Good Quality Embryos Research Articles

The Impact of Endometrioma on Embryo Quality in In Vitro Fertilization: A Retrospective Cohort Study

The influence of endometrioma on oocyte and embryo competence is inconclusive. Furthermore, the benefits of surgical treatment remain uncertain. This study aimed to investigate the effect of endometrioma on oocyte and embryo quality from a morphological perspective and further explore whether surgery could contribute to improving oocyte and embryo competence. A total of 664 IVF cycles with endometrioma (538 cycles underwent surgeries) and 3133 IVF cycles from the control group were included. The propensity score matching was used to balance the baseline differences between groups. There was a lower MII oocyte rate (85.0% versus 87.8%, p < 0.001; 84.9% versus 87.6%, p = 0.001) and a similar good-quality embryos rate in women with endometrioma (and those who underwent surgeries) compared with control group. For women with endometrioma, the rates of blastocyst development (67.1% versus 60.2%; p = 0.013) and good blastocyst development (40.7% versus 35.2%; p = 0.049) were significantly higher in those who had undergone surgical treatment compared with those who had not, but the rates of MII oocytes (79.9% versus 87.7%; p < 0.001) and normal fertilization (55.2% versus 66.2%; p < 0.001) were lower. The study indicates that endometrioma, including its surgical treatment, compromises the oocyte maturity not the embryo quality at the cleavage stage; however, the surgery seems to contribute to improving blastocyst development.

Pregnancy Outcomes for Day 5 Versus Day 6 Single Frozen-thawed Blastocyst Transfer with Different Qualities of Embryos: A Large Matched-cohort Study.

This study aimed to determine whether the day of blastocyst expansion affects pregnancy outcomes in frozen-thawed blastocyst transfer (FBT) cycles. A retrospective match-cohort study was conducted. Patients who underwent blastocyst transfer in frozen-thawed cycles at day 5 or 6 were matched for potential confounding factors. A total of 2207 matched pairs of FBT cycles were included from January 2016 to December 2019 in our Reproductive Medicine Center. The clinical pregnancy rate (CPR) and live birth rate (LBR) were significantly increased in day 5 blastocyst transfers when compared to day 6 blastocyst transfers, in terms of the same embryo quality. For FBT cycles with good-quality embryo, the CPR at day 5 and 6 was 61.30% and 57.56%, respectively (P=0.045), and the LBR was 44.79% and 36.16%, respectively (P<0.001). For FBT cycles with poor-quality embryo, the CPR at day 5 and 6 was 48.61% and 40.89%, respectively (P=0.006), and the LBR was 31.71% and 25.74%, respectively (P=0.019). The CPR for FBT cycles with good-quality embryo was statistically higher at day 6 than that at day 5 with poor-quality embryo transferred (57.56% vs. 48.61%, P=0.001). Maternal age, anti-Müllerian hormone (AMH), endometrial thickness, embryo quality, and the day of blastocyst expansion were independently correlated with the CPR and LBR. The FBT cycles at day 5 had significantly higher CPR (adjusted odds ratio [OR]=1.246, 95% confidence intervals [CI]: 1.097-1.415, P=0.001) and LBR (adjusted OR=1.435, 95% CI: 1.258-1.637, P<0.001) than those at day 6. The embryo quality is the primary indicator for FBT cycles. Day 5 blastocysts should be preferred when the quality of embryo at day 5 is the same as that at day 6.

Influence of a hyaluronan-binding system for sperm selection in intracytoplasmic sperm injection cycles on embryo morphokinetic parameters and in vitro fertilization cycle outcomes.

Although the impact of the paternal contribution to embryo quality and blastocyst formation is a well-known phenomenon, the current literature provides insufficient evidence that hyaluronan-binding sperm selection methods improve assisted reproductive treatment outcomes. Thus, we compared the cycle outcomes of morphologically selected intracytoplasmic sperm injection (ICSI) with hyaluronan binding physiological intracytoplasmic sperm injection (PICSI) cycles. A total of 2415 ICSI and 400 PICSI procedures of 1630 patients who underwent in vitro fertilization cycles using a time-lapse monitoring system between 2014 and 2018 were analyzed retrospectively. Fertilization rate, embryo quality, clinical pregnancy rate, biochemical pregnancy rate and miscarriage rate were evaluated, differences in morphokinetic parameters and cycle outcomes were compared. In total, 85.8 and 14.2% of the whole cohort were fertilized with standard ICSI and PICSI, respectively. The proportion of fertilized oocytes did not significantly differ between groups (74.53 ± 1.33 vs. 72.92 ± 2.64, p > 0.05). Similarly, the proportion of good-quality embryos according to the time-lapse parameters and the clinical pregnancy rate did not significantly differ between groups (71.93 ± 4.21 vs. 71.33 ± 2.64, p > 0.05 and 45.55 ± 2.91 vs. 44.96 ± 1.25, p > 0.05). No statistically significant differences were found between groups in clinical pregnancy rates (45.55 ± 2.91 vs. 44.96 ± 1.25, p > 0.05). Biochemical pregnancy rates (11.24 ± 2.12 vs. 10.85 ± 1.83, p > 0.05) and miscarriage rates (24.89 ± 3.74 vs. 27.91 ± 4.91, p > 0.05) were not significantly different between groups. The effects of the PICSI procedure on fertilization rate, biochemical pregnancy rate, miscarriage rate, embryo quality, and clinical pregnancy outcomes were not superior. The effect of the PICSI procedure on embryo morphokinetics was not apparent when all parameters were considered.

Relationship of the levels of reactive oxygen species in the fertilization medium with the outcome of in vitro fertilization following brief incubation.

Embryo selection in in vitro fertilization-embryo transfer (IVF-ET) mostly relies on morphological assessment using a conventional microscope or the time-lapse monitoring system, which is not comprehensive. Inappropriate levels of reactive oxygen species (ROS) in the fertilization medium may cause damage to gametes, eventually leading to adverse IVF outcomes. The present study aimed to identify the optimal oxidation-reduction level in the fertilization medium for IVF outcomes by measuring the static oxidation-reduction potential (sORP) using a highly accurate and sensitive MiOXSYS system. A total of 136 patients undergoing IVF following brief incubation were divided equally into 4 groups in this prospective cohort study. The sORP value in the fertilization medium was detected using the MiOXSYS system, and its relationship with IVF outcomes was analyzed. The primary outcome was pregnancy outcomes, including live birth rate (LBR), clinical pregnancy rate (CPR), biochemical pregnancy rate (BPR), and implantation rate (IR). The secondary outcome was embryo quality, including fertilization rate (FR), cleavage rate (CR), available embryo rate (AER), and good-quality embryo rate (GQER). Group II (sORP: 228.7-235.3 mV) showed a higher LBR, CPR, BPR, and IR compared with Group III (sORP: 235.4-242.7 mV), presented as follows: LBR (32.0% for Group II vs 3.6% for Group III, P = 0.033), CPR (32.0% for Group II vs 3.6% for Group III, P = 0.033), BPR (36.0% for Group II vs 3.6% for Group III, P = 0.019), and IR (31.3% for Group II vs 2.7% for Group III, P = 0.003). The FR in Groups I and II had lower significant differences compared with that in Groups III and IV (71.7% and 70.3% for Groups I and II vs 83.5% and 80.4% for Groups III and IV, P = 0.000). The GQER in Group I to Group IV was 32.7%, 37.4%, 26.5%, and 33.3%, respectively (P = 0.056). This study indicated that the sORP value in the fertilization medium might be a potential indicator of embryo quality and pregnancy outcome.

Effectiveness, Flexibility and Safety of Switching IVF to IVM as a Rescue Strategy in Unexpected Poor Ovarian Response for PCOS Infertility Patients

According to the latest practice committee document, in vitro maturation (IVM) is a simple and safe procedure, especially in patients with polycystic ovary syndrome (PCOS). Does switching from in vitro fertilization (IVF) to IVM (IVF/M) help as a rescue infertility treatment for PCOS patients with an unexpected poor ovarian response (UPOR) tendency? This retrospective cohort study included 531 women with PCOS who had undergone 588 natural IVM cycles or had switched to IVF/M cycles from 2008 to 2017. Natural IVM was performed in 377 cycles, and switching IVF/M was performed in 211 cycles. The primary outcome measure was the cumulative live birth rates (cLBRs), and the secondary outcomes included laboratory and clinical outcomes, maternal safety, and obstetric and perinatal complications. No significant difference was found in the cLBRs between the natural IVM and switching IVF/M groups (23.6% vs. 17.4%, p = 0.05). Meanwhile, the natural IVM group had a higher cumulative clinical pregnancy rate (36.0% vs. 26.0%, p = 0.01), and a decrease in the number of oocytes was obtained in the switching IVF/M group (13.5 vs. 12.0, p < 0.01). The number of good quality embryos in the natural IVM group was 2.2 ± 2.5, and 2.1 ± 2.3 (p = 0.64) in the switching IVF/M group. No statistically significant differences were observed in the number of 2 pronuclear (2PN) and available embryos. Ovarian hyperstimulation syndrome (OHSS) did not occur in the switching IVF/M and natural IVM groups, indicating a highly favorable outcome. In PCOS infertile women with UPOR, timely switching IVF/M is a viable option that markedly reduces the canceled cycle, results in reasonable oocyte retrieval, and leads to live births.

Breeding and Reproduction of the African Turquoise Killifish Nothobranchius furzeri.

The successful breeding and reproduction of the African turquoise killifish Nothobranchius furzeri in a controlled laboratory setting are required to establish this fish species as a model system for studying vertebrate development and aging. Here, we describe a protocol to care for and hatch African turquoise killifish embryos, raise the juvenile fish to adulthood, and breed this species using sand as the breeding bedding. We also provide suggestions for generating a large quantity of good-quality embryos.

RNA sequencing-based transcriptome analysis of granulosa cells from follicular fluid: Genes involved in embryo quality during in vitro fertilization and embryo transfer.

Granulosa cells play an important role in folliculogenesis, however, the role of RNA transcripts of granulosa cells in assessing embryo quality remains unclear. Therefore, we aims to investigate that RNA transcripts of granulosa cells be used to assess the probability of the embryonic developmental capacity. This prospective cohort study was attempted to figure out the probability of the embryonic developmental capacity using RNA sequencing of granulosa cells. Granulosa cells were collected from 48 samples in good-quality embryo group and 79 in only poor- quality embryo group from women undergoing in vitro fertilization and embryo transfer treatment. Three samples from each group were used for RNA sequencing. 226 differentially expressed genes (DEGs) were related to high developmental competence of embryos. Gene Ontology enrichment analysis indicated that these DEGs were primarily involved in biological processes, molecular functions, and cellular components. Additionally, pathway analysis revealed that these DEGs were enriched in 13 Kyoto Encyclopedia of Genes and Genomes pathways. Reverse transcription quantitative polymerase chain reaction verified the differential expression of the 13 selected DEGs. Among them,10 genes were differently expressed in the poor-quality embryo group compared to good-quality embryo group, including CSF1R, CTSH, SERPINA1, CYP27A1, ITGB2, IL1β, TNF, TAB1, BCL2A1, and CCL4. RNA sequencing data provide the support or confute granulosa expressed genes as non-invasive biomarkers for identifying the embryonic developmental capacity.

The influence of preincubation time of prepared sperm before IVF on fertilization, embryo developmental competence and the reproductive outcomes.

It has been provided that if incubation time of prepared sperm can affect sperm motility and DNA fragment, but little is known about the influence of sperm preincubation time (SI) on the sperm's fertilizing ability, subsequent embryonic development and pregnancy outcomes in in vitro fertilization (IVF). The aim of this study was to explore the association of SI with fertilization rate, embryo development and clinical outcomes in IVF, further, to find an optimal preincubation time for prepared sperm before insemination in IVF. This retrospective cohort study included a total of 1453 infertile couples undergoing IVF in our center performed from January 2016 to January 2019. Sperm were preincubated at 37℃ 6% CO₂ for different times before insemination. Preincubation time associated with fertilization rate (FR), 2PN rate, D3 good quality embryo rate, fresh embryo implantation rate (IR), blastocyst formation rate, cumulative pregnancy rate (CPR), cumulative ongoing pregnancy rate (COPR), cumulative live birth rate (CLBR), newborn health and gender ratio were analyzed by chi-square analysis. FR and 2PN rate of SI more than four hours SI groups (> 4 h SI group) decreased significantly compared with other SI groups (p < 0.01). There were no significant differences of the D3 high quality embryo rate among five SI groups. The blastocyst formation rate of > 4 h SI group was significantly lower than that of 2-3 h SI group (45.5% vs 56.1%, p < 0.05); and 1-2 h SI group also had significant difference with 2-3 h and 3-4 h SI group (48.9% vs 56.1% and 54.6%, p < 0.05). There were a significant decrease of fresh IR and CPR in ≤1 h SI group compared with 1-2 h SI group (19.6% vs. 38.0%, p < 0.05; 62.7% vs 73.7%, p < 0.05); ≤ 1 h SI group also have the lowest CLBR (45.6%), it had statistic differences with 1-2 SI group and 3-4 SI group (45.6% vs 63.2%, p < 0.01; 45.6% vs 61.2%, p < 0.05). The sperm preincubated time at 37℃ 6% CO₂ before insemination could influence sperm fertilizing ability, blastocyst formation, embryo implantation and CLBR in IVF cycles. The best time for prepared sperm preincubation at 37℃ is one to four hours before insemination in IVF.

Ganirelix and the prevention of premature luteinizing hormone surges

Ganirelix is a gonadotropin-releasing hormone (GnRH) antagonist with high antagonistic activity that blocks the GnRH receptor by competitive binding. A daily dose of 0.25 mg of ganirelix was sel5ected after a phase II study because it was the minimal, effective daily dose to prevent premature luteinizing hormone surges and this dose yielded the highest ongoing pregnancy rate per started cycle. After subcutaneous administration, ganirelix is rapidly absorbed, reaching peak levels within 1-2 hours (tmax), and has a high absolute bioavailability (>90%). Prospective, comparative studies have demonstrated the advantages of GnRH antagonists over long GnRH agonist treatment in assisted reproduction, including the immediate reversibility of drug effects, a requirement for less follicle-stimulating hormone, a shortened duration of stimulation, a reduced incidence of ovarian hyperstimulation syndrome, and reduced patient burden. Combined analyses concluded that in the general invitro fertilization population, there is a trend for a slightly lower ongoing pregnancy rate and a lower risk of ovarian hyperstimulation syndrome that is largely eliminated when considering triggering with GnRH agonist instead of human chorionic gonadotropin. Regardless of all the research, it is still not fully elucidated why the long GnRH agonist protocol has a trend for higher pregnancy rates after fresh transfer of the same number of good-quality embryos.

Impact of vaccination against COVID-19 on the outcomes of in vitro fertilization-embryo transfer: a retrospective cohort study.

Vaccination against coronavirus disease 2019 (COVID-19) has become the primary approach in the fight against the spread of COVID-19. Studies have shown that vaccination against COVID-19 has adverse effects, particularly on human reproductive health, despite the fact that vaccination rates are still on the rise. However, few studies have reported whether vaccination affects the outcome of in vitro fertilization-embryo transfer (IVF-ET) or not. In this study, we compared the outcome of IVF-ET and the development of follicles and embryos between vaccinated and unvaccinated groups. A single-center retrospective cohort study of 10,541 in vitro fertilization (IVF) cycles was conducted from June 2020 to August 2021. 835 IVF cycles with a history of vaccination against COVID-19 and 1670 IVF cycles that served as negative controls were selected and analyzed utilizing the Matchlt package of R software (http://www.R-project.org/) and the nearest neighbor matching algorithm for propensity-matched analysis at a 1:2 ratio. The number of oocytes collected in the vaccinated group and the unvaccinated group were 8.00 (0, 40.00) and 9.00 (0, 77.00) (P = 0.073) and the good-quality embryo rates of the two groups were 0.56±0.32 and 0.56±0.31 averagely (P = 0.964). Clinical pregnancy rates for the vaccinated group and unvaccinated group were 42.4% (155/366) and 40.2% (328/816) (P = 0.486) and biochemical pregnancy rates were 7.1% (26/366) and 8.7% (71/816) (P = 0.355). Two other factors were analyzed in this study; vaccination among different genders and different types (inactivated vaccine or recombinant adenovirus vaccine) showed no statistically significant effect on the above outcomes. In our findings, vaccination against COVID-19 showed no statistically significant effect on the outcomes of IVF-ET and the development of follicles and embryos, nor did the gender of the vaccinated person or the formulation of vaccines showed significant effects.

Effects of different sperm sources on the clinical outcomes of in vitro oocyte maturation cycles combined with intracytoplasmic sperm injection.

To evaluate the embryonic developments and clinical outcomes of different sperm sources with cycles of intracytoplasmic sperm injection (ICSI) and in vitro maturation (IVM). This retrospective study was approved by the hospital ethics committee and conducted in the hospital in vitro fertilization (IVF) clinic. From January 2005 to December 2018, 239 infertile couples underwent IVM-ICSI cycles and were divided into three groups according to different sperm sources. Group 1 comprised patients with percutaneous epididymal sperm aspiration (PESA; n = 62, 62 cycles), group 2 comprised patients with testicular sperm aspiration (TESA; n = 51, 51 cycles), and group 3 comprised patients with ejaculated sperm (n = 126, 126 cycles). We calculated the following outcomes: 1) outcomes per IVM-ICSI cycle: fertilization rate, cleavage rate, and embryo quality; 2) outcomes per embryo transfer cycle: endometrial thickness, implantation rate, biochemical pregnancy rate, clinical pregnancy rate, and live birth rate. There was no difference in basic characteristics among the three groups, such as the female partner's age, basal follicle-stimulating hormone (FSH), basal luteinizing hormone (LH), and antral follicle count (p > 0.1). There were no statistically significant differences according to the IVM-ICSI cycle among the three groups in fertilization rate, cleavage rate, and rate of good-quality embryos (p > 0.05). The results were similar among cycles regarding the number of transfer embryos and endometrial thickness per embryo transfer cycle among the three groups (p > 0.05). There were also similar clinical outcomes per embryo transfer cycle among the three groups, such as the biochemical pregnancy rate, clinical pregnancy rate, and live birth rate (p > 0.05). Different sperm sources, percutaneous epididymal sperm aspiration, testicular sperm aspiration, and ejaculated sperm, do not affect the embryo and clinical outcomes after IVM-ICSI cycles.

The Influence of Follicular Fluid Metals on Assisted Reproduction Outcome.

Infertility has become more common, with an increased exposure to toxic compounds including heavy metals (HM). Follicular fluid (FF) surrounds the developing oocyte in the ovary and can be analysed to assess metal content. The levels of twenty-two metals were measured in the FF of ninety-three females in a reproduction unit, and their influence on assisted reproduction technique (ART), were examined. The metals were determined by optical emission spectrophotometry. Low values of copper, zinc, aluminium, and calcium favour polycystic ovary syndrome. The relationships between the number of oocytes and metals: iron (rs=0.303; p=0.003) and calcium (rs=-0.276; p=0.007) are significant, as well as between the number of mature oocytes with iron (rs=0.319; p=0.002), calcium (rs=-0.307; p=0.003) and sodium (rs=-0.215; p=0.039) and are near to significance in the case of aluminium (rs=-0.198; p=0.057). In the group with a fertilisation rate ≤ 75%, 36% of the women presented calcium >176.62 mg/kg compared to the group with a fertilisation rate ≥ 75% where this percentage was only 10% (p=0.011). An excess of iron and calcium reduces the good quality embryo rate, and an excess of potassium impairs the blastocyst rate. If potassium is above 237.18 mg/kg and calcium is below 147.32 mg/kg, these conditions favour embryo implantation. Pregnancy is influenced by high potassium and low copper levels. Controlling exposure to toxic elements is recommended for all couples with reduced fertility or receiving an ART.

Freeze-all embryos during treatment with assisted reproduction: Health economic aspects.

Assisted reproductive technologies are evolving, with the most recent example being the introduction of the freeze-all policy during which a fresh embryo transfer does not take place and all embryos of good quality are cryopreserved to be used in future frozen embryo transfers. As the freeze-all policy is becoming more prevalent, it is important to review the economic aspects of this approach, along with considerations of efficacy and safety, and the role of emerging freeze-all-specific ovarian stimulation strategies. Based on the available evidence, the freeze-all policy presents distinct clinical advantages, particularly for high responders. Available health economic evaluations are limited. Two good-quality cost-effectiveness analyses based on randomized controlled trials suggest that the freeze-all strategy is unlikely to be cost-effective in non-polycystic ovarian syndrome (non-PCOS), normally responding patients. However, the cost-effectiveness of the freeze-all strategy in different populations of patients and in different settings has not been evaluated, nor has the clinical and economic efficacy of modern freeze-all-specific ovarian stimulation protocols that are likely to simplify treatment and make it more affordable for patients. Economic evaluations that incorporate good practice health technology assessment (HTA) methods are needed to compare freeze-all with conventional embryo transfer strategies. Furthermore, future research should address the unique limitation of traditional HTA methods in valuing a life conceived through fertility treatment.

Mitochondrial Transfer into Human Oocytes Improved Embryo Quality and Clinical Outcomes in Recurrent Pregnancy Failure Cases.

One of the most critical issues to be solved in reproductive medicine is the treatment of patients with multiple failures of assisted reproductive treatment caused by low-quality embryos. This study investigated whether mitochondrial transfer to human oocytes improves embryo quality and provides subsequent acceptable clinical results and normality to children born due to the use of this technology. We transferred autologous mitochondria extracted from oogonia stem cells to mature oocytes with sperm at the time of intracytoplasmic sperm injection in 52 patients with recurrent failures (average 5.3 times). We assessed embryo quality using the following three methods: good-quality embryo rates, transferable embryo rates, and a novel embryo-scoring system (embryo quality score; EQS) in 33 patients who meet the preset inclusion criteria for analysis. We also evaluated the clinical outcomes of the in vitro fertilization and development of children born using this technology and compared the mtDNA sequences of the children and their mothers. The good-quality embryo rates, transferable embryo rates, and EQS significantly increased after mitochondrial transfer and resulted in 13 babies born in normal conditions. The mtDNA sequences were almost identical to the respective maternal sequences at the 83 major sites examined. Mitochondrial transfer into human oocytes is an effective clinical option to enhance embryo quality in recurrent in vitro fertilization-failure cases.

Correlation study of male semen parameters and embryo aneuploidy in preimplantation genetic testing for aneuploidy.

The purpose of this study was to evaluate the influence of abnormal semen parameters on embryo aneuploidy based on single nucleotide polymorphism microarray (SNP array). A total of 464 blastocysts from 103 PGT-A cycles were analyzed. The embryo quality and embryo aneuploidy rates were compared between different groups which divided by male semen parameters (sperm concentration, motility, morphology, and DFI) according the WHO criteria (2021). The total blastocysts chromosome aneuploidy rate was 42.3% (191/452). In the teratozoospermia group, the good-quality embryo and blastocyst formation rate were lower than the normal group(44.4% vs 60.7%, P <0.01; 33.3% vs 43.5%, P<0.05), The good-quality embryo rate in normal DFI group was significantly higher than high-DFI group (59.0% vs 48.4%, P < 0.05). The blastocyst aneuploidy rate in low sperm concentration group, and high DFI group was no differences between with that in normal sperm concentration and DFI group (47.7% vs 37.8% and 44.7% vs 37.8%, P>0.05). The aneuploid rate of blastocyst in teratozoospermic and asthenozoospermia group was significantly higher than that of normal morphology and motility group (50.0% vs 34.0% and 46.7% vs 33.7%, P<0.05). Our study revealed that sperm DFI were positively correlated with blastocyst aneuploidy rate, while sperm motility and sperm morphology rate were negatively correlated with blastocyst aneuploidy rate. Abnormal semen parameters may affect embryo quality and increase the aneuploidy rate of blastocyst chromosomes, suggesting that in clinical practice of assisted reproduction patients with abnormal semen parameters can be treated in advance to improve sperm quality, so as to reduce the impact on embryo quality and achieve a better pregnancy outcome.

Follicular fluid biomarkers for prediction of human IVF outcome in women with poor ovarian response

BackgroundThe aim of controlled ovarian stimulation is to achieve an optimal number of mature oocytes to obtain good-quality embryos. High follicular fluid (FF) concentrations of FSH, hCG, and LH promote oocyte maturation and are associated with a higher probability of fertilization. LH concentrations in FF are consistently higher in follicles that will lead to a successful IVF outcome. The levels of some of these FF biomarkers may vary among different ovarian stimulation schemes; however, the effects of corifollitropin alfa, recombinant FSH (rFSH), LH (rLH), and highly purified urinary menotropins uhMG on these biomarkers are still unknown. The objective of this study was to characterize the profile of FF biomarkers (leptin, vascular endothelial growth factor (VEGF), metalloproteinases (MMPs), and NO2−/NO3−) according to three different protocols of controlled ovarian stimulation (COS) in poor ovarian responders (POR) and to evaluate the association between these profiles and clinical outcomes. Three groups of POR patients were examined according to the protocols used.ResultsGroup C showed significant higher levels in all biomarkers (p < 0001). FF samples from Group B had the lowest levels of VEGF and Pro-MMP-9. Group A showed the lowest concentration of pro-MMP-2. The VEGF level and number of captured oocytes were positively correlated in Group C (r = 0.534, p = 0.01). MMP-9 and fertilization rate were negatively correlated in Group C (r = −0.476, p = 0.02). We found negative correlations between proMMP-2 and serum estradiol levels on the day of rhCG administration.ConclusionWe found significant variations in the biomarker concentrations between the different controlled ovarian stimulation schemes used in POR patients. These differences can be potentially explained by the nature and composition of the gonadotropins. Our results support the hypothesis that some of these molecules should be thoroughly investigated as noninvasive predictors of egg quality.

Serum C-reactive protein levels are associated with clinical pregnancy rate after in vitro fertilization among normal-weight women.

To assess whether low-grade inflammation, measured by serum high-sensitivity C-reactive protein (hsCRP) levels, is associated with in vitro fertilization (IVF) outcomes. A retrospective study. University-affiliated IVF center. In the present study, 875 women of normal weight who underwent their first fresh embryo transfer (ET) cycles for IVF treatment were divided into three groups according to serum concentrations of hsCRP. Serum from women undergoing IVF was collected on days 2-4 of a spontaneous menstrual cycle prior to the commencement of ovarian stimulation. The IVF outcomes included implantation, biochemical pregnancy, clinical pregnancy, miscarriage and live birth rates. The women were divided into three groups according to the baseline serum levels of hsCRP as follows: low hsCRP (<1 mg/L; n=517), medium hsCRP (1-3 mg/L; n= 270), high hsCRP (>3 mg/L; n=88). The maternal age was similar among the three groups. The women in the high and medium hsCRP group had significantly higher BMI compared with those in the low hsCRP group. The protocol of controlled ovarian hyperstimulation, the gonadotropin dose administered, the serum estradiol levels, progesterone levels and the endometrial thickness on the day of triggering, as well as the number of retrieved oocytes, fertilized oocytes and good quality embryos, and the oocyte maturation rate were similar among the three groups. Implantation, biochemical pregnancy and clinical miscarriage rates did not differ significantly were not significantly different among three groups. The clinical pregnancy rate was significantly lower in the high hsCRP group compared with that in the low hsCRP group (50.0% versus 63.4%; P<0.0167), which contributed to a significant decrease in birth rate (39.8% versus 53.8%; P<0.0167). High serum hsCRP levels was found to be a factor affecting live birth rate. Among women of normal weight undergoing their first IVF treatment, it was found that low-grade inflammation was associated with reduced clinical pregnancy and live birth rates following fresh ET cycles.

Association between transferred embryos and multiple pregnancy/live birth rate in frozen embryo transfer cycles: A retrospective study.

Physicians need an appropriate embryo transfer strategy to address the challenge of reducing multiple birth rates, while maintaining the couples' live birth rate during assisted reproductive technology. We included 10,060 frozen embryo transfer cycles from January 2015 to March 2020 in reproductive medical center of Ruijin hospital, Shanghai, China. Patients were grouped according to the number and grade of cleavage-stage embryo or blastocysts transferred. Live birth rate and multiple live birth rate were compared among groups of women of different ages. Multivariable logistic regression models were used to estimate the risk of multiple live birth using different combinations of transferred embryos. The transfer of double good-quality embryos was an independent predictor for multiple birth in women aged <30 years and those aged 36-39 years [<30 years: aOR =1.54 (95% CI: 1.14-2.06, P < 0.01); 36-39 years: aOR =1.84 (95% CI: 1.0-3.4, P < 0.01)]. Further, for women aged <36 years, the transfer of good-quality + poor-quality blastocysts was an independent predictor for multiple birth rate [<30 years: aOR=2.46 (95% CI: 1.45-4.18, P < 0.01); 31-35 years: aOR =4.45 (95% CI: 1.97-10.06, P < 0.01)]. Single-good-quality blastocyst transfer is recommended for women of all ages. When good-quality cleavage embryos are available, the choice of single or double embryo transfer with good- or average-quality embryo should depend on the age of women. Double embryo transfer with the highest possible grade of embryos is recommended for women aged ≥40 years.

Ovarian Stimulation in Patient-oriented Strategies Encompassing Individualised Oocyte Number-4 Category; Antagonist versus Short-agonist Protocols.

Recently POSEIDON (Patient-Oriented Strategies Encompassing Individualized Oocyte Number) classification was proposed to categorize patients with expected poor response to conventional stimulation. Searching for the ideal management of poor responders in IVF is still an active research area. This study compares GnRH-antagonist and GnRH-agonist short protocols in ICSI cycles for the POSEIDON-4 group. This retrospective study was conducted in a tertiary infertility unit between January 2016 and December 2020. Infertile women who met the criteria for POSEIDON 4 group and underwent fresh ICSI-ET in using GnRH-antagonist and GnRH-agonist short protocols was performed. POSEIDON-4 includes patients ≥ 35 years with poor ovarian reserve markers; AFC < 5 and AMH < 1.2 ng/ml. Numerical variables were compared between both groups by student's t test and Mann Whitney test when appropriate. Chi-square test used to compare categorical variables. Multivariate logistic regression models were utilized to adjust for the effect of the different study confounders on live birth rate. One hundred ninety fresh ICSI cycles were analyzed. Of the total cohort, 41.6 % (79) patients pursued antagonist protocol compared to 58.4% (111) underwent short agonist protocol. Fresh embryo transfer was accomplished in 55.7 % (44/79) vs. 61.3 % (68/111), P = 0.44 in antagonist vs. short protocol respectively. Cycle cancellation due to poor ovarian response was encountered in (32.9%vs. 27.9%, P = 0.50) in the antagonist and short groups, whereas no good-quality embryos were developed after ovum pickup in 11.4% vs. 10.8%, P>0.05. Comparable total gonadotropins dose, number of retrieved and mature oocytes, and good-quality embryos were found in both groups. Likewise, clinical pregnancy rate was not different for the antagonist and short groups [11/79 (13.9%) vs. 20/111 (18%), P = 0.45]. The live birth rate was comparable between both groups (8.9% vs. 10.8%, P = 0.659) for antagonist and short groups respectively. No significant impact for the protocol type on live birth rate was revealed after adjusting to cycle confounders in multivariate analysis (OR: 0.439, 95%CI 0.134-1.434, P = 0.173). This study shows comparable pregnancy outcomes for antagonist and short-agonist protocols in IVF/ICSI cycles for POSEIDON-4 category.

Clinical Outcomes in Patients Receiving Originator Follitropin Alfa and Follitropin Alfa Biosimilars in Real-world Clinical Practice: A Retrospective Study.

Biosimilar drugs have broadened the treatment options in assisted reproductive technology (ART). Real-world data comparing clinical outcomes of originator follitropin alfa (Gonal-f®) with its biosimilars are required to enrich the body of evidence for clinical decision-making on choice of drug. To compare the ART outcomes in patients receiving originator follitropin (Gonal-f®) and its biosimilars in clinical setting. Medical records of 364 infertile women who underwent ART between 2016 and 2020 at Akanksha Hospital and Research Institute, Gujrat, India, were retrospectively analysed. Participants were divided into two cohorts based on treatment (Gonal-f® cohort; N = 174 and biosimilar cohort; N = 190), each cohort further subdivided into group A (age <35 years) and group B (age ≥35 years). Fresh or frozen embryo transfer was performed as per the standard procedures of the clinic. Pregnancy rates and live birth rate (LBR) were the primary main outcome measures in this study. Descriptive statistics and Chi-square test were used for analysis. The number of oocytes retrieved from Gonal-f® and biosimilar cohorts were comparable (13.3 vs. 14.4). Compared to biosimilars, Gonal-f® treatment resulted in higher yield of cleavage stage and blastocyst stage embryos, and the proportion of women with good quality embryos was higher in the Gonal-f® cohort than the biosimilar cohort (83.3% vs. 69.5%). Patients receiving Gonal-f® reported higher pregnancy rates (59.2% vs. 39.7%) and LBR (43% vs. 17.7%) compared to those receiving biosimilars. Gonal-f® (originator follitropin) treatment could result in higher pregnancy rates and LBR in comparison to biosimilars in real-world setting.