI: 1.157‐1.731, P = .001), and E2 levels on HCG day >6781 pg/mL (OR = 1.344, 95% CI: 1.069‐1.690, P = .011) between live‐birth and non‐live‐birth groups. The area under the curve (AUC) for E2 levels on HCG day was 0.558, the sensitivity was 54.75%, and the specificity was 55.10%. Conclusion Serum E2 level on HCG day was an independent predictor of live‐birth achievement in patients with FET.

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“…Remaining embryos are in most cases cryopreserved and available for future embryo transfers [5]. Use of frozen and thawed embryo transfers (FET) was previously considered to lead to fewer successful pregnancies as compared to fresh embryo transfer, but technical advances such as innovative freezing techniques, vitrification [8,9] and visual embryo selection of embryos or blastocysts have improved the success rate of FET to a level on par with that of fresh embryo transfers [10,11]. In women with the polycystic ovary syndrome (PCOS), the success rate after FET is substantially higher than that after fresh embryo transfers [12].…”

Section: In Vitro Fertilization (Ivf)mentioning

confidence: 99%

Cardiovascular problems associated with IVF therapy

Henriksson

2020

J. Intern. Med.

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We are now in the beginning of the fifth decade of in vitro fertilization (IVF) with more than ten million children born and an annual growth rate of half a million. It was recently found that there is a sevenfold increase in the incidence of pulmonary embolism (PE) during the first trimester of an IVF pregnancy as compared to spontaneous pregnancy. PE is a major cause of maternal mortality, and it is thus of outmost importance to understand the pathophysiological mechanism. The oestrogen surge during the ovarian stimulation has been hypothesized to be the initiating pathophysiological event. A support of this is a current report showing that embryo transfer performed directly after ovarian stimulation increased the risk of PE more than eightfold, whereas no such increase was noted after delayed embryo transfer. This increased risk coincides with a persisting increased oestrogen level. Further reported cardiovascular problems are arterial thromboses, pre‐eclampsia and gestational hypertension. Global haemostasis tests change in the direction of increased coagulability, but mostly within normal limits. Cell‐bound haemostasis and in particular platelet activation are less studied. However, a major increase in the number of microvesicles (MVs) and markers indicating platelet activation was reported during ovarian stimulation. We now need longitudinal data concerning haemostatic variables that extends into the first trimester. A major research focus should be to identify biomarkers that could be used already before instigation of IVF. Another way to avoid risk could be to delay embryo transfer by adapting a freeze‐all strategy.

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Transfer of Fresh Versus Frozen Embryos in Ovulatory Women

Cited by 28 publications

References 0 publications

A prospective double-blinded non-selection trial of reproductive outcomes and chromosomal normalcy of newborns derived from putative low/moderate-degree mosaic IVF embryos

A prospective double-blinded non-selection trial of reproductive outcomes and chromosomal normalcy of newborns derived from putative low/moderate-degree mosaic IVF embryos

Roles of estradiol levels on the day of human chorionic gonadotrophin administration in the live birth of patients with frozen embryo transfer

Cardiovascular problems associated with IVF therapy

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