scholarly journals Dehydroepiandrosterone Shifts Energy Metabolism to Increase Mitochondrial Biogenesis in Female Fertility with Advancing Age

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2449
Author(s):  
Chia-Jung Li ◽  
Li-Te Lin ◽  
Kuan-Hao Tsui

Female reproductive aging is an irreversible process associated with a decrease in oocyte quality, which is a limiting factor for fertility. Previous studies have shown that dehydroepiandrosterone (DHEA) has been shown to improve in vitro fertilization (IVF) outcomes in older women. Herein, we showed that the decline in oocyte quality with age is accompanied by a significant decrease in the level of bioenergetic metabolism genes. We compared the clinical characteristics between groups of infertile women who either received DHEA or did not. Treatment with DHEA may enhance oocyte quality by improving energy production and metabolic reprogramming in cumulus cells (CCs) of aging women. Our results showed that compared with the group without DHEA, the group with DHEA produced a large number of day-three (D3) embryos, top-quality D3 embryos, and had improved ongoing pregnancy rate and clinical pregnancy rate. This may be because DHEA enhances the transport of oxidative phosphorylation and increases mitochondrial oxygen consumption in CCs, converting anaerobic to aerobic metabolism commonly used by aging cells to delay oocyte aging. In conclusion, our results suggest that the benefit of DHEA supplementation on IVF outcomes in aging cells is significant and that this effect may be mediated in part through the reprogramming of metabolic pathways and conversion of anaerobic to aerobic respiration.

2020 ◽  
Author(s):  
Meiling Yang ◽  
li Lin ◽  
Chunli Sha ◽  
Taoqiong Li ◽  
Wujiang Gao ◽  
...  

Abstract Background: In recent years, there have been emerging many reports on the pregnancy outcomes of fresh blastocyst transfer (BT) and freeze-thaw BT, but these couclusions are controversial and incomplete. To compare the pregnancy outcomes, maternal complications and neonatal outcomes of fresh and frozen-thawed BT in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) cycles, we conducted a meta-analysis. Methods: A meta-analysis was conducted by searching PubMed, Embase, and Cochrane Library until January 2020. Data were extracted independently by two authors. Results: 42 studies, including 12 randomized controlled trials (RCT) met the inclusion criteria. Fresh BT showed lower implantation rate (IR), pregnancy rate (PR), ongoing pregnancy rate (OPR) and higher eptopic pregnancy rate (EPR) compared with frozen-thawed BT consistent with the results of RCT. The risks of moderate or severe ovarian hyperstimulation syndrome (OHSS), placental abruption (PA) and preterm were higher in fresh BT than in the frozen-thawed BT. The risk of pregnancy-induced hypertension (PIH) and pre-eclampsia was decreased in fresh BT , however, no significant differences of risks for PIH, pre-eclampsia, OHSS, and preterm was found between the two group in the 2 RCT included. Compared with frozen-thawed BT, fresh BT appears to be associated with small for gestational age (SGA) and low birth weight (LBW). No differences in the incidences of neonatal mortality and neonatal malformations were observed between fresh and frozen-thawed BT. Conclusions: In summary, Considering the higher IR, PR, OPR, lower EPR, and the decreased risks of OHSS, PA and preterm, as well as the incidences of SGA and LBW in frozen-thawed BT, this meta-analysis indicates that frozen-thawed BT may be a better choice for mothers and babies compared with fresh BT. Key words: Fresh blastocyst transfer, frozen thawed blastocyst transfer, pregnancy outcome, maternal complications, neonatal outcomes


2017 ◽  
Vol 29 (1) ◽  
pp. 188 ◽  
Author(s):  
L. Landeo ◽  
J. Mendoza ◽  
L. Manrique ◽  
E. Taipe ◽  
R. Molina ◽  
...  

The aim was to transfer alpaca and llama embryos obtained by IVF into recipient llamas and evaluate pregnancy and birth rates. Gametes were collected from samples of ovaries and testes collected from a local abattoir. Cumulus-oocyte complexes (COC) were recovered by aspiration of ovarian follicles using a 5-mL syringe, where oocytes with at least 3 layers of cumulus cells and a homogenous cytoplasm were matured in TCM-199 supplemented with 10% FCS, FSH (0.1 IU), and oestradiol 17β for 30 and 36 h with 5% CO2 in air, for alpaca and llama, respectively. After the maturation time, COC were placed in FERT-TALP solution 30 min before in vitro insemination with epididymal sperm of alpaca and llama as appropriate, the sperm were selected by swim-up method with centrifuging twice in 2 mL of SPERM-TALP supplemented with 6 mg mL−1 of fatty-free BSA, in an incubator with 5% CO2 in air set at 39°C for 45 min, oocytes were co-incubated with sperm concentration of 3 × 106 mL−1 for 18 to 20 h at 39°C with 5% CO2 in air. The IVF was carried out the day of ovulation induction of recipients. A group of 15 morphologically intact Day-8 blastocysts derived from in vitro culture with SOF serum were transferred nonsurgically into the uterine horn ipsilateral to the corpus luteum of 15 synchronized recipient llamas with an intravaginal device (controlled internal drug release) for 8 days. Then, 6 days after controlled internal drug release removal, ovulation was induced in recipients with the application of 1 mL of GnRH with previous ultrasound confirmation of the presence of a dominant follicle greater than 7 mm in diameter. Nine alpaca blastocysts and 6 llama blastocysts were transferred. The pregnancy rate was assessed by ultrasound at 45 days after transfer. The results obtained were as follows: for pregnancy rate, 33.3% (3/9) and 50% (3/6) for alpaca and llama embryos, respectively; for birth rate, 0.0% (0/9) and 16.7% (1/6) for alpaca and llama embryos, respectively. An alpaca fetus and 2 llama fetuses were aborted between 7 and 10 months of pregnancy, and only a llama gestation ended successfully, producing the first birth of the world of a llama bred by IVF in South American camelids, demonstrating that it is possible to obtain viable offspring in these species using this biotechnology.


2017 ◽  
Vol 114 (29) ◽  
pp. E5796-E5804 ◽  
Author(s):  
Ye Yuan ◽  
Lee D. Spate ◽  
Bethany K. Redel ◽  
Yuchen Tian ◽  
Jie Zhou ◽  
...  

Assisted reproductive technologies in all mammals are critically dependent on the quality of the oocytes used to produce embryos. For reasons not fully clear, oocytes matured in vitro tend to be much less competent to become fertilized, advance to the blastocyst stage, and give rise to live young than their in vivo-produced counterparts, particularly if they are derived from immature females. Here we show that a chemically defined maturation medium supplemented with three cytokines (FGF2, LIF, and IGF1) in combination, so-called “FLI medium,” improves nuclear maturation of oocytes in cumulus–oocyte complexes derived from immature pig ovaries and provides a twofold increase in the efficiency of blastocyst production after in vitro fertilization. Transfer of such blastocysts to recipient females doubles mean litter size to about nine piglets per litter. Maturation of oocytes in FLI medium, therefore, effectively provides a fourfold increase in piglets born per oocyte collected. As they progress in culture, the FLI-matured cumulus–oocyte complexes display distinctly different kinetics of MAPK activation in the cumulus cells, much increased cumulus cell expansion, and an accelerated severance of cytoplasmic projections between the cumulus cells outside the zona pellucida and the oocyte within. These events likely underpin the improvement in oocyte quality achieved by using the FLI medium.


2019 ◽  
Vol 24 (1) ◽  
Author(s):  
Maryam Eftekhar ◽  
Sara Zare Mehrjardi ◽  
Behnaz Molaei ◽  
Fatemeh Taheri ◽  
Esmat Mangoli

Abstract Background In assisted reproductive technology (ART) cycles in addition to embryo quality, the receptivity of the endometrium plays the main role in clinical outcomes. Endometrial receptivity is necessary to implantation of an embryo, and ultrasound has been established as an appreciated, simple, and non-invasive technique in the evaluation of the endometrial preparation before embryo transfer in fresh in vitro fertilization (IVF) cycles. Debate on the predictive value measuring endometrial thickness before administering human chorionic gonadotropin (HCG) for ovulation triggering in ART is ongoing. In order to explore the impact of endometrial thickness on triggering day on ongoing pregnancy rate (OPR) in ART cycles, we retrospectively analyzed data from 1000 patients undergoing IVF/ICSI cycles. Results The data showed pregnancy rate was increased in the endometrial thickness of 8 mm to 11 mm then decreased, and in endometrial thickness (Ent) > 14 mm, pregnancy rate was zero. There were significant differences in endometrial thickness and pregnancy outcomes between different age groups. The pregnancy rate was higher (32%) in 23–30 years old women, and the range of Ent in this group was 6–12 mm. Also, the data showed a positive correlation between Ent with AMH and estradiol levels and the number of COC and MII oocytes and a negative correlation between female age with Ent. Conclusion The result showed that Ent on hCG administration day is associated with pregnancy outcomes in fresh IVF/ICSI cycles with different age groups, although some of the clinical parameters may have an effect on Ent. Large studies are needed to make a definitive conclusion.


1995 ◽  
Vol 7 (2) ◽  
pp. 263 ◽  
Author(s):  
L Hamberger ◽  
A Sjogren ◽  
K Lundin ◽  
B Soderlund ◽  
L Nilsson ◽  
...  

Intracytoplasmic sperm injection (ICSI) has been studied in this animal research programme since 1990. In 1993, the technique was first applied clinically and up to the present time (September 1994), a total of 456 couples have been studied in 538 cycles. The principal indication for the use of ICSI has been severe male sub-fertility as judged by a semen analysis. In addition, men with high titres of antisperm antibodies, blockage of the vas deferens and neurological disorders such as spinal cord lesions have been included in the programme. Men with genetic disorders such as cystic fibrosis and acrosome-deficient spermatozoa have also been treated successfully. The overall fertilization rate using ICSI was 59%, which is similar to the conventional in vitro fertilization (IVF) programme in Goteborg, however, the pregnancy rate per embryo transfer (29%) and the ongoing pregnancy rate per transfer (22%) were slightly lower. The total number of pregnancies was 144 with 111 of the pregnancies either ongoing or already delivered. To date, 36 healthy children have been born following 29 deliveries and no major malformations have been diagnosed. Being the first programme in Scandinavia to perform ICSI, this unit has experienced long waiting lists which indicates that severe male sub-fertility will be one of the major groups for treatment with assisted reproductive technologies in the future.


2021 ◽  
Author(s):  
Han Yang ◽  
Juan Li ◽  
Guixing Xu ◽  
Zihao Zou ◽  
Mingsheng Sun ◽  
...  

Abstract Background Infertility is a common health problem affecting couples at childbearing age. The proposal of in vitro fertilization (IVF) solves the problem of infertility to a certain extent. However, the average IVF success rates are low. Some studies conclude that transcutaneous electrical acupoint stimulation (TEAS) could improve pregnancy outcomes in women undergoing IVF. In consideration of the lack of comprehensive synthesis and evaluation of existing evidence, conducting a systematic review and meta-analysis is planned to determine whether TEAS is effective and safe to improve the pregnancy outcomes for women undergoing IVF. Methods Eight online databases will be searched from inception to June 2021. In addition, four clinical trial registries will also be searched, relevant references will be screened, and experts will be consulted for possible eligible studies. Randomized controlled trials (RCTs) which included patients with infertility who underwent IVF and used TEAS as the main adjuvant treatment versus non-TEAS or sham TEAS control will be included. The clinical pregnancy rate will be considered as the primary outcome. Ongoing pregnancy rate, miscarriage rate, live birth rate, emotion-related indicators, adverse events related to interventions, and other relevant indicators will be regarded as secondary outcomes. The selection, data extraction, and risk of bias assessment will be conducted by two independent researchers using Endnote software V.9.1 and RevMan software V.5.3. Moreover, data synthesis will be conducted using RevMan software V.5.3 and R software V.3.6.1. Ethics and dissemination: Ethical approval is not necessary because the current study will not include the original information of the individuals. We plan to publish the results in a peer-reviewed journal or disseminated in relevant conferences. Systematic review registration: PROSPERO registration number: CRD42021238871


2010 ◽  
Vol 22 (1) ◽  
pp. 322
Author(s):  
I. Carvalhais ◽  
M. Faheem ◽  
A. Habibi ◽  
A. Geraldo ◽  
R. Agrícola ◽  
...  

Many factors act together to prepare the immature oocyte for successful development to a competent embryo after fertilization. Defects in oocyte maturation and further development can possibly be caused by the oocyte quality or an inadequate nuclear maturation or even by a failure of both. In the present study, the effect of COCs quality on meiotic development and further embryo-development after in vitro fertilization was evaluated. A total of 3604 COCs was separated according to their morphological aspect and were classified as A, B, and C categories. Briefly, in class A, oocytes possessed compact layers of cumulus cells, being difficult to evaluate their number having a homogenous ooplasm with uniform color. In class B, oocytes show more or equal to five layers of cumulus cells, easily identifiable under a stereomicroscope and/or granulations in the ooplasm. In class C, some granulation was observed in oocytes with about three layers of cumulus cells. The total number of oocytes was divided into two groups (I and II) in which in the group I, COCs (n = 540) were fixed 0, 6, 12, 18, 24, and 30 h following ovarian aspiration, DNA was stained with aceto-orcein, and the nucleus were observed under a phase contrast microscope. In the Group II, COCs (n = 3064) were fertilized with frozen/thawed bull semen after 24 h of maturation, which was made in M199 medium (Sigma, St, Louis, MO, USA). The development of the embryos was evaluated on the third and seventh day after fertilization. Embryos were co-cultured with monolayers of granulosa cells in 45 μL droplets of B2 medium (CCD Laboratory, Paris, France), supplemented with 10% serum under mineral oil, at 39°C and 5% CO2 in air. It was observed that, other than the oocytes achieved metaphase II at 24 h was greater for the oocytes classified as A (65.4%), and B (61.0%) greater than C (51.2%), no statistical difference was observed between oocyte quality and capability to maturation. As far as the embryonic development is concerned, the same tendency was observed for the cleavage and for the morulae/blastocyst stage after 7 days after fertilization (P < 0.001). The percentages of cleaved oocytes classified as A, B, and C, were respectively 65.2%, 58.4%, and 48.0%. The development to the morulae/blastocyst stage of the cleaved embryos was A = 38.5%/27.4%, B = 33.6%/25.0%, and C = 30.9%/17.2% (Table 1). The results of our study clearly demonstrate that the morphology of the oocytes plays an important role on the in vitro embryonic developmental competence after fertilization. Table 1.Development of oocytes according to COCs quality, evaluated 3 and 7 days after fertilization The first author is supported by the Regional Foundation for Science and Technology of the Azores Government. This study was supported by the IBBA Institute grant number M2.1.2/I/022/2008 CITA-A is fully acknowledged.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Qiwei Liu ◽  
Junhui Zhang ◽  
Huihui Wen ◽  
Yun Feng ◽  
Xunyi Zhang ◽  
...  

Selecting excellent oocytes is required to improve the outcomes of in vitro fertilization (IVF). Cumulus cells (CCs) are an integral part of the oocyte maturation process. Therefore, we sought to identify differentially expressed genes in CCs to assess oocyte quality and embryo development potential. We divided the participants’ embryos into the high-quality embryo group and low-quality embryo group by the information including age, body mass index, and the levels of luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone. We analyzed a total of 7 CC samples after the quality control in RNA sequencing. We found that 2499 genes were unregulated and 5739 genes were downregulated in high-quality embryo group compared to the low-quality embryo group (Padj < 0.05). Interestingly, MSTN, CTGF, NDUFA1, VCAN, SCD5, and STAR were significantly associated with the quality of embryo. In accordance with the results of RNA sequencing, the association of the expression levels of MSTN, CTGF, NDUFA1, VCAN, SCD5, and STAR with the embryo quality was verified by quantitative reverse-transcription polymerase chain reaction (RT-qPCR) in 50 CC samples. Despite the small sample size and lack of validation in animal models, our study supports the fact that differential gene expression profile of human CCs, including MSTN, CTGF, NDUFA1, VCAN, SCD5, and STAR, can serve as potential indicator for embryo quality.


2006 ◽  
Vol 18 (2) ◽  
pp. 193
Author(s):  
S. Menges ◽  
C. Bormann ◽  
B. Stroud ◽  
D. Kraemer ◽  
M. Westhusin ◽  
...  

In vitro culture of bovine embryos is usually associated with poor pregnancy rate following cryopreservation. The objective of this study was to compare the post-thaw viability of in vitro-produced bovine zygotes, cultured in vitro or in the reproductive tract of a host goat. Cumulus-oocyte complexes were matured in vitro, and in vitro fertilization was carried out with frozen-thawed semen as per standard laboratory procedures. At 18-20 h post-fertilization, zygotes were stripped of remaining cumulus cells and randomly separated into culture treatments. In three replicates, a total of 606 embryos were surgically transferred 12 to 24 h post-ovulation to the oviducts of an estrous-synchronized goat (VIVO) and 550 embryos were cultured in G1.3 for 72 h and then moved to G2.3 medium for 96 h and in a humidified atmosphere of 5% CO2, 5% O2, and 90% N2 (IVC). On Day 7, embryos were flushed from the excised tract with a 69.5% recovery rate or removed from culture. Embryos were classified according to IETS criteria with grades and stages recorded. All data were analyzed using the one-way analysis of variance and means were compared using Student's t-test. No differences were seen in the percentage of freezable quality embryos per total recovered between the two groups (34.3% vs. 32.3% for IVC and VIVO, respectively). However, there was a significant difference in the pre-freezing stage between the two culture groups (Stage 5.5 � 0.22 vs. Stage 4.8 � 0.26 for IVC and VIVO, respectively; P < 0.05), but no difference in the quality grade. All embryos greater than Stage 4, Grade 2 were frozen in groups of 5-10 in ethylene glycol with sucrose (Vigro Ethylene Glycol Freeze Plus; Bioniche Animal Health, Belleville, Ontario, Canada) in 0.25-mL straws. After thawing, embryo groups were washed, rehydrated, and incubated in G2.3 as above. Morphology was assessed by assigning grade and stage objectively at 24 h and 48 h post-thaw. Post-thaw viability in vitro was not different between groups (73.4% vs. 72.7% for IVC and VIVO, respectively). The average changes in morphology post-thaw from pre-freezing to 24 h and from 24 h to 48 h within each freezing group were determined. There was no significant difference in the mean change in stage (0.67 � 0.15 vs. 0.82 � 0.17 at 24 h and 0.31 � 0.09 vs. 0.37 � 0.10 at 48 h for IVC and VIVO, respectively) or grade (0.60 � 0.15 vs. 0.41 � 0.17 at 24 h and 0.03 � 0.06 vs. 0.14 � 0.07 at 48 h for IVC and VIVO, respectively) at either observation point. These results suggest that culture of in vitro-fertilized bovine embryos in the caprine reproductive tract did not alter post-thaw development or improve post thaw viability compared to in vitro cultured controls. However, morphological evaluation is too subjective to successfully predict pregnancy rate after transfer; therefore, further study is needed to determine if there are differences in pregnancy rates between these culture methods.


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