Oocyte Quality In Women Research Articles

High dose of d-chiro-inositol improves oocyte quality in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial

The aim of this study was to evaluate the effect of two doses of d-chiro-inositol (DCI) in combination with Myo-inositol (MYO) on the oocyte quality (OQ) of women with polycystic ovarian syndrome (PCOS) undergoing intracytoplasmic sperm injection (ICSI). Methods: This was a controlled, randomized, double-blind, parallel group study on 172 oocytes from 11 women. The study compared the effect of two MYO-DCI formulations given over 12 weeks on OQ. Five women received 550 mg of MYO + 300 mg of DCI daily (high DCI content group), while 6 women were given a daily dose of 550 mg of MYO with the only 27.6 mg of DCI (low DCI content group). Results: According to a multivariate analysis using linear mixed effect models, high doses of DCI have a positive influence on the quality of the cytoplasm of the oocyte (β = 1.631, χ2 = 7.347, d.f. = 1, p = .00672). Zona pellucida, plasma membrane, cytoplasm, and sperm reception have also been improved with any combination of MYO/DCI by decreasing testosterone or improving insulin sensitivity, regardless of age and body mass index. Conclusion: The combination of MYO with high doses of DCI improved oocyte cytoplasm quality in women with PCOS undergoing ICSI.

Oocyte quality in women with infertility associated endometriosis

The mechanisms of endometriosis-related infertility remain still unknown. Endometriosis and clinical markers of oocyte quality are a very important problem of reproduction. The purpose of the study is to assess the quality of oocytes in women with infertility associated with endometriosis. The study included infertile reproductive aged women, between 29 and 40 years who underwent IVF and ICSI procedures. The patients were divided into three groups: group I involved 50 (n = 50) patients with recurrent unilateral endometriomas, group II included 50 patients (n = 50) unilateral endometriomas after surgical treatment and control group with 30 (n = 30) patients with tubal factor infertility. Clinical and morphological assessment of oocyte quality was performed in all IVF/ICSI cycles. The results of the study demonstrate a statistically significant increase in the number of immature oocytes of metaphase MI and immature oocytes at the GV germinal vesicle stage in patients with infertility associated with endometriosis, compared with the control group (p<.005). There is deterioration in the quality of the obtained oocytes in patients with the presence of endometrioma more than 3 cm in diameter. The results of this study allow to conclude that endometriomas negatively affect quality of oocyte and ovarian reserve, whereas endometriomas after cystectomy, have a deleterious and sustained effect on ovarian reserve.

Diminished ovarian reserve versus ovarian aging: overlaps and differences.

Diminished ovarian reserve, in general, implies a quantitative decline in the oocyte pool. However, whether this quantitative decline is necessarily accompanied by a qualitative decline, remains to be determined. Studies of natural conception suggest that fecundity of women with a quantitative decline in ovarian reserve is similar to age-matched women with normal ovarian reserve. Data on rates of pregnancy loss and fetal chromosomal abnormality do not consistently suggest a decline in oocyte quality in women who has a lower ovarian reserve. In assisted reproductive technology (ART) cycles, oocytes from women with diminished ovarian reserve have similar potential for euploid blastocyst development. Likewise, available evidence does not strongly suggest an increased risk of pregnancy loss in women with diminished reserve undergoing ART treatment as compared with similarly aged woman with normal ovarian reserve. Quantitative decline in ovarian reserve may not be necessarily accompanied by a qualitative decline. Although a decreased number of follicles and poor response to ovarian stimulation are hallmarks of ovarian aging, younger women with diminished ovarian reserve may not be experiencing the distinct effects of aging on oocyte quality.

Oocyte quality in women with thalassaemia major: insights from IVF cycles.

BackgroundWomen with thalassaemia major typically experience hypogonadotropic hypogonadism because of the toxic effects of iron overload on the anterior pituitary. Moreover, in affected women, serum anti-Mullerian hormone (AMH) and antral follicle count (AFC) are also shown to be reduced, suggesting that the peripheral excess of iron could also harm the ovarian reserve. To date, the detrimental effects of the disease on oocyte quality have not been investigated.Materials and methodsWomen with thalassaemia major who underwent in vitro fertilization (IVF) cycles were retrospectively identified over a 9 years period. They were matched (with a 1:5 ratio) by study period and age to a control group of infertile women undergoing IVF. Embriological variables were compared between the two groups. The primary outcome was the rate of top quality embryos.ResultsTwenty-one women with thalassaemia major (exposed group) and 105 controls (unexposed group) were ultimately included. Serum AMH was 0.6 [0.2–1.8] and 1.5 [0.7–3.5] ng/ml, respectively (p = 0.05). AFC was 4 (1–7.5) and 11 (5.5–16), respectively (p < 0.001). The total dose of gonadotropins used was higher in exposed women but the number of retrieved oocytes and oocytes used did not differ. The fertilization rate was higher in exposed compared to unexposed women, being 100% (76–100%) and 75% (50–100%). respectively (p = 0.03). The cleavage rate was also higher, being 75% (39–100%) and 50% (29–64%), respectively (p = 0.04). In contrast, the rate of top quality embryos did not differ, being 20% (0–76%) and 25% (5–50%), respectively (p = 0.98).ConclusionsDespite lower ovarian reserve, oocyte quality is not significantly affected in women with thalassaemia major.

SAT-LB042 Effect of Dehydroepiandrosterone on the Perimenopausal Ovary

Dehydroepiandrosterone (DHEA) supplementation can improve oocyte quality in women with diminished ovarian function1-2. However, it is unclear if similar beneficial effects of DHEA supplementation can be obtained during the perimenopause, a period when the number of ovarian follicles shows a marked age-associated decline. To address this question we examined the impact of 2.5-months of daily oral DHEA supplementation (5 mg) on the number of ovarian follicles as well as on the concentration of anti-Müllerian hormone (AMH) – a marker of ovarian function. The study used perimenopausal adult rhesus monkeys; like women, these long-lived nonhuman primates show ~28-day menstrual cycles and eventually undergo menopause. Furthermore, they show similar age-related neuroendocrine changes, including a marked decrease in circulating DHEA concentrations3-4. Our experimental design involved the following three groups (N = 6 per group): Young adult (mean age = 11.6 years), Old control (mean age = 23.1 years), and Old DHEA-treated (mean age = 23.5 years). Histological examination of the ovaries revealed a significant (P<0.05) age-related decrease in the mean number of pre-antral follicles but no obvious beneficial effect of DHEA supplementation. Similarly, AMH concentrations within the ovaries and serum, assessed by Western analysis and ELISA respectively, showed a significant (P<0.05) age-related decrease but no obvious beneficial effect of DHEA supplementation. Taken together, the results indicate that short-term DHEA supplementation alone is insufficient to enhance ovarian function during the perimenopause and they complement findings from our earlier studies, which showed no obvious benefit of DHEA supplementation on cognitive function5. On the other hand, it remains plausible that chronic DHEA supplementation, earlier DHEA intervention, and supra-physiological DHEA doses may have more therapeutic potential. 1Gleicher N et al.Reprod Biomed Online, 21:360-365, 2010. 2Yilmaz N et al. Eur J Obstet Gynecol Reprod Biol, 169:257-260, 2013. 3Downs JL & Urbanski HF. Biol Reprod, 75: 539-546, 2006. 4Sorwell KG et al. Neurobiol Aging, 33:1487.e1-e13, 2012. 5Sorwell KG et al. Genes Brain Behav, 16:361-368, 2017. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

GDF-9 and BMP-15 direct the follicle symphony.

Understanding the physiology underlying the complex dialog between the oocyte and its surrounding somatic cells within the ovarian follicle has been crucial in defining optimal procedures for the development of clinical approaches in ART for women suffering from infertility and ovarian dysfunction. Recent studies have implicated oocyte-secreted factors like growth differentiation factor 9 (GDF-9) and bone morphogenetic protein 15 (BMP-15), members of the transforming growth factor-beta (TGFβ) superfamily, as potent regulators of folliculogenesis and ovulation. These two factors act as biologically active heterodimers or as homodimers in a synergistic cooperation. Through autocrine and paracrine mechanisms, the GDF-9 and BMP-15 system has been shown to regulate growth, differentiation, and function of granulosa and thecal cells during follicular development playing a vital role in oocyte development, ovulation, fertilization, and embryonic competence. The present mini-review provides an overview of recent findings relating GDF-9 and BMP-15 as fundamental factors implicated in the regulation of ovarian function and discusses their potential role as markers of oocyte quality in women.

Poor Ovarian Responder: A Challenge

Assisted reproductive technology (ART) is rapidly progressing field with many new advances in the last decade in terms of clinical knowledge and technological development. The number of oocytes obtained after controlled ovarian stimulation is of central importance to reach the success in IVF. Poor ovarian responder poses a great challenge to present era of reproductive medicine. It is an important limiting factor in success of any treatment modality for Infertility. It indicates a reduction in quantity and quality of oocytes in women of reproductive age group. Evaluating Ovarian Reserve and individualizing the therapeutic strategies are very important for optimizing success rate. Early detection and active management are essential to minimize the need for egg donation.

Poor ovarian reserve.

Poor ovarian reserve (POR) is an important limiting factor for the success of any treatment modality for infertility. It indicates a reduction in quantity and quality of oocytes in women of reproductive age group. It may be age related as seen in advanced years of reproductive life or may occur in young women due to diverse etiological factors. Evaluating ovarian reserve and individualizing the therapeutic strategies are very important for optimizing the success rate. Majority or women with POR need to undergo in vitro fertilization to achieve pregnancy. However, pregnancy rate remains low despite a plethora of interventions and is associated with high pregnancy loss. Early detection and active management are essential to minimize the need for egg donation in these women.

Telomeres and Female Reproductive Aging.

Reproductive aging involves declines both in oocyte number and developmental capacity. Declining oocyte number alone cannot explain the manifestations of reproductive aging in women. We have proposed the Telomere Theory of Reproductive Aging to explain the complex phenotype found in oocytes from older women. Telomeres are TTAGGG repeats and associated proteins, which form loops at the ends of chromosomes to provide structural and genomic stability. Studies in mice and women show that telomere shortening in oocytes provides a parsimonious explanation for the effects of reproductive aging on oocyte quality. Measurement of polar body telomere length may predict oocyte quality in women undergoing ART.

Oogonial Precursor Cell-Derived Autologous Mitochondria Injection to Improve Outcomes in Women With Multiple IVF Failures Due to Low Oocyte Quality: A Clinical Translation.

Mitochondrial dysfunction has been suggested as a major cause of age-induced decline in oocyte quality. In the past, donor oocyte cytoplasmic transfer showed some success but was abandoned due to the concerns with heteroplasmy. Recent studies indicated presence of oogonial precursor cells (OPCs) in the human ovary, which could be an autologous source of "healthy mitochondria." We sought to investigate the clinical efficacy of OPC-derived autologous mitochondrial injection (AMI) to improve oocyte quality in women with multiple in vitro fertilization (IVF) failures. The OPCs were isolated from laparoscopically obtained ovarian cortical pieces by cell sorting using a monoclonal anti-vasa homolog (anti-DDX) antibody. They were then disrupted and mitochondria were isolated. Reconstituted mitochondria were injected into each oocyte during intracytoplasmic sperm injection. Paired comparisons were made between the first failed cycles and the post-AMI cycles. Of the 15 women undergoing ovarian stimulation, 2 were canceled and 3 decided to pool oocytes for later AMI. In remaining 10 (mean age 34.7 ± 4.1), AMI significantly improved fertilization rates (49.7 ± 31.3 vs 78.3 ± 18.9; P = .03) with a trend for better embryo grades (2.3 ± 0.3 vs 3.1 ± 0.7; P = .08). Four of 10 women conceived after single frozen embryo transfer and 3 after confirmation of diploidy via array comparative genomic hybridization (aCGH) (clinical pregnancy/embryo transfer = 4/10). These data show encouraging results for AMI in comparison to previous failed IVF cycles.

Protein modification as oxidative stress marker in follicular fluid from women with polycystic ovary syndrome: the effect of inositol and metformin.

The purpose of this study was to evaluate the oxidative stress status (OS) of follicular fluid (FF) and the oocyte quality in women with polycystic ovary syndrome (PCOS) undergoing different ovarian stimulation protocols. FF samples were collected after gonadotropin administration in association or not with metformin or D-chiro-inositol (DCI). OS status was then evaluated by checking the follicular fluid protein oxidation profile after specific labeling of aminoacidic free-SH groups, and two-dimensional electrophoresis followed by qualitative and semiquantitative analysis. Oocyte quality was assessed by international morphological criteria. Our data indicated that both treatments, even if to different extent, recovered a significantly high level of free-SH groups in FF proteins of PCOS women clearly indicating a decrease of OS level with respect to that found in FF samples from gonadotropins alone treated women. A higher number of good quality MII oocytes was also observed in DCI (P < 0.05) or metformin (P < 0.05) study groups in comparison to untreated control group. A natural supplement and a drug both showed a statistically significant positive effect on follicular milieu by decreasing the oxidative damage on FF proteins, as well as in recovering good quality oocytes.

Dynamics of nitric oxide, altered follicular microenvironment, and oocyte quality in women with endometriosis

To study follicular microenvironment in terms of free radical dynamics, oocyte quality, and assisted reproductive technology (ART) outcomes among women with (group A) and without (group B) endometriosis. Prospective cohort study. University ART center. Women with and without endometriosis undergoing ART (n=28). Follicular fluid (FF), granulosa cells (GCs), immature oocytes (IOs), and ART data on sibling cohort oocytes in groups A and B were compared. ART live birth outcomes, maturation, and aging among in vitro matured (IVM) oocytes, nitrate levels in FF, and nitrotyrosine (NT) footprints and apoptosis in the GCs. Clinical characteristics and ART live birth outcomes were no different between groups A and B. Women from group A had significantly lower peak serum E2 (2,068.8±244.6 pg/mL vs. 2,756.2±205.0 pg/mL) and higher apoptosis (80.0% vs. 22.2%) and NT staining (70.0% vs. 22.2%) in GCs compared with group B. Fewer IOs underwent IVM to MII (0.6±0.3) in group A compared with group B (1.4±0.2). IVM oocytes had significantly higher incidence of cortical granule loss (83.3% vs. 24.0%) and spindle disruption (66.7% vs. 16.0%) and higher zona pellucida dissolution timing (133.8±9.4 s vs. 90.5±5.8 s) in group A compared with group B. FF nitrate levels were significantly higher in women who failed to conceive in group A (478.2±43.1 nmol/L) compared with those that did conceive (173.3±19.0 nmol/L). Increased protein nitration, GC apoptosis, resistance to IVM, and oocyte aging indicate the involvement of oxidative dysregulation of NO in the pathophysiology of altered follicular milieu and poor oocyte quality in women with endometriosis.

Correlation between Expression of Glucose Transporters in Granulosa Cells and Oocyte Quality in Women with Polycystic Ovary Syndrome.

BackgroundThe glucose transporters (GLUTs) exhibit different tissue-specific expression. This study aimed to investigate the types of GLUTs expressed in human granulosa cells (GCs) obtained from women with polycystic ovary syndrome (PCOS) and their relationship with insulin resistance (IR) and the outcomes of in vitro maturation (IVM) of immature oocytes.MethodsExpression of GLUTs was evaluated in GCs from women with PCOS with or without IR. Thirty-six women with PCOS undergoing an IVM program were included. Differential gene expression between the insulin sensitive (IS) and IR group was measured by reverse transcription polymerase chain reaction.ResultsExpression of GLUTs 1, 3, 5, 8, and 13 was constitutive, whereas expression of GLUTs 2 and 7 was not observed in human GCs. The remaining GLUTs, 4, 6, 9, 10, 11, and 12, were differentially expressed among patients according to metabolic status, such as insulin sensitivity. A higher number of GCs from patients with IR (92%) expressed GLUT6 than GCs from IS PCOS patients (46.3%). Logistic regression showed that expression of GLUTs 9, 11, and 12 correlates with rates of IVM at 48 hours, fertilization, and implantation, respectively.ConclusionThis is the first report describing the expression pattern of all 13 members of the GLUT family in human GCs. Results of the present study suggest that patients' insulin sensitivity regulates GLUT expression in GCs in PCOS patients, and this may control oocyte quality for IVM and subsequent processes such as fertilization and implantation in patients taking part in an in vitro fertilization program.

Twice-daily dosing of gonadotropins does not improve embryo quality during in vitro fertilization cycles in women with polycystic ovary syndrome, when compared to once-daily dosing: a pilot study

To determine whether overexpression of the FSH receptor in polycystic ovary syndrome (PCOS) results in a relative deficiency of gonadotropins and poor oocyte and embryo quality during in vitro fertilization (IVF) cycles. Whether twice-daily dosing of gonadotropins could therefore result in improved embryo quality, by fixing this hypothesized relative deficiency of gonadotropins. Embryos generated at a university-based fertility center in women with PCOS were compared from twice-daily dosing to once-daily dosing of gonadotropins during IVF cycles. Oocyte and embryo quality was compared. A single patient's embryos were included in the analysis from only one IVF cycle and all embryos from that cycle were included. 254 embryos were compared. Twice-daily vs. once-daily dosing of gonadotropins does not improve embryo or oocyte quality in women with PCOS. The defect in response to gonadotropins in PCOS is most likely due to an inherent defect in the ovary and not a relative deficiency of gonadotropins due to overexpression of the FSH receptors. More studies are needed to confirm this finding.

Post-genomic networks of folicular fluid and their relation to ageing in controlled ovarian stimulation cycles

Although increase in age is the single most important factor associated with decreased pregnancy rates and oocyte quality in women, molecular mechanisms of this decreased quality is still poorly understood. Current advances in metabolomics and post-genomic pathway analysis have allowed a better comprehension of these mechanisms in a number of biological conditions. Thus, the aim of this study was to determine the comparative lipid profile and to understand its role in biological systems, in follicular fluid, between women up to 35 years old and women above 35 years old. Prospective study. Follicular fluid samples from 81 women were collected and grouped as: up to 35 years old (n = 52) and above 35 years old (n = 29). Lipids were extracted and spectra were acquired using a Waters Synapt G1 Q-TOF in MS mode. Lipids were identified by mass using the online databases Lipid Maps and KEGG and compared using the Mann-Whitney test (P<0.05). Statistically identified lipids were analyzed for their pathway networks and functional enrichment of Gene Ontology (GO) terms was analyzed (P<0.01). 29 lipid markers were identified, present in three main classes, glycerophosphoglycerol (36%), glycerol-phosphoserine (9%), and glycerophosphocholine (55%). These compounds are involved in numerous biological and molecular processes. Women over 35 presented enrichment in arachidonic acid metabolism, gycosilation of proteins, response to steroid hormones, binding to calcium, increased Co-enzyme A activity and lipid and phospholipid catabolic process and metabolism. Systems biology based on post-genomic medicine is a new approach that may help unravel a number of altered mechanisms not previously understood. In this study, we observed that aging may influence mechanisms of lipid degradation which participate in a downstream cascade leading ultimately to decreased oocyte quality and pregnancy rates.

The efficacy of melatonin administration on oocyte quality

The aim of the study was to evaluate the efficacy of melatonin administration on oocyte quality in women underwent in vitro fertilization (IVF) cycles. Eighty-five women undergoing IVF cycles were randomized in two groups during IVF–embryo transfer (ET) procedure, 40 women with melatonin treatment (A) and 45 women without melatonin treatment (B). Primary endpoint was the number of morphologically mature oocytes retrieved (MII oocytes). Secondary endpoints were fertilization rate per number of mature oocytes, embryo quality and pregnancy rate. There were no differences between two groups according to age, and peak estradiol levels. The mean number of oocytes (15.33 vs. 14.27) and the mean number of mature oocytes did not differ between the two groups (12.63 vs. 10.94), whereas the percentage of mature oocytes (M2/oocytes retrieved) was significantly different in melatonin-treated group (p < 0.05). Fertilization rate (72.75 vs. 71.16) did not differ between the two groups. The mean number of class 1 embryos resulted higher in the group A (3.28 vs. 2.53) (p < 0.05). Clinical pregnancy rate was in tendency higher in the group treated with melatonin, although the differences did not reach statistical significance. Melatonin is likely to improve oocyte and embryo quality in women undergoing IVF or intracytoplasmic sperm insemination (ICSI).

Effect of a supplementation with myo-inositol plus melatonin on oocyte quality in women who failed to conceive in previous in vitro fertilization cycles for poor oocyte quality: a prospective, longitudinal, cohort study

Background. Several factors can affect oocyte quality and therefore pregnancy outcome in assisted reproductive technology (ART) cycles. Recently, a number of studies have shown that the presence of several compounds in the follicular fluid positively correlates with oocyte quality and maturation (i.e., myo-inositol and melatonin).Aim. In the present study, we aim to evaluate the pregnancy outcomes after the administration of myo-inositol combined with melatonin in women who failed to conceive in previous in vitro fertilization (IVF) cycles due to poor oocyte quality.Materials and methods. Forty-six women were treated with 4 g/day myo-inositol and 3 mg/day melatonin (inofolic® and inofolic® Plus, Lo.Lipharma, Rome) for 3 months and then underwent a new IVF cycle.Results. After treatment, the number of mature oocytes, the fertilization rate, the number of both, total and top-quality embryos transferred were statistically higher compared to the previous IVF cycle, while there was no difference in the number of retrieved oocyte. After treatment, a total of 13 pregnancies occurred, 9 of them were confirmed echographically; four evolved in spontaneous abortion.Conclusion. The treatment with myo-inositol and melatonin improves ovarian stimulation protocols and pregnancy outcomes in infertile women with poor oocyte quality.

Cumulus Cell Gene Expression Profile A Potential Indicator of Oocyte Quality in Women Undergoing Assisted Reproductive Technology (ART).

Cumulus Cell Gene Expression Profile A Potential Indicator of Oocyte Quality in Women Undergoing Assisted Reproductive Technology (ART).

Response to controlled ovarian stimulation and oocyte quality in women with myotonic dystrophy type I

In women the relationship between myotonic dystrophy type I and fertility remains controversial. The objective of this study was to evaluate the ovarian reserve, ovarian response to stimulation and oocyte quality in these patients. We compared 15 myotonic dystrophy type I patients with 39 age matched controls with isolated male factor infertility necessitating ICSI. All parameters of ovarian reserve (day 3 FSH and E2, antral follicle count and delta E2) were significantly better in the controls. Despite having significantly lower doses of gonadotrophin, the control group attained a higher number of retrieved oocyte-cumulus complexes (p < 0.04). Analysis of cytoplasmic and extracytoplasmic dysmorphism did not reveal any difference between the two groups. Fertilisation rate and top grade embryos on day 3 were similar in both groups. The present study suggests that though women with myotonic dystrophy type I have a reduced ovarian reserve and respond poorly to controlled ovarian stimulation, there is no impact on oocyte and embryo quality. Hence suggesting that successful ART is feasible with appropriate selection in women with mild myotonic dystrophy.

Oocyte degeneration after intracytoplasmic sperm injection: a multivariate analysis to assess its importance as a laboratory or clinical marker

Oocyte degeneration has historically been associated with the intracytoplasmic (ICSI) technique. We sought to determine whether oocyte degeneration rates were associated with the technician performing the procedure, the baseline characteristics of the patient, and/or ovarian stimulation variables. We also evaluated whether the degeneration rate could serve as a surrogate marker for implantation potential. Cohort study. Academic medical center. Couples undergoing ICSI. Six thousand six hundred fifty-three injected oocytes were analyzed to determine whether the degeneration rate was technician dependent. Two hundred thirty first-entry down-regulated cycles were examined to identify predictors associated with oocyte degeneration. Multivariate analyses were performed using generalized linear model routines. Oocyte degeneration rates and implantation rates. Neither the ICSI technician nor the stripping technician was associated with the oocyte degeneration rate. However, the day 3 FSH, number of mature oocytes retrieved, and E2 levels on the day of hCG were significant independent predictors of degeneration rate. Physician-adjustable ovarian stimulation variables were not associated with the degeneration rate. The degeneration rate did not appear to be associated with the implantation rate. These data suggest that oocyte degeneration is not technician or physician dependent. Degeneration is likely a function of the inherent oocyte quality in women who underwent ovarian stimulation. However, the remaining cohort of retrieved oocytes appears to be unaffected by virtue of an uncompromised implantation rate.