scholarly journals Mitochondrial DNA Content May Not Be a Reliable Screening Biomarker for Live Birth After Single Euploid Blastocyst Transfer

2021 ◽  
Vol 12 ◽  
Author(s):  
Xuanyou Zhou ◽  
Xueli Liu ◽  
Weihui Shi ◽  
Mujin Ye ◽  
Songchang Chen ◽  
...  

An increasing number of studies have related the mitochondrial DNA (mtDNA) content to embryo viability and transfer outcomes. However, previous studies have focused more on the relationship between mtDNA and embryo implantation, few studies have studied the effect of the mtDNA content on live birth. In the study, we investigated whether mtDNA content is a reliable screening biomarker for live birth after single blastocyst transfer. A total of 233 couples with 316 blastocyst stage embryos undergoing in vitro fertilization treatment and pre-implantation genetic testing analysis were included in the study. All embryos were chromosomally normal and had undergone single-embryo transfers. There was no significant difference observed in the blastocyst mtDNA content among the live birth, miscarriage and non-implanted groups (p=0.999), and the mtDNA content in blastocysts from the miscarriage and live birth groups was similar [median (interquartile range), 1.00*108(7.59*107- 1.39*108) vs 1.01*108 (7.37*107- 1.32*108)]. Similarly, no significant association was observed between mtDNA content and embryo implantation potential (p=0.965). After adjusting for multiple confounders in a logistic regression analysis with generalized estimating equations, no associations between mtDNA content and live birth were observed in all blastocysts, Day-5 and Day-6 blastocysts (p=0.567, p=0.673, p=0.165, respectively). The live birth rate was not significantly different between blastocysts with an elevated mtDNA content and blastocysts with a normal mtDNA content (26.7% vs 33.6% p=0.780). Additionally, there was no linear correlation between the mtDNA content and maternal age (p=0.570). In conclusion, the mtDNA content does not seem to be a potential biomarker for embryo transfer outcomes (i.e., implantation and live birth) based on the existing testing tools. Embryos with an elevated mtDNA content also have development potential for successful live birth.

Author(s):  
Akshaya Kumar Mahapatro ◽  
Abhishek Radhakrishan

Background: Purpose of this study was to evaluate the in vitro fertilisation outcome in patients having normal or elevated day-2 serum progesterone level undergone IVF by using GnRH antagonist.Methods: A retrospective study conducted in Institute of Reproductive Medicine, Chennai during January 2013 to March 2014. According to patient’s Day-2 serum progesterone level the total no of cases (N=151) were divided into two groups group-1 (N=116) with progesterone value ≤1.5ng/ml and group-2 (N=35) with progesterone value>1.5ng/ml. Ovarian stimulation was started with recombinant FSH on day 2 and GnRH antagonist injections started from day 6 of stimulation. Total dose of gonadotropins, days of gonadotrophin injections, no of eggs collected, Clinical pregnancy rate and live birth rate were compared between two groups.Results: Two groups were similar with regards to age, BMI, days of gonadotrophins and total doses of gonadotrophins. Incidence of elevated P level was 23.17%. Total pregnancy rate was 36.42%. A non-statistically-significant difference was observed in clinical pregnancy (37.06% vs 34.28%) and live birth (32.75% vs 28.57%) between the normal and elevated progesterone groups.Conclusions: Elevated day-2 serum progesterone level   was associated with lower clinical pregnancy rate but it was not statistically-significant.


2007 ◽  
Vol 19 (1) ◽  
pp. 185
Author(s):  
Y. Takagi ◽  
M. Shimizu ◽  
M. Morimura ◽  
S. Yokomizo ◽  
K. Hara ◽  
...  

Embryos of various species are successfully vitrified and cryopreserved in liquid nitrogen (<−150°C). Like the preservation of frozen somatic cells cooled by dry ice (−79°C), the cryopreservation of embryos at −79°C is useful for a reduction in the shipping costs. The purpose of this study was to evaluate the effect of the cryopreservation period at −79°C on the in vitro embryo viability of vitrified mouse morulae after thawing. Morula-stage mouse embryos were collected from superovulated ICR donors 70 h after hCG injection. The embryos were exposed first to 5% DMSO + 5% ethylene glycol (EG) in Dulbecco's PBS + 20% FCS (mPBS) for 2 min, and then equilibrated for 20–30 s in a vitrification solution composed of 10% DMSO + 10% EG + 0.6 M sucrose in mPBS. The embryos were loaded onto cryoloops (Lane et al. 1999 Nat. Biotech. 17, 1234–1236) and plunged directly into liquid nitrogen. The cryoloops were placed in 1.2-mL cryotubes and stored in a −79°C freezer for 1–7 days. The embryos were warmed by passing through 4 dilution media and rinsed with mWM culture medium. They were then cultured at 37°C in 5% CO2 for 44 h. Non-cryopreserved embryos and embryos cryopreserved in liquid nitrogen served as controls. Data were analyzed by the chi-square test and the Student's t-test. Results are shown in Table 1. There was no significant difference (P > 0.01) in the developmental abilities to the blastocyst stage of the vitrified embryos that were cryopreserved at −79°C for 1 day, 3 days, and 5 days, the embryos cryopreserved in liquid nitrogen, and the non-vitrified control. The blastocyst rate of embryos was significantly lower (P < 0.01) for the Day 7 group than for the control group. The cell numbers of blastocysts were significantly lower (P < 0.01) for the Day 1, Day 3, Day 5, and Day 7 groups than for the control group. This study suggests that vitrified mouse morulae can be successfully cryopreserved at −79°C for 5 days. Table 1. Effect of the cryopreservation period on the viability of vitrified mouse morulae preserved at −79°C


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Reignier ◽  
J Joly ◽  
M Rosselot ◽  
T Goronflot ◽  
P Barrière ◽  
...  

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 > 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


2018 ◽  
Author(s):  
M.S. Yong Qiu ◽  
M.S. Songchang Chen ◽  
Chen Dayang ◽  
M.S. Ping Liu ◽  
M.S. Jun Xia ◽  
...  

ABSTRACTObjectiveTo investigate whether the mitochondrial DNA content could predict the embryo viabilityDesignRetrospective analysis.SettingReproductive genetics laboratoryPatient(s)A total of 421 biopsied samples obtained from 129 patientsIntervention(s)Embryo biopsies samples underwent whole genome amplification (WGA) and were tested by next generation sequencing (NGS) and array Comparative Genomic Hybridization (aCGH), 30 samples were selected randomly to undergo quantitative real-time polymerase chain reaction (qPCR).Main Outcome Measure(s)Those embryos which obtained the consistent chromosome status determined both aCGH and NGS platform were further classified. We investigated the relationship of mtDNA content with several factors including female patient age, embryo morphology, chromosome status, and live birth rate of both blastocysts and blastomeres.Result(s)A total of 386 (110 blastomeres and 276 blastocysts) out of 399 embryos showed consistent chromosome status outcome. We found no statistically difference was observed in aneuploid and euploid blastocysts (p=0.14), the same phenomenon was observed in aneuploid and euploid blastomeres (p=0.89). Similarly, the mtDNA content was independent of female patient age, embryo morphology and live birth rate.Conclusion(s)The mtDNA content did not provide a reliable prediction of the viability of blastocysts to initiate a pregnancy.


2021 ◽  
Author(s):  
Shui-Ying Ma ◽  
Lian-Jie Li ◽  
Hui Zhao ◽  
Cheng Li ◽  
Haibin Zhao ◽  
...  

Abstract Background Assisted hatching is a widely accepted technique in assisted reproductive technology, however, it’s efficiency remains controversial and lack of data on safety. The aim of this study was to assess whether laser-assisted hatching improves clinical pregnancy results of vitrified-warmed blastocyst transfer cycles.Methods This was a retrospective cohort study of 4143 vitrified-warmed blastocyst transfer cycles from October 2014 to December 2015 at a single, university-based hospital. Cases involving blastocysts that survived after warming were divided into the assisted hatching (AH) group (n=1975) and non-AH group (n=2168). In the AH group, laser AH was performed for the warmed blastocysts before transfer. In the non-AH group, the warmed blastocysts were transferred without AH. The primary outcome was live birth rate after survived vitrified-warmed blastocyst transfers.Results No significant differences in age, endometrial preparation regimen, number of embryos transferred, or blastocyst developmental stage were found between the two groups (P>0.05). The biochemical pregnancy (67.0% vs. 63.6%; P=0.023; odds ratio [OR], 1.177; 95% confidence interval [CI], 1.032–1.344), clinical pregnancy (59.2% vs. 56.0%; P=0.041; OR, 1.163; 95% CI, 1.024–1.321), live birth (48.6% vs. 45.4%; P=0.041; OR, 1.160; 95% CI, 1.022–1.316), and implantation (52.1% vs. 49.3%; P=0.039) rates of the AH group were significantly higher than those of the non-AH group. The early miscarriage (17.1% vs. 17.8%; P=0.674), monozygotic twin (1.5% vs. 0.90%; P=0.214), and birth defect (3.1% vs. 3.6%; P=0.571) rates were similar in both groups. Conclusions In vitrified-warmed blastocyst transfer cycles, laser AH is associated with high clinical pregnancy and live birth rates. The benefits of AH outweigh its drawbacks, which include prolonged in vitro procedure, thermal damage, and higher workload in the in vitro fertilization laboratory.Trial registration: retrospectively registered


2018 ◽  
Vol 17 (2) ◽  
Author(s):  
Lokman Md Isa ◽  
Afzan Mat Yusof ◽  
Roszaman Ramli ◽  
Syamsul Ahmad Arifin ◽  
Fatin Emalina ◽  
...  

Expression of beta-human chorionic gonadotropin (bHCG) mRNA in early cleavage cell stages is important in predicting embryo viability at blastocyst stage of development. Embryo viability is crucial for in vitro fertilization (IVF) treatment to be successful in terms of increment of implantation and pregnancy rate. In order to establish fertilization outside the human body, optimum condition mimicking the natural body environment like hormones and growth factors as well as impeccable timing must be established. Imam Muslim narrated from Hudhayfa ibn Asad that the Prophet Muhammad (SAW) said: “After the sperm-andovum drop (nut.fa) has been [in the uterus] forty-two days, Allah sends it an angel that gives it form and fashions its hearing, sight, skin, flesh, and skeleton”. Therefore the aim of this study is to find the significant association of bHCG expression with early cell stage cleavages and its relationship as predictive marker for potential embryo implantation. Our study focuses on leftover frozen embryos from eight patients consists of six pregnant patients and two non-pregnant patients. We assessed the human bHCG mRNA expression at different cell cleavage stages in these frozen embryos using reverse transcriptasepolymerase chain reaction (RT-PCR). Our results have shown three out of eight patients with five to ten cells of blastomeres were expressed with bHCG. This study indicated that bHCG was expressed on frozethawed late cleavage stage of embryos in IVF patients.


2021 ◽  
Author(s):  
Conghui Liu ◽  
Yu Li ◽  
Hong Jiang ◽  
Xuemei Wang ◽  
Feng Ni ◽  
...  

Abstract Background Previous studies have reported that live birth rate (LBR) decreased with aging, however, no study has evaluated the cumulative LBR (CLBR) in accordance with the ovarian response in advanced maternal age (AMA) patients. This study aims to investigate the relationship between the ovarian response and the CLBR in AMA patients. Methods 913 women ≥ 38 years underwent in vitro fertilization (IVF) and fresh embryo transfer (ET) between January 2014 and June 2019 were enrolled in this retrospective study. All subjects were categorized into three groups, poor ovarian response (POR) group: 1–3 oocytes retrieved (n = 127), normal ovarian response (NOR) group: 4–15 oocytes retrieved, and high ovarian response (HOR) group: more than 15 oocytes retrieved. The primary outcome was the CLBR in one oocyte retrieval cycle after transfer of all fresh and frozen embryos. Logistic regression models were used to derive the odds ratio (OR) to identify the relationship of CLBR with different ovarian response, adjusting for age and body mass index. Results Compared with women in POR group, the women in other groups (NOR and HOR groups) achieved higher CLBR [adjusted OR (aOR) = 2.12, 95% confidence interval (CI), 1.16–4.38 for NOR group; aOR = 2.93, 95% CI, 1.44–5.97 for HOR]. The LBR of the fresh ET and the neonate characteristics showed no significant difference among the three groups. Conclusion Ovarian response is significantly associated with CLBR in women with advanced age.


MedPharmRes ◽  
2018 ◽  
Vol 2 (2) ◽  
pp. 5-20
Author(s):  
Vu Ho ◽  
Toan Pham ◽  
Tuong Ho ◽  
Lan Vuong

IVF carries a considerable physical, emotional and financial burden. Therefore, it would be useful to be able to predict the likelihood of success for each couple. The aim of this retrospective cohort study was to develop a prediction model to estimate the probability of a live birth at 12 months after one completed IVF cycle (all fresh and frozen embryo transfers from the same oocyte retrieval). We analyzed data collected from 2600 women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) at a single center in Vietnam between April 2014 and December 2015. All patients received gonadotropin-releasing hormone (GnRH) antagonist stimulation, followed by fresh and/or frozen embryo transfer (FET) on Day 3. Using Cox regression analysis, five predictive factors were identified: female age, total dose of recombinant follicle stimulating hormone used, type of trigger, fresh or FET during the first transfer, and number of subsequent FET after the first transfer. The area under the receiver operating characteristics curve for the final model was 0.63 (95% confidence interval [CI] 0.60‒0.65) and 0.60 (95% CI 0.57‒0.63) for the validation cohort. There was no significant difference between the predicted and observed probabilities of live birth (Hosmer-Lemeshow test, p > 0.05). The model developed had similar discrimination to existing models and could be implemented in clinical practice.


BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e042395
Author(s):  
Simone Cornelisse ◽  
Liliana Ramos ◽  
Brigitte Arends ◽  
Janneke J Brink-van der Vlugt ◽  
Jan Peter de Bruin ◽  
...  

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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