Gavi: 世界第一部全自動胚胎玻璃化冷凍儀器

https://vimeo.com/113990868

J Gynecol Obstet Hum Reprod. 2019 May 8. pii: S2468-7847(19)30109-6. doi: 10.1016/j.jogoh.2019.05.012. [Epub ahead of print]

The first report of pregnancies following blastocyst automated vitrification in Europe.

Dal Canto M1, Moutier C2, Brambillasca F3, Guglielmo MC4, Bartolacci A5, Fadini R6, Renzini MM7, Buratini J8.

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Abstract

Embryo cryopreservation is a valuable technique in assisted reproductive technology (ART) that increases cumulative pregnancy rates and allows postponement of embryo transfer in patients with undesirable uterine or clinical conditions. Although vitrification has been considered the most efficient method to freeze oocytes and embryos, it is time-consuming and highly operator-dependent. Gavi® is the first semi-automated machine for vitrification capable of controlling crucial variables such as temperature, volume, concentration and exposure time during the vitrification process. We report the first two pregnancies obtained with blastocysts cryopreserved with the Gavi® semi-automated vitrification system in Europe. These outcomes suggest that the utilization of semi-automated vitrification may contribute to improve the outcomes and laboratory logistics of fertility clinics.

Day5囊胚著床率高於Day6囊胚著床率 (47%  vs 28%)

Cell Mol Biol (Noisy-le-grand). 2019 Apr 30;65(4):1-5.

Delayed development influences the outcome of different grades of D5 and D6 blastocysts during freeze-thaw cycle.

Zhang H1, Arhin SK1, Zhao J1, Hou X1, Chen Y1, Huang Z1.

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Abstract

To analyze the effects of blastocysts on the 5th day (D5) and 6th day (D6) of frozen-thawed blastocyst transplantation on pregnancy outcome and provide evidence for further improvement of the strategy. This study included transfers from the Reproductive Medicine Center of the Second Affiliated Hospital of Wenzhou Medical University during freeze-thaw cycles from January 2016 to December 2017. They were divided into D5 group (1616 cases) and D6 group (619 cases) according to blastocyst formation and development. Each group was further divided into 5 groups according to the quality of the blastocyst and the number of transplants, making a total of 10 groups. Following the frozen transplantation cycle, the transplanting rate was significantly higher for D5 (41.73%) than for D6 (23.98%) (P < 0.05); the ongoing pregnancy rate (47,40%) was also significantly higher than that of D6 (28.43%) (P < 0.05).In the frozen-thawed blastocyst resuscitation transplantation, compared to D6 blastocysts, D5 blastocysts were more conducive to blastocyst implantation and could be used to achieve better clinical pregnancy outcome. In blastocyst selection, a single D5 excellent blastocyst transplant is preferred. Only at the 6th day of non-excellent D6, 2 blastocysts are recommended for transplantation.

子宮外孕輸卵管切除手術對於卵巢排卵反應沒有明顯不良影響

J Gynecol Obstet Hum Reprod. 2019 May 17. pii: S2468-7847(19)30061-3. doi: 10.1016/j.jogoh.2019.05.009. [Epub ahead of print]

Impact of salpingectomy for ectopic pregnancy on the ovarian response during IVF stimulation.

Gay C1, Perrin J2, Courbiere B2, Bretelle F3, Agostini A4.

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Abstract

INTRODUCTION:

Ovarian reserve is a major prognosic factor for Medical Assisted Procreation. Tubal surgery, realised close to mesosalpinx and ovarian vascularization, could impare ovarian function. However, salpingectomy is currently used to treat ectopic pregnancies or hydrosalpinx before IVF attempt. Disponible studies on this subject are unclear. The aim of this study is to evaluate the impact of salpingectomy for ectopic pregnancy on the ovarian response during IVF attempt.

MATERIAL AND METHODS:

It was a single center comparative study. Included patients were the one receiving oocyte puncture for IVF attempt, with a history of unilateral tubal surgery: salpingectomy for ectopic pregnancy. We conducted a case-control study, comparing the sonographic parameters of the surgery ovary (case) to those of the safe ovary (control) during the first IVF attempt after salpingectomy. The ovarian sonographic response was evaluated according to the follicular antral count on day 3 and the sonographic follicular count on trigger day.

RESULTS:

55 patients were included. There was no significant difference in the number of recruited follicles on the operated side versus control side (p = 0.85 for >14 mm follicles, p = 0,46 for 10 to 14 mm, p = 0,52 for total amount of recruited follicles). There was no significant difference for the follicular antral count neither (p = 0.79).

DISCUSSION:

In our population, there was no significant difference in the sonographic ovarian response to IVF stimulation between the ovary on the operated side and the control ovary among patients treated by unilateral salpingectomy for ectopic pregnancy.

HCG合併FSH用於破卵, IVF懷孕結果優於傳統ＨＣＧ破卵

Int J Fertil Steril. 2019 Jul;13(2):102-107. doi: 10.22074/ijfs.2019.5701. Epub 2019 Apr 27.

Comparison of Oocyte Maturation Trigger Using Follicle Stimulating Hormone Plus Human Chorionic Gonadotropin versus hCG Alone in Assisted Reproduction Technology Cycles.

Dashti S1, Aflatoonian A2, Tabibnejad N1.

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Abstract

BACKGROUND:

The goal of this study was to investigate oocyte maturation, fertilization and pregnancy rates among infertile women, by concomitant follicle stimulating hormone (FSH) administration at the time of human chorionic gonadotropin (hCG) trigger, compared to hCG trigger alone.

MATERIALS AND METHODS:

In this prospective randomized controlled trial, 109 infertile women between the ages of 20 and 40 years, received gonadotropin-releasing hormone (GnRH) antagonist and fresh embryo transfer. Following the procedure, the subjects were randomly divided into two groups on the oocyte-triggering day. In the experimental group, final oocyte maturation was achieved by 5000 IU hCG plus 450 IU FSH. In the control group, however, oocyte triggering was performed by 5000 IU hCG, only. The primary outcome was clinical pregnancy and the secondary outcomes included oocyte recovery rate, oocyte maturity rate, fertilization proportion rate, fertilization rate, implantation rate and chemical pregnancy rate.

RESULTS:

Fifty-four women were appointed to the group with the FSH bolus injection at the time of hCG trigger and 55 women were assigned to the hCG alone group. Women in the FSH group had a significantly higher metaphase II (MII) oocyte (7.17 ± 3.50 vs. 5.87 ± 3.19), 2 pronuclear embryos (2PNs) (5.44 ± 3.20 vs. 3.74 ± 2.30) and total embryos (4.57 ± 2.82 vs. 3.29 ± 2.13) compared to hCG alone group, respectively. Furthermore, fertilization rate (0.75 ± 0.19 vs. 0.68 ± 0.25), implantation rate (14.2 vs. 8.5%) as well as clinical (27.9 vs. 15.9%) and chemical (32.6 vs. 20.5%) pregnancy rates were higher in the FSH group, but no statistically significant difference was found (P>0.05).

CONCLUSION:

Combination of FSH and hCG for oocyte triggering improves oocyte maturity and fertilization proportion rates without increasing the chance of implantation, chemical and clinical pregnancy rates (Registration number: IRCT2017082724512N5).

AMH比FSH 具有更高之卵巢功能預測率
當AMH & FSH不一致時  應以AMH優先評估根據

Fertil Steril. 2019 May 2. pii: S0015-0282(19)30295-X. doi: 10.1016/j.fertnstert.2019.03.022. [Epub ahead of print]

Low antimüllerian hormone (AMH) is associated with decreased live birth after in vitro fertilization when follicle-stimulating hormone and AMH are discordant.

Ligon S1, Lustik M2, Levy G1, Pier B3.

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Abstract

OBJECTIVE:

To evaluate which factor, AMH or FSH, was superior in predicting live birth after assisted reproductive technologies (ART) when the tests are discordant, using data from the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System database.

DESIGN:

Retrospective cohort.

SETTING:

Clinic-based data.

PATIENT(S):

The study population included 44,696 fresh embryo transfer cycles using autologous oocytes.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Live birth (≥22 wk gestation and ≥300 g birth weight).

RESULT(S):

Live birth rate per started cycle was lower in patients with low AMH and normal FSH than in patients with normal AMH and elevated FSH (26% vs. 39%). A multivariate analysis was performed on patients with normal FSH and low AMH, and the following factors were independently associated with live birth: AMH, age >40 years, body mass index >30 kg/m2, race African-American or Asian, IVF clinic region West, uterine factor infertility diagnosis, agonist suppression, and FSH dosage. IVF cycle cancellation rate was higher in patients with low AMH and normal FSH (30%).

CONCLUSION(S):

AMH is a superior predictor of live birth in patients undergoing IVF when FSH and AMH values are discordant. Lower AMH is independently associated with lower live birth and higher IVF cycle cancellation rates than elevated FSH in patients with discordant values.

Published by Elsevier Inc.

PGS可能提高妊娠高血壓之機率 (10.5% versus 4.1%)

Fertil Steril. 2019 May 15. pii: S0015-0282(19)30316-4. doi: 10.1016/j.fertnstert.2019.03.033. [Epub ahead of print]

Maternal and neonatal outcomes associated with trophectoderm biopsy.

Zhang WY1, von Versen-Höynck F2, Kapphahn KI3, Fleischmann RR4, Zhao Q4, Baker VL5.

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Abstract

OBJECTIVE:

To assess whether pregnancies achieved with trophectoderm biopsy for preimplantation genetic testing (PGT) have different risks of adverse obstetric and neonatal outcomes compared with pregnancies achieved with IVF without biopsy.

DESIGN:

Observational cohort.

SETTING:

University-affiliated fertility center.

PATIENT(S):

Pregnancies achieved via IVF with PGT (n = 177) and IVF without PGT (n = 180) that resulted in a live birth.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Maternal outcomes including preeclampsia and placenta previa and neonatal outcomes including birth weight and birth defects.

RESULT(S):

There was a statistically significant increase in the risk of preeclampsia among IVF+PGT pregnancies compared with IVF without PGT pregnancies, with an incidence of 10.5% versus 4.1% (adjusted odds ratio [aOR] = 3.02; 95% confidence interval [95% CI], 1.10, 8.29). The incidence of placenta previa was 5.8% in IVF+PGT pregnancies versus 1.4% in IVF without PGT pregnancies (aOR = 4.56; 95% CI, 0.93, 22.44). Similar incidences of gestational diabetes, preterm premature rupture of membranes, and postpartum hemorrhage were observed. IVF+PGT and IVF without PGT neonates did not have a significantly different gestational age at delivery or rate of preterm birth, low birth weight, neonatal intensive care unit admission, neonatal morbidities, or birth defects. All trends, including the significantly increased risk of preeclampsia in IVF+PGT pregnancies, persisted upon stratification of analysis to only singleton live births.

CONCLUSION(S):

To date, this is the largest and most extensively controlled study examining maternal and neonatal outcomes after trophectoderm biopsy. There was a statistically significant three-fold increase in the odds of preeclampsia associated with trophectoderm biopsy. Given the rise in PGT use, further investigation is warranted.

PGS若TE cell出現segmental aneuploids, ICM僅42％出現aneuploids
PGS若TE cell出現whole chromosome aneuploids, ICM98％出現aneuploids

Hum Reprod. 2019 Jan 1;34(1):181-192. doi: 10.1093/humrep/dey327.

Assessment of aneuploidy concordance between clinical trophectoderm biopsy and blastocyst.

Victor AR1,2, Griffin DK2, Brake AJ1, Tyndall JC1, Murphy AE1, Lepkowsky LT1, Lal A1, Zouves CG1,3, Barnes FL1,3, McCoy RC4, Viotti M1,3.

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Abstract

STUDY QUESTION:

Is a clinical trophectoderm (TE) biopsy a suitable predictor of chromosomal aneuploidy in blastocysts?

SUMMARY ANSWER:

In the analyzed group of blastocysts, a clinical TE biopsy was an excellent representative of blastocyst karyotype in cases of whole chromosome aneuploidy, but in cases of only segmental (sub-chromosomal) aneuploidy, a TE biopsy was a poor representative of blastocyst karyotype.

WHAT IS KNOWN ALREADY:

Due to the phenomenon of chromosomal mosaicism, concern has been expressed about the possibility of discarding blastocysts classified as aneuploid by preimplantation genetic testing for aneuploidy (PGT-A) that in fact contain a euploid inner cell mass (ICM). Previously published studies investigating karyotype concordance between TE and ICM have examined small sample sizes and/or have utilized chromosomal analysis technologies superseded by Next Generation Sequencing (NGS). It is also known that blastocysts classified as mosaic by PGT-A can result in healthy births. TE re-biopsy of embryos classified as aneuploid can potentially uncover new instances of mosaicism, but the frequency of such blastocysts is currently unknown.

STUDY DESIGN, SIZE, DURATION:

For this study, 45 patients donated 100 blastocysts classified as uniform aneuploids (non-mosaic) using PGT-A by NGS (n = 93 whole chromosome aneuploids, n = 7 segmental aneuploids). In addition to the original clinical TE biopsy used for PGT-A, each blastocyst was subjected to an ICM biopsy as well as a second TE biopsy. All biopsies were processed for chromosomal analysis by NGS, and karyotypes were compared to the original TE biopsy.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

The setting for this study was a single IVF center with an in-house PGT-A program and associated research laboratory.

MAIN RESULTS AND THE ROLE OF CHANCE:

When one or more whole chromosomes were aneuploid in the clinical TE biopsy, the corresponding ICM was aneuploid in 90 out of 93 blastocysts (96.8%). When the clinical TE biopsy contained only segmental (sub-chromosomal) aneuploidies, the ICM was aneuploid in three out of seven cases (42.9%). Blastocysts showing aneuploidy concordance between clinical TE biopsy and ICM were also aneuploid in a second TE biopsy in 86 out of 88 cases (97.7%). In blastocysts displaying clinical TE-ICM discordance, a second TE biopsy was aneuploid in only two out of six cases (33.3%).

囊胚染色體正常率僅3-4成
年輕病患的卵子僅有16%會形成染色體正常之胚胎
超高齡>41歲病患的卵子僅有4%會形成染色體正常之胚胎

Fertil Steril. 2019 May 15. pii: S0015-0282(19)30323-1. doi: 10.1016/j.fertnstert.2019.03.040. [Epub ahead of print]

Euploidy rates between cycles triggered with gonadotropin-releasing hormone agonist and human chorionic gonadotropin.

Thorne J1, Loza A1, Kaye L1, Nulsen J1, Benadiva C1, Grow D1, Engmann L2.

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Abstract

OBJECTIVE:

To evaluate differences in euploidy rates between IVF cycles triggered with either GnRH agonist (GnRHa) or hCG.

DESIGN:

Retrospective cohort study.

SETTING:

University-affiliated fertility center.

PATIENT(S):

A total of 366 patients performing 539 IVF cycles utilizing preimplantation genetic testing for aneuploidy (PGT-A).

INTERVENTION(S):

Gonadotropin-releasing hormone agonist or hCG trigger of oocyte maturation during IVF cycles.

MAIN OUTCOME MEASURE(S):

Rate of euploid embryos.

RESULT(S):

Patients in the GnRHa trigger arm were younger, with a lower body mass index and higher antimüllerian hormone level, and they had a higher number of oocytes retrieved and embryos biopsied. Euploid rate per embryo biopsied was higher after GnRHa trigger than after hCG trigger (37.8% ± 2.1% vs. 30.3% ± 1.8%), but multivariate regression analysis controlling for potential confounding factors did not show any differences between the two groups. Moreover, the euploid rate per oocyte retrieved was not significantly different overall (GnRHa vs. hCG: 33.9% ± 2.2% vs. 28.0% ± 1.9%). The anticipated decline in the rate of euploid embryos per oocyte retrieved went from 15.8% ± 1.2% for age <35 years to 4.3% ± 0.9% for patients aged ≥41 years. There were no significant differences between the two groups after stratifying by age and controlling for PGT-A testing modality.

CONCLUSION(S):

Both GnRHa and hCG trigger result in comparable euploid rates. Trigger with GnRHa should therefore be considered a valid option for trigger modality in freeze-all PGT-A cycles, in view of its demonstrated effectiveness and known safety enhancement.

Copyright © 2019. Published by Elsevier Inc.

母體B肝帶原較容易不孕, 接受IVF-ET後胚胎著床率較低 

ertil Steril. 2019 May 15. pii: S0015-0282(19)30322-X. doi: 10.1016/j.fertnstert.2019.03.039. [Epub ahead of print]

Maternal chronic hepatitis B virus infection does not affect pregnancy outcomes in infertile patients receiving first in vitro fertilization treatment.

Wang L1, Li L2, Huang C1, Diao L1, Lian R1, Li Y1, Xiao S1, Hu X1, Mo M1, Zeng Y3.

Abstract

OBJECTIVE:

To evaluate whether maternal chronic hepatitis B virus (HBV) infection affects pregnancy outcomes in infertile patients undergoing their first in vitro fertilization (IVF) treatment.

DESIGN:

A retrospective case control study.

SETTING:

Fertility center.

PATIENT(S):

Female patients, comprising 8,550 infertile women including 180 HBsAg+HBeAg+, 714 HBsAg+HBeAg-, and 7,656 HBsAg seronegative controls undergoing their first IVF treatments.

INTERVENTION(S):

Clinical characteristics, pregnancy and neonatal outcomes were analyzed by Kruskal-Wallis test, analysis of variance, or chi-square test. Logistic regression was employed to verify the contribution of maternal HBV to clinical pregnancy, live birth, and miscarriage.

MAIN OUTCOME MEASURE(S):

Primary outcome: live-birth rate; secondary outcomes: implantation, clinical pregnancy, and miscarriage rates.

RESULT(S):

An increased duration of infertility and more secondary infertility and ovulatory disorders were observed in the HBV patients. The implantation rate was statistically significantly lower in the HBsAg+HBeAg- group compared with the controls. However, the clinical pregnancy rate, miscarriage rate, live-birth rate, neonatal outcomes, and pregnancy complications showed no statistically significant differences among the groups. The logistic regression analysis showed that HBV infection status did not affect the clinical pregnancy, miscarriage, or live-birth rates, unlike maternal age, endometrial thickness, and use of high-quality embryos.

CONCLUSION(S):

Hepatitis B virus infection is not an independent contributor to pregnancy outcomes, although it is associated with prolonged infertility duration, a high frequency of secondary infertility and ovulatory disorders, and a reduced implantation rate.

體重過重女性胚胎分裂速度較慢 (胖 vs Ｎ 病人）
T5: 50.84 h vs. 49.24 h 
T8: 57.89 hvs. 55.66 h 

J Assist Reprod Genet. 2019 May 6. doi: 10.1007/s10815-019-01456-3. [Epub ahead of print]

Maternal body mass index affects embryo morphokinetics: a time-lapse study.

Bartolacci A1, Buratini J1,2, Moutier C1, Guglielmo MC1, Novara PV1, Brambillasca F1, Renzini MM1, Dal Canto M3.

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Abstract

PURPOSE:

To assess the effect of body mass index (BMI) on morphokinetic parameters of human embryos evaluated with time-lapse technology during in vitro culture.

METHODS:

A retrospective analysis of ART cycles utilizing time-lapse technology was undertaken to assess the potential impact of maternal BMI on morphokinetic and static morphological parameters of embryo development. The cohort of patients was divided into four groups: 593 embryos from 128 underweight women in group A; 5248 embryos from 1107 normal weight women in group B; 1053 embryos from 226 overweight women in group C; and 286 embryos from 67 obese women in group D.

RESULTS:

After adjusting for maternal age, paternal age, and cause of infertility, time to reach five blastomeres (t5) and time to reach eight blastomeres (t8) were longer in obese women compared with normoweight women [50.84 h (46.31-55.29) vs. 49.24 h (45.69-53.22) and 57.89 h (51.60-65.94) vs. 55.66 h (50.89-62.89), adjusted p < 0.05 and adjusted p < 0.01, respectively]. In addition, t8 was also delayed in overweight compared with normoweight women [56.72 h (51.83-63.92) vs. 55.66 h (50.89-62.89), adjusted p < 0.01]. No significant differences were observed among groups with regard to embryo morphology and pregnancy rate. Miscarriage rate was higher in underweight compared with normoweight women (OR = 2.1; 95% CI 1.12-3.95, adjusted p < 0.05).

CONCLUSION:

Assessment with time-lapse technology but not by classical static morphology evidences that maternal BMI affects embryo development. Maternal obesity and overweight are associated with slower embryo development.

男性不孕精蟲經過grading分離後DNA fragment 增加

J Assist Reprod Genet. 2019 May 14. doi: 10.1007/s10815-019-01476-z. [Epub ahead of print]

DNA fragmentation in concert with the simultaneous assessment of cell viability in a subfertile population: establishing thresholds of normality both before and after density gradient centrifugation.

Punjabi U1,2, Van Mulders H3, Goovaerts I3, Peeters K3, Roelant E4, De Neubourg D3,5.

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Abstract

PURPOSE:

TUNEL assay is the most common, direct test for sperm chromatin integrity assessment. But, lack of standardized protocols makes interlaboratory comparisons impossible. Consequently, clinical thresholds to predict the chance of a clinical pregnancy also vary with the technique adopted. This prospective study was undertaken to assess the incidence of sperm DNA fragmentation in a subfertile population and to establish threshold values of normality as compared to a fertile cohort, both before and after density gradient centrifugation in the total and vital fractions.

METHOD:

Men presenting at a university hospital setup for infertility treatment. DNA damage via TUNEL assay was validated on fresh semen samples, as conventional semen parameters, to reduce variability of results.

RESULTS:

Total DNA fragmentation in the neat semen was significantly higher in the subfertile group, but the vital fraction was not significantly different between the two cohorts. After gradient centrifugation, DNA fragmentation increased significantly in the total fraction of the subfertile group but decreased significantly in the vital fraction. In the fertile cohort, there was a non-significant increase in total fragmentation and in the vital fraction the trend was unclear.

CONCLUSIONS:

Estimating total and vital sperm DNA fragmentation, after density gradient centrifugation, increased both the sensitivity and the specificity, thereby lowering the number of false negatives and false positives encountered. These findings provide opportunities to investigate the significance of the total and the vital fractions after different assisted reproductive technologies.

傳統胚胎植入時機為D3 or D5   本篇指出 D4胚胎植入之可行性 & PR並無統計差異

J Assist Reprod Genet. 2019 May 20. doi: 10.1007/s10815-019-01475-0. [Epub ahead of print]

Should the flexibility enabled by performing a day-4 embryo transfer remain as a valid option in the IVF laboratory? A systematic review and network meta-analysis.

Simopoulou M1,2, Sfakianoudis K3, Tsioulou P4, Rapani A4, Maziotis E4, Giannelou P4, Grigoriadis S4, Pantou A3, Nikolettos K5, Vlahos N6, Pantos K3, Koutsilieris M4.

Author information

Abstract

PURPOSE:

The present systematic review and network meta-analysis aims to uniquely bring to literature data supporting the true place of the alternative practice of day-4 embryo transfer (D4 ET) in an IVF laboratory, beyond the one-dimensional option of facilitating a highly demanding program.

METHODS:

A systematic search was conducted in the databases of PubMed/Medline, Embase, and Cochrane Central Library, resulting to six prospective along with nine retrospective cohort studies meeting eligibility criteria for inclusion. A comparison of D4 ET with day-2 (D2), day-3 (D3), and day-5 (D5) ET, respectively, was performed employing R statistics.

RESULTS:

The sourced results indicate no statistically significant difference regarding clinical pregnancy rates, and ongoing pregnancy/live birth rates stemming from the comparison of D4 with D2, D4 with D3, and D4 with D5 ET, respectively. Additionally, no statistically significant difference could be established in respect to cancelation, and miscarriage rates, following the comparison of D4 with D3 and D4 with D5 ET. Interestingly, we report statistically significant lower preterm birth rates associated with D4 ET, in contrast with D5 ET (RR, 0.19; 95% CI, 0.05-0.67; p value = 0.01).

CONCLUSIONS:

The aforementioned results may serve as advocates buttressing the option of D4 ET as a valid candidate in the ET decision-making process. Possible limitations of the current study are the publication bias stemming from the retrospective nature of certain included studies, along with various deviations among studies' design, referring to number and quality of transferred embryos, or different culture conditions referring to studies of previous decades.

取卵後施行ICSI之時間間距對懷孕率無明顯差異 ( 3-6h)

取卵後脫卵丘細胞之之時間間距對懷孕率無明顯差異 (2-5h)

Hum Reprod. 2016 Jun;31(6):1182-91. doi: 10.1093/humrep/dew070. Epub 2016 Apr 12.

Should we worry about the clock? Relationship between time to ICSI and reproductive outcomes in cycles with fresh and vitrified oocytes.

Bárcena P1, Rodríguez M1, Obradors A1, Vernaeve V1, Vassena R2.

Author information

Abstract

STUDY QUESTION:

Is there an optimal time to perform ICSI with respect to the times of oocyte pick-up (OPU), in order to maximize the reproductive outcomes in cycles with fresh and vitrified/warmed donor oocytes?

SUMMARY ANSWER:

We found no significant differences in reproductive outcomes of ICSI cycles within a wide range of times between OPU and ICSI.

WHAT IS KNOWN ALREADY:

In assisted reproduction, the oocyte is subject to denudation, vitrification/warming and ICSI. As shorter interaction with cumulus cells, oocyte ageing in vitro and insufficient recovery after warming may all impact the resulting embryo developmental competence, strictly controlled times between procedures are often implemented. However, most protocols have not been tested with the aim to improve reproductive results, and little information is available on the ideal times to be followed during these steps in order to optimize fertilization rates and embryo quality, and to achieve the highest pregnancy rate.

STUDY DESIGN, SIZE, DURATION:

Data from 3986 ICSI cycles performed between December 2012 and May 2014 were included (3178 with fresh and 808 with vitrified/warmed donor oocytes).

PARTICIPANTS/MATERIALS, SETTING, METHODS:

ICSI was performed using donor oocytes and either partner or donor sperm. Exact times between OPU, denudation, vitrification, warming and ICSI were recorded automatically by a radiofrequency-based system. OPU was performed strictly 36 h after GnRH agonist trigger. Biochemical pregnancy was defined as a positive serum βHCG 15 days after transfer, clinical pregnancy was defined as a visible embryo with heartbeat 5 weeks after transfer, and ongoing pregnancy was defined as a normally developing pregnancy at 12 weeks after transfer.

MAIN RESULTS AND THE ROLE OF CHANCE:

Times between OPU and ICSI (OPU-ICSI) ranged from 1 h 25 min to 17 h 13 min (averagefresh ± SD = 4 h 58 m ± 1 h; averagevitrified= 9 h 18 m ± 2 h). We found no effect of OPU-ICSI time on fertilization rate (pfresh=0.39; pvitrified=0.86) or embryo quality at Days 2 and 3 (pfresh=0.08; pvitrified=0.22). There was no difference in average OPU-ICSI times between positive and negative pregnancies (biochemical, clinical, ongoing and live birth rates) in either fresh (P = 0.71, 0.43, 0.79, 0.96) or vitrified (P = 0.59, 0.33, 0.73, 0.87) oocytes, respectively. Data were adjusted for oocyte donor age, semen status, number of motile spermatozoa and sperm concentration, and no effect of OPU-ICSI time on pregnancy and live birth rates for either fresh (P = 0.57, 0.16, 0.11, 0.46) or vitrified (P = 0.80, 0.73, 0.91, 0.95) oocytes was found. Further analysis for linear trend using OPU-ICSI time categorized in deciles showed that pregnancy rates and live birth rates do not increase or decrease across deciles. We found no effect of time taken for denudation to vitrification, warming to ICSI and denudation to ICSI on pregnancy rates.